Predicting the use of antibiotics after initial symptomatic treatment of an uncomplicated urinary tract infection:analyses performed after a randomised controlled trial

Objective To predict antibiotic use after initial treatment with ibuprofen using data from a randomised controlled trial comparing ibuprofen to pivmecillinam in the treatment of women with symptoms of an uncomplicated urinary tract infection (UTI). Setting 16 sites in a primary care setting in Norway, Sweden and Denmark. Participants Data from 181 non-pregnant women aged 18–60 presenting with symptoms of uncomplicated UTI, initially treated with ibuprofen. Methods Using the least absolute shrinkage and selection operator logistic regression model, we conducted analyses to see if baseline information could help us predict which women could be treated with ibuprofen without risking treatment failure and which women should be recommended antibiotics. Results Of the 143 women included in the final analysis, 77 (53.8%) recovered without antibiotics and 66 (46.2 %) were subsequently prescribed antibiotics. In the unadjusted binary logistic regression, the number of days with symptoms before inclusion (<3 days) and feeling moderately unwell or worse (≥4 on a scale of 0–6) were significant predictors for subsequent antibiotic use. In the adjusted model, no predictors were significantly associated with subsequent antibiotic use. The area under the curve of the final model was 0.66 (95% CI: 0.57 to 0.74). Conclusion We did not find any baseline information that significantly predicted the use of antibiotic treatment. Identifying women who need antibiotic treatment to manage their uncomplicated UTI is still challenging. Larger data sets are needed to develop models that are more accurat

Urinary Tract Infections in General Practice: Diagnostic strategies, bacteriology, and treatment options for multi-resistant bacteria

Urinary tract infections are commonly handled in primary care. The thesis explored diagnostic strategies and bacteriology of uncomplicated urinary tract infections. A possible narrow-spectrum antibiotic treatment for urinary tract infections caused by extended spectrum β-lactamase (ESBL) producing E. coli was also evaluated. The data were collected by reviewing medical records, performing structured interviews and using self-report questionnaires. A validated and standardised clinical registration form was found to be a safe method to identify women with uncomplicated urinary tract infections who were likely to respond to antibiotic treatment. Stronger symptoms did not correlate with significant bacteriuria at presentation or protracted duration of symptoms following empiric treatment. However, strong symptoms could still be an indication for immediate antibiotics due to discomfort. Nitrofurantoin and pivmecillinam were found to be appropriate first choice agents for empiric treatment of uncomplicated urinary tract infections, and increased consumption of pivmecillinam had not caused marked increase in resistance rates for E. coli. ESBL producing isolates demonstrated marked co-resistance to several oral treatment options. However, pivmecillinam treatment in dosage of 400 mg x 3 was deemed a viable treatment option for community acquired urinary tract infections caused by ESBL producing E. coli. The findings suggest that a commonly used, narrow spectrum antibiotic can be used as an oral treatment option for multi-resistant bacteria causing urinary tract infections. This can possibly avoid hospitalisation of affected persons and reduce future resistance rates

Predictors of Symptom Duration and Bacteriuria in Uncomplicated Urinary Tract Infection

Objective: To identify baseline predictors of symptom duration after empirical treatment for uncomplicated urinary tract infection (UTI) and significant bacteriuria in a cohort of women treated for UTI. Design: Prospective single-centre cohort study. Setting: Outpatient clinic in Norway. Patients: From September 2010 to November 2011, 441 women aged 16–55 years with symptoms of uncomplicated UTI were included. Results: Dipstick findings of leukocyte esterase 1 + (incidence rate ratio (IRR) 1.93, 95% confidence interval (CI) 1.23–3.01, p < 0.01) and microbe resistant to mecillinam treatment (IRR 1.41, 95% CI 1.07–1.89, p = 0.02) predicted longer symptom duration. More pronounced symptoms did not predict longer symptom duration (IRR 1.18, 95% CI 0.94–1.46, p = 0.15) or significant bacteriuria (odds ratio [OR] 1.16, 95% CI 0.72–1.88, p = 0.54). Leukocyte esterase 2 + (OR 2.51, 95% CI 0.92–6.83, p = 0.07) or 3 + (OR 2.40, 95% CI 0.88–6.05, p = 0.09) and nitrite positive urine dipstick test (OR 3.22, 95% CI 1.58–7.01, p = <0.01) were associated with bacteriuria. Conclusion: More pronounced symptoms did not correlate with significant bacteriuria or symptom duration after empirical treatment for acute cystitis. One might reconsider the current practice of treating uncomplicated UTI based on symptoms alone.Key Points Treatment strategies for milder infectious diseases must consider ways of reducing antibiotic consumption to decelerate the increase in antibiotic resistance. Our findings suggest that more emphasis should be put on urine dipstick results and bacteriological findings in the clinical setting. One might reconsider the current practice of treating uncomplicated UTIs based on symptoms alone

Bacteriology in uncomplicated urinary tract infections in Norwegian general practice from 2001–2015

Background: Uncomplicated urinary tract infections in women are common, and urine samples from these patients are not routinely cultured. Empirical treatment is based on knowledge of resistance patterns for common uropathogens. Aim: To evaluate the bacteriological findings and resistance patterns in urine samples from women with uncomplicated urinary tract infections, and to assess the relationship between antimicrobial use and resistance patterns from 2000–2015 in Norway. Method: Bacteriology and resistance patterns were compared in 184 urine cultures from 2001, 406 urine cultures from 2010–2011 and 259 urine cultures from 2013–2015. Antibiotic use data from 2000–2015 were obtained from national databases. Results: Escherichia coli (E. coli) was the main bacterial agent in 80% of the cultures. Staphylococcus saprophyticus (Staph. saprophyticus) represented 6–17%. For E. coli, resistance to mecillinam showed some variation but remained below 9%. There was negligible resistance to nitrofurantoin. Resistance to trimethoprim seemed to stabilise over the last 5 years at around 20%. Amoxicillin resistance had some variations, but remained stable around 30%. There was a steady rise in total consumption of selected antibiotics commonly used to treat urinary tract infections for the period 2000–2015. Conclusion: Mecillinam and nitrofurantoin are both excellent first choices for empirical treatment of uncomplicated urinary tract infections. This study suggests that increasing resistance to trimethoprim challenges the rationale for its use as a first-line agent

Ibuprofen versus mecillinam for uncomplicated cystitis - a randomized controlled trial study protocol

Background: Although uncomplicated cystitis is often self-limiting, most such patients will be prescribed antibiotic treatment. We are investigating whether treatment of cystitis with an NSAID is as effective as an antibiotic in achieving symptomatic resolution. Methods/Design: This is a randomized, controlled, double blind trial following the principles of Good Clinical Practice. Women between the ages of 18 to 60 presenting with symptoms of uncomplicated cystitis are screened for eligibility. 500 women from four sites in Norway, Sweden and Denmark are allocated to treatment with 600 mg ibuprofen three times a day or 200 mg mecillinam three times a day for three days. Allocation is conducted using block randomization. The primary outcome is the number of patients who feel cured by day four as recorded in a diary. Adverse events will be handled and reported in accordance with Good Clinical Practice. Discussion: If treatment of uncomplicated cystitis with ibuprofen is as effective as mecillinam for symptom relief, we can potentially reduce the use of antibiotics on a global scale

Ibuprofen versus mecillinam for uncomplicated cystitis - a randomized controlled trial study protocol

Background: Although uncomplicated cystitis is often self-limiting, most such patients will be prescribed antibiotic treatment. We are investigating whether treatment of cystitis with an NSAID is as effective as an antibiotic in achieving symptomatic resolution. Methods/Design: This is a randomized, controlled, double blind trial following the principles of Good Clinical Practice. Women between the ages of 18 to 60 presenting with symptoms of uncomplicated cystitis are screened for eligibility. 500 women from four sites in Norway, Sweden and Denmark are allocated to treatment with 600 mg ibuprofen three times a day or 200 mg mecillinam three times a day for three days. Allocation is conducted using block randomization. The primary outcome is the number of patients who feel cured by day four as recorded in a diary. Adverse events will be handled and reported in accordance with Good Clinical Practice. Discussion: If treatment of uncomplicated cystitis with ibuprofen is as effective as mecillinam for symptom relief, we can potentially reduce the use of antibiotics on a global scale

Microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections caused by ESBL‐producing Escherichia coli

The aim of this study was to identify microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections (ca‐UTIs) caused by ESBL‐producing Escherichia coli. Eighty‐nine ESBL‐producing E. coli isolated from women suffering from ca‐UTIs were included. The susceptibilities to mecillinam were determined using MIC gradient strip. Whole genome sequencing was performed on a MiSeq platform, and genome assembly was performed using SPAdes v3.11.0. Neither mecillinam MICs nor ESBL genotypes were associated with treatment outcome of patients treated with pivmecillinam. Specific STs, however, showed significant differences in treatment outcome. Patients infected with ST131 were more likely to experience treatment failure compared to patients infected with non‐ST131 (p 0.02) when adjusted for pivmecillinam dose, mecillinam MIC and severity of infection. Patients infected with ST69 were more often successfully treated compared to patients infected with non‐ST69 (p 0.04). Patients infected with blaCTX‐M‐15 ST131 strains were more likely to experience treatment failure than those infected with non‐blaCTX‐M‐15 ST131 strains (p 0.02). The results suggest that specific STs are associated with the clinical efficacy of pivmecillinam. Further studies with a larger number of strains, including a larger number of mecillinam resistant strains, are needed to confirm these results

Microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections caused by ESBL‐producing Escherichia coli

The aim of this study was to identify microbial risk factors for treatment failure of pivmecillinam in community‐acquired urinary tract infections (ca‐UTIs) caused by ESBL‐producing Escherichia coli. Eighty‐nine ESBL‐producing E. coli isolated from women suffering from ca‐UTIs were included. The susceptibilities to mecillinam were determined using MIC gradient strip. Whole genome sequencing was performed on a MiSeq platform, and genome assembly was performed using SPAdes v3.11.0. Neither mecillinam MICs nor ESBL genotypes were associated with treatment outcome of patients treated with pivmecillinam. Specific STs, however, showed significant differences in treatment outcome. Patients infected with ST131 were more likely to experience treatment failure compared to patients infected with non‐ST131 (p 0.02) when adjusted for pivmecillinam dose, mecillinam MIC and severity of infection. Patients infected with ST69 were more often successfully treated compared to patients infected with non‐ST69 (p 0.04). Patients infected with blaCTX‐M‐15 ST131 strains were more likely to experience treatment failure than those infected with non‐blaCTX‐M‐15 ST131 strains (p 0.02). The results suggest that specific STs are associated with the clinical efficacy of pivmecillinam. Further studies with a larger number of strains, including a larger number of mecillinam resistant strains, are needed to confirm these results