What are the recommended antibiotics for treating Klebsiella pneumonia?

Recommended Antibiotics for Treating Klebsiella pneumoniae

For Klebsiella pneumoniae infections, ceftazidime-avibactam is recommended as first-line treatment for carbapenem-resistant strains, particularly KPC-producing K. pneumoniae, with combination therapy recommended for severe infections. 1

Treatment Based on Resistance Pattern

For Non-Resistant K. pneumoniae

• Third- and fourth-generation cephalosporins (e.g., ceftriaxone, cefepime) are effective for susceptible strains 2
• Quinolones (e.g., levofloxacin, ciprofloxacin) are alternative options for susceptible strains 2, 3
• Carbapenems (e.g., meropenem, imipenem) can be used for more serious infections but should be reserved when possible to prevent resistance 2, 3

For ESBL-Producing K. pneumoniae

• Carbapenems remain effective but should be used judiciously 3
• β-lactam/β-lactamase inhibitor combinations (e.g., piperacillin-tazobactam) may be considered as carbapenem-sparing alternatives 3
• Ceftolozane/tazobactam is another option for ESBL-producing strains 3

For Carbapenem-Resistant K. pneumoniae (CRKP)

• Ceftazidime-avibactam is recommended as first-line therapy for KPC-producing strains with clinical success rates of 60-80% 1, 4
• For MBL-producing strains, ceftazidime-avibactam plus aztreonam is recommended (70-90% efficacy) 1
• Imipenem-relebactam or cefiderocol are alternatives when first-line options are unavailable 1, 5
• Tigecycline shows favorable in vitro activity against carbapenemase-producing Enterobacteriaceae 1, 4
• Polymyxins (colistin) may be used in combination therapy for highly resistant strains 3, 6

Combination Therapy for Severe CRKP Infections

• Combination therapy with two or more in vitro active antibiotics is recommended for severe CRKP infections, particularly in critically ill patients 3
• Combination therapy is associated with lower 14-day mortality compared to monotherapy in bloodstream infections and non-bacteremic infections 3
• For polymyxin or tigecycline-based regimens, adding a companion drug is advisable 3
• Meropenem-colistin combination shows synergistic effect in 25% of cases against CRKP 6

Special Considerations for Highly Resistant Strains

• For pan-resistant or extensively drug-resistant K. pneumoniae:
  • Ceftazidime-avibactam remains active against many KPC-producing strains 7, 1
  • Cefiderocol shows high activity (96% susceptibility) against carbapenem-resistant K. pneumoniae 6
  • Double-carbapenem therapy (e.g., ertapenem plus another carbapenem) may be considered in limited options, though evidence is insufficient 3
  • High-dose extended-infusion meropenem (6g/day, 3-hour infusion) in combination with polymyxin may be effective even with higher MICs (≤16 mg/L) 3

Therapeutic Drug Monitoring (TDM)

• TDM is recommended when using polymyxins, aminoglycosides, or carbapenems for CRKP infections 3
• TDM is particularly important in:
  • Critically ill patients with CRKP infections 3
  • Patients with renal dysfunction or hyperfunction 3
  • When treating difficult-to-reach infection sites (e.g., central nervous system) 3
  • Severe infections like bloodstream infections and sepsis 3

Antimicrobial Stewardship Considerations

• Carbapenem-sparing strategies are recommended, particularly in settings with high incidence of CRKP 3
• Novel β-lactam/β-lactamase inhibitor combinations are valuable for preserving carbapenems 3, 1
• Limiting extended use of carbapenems can reduce carbapenem resistance by 20-30% 1

Clinical Efficacy Data

• In clinical trials, ceftazidime-avibactam demonstrated efficacy against K. pneumoniae in complicated intra-abdominal infections with clinical cure rates of 78.4% 8
• For complicated urinary tract infections, ceftazidime-avibactam showed microbiological cure rates of 75.0% for K. pneumoniae 8
• Against ceftazidime non-susceptible K. pneumoniae, ceftazidime-avibactam demonstrated superior efficacy compared to best available therapy 8

Pitfalls and Caveats

• Resistance to ceftazidime-avibactam in KPC-producing isolates has been reported (0-12.8%) 1
• Mutations in the blaKPC-3 gene can confer resistance to ceftazidime-avibactam 1
• Monotherapy with older agents may lead to treatment failure due to K. pneumoniae's thick capsule 2
• Tigecycline performs poorly in bacteremic patients and should not be used as first-line therapy in patients with bacteremia 3
• Source control (drainage of collections, removal of infected devices) is essential alongside appropriate antimicrobial therapy 1