cefiderocol and Acinetobacter-Infections

We report on 11 critically ill burn patients treated with cefiderocol for carbapenem-resistant Acinetobacter baumannii infections. Clinical success was achieved in 36% and complicated by treatment-emergent resistance and interpatient transmission of cefiderocol-resistant A. baumannii. Resistant isolates harbored disrupted pirA and piuA genes that were not disrupted among susceptible isolates.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cefiderocol; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Microbial Sensitivity Tests

No clear evidence supports the use of cefiderocol as first line treatment in A. baumannii infections.. We conducted an observational retrospective/prospective multicenter study including all patients> 18 years with carbapenem-resistant A. baumannii (CRAB) infections treated with cefiderocol, from June 12021 to October 30 2022. Primary endpoint was 30-day mortality, secondary end-points the clinical and microbiological response at 7 days and at the end of treatment. Furthermore, we compared the clinical and microbiological outcomes among patients who received cefiderocol in monotherapy or in combination.. Thirty-eight patients with forty episodes of infection were included [mean age 65 years (SD+16.3), 75% males, 90% with hospital-acquired infections and 70% showing sepsis or septic shock]. The most common infections included unknown source or catheter-related bacteremia (45%) and pneumonia (40%). We observed at 7 days and at the end of therapy a rate of microbiological failure of 20% and 10%, respectively, and of clinical failure of 47.5% and 32.5%, respectively; the 30-day mortality rate was 47.5%. At multivariate analysis clinical failure at 7 days of treatment was the only independent predictor of 30-day mortality. Comparing monotherapy (used in 72.5%) vs. combination therapy (used in 27.5%), no differences were observed in mortality (51.7 vs 45.5%) and clinical (41.4 vs 63.7%) or microbiological failure (24.1 vs 9.1%).. The findings of this study reinforce the effectiveness of cefiderocol in CRAB infections, also as monotherapy. However, prospective multicenter studies with larger sample sizes and a control group treated with standard of care are needed to identify the best treatment for CRAB infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Cefiderocol; Female; Humans; Male; Prospective Studies; Retrospective Studies

Infections caused by Carbapenem-resistant

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cefiderocol; Humans; Iron; Microbial Sensitivity Tests

Cefiderocol is a novel siderophore cephalosporin with promising activity against most carbapenem-resistant Gram-negative bacteria (CRGNB). However, extensive postmarketing experiences are lacking. This study aimed to analyse the early experience on cefiderocol postmarketing use at three tertiary care hospitals in Italy.. We retrospectively included patients with infections caused by CRGNB treated with cefiderocol at three Italian tertiary care hospitals from 1 March 2021 to 30 June 2022. A multivariate Cox model was used to identify predictors of 30 day mortality. A propensity score (PS) analysis with inverse probability weighting (IPW) was also performed to compare the treatment effect of cefiderocol monotherapy (CM) versus combination regimens (CCRs).. The cohort included 142 patients (72% male, median age 67 years, with 89 cases of Acinetobacter baumannii infection, 22 cases of Klebsiella pneumoniae, 27 cases of Pseudomonas aeruginosa and 4 of other pathogens). The 30 day all-cause mortality was 37% (52/142). We found no association between bacterial species and mortality. In multivariate analysis, a Charlson Comorbidity Index >3 was an independent predictor of mortality (HR 5.02, 95% CI 2.37-10.66, P < 0.001). In contrast, polymicrobial infection (HR 0.41, 95% CI 0.21-0.82, P < 0.05) was associated with lower mortality. There was no significant difference in mortality between patients receiving CM (n = 70) and those receiving a CCR (n = 72) (33% versus 40%, respectively), even when adjusted for IPW-PS (HR 1.11, 95% CI 0.63-1.96, P = 0.71).. Real-life data confirm that cefiderocol is a promising option against carbapenem-resistant Gram-negative infections, even as monotherapy.

Topics: Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Cefiderocol; Cephalosporins; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Retrospective Studies

Carbapenem-resistant Acinetobacter baumannii (CRAB) can cause significant infections with limited treatment options available. Falcone et al. (https://doi.org/10.1128/aac.02142-21) describe a single-center retrospective study comparing clinical outcomes among patients with CRAB infections treated with cefiderocol-containing versus colistin-containing regimens. Patients who received cefiderocol-containing regimens had lower 30-day mortality, though there are several limitations raised here, which make interpretation and applicability difficult.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Cefiderocol; Cephalosporins; Humans; Microbial Sensitivity Tests; Retrospective Studies

We investigated activities of cefiderocol combination therapy against carbapenem-resistant Acinetobacter baumannii (CR-AB). A total of 123 clinical isolates of CR-AB, including 44 cefiderocol-resistant isolates were tested. Cefiderocol functioned synergistically with tigecycline in most cefiderocol-susceptible isolates (84.8%, 67/79), but not with colistin or meropenem by checkerboard method. Cefiderocol functioned synergistically with tigecycline, colistin, and meropenem in 90.9% (40/44), 47.7% (21/44), and 79.5% (35/44) cefiderocol-resistant isolates, respectively. The time-kill assay and the in vivo Galleria mellonella model confirmed these observations. In summary, cefiderocol combined with tigecycline showed synergistic effects against both cefiderocol-susceptible and -resistant CR-AB, suggesting a potentially valuable combination regimen.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Cefiderocol; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Tigecycline

Due to the poor permeability across Gram-negative bacterial membranes and the troublesome bacterial efflux mechanism, only a few GyrB/ParE inhibitors with potent activity against Gram-negative pathogens have been reported. Among them, pyrimido[4,5-

Topics: Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bacteria; DNA Gyrase; Drug Design; Drug Resistance, Multiple, Bacterial; Drug Stability; HEK293 Cells; Humans; Indoles; Microbial Sensitivity Tests; Microsomes, Liver; Molecular Docking Simulation; Molecular Structure; Pyrimidines; Rats; Structure-Activity Relationship

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Anti-Bacterial Agents; Cefiderocol; Cephalosporins; Compassionate Use Trials; Critical Illness; Drug Resistance, Multiple, Bacterial; Humans; Influenza, Human; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pneumonia; Treatment Outcome

Cefiderocol (S-649266), a novel siderophore cephalosporin, shows potent activity against carbapenem-resistant Gram-negative bacilli. In this study, we evaluated the efficacy of cefiderocol against carbapenem-resistant Gram-negative bacilli (

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; beta-Lactam Resistance; Cefiderocol; Cephalosporins; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Klebsiella Infections; Klebsiella pneumoniae; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections