Novel beta-lactam/beta-lactamase inhibitor (BIBLI) combinations are commercially available and have been used for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Continuous surveillance of susceptibility profiles and resistance mechanism identification are necessary to monitor the evolution of resistance within these agents. The purpose of this study was to evaluate the susceptibility rates of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in CRKP isolated from patients with bloodstream infections who underwent screening for a randomized clinical trial in Brazil. Minimum inhibitory concentrations (MICs) were determined for meropenem, ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam using the gradient diffusion strip method. Carbapenemase genes were detected by multiplex real-time polymerase chain reaction. Klebsiella pneumoniae carbapenemase (KPC)-producing isolates showing resistance to any BLBLI and New Delhi Metallo-beta-lactamase (NDM)-producing isolates with susceptibility to any BLBLI isolates were further submitted for whole-genome sequencing. From a total of 69 CRKP isolates, 39 were positive for bla_KPC, 19 for bla_NDM and 11 for bla_KPC and bla_NDM. KPC-producing isolates demonstrated susceptibility rates above 94 % for all BLBLIs. Two isolates with resistance to meropenem/vaborbactam demonstrated a Gly and Asp duplication at the porin OmpK36 as well as a truncated OmpK35. All NDM-producing isolates, including KPC and NDM coproducers, demonstrated susceptibility rates to ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam of 0 %, 9.1-21.1 % and 9.1-26.3 %, respectively. Five NDM-producing isolates that presented susceptibility to BLBLIs also had porin alterations CONCLUSIONS: This study showed that, although high susceptibility rates to BLBLIs were found, KPC-2 isolates were able to demonstrate resistance probably as a result of porin mutations. Additionally, NDM-1 isolates showed susceptibility to BLBLIs in vitro.

This study aimed to evaluate the clinical and microbiological risk factors associated with mortality in patients treated with ceftazidime-avibactam for carbapenem-resistant gram-negative bacterial infections. This multicentric prospective cohort study included hospitalized adult patients with a microbiologically confirmed infection treated with ceftazidime-avibactam for ≥48 hours. The clinical and microbiological risk factors for 30-day mortality were evaluated using a Cox regression model. Of the 193 patients evaluated from the five tertiary hospitals, 127 were included in the study. Thirty-five patients (27.5 %) died within 30 days. Infections with AmpC beta-lactamase-carrying bacteria were independently related to 30-day mortality (adjusted hazard ratio [aHR] 2.49, 95% confidence interval [CI] 1.28-4.84, P < 0.01) after adjusting for time from infection to antimicrobial prescription (P = 0.04). Further, these bacterial infections were also related to higher in-hospital mortality (aHR 2.17, 95% CI 1.24-3.78, P < 0.01). Only one patient developed resistance to ceftazidime-avibactam during treatment. Treatment with ceftazidime-avibactam had worse clinical outcomes in patients with infections with bacteria with chromosomally encoded AmpC beta-lactamase. However, these findings should be confirmed in future studies.

Determination of the susceptibility profile of isolates of Candida from blood culture bottles is extremely important for correctly guiding patient pharmacotherapy. The aim of this study was to compare the results of analysis of Candida isolated directly from blood culture bottles by the VITEK MS MALDI-TOF identification system and the fluconazole disk diffusion assay with those of standard identification methods. Testing directly from the bottle allowed results 24 to 48 hours quicker than the standard method. There was a categorical agreement of 51.64 (47 of 91 samples) between the results of analysis directly from the bottle and analysis by the standard method. Regarding species identification, there was 96.15 agreement for Candida parapsilosis (25 of 26 samples). Categorical agreement between the rapid and standard disk diffusion methods was 95, and the agreement between the rapid disk diffusion method and the broth microdilution method was 97. Only minor errors in the rapid method were observed: 3 (5) in the standard disk diffusion method and 2 (3) in the broth microdilution method. Our study concluded that the rapid disk diffusion method for fluconazole is a fast, easy, reproducible, and consistent method. Its timely implementation for testing antifungal agents in the clinical microbiology laboratory can help reduce profile release times, thus helping to determine the most appropriate antifungal treatment.

Background/Objectives: Klebsiella spp., particularly K. pneumoniae, are major opportunistic pathogens in healthcare settings driven by carbapenemase- and ESBL-producing strains. We assessed antimicrobial resistance and biofilm formation abilities in Klebsiella spp. from a Brazilian tertiary hospital and related environments and characterized capsular types. Methods: Over six months (July–December 2023), 303 carbapenem-resistant Klebsiella spp. were collected from clinical specimens (n = 198), ICU/non-ICU surfaces (n = 79), hospital sewage (n = 22), and stream water (n = 4). Species were identified by MALDI-TOF. Susceptibility testing covered eight antibiotic classes, focusing on carbapenems and polymyxin B. Biofilm formation was quantified by crystal violet, and capsular typing used wzi/K-locus approaches. Results: Most isolates (70.95%) had meropenem MICs ≥ 128 μg/mL, while 77.6% (n = 235) remained susceptible to polymyxin B. Resistance profiles largely consisted of extensive drug resistance (95.4%), with 1.3% exhibiting pandrug resistance, including isolates from bed rails. Biofilm formation was detected in 96.7% of isolates, mainly weak (67.6%) or moderate (28%), with 4.4% being strong producers. Among the Klebsiella isolates analyzed, 21 K types were identified with an uneven distribution dominated by K64, followed by K24, K173, and K50. K75 was the only K type detected across all sources—clinical isolates, bed-rail surfaces (non-ICU), wastewater, and fluvial water. Conclusions: Carbapenem-resistant Klebsiella spp. exhibited widespread resistance, with residual susceptibility to aminoglycosides, ceftazidime–avibactam, and polymyxins. Environmental reservoirs—hospital surfaces, sewage, and stream water—harbored resistant biofilm producers, reinforcing their role in persistence and dissemination. K-typing revealed concentrated distribution (predominantly K64) and cross-source K75. These findings underscore the urgency of integrated strategies combining molecular surveillance, antimicrobial stewardship, and environmental control.