Interaction between Antibiotic Resistance, Resistance Genes, and Treatment Response for Urinary Tract Infections in Primary Care.

Given increasing antimicrobial resistance, we aimed to determine antibiotic susceptibility and presence of resistance genes in uropathogens in primary care, factors associated with resistance to commonly prescribed antibiotics, and effect of treatment on early symptom resolution. We conducted a prospective study of primary care patients with urinary tract infection (UTI) symptoms and culture-confirmed UTI in Singapore from 2015 to 2016. Cohort characteristics and antimicrobial susceptibility of cultured isolates were analyzed. Among Enterobacteriaceae isolates, early symptom resolution (within 3 days) according to antibiotic prescribed and isolate susceptibility and factors associated with antibiotic resistance were evaluated. Of 695 symptomatic patients, 299 were urine culture positive; of these 299 patients, 259 (87%) were female. Escherichia coli was the most common uropathogen (76%). Enterobacteriaceae isolates (n = 283) were highly susceptible to amoxicillin-clavulanate (86%), nitrofurantoin (87%), and fosfomycin (98%), but >20% were resistant to ciprofloxacin and co-trimoxazole. Isolates resistant to appropriate indicator antibiotics were further tested to determine proportions positive for blaCTX-M (14/26, 54%), plasmid-mediated ampC (12/24, 50%), qnr (7/69, 10%), and fos (1/6, 17%) resistance genes. A total of 67% of patients given antibiotics with susceptible isolates reported early resolution versus 45% given antibiotics with nonsusceptible isolates (P = 0.001) and 27% not treated (P = 0.018). On multivariable analysis, Indian ethnicity and diabetes mellitus were associated with amoxicillin-clavulanate resistance. Genitourinary abnormalities, UTI in the past 12 months, and hospitalization in the past 6 months were associated with ciprofloxacin and co-trimoxazole resistance. Patients given active empirical antibiotics were most likely to report early symptom resolution, but correlation with in vitro susceptibility was imperfect. Factors associated with resistance may guide the decision to obtain initial urine culture.

Surveillance and correlation of antibiotic prescription and resistance of Gram-negative bacteria in Singaporean hospitals.

A surveillance study was performed in four Singapore public hospitals from 2006 to 2008 to determine the correlation between antibiotic prescription and Gram-negative bacterial antimicrobial resistance. Targeted organisms included ceftriaxone- and ciprofloxacin-resistant Escherichia coli and Klebsiella pneumoniae, as well as imipenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days every quarter. Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated via cross-correlation analysis. Results over 3 years indicated significantly rising incidence densities of ceftriaxone- and ciprofloxacin-resistant E. coli and imipenem-resistant Acinetobacter spp. (blood isolates only). Antimicrobial-resistant Klebsiella pneumoniae rates declined. The prescription rates of piperacillin-tazobactam, ertapenem, meropenem, ciprofloxacin, and levofloxacin increased significantly, while imipenem and moxifloxacin prescription decreased. Cross-correlation analysis demonstrated possible associations between prescription of fluoroquinolones and ciprofloxacin-resistant E. coli (R(2) = 0.46), fluoroquinolones and ceftriaxone-resistant E. coli (R(2) = 0.47), and carbapenems and imipenem-resistant Acinetobacter spp. (R(2) = 0.48), all at zero time lag. Changes in meropenem prescription were associated with a similar trend in imipenem-resistant Acinetobacter blood isolates after a 3-month time lag. No correlation was found between cephalosporin use and resistance. In conclusion, our data demonstrated correlation between prescription of and Gram-negative bacterial resistance to several, but not all, key antimicrobial agents in Singapore hospitals. In areas where Gram-negative bacterial resistance is endemic and prescription of broad-spectrum antimicrobial agents is high, factors other than antimicrobial usage may be equally important in maintaining high resistance rates.