Correlation between Mechanism of Carbapenem Resistance and in vitro Efficacy of Ceftazidime-Avibactam and Meropenem-Vaborbactam on Carbapenem-Resistant Enterobacterales and Pseudomonas Aeruginosa
DOI:
https://doi.org/10.51253/pafmj.v73i6.7377Keywords:
Carbapenem -resistant enterobacterial, Carbapenem -resistant pseudomonas aeruginosa, Ceftazidime-avibactam, meropenem-vaborbactam, EDTA-modified Carbapenem inactivation method, Modified carbapenem inactivation methodAbstract
Objective: To determine the mechanism of Carbapenem resistance, type of Carbapenemase produced and in vitro efficacy of Ceftazidime-Avibactam (CAZ-AVI) and Meropenem-Vaborbactam (MEV) against Carbapenem-resistant Enterobacterales and in vitro efficacy of Ceftazidime-Avibactam against Carbapenem-resistant Pseudomonas aeruginosa.
Study Design: Cross-sectional study.
Place and Duration of Study: Microbiology Department, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Mar to Aug 2020.
Methodology: The mechanism of Carbapenem resistance in Enterobacterales and P.aeruginosa was determined by mCIM and eCIM methods. In vitro, the susceptibility of isolates to Ceftazidime-Avibactam and Meropenem-Vaborbactam was
determined by disk diffusion technique according to CLSI 2020 guidelines.
Results: Out of 249 Carbapenem -resistant isolates, there were 192(77.1%) Enterobacterales and 57(22.9%) P.aeruginosa. From 192 Enterobacterales, 174(90.6%) were Carbapenemase producers while 18(9.4%) used ‘other mechanisms. From 174
Carbapenemase producers, metallo-β-lactamases were produced by 141(73.4%) while serine Carbapenemases by 33(17.2%). Out of 33 serine Carbapenemase producers,19(57.6%) were sensitive to CAZ-AVI and 6(18.2%) to MEV. Out of 141 MBL producers, 31(22%) were sensitive to CAZ-AVI and 18(12.8%) to MEV. Out of 57 P.aeruginosa, 30(52.6%) were Carbapenemase producers and 1(3.4%) were sensitive to CAZ-AVI while 27(47.4%) were non-Carbapenemase producers and 13(48%) were sensitive to CAZ-AVI. MBL production predominated.
Conclusion: The in vitro efficacy of these antibiotics against MBL producers and serine Carbapenemase producers was not
satisfactory.
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Sabir N, Hussain W, Ahmed A, Zaman G, Mirza IA, Ikram A, et
al. Burden of multi-drug resistant, extensively-drug resistant and
pan-drug resistant superbugs isolated from various indoor
microbiological specimens at tertiary care centers Rawalpindi.
Pak Armed Forces Medical J 2020; 70(1): 79-85.
Andrei S, Valeanu L, Chirvasuta R, Stefan MG. New FDA
approved antibacterial drugs: 2015-2017. Discoveries (Craiova)
; 6(1): e81. https://doi.org/10.15190%2Fd.2018.1.
Shirley M. Ceftazidime-avibactam: a review in the treatment of
serious gram-negative bacterial infections. Drugs 2018; 78(6):
-692. https://doi.org/10.1007/s40265-018-0902-x.
Lee S, Phuan PW, Felix CM, Tan JA, Levin MH, Verkman AS, et
al. Nanomolar-potency aminophenyl-1, 3, 5-triazine activators of
the cystic fibrosis transmembrane conductance regulator (CFTR)
chloride channel for prosecretory therapy of dry eye diseases. J
Med Chem Drug Des 2017; 60(3): 1210-1218.
https://doi.org/10.1021/acs.jmedchem.6b01792.
Tsai YM, Wang S, Chiu HC, Kao CY, Wen LL. Combination of
modified carbapenem inactivation method (mCIM) and EDTACIM (eCIM) for phenotypic detection of carbapenemaseproducing Enterobacteriaceae. BMC Microbiol 2020; 20(1): 1-7.
https://doi.org/10.1186/s12866-020-02010-3.
Castanheira M, Doyle TB, Smith CJ, Mendes RE, Sader HS.
Combination of MexAB-OprM overexpression and mutations in
efflux regulators, PBPs and chaperone proteins is responsible for
ceftazidime/avibactam resistance in Pseudomonas aeruginosa
clinical isolates from US hospitals. J Antimicrob Chemother 2019;
(9): 2588-2595. https://doi.org/10.1093/jac/dkz243.
Gajdács M, Kárpáti K, Stájer A. Insights on carbapenem-resistant
Pseudomonas aeruginosa: phenotypic characterization of
relevant isolates. Acta Biologica Szegediensis 2021; 65(1): 105-102.
https://doi.org/10.14232/abs.2021.1.105-112.
Ye Y, Xu L, Han Y, Chen Z. Mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates. Exp Ther Med 2018;
(1): 1143-1149. https://doi.org/10.3892%2Fetm.2017.5485.
Zhou H, Zhang K, Chen W, Chen J, Zheng J, Liu C, et al.
Epidemiological characteristics of carbapenem-resistant
Enterobacteriaceae collected from 17 hospitals in Nanjing district
of China. Antimicrob Resist Infect Control 2020; 9(1): 1-4.
https://doi.org/10.1186/s13756-019-0674-4.
Javed H, Ejaz H, Zafar A, Rathore AW, ul Haq I. Metallo-betalactamase producing Escherichia coli and Klebsiella pneumoniae:
a rising threat for hospitalized children. J Pak Med Assoc 2016;
(9): 1068-1072.
El-Mahdy R, El-Kannishy G. Virulence factors of carbapenemresistant Pseudomonas aeruginosa in hospital-acquired
infections in Mansoura, Egypt. Infect Drug Resist 2019; 12: 3455.
https://doi.org/10.2147%2FIDR.S222329.
Mohanty S, Mittal G, Gaind R. Identification of carbapenemasemediated resistance among Enterobacteriaceae bloodstream
isolates: a molecular study from India. Indian J Med Microbiol
; 35(3): 421-425.
https://doi.org/10.4103/ijmm.ijmm_16_386.
Sonnevend Á, Ghazawi A, Darwish D, Barathan G, Hashmey R,
Ashraf T, et al. In vitro efficacy of ceftazidime-avibactam,
aztreonam-avibactam and other rescue antibiotics against
carbapenem-resistant Enterobacterales from the Arabian
Peninsula. Int J Infect Dis 2020; 99(1): 253-259.
https://doi.org/10.1016/j.ijid.2020.07.050.
Alatoom A, Elsayed H, Lawlor K, AbdelWareth L, El-Lababidi R,
Cardona L, et al. Comparison of antimicrobial activity between
ceftolozane–tazobactam and ceftazidime–avibactam against
multidrug-resistant isolates of Escherichia coli, Klebsiella
pneumoniae, and Pseudomonas aeruginosa. Int J Infect Dis 2017;
: 39-43. https://doi.org/10.1016/j.ijid.2017.06.007.
Wilson WR, Kline EG, Jones CE, Morder KT, Mettus RT. Effects
of KPC variant and porin genotype on the in vitro activity of
meropenem-vaborbactam against carbapenem-resistant
Enterobacteriaceae. Antimicrob Agents Chemother 2019; 63(3):
e02048. https://doi.org/10.1128/aac.02048-18.
Castanheira M, Doyle TB, Kantro V, Mendes RE, Shortridge D.
Meropenem-vaborbactam activity against carbapenem-resistant
Enterobacterales isolates collected in US hospitals during 2016 to
Antimicrob Agents Chemother 2020; 64(2): e01951.
https://doi.org/10.1128%2FAAC.01951-19.
Pogue JM, Bonomo RA, Kaye KS. Ceftazidime/avibactam,
meropenem/vaborbactam, or both? Clinical and formulary
considerations. Clin Infect Dis 2019; 68(3): 519-524.
https://doi.org/10.1093/cid/ciy576.
Dhillon S. Meropenem/vaborbactam: a review in complicated
urinary tract infections. Drugs 2018; 78(12): 1259-1270.
https://doi.org/10.1007/s40265-018-0966-7.
Li J, Li C, Cai X, Shi J, Feng L, Tang K, et al. Performance of
modified carbapenem inactivation method and inhibitor-based
combined disk test in the detection and distinguishing of
carbapenemase producing Enterobacteriaceae. Ann Transl Med
; 7(20): 566. https://doi.org/10.21037/atm.2019.09.43.
Sfeir MM, Hayden JA, Fauntleroy KA, Mazur C, Johnson JK,
Simner PJ, et al. EDTA-modified carbapenem inactivation
method: a phenotypic method for detecting metallo-β-lactamaseproducing Enterobacteriaceae. J Clin Microbiol 2019; 57(5):
e01757. https://doi.org/10.1128/jcm.01757-18.
Caméléna F, Cointe A, Mathy V, Hobson C, Doit C, Bercot B, et
al. Within-a-day detection and rapid characterization of
carbapenemase by use of a new carbapenem inactivation
method-based test, CIMplus. J Clin Microbiol 2018; 56(9): e00137.
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