Predictive value of antimicrobial susceptibility from previous urinary tract infection in the treatment of re-infection

INTRODUCTION

Urinary tract infection (UTI) is considered to be one of the most common bacterial infections.1 Approximately 5% of young adults have bacteriuria at any one time,2 with up to 50% of adult women reporting a UTI at some time in their life.1 The incidence of UTI increases with age, at the rate of 1–2% per decade.2 Recurrence happens frequently, in 27–48% of healthy women,3 after spontaneous clearance as well as after antimicrobial treatment.2^,4 Prospective studies have shown that the vast majority of recurrent UTIs are re-infections by a previously identified strain.3

Guidelines on empirical treatment of acute uncomplicated UTI suggest that agents may not be suitable for empirical use when the community prevalence of resistance to the antimicrobial in Escherichia coli exceeds 10–20%.5 Empirical antimicrobial therapy requires a balance between the need to achieve effective therapy as well as to limit the use of broad-spectrum antimicrobial agents. Antimicrobial susceptibility test results from previous episodes of UTI may guide the decision-making process in the selection of empiric therapy in a subsequent episode of UTI, and indicate the use of antimicrobials with high community resistance levels.

There are limited data to confirm or quantify the predictive value of the antimicrobial resistance pattern of previous isolates. This analysis assesses the value of the antimicrobial susceptibility of a previously isolated E. coli on predicting the susceptibility of a subsequent isolation of E. coli from a UTI in routine clinical practice.

METHOD

The laboratory at Galway University Hospital is the main regional laboratory for over 200 000 patients (of a total Irish population of around 4 million) and provides a microbiology service to GPs in the West of Ireland as well as to the hospital.

All records from general practices of patients with more than one sample of significant bacteriuria (>10⁵ pure culture/ml), that is, recurrent infections, were extracted from the database over a 4.5-year period (April 2004 to September 2008). The first isolate during this period was identified for each patient, and the time to each subsequent isolate was calculated. A recurrence was defined as a re-infection if it was caused by the same species and if it occurred more than 2 weeks after the original UTI.3 Relapse isolates, defined as recurrence with the same species within 2 weeks from the previous sample, were excluded from this analysis.3 If more than one sample was given during a 3-month period, only the first of these samples was considered.

The positive predictive value (PPV) was calculated as the proportion of patients with an E. coli resistant to an antimicrobial at first isolate that remain resistant to this antimicrobial at the subsequent isolate. Similarly, the negative predictive value (NPV) gives the proportion of patients with an E. coli infection susceptible to an antimicrobial at the first isolate, who show the same susceptibility in a subsequent isolate. As the PPV and NPV are directly proportional to the prevalence of resistance in the population, a correction (Bayes theorem) is applied,6 with a correction for the variability introduced by the prevalence according to Zou.7 The PPV is calculated as P(disease|+test) = (sensitivity × prevalence)/([sensitivity × prevalence] + [{1 — specificity}{1 — prevalence}]). PPV and NPV and their 95% confidence intervals (CIs) were calculated using WINPEPI.8 The prevalence was obtained from the full database (all general practice samples over the period of 4.5 years). For simplicity, PPV and NPV are only presented for re-infection within 3 months and between 9 and 12 months.

RESULTS

Over the 4.5-year period, 147 306 urine samples were analysed; in 21.3% an organism and in 14.4% E. coli was identified. A total of 3413 patients provided at least two E. coli-positive samples over the study period. The mean age of the prospective cohort was 51.7 years (standard deviation [SD] 25.7 years) and median 56.0 years. The study population consisted of 90.9% females and 11.0% were under 18 years of age. No changes in age or sex were observed over the time period.

A total of 1092 of patients had a re-infection within 3 months, 693 patients had a re-infection between 3 and 6 months after the first sample, 543 between 6 and 9 months, and 450 between 9 and 12 months. Little difference was found between age and sex when comparing the full database from the 4.5-year period to the re-infection database (Table 1). Table 2 gives an overview of the PPV and NPV of the first sample when the subsequent sample is within 3 months and between 9 and 12 months; the PPV and NPV for the periods in between (3–6 months and 6–9 months) declines gradually between these periods.

There is an 84.6% probability that a patient with an ampicillin-resistant E. coli in a previous sample will still have an ampicillin-resistant E. coli in a subsequent episode of bacteriuria within 3 months. PPVs are obtained for ciprofloxacin (83.8%) and trimethoprim (78.3%). The probability of a nitrofurantoin resistant re-infection within 3 months if the previous isolate is resistant is particularly low (20.2%). The probability that a re-infection between 9 months and a year remains resistant is high, at 75.9% for ampicillin and 59.2% for trimethoprim. In contrast, the probability that a re-infection within 3 months and up to a year is susceptible if the initial E. coli was susceptible is nearly 100% for ciprofloxacin and nitrofurantoin, and 86.3% for trimethoprim.

DISCUSSION