LITERATURE UPDATE


into three themes: potential clinical situations in which phage therapy might be considered, laboratory testing, and pharmacokinetic considerations. In this article, suggestions are provided as answers to a series of questions intended to inform clinicians considering experimental phage therapy for patients in their clinical practices.


Helicobacter pylori infection: from standard to alternative treatment strategies Sousa C, Ferreira R, Azevedo NF et al. Crit Rev Microbiol. 2022 May; 48 (3): 376–96. doi: 10.1080/1040841X.2021.1975643.


Helicobacter pylori is the major component of the gastric microbiome of infected individuals and one of the aetiological factors of chronic gastritis, peptic ulcer disease and gastric cancer. The increasing resistance to antibiotics worldwide has made the treatment of H. pylori infection a challenge. As a way to overhaul the efficacy


of currently used H. pylori antibiotic- based eradication therapies, alternative treatment strategies are being devised. These include probiotics and prebiotics as adjuvants in H. pylori treatment, antimicrobial peptides as alternatives to antibiotics, photodynamic therapy ingestible devices, microparticles and nanoparticles applied as drug delivery systems, vaccines, natural products, and phage therapy. This review provides an updated synopsis of these emerging H. pylori control strategies and discusses the advantages, hurdles and challenges associated with their development and implementation. An effective human vaccine would be a major achievement although, until now, projects regarding vaccine development have failed or were discontinued. Numerous natural products have demonstrated anti-H. pylori activity, mostly in vitro, but further clinical studies are needed to fully disclose their role in H. pylori eradication. Finally, phage therapy has the potential to emerge as a valid alternative, but major challenges remain, namely the isolation of more H. pylori strictly virulent bacterio(phages).


Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far


Łusiak-Szelachowska M, Międzybrodzki R, Drulis-Kawa Z et al. J Biomed Sci. 2022 Mar 30; 29 (1): 23. doi: 10.1186/s12929- 022-00806-1.


Bacteriophages (phages) may be used as an alternative to antibiotic therapy


for combating infections caused by multidrug-resistant bacteria. In the last decades, there have been studies concerning the use of phages and antibiotics separately or in combination, both in animal models as well as in humans.


The phenomenon of phage-antibiotic


synergy, in which antibiotics may induce the production of phages by bacterial hosts has been observed. The potential mechanisms of phage and antibiotic synergy is presented in this paper. Studies of a biofilm model showed that a combination of phages with antibiotics may increase removal of bacteria and sequential treatment, consisting of phage administration followed by an antibiotic, was most effective in eliminating biofilms. In vivo studies predominantly show the phenomenon of phage and antibiotic synergy. A few studies also describe antagonism or indifference between phages and antibiotics. Recent papers regarding the application of phages and antibiotics in patients with severe bacterial infections show the effectiveness of simultaneous treatment with both antimicrobials on the clinical outcome.


Bacteriophages: An alternative to combat antibiotic resistance? Gupta M, Anzelc M, Stetkevich S, Burkhart C. J Drugs Dermatol. 2022 Dec 1; 21 (12): 1311–5. doi: 10.36849/ JDD.6638.


Antibiotic resistance has become one of the largest pitfalls of modern medicine, and this has fueled the search for a safe and effective alternative. Of these alternatives, bacteriophage (phage) therapy has emerged as a potential option since it is capable of destroying pathogenic bacteria, without disrupting commensal bacterial populations. Although numerous studies have shown its efficacy in various conditions such as dysentery, sepsis and meningitis, very little research has focused on its prospective usage to treat dermatological conditions. This review discusses the emerging phage therapy studies surrounding infections caused by Cutibacterium acnes, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae. Phage therapy shows major potential for future usage in the field of dermatology, yet further research must be performed to assure safety and efficacy in humans.


MDR pumps as crossroads of resistance: antibiotics and bacteriophages. Nazarov PA. Antibiotics (Basel). 2022 May 30; 11 (6): 734.


WWW.PATHOLOGYINPRACTICE.COM JUNE 2023


Antibiotic resistance represents a global problem in modern medicine. In the near future, humanity may face a situation where medicine will be powerless against resistant bacteria and a post-antibiotic era will come. The development of new antibiotics is either very expensive or ineffective due to rapidly developing bacterial resistance.


The need to develop alternative


approaches to the treatment of bacterial infections, such as phage therapy, is beyond doubt. The cornerstone of bacterial defence against antibiotics are multidrug resistance (MDR) pumps, which are involved in antibiotic resistance, toxin export, biofilm, and persister cell formation. MDR pumps are the primary non-specific defence of bacteria against antibiotics, while drug target modification, drug inactivation, target switching, and target sequestration are the second specific line of their defense. All bacteria have MDR pumps, and bacteriophages have evolved along with them and use a bacterium’s need for MDR pumps to bind and penetrate into bacterial cells. The study and understanding of the mechanisms of the pumps and their contribution to the overall resistance and to the sensitivity to bacteriophages will allow us to either seriously delay the onset of the post- antibiotic era or even prevent it altogether due to phage-antibiotic synergy.


The urinary microbiome and biological therapeutics: Novel therapies for urinary tract infections Kenneally C, Murphy CP, Sleator RD, Culligan EP. Microbiol Res. 2022 Jun; 259: 127010. doi: 10.1016/j. micres.2022.127010.


The discovery of microbial communities in the urinary tract (the urobiome) has fundamentally altered the previous doctrine regarding urine sterility and associated urinary disorders. Recent advances in culturing and culture- independent DNA sequencing technologies have characterised the resident microbial community in the urobiome, and has, in turn, demonstrated how community imbalances potentially contribute to infection and disease. As we enter a post-antibiotic era, the


effectiveness of standard antimicrobial treatments against multidrug-resistant (MDR) uropathogens is vastly diminished. Preliminary research is accumulating surrounding microbiome-based therapies, and their potential as non-antibiotic therapeutics. In this context, the urobiome is significantly underexplored, and knowledge regarding the fundamental role of its constituents is lacking.


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