Phenotypic synergy testing of ceftazidime–avibactam with aztreonam in a university hospital having high number of metallobetalactamase producing bacteria

Abstract Background Ceftazidime–avibactam combination with aztreonam and role of rapid synergy reporting has not been widely evaluated. Also the synergy correlation with various betalactamases has not been widely studied. Methods We studied phenotypic synergy testings and molecular detection of betalactamases in our university hospital where we have large number of mellatobetalactmase producing bacteria. We tested two phenotypic synergy methods for ceftazidime-avibactam with aztreonam (Disc-E strip method, E strip-Agar method) for rapid reporting to clinicians (153 isolates). The treatment (colistin, ceftazidime-avibactam, ceftazidime-avibactam with aztreonam) was guided as indicated in the synergy testings. The resistance genes in bacteria were identified by polymerase chain reaction (PCR) and correlated with synergy results. Results The highest synergy was seen in Klebsiella pneumoniae by Disc-E strip and E strip-Agar method (86% and 84% respectively). About 70% of Pseudomonas aeruginosa and 29% of Escherichia coli showed synergy. Molecular methods revealed multiple resistance gene combinations and bla NDM (96%) was predominant gene in isolates showing synergy. Among isolates that were sensitive to ceftazidime–avibactam, the predominant genes were bla OXA-48 and bla IMP. Rapid laboratory reporting led to proper utilization of antibiotic combinations. Conclusions Ceftazidime–avibactam and aztreonam rapid synergy testing will be highly beneficial in treatment of infections by metallobetalactamase producing resistant bacteria, especially K. pneumoniae and P. aeruginosa.

[1]  R. Shrivastava,et al.  High prevalence of Escherichia coli clinical isolates in India harbouring four amino acid inserts in PBP3 adversely impacting activity of aztreonam/avibactam. , 2020, The Journal of antimicrobial chemotherapy.

[2]  B. George,et al.  Will ceftazidime/avibactam plus aztreonam be effective for NDM and OXA-48-Like producing organisms: Lessons learnt from In vitro study , 2019, Indian journal of medical microbiology.

[3]  J. Chow,et al.  Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme , 2018, The Journal of antimicrobial chemotherapy.

[4]  M. Shirley Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections , 2018, Drugs.

[5]  M. Kollef,et al.  Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. , 2017, The Lancet. Infectious diseases.

[6]  B. Veeraraghavan,et al.  An update on technical, interpretative and clinical relevance of antimicrobial synergy testing methodologies , 2017, Indian journal of medical microbiology.

[7]  M. Castanheira,et al.  1686. Antimicrobial Activity of Aztreonam-avibactam, Ceftazidime-Avibactam, and Comparator Agents against Pseudomonas aeruginosa from Cystic Fibrosis Patients , 2017, Open Forum Infectious Diseases.

[8]  E. Wenzler,et al.  Synergistic activity of ceftazidime-avibactam and aztreonam against serine and metallo-β-lactamase-producing gram-negative pathogens. , 2017, Diagnostic microbiology and infectious disease.

[9]  S. Mohanty,et al.  Identification of carbapenemase-mediated resistance among Enterobacteriaceae bloodstream isolates: A molecular study from India , 2017, Indian journal of medical microbiology.

[10]  M. Rottman,et al.  Ceftazidime-Avibactam and Aztreonam, an Interesting Strategy To Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae and Pseudomonas aeruginosa , 2017, Antimicrobial Agents and Chemotherapy.

[11]  E. Larson,et al.  Antibiotic resistance: What is so special about multidrug-resistant Gram-negative bacteria? , 2017, GMS hygiene and infection control.

[12]  R. Humphries,et al.  Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae? , 2017, Antimicrobial Agents and Chemotherapy.

[13]  J. Rolain,et al.  Plasmid-Mediated mcr-1 Gene in Colistin-Resistant Clinical Isolates of Klebsiella pneumoniae in France and Laos , 2016, Antimicrobial Agents and Chemotherapy.

[14]  Y. Carmeli,et al.  Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. , 2016, The Lancet. Infectious diseases.

[15]  N. Indrawattana,et al.  Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens , 2016, BioMed research international.

[16]  L. Hoang,et al.  Rapid Detection of KPC, NDM, and OXA-48-Like Carbapenemases by Real-Time PCR from Rectal Swab Surveillance Samples , 2015, Journal of Clinical Microbiology.

[17]  D. Nair,et al.  Extended-spectrum β-lactamases in Gram Negative Bacteria , 2010, Journal of global infectious diseases.

[18]  T. Bannerman,et al.  Synergy Testing by Etest, Microdilution Checkerboard, and Time-Kill Methods for Pan-Drug-Resistant Acinetobacter baumannii , 2010, Antimicrobial Agents and Chemotherapy.

[19]  D. Mathai,et al.  Detection and characterization of metallo beta lactamases producing Pseudomonas aeruginosa. , 2010, Indian journal of medical microbiology.

[20]  N. Masuda,et al.  Substrate Specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM Efflux Pumps in Pseudomonas aeruginosa , 2000, Antimicrobial Agents and Chemotherapy.

[21]  J. Verweij,et al.  Extended-spectrum β-lactamase (ESBL) polymerase chain reaction assay on rectal swabs and enrichment broth for detection of ESBL carriage. , 2018, The Journal of hospital infection.