Adapted Bacteriophages for Treating Urinary Tract Infections
Urinary tract infections (UTIs) are among the most widespread microbial diseases and their economic impact on the society is substantial. The continuing increase of antibiotic resistance worldwide is worrying. As a consequence, well-tolerated, highly effective therapeutic alternatives are without de...
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| Format: | Article |
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.01832/full |
| _version_ | 1818150140269035520 |
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| author | Aleksandre Ujmajuridze Nina Chanishvili Marina Goderdzishvili Lorenz Leitner Ulrich Mehnert Archil Chkhotua Thomas M. Kessler Wilbert Sybesma |
| author_facet | Aleksandre Ujmajuridze Nina Chanishvili Marina Goderdzishvili Lorenz Leitner Ulrich Mehnert Archil Chkhotua Thomas M. Kessler Wilbert Sybesma |
| author_sort | Aleksandre Ujmajuridze |
| collection | DOAJ |
| description | Urinary tract infections (UTIs) are among the most widespread microbial diseases and their economic impact on the society is substantial. The continuing increase of antibiotic resistance worldwide is worrying. As a consequence, well-tolerated, highly effective therapeutic alternatives are without delay needed. Although it has been demonstrated that bacteriophage therapy may be effective and safe for treating UTIs, the number of studied patients is low and there is a lack of randomized controlled trials (RCTs). The present study has been designed as a two-phase prospective investigation: (1) bacteriophage adaptation, (2) treatment with the commercially available but adapted Pyo bacteriophage. The aim was to evaluate feasibility, tolerability, safety, and clinical/microbiological outcomes in a case series as a pilot for a double-blind RCT. In the first phase, patients planned for transurethral resection of the prostate were screened (n = 130) for UTIs and enrolled (n = 118) in the study when the titer of predefined uropathogens (Staphylococcus aureus, E. coli, Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis) in the urine culture was ≥104 colony forming units/mL. In vitro analysis showed a sensitivity for uropathogenic bacteria to Pyo bacteriophage of 41% (48/118) and adaptation cycles of Pyo bacteriophage enhanced its sensitivity to 75% (88/118). In the second phase, nine patients were treated with adapted Pyo bacteriophage and bacteria titer decreased (between 1 and 5 log) in six of the nine patients (67%). No bacteriophage-associated adverse events have been detected. The findings of our prospective two-phase study suggest that adapted bacteriophage therapy might be effective and safe for treating UTIs. Thus, well-designed RCTs are highly warranted to further define the role of this potentially revolutionizing treatment option. |
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| id | doaj.art-2b4d6c387d20421689f96e3c2620153d |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-11T13:18:12Z |
| publishDate | 2018-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-2b4d6c387d20421689f96e3c2620153d2022-12-22T01:05:57ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-08-01910.3389/fmicb.2018.01832384911Adapted Bacteriophages for Treating Urinary Tract InfectionsAleksandre Ujmajuridze0Nina Chanishvili1Marina Goderdzishvili2Lorenz Leitner3Ulrich Mehnert4Archil Chkhotua5Thomas M. Kessler6Wilbert Sybesma7The Alexander Tsulukidze National Center of Urology, Tbilisi, GeorgiaThe George Eliava Institute of Bacteriophage, Microbiology and Virology, Tbilisi, GeorgiaThe George Eliava Institute of Bacteriophage, Microbiology and Virology, Tbilisi, GeorgiaDepartment of Neuro-Urology, Balgrist University Hospital, University of Zurich, Zurich, SwitzerlandDepartment of Neuro-Urology, Balgrist University Hospital, University of Zurich, Zurich, SwitzerlandThe Alexander Tsulukidze National Center of Urology, Tbilisi, GeorgiaDepartment of Neuro-Urology, Balgrist University Hospital, University of Zurich, Zurich, SwitzerlandDepartment of Neuro-Urology, Balgrist University Hospital, University of Zurich, Zurich, SwitzerlandUrinary tract infections (UTIs) are among the most widespread microbial diseases and their economic impact on the society is substantial. The continuing increase of antibiotic resistance worldwide is worrying. As a consequence, well-tolerated, highly effective therapeutic alternatives are without delay needed. Although it has been demonstrated that bacteriophage therapy may be effective and safe for treating UTIs, the number of studied patients is low and there is a lack of randomized controlled trials (RCTs). The present study has been designed as a two-phase prospective investigation: (1) bacteriophage adaptation, (2) treatment with the commercially available but adapted Pyo bacteriophage. The aim was to evaluate feasibility, tolerability, safety, and clinical/microbiological outcomes in a case series as a pilot for a double-blind RCT. In the first phase, patients planned for transurethral resection of the prostate were screened (n = 130) for UTIs and enrolled (n = 118) in the study when the titer of predefined uropathogens (Staphylococcus aureus, E. coli, Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis) in the urine culture was ≥104 colony forming units/mL. In vitro analysis showed a sensitivity for uropathogenic bacteria to Pyo bacteriophage of 41% (48/118) and adaptation cycles of Pyo bacteriophage enhanced its sensitivity to 75% (88/118). In the second phase, nine patients were treated with adapted Pyo bacteriophage and bacteria titer decreased (between 1 and 5 log) in six of the nine patients (67%). No bacteriophage-associated adverse events have been detected. The findings of our prospective two-phase study suggest that adapted bacteriophage therapy might be effective and safe for treating UTIs. Thus, well-designed RCTs are highly warranted to further define the role of this potentially revolutionizing treatment option.https://www.frontiersin.org/article/10.3389/fmicb.2018.01832/fullbacteriophage therapyPyo bacteriophageadaptationurinary tract infectionantibiotic resistance |
| spellingShingle | Aleksandre Ujmajuridze Nina Chanishvili Marina Goderdzishvili Lorenz Leitner Ulrich Mehnert Archil Chkhotua Thomas M. Kessler Wilbert Sybesma Adapted Bacteriophages for Treating Urinary Tract Infections Frontiers in Microbiology bacteriophage therapy Pyo bacteriophage adaptation urinary tract infection antibiotic resistance |
| title | Adapted Bacteriophages for Treating Urinary Tract Infections |
| title_full | Adapted Bacteriophages for Treating Urinary Tract Infections |
| title_fullStr | Adapted Bacteriophages for Treating Urinary Tract Infections |
| title_full_unstemmed | Adapted Bacteriophages for Treating Urinary Tract Infections |
| title_short | Adapted Bacteriophages for Treating Urinary Tract Infections |
| title_sort | adapted bacteriophages for treating urinary tract infections |
| topic | bacteriophage therapy Pyo bacteriophage adaptation urinary tract infection antibiotic resistance |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.01832/full |
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