LITERATURE UPDATE
A focus for phage research, Helicobacter pylori is seen here colonising the surface of regenerating epithelium (Warthin-Starry silver stain).
Herein, the authors review the current state of the art concerning the urobiome; specifically, how it impacts health and disease states, in the context of urinary tract infections (UTIs). Furthermore, they discuss the development of novel biological therapeutics that may have the potential to provide significant advancements in UTI therapy, with a particular focus on bacterial interference, probiotics, antimicrobial peptides, bacteriocins and bacteriophage.
Bacteriophage and bacterial susceptibility, resistance, and tolerance to antibiotics. Chen Q, Dharmaraj T, Cai PC et al. Pharmaceutics. 2022 Jul 7; 14 (7): 1425. doi: 10.3390/pharmaceutics14071425.
Bacteriophages, viruses that infect and replicate within bacteria, impact bacterial responses to antibiotics in complex ways. Recent studies using lytic bacteriophages to treat bacterial infections (phage therapy) demonstrate that phages can promote susceptibility to chemical antibiotics and that phage/antibiotic synergy is possible. However, both lytic and lysogenic bacteriophages can contribute to antimicrobial resistance. In particular, some phages mediate the horizontal transfer of antibiotic resistance genes between bacteria via transduction and other mechanisms. In addition, chronic infection filamentous phages can promote antimicrobial tolerance, the ability of bacteria to persist in the face of antibiotics. In particular, filamentous phages serve as structural elements in bacterial biofilms and prevent the penetration of antibiotics. Over
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time, these contributions to antibiotic tolerance favour the selection of resistance clones.
In this article, the authors review
recent insights into bacteriophage contributions to antibiotic susceptibility, resistance and tolerance, and they discuss the mechanisms involved in these effects and address their impact on bacterial fitness.
Phage therapy of Mycobacterium infections: compassionate use of phages in 20 patients with drug-resistant mycobacterial disease
Dedrick RM, Smith BE, Cristinziano M et al. Clin Infect Dis. 2023 Jan 6; 76 (1): 103–12. doi: 10.1093/cid/ciac453.
Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalised phage identification. Mycobacterium isolates from 200
culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolisation, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and
phage neutralisation in serum, sputum, or bronchoalveolar lavage fluid. No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favourable clinical or microbiological responses were observed in 11 patients. Neutralising antibodies were identified in serum after initiation of phage delivery intravenously in eight patients, potentially contributing to lack of treatment response in four cases, but were not consistently associated with unfavourable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favourable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.
Phage therapy in the era of multidrug resistance in bacteria: a systematic review
Aranaga C, Pantoja LD, Martínez EA, Falco A. Int J Mol Sci. 2022 Apr 21; 23 (9): 4577. doi: 10.3390/ijms23094577.
Bacteriophages offer an alternative for the treatment of multidrug-resistant bacterial diseases as their mechanism of action differs from that of antibiotics. However, their application in the clinical field is limited to specific cases of patients with few or no other alternative therapies.
This systematic review assesses
the effectiveness and safety of phage therapy against multidrug-resistant bacteria through the evaluation of studies published over the past decade. To that end, a bibliographic search was carried out in the PubMed, Science Direct, and Google Scholar databases. Of the 1500 studies found, 27 met the inclusion criteria, with a total of 165 treated patients. Treatment effectiveness, defined as the reduction in, or elimination of, the bacterial load, was 85%. Except for two patients who died from causes unrelated to phage therapy, no serious adverse events were reported.
This shows that phage therapy could be an alternative treatment for patients with infections associated with multidrug- resistant bacteria. However, due to the phage specificity required for the treatment of various bacterial strains, this therapy must be personalised in terms of bacteriophage type, route of administration, and dosage.
JUNE 2023
WWW.PATHOLOGYINPRACTICE.COM
Yutaka Tsutsumi, M.D.
Fujita Health University School of Medicine Wikimedia Commons
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