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IMPORTANCEDespite the high 3-dose vaccination rate among health care workers (HCWs) in Israel, a high rate of SARS-CoV-2 breakthrough infections in this group was observed during the Omicron wave. As a result, the Israeli Ministry of Health decided to recommend a fourth vaccine dose to medical staff. OBJECTIVE To evaluate the benefit of a fourth BNT162b2 vaccine dose on the breakthrough infection rate among HCWs. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study was performed in January 2022, the first month of the 4-dose vaccination campaign, during a surge of the Omicron variant wave. All health care workers at 11 general hospitals in Israel who had been vaccinated with 3 doses up to September 30, 2021, and had not contracted COVID-19 before the vaccination campaign were included. EXPOSURES Vaccination with a fourth dose of the BNT162b2 vaccine during January 2022. MAIN OUTCOMES AND MEASURES Breakthrough COVID-19 infections in 4-dose recipients vs 3-dose recipients measured by a polymerase chain reaction test result positive for SARS-CoV-2. Health care workers were tested based on symptoms or exposure. RESULTS A total of 29 611 Israeli HCWs (19 381 [65%] female; mean [SD] age, 44 [12] years) had received 3 vaccine doses between August and September 2021; of these, 5331 (18%) received the fourth dose in January 2022 and were not infected by the first week after vaccination. Overall breakthrough infection rates were 368 of 5331 (7%) in the 4-dose group and 4802 of 24280 (20%)in the 3-dose group (relative risk, 0.35; 95% CI, 0.32-0.39). Similar reductions were found in a matched analysis by the exact day of receiving the third vaccine (relative risk, 0.61; 95% CI, 0.54-0.71) and in a time-dependent Cox proportional hazards regression model (adjusted hazard ratio, 0.56; 95% CI, 0.50-0.63). In both groups, no severe disease or death occurred. CONCLUSIONS AND RELEVANCEIn this cohort study, the fourth BNT162b2 vaccine dose resulted in a reduced breakthrough infection rate among hospital staff. This reduction was lower than that observed after the third dose; nevertheless, considering the high infectivity of the Omicron variant, which led to critical medical staff shortages, a fourth vaccine dose should be considered to mitigate the infection rate among HCWs.

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.

Adjunctive phage therapy was used in an attempt to avoid catastrophic outcomes from extensive chronic Pseudomonas aeruginosa osteoarticular infection in a 7-year-old child. Monitoring of phage and bacterial kinetics allowed real-time phage dose adjustment, and along with markers of the human host response, indicated a significant therapeutic effect within two weeks of starting adjunctive phage therapy. These findings strongly suggested the release of bacterial cells or cell fragments into the bloodstream from deep bony infection sites early in treatment. This was associated with transient fever and local pain and with evidence of marked upregulation of innate immunity genes in the host transcriptome. Adaptive immune responses appeared to develop after a week of therapy and some immunomodulatory elements were also observed to be upregulated.