Abstract
BackgroundThe problem of emerging ciprofloxacin resistance is compounded by its frequent association with multiresistance, the reason for which is not fully understood. In this study we compare multiresistance, clonal similarities and phylogenetic group in urinary tract isolates of Escherichia coli sensitive and resistant to the quinolone antimicrobials nalidixic acid and ciprofloxacin.ResultsQuinolone resistant isolates were more resistant to non-quinolone antibiotics than sensitive isolates, with resistance to ampicillin, mecillinam, sulphonamide, trimethoprim, tetracycline, kanamycin and chloramphenicol significantly increased. Fifty-one percent of quinolone-resistant isolates were multiresistant. Although multiresistance was most prevalent (63%) in isolates showing high-level ciprofloxacin resistance, it was still highly prevalent (41%) in nalidixic acid resistant isolates with low-level ciprofloxacin resistance. Multiresistance was more frequent among singleton isolates (61%) than clonal isolates (40%) of quinolone resistant Escherichia coli. Ciprofloxacin resistance was associated with certain specific clones, among them the globally distributed clonal Group A. However, there was no significant difference in the overall degree of clonality between quinolone sensitive and resistant isolates. Ciprofloxacin resistance was positively associated with phylogroup D and negatively associated with phylogroup B2. This correlation was not associated with clonal isolates.ConclusionThis study supports earlier findings of association between ciprofloxacin resistance and resistance to other antibiotics. The prevalence of multiresistance in quinolone-resistant isolates that have not yet developed high-level ciprofloxacin resistance suggest that multiresistance arises early in the development of quinolone resistance. This is consistent with exposure to quinolones causing quinolone resistance by mutations and mobilization of multiresistance elements by induction of the SOS response. The spread of clones seems to be less important than previously reported in regard to emergence of quinolone resistance and multiresistance as both are associated primarily with singleton isolates.
Highlights
The problem of emerging ciprofloxacin resistance is compounded by its frequent association with multiresistance, the reason for which is not fully understood
Since the broad spectrum fluoroquinolone antibiotics were introduced in clinical practice, fluoroquinolone resistant E. coli (FQREC) strains have been isolated with increasing frequency, with prevalence as high as 25 – 50% being reported from some southern European countries
In order to avoid confusion with the established sensitive-intermediateresistant terminology, we refer to our three subpopulations as Cipro0.032- nalidixic acid sensitive isolates with ciprofloxacin MIC ≤ 0.064 and modal MIC 0.032 mg/L (N = 43); Cipro0.5 – nalidixic acid resistant isolates with ciprofloxacin MIC ≥ 0.125 and ≤ 2 and modal MIC 0.5 mg/L (N = 75) and Cipro64 – nalidixic acid resistant, ciprofloxacin resistant isolates with ciprofloxacin MIC ≥ 4 and modal MIC 32–64 mg/L (N = 75)
Summary
The problem of emerging ciprofloxacin resistance is compounded by its frequent association with multiresistance, the reason for which is not fully understood. In this study we compare multiresistance, clonal similarities and phylogenetic group in urinary tract isolates of Escherichia coli sensitive and resistant to the quinolone antimicrobials nalidixic acid and ciprofloxacin. The problem of emerging ciprofloxacin resistance is further compounded by its frequent association with multiresistance to other antibiotics [8,9,10,11,12,13]. The reason for this association is not understood, but several possibilities may be considered. Quinolones are mutagenic and induce the SOS response which in turn activates the mobility of transposable elements [22,23,24], suggesting that chromosomal mutations and/or the spread of mobile resistance factors might be involved
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