Pharmacokinetics, efficacy and tolerance of cefoxitin in the treatment of cefoxitin-susceptible extended-spectrum beta-lactamase producing Enterobacterales infections in critically ill patients: a retrospective single-center study
Abstract Background Cefoxitin is active against some extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE), but has not been evaluated so far in the intensive care unit (ICU) settings. Data upon its pharmacokinetics (PK), tolerance and efficacy in critical conditions are scanty. We p...
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SpringerOpen
2022-09-01
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Series: | Annals of Intensive Care |
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Online Access: | https://doi.org/10.1186/s13613-022-01059-9 |
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author | Paul Chabert Judith Provoost Sabine Cohen Céline Dupieux-Chabert Laurent Bitker Tristan Ferry Sylvain Goutelle Jean-Christophe Richard |
author_facet | Paul Chabert Judith Provoost Sabine Cohen Céline Dupieux-Chabert Laurent Bitker Tristan Ferry Sylvain Goutelle Jean-Christophe Richard |
author_sort | Paul Chabert |
collection | DOAJ |
description | Abstract Background Cefoxitin is active against some extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE), but has not been evaluated so far in the intensive care unit (ICU) settings. Data upon its pharmacokinetics (PK), tolerance and efficacy in critical conditions are scanty. We performed a retrospective single-center study in a university hospital medical ICU, in subjects presenting with cefoxitin-susceptible ESBL-PE infection and treated with cefoxitin. The primary aim was to determine cefoxitin PK. Secondary endpoints were efficacy, tolerance, and emergence of cephamycin-resistance. Results Forty-one patients were included in this study, mainly with ESBL-PE pneumonia (35 patients, 85%). Cefoxitin was administered during a median [interquartile range (IQR)] duration of 5 [4–7] days. Cefoxitin serum concentrations strongly depended on renal function. Target serum concentration (> 5 × minimum inhibitory concentration (MIC) 24 h after cefoxitin onset was obtained in 34 patients (83%), using a median [IQR] daily dose of 6 [6–6] g with continuous administration. The standard dosage of 6 g/24 h was not sufficient to achieve the PK/PD target serum concentration for MIC up to 4–8 mg/L, except in patients with severe renal impairment and those treated with renal replacement therapy. Treatment failure occurred in 26 cases (63%), among whom 12 patients (29%) died, 13 patients (32%) were switched to alternative antibiotic therapy and 11 patients (27%) presented with relapse of infection with the same ESBL-PE. Serious adverse events attributed to cefoxitin occurred in 7 patients (17%). Acquisition of cephamycin-resistance with the same Enterobacterales was identified in 13 patients (32%), and was associated with underdosage. Conclusion Continuous administration of large doses of cefoxitin appears necessary to achieve the PK/PD target in patients with normal renal function. Renal status, MIC determination and therapeutic drug monitoring may be useful for treatment individualization in this setting. The treatment failure rate was 63%. The cefoxitin safety profile was favorable, but we observed a high rate of cephamycin-resistance emergence. |
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spelling | doaj.art-7ba14b2686d2460aba013f46de1c987c2022-12-22T03:52:08ZengSpringerOpenAnnals of Intensive Care2110-58202022-09-0112111310.1186/s13613-022-01059-9Pharmacokinetics, efficacy and tolerance of cefoxitin in the treatment of cefoxitin-susceptible extended-spectrum beta-lactamase producing Enterobacterales infections in critically ill patients: a retrospective single-center studyPaul Chabert0Judith Provoost1Sabine Cohen2Céline Dupieux-Chabert3Laurent Bitker4Tristan Ferry5Sylvain Goutelle6Jean-Christophe Richard7Hospices Civils de Lyon, Médecine Intensive – Réanimation, Hôpital de La Croix RousseHospices Civils de Lyon, Médecine Intensive – Réanimation, Hôpital de La Croix RousseUnité Fonctionnelle de Pharmacologie Spécialisée, Hospices Civils de Lyon, UM de Pharmaco-Toxicologie, Centre Hospitalier Lyon SudHospices Civils de Lyon, Institut Des Agents Infectieux, Hôpital de La Croix RousseHospices Civils de Lyon, Médecine Intensive – Réanimation, Hôpital de La Croix RousseHospices Civils de Lyon, Maladies Infectieuses et Tropicales, Hôpital de La Croix RousseUniversité de LyonHospices Civils de Lyon, Médecine Intensive – Réanimation, Hôpital de La Croix RousseAbstract Background Cefoxitin is active against some extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE), but has not been evaluated so far in the intensive care unit (ICU) settings. Data upon its pharmacokinetics (PK), tolerance and efficacy in critical conditions are scanty. We performed a retrospective single-center study in a university hospital medical ICU, in subjects presenting with cefoxitin-susceptible ESBL-PE infection and treated with cefoxitin. The primary aim was to determine cefoxitin PK. Secondary endpoints were efficacy, tolerance, and emergence of cephamycin-resistance. Results Forty-one patients were included in this study, mainly with ESBL-PE pneumonia (35 patients, 85%). Cefoxitin was administered during a median [interquartile range (IQR)] duration of 5 [4–7] days. Cefoxitin serum concentrations strongly depended on renal function. Target serum concentration (> 5 × minimum inhibitory concentration (MIC) 24 h after cefoxitin onset was obtained in 34 patients (83%), using a median [IQR] daily dose of 6 [6–6] g with continuous administration. The standard dosage of 6 g/24 h was not sufficient to achieve the PK/PD target serum concentration for MIC up to 4–8 mg/L, except in patients with severe renal impairment and those treated with renal replacement therapy. Treatment failure occurred in 26 cases (63%), among whom 12 patients (29%) died, 13 patients (32%) were switched to alternative antibiotic therapy and 11 patients (27%) presented with relapse of infection with the same ESBL-PE. Serious adverse events attributed to cefoxitin occurred in 7 patients (17%). Acquisition of cephamycin-resistance with the same Enterobacterales was identified in 13 patients (32%), and was associated with underdosage. Conclusion Continuous administration of large doses of cefoxitin appears necessary to achieve the PK/PD target in patients with normal renal function. Renal status, MIC determination and therapeutic drug monitoring may be useful for treatment individualization in this setting. The treatment failure rate was 63%. The cefoxitin safety profile was favorable, but we observed a high rate of cephamycin-resistance emergence.https://doi.org/10.1186/s13613-022-01059-9Antibacterial chemotherapyIntensive careHealthcare-associated pneumoniaExtended-spectrum beta-lactamaseCarbapenem-sparing agentsCefoxitin |
spellingShingle | Paul Chabert Judith Provoost Sabine Cohen Céline Dupieux-Chabert Laurent Bitker Tristan Ferry Sylvain Goutelle Jean-Christophe Richard Pharmacokinetics, efficacy and tolerance of cefoxitin in the treatment of cefoxitin-susceptible extended-spectrum beta-lactamase producing Enterobacterales infections in critically ill patients: a retrospective single-center study Annals of Intensive Care Antibacterial chemotherapy Intensive care Healthcare-associated pneumonia Extended-spectrum beta-lactamase Carbapenem-sparing agents Cefoxitin |
title | Pharmacokinetics, efficacy and tolerance of cefoxitin in the treatment of cefoxitin-susceptible extended-spectrum beta-lactamase producing Enterobacterales infections in critically ill patients: a retrospective single-center study |
title_full | Pharmacokinetics, efficacy and tolerance of cefoxitin in the treatment of cefoxitin-susceptible extended-spectrum beta-lactamase producing Enterobacterales infections in critically ill patients: a retrospective single-center study |
title_fullStr | Pharmacokinetics, efficacy and tolerance of cefoxitin in the treatment of cefoxitin-susceptible extended-spectrum beta-lactamase producing Enterobacterales infections in critically ill patients: a retrospective single-center study |
title_full_unstemmed | Pharmacokinetics, efficacy and tolerance of cefoxitin in the treatment of cefoxitin-susceptible extended-spectrum beta-lactamase producing Enterobacterales infections in critically ill patients: a retrospective single-center study |
title_short | Pharmacokinetics, efficacy and tolerance of cefoxitin in the treatment of cefoxitin-susceptible extended-spectrum beta-lactamase producing Enterobacterales infections in critically ill patients: a retrospective single-center study |
title_sort | pharmacokinetics efficacy and tolerance of cefoxitin in the treatment of cefoxitin susceptible extended spectrum beta lactamase producing enterobacterales infections in critically ill patients a retrospective single center study |
topic | Antibacterial chemotherapy Intensive care Healthcare-associated pneumonia Extended-spectrum beta-lactamase Carbapenem-sparing agents Cefoxitin |
url | https://doi.org/10.1186/s13613-022-01059-9 |
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