Rapid diagnostics and ceftazidime/avibactam for KPC-producing Klebsiella pneumoniae bloodstream infections: impact on mortality and role of combination therapy.

This study was aimed at investigating risk factors for mortality in patients suffering from KPC-producing Klebsiella pneumoniae (KPC-Kp) bloodstream infections (BSIs), evaluating the impact of rapid diagnostics and ceftazidime/avibactam use. This observational retrospective study (January 2017-May 2021) included all patients with a KPC-Kp BSI. Uni-multivariable analyses were carried out to evaluate the effect of clinical variables on both in-hospital death (IHD) and 30-day all-cause mortality, and the role of the combination of ceftazidime/avibactam plus polymyxin. One hundred and ninety-six patients met the study's inclusion criteria. Older age, having undergone renal replacement therapy during the 30 days preceding the KPC-Kp BSI onset, having an INCREMENT-CPE score ≥ 8, and having suffered from a superimposed and/or following KPC-Kp BSI treatment candidemia were found to be the main factors associated with both mortality rates. Among protective factors, the centrality of ceftazidime/avibactam in monotherapy (IHD: OR: 0.34; CI 95%: 0.11-1.00-30-day all-cause mortality: OR: 0.18; CI 95%: 0.04-0.77) or combination (IHD: OR: 0.51; CI 95%: 0.22-1.19-30-day all-cause mortality: OR: 0.62; CI 95%: 0.21-1.84) emerged and became even more evident once the effect of ceftazidime/avibactam plus polymyxin was removed. Rapid diagnostics may be useful to adopt more effective strategies for the treatment of KPC-Kp BSI patients and implement infection control measures, even if not associated with higher patient survival. Ceftazidime/avibactam, even when used alone, represents an important option against KPC-Kp, while combined use with polymyxin might not have altered its efficacy. Patient comorbidities, severity of BSI, and complications such as candidemia were confirmed to have a significant burden on survival.

Detection of Carbapenemase and CTX-M Encoding Genes Directly from Bronchoalveolar Lavage Using the CRE and ESBL ELITe MGB Assays: Toward Early and Optimal Antibiotic Therapy Management of Critically Ill Patients with Pneumonia.

The detection of carbapenemase extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (EB) has become a major issue among critically ill patients, especially due to their impact on appropriate antimicrobial therapy. This study aimed at evaluating the potential contribution of molecular assays to early optimization of empirical antibiotic therapy among critically ill patients with carbapenemase- and/or CTX-M-producing EB pneumonia. The CRE and ESBL ELITe MGB® assays were evaluated directly on 197 bronchoalveolar lavage (BAL) samples obtained from 120 patients. Molecular results were then compared to routine culture-based diagnostic results, and a retrospective analysis of the therapeutic antimicrobial management was performed. Among the 197 clinical specimens, blaKPC-like and blaCTX-M-like were detected in 20 (10.2%) and 12 (6.1%) specimens belonging to 15 and 11 patients, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of the CRE ELITe MGB Kit were 85% [95% confidence interval [CI]: 64.9-94.6] and 100%, respectively. PPV and NPV of the ESBL ELITe MGB Kit were 75% [95% CI: 49.4-90.2] and 100%, respectively. Retrospective analysis of the therapeutic antimicrobial management at the time of BAL collection showed that in ∼50% of patients with carbapenemase- and CTX-M-producing EB pneumonia empirical antibiotic therapy could have been optimized at least 48-72 hr earlier if positive molecular data had been used. The CRE and ESBL ELITe MGB assays might be an interesting tool for expediting optimization of empirical antibiotic therapy in critically ill patients with pneumonia, depending on local epidemiology of antibiotic resistance, patient risk stratification for EB infection, and availability of an antimicrobial stewardship team.