Abstract
Colistin has become a critical antibiotic for fatal Gram-negative infections owing to the proliferation of multidrug-resistant carbapenemase-producing bacteria. Thus, cheaper, faster, efficient and easier-to-use colistin diagnostics are required for clinical surveillance, diagnoses and therapeutics. The sensitivity, specificity, major error (ME), very major error (VME), categorial agreement, essential agreement, turnaround time (TAT), average cost, and required skill for four colistin resistance diagnostics viz., CHROMagar COL-APSE, ComASP Colistin, MicroScan, and Colistin MAC Test (CMT) were evaluated against broth microdilution (BMD) using 84 Gram-negative bacterial isolates. A multiplex PCR (M-PCR) was used to screen all isolates to detect the presence of the mcr-1 to mcr-5 genes. A 15-point grading scale was used to grade the tests under skill, ease, processing time etc. mcr-1 was detected by both M-PCR and CMT in a single E. coli isolate, with other PCR amplicons suggestive of mcr-2, -3 and -4 genes being also observed on the gel. The sensitivity and specificity of CHROMagar COL-APSE, MicroScan, and ComASP Colistin, were 82.05% and 66.67%, 92.31% and 76.92%, and 100% and 88.89% respectively. The MicroScan was the most expensive at a cost (per sampe tested) of R221.6 ($15.0), followed by CHROMagar COL-APSE (R118.3; $8.0), M-PCR (R75.1; $5.1), CMT (R20.1; $1.4) and ComASP Colistin (R2.64; $0.2). CHROMagar was the easiest to perform, followed by ComASP Colistin, M-PCR, MicroScan, CMT and BMD whilst M-PCR and MicroScan required higher skill. The ComASP Colistin was the best performing diagnostic test, with low VME and ME, making it recommendable for routine colistin sensitivity testing in clinical laboratories; particularly, in poorer settings. It is however limited by a TAT of 18–24 hours.
Highlights
Colistin has become a critical antibiotic for fatal Gram-negative infections owing to the proliferation of multidrug-resistant carbapenemase-producing bacteria
A 15-point grading scale was used to grade the tests under skill, ease, processing time etc. mcr-1 was detected by both multiplex polymerase chain reaction (PCR) (M-PCR) and Colistin MAC Test (CMT) in a single E. coli isolate, with other PCR amplicons suggestive of mcr-2, -3 and -4 genes being observed on the gel
The isolates were identified by the MicroScan Walkaway to comprise of 12 species viz., Enterobacter cloacae (n = 27), Klebsiella pneumoniae (n = 12), Salmonella enterica (n = 12), Acinetobacter baumannii (n = 10), Escherichia coli (n = 9), Klebsiella oxytoca (n = 4), Pseudomonas aeruginosa (n = 4), Proteus mirabilis (n = 2), Burkholderia cepacia (n = 1), Hafnia alvei (n = 1), Providencia stuartii (n = 1), and Tatumella spp. (n = 1) (Fig. 2A)
Summary
Colistin has become a critical antibiotic for fatal Gram-negative infections owing to the proliferation of multidrug-resistant carbapenemase-producing bacteria. The sensitivity, specificity, major error (ME), very major error (VME), categorial agreement, essential agreement, turnaround time (TAT), average cost, and required skill for four colistin resistance diagnostics viz., CHROMagar COL-APSE, ComASP Colistin, MicroScan, and Colistin MAC Test (CMT) were evaluated against broth microdilution (BMD) using 84 Gram-negative bacterial isolates. To date, settling on an efficient, fast, cheaper and easy-to-use diagnostic for detecting colistin resistance in routine microbiology laboratories remains a challenge, in developing countries[9,10,11]. This is inspite of the fact that several colistin-resistance diagnostics exist, broadly categorised under phenotypic and molecular tests[9]. By including a cost and required-skill component, we aim to provide data for informing colistin resistance diagnostic choices for under-resourced laboratories
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