RESUMEN
Background: In low- and middle-income countries, symptomatic urinary tract infection (UTI) patients are often prescribed antibiotics without microbiological confirmation. UTIs caused by antibiotic-resistant bacteria are increasingly common, and this heightens the risk of empirical treatment failure. This study evaluates the appropriateness of empirical antibiotic therapy to UTI patients in Nairobi County, Kenya. Methods: A hospital-based, cross-sectional study was conducted in Nairobi County, Kenya, amongst symptomatic adult and child patients. UTI was defined as a monoculture growth with colony counts of ≥104 cfu/mL. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disc diffusion method. Empirical therapy was considered appropriate if the pathogen isolated was susceptible to the prescribed antibiotic and inappropriate if the pathogen was resistant to the prescribed antibiotic. Results: A total of 552 participants were enrolled with a median age of 29 years (interquartile range: 24-36). The majority were female, 398 (72%). Of the 552, 274 (50%) received empirical antibiotic therapy, and 95/274 (35%) were confirmed to have UTI by culture. The antibiotics most frequently prescribed were fluoroquinolones [ciprofloxacin in 80 (30%) and levofloxacin 43 (16%)], amoxicillin-clavulanic acid in 48 (18%) and nitrofurantoin in 32 (12%). Amongst the 95 patients with bacteriological confirmation of UTI, 50 (53%) received appropriate empirical antibiotic therapy, whilst for 38 (40%) participants, the therapy was inappropriate. Conclusions: The complexity of appropriate empirical treatment for UTIs is compounded by high levels of resistance in UTI pathogens. Antimicrobial resistance surveillance strategies that could help in designing appropriate empirical regimens in resource constrained settings should be adopted for optimal empiric therapy.
RESUMEN
Urinary tract infection (UTI) develops after a pathogen adheres to the inner lining of the urinary tract. Cases of UTIs are predominantly caused by several Gram-negative bacteria and account for high morbidity in the clinical and community settings. Of greater concern are the strains carrying antimicrobial resistance (AMR)-conferring genes. The gravity of a UTI is also determined by a spectrum of other virulence factors. This study represents a pilot project to investigate the burden of AMR among uropathogens in East Africa. We examined bacterial samples isolated in 2017-2018 from in- and out-patients in Kenya (KY) and Uganda (UG) that presented with clinical symptoms of UTI. We reconstructed the evolutionary history of the strains, investigated their population structure, and performed comparative analysis their pangenome contents. We found 55 Escherichia coli and 19 Klebsiella pneumoniae strains confirmed uropathogenic following screening for the prevalence of UTI virulence genes including fimH, iutA, feoA/B/C, mrkD, and foc. We identified 18 different sequence types in E. coli population while all K. pneumoniae strains belong to ST11. The most prevalent E. coli sequence types were ST131 (26%), ST335/1193 (10%), and ST10 (6%). Diverse plasmid types were observed in both collections such as Incompatibility (IncF/IncH/IncQ1/IncX4) and Col groups. Pangenome analysis of each set revealed a total of 2862 and 3464 genes comprised the core genome of E. coli and K. pneumoniae population, respectively. Among these are acquired AMR determinants including fluoroquinolone resistance-conferring genes aac(3)-Ib-cr and other significant genes: aad, tet, sul1, sul2, and cat, which are associated with aminoglycoside, tetracycline, sulfonamide, and chloramphenicol resistance, respectively. Accessory genomes of both species collections were detected several ß-lactamase genes, blaCTX-M, blaTEM and blaOXA, or blaNDM. Overall, 93% are multi-drug resistant in the E. coli collection while 100% of the K. pneumoniae strains contained genes that are associated with resistance to three or more antibiotic classes. Our findings illustrate the abundant acquired resistome and virulome repertoire in uropathogenic E. coli and K. pneumoniae, which are mainly disseminated via clonal and horizontal transfer, circulating in the East African region. We further demonstrate here that routine genomic surveillance is necessary for high-resolution bacterial epidemiology of these important AMR pathogens.