Pneumonia medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hamid Qazi, MD, BSc [2], Alejandro Lemor, M.D. [3]; Priyamvada Singh, M.D. [4]

Overview

The majority of pneumonia cases can be treated with outpatient therapy. However, patients with severe disease, comorbidities, and/or complications usually require hospitalization. Antimicrobial therapy is indicated in pneumonia and it depends on whether the patient is receiving inpatient or outpatient therapy and whether the infection was community or hospital-acquired. Supportive therapy includes adequate hydration, rest, and home care.

Medical Therapy

General Considerations

  • The treatment of pneumonia involves three critical decisions: first whether the patient truly has pneumonia, second what is the severity of the pneumonia, and last whether hospitalization is required for adequate management.
  • Treatment for pneumonia should ideally be based on the causative microorganism and its known antibiotic sensitivity. However, a specific cause for pneumonia is identified in only 50% of people, even after extensive evaluation.
  • Since treatment should generally not be delayed in any person with a serious pneumonia, empiric treatment is usually started well before laboratory reports are available. In both cases, a person's risk factors for different organisms must be remembered when choosing the initial antibiotics (empiric therapy).
  • In general, all therapies in older children and adults will include treatment for atypical bacteria. Typically this is a macrolide antibiotic such as azithromycin or clarithromycin although a fluoroquinolone such as levofloxacin can substitute.
  • Treatment of viral pneumonia caused by influenza is beneficial only if they are started within 48 hours of the onset of symptoms.
  • Many strains of H5N1 influenza A, also known as avian influenza or "bird flu," have shown resistance to rimantadine and amantadine.
  • There are no known effective treatments for viral pneumonias caused by the SARS coronavirus, adenovirus, hantavirus, or parainfluenza virus.
  • Fungal pneumonia can be treated with antifungal drugs and sometimes by surgical debridement.
  • Antibiotics are used to treat bacterial pneumonia. In contrast, antibiotics are not useful for viral pneumonia, although they sometimes are used to treat or prevent bacterial infections that can occur in the lungs that are damaged by a viral pneumonia. The antibiotic choice depends on:
    • Nature of the pneumonia
    • Microorganisms endemic to a local geographic area
    • Immune status
    • Underlying health of the individual

Initiation of treatment

Starting effective treatment within 4-8 hours may reduce mortality.[1]

Duration of treatment

Randomized controlled trials have addressed short course of therapy:

  • For outpatients, less than 7 days[2][3]
  • For inpatients, the role of individualizing duration of treatment is uncertain.[4]

Serial measurement of procalcitonin levels can reduce length of exposure to antibiotics from 6.2 to 5.7 days (95% CI: -2.71 to -2.15; P < 0.001)[5] or 10.5 to 8.0 (95% CI: -2.87 to -2.02; P < 0.001)[6]

Pediatrics

Antimicrobial Regimens

  • 1. Community-acquired pneumonia
  • 1.1 Empiric therapy in adults [7]
  • 1.1.1 Outpatient treatment
  • 1.1.1.1 Previously healthy and no use of antimicrobials within the previous 3 months
  • Preferred regimen (1): (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days) OR Azithromycin 500 mg IV single dose
  • Preferred regimen (2): Clarithromycin 250 mg PO bid for 7-14 days OR Clarithromycin 1000 mg PO qd for 7 days
  • Preferred regimen (3): Erythromycin 250-500 mg PO bid or tid (maximum daily dose 4 g)
  • Alternative regimen: Doxycycline 100 mg PO/IV q12h
  • 1.1.1.2 Presence of comorbidities, use of immunosuppressing drugs, or use of antimicrobials within the previous 3 months
  • 1.1.2 Inpatient treatment
  • 1.1.2.1 Non-ICU treatment
  • 1.1.2.2 ICU treatment
  • 1.1.3 Special considerations
  • 1.1.3.1 Suspected Pseudomonas
  • 1.1.3.2 Suspected methicillin resistant Staphylococcus aureus (add the following)
  • Preferred regimen: Vancomycin 45-60 mg/kg/day divided q8-12h OR Linezolid 600 mg PO/IV q12h for 10-14 days
  • 1.1.3.3 Neutropenic patient [8]
  • 1.1.3.3.1 No risk for multi-drug resistance
  • 1.1.3.3.2 Risk for multi drug resistance
  • 1.2 Pathogen-directed antimicrobial therapy
  • 1.2.1 Bacterial pathogens
  • 1.2.1.1 Streptococcus pneumoniae
  • 1.2.1.1.1 Penicillin sensitive (minimum inhibitory concentration < 2 mg/mL)
  • 1.2.1.1.2 Penicillin resistant (minimum inhibitory concentration > 2 mg/mL)
  • Preferred regimen (Agents chosen on the basis of susceptibililty) : Cefotaxime 1 g IM/IV q12h OR Ceftriaxone 1 g IV q24h, 2 g daily for patients at risk OR Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h
  • Alternative regimen: Vancomycin 45-60 mg/kg/day divided q8-12h (maximum: 2000 mg/dose) for 7-21 days depending on severity OR Linezolid 600 mg PO/IV q12h for 10-14 days OR Amoxicillin 875 mg PO q12h or 500 mg q8 ( 3 g/day with penicillin, minimum inhibitory concentration 4 ≤ microgram / mL)
  • 1.2.1.2 Haemophilus influenzae
  • 1.2.1.2.1 Non-beta lactamase producing
  • 1.2.1.2.2 Beta lactamase producing
  • 1.2.1.2 Bacillus anthracis (inhalational)
  • 1.2.1.3 Enterobacteriaceae
  • 1.2.1.4 Pseudomonas aeruginosa
  • 1.2.1.5 Staphylococcus aureus
  • 1.2.1.5.1 Methicillin sensitive
  • 1.2.1.5.2 Methicillin resistant
  • Preferred Regimen : Vancomycin 45-60 mg/kg/day divided q8-12h (max: 2000 mg/dose) for 7-21 days OR Linezolid 600 mg PO/IV q12h for 10-14 days
  • Alternative Regimen: Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h
  • 1.2.1.6 Klebsiella pneumonia[9]
  • 1.2.1.6.1 Resistant to third generation cephalosporins and aztreonam
  • 1.2.1.6.2 Klebsiella pneumoniae Carbapenemase producers
  • Preferred regimen (1): Colistin (=Polymyxin E).In USA : Colymycin-M 2.5-5 mg/kg per day of base divided into 2-4 doses 6.7-13.3 mg/kg per day of colistimethate sodium (max 800 mg/day). Elsewhere: Colomycin and Promixin ≤60 kg, 50,000-75,000 IU/kg per day IV in 3 divided doses (=4-6 mg/kg per day of colistimethate sodium). >60 kg, 1-2 mill IU IV tid (= 80-160 mg IV tid) OR Polymyxin B (Poly-Rx) 15,000–25,000 units/kg/day divided q12h
  • Note (1): some strains which hyperproduce extended spectrum beta-lactamase are primarily resistant to Ticarcillin-Clavulanate, Piperacillin-Tazobactam
  • Note (2): Extended spectrum beta-lactamases inactivates all Cephalosporins, beta-lactam/beta-lactamase inhibitor drug activation not predictable; co-resistance to all Fluoroquinolones & often Aminoglycosides.
  • Note (3): Can give IM, but need to combine with “caine” anesthetic due to pain.
  • 1.2.1.7 Moraxella catarrhalis
  • 1.2.1.8 Stenotrophomonas maltophilia
  • 1.2.1.9 Bordetella pertussis
  • 1.2.1.10 Anaerobes (aspiration pneumonia)
  • 1.2.1.11 Mycobacterium tuberculosis
  • 1.2.1.11.1 Intensive phase
  • Preferred Regimen: Isoniazid 5 mg/kg/day q24h daily for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day daily for 2 months (maximum: 600 mg / day) AND Ethambutol 5-25 mg/kg daily for 2 months (maximum dose: 1.6 g) AND Pyrazinamide 1000 - 2000 mg / day daily for 2 months.
  • Alternative regimen (1): Isoniazid 5 mg/kg/day q24h daily for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day daily for 2 months (maximum: 600 mg / day) AND Ethambutol 5-25 mg/kg daily for 2 months (maximum dose: 1.6 g) AND Pyrazinamide 1000 - 2000 mg / day daily for 2 months.
  • Alternative regimen (2): Isoniazid 5 mg/kg/day q24h 3 times per week for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day 3 times per week for 2 months (maximum: 600 mg / day) s AND Ethambutol 5-25 mg/kg (maximum dose: 1.6 g) 3 times per week for 2 months AND Pyrazinamide 1000 - 2000 mg / day 3 times per week for 2 months.
  • 1.2.1.11.2 Continuation phase
  • Preferred Regimen:Isoniazid 300 mg/day PO daily for 4 months (5 mg/kg/day) AND Rifampicin 600 mg/day PO daily for 4 months (10 mg/kg/day)
  • Alternative regimen (1): Isoniazid 300 mg/day PO 3 times per week for 4 months (5 mg/kg/day) AND Rifampicin 600 mg/day PO 3 times per week for 4 months (10 mg/kg/day)
  • 1.2.1.12 Yersinisa pestis
  • 1.2.1.13 Atypical bacteria
  • 1.2.1.13.1 Mycoplasma pneumoniae
  • 1.2.1.13.2 Chlamydophila pneumoniae
  • 1.2.1.13.3 Legionella spp.
  • 1.2.1.13.4 Chlamydophila psittaci
  • Preferred Regimen: Tetracycline 250-500 mg PO q6h
  • Alternate Regimen: Azithromycin 500 mg PO on day 1 followed by 250 mg q24h
  • 1.2.1.13.5 Coxiella burnetii
  • Preferred Regimen: Tetracycline 250-500 mg PO q6h
  • Alternate Regimen: Azithromycin 500 mg PO on day 1 followed by 250 mg q24h
  • 1.2.1.13.6 Francisella tularensis
  • 1.2.1.13.7 Burkholderia pseudomallei
  • 1.2.1.13.8 Acinetobacter species
  • 1.2.1.14 Gram-positive filamentous bacteria
  • 1.2.1.14.2.1 Initial intravenous therapy (induction therapy)
  • Preferred regimen: Trimethoprim-Sulfamethoxazole (15 mg/kg/day IV of the trimethoprim component in 2 to 4 divided doses) for at least three to six weeks AND Amikacin (7.5 mg/kg IV q12h) for at least three to six weeks
  • Alternative regimen: Imipenem (500 mg IV q6h) AND Amikacin (7.5 mg/kg IV q12h)
  • Note (1): If the patient is allergic to Sulfonamides, desensitization should be performed when possible.
  • Note (2): If the isolate is susceptible to the third-generation cephalosporins (Ceftriaxone, Cefotaxime), Imipenem can be switched to one of these agents.
  • Note (3): Selected patients who clinically improve with induction intravenous therapy and do not have CNS disease may be switched to oral monotherapy (usually after three to six weeks) based upon susceptibility results.
  • 1.2.1.14.2.2 Oral maintenence therapy
  • Preferred regimen: A sulfonamide (eg,Trimethoprim-Sulfamethoxazole 10 mg/kg/day of the trimethoprim component in 2 or 3 divided doses) AND / OR Minocycline (100 mg bd) AND / OR Amoxicillin-Clavulanate (875 mg bd)
  • Note (1): Selected patients who clinically improve with induction intravenous therapy and do not have CNS disease may be switched to oral monotherapy (usually after three to six weeks) based upon susceptibility results.
  • Note (2): The duration of intravenous therapy varies with the patient's immune status. In immunocompromised patients, maximal tolerated doses should be given intravenously for at least six weeks and until clinical improvement has occurred; in contrast, immunocompetent patients may be successfully treated with a shorter duration of intravenous therapy. Following the intravenous induction phase, patients may be stepped down to oral antibiotics based upon susceptibility studies
  • Note (3): Serious pulmonary infection is treated for 6 to 12 months or longer.
  • 1.2.2 Viral pathogens
  • 1.2.2.1 Influenza virus
  • Preferred Regimen: Oseltamivir 75 mg PO q12h for 5 days (initiated within 48 hours of onset of symptoms) OR Zanamivir Two inhalations (10 mg total) q12h for 5 days (Doses on first day should be separated by at least 2 hours; on subsequent days, doses should be spaced by ~12 hours)
  • 1.2.2.2 Cytomegalovirus[15]
  • Preferred regimen (1): Ganciclovir Induction therapy 5 mg/ kg IV every 12 h for normal GFR; maintenance therapy 5 mg/kg IV daily; 1 g orally every 8 h with food.
  • Preferred regimen (2): Valganciclovir Induction therapy 900 mg orally every 12 h; maintenance therapy 900 mg daily.
  • Alternative regimen (1): Foscarnet Induction therapy 60 mg/ kg every 8 h for 14–21 days or 90 mg/kg every 12 h for 14–21 days; maintenance therapy 90–120 mg/kg per day as a single infusion.
  • Alternative regimen (2): Cidofovir Induction therapy 5 mg/ kg per week for 2 weeks, followed by maintenance therapy every 2 weeks.
  • 1.2.3 Fungal pathogens
  • 1.2.3.1 Coccidioides species
  • Preferred Regimen: Itraconazole 200 mg q12h OR Fluconazole 200-400 mg daily for 3-6 month
  • Alternative Regimen: Amphotericin B 0.5-0.7 mg/kg/day
  • Note: No therapy is indicated for uncomplicated infection, treat only if complicated infection
  • 1.2.3.2 Histoplasmosis
  • 1.2.3.3 Blastomycosis
  • 2. Health care-associated pneumonia[8]
  • 2.1 Empiric antimicrobial therapy
  • 2.1.1 No risk factors for multi drug resistance
  • 2.1.2 Risk factors for multi drug resistance
  • Preferred Regimen: (Cefepime 1-2 g q8-12h OR Ceftazidime 2 g q8h OR Imipenem 500 mg q6h or 1g q8h OR Meropenem 1 g q8h OR Piperacillin-tazobactam 4.5 g q6h) AND (Ciprofloxacin 400 mg q8h OR Levofloxacin 750 mg q24h OR Amikacin 20 mg/kg per day OR Gentamycin 7 mg/kg per day OR Tobramycin 7 mg/kg per day) AND (Linezolid 600 mg q12h OR Vancomycin 15 mg/kg q12h).
  • Note (1): Health care-associated pneumonia used to designate large diverse population of patients with many co-morbidities who reside in nursing homes, other long-term care facilities, require home intravenous therapy (or) are dialysis patients. Pneumonia in these patients frequently resembles hospital-acquired pneumonia.
  • Note (2): Trough levels for Gentamycin and Tobramycin should be less than 1 g/ml, and for Amikacin they should be less than 4-5 g/ml.
  • Note (3): Trough levels for Vancomycin should be 15-20 g/ml.

Pneumonia Site of Care Decision

Infectious Diseases Society of America/American Thoracic Society consensus recommendation on site of care for community-acquired pneumonia in adults

Hospital Admission Decision

  • Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater), or prognostic models, such as the Pneumonia Severity Index (PSI), can be used to identify patients with CAP who may be candidates for outpatient treatment. (Strong recommendation; level I evidence)[7]
  • Objective criteria or scores should always be supplemented with physician determination of subjective factors, including the ability to safely and reliably take oral medication and the availability of outpatient support resources. (Strong recommendation; level II evidence)
  • For patients with CURB-65 scores >2, more-intensive treatment—that is, hospitalization or, where appropriate and available, intensive in-home health care services—is usually warranted. (Moderate recommendation; level III evidence)

Intensive Care Unit (ICU) Admission Decision

  • Direct admission to an ICU is required for patients with septic shock requiring vasopressors or with acute respiratory failure requiring intubation and mechanical ventilation. (Strong recommendation; level II evidence)
  • Direct admission to an ICU or high-level monitoring unit is recommended for patients with 3 of the minor criteria for severe CAP listed in the Table below. (Moderate recommendation; level II evidence)

For Level of evidence classification click here.

Infectious Diseases Society of America/American Thoracic Society Consensus Recommendation on Empiric Antibiotic Treatment of community-acquired pneumonia in adults

Previously Healthy and No Risk Factors for Drug-resistant Streptococcus Pneumoniae

Presence of Comorbidities or Other Risks for Drug-resistant Streptococcus Pneumoniae

Presence of comorbidities, such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs; use of antimicrobials within the previous 3 months (in which case an alternative from a different class should be selected); or other risks for DRSP infection:

In Regions with a High Rate (>25%) of Infection

In regions with a high rate (>25%) of infection with high-level (minimal inhibitory concentration [MIC], >16 micrograms/mL) macrolide-resistant S. pneumoniae, consider the use of alternative agents for any patient, including those without comorbidities. (Moderate recommendation; level III evidence)

Inpatient, Non-ICU Treatment

The following regimens are recommended for hospital ward treatment.

  • A respiratory fluoroquinolone (Strong recommendation; level I evidence)
  • A beta-lactam plus a macrolide (Strong recommendation; level I evidence) (Preferred beta-lactam agents include cefotaxime, ceftriaxone, and ampicillin; ertapenem for selected patients; with doxycycline (level III evidence) as an alternative to the macrolide. A respiratory fluoroquinolone should be used for penicillin-allergic patients.)

Inpatient, ICU Treatment

The following regimen is the minimal recommended treatment for patients admitted to the ICU.

or the above beta-lactam plus an aminoglycoside and azithromycin or the above beta-lactam plus an aminoglycoside and an antipneumococcal fluoroquinolone (for penicillin-allergic patients, substitute aztreonam for the above beta-lactam). (Moderate recommendation; level III evidence)

For Level of evidence classification click here.

Infectious Diseases Society of America/American Thoracic Society consensus recommendation on pandemic Influenza community-acquired pneumonia in adults

Pathogen-Directed Therapy

  • Once the etiology of CAP has been identified on the basis of reliable microbiological methods, antimicrobial therapy should be directed at that pathogen (Moderate recommendation; level III evidence)[7]
  • Early treatment (within 48 h of the onset of symptoms) with oseltamivir or zanamivir is recommended for influenza A. (Strong recommendation; level I evidence)
  • Use of oseltamivir and zanamivir is not recommended for patients with uncomplicated influenza with symptoms for >48 h (level I evidence), but these drugs may be used to reduce viral shedding in hospitalized patients or for influenza pneumonia. (Moderate recommendation; level III evidence)

Pandemic Influenza

  • Patients with an illness compatible with influenza and with known exposure to poultry in areas with previous H5N1 infection should be tested for H5N1 infection. (Moderate recommendation; level III evidence)
  • In patients with suspected H5N1 infection, droplet precautions and careful routine infection control measures should be used until an H5N1 infection is ruled out. (Moderate recommendation; level III evidence)
  • Patients with suspected H5N1 infection should be treated with oseltamivir (level II evidence) and antibacterial agents targeting S. pneumoniae and S. aureus, the most common causes of secondary bacterial pneumonia in patients with influenza. (Moderate recommendation; level III evidence)

For Level of evidence classification click here.

Infectious Diseases Society of America/American Thoracic Society Consensus Recommendation on Time, Route, and Duration of Community-acquired Pneumonia in Adults

Insert the text of the quote here, without quotation marks.

For Level of evidence and classes click here.

Other Treatments Consideration

Infectious Diseases Society of America/American Thoracic Society Consensus Recommendation on other Treatments Considerations for Acquired Pneumonia in adults

  • This recommendation has been removed due to the market withdrawal of drotrecogin alfa.[7]
  • Hypotensive, fluid-resuscitated patients with severe CAP should be screened for occult adrenal insufficiency. (Moderate recommendation; level II evidence)
  • Patients with hypoxemia or respiratory distress should receive a cautious trial of noninvasive ventilation (NIV) unless they require immediate intubation because of severe hypoxemia (arterial oxygen pressure/fraction of inspired oxygen [PaO2/FiO2] ratio <150) and bilateral alveolar infiltrates. (Moderate recommendation; level I evidence)
  • Low-tidal-volume ventilation (6 cm3/kg of ideal body weight) should be used for patients undergoing ventilation who have diffuse bilateral pneumonia or acute respiratory distress syndrome. (Strong recommendation; level I evidence)

For Level of evidence and classes click here.

Infectious Diseases Society of America/American Thoracic Society Consensus Recommendation on Non Responding Acquired Pneumonia in Adults

  • Because of the limitations of diagnostic testing, the majority of CAP is still treated empirically. Critical to empirical therapy is an understanding of the management of patients who do not follow the normal response pattern.[7]

For Level of evidence and classes click here.

References

  1. Lee JS, Giesler DL, Gellad WF, Fine MJ (2016). "Antibiotic Therapy for Adults Hospitalized With Community-Acquired Pneumonia: A Systematic Review". JAMA. 315 (6): 593–602. doi:10.1001/jama.2016.0115. PMID 26864413.
  2. Li JZ, Winston LG, Moore DH, Bent S (2007). "Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis". Am J Med. 120 (9): 783–90. doi:10.1016/j.amjmed.2007.04.023. PMID 17765048. Review in: J Fam Pract. 2007 Dec;56(12):1003
  3. Dimopoulos G, Matthaiou DK, Karageorgopoulos DE, Grammatikos AP, Athanassa Z, Falagas ME (2008). "Short- versus long-course antibacterial therapy for community-acquired pneumonia : a meta-analysis". Drugs. 68 (13): 1841–54. PMID 18729535.
  4. Aliberti S, Ramirez J, Giuliani F, Wiemken T, Sotgiu G, Tedeschi S; et al. (2017). "Individualizing duration of antibiotic therapy in community-acquired pneumonia". Pulm Pharmacol Ther. 45: 191–201. doi:10.1016/j.pupt.2017.06.008. PMID 28666965.
  5. Schuetz et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infectious Disease. 2017 doi:10.1016/S1473-3099(17)30592-3
  6. Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M; et al. (2017). "Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections". Cochrane Database Syst Rev. 10: CD007498. doi:10.1002/14651858.CD007498.pub3. PMID 29025194.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC; et al. (2007). "Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults". Clin Infect Dis. 44 Suppl 2: S27–72. doi:10.1086/511159. PMID 17278083.
  8. 8.0 8.1 American Thoracic Society. Infectious Diseases Society of America (2005). "Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia". Am J Respir Crit Care Med. 171 (4): 388–416. doi:10.1164/rccm.200405-644ST. PMID 15699079.
  9. Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
  10. Song JU, Park HY, Jeon K, Um SW, Kwon OJ, Koh WJ (2010). "Treatment of thoracic actinomycosis: A retrospective analysis of 40 patients". Ann Thorac Med. 5 (2): 80–5. doi:10.4103/1817-1737.62470. PMC 2883202. PMID 20582172.
  11. Sudhakar SS, Ross JJ (2004). "Short-term treatment of actinomycosis: two cases and a review". Clin Infect Dis. 38 (3): 444–7. doi:10.1086/381099. PMID 14727221 PMID: 14727221 Check |pmid= value (help).
  12. Lerner PI (1996). "Nocardiosis". Clin Infect Dis. 22 (6): 891–903, quiz 904-5. PMID 8783685.
  13. Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ (2006). "Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy". Clin Microbiol Rev. 19 (2): 259–82. doi:10.1128/CMR.19.2.259-282.2006. PMC 1471991. PMID 16614249.
  14. Brown-Elliott BA, Biehle J, Conville PS, Cohen S, Saubolle M, Sussland D; et al. (2012). "Sulfonamide resistance in isolates of Nocardia spp. from a US multicenter survey". J Clin Microbiol. 50 (3): 670–2. doi:10.1128/JCM.06243-11. PMC 3295118. PMID 22170936.
  15. Torres-Madriz G, Boucher HW (2008). "Immunocompromised hosts: perspectives in the treatment and prophylaxis of cytomegalovirus disease in solid-organ transplant recipients". Clin Infect Dis. 47 (5): 702–11. doi:10.1086/590934. PMID 18652557.

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