To assess the impact of carbapenem resistance on mortality in Klebsiella pneumoniae bloodstream infection (BSI) in the era of novel β-lactam/β-lactamase inhibitor combinations. Retrospective study of patients with K. pneumoniae BSI between January and August 2020 in 16 centres (CARBANEW study within the MULTI-SITA project). Overall, 426 patients were included: 107/426 (25%) had carbapenem-resistant K. pneumoniae (CR-Kp) BSI and 319/426 (75%) had carbapenem-susceptible K. pneumoniae (CS-Kp) BSI. Crude cumulative 30 day mortality was 33.8% and 20.7% in patients with, respectively, CR-Kp BSI and CS-Kp BSI (P = 0.027). Carbapenemase production or carbapenemase-encoding genes were detected in 84/98 tested CR-Kp isolates (85.7%), mainly KPC (78/84; 92.9%). Ceftazidime/avibactam was the most frequently used appropriate therapy for CR-Kp BSI (80/107; 74.7%). In multivariable analyses, variables showing an unfavourable association with mortality after correction for multiple testing were age-adjusted Charlson comorbidity index (HR 1.20; 95% CI 1.10–1.31, P < 0.001) and Pitt score (HR 1.33; 95% CI 1.15–1.55, P < 0.001), but not carbapenem resistance (HR 1.28, 95% CI 0.74–2.22, P = 0.410). In a propensity score-matched analysis, there was no difference in mortality between patients appropriately treated with ceftazidime/avibactam for CR-Kp BSI and patients appropriately treated with other agents (mainly meropenem monotherapy or piperacillin/tazobactam monotherapy) for CS-Kp BSI (HR 1.07; 95% CI 0.50–2.29, P = 0.866). Our results suggest that the increased mortality in CR-Kp BSI compared with CS-Kp BSI is not (or no longer) dependent on the type of therapy in areas where ceftazidime/avibactam-susceptible KPC-producing isolates are the most prevalent type of CR-Kp.

This study assesses the impact of fluconazole resistance on 30-day all-cause mortality and 1-year recurrence in patients with Candida parapsilosis bloodstream infections (BSI). A multicenter retrospective study was performed at 3 hospitals in Italy and Spain between 2018 and 2022. Adult patients with positive blood cultures for C. parapsilosis who received appropriate targeted therapy with either echinocandins or fluconazole were included. Among 457 patients, 196 (42.9%) had fluconazole-resistant C. parapsilosis (FLZR-CP) BSI and 261 (57.1%) had fluconazole-susceptible C. parapsilosis (FLZS-CP) BSI. All FLZR-CP patients received targeted echinocandins, while FLZS-CP patients received either echinocandins (60.5%) or fluconazole (39.5%). Unadjusted 30-day all-cause mortality rates were 28.6% for FLZR-CP and 28.4% for FLZS-CP (log-rank test, P = .998). In multivariable analysis, increased mortality was associated with age (adjusted hazard ratio [aHR] 1.03 per year; 95% confidence interval [CI], 1.01–1.05; P = .0005), solid tumor (aHR 1.91; 95% CI, 1.06–3.46; P = .0302), previous antifungal treatment (aHR 1.84; 95% CI, 1.12–3.10; P = .0192), and septic shock (aHR 2.39; 95% CI, 1.42–4.06; P = .0010), but not fluconazole resistance (aHR 1.00; 95% CI, .62–1.63; P = .9864) nor the type of initial antifungal therapy (aHR 1.46; 95% CI, .69–3.06; P = .3202). Propensity score-matched analysis showed no 30-day all-cause mortality difference between echinocandin-treated FLZR-CP and fluconazole-treated FLZS-CP patients (HR 0.81; 95% CI, .37–1.75; P = .5915). However, a higher 1-year recurrence risk was observed in FLZR-CP patients (odds ratio, 7.37; 95% CI, 2.11–25.80; P = .0018). Our results suggest that fluconazole resistance is not associated with a higher mortality risk in patients with C. parapsilosis BSI, though 1-year recurrence rates were higher in the FLZR-CP group.

Candidemia is associated with a heavy burden of morbidity and mortality in hospitalized patients. The availability of blood culture results could require up to 48-72 h after blood draw; thus, early treatment decisions are made in the absence of a definite diagnosis. In this retrospective study, we assessed the performance of different supervised machine learning algorithms for the early differential diagnosis of candidemia and bacteremia in adult patients on a large dataset automatically extracted within the AUTO-CAND project. Overall, 12,483 episodes of candidemia (1275; 10%) or bacteremia (11,208; 90%) were included in the analysis. A random forest classifier achieved the best diagnostic performance for candidemia, with sensitivity 0.98 and specificity 0.65 on the training set (true skill statistic [TSS] = 0.63) and sensitivity 0.74 and specificity 0.57 on the test set (TSS = 0.31). Then, the random classifier was trained in the subgroup of patients with available serum β-D-glucan (BDG) and procalcitonin (PCT) values by exploiting the feature ranking learned in the entire dataset. Although no statistically significant differences were observed from the performance measures obtained by employing BDG and PCT alone, the performance measures of the classifier that included the features selected in the entire dataset, plus BDG and PCT, were the highest in most cases. Random forest classifiers trained on large datasets of automatically extracted data have the potential to improve current diagnostic algorithms for candidemia. However, further development through implementation of automatically extracted clinical features may be necessary to achieve crucial improvements.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening disease. In the intensive care unit (ICU), PJP is most frequently observed among patients with several conditions not related to the human immunodeficiency virus (HIV) infection. The primary objective of the present post-hoc analysis of a multicenter, multinational, retrospective study was to assess factors impacting prognosis in ICU patients with PJP through univariable and multivariable analyses. A total of 107 patients were included; 28 had proven PJP (26.2%), and 79 had presumptive PJP (73.8%). The overall 30-day mortality was 52.7% (95% confidence interval [CI] 42.1–62.2). In the multivariable analysis, metastatic solid tumor (hazard ratio [HR] 3.49; 95% CI 1.71–7.13, p < 0.001) and chronic liver disease (HR 2.44; 95% CI 1.03–5.80, p = 0.044) showed an independent association with 30-day mortality. The direction of effect remained consistent when center was added to the multivariable model as random effect. PJP mortality remains high in ICU patients. Conditions other than HIV infection are emerging not only as non-classical risk factors for PJP development, but also as important mortality predictors. A better understanding of the reasons underlying this evolving landscape could be crucial to improve PJP management and survival.