Cefepime/Sulbactam — A New Innovative Antibiotic for In-Hospital Treatment of Severe Infections and the Implementation of Carbapenem-Replacement Strategy to Contain Antibiotic Resistance

Cefepime/sulbactam is a combined antibiotic consisting of the 4 th generation cephalosporin cefepime and the beta-lactamase inhibitor sulbactam in 1:1 ratio. Cefepime/sulbactam antibiotic was developed in Russia in 2006, it had passed preclinical and clinical studies, was approved for medical use, a...

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Main Authors: S. V. Yakovlev, M. P. Suvorova, A. O. Bykov
Format: Article
Language:Russian
Published: LLC "Publishing House OKI" 2021-06-01
Series:Антибиотики и Химиотерапия
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Online Access:https://www.antibiotics-chemotherapy.ru/jour/article/view/807
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author S. V. Yakovlev
M. P. Suvorova
A. O. Bykov
author_facet S. V. Yakovlev
M. P. Suvorova
A. O. Bykov
author_sort S. V. Yakovlev
collection DOAJ
description Cefepime/sulbactam is a combined antibiotic consisting of the 4 th generation cephalosporin cefepime and the beta-lactamase inhibitor sulbactam in 1:1 ratio. Cefepime/sulbactam antibiotic was developed in Russia in 2006, it had passed preclinical and clinical studies, was approved for medical use, and has been produced in Russia since 2019. Cefepime has a wide spectrum of antimicrobial activity against gram-positive and gram-negative microorganisms, sulbactam adds two clinically important pathogens to the antimicrobial spectrum of cefepime — Acinetobacter baumannii and Bacteroides fragilis. In addition, sulbactam protects cefepime from hydrolysis by class A broad- and extended-spectrum beta-lactamases, and cefepime itself is stable against class C chromosomal beta-lactamases and partially stable to OXA-type class D carbapenemases. In vitro studies have shown that most clinical strains of ESBL-producing Klebsiella pneumoniae, Escherichia coli, Proteus spp. are sensitive to cefepime/sulbactam, as well as some strains of K.pneumoniae and A.baumannii that are resistant to carbapenems as a result of the production of class D carbapenemases. The efficacy and safety of cefepime/sulbactam have been determined in three clinical studies. Clinical and bacteriological efficacy of the drug was 97.9% and 97.6% in patients with acute community-acquired pyelonephritis. In the MAXI-19 multicenter study, the clinical efficacy of cefepime/sulbactam in patients with intra-abdominal infections, nosocomial pneumonia, and ventilator-associated pneumonia was 78.4, 90.3, and 80.7%, respectively. A comparative study examined the efficacy of cefepime/sulbactam and carbapenems in severe nosocomial infections (84% of patients had sepsis or septic shock). Clinical efficacy of cefepime/sulbactam and carbapenems was high and did not significantly differ (71% vs. 62%), as well as the bacteriological efficacy — 87% vs. 73%, while typical hospital pathogens characterized by MDR or XDR were identified in the majority of patients (most often — K.pneumoniae, A.baumannii, E.coli). During treatment with carbapenems, carbapenem-resistant bacteria were detected significantly more often (74.5%, most often A.baumannii — 44.7%, K.pneumoniae — 38.3%), compared to cefepime/sulbactam (20.0%, P.aeruginosa and K.pneumoniae, both at 15.5%), P=0.0001. The risk of superinfection was also significantly higher with carbapenems than with cefepime/sulbactam (53.3% vs. 22.2%, P=0.001). For severe infections, cefepime/sulbactam was administered at a dose of 4 g (2 g + 2 g) every 12 hours or 2 g (1 g + 1 g) every 8 hours. Currently, cefepime/sulbactam should be considered as a reliable option for the treatment of severe infections in the hospital as a carbapenem-replacement strategy to reduce the risks of selection of carbapenem-resistant gram-negative bacteria.
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spelling doaj-art-143f840f140c42408d729fa3b495d8a72025-08-20T03:59:08ZrusLLC "Publishing House OKI"Антибиотики и Химиотерапия0235-29902021-06-01663-4829810.37489/0235-2990-2021-66-3-4-82-98779Cefepime/Sulbactam — A New Innovative Antibiotic for In-Hospital Treatment of Severe Infections and the Implementation of Carbapenem-Replacement Strategy to Contain Antibiotic ResistanceS. V. Yakovlev0M. P. Suvorova1A. O. Bykov2I. M. Sechenov First Moscow State Medical University; S. S. Yudin City Clinical HospitalI. M. Sechenov First Moscow State Medical University; S. S. Yudin City Clinical HospitalPirogov Russian National Research Medical University; City Clinical Hospital No. 40Cefepime/sulbactam is a combined antibiotic consisting of the 4 th generation cephalosporin cefepime and the beta-lactamase inhibitor sulbactam in 1:1 ratio. Cefepime/sulbactam antibiotic was developed in Russia in 2006, it had passed preclinical and clinical studies, was approved for medical use, and has been produced in Russia since 2019. Cefepime has a wide spectrum of antimicrobial activity against gram-positive and gram-negative microorganisms, sulbactam adds two clinically important pathogens to the antimicrobial spectrum of cefepime — Acinetobacter baumannii and Bacteroides fragilis. In addition, sulbactam protects cefepime from hydrolysis by class A broad- and extended-spectrum beta-lactamases, and cefepime itself is stable against class C chromosomal beta-lactamases and partially stable to OXA-type class D carbapenemases. In vitro studies have shown that most clinical strains of ESBL-producing Klebsiella pneumoniae, Escherichia coli, Proteus spp. are sensitive to cefepime/sulbactam, as well as some strains of K.pneumoniae and A.baumannii that are resistant to carbapenems as a result of the production of class D carbapenemases. The efficacy and safety of cefepime/sulbactam have been determined in three clinical studies. Clinical and bacteriological efficacy of the drug was 97.9% and 97.6% in patients with acute community-acquired pyelonephritis. In the MAXI-19 multicenter study, the clinical efficacy of cefepime/sulbactam in patients with intra-abdominal infections, nosocomial pneumonia, and ventilator-associated pneumonia was 78.4, 90.3, and 80.7%, respectively. A comparative study examined the efficacy of cefepime/sulbactam and carbapenems in severe nosocomial infections (84% of patients had sepsis or septic shock). Clinical efficacy of cefepime/sulbactam and carbapenems was high and did not significantly differ (71% vs. 62%), as well as the bacteriological efficacy — 87% vs. 73%, while typical hospital pathogens characterized by MDR or XDR were identified in the majority of patients (most often — K.pneumoniae, A.baumannii, E.coli). During treatment with carbapenems, carbapenem-resistant bacteria were detected significantly more often (74.5%, most often A.baumannii — 44.7%, K.pneumoniae — 38.3%), compared to cefepime/sulbactam (20.0%, P.aeruginosa and K.pneumoniae, both at 15.5%), P=0.0001. The risk of superinfection was also significantly higher with carbapenems than with cefepime/sulbactam (53.3% vs. 22.2%, P=0.001). For severe infections, cefepime/sulbactam was administered at a dose of 4 g (2 g + 2 g) every 12 hours or 2 g (1 g + 1 g) every 8 hours. Currently, cefepime/sulbactam should be considered as a reliable option for the treatment of severe infections in the hospital as a carbapenem-replacement strategy to reduce the risks of selection of carbapenem-resistant gram-negative bacteria.https://www.antibiotics-chemotherapy.ru/jour/article/view/807cefepime/sulbactambeta-lactam/beta-lactamase inhibitor combinationmulti-drug resistant pathogensextensively-drug resistant pathogensselection of resistancecarbapenem-replacement strategycarbapenem-sparing strategy
spellingShingle S. V. Yakovlev
M. P. Suvorova
A. O. Bykov
Cefepime/Sulbactam — A New Innovative Antibiotic for In-Hospital Treatment of Severe Infections and the Implementation of Carbapenem-Replacement Strategy to Contain Antibiotic Resistance
Антибиотики и Химиотерапия
cefepime/sulbactam
beta-lactam/beta-lactamase inhibitor combination
multi-drug resistant pathogens
extensively-drug resistant pathogens
selection of resistance
carbapenem-replacement strategy
carbapenem-sparing strategy
title Cefepime/Sulbactam — A New Innovative Antibiotic for In-Hospital Treatment of Severe Infections and the Implementation of Carbapenem-Replacement Strategy to Contain Antibiotic Resistance
title_full Cefepime/Sulbactam — A New Innovative Antibiotic for In-Hospital Treatment of Severe Infections and the Implementation of Carbapenem-Replacement Strategy to Contain Antibiotic Resistance
title_fullStr Cefepime/Sulbactam — A New Innovative Antibiotic for In-Hospital Treatment of Severe Infections and the Implementation of Carbapenem-Replacement Strategy to Contain Antibiotic Resistance
title_full_unstemmed Cefepime/Sulbactam — A New Innovative Antibiotic for In-Hospital Treatment of Severe Infections and the Implementation of Carbapenem-Replacement Strategy to Contain Antibiotic Resistance
title_short Cefepime/Sulbactam — A New Innovative Antibiotic for In-Hospital Treatment of Severe Infections and the Implementation of Carbapenem-Replacement Strategy to Contain Antibiotic Resistance
title_sort cefepime sulbactam a new innovative antibiotic for in hospital treatment of severe infections and the implementation of carbapenem replacement strategy to contain antibiotic resistance
topic cefepime/sulbactam
beta-lactam/beta-lactamase inhibitor combination
multi-drug resistant pathogens
extensively-drug resistant pathogens
selection of resistance
carbapenem-replacement strategy
carbapenem-sparing strategy
url https://www.antibiotics-chemotherapy.ru/jour/article/view/807
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AT mpsuvorova cefepimesulbactamanewinnovativeantibioticforinhospitaltreatmentofsevereinfectionsandtheimplementationofcarbapenemreplacementstrategytocontainantibioticresistance
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