What IV antibiotics (abx) are used to treat Klebsiella infections?

IV Antibiotics for Klebsiella Infections

For carbapenem-susceptible Klebsiella infections, use carbapenems (meropenem, imipenem, or ertapenem) as first-line therapy; for carbapenem-resistant strains, ceftazidime-avibactam or meropenem-vaborbactam are the preferred agents, with ceftazidime-avibactam demonstrating superior outcomes compared to traditional regimens including colistin and aminoglycosides. 1, 2

Treatment Algorithm Based on Resistance Pattern

Carbapenem-Susceptible Klebsiella

• Third- and fourth-generation cephalosporins (ceftriaxone, cefotaxime, cefepime) are effective for community-acquired infections 3
• Carbapenems remain the treatment of choice for susceptible strains, including ertapenem, meropenem, and imipenem 4
• Ertapenem shows similar or better outcomes compared to imipenem/meropenem for bloodstream infections, with moderate certainty of evidence 1
• Piperacillin-tazobactam is an option for severe infections with anti-Pseudomonas coverage needed 1

Carbapenem-Resistant Klebsiella (CRKP)

KPC-Producing Strains (Most Common)

• Ceftazidime-avibactam 2.5g IV q8h is first-line (STRONG recommendation, MODERATE certainty) 1, 4

  • Clinical success rate of 81.6% in complicated intra-abdominal infections 5
  • 30-day mortality of 18.3% vs 40.8% with traditional regimens (p=0.005) 1, 4
  • Superior to aminoglycoside-carbapenem combinations (p=0.04) and colistin-carbapenem combinations (p=0.009) 2

• Meropenem-vaborbactam 4g IV q8h is equally effective as first-line (STRONG recommendation, MODERATE certainty) 1

  • Preferred for pneumonia due to superior epithelial lining fluid penetration (63% for meropenem, 65% for vaborbactam) 1, 4
  • Higher clinical cure rate and decreased mortality vs best available therapy in TANGO II trial 1

• Imipenem-cilastatin-relebactam 1.25g IV q6h is an alternative (CONDITIONAL recommendation, LOW certainty) 1, 4

  • Suppresses resistant mutant emergence better than imipenem alone 6
  • Attractive option for ceftazidime-avibactam-resistant KPC strains 6

OXA-48-Like Producing Strains

• Ceftazidime-avibactam is first-line (CONDITIONAL recommendation, VERY LOW certainty) 4
• Carbapenems may retain activity when MIC ≤8 mg/L with extended infusion (3 hours) 1

MBL-Producing Strains (NDM, VIM, IMP)

• Ceftazidime-avibactam PLUS aztreonam is preferred 4
• Cefiderocol is an alternative monotherapy option 4
• Polymyxins (colistin) combined with carbapenem, rifampicin, or tigecycline show effectiveness 7

Dosing Regimens for CRKP

Bloodstream Infections

• Duration: 7-14 days 1
• Ceftazidime-avibactam 2.5g IV q8h 1
• Meropenem-vaborbactam 4g IV q8h 1
• Imipenem-cilastatin-relebactam 1.25g IV q6h 1

Complicated Urinary Tract Infections

• Duration: 5-7 days 1
• Same agents as bloodstream infections 1
• Aminoglycosides (gentamicin 5-7 mg/kg/day IV QD or amikacin 15 mg/kg/day IV QD) are alternatives 1

Complicated Intra-Abdominal Infections

• Duration: 5-7 days 1
• Ceftazidime-avibactam 2.5g q8h PLUS metronidazole 500mg q6h 1
• Imipenem-cilastatin-relebactam 1.25g IV q6h 1

Hospital-Acquired/Ventilator-Associated Pneumonia

• Duration: 10-14 days 1
• Meropenem-vaborbactam preferred due to lung penetration 1
• Ceftazidime-avibactam 2.5g IV q8h is alternative 1

Combination Therapy Considerations

• For severe CRKP infections with high mortality risk (INCREMENT score 8-15), use two or more in vitro active antibiotics (adjusted HR 0.56,95% CI 0.34-0.91) 1
• Combination therapy is most beneficial when limited to older agents (polymyxins, tigecycline, aminoglycosides) with suboptimal pharmacokinetics 1
• Monotherapy with newer agents (ceftazidime-avibactam, meropenem-vaborbactam) is sufficient for non-severe infections 4
• Polymyxin-based combinations require colistin 5mg CBA/kg IV loading dose, then 2.5mg CBA × (1.5 × CrCl + 30) IV q12h PLUS tigecycline 100mg IV load, then 50mg IV q12h 1

Critical Pitfalls and Caveats

• Avoid cefepime for ESBL-producing Klebsiella when MIC is in the susceptible dose-dependent category (associated with higher mortality, p=0.045) 1
• Cephamycins (flomoxef, cefmetazole) show increased mortality when MIC is 2-8 mg/L despite susceptibility (adjusted OR 5.7,95% CI 1.9-16.8) 1
• Fluoroquinolones are no longer appropriate first-line due to widespread resistance 1
• Piperacillin-tazobactam use is controversial for ESBL infections despite in vitro susceptibility 1
• Aminoglycoside and colistin regimens carry significantly increased nephrotoxicity risk (p=0.002) 2
• Ceftazidime-avibactam resistance emergence occurs in 0-12.8% of KPC-producing isolates during treatment 4
• Obtain rapid molecular testing to identify specific carbapenemase types (KPC vs OXA-48 vs MBL) to guide appropriate therapy 4
• For carbapenem combinations in CRKP, only use when meropenem MIC ≤8 mg/L with extended 3-hour infusion 1