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

Karruli, Arta; Massa, Alessia; Andini, Roberto; Marrazzo, Tommaso; Ruocco, Giuseppe; Zampino, Rosa; Durante‐Mangoni, Emanuele

doi:10.1016/j.ijantimicag.2023.106723

Cited by 13 publications

(7 citation statements)

References 18 publications

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“…Moreover, cefiderocol appeared to be well tolerated by patients in our study and had minimal adverse effects, such as mild AKI and mild transaminitis. This outcome is in alignment with the experiences of other centers [21]. This outcome could also have an important implication for using cefiderocol more widely in clinical practice due to its generally favorable side effect profile.…”

Section: Discussionsupporting

confidence: 81%

Clinical Outcome of Cefiderocol for Infections with Carbapenem-Resistant Organisms

Sajib

Monteforte

2023

Antibiotics

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Cefiderocol is a novel cephalosporin recently approved by the FDA to aid clinicians in the fight against multidrug-resistant (including carbapenem-resistant) gram-negative organisms. The primary objective of this study is to evaluate the 14- and 28-day mortality associated with cefiderocol. We performed a retrospective chart review of all adult patients admitted at Stony Brook University Hospital between October 2020 and December 2021 and received cefiderocol for at least 3 days. Patients were excluded if they received more than one course of cefiderocol therapy or remained hospitalized at the time of this study. A total of 22 patients met the inclusion criteria. The all-cause mortality on day 28 for all patients was 13.6%, whereas this rate for patients with BSI was 0%, with cUTI was 0% and with LRTI was 16.7%. The all-cause mortality on day 28 for patients who received the dual antibiotics (in conjunction with cefiderocol) was 0%, compared to 25% for patients who only received cefiderocol (p = 0.25). We noted treatment failure in two patients (9.1%). Our findings suggest that cefiderocol could possibly be associated with lower all-cause mortality than previously thought. In our study, we did not find any significant difference between cefiderocol’s use in combination with another antibacterial agent and its use as a monotherapy.

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Section: Discussionsupporting

confidence: 81%

Clinical Outcome of Cefiderocol for Infections with Carbapenem-Resistant Organisms

Sajib

Monteforte

2023

Antibiotics

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“…Moreover, cefiderocol has been shown an antibiotic with excellent tolerability in highly comorbid patients with a diversity of multidrug‐resistant infections. No adverse effects on renal, hepatic or bone marrow function were seen during cefiderocol treatment, confirming its wide margin of safety 22 …”

Section: Discussionmentioning

confidence: 61%

“…No adverse effects on renal, hepatic or bone marrow function were seen during cefiderocol treatment, confirming its wide margin of safety. 22 The patients' exposure to total cefiderocol was approximately 915 mg h/L based on the 3 arterial cefiderocol concentrations during CI. These 3 data points were measured over a time course of 21 h, calculating the area under the concentration-time curve (AUC) using the trapezoidal rule and extrapolated to the AUC over 24 h (AUC 0-24 ).…”

Section: Discussionmentioning

confidence: 99%

Continuous infusion of cefiderocol in a critically ill patient with continuous venovenous haemofiltration

Möhlmann,

van Luin,

Uijtendaal

et al. 2023

Brit J Clinical Pharma

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Cefiderocol is a broad spectrum cephalosporin antibiotic and is indicated in patients with difficult‐to‐treat Gram‐negative bacterial infections. Cefiderocol is applied as a 2 to 4 times daily prolonged 3‐hour infusion. The therapeutic target of cefiderocol suggests that continuous infusion (CI) may be advantageous, since it is more likely to achieve 100% of time of the unbound concentration above the minimal inhibitory concentration (fT>MIC). Yet, limited information on cefiderocol as CI has been assessed. We present a case of a critically ill 37‐year‐old woman with continuous venovenous haemofiltration (CVVH) treated with a CI of cefiderocol for multi‐drug resistant Pseudomonas aeruginosa. She received 4 grams per 24 hours, in accordance with the recommendations for the total daily dose during CVVH with an effluent flow rate of 2.1 to 3 L/h. We evaluated intraperitoneal, plasma arterial pre and post filter and ultrafiltrate (urine) total cefiderocol concentrations and discussed the pharmacokinetics in respect to the CVVH settings. The predicted unbound plasma concentrations during CI resulted in 6.8 to 9.5‐fold higher concentrations than the adopted MIC of 2 mg/L for cefiderocol against Pseudomonas aeruginosa. The optimal 100% fT>MIC target of cefiderocol was met during the sampling period, suggesting adequate exposure during the total treatment period. The obtained intraperitoneal concentration indicated adequate cefiderocol exposure at the site of infection. Continuous infusion of 4 grams cefiderocol per 24 hours led to sufficient plasma concentrations in our anuric critically ill patient treated with CVVH. This case is supportive to the use of cefiderocol as continuous infusion.

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“…However, only one of the 3 trials [9] specifically included patients with infections due to carbapenem-resistant bacteria. Instead, case reports and series showed that cefiderocol is a promising therapeutic agent in carbapenem-resistant infections [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Outcome of patients with Carbapenem-Resistant Acinetobacter baumannii infections treated with cefiderocol: a multicenter observational study

Calò

Onorato

Luca

et al. 2023

Preprint

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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 1 2021 to October 30 2022. Primary endpoint was in-hospital 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: Forty infections 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 in-hospital mortality rate was 50%. At multivariate analysis McCabe score of 2-3 and clinical failure at 7 days of treatment were the only independent predictors of in-hospital 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.

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

Cited by 13 publications

References 18 publications

Clinical Outcome of Cefiderocol for Infections with Carbapenem-Resistant Organisms

Clinical Outcome of Cefiderocol for Infections with Carbapenem-Resistant Organisms

Continuous infusion of cefiderocol in a critically ill patient with continuous venovenous haemofiltration

Outcome of patients with Carbapenem-Resistant Acinetobacter baumannii infections treated with cefiderocol: a multicenter observational study

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