Background Streptococcus pyogenes causes acute pharyngitis and type II necrotizing fasciitis. Seasonal variations in the incidence of S. pyogenes infections are not robustly characterized. We aim to identify seasonal variations and risk factors of S. pyogenes infections and all causes of necrotizing fasciitis. Methods From 2010 to 2019, we identified all infectious adult cases of S. pyogenes using ICD-10 diagnoses and lab results (PCR and antigen-based assays) and cases of necrotizing fasciitis using ICD-10 diagnoses within a federated research network. We extracted seasonal (quarterly) incidence rates. We used an autoregressive integrated moving average (ARIMA) model to assess the seasonality of the cases (6-month intervals). Demographic characteristics and 3-month outcomes of S. pyogenes pharyngitis were compared to a cohort of patients with acute upper respiratory illnesses excluding S. pyogenes. Results We identified 238,088 cases of S. pyogenes pharyngitis and 26,931 cases of necrotizing fasciitis in adults. S. pyogenes infection average incidence was higher during the winter than the summer: 0.34 vs. 0.20 cases per 1,000 patients. Necrotizing fasciitis diagnoses were highest during the summer months (average 0.026 per 1000 patients). There was a significant ARIMA seasonal variation in the time series analysis for S. pyogenes infections (p=0.006) (figure 1). However, necrotizing fasciitis was not significant (p=0. 0.79) (Figure 2). Compared to adults with acute respiratory infections other than S. pyogenes, adults with S. pyogenes pharyngitis were more likely to be younger (25.8 ± 14.9 vs. 45.4 ± 19.9 years old, p< 0.0001) and of Hispanic or Latino ethnicity (11% vs. 8%, p < 0.0001). For age-matched outcomes, adults with S. pyogenes pharyngitis had lower rates of hospitalization (0.888% vs. 1.714%, p< 0.0001) and mortality (0.114% vs. 0.174%, p< 0.0001) at three months relative to adults with acute respiratory infections other than S. pyogenes. Figure 1.Seasonal variation of adults with established ICD code or testing for Streptococcus pyogenes (GAS) infectionsFigure 2.Seasonal variation of adults with established ICD code for necrotizing fasciitis Conclusion Peaks in S. pyogenes infections are more likely to occur in the winter months, although spring and fall seasons can display variably high rates of S. pyogenes year over year. Necrotizing fasciitis of any microbiological did not show a significant seasonal variation. Disclosures All Authors: No reported disclosures.

Cryptococcosis is an opportunistic fungal infection of worldwide distribution with significant associated morbidity and mortality. HIV, organ transplantation, malignancy, cirrhosis, sarcoidosis, and immunosuppressive medications, are established risk factors for cryptococcosis. Type 2 diabetes mellitus (DM2) has been hypothesized as a risk factor and an outcome modifier for cryptococcosis. We aimed to compare outcomes among HIV-negative, non-transplant (NHNT) patients with and without DM2. We also characterized a cohort of patients with cryptococcosis and DM2 as the only identifiable risk factor. We queried a global research network to identify NHNT patients (n = 3,280). We performed a propensity score-matched (PSM) analysis comparing clinical outcomes among cryptococcosis patients with DM2 (n = 995) versus those without DM2 (n = 2,285). We also characterize adults with cryptococcosis and DM2 as the only risk factor. After PSM, NHNT patients with DM2 were more likely to develop cognitive dysfunction [9% vs. 6%, OR = 1.6; 95% CI (1.1–2.3); p = 0.01] but had similar mortality, hospitalization, ICU, and stroke risk after acquiring cryptococcosis when compared to NHNT patients without DM2. We identified 44 patients with cryptococcosis who had DM2 as the only identifiable risk factor for infection. Patients with cryptococcosis and isolated DM2 commonly had chronic kidney and end-stage renal disease. The most common anatomic site of cryptococcal infection was pulmonary. The annual incidence of cryptococcosis in patients with DM2 as their only identifiable risk factor was only 0.001%, and the prevalence was 0.002%. DM2 is associated with increased cognitive dysfunction risk in NHNT patients with cryptococcosis. It is rare for DM2 to be the only identified risk factor for developing cryptococcosis. Kidney disease, hyperglycemia, and immune dysfunction can increase risk in this setting.

Background Diabetes mellitus type 2 (DM2) is a common medical condition that increases the risk of bacterial infections, and is often present in patients with cryptococcosis. The role of DM2 as an independent risk factor for cryptococcosis is debatable. We aim to better characterize the natural history of cryptococcosis in patients with DM2 as their only comorbidity. Methods We utilized TrinetX, a federal national network, to identify HIV-negative patients who had cryptococcosis without known risk factors. Demographic characteristics and outcomes were compared between patients with DM2 and those without DM2, who tested positive or had ICD based diagnoses of Cryptococcus infection within five years of diagnosis of DM2. Results Sixty patients with DM2 (as the sole risk factor) and 707 patients without DM2 had cryptococcosis. Patients with DM2 and cryptococcosis were older (61 ± 13.6 years vs. 55.8 ± 16.2 years, p=0.0219), and more likely to be Hispanic or Latino (18% vs. 9%, p=0.023). They had higher rates of hypertension (77% vs 44%, p< 0.0001), cystic fibrosis (18% vs 1%, p< 0.0001), tuberculosis (18% vs 1%, p< 0.0001), and chronic kidney disease (33% vs 18%, p=0.0026). The mean HbA1c among patients with DM2 who developed cryptococcosis was 8.16 (SD 2.62). The most common sites of cryptococcus infection were pulmonary (56% vs 55%, p=0.8930) and cerebral (36% vs 40%, p=0.5589), in both groups. The two groups had similar mortality (20% vs 25.47%, p=0.3676) (Figure 1), and hospitalization rates (20% vs 31.3%, p=0.08). The overall annual cryptococcosis risk among HIV-negative patients with DM2 without any additional risk factors was 0.001%. Conclusion Cryptococcosis occurs rarely in HIV-negative patients with DM2 and without additional risk factors. Hispanic or Latino ethnicity, uncontrolled hyperglycemia, and chronic kidney disease may increase the risk of cryptococcosis among patients with DM2. Cryptococcosis in patients whose only comorbidity is DM2 have as high of mortality as that seen with more established comorbitidies. Disclosures All Authors: No reported disclosures.