Assessment of Colistin Susceptibility among Carbapenem-Resistant Clinical Isolates

Abstract

Background: Colistin is the last treatment option for infections caused by carbapenem resistant Gram-negative bacilli (CRGNB). The increasing spread of chromosomally encoded and plasmid-mediated colistin resistance made colistin susceptibility assessment a necessity. Objectives: Assessment of colistin susceptibility in CRGNB by broth micro dilution method (BMD), as the standard method and colistin broth disk elution method (CBDE), as a substitute procedure with genotypic determination of plasmid mediated colistin resistance (mcr) genes. Methodology: CRGNB were collected and identified by conventional methods. Testing carbapenemase production by modified Carbapenem Inactivation Method (mCIM) and colistin susceptibility (by BMD and CBDE) were done and results were interpreted regarding CLSI ( 2022) guidelines followed by genotypic detection of mcr-1, -2, -3, -4, and -5 genes by multiplex PCR. Results: 155 out of 308 GNB (50.3%) were carbapenem resistant. Among them, 129 (83.2%) isolates were carbapenemase positive by mCIM. Colistin susceptibility testing by BMD revealed 43 out of 155 CRGNB isolates (27.7%) were colistin resistant. Sensitivity, specificity, PPV, NPV and accuracy of CBDE were 99.09%, 93.33%, 97.32% 97.67%, 97.42% respectively with almost perfect agreement with BMD. By PCR, only 3 CRGNB isolates (6.98%) carried mcr-1 while other mcr genes were not detected at all. Conclusion: Colistin resistance rate among CRGNB is concerning, causing serious and even deadly infections so prospective surveillance is essential. Broth disk elusion method is a simple, non-expensive reliable option to test colistin susceptibility.

Colistin Susceptibility among Carbapenem Resistant Klebsiella pneumoniae Isolated from Menoufia University Hospitals

“…Regarding colistin resistant CRKp clinical isolates (n=22), only mcr-1 was detected in 2 isolates (9.1%) with negative mcr2, mcr3, mcr4, and mcr5. This runs in accordance with Ajlan et al 19 , who found only 3 out of 43 colistin-resistant CRGNB isolates had mcr1, with negative mcr2, mcr3, mcr4, and mcr5. Also, studies on CRE in Hong Kong 33 and Oman 34 revealed presence of mcr1 in only 6.5% and 4.5% respectively.…”

“…Out of them, 135 (40.4%) were carbapenem resistant by disc diffusion method that is nearly lesser than study by Tsai et al 3 who detected 310 CRKp out of 419 CRE. And nearly similar to results of Ajlan et al 19 who found that, 36.1% of Klebsiella spp. isolated showed carbapenem resistance, and more than detected by Ngbede et al 20 where 57 Klebsiella spp.…”

“…Our results detected good agreement (K= 0.87) of CBDE in relation to the golden standard test, BMD method for detection of colistin susceptibility, where sensitivity, specificity, PPV, NPV and accuracy were as follow, 97.3%, 90.9%, 98.2%, 87% and 96.3% respectively. That goes in line with other invistigators 19,29 .…”

“…In this study, 93 of CRKp (68.9%) showed positive carbapenemases production with 31 isolate out of them (33.3%) showed positive Metallo-β-lactamases by combined mCIM/ eCIM. That varies from previous study 19 , where 83.2% of tested CRGNB showed positive carbapenemases with 65.9% showed positive MBLs by combined mCIM/ eCIM testing. Our results nearly matched with the Tsai et al 3 study, that detected 105 out of 193 (54.4%) ertapenem resistant enterobacteria showed positive carbapenemases with 26 out of them (24.7%) were MBLs positive.…”

“…That is higher than the susceptibility in Kar et al 26 study who found that, netilmicin, amikacin, gentamicin, trimethoprimsulfamethoxazole, piperacillin-tazobactam and fosfomycin were the most effective against CRE by only 23%, 21%, 20.5%, 15.5%, 8.5% and 5.5% respectively. And around the susceptibility pattern of Ajlan et al 19 study, who detected that the most effective drug against CRGNB isolates was colistin (72.3%), followed by ceftazidime-avibactam (67.7%), then tigecycline (63.2%).…”