During the study period, 4778 patients were colonized with C. auris or diagnosed with C. auris in a clinical specimen in Florida (Supplementary Figure 1). We reviewed records from 1073 unique patients eligible for inclusion (Figure 1). Of those reviewed, 137 patients met the clinical case definition and 32 were excluded for missing medical records or CRFs, leaving 105 case-patients for inclusion in the analysis. Of the eligible control subjects (n = 635), 57 were excluded for missing medical records or CRFs, leaving 578 for inclusion.

A total of 63 (60.0%) case-patients and 317 (54.8%) control subjects were male (Table 1). A greater proportion of case-patients were aged 50–64 years (39.0% vs 25.3%) and a lower proportion were aged ≥80 years (9.5% vs 18.2%), compared with control subjects. Median age was 64 years (range, 25–93 years) for case-patients and 69 years (range, 19–101 years) for control subjects. Case-patients and control subjects were similar with regard to race and ethnicity. Case-patients and control subjects mostly identified as White, non-Hispanic at 39% (n = 41) and 44% (n = 256), respectively. Of the 105 case-patients, 59 (56.2%) had laboratory-confirmed C. auris bloodstream infections (ie candidemia). Patients first screened positive for C. auris in various healthcare settings, including ACHs (n = 382 [56%]), LTACHs (n = 287 [42%]), SNFs and long-term care facilities (n = 13 [2%]), and inpatient rehabilitation facilities (n = 1 [0.15%]). The median time from first positive screening (colonization) to progression to clinical specimens based on laboratory collection dates was 91.3 days (range, 1–774 days). Although 30-day all-cause mortality was higher among control subjects (13.8%) than case-patients (3.8%), 90-day all-cause mortality was similar among case-patients (20.0%) and control subjects (19.6%) (OR, 1.03 [95% CI, .61–1.73]; P = .91).

Unadjusted measures revealed that case-patients had greater odds of being in the age group 50–64 years when compared to control subjects (OR, 1.77 [95% CI, 1.09–2.87]; P = .0195) (Table 2). The majority of case-patients (100%) and control subjects (95%) had at least 1 medical comorbidity documented. Presence of a neurologic condition was higher among case-patients (52.4%) compared to control subjects (36.7%) (OR, 1.90 [95% CI, 1.25–2.89]; P = .002). Chronic kidney disease was also significantly associated with clinical cases (OR, 2.12 [95% CI, 1.39–3.23]; P = .0004). Most case-patients and control subjects had at least 1 invasive medical device (89.5% of case-patients vs 84.4% of control subjects). Certain medical devices were more likely to be associated with clinical cases, including tracheostomy (OR, 2.09 [95% CI, 1.37–3.18]; P = .0005), mechanical ventilation (OR, 1.90 [95% CI, 1.24–2.92]; P = .003), and gastrointestinal feeding tube (OR, 1.94 [95% CI, 1.25–3.02]; P = .003). Of note, the presence of ≥4 invasive devices (OR, 2.92 [95% CI, 1.70–5.03]; P < .0001) was significantly associated with a C. auris clinical case. Central venous catheters were not significantly associated with clinical cases (OR, 1.37 [95% CI, .90–2.08]; P = .14). Recent medical procedures were common among both case-patients and control subjects (78.1% and 73.2%, respectively). Case-patients had greater odds of a recent bronchoscopy (OR, 3.29 [95% CI, 1.41–7.66]; P = .004) and ≥3 procedures (OR, 2.32 [95% CI, 1.19–4.55]; P = .012). A previous MDRO infection or colonization was also more common among case-patients than control subjects (48.6% vs 29.1%, respectively; OR, 2.09 [95% CI, 1.32–3.31]; P = .001). No significant difference was found between case-patients (12.4%) and control subjects (15.1%) who shared a room (OR, 0.73 [95% CI, .39–1.37]; P = .33). Both case-patients (73.3%) and control subjects (68.2%) commonly had >1 healthcare facility admission during the year before testing positive for C. auris colonization, with no significant difference between groups (OR, 1.28 [95% CI, .81–2.05]; P = .29).

ADL scores were assessed separately for each category in eating, mobility, transferring, and toileting tasks (Table 2). Both case-patients and control subjects were likely to be assessed as fully dependent (ie, unable to complete self-care tasks) in each of these areas. Tube feeding or TPN (eating ADL score of 5) (75.2% vs 54.8%; OR, 2.80 [95% CI, 1.59–4.95]; P = .0002), a bedfast or chairfast state (mobility ADL score of 5) (64.8% vs 52.2%; OR, 2.15 [95% CI, 1.24–3.74]; P = .006), and an inability to transfer (61.9% vs 51.6%; OR, 1.82 [95% CI, 1.07–3.08]; P = .025) were significantly associated with clinical cases. ADL data were missing for 21.9% (n = 23) of case-patients and 23.4% (n = 135) of control subjects.

In this analysis of risk factors associated with progression of C. auris colonization, we found a significant association between presence of C. auris in a clinical specimen and age group, presence of multiple comorbidities, invasive devices, medical procedures, and low patient functional status. Similar to other studies, we found association of invasive devices such as tracheostomy, mechanical ventilation, and feeding tubes with C. auris clinical progression [10, 15, 16, 20]. Our analysis also demonstrates a possible association of infection among case-patients with neurologic conditions and recent bronchoscopy procedures, which is consistent with prior studies that suggested certain conditions and invasive procedures increase the likelihood of candidemia [10, 17, 20, 32].

We found case-patients had greater odds of being in the age group 50–64 years. This finding is unexpected and differs from a previous risk factor analysis that demonstrated significant susceptibility to C. auris infection in patients aged ≥65 years [6]. The ratio observed for 30-day mortality is likely due to a small number of case-patients (n = 4) for this variable. The 90-day all-cause mortality findings did not demonstrate a significantly greater odds for clinical cases over colonization. However, we cannot determine a causal relationship between mortality and the presence of C. auris due to underlying conditions or other confounding factors. This analysis also provides a unique assessment of the association of ADLs with clinical progression of C. auris. Persons fully dependent on care were more likely to experience clinical indications, especially if bedridden and fed by gastrointestinal feeding tube or TPN. Our results reinforce focused screening and clinical assessment and demonstrate the need for robust IPC measures to prevent C. auris transmission, particularly focusing on patient functional status (ADL assessment) and healthcare environment [18].

Because Florida continues to be a state with a high prevalence of C. auris colonization and clinical cases, this state-level study provides a broader perspective of patients cared for within different facilities (ie, ACHs, long-term care facilities, LTACHs, SNFs, and rehabilitation facilities). These results could be used to improve facility screening protocols, healthcare provider knowledge, and IPC measures to improve patient outcomes within Florida healthcare facilities. Furthermore, case-patients in our analysis were often screened for C. auris multiple times despite current recommendations discouraging rescreening after a patient has tested positive for C. auris colonization. Rescreening incidence might indicate a need to improve interfacility communication regarding MDRO status during patient transfers.

This analysis has several limitations. Although C. auris is nationally notifiable, it is not a reportable condition in the state of Florida other than in healthcare-associated outbreaks. Thus, data used for this analysis were not derived from population-based surveillance, which might limit the generalizability of findings. The first patient with C. auris in Florida was identified in 2017, but Florida’s electronic reportable disease system was not used for case documentation and reporting purposes until September 2019, resulting in limited case and laboratory data. Lack of a formal FDOH case definition until 2020 also affected identification and documentation of cases. No case-patients or control subjects before 2020 met inclusion criteria for this analysis. A variety of clinical specimens were documented as clinical cases. Though the majority represented candidemia (56.2%), the severity of clinical illness experienced by case-patients was not accounted for in this retrospective analysis. In addition, the associations described are based on unadjusted analysis and the observational study design limits conclusions regarding causality. Healthcare facilities’ admission screening protocols for C. auris varied and might have resulted in selection bias in certain facilities or geographic areas. Quality and completeness of data submitted to the local and state public health departments varied depending on who was reporting the information on the CRF. Missing medical records and incomplete CRFs affected the number of patients who met the criteria for inclusion in our analysis and resulted in a smaller sample size with lower statistical power to detect associations and might have introduced selection bias. Finally, we did not assess recent medication use for possible contributions to antifungal resistance or clinical progression.

This analysis is one of the largest of its kind to use data collected from different healthcare facility types in a large US state to assess factors associated with clinical progression among patients colonized with C. auris. We found that clinical case-patients were more likely than control subjects to be aged 50–64 years and to have markers of increased morbidity, such as a high number of chronic conditions, invasive devices, medical procedures, and poor functional status. Facilities could consider prioritizing high-acuity patients for early C. auris screening, transmission-based precautions, and infection prevention interventions. Identifying risk factors for clinical progression of C. auris after colonization could enable facilities to implement more efficient testing protocols and help prevent morbidity associated with invasive infections. Further analysis to understand clinical implications and risk factors for C. auris progression after colonization is needed. Future efforts might include an adjusted analysis to more fully understand the risk that individual medical conditions and functional status have on C. auris clinical outcomes.

Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.