Sandbox ID Musculoskeletal

Osteomyelitis, chronic

• Chronic Osteomyelitis in Adults – Pathogen-Based Therapy

• OSSA

• Preferred regimen: Oxacillin 1.5–2 g IV q4h for 4–6 wk OR Cefazolin 1–2 g IV q8h for 4–6 wk

• Alternative regimen (1): Vancomycin 15 mg/kg IV q12h for 4–6 wk
• Alternative regimen (2): Oxacillin 1.5–2 g IV q4h for 4–6 wk AND Rifampin 600 mg PO qd

• ORSA

• Preferred regimen: Vancomycin 15 mg/kg IV q12h for 4–6 wk OR Daptomycin 6 mg/kg IV q24h
• Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 6 wk ± Rifampin 600–900 mg PO qd
• Alternative regimen (2): Levofloxacin 500–750 mg PO/IV daily ± Rifampin 600–900 mg PO qd

• Penicillin-sensitive Streptococcus

• Preferred regimen: Penicillin G 20 MU/day IV continuously or q4h for 4–6 wk OR Ceftriaxone 1–2 g IV/IM q24h for 4–6 wk OR Cefazolin 1–2 g IV q8h for 4–6 wk
• Alternative regimen: Vancomycin 15 mg/kg IV q12h for 4–6 wk

• Enterococcus or Streptococcus (MIC≥0.5 μg/mL) or Abiotrophia or Granulicatella

• Preferred regimen: Penicillin G 20 MU/day IV continuously or q4h for 4–6 wk ± Gentamicin 1 mg/kg IV or IM q8h for 1–2 wk OR Ampicillin 12 g/day IV continuously or q4h for 4–6 wk ± Gentamicin 1 mg/kg IV or IM q8h for 1–2 wk

• Alternative regimen: Vancomycin 15 mg/kg IV q12h for 4–6 wk ± Gentamicin 1 mg/kg IV or IM q8h for 1–2 wk

• Enterobacteriaceae

• Preferred regimen: Ceftriaxone 1–2 g IV/IM q24h for 4–6 wk OR Ertapenem 1 g IV q24h
• Alternative regimen: Levofloxacin 500–750 mg PO q24h OR Ciprofloxacin 500–750 mg PO q12h for 4–6 wk

• Pseudomonas aeruginosa

• Preferred regimen: Cefepime 2 g IV q12h OR Meropenem 1 g IV q8h OR Imipenem 500 mg IV q6h for 4–6 wk
• Alternative regimen: Ciprofloxacin 750 mg PO q12h OR Ceftazidime 2 g IV q8h for 4–6 wk

• Chronic Osteomyelitis in Children – Pathogen-Based Therapy

• Group A beta-hemolytic Streptococcus, Haemophilus influenzae type b, andStreptococcus pneumoniae

• Preferred regimen: Ampicillin 150–200 mg/kg/day administered in 4 equal doses OR Amoxicillin 150–200 mg/kg/day administered in 4 equal doses

• Alternative regimen: Chloramphenicol 75 mg/kg/day administered in 3 equal doses

Osteomyelitis, spinal implant

• Vertebral Osteomyelitis – Pathogen-Based Therapy

• OSSA or coagulase-negative staphylococci

• Preferred regimen: Oxacillin 2 g IV q6h OR Cefazolin 1–2 g IV q8h
• Alternative regimen: Levofloxacin 750 mg PO qd AND Rifampin 300 mg PO bid

• ORSA

• Preferred regimen: Vancomycin 1 g IV q12h
• Alternative regimen (1): Daptomycin ≥ 6 mg/kg IV q24h
• Alternative regimen (2): Levofloxacin 500–750 mg PO/IV daily AND Rifampin 600–900 mg PO qd

• Streptococcus

• Preferred regimen: Penicillin G 5 MU IV q6h
• Alternative regimen: Ceftriaxone 2 g IV q24h

• Enterobacteriaceae, quinolone-susceptible

• Preferred regimen: Ciprofloxacin 750 mg PO q12h
• Alternative regimen: Ceftriaxone 2 g IV q24h

• Enterobacteriaceae, quinolone-resistant

• Preferred regimen: Imipenem 500 mg IV q6h

• Pseudomonas aeruginosa

• Preferred regimen: Cefepime 2 g IV q8h OR Ceftazidime 2 g IV q8h x 2–4 wk, followed by Ciprofloxacin 750 mg PO bid
• Alternative regimen:

• Anaerobes

• Preferred regimen:
• Alternative regimen:

Reactive arthritis, post-streptococcal arthritis

• Preferred regimen: Treat strep pharyngitis and then NSAIDs (Prednisone needed in some patients)

Reactive arthritis, Reiter's syndrome

• Preferred regimen: Only treatment is non-steroidal anti-inflammatory drugs

Septic arthritis, Brucella melitensis

• Preferred Regimen: Doxycycline 100 mg PO bid for ≥ 6 weeks AND Streptomycin 15 mg/kg IM qd for 2–3 weeks OR Rifampin 600–900 mg qd for ≥ 6 weeks
• Alternative Regimen: Doxycycline 100 mg PO bid for ≥ 6 weeks AND Gentamicin 5 mg/kg IV qd for 7 days

Septic arthritis, candidal

• Preferred regime: Fluconazole 400 mg (6 mg/kg) daily for at least 6 weeks OR lipid formulation of amphotericin B 3–5 mg/kg daily for several weeks, then Fluconazole to completion
• Alternative regime: Anidulafungin 200-mg loading dose, then 100 mg/day OR Caspofungin 70-mg loading dose, then 50 mg/day OR Micafungin 100 mg/day OR Amphotericin B deoxycholate 0.5–1 mg/kg daily for several weeks then Fluconazole to completion
• NOTE: Duration of therapy usually is for at least 6 weeks, but few data are available; Surgical debridement is recommended for all cases; For infected prosthetic joints, removal is recommended for most cases.

Septic arthritis, gonococcal

• Preferred regime: Ceftriaxone 1 g intramuscularly IM/IV every 24 h
• Alternative regime: Cefotaxime 1 g IV every 8 hours OR Ceftizoxime 1 g IV every 8 hours
• NOTE: The tetracyclines (except in pregnant women) or penicillins may be used if the infecting organism is proven to be susceptible; Penicillin allergies should be given Spectinomycin (2 g IV every 12 h);Alternative antibiotics in the β-lactam-allergic patient may be Ciprofloxacin (500 mg IV every 12 h) or Ofloxacin (400 mg IV every 12 h)
• Pediatric regime: (>45 kg) single daily dose of Ceftriaxone (50 mg/kg and a maximum dose of 2 g, IM or IV) for 10 to 14 days; (<45 kg) Ceftriaxone (50 mg/kg and a maximum dose of 1 g, IM or IV in a single daily dose for 7 days)

Septic arthritis, Gram-negative bacilli

• Preferred regime: Ceftazidime 2 g IV q8h OR Cefepime 2 g IV q8–12h OR Piperacillin-Tazobactam 4.5 g IV q6h

• Alternative regime: Aztreonam 2 g IV q8h OR Imipenem 500 mg IV q6h OR Meropenem 1 g IV q8h {or}} Doripenem 500 mg IV q8h OR Carbapenems

Septic arthritis, Histoplasmosis

• Septic arthritis, histoplasmosis

• Mild disease

• Preferred regimen: Nonsteroidal anti-inflammatory drug

• Severe disease

• Preferred regimen: Prednisone 0.5–1.0 mg/kg/day (maximum: 80 mg daily) in tapering doses over 1–2 weeks AND Itraconazole 200 mg tid for 3 days, followed by qd or bid for 6–12 weeks

Septic arthritis, Lyme disease

• Septic arthritis, Lyme disease

• Patients without clinical evidence of neurologic disease

• Preferred regime: Doxycycline 100 mg twice per day OR Amoxicillin 500 mg 3 times per day OR Cefuroxime Axetil 500 mg twice per day for 28 days
• Pediatric regime: Amoxicillin 50 mg/kg per day in 3 divided doses maximum of 500 mg per dose OR Cefuroxime Axetil 30 mg/kg per day in 2 divided doses maximum of 500 mg per dose OR (if the patient is ≥8 years of age) Doxycycline 4 mg/ kg per day in 2 divided doses (maximum of 100 mg per dose)

• Patients with arthritis and objective evidence of neurologic disease

• Preferred regime: Ceftriaxone administered parenterally for 2–4 weeks
• Alternative regime: Cefotaxime OR Penicillin G administered parenterally
• Pediatric regime: Ceftriaxone OR Cefotaxime OR Penicillin G administered intravenously

• NOTE (1): For patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy, we recommend re-treatment with another 4-week course of oral antibiotics or with a 2–4-week course of Ceftriaxone IV
• NOTE (2): If patients have no resolution of arthritis despite intravenous therapy and if PCR results for a sample of synovial fluid (and synovial tissue if available) are negative, symptomatic treatment is recommended, which consist of nonsteroidal anti-inflammatory agents, intra-articular injections of corticosteroids, or disease-modifying antirheumatic drugs (DMARDs), such as Hydroxychloroquine.

Septic arthritis, Mycobacterium tuberculosis

• Septic arthritis, Mycobacterium tuberculosis

• Septic arthritis caused by susceptible Mycobacterium tuberculosis

• Intensive phase (adult)

• Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 2 months AND Rifampin 10 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months

• Continuation phase (adult)

• Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 7 months AND Rifampin 10 mg/kg (max: 600 mg) for 7 months

• Intensive phase (pediatric)

• Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 2 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months

• Continuation phase (pediatric)

• Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 7 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 7 months

• Specific considerations

• Pregnancy and breastfeeding

• With the exception of streptomycin, the first line anti-TB drugs are safe for use in pregnancy: streptomycin is ototoxic to the fetus and should not be used during pregnancy.
• After active TB in the baby is ruled out, the baby should be given 6 months of isoniazid preventive therapy, followed by BCG vaccination.
• Pyridoxine supplementation is recommended for all pregnant or breastfeeding women taking isoniazid.

• Liver disorders

• Two hepatotoxic drugs (rather than the three in the standard regimen):

• 9 months of isoniazid and rifampicin, plus ethambutol (until or unless isoniazid susceptibility is documented).
• 2 months of isoniazid, rifampicin, streptomycin and ethambutol, followed by 6 months of isoniazid and rifampicin.
• 6–9 months of rifampicin, pyrazinamide and ethambutol.

• One hepatotoxic drug:

• 2 months of isoniazid, ethambutol and streptomycin, followed by 10 months of isoniazid and ethambutol.

• No hepatotoxic drugs:

• 18–24 months of streptomycin, ethambutol and a fluoroquinolone.

• Renal failure and severe renal insufficiency

• The recommended initial TB treatment regimen for patients with renal failure or severe renal insufficiency is 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by 4 months of isoniazid and rifampicin.
• There is significant renal excretion of ethambutol and metabolites of pyrazinamide, and doses should therefore be adjusted.
• Three times per week administration of these two drugs at the following doses is recommended: pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg)
• While receiving isoniazid, patients with severe renal insufficiency or failure should also be given pyridoxine in order to prevent peripheral neuropathy.
• Because of an increased risk of nephrotoxicity and ototoxicity, streptomycin should be avoided in patients with renal failure. If streptomycin must be used, the dosage is 15 mg/kg, two or three times per week, to a maximum of 1 gram per dose, and serum levels of the drug should be monitored.

• Previously treated patients in settings with rapid DST

• TB patients whose treatment has failed or other patient groups with high likelihood of multidrug-resistant TB (MDR) should be started on an empirical MDR regimen.
• TB patients returning after defaulting or relapsing from their first treatment course may receive the retreatment regimen containing first-line drugs 2HRZES/1HRZE/5HRE if country-specific data show low or medium levels of MDR in these patients or if such data are not available.

• TB treatment in people living with HIV

• TB patients with known positive HIV status and all TB patients living in HIV prevalent settings should receive daily TB treatment at least during the intensive phase.
• For the continuation phase, the optimal dosing frequency is also daily for these patients.
• If a daily continuation phase is not possible for these patients, three times weekly dosing during the continuation phase is an acceptable alternative.
• It is recommended that TB patients who are living with HIV should receive at least the same duration of TB treatment as HIV-negative TB patients.

Septic arthritis, post-intraarticular injection

• NO empiric therapy.

Septic arthritis, prosthetic joint infection

• Septic arthritis, prosthetic joint infection (device-related osteoarticular infections)

• Empiric antimicrobial therapy

• It is preferable to delay antibiotic therapy until specimens for culture are obtained by joint aspiration, joint debridement, and/or prosthesis removal.

• Pathogen-directed antimicrobial therapy

• Staphylococcus aureus, methicillin-susceptible (MSSA)

• Preferred regimen: Nafcillin 2 g IV q4–6h OR Oxacillin 2 g IV q4–6h

• Alternative regimen: Cefazolin 1–2 g IV q8h OR Ceftriaxone 2 g IV q24h
• Alternative regimen (if allergic to penicillins): Clindamycin 900 mg IV q8h OR Vancomycin 15–20 mg/kg IV q8–12 hours, not to exceed 2 g per dose

• Staphylococcus, methicillin-resistant (MRSA)

• Early-onset (< 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (< 3 weeks) of symptoms and debridement (but device retention)

• Preferred regimen: Vancomycin AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
• Alternative regimen: (Daptomycin 6 mg/kg IV q24h OR Linezolid 600 IV q8h) AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks

Note: The above regimen should be followed by Rifampin plus a fluoroquinolone, TMP/SMX, a tetracycline or clindamycin for 3 or 6 months for hips and knees, respectively.

• Early-onset spinal implant infections (< 30 days after surgery), or implants in an actively infected site

• Initial parenteral therapy plus rifampin followed by prolonged oral therapy is recommended.
• Long-term oral suppressive antibiotics (eg, TMP-SMX, a tetracycline, a fluoroquinolone [which should be given in conjunction with rifampin due to the potential emergence of fluoroquinolone resistance)

• Streptococci, beta-hemolytic

• Preferred regimen: Penicillin 12–18 MU/day IV q6h OR Ampicillin 2 g IV q6h OR Ceftriaxone 1–2 g IV q24h
• Alternative regimen (allergic to penicillin): Clindamycin 900 mg IV q8h OR Vancomycin 15–20 mg/kg q8–12h, not to exceed 2 g per dose

• Enterococci

• Monotherapy

• Preferred regimen (1): Ampicillin 6 to 12 g per 24 hours in four to six equally divided doses
• Preferred regimen (2): Penicillin G 18 to 30 million units per 24 hours either continuously or in six equally divided doses
• Preferred regimen (3): Vancomycin 15 to 20 mg/kg/dose every 8 to 12 hours, not to exceed 2 g per dose

• Combination therapy (one of the monotherapy agents, and one of the following agents)

• Preferred regimen (1): Gentamicin 1 mg/kg IV q8h
• Preferred regimen (2): Streptomycin 7.5 mg/kg IV q12h
• Preferred regimen (3): Ampicillin 2 g/day IV q6h AND Ceftriaxone 2 g IV q12h

• Gram-negative bacilli

• Patients susceptible to fluoroquinolones

• Preferred regimen: Ciprofloxacin 500 to 750 mg bid

• P. aeruginosa

• Preferred regimen: Cefepime 2 g intravenously every 12 hours OR Meropenem 1 g intravenously every 8 hours
• Alternative regimen (1): Ciprofloxacin 750 mg orally every 12 hours Ceftazidime 2 g intravenously every 8 hours (alternative)
• Alternative regimen (2): Ceftazidime 2 g intravenously every 8 hours

• Anaerobes

Propionibacterium acnes

• Preferred regimen: Penicillin 24 million units intravenously every 24 hours given in six equally divided doses or as continuous infusion OR Ceftriaxone 1 to 2 g intravenously once daily
• Alternative regimen: Vancomycin OR Clindamycin

Not Propionibacterium acnes

• Preferred regimen: Metronidazole 500 mg orally three times a day.

• Mycobacterium tuberculosis

• Preferred regimen: see (Septic arthritis, Mycobacterium tuberculosis)

• Fungi

• Preferred regimen: see (Septic arthritis, candidal)

• Culture negative

• Preferred regimen: vancomycin AND Ciprofloxacin OR Cefazolin AND Ciprofloxacin

Septic arthritis, staphylococcal

Staphylococcus aureus (methicillin-resistant)

• Preferred regime: Vancomycin 15–20 mg/kg IV q8–12h

• Alternative regimen (1): Daptomycin 6 mg/kg IV q24h in adults
• Alternative regimen (2): Linezolid 600 mg PO/IV q12h

• Alternative regimen (3): Clindamycin 600 mg PO/IV q8h
• Alternative regimen (4): TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h

• Pediatric regime: Vancomycin 15 mg/kg IV q6h OR Daptomycin 6–10 mg/kg IV q24h OR Linezolid 10 mg/kg PO/IV q8h OR Clindamycin 10–13 mg/kg/dose PO/IV q6–8h

Staphylococcus aureus (methicillin-susceptible)

• Preferred regime: Nafcillin 2 g IV q6h OR Clindamycin 900 mg IV q8h
• Alternative regime: Cefazolin 0.25–1 g IV/IM q6–8h OR Vancomycin 500 mg IV q6h or 1 g IV q12h

Staphylococcus epidermidis (methicillin-resistant)

• Preferred regime: Vancomycin 500 mg IV q6h or 1 g IV q12h OR Linezolid 600 mg IV q12h
• Alternative regime: TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h (TMP component) OR Minocycline 200 mg PO x 1 dose, then 100 mg PO q12h AND Rifampin 300–600 mg PO/IV q12h

Staphylococcus epidermidis (methicillin-susceptible)

• Preferred regime: Nafcillin 2 g IV q6h OR Clindamycin 900 mg IV q8h
• Alternative regime: Cefazolin 0.25–1 g IV/IM q6–8h OR Vancomycin 500 mg IV q6h or 1 g IV q12h

Septic arthritis, streptococcal

Streptococcus agalactiae

• Preferred regime: Penicillin G 2 MU IV/IM q4h OR Ampicillin 2 g IV q6h

• Alternative regime: Clindamycin 600–1200 mg/day IV/IM q6–12h OR Cefazolin 0.25–1 g IV/IM q6–8h

Streptococcus pyogenes

• Preferred regime: Penicillin G 2 MU IV/IM q4h OR Ampicillin 2 g IV q6h

• Alternative regime: Clindamycin 600–1200 mg/day IV/IM q6–12h OR Cefazolin 0.25–1 g IV/IM q6–8h