Clinical efficacy and safety of cefiderocol for resistant Gram-negative infections: a real-life, single-centre experience.

OBJECTIVES: Cefiderocol is a 'siderophore' cephalosporin active against Gram-negative bacteria, including carbapenem-resistant strains. Data on the use of cefiderocol in real life are limited. We evaluated the efficacy and safety of cefiderocol in the context of our hospital clinical practice. METHODS: This was a single-centre, observational, retrospective clinical study. We collected data for all patients who received cefiderocol therapy in our hospital, with a focus on clinical outcomes and adverse events. RESULTS: The study cohort included 28 patients, with a median age of 73 years (25-83 years) and a high burden of co-morbidities. Up to 45 Gram-negative isolates were cultured from the study patients, the most common pathogen being Acinetobacter baumannii (31.1%). Cefiderocol was mostly prescribed for pneumonia (37.8% of cases), bloodstream infection (24.4%), urinary tract infection (22.2%) and intra-abdominal infection (20%), and largely as salvage therapy (92.8%). Of the 18 patients for whom follow-up cultures were available, 14 (77.8%) achieved eradication of the causative micro-organism. Therapeutic success (improvement/resolution of infection) occurred in 64.3% of cases at 7 days and 50% at 14 days from treatment start. Treatment failed in 9 cases (32.1%). No effects on kidney, liver or bone marrow function were observed. CONCLUSIONS: Cefiderocol showed fair efficacy and excellent tolerability in highly co-morbid patients with a range of multiresistant infections. It may be an option for infections due to colistin-resistant pathogens, when other regimens fail or in cases at risk of kidney dysfunction.

Outcome of patients with carbapenem-resistant Acinetobacter baumannii infections treated with cefiderocol: A multicenter observational study.

BACKGROUND: No clear evidence supports the use of cefiderocol as first line treatment in A. baumannii infections. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Clinical Characteristics and Outcome of MDR/XDR Bacterial Infections in a Neuromuscular Semi-Intensive/Sub-Intensive Care Unit.

(1) Background: The aim of this study was to assess the clinical and microbiological characteristics of multidrug-resistant infections in a neuromuscular semi-intensive/sub-intensive care unit; (2) Methods: Retrospective analysis on data from 18 patients with NMD with proven MDRO/XDRO colonisation/infection from August 2021 to March 2022 was carried out; (3) Results: Ten patients were males (55.6%), with a median age of 54 years, and there were fourteen patients (77.8%) with amyotrophic lateral sclerosis. All patients had at least one invasive device. Ten (55.6%) patients developed MDRO/XDRO infection (with a median time of 24 days) while six (33.3%) were colonised. The Charlson comorbidity index was >2 in both groups but higher in the infected compared with the colonised (4.5 vs. 3). Infected patients were mostly females (seven patients) with a median age of 62 years. The most common pathogens were Acinetobacter baumannii and Pseudomonas aeruginosa, infecting four (28.6%) patients each. Of eighteen infectious episodes, nine were pneumonia (hospital-acquired in seven cases). Colistin was the most commonly active antibiotic while carbapenems were largely inactive. Eradication of infection occurred in seven infectious episodes (38.9%). None of those with infection died; (4) Conclusions: MDRO/XDRO infections are common in patients with neuromuscular diseases, with carbapenem-resistant non-fermenting Gram-negative bacilli prevailing. These infections were numerically associated with the female sex, greater age, and comorbidities. Both eradication and infection-related mortality appeared low. We highlight the importance of infection prevention in this vulnerable population.