anti-bacterial agents

Background
Bacterial vaginosis affects one third of reproductive-aged women, and recurrence is common. Evidence of sexual exchange of bacterial vaginosis–associated organisms between partners suggests that male-partner treatment may increase the likelihood of cure.

Methods
This open-label, randomized, controlled trial involved couples in which a woman had bacterial vaginosis and was in a monogamous relationship with a male partner. In the partner-treatment group, the woman received first-line recommended antimicrobial agents and the male partner received oral and topical antimicrobial treatment (metronidazole 400-mg tablets and 2% clindamycin cream applied to penile skin, both twice daily for 7 days). In the control group, the woman received first-line treatment and the male partner received no treatment (standard care). The primary outcome was recurrence of bacterial vaginosis within 12 weeks.

Results
A total of 81 couples were assigned to the partner-treatment group, and 83 couples were assigned to the control group. The trial was stopped by the data and safety monitoring board after 150 couples had completed the 12-week follow-up period because treatment of the woman only was inferior to treatment of both the woman and her male partner. In the modified intention-to-treat population, recurrence occurred in 24 of 69 women (35%) in the partner-treatment group (recurrence rate, 1.6 per person-year; 95% confidence interval [CI], 1.1 to 2.4) and in 43 of 68 women (63%) in the control group (recurrence rate, 4.2 per person-year; 95% CI, 3.2 to 5.7), which corresponded to an absolute risk difference of −2.6 recurrences per person-year (95% CI, −4.0 to −1.2; P<0.001). Adverse events in treated men included nausea, headache, and metallic taste.

Conclusions
The addition of combined oral and topical antimicrobial therapy for male partners to treatment of women for bacterial vaginosis resulted in a lower rate of recurrence of bacterial vaginosis within 12 weeks than standard care. (Funded by the National Health and Medical Research Council of Australia; StepUp Australian New Zealand Clinical Trials Registry number, ACTRN12619000196145.)

Objective: To evaluate the cost-effectiveness of tympanostomy tube placement vs. nonsurgical medical management, with the option of tympanostomy tube placement in the event of treatment failure, in children with recurrent acute otitis media (AOM).

Study design: A Markov decision model compared management strategies in children ages 6 to 35 months, using patient-level data from a recently completed, multicenter, randomized clinical trial of tympanostomy tube placement vs. medical management. The model ran over a two-year time horizon using a societal perspective. Probabilities, including risk of AOM symptoms, were derived from prospectively collected patient diaries. Costs and quality-of-life measures were derived from the literature. We performed one-way and probabilistic sensitivity analyses, and secondary analyses in predetermined low- and high-risk subgroups. The primary outcome was incremental cost per quality-adjusted life-year gained.

Results: Tympanostomy tubes cost $989 more per child than medical management. Children managed with tympanostomy tubes gained 0.69 more quality-adjusted life-days than children managed medically, corresponding to $520,855 per quality-adjusted life-year gained. Results were sensitive to the costs of oral antibiotics, missed work, special childcare, the societal cost of antibiotic resistance, and the quality of life associated with AOM. In probabilistic sensitivity analyses, medical management was favored in 66% of model iterations at a willingness-to-pay threshold of $100,000/quality-adjusted life-year. Medical management was preferred in secondary analyses of low- and high-risk subgroups.

Conclusions: For young children with recurrent AOM, the additional cost associated with tympanostomy tube placement outweighs the small improvement in quality of life. Medical management for these children is an economically reasonable strategy.

Keywords: acute otitis media; economic analysis; tympanostomy tubes.

Background: Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship.

Methods: A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen experts ranked recommendations on a 9-point Likert scale. Recommendations on which the panel did not reach agreement were discussed during a virtual meeting, then a second round of ranking by email was completed. After secondary review of results and panel discussion, a series of guidance statements was developed.

Results: One hundred and sixty-five questions were reviewed. The panel reaching agreement on 104, leading to 18 overarching guidance statements. The following strategies were recommended to optimize ordering urine cultures: requiring documentation of symptoms, sending alerts to discourage ordering in the absence of symptoms, and cancelling repeat cultures. For urine culture processing, conditional urine cultures and urine white blood cell count as criteria were supported. For urine culture reporting, appropriate practices included nudges to discourage treatment under specific conditions and selective reporting of antibiotics to guide therapy decisions.

Conclusions: These 18 guidance statements can optimize use of urine cultures for better patient outcomes.

Keywords: diagnostic stewardship; expert consensus; modified Delphi; urinary tract infection; urine cultures.

Importance
The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear.

Objective
To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days.

Design, Setting, and Participants
Multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019.

Interventions
Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401).

Main Outcomes and Measures
The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates.

Results
Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI –∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI –∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, –∞ to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, –∞ to 7.4%]; P value for interaction = .73).

Conclusions and Relevance
Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.

Trial Registration
ISRCTN Identifier: ISRCTN76888927