Background & objectives:
The escalation in carbapenem resistance among
Enterobacteriaceae
has resulted in a lack of effective therapeutic alternatives. Older antimicrobials, fosfomycin, nitrofurantoin and colistin for urinary tract infections (UTIs) caused by carbapenem-resistant
Enterobacteriaceae
(CRE) may be effective treatment options. The objectives of this study were to evaluate the utility of fosfomycin, nitrofurantoin and colistin in treating UTI caused by CRE and molecular characterization of the plasmid-mediated carbapenem resistance mechanisms.
Methods:
Consecutive, non-duplicate isolates of CR
Escherichia coli
and
Klebsiella
spp. from urine cultures were included (n=150). Minimum inhibitory concentrations (MIC) were determined by
E
-test (fosfomycin and nitrofurantoin) and broth microdilution (colistin). Efficacy ratios were derived by dividing susceptibility breakpoints by observed MIC values of the drugs for the isolates. Isolates were screened for genes coding for carbapenemases using multiplex PCR. Fosfomycin, nitrofurantoin and colistin-resistant isolates were screened for plasmid-borne resistance genes
fos
A3,
oqx
AB and
mcr
-1, respectively using PCR.
Results:
Among
E. coli
, 98.9, 56 and 95 per cent isolates were susceptible to fosfomycin, nitrofurantoin and colistin, respectively, while 94 and 85 per cent of
Klebsiella
spp. were susceptible to fosfomycin and colistin, respectively. The efficacy ratios indicated fosfomycin as the drug of choice for UTI caused by CR
E. coli
and
Klebsiella
spp., followed by colistin. The
bla
NDM
gene was most common, followed by
bla
OXA48-like
. Plasmid-borne genes encoding resistance to fosfomycin, nitrofurantoin and colistin were absent.
Interpretation & conclusions:
With increasing resistance against the current treatment options, older drugs may emerge as effective options. Molecular screening of resistant isolates is essential to prevent the spread of plasmid-borne resistance against these drugs.