Abstract
Background: AmpC beta-lactamase-producing bacteria are associated with increased resistance to third-generation cephalosporins. Here, we describe plasmid-mediated AmpC beta-lactamase-producing enterobacteria isolated from urban and rural dwellers in Uganda. Methods: Stool and urine from 1,448 individuals attending outpatient clinics in Kampala and two rural districts in central Uganda were processed for isolation of Escherichia coli and Klebsiella. Following antibiotic susceptibility testing, cefoxitin resistant isolates, and amoxicillin/clavulanate resistant but cefoxitin susceptible isolates, were tested for AmpC beta-lactamase production using the cefoxitin-cloxacillin double-disc synergy test. Carriage of plasmid-mediated AmpC beta-lactamase-encoding genes (pAmpC) and extended spectrum beta-lactamase (ESBL) encoding genes was determined by PCR. Results: Nine hundred and thirty E. coli and 55 Klebsiella were recovered from the cultured samples, yielding 985 isolates investigated (one per participant). One hundred and twenty-nine isolates (13.1%, 129/985) were AmpC beta-lactamase producers, of which 111 were molecularly characterized for pAmpC and ESBL gene carriage. pAmpC genes were detected in 60% (67/111) of the AmpC beta-lactamase producers; pAmpC genes were also detected in 18 AmpC beta-lactamase non-producers and in 13 isolates with reduced susceptibility to third-generation cephalosporins, yielding a total of 98 isolates that carried pAmpC genes. Overall, the prevalence of pAmpC genes in cefoxitin resistant and/or amoxicillin/clavulanate resistant E. coli and Klebsiella was 59% (93/157) and 26.1% (5/23), respectively. The overall prevalence of pAmpC-positive enterobacteria was 10% (98/985); 16.4% (45/274) in Kampala, 6.2% (25/406) Kayunga, and 9.2% (28/305) Mpigi. Ciprofloxacin use was associated with carriage of pAmpC-positive bacteria while residing in a rural district was associated with protection from carriage of pAmpC-positive bacteria. Conclusion: pAmpC beta-lactamase producing enterobacteria are prevalent in urban and rural dwellers in Uganda; therefore, cefoxitn should be considered during routine susceptibility testing in this setting.
Highlights
Enterobacteriaceae is a family of Gram-negative bacteria that inhabit the mammalian gut and includes the leading causes of community- and hospital-acquired infections[1]
We show that plasmid-mediated AmpC beta-lactamase-encoding genes (pAmpC) β-lactamase producing bacteria are prevalent in enterobacteriaceae isolated from urban and rural dwellers in Uganda, implying that ceftriaxone, an antibiotic commonly used to treat systemic infections in Uganda, could be associated with treatment failure
Findings in this study suggest that antibiotic susceptibility testing of enterobacteria in Uganda may yield false results for third-generation cephalosporins e.g. ceftriaxone, cefotaxime and ceftazidime
Summary
Enterobacteriaceae is a family of Gram-negative bacteria that inhabit the mammalian gut and includes the leading causes of community- and hospital-acquired infections[1]. One of the main mechanisms underlying resistance to β-lactam antibiotics among the enterobacteriaceae are the AmpC β-lactamases. These enzymes are clinically relevant as they confer resistance to most β-lactam antibiotics, except the fourth-generation cephalosporins and carbapenems[2,3,4]. Escherichia coli and other enterobacteria, notably Proteus mirabilis, Salmonella and Klebsiella spp., can acquire plasmid-encoded AmpC β-lactamases (pAmpC), which are highly transferable between species. AmpC beta-lactamase-producing bacteria are associated with increased resistance to third-generation cephalosporins. We describe plasmid-mediated AmpC beta-lactamase-producing enterobacteria isolated from urban and rural dwellers in Uganda. One hundred and twenty-nine isolates (13.1%, 129/985) were AmpC beta-lactamase producers, of which 111 were molecularly characterized for pAmpC and ESBL gene carriage. One hundred and twenty-nine isolates (13.1%, 129/985) were AmpC beta-lactamase producers, of which 111 were molecularly characterized for pAmpC and ESBL gene carriage. pAmpC genes were detected in 60% (67/111) of the AmpC
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