Mycoplasma genitalium infections were as frequent a cause of nongonococcal urethritis as Chlamydia trachomatis, had high rates of macrolide-associated genotypic resistance, and were nonclonal, suggesting an established community infection. Detection of genotypic resistance to fluoroquinolones is cause for concern.

Mycobacteria are a large family of over 100 species, most of which do not cause diseases in humans. The majority of the mycobacterial species are referred to as nontuberculous mycobacteria (NTM), meaning they are not the causative agent of tuberculous (TB) or leprosy, i.e., Mycobacterium tuberculous complex and Mycobacterium leprae, respectively. The latter group is undoubtedly the most infamous, with TB infecting an estimated 10 million people and causing over 1.2 million deaths in 2017 alone TB and leprosy also differ from NTM in that they are only transmitted from person to person and have no environmental reservoir, whereas NTM infections are commonly acquired from the environment. It took until the 1950′s for NTM to be recognised as a potential lung pathogen in people with underlying pulmonary disease and another three decades for NTM to be widely regarded by the medical community when Mycobacterium avium complex was identified as the most common group of opportunistic pathogens in AIDS patients. This review focuses on an emerging NTM called Mycobacterium abscessus (M. abs). M. abs is a rapidly growing NTM that is responsible for opportunistic pulmonary infections in patients with structural lung disorders such as cystic fibrosis and bronchiectasis, as well as a wide range of skin and soft tissue infections in humans. In this review, we discuss how we came to understand the pathogen, how it is currently treated and examine drug resistance mechanisms and novel treatments currently in development. We highlight the urgent need for new and effective treatments for M. abs infection as well as improved in vivo methods of efficacy testing.

Infections caused by Mycobacterium abscessus are increasing in prevalence in cystic fibrosis patients. This opportunistic pathogen′s intrinsic resistance to most antibiotics has perpetuated an urgent demand for new, more effective therapeutic interventions. Here we report a prospective advance in the treatment of M. abscessus infection; increasing the susceptibility of the organism to amoxicillin, by repurposing the β-lactamase inhibitor, relebactam, in combination with the front line M. abscessus drug imipenem. We establish by multiple in vitro methods that this combination works synergistically to inhibit M. abscessus. We also show the direct competitive inhibition of the M. abscessus β-lactamase, Bla Mab , using a novel assay, which is validated kinetically using the nitrocefin reporter assay and in silico binding studies. Furthermore, we reverse the susceptibility by overexpressing Bla Mab in M. abscessus, demonstrating relebactam-Bla Mab target engagement. Finally, we highlight the in vitro efficacy of this combination against a panel of M. abscessus clinical isolates, revealing the therapeutic potential of the amoxicillin-imipenem-relebactam combination. Mycobacterium abscessus is a rapidly growing, non-tuberculous mycobacteria (NTM) and increasingly prevalent opportunistic human pathogen. It is capable of causing pulmonary infections in patients with structural lung disorders such as cystic fibrosis (CF) and bronchiectasis as well as skin and soft tissue infections (SSTIs) in humans 1-6. However, monitoring the incidence of M. abscessus infection is difficult, mainly due to incorrect or non-specific species identification (i.e. isolates being referred to as M. chelonae/abscessus group or simply nontuberculous mycobacteria) obscuring its true prevalence, which is estimated to be much higher than currently thought 7,8. As with other NTMs, M. abscessus is resistant to the frontline antibiotics used for tuberculosis treatment; rifampicin, ethambutol, pyrazinamide and isoniazid 9-12. Despite reports that novel drugs developed to treat tuberculosis, such as bedaquiline and rifabutin may have some efficacy against M. abscessus, the paucity of available and potential treatments for this disease remains clear 13,14. Infection with M. abscessus is treated with a combination therapy of amikacin, tigecycline and imipenem, supplemented with oral clarithromycin or azithromycin, if the patient's isolate is macrolide susceptible, for 1 month. This is followed by a 12-month continuation phase comprising of nebulised amikacin, and a combination of clofazimine, linezolid, minocycline, moxifloxacin or co-trimoxaole, once the patient′s isolate has been susceptibility tested 15,16. The ubiquitous environmental nature of M. abscessus may go some way to explaining the high levels of intrinsic drug resistance to most major classes of antibiotic that is observed clinically 17. As a consequence of this, the efficacy of the current drug regime is poor and often does not successfully treat M. abscessus infections 16. M. abscessus expr...

A key element for the prevention and management of COVID-19 is the development of effective therapeutics. Drug combination strategies of repurposed drugs offer several advantages over monotherapies, including the potential to achieve greater efficacy, the potential to increase the therapeutic index of drugs and the potential to reduce the emergence of drug resistance. Here, we report on the in vitro synergistic interaction between two FDA approved drugs, remdesivir and ivermectin resulting in enhanced antiviral activity against SARS-CoV-2. Whilst the in vitro synergistic activity reported here does not support the clinical application of this combination treatment strategy, due to insufficient exposure of ivermectin in vivo , the data do warrant further investigation. Efforts to define the mechanisms underpinning the observed synergistic action, could lead to the development of novel therapeutic treatment strategies.

A key element to the prevention and management of the COVID-19 pandemic is the development of effective therapeutics. Drug combination strategies of repurposed drugs offer a number of advantages to monotherapies including the potential to achieve greater efficacy, the potential to increase the therapeutic index of drugs and the potential to reduce the emergence of drug resistance. Combination of agents with antiviral mechanisms of action with immune-modulatory or anti-inflammatory drug is also worthy of investigation. Here, we report on the in vitro synergistic interaction between two FDA approved drugs, remdesivir (RDV) and ivermectin (IVM) resulting in enhanced antiviral activity against SARS-CoV-2, the causative pathogen of COVID-19. These findings warrant further investigations into the clinical potential of this combination, together with studies to define the underlying mechanism.