Cefiderocol for compassionate use in the treatment of complicated infections caused by extensively and pan-resistant Acinetobacter baumannii

Oliva, Alessandra; Ceccarelli, Giancarlo; Angelis, Massimiliano De; Sacco, Federica; Miele, Maria Claudia; Mastroianni, Claudio Maria; Venditti, Mario

doi:10.1016/j.jgar.2020.09.019

Cited by 48 publications

(54 citation statements)

References 20 publications

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“… 23 However, as stated in the introduction, current clinical data are extremely controversial. 7 , 8 , 10 , 22 We found that cefiderocol remained as a protective factor against mortality in our multivariable analysis but at a non-statistically significant value. It remains to be established whether the lack of significance was true or related to the limitations of our study.…”

Section: Discussionmentioning

confidence: 53%

“…A compassionate programme allowed access to cefiderocol during the study period. In such contexts, administrative and ethical issues may cause a delay in drug onset that is crucial in time-dependent severe infections 22 such as septic shock, which was present in 41% of our patients. For this reason, this variable was also included in the multivariable analysis.…”

Section: Discussionmentioning

confidence: 99%

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Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: a multicentre cohort study

Pascale

Pasquini

Bartoletti

et al. 2021

JAC-Antimicrobial Resistance

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Objectives To analyse the impact of cefiderocol use on outcome in patients admitted to the ICU for severe COVID-19 and further diagnosed with carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. Methods Retrospective multicentre observational study was performed at four Italian hospitals, from January 2020 to April 2021. Adult patients admitted to ICU for severe COVID-19 and further diagnosed with CR-Ab infections were enrolled. Patients treated with cefiderocol, as compassionate use, for at least 72 h were compared with those receiving alternative regimens. Primary endpoint was all-cause 28 day mortality. The impact of cefiderocol on mortality was evaluated by multivariable Cox regression model. Results In total, 107 patients were enrolled (76% male, median age 65 years). The median time from ICU admission to CR-Ab infection diagnosis was 14 (IQR 8–20) days, and the main types of CR-Ab infections were bloodstream infection (58%) and lower respiratory tract infection (41%). Cefiderocol was administered to 42 patients within a median of 2 (IQR 1–4) days after CR-Ab infection diagnosis and as monotherapy in all cases. The remaining patients received colistin, mostly (82%) administered as combination therapy. All-cause 28 day mortality rate was 57%, without differences between groups (cefiderocol 55% versus colistin 58% P = 0.70). In multivariable analysis, the independent risk factor for mortality was SOFA score (HR 1.24, 95% CI 1.15–1.38, P < 0.001). Cefiderocol was associated with a non-significant lower mortality risk (HR 0.64, 95% CI 0.38–1.08, P = 0.10). Conclusions Our study confirms the potential role of cefiderocol in the treatment of CR-Ab infection, but larger clinical studies are needed.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: a multicentre cohort study

Pascale

Pasquini

Bartoletti

et al. 2021

JAC-Antimicrobial Resistance

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“…Real-life experiences with CFDC are limited but slowly expanding. In a case series, three critically ill patients with DTR- Ab infection obtained clinical improvement and microbiological eradication [ 73 ]. An Italian casuistry included 10 ICU subjects that received compassionate use of CFDC after failure to respond to previous therapy for CR non-fermenting GNs and CRE.…”

Section: Resultsmentioning

confidence: 99%

“…At present, DTR- Ab is probably the pathogen with the most limited available treatment options. In vitro and early clinical evidence showed CFDC to be a promising and effective tool for Acinetobacter infections [ 60 , 73 , 74 ].…”

Section: Algorithm Constructionmentioning

confidence: 99%

Place in Therapy of the Newly Available Armamentarium for Multi-Drug-Resistant Gram-Negative Pathogens: Proposal of a Prescription Algorithm

et al. 2021

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The worldwide propagation of antimicrobial resistance represents one of the biggest threats to global health and development. Multi-drug-resistant organisms (MDROs), including carbapenem-resistant non-fermenting Gram-negatives and Enterobacterales, present a heterogeneous and mutating spread. Infections by MDRO are often associated with an unfavorable outcome, especially among critically ill populations. The polymyxins represented the backbone of antibiotic regimens for Gram-negative MDROs in recent decades, but their use presents multiple pitfalls. Luckily, new agents with potent activity against MDROs have become available in recent times and more are yet to come. Now, we have the duty to make the best use of these new therapeutic tools in order not to prematurely compromise their effectiveness and at the same time improve patients’ outcomes. We reviewed the current literature on ceftazidime/avibactam, meropenem/vaborbactam and cefiderocol, focusing on antimicrobial spectrum, on the prevalence and mechanisms of resistance development and on the main in vitro and clinical experiences available so far. Subsequently, we performed a step-by-step construction of a speculative algorithm for a reasoned prescription of these new antibiotics, contemplating both empirical and targeted use. Attention was specifically posed on patients with life-risk conditions and in settings with elevated prevalence of MDRO.

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“…Case reports and case series of patients with severe GNB infections treated with cefiderocol in compassionate use are detailed in Table 3. [54][55][56][57][58][59][60][61][62][63][64][65][66] All these cases highlight unique challenges in managing patients infected by MDR-GNB including MBL-producing GNB.…”

Section: Case Reports and Case Seriesmentioning

confidence: 99%

Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data

Giacobbe¹,

Ciacco²,

Girmenia³

et al. 2020

IDR

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Cefiderocol for compassionate use in the treatment of complicated infections caused by extensively and pan-resistant Acinetobacter baumannii

Cited by 48 publications

References 20 publications

Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: a multicentre cohort study

Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: a multicentre cohort study

Place in Therapy of the Newly Available Armamentarium for Multi-Drug-Resistant Gram-Negative Pathogens: Proposal of a Prescription Algorithm

Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data

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