Generic placeholder image

Current Drug Safety

Author(s): Bhawna Sharma, Priya Sreenivasan, Archana Angrup*, Satinder Kaur, Sudesh Rana, Jyoti Kundu, Manisha Biswal and Pallab Ray

DOI: 10.2174/1574886318666221209160323

DownloadDownload PDF Flyer Cite As
In-vitro Susceptibility Testing Methods for Ceftazidime-avibactam against Carbapenem-resistant Enterobacterales: Comparison with Reference Broth Microdilution Method

Page: [563 - 570] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Introduction: β-lactam antibiotics, mainly cephalosporins, and carbapenems, have been the mainstay of treatment for infections caused by Enterobacterales. However, their role in treating clinical infections has become limited because of the increase in resistance. There is a need to have cost-effective and rapid methods for antimicrobial susceptibility testing methods for newer antibiotics like ceftazidime-avibactam against carbapenem-resistant Enterobacterales (CRE), which can be applied in routine clinical microbiology laboratories. With this aim, the present study was conducted to compare the disk diffusion and gradient diffusion, i.e., the E-test method with the reference broth microdilution (BMD) method for in-vitro testing of ceftazidime-avibactam against CRE.

Materials and Methods: A total of 111 CRE isolates from various clinical samples were included. Conventional PCR (Polymerase Chain Reaction) was done for the detection of genes encoding carbapenemases and to see their expression, modified carbapenem inactivation method (mCIM) along with EDTA (Ethylenediaminetetraacetic acid) carbapenem inactivation method (eCIM) was done.

Results: 42.3% (47/111) isolates were resistant to ceftazidime-avibactam by the standard broth microdilution method; however, 45.9% (51/111) were resistant by both disk diffusion and E-test. In 5.4% of isolates (similar in both methods), microbroth dilution method results did not match with E-strip and disk diffusion. Very major errors (VME) by both disk diffusion and E-test were found in 2.1% (1/47), and major errors (ME) were found in 7.8% (5/64) isolates (similar isolates in both methods). The overall categorical agreement (CA) rate was 94.6% for both E-test and disk diffusion, and the essential agreement (EA) rate was 90.1% (100/111) for E-test. 98% (109/111) of CRE harbored carbapenemase genes either singly (30.3%) or in combination with others (69.7%).

Conclusion: In conclusion, for CRE, E-test and the disk diffusion method for ceftazidimeavibactam depicted an acceptable performance as an alternative to the reference broth microdilution method.

Graphical Abstract

[1]
Micek ST, Wunderink RG, Kollef MH, et al. An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance. Crit Care 2015; 19(1): 219.
[http://dx.doi.org/10.1186/s13054-015-0926-5] [PMID: 25944081]
[2]
van Duin D, Kaye KS, Neuner EA, Bonomo RA. Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. Diagn Microbiol Infect Dis 2013; 75(2): 115-20.
[http://dx.doi.org/10.1016/j.diagmicrobio.2012.11.009] [PMID: 23290507]
[3]
Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018; 18(3): 318-27.
[http://dx.doi.org/10.1016/S1473-3099(17)30753-3] [PMID: 29276051]
[4]
Zilberberg MD, Nathanson BH, Sulham K, Fan W, Shorr AF. Carbapenem resistance, inappropriate empiric treatment and outcomes among patients hospitalized with Enterobacteriaceae urinary tract infection, pneumonia and sepsis. BMC Infect Dis 2017; 17(1): 279.
[http://dx.doi.org/10.1186/s12879-017-2383-z] [PMID: 28415969]
[5]
Adeolu M, Alnajar S, Naushad SS, Gupta R. Genome-based phylogeny and taxonomy of the ‘Enterobacteriales’: proposal for Enterobacterales ord. nov. divided into the families Enterobacteriaceae, Erwiniaceae fam. nov., Pectobacteriaceae fam. nov., Yersiniaceae fam. nov., Hafniaceae fam. nov., Morganellaceae fam. nov., and Budviciaceae fam. nov. Int J Syst Evol Microbiol 2016; 66(12): 5575-99.
[http://dx.doi.org/10.1099/ijsem.0.001485] [PMID: 27620848]
[6]
Castanheira M, Deshpande LM, Mendes RE, Canton R, Sader HS, Jones RN. Variations in the occurrence of resistance phenotypes and carbapenemase genes among Enterobacteriaceae isolates in 20 years of the SENTRY antimicrobial surveillance program. Open Forum Infect Dis 2019; 6(S1): S23-33.
[http://dx.doi.org/10.1093/ofid/ofy347] [PMID: 30895212]
[7]
Resistance map- center for disease dynamics. 2021. Available from: https://resistancemap.cddep.org/
[8]
Bush K. Past and present perspectives on β-lactamases. Antimicrob Agents Chemother 2018; 62(10): e01076-18.
[http://dx.doi.org/10.1128/AAC.01076-18] [PMID: 30061284]
[9]
van Duin D, Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence 2017; 8(4): 460-9.
[http://dx.doi.org/10.1080/21505594.2016.1222343] [PMID: 27593176]
[10]
de Jonge BLM, Karlowsky JA, Kazmierczak KM, Biedenbach DJ, Sahm DF, Nichols WW. In vitro susceptibility to ceftazidime-avibactam of carbapenem-nonsusceptible Enterobacteriaceae isolates collected during the INFORM global surveillance study. Antimicrob Agents Chemother 2016; 60(5): 3163-9.
[http://dx.doi.org/10.1128/AAC.03042-15] [PMID: 26926648]
[11]
Kazmierczak KM, de Jonge BLM, Stone GG, Sahm DF. In vitro activity of ceftazidime/avibactam against isolates of Pseudomonas aeruginosa collected in European countries: INFORM global surveillance 2012–15. J Antimicrob Chemother 2018; 73(10): 2777-81.
[http://dx.doi.org/10.1093/jac/dky267] [PMID: 30010951]
[12]
Lahiri SD, Johnstone MR, Ross PL, McLaughlin RE, Olivier NB, Alm RA. Avibactam and class C β-lactamases: mechanism of inhibition, conservation of the binding pocket, and implications for resistance. Antimicrob Agents Chemother 2014; 58(10): 5704-13.
[http://dx.doi.org/10.1128/AAC.03057-14] [PMID: 25022578]
[13]
Pfizer Pharmaceuticals. Zavicefta Summary of Product Characteristics. 2017. Available from: http://www.ema.europa.eu/docs/en_ GB/document_library/EPAR_-Product_Information/human/00402 7/WC500210234.pdf
[14]
Allergan. Avycaz (ceftazidime-avibactam) for injection, for intravenous use: Prescribing information. Allergan. (2018). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206494s004lbl.pdf. Accessed May 8, 2019.
[15]
CLSI. Performance standards for antimicrobial susceptibility testing 2020. https://clsi.org/media/wi0pmpke/m100ed32_sample.pdf
[16]
Humphries RM, Ambler J, Mitchell SL, et al. CLSI Methods development and standardization working group of the subcommittee on antimicrobial susceptibility testing. clsi methods development and standardization working group best practices for evaluation of antimicrobial susceptibility tests. J Clin Microbiol 2018; 56(4): e01934-17.
[http://dx.doi.org/10.1128/JCM.01934-17] [PMID: 29367292]
[17]
Dallenne C, Da Costa A, Decré D, Favier C, Arlet G. Development of a set of multiplex PCR assays for the detection of genes encoding important β-lactamases in Enterobacteriaceae. J Antimicrob Chemother 2010; 65(3): 490-5.
[http://dx.doi.org/10.1093/jac/dkp498] [PMID: 20071363]
[18]
Parveen RM, Harish BN, Parija SC. Emerging carbapenem resistance among nosocomial isolates of Klebsiella pneumoniae in South India. Int J Pharma Bio Sci 2010; 1(2): 1-11.
[19]
Gugliandolo A, Caio C, Mezzatesta ML, et al. Successful ceftazidime-avibactam treatment of MDR-KPC-positive Klebsiella pneumoniae infection in a patient with traumatic brain injury. Medicine 2017; 96(31): e7664.
[http://dx.doi.org/10.1097/MD.0000000000007664] [PMID: 28767588]
[20]
Temkin E, Torre-Cisneros J, Beovic B, et al. Ceftazidime-avibactam as salvage therapy for infections caused by Carbapenem-resistant organisms. Antimicrob Agents Chemother 2017; 61(2): e01964-16.
[http://dx.doi.org/10.1128/AAC.01964-16] [PMID: 27895014]
[21]
Holyk A, Belden V, Lee JJ, et al. Ceftazidime/avibactam use for carbapenem-resistant Klebsiella pneumoniae meningitis: a case report. J Antimicrob Chemother 2018; 73(1): 254-6.
[http://dx.doi.org/10.1093/jac/dkx358] [PMID: 29040635]
[22]
van Duin D, Lok JJ, Earley M, et al. Colistin versus ceftazidime-avibactam in the treatment of infections due to Carbapenemresistant Enterobacteriaceae. Clin Infect Dis 2018; 66(2): 163-71.
[http://dx.doi.org/10.1093/cid/cix783] [PMID: 29020404]
[23]
Shields RK, Clancy CJ, Pasculle AW, et al. Verification of ceftazidime-avibactam and ceftolozanetazobactam susceptibility testing methods against carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa. J Clin Microbiol 2018; 56(2): e01093-17.
[http://dx.doi.org/10.1128/JCM.01093-17] [PMID: 29167294]
[24]
Wang Q, Zhang F, Wang Z, et al. Evaluation of the Etest and disk diffusion method for detection of the activity of ceftazidime-avibactam against Enterobacterales and Pseudomonas aeruginosa in China. BMC Microbiol 2020; 20(1): 187.
[http://dx.doi.org/10.1186/s12866-020-01870-z] [PMID: 32600252]
[25]
Wenzler E, Lee M, Wu TJ, et al. Performance of ceftazidime/avibactam susceptibility testing methods against clinically relevant Gram-negative organisms. J Antimicrob Chemother 2019; 74(3): 633-8.
[http://dx.doi.org/10.1093/jac/dky483] [PMID: 30534964]
[26]
Sader HS, Rhomberg PR, Chandrasekaran S, et al. Correlation between broth microdilution and disk diffusion results when testing ceftazidime-avibactam against a challenge collection of enterobacterales isolates: results from a multilaboratory study. J Clin Microbiol 2020; 58(4): e01757-19.
[http://dx.doi.org/10.1128/JCM.01757-19] [PMID: 31996445]
[27]
Sader HS, Rhomberg PR, Huband MD, et al. Assessment of 30/20-microgram disk content versus MIC results for ceftazidime-avibactam tested against Enterobacteriaceae and Pseudomonas aeruginosa. J Clin Microbiol 2018; 56(6): e01960-17.
[http://dx.doi.org/10.1128/JCM.01960-17] [PMID: 29563198]
[28]
Clinical Laboratory Testing and in vitro Diagnostic Test Systems. Susceptibility Testing of Infectious Agents and Evaluation of Performance of Antimicrobial Susceptibility Test Devices. 2007.
[29]
Zhang W, Guo Y, Li J, et al. In vitro and in vivo bactericidal activity of ceftazidime-avibactam against Carbapenemase–producing Klebsiella pneumoniae. Antimicrob Resist Infect Control 2018; 7(1): 142.
[http://dx.doi.org/10.1186/s13756-018-0435-9] [PMID: 30479755]