Effectiveness, safety and risk of selection of carbapenem-resistant bacteria in the treatment of severe in-hospital infections with cefepime/sulbactam in comparison with carbapenems

Suvorova M.P.

GBOU VPO "Pervyĭ MGMU im. I.M. Sechenova" Minzdrava Rossii;
gorodskaia klinicheskaia bol'nitsa #7 DZ Moskvy

Bykov A.O.

Pirogov Russian National Research Medical University, Moscow, Russia

Yakovlev S.V.

Department of Pediatric Oromaxillofacial Surgery Faculty of Stomatology Moscow State University of Medicine and Dentistry named after A.I. Evdokimov Russian Ministry of Health, Moscow, Russia

Protsenko D.N.

GBUZ «City clinical hospital named after S.S. Yudin» of Moscow health department, Moscow, Russia;
FGBOU VO «Russian national research medical University named after N.I. Pirogov» of Ministry of health of Russia, Moscow, Russia

SPIN RSCI: 1019-8216
Scopus AuthorID: 6603277055
ResearcherID: P-9224-2018
ORCID: 0000-0002-5166-3280

Sychev I.N.

Yudin Municipal Clinical Hospital, Moscow, Russia

Mirzakhamidova S.S.

Yudin Municipal Clinical Hospital, Moscow, Russia

Burmistrova E.N.

GBOU VPO "Pervyĭ MGMU im. I.M. Sechenova" Minzdrava Rossii;
gorodskaia klinicheskaia bol'nitsa #7 DZ Moskvy

Effectiveness, safety and risk of selection of carbapenem-resistant bacteria in the treatment of severe in-hospital infections with cefepime/sulbactam in comparison with carbapenems

Authors:

Suvorova M.P., Bykov A.O., Yakovlev S.V., Protsenko D.N., Sychev I.N., Mirzakhamidova S.S., Burmistrova E.N.

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Journal: Russian Journal of Anesthesiology and Reanimatology. 2020;(3): 59‑69

DOI: 10.17116/anaesthesiology202003159

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To cite this article:

Suvorova MP, Bykov AO, Yakovlev SV, Protsenko DN, Sychev IN, Mirzakhamidova SS, Burmistrova EN. Effectiveness, safety and risk of selection of carbapenem-resistant bacteria in the treatment of severe in-hospital infections with cefepime/sulbactam in comparison with carbapenems. Russian Journal of Anesthesiology and Reanimatology. 2020;(3):59‑69. (In Russ.)
https://doi.org/10.17116/anaesthesiology202003159

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Objective. To analyze application of a new combination of beta-lactam antibiotic and beta-lactamase inhibitor (cefepime/sulbactam) as a carbapenem-replacement technology for the treatment of severe in-hospital infections. Material and methods. We conducted a single-center, comparative, retrospective, non-interventional study. The trial included patients who received cefepime/sulbactam or carbapenem as a first-line treatment in an emergency hospital for the period from July to November 2019. The target number of patients who received at least one dose of the antibiotic was 50 in each group. Clinical and bacteriological effectiveness of the treatment, incidence of superinfection and selection of carbapenem-resistant bacteria after the onset of therapy were evaluated in both groups. Results. Treatment outcomes were evaluated in 45 patients treated with cefepime/sulbactam and in 47 patients treated with carbapenem (meropenem, ertapenem, imipenem or doripenem). The majority of patients in both groups had severe infection: 58.7% — sepsis, 29.3% — septic shock, over 80% of patients were at the ICU. The most common infection (43.5%) was nosocomial pneumonia including VAP. The studied antibiotics were prescribed empirically in most cases (83 patients) including monotherapy in 80.4% of patients. Positive clinical effect (71.1 and 61.7%, respectively) and eradication of the pathogen (87.5 and 73.0%) were observed in the majority of patients who received cefepime/sulbactam or carbapenem (p>0.05). There was significantly less incidence of superinfection in cefepime/sulbactam group compared to carbapenem therapy (22.2 and 53.3%, respectively, p=0.001). K. pneumoniae (44.8%) and A. baumannii (34.5%) predominated among the microorganisms that caused superinfection during treatment with carbapenems. Selection of carbapenem-resistant microorganisms after antibacterial therapy onset (in 5.3 days on the average) was more common in case of carbapenems (74.5%) compared to cefepime/sulbactam (20%) (p=0.0001). Carbapenem-resistant bacteria were represented by K. pneumoniae, P. aeruginosa and A. baumannii. Moreover, the last one was found only if carbapenems were administered (21 out of 35 patients) (p=0.0001). Administration of cefepime/sulbactam was associated with reduced ICU-stay after antibacterial therapy onset by 6 days (10.7±1.56 and 16.3±2.11 days, p=0.037). Conclusion. Cefepime/sulbactam is characterized by equal effectiveness with carbapenems as a first-line antibiotic therapy of severe infections in the ICU. Moreover, these drugs result significantly less risk of superinfection (RR=0.402, 95% CI 0.220—0.735) and selection of carbapenem-resistant bacteria (RR=0.269, 0.146—0.493) compared to carbapenems. As a result, reduced ICU-stay is observed.

Keywords:

cefepime/sulbactam

carbapenem

carbapenem-sparing treatment

carbapenem-replacement therapy

multidrug-resistant infections

superinfection

carbapenem-resistant pathogens

gram-negative

resistance selection

clinical study

Authors:

Suvorova M.P.

GBOU VPO "Pervyĭ MGMU im. I.M. Sechenova" Minzdrava Rossii;
gorodskaia klinicheskaia bol'nitsa #7 DZ Moskvy

Bykov A.O.

Pirogov Russian National Research Medical University, Moscow, Russia

Yakovlev S.V.

Department of Pediatric Oromaxillofacial Surgery Faculty of Stomatology Moscow State University of Medicine and Dentistry named after A.I. Evdokimov Russian Ministry of Health, Moscow, Russia

Protsenko D.N.

SPIN RSCI: 1019-8216
Scopus AuthorID: 6603277055
ResearcherID: P-9224-2018
ORCID: 0000-0002-5166-3280

Sychev I.N.

Yudin Municipal Clinical Hospital, Moscow, Russia

Mirzakhamidova S.S.

Yudin Municipal Clinical Hospital, Moscow, Russia

Burmistrova E.N.

GBOU VPO "Pervyĭ MGMU im. I.M. Sechenova" Minzdrava Rossii;
gorodskaia klinicheskaia bol'nitsa #7 DZ Moskvy

List of references:

Sidorenko SV. Investigation of the spread of antibiotic resistance: practical significance for medicine. 2002;4(2):38. (In Russ.).
Sidorenko SV, Strachunsky LS, Akhmedova LI, Beloborodov VB, Bogomolova NS, Bolshakov LV, Dekhnich AV, Karabak VI, Malikov VE, Pavlova MV, Polikarpova SV, Rudnov VA, Yakovlev VP. Results of a multicenter study of the comparative activity of cefepime and other antibiotics against pathogens of severe hospital infections (MICROMAX program). 1999;44(11):7-16. (In Russ.).
Paterson DL, Ko WC, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, Mulazimoglu L, Trenholme G, Klugman KP, Bonomo RA, Rice LB, Wagener MM, McCormack JG, Yu VL. Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases. 2004;39(1):31-37.
Schiappa DA, Hayden MK, Matushek MG, Hashemi FN, Sullivan J, Smith KY, Miyashiro D, Quinn JP, Weinstein RA, Trenholme GM. Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation. 1996;174(3):529-536.
Goethaert K, Van Looveren M, Lammens C, Jansens H, Baraniak A, Gniadkowski M, Van Herck K, Jorens PG, Demey HE, Ieven M, Bossaert L, Goossens H. High-dose cefepime as an alternative treatment for infections caused by TEM-24 ESBL-producing Enterobacter aerogenes in severity-ill patients. 2006;12(1):56-62.
Chopra T, Marchaim D, Veltman J, Johnson P, Zhao JJ, Tansek R, Hatahet D, Chaudhry K, Pogue JM, Rahbar H, Chen TY, Truong T, Rodriguez V, Ellsworth J, Bernabela L, Bhargava A, Yousuf A, Alangaden G, Kaye KS. Impact of cefepime therapy on mortality among patients with bloodstream infections caused by aextended-spectrum-beta-kactamase-producing Klebsiella pneumoniae and Escherichia coli. 2012;56(7):3936-3942.
Zanetti G, Bally F, Greub G, Garbino J, Kinge T, Lew D, Romand JA, Bille J, Aymon D, Stratchounski L, Krawczyk L, Rubinstein E, Schaller MD, Chiolero R, Glauser MP, Cometta A; Cefepime Study Group. Cefepime versus imipenem-cilastatin for treatment of nosocomial pneumonia in intensive care unit patients: a multicenter, evaluator-blind, prospective, randomized study. 2003;47(11):3442-3447.
Lee NY, Lee CC, Huang WH, Tsui KC, Hsueh PR, Ko WC. Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended-spectrum beta-lactamase-producing Enterobacteriaceae: MIC matters. 2012;56(4):488-495.
Reshedko GK, Ryabkova EL, Krechikova OI, Sukhorukova MV, Shevchenko OV, Einstein MV, Kozlov RS, Turgutyukov VB, Nekhaeva GI, Bochkarev DN, Rozanova SM, Boronina LG, Agapova ED, Marusina NE, Multih IG, Taraban VK, Zdzitovetskyy DE, Sarmatova NI, Tikhonov YuG, Polikarpova SV. Antibiotic resistance of gram-negative pathogens of nosocomial infections in the ICU of multidisciplinary hospitals in Russia. 2008;10(2):96-112. (In Russ.).
Yakovlev SV, Suvorova MP, Beloborodov VB, Basin EE, Eliseeva EV, Kovelenov SV, Portnyagina US, Rog AA, Rudnov VA, Barkanova ON. The prevalence and clinical significance of nosocomial infections in hospitals of Russia: a study ARGINI. 2016;61(5-6):32-42. (In Russ.).
Rossijskie klinicheskie rekomendacii. Pod red. Yakovleva S.V., Briko N.I., Sidorenko S.V., Procenko D.N. M.: Izdatel’stvo «Pero»; 2018. (In Russ.).
Lazareva IV, Ageyevets VA, Yershova TA, Zueva LP, Goncharov AE, Darina MG, Svetlichnaya YuS, Uskov AN, Sidorenko SV. Prevalence and antibacterial resistance of gram-negative bacteria, producers of carbapenemases, in Saint Petersburg and some other regions of the Russian Federation. 2016;61(11-12):28-38. (In Russ.).
Mariappan S, Sekar U, Kamalanthan A. Carbapenemase-producing Enterobacteriaceae. Risk factors for infection and impact of resistance on outcomes. 2017;7(1):32-39.
Bykov A, Suvorova M, Sychev I. 29th European Conference on Clinical Microbiology and Infectious Diseases. Amsterdam, the Netherlands, April 13—16, 2019.
Logan LK, Weinstein RA. The epidemiology of carbapenem-resistant Enterobacteriaceae: the impact and evolution of a global menace. 2017;215(1):28-36.
Bassetti M, Carnelutti A, Peghin M. Patient specific risk stratification for antimicrobial resistance and possible treatment strategies in gram-negative bacterial infections. 2017;15(1):55-65.
Lambregts MM, Hendriks BJC, Visser LG, Bernards ST, de Boer MG. Using local clinical and microbiological data to develop an institution specific carbapenem-sparing strategy in sepsis: a nested case-control study. Resista 2019;8:19-27.
Karaiskos I, Giamarellou H. Carbapenem-sparing strategies for ESBL producers: when and how. 2020;9(2):61-84.
Corcione S, Lupia T, Maraolo AE, Mornese Pinna S, Gentile I, De Rosa FG. Carbapenem-sparing strategy: carbapenemase, treatment, and stewardship. 2019;32(6):663-673.
Roussel-Delvallez M, Wallet F, Dao A, Marti V, Sirot D, Beaucaire G, Courcol R. Bactericidal activity of three beta-lactams alone or in combination with a beta-lactamase inhibitor and two aminoglycosides against Klebsiella pneumoniae harboring extended-spectrum beta-lactamases. 1998;4(10):570-576.
Tong W, Wang R, Chai D, Li Z, Pei F. In vitro activity of cefepime combined with sulbactam against clinical isolates of carbapenem-resistant Acinetobacter spp. 2006;28(5):454-456.
Wareham DW, Momin MHFA, Phee LM, Hornsey M, Standing JF. Cefepime/sulbactam as an enhanced antimicrobial combination therapy for the treatment of MDR Gram-negative infections. 2020;75(1):135-139.
Luyt CE, Faure M, Bonnet I, Besset S, Huang F, Junot H, Hékimian G, Schmidt M, Bréchot N, Combes A, Aubry A, Mayaux J, Chastre J. Use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae infections in intensive care unit patients 2019;53(5):547-552.
Gudiol C, Royo-Cebrecos C, Abdala E, Akova M, Álvarez R, Maestro-de la Calle G, Cano A, Cervera C, Clemente WT, Martín-Dávila P, Freifeld A, Gómez L, Gottlieb T, Gurguí M, Herrera F, Manzur A, Maschmeyer G, Meije Y, Montejo M, Peghin M, Rodríguez-Baño J, Ruiz-Camps I, Sukiennik TC, Tebe C, Carratalà J; BICAR Study Group. Efficacy of β-lactam/β-lactamase inhibitor combinations for the treatment of bloodstream infections due to extended-spectrum- β-lactamase-producing Enterobacteriaceae in hematological patients with neutropenia. 2017;61(8):00164-00217.
Harris PN, Yin M, Jureen R, Chew J, Ali J, Paynter S, Paterson DL, Tambyah PA. Comparable outcomes for β-lactam/β-lactamase inhibitor combinations and carbapenems in definitive treatment of bloodstream infections caused by cefotaxime-resistant Escherichia coli or Klebsiella pneumoniae. 2015;4:14.
Sfeir MM, Askin G, Christos P. Beta-lactam/beta-lactamase inhibitors versus carbapenem for bloodstream infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae: systematic review and meta-analysis. 2018;52(5):554-570.
Ko JH, Lee NR, Joo EJ, Moon SY, Choi JK, Park DA, Peck KR. Appropriate non-carbapenems are not inferior to carbapenems as initial empirical therapy for bacteremia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a propensity score weighted multicenter cohort study. 2018;37(2):305-311.
Dizbay M, Özger HS, Karaşahin Ö, Karaşahin EF. Treatment efficacy and superinfection rates in complicated urinarytract infections treated with ertapenem or piperacillin tazobactam. 2016;46(6):1760-1764.
Eljaaly K, Enani MA, Al-Tawfiq JA. Impact of carbapenem versus non-carbapenem treatment on the rates of superinfection: A meta-analysis of randomized controlled trials. 2018;24(11):915-920.

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