Published data on the epidemiology of idiopathic thrombocytopenic purpura (ITP) among adults are very limited. We conducted a study of ITP incidence using the General Practice Research Database in the United Kingdom. From 1992 to 2005, there were 840 cases of ITP among adults considering 21 749 623 person-years (PYs) of follow-up, for a crude incidence of 3.9 per 100 000 PYs [95% confidence interval (CI): 3.6, 4.1]. The incidence was higher among women [4.5 per 100 000 PYs (95% CI: 4.2, 4.9)] than men [3.2 per 100 000 PYs (95% CI: 2.8, 3.5)]. Among both women and men, incidence was higher at older ages and in later study years. In a systematic review of previously published literature, incidence of ITP among adults ranged from 1.6 to 2.68 per 100 000 persons per year; prevalence ranged from 9.5 to 23.6 per 100 000 persons. In order to improve the understanding of the disease burden of ITP, future studies should include a clearly defined definition of ITP and focus on well-described source populations that are geographically and ethnically diverse.

The majority of case reports with NDM-1-producing bacteria had presumed colonization, not infection, with one or more bacteria. The available human case reports and surveillance data suggest a global distribution of NDM-1-producing Enterobacteriaceae and non-Enterobacteriaceae.

Background Uncomplicated urinary tract infection (uUTI) is predominantly caused by Escherichia coli, which has increasing antimicrobial resistance (AMR) at the US-community level. As uUTI is often treated empirically, assessing AMR is challenging and there are limited contemporary data characterizing period prevalence in the US. Methods This was a retrospective study of AMR using Becton, Dickinson and Company Insights Research Database (Franklin Lakes, NJ) data collected 2011–2019. Thirty-day, non-duplicate Escherichia coli urine isolates from US female outpatients (aged ≥12 years) were included. Isolates were evaluated for not-susceptibility (intermediate/resistant) to trimethoprim-sulfamethoxazole, fluoroquinolones, or nitrofurantoin, and assessed for extended-spectrum β-lactamase production (ESBL+) and for ≥2 or ≥3 drug-resistance phenotypes. Generalized estimating equations were used to model AMR trends over time and by US census region. Results Among 1,513,882 Escherichia coli isolates, the overall prevalence of isolates not-susceptible to trimethoprim-sulfamethoxazole, fluoroquinolones, and nitrofurantoin was 25.4%, 21.1%, and 3.8%, respectively. Among the isolates, 6.4% were ESBL+, 14.4% had ≥2 drug-resistance phenotypes, and 3.8% had ≥3. Modelling demonstrated a relative average yearly increase of 7.7% (95% confidence interval [CI], 7.2–8.2%) for ESBL+ isolates and 2.7% (95% CI, 2.2–3.2%) for ≥3 drug-phenotypes (both p<0.0001). Modelling also demonstrated significant variation in AMR prevalence between US census regions (p<0.001). Conclusions Period prevalence of AMR among US outpatient urine-isolated Escherichia coli was high, and for multi-drug-resistance phenotypes increased during the study period with significant variation between census regions. Knowledge of regional AMR rates helps inform empiric treatment of community-onset uUTI and highlights the AMR burden to physicians.

bNoninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations. Complicated urinary tract infections (cUTI) occur in persons with structural or functional abnormalities of the urinary tract and in hospitalized patients with significant medical or surgical comorbidities (1, 2). These infections are a major cause of hospital admission, morbidity, mortality, and excess health care costs (3-6). National and international treatment guidance for urinary tract infections includes recommendations for targeted and empirical treatment of the major causative pathogens, including Escherichia coli, Klebsiella pneumoniae, and non-Enterobacteriaceae organisms such as Pseudomonas aeruginosa (7-9).Of notable concern for the clinical care of patients with cUTI and other serious infections is effective antimicrobial treatment amid the emergence and spread of drug-resistant pathogens (10, 11). To demonstrate efficacy of a new or test antimicrobial agent for the treatment of adult subjects with cUTI, randomized parallel-group noninferiority phase 3 trials have traditionally been used to meet regulatory requirements for approval of the test drug (12). An active-comparator, noninferiority study design is generally used in cUTI trials given the ethical implications of placebo treatment (13,14). In order to conduct a noninferiority trial, an estimate of the treatment effect of the planned antimicrobial comparator must be obtained from historical data (12). Once an estimate of the treatment effect of the antimicrobial comparator is determined, the largest clinically acceptable difference of the test drug compared to the comparator must be decided. This decision is critical to the design, analysis, and interpretation of a noninferiority trial.We conducted a systematic review and me...

Background We evaluated associations between antibiotic prescription and healthcare resource use and costs (Part A), and between antibiotic switching and healthcare resource use, costs, and uncomplicated urinary tract infection recurrence (Part B) in female patients with uncomplicated urinary tract infection in the United States. Methods This retrospective cohort study of linked Optum and Premier Healthcare Database data included female patients ≥12 years old with an uncomplicated urinary tract infection diagnosis (index date), who were prescribed antibiotics during an outpatient/emergency department visit between January 1, 2013 and December 31, 2018. In Part A, patients were stratified by antibiotic prescription appropriateness: appropriate and optimal (compliant with Infectious Diseases Society of America 2011 guidelines for drug class/treatment duration) versus inappropriate/suboptimal (inappropriate drug class/treatment duration per Infectious Diseases Society of America 2011 guidelines, and/or treatment failure). In Part B, patients were stratified by treatment pattern (antibiotic switch vs no antibiotic switch). Healthcare resource use and costs during index episode (within 28 days of index date) and 12-month follow-up were compared. Results Of 5870 patients (mean age 44.5 years), 2762 (47.1%) had inappropriate/suboptimal prescriptions and 567 (9.7%) switched antibiotic. Inappropriate/suboptimal prescriptions were associated with higher healthcare resource use (mean number of ambulatory care and pharmacy claims [both p < 0.001]), and higher total mean cost (inpatient, outpatient/emergency department, ambulatory visits, and pharmacy costs) per patient ($2616) than appropriate and optimal prescriptions ($649; p < 0.001) (Part A). Antibiotic switching was associated with more pharmacy claims and higher total mean costs (p ≤ 0.01), and a higher incidence of recurrent uncomplicated urinary tract infection (18.9%) than no antibiotic switching (14.2%; p < 0.001) (Part B). Conclusions Inappropriate/suboptimal prescriptions and antibiotic switching were associated with high costs, ambulatory care, and pharmacy claims, suggesting a need for improved uncomplicated urinary tract infection prescribing practices in the United States.

Background The first cases of extensively drug resistant gonorrhoea were recorded in the United Kingdom in 2018. There is a public health need for strategies on how to deploy existing and novel antibiotics to minimise the risk of resistance development. As rapid point-of-care tests (POCTs) to predict susceptibility are coming to clinical use, coupling the introduction of an antibiotic with diagnostics that can slow resistance emergence may offer a novel paradigm for maximising antibiotic benefits. Gepotidacin is a novel antibiotic with known resistance and resistance-predisposing mutations. In particular, a mutation that confers resistance to ciprofloxacin acts as the ‘stepping-stone’ mutation to gepotidacin resistance. Aim To investigate how POCTs detecting Neisseria gonorrhoeae resistance mutations for ciprofloxacin and gepotidacin can be used to minimise the risk of resistance development to gepotidacin. Methods We use individual-based stochastic simulations to formally investigate the aim. Results The level of testing needed to reduce the risk of resistance development depends on the mutation rate under treatment and the prevalence of stepping-stone mutations. A POCT is most effective if the mutation rate under antibiotic treatment is no more than two orders of magnitude above the mutation rate without treatment and the prevalence of stepping-stone mutations is 1–13%. Conclusion Mutation frequencies and rates should be considered when estimating the POCT usage required to reduce the risk of resistance development in a given population. Molecular POCTs for resistance mutations and stepping-stone mutations to resistance are likely to become important tools in antibiotic stewardship.

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Background Uncomplicated urinary tract infections (uUTIs) are one of the most common bacterial infections in the United States (US). Contemporary data are important for understanding the health economic impact of antimicrobial-resistant uUTIs. We compared the economic burden among patients with uUTI isolates susceptible or not-susceptible to the initial antibiotic prescription. Methods This retrospective cohort study utilized electronic health record data (1 July 2016–31 March 2020) from a large Mid-Atlantic US integrated delivery network database. Patients were females aged ≥ 12 years with a uUTI, who received oral antibiotic treatment and had ≥ 1 urine culture within ± 5 days of diagnosis. The primary outcome was the difference in healthcare resource use and costs (all-cause, urinary tract infection [UTI]-related) among patients with susceptible versus not-susceptible isolates during the 6 months after the index uUTI diagnosis. Secondary outcomes included: pharmacy costs, hospital admissions and emergency department visits, as well as the probability of uUTI progressing to complicated UTI (cUTI) between patients with susceptible and not-susceptible isolates. Patient outcomes were compared using 1:1 propensity score matching. Winsorized costs were adjusted to 2020 quarter 1 US dollars ($). Results A total of 2565 patients were eligible for analysis. The propensity score-matched sample comprised 2018 patients, with an average age of 44.0 and 41.0 years for the susceptible and not-susceptible populations, respectively. In the 6 months post-index uUTI event, patients with not-susceptible isolates had significantly more all-cause prescriptions orders (+ 1.41 [P = 0.001]), UTI-related prescriptions orders (+ 0.26 [P < 0.001]) and a higher probability of all-cause inpatient (+ 1.4% [P = 0.009]), outpatient (+ 6.1% [P = 0.006]), or UTI-related outpatient (+ 3.7% [P = 0.039]) encounters. Patients with a uUTI and an antibiotic-not-susceptible isolate were significantly more likely to progress to cUTI than those with susceptible isolates (odds ratio: 2.35 [confidence interval: 1.66–3.33; P < 0.001]). Over 6 months, patients with not-susceptible versus susceptible isolates had significantly higher all-cause costs (+ $426 [P = 0.031]) and UTI-related costs (+ $157 [P = 0.034]). Conclusions Patients with a uUTI caused by antibiotic-not-susceptible isolates had higher healthcare resource usage, costs, and increased likelihood of progressing to cUTI than those with antibiotic-susceptible isolates.