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Acne vulgaris is a common neutrophil-driven inflammatory skin disorder in which Cutibacterium acnes (C. acnes) plays a significant role. For decades antibiotics have been widely used to treat acne vulgaris, with the inevitable increase in bacterial antibiotic resistance.Phage therapy is a promising solution to the rising problem of antibiotic-resistant bacteria, utilizing viruses that specifically lyse bacteria.Here, we explored the feasibility of phage therapy against C. acnes. Combining eight novel phages we had isolated and commonly used antibiotics, 100% of clinically isolated C. acnes strains were eradicated.Using topical phage therapy in a C. acnes-induced acne-like lesions mouse model resulted in significantly superior clinical and histological scores. Moreover, the inflammatory response decreased as reflected by reducing the chemokine CXCL2, infiltration of neutrophils, and other inflammatory cytokines, compared to the untreated group.These results demonstrate the potential of phage therapy in acne vulgaris treatment, especially when antibiotic-resistant strains are involved.

SUMMARYAcne vulgaris is a common neutrophile-driven inflammatory skin disorder in whichCutibacterium acnes(C. acnes) bacteria play a significant role. Until now, antibiotics have been widely used to treat acne vulgaris, with the inevitable increase in bacterial antibiotic resistance. Phage therapy is a promising solution to the rising problem of antibiotic-resistant bacteria, utilizing viruses that specifically lyse bacteria.Here, we explored the feasibility of phage therapy againstC. acnes. By combining eight novel phages we had isolated, together with commonly used antibiotics, we achieved 100% eradication of clinically isolatedC. acnesstrains. Using topical phage therapy in an acne mouse model resulted in significantly superior clinical scores, as well as a reduction in neutrophil infiltration compared to the control group. These results demonstrate the potential of phage therapy in acne vulgaris treatment, especially when antibiotic-resistant strains are involved.

Providencia spp. are emerging pathogens mainly in nosocomial infections. Providencia stuartii in particular is involved in urinary tract infections and contributes significantly to the high incidence of biofilm-formation in catheterized patients. Furthermore, recent reports suggested a role for multiple drug resistant (MDR) P. stuartii in hospital-associated outbreaks which leads to excessive complications resulting in challenging treatments. Phage therapy is currently one of the most promising solutions to combat antibiotic-resistant infections. However, the number of available phages targeting Providencia spp. is extremely limited, restricting the use of phage therapy in such cases. In the present study, we describe the isolation and characterization of 17 lytic and lysogenic bacteriophages targeting clinical isolates of Providencia spp. as part of the Israeli Phage Bank (IPB). These phages, isolated from sewage samples, were evaluated for host range activity and effectively eradicated 95% of the tested bacterial strains isolated from different geographic locations and displaying a wide range of antibiotic resistance. Their lytic activity is demonstrated on agar plates, planktonic cultures, and biofilm formed in a catheter model. The results suggest that these bacteriophages can potentially be used for treatment of antibiotic-resistant Providencia spp. infections in general and of urinary tract infections in particular.

Personalized-phage-therapy is a promising solution for the emerging crisis of bacterial infections that fail to be eradicated by conventional antibiotics.One of the most crucial elements of personalized-phage-therapy is the proper matching of phages and antibiotics to the target bacteria in a given clinical setting. However, to date, there is no consensus guideline for laboratory procedures that enablein vitroevaluation of phages intended for treatment.In this work, we suggest a framework and strategies identify appropriate phages and combine them with antibiotics in clinical microbiology laboratories. This framework, which we term here “Clinical Phage Microbiology” is based on our experience and other previously reported cases of both, successful and failed phage treatments.Additionally, we discuss troubleshooting methodologies for possible pitfalls and special cases that may need to be assessed before treatment including interactions with the host immune system, biofilms, and polymicrobial infections.We believe that the “Clinical Phage Microbiology” pipeline presented here should serve as the basis for standardization of laboratory protocols to match phages for personalized therapy.

Summary Phage therapy is a promising solution for bacterial infections that are not eradicated by conventional antibiotics. A crucial element of this approach is appropriate matching of bacteriophages and antibiotics to the bacterial target according to the clinical setting. However, there is currently little consistency in the protocols used for the laboratory evaluation of bacteriophages intended for antibacterial treatment. In this Personal View, we suggest a framework aimed to match appropriate bacteriophage-based treatments in clinical microbiology laboratories. This framework, which we have termed Clinical Phage Microbiology, is based on the current research on phage treatments. In addition, we discuss special cases that might require additional relevant evaluation, including bacteriophage interactions with the host immune response, biofilm-associated infections, and polymicrobial infections. The Clinical Phage Microbiology pipeline could serve as the basis for future standardisation of laboratory protocols for personalised phage therapy.

A key element in phage therapy is the establishment of large phage collections, termed herein &ldquo, banks&rdquo, where many well-characterized phages, ready to be used in the clinic, are stored. These phage banks serve for both research and clinical purposes. Phage banks are also a key element in clinical phage microbiology, the prior treatment matching of phages and antibiotics to specific bacterial targets. A worldwide network of phage banks can promote a phage-based solution for any isolated bacteria. Herein, we describe the Israeli Phage Bank (IPB) established in the Hebrew University, Jerusalem, which currently has over 300 phages matching 16 bacteria, mainly pathogens. The phage bank is constantly isolating new phages and developing methods for phage isolation and characterization. The information on the phages and bacteria stored in the bank is available online.

Antibiotic-resistant Cutibacterium acnes has been reported worldwide, but data from Israeli patients with acne is currently lacking. This study evaluated the antibiotic susceptibility of C. acnes, isolated from 50 Israeli patients with acne to commonly prescribed antibiotics, using the Epsilometer test (E-test). Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis, 16S rRNA sequencing and single locus sequence typing (SLST) molecular typing were used to identify and characterize C. acnes. Among 36 strains isolated, phylotype IA1 was most common. Resistance to at least one antibiotic was found in 30.6% of tested strains. Resistance rates were highest for erythromycin (25.0%), followed by doxycycline (19.4%), clindamycin (16.7%), minocycline (11.1%) and tetracycline (8.3%). Significant correlation was found between resistance to multiple antibiotics, with 5.6% of isolates resistant to all antibiotics tested. When reviewing resistances rate worldwide antibiotic resistance was found to be prevalent in Israel. Measures to limit the emergence of antibiotic-resistant strains of Cutibacterium acnes should be taken and alternative treatments should be sought.