avibactam and Bacteremia

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.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacteremia; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Ceftazidime; Disease Susceptibility; Drug Combinations; Humans; Klebsiella Infections; Klebsiella pneumoniae; Retrospective Studies; Sepsis

To describe the clinical and microbiological features of a case of community-acquired infection by KPC-producing K. pneumoniae (KPCKP) resistant to ceftazidime/avibactam (CAZ-AVI).. Identification of microorganisms was performed with MALDI Biotyper CA System (BrukerDaltonics, Madrid, Spain). Antimicrobial susceptibility testing was performed using Sensitre EURGNCOL panels (Thermo Fisher Scientific, Madrid, Spain) and gradient strips (Etest, bioMérieux, Madrid, Spain) in the case of CAZ-AVI, using EUCAST breakpoints for interpretation. Whole genome sequencing of blood culture and rectal swab isolates was performed using the Illumina NovaSeq 6000 sequencing system, with 2 × 150-bp paired-end reads (Illumina, Inc.).. Blood culture and rectal swab KPCKP isolates were resistant to carbapenems and to CAZ-AVI. The blood culture isolate showed susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX), but the rectal swab culture isolate was resistant to this antibiotic. Both isolates belonged to clonal lineage ST512, harboured a single copy of bla. Resistance to ceftazidime-avibactam is an emerging nosocomial problem. This case shows that CAZ-AVI-resistant KPCKP strains may disseminate into the community and cause serious infections.

Topics: Azabicyclo Compounds; Bacteremia; Ceftazidime; Drug Combinations; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Azabicyclo Compounds; Aztreonam; Bacteremia; Humans; Stenotrophomonas maltophilia

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacteremia; Bacterial Proteins; beta-Lactamases; Ceftazidime; Drug Combinations; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

The primary objective was to describe clinical features, treatment and outcomes in patients with carbapenemase-producing Enterobacteriaceae (CPE) bacteremia. Additionally, patients treated with ceftazidime/avibactam (study group) were compared to the rest of the patients (comparator group) to determine the influence of the treatment in both crude mortality and clinical cure.. Multicenter and retrospective study that included patients with hematologic malignancies who had CPE bacteremia. A bivariate analysis was performed to compare the clinical variables between the study group and the control group.. 31 patients were included. Bacteremia was considered primary in 14 (45%) patients. Overall crude mortality at 30days was 45.2% (n=14). Mortality was more frequent when septic shock (78.6% vs 11.8%; p>0.001) and higher Pitt score (6+14 vs 1.5+4; p<0.01) were present. 8 patients (25.8%) received treatment with ceftazidime/avibactam. No significant differences in crude mortality were found between study and comparator groups (p=0.19). In contrast, patients in study group had higher clinical cure rates than the comparator group within 14days of initiating treatment (85.7% vs. 34.8%, respectively, p=0.031).. CPE bacteremia is associated with high mortality in patients with hematologic malignancies. Ceftazidime/avibactam may be an effective alternative for treating these patients.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacteremia; Bacterial Proteins; beta-Lactamases; Ceftazidime; Cohort Studies; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Hematologic Neoplasms; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Retrospective Studies; Treatment Outcome