Neisseria gonorrhoeae is one of the leading antimicrobial resistance threats worldwide. This study determined the MICs of closthioamide to be 0.008 to 0.5 mg/liter for clinical N. gonorrhoeae strains and related species. Cross-resistance with existing antimicrobial resistance was not detected, indicating that closthioamide could be used to treat drug-resistant N. gonorrhoeae.

Mycobacterial infections are difficult to treat, requiring a combination of drugs and lengthy treatment times, thereby presenting a substantial burden to both the patient and health services worldwide. The limited treatment options available are under threat due to the emergence of antibiotic resistance in the pathogen, hence necessitating the development of new treatment regimens. Drug development processes are lengthy, resource intensive, and high-risk, which have contributed to market failure as demonstrated by pharmaceutical companies limiting their antimicrobial drug discovery programmes. Pre-clinical protocols evaluating treatment regimens that can mimic in vivo PK/PD attributes can underpin the drug development process. The hollow fibre infection model (HFIM) allows for the pathogen to be exposed to a single or a combination of agents at concentrations achieved in vivo–in plasma or at infection sites. Samples taken from the HFIM, depending on the analyses performed, provide information on the rate of bacterial killing and the emergence of resistance. Thereby, the HFIM is an effective means to investigate the efficacy of a drug combination. Although applicable to a wide variety of infections, the complexity of anti-mycobacterial drug discovery makes the information available from the HFIM invaluable as explored in this review.

Non-tuberculous mycobacteria (NTM) are opportunistic pathogens commonly causing chronic, pulmonary disease which is notoriously hard to treat. Current treatment for NTM infections involves at least three active drugs (including one macrolide: clarithromycin or azithromycin) over 12 months or longer. At present there are limited phenotypic in vitro drug susceptibility testing options for NTM which are standardised globally. As seen with tuberculosis, whole genome sequencing has the potential to transform drug susceptibility testing in NTM, by utilising a genotypic approach. The Comprehensive Resistance Prediction for Tuberculosis is a database used to predict Mycobacterium tuberculosis resistance: at present there are no similar databases available to accurately predict NTM resistance. Recent studies have shown concordance between phenotypic and genotypic NTM resistance results. To benefit from the advantages of whole genome sequencing, further advances in resistance prediction need to take place, as well as there being better information on novel drug mutations and an understanding of the impact of whole genome sequencing on NTM treatment outcomes.