Sandbox sss

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Streptococcus pneumoniae

Penicillin MIC ≤0.06 μg/mL Preferred Regimen ▸ Penicillin G Low: 600,000–1.2 million units/day IM; High:≥ 20 million units IV q24h(=12 g) OR ▸ Ampicillin 150–200 mg/kg IV q3-4h Alternative Regimen ▸ Cefotaxime 1 g q8–12h to 2 g IV q4h OR ▸ Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine) OR ▸ Chloramphenicol 0.25–1 g po IV q6h to max. of 4 g/day

Penicillin MIC ≥0.12 μg/mL Cefotaxime or Ceftriaxone MIC† <1.0 μg/mL Preferred Regimen ▸ Cefotaxime 1 g q8–12h to 2 g IV q4h OR ▸ Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine) Alternative Regimen ▸ Cefepime 1–2 g IV q12h OR ▸ Meropenem 2 g IV q8h Cefotaxime or Ceftriaxone MIC† >1.0 μg/mL Preferred Regimen ▸ Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h(Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. ) AND ▸ Cefotaxime 1 g q8–12h to 2 g IV q4h OR ▸ Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine)‡ Alternative Regimen ▸ Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h(Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. ) AND ▸ Moxifloxacin 400 mg po IV q24h ɸ

Neisseria meningitidis

Neisseria meningitidis Penicillin MIC <0.1 μg/mL Preferred Regimen ▸ Penicillin G Low: 600,000–1.2 million units/day IM; High:≥ 20 million units IV q24h(=12 g) OR ▸ Ampicillin 0.25–0.5 g po q6h.150–200 mg/kg/day IV Alternative Regimen ▸ Cefotaxime 1 g q8–12h to 2 g IV q4h OR ▸ Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine) OR ▸ Chloramphenicol 0.25–1 g po IV q6h to max. of 4 g/day

Neisseria meningitidis Penicillin MIC ≥0.1 μg/mL Preferred Regimen ▸ Cefotaxime 1 g q8–12h to 2 g IV q4h OR ▸ Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine) Alternative Regimen ▸ Cefepime 1–2 g IV q12h OR ▸ Chloramphenicol 0.25–1 g po IV q6h to max. of 4 g/day OR ▸ FluoroquinoloneΔ OR ▸ Meropenem 2 g IV q8h

Listeria Monocytogenes and Streptococcus agalactiae

Listeria Monocytogenes Preferred Regimen ▸ Ampicillin 0.25–0.5 g po q6h.150–200 mg/kg/day IV OR ▸ Penicillin G Low: 600,000–1.2 million units/day IM ;High:≥ 20 million units IV q24h(=12 g)£ Alternative Regimen ▸ Trimethoprim-sulfamethoxazole 5–20 mg/kg/day q6-12h

Streptococcus agalactiae Preferred Regimen ▸ Ampicillin 0.25–0.5 g po q6h.150–200 mg/kg/day IV OR ▸ Penicillin G Low: 600,000–1.2 million units/day IM ;High:≥ 20 million units IV q24h(=12 g)£ Alternative Regimen ▸ Cefotaxime 1 g q8–12h to 2 g IV q4h OR ▸ Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine) OR ▸ Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h(Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. )

Haemophilus influenzae

Haemophilus influenzae β-lactamase negative Preferred Regimen ▸ Ampicillin 0.25–0.5 g po q6h.150–200 mg/kg/day IV Alternative Regimen ▸ Cefotaxime 1 g q8–12h to 2 g IV q4h OR ▸ Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine) OR ▸ Cefepime 1–2 g IV q12h OR ▸ Chloramphenicol 0.25–1 g po IV q6h to max. of 4 g/day OR ▸ Aztreonam 1 g IV q8h–2 g IV q6h OR ▸ FluoroquinoloneΔ β-lactamase negative, ampicillin resistant Preferred Regimen ▸ Meropenem 2 g IV q8h Alternative Regimen ▸ FluoroquinoloneΔ

Haemophilus influenzae β-lactamase positive Preferred Regimen ▸ Cefotaxime 1 g q8–12h to 2 g IV q4h OR ▸ Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine) Alternative Regimen ▸ Cefepime 1–2 g IV q12h OR ▸ Chloramphenicol 0.25–1 g po IV q6h to max. of 4 g/day OR ▸ Aztreonam 1 g q8h–2 g IV q6h OR ▸ FluoroquinoloneΔ

Staphylococcus aureus

Staphylococcus aureus Meticillin sensitive Preferred Regimen ▸ Nafcillin 1–2 g IV/IM q4h OR ▸ Oxacillin 1–2 g IV/IM q4h Alternative Regimen ▸ Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h(Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. ) OR ▸ linezolid 600 mg IV/PO q12h OR ▸ Daptomycin 6 mg/kg IV q24h

Staphylococcus aureus Meticillin resistant₦ Preferred Regimen ▸ Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h(Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. ) Alternative Regimen ▸ Trimethoprim-sulfamethoxazole 5–20 mg/kg/day q6-12h OR ▸ linezolid 600 mg IV/PO q12h OR ▸ Daptomycin 6 mg/kg IV q24h

Staphylococcus epidermidis and Acinetobacter baumannii^Ω

Staphylococcus epidermidis₦ Preferred Regimen ▸ Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h(Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. ) Alternative Regimen ▸ Linezolid 600 mg IV/PO q12h Acinetobacter baumannii Preferred Regimen ▸ Meropenem 2 g IV q8h Alternative Regimen ▸ Colistin in US:2.5-5 mg/kg/day q6-12h( 6.7-13.3 mg/kg/day of colistimethate sodium (CMS),max 800 mg/day); Elsewhere: ≤60 kg, 50,000-75,000 IU/kg/day IV q8h (=4-6 mg/kg per day of CMS). >60 kg, 1-2 mill IU IV q8h (= 80-160 mg IV tid). OR ▸ Polymyxin B 15,000–25,000 units/kg/day q12hǂ Enterobacteriaceae and Pseudomonas aeruginosa EnterobacteriaceaeΩ Preferred Regimen ▸ Cefotaxime 1 g q8–12h to 2 g IV q4h OR ▸ Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine) Alternative Regimen ▸ Aztreonam 1 g q8h–2 g IV q6h OR ▸ FluoroquinoloneΔ OR ▸ Trimethoprim-sulfamethoxazole 5–20 mg/kg/day q6-12h OR ▸ Meropenem 2 g IV q8h OR ▸ Ampicillin 150–200 mg/kg/day IV Pseudomonas aeruginosa Preferred Regimen ▸ Ceftazidime 1–2 g IV/IM q8–12h OR ▸ Cefepime 1–2 g IV q12h£ Alternative Regimen ▸ Aztreonam 1 g q8h–2 g IV q6h OR ▸ Meropenem 2 g IV q8h OR ▸ Ciprofloxacin 500-750 mg po bid£ †MIC=minimum inhibitory concentration.‡Addition of rifampicin can be considered if the organism is susceptible, the expected clinical or bacteriological response is delayed, or the cefotaxime/ceftriaxone MIC of the pneumococcal isolate is >4·0 μg/mLorganism is susceptible, the expected clinical or bacteriological response is delayed, or the cefotaxime/ceftriaxone MIC.ΦNo clinical data exist for use of this agent in patients with pneumococcal meningitis; recommendation is based on cerebrospinal fluid penetration and in-vitro activity against S pneumoniae.£Addition of an aminoglycoside should be considered; might need intraventricular or intrathecal administration in Gram-negative meningitis. ||Addition of rifampicin should be considered.Ω Choice of a specifi c agent should be based on in-vitro susceptibility testing. ††Might also need to be administered by the intraventricular or intrathecal routes. ǂ Might also need to be administered by the intraventricular or intrathecal routes. ₦ Addition of rifampicin should be considered.Δ The fluoroquinolones gatifl oxacin and moxifl oxacin pene trate the CSF eff ectively and have greater in-vitro activity against Gram-positive bacteria than do their earlier counterparts (eg, ciprofl oxacin). Findings from experi mental meningitis models suggested their effi cacy in S pneumoniae meningitis, including that caused by penicillin-resistant and cephalosporin-resistant strains. Although one controlled trial suggested the fluoroquinolone trovafl -oxacin mesilate to be as eff ective as ceftriaxone, with or without the addition of vancomycin, for paediatric bacterial meningitis, no clinical trials describe the use of gatifl oxacin or moxifl oxacin to treat bacterial meningitis in human beings. Trovafl oxacin and gatifl oxacin have been asso ciated with serious hepatic toxicity and dysglycaemia, respectively, and were with drawn from many markets.51 The IDSA guidelines recom mend moxifl oxacin as an alternative to third-generation cephalosporins plus vancomycin for menin-gitis caused by S pneumoniae strains resistant to penicillin and third-generation cephalosporins, although some experts recom mend that this agent should not be used alone but rather should be combined with another drug (either vancomycin or a third-generation cephalo sporin), because of the absence of clinical data supporting its use.