Background: Pneumocystis jirovecii pneumonia (PJP) is an important infection-related complication, whose mode of transmission remains uncertain. Methods: We investigated a nosocomial cluster of 14 PJP cases (11 confirmed and 3 probable) in kidney transplant recipients using epidemiological and genotyping methods. Results: Poisson regression calculated an incidence density ratio of 42.8 (95% confidence interval [CI], 14.1-129.3) versus background 0.64 cases of 1000 patient-years (Pandlt;0.001). All patients presented with respiratory failure, 10 required ventilation, two died, and six transplants failed, costing $31,854 (±SD $26,048) per patient. Four-locus multilocus sequence typing analysis using DNA extracts from 11 confirmed cases identified two closely related genotypes, with 9 of 11 sharing an identical composite multilocus sequence typing genotype. Contact tracing found colocalization of cases within clinic waiting areas, suggesting person-to-person transmission. Minimal and maximal PJP incubation periods were 124±83 to 172±71 days, respectively. Oropharyngeal washes from outpatient staff and ambient air samples were negative for P. jirovecii DNA. Cohort analysis (14 cases vs. 324 unaffected clinic control patients) identified independent risk factors including previous cytomegalovirus infection (odds ratio [OR], 65.9; 95% CI, 7.9 -550; Pandlt;0.001), underlying pulmonary disease (OR, 10.1; 95% CI, 2.3- 45.0; Pandlt;0.002), and transplant dysfunction (OR=1.61 per 10 mL/min/1.73 m2, 95% CI, 1.15-2.25, Pandlt;0.006). The outbreak was controlled by reintroduction of trimethoprim/sulfamethoxazole prophylaxis to all potentially exposed clinic patients and its extension to 12 months in recent recipients. Conclusions. Nosocomial PJP clusters are likely due to interhuman transmission by airborne droplets to susceptible hosts. Prompt recognition and a strategy of early preemptive blanket PJP prophylaxis to all exposed transplant clinic recipients from the third confirmed case are recommended to limit outbreak escalation.
