What is the treatment for Klebsiella (Klebsiella pneumoniae) infections?

Treatment of Klebsiella pneumoniae Infections

For Klebsiella pneumoniae infections, ceftazidime/avibactam or meropenem/vaborbactam are the first-line treatment options, particularly for carbapenem-resistant strains, with strong recommendation and moderate certainty of evidence. 1, 2

Treatment Algorithm Based on Resistance Pattern

For Susceptible K. pneumoniae:

• Third and fourth-generation cephalosporins (ceftriaxone, cefotaxime, cefepime) are effective first-line treatments 3
• Fluoroquinolones (levofloxacin, ciprofloxacin) may be used in patients with beta-lactam allergies, though resistance rates are increasing 3
• Carbapenems (ertapenem, meropenem, imipenem) offer broad-spectrum activity against susceptible strains 3

For ESBL-producing K. pneumoniae:

• Carbapenems (meropenem, imipenem-cilastatin, or ertapenem) remain the first-line treatment options 2
• Ceftolozane/tazobactam combined with metronidazole may be valuable for treating ESBL infections to preserve carbapenems 1

For KPC-producing K. pneumoniae:

• Ceftazidime/avibactam (2.5g IV every 8 hours) or meropenem/vaborbactam (2g IV every 8 hours) should be used as first-line treatment options 1, 2
• Imipenem/relebactam and cefiderocol may be considered as alternatives when first-line agents are unavailable (conditional recommendation, low certainty of evidence) 1, 2

For OXA-48-like producing CRE:

• Ceftazidime/avibactam should be the first-line treatment option (conditional recommendation, very low certainty of evidence) 1

Site-Specific Considerations

• For respiratory infections (pneumonia), meropenem/vaborbactam may be preferred due to better epithelial lining fluid concentrations 1, 2
• For complicated intra-abdominal infections, ceftazidime/avibactam should be combined with metronidazole 4
• For complicated urinary tract infections including pyelonephritis, ceftazidime/avibactam monotherapy is FDA-approved 4

Duration of Therapy

• For uncomplicated infections: 7-14 days of appropriate therapy 2
• For complicated intra-abdominal infections: 5-14 days 4
• For complicated UTIs: 7-14 days 4
• For hospital-acquired or ventilator-associated pneumonia: 7-14 days 4

Evidence Supporting Novel Agents

• In a multicentre prospective registry, patients with KPC-producing K. pneumoniae bloodstream infections treated with ceftazidime/avibactam had significantly lower 28-day mortality compared to those treated with other active agents (18.3% vs. 40.8%, p=0.005) 1
• Meropenem/vaborbactam demonstrated higher clinical cure rates, decreased mortality, and reduced nephrotoxicity compared to best available therapy in the TANGO II study 1
• Recent U.S. surveillance data showed 99.1% susceptibility of multidrug-resistant Enterobacterales to meropenem/vaborbactam, including 98.9% susceptibility among KPC-producing isolates 5

Treatment Pitfalls to Avoid

• Traditional antibiotic regimens including colistin have shown poor efficacy and unfavorable toxicity profiles compared to newer agents 6
• Inappropriate use of carbapenems should be avoided to reduce selective pressure and association with increasing carbapenem-resistant Enterobacteriaceae 1
• Tigecycline performs poorly in bacteremic patients and should not be considered first-line therapy in patients with healthcare-associated pneumonia and bacteremia 1
• Local epidemiology and the emergence of ceftazidime/avibactam resistance in KPC-producing isolates (ranging from 0% to 12.8%) should be considered when selecting therapy 1

Diagnostic Considerations

• Rapid molecular testing should be used to identify specific carbapenemase types to guide appropriate therapy 2
• Susceptibility testing is essential as K. pneumoniae may have variable resistance patterns 6
• Blood cultures should be repeated to document clearance of bacteremia 6