Meningitis medical therapy

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Meningitis Main Page

Patient Information

Overview

Causes

Classification

Viral Meningitis
Bacterial Meningitis
Fungal Meningitis

Differential Diagnosis

Diagnosis

Treatment

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [3], Sheng Shi, M.D. [4]

Overview

Acute bacterial meningitis is a medical emergency. Empiric antimicrobial therapy must be administered after obtaining blood and/or cerebrospinal fluid (CSF) cultures in cases of suspected meningitis. Once a bacterial etiology has been identified on a CSF Gram stain, treatment regimen should be individualized accordingly. Neither neuroimaging (such as CT scan and MRI) nor lumbar puncture should delay the administration of antimicrobial therapy. For neonates (age < 1 month), empirical antimicrobial therapy generally includes Ampicillin 12 g/day IV q4h AND (Cefotaxime 8–12 g/day q4–6h OR Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h). For children older than 1 month and adults < 50 years, the preferred regimen is usually Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h). For adults ≥ 50 years of age, Ampicillin 12g/day IV q4h is added to the usual adult regimen. The duration of therapy is variable depending on the causative pathogen, but generally the duration is between 1-3 weeks. Adjunctive Dexamethasone at a dose of 0.15 mg/kg q6h for 2—4 days may be effective when administered early (0-20 minutes prior to administration of antimicrobial therapy) among pediatric patients with H. influenzae meningitis and among adults with S. pneumoniae meningitis.

Principles of Therapy for Bacterial Meningitis

Factors Determining Antimicrobial Activity

  • Aminoglycosides and fluoroquinolones express a concentration-dependent manner of bactericidal activity; beta-lactams typically follow a a time-dependent antimicrobial pattern (i.e., the activity is dependent on the time that CSF concentration exceeds MIC as a proportion of the dosing interval).
Recommended Doses of Antimicrobial Agents via the Intraventricular Route.[3][4][5]
Antimicrobial Agent Daily Intraventricular Dose
 ▸ Vancomycin 5—20 mg
 ▸ Gentamicin 4—8 mg
 ▸ Tobramycin 5—20 mg
 ▸ Amikacin 5—50 mg
 ▸ Polymyxin B 5 mg
 ▸ Colistin 10 mg
 ▸ Quinupristin/Dalfopristin 2—5 mg
 ▸ Teicoplanin 5—40 mg
 ▸ Amphotericin B 0.1—0.5 mg/day

Duration of Antimicrobial Therapy

  • The duration of therapy in patients with bacterial meningitis has not been well-supported by evidence-based data.
  • The IDSA Practice Guideline provides recommendations on the duration of antimicrobial agents based on microorganisms (see table below). However, the duration of antimicrobial therapy should be individualized in accordance with patient's clinical response.
  • Maximum parenteral dosage should be maintained throughout the recommended duration of therapy to ensure adequate bactericidal concentrations are attained since antimicrobial entry attenuates as meningeal inflammation subsides, especially when dexamethasone is co-administered.
Recommended Duration of Antimicrobial Therapy Based on Isolated Pathogen.[6]
Microorganism Duration of Therapy
 ▸ Neisseria meningitidis 7 days
 ▸ Haemophilus influenzae 7 days
 ▸ Streptococcus pneumoniae 10—14 days
 ▸ Streptococcus agalactiae 14—21 days
 ▸ Aerobic Gram-negative bacilli 21 days
 ▸ Listeria monocytogenes ≥21 days

Adjunctive Dexamethasone Therapy

  • Evidences for beneficial effects of dexamethasone are variable.
  • Adjunctive use of dexamethasone for bacterial meningitis in selected groups may be associated with an improved survival or prognosis.[7][8][9][10][11][12] However, other studies fail to demonstrate a substantial reduction of death or neurological disability.[3][13][14][15] The occurrence of delayed cerebral thrombosis with dexamethasone therapy has been reported.[16]
  • In infants and children with Haemophilus influenzae type b meningitis, the IDSA Practice Guideline supports the use of adjunctive Dexamethasone at 0.15 mg/kg q6h for 2—4 days with the first dose administered 10—20 minutes prior to, or at least concomitant with, the first antimicrobial dose.[6]
  • In adults with suspected or proven Streptococcus pneumoniae meningitis, the IDSA also recommends Dexamethasone at 0.15 mg/kg q6h for 2—4 days with the first dose administered 10—20 minutes prior to, or at least concomitant with, the first antimicrobial dose. Dexamethasone should only be continued either if the CSF Gram stain demonstrates Gram-positive diplococci or if blood or CSF cultures are positive for S. pneumoniae. In this scenario, certain authorities advocate the addition of rifampin to the empirical combination of vancomycin plus a third-generation cephalosporin pending culture results and in vitro susceptibility testing.[6][17]
  • Dexamethasone should not be administered to patients who have already received animicrobial therapy because it is unlikely to improve clinical outcome.[6]

Antimicrobial Regimen

  • Bacterial meningitis[18]
  • 1. Empiric antimicrobial therapy based on specific predisposing factors
  • 1.1 Age
  • 1.1.1 Age < 1 month
  • Common causative pathogens: Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella species
  • Preferred regimen: Ampicillin 12 g/day IV q4h AND (Cefotaxime 8–12 g/day q4–6h OR Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h)
  • 1.1.2 Age 1–23 months
  • Common causative pathogens: Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli
  • Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
  • 1.1.3 Age 2–50 years
  • Common causative pathogens: N . meningitidis, S. pneumoniae
  • Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
  • 1.1.4 Age > 50 years
  • Common causative pathogens: S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic Gram-negative bacilli
  • Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Ampicillin 12 g/day IV q4h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
  • 1.2 Head trauma
  • 1.2.1 Basilar skull fracture
  • Common causative pathogens: S. pneumoniae, H. influenzae, group A β-hemolytic streptococci
  • Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
  • 1.2.2 Penetrating trauma
  • Common causative pathogens: Staphylococcus aureus, coagulase-negative staphylococci (especially Staphylococcus epidermidis), aerobic Gram-negative bacilli (including Pseudomonas aeruginosa)
  • Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h)
  • 1.3 Postneurosurgery
  • Common causative pathogens: Aerobic Gram-negative bacilli (including P. aeruginosa), S. aureus, coagulase-negative staphylococci (especially S. epidermidis)
  • Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h)
  • 1.4 CSF shunt
  • Common causative pathogens: Coagulase-negative staphylococci (especially S. epidermidis), S. aureus, aerobic Gram-negative bacilli (including P. aeruginosa), Propionibacterium acnes
  • Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h)
  • 2. CSF Gram stain-directed antimicrobial therapy
  • 2.1 Gram positive, lancet-shaped diplococci suggestive of Streptococcus pneumoniae
  • 2.2 Gram negative diplococci suggestive of Neisseria meningitidis
  • 2.3 Gram positive, short bacilli suggestive of Listeria monocytogenes
  • 2.4 Gram positive cocci in short chains suggestive of Streptococcus agalactiae
  • 2.5 Gram negative coccobacilli suggestive of Haemophilus influenzae
  • 2.6 Gram negative bacilli suggestive of Escherichia coli
  • 3. Pathogen-directed antimicrobial therapy
  • 3.1 Acinetobacter baumannii
  • 3.2 Borrelia burgdorferi[19]
  • Preferred regimen: Ceftriaxone 2 g IV q24h for 10—28 days
  • Alternative regimen: Cefotaxime 2 g IV q8h for 10—28 days OR Penicillin G 3—4 MU IV q4h for 10—28 days OR Doxycycline 100—200 mg PO q12h for 10—28 days
  • 3.3 Enterococcus species
  • 3.3.1 Ampicillin susceptible
  • 3.3.2 Ampicillin resistant
  • 3.3.3 Ampicillin and vancomycin resistant
  • 3.4 Escherichia coli and other Enterobacteriaceae
  • 3.5 Haemophilus influenzae
  • 3.5.1 β-Lactamase negative
  • 3.5.2 β-Lactamase positive
  • 3.6 Listeria monocytogenes
  • 3.7 Mycobacterium tuberculosis
  • 3.7.1 First-line therapy (dosing information: [5][6][7])
  • 3.7.2 Second-line therapy (dosing information: [8][9][10])
  • 3.7.3 Tuberculous meningitis caused by susceptible Mycobacterium tuberculosis[20][21][22][23]
  • 3.7.3.1 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
  • 3.7.3.2 Continuation phase (adult)
  • Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10 mg/kg (max: 600 mg) for 7–10 months
  • 3.7.3.3 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
  • 3.7.3.3 Continuation phase (pediatric)
  • Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 7–10 months
  • Note (1): World Health Organization guidelines recommend that Ethambutol should be replaced by Streptomycin in tuberculous meningitis.[24] Streptomycin is contraindicated in pregnancy.
  • Note (2): A 9– to 12–month course of treatment is recommended for tuberculous meningitis.[25][26]
Note (3): Adjuvant Dexamethasone 0.3–0.4 mg/kg/day (max: 24 mg) is recommended unless drug resistance is suspected.[27][28]
Note (4): Liaise with microbiology laboratory about genotype testing for drug resistance if there is high risk for MDR-TB.[29]
  • 3.7.4 Tuberculous meningitis caused by Mycobacterium tuberculosis resistant to isoniazid or rifampin
  • 3.7.4.1 Isoniazid monoresistance[30]
  • 3.7.4.2 Rifampin monoresistance[31]
  • 3.7.4.3 MDR-TB (resistant to Isoniazid and Rifampin)[32]
  • MDR tuberculosis therapy should be considered if there is a history of prior tuberculosis treatment, contact with a patient with MDR tuberculosis, or a poor clinical response to first-line TB therapy within 2 weeks despite a firm diagnosis and an adequate adherence to treatment.
  • Second-line agents such as Aminoglycosides penetrate the BBB only in the presence of inflamed meninges, and Fluoroquinolones, while able to penetrate into the CNS, have lower CSF levels than in the serum or brain parenchyma.
  • Consult infectious disease specialist.
  • 3.7.4.4 XDR-TB (resistant to Isoniazid, Rifampin, Fluoroquinolones, and either Capreomycin, Kanamycin, or Amikacin)[33]
  • Preferred regimen: Ceftriaxone 1–2 g IV q12h for 10–14 days
  • 3.9 Neisseria meningitidis
  • 3.9.1 Penicillin MIC < 0.1 μg/mL
  • 3.9.2 Penicillin MIC 0.1–1.0 μg/mL
  • 3.10 Pseudomonas aeruginosa
  • 3.11 Staphylococcus aureus
  • 3.11.1 Methicillin susceptible (MSSA)
  • 3.11.2 Methicillin resistant (MRSA)
  • 3.12 Staphylococcus epidermidis
  • Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
  • Alternative regimen: Linezolid 600 mg IV q12h
  • 3.13 Streptococcus agalactiae
  • 3.14 Streptococcus pneumoniae
  • 3.14.1 Penicillin MIC < 0.1 μg/mL
  • 3.14.2 Penicillin MIC 0.1–1.0 μg/mL
  • 3.14.3 Penicillin MIC ≥ 2.0 μg/mL
  • 3.14.4 Cefotaxime or ceftriaxone MIC ≥ 1.0 μg/mL
  • 3.15 Treponema pallidum (neurosyphilis)[36]
  • 3.16 Borrelia burgdorferi (Lyme meningitis)
  • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 14 days
  • Preferred regimen (2):Cefotaxime 2 g IV q8h for 14 days
  • Preferred regimen (3):Penicillin G 18–24 MU/day q4h for 14 days
  • Alternative regimen: Doxycycline 100–200 mg BID for 14 days
  • Pediatric regimen: Ceftriaxone 50–75 mg/kg/day IV q24h, max 2 g/day OR Cefotaxime 150–200 mg/kg/day IV q6–8h, max 6 g/day OR Penicillin G 200,000–400,000 U/kg/day IV q4h, max 18–24 MU/day OR Doxycycline (≥ 8 y/o) 4–8 mg/kg/day q12h, max 200 mg/day
  • 4. Pediatric dose:
  • Neonates age 0–7 days: 15–20 mg/kg/day q12h
  • Neonates age 8–28 days: 30 mg/kg/day q8h
  • Infants and children: 20–30 mg/kg/day q8h
  • Neonates age 0–7 days: 150 mg/kg/day q8h
  • Neonates age 8–28 days: 200 mg/kg/day q6–8h
  • Infants and children: 300 mg/kg/day q6h
  • Infants and children: 150 mg/kg/day q8h
  • Neonates age 0–7 days: 100–150 mg/kg/day q8–12h
  • Neonates age 8–28 days: 150–200 mg/kg/day q6–8h
  • Infants and children: 225–300 mg/kg/day q6–8h
  • Neonates age 0–7 days: 100–150 mg/kg/day q8–12h
  • Neonates age 8–28 days: 150 mg/kg q8h
  • Infants and children: 150 mg/kg
  • Infants and children: 80–100 mg/kg/day q12–24h
  • Neonates age 0–7 days: 25 mg/kg/day q24h
  • Neonates age 8–28 days: 50 mg/kg/day q12–24h
  • Infants and children: 75–100 mg/kg/day q6h
  • Neonates age 0–7 days: 5 mg/kg/day q12h
  • Neonates age 8–28 days: 7.5 mg/kg/day q8h
  • Infants and children: 7.5 mg/kg/day q8h
  • Infants and children: 120 mg/kg/day q8h
  • Neonates age 0–7 days: 75 mg/kg/day q8–12h
  • Neonates age 8–28 days: 100–150 mg/kg/day q6–8h
  • Infants and children: 200 mg/kg/day q6h
  • Neonates age 0–7 days: 75 mg/kg/day q8–12h
  • Neonates age 8–28 days: 150–200 mg/kg/day q6–8h
  • Infants and children: 200 mg/kg/day q6h
  • Neonates age 0–7 days: 0.15 MU/kg/day q8–12h
  • Neonates age 8–28 days: 0.2 MU/kg/day q6–8h
  • Infants and children: 0.3 MU/kg/day q4–6h
  • Neonates age 8–28 days: 10–20 mg/kg/day q12h
  • Infants and children: 10–20 mg/kg/day q12–24h
  • Neonates age 0–7 days: 5 mg/kg/day q12h
  • Neonates age 8–28 days: 7.5 mg/kg/day q8h
  • Infants and children: 7.5 mg/kg/day q8h
  • Infants and children: 10–20 mg/kg q6–12h
  • Neonates age 0–7 days: 20–30 mg/kg/day q8–12h
  • Neonates age 8–28 days: 30–45 mg/kg/day q6–8h
  • Infants and children: 60 mg/kg/day q6h

References

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  2. ↑ Nau, R.; Sörgel, F.; Eiffert, H. (2010). "Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections". Clin Microbiol Rev. 23 (4): 858–83. doi:10.1128/CMR.00007-10. PMID 20930076. Unknown parameter |month= ignored (help)
  3. ↑ 3.0 3.1 van de Beek, D.; Drake, JM.; Tunkel, AR. (2010). "Nosocomial bacterial meningitis". N Engl J Med. 362 (2): 146–54. doi:10.1056/NEJMra0804573. PMID 20071704. Unknown parameter |month= ignored (help)
  4. ↑ Rodríguez Guardado, A.; Blanco, A.; Asensi, V.; Pérez, F.; Rial, JC.; Pintado, V.; Bustillo, E.; Lantero, M.; Tenza, E. (2008). "Multidrug-resistant Acinetobacter meningitis in neurosurgical patients with intraventricular catheters: assessment of different treatments". J Antimicrob Chemother. 61 (4): 908–13. doi:10.1093/jac/dkn018. PMID 18281693. Unknown parameter |month= ignored (help)
  5. ↑ Cruciani, M.; Navarra, A.; Di Perri, G.; Andreoni, M.; Danzi, MC.; Concia, E.; Bassetti, D. (1992). "Evaluation of intraventricular teicoplanin for the treatment of neurosurgical shunt infections". Clin Infect Dis. 15 (2): 285–9. PMID 1387805. Unknown parameter |month= ignored (help)
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  7. ↑ Lebel, MH.; Freij, BJ.; Syrogiannopoulos, GA.; Chrane, DF.; Hoyt, MJ.; Stewart, SM.; Kennard, BD.; Olsen, KD.; McCracken, GH. (1988). "Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials". N Engl J Med. 319 (15): 964–71. doi:10.1056/NEJM198810133191502. PMID 3047581. Unknown parameter |month= ignored (help)
  8. ↑ Odio, CM.; Faingezicht, I.; Paris, M.; Nassar, M.; Baltodano, A.; Rogers, J.; Sáez-Llorens, X.; Olsen, KD.; McCracken, GH. (1991). "The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis". N Engl J Med. 324 (22): 1525–31. doi:10.1056/NEJM199105303242201. PMID 2027357. Unknown parameter |month= ignored (help)
  9. ↑ Thwaites, GE.; Nguyen, DB.; Nguyen, HD.; Hoang, TQ.; Do, TT.; Nguyen, TC.; Nguyen, QH.; Nguyen, TT.; Nguyen, NH. (2004). "Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults". N Engl J Med. 351 (17): 1741–51. doi:10.1056/NEJMoa040573. PMID 15496623. Unknown parameter |month= ignored (help)
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  11. ↑ Fritz, D.; Brouwer, MC.; van de Beek, D. (2012). "Dexamethasone and long-term survival in bacterial meningitis". Neurology. 79 (22): 2177–9. doi:10.1212/WNL.0b013e31827595f7. PMID 23152589. Unknown parameter |month= ignored (help)
  12. ↑ Peltola, H.; Roine, I.; Fernández, J.; Zavala, I.; Ayala, SG.; Mata, AG.; Arbo, A.; Bologna, R.; Miño, G. (2007). "Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial". Clin Infect Dis. 45 (10): 1277–86. doi:10.1086/522534. PMID 17968821. Unknown parameter |month= ignored (help)
  13. ↑ Peltola, H.; Roine, I.; Fernández, J.; González Mata, A.; Zavala, I.; Gonzalez Ayala, S.; Arbo, A.; Bologna, R.; Goyo, J. (2010). "Hearing impairment in childhood bacterial meningitis is little relieved by dexamethasone or glycerol". Pediatrics. 125 (1): e1–8. doi:10.1542/peds.2009-0395. PMID 20008417. Unknown parameter |month= ignored (help)
  14. ↑ Nguyen, TH.; Tran, TH.; Thwaites, G.; Ly, VC.; Dinh, XS.; Ho Dang, TN.; Dang, QT.; Nguyen, DP.; Nguyen, HP. (2007). "Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis". N Engl J Med. 357 (24): 2431–40. doi:10.1056/NEJMoa070852. PMID 18077808. Unknown parameter |month= ignored (help)
  15. ↑ Molyneux, EM.; Walsh, AL.; Forsyth, H.; Tembo, M.; Mwenechanya, J.; Kayira, K.; Bwanaisa, L.; Njobvu, A.; Rogerson, S. (2002). "Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial". Lancet. 360 (9328): 211–8. PMID 12133656. Unknown parameter |month= ignored (help)
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  17. ↑ van de Beek D, de Gans J, Tunkel AR, Wijdicks EF (2006) Community-acquired bacterial meningitis in adults. N Engl J Med 354 (1):44-53. DOI:10.1056/NEJMra052116 PMID: 16394301
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  19. ↑ Wormser, GP.; Dattwyler, RJ.; Shapiro, ED.; Halperin, JJ.; Steere, AC.; Klempner, MS.; Krause, PJ.; Bakken, JS.; Strle, F. (2006). "The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America". Clin Infect Dis. 43 (9): 1089–134. doi:10.1086/508667. PMID 17029130. Unknown parameter |month= ignored (help)
  20. ↑ Blumberg, Henry M.; Burman, William J.; Chaisson, Richard E.; Daley, Charles L.; Etkind, Sue C.; Friedman, Lloyd N.; Fujiwara, Paula; Grzemska, Malgosia; Hopewell, Philip C.; Iseman, Michael D.; Jasmer, Robert M.; Koppaka, Venkatarama; Menzies, Richard I.; O'Brien, Richard J.; Reves, Randall R.; Reichman, Lee B.; Simone, Patricia M.; Starke, Jeffrey R.; Vernon, Andrew A.; American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society (2003-02-15). "American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis". American Journal of Respiratory and Critical Care Medicine. 167 (4): 603–662. doi:10.1164/rccm.167.4.603. ISSN 1073-449X. PMID 12588714.
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  22. ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
  23. ↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
  24. ↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786. Retrieved 2015-06-08.
  25. ↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786. Retrieved 2015-06-08.
  26. ↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
  27. ↑ Thwaites, Guy E.; Nguyen, Duc Bang; Nguyen, Huy Dung; Hoang, Thi Quy; Do, Thi Tuong Oanh; Nguyen, Thi Cam Thoa; Nguyen, Quang Hien; Nguyen, Tri Thuc; Nguyen, Ngoc Hai; Nguyen, Thi Ngoc Lan; Nguyen, Ngoc Lan; Nguyen, Hong Duc; Vu, Ngoc Tuan; Cao, Huu Hiep; Tran, Thi Hong Chau; Pham, Phuong Mai; Nguyen, Thi Dung; Stepniewska, Kasia; White, Nicholas J.; Tran, Tinh Hien; Farrar, Jeremy J. (2004-10-21). "Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults". The New England Journal of Medicine. 351 (17): 1741–1751. doi:10.1056/NEJMoa040573. ISSN 1533-4406. PMID 15496623.
  28. ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
  29. ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
  30. ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
  31. ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
  32. ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)
  33. ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)
  34. ↑ Workowski, Kimberly A.; Berman, Stuart; Centers for Disease Control and Prevention (CDC) (2010–12–17). "Sexually transmitted diseases treatment guidelines, 2010". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 59 (RR–12): 1–110. ISSN 1545-8601. PMID 21160459. Check date values in: |date= (help)
  35. ↑ Centers for Disease Control and Prevention (CDC) (2012–08–10). "Update to CDC's Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections". MMWR. Morbidity and mortality weekly report. 61 (31): 590–594. ISSN 1545-861X. PMID 22874837. Check date values in: |date= (help)
  36. ↑ Workowski, Kimberly A.; Berman, Stuart; Centers for Disease Control and Prevention (CDC) (2010–12–17). "Sexually transmitted diseases treatment guidelines, 2010". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 59 (RR–12): 1–110. ISSN 1545-8601. PMID 21160459. Check date values in: |date= (help)
  • Tuberculous meningitis (TB meningitis)
  • Tuberculous meningitis caused by susceptible Mycobacterium tuberculosis[1][2][3][4]
  • 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 7–10 months AND Rifampin 10 mg/kg (max: 600 mg) for 7–10 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 7–10 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 7–10 months
Note (1): World Health Organization guidelines recommend that Ethambutol should be replaced by Streptomycin (contraindicated in pregnancy) in tuberculous meningitis.[5]
Note (2): A 9– to 12–month course of treatment is recommended for tuberculous meningitis.[6][7]
Note (3): Adjuvant Dexamethasone 0.3–0.4 mg/kg/day (max: 24 mg) is recommended unless drug resistance is suspected.[8][9]
Note (4): Liaise with microbiology laboratory about genotype testing for drug resistance if there is high risk for MDR-TB.[10]
  • Tuberculous meningitis caused by Mycobacterium tuberculosis resistant to isoniazid or rifampin
  • Isoniazid monoresistance[11]
  • Substitute fluoroquinolone for isoniazid in intensive phase regimen.
  • Continue treatment with rifampin, pyrazinamide, and fluoroquinolone for 12 months.
  • Rifampin monoresistance[12]
  • Substitute Fluoroquinolones for Rifampin in intensive phase regimen.
  • Continue treatment with isoniazid, pyrazinamide, and fluoroquinolone for 18 months.
  • MDR-TB (resistant to Isoniazid and Rifampin)[13]
  • MDR tuberculosis therapy should be considered if there is a history of prior tuberculosis treatment, contact with a patient with MDR tuberculosis, or a poor clinical response to first-line TB therapy within 2 weeks despite a firm diagnosis and an adequate adherence to treatment.
  • Second-line agents such as Aminoglycosides penetrate the BBB only in the presence of inflamed meninges, and Fluoroquinolones, while able to penetrate into the CNS, have lower CSF levels than in the serum or brain parenchyma.
  • Consult infectious disease specialist.
  • XDR-TB (resistant to Isoniazid, Rifampin, Fluoroquinolones, and either Capreomycin, Kanamycin, or Amikacin)[14]
  • Consider Ethionamide or Cycloserine to build the treatment regimen.
  • Consult infectious disease specialist.

References

  1. ↑ Blumberg, Henry M.; Burman, William J.; Chaisson, Richard E.; Daley, Charles L.; Etkind, Sue C.; Friedman, Lloyd N.; Fujiwara, Paula; Grzemska, Malgosia; Hopewell, Philip C.; Iseman, Michael D.; Jasmer, Robert M.; Koppaka, Venkatarama; Menzies, Richard I.; O'Brien, Richard J.; Reves, Randall R.; Reichman, Lee B.; Simone, Patricia M.; Starke, Jeffrey R.; Vernon, Andrew A.; American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society (2003-02-15). "American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis". American Journal of Respiratory and Critical Care Medicine. 167 (4): 603–662. doi:10.1164/rccm.167.4.603. ISSN 1073-449X. PMID 12588714.
  2. ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)
  3. ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
  4. ↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
  5. ↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786.
  6. ↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786.
  7. ↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
  8. ↑ Thwaites, Guy E.; Nguyen, Duc Bang; Nguyen, Huy Dung; Hoang, Thi Quy; Do, Thi Tuong Oanh; Nguyen, Thi Cam Thoa; Nguyen, Quang Hien; Nguyen, Tri Thuc; Nguyen, Ngoc Hai; Nguyen, Thi Ngoc Lan; Nguyen, Ngoc Lan; Nguyen, Hong Duc; Vu, Ngoc Tuan; Cao, Huu Hiep; Tran, Thi Hong Chau; Pham, Phuong Mai; Nguyen, Thi Dung; Stepniewska, Kasia; White, Nicholas J.; Tran, Tinh Hien; Farrar, Jeremy J. (2004-10-21). "Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults". The New England Journal of Medicine. 351 (17): 1741–1751. doi:10.1056/NEJMoa040573. ISSN 1533-4406. PMID 15496623.
  9. ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
  10. ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
  11. ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
  12. ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
  13. ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)
  14. ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)
  • Meningitis, parasitic
  • 1. Protozoal meningitis
  • 1.1 Naegleria fowleri (primary amebic meningoencephalitis)[1][2]
  • 1.2 Toxoplasma gondii[3]
  • 2. Helminthic meningitis
  • 2.1 Angiostrongylus cantonensis[4][5]
  • Preferred regimen: Albendazole 15–20 mg/kg/day PO qd–bid for 10–20 days AND Dexamethasone 10–20 mg PO qd for 10–20 days
  • Alternative regimen: Mebendazole 100 mg PO bid for 10–20 days AND Dexamethasone 10–20 mg PO qd for 10–20 days
  • 2.2 Baylisascaris procyonis[6][7]
  • 2.3 Gnathostoma spinigerum[8][9]


References

  1. ↑ Linam, W. Matthew; Ahmed, Mubbasheer; Cope, Jennifer R.; Chu, Craig; Visvesvara, Govinda S.; da Silva, Alexandre J.; Qvarnstrom, Yvonne; Green, Jerril (2015-03). "Successful treatment of an adolescent with Naegleria fowleri primary amebic meningoencephalitis". Pediatrics. 135 (3): –744-748. doi:10.1542/peds.2014-2292. ISSN 1098-4275. PMID 25667249. Check date values in: |date= (help)
  2. ↑ Vargas-Zepeda, Jesús; Gómez-Alcalá, Alejandro V.; Vásquez-Morales, José Alfonso; Licea-Amaya, Leonardo; De Jonckheere, Johan F.; Lares-Villa, Fernando (2005-02). "Successful treatment of Naegleria fowleri meningoencephalitis by using intravenous amphotericin B, fluconazole and rifampicin". Archives of Medical Research. 36 (1): 83–86. ISSN 0188-4409. PMID 15900627. Check date values in: |date= (help)
  3. ↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
  4. ↑ Wang, Qiao-Ping; Lai, De-Hua; Zhu, Xing-Quan; Chen, Xiao-Guang; Lun, Zhao-Rong (2008-10). "Human angiostrongyliasis". The Lancet. Infectious Diseases. 8 (10): 621–630. doi:10.1016/S1473-3099(08)70229-9. ISSN 1473-3099. PMID 18922484. Check date values in: |date= (help)
  5. ↑ Ramirez-Avila, Lynn; Slome, Sally; Schuster, Frederick L.; Gavali, Shilpa; Schantz, Peter M.; Sejvar, James; Glaser, Carol A. (2009-02-01). "Eosinophilic meningitis due to Angiostrongylus and Gnathostoma species". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 48 (3): 322–327. doi:10.1086/595852. ISSN 1537-6591. PMID 19123863.
  6. ↑ Gavin, Patrick J.; Kazacos, Kevin R.; Shulman, Stanford T. (2005-10). "Baylisascariasis". Clinical Microbiology Reviews. 18 (4): 703–718. doi:10.1128/CMR.18.4.703-718.2005. ISSN 0893-8512. PMC 1265913. PMID 16223954. Check date values in: |date= (help)
  7. ↑ Murray, William J.; Kazacos, Kevin R. (2004-11-15). "Raccoon roundworm encephalitis". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 39 (10): 1484–1492. doi:10.1086/425364. ISSN 1537-6591. PMID 15546085.
  8. ↑ Herman, Joanna S.; Chiodini, Peter L. (2009-07). "Gnathostomiasis, another emerging imported disease". Clinical Microbiology Reviews. 22 (3): 484–492. doi:10.1128/CMR.00003-09. ISSN 1098-6618. PMC 2708391. PMID 19597010. Check date values in: |date= (help)
  9. ↑ Ramirez-Avila, Lynn; Slome, Sally; Schuster, Frederick L.; Gavali, Shilpa; Schantz, Peter M.; Sejvar, James; Glaser, Carol A. (2009-02-01). "Eosinophilic meningitis due to Angiostrongylus and Gnathostoma species". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 48 (3): 322–327. doi:10.1086/595852. ISSN 1537-6591. PMID 19123863.
  • Fungal meningitis
  • 1. Blastomyces dermatitidis[1]
  • 2. Candida spp.[2]
  • Preferred regimen: Liposomal Amphotericin B 3–5 mg/kg/day IV ± Flucytosine 25 mg/kg PO qid for several weeks, followed by Fluconazole 400–800 mg (6–12 mg/kg) PO qd until CSF abnl resolves
  • Alternative regimen: Fluconazole 400–800 mg PO qd (6–12 mg/kg IV q24h) OR Voriconazole 400 mg PO bid for 2 doses, followed by 200 mg PO bid OR Voriconazole 6 mg/kg IV q12h for 2 doses, followed by 3 mg/kg IV q12h
Note: Removal of intraventricular devices is recommended.
  • 3. Coccidioides immitis[3]
  • 4. Cryptococcus neoformans[4]
  • 4.1 Non–HIV/AIDS hosts, non–transplant recipients
  • 4.2 HIV/AIDS hosts
  • 4.3 Transplant recipients
  • 5. Histoplasma capsulatum[5]
  • Viral meningitis[6]
  • 1. Chronic enterovirus meningoencephalitis
  • Preferred regimen: supportive care ± Pleconaril (investigational)
  • 2. HSV-2 meningitis
  • Preferred regimen: supportive care AND Acyclovir 10 mg/kg IV q8h for 10–14 days, followed by Valacyclovir 1 g PO tid
  • 3. Mollaret's meningitis
  • 4. VZV meningitis
  • Preferred regimen: supportive care AND Acyclovir 10 mg/kg IV q8h for 10–14 days, followed by Valacyclovir 1 g PO tid


References

  1. ↑ Chapman, Stanley W.; Dismukes, William E.; Proia, Laurie A.; Bradsher, Robert W.; Pappas, Peter G.; Threlkeld, Michael G.; Kauffman, Carol A.; Infectious Diseases Society of America (2008-06-15). "Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 46 (12): 1801–1812. doi:10.1086/588300. ISSN 1537-6591. PMID 18462107.
  2. ↑ Pappas, Peter G.; Kauffman, Carol A.; Andes, David; Benjamin, Daniel K.; Calandra, Thierry F.; Edwards, John E.; Filler, Scott G.; Fisher, John F.; Kullberg, Bart-Jan; Ostrosky-Zeichner, Luis; Reboli, Annette C.; Rex, John H.; Walsh, Thomas J.; Sobel, Jack D.; Infectious Diseases Society of America (2009-03-01). "Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 48 (5): 503–535. doi:10.1086/596757. ISSN 1537-6591. PMID 19191635.
  3. ↑ Galgiani, John N.; Ampel, Neil M.; Blair, Janis E.; Catanzaro, Antonino; Johnson, Royce H.; Stevens, David A.; Williams, Paul L.; Infectious Diseases Society of America (2005-11-01). "Coccidioidomycosis". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 41 (9): 1217–1223. doi:10.1086/496991. ISSN 1537-6591. PMID 16206093.
  4. ↑ Perfect, John R.; Dismukes, William E.; Dromer, Francoise; Goldman, David L.; Graybill, John R.; Hamill, Richard J.; Harrison, Thomas S.; Larsen, Robert A.; Lortholary, Olivier; Nguyen, Minh-Hong; Pappas, Peter G.; Powderly, William G.; Singh, Nina; Sobel, Jack D.; Sorrell, Tania C. (2010-02-01). "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 50 (3): 291–322. doi:10.1086/649858. ISSN 1537-6591. PMID 20047480.
  5. ↑ Wheat, L. Joseph; Freifeld, Alison G.; Kleiman, Martin B.; Baddley, John W.; McKinsey, David S.; Loyd, James E.; Kauffman, Carol A.; Infectious Diseases Society of America (2007-10-01). "Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 45 (7): 807–825. doi:10.1086/521259. ISSN 1537-6591. PMID 17806045.
  6. ↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.

References

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