Sandbox Jose2

Yersinia pseudotuberculosis

• 1. Enterocolitis treatment

• Preferred regimen: There is also no evidence that early antimicrobial therapy reduces the frequency or severity of chronic sequelae for either Y. enterocolitica or Y. pseudotuberculosis
• Note: Susceptible to Ampicillin, third generation cephalosporins, aminoglycosides, tetracyclines, and chloramphenicol

• 2. Septicemia treatment

• Preferred regimen: Ceftriaxone 1 g IM/IV q12h
• Note: Pediatric dose: Ceftriaxone 100 mg/kg/day (up to 2 g/day) IM/IV q12h
• Note: There is no duration of treatment established but some Yersinia spp infections have been treat for at least 3 weeks.

Yersinia pestis

• 1. Plague treatment

• Preferred regimen (1): Streptomycin 2 g/day IM q12h for at least 10 days

• Note: Pediatric dose: Streptomycin 30 mg/kg/day (up to 2 g/day) IM q6-12h for at least 10 days

• Preferred regimen (2): Gentamicin 3 mg/kg/day IM or IV q8h for at least 10 days

• Note: Pediatric dose: Gentamicin 6-7.5 mg/kg/day IM or IV q8h for at least 10 days - if neonates/infants use 7.5 mg/kg/day.

• Alternative regimen (1): Chloramphenicol 50 mg/kg/day IV or PO q6h for 10 days
• Alternative regimen (2): Tetracycline 2 g/day PO qid for 10 days

• Note: Pediatric dose: Tetracycline 15 mg/kg of loading dose THEN 25-50 mg/kg/day (up to 2 g/day) PO qid for 10 days

• Alternative regimen (3): Sulfadiazine 2-4 g loading dose THEN 1 g PO q4-6h
• Alternative regimen (4): Doxycycline 200 mg/day PO q12-24h
• Note (1): Fluoroquinolones have good effect against Y. pestis in both in vitro and animal studies, but no studies have been published on its use in treating human plague.
• Note (2): Other antibiotics have been shown ineffective against plague.

• 2. Plague prophylaxis

• Preferred regimen: Tetracycline 1-2 g/day PO bid-qid

• Note: Pediatric dose: Tetracycline 25-50 mg/kg/day (up to 2 g/day) PO qid for 10 days

• Alternative regimen (1): Doxycycline 100-200 mg/day PO q12-24h
• Alternative regimen (2): Sulfamethoxazole-Trimethoprim 1.6 g/day PO bid

• Note: Pediatric dose: Sulfamethoxazole-Trimethoprim 40 mg/kg/day PO bid

Neutropenic fever

• 1. Empiric initial treatment

• 1.1 Low-risk (anticipated neutropenia for less than 7 days, clinically stable and no medical comorbidities, MASCC score ≥21)

• Preferred regimen: Ciprofloxacin PLUS Amoxicillin-clavulanate

• 1.2 High-risk (anticipated neutropenia for more than 7 days, clinically unstable or any medical comorbidities, MASCC score <21)

• Preferred regimen (1): Piperacillin-tazobactam 4.5 g IV q6-8h
• Preferred regimen (2): Imipenem 500 mg IV q6h
• Preferred regimen (3): Meropenem 1 g IV q8h
• Preferred regimen (4): Cefepime 2 g IV q8h
• Preferred regimen (5): Ceftazidime 2 g IV q8h
• Alternative regimen (1): (for penicillin allergic patients) (Ciprofloxacin PLUS Clindamycin)

• Alternative regimen (2): Aztreonam PLUS Vancomycin
• Note (1): monotherapy is preferred since no study has shown superiority for combination therapy.
• Note (2): add Vancomycin to the regimen if patient has signs of severe sepsis, hemodynamic instability, pneumonia, positive blood cultures for gram-positive bacteria while awaiting susceptibility results, suspected central venous catheter related infection, skin or soft tissue infection, severe mucositis in patients receiving prophylaxis with a fluoroquinolone lacking acitvity against streptococci and in whom ceftazidime is being used as empiric therapy (addition of gram-positive coverage is recommended in this situation because of the increased risk of Streptococcus viridans infections, which can result in sepsis and the acute respiratory distress syndrome).
• Note (3): modify the initial regimen if patient is at risk of infection with the following antibiotic-resistant organisms:

• MRSA: consider early addition of Vancomycin OR Linezolid OR Daptomycin
• VRE: consider early addition of Linezolid OR Daptomycin
• ESBLs: consider early use of a Carbapenem
• KPCs: consider early use of Polymyxin-colistin OR Tigecycline

• Note (4): the initial regimen should not be changed because of unexplained persistent fever if the patient is stable. However, if an infection is identified, the patient must be treated accordingly.
• Note (5): if Vancomycin or other gram-positive coverage was started initially, it may be stopped after two to three days if there is no evidence of a gram-positive infection.
• Note (6): empiric antifungal coverage should be considered in high-risk neutropenic patients who are expected to have a total duration of neutropenia >7 days and have persistent fever after four to seven days of a broad-spectrum antibacterial regimen and no identified source of fever. Clinically unstable patients with suspected fungal infection should be considered for antifungal therapy even earlier than what is recommended for empiric therapy.Candida spp are the most likely cause of invasive fungal infection in patients who are not receiving prophylaxis. In patients receiving fluconazole prophylaxis, fluconazole-resistant Candida spp and invasive mold infections, particularly Aspergillus spp, are the most likely causes. Recommended antifungal regimen:

• Caspofungin 70 mg IV on day one THEN 50 mg IV qd
• Voriconazole 6 mg/kg IV q12h on day one THEN 4 mg/kg IV q12h
• Amphotericin B lipid complex 5 mg/kg IV qd
• Liposomal amphotericin B 3 to 5 mg/kg IV qd

• 2. Prophylaxis

• 2.1 Antifungal prophylaxis
• Indications:

• Prophylaxis against Candida infections is recommended in patient groups in whom the risk of invasive candidal infections is substantial, such as allogeneic HSCT recipients or those undergoing intensive remission-induction or salvage induction chemotherapy for acute leukemia.
• Prophylaxis against invasive Aspergillus infections with Posaconazole should be considered for selected patients >13 years of age who are undergoing intensive chemotherapy for AML/MDS in whom the risk of invasive aspergillosis without prophylaxis is substantial.
• Prophylaxis against Aspergillus infection in pre- engraftment allogeneic or autologous transplant recipients has not been shown to be efficacious. However, a mold-active agent is recommended in patients with prior invasive aspergillosis, anticipated prolonged neutropenic periods of at least 2 weeks, or a prolonged period of neutropenia immediately prior to HSCT.

• Recommended drugs:

• Preferred regimen: Fluconazole
• Alternative regimen (1): Posaconazole
• Alternative regimen (2): Voriconazole
• Alternative regimen (3): Caspofungin
• Alternative regimen (4): Micafungin

• 2.2 Antiviral prophylaxis

• There is usually no indication for the prophylactic use of antiviral drugs in patients with neutropenia. However, if skin or mucous membrane lesions due to herpes simplex or varicella-zoster viruses are present, even if they are not the cause of fever, prophylaxis with Acyclovir can be considered.

• Recommended drugs:

• Preferred regimen: Acyclovir

• 2.3 Antibacterial prophylxis

• Fluoroquinolone prophylaxis should be considered for high-risk patients with expected durations of prolonged and profound neutropenia (ANC <100 cells/mm3 for >7 days)

• Recommended drugs:

• Preferred regimen (1): Levofloxacin
• Preferred regimen (2): Ciprofloxacin

Sporotrichosis

• Sporotrichosis Return to Top

• Lymphocutaneous/cutaneous

• Preferred regimen: Itraconazole 200mg PO qd
• Alternative regimen: Itraconazole 200 mg PO bid OR Terbinafine 500 mg PO bid OR Saturated solution potassium iodide with increasing doses OR Fluconazole 400–800 mg PO qd OR local hyperthermia
• Note (1): Treat for 2–4 weeks after lesions resolved
• Note (2): SSKI initiated at a dosage of 5 drops (using a standard eyedropper) q8h, increasing as tolerated to 40–50 drops q8h

• Osteoarticular

• Preferred regimen: Itraconazole 200mg PO bid for 12 months
• Alternative regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV OR Amphotericin B deoxycholate 0.7–1 mg/kg/day IV
• Note (1): Switch to Itraconazole after favorable response if AmB used
• Note (2): Treat for a total of at least 12 months

• Pulmonary

• Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV for severe or life-threatening pulmonary sporotrichosis, then Itraconazole 200 mg PO bid
• Preferred regimen(2): Itraconazole 200 mg PO bid for 12 months for less severe disease
• Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d IV THEN Itraconazole 200 mg PO bid OR surgical removal
• Note (1): Treat severe disease with an AmB formulation followed by Itraconazole
• Note (2): Treat less severe disease with Itraconazole
• Note (3): Treat for a total of at least 12 monthsSurgery combined with amphotericin B therapy is rec- ommended for localized pulmonary disease

• Meningitis

• Preferred regimen: Lipid amphotericin B (Lipid AmB) 5 mg/kg daily for 4–6 weeks, then Itraconazole 200 mg PO bid
• Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d, then Itraconazole 200 mg PO bid
• Note (1): Length of therapy with AmB not established, but therapy for at least 4–6 weeks is recommended.
• Note (2): Treat for a total of at least 12 months.
• Note (3): May require long-term suppression with Itraconazole.

• Disseminated

• Preferred regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day, then Itraconazole 200 mg PO bid
• Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/day, then Itraconazole 200 mg PO bid
• Note(1): Therapy with AmB should be continued until the patient shows objective evidence of improvement.
• Note(2): Treat for a total of at least 12 months.
• Note(3): May require long-term suppression with Itraconazole.

• Pregnant women

• Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV OR Amphotericin B deoxycholate 0.7–1 mg/kg/day IV for severe sporotrichosis
• Preferred regimen(2): Local hyperthermia for cutaneous disease.
• Note (1): It is preferable to wait until after delivery to treat non–life-threatening forms of sporotrichosis.
• Note (2): Azoles should be avoided.

• Children

• Preferred regimen:

• Mild disease: Itraconazole 6–10 mg/kg/day PO (400 mg/day maximum)
• Severe disease: Amphotericin B deoxycholate 0.7 mg/kg/day IV followed by Itraconazole 6–10 mg/kg PO up to a maximum of 400 mg PO daily, as step-down therapy::* Alternative regimen: Saturated solution potassium iodide with increasing doses for mild disease initiated at a dosage of 1 drop (using a standard eyedropper) q8h and increased as tolerated up to a maximum of 1 drop/kg or 40–50 drops q8h, whichever is lowest

MERS

• Middle East Respiratory Syndrome

• Preferred regimen: supportive care. There is no antiviral recommended for this infection at this moment, even though experimental therapies are at research (IFNs, Ribavirin, Lopinavir, Mycophenolic acid, Cyclosporine, Chloroquine, Chlorpromazine, Loperamide, 6-mercaptopurine and 6-thioguanine). Supportive care include: administer oxygen to patients with severe acute pulmonary infection with signs of respiratory distress, hypoxaemia or shock; use conservative fluids management, avoid administering high-dose systemic glucocorticoids, use non-invasive ventilation, but, if its nor effective, do not delay endotracheal intubation; use lung-protective strategy for intubated patients, recognize sepsis as early as possible and treat it accordingly.

Penicilliosis

• Penicilliosis treatment

• 1. Mild disease

• Preferred regimen: Itraconazole 200 mg PO bid for 8 to 12 weeks without amphotericin B induction therapy
• Alternative regimen: Voriconazole 400 mg PO bid on day 1 THEN 200 mg PO bid for 12 weeks

• 2. Moderate-severe disease

• Preferred regimen: Liposomal Amphotericin B 3-5 mg/kg/day IV qd OR Amphotericin B lipid complex 5 mg/kg/day IV qd for 2 weeks THEN Itraconazole 200 mg PO bid for 10 weeks
• Alternative regimen: Voriconazole 6 mg/kg IV q12h on day 1 THEN 4 mg/kg q12h for at least 3 days THEN Voriconazole 200 mg PO bid for a total of 12 weeks

• 3. Maintenance therapy

• Preferred regimen Itraconazole 200 mg PO qd
• Alternative regimen: Voriconazole 200 mg PO bid

• Note: Voriconazole and Itraconazole use require serum levels to be monitored to ensure adequate absorption.

Mucormycosis

• Mucormycosis Return to Top
• Mucormycosis

• Treatment include surgical debridement of involved tissues, antifungal therapy, use of growth factors to accelerate recovery from neutropenia, provision of granulocyte transfusions with sustained circulating neutrophils until the patient recovers from neutropenia, and discontinuation or reduction in the dose of glucocorticoids, correction of metabolic acidosis and hyperglycemia.
• Preferred regimen (1): Amphotericin B Deoxycholate 1.0-1.5 mg/kg/day IV q24h
• Preferred regimen (2): Lipid Amphotericin B 5-10 mg/kg/day IV q24h
• Preferred regimen (3): Amphotericin B lipid complex 5-7.5 mg/kg/day IV q24h
• Alternative regimen (1):Caspofungin 70 mg IV load dose, 50 mg/day for >2 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h

• Pediatric dose: Caspofungin 50 mg/m² IV q24h PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h

• Alternative regimen (2): Micafungin OR Anidulafungin 100 mg/day for 2 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h

• Pediatric dose: Micafungin 4 mg/kg/day; Micafungin 10mg/kg/day for low-birth weight infants; Anidulafungin 1.5 mg/kg/day

• Alternative regimen (3): Deferasirox 20 mg/kg PO qd for 2–4 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h
• Alternative regimen (4): Posaconazole 800 mg/day PO qid or bid
• Alternative regimen (5): Initial: Isavuconazole 200 mg PO/IV q8h for 6 doses; maintenance: 200 mg PO/IV qd
• Note (1): start maintenance dose 12 to 24 hours after the last loading dose.
• Note (2): For salvage therapy: (Posaconazole 800 mg/day PO qid or bid ± Lipid Amphotericin B 5-10 mg/kg/day IV q24h) OR (Deferasirox 20 mg/kg PO qd for 2–4 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h) OR Granulocyte transfusions (for persistently neutropenic patients) ∼10ˆ9 cells/kg OR Recombinant cytokines G-CSF 5 μg/kg/day, GM-CSF 100–250 μg/m², or IFN-g at 50 μg/m² for those with body surface area ≥ 0.5 m² and 1.5 μg/kg for those with body surface area <0.5 m²

Herpes Virus

• Human herpesvirus 6 Return to Top

• Human herpesvirus 6 treatment

• Preferred regimen: supportive therapy
• Note: If patient is immunocompromised, there are no antiviral regimens stablished as there are no clinical trials to validate their use on these cases. Consider administering Ganciclovir, Acyclovir, Foscarnet OR Cidofovir.

• Roseola Return to Top

• Human herpesvirus 7 (roseola virus) treatment

• Preferred regimen: Supportive therapy
• Note (1): Immunocompetent hosts with uncomplicated skin manifestations associated with HHV-7, particularly roseola infantum and pityriasis rosea, need only symptomatic management
• Note (2): For HIV-positive patients, antiretroviral therapy may be advisable
• Note (3): The most active antiviral compounds against HHV-7 are Cidofovir and Foscarnet

Hepatitis E

• Hepatitis E virus Return to Top
• Hepatitis E treatment

• Preferred regimen: supportive therapy. There is no specific treatment available.

• Note (1): Hepatitis E is usually self-limiting, hospitalization is generally not required.
• Note (2): Hospitalization is required for people with fulminant hepatitis and should also be considered for symptomatic pregnant women.

Enterovirus D68

• Enterovirus D68 Return to Top

• Enterovirus treatment

• Preferred regimen: supportive therapy
• Note: A new drug Pleconaril designed to affect Rhinovirus is being suggested to be effective against Enterovirus D68 but further investigation is required

Adenovirus

• Adenovirus Return to Top

• Adenovirus

• 1. In severe cases of pneumonia or post hematopoietic stem cell transplantation

• Preferred regimen (1): Cidofovir 5 mg/kg/week IV for 2 weeks, then every 2 weeks AND Probenecid 1.25 g/M² PO given 3 hours before Cidofovir and 3 & 9 hours after each infusion
• Preferred regimen (2): Cidofovir 1 mg/kg IV 3 times per week
• Note: Ganciclovir, Foscarnet and Ribavirin are not recommended for use on adenovirus infection.

• 2. For hemorrhagic cystitis

• Preferred regimen: Cidofovir (5 mg/kg in 100 mL saline instilled into bladder) intravesical

• 3. Pink eye (viral conjunctivitis)

• Preferred regimen: No specific treatment available. If symptomatic, cold artificial tears may help.

• 4.Bronchitis

• Preferred regimen: No specific therapy recommended, treatment is symptomatic.

SARS

• SARS Return to Top
• Severe acute respiratory distress syndrome- coronavirus

• Preferred regimen: supportive therapy
• Note: New therapies were studied for SARS during the last outbreaks which concluded:

• Ribavirin ineffective and probably harmful due to haemolytic anaemia
• Lopinavir PLUS Ritonavir is still controversial and need further investigation
• Interferon has no benefit and its studies are inconclusive
• Corticosteroids increases risk of fungal infections, some studies showed a higher incidence of psychosis, diabetes, avascular necrosis and osteoporosis
• Inhaled Nitric oxide potent mediator of airway inflammation, its has improved oxygenation in some studies

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CMV

• Cytomegalovirus Return to Top

• Cytomegalovirus treatment

• 1. Immunocompetent patients

• 1.1 Mononucleosis syndrome

• Preferred regimen: supportive therapy

• 1.2 CMV in pregnancy

• Preferred regimen: Hyperimmune 200 IU/kg of maternal weight as single-dose during pregnancy

• 2. Immunocompromised patients

• 2.1 Retinitis

• Preferred regimen (1): Ganciclovir intraocular implant PLUS Valganciclovir 900 mg PO bid for 14-21 days THEN Valganciclovir 900mg PO qq for maintenance therapy - for immediate sight-threatening lesions
• Preferred regimen (2): Valganciclovir 900 mg PO bid for 14-21 days THEN Valganciclovir 900 mg PO qq for maintenance therapy - for peripheral lesions
• Alternative regimen (1): Foscarnet 60 mg/kg IV q8h OR Foscarnet 90 mg/kg IV q12h for 14-21 days THEN Foscarnet 90-120 mg/kg IV q24h
• Alternative regimen (2): Cidofovir 5 mg/kg IV for 2 weeks THEN Cidofovir 5 mg/kg IV every other week - each dose should be admnistered with IV saline hydration and probenecid
• Alternative regimen (3): Ganciclovir 5 mg/kg IV q12h for 14-21 days THEN Valganciclovir 900 mg PO bid
• Alternative regimen (4): Fomivirsen intravitreal injection - for relapses
• Note: keep a maintenance dose of Valganciclovir 900 mg PO qd until CD4 >100/mm³

• 2.2 Transplant patients

• Preferred regimen: Valganciclovir 900 mg PO bid OR Ganciclovir 5 mg/kg IV q12h for at least 2-3 weeek
• Note: Use Valganciclovir 900 mg PO qd for 1-3 months if high dose of immunosuppression.

• 2.3 Colitis, esophagitis, gastritis

• Preferred regimen: Ganciclovir 5 mg/kg/dose IV q12h for 3-6 weeks weeks for induction. There is no agreement on the use of maintenance.
• Alternative regimen: Cidofovir 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid 2 g PO 3h before each dose and further 1 g doses after 2h and 8h.
• Note: Switch to oral Valganciclovir when PO tolerated & when symptoms not severe enough to interfere with absorption.

• 2.4 Pneumonia

• Preferred regimen: Valganciclovir 900 mg PO bid for 14–21 days, then 900 mg PO qd for maintenance therapy
• Alternative regimen for retinitis: Ganciclovir 5 mg/kg IV q12h for 14–21 days, then Valganciclovir 900 mg PO qd
• Note: In bone marrow transplant patients, combine therapy with CMV immune globulin.

• 2.5 Encephalitis, ventriculitis

• Note: Treatment not defined, but should be considered the same as retinitis. Disease may develop while taking Ganciclovir as suppressive therapy.

• 2.6 Lumbosacral polyradiculopathy

• Preferred regimen: Ganciclovir, as with retinitis
• Alternative regimen: Foscarnet 40 mg/kg IV q12h another option
• Alternative regimen: Cidofovir 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid 2 g PO 3h before each dose and further 1 g doses after 2h and 8h.
• Note (1): Switch to Valganciclovir when possible.
• Note (2): Suppression continued until CD4 remains >100/mm³ for 6 months.

• 2.7 Peri/postnatal severe CMV infection in very low birth weight infants

• Preferred regimen: Ganciclovir 6 mg/kg/dose IV q12h for 3 weeks

Ebola

• Ebola virus Return to Top

• Ebola virus treatment

• Preferred regimen: supportive therapy. There is no specific antiviral drug available for Ebola thus far. For information of investigational therapies including Favipiravir, Brincidofovir, ZMapp, TKM-Ebola, AVI-6002, and BCX4430, see here.

• Isolate patient
• Provide intravenous fluids (IV) (patients need large volumes in some cases) and maintain electrolytes at normal levels
• Maintain oxygen saturation and blood pressure
• Administer blood products if coagulopathy or bleeding, antiemetics if vomiting , antipyretics if fever, analgesics, anti-motility if severe diarrhea, total parenteral nutrition if patient has poor oral intake and dialysis if there's renal failure
• Treat other infections if they occur. Provide adequate Gram-negative coverage and gram-positive if the patient has any catheter or hospital-acquired pneumonia.
• If there's respiratory failure, invasive mechanical ventilation may be the best option to offer respiratory support

• Note (1): Recovery from Ebola depends on good supportive care and the patient’s immune response.
• Note (2): While there is no proven treatment available for Ebola virus disease, human convalescent whole blood has been used as an empirical treatment with promising results in a small group of EVD cases.
• Note (3): People who recover from Ebola infection develop antibodies that last for at least 10 years, possibly longer. It is not known if people who recover are immune for life or if they can become infected with a different species of Ebola.
• Note (4): Some people who have recovered from Ebola have developed long-term complications, such as joint and vision problems.

Marburg

• Marburg virus Return to Top

• Marburg virus treatment

• Preferred regimen: supportive therapy including maintenance of blood volume and electrolyte balance, as well as analgesics and standard nursing care

Hantavirus

• Hantavirus Return to Top

• Hantavirus cardiopulmonary syndrome treatment

• Preferred regimen: Supportive therapy, there is no specific treatment for hantavirus cardiopulmonary syndrome
• Note (1): ICU management should include careful assessment, monitoring and adjustment of volume status and cardiac function, including inotropic and vasopressor support if needed
• Note (2): Fluids should be administered carefully due to the potential for capillary leakage
• Note (3): Supplemental oxygen should be administered if patients become hypoxic
• Note (4): Equipment and materials for intubation and mechanical ventilation should be readily available since onset of respiratory failure may be precipitous
• Note (5): Extracorporeal membrane oxygenation was used with survival rates of 50% in some studies in patients with cardiac index output <2.5L/min/m²

Streptococcus pyogenes

• Streptococcus pyogenes Return to Top
• 1. Streptococcus pyogenes tonsilitis

• Preferred regimen (1): Penicillin V 250 mg PO bid or tid (for children) 250 mg PO qid or 500 mg PO bid (for adults) for 10 days
• Preferred regimen (2): Benzathine penicillin G if <27kg: 600,000 U, if >27kg 1,200,000 U IM single-dose
• Alternative regimen (1): Amoxicillin 50 mg/kg/day PO qd for 10 days OR 25 mg/kg/day PO bid for 10 days. Its oral suspension is more tolerable to children and it is better absorbed by the GI tract
• Alternative regimen (2): first generation Cephalosporins are acceptable for treating recurrent group A streptococcus infection but not as first-line therapy
• Alternative regimen (3): Clarithromycin 250 mg PO bid for 10 days OR Azithromycin 12 mg/kg maximum 500 mg PO on day 1 THEN 6 mg/kg maximum 250 mg PO qd on days 2 through 5 OR Erythromycin 20 mg/kg/day PO or 40 mg/kg/day (ethylsuccinate) PO bid for 10 days.
• Alternative regimen (4): Clindamycin for penicillin-intolerant patients with erythromycin-resistant strains.
• Note: Intramuscular penicillin is the only therapy that has been shown to prevent initial attacks of rheumatic fever in controlled studies

• 2. Recurrent Streptococcus pyogenes tonsilitis

• Preferred regimen (1): Clindamycin 20-30 mg/kg/day PO tid (for children), 600 mg/day bid, tid or qid (for adults) for 10 days
• Preferred regimen (2): Amoxicillin-clavulanic acid 40 mg/kg/day PO tid (for children), 500 mg bid (for adults) for 10 days
• Alternative regimen: Benzathine penicillin G if <27kg: 600,000 U, if >27kg 1,200,000 U IM single-dose ± Rifampin 20 mg/kg/day PO bid for 4 days

• 3. Secondary prophylaxis for rheumatic fever

• Preferred regimen (1): Benzathine penicillin G if <27kg: 600,000 U, if >27kg 1,200,000 U IM every 4 weeks
• Alternative regimen (1): Penicillin V potassium 250 mg PO bid
• Alternative regimen (2): Sulfadiazine if <27kg 0.5 g PO qd, if >27kg 1 g PO qd
• Duration of treatment: if residual cardiac disease, keep treatment until 40 patient is 40 years old or for 10 years (whichever is longer); if there's no residual cardiac disease keep treatment for 10 years or until age 21 years (whichever is longer); if there's rheumatic fever without carditis keep it for 5 years or until age 21 years (whichever is longer).
• Note: For patients allergic to penicillin and sulfadiazine, consider a macrolide or azalide antibiotic

• 4. Streptococcus pyogenes bacteremia

• Preferred regimen: Penicillin G 4 million units IV q4h AND Clindamycin 900 mg IV q8h for at least 14 days
• Penicillin is added to the regimen to cover any other group A streptococcus which might be resistant to Clindamycin.
• Alternative regimen (1): Erythromycin
• Alternative regimen (2): Azithromycin
• Alternative regimen (3): Clarithromycin
• Alternative regimen (4): any other β-lactam
• Note (1): Macrolide resistance is increasing.
• Note (2): Consider using intravenous immune globulin in patients with invasive infection and signs of shock. Immunoglobulin-G IV 1 g/kg day 1, then 0.5 g/kg days 2 & 3.
• Note (3): If shock, administer massive IV fluids (10-20 L/day), Albumin if <2 g/dL, debridement of necrotic tissue.

• 5. Streptococcus pyogenes celulitis

• Preferred regimen: treat as Streptococcus pyogenes bacteremia

• 6 Epiglottitis in childern

• Preferred regimen (1): Cefotaxime 50 mg/kg IV q8h
• Preferred regimen (2): Ceftriaxone 50 mg/kg IV q24h
• Alternative regimen (1): Amoxicillin-SB 100–200 mg/kg qd q6h
• Alternative regimen (2): Trimethoprim-Sulfamethoxazole 8–12 mg/kg bid
• Note: Have tracheostomy set “at bedside.” Chloro is effective, but potentially less toxic alternative agents available.

• 7 Burn wound sepsis

• Preferred regimen: Vancomycin 1 gm IV q12h AND (Amikacin 10 mg/kg IV loading dose then 7.5 mg/kg IV q12h) AND [ Piperacillin 4 g IV q4h (give ½ q24h dose of Piperacillin into subeschar tissues with surgical eschar removal within 12 hours]. Can use Piperacillin-Tazobactam if Piperacillin not available.

• 8. Soft tissue

• Note: For necrotizing fasciitis, surgical consultation for emergent fasciotomy and debridement; repeat debridements usually necessary.

• 9. Muscle

• Note: For myositis-debirdement is recommended.

• 10. Eye

• 10.1 Keratitis

• 10.1.1 Acute bacterial keratitis

• Preferred regimen: Moxifloxacin eye gtts. 1 gtt tid for 7 days
• Alternative therapy: Gatifloxacin eye gtts. 1-2 gtts q2h while awake for 2 days, then q4h for 3-7 days.
• Note: Prefer Moxifloxacin due to enhanced lipophilicity and penetration into aqueous humor (1 gtt = 1 drop).

• 10.1.2 Keratitis due to dry cornea, diabetes, immunosuppression

• Preferred regimen: Cefazolin (50 mg/mL) AND (Gentamicin OR Tobramycin (14 mg/mL) q15–60 min around clock for 24–72 hrs, then slow reduction)
• Alternative therapy: Vancomycin (50 mg/mL) AND Ceftazidime (50 mg/mL) q15–60 min around clock for 24–72 hrs, then slow reduction.
• Note: Specific therapy guided by results of alginate swab culture and sensitivity. Ciprofloxacin 0.3% found clinically equivalent to CefazolinAND Tobramycin; only concern was efficacy of Ciprofloxacin vs S. pneumoniae

• 10.2 Dacryocystitis (lacrimal sac)

• Preferred regimen: Moxifloxacin 1 gtt tid for 7 days OR Cefazolin (50 mg/mL) (1 gtt = 1 drop)

• 11. Suppurative phlebitis

• Preferred regimen: Vancomycin 15 mg/kg IV q12h (normal weight)
• Alternative regimen: Daptomycin 6 mg/kg IV q12h
• Note: Retrospective study for suppurative phlebitis recommends 2-3 weeks IV therapy and 2 weeks PO therapy.

• 12. Infected prosthetic joint

• Preferred regimen: Penicillin G 2 million units IV q4h OR Ceftriaxone 2 g IV q24h for 4 weeks
• Note: Debridement & prosthesis retention with intravenous antibiotics.

• 13. “Hot” tender parotid swelling

• Preferred regimen: Nafcillin OR Oxacillin 2 g IV q4h
• Note: Predisposing factors are stone(s) in Stensen’s duct, dehydration. Therapy depends on ID of specific etiologic organism.

• 14. Diabetic foot ulcer (ulcer with <2 cm of superficial inflammation)

• Preferred regimen: (Trimethoprim-Sulfamethoxazole 800/160 mg 1-2 tabs PO bid OR Minocycline 100 mg PO bid) AND (Penicillin VK 500 mg PO qid OR selected Cephalosporins 2nd, 3rd generation - cefprozil 500 mg PO bid OR cefuroxime axetil 500 mg PO bid OR cefdinir 300 mg PO bid or 600 mg PO qd OR cefpodoxime 200 mg PO bid OR Fluoroquinolones Levofloxacin 750 mg PO qd).

• 15. Recurrent cellulitis, chronic lymphedema prophylaxis

• Preferred regimen: Clindamycin 150 mg PO qd OR Trimethoprim-Sulfamethoxazole 800/160 mg 1 tablet PO qd OR “stand-by therapy” immediate treatment with Penicillin V OR Amoxicillin 500-750 mg PO bd at onset of symptoms.

Staphylococcus epidermidis

• Staphylococcus epidermidis Return to Top
• Staphylococcus epidermidis

• 1. Methicillin-sensitive Staphylococcus epidermidis

• Preferred regimen (1): Oxacillin 1-2 g IV q4h
• Preferred regimen (2): Nafcillin 1-2 g IV q4h
• Preferred regimen (3): Cephalothin
• Alternative regimen: Rifampin 600 mg/day PO qd PLUS Sulfamethoxazole and Trimethoprim OR Fluoroquinolones AND Daptomycin 600 mg PO/IV q12h
• Note: 75% of the S. epidermidis are methicillin-resistant.

• 2. Methicillin-resistant Staphylococcus epidermidis

• Preferred regimen: Vancomycin 1 g IV q12h ± Rifampin 600 mg/day PO qd

• Note: For deep-seated infections consider adding Gentamicin AND/OR Rifampin 600 mg/day PO qd to the regimen
• 3. Prosthetic device infections

• Preferred regimen: Oxacillin 1-2 g IV q4h OR Vancomycin 1 g IV q12h PLUS Rifampin 600 mg/day PO qd AND Gentamicin 3 mg/kg/day IV/IM q8-24h is appropriate

• Note: Duration depends on site of infection and severity.

Actinomycosis

• Actinomycosis Return to Top
• Actinomyces species including A. israeli

• Preferred regimen: Penicillin 3-4 million units IV q4h for 2-6 weeks THEN Penicillin V 2-4 g/day PO qid for 6-12 months
• Alternative regimen (1): Erythromycin 500-1000 mg IV q6h OR 500 mg PO qid
• Alternative regimen (2): Tetracyclin 500 mg PO qid
• Alternative regimen (3): Doxycycline 100 mg IV q12h OR 100 mg PO bid
• Alternative regimen (4): Clindamycin 900 mg IV q8h OR 300-450 mg PO qd
• Alternative regimen (5): Minocycline 100 mg IV q12h OR 100 mg PO bid

Sparganosis

• Sparganosis Return to Top

• Sparganosis (Spirometra mansonoides) treatment

• Preferred treatment: Surgical resection or ethanol injection of subcutaneous masses
• Note: Praziquantel 75 mg/kg/day PO qd for 3 days is controversial. It's been innefective in some cases, but has had some results in patients when surgical therapy wasn't an option.

Filariasis

• Filariasis Return to Top

• Filariasis

• 1. Lymphatic filariasis - Wuchereria bancrofti, Brugia malayi Brugia timori

• Preferred regimen: Diethylcarbamazine 6 mg/day PO qd for 12 days (single dose if patient will continue to live in endemic area or is younger than 9 years old) ± Albendazole 400 mg PO qd
• Alternative regimen: Doxycycline 200 mg/day for 4 weeks ± Ivermectin 150 μg/kg single dose (do not administer Ivermectin if there's a risk of serious adverse effects in areas where L loa is coendemic)
• Note: Do not administer Diethylcarbamazine where onchocerciasis is endemic due to the risk of causing severe local inflammation in patients with ocular microfilariae.

• 2. Cutaneous filariasis - Onchocercia volvulus, Loa loa

• Preferred regimen: Doxycycline 150 μg/kg single dose
• Preferred regimen: (Doxycyclin 100 mg PO qd for 6 weeks OR 200 mg PO qd for 4 weeks) THEN Ivermectin after 4-6 months 150 μg/kg single dose; OR Doxycyclin 200 mg PO qd for 6 weeks THEN Ivermectin after 4-6 months 150 μg/kg single dose

Echinococcosis

• Echinococcus Return to Top

• 1.1 Echinococcus granulosus (hydatid disease) treatment

• Preferred regimen: Albendazole ≥60 kg 400 mg PO bid or <60 kg 10-15 mg/kg/day PO bid with meals for 3-6 months
• Alternative regimen: Mebendazole 40-50mg/kg/day PO tid for 3-6 months
• Note: Percutaneous aspiration-injection-reaspiration (PAIR). Puncture & needle aspirate cyst content. Instill hypertonic saline (15–30%) or absolute alcohol, wait 20–30 min, then re-aspirate with final irrigation. Administer Albendazole at least 4 hours before PAIR.
• Note: If surgery is needed, make sure to administer Albendazole for at least a week before the surgery, and to keep the medication for at least 4 weeks after the procedure.

• 1.2 Echinococcus multilocularis (alveolar cyst disease) treatment

• Preferred regimen: Albendazole ≥60 kg 400 mg PO bid or <60 kg 15 mg/kg/day PO bid with meals for at least 2 years. Long-term follow up needed to evaluate progression of the lesions.

Note: Wide surgical resection only reliable treatment; technique evolving.

Parvovirus B19

• Parvovirus B19 Return to Top

• Parvovirus B19

• 1. Erythema infectiosum

• Supportive therapy: Symptomatic treatment only

• 2. Arthritis/arthalgia

• Preferred regimen: Nonsteroidal anti-inflammatory drugs (NSAID)

• 3.Transient aplastic crisis

• Supportive therapy: Transfusions and oxygen

• 4. Fetal hydrops

• Supportive therapy: Intrauterine blood transfusion

• 5. Chronic infection with anemia

• Preferred regimen: transfusion and IVIG (there are different IVIG regimens such as 400 mg/kg of commercial IVIG for 5 or 10 days or 1000 mg/kg for 3 days both with good results). Relapses have been treated with maintenance IVIG at doses of 0.4 grams/kg/day every four weeks.

• 6.Chronic infection without anemia

• Preferred regimen: IVIG is controversial. Further studies needed.

JC virus

• JC virus Return to Top

• Progressive Multifocal Leukoencephalopathy (PML) caused by JC Virus ( John Cunningham virus) infections

• There is no specific antiviral therapy for JC virus infection. The main treatment approach is to reverse the immunosuppression caused by HIV.
• Initiate anti retroviral therapy (ART) immediately in ART-naive patients, and optimize ART in patients who develop Progressive Multifocal Leukoencephalopathy in phase of HIV viremia on ART .
• Corticosteroids may be used for Progressive Multifocal Leukoencephalopathy- immune reconstitution inflammatory syndrome (IRIS) characterized by contrast enhancement, edema or mass effect, and with clinical deterioration

RSV

• Respiratory Syncytial Virus Return to Top

• Preferred regimen: Supportive therapy

• Hydration and supplemental oxygen.
• Routine use of Ribavirin not recommended. Ribavirin therapy associated with small increases in O2 saturation.
• No consistent decrease in need for mechanical ventilation or ICU stays. High cost, aerosol administration and potential toxicity
• Note (1): Its is FDA-approved for RSV infection in children, but not for RSV infection in adults. Dose: Ribavirin 20mg/dl 6 g inhaled continuosly for 12-18h.
• Note (2): Respiratory Syncytial Virus major cause of morbidity in neonates/infants.

• Prevention of Respiratory syncytial virus

• 1. In children <24 months old with chronic lung disease of prematurity (formerly broncho-pulmonary dysplasia) requiring supplemental oxygen or
• 2. In premature infants (<32 wks gestation) and <6 months old at start of Respiratory syncytial virus season or
• 3. In children with selected congenital heart diseases.

• Preferred regimen for prevention of Respiratory syncytial virus: Palivizumab (Synagis) 15 mg per kg IM q month Nov.-April

• Note: Significant reduction in Respiratory syncytial virus hospitalization among children with congenital heart disease

Rhinovirus

• Rhinovirus Return to Top
• Rhinovirus treatment (commom cold)

• Supportive therapy

• Preferred regimen: An association of antihistamines and decongestants (such as brompheniramine and sustained-release pseudoephedrine) can be used to treat acute cough.
• Alternative regimen: Naproxen - no dose established yet, maximum 1g/day

Rotavirus

• Rotavirus Return to Top
• Rotavirus treatment

• Treatment of diarrhea caused by rotavirus

• Preferred regimen: Suportive therapy. No specific antiviral available.

• Rehydration with oral rehydration salts (ORS) solution.
• Rehydration with intravenous fluids in case of severe dehydration or shock.

Clostridium

• Clostridium botulinum Return to Top
• 1. Antibiotics

• Antibiotics are not recommended in gastrointestinal botulism due to the risk of worsening of neurological symptoms caused by the lysis of the bacteria. For wound botulism antibiotics are indicated with surgical treatment as followed:

• Preferred regimen: Metronidazole 500 mg IV q8h
• Alternative regimen: Penicillin G 3 million units IV q4h

• 2. Antitoxin

• Preferred regimen: Trivalent antitoxin (A 7,500 IU, B 5,000 IU, and E 5,000 IU) 1 vial diluted 1:10, IV infusion over 30 min
• Alternative regimen: Equine antitoxin

• 3. General Therapy

• Preferred regimen: Mechanical ventilation; IV hydration; tube feedings

• Clostridium perfringens Return to Top

• Clostridium perfringens
• Gas gangrene

• Preferred regimen: Penicillin G 3-4 million units IV q4h AND (Clindamycin 900 mg IV q8h OR Tetracycline 500 mg IV q6h)

• Clostridium tetani Return to Top

• 1. General measures

• Preferred regimen: Patients should be placed in a quiet shaded area and protected from tactile and auditory stimulation as much as possible; All wounds should be cleaned and debrided as indicated

• 2. Immunotherapy

• Preferred regimen: Human TIG 500 units IV/IM as soon as possible AND Age-appropriate TT-containing vaccine, 0.5 cc IM at a separate site
• Note: patients without a history of primary TT vaccination should receive a second dose 1–2 months after the first dose and a third dose 6–12 months later

• 3. Antibiotic treatment

• Preferred regimen: Metronidazole 500 mg IV/PO q6h OR Penicillin G 100,000–200,000 IU/kg/day IV, administered in 2–4 divided doses
• Alternative regimen: Tetracyclines OR Macrolides OR Clindamycin OR Cephalosporins OR Chloramphenicol

• 4. Muscle spasm control

• Preferred regimen: Diazepam 5 mg IV OR Lorazepam 2 mg IV titrating to achieve spasm control without excessive sedation and hypoventilation
• Alternative regimen (1): Magnesium sulphate 5 g (or 75mg/kg) IV loading dose, then 2–3 g per hour until spasm control is achieved ± Benzodiazepines
• Note: Monitor patellar reflex as areflexia (absence of patellar reflex) occurs at the upper end of the therapeutic range (4mmol/L). If areflexia develops, dose should be decreased
• Alternative regimen (2): Baclofen OR Dantrolene 1–2 mg/kg IV/PO q4h
• Alternative regimen (3): Barbiturates 100–150 mg q1-4h by any route
• Alternative regimen (4): Chlorpromazine 50–150 mg IM q4–8h
• Pediatric regimen: Lorazepam 0.1–0.2 mg/kg IV q2–6h, titrating upward as needed; Barbiturates 6–10 mg/kg in children by any route; Chlorpromazine 4–12 mg IM every q4–8h
• Note: As for Benzodiazepines, large amounts may be required (up to 600 mg/day); Oral preparations could be used but must be accompanied by careful monitoring to avoid respiratory depression or arrest

• 5. Autonomic dysfunction control

• Preferred regimen: Magnesium sulphate OR Morphine OR Esmolol

• 6. Airway/respiratory control

• Note: Drugs used to control spasm and provide sedation can result in respiratory depression. If spasm, including laryngeal spasm, is impeding or threatening adequate ventilation, mechanical ventilation is recommended when possible. Early tracheostomy is preferred as endotracheal tubes can provoke spasm and exacerbate airway compromise.

• Clostridium difficile Return to Top

• 1. Pseudomembranous colitis - mild to moderate

• Preferred regimen:Metronidazole 500 mg PO tid for 10-14 days
• Alternative regimen: Vancomycin 125 mg PO qid for 10-14 days
• Note: If significant risk of recurrence: Vancomycin 125 mg PO qid for 10-14 days OR Fidaxomicin 200 mg PO bid for 10 days

• 2. Pseudomembranous colitis - severe

• Preferred regimen: Vancomycin 125 mg PO qid for 10-14 days
• Note: If significant risk of recurrence: Vancomycin 125 mg PO qid for 10-14 days OR Fidaxomicin 200 mg PO bid for 10 days

• 3 . Pseudomembranous colitis - severe, complicated

• Preferred regimen: Vancomycin 125-500 mg PO qid for 10-14 days AND Vancomycin 500 mg diluted in 500 ml of saline as enema per rectum q6h AND Metronidazole 500 mg IV q8h
• Note: Consider urgent surgical consult

• 4. Recurrent pseudomembranous colitis

• First recurrence treatment

• Preferred regimen: same as first episode or [Fidaxomicin]] 200 mg PO bid for 10 days

• Second or more recurrence treatment

• Preferred regimen: Vancomycin 125 mg PO qid for 14 days THEN Vancomycin 125 mg PO tid for 7 days THEN Vancomycin 125 mg PO bid for 7 days THEN Vancomycin 125 mg PO qd for 7 days THEN Vancomycin 125 mg PO q48h for 7 days THEN Vancomycin 125 mg PO q72h for 7 days OR Fidaxomicin 200 mg PO bid for 10 days
• Note: Consider expert consult for fecal microbiota transplantation

Plasmodium

• Plasmodium Return to Top
• 1. Plasmodium falciparum

• 1.1 Treatment of uncomplicated P. falciparum malaria

• 1.1.1 Treat children and adults with uncomplicated P. falciparum malaria (except pregnant women in their first trimester) with one of the following recommended ACT (artemisinin-based combination therapy)

• Preferred regimen (1): Artemether 5–24 mg/kg/day PO bid AND Lumefantrine 29–144 mg/kg/day PO bid for 3 days.
• Note: The first two doses should, ideally, be given 8 h apart.

• Dosage regimen based on Body weight (kg)
• Body weight (kg)-5 to < 15- Artemether 20 mg PO bid AND Lumefantrine 120 mg PO bid for 3 days
• Body weight (kg)-15 to < 25- Artemether 40 mg PO bid AND Lumefantrine 240 mg PO bid for 3 days
• Body weight (kg)-25 to < 35- Artemether 60 mg PO bid AND Lumefantrine 360 mg PO bid for 3 days
• Body weight (kg) ≥ 35- Artemether 80 mg PO bid AND Lumefantrine 480 mg PO bid for 3 days

• Preferred regimen (2): Artesunate 2–10 mg/kg/day PO qd AND Amodiaquine 7.5–15 mg/kg/day PO qd for 3 days
• Note: A total therapeutic dose range of 6–30 mg/kg/day artesunate and 22.5–45 mg/kg/day per dose amodiaquine is recommended.

• Dosage regimen based on Body weight (kg)
• Body weight (kg)-4.5 to < 9- Artesunate 25 mg PO qd AND Amodiaquine 67.5 mg PO qd for 3 days
• Body weight (kg)-9 to < 18 - Artesunate 50 mg PO qd AND Amodiaquine 135 mg PO qd for 3 days
• Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Amodiaquine 270 mg PO qd for 3 days
• Body weight (kg) ≥ 36 - Artesunate 200 mg PO qd AND Amodiaquine 540 mg PO qd for 3 days

• Preferred regimen (3): Artesunate 2–10 mg/kg/day PO qd AND Mefloquine 2–10 mg/kg/day PO qd for 3 days

• Dosage regimen based on Body weight (kg)
• Body weight (kg)-5 to < 9- Artesunate 25 mg PO qd AND Mefloquine 55 mg PO qd for 3 days
• Body weight (kg)-9to < 18- Artesunate 50 mg PO qd AND Mefloquine 110 mg PO qd for 3 days
• Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Mefloquine 220 mg PO qd for 3 days
• Body weight (kg)- ≥ 36 - Artesunate 200 mg PO qd AND Mefloquine 440 mg PO qd for 3 days

• Preferred regimen (4): Artesunate 2–10 mg/kg/day PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1.25 (25–70 / 1.25–3.5) mg/kg/day PO given as a single dose on day 1

• Dosage regimen based on Body weight (kg)
• Body weight (kg)-5 to < 10- Artesunate 25 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 250/12 mg PO given as a single dose on day 1
• Body weight (kg)-10 to < 25- Artesunate 50 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 500/25 mg PO given as a single dose on day 1
• Body weight (kg)-25 to < 50- Artesunate 100 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1000/50 mg PO given as a single dose on day 1
• Body weight (kg)- ≥50- Artesunate 200 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1500/75 mg PO given as a single dose on day 1

• Preferred regimen (5): Dihydroartemisinin 2–10 mg/kg/day PO qd AND Piperaquine16–27 mg/kg/day PO qd for 3 days

• Dosage regimen based on Body weight (kg)
• Body weight (kg)-5 to < 8- Dihydroartemisinin 20 mg PO qd AND Piperaquine 160 mg PO qd for 3 days
• Body weight (kg)-8 to < 11- Dihydroartemisinin 30 mg PO qd AND Piperaquine 240 mg PO qd for 3 days
• Body weight (kg)-11 to < 17 - Dihydroartemisinin 40 mg PO qd AND Piperaquine 320 mg PO qd for 3 days
• Body weight (kg)-17 to < 25- Dihydroartemisinin 60 mg PO qd AND Piperaquine 480 mg PO qd for 3 days
• Body weight (kg)-25 to < 36- Dihydroartemisinin 80 mg PO qd AND Piperaquine 640 mg PO qd for 3 days
• Body weight (kg)-36 to < 60- Dihydroartemisinin 120 mg PO qd AND Piperaquine 960 mg PO qd for 3 days
• Body weight (kg)-60 < 80 - Dihydroartemisinin 160 mg PO qd AND Piperaquine 1280 mg PO qd for 3 days
• Body weight (kg)- >80- Dose of Dihydroartemisinin 200 mg PO qd AND Piperaquine 1600 mg PO qd for 3 days

• 1.1.2 Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)

• Preferred regimen: Single dose of 0.25 mg/kg Primaquine with ACT

• 1.2 Recurrent Falciparum Malaria

• 1.2.1 Failure within 28 days

• Note:The recommended second-line treatment is an alternative ACT known to be effective in the region. Adherence to 7-day treatment regimens (with artesunate or quinine both of which should be co-administered with + tetracycline, or doxycycline or clindamycin) is likely to be poor if treatment is not directly observed; these regimens are no longer generally recommended.

• 1.2.2 Failure after 28 days

• Note: all presumed treatment failures after 4 weeks of initial treatment should, from an operational standpoint, be considered new infections and be treated with the first-line ACT. However, reuse of mefloquine within 60 days of first treatment is associated with an increased risk for neuropsychiatric reactions, and an alternative ACT should be used.

• 1.3 Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)

• Note: Single dose of 0.25 mg/kg bw Primaquine with ACT

• 1.4 Treating uncomplicated P. falciparum malaria in special risk groups

• 1.4.1 Pregnancy

• First trimester of pregnancy : Quinine AND Clindamycin 10mg/kg/day PO bid for 7 days
• Second and third trimesters : Mefloquine is considered safe for the treatment of malaria during the second and third trimesters; however, it should be given only in combination with an artemisinin derivative.
• Note (1): Quinine is associated with an increased risk for hypoglycaemia in late pregnancy, and it should be used (with clindamycin) only if effective alternatives are not available.
• Note (2): Primaquine and tetracyclines should not be used in pregnancy.

• 1.4.2 Infants less than 5kg body weight : with an ACT at the same mg/kg bw target dose as for children weighing 5 kg.
• 1.4.3 Patients co-infected with HIV: should avoid Artesunate + SP if they are also receiving Co-trimoxazole, and avoid Artesunate AND Amodiaquine if they are also receiving efavirenz or zidovudine.
• 1.4.4 Large and Obese adults: For obese patients, less drug is often distributed to fat than to other tissues; therefore, they should be dosed on the basis of an estimate of lean body weight, ideal body weight. Patients who are heavy but not obese require the same mg/kg bw doses as lighter patients.
• 1.4.5 Patients co-infected with TB: Rifamycins, in particular rifampicin, are potent CYP3A4 inducers with weak antimalarial activity. Concomitant administration of rifampicin during quinine treatment of adults with malaria was associated with a significant decrease in exposure to quinine and a five-fold higher recrudescence rate
• 1.4.6 Non-immune travellers : Treat travellers with uncomplicated P. falciparum malaria returning to nonendemic settings with an ACT.
• 1.4.7 Uncomplicated hyperparasitaemia: People with P. falciparum hyperparasitaemia are at increased risk of treatment failure, severe malaria and death so should be closely monitored, in addition to receiving an ACT.

• 2. Treatment of uncomplicated malaria caused by P. vivax, P. ovale, P. malariae or P. knowlesi

• 2.1 Blood Stage infection

• 2.1.1. Uncomplicated malaria caused by P. vivax

• 2.1.1.1 In areas with chloroquine-sensitive P. vivax

• Preferred regimen: Chloroquine total dose of 25 mg/kg PO. Chloroquine is given at an initial dose of 10 mg/kg, followed by 10 mg/kg on the second day and 5 mg/kg on the third day.

• 2.1.1.2 In areas with chloroquine-resistant P. vivax

• Note: ACTs containing Piperaquine, Mefloquine OR Lumefantrine are the recommended treatment, although Artesunate + Amodiaquine may also be effective in some areas. In the systematic review of ACTs for treating P. vivax malaria, Dihydroartemisinin + Piperaquine provided a longer prophylactic effect than ACTs with shorter half-lives (Artemether + Lumefantrine, Artesunate + Amodiaquine), with significantly fewer recurrent parasitaemias during 9 weeks of follow-up.

• 2.1.2 Uncomplicated malaria caused by P. ovale, P. malariae or P. knowlesi malaria

• Note: Resistance of P. ovale, P. malariae and P. knowlesi to antimalarial drugs is not well characterized, and infections caused by these three species are generally considered to be sensitive to chloroquine. In only one study, conducted in Indonesia, was resistance to chloroquine reported in P. malariae. The blood stages of P. ovale, P. malariae and P. knowlesi should therefore be treated with the standard regimen of ACT or Chloroquine, as for vivax malaria.

• 2.1.3 Mixed malaria infections

• Note: ACTs are effective against all malaria species and so are the treatment of choice for mixed infections.

• 2.2 Liver stages (hypnozoites) of P. vivax and P. ovale

• Note: To prevent relapse, treat P. vivax or P. ovale malaria in children and adults (except pregnant women, infants aged < 6 months, women breastfeeding infants < 6 months, women breastfeeding older infants unless they are known not to be G6PD deficient and people with G6PD deficiency) with a 14-day course of primaquine in all transmission settings. Strong recommendation, high-quality evidence In people with G6PD deficiency, consider preventing relapse by giving primaquine base at 0.75 mg base/kg bw once a week for 8 weeks, with close medical supervision for potential primaquine-induced adverse haematological effects.]
• 2.2.1 Primaquine for preventive relapse

• Preferred regimen: Primaquine 0.25–0.5 mg/kg/day PO qd for 14 days

• 2.2.2 Primaquine and glucose-6-phosphate dehydrogenase deficiency

• Preferred regimen: Primaquine 0.75 mg base/kg/day PO once a week for 8 weeks.
• Note: The decision to give or withhold Primaquine should depend on the possibility of giving the treatment under close medical supervision, with ready access to health facilities with blood transfusion services.

• 2.2.3 Prevention of relapse in pregnant or lacating women and infants

• Note: Primaquine is contraindicated in pregnant women, infants < 6 months of age and in lactating women (unless the infant is known not to be G6PD deficient).

• 3. Treatment of severe malaria

• 3.1 Treatment of severe falciparum infection with Artesunate

• 3.1.1 Adults and children with severe malaria (including infants, pregnant women in all trimesters and lactating women):-

• Preferred regimen: Artesunate IV/IM for at least 24 h and until they can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate oral therapy, complete treatment with 3 days of an ACT (add single dose Primaquine in areas of low transmission).

• 3.1.2 Young children weighing < 20 kg

• Preferred regimen: Artesunate 3 mg/kg per dose IV/IM q24h
• Alternatives regimen: use Artemether in preference to quinine for treating children and adults with severe malaria

• 3.2.Treating cases of suspected severe malaria pending transfer to a higher-level facility (pre-referral treatment)

• 3.2.1 Adults and children

• Preferred regimen: Artesunate IM qd
• Alternative regimen: Artemether IM OR Quinine IM

• 3.2.2 Children < 6 years

• Preferred regimen: Where intramuscular injections of artesunate are not available, treat with a single rectal dose (10 mg/kg) of Artesunate, and refer immediately to an appropriate facility for further care.
• Note: Do not use rectal artesunate in older children and adults.

• 3.3 Pregancy

• Note: Parenteral artesunate is the treatment of choice in all trimesters. Treatment must not be delayed.

• 3.4 Treatment of severe P. Vivax infection

• Note: parenteral artesunate, treatment can be completed with a full treatment course of oral ACT or chloroquine (in countries where chloroquine is the treatment of choice). A full course of radical treatment with primaquine should be given after recovery.

• 3.5 Additional aspects of management in severe malaria

• Fluid therapy: It is not possible to give general recommendations on fluid replacement; each patient must be assessed individually and fluid resuscitation based on the estimated deficit.
• Blood Transfusion :In high-transmission settings, blood transfusion is generally recommended for children with a haemoglobin level of < 5 g/100 mL(haematocrit < 15%). In low-transmission settings, a threshold of 20% (haemoglobin, 7 g/100 mL) is recommended.
• Exchange blood transfusion: Exchange blood transfusion requires intensive nursing care and a relatively large volume of blood, and it carries significant risks. There is no consensus on the indications, benefits and dangers involved or on practical details such as the volume of blood that should be exchanged. It is, therefore, not possible to make any recommendation regarding the use of exchange blood transfusion.

Bartonella

• Bartonella Return to Top

• 1. Bartonella quintana

• 1.1 Acute or chronic infections without endocarditis

• Preferred regimen: Doxycycline 200 mg PO qd or 100 mg bid for 4 weeks PLUS Gentamicin 3 mg/kg IV q24h for the first 2 weeks

• 1.2 Endocarditis

• Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g/day IV for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks

• 2. Bartonella elizabethae

• 2.2 Endocarditis

• Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g/day IV for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks

• 3. Bartonella bacilliformis

• 3.1 Oroya fever

• Preferred regimen: Ciprofloxacin 500 mg PO bid for 14 days
• Note: if severe disease, associate Ceftriaxone 1 g IV q24h for 14 days

• 3.2 Verruga peruana

• Preferred regimen: Azithromycin 500 mg PO qd for 7 days
• Alternative regimen (1): Rifampin 600 mg PO qd for 14-21 days
• Alternative regimen (2): Ciprofloxacin 500 mg bid for 7-10 days

• 4. Bartonella hansealae

• 4.1 Cat scratch disease

• If extensive adenopathy

• Preferred regimen: Azithromycin 500 mg PO at day 1 THEN 250 mg PO for 4 days for patients weighting less than 45kg, 1 g PO at day 1 THEN 500 mg PO for 4 days for patients weighting more than 45 kg

• Alternative regimen (1): Clarithromycin 500 mg PO bid
• Note: Pediatric dose: 15-20 mg/kg/day PO bid (maximum dose 500 mg bid)
• Alternative regimen (2): Rifampin 300 mg PO bid
• Note Pediatric dose: Rifampin 10 mg/kg bid (maximum dose 600 mg daily)
• Alternative regimen (3): Ciprofloxacin 500 mg PO bid for patients >17 years of age for 7-10 days
• Alternative regimen (4): Trimethoprim-sulfamethoxazole one double strength tablet bid for 7-10 days
• Note: Pediatric dose: trimethoprim 8 mg/kg per day, sulfamethoxazole 40 mg/kg per day bid for 7-10 days

• 4.2 Endocarditis

• Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g/day IV for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks

• 4.3 Retinitis

• Preferred regimen: Doxycycline 100 mg bid AND Rifampin 300 mg bid PO for 4-6 weeks

• 4.4 Bacillary angiomatosis

• Preferred regimen (1): Erythromycin 500 mg PO qid for 2 months at least
• Preferred regimen (2): Doxycycline 100mg PO bid for 2 months at least

• 4.5 Bacillary Pelliosis

• Preferred regimen (1): Erythromycin 500 mg PO qid for 4 months at least
• Preferred regimen (2): Doxycycline 100 mg PO bid for 4 months at least

Blastomycosis

• Blastomycosis Return to Top
• Blastomycosis

• 1. Mild to moderate pulmonary blastomycosis

• Preferred regimen: Itraconazole 200 mg PO qd or bid for 6–12 months
• Note: Oral Itraconazole, 200 mg tid PO for 3 days and THEN 200 mg PO qd or bid for 6–12 months

• 2. Moderately severe to severe pulmonary blastomycosis

• Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV q24h for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
• Preferred regimen (2): Amphotericin B deoxycholate 0.7–1 mg/kg IV q24h for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
• Note: Oral Itraconazole, 200 mg tid PO for 3 days THEN 200 mg PO bid, for a total of 6–12 months

• 3. Mild to moderate disseminated blastomycosis

• Preferred regimen: Itraconazole 200 mg PO qd or bid for 6–12 months
• Note (1): Treat osteoarticular disease for 12 months
• Note (2): Oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 6–12 months

• 4. Moderately severe to severe disseminated blastomycosis

• Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV q24h, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
• Preferred regimen (2): Amphotericin B deoxycholate 0.7–1 mg/kg IV q24h, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
• Note: oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 6–12 months

• 5. CNS disease

• Preferred regimen: Lipid Amphotericin B 5 mg/kg IV q24h for 4–6 weeks AND an oral azole for at least 1 year
• Note (1): Step-down therapy can be with Fluconazole, 800 mg/day PO qd or bid OR Itraconazole, 200 mg bid or tid OR voriconazole, 200–400 mg bid.
• Note (2): Longer treatment may be required for immunosuppressed patients.

• 6. Immunosuppressed patients

• Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV q24h, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
• Preferred regimen (2): Amphotericin B deoxycholate, 0.7–1 mg/kg IV q24h, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
• Note (1): Oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 12 months
• Note (2): Life-long suppressive treatment may be required if immunosuppression cannot be reversed.

• 7. Pregnant women

• Preferred regimen: Lipid Amphotericin B 3–5 mg/kg IV q24h
• Note (1): Azoles should be avoided because of possible teratogenicity
• Note (2): If the newborn shows evidence of infection, treatment is recommended with Amphotericin B deoxycholate, 1.0 mg/kg IV q24h

• 8. Children with mild to moderate disease

• Preferred regimen: Itraconazole 10 mg/kg PO qd for 6–12 months
• Note: Maximum dose 400 mg/day

• 9. Children with moderately severe to severe disease

• Preferred regimen (1): Amphotericin B deoxycholate 0.7–1 mg/kg IV q24h for 1–2 weeks AND Itraconazole 10 mg/kg PO qd to a maximum of 400 mg/day for 6–12 months
• Preferred regimen (2): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg IV q24h for 1–2 weeks AND Itraconazole 10 mg/kg PO qd to a maximum of 400 mg/day for 6–12 months
• Note: Children tolerate Amphotericin B deoxycholate better than adults do.

Chromoblastomycosis

• Chromoblastomycosis Return to Top

• Preferred regimen: Itraconazole 200-400 mg PO q24h OR 400 mg pulse therapy once daily for 1 week monthly for 6-12 months
• Note: Pulse therapy reduces cost but it is questionable if it produces resistance to the drug.
• Alternative regimen (1): Terbinafine 500-1000 mg PO qd for 6-12 months
• Alternative regimen (2): Posaconazole 800 mg PO qd for 6-12 months
• Alternative regimen (3): 5-fluorocytosine 100-150 mg/kg/day PO qd for 6-12 months
• Note: This disease has a low cure ratio and high relapse ratio. Physical treatment is needed to achieve better results:

• Cryosurgery with liquid nitrogen - most used physical therapy, it's used in localized lesions and it has a very good treatment response, probably achieved by immune mechanisms since fungi are eliminated from lesions as late as 1-2 weeks after the therapy.
• Thermotherapy - used in conjunction with systemic therapy, was developed by Japanese authors and consists in placing "pocket warmers" in the lesions for 24h/day for some months, as the fungi is sensible to heat.
• Laser vaporization - studied in Germany as an alternative therapy, reported to successfully treat relapsing lesions.

Hepatitis C

• Hepatitis C virus Return to Top

Chronic Hepatitis C

• 1. Treatment regimens for chronic hepatitis C virus genotype 1

• 1.1. Treatment regimens for genotype 1a:

• Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
• Preferred regimen (2): Paritaprevir 150 mg PO qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND Dasabuvir 250 mg PO bid AND weight-based Ribavirin PO qd ([1000 mg <75 kg] to [1200 mg >75 kg]) for 12 weeks (no cirrhosis) OR 24 weeks (cirrhosis)
• Preferred regimen (3): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd ± weight-based Ribavirin PO qd ([1000 mg <75 kg] to [1200 mg >75 kg]) for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
• Note: these regimens are recommended for treatment-naive patients with HCV genotype 1a infection.

• 1.2. Treatment regimens for genotype 1b:

• Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
• Preferred regimen (2): Paritaprevir PO 150 mg qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND Dasabuvir 250 mg PO bid for 12 weeks. The addition of weight-based Ribavirin PO qd (1000 mg [<75kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis
• Preferred regimen (3): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
• Note: these regimens are recommended for treatment-naive patients with HCV genotype 1b infection.

• 2. Treatment regimens for chronic hepatitis C virus genotype 2

• Preferred regimen: Sofosbuvir 400 mg PO qd AND weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
• Note (1): This regimen are recommended for treatment-naive patients with HCV genotype 2 infection.
• Note (2): Extending treatment to 16 weeks is recommended in patients with cirrhosis.

• 3. Treatment regimens for chronic hepatitis C virus genotype 3

• Preferred regimen: Sofosbuvir 400 mg PO qd and weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) PO qd for 24 weeks
• Alternative regimen: Sofosbuvir 400 mg and weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) PO qd AND weekly PEG-IFN for 12 weeks is an acceptable regimen for IFN-eligible, treatment-naive patients with HCV genotype 3 infection.
• Note: These regimens are recommended for treatment-naive patients with HCV genotype 3 infection.

• 4. Treatment regimens for chronic hepatitis C virus genotype 4

• Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
• Preferred regimen (2): Paritaprevir 150 mg PO qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
• Preferred regimen (3): Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks
• Alternative regimen (1): Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) AND weekly PEG-IFN for 12 weeks
• Alternative regimen (2): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd ± weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
• Note: These regimens are accpetable for treatment-naive patients with HCV genotype 3 infection.

• 5. Treatment regimens for chronic hepatitis C virus genotype 5

• Preferred regimen: Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd(1000 mg [<75 kg] to 1200 mg [>75 kg]) AND weekly PEG-IFN for 12 weeks is recommended for treatment-naive patients with HCV genotype 5 infection.
• Alternative regimen: Weekly PEG-IFN AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 48 weeks is an alternative regimen for IFN-eligible, treatment-naive patients with HCV genotype 5 infection.

• 6. Treatment regimens for chronic hepatitis C virus genotype 6

• Preferred regimen: Ledipasvir 90 mg PO qd AND Sofosbuvir PO qd 400 mg for 12 weeks is recommended for treatment-naive patients with HCV genotype 6 infection.
• Alternative regimen: Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) AND weekly PEG-IFN for 12 weeks is an alternative regimen for IFN-eligible, treatment-naive patients with HCV genotype 6 infection.

Toxocariasis

• Toxocariasis Return to Top

• 1.1.Visceral toxocariasis

• Preferred regimen: Albendazole 400 mg PO bid for five days (both adult and pediatric dosage)
• Alternative regimen: Mebendazole 100-200 mg PO bid for five days (both adult and pediatric dosage)
• Note: Treatment is indicated for moderate-severe cases. Patients with mild symptoms of toxocariasis may not require anthelminthic therapy as symptoms are limited.

• 1.2.Ocular toxocariasis

• Preferred regimen: Prednisone 0.5-1 mg/kg/day PO q24h AND Albendazole 400 mg PO bid for 2 to 4 weeks (pediatric dose: 400 mg PO qd)
• Note: Surgical therapy might be neeeded.

Hep B

• Hepatitis B virus Return to Top
• Acute Hepatitis B

• Chronic Hepatitis B

• 1. Patients with HBeAg-positive chronic hepatitis B

• 1.1. HBV DNA >20,000, ALT <2 times upper limit normal (ULN)

• Observe; consider treatment when ALT becomes elevated.
• Consider biopsy in persons 40 years, ALT persistently high normal >2 times upper limit normal (ULN), or with family history of HCC.
• Consider treatment if HBV DNA >20,000 IU/mL and biopsy shows moderate/severe inflammation or significant fibrosis.

• 1.2. HBV DNA >20,000, ALT >2 times upper limit normal (ULN)

• Preferred regimen (1): Pegylated IFN-alpha 180 mcg weekly SC for 48 weeks
• Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
• If creatinine clearance 30–49 give 300 mg q48 hrs
• If creatinine clearance 10–29 give 300 mg q72-96 hrs
• If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
• If creatinine clearance <10 without dialysis there is no recommendation
• Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion

• Preferred regimen (3): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
• If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
• If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
• If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
• Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion

• Alternative regimen (1): Interferon alpha (IFNα) 5 MU daily or 10 MU thrice weekly SC for 16 weeks
• Alternative regimen (2): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 100 mg PO qd
• If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
• If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
• If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
• If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
• The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
• Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion

• Alternative regimen (3): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 10 mg PO daily
• If creatinine clearance 30–49 give 10 mg PO every other day
• If creatinine clearance 10–19 10 mg PO every third day
• If hemodialysis patients give 10 mg PO every week following dialysis
• Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion

• Alternative regimen (4): Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 600 mg PO once daily
• If creatinine clearance 30–49 600 give mg PO once every 48 hours
• If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
• If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis

• Note (1): duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
• Note (2): Observe for 3-6 months and treat if no spontaneous HBeAg loss.
• Note (3): Consider liver biopsy prior to treatment if compensated.
• Note (4): Immediate treatment if icteric or clinical decompensation.
• Note (5): Interferon alpha (IFNα)/ pegylated interferon-alpha (peg-IFNα), Lamivudine (LAM), Adefovir (ADV), Entecavir (ETV), tenofovir disoproxil fumarate (TDF) or telbivudine (LdT) may be used as initial therapy.
• Note (6): Adefovir (ADV) not preferred due to weak antiviral activity and high rate of resistance after 1st year.
• Note (7): Lamivudine (LAM) and Telbivudine (LdT) not preferred due to high rate of drug resistance.
• Note (8): End-point of treatment – Seroconversion from HBeAg to anti-HBe.
• Note (9): Interferon alpha (IFNα) non-responders / contraindications to IFNα change to Tenofovir (TDF)/Entecavir (ETV).

• 1.3. Children with elevated ALT greater than 2 times normal

• Preferred regimen(1): Interferon alpha (IFNα) 6 MU/m2 SC thrice weekly with a maximum of 10 MU
• Preferred regimen(2): Lamivudine (LAM) 3 mg/kg/d PO with a maximum of 100 mg/d.

• 2. Patients with HBeAg-negative chronic hepatitis B

• 2.1. HBV DNA >2,000 IU/mL and elevated ALT >2 times normal

• Preferred regimen (1): Pegylated IFN-alpha 180 mcg weekly SC for 1 year
• Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
• If creatinine clearance 30–49 give 300 mg q48 hrs
• If creatinine clearance 10–29 give 300 mg q72-96 hrs
• If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
• If creatinine clearance <10 without dialysis there is no recommendation
• Note: duration of treatment is more than 1 year

• Preferred regimen (3): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine
• If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine
• If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine
• If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
• Note: duration of treatment is more than 1 year

• Alternative regimen (1): Interferon alpha (IFNα) 5 MU daily or 10 MU thrice weekly SC for 1 year
• Alternative regimen (2): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 100 mg PO qd
• If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
• If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
• If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
• If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
• The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
• Note: duration of treatment is more than 1 year

• Alternative regimen (3): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 10 mg PO daily
• If creatinine clearance 30–49 give 10 mg PO every other day
• If creatinine clearance 10–19 10 mg PO every third day
• If hemodialysis patients give 10 mg PO every week following dialysis
• Note: duration of treatment is more than 1 year

• Alternative regimen (4): Telbivudine (LdT)Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 600 mg PO once daily
• If creatinine clearance 30–49 600 give mg PO once every 48 hours
• If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
• If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis

• Note (1): duration of treatment is more than 1 year
• Note (2): Interferon alpha (IFNα)/ pegylated interferon-alpha (peg-IFNα), Lamivudine (LAM), Adefovir (ADV), Entecavir (ETV), tenofovir disoproxil fumarate (TDF) or telbivudine (LdT) may be used as initial therapy.
• Note (3): Adefovir (ADV) not preferred due to weak antiviral activity and high rate of resistance after 1st year.
• Note (4): Lamivudine (LAM) and Telbivudine (LdT) not preferred due to high rate of drug resistance.
• Note (5): End-point of treatment – not defined
• Note (6): Interferon alpha (IFNα) non-responders / contraindications to IFNα change to Tenofovir (TDF)/Entecavir (ETV).

• 3. HBV DNA >2,000 IU/mL and elevated ALT 1->2 times normal

• Consider liver biopsy and treat if liver biopsy shows moderate/severe necroinflammation or significant fibrosis.

• 4. HBV DNA <2,000 IU/mL and ALT < upper limit normal (ULN)

• Observe, treat if HBV DNA or ALT becomes higher.

• 5. +/- HBeAg and detectable HBV DNA with Cirrhosis

• 5.1. Compensated Cirrhosis and HBV DNA >2,000

• Preferred regimen (1): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine.
• If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine.
• If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine.
• If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.

• Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
• If creatinine clearance 30–49 give 300 mg q48 hrs
• If creatinine clearance 10–29 give 300 mg q72-96 hrs
• If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
• If creatinine clearance <10 without dialysis there is no recommendation

• Alternative regimen (1): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 100 mg PO qd
• If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
• If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
• If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
• If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
• The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.

• Alternative regimen (2): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 10 mg PO daily
• If creatinine clearance 30–49 give 10 mg PO every other day
• If creatinine clearance 10–19 give 10 mg PO every third day
• If hemodialysis patients give 10 mg PO every week following dialysis

• Alternative regimen (3): Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 600 mg PO once daily
• If creatinine clearance 30–49 600 give mg PO once every 48 hours
• If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
• If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis

• Note (1): LAM and LdT not preferred due to high rate of drug resistance.
• Note (2): ADV not preferred due to weak antiviral activity and high risk of resistance after 1st year.
• Note (3): These patients should receive long-term treatment. However, treatment may be stopped in HBeAg-positive patients if they have confirmed HBeAg seroconversion and have completed at least 6 months of consolidation therapy and in HBeAg-negative patients if they have confirmed HBsAg clearance.

• 5.2. Compensated Cirrhosis and HBV DNA <2,000

• Consider treatment if ALT elevated.

• 5.3. Decompensated Cirrhosis

• Preferred regimen (1): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
• If creatinine clearance 30–49 give 300 mg q48 hrs
• If creatinine clearance 10–29 give 300 mg q72-96 hrs
• If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
• If creatinine clearance <10 without dialysis there is no recommendation

• Preferred regimen (2): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine.
• If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine.
• If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine.
• If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.

• Preferred regimen (3): Lamivudine (LAM) AND Adefovir (ADV)

• Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 100 mg PO qd
• If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
• If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
• If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
• If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
• The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.

• Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 10 mg PO daily
• If creatinine clearance 30–49 give 10 mg PO every other day
• If creatinine clearance 10–19 give 10 mg PO every third day
• If hemodialysis patients give 10 mg PO every week following dialysis

• Preferred regimen (4): Telbivudine (LdT) AND Adefovir (ADV)

• Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 600 mg PO once daily
• If creatinine clearance 30–49 600 give mg PO once every 48 hours
• If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
• If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis

• Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

• If creatinine clearance >50 or normal renal function give 10 mg PO daily
• If creatinine clearance 30–49 give 10 mg PO every other day
• If creatinine clearance 10–19 give 10 mg PO every third day
• If hemodialysis patients give 10 mg PO every week following dialysis

• Note: coordinate treatment with transplant center and refer for liver transplant.
• Life-long treatment is recommended.

• 6. +/- HBeAg and undetectable HBV DNA with Cirrhosis

• Compensated Cirrhosis: Observe
• Uncompensated Cirrhosis: Refer for liver transplant

Schistosomiasis

• Schistosomiasis Return to Top

• 1. Schistosoma mansoni, S. haematobium, S. intercalatum

• Preferred regimen: Praziquantel 40 mg/kg per day PO in qd or bid for one day
• Alternative regimen (1): Oxamniquine 20 mg/kg PO single dose
• Alternative regimen (2): Artemisinin no dose is established yet
• Alternative regimen (3): Mefloquine 250 mg PO single dose
• Note: There is no benefit in associating the alternative therapies to Praziquantel.
• Note: Praziquantel is not effective against larval/egg stages of the disease.

• 2. S. japonicum, S. mekongi

• Preferred regimen: Praziquantel 60 mg/kg per day PO bid for one day
• Alternative regimen (1): Artemisinin no dose is established yet
• Alternative regimen (2): Mefloquine 250 mg PO single dose
• Note: There is no benefit in associating the alternative therapies to Praziquantel.

• 3. Katayama Fever

• Preferred regimen: Prednisone 20-40 mg/day PO for 5 days, THEN Praziquantel
• Note: Praziquantel should be used after 4-6 weeks of exposure, because it cannot kill the larvae stages of the Schistosoma. Praziquantel should be used after acute schistosomiasis syndrome symptoms have resolved always together with corticosteroids, only when ova are detected in stool or urine samples.

• 4. Neuroschistosomiasis

• Preferred regimen: prednisone 1-2 mg/kg
• Note: Praziquantel should only be introduced after a few days of the initiation of corticosteroid therapy, due to the risk of increasing the inflammatory response.

Clonorchis sinensis

• Clonorchis sinensis Return to Top

• Preferred regimen: Praziquantel 75 mg/kg/day PO tid for 2 days
• Alternative regimen (1): Albendazole 10 mg/kg/day PO qd for 7 days
• Alternative regimen (2): Tribendimidine 400 mg PO single dose
• Note: This regimen is still under investigation, but it appears to be as effective as Praziquantel.
• Note: Urgent biliary decompression might be required for patients with acute cholangitis.

Dicrocoelium dendriticum

• Dicrocoelium dendriticum Return to Top

• Preferred regimen: Praziquantel 25 mg/kg PO tid for 2 days

• Note: Praziquantel is not approved for treatment of children less than 4 years old

• Alternative regimen (1): Myrrh (commiphora molmol) 12 mg/kg/day PO for 6 days
• Alternative regimen (2): Triclabendazole 10 mg/kg PO single dose

Fasciola hepatica

• Fasciola hepatica Return to Top

• Preferred regimen: Triclabendazole 10 mg/kg PO one dose
• Note: Two-dose (double-dose) triclabendazole therapy can be given to patients who have severe or heavy Fasciola infections (many parasites) or who did not respond to single-dose therapy.
• Alternative regimen: Nitazoxanide 500 mg PO bid for 7 days

Paragonimus westermani

• Paragonimus westermani Return to Top

• Preferred regimen (1): Praziquantel 25 mg/kg PO tid for 3 days
• Preferred regimen (2): Triclabendazole 10 mg/kg PO qd or bid
• Alternative regimen (1): Bithinol 30-50 mg/kg PO on alternate days for 10-15 doses
• Alternative regimen (2): Niclosamide 2 mg/kg PO single dose

Gnasthostoma spinigerum

• Gnathostoma spinigerum Return to Top

• Eosinophilic Meningitis
  • Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.
• Cutaneous disease:

• Preferred regimen: Albendazole 400 mg bid for 21 days OR Ivermectin 200 mcg/kg qd for 2 days
• Alternative regimen: Albendazole 400 mg qd for 21 days OR Ivermectin 200 mcg/kg qd single dose

Ancylostoma braziliense

• Ancylostoma braziliense Return to Top

• Preferred regimen

• Adult: Albendazole 400 mg PO qd for 3 to 7 days
• Pediatric: Albendazole > 2 years 400 mg PO qd for 3 days
• Note: This drug is contraindicated in children younger than 2 years age

• Alternative regimen

• Adult: Ivermectin 200 mcg/kg PO qd for one or two days
• Pediatric: Ivermectin >15 kg give 200 mcg/kg single dose

Angiostrongylus cantonensis

• Angiostrongylus cantonensis Return to Top

• Preferred: Symptomatic therapy, serial lumber puncture, corticosteroids (prednisone 60 mg qd for 2 weeks) and analgesics.
• Note: Albendazole and Mebendazole are generally not recommended due to the risk of exacerbation of neurological symptoms following anthelminthic therapy.

Ascaris lumbricoides

• Ascaris lumbricoides Return to Top

• Preferred regimen: Albendazole 400 mg PO qd OR Mebendazole 500 mg PO qd or 100 mg bid for 3 days

• Note: Albendazole dose for children of 1-2 years is 200 mg instead of 400 mg.

• Alternative regimen (1): Ivermectin 150 to 200 µg/kg PO single dose
• Alternative regimen (2): Nitazoxanide 500 mg bid for 3 days
• Alternative regimen (3): Levamisole 150 mg PO single dose
• Note: Pediatric dose: 2.5 mg/kg single dose
• Alternative regimen (4): Pyrantel Pamoate 11 mg/kg single dose PO - maximum 1.0 g
• Alternative regimen (5): Piperazine citrate 75 mg/kg qd for 2 days - maximum 3.5 g

Capillaria philippinensis

• Capillaria philippinensis Return to Top

• 1. Intestinal capillariasis

• Preferred regimen: Albendazole 400 mg/day PO for 10-30 days
• Alternative regimen: Mebendazole 200 mg PO bid for 20-30 days

Enterobius vermicularis

• Enterobius vermicularis Return to Top

• Preferred regimen (1): Albendazole 400 mg PO single dose - repeat in 2 weeks
• Preferred regimen (2): Mebendazole 100 mg PO single dose - repeat in 2 weeks
• Alternative regimen (1): Ivermectin 200 µg/kg PO single dose - repeat in 10 days
• Alternative regimen (2): Pyrantel pamoate 11 mg/kg up to 1.0 g PO single dose - repeat in 2 weeks

Necator americanus

• Necator americanus Return to Top

• Preferred regimen: Albendazole 400 mg PO single dose
• Alternative regimen (1): Mebendazole 100 mg PO bid or 500 mg daily for 3 days
• Alternative regimen (2): Pyrantel pamoate 11 mg/kg PO qd (maximum 1 g/day) for 3 days

Ancylostoma duodenale

• Ancylostoma duodenale Return to Top

• Preferred regimen: Albendazole 400 mg PO single dose
• Alternative regimen (1): Mebendazole 100 mg PO bid or 500 mg daily for 3 days
• Alternative regimen (2): Pyrantel pamoate 11 mg/kg PO qd (maximum 1 g/day) for 3 days

Strongyloides stercoralis

• Strongyloides stercoralis Return to Top

• Preferred regimen: Ivermectin 200 mcg/kg/day PO qd for 2 days or two doses 2 weeks apart from each other
• Alternative regimen: Albendazole 400 mg PO bid for 3-7 days

Trichuris trichiura

• Trichuris trichiura Return to Top

• Preferred regimen: Albendazole 400 mg PO qd for 3 days
• Alternatie regimen (1): Mebendazole 100 mg PO bid for 3 days
• Alternative regimen (2): Ivermectin 200 mcg/kg/day PO qd for 3 days

Entamoeba histolytica

• 1. Amebic Liver Abscess

• Preferred regimen: (Metronidazole 750 mg PO tid for 10 days OR Tinidazole 2 g PO qd for 5 days) AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
• Alternative regimen (1): Nitazoxanide 500 mg bid for 10 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
• Alternative regimen (2): Tinidazole 2 g PO qd for 5 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
• Alternative regimen (2): Tinidazole 2 g PO qd for 5 days

• 2. Amebic Colitis

• Preferred regimen: Metronidazole 500-750 mg PO tid for 7-10 days. Pediatric dose: 35-50 mg/kg per day tid AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
• Alternative regimen: Tinidazole 2 g PO qd for 5 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)

• 3. Asymptomatic Intestinal Colonization

• Preferred regimen: Paromomycin 30 mg/kg/day PO tid for 5-10 days
• Alternative regimen (1): Diloxanide furoate 500 mg PO tid for 10 days
• Alternative regimen (2): Diiodohydroxyquin 650 mg PO tid for 20 days for adults and 30 to 40 mg/kg per day tid for 20 days for children

Paracoccidiodomycosis

• Preferred regimen (1):

• Adults: Itraconazole 200 mg/day PO
• Children: Itraconazole (<30/kg and >5 yr) 5-10 mg/kg/day PO
• Note: Treatment duration based on organ involvement:

• Mild involvement: 6-9 months
• Moderate involvement: 12-18 months

• Preferred regimen (2):

• Adults Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 160-240 mg/day PO/IV, SMX: 800-1200 mg/day PO/IV q12h
• Children Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 8-10 mg/kg PO/IV, SMX: 40-50 mg/kg PO/IV q12h
• Note (1): Treatment duration based on organ involvement:

• Minor involvement: 12 months
• Moderate involvement: 18-24 months

• Note (2): Preferred treatment in children due to larger experience.
• Note (3): Preferred in IV formulation in severe forms of the disease - 2 ampules IV q8h until patient condition improves so that oral medication can be given.

• Preferred regimen (3): Amphotericin B deoxycholate 1 mg/kg/day IV until patient improves and can be treated by the oral route.

• Note: Preferred in severe forms of the disease.

• Alternative regimen (4): Ketoconazole 200-400 mg/day PO for 9-12 months
• Alternative regimen (5): Voriconazole initial dose 400 mg PO/IV q12h for one day, then 200 mg q12h for 6 months

• Note: Diminish the dose to 50% if weight is <40 kg.

Aspergillosis

• Aspergillosis Return to Top
• 1. Invasive pulmonary aspergillosis

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

• 2. Invasive sinus aspergillosis

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

• 3. Tracheobronchial aspergillosis

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

• 4. Chronic necrotizing pulmonary aspergillosis

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

• 5. Aspergillosis of the CNS

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

• Note: There are drug interactions with anticonvulsant therapy.

• 6. Aspergillus infections of the heart (endocarditis, pericarditis, and myocarditis)

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
• Note: endocardial lesions generally require surgical treatment. Aspergillus pericarditis usually requires pericardiectomy.

• 7. Aspergillus osteomyelitis and septic arthritis

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
• Note: Surgical resection of devitalized bone and cartilage is important for curative intent.

• 8. Aspergillus infections of the eye (endophthalmitis and keratitis)

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
• Note: Topical therapy is indicated for keratitis, ophthalmologic intervention and management is recommended for all forms of ocular infection. Systemic therapy may be beneficial when treating aspergillus endophthalmitis.

• 9. Cutaneous aspergillosis

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
• Note: Surgical resection is indicated when feasible.

• 10. Aspergillus peritonitis

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

• 11. Prophylaxis against invasive aspergillosis

• Preferred regimen: Posaconazole PO 200 mg tid
• Alternative regimen: (1) Itraconazole 200 mg IV q12h for 2 days then 200 mg IV q24h OR Itraconazole PO 200mg bid
• Alternative regimen: (2) Micafungin 50 mg/day PO qd

• 12. Aspergilloma

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h

• 13. Chronic cavitary pulmonary aspergillosis

• Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
• Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV q24h
• Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV q24h
• Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV q24h
• Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
• Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (6): Micafungin 100–150 mg/day PO qd
• Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

• Note: long-term therapy might be needed.

• 14. Allergic bronchopulmonary Itraconazole aspergillosis

• Preferred regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Alternative regimen (1): Voriconazole PO 200 mg bid
• Alternative regimen (2): Posaconazole PO 400 mg bid
• Note: Corticosteroids are a cornerstone of the therapy.

• 15. Allergic aspergillus sinusitis

• Preferred regimen: None or Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV q24h
• Note: Few data available for other agents.

• 16. Relative indications for surgical treatment of invasive aspergillosis

• Pulmonary lesion in proximity to great vessels or pericardium;
• Pericardial infection;
• Invasion of chest wall from contiguous pulmonary lesion;
• Aspergillus empyema;
• Persistent hemoptysis from a single cavitary lesion;
• Infection of skin and soft tissues;
• Infected vascular catheters and prosthetic devices;
• Endocarditis;
• Osteomyelitis;
• Sinusitis;
• Cerebral lesions.

Yellow Fever Virus

• 1. Yellow fever

• 1.1. Summary

• Yellow fever was one of the most lethal diseases before the development of the vaccine. It is a major health concern for unvaccinated travellers to tropical regions in South America and Africa. It is transmitted by mosquitoes (Aedes aegypti) bites in a cycle which involve these mosquitoes biting also monkeys and human beings, which act as hosts for the virus. The yellow fever virus is a member of the Flaviviridae family, which comprises about 70 viruses, most of which are arthropod-borne.

• 1.2. Epidemiology

• Up to 5000 cases are reported annually in Africa and 300 annually in South America, although it is believed that numbers are underestimated. In Africa the human population is seasonally exposed in and around villages and small cities so the highest risk of disease are children without naturally acquired immunity. In South America the virus is transmitted in poorly populated forested areas and it occurs mainly with workers and farmers in the borders of the forested areas.

• 1.3. Clinical Manifestations

• Yellow fever can present itself in three forms: subclinical infection, nonspecific abortive febrile disease and fatal hemorrhagic fever. The incubation time for the disease is 3-6 days. After this period, the onset of fever, myalgia, lower back pain, irritability, nausea, malaise, headache, fotofobia and dizziness is oftenly abrupt. These findings are not specific to Yellow Fever and can be found in any acute infection. During this period the patient can be a source of virus for mosquitoes.
• On physical examination the liver can be enlarged with tenderness, Faget sign (slow pulse rate despite high fever) can be found. Skin might appear flushed with reddening of conjunctivae and gums. Between 48-72h after onset and before the jaundice, hepatic enzymes starts to rise. Laboratory studies may show leukopenia with relative neutropenia. This is called period of infection and may last for several days and may be THEN a remission period which last about 48h, with the disappearance of the fever and the symptoms. Patients with the abortive form of the disease recover at this stage.
• After the third to sixth day of the onset of the symptoms the patient may present return of the fever, vomiting, renal failure (oliguria), jaundice, epigastric pain and hemorrhagic diathesis. The viremia terminates during this stage and the antibodies appear in the blood. The patient may evolve with multiorgan failure during this phase. Also in this stage, AST concentrations might exceed ALT, probably due to myocardial and skeletal muscle damage. Serum creatinine and bilirubin levels also rise at this stage. Hemorrhagic manifestations may include petechiae, ecchymoses, epistaxis, melena, metrorrhagia, haematemesis. Laboratory studies may show thrombocytopenia, reduced fibrinogen levels, presence of fibrin split products, reduced factors II, V, VII, VIII, IX and X, which suggest a multifactorial cause for the bleeding with a consumption coagulopathy. Myocardial disfunction may be demonstrated by abnormalities in the ST-T segment in the electrocardiogram. Encephalitis is very rare.
• 20-50% of the patients with the hepatorenal disease die after 7-10 days of the onset.

• 1.4. Diagnosis

• Diagnosis can be made by serology, detection of viral genome by polymerase chain reaction, immunohistochemistry on postmortem tissues, viral isolation or histopathology. No commercial test is available and diagnostic capabilities are restricted to selected laboratories only. Serologic diagnosis is made by dosing IgM antibodies with ELISA. The virus might be isolated by inoculating it in mice, cell cultures or mosquitoes. PCR is generally used to detect viral genome in clinical samples that were negative by virus isolation or other method.

• 1.5. Treatment

• Preferred regimen: No specific treatment is available for yellow fever. In the toxic phase, supportive treatment includes therapies for treating dehydration and fever. Ribavirin has failed in several studies in the monkey model.

• Note: An international seminar held by WHO in 1984 recommended maintenance of nutrition, prevention of hypoglycemia, maintenance of the blood pressure with fluids and vasoactive drugs, prevention of bleeding with fresh-frozen plasma, dialysis if renal failure, correction of metabolic acidosis, administration of cimetidine IV to avoid gastric bleeding and oxygen if needed.

• 1.6. Prevention

• The Yellow fever 17D is highly effective, safe, attenuated vaccine that has been used for over 60 years. It should be taken my travellers who are going to endemic areas of the disease. Revaccination is needed after 10 years from the first dose. The side effects of the vaccines are rare but they include yellow fever associated viscerotropic disease and neurotropic disease. Immunization is contraindicated during pregnancy and in patients with immunodeficiency due to cancers, HIV/AIDS, or treatment with immunosuppressive agents.

Chikungunya Fever

Chikungunya Fever

• Preferred regimen: no specific therapeutics agents are available and there are no licensed vaccines to prevent Chikungunya Fever.

• Note: Anti inflammatory drugs can be used to control joint swelling and arthritis.

Rabies

• Rabies

• Preferred regimen: no specific therapeutics agents are available once the disease is established.

• Note: There are vaccines and immune globulins available for postexposure prophylaxis:

• Postexposure Prophylaxis for non immunized individuals: Wound cleansing, human rabies immune globulin - administer full dose infiltrated around any wound. Administer any remaining volume IM at other site anatomically distant from the wound. Administer vaccine 1,0ml, IM at deltoid area one each on days 0, 3, 7 and 14.
• Postexposure Prophylaxis for immunized individuals: Wound cleansing, do not administer human rabies immune globulin. Administer vaccine 1,0ml, IM at deltoid area one each on days 0 and 3.

Cryptococcus

• Cryptococcus Return to Top

• 1. Cryptococcus neoformans

• 1.1 Cryptococcus neoformans meningitis in HIV infected patients

• Preferred regimen for induction and consolidation: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV q24h OR Liposomal AmB 3-4 mg/kg IV q24h OR Amphotericin B lipid complex 5 mg/kg IV q24h) AND Flucytosine 100 mg/kg/day PO/IV q6h for at least 2 weeks THEN Fluconazole 400 mg (6 mg/kg) PO qd for at least 8 weeks
• Alternative regimen for induction and consolidation (1): Amphotericin B deoxycholate 0.7-1.0 mg/kg IV q24h OR Liposomal AmB 3-4 mg/kg IV q24h OR AmB lipid complex 5 mg/kg IV q24h for 4-6 weeks
• Alternative regimen for induction and consolidation (2): Amphotericin B deoxycholate 0.7 mg/kg IV q24h AND Fluconazole 800 mg PO qd for 2 weeks, THEN Fluconazole 800 mg PO qd for at least 8 weeks
• Alternative regimen for induction and consolidation (3): Fluconazole 800-1200 mg PO qd AND Flucytosine 100 mg/kg/day PO qid for 6 weeks
• Alternative regimen for induction and consolidation (4): Fluconazole PO 800-2000 mg qd for 10-12 weeks
• Preferred regimen for maintenance and prophylactic therapy: Initiate HAART 2-10 weeks after commencing initial antifungal therapy AND Fluconazole 200 mg PO qd
• Alternative regimen for maintenance and prophylactic therapy: Itraconazole 200 mg PO bid - monitor drug-level (trough concentration must be higher than 0.5 μg/ml) OR Amphotericin B deoxycholate 1 mg/kg per week IV (should be used in azole-intolerant patients)
• Note (1): Consider discontinuing supressive therapy if CD4 count is higher than 100 cells/uL AND undetectable OR very low HIV RNA level for more than 3 months. Consider reinstitution of maintenance therapy if CD4 count <100 cels/uL.
• Note (2): Do not use acetazolamide OR mannitol OR corticosteroids to treat increased intracranial pressure, instead it should be used lombar puncture in the absence of focal neurologic signs or impaired mentation (which, if present, patient must be submitted to CT or MRI scan first).

1.2. Cerebral cryptococcomas

• Preferred regimen for induction and consolidation: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV q24h OR Liposomal AmB 3-4 mg/kg IV q24h OR Amphotericin B lipid complex 5 mg/kg IV q24h) AND Flucytosine 100 mg/kg/day PO/IV q6h for at least 2 weeks THEN Fluconazole 400 mg (6 mg/kg) PO qd for at least 8 weeks
• Note: Consider surgery if lesions are larger than 3 cm, accessible lesions with mass effect or lesions that are enlarging and not explained by IRIS.

1.3. Cryptococcus neoformans meningitis in HIV negative patients

• Preferred regimen: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV q24h AND Flucytosine 100 mg/kg/day PO or IV q6h for at least 4 weeks (which may be extended to 6 weeks if there is any neurological complication) THEN Fluconazole 400 mg PO qd for 8 weeks.
• Note (1): If there's toxicity to Amphotericin B deoxycholate, consider changing to Liposomal AmB or Amphotericin B lipid complex in the second 2 weeks.
• Note (2): After induction and consolidation therapy, start Fluconazole 200 mg (3 mg/kg) PO qd for 6-12 months.
• Note (3): If Flucytosine is not given, consider lengthening the induction therapy for at least 2 weeks.

1.4. Cryptococcus neoformans pulmonary disease - immunosupressed

• Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:

• Preferred regimen: Fluconazole 400 mg PO qd for 6-12 months

• Severe pneumonia or disseminated disease or CNS infection:

• Preferred regimen: treat like CNS cryptococcosis.

• Note (1): In HIV- infected patients, treatment should be stopped after 1 year if CD4 count is >100 and a cryptococcal antigen titer is <1:512 and not increasing.
• Note (2): Consider corticosteroid if ARDS is present in a context which it might be attributed to IRIS.

1.5 Cryptococcus neoformans pulmonary disease - non-immunosupressed

• Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:

• Preferred regimen: Fluconazole 400 mg PO qd for 6-12 months
• Alternative regimen: if Fluconazole is unavailable or contraindicated, Itraconazole 200 mg PO bid, Voriconazole 200 mg PO bid, and Posaconazole 400 mg PO bid

• If there's severe pneumonia, disseminated disease or CNS infection:

• Preferred regimen: treat like CNS cryptococcosis for 6-12 months.

1.6 Cryptococcus neoformans non-lung, non-CNS infection

• Cryptococcemia or disseminated cryptococcic disease (involvement of at least 2 noncontiguous sites or cryptococcal antigen titer >1:512):

• Preferred regimen: treat like CNS infection.

• If infection occurs at a single site and no immunosupressive risk factors

• Preferred regimen: Fluconazole 400 mg PO qd for 6-12 months

1.7. Cryptococcosis in Children

• Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 1.0 mg/kg qd IV AND Flucytosine 100 mg/kg PO or IV q6h for 2 weeks THEN Fluconazole 10-12 mg/kg PO qd for 8 weeks
• Alternative regimen: patients with renal dysfunction: change Amphotericin B deoxycholate by Liposomal AmB 5 mg/kg IV q24h or Amphotericin B lipid complex (ABLC) 5 mg/kg IV q24h
• Preferred regimen for maintenance: Fluconazole 6 mg/kg PO qd. Discontinuation of maintenance therapy is poorly studied and should be individualized.

• Cryptococcal pneumonia:

• Preferred regimen Fluconazole 6-12 mg/kg PO qd for 6-12 months

1.8. Cryptococcosis in Pregnant Women

• Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV q24h. Start Fluconazole after delivery. Avoid use during first trimester and consider use in the last 2 trimesters with the need for continuous antifungal therapy during pregnancy.
• Note (1): Consider using lipid formulations for patients with renal dysfunction - Liposomal AmB 3-4 mg/kg IV q24h OR Amphotericin B lipid complex (ABLC) 5 mg/kg IV q24h.
• Note (2): Consider using Flucytosine in relationship to benefit risk basis, since it is a Category C drug for pregnancy.
• Note (3): If pulmonary cryptococcosis: perform close follow-up and administer fluconazole after delivery.

2. Cryptococcus gatti

• Disseminated cryptococcosis or CNS disease:

• Preferred regimen: treatment is the same as C. neoformans

• Pulmonary disease: single and small cryptococcoma:

• Preferred regimen: Fluconazole 400 mg per day PO for 6-18 months

• Pulmonary disease: Very large or multiple cryptococcomas:

• Preferred regimen: administer Flucytosine AND AmB deocycholate for 4-6 weeks, THEN Fluconazole for 6-18 months
• Note: Surgery should be considered if there is compression of vital structures OR failure to reduce the size of the cryptococcoma after 4 weeks of therapy

Dermatophytosis

• Dermatophytosis

• 1. Tinea Cruris

• Preferred regimen (1): Interdigital: Topical cream/ointment: terbinafine, imidazoles (miconazole, econazole OR clotrimazole)
• Preferred regimen (2): Griseofulvin 250 mg PO tid for 14 days should be used in resistant to topic therapy cases

• 2. Tinea Corporis

• 2.1 Small, well-defined lesions:

• Preferred regimen: Topical cream/ointment: terbinafine, imidazoles (miconazole, econazole, clotrimazole).

• 2.2 Larger lesions:

• Preferred regimen: Larger lesions: terbinafine 250 mg/day PO for 2 weeks; itraconazole 200 mg/day PO for 1 week, fluconazole 250 mg PO weekly for 2-4 weeks

• 3. Tinea Pedis

• Preferred regimen: Interdigital: Topical cream/ointment: terbinafine, imidazoles (miconazole, econazole, clotrimazole), undecenoic acid, tolnaftate.
• Note (1): If "Dry type": Oral: terbinafine 250 mg/day PO for 2-4 weeks, itraconazole 400 mg/day PO for 1 week per month (repeat if necessary), fluconazole 200 mg PO weekly for 4-8 weeks

• 4. Tinea Capitis

• Preferred regimen: Griseofulvin 10-20 mg/kg/day PO qd for at least 6 weeks (Preferred for children).
• Alternative regimens: Terbinafine 62.5 mg/day if <20kg; 125 mg/day if 20-40kg; 250 mg/day if >40kg PO qd for 8 weeks OR Itraconazole 4-6 mg/kg/day (maximum 400 mg) PO for 4-6 weeks

• Note: Nistatin is not effective in the treatment of dermatophytosis.

• 5. Tinea Barbae

• Preferred regimen: Terbinafine 250 mg/day PO qd for 4 weeks
• Alternative regimen: Itraconazole 200 mg/day PO qd for 2 weeks

• 6. Tinea Incognito

• Preferred regimen: Stop topical steroids and treat with topical 1% terbinafine cream for 6 weeks

• 7. Tinea Manuum

• Preferred regimen: topical or systemic terbinafine 250 mg/day PO qd por 2-4 weeks

• 8.Tinea Versicolor

• Preferred regimen: Itraconazole 200 mg PO qd for a week
• Alternative regimen: Ketoconazole 200 mg PO qd for 4 weeks

• 9. Majocchi's Granuloma

• Preferred regimen: Terbinafine 250 mg/day PO for 2-4 weeks or Itraconazole 200 mg PO bid for 1 week, per month for 2 months

Onychomycosis

• 10. Onychomycosis

• 10.1 Fingernails

• Preferred regimen: Terbinafine 250 mg/day PO for 6 weeks OR Itraconazole 200 mg PO bid for one week per month for 2 months (European guidelines)

• 10.2 Toenails

• Preferred regimen: Toenails Terbinafine 250 mg/day PO for 12 weeks OR Itraconazole 200 mg/day PO for 12 weeks (U.S. guidelines) OR Itraconazole 200 mg PO bid for one week per month for 3 months (European guidelines)

• Note: There is no evidence that combining systemic and topic treatments has any benefit to the patient.