What is the recommended antibiotic treatment for a Klebsiella pneumoniae infection that is resistant to ceftazidime and meropenem but shows intermediate sensitivity to colistin?

Treatment of Carbapenem-Resistant, Ceftazidime-Resistant Klebsiella pneumoniae with Intermediate Colistin Sensitivity

For this highly resistant Klebsiella pneumoniae isolate, ceftazidime-avibactam 2.5g IV q8h or meropenem-vaborbactam 4g IV q8h should be the first-line treatment, NOT colistin, regardless of the intermediate colistin sensitivity. 1, 2

Primary Treatment Recommendations

First-Line Agents (Choose One)

• Ceftazidime-avibactam 2.5g IV every 8 hours (infused over 3 hours) is the preferred first-line option for KPC-producing carbapenem-resistant K. pneumoniae, with clinical success rates of 81.6% in complicated intra-abdominal infections and significantly lower 28-day mortality (18.3% vs. 40.8%) compared to other active agents including colistin. 1, 2

• Meropenem-vaborbactam 4g IV every 8 hours is equally effective as first-line therapy and should be specifically preferred for pneumonia due to superior epithelial lining fluid penetration, with concentrations remaining several-fold higher than the MIC90 of KPC-producing K. pneumoniae. 1, 2

• Both agents demonstrated higher clinical cure rates, decreased mortality, and reduced nephrotoxicity compared to traditional therapies including colistin-based regimens. 1

Alternative Agents

• Imipenem-cilastatin-relebactam 1.25g IV every 6 hours can be used when first-line options are unavailable, though clinical evidence is more limited. 1, 2

• Cefiderocol may be considered as an alternative, with 96% of carbapenem-resistant K. pneumoniae isolates showing susceptibility in recent studies. 2

Critical Diagnostic Step Required

Immediately obtain rapid molecular testing to identify the specific carbapenemase type (KPC vs. OXA-48 vs. MBL), as this determines optimal therapy selection. 2

• If MBL-producing strain is identified: Use ceftazidime-avibactam PLUS aztreonam combination, which has 70-90% efficacy against MBL producers where other options fail. 2, 3

• If OXA-48-like producing strain: Ceftazidime-avibactam remains first-line. 2

• If KPC-producing strain with ceftazidime-avibactam resistance (occurs in 0-12.8% of cases): Switch to meropenem-vaborbactam. 1, 2

Why Colistin Should NOT Be Used Despite Intermediate Sensitivity

• Colistin monotherapy has poor efficacy, with approximately one in three patients dying and <70% achieving clinical/microbiological response in traditional regimens. 1, 2

• Colistin exhibits no or very modest post-antibiotic effect against K. pneumoniae and shows substantial bacterial regrowth as early as 2 hours after treatment, even at concentrations up to 64× MIC. 4

• Colistin heteroresistance is observed in 15 of 16 isolates considered susceptible based on MIC testing, meaning apparent susceptibility may not translate to clinical efficacy. 4

• Higher nephrotoxicity risk with colistin compared to newer agents (adjusted HR 2.27,95% CI 1.35-3.82). 1

• Intermediate sensitivity is particularly problematic as monotherapy with long dosage intervals may fail, especially for colistin-heteroresistant strains. 4

Combination Therapy Considerations

• For severe infections with high mortality risk, combination therapy with two or more in vitro active antibiotics is recommended, with lower 14-day mortality compared to monotherapy (adjusted HR 0.56,95% CI 0.34-0.91). 2

• If colistin must be used due to lack of alternatives, always combine with another active agent (such as meropenem or amikacin), never use as monotherapy. 5

• For critically ill patients, combination therapy is particularly important when using polymyxin-based regimens. 2

Treatment Duration by Infection Site

• Bloodstream infections: 7-14 days 2
• Complicated urinary tract infections: 5-7 days 2
• Complicated intra-abdominal infections: 5-7 days 2
• Hospital-acquired/ventilator-associated pneumonia: 10-14 days 2

Critical Pitfalls to Avoid

• Never use tigecycline as monotherapy for pneumonia or bacteremia, as it performs poorly in bacteremic patients despite in vitro susceptibility. 2, 6

• Avoid fluoroquinolones as first-line due to widespread resistance. 2

• Do not delay appropriate therapy while awaiting carbapenemase testing—initiate ceftazidime-avibactam or meropenem-vaborbactam empirically for suspected carbapenem-resistant K. pneumoniae. 2

• Obtain infectious disease consultation for all multidrug-resistant organism infections. 2

• Monitor for resistance emergence during ceftazidime-avibactam therapy, which occurs in 0-12.8% of KPC-producing isolates. 1, 2