The proposed research represents a novel approach to controlling the spread of drug-resistant Neisseria gonorrhea through the use of real-time polymerase chain reaction (PCR) to determine antimicrobial susceptibility of an individual infection and reduce the unnecessary use of broad spectrum antibiotics. Over the past 75 years, gonorrhea has become increasingly resistant to antimicrobial therapy. The continued emergence of drug-resistance in gonorrhea has many experts stating that gonorrhea might become an untreatable """"""""superbug"""""""". Yet, the response to this serious public health problem continues to rely on clinical vigilance for treatment failure, partner treatment, maintenance of culture-based surveillance, risk-reduction counseling, condom use, repeat screening and calls for novel antimicrobial drug development. The use of molecular assays for antimicrobial susceptibility determination has been successfully used to treat M. tuberculosis and Staphylococcus aureus infections, but not yet with gonorrhea. The use of real-time PCR to determine antimicrobial susceptibility could be a """"""""game changer"""""""" that alters the course of sexually transmitted disease medicine and leads to a critical reduction in gonorrhea drug-resistance. There are three specific aims to our proposal: 1) we will verify the real-time PCR assay in the Los Angeles County Public Health Laboratory to enable its clinical use and comply with federal regulations providing for the use of laboratory tests in clinical practice. 2) We will develop an antimicrobial susceptibility testing program that ensures that all specimens in Los Angeles County tested at the Public Health Laboratory for gonorrhea will also be tested for antimicrobial susceptibility and those results provided to the testing clinicians within two business days to use to guide antibiotic treatment. 3) We will evaluate the effect of the new assay among clinicians treating their patients with gonorrhea, including monitoring the turn-around time of susceptibility results relative to treatment, treatment selection, and surveying clinicians regarding their knowledge, attitudes, and practices regarding the molecular susceptibility results. The primary outcome of this study is the difference in the proportion of gonorrhea cases treated with an extended-spectrum cephalosporin before and after the provision of gonorrhea antimicrobial susceptibility results. Based on prior research, we hypothesize a 50% reduction in extended-spectrum cephalosporin use from 95% to 50%. Secondary outcomes will explore the association of non-extended-spectrum cephalosporin use based on both provider and case- patient characteristics. Overall, the results of this study will potentially transform the management of gonorrhea and impact the frequency of drug-resistant gonorrhea.
This project is highly relevant to public health given its focus on addressing a critical, increasing threat to our public's health: multi-drug resistant Neisseria gonorrhea infection. Over the past 75 years, Neisseria gonorrhea infections have become increasingly resistant to antimicrobial therapy: first to sulfa-based antibiotics, then penicillin', followed by tetracyclines, fluoroquinolones and now extended-spectrum cephalosporins. Many experts believe that there is real danger of gonorrhea turning into an untreatable superbug. Current strategies to limit drug resistance of N. gonorrhea have thus far proven to be insufficient;this proposal utilizes a novel, more tailored approach to N. gonorrhea treatment that shows promise for real reduction of antibiotic drug-resistance. If shown to be successful, this strategy will transform the management of gonorrhea in the United States, and significantly reduce morbidity and even mortality by reducing drug-resistant gonorrhea.
|Refugio, Oliver N; Klausner, Jeffrey D (2018) Syphilis incidence in men who have sex with men with human immunodeficiency virus comorbidity and the importance of integrating sexually transmitted infection prevention into HIV care. Expert Rev Anti Infect Ther 16:321-331|
|Allan-Blitz, Lao-Tzu; Hemarajata, Peera; Humphries, Romney M et al. (2018) A Cost Analysis of Gyrase A Testing and Targeted Ciprofloxacin Therapy Versus Recommended 2-Drug Therapy for Neisseria gonorrhoeae Infection. Sex Transm Dis 45:87-91|
|Allan-Blitz, Lao-Tzu; Mokany, Elisa; Campeau, Shelley et al. (2018) Prevalence of Mycoplasma genitalium and Azithromycin-resistant Infections Among Remnant Clinical Specimens, Los Angeles. Sex Transm Dis 45:632-635|
|Allan-Blitz, Lao-Tzu; Hemarajata, Peera; Humphries, Romney M et al. (2018) Ciprofloxacin May be Efficacious in Treating Wild-Type Gyrase A Genotype Neisseria gonorrhoeae Infections. Sex Transm Dis 45:e18|
|Bhatti, Ashima A; Allan-Blitz, Lao-Tzu; Castrejon, Mariana et al. (2017) Epidemiology of Neisseria gonorrhoeae Gyrase A Genotype, Los Angeles, California, USA. Emerg Infect Dis 23:1581-1584|
|Allan-Blitz, Lao-Tzu; Humphries, Romney M; Hemarajata, Peera et al. (2017) Implementation of a Rapid Genotypic Assay to Promote Targeted Ciprofloxacin Therapy of Neisseria gonorrhoeae in a Large Health System. Clin Infect Dis 64:1268-1270|
|Allan-Blitz, Lao-Tzu; Wang, Xiaoyan; Klausner, Jeffrey D (2017) Wild-Type Gyrase A Genotype of Neisseria gonorrhoeae Predicts In Vitro Susceptibility to Ciprofloxacin: A Systematic Review of the Literature and Meta-Analysis. Sex Transm Dis 44:261-265|
|Allan-Blitz, Lao-Tzu; Klausner, Jeffrey D (2017) Codon 91 Gyrase A Testing Is Necessary and Sufficient to Predict Ciprofloxacin Susceptibility in Neisseria gonorrhoeae. J Infect Dis 215:491|
|Hemarajata, P; Yang, S; Soge, O O et al. (2016) Performance and Verification of a Real-Time PCR Assay Targeting the gyrA Gene for Prediction of Ciprofloxacin Resistance in Neisseria gonorrhoeae. J Clin Microbiol 54:805-8|
|Bristow, Claire C; Dong, Huan; Klausner, Jeffrey D (2016) Technological Solutions to Address Drug-Resistant Neisseria gonorrhoeae. Emerg Infect Dis 22:939-40|