Prevalence and mortality of ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae bloodstream infections (2018-2022)

Abstract

Introduction: Ceftazidime/avibactam-resistance in Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is a topic of great interest for epidemiological, diagnostic, and therapeutical reasons. However, data on its prevalence and burden on mortality in patients with bloodstream infection (BSI) are lacking. This study was aimed at identifying risk factors for mortality in patients suffering from ceftazidime/avibactam-resistant KPC-Kp BSI.

Methods: An observational retrospective study (January 2018-December 2022) was conducted at a tertiary hospital including all consecutive hospitalized adult patients with a ceftazidime/avibactam-resistant KPC-Kp BSI. Data on baseline clinical features, management, and admission outcomes were analyzed.

Results: Over the study period, among all the KPC-Kp BSI events recorded, 38 (10.5%) were caused by ceftazidime/avibactam-resistant KPC-Kp strains, 37 events being finally included. The ceftazidime/avibactam-resistant KPC-Kp strains revealed susceptibility restoration to at least one carbapenem in more than 60% of cases. In-hospital and 30-day all-cause mortality rates were 22% and 16.2%, respectively. Non-survivors suffered from more baseline comorbidities and experienced a more severe ceftazidime/avibactam-resistant KPC-Kp BSI presentation (i.e., both the Pitt Bacteremia and INCREMENT-CPE scores were significantly higher). Presenting with a higher Charlson Comorbidity Index, chronic kidney disease-KDIGO stage 3A or worse-having recently gone through renal replacement therapy, having suffered from an acute kidney injury following the ceftazidime/avibactam-resistant KPC-Kp BSI, and being admitted for cardiac surgery were the strongest predictors of mortality.

Conclusion: Ceftazidime/avibactam resistance in KPC-Kp BSI easily emerged in our highly KPC-Kp endemic area with remarkable mortality rates. Our findings might provide physicians possibly actionable information when managing patients with a ceftazidime/avibactam-resistant KPC-Kp BSI.

Keywords: Bloodstream infection; Ceftazidime/avibactam resistance; KPC; Klebsiella pneumoniae; Mortality; Sepsis.

Fig. 1

Variable importance (weighted average mean decrease Gini / node impurity) for the random forest classifiers in explanatory mode including every single variable under analysis for in-hospital (left) and 30-day all-cause mortality (right) among patients with ceftazidime/avibactam resistant KPC-producing Klebsiella pneumoniae bloodstream infection

Fig. 2

Breakdown plots with the contribution of each individual explanatory variable at the individual patient level. Two representative examples of both positive and negative cases for in-hospital and 30-day all-cause mortality in ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae bloodstream infections. Absolute values for continuous features and 0/1 (no/yes) for categorial ones. The intercept term represents the average predicted probability of death across the entire cohort, and subsequent entries display how that prediction changes based on the observed value of each explanatory variable (fixing the effect of every other variable). An individual feature contribution is influenced not only by its overall importance across the entire cohort but also by how much of an effect that variable had in explaining that specific patient’s outcome. Explanatory analysis, not intended for prediction/classification purposes