Yetmar, Zachary A.

Abstract Background Statins up-regulate angiotensin-converting enzyme 2, the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while also exhibiting pleiotropic antiviral, antithrombotic, and anti-inflammatory properties. Uncertainties exist about their effect on the course of SARS-CoV-2 infection. We sought to systematically review the literature and perform a meta-analysis to examine the association between prior statin use and outcomes of patients with coronavirus disease 2019 (COVID-19). Methods We searched Ovid Medline, Web of Science, Scopus, and the preprint server medRxiv from inception to December 2020. We assessed the quality of eligible studies with the Newcastle-Ottawa quality scale. We pooled adjusted relative risk (aRRs) of the association between prior statin use and outcomes of patients with COVID-19 using the DerSimonian-Laird random-effects model and assessed heterogeneity using the I2 index. Results Overall, 19 (16 cohorts and 3 case-control) studies were eligible, with a total of 395 513 patients. Sixteen of 19 studies had low or moderate risk of bias. Among 109 080 patients enrolled in 13 separate studies, prior statin use was associated with a lower risk of mortality (pooled aRR, 0.65 [95% confidence interval {CI}, .56–.77], I2 = 84.1%) and a reduced risk of severe COVID-19 was also observed in 48 110 patients enrolled in 9 studies (pooled aRR, 0.73 [95% CI, .57–.94], I2 = 82.8%), with no evidence of publication bias. Conclusions Cumulative evidence suggests that prior statin use is associated with lower risks of mortality or severe disease in patients with COVID-19. These data support the continued use of statins medications in patients with an indication for lipid-lowering therapy during the COVID-19 pandemic.

Abstract Background Capnocytopha ga is a gram-negative, facultative anaerobe. Human infection is rare but can lead to devastating outcomes. Capnocytophaga canimorsus can cause sepsis following an animal bite, whereas human-oral–associated Capnocytophaga infections were reported in immunocompromised patients. Current data on these infections are not robust. Our goal is to provide a contemporary description of a unique characteristic of Capnocytophaga infections. Methods We performed a retrospective review of all patients with Capnocytophaga infection from January 2010 to August 2020 at 3 main hospitals of Mayo Clinic in Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida. We collected baseline demographic data, clinical characteristics, microbiological data, and outcomes of C. canimorsus and human-oral–associated Capnocytophaga infection. Results Among 82 patients with Capnocytophaga infection, 46 patients (56.0%) had bacteremia. The most common species identified in this group was C. sputigena (57.9%), followed by C. canimorsus (34.8%). Patients with human-oral–associated Capnocytophaga bacteremia were often immunocompromised, presented with neutropenic fever, and had worse 6-month all-cause mortality compared to C. canimorsus bacteremia (36.4% vs 6.2%, P = .03). They also had a higher β-lactamase production rate (36.4% vs 0.0%, P = .02). Among patients without bacteremia, the main clinical syndrome was polymicrobial head and neck infections (47.2%). Conclusions Human-oral–associated Capnocytophaga bacteremia occurs primarily in immunocompromised patients, particularly those with hematologic malignancy. In contrast, C. canimorsus bacteremia is more likely to present with community-onset infection related to zoonotic exposure. Human-oral–associated Capnocytophaga infection without bacteremia is frequently isolated in polymicrobial infection; this phenomenon’s significance is yet to be fully understood.

Abstract Cefazolin is commonly used as an alternative to antistaphylococcal penicillins (ASPs) in treating methicillin-susceptible Staphylococcus aureus (MSSA) infections; however, no study has compared these agents in MSSA spinal epidural abscess (SEA). We describe our experience in managing MSSA SEA and compare the clinical efficacy of cefazolin with ASPs. This retrospective multicenter study reviewed 79 adult patients diagnosed with SEA between January 2006 and July 2020 using data collected from electronic health records and clinical microbiology laboratory databases. Forty-five patients received cefazolin, while 34 received ASPs. The total antibiotic duration was longer in the ASPs group but not statistically significant. There were no significant differences in treatment failure at week 6 vs week 12, 30-day vs overall mortality, or in 90-day recurrence rates between the treatment groups. Cefazolin was equally as effective as ASPs, and our findings suggest that it can be an alternative to ASPs in the treatment of MSSA SEA.

Abstract Background Invasive fungal infection (IFI) in heart transplant recipients is associated with increased mortality and poor outcome. Reports have estimated the risk of 1-year IFI to be 3.4-8.6% with renal replacement therapy, delayed chest closure, and reoperation suggested as risk factors. However, the role of antifungal prophylaxis is unclear, though previous studies have suggested a reduced incidence of invasive Aspergillosis. The transplant program in Mayo Arizona provides 6 months of universal azole prophylaxis for Coccidioides, while Rochester and Florida only provide prophylaxis to high risk patients. We sought to define epidemiology and risk factors for 1-year IFI and determine the effect of antifungal prophylaxis. Methods We conducted a retrospective cohort study of patients undergoing single-organ heart transplantation at Mayo Rochester, Florida, or Arizona from January 2000 to March 2019. We identified baseline characteristics, details of transplant hospitalization such as need for renal replacement therapy, open chest, reoperation, and operative time, receipt of antifungal prophylaxis, and diagnosis of IFI. Multivariable Cox analysis was performed to identify risk factors of time to 1-year IFI. Results A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62) and 72% male. 444 patients received antifungal prophylaxis which included 32% fluconazole, 34% itraconazole, 18% voriconazole, 15% echinocandin, and < 1% amphotericin or posaconazole. Over 1-year follow-up, 62 patients developed IFI with a cumulative prevalence of 6.4%. The most common organisms were Aspergillus (50%) and Candida (27%). In a multivariable model, factors associated with 1-year IFI were post-transplant renal replacement therapy (HR 3.34, 95% CI 1.69-6.60; P < 0.001) and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96; P=0.042). Operative time, recent hospitalization, open chest, and post-transplant mechanical circulatory support were not associated with 1-year IFI. Conclusion Renal replacement therapy after transplantation is associated with 1-year IFI. Antifungal prophylaxis appears to be protective and further prospective study is warranted to verify this finding. Disclosures All Authors: No reported disclosures

Abstract Background Cryptococcus spp is a major cause of opportunistic infections in immunocompromised patients, primarily due to Cryptococcus neoformans and Cryptococcus gattii. There are occasional reports of other Cryptococcus species causing invasive human disease. However, their epidemiology and clinical significance are not fully defined. We sought to describe cases with cultures positive for Cryptococcus species other than C neoformans and C gattii. Methods A retrospective descriptive analysis of clinical and laboratory data of patients with cultures growing Cryptococcus species other than C neoformans and C gattii from November 2011 to February 2019 was performed. Three Mayo Clinic sites in Arizona, Florida, and Minnesota were included. Results From 176 cases with a culture growing Cryptococcus spp, 54 patients (30%) had a culture for Cryptococcus other than C neoformans and C gattii in the study time frame. The most common species were Cryptococcus magnus, Cryptococcus laurentii, and Cryptococcus ater. The organisms were isolated and identified in culture of bronchoalveolar lavage (11), skin (11), urine (7), oral (4), sinus (3), intraoperative soft tissue (3), sputum (2), synovial fluid (2), cerebrospinal fluid (2), and intravenous catheter (2), among others (7). Only 8 (15%) cases were considered to be potentially pathogenic, with 1 case of invasive disease. Antifungal treatment was fluconazole, itraconazole, and griseofulvin, for a mean systemic antifungal duration of 42 days. Conclusions This large series of patients with Cryptococcus spp other than C neoformans and C gattii suggests that these species rarely cause clinically significant infection in humans. Only 1 case of invasive disease was found.

Abstract Background Over 80% of patients with hematologic malignancies develop some form of infectious complication, most commonly febrile neutropenia. Patients with febrile neutropenia have 10% mortality, which increases if antibiotic administration is delayed past 30 minutes. Studies have suggested β-lactam allergy may delay administration of antibiotic while putting patients at greater risk for inappropriate antibiotic choice and adverse effects stemming from this. We sought to describe the risks associated with β-lactam allergy in the neutropenic population. Methods We conducted a retrospective, descriptive study from January 2016 to December 2017 identifying patients with febrile neutropenia and a reported history of β-lactam allergy. Baseline characteristics, allergy data, treatment data, and outcomes were collected and analyzed. Results We identified 31 patients with febrile neutropenia and β-lactam allergy during this time period. Etiologies of neutropenia were hematologic malignancy (61.2%), stem cell transplantation (12.9%), solid-organ malignancy (22.6%), and autoimmune (3.3%). Reported reactions to β-lactams were rash (41.9%), hives (9.7%), anaphylaxis (3.2%), other (9.7%), and unknown (35.5%). Average time to antibiotic administration was 142.5 minutes. Antibiotic choice was cefepime (61.3%), piperacillin–tazobactam (6.5%), carbapenem (22.6%), fluoroquinolone (6.5%), cefepime and fluoroquinolone (3.2%), and vancomycin (58.1%). 51.6% received initial antibiotics consistent with the 2010 IDSA guidelines. Six patients underwent penicillin skin testing, all negative. 1 patient developed C. difficile infection, 1 developed MRSA colonization, and 3 developed VRE colonization. Mortality was 3.2% at 30 days and 16.1% at 90 days. Conclusion Our study estimated the antibiotic usage patterns and outcomes in patients with febrile neutropenia and reported β-lactam allergy. This showed low adherence to an established guideline for antibiotic choice in these patients. With rising antimicrobial resistance, there is a need to develop strategies to reduce inappropriate antimicrobial use, especially in patients with febrile neutropenia. Preemptive β-lactam allergy evaluation warrants further evaluation in the neutropenic population. Disclosures All authors: No reported disclosures.

Abstract Background Optimum duration of antimicrobial therapy for acute bacteremic cholangitis is not well established; however, 4–7 days is recommended by the 2018 Tokyo guidelines in those without Gram-positive bacteremia. Methods A retrospective study performed at Mayo Clinic - Rochester, Florida and Arizona sites was conducted, reviewing all adult patients with the first episode of acute cholangitis secondary to biliary stone obstruction, between January 1, 2012 and December 31, 2017. We reviewed the duration of prescribed antimicrobials. Results Among 331 included cases, 197(60%) were men, 66 (20%) were immuno-compromised. Presenting symptoms included fever in 202 (61.5%), abdominal pain in 289 (87%), jaundice 128(38.7%), and altered mentation in 49 (15%). Among these, 256 (77%) were classified as “definite” and 38 (11.5%) were “suspected” using the 2018 Tokyo guideline classification. Cholangitis grade was grade III in 134 (40.5%); grade II in 115 (34.7%); and grade I in 82 (24.8%). Majority of cases, 321 (97%), underwent source control—most commonly 309 (96%) achieved by endoscopic retrograde cholangiopancreatography (ERCP). Source control occurred within 24 hr of presentation in 197 (61.4%) of the cases. Bacteremia was documented in 131/277 (47%). Majority of bacteremias were due to Gram-negative organisms in 119 (91%). Mean duration of antibiotic therapy following “source control” was 9.6 days (SD 7.0). Cases with bacteremia, resulted in longer treatment duration, mean of 13 days (SD 5.6), regardless of the isolated organism. Overall 30 day mortality was 14/331 (4.2%). No mortality difference was noted in patients who underwent early (within 12 hours) vs. later source control (4.55% Vs. 4.53%), nor in those who received more or less than 6 days of antibiotic therapy after source control (4.7% Vs. 3.9%, P = 0.76). No difference in mortality was observed in those with or without bacteremia. Conclusion Our results note the use of longer courses of antimicrobials for management of bacteremic cholangitis, regardless of the organism type. This population could be a prime target for an antimicrobial stewardship intervention, to decrease the duration of prescribed antimicrobials in accordance with recent guidelines. Disclosures All authors: No reported disclosures.

Abstract Background Cryptococcus sp. is a major cause of opportunistic infections in immunocompromised patients, with nearly all cases due to C. neoformans or C. gattii. There are occasional reports of other Cryptococcus species causing invasive human disease. However, their epidemiology and clinical significance are not fully defined. We sought to describe the patients with cultures positive for Cryptococcus species other than neoformans and gattii. Methods A retrospective descriptive review of patients with cultures growing Cryptococcus species other than neoformans and gattii from November 2011 to February 2019. Clinical and laboratory data were analyzed. Results Out of 177 cases with a culture positive for Cryptococcus sp., 54 patients (mean age, 53.3 years; 61% men) had a culture for Cryptococcus other than neoformans and gattii. The most common species were unspecified non-neoformans/gattii (10), magnus (9), laurentii (8), and ater (7). Three patients had active malignancies and 15 were on immunosuppressive drugs, 6 due to transplant. The most common sites or specimens were skin (16), respiratory (16), urine (7), joint (3), intravascular catheter (2), cerebrospinal fluid (2), oral (2), peritoneal fluid, donor liver transplant, bone marrow, sinus, nail, and cornea. Whereas 21 (38.9%) cultures were obtained due to local symptoms, there was only one case of invasive disease, affecting the peritoneum, while the majority was either unaddressed (25) or considered contaminants (17). Only 12 patients received antifungal treatment, where sources were skin (4), oral (2), peritoneum, donor liver, respiratory, vascular catheter, urine, and nail. Antifungal drugs were fluconazole, itraconazole, clotrimazole, caspofungin, and griseofulvin, for a mean duration of 37.6 days. Among patients who were not treated, four died within 6 months but mostly of unrelated causes (3) or not known (1). Conclusion This large series of patients with Cryptococcus sp. other than neoformans and gattii suggests that these species rarely cause clinically significant infection in humans. Only one case of invasive disease was found. Disclosures All authors: No reported disclosures.