Evaluation of a combination of third generation cephalosporin, ESBL inhibitor and MBL inhibitor: An in vitro study to assess the efficacy for treatment of carbapenemase producing Gram negative bacilli.

Jyoti Bade; Kanupriya Rohilla; Chhaya Chande; Ritesh Shirpurkar; Kavita Chopdekar; Sunil Lilani; Abhay Chowdhary

Volume : VII, Issue : VIII, August - 2018

Evaluation of a combination of third generation cephalosporin, ESBL inhibitor and MBL inhibitor: An in vitro study to assess the efficacy for treatment of carbapenemase producing Gram negative bacilli.

Jyoti Bade, Kanupriya Rohilla, Chhaya Chande, Ritesh Shirpurkar, Kavita Chopdekar, Sunil Lilani, Abhay Chowdhary

Abstract :

Gram negative bacteria belonging to Enterobacteriaceae and non–fermenting gram negative bacilli are the major causes of infections in hospitalized patients. In the past two decades there has been remarkable increase in the resistance to beta–lactam antibiotics in these organisms.Beta–lactam ases enzymes are one of the major causes.^{ADDIN
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"PMID" : "27221683", "abstract" : "PURPOSE
Extended–spectrum beta–lactamases (ESBLs) mediated resistance is more prevalent
worldwide, especially among Gram–negative bacterial isolates, conferring
resistance to the expanded spectrum cephalosporins. As limited data were
available on the prevalence of ESBLs in this area, the current study was
undertaken to determine the prevalence, antibacterial resistance patterns, and
molecular detection and characterization of ESBL encoding resistance genes
among ocular Gram–negative bacterial isolates from ocular infections. MATERIALS
AND METHODS A prospective study was done on 252 ocular Gram–negative bacterial
isolates recovered from ocular infections during a study period from Feuary
2011 to January 2014. All isolates were subjected to detection of ESBLs by
cephalosporin/clavulanate combination disc test and their antibacterial
resistance pattern was studied. Molecular detection and characterization of
ESBL encoding blaTEM –, blaSHV , blaOXA –, and blaCTX–M (phylogenetic groups 1,
2, 9, and 8/25) resistance genes by multiplex polymerase chain reaction and DNA
sequence analysis. RESULTS Of all Gram–negative bacteria, Pseudomonas
aeruginosa (44%) was the most common strain, followed by Enterobacter
agglomerans and Klebsiella pneumoniae each (10%). Among the 252, 42 (17%) were
ESBL producers. The major source of ESBL producers were corneal scraping
specimens, highest ESBL production was observed in P. aeruginosa 16 (38%) and
Escherichia coli 7 (16.6%). Among ESBL–producing genes, the prevalence of blaTEM
–gene was the highest (83%) followed by blaOXA –gene (35%), blaSHV –gene
(18.5%), and blaCTX–M–1 –gene (18.5%) alone or together. CONCLUSION The higher
rate of prevalence of ESBLs–encoding genes among ocular Gram–negative bacteria
is of great concern, as it causes limitation to therapeutic options. This
regional knowledge will help in guiding appropriate antibiotic use which is
highly warranted.", "author" : [ { "dropping–particle"
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}}^{(1, 2)}. A therapeutic preparation of third generation cephalosporin combined with ESBL inhibitor sulbactam and metallo –beta–lactamase inhibitor EDTA is available for intravenous useADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM–1", "itemData" : { "DOI" : "10.1016/j.bjid.2017.02.007", "ISSN" : "14138670", "PMID" : "28376315", "abstract" : "OBJECTIVE In India, Elores (CSE–1034: ceftriaxone+sulbactam+disodium edetate) was approved as a oad spectrum antibiotic in year 2011 and is used for management of Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections in tertiary care centers. The objective of this study was to investigate the efficacy of this drug in patients with Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections and identify the incidence of adverse events in real clinical settings. METHODS This Post Marketing Surveillance study was conducted at 17 centers across India and included 2500 patients of all age groups suffering from various bacterial infections and treated with Elores (CSE1034). Information regarding demographic, clinical and microbiological parameters, dosage and treatment duration, efficacy and adverse events (AEs) associated with the treatment were recorded. RESULTS A total of 2500 patients were included in the study and efficacy was evaluated in 2487 patients. In total, 409 AEs were reported in 211 (8.4%) patients. The major AEs reported were vomiting (3.0%), pain at injection site (2.5%), nausea (2.3%), redness at site (1.96%), thrombophlebitis (1.4%). Of total reported AEs, 40 (5.3%) AEs were reported in pediatric, 310 (20.6%) in adult, and 59 (23.6%) in geriatric group. No AE belonging to grade IV or V was reported in any patient. In terms of efficacy, 1977 (79.4%) patients were cured, 501 (20.1%) patients showed clinical improvement and 5 (0.2%) patients were complete failure. The treatment duration varied from 5 to 7 days in different patients depending on the infection type. CONCLUSION In this post–marketing surveillance study, CSE–1034 was found to be an effective and safe option against Pip tazo and meropenem in management of patients with multi–drug resistant (MDR) bacterial infections under routine ward settings.", "author" : [ { "dropping–particle" : "", "family" : "Chaudhary", "given" : "Manu", "non–dropping–particle" : "", "parse–names" : false, "suffix" : "" }, { "dropping–particle" : "", "family" : "Mir", "given" : "Mohd Amin", "non–dropping–particle" : "", "parse–names" : false, "suffix" : "" }, { "dropping–particle" : "", "family" : "Ayub", "given" : "Shiekh Gazalla", "non–dropping–particle" : "", "parse–names" : false, "suffix" : "" }, { "dropping–particle" : "", "family" : "Protocol 06 Group", "given" : "", "non–dropping–particle" : "", "parse–names" : false, "suffix" : "" } ], "container–title" : "The Brazilian Journal of Infectious Diseases", "id" : "ITEM–1", "issue" : "4", "issued" : { "date–parts" : [ [ "2017", "7" ] ] }, "page" : "408–417", "title" : "Safety and efficacy of a novel drug elores (ceftriaxone + sulbactam + disodium edetate) in the management of multi–drug resistant bacterial infections in tertiary care centers: a post–marketing surveillance study", "type" : "article–journal", "volume" : "21" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=dbf502e0–9df3–3178–bcfe–861382ebdc07" ] }, { "id" : "ITEM–2", "itemData" : { "DOI" : "10.7860/JCDR/2016/20904.9014", "ISSN" : "2249782X", "PMID" : "28208889", "abstract" : "INTRODUCTION Nosocomial infections have been considered as a major health problem causing incremental morbidity, mortality and costs of therapy. AIM This retrospective study was initiated with aim to analyse the comparative efficacy of a novel Antibiotic Adjuvant Entity (AAE), a combination of ceftriaxone + sulbactam + disodium edetate and meropenem in combination with colistin, for the management of Multi Drug Resistant (MDR) nosocomial Gram–negative bacterial infections. MATERIALS AND METHODS Case history sheets of patients with documented MDR nosocomial Gram–negative infections who received either AAE or meropenem in combination with colistin for management of infections over a period of 3 years (November 2012 – October 2015) were included in the study. Data related to clinical management, demographics, vital signs and laboratory parameters along with prior antibiotic therapy, dose and clinical outcomes were evaluated thoroughly to analyse the clinical benefits of this new AAE+ colistin therapy for management of MDR nosocomial infections. RESULTS Out of 115 patients short listed for the study, 52 patients had received AAE + colistin therapy and 63 patients have received meropenem + colistin. AAE + colistin therapy resulted in significantly higher efficacy (86.53%) as compared to meropenem + colistin (63.49%). A rising trend in clinical cure rates was observed in AAE based combination therapy in contrast to the decreasing trend in meropenem based combination therapy. A progressive decline in clinical cure rates was observed in meropenem treated group over a period of 3 years due to rising carbapenemases and multiple resistance by pathogens, where as AAE maintained the same efficacy. CONCLUSION The AAE + colistin therapy has shown better bacteriological and clinical efficacy as compared to meropenem + colistin in the management of various nosocomial MDR Gram–negative infections. A significant number of meropenem failure patients responded to the AAE therapy highlighting the new hope to spare carbapenems.", "author" : [ { "dropping–particle" : "", "family" : "Shameem", "given" : "Mohammad", "non–dropping–particle" : "", "parse–names" : false, "suffix" : "" }, { "dropping–particle" : "", "family" : "Mir", "given" : "Mohammad Amin", "non–dropping–particle" : "", "parse–names" : false, "suffix" : "" } ], "container–title" : "JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH", "id" : "ITEM–2", "issue" : "12", "issued" : { "date–parts" : [ [ "2016", "12" ] ] }, "page" : "LC23–LC27", "title" : "Management of Pneumonia and Blood Stream Infections with New Antibiotic Adjuvant Entity (Ceftriaxone + Sulbactam + Disodium Edetate)– A Novel Way to Spare Carbapenems", "type" : "article–journal", "volume" : "10" }, "uris" : [ "http://www.mendeley.com/documents/?uuid=96be362f–b26f–32e3–bf1b–47dc4233a610" ] } ], "mendeley" : { "formattedCitation" : "(3,4)", "plainTextFormattedCitation" : "(3,4)", "previouslyFormattedCitation" : "(3,4)" }, "properties" : { "noteIndex" : 1 }, "schema" : "https://github.com/citation–style–language/schema/raw/master/csl–citation.json" }^(3,4). The present study was aimed at testing the sensitivity of combination of these antimicrobials for the gram negative bacilli of Enterobacteriaceae and non–fermenting GNBs showing in–vitro resistance to third generation cephalosporins. Thisceftriaxone combination appears to be a suitable option for management of infections by GNBs occurring in CCUs.