Outbreaks of Fungal Infections in Hospitals: Epidemiology, Detection, and Management.

Nosocomial clusters of fungal infections, whilst uncommon, cannot be predicted and are associated with significant morbidity and mortality. Here, we review reports of nosocomial outbreaks of invasive fungal disease to glean insight into their epidemiology, risks for infection, methods employed in outbreak detection including genomic testing to confirm the outbreak, and approaches to clinical and infection control management. Both yeasts and filamentous fungi cause outbreaks, with each having general and specific risks. The early detection and confirmation of the outbreak are essential for diagnosis, treatment of affected patients, and termination of the outbreak. Environmental sampling, including the air in mould outbreaks, for the pathogen may be indicated. The genetic analysis of epidemiologically linked isolates is strongly recommended through a sufficiently discriminatory approach such as whole genome sequencing or a method that is acceptably discriminatory for that pathogen. An analysis of both linked isolates and epidemiologically unrelated strains is required to enable genetic similarity comparisons. The management of the outbreak encompasses input from a multi-disciplinary team with epidemiological investigation and infection control measures, including screening for additional cases, patient cohorting, and strict hygiene and cleaning procedures. Automated methods for fungal infection surveillance would greatly aid earlier outbreak detection and should be a focus of research.

Epidemiology, Modern Diagnostics, and the Management of Mucorales Infections.

Mucormycosis is an uncommon, yet deadly invasive fungal infection caused by the Mucorales moulds. These pathogens are a WHO-assigned high-priority pathogen group, as mucormycosis incidence is increasing, and there is unacceptably high mortality with current antifungal therapies. Current diagnostic methods have inadequate sensitivity and specificity and may have issues with accessibility or turnaround time. Patients with diabetes mellitus and immune compromise are predisposed to infection with these environmental fungi, but COVID-19 has established itself as a new risk factor. Mucorales also cause healthcare-associated outbreaks, and clusters associated with natural disasters have also been identified. Robust epidemiological surveillance into burden of disease, at-risk populations, and emerging pathogens is required. Emerging serological and molecular techniques may offer a faster route to diagnosis, while newly developed antifungal agents show promise in preliminary studies. Equitable access to these emerging diagnostic techniques and antifungal therapies will be key in identifying and treating mucormycosis, as delayed initiation of therapy is associated with higher mortality.

Knowledge at what cost? An audit of the utility of panfungal PCR performed on bronchoalveolar lavage fluid specimens at a tertiary mycology laboratory.

The diagnostic utility and costs of panfungal PCR assays for invasive fungal disease (IFD) from bronchoalveolar lavage fluid (BALF) specimens are incompletely defined. In a retrospective audit, panfungal PCR results from 2014-2018 were matched with information on request forms and the registrar/microbiologist diary of clinical liaison. Identification of a single fungus other than a commensal was considered potentially clinically significant, and assessed for clinical relevance. Of 1002 specimens tested, an estimated 90% were requested in patients without clinical suspicion of IFD. There were 530 (52.9%) PCR-positive results of which 485/530 (91.5%) identified multiple fungal species or commensal fungi; 45 (8.5%) were clinically significant but only in 12 (1.2%) was panfungal PCR the sole diagnostic test leading to IFD diagnosis, all in immunocompromised patients with clinical suspicion of IFD. Costs of panfungal PCR tests averaged AUD 133 per test, or AUD 26,767/annum. However, the average cost-per-diagnosis achieved was AUD 15,978/annum. Limiting testing to patients at risk and with clinical suspicion of IFD, may save over AUD 13,383/annum (assuming 50-90% reduction in testing). The value-added utility of panfungal PCR on BALF is 1.2% (12/1002). We have since introduced pre-analytical stewardship limiting routine panfungal PCR testing of BALF to high-risk patients in our hospital.

Nosocomial Pneumocystis jirovecii pneumonia: lessons from a cluster in kidney transplant recipients.

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 (P<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; P<0.001), underlying pulmonary disease (OR, 10.1; 95% CI, 2.3-45.0; P=0.002), and transplant dysfunction (OR=1.61 per 10 mL/min/1.73 m, 95% CI, 1.15-2.25, P=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.