RESUMO
Nontuberculous mycobacteria (NTM) are a group of acid-fast mycobacteria other than Mycobacterium tuberculosis complex (MTBC) that cause pulmonary disease that is similar to the disease caused by MTBC. International guidelines for the diagnosis of pulmonary NTM disease are rigid and have remained unchanged for nearly 2 decades. In this opinion piece, we provide a new perspective on the traditional criteria by suggesting a diagnostic algorithm that incorporates direct molecular identification of NTM performed on raw sputum specimens (using Sanger or targeted deep sequencing approaches, among others) paired with traditional culture methods. Our approach ensures a more rapid diagnosis of pulmonary NTM disease, thus, facilitating timeous clinical diagnosis, and prompt treatment initiation, where indicated, and leverages recent advances in novel molecular techniques into routine NTM identification practice.
RESUMO
Highly drug-resistant strains are not uncommon among the Mycobacterium genus, with patients requiring lengthy antibiotic treatment regimens with multiple drugs and harmful side effects. This alarming increase in antibiotic resistance globally has renewed the interest in mycobacteriophage therapy for both Mycobacterium tuberculosis complex and non-tuberculosis mycobacteria. With the increasing number of genetically well-characterized mycobacteriophages and robust engineering tools to convert temperate phages to obligate lytic phages, the phage cache against extensive drug-resistant mycobacteria is constantly expanding. Synergistic effects between phages and TB drugs are also a promising avenue to research, with mycobacteriophages having several additional advantages compared to traditional antibiotics due to their different modes of action. These advantages include less side effects, a narrow host spectrum, biofilm penetration, self-replication at the site of infection and the potential to be manufactured on a large scale. In addition, mycobacteriophage enzymes, not yet in clinical use, warrant further studies with their additional benefits for rupturing host bacteria thereby limiting resistance development as well as showing promise in vitro to act synergistically with TB drugs. Before mycobacteriophage therapy can be envisioned as part of routine care, several obstacles must be overcome to translate in vitro work into clinical practice. Strategies to target intracellular bacteria and selecting phage cocktails to limit cross-resistance remain important avenues to explore. However, insight into pathophysiological host-phage interactions on a molecular level and innovative solutions to transcend mycobacteriophage therapy impediments, offer sufficient encouragement to explore phage therapy. Recently, the first successful clinical studies were performed using a mycobacteriophage-constructed cocktail to treat non-tuberculosis mycobacteria, providing substantial insight into lessons learned and potential pitfalls to avoid in order to ensure favorable outcomes. However, due to mycobacterium strain variation, mycobacteriophage therapy remains personalized, only being utilized in compassionate care cases until there is further regulatory approval. Therefore, identifying the determinants that influence clinical outcomes that can expand the repertoire of mycobacteriophages for therapeutic benefit, remains key for their future application.
RESUMO
In vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against modified carbapenem inactivation method (mCIM)-positive Pseudomonas aeruginosa isolates harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2 g every 8 h [q8h] HSR) and cefepime (2 g and 1 g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log10 killing in all isolates. Cefepime activity was dose dependent and MIC driven. This approach may be useful in assessing the implications of ß-lactamase variants.
