The Use of Gentamicin for Treatment of Urogenital and Extragenital Gonorrhea: A Systematic Review of Efficacy Data.

OBJECTIVE: To evaluate clinical efficacy data for gentamicin in the treatment of gonorrhea. DATA SOURCES: A keyword search of PubMed (1966 to April 2020), EMBASE (1947 to April 2020), and International Pharmaceutical Abstracts (1970 to April 2020) was conducted. The electronic search was supplemented with manual screening of references from identified articles and a search of ClinicalTrials.gov to identify ongoing trials. STUDY SELECTION AND DATA EXTRACTION: Comparator and noncomparator studies reporting microbiological outcomes of treatment with gentamicin for gonorrhea in humans were included. Data extracted included study year, authors, aim, setting, population, dosing protocols, and outcome results. Risk of bias was assessed according to the Cochrane Risk of Bias Assessment Tool. DATA SYNTHESIS: A total of 407 articles were identified, of which 11 met inclusion criteria. Two studies were randomized controlled trials, and 1 additional randomized noncomparator study was identified. All other studies were nonrandomized and noncomparator in nature. The highest quality evidence suggests that gentamicin is not noninferior to ceftriaxone (both in addition to azithromycin) for treatment of gonorrhea but may achieve cure rates >90%. Conflicting evidence exists regarding the efficacy of gentamicin-based regimens for the specific treatment of extragenital gonorrhea. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Results of this review could affect patient care and clinical practice because they clearly demonstrate the role of gentamicin for the treatment of gonorrhea as a second-line agent. Future research should confirm findings, especially for the role of gentamicin in extragenital infections. CONCLUSIONS: Gentamicin-based regimens should be reserved for second-line treatment of urogenital and extragenital gonorrhea infections.

The Future of Collaborative Human-Artificial Intelligence Decision-Making for Mission Planning.

In an increasingly complex military operating environment, next generation wargaming platforms can reduce risk, decrease operating costs, and improve overall outcomes. Novel Artificial Intelligence (AI) enabled wargaming approaches, based on software platforms with multimodal interaction and visualization capacity, are essential to provide the decision-making flexibility and adaptability required to meet current and emerging realities of warfighting. We highlight three areas of development for future warfighter-machine interfaces: AI-directed decisional guidance, computationally informed decision-making, and realistic representations of decision spaces. Progress in these areas will enable development of effective human-AI collaborative decision-making, to meet the increasing scale and complexity of today's battlespace.

Synthesis and Biological Evaluation of Aurachin D Analogues as Inhibitors of Mycobacterium tuberculosis Cytochrome bd Oxidase.

A revised total synthesis of aurachin D (1a), an isoprenoid quinolone alkaloid that targets Mycobacterium tuberculosis (Mtb) cytochrome bd (cyt-bd) oxidase, was accomplished using an oxazoline ring-opening reaction. The ring opening enabled access to a range of electron-poor analogues, while electron-rich analogues could be prepared using the Conrad-Limpach reaction. The aryl-substituted and side-chain-modified aurachin D analogues were screened for inhibition of Mtb cyt-bd oxidase and growth inhibition of Mtb. Nanomolar inhibition of Mtb cyt-bd oxidase was observed for the shorter-chain analogue 1d (citronellyl side chain) and the aryl-substituted analogues 1g/1k (fluoro substituent at C6/C7), 1t/1v (hydroxy substituent at C5/C6) and 1u/1w/1x (methoxy substituent at C5/C6/C7). Aurachin D and the analogues did not inhibit growth of nonpathogenic Mycobacterium smegmatis, but the citronellyl (1d) and 6-fluoro-substituted (1g) inhibitors from the Mtb cyt-bd oxidase assay displayed moderate growth inhibition against pathogenic Mtb (MIC = 4-8 µM).