Non-polymyxin regimens improve clinical cure, reduce mortality in CRKP bacteraemia vs. polymyxins.
Background
Carbapenem-resistant Klebsiella pneumoniae (CRKP) bacteraemia represents a critical therapeutic challenge due to its limited treatment options and high mortality rates. While polymyxins have been widely used as a last-resort antibiotic for multidrug-resistant Gram-negative infections, concerns regarding their efficacy and safety, particularly nephrotoxicity, have grown. This study addresses the urgent need to compare the clinical and microbiological outcomes of polymyxin-based versus non-polymyxin regimens to identify superior definitive therapies for CRKP bloodstream infections (BSI).
Study Design
This multicentric, retrospective observational study included 244 adult patients (≥18 years) with confirmed CRKP bacteraemia admitted between January 2019 and December 2023. Patients were categorized into two groups based on their definitive therapy: Polymyxin-Based Therapy (PBT) (n=143) or Non-Polymyxin Regimens (NPR) (n=101). Baseline characteristics, disease severity (SOFA, CCI scores), and clinical outcomes were compared. Predictors of in-hospital mortality were identified using multivariable Cox regression, validated by bootstrap resampling, and assessed via landmark sensitivity analysis. Kaplan-Meier survival analyses were performed for mortality and microbiological clearance.
Results
Out of 1,009 patients with K. pneumoniae bacteraemia, 244 met the inclusion criteria for CRKP. While baseline demographics were similar, PBT recipients presented with higher disease severity, indicated by higher SOFA scores (4[0-12] vs. 3[0-12]; p<0.001) and CCI scores (4[0-8] vs. 3[0-10]; p=0.025). Clinical cure rates were significantly higher with NPR (58.4% vs. 15.4%; p=0.02). Conversely, in-hospital mortality was substantially higher in the PBT group (68.5% vs. 38.6%; p<0.001), as was the incidence of acute kidney injury (55.9% vs. 28.7%; p=0.008). Microbiological clearance and time to clearance were comparable between the two groups. Independent predictors of mortality included treatment with polymyxins (adjusted Hazard Ratio [aHR]: 1.595; 95%CI: 1.392-1.903; p=0.015), SOFA score >6 (aHR: 1.514; 95%CI: 1.285-1.928; p=0.027), history of chronic liver disease (aHR: 2.31; 95%CI: 1.884-3.642; p=0.02), and post-therapy dialysis (aHR: 3.11; 95%CI: 1.884-3.642).
Key Findings
- Non-polymyxin regimens achieved significantly higher clinical cure rates (58.4%) compared to polymyxin-based therapy (15.4%; p=0.02).
- In-hospital mortality was significantly lower with non-polymyxin regimens (38.6%) versus polymyxin-based therapy (68.5%; p<0.001).
- Acute kidney injury occurred less frequently in the non-polymyxin group (28.7%) compared to the polymyxin group (55.9%; p=0.008).
- Treatment with polymyxins was an independent predictor of mortality (aHR: 1.595; p=0.015).
- Microbiological clearance and time to clearance were comparable between both treatment groups.
Why It Matters
This study provides compelling evidence that non-polymyxin regimens offer superior clinical outcomes for patients with CRKP bacteraemia compared to polymyxin-based therapy. The significantly higher clinical cure rates and lower mortality, coupled with reduced acute kidney injury, suggest a critical need to re-evaluate current treatment guidelines. Clinicians should prioritize non-polymyxin options where susceptibility allows, potentially shifting away from polymyxins as a first-line definitive therapy for CRKP. This could lead to improved patient survival and reduced adverse drug events, moving towards more effective and safer protocols for managing these highly resistant infections. The findings underscore the importance of continuous surveillance and development of novel non-polymyxin agents.
carbapenem-resistant klebsiella pneumoniae
crkp
bacteraemia
polymyxins
antibiotics
antimicrobial resistance