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Part V: Guidelines for known-pathogen therapy

Guidelines for known-pathogen therapy

Table 5.1 Guidelines for known-pathogen therapy

  Drug of choice Alternatives Remarks
Acinetobacter baumannii I.V. ampicillin-sulbactam + an aminoglycoside
  • I.V. cefoperazone-sulbactam + an aminoglycoside (mixed infection with P. aeruginosa)
  • Fluoroquinolone + an aminoglycoside (if allergic to penicillin)
  • Sulbactam is highly active against Acinetobacter
  • Resistance rates in 2010: ampicillin-sulbactam (24%), cefoperazone-sulbactam (24%), imipenem (37%), gentamicin (32%), amikacin (25%), ciprofloxacin (50%)
  • For multidrug-resistant isolates: consult microbiologist or infectious disease physician
Clostridium difficile P.O. metronidazole (404–405) P.O. vancomycin (if metronidazole fails as documented microbiologically)
  • Mild/moderate disease: clinical efficacy of metronidazole = vancomycin
  • Severe disease, ileus or toxic megacolon: I.V. metronidazole + P.O. vancomycin + consult surgeon
  • First recurrence: same as primary infection based on severity of disease
  • Multiple recurrence: consult microbiologist or infectious disease physician, options include vancomycin taper or faecal microbiota transplant (406)
Enterobacter cloacae complex
  • P.O./I.V. levofloxacin/ ciprofloxacin for urinary tract infection
  • I.V. cefepime (± an aminoglycoside) for severe infection
  • I.V. piperacillin-tazobactam
  • I.V. carbapenem (for severe
    infection and/or ESBL-producing strain)
  • Cefepime is highly active in vitro against almost all Enterobacter isolates
  • Emergence of AmpC derepressed mutants emerge in 20–40% of infections treated with the second or third generation cephalosporins. Use of these agents for serious infections is not recommended
  • One study in HK found high prevalence of ESBL production among E. hormaechei (a member of the E. cloacae complex) (407)
  • Resistance rate in 2010: levofloxacin (8%), gentamicin (4%), amikacin (1%)
  • For multidrug-resistant isolates: consult microbiologist or infectious disease physician
E. coli (ESBL-neg)
  • I.V./P.O. ampicillin-sulbactam or
    amoxicillin-clavulanate (add an aminoglycoside if rapid Bactericidal action desirable on clinical grounds)
  • I.V./P.O. cefuroxime (if resistant to amoxicillin-clavulanate), add I.V./P.O. metronidazole (if mixed infection with anaerobes likely)
  • I.V. piperacillin-tazobactam + an aminoglycoside (if P. aeruginosa or Acinetobacter are co-pathogens)
 
Haemophilus influenzae
  • P.O. amoxicillin or P.O./I.V. ampicillin-sulbactam or amoxicillin-clavulanate or cefotaxime or ceftriaxone
  • Fluoroquinolones (if allergic to penicillin)
  • Amoxicillin-clavulanate also
    provides good coverage for M. catarrhalis and S. pneumoniae
Klebsiella pneumoniae (ESBL-neg)
  • I.V./P.O. ampicillin-sulbactam
    or amoxicillin-clavulanate (add an aminoglycoside if rapid bactericidal action desirable on clinical grounds)
  • I.V./P.O. cefuroxime (if resistant to amoxicillin-clavulanate), add I.V./P.O. metronidazole (if mixed infection with anaerobes likely)
  • I.V. piperacillin-tazobactam + an aminoglycoside (if P. aeruginosa or Acinetobacter are co-pathogens)
  • Ampicillin-sulbactam less satisfactory because of poor inhibitory activity of sulbactam for SHV-1 ß-lactamase
E. coli / K. pneumoniae (ESBL-pos)
  • P.O. nitrofurantoin or P.O. amoxicillin-clavulanate (uncomplicated urinary tract infection and other mild infections)
  • Carbapenem or I.V. β-lactam/β-lactamase inhibitor for bacteraemia or other serious infection
  • Carbapenem has been shown to be effective clinically and is currently the ß-lactam agent of choice for serious infection by ESBL-pos E. coli / Klebsiella spp.
Pseudomonas aeruginosa I.V. piperacillin or ticarcillin-clavulanate or piperacillin-tazobactam + an aminoglycoside
  • I.V. cefoperazone-sulbactam
    + an aminoglycoside (mixed
    infection with Acinetobacter)
  • I.V./P.O. levofloxacin/ ciprofloxacin + an aminoglycoside (if allergic to penicillin)
  • Combination therapy recommended (for synergism) for all serious infection except for uncomplicated catheter-related bacteraemia
  • Piperacillin-tazobactam used instead of ceftazidime due to rapid rise in AmpC type and ESBL-producers in Enterobacteriaceae
  • For multidrug-resistant isolates: consult microbiologist or infectious disease physician
Methicillin-sensitive S. aureus P.O./I.V. cloxacillin or amoxicillin-clavulanate or ampicillin-sulbactam or first generation cephalosporin
  • I.V. cefazolin (if allergic to penicillin, but limited to those with minor allergy such as rash alone)
  • Clindamycin (if allergic to penicillin)
 
Methicillin-resistant S. aureus I.V. vancomycin (bacteraemia or other invasive infections)
  • I.V./P.O. linezolid or I.V. daptomycin if (1) vancomycin allergy - extensive rash, other than red-man syndrome develop after vancomycin, or (2) bacteraemia caused by MRSA with vancomycin ≥ 2 μg/mL
  • Cotrimoxazole, fusidic acid or rifampicin are useful adjuncts for deep-seated infections (e.g. osteomyelitis) but these agents should not be administered as monotherapy
  • Most abscesses or uncomplicated skin and soft tissue infection caused by CA-MRSA could be treated with drainage and oral antibiotics with in vitro activities (e.g. clindamycin or cotrimoxazole)
  • Vancomycin intermediate Staphylococcus aureus / vancomycin resistant Staphylococcus aureus: consult microbiologist or infectious disease physician
Mycoplasma pneumoniae
  • P.O. doxycycline (or I.V. minocycline)
  • P.O. azithromycin
  • I.V./P.O. levofloxacin or moxifloxacin
  • Doxycycline preferred over azithromycin in view of increasing macrolide resistant Mycoplasma pneumoniae (379)
Stenotrophomonas maltophilia P.O./I.V. cotrimoxazole + I.V. ticarcillin-clavulanate
  • I.V./P.O. cotrimoxazole + fluoroquinolone
  • Cotrimoxazole + ticarcillin-clavulanate is synergistic in vitro. Cotrimoxazole is a key component in therapy
  • Combination therapy recommended for synergy and to prevent resistance
  • For cotrimoxazole-resistant strain, consult microbiologist or infectious disease physician
Streptococcus pneumoniae
(for infection outside the central nervous system)
  • Penicillin-sensitive: I.V. penicillin G (4–8 million unit/day, q6h)
  • Penicillin-intermediate: I.V. penicillin G (high dose, 12–18 million unit/day, q4h)1
  • Penicillin-resistant: I.V. cefotaxime or ceftriaxone
  • ß-lactam/ß-lactamase inhibitor combination with the exception of cefoperazone-sulbactam (for mixed infections)
  • P.O./I.V. levofloxacin or P.O./I.V. moxifloxacin (if allergic to penicillin) for non-meningeal infections and penicillin-sensitive strains
  • Most pneumococcal pneumonia can be treated with high dose amoxicillin or high dose amoxicillin-clavulanate
  • For pure pneumococcal infection, penicillin G instead of amoxicillin-clavulanate is preferred, switch therefore recommended
  • >70% resistant to erythromycin. Cross-resistance to clindamycin is very common
  • Resistance to erythromycin = resistance to other newer macrolides (clarithromycin, azithromycin)
Streptococcus pneumoniae
(for central nervous system infection)
  • Penicillin-sensitive (MIC ≤ 0.06 μg/mL): I.V. penicillin G (18–24 million unit/day, q4h) or I.V. ampicillin 2 g q4h
  • Penicillin-resistant (MIC ≥ 0.12 μg/mL) and third-generation cephalosporin (MIC <1 μg/mL): I.V. cefotaxime 2 g q4h or I.V. ceftriaxone 2 g q12h
  • Penicillin-resistant (MIC ≥ 0.12 μg/mL) and third-generation cephalosporin (MIC ≥ 1 μg/mL): I.V. vancomycin plus I.V. cefotaxime 2 g q4h or ceftriaxone 2 g q12h
 
  • MIC (meningitis) breakpoints for penicillin, ceftriaxone and cefotaxime to be used here
  • In S. pneumoniae, cross resistance between penicillin and ceftriaxone / cefotaxime is common (391,408). Local data indicates that approximately half of the penicillin-resistant (meningitis) isolates are intermediate / resistant (meningitis) to cefotaxime

 

Note:

  1. 1CLSI MIC (μg/mL) breakpoints for penicillin G: sensitive ≤ 0.06; intermediate 0.12–1; resistant ≥ 2. These breakpoints were decided mainly for the relevance on meningitis. For pneumococcal pneumonia, pharmacokinetic/dynamic data indicates that isolates with MIC of up to 1–2 μg/mL should be considered ‘sensitive’ to appropriate dose of penicillin, ampicillin and amoxicillin.