Cefiderocol utilization in lung transplant recipients at a single center.

BACKGROUND: Multidrug-resistant organisms are increasing and are a significant cause of mortality among lung transplant recipients (LTRs). To assist with this issue, novel pharmacotherapies are being developed. This study describes the utilization of a novel antibiotic, cefiderocol (FDC), in LTRs where limited data exists in the current literature. We primarily assessed the clinical indications, duration of therapy, resistance, and adverse effects. METHODS: Conducted as a single-center retrospective review, this study included adult LTRs who received FDC for at least 24 h. Data, extracted from electronic medical records, encompassed patient demographics, transplant history, antimicrobial dosing, adverse effects, bacterial cultures, and outcomes. The research protocol received institutional review board approval. RESULTS: FDC exhibited effectiveness against multidrug-resistant Pseudomonas aeruginosa, with 26% 30-day mortality and microbiological clearance observed in nine out of 13 cases. Notably, FDC was used in diverse clinical settings, including for prophylaxis, empiric, and targeted treatment. CONCLUSION: Further studies are needed to evaluate optimal clinical indications for FDC use in LTRs.

Cefiderocol: early clinical experience for multi-drug resistant gram-negative infections.

Multi-drug resistant gram-negative bacteria present a significant global health threat. Cefiderocol (CFDC), a siderophore cephalosporin, has shown potential in combating this threat, but with the currently available data, its role in therapy remains poorly defined. This multi-center, retrospective cohort study evaluated the real-world application of CFDC across six U.S. medical centers from January 2018 to May 2023. Patients aged ≥18 years and who had received ≥72 hours of CFDC were included. The primary outcome was a composite of clinical success: survival at 30 days, absence of symptomatic microbiologic recurrence at 30 days following CFDC treatment initiation, and resolution of signs and symptoms. Secondary outcomes included time to CFDC therapy and on-treatment non-susceptibility to CFDC. A total of 112 patients were included, with median (interquartile range [IQR]) APACHE II scores of 15 (19-18). Clinical success was observed in 68.8% of patients, with a mortality rate of 16.1% and comparable success rates across patients infected with carbapenem-resistant gram-negative infections. The most common isolated organisms were Pseudomonas aeruginosa (61/112, 54.5%, of which 55/61 were carbapenem-resistant) and carbapenem-resistant Acinetobacter baumannii (32/112, 28.6%). Median (IQR) time to CFDC therapy was 77 (14-141) hours. Two patients experienced a non-anaphylactic rash as an adverse drug reaction. On-treatment non-susceptibility to CFDC was found in six patients, notably due to P. aeruginosa and A. baumannii.IMPORTANCECFDC was safe and clinically effective as a monotherapy or in combination in treating a variety of carbapenem-resistant gram-negative infections. Further prospective studies are warranted to confirm these findings.

Evaluation of dalbavancin alone and in combination with ß-lactam antibiotics against resistant phenotypes of Staphylococcus aureus.

Background: Emergence of reduced susceptibility to vancomycin warrants the development of new antimicrobial agents for the treatment of MRSA. We evaluated the activity of dalbavancin, a novel lipoglycopeptide antibiotic, both alone and combined with ß-lactams, in combination MIC testing and time-kill assays against resistant phenotypes of Staphylococcus aureus. Methods: S. aureus isolates included 50 organisms with varying susceptibility patterns. Dalbavancin was tested alone and in combination with five ß-lactams: cefazolin, cefepime, ceftaroline, ertapenem and oxacillin. MIC values of the antibiotics were determined for all isolates. After initial MIC testing, dalbavancin MICs were determined in the presence of 0.5 × MIC of each ß-lactam to determine the effect of each ß-lactam on dalbavancin MIC. Time-kill assays were performed with dalbavancin and ß-lactams tested at 0.5 × MIC for randomly selected organisms representing each MRSA phenotype. Time-kill curves were generated by plotting mean colony counts (log10 cfu/mL) versus time. Results: Dalbavancin MIC50 was 0.0313 mg/L and MIC90 was 0.0625 mg/L. Dalbavancin MICs decreased by zero to greater than five 2-fold dilutions in combination with each ß-lactam. In time-kill assays, dalbavancin was synergistic with cefazolin, cefepime and ertapenem against all strains and the combination of dalbavancin and ceftaroline was synergistic against all but one. The combination of dalbavancin and oxacillin was synergistic against 5/8 strains. Conclusions: Dalbavancin was active against all MRSA strains tested, including heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus, daptomycin-non-susceptible and linezolid-resistant isolates. The synergy demonstrated against these organisms supports the use of dalbavancin in combination with ß-lactams against resistant phenotypes of S. aureus. Further evaluation is warranted.