Resistance-minimizing strategies for introducing a novel antibiotic for gonorrhea treatment: a mathematical modeling study.

Background: Gonorrhea is a highly prevalent sexually transmitted infection and an urgent public health concern due to increasing antibiotic resistance. Only ceftriaxone remains as the recommended treatment in the U.S. The prospect of approval of new anti-gonococcal antibiotics raises the question of how to deploy a new drug to maximize its clinically useful lifespan. Methods: We used a compartmental model of gonorrhea transmission in the U.S. population of men who have sex with men to compare strategies for introducing a new antibiotic for gonorrhea treatment. The strategies tested included holding the new antibiotic in reserve until the current therapy reached a threshold prevalence of resistance; using either drug, considering immediate and gradual introduction of the new drug; and combination therapy. The primary outcome of interest was the time until 5% prevalence of resistance to both the novel drug and to the current first-line drug (ceftriaxone). Findings: The reserve strategy was consistently inferior for mitigating antibiotic resistance under the parameter space explored. The reserve strategy was increasingly outperformed by the other strategies as the probability of de novo resistance emergence decreased and as the fitness costs associated with resistance increased. Combination therapy tended to prolong the development of antibiotic resistance and minimize the number of annual gonococcal infections. Interpretation: Our study argues for rapid introduction of new anti-gonococcal antibiotics, recognizing that the feasibility of each strategy must incorporate cost, safety, and other practical concerns. The analyses should be revisited once robust estimates of key parameters-likelihood of emergence of resistance and fitness costs of resistance for the new antibiotic-are available. Funding: U.S. Centers for Disease Control and Prevention (CDC), National Institute of Allergy and Infectious Diseases.

State-level gonorrhea rates and expedited partner therapy laws: insights from time series analyses.

OBJECTIVE: In this study, we examined state-level monthly gonorrhea morbidity and assessed the potential impact of existing expedited partner therapy (EPT) laws in relation to the time that the laws were enacted. STUDY DESIGN: Longitudinal study. METHODS: We obtained state-level monthly gonorrhea morbidity (number of cases/100,000 for males, females and total) from the national surveillance data. We used visual examination (of morbidity trends) and an autoregressive time series model in a panel format with intervention (interrupted time series) analysis to assess the impact of state EPT laws based on the months in which the laws were enacted. RESULTS: For over 84% of the states with EPT laws, the monthly morbidity trends did not show any noticeable decreases on or after the laws were enacted. Although we found statistically significant decreases in gonorrhea morbidity within four of the states with EPT laws (Alaska, Illinois, Minnesota, and Vermont), there were no significant decreases when the decreases in the four states were compared contemporaneously with the decreases in states that do not have the laws. CONCLUSION: We found no impact (decrease in gonorrhea morbidity) attributable exclusively to the EPT law(s). However, these results do not imply that the EPT laws themselves were not effective (or failed to reduce gonorrhea morbidity), because the effectiveness of the EPT law is dependent on necessary intermediate events/outcomes, including sexually transmitted infection service providers' awareness and practice, as well as acceptance by patients and their partners.

Risk-based versus alternative algorithms for antibiotic prophylaxis among women seeking early suction abortion: a cost-effectiveness simulation.

BACKGROUND: Particularly in resource-poor settings, simple, inexpensive, and cost-effective algorithms are needed to direct antibiotic prophylaxis to prevent sequelae of infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and bacterial vaginosis-associated organisms among women undergoing abortion. GOAL: To assess the prevalence of and risk factors for infections among women seeking abortion in Bali, Indonesia, and to use these data in designing a cost-effective risk-based prophylaxis algorithm. STUDY DESIGN: A cross-sectional analysis and data-based simulation of risk-based and alternative prophylaxis algorithms were performed. RESULTS: The risk-based algorithm would have provided prophylaxis to 70% (95% CI, 53-83%) of women with cervical infection, 64% (95% CI, 54-74%) of those with bacterial vaginosis, and 57% (95% CI, 42-72%) of those with trichomoniasis. For cervical infection, the algorithm was more cost effective than all others evaluated. The cost-effectiveness was acceptable for bacterial vaginosis. CONCLUSIONS: Risk-based algorithms may be cost effective in identifying women likely to benefit from preabortion prophylaxis. Prospective evaluation is needed to validate these findings.

The increasing marginal benefit of condom usage.

PURPOSE: Condom use is promoted as a primary strategy for preventing sexual transmission of human immunodeficiency virus (HIV). This paper analyzes how incremental changes in condom compliance rates can affect an individual's risk of acquiring HIV. METHODS: We developed a simple mathematical model of HIV transmission in which the cumulative probability of HIV infection depended in part upon the percentage of acts in which a condom was used. We applied basic methods of calculus to differentiate the mathematical model with respect to the probability of condom usage. We applied values from published studies to the model to illustrate how the marginal benefits of condom usage vary across different populations. RESULTS: In general, the marginal benefit of condom usage increases as condom compliance increases. CONCLUSIONS: The marginal benefits of increased condom usage vary across different risk groups and across different levels of condom compliance. These results offer insight into the motivation behind the decision of whether or not to use condoms, and indicate possible ways to optimize the use of resources devoted to increasing condom usage by at-risk populations.

The rapid test paradox: when fewer cases detected lead to more cases treated: a decision analysis of tests for Chlamydia trachomatis.

BACKGROUND AND OBJECTIVES: Screening tests for detection of Chlamydia trachomatis include those processed in laboratories and those designed to be processed at the point of care. The latter tests can yield results at the time of the initial patient visit, but most available lab-processed tests have greater sensitivity. In settings where a proportion of patients do not return for treatment after positive test results, the less sensitive rapid tests could lead to the treatment of more patients and be more cost-effective. GOAL OF THIS STUDY: To determine the situations, if any, in which a rapid test might be more cost-effective and treat more infections than lab-based tests. STUDY DESIGN: A decision analysis framework was used to compare one point-of-care test (the BioStar Chlamydia OIA) with two lab-based tests (cell culture and the polymerase chain reaction [PCR] assay). It was assumed that all women in the model would be screened. Variables included in the analysis were the prevalence, test sensitivity and specificity, the probability of developing pelvic inflammatory disease after treated and untreated chlamydial infections, and the likelihood that patients would wait for rapid test results or return to the facility for treatment. RESULTS: The rapid test treated more cases of infection than the PCR alone if the return rate was less than 65%. A two-test algorithm of the rapid test followed by a PCR test on those initially testing negative identified and treated the greatest number of chlamydial infections and was the most cost-effective at all prevalences above 9%, but this finding was sensitive to the cost estimate for pelvic inflammatory disease. CONCLUSION: In settings where patient return for treatment is a problem, point-of-care tests contribute significantly to the detection and treatment of chlamydial infections among women.