Treatment of MDR Klebsiella pneumoniae Bacteremia and Urinary Infection
For MDR Klebsiella pneumoniae bacteremia and urinary infection susceptible to ceftazidime-avibactam and aztreonam, administer ceftazidime-avibactam 2.5 g IV every 8 hours infused over 3 hours as first-line therapy. 1
Primary Dosing Regimen
Ceftazidime-avibactam 2.5 g IV every 8 hours is the recommended dose for both bacteremia and complicated urinary tract infections caused by carbapenem-resistant Enterobacterales. 1 This regimen has demonstrated:
- Clinical success rates of 81.6% in complicated infections 2
- Significantly lower 28-day mortality (18.3% vs 40.8%) compared to other active agents 1, 2
- Superior safety profile with lower nephrotoxicity risk compared to colistin 1
Critical Administration Detail
Administer ceftazidime-avibactam as a prolonged 3-hour infusion rather than standard infusion. 3 Prolonged infusion has been independently associated with improved 30-day survival in multivariate analysis (P = 0.006) and is critical for optimizing pharmacodynamics against high-MIC pathogens. 4, 2, 3
Duration of Therapy
Treatment should continue for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. 4
Renal Dose Adjustments
Ensure appropriate renal dose adjustment for ceftazidime-avibactam, as this is critical for both efficacy and safety. 2 Failure to adjust for renal function was independently associated with increased mortality in multivariate analysis (P = 0.01). 3
When to Consider Aztreonam Addition
Do NOT routinely add aztreonam if the organism is susceptible to ceftazidime-avibactam alone. 1 Aztreonam should only be added in specific scenarios:
Indications for Ceftazidime-Avibactam PLUS Aztreonam:
- Metallo-β-lactamase (MBL) producers (NDM, VIM, IMP types) where ceftazidime-avibactam alone is ineffective 4, 5, 2
- This combination shows 70-90% efficacy against MBL producers with significant reduction in 30-day mortality (HR 0.37,95% CI 0.13-0.74) 5, 2
- Synergistic bactericidal effects occur in 90% of NDM-producing strains 6
Since your isolate is susceptible to ceftazidime-avibactam, monotherapy is sufficient and combination therapy is not indicated. 1
Combination Therapy Considerations
Monotherapy with ceftazidime-avibactam is appropriate for your case. 2 A large multicenter study of 577 patients with KPC-producing K. pneumoniae infections found no significant difference in mortality between monotherapy and combination regimens (26.1% vs 25.0%, P = 0.79). 3
When Combination Therapy IS Indicated:
- Septic shock at infection onset 3
- Neutropenia 3
- INCREMENT score ≥8 3
- Critically ill patients with high mortality risk (adjusted HR 0.56 for combination therapy) 2
Critical Pitfalls to Avoid
Do not use standard 30-minute infusion. Prolonged 3-hour infusion is essential for optimal outcomes. 4, 2, 3
Monitor for resistance emergence. Ceftazidime-avibactam resistance can develop in 0-12.8% of KPC-producing isolates during treatment, particularly with prior ceftazidime-avibactam exposure. 1, 2 If resistance emerges, consider meropenem-vaborbactam as an alternative. 1, 2
Ensure rapid molecular testing was performed to confirm the carbapenemase type (KPC vs OXA-48 vs MBL), as this guides appropriate therapy selection. 2 Each class confers different susceptibility profiles requiring distinct treatment strategies.
Lower respiratory tract infections may have more limited efficacy with ceftazidime-avibactam compared to other infection sites (P = 0.04 for increased mortality). 3 However, for bacteremia and urinary infections, outcomes are excellent.