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Background Previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides strong protection against future infection. There is limited evidence on whether such protection extends to the Omicron variant. Methods This retrospective cohort study included 635 341 patients tested for SARS-CoV-2 via polymerase chain reaction from 9 March 2020 to 1 March 2022. Patients were analyzed according to the wave in which they were initially infected. The primary outcome was reinfection during the Omicron period (20 December 2021–1 March 2022). We used a multivariable model to assess the effects of prior infection and vaccination on hospitalization. Results Among the patients tested during the Omicron wave, 30.6% tested positive. Protection of prior infection against reinfection with Omicron ranged from 18.0% (95% confidence interval [CI], 13.0–22.7) for patients infected in wave 1 to 69.2% (95% CI, 63.4–74.1) for those infected in the Delta wave. In adjusted models, previous infection reduced hospitalization by 28.5% (95% CI, 19.1–36.7), whereas full vaccination plus a booster reduced it by 59.2% (95% CI, 54.8–63.1). Conclusions Previous infection offered less protection against Omicron than was observed in past waves. Immunity against future waves will likely depend on the degree of similarity between variants.

Background Infective endocarditis due to Bartonella species is rare. The clinical and echocardiographic characteristics are not well defined. We aimed to investigate the clinical and echocardiographic findings of Bartonella endocarditis in the contemporary era. Methods The infective endocarditis (IE) registry and echocardiographic database at our institution were retrospectively analysed to evaluate the clinical and echocardiographic features of Bartonella endocarditis. Results Between January 2008 and December 2015, there were 11 patients with Bartonella IE (0.84% among a total of 1,308 cases of definite IE): median age 54 (30–69) years, all male, 9 Caucasian, 10 had a history of cat exposure, 10 had a pre-existing valvulopathy including 6 patients with a prosthetic valve with prosthesis age range between 3 to 5 years and 1 patient with implantable cardioverter defibrillator (ICD). Bartonella henselae was responsible for all the cases. Echocardiographic evidence of IE was found in 6 of 11 patients on transthoracic echocardiography (TTE), and 6 of 8 on transoesophageal echocardiography (TEE). Bartonella IE was associated with significant valvular destruction and dysfunction on echocardiography. Nine (9) patients were managed surgically with excellent outcomes, including two patients who failed initial medical therapy. Two (2) patients who were managed medically had progression of valvular dysfunction. At a median follow-up of 6 months, there were no deaths attributable to IE or other cardiovascular causes. Conclusion In a contemporary single-centre cohort in the United States, Bartonella IE remains rare, but should be considered when pathogen could not be identified in patients with suspected IE, especially those with prosthetic valves or bicuspid aortic valve (BAV). The vast majority of patients with Bartonella IE were managed surgically with excellent outcomes.

Background The aim was to evaluate the necessity of coronavirus disease 2019 (COVID-19) vaccination in persons with prior COVID-19. Methods Employees of the Cleveland Clinic working in Ohio on 16 December 2020, the day COVID-19 vaccination was started, were included. Anyone who tested positive for COVID-19 at least once before the study start date was considered previously infected. One was considered vaccinated 14 days after receiving the second dose of COVID-19 mRNA vaccine. Cumulative incidences of COVID-19, symptomatic COVID-19, and hospitalizations for COVID-19 were examined over the next year. Results Among 52 238 employees, 4718 (9%) were previously infected and 36 922 (71%) were vaccinated by the study’s end. Cumulative incidence of COVID-19 was substantially higher throughout for those previously uninfected who remained unvaccinated than for all other groups, lower for the vaccinated than unvaccinated, and lower for those previously infected than those not. Incidence of COVID-19 increased dramatically in all groups after the Omicron variant emerged. In multivariable Cox proportional hazards regression, both prior COVID-19 and vaccination were independently associated with significantly lower risk of COVID-19. Among previously infected subjects, a lower risk of COVID-19 overall was not demonstrated, but vaccination was associated with a significantly lower risk of symptomatic COVID-19 in both pre-Omicron (HR, .60; 95% CI, .40–.90) and Omicron (HR, .36; 95% CI, .23–.57) phases. Conclusions Both previous infection and vaccination provide substantial protection against COVID-19. Vaccination of previously infected individuals does not provide additional protection against COVID-19 for several months, but after that provides significant protection at least against symptomatic COVID-19.

BackgroundThe purpose of this study was to evaluate whether a bivalent COVID-19 vaccine protects against COVID-19.MethodsEmployees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available, were included. Cumulative incidence of COVID-19 over the following 26 weeks was examined. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with change in dominant circulating lineages over time accounted for by time-dependent coefficients. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses.ResultsAmong 51017 employees, COVID-19 occurred in 4424 (8.7%) during the study. In multivariable analysis, the bivalent vaccinated state was associated with lower risk of COVID-19 during the BA.4/5 dominant (HR, .71; 95% C.I., .63-.79) and the BQ dominant (HR, .80; 95% C.I., .69-.94) phases, but decreased risk was not found during the XBB dominant phase (HR, .96; 95% C.I., .82-.1.12). Estimated vaccine effectiveness (VE) was 29% (95% C.I., 21%-37%), 20% (95% C.I., 6%-31%), and 4% (95% C.I., -12%-18%), during the BA.4/5, BQ, and XBB dominant phases, respectively. Risk of COVID-19 also increased with time since most recent prior COVID-19 episode and with the number of vaccine doses previously received.ConclusionsThe bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.SummaryAmong 51017 working-aged Cleveland Clinic employees, the bivalent COVID-19 vaccine was 29% effective in preventing infection while the BA.4/5 lineages were dominant, and 20% effective while the BQ lineages were. Effectiveness was not demonstrated when the XBB lineages were dominant.

Background Best practice guidelines recommend that patients at risk for sexually transmitted infections (STIs), such as gonorrhea (GC) and chlamydia, should also be tested for human immunodeficiency virus (HIV) and syphilis. This prospective quality assurance study aimed to increase HIV and syphilis testing rates in emergency departments (EDs) across the Cleveland Clinic Health System from January 1, 2020 through January 1, 2022. Methods A multidisciplinary team of emergency medicine, infectious diseases, pharmacy, and microbiology personnel convened to identify barriers to HIV and syphilis testing during ED encounters at which GC/chlamydia were tested. The following interventions were implemented in response: rapid HIV testing with new a workflow for results follow-up, a standardized STI-screening order panel, and feedback to clinicians about ordering patterns. Results There were 57 797 ED visits with GC/chlamydia testing completed during the study period. Human immunodeficiency virus testing was ordered at 5% of these encounters before the interventions were implemented and increased to 8%, 23%, and 36% after each successive intervention. Syphilis testing increased from 9% before the interventions to 12%, 28%, and 39% after each successive intervention. In multivariable analyses adjusted for age, gender, and location, the odds ratio for HIV and syphilis testing after all interventions was 11.72 (95% confidence interval [CI], 10.82–12.71; P ≤.001) and 6.79 (95% CI, 6.34–7.27; P ≤.001), respectively. Conclusions The multidisciplinary intervention resulted in improved testing rates for HIV and syphilis.

Background Vancomycin is a first line agent in the treatment of methicillin-resistant Staphylococcus aureus infections. The ability to predict sub-therapeutic troughs would limit potential for development of resistance. The purpose of this study was to develop a predictive model for sub-therapeutic vancomycin troughs in adults. Methods This retrospective cohort study included adults 18 years and older ordered a pharmacy to dose vancomycin consult. Exclusion criteria included patients with cystic fibrosis, pregnancy, no steady-state trough, or required dialysis during therapy. Patients with sub-therapeutic vancomycin troughs (< 10 mg/L) were compared to patients with therapeutic troughs (10-20 mg/L). A K-nearest neighbors (KNN) regression model to predict an initial sub-therapeutic vancomycin level based on age, gender, race, BMI, loading dose, frequency, creatinine clearance, and institutional vancomycin dosing guideline adherence was developed and validated using 10-fold cross validation. The association of vancomycin dosing guideline adherence with initial sub-therapeutic vancomycin trough was evaluated in a multivariable logistic regression model adjusted for age and creatinine clearance. Results A total of 1,615 subjects were included; 494 (30.5%) subjects experienced a sub-therapeutic trough. A KNN regression model to predict an initial sub-therapeutic vancomycin level had an area under the ROC curve of 0.82, and an accuracy of 0.77 (95% CI 0.75-0.79, baseline accuracy 0.69). After adjusting for age and creatinine clearance, guideline dosing adherence was associated with significantly lower odds of an initial sub-therapeutic vancomycin level compared to guideline dosing non-adherence (OR 0.37, 95% CI 0.20-0.66, p-value 0.001). Conclusion A predictive model, based on readily available data points, for an initial sub-therapeutic vancomycin level was reasonably accurate. Adherence to the institutional vancomycin dosing guideline was associated with greater than 60% lower odds of an initial sub-therapeutic vancomycin level. Disclosures All Authors: No reported disclosures.

Background Ventricular assist device (VAD) infections caused Pseudomonas aeruginosa (PA) are difficult to treat given limited antibiotic options, development of resistance and biofilm formation in the presence of retained hardware. We looked at outcomes of patients who developed Pseudomonas aeruginosa LVAD infection (PA-LVADI) Methods Single center retrospective study of patients older than 18 years who received LVAD from 7/1/2007 to 2/1/2021 and subsequently developed PA-LVADI. Patients with proven or probable VAD-specific infections: driveline infection (DLI), pump pocket, and pump/cannula infections were included. The cumulative incidences of death, transplant, and LVAD explant, following Pseudomonas aeruginosa infection, were evaluated as competing outcomes. Fig 1:Classification of Pseudomonas aeruginosa LVAD Infections at diagnosisFigure 3:Cumulative incidence of death, transplant, or explant following Pseudomonas aeruginosa LVAD infection Results 51 patients with VAD-specific PA-LVADI were identified (Fig 1). Median age at the time of first LVAD placement was 55 years (23 – 74). Of the 28 patients ever listed for transplant, 13 (46%) received heart transplant, 8 (29%) were delisted, 7 (25%) were alive on transplant list (Fig 2). The median number of days from LVAD placement to first PA infection was 587 (54 – 3389). 30 (59%) had PA as the first causative organism. The extent of first PA-LVADI was superficial DLI in 43(84%), deep DLI in 5 (10%), pump pocket in 2(4%) and pump/cannula in 1(2%). 46 (90%) of patients received intravenous (IV) therapy with median duration of 84 (2 – 525) total IV antibiotic days. Antibiotic resistance emerged in 25/51 (49%) patients, with 32% being multi-drug resistant (MDR). Surgery was performed in 30 (58%). 12/13 who received heart transplants were followed for at least 1 year post-transplant and all were alive. 5 of the remaining 38 patients underwent pump exchange or explant. 20/38 (53%) of patients who were not transplanted died (Fig 3). Conclusion This is the largest study on PA-LVADI to date. We noted significant morbidity and mortality, with 90% of patients requiring prolonged IV antibiotics and over half requiring surgical treatment. Drug resistance emerged in a significant proportion of patients. Survival after transplant was excellent, but by 2 years of infection over half of the patients have been transplanted, explanted, or died. Disclosures All Authors: No reported disclosures.

Background Severe acute respiratory syndrome coronavirus 2 immunity has declined with subsequent waves and accrual of viral mutations. In vitro studies raise concern for immune escape by BA.4/BA.5, and a study in Qatar showed moderate protection, but these findings have yet to be reproduced. Methods This retrospective cohort study included individuals tested for coronavirus disease 2019 by polymerase chain reaction during Delta or BA.1/BA.2 and retested during BA.4/BA.5. The preventable fraction (PF) was calculated as ratio of the infection to the hospitalization rate for initially positive patients divided by the ratio for initially negative patients, stratified by age and adjusted for age, sex, comorbid conditions, and vaccination using logistic regression. Results A total of 20 987 patients met inclusion criteria. Prior Delta infection provided no protection against BA.4/BA.5 infection (adjusted PF, 11.9% [95% confidence interval, .8%–21.8%]); P = .04) and minimal protection against hospitalization (10.7% [4.9%–21.7%]; P = .003). In adjusted models, prior BA.1/BA.2 infection provided 45.9% (95% confidence interval, 36.2%–54.1%; P < .001) protection against BA.4/BA.5 reinfection and 18.8% (10.3%–28.3%; (P < .001) protection against hospitalization. Up-to-date vaccination provided modest protection against reinfection with BA.4/BA.5 and hospitalization. Conclusions Prior infection with BA.1/BA.2 and up-to-date vaccination provided modest protection against infection with BA.4/BA.5 and hospitalization, while prior Delta infection provided minimal protection against hospitalization and none against infection.

Objective A substantial proportion of infective endocarditis (IE) cases are complicated by local invasion. The purpose of this study was to identify patient and disease characteristics associated with local invasion in surgically treated IE patients. Methods This was a nested case–control study. All episodes of IE for patients admitted to Cleveland Clinic from 1 January 2013 to 30 June 2016 were identified from the Cleveland Clinic IE Registry. Patients ≥18 years of age who underwent surgery for IE were included. Among these, cases were those with local invasion, controls were those without. Local invasion, defined as periannular extension, paravalvular abscess, intracardiac fistula or pseudoaneurysm, was ascertained from the surgical operative note. Associations of selected factors with local invasion were examined in a multivariable logistic regression model. Results Among 511 patients who met inclusion criteria, 215 had local invasion. Mean age was 56 years; 369 were male. Overall 345 (68%) had aortic valve, 228 (45%) mitral valve, and 66 (13%) tricuspid or pulmonic valve involvement. Aortic valve involvement (OR 6.23, 95% CI 3.55–11.44), bioprosthetic valve (OR 3.88, 95% CI 2.36–6.44), significant paravalvular leak (OR 3.80, 95% CI 1.60–9.89), new atrioventricular nodal block (OR 3.77, 95% CI 1.87–7.90), infection with streptococci other than viridans group streptococci (OR 7.54, 95% CI 2.42–24.87) and presence of central nervous system emboli (OR 1.85, 95% CI 1.13–3.04) were associated with local invasion. Discussion Intracardiac and microorganism factors, but not comorbid conditions, are associated with local invasion in IE.

Among 1282 patients with a positive Clostridioides difficile PCR test who were retested within 14 days, the proportion of positive tests rapidly decreased on successive days within the first week since initiation of treatment. Between days 7 and 14 after treatment initiation, approximately 25% of tests remained positive.

Objective Intrinsic risk of infection of cryopreserved allograft aortic root replacements remains poorly understood despite their long history of use. The objective of this study was to determine this intrinsic risk of allograft infection and its risk factors when allografts are implanted for both nonendocarditis indications and infective endocarditis. Methods From January 1987 to January 2017, 2042 patients received 2110 allograft aortic valves at a quaternary medical center, 1124 (53%) for nonendocarditis indications and 986 (47%) for endocarditis indications (670 [68%] prosthetic valve endocarditis). Staphylococcus aureus caused 193 of 949 cases of endocarditis (20%), 71 (7.3%) in persons who injected drugs. Periodic surveillance and cross-sectional follow-up achieved 85% of possible follow-up time. The primary end point was allograft infection in patients with nonendocarditis and endocarditis indications. Risk factors were identified by hazard function decomposition and machine learning. Results During follow-up, 30 allografts (26 explanted) became infected in patients in the nonendocarditis group and 49 (41 explanted) in patients with endocarditis. At 20 years, the probability of allograft infection was 5.6% in patients in the nonendocarditis group and 14% in patients with endocarditis. Risk factors for allograft infection in patients in the nonendocarditis group were younger patient age and older donor age. Risk factors for allograft infection in patients with endocarditis were earlier implant year, injection drug use, and younger age. In patients with endocarditis, 18% of allograft infections were caused by the original organism. Conclusions The low infection rates, both in patients without and with endocarditis, support continued use of allografts in the modern era, in particular for the treatment of invasive endocarditis of the aortic root.

BACKGROUND Limited data exist regarding the clinical characteristics and contemporary outcomes of patients with pulmonary valve (PoV) infective endocarditis (IE). METHODS This is a retrospective cohort study of patients with a confirmed diagnosis of IE affecting the PoV at our centre between January 2002 and October 2018. Electronic medical records were reviewed to gather the clinical and echocardiographic variables. The population was subdivided according to risk factor profiles: group 1: miscellaneous risk factors; group 2: patients with congenital heart disease (CHD); and group 3: patients who inject drugs (PWID). The primary outcome was all-cause mortality. RESULTS Out of 2,124 cases of IE during the study period, 24 (1.1%) patients had PoV IE. The majority of cases of PoV IE occurred in patients with prosthetic valves (54.2%). Coagulase-negative Staphylococci species were the most common micro-organisms. Seventy-five per cent (75%) of the patients required surgical management. The median follow-up was 2.8 years (interquartile range: 0.2-5.3 years). Patients with miscellaneous risk factors were older (p

We review a series of isolated septic facet joints (ISFJ) that present as a distinct clinical entity compared with spondylodiscitis. We aim to raise awareness that septic facet joints are not a rare entity in the era of modern imaging. We reviewed 353 patients with confirmed spine infections from 2008 to 2017. Of the 353 cases, there were 152 septic facet joints based on MR imaging. Sixty-two presented as ISFJ without evidence of spondylodiscitis and were reviewed. Patients were predominantly male 38/62 (61%). The mean age was 56.7 years. Onset of back pain was more acute compared with spondylodiscitis and usually unilateral. The distribution was as follows: 6 cervical, 12 thoracic, and 44 lumbar facets. The majority of ISFJ, 53/62 (85%), were associated with an epidural abscess (EDA) 53/62. The cervical and thoracic EDA required surgical decompression more frequently than lumbar; 100%, 75%, and 53% respectively. Pathogen was identified in 59/62 (95%) cases. Most cases were associated with bacteremia 50/62 (81%). Seven ISFJ were introduced iatrogenically. All iatrogenic ISFJ required surgical decompression. Septic facet joints are not rare, but frequently overlooked as the origin of an epidural abscess. The majority of cases are hematogenously seeded and associated with bacteremia. Surgical decompression is frequently required secondary to the high incidence of associated epidural abscess. Iatrogenic septic facet joints are rare but associated with significant morbidity. From a clinical standpoint, it is helpful to delineate the origin of EDA as either secondary to spondylodiscitis or SFJ.

Osteoarticular infections (OAIs) in the setting of infective endocarditis (IE) are uncommon. Although morbidity and mortality have been widely studied, details of the characteristics of patients with concurrent IE and OAI are limited. Therefore, the purpose of this study was to determine the (1) incidence, (2) mortality, (3) clinical features, and (4) microbiological profiles of OAIs in the setting of IE. A retrospective review was conducted of 1280 IE cases at a large academic institution between 2009 and 2015. Patients were categorized according to the following OAI types: spondylodiskitis, large joint septic arthritis, other site infections, or multiple affected joints. Inpatient mortality rates, clinical findings, and microbiological characteristics were compared between OAI types. Overall, the incidence of OAI among IE patients was 6.8% (n=87). The in-hospital mortality rate was 9.2% (n=8) and was not significantly associated with OAI type ( P =.801). Eighteen patients had multiple affected joints resulting in a total of 114 infected sites. Of these, 39% (n=44) were spondylodiskitis, 29% (n=33) were large joint septic arthritis, and 32% (n=37) were infections of smaller joints. Back pain was most common among patients with spondylodiskitis ( P P Staphylococcus aureus was the most common IE pathogen in patients with both IE and OAI (63%). Clinicians should maintain a high suspicion for OAI in patients with IE caused by Staphylococcus aureus , particularly spondylodiskitis among those presenting with back pain. [ Orthopedics 2020; 43(1):24–29.]

Previous infection with SARS-CoV-2 provides strong protection against future infection. There is limited evidence on whether such protection extends to the Omicron variant.This retrospective cohort study included 635,341 patients tested for SARS-CoV-2 via polymerase chain reaction (PCR) from 09 March 2020 to 01 March 2022. Patients were analyzed according to the wave in which they were initially infected. The primary outcome was reinfection during the Omicron period (20 December 2021, to 01 March 2022). We used a multivariable model to assess the effects of prior infection and vaccination on hospitalization.Among the patients tested during the Omicron wave, 30.6% tested positive. Protection of prior infection against reinfection with Omicron ranged from 18.0% (95% confidence interval [CI], 13.0-22.7) for patients infected in wave 1 to 69.2% (95% CI, 63.4-74.1) for those infected in the Delta wave. In adjusted models, previous infection reduced hospitalization by 28.5% (95% CI, 19.1-36.7), while full vaccination plus a booster reduced it by 59.2% (95% CI, 54.8-63.1).

BackgroundThe purpose of this study was to evaluate whether boosting healthcare personnel, already reasonably protected by prior infection or vaccination, with a vaccine developed for an earlier variant of COVID-19 protects against the Omicron variant.MethodsEmployees of Cleveland Clinic who were previously infected with or vaccinated against COVID-19, and were working in Ohio the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over two months during an Omicron variant surge. Protection provided by boosting (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate overt immunologic challenge (POIC) as a time-dependent covariate.ResultsAmong 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since POIC. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those with vaccine-induced immunity (HR, .43; 95% CI, .41-.46) as well as those with natural immunity (HR, .66; 95% CI, .58-.76). Among those with natural immunity, receiving 2 compared to 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97).ConclusionsAdministering a COVID-19 vaccine not designed for the Omicron variant, 6 months or more after prior infection or vaccination, protects against Omicron variant infection in both previously infected and previously vaccinated individuals. There is no evidence of an advantage to administering more than 1 dose of vaccine to previously infected persons.SummaryAmong 39 766 Cleveland Clinic employees already protected by prior infection or vaccination, vaccine boosting after 6 months was associated with significantly lower risk of COVID-19. After COVID-19 infection, there was no advantage to more than one dose of vaccine.

Background The purpose of this study was to determine whether boosting previously infected or vaccinated individuals with a vaccine developed for an earlier variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protects against the Omicron variant. Methods Employees of Cleveland Clinic, previously infected with or vaccinated against coronavirus disease 2019 (COVID-19) and working the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over 2 months during an Omicron variant surge. Protection provided by boosting was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate SARS-CoV-2 exposure. Results Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since proximate SARS-CoV-2 exposure, and boosting protected those >6 months since prior infection or vaccination. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those vaccinated but not previously infected (hazard ratio [HR], .43; 95% confidence interval [CI], .41–.46) as well as those previously infected (HR, .66; 95% CI, .58–.76). Among those previously infected, receipt of 2 compared with 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21–1.97). Conclusions Administering a COVID-19 vaccine not designed for the Omicron variant >6 months after prior infection or vaccination protects against Omicron variant infection. There is no advantage to administering more than 1 dose of vaccine to previously infected persons.

Background The purpose of this study was to evaluate the necessity of COVID-19 vaccination in persons previously infected with SARS-CoV-2. Methods Employees of the Cleveland Clinic Health System working in Ohio on Dec 16, 2020, the day COVID-19 vaccination was started, were included. Any subject who tested positive for SARS-CoV-2 at least 42 days earlier was considered previously infected. One was considered vaccinated 14 days after receipt of the second dose of a SARS-CoV-2 mRNA vaccine. The cumulative incidence of SARS-CoV-2 infection over the next five months, among previously infected subjects who received the vaccine, was compared with those of previously infected subjects who remained unvaccinated, previously uninfected subjects who received the vaccine, and previously uninfected subjects who remained unvaccinated. Results Among the 52238 included employees, 1359 (53%) of 2579 previously infected subjects remained unvaccinated, compared with 22777 (41%) of 49659 not previously infected. The cumulative incidence of SARS-CoV-2 infection remained almost zero among previously infected unvaccinated subjects, previously infected subjects who were vaccinated, and previously uninfected subjects who were vaccinated, compared with a steady increase in cumulative incidence among previously uninfected subjects who remained unvaccinated. Not one of the 1359 previously infected subjects who remained unvaccinated had a SARS-CoV-2 infection over the duration of the study. In a Cox proportional hazards regression model, after adjusting for the phase of the epidemic, vaccination was associated with a significantly lower risk of SARS-CoV-2 infection among those not previously infected (HR 0.031, 95% CI 0.015 to 0.061) but not among those previously infected (HR 0.313, 95% CI 0 to Infinity). Conclusions Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination, and vaccines can be safely prioritized to those who have not been infected before. Summary Cumulative incidence of COVID-19 was examined among 52238 employees in an American healthcare system. COVID-19 did not occur in anyone over the five months of the study among 2579 individuals previously infected with COVID-19, including 1359 who did not take the vaccine.

IntroductionWe systematically reviewed studies to estimate the risk of SARS-CoV-2 reinfection among those previously infected with SARS-CoV-2.MethodsFor this systematic review, we searched scientific publications on PubMed and, the pre-print server, MedRxiv through August 18, 2021. Eligible studies were retrieved on August 18, 2021. We used the following search term on PubMed: (((“Cohort Studies”[Majr]) AND (“COVID-19”[Mesh] OR “SARS-CoV-2”[Mesh])) OR “Reinfection”[Majr]) OR “Reinfection”[Mesh]. We used the following search term on MedRxiv: “Cohort Studies” AND “COVID-19” OR “SARS-CoV-2” AND “Reinfection”. The search terms were broad to encompass all possibilities for applicable studies. There were no restrictions on the date of publication. Studies that did not describe cohorts with estimates of the risk of SARS-CoV-2 reinfection among those with previous infection were excluded. Studies that included vaccinated participants were either excluded or limited to sub-groups of non-vaccinated individuals. To identify relevant studies with appropriate control groups, we developed the following criteria for studies to be included in the systematic analysis: (1) baseline polymerase chain reaction (PCR) testing, (2) a negative comparison group, (3) longitudinal follow-up, (4) a cohort of human participants, i.e., not a case report or case series, and (5) outcome determined by PCR. The review was conducted following PRISMA guidelines. We assessed for selection, information, and analysis bias, per PRISMA guidelines.ResultsWe identified 1,392 reports. Of those, 10 studies were eligible for our systematic review. The weighted average risk reduction against reinfection was 90.4% with a standard deviation of 7.7%. Protection against SARS-CoV-2 reinfection was observed for up to 10 months. Studies had potential information, selection, and analysis biases.ConclusionsThe protective effect of prior SARS-CoV-2 infection on re-infection is high and similar to the protective effect of vaccination. More research is needed to characterize the duration of protection and the impact of different SARS-CoV-2 variants.

The objectives of this study were to investigate patient characteristics, valve pathology, bacteriology, and surgical techniques related to outcome of patients who underwent surgery for isolated native (NVE) or prosthetic (PVE) mitral valve endocarditis.From January 2002 to January 2020, 447 isolated mitral endocarditis operations were performed, 326 for NVE and 121 for PVE. Multivariable analysis of time-related outcomes used random forest machine learning.Staphylococcus aureus was the most common causative organism. Of 326 patients with NVE, 88 (27%) underwent standard mitral valve repair, 43 (13%) extended repair, and 195 (60%) valve replacement. Compared with NVE with standard repair, patients who underwent all other operations were older, had more comorbidities, worse cardiac function, and more invasive disease. Hospital mortality was 3.8% (n = 17); 0 (0%) after standard valve repair, 3 (7.0%) after extended repair, 8 (4.1%) after NVE replacement, and 6 (5.0%) after PVE re-replacement. Survival at 1, 5, and 10 years was 91%, 75%, and 62% after any repair and 86%, 62%, and 44% after replacement, respectively. The most important risk factor for mortality was renal failure. Risk-adjusted outcomes, including survival, were similar in all groups. Unadjusted extended repair outcomes, particularly early, were similar or worse than replacement in terms of reinfection, reintervention, regurgitation, gradient, and survival.A patient- and pathology-tailored approach to surgery for isolated mitral valve endocarditis has low mortality and excellent results. Apparent superiority of standard valve repair is related to patient characteristics and pathology. Renal failure is the most powerful risk factor. In case of extensive destruction, extended repair shows no benefit over replacement.

Infection has been associated with stroke in patients with left ventricular assist devices (LVAD); however, little data exist on the timing, type and mortality impact of infection-related stroke. Prospectively collected data of HeartMate II (N = 332) and HeartWare (N = 70) LVAD patients from a single center were reviewed. Only strokes (ischemic or hemorrhagic) that occurred within 6 weeks following a LVAD infection were considered in analyses. The association between LVAD infections (wound, pump pocket, driveline and/or bloodstream infection [BSI]), specific pathogens and ischemic and hemorrhagic strokes was evaluated using multivariable logistic regression analysis. The impact of infection-related stroke on cumulative survival was assessed using Kaplan–Meier analysis. Of 402 patients, LVAD infection occurred in 158 (39%) including BSI in 107 (27%), driveline infection in 67 (17%), wound infection in 31 (8%) and pump pocket infection in 24 (6%). LVAD infection-related stroke occurred in 20/158 (13%) patients in a median of 4 days (0–36 days) from documented infection. In multivariable analysis, ischemic stroke was associated with wound infection (aOR 9.0, 95% CI 2.4–34.0, P = 0.001) and BSI (aOR 7.7, 95% CI 0.9–66.0, P = 0.064), and hemorrhagic stroke was associated with BSI in 100% of cases (P = 0.01). There was no association with driveline or pump pocket infection. The cumulative survival rate among patients with infection-related stroke was significantly lower compared to those with LVAD infection but no stroke (log-rank P

BackgroundThe mRNA SARS-CoV-2 vaccines have shown great promise in clinical trials. The purpose of this study was to evaluate the effectiveness of these vaccines under real-world conditions in the USA.MethodsEmployees of the Cleveland Clinic Health System, previously not infected with SARS-CoV-2, and working in Ohio on Dec 16, 2020, the day COVID-19 vaccination began, were included. The cumulative incidence of SARS-CoV-2 infection, over the next 5 months, was compared among those who received the vaccine and those who did not, by modeling vaccination as a time-dependent covariate in Cox proportional hazards regression analyses adjusted for the slope of the epidemic curve as a continuous time-dependent covariate.ResultsOf the 46866 included employees, 28223 (60%) were vaccinated by the end of the study period. The cumulative incidence of SARS-CoV-2 infection was much higher among those not vaccinated than those vaccinated. Only 15 (0.7%) of the 2154 SARS-CoV-2 infections during the study occurred among those vaccinated. After adjusting for the slope of the epidemic curve, age, and job type, vaccination was associated with a significantly reduced risk of SARS-CoV-2 infection (HR 0.03, 95% C.I. 0.02 – 0.06, p < 0.001), corresponding to a vaccine effectiveness rate of 97.1% (95% CI 94.3 – 98.5). Vaccine effectiveness was 89.2% at 7 days and 95.0% at 14 days after the first vaccine dose.ConclusionsThe mRNA SARS-CoV-2 vaccines are over 97% protective against COVID-19 in the working-age population, with substantial protection possibly apparent within a few days of the first dose.SummaryThe effectiveness of mRNA SARS-CoV-2 vaccines was evaluated among 46866 employees in an American healthcare system. After adjusting for age, job type, and the phase of the epidemic, vaccination was 97.1% effective in preventing COVID-19 among the fully vaccinated, and 89.2% protective within 7 days of the first dose.

The purpose of this study was to compare survival, relapse, and stroke for patients with methicillin-resistant Staphylococcus aureus (MRSA) vs methicillin-susceptible S. aureus (MSSA) infective endocarditis (IE). In this retrospective study, the primary outcome of death and secondary outcomes of stroke and relapse were compared using multivariable Cox proportional hazards regression. Surgical treatment was adjusted for as a time-dependent variable. In total, 355 patients with at least one episode of IE caused by S. aureus were included. Patients with MRSA IE had higher mortality than those with MSSA IE (HR 1.34, 95% CI 1.01-1.77), but did not have a higher risk of stroke (HR 0.75, 95% CI 0.43-1.32) or relapse (HR 0.89, 95% CI 0.26-3.05). The cumulative incidence of relapse was very small. Among patients with IE caused by S. aureus MRSA infection is associated with higher mortality than MSSA infection.

Introduction: Transcatheter aortic valve replacement associated infective endocarditis (TAVR-IE) is a relatively rare complication of TAVR. Little is known about the characteristics of early, intermediate versus late onset TAVR-IE. Methods: We studied the risk factors, microbiological patterns, diagnostic and treatment strategies in patients with early (1 year) TAVR-IE. Results: Ten out of 494 definite cases of prosthetic valve IE between 2007 and 2019, were confirmed to have TAVR-IE from the IE registry at our center. The mean age was 78.1 ± 13.7 years, with 50% being female. Most (90%) TAVR procedures were performed via transfemoral route, and one underwent transapical TAVR. Baseline comorbidities were common, with mean BMI 33.1 ± 5.5 kg/m2, diabetes and hypertension in 60% and chronic kidney disease in 50% of cases. Mean STS risk score was 7.8 ± 5.7. Most (60%) TAVR-IE cases had intermediate onset, with Staphylococcus aureus being the most common organism (66.6%). Diagnostic modalities and complications are described in Table 1. Two cases had early onset TAVR-IE, one of which was due to Pseudomonas aeruginosa, and underwent successful surgical treatment. Late onset TAVR-IE was observed in 20% of cases. 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET) aided in diagnosis of TAVR-IE in 20% of cases. Mortality due to IE was observed in 40% of cases. Most of the patients underwent conservative management, and 37.5% survived over a mean follow up of 709 ± 453 days. Two patients underwent surgery, of whom one died day 30 post-operatively from sepsis. Mortality due to IE occurred in 25% of cases in the early and intermediate onset groups, while there was 100% mortality in the late onset group. Conclusions: In a single-center cohort, most TAVR-IE cases had an intermediate onset, with Staphylococcus aureus being the most common organism. Late onset TAVR-IE was associated with higher mortality at follow-up.

Background: Cardiac computed tomography (CT) is emerging as an adjunctive modality to echocardiography in the evaluation of infective endocarditis (IE) and surgical planning. CT studies in IE have, however, focused on its diagnostic rather than prognostic utility, the latter of which is important in high-risk diseases like IE. We evaluated the associations between cardiac CT and transesophageal echocardiography (TEE) findings and adverse outcomes after IE surgery. Methods: Of 833 consecutive patients with surgically proven IE during 5/1/2014-5/1/2019 at Cleveland Clinic, 155 underwent both pre-operative ECG-gated contrast-enhanced CT and TEE. Multivariable analyses were performed to identify CT and TEE biomarkers that predict adverse outcomes after IE surgery, adjusting for EuroSCORE II. Results: CT and TEE were positive for IE in 123 (75.0%) and 124 (75.6%) of patients respectively. CT identified an additional 11% of vegetations, 13% of pseudoaneurysms or abscesses, 5% of dehiscences and 14% of fistulae when TEE was negative. Thirty-day mortality occurred in 3 (1.9%) patients, and composite mortality and/or morbidities in 72 (46.5%). Pseudoaneurysm or abscess detected on TEE was the only imaging biomarker to show independent association with composite mortality and/or morbidities in-hospital, with odds ratio (95%CI) of 3.66 (1.76-7.59), P=0.001. There were 17 late deaths, and both pseudoaneurysm or abscess detected on CT and fistula detected on CT were the only independent predictors of total mortality during follow-up, with hazards ratios (95%CI) of 3.82 (1.25, 11.7), P Conclusion: We identified cardiac CT and TEE features that predicted separate adverse outcomes after IE surgery. Imaging biomarkers can play important roles incremental to conventional clinical factors for risk stratification in patients undergoing IE surgery.

Background Mycotic aneurysms are a serious complication of infective endocarditis and bloodstream infection with high mortality and morbidity. Computed tomography (CT) and magnetic resonance (MRI) play major roles in detecting mycotic aneurysms, but their accuracy is not well established warranting this meta-analysis. Purpose We aimed to assess the diagnostic performance of CT and MRI for mycotic aneurysms in this meta-analysis. Methods Pubmed, Cochrane and Embase were searched from 1 January 1980–30 June 2019 for diagnostic studies reporting both sensitivity and specificity of CT and/or MRI for detecting mycotic aneurysms, and pooled using random effects models and Meta-DiSc 1.4 software. Results Amongst 1507 articles searched, 15 studies with 622 scans for 249 mycotic aneurysms included. CT was performed in 13 studies and MRI in 5 studies, looking at aortic and cerebral mycotic aneurysm in 12 and 3 studies respectively. The pooled sensitivities and specificities for all mycotic aneurysms with 95% confidence intervals were for CT 0.82 (0.77–0.87) and 0.93 (0.89–0.95) respectively, and for MRI 0.79 (0.61–0.91) and 0.89 (0.81–0.95) (Figure). CT or MRI had pooled sensitivities and specificities of 0.84 (0.78–0.89) and 0.92 (0.89–0.95) for aortic and 0.71 (0.54–0.85) and 0.90 (0.83–0.95) for cerebral mycotic aneurysms. Heterogeneity and publication bias was observed in some pooled analysis. Conclusion CT and MRI had moderately high diagnostic accuracy for mycotic aneurysms. Sensitivity was numerically higher for detecting aortic than cerebral mycotic aneurysms, with similar specificity. Study heterogeneity, publication bias and modest sample size from the literature were important limitations, warranting larger and higher quality studies. Forrest plots for CT and MRI pooled data Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation of New Zealand - Overseas Clinical and Research Fellowship

Objectives Comparative assessments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular assays that have been operationalized through the US Food and Drug Administration’s Emergency Use Authorization process are warranted to assess real-world performance. Characteristics such as sensitivity, specificity, and false-negative rate are important to inform clinical use. Methods We compared five SARS-CoV-2 assays using nasopharyngeal and nasal swab specimens submitted in transport media; we enriched this cohort for positive specimens, since we were particularly interested in the sensitivity and false-negative rate. Performance of each test was compared with a composite standard. Results The sensitivities and false-negative rates of the 239 specimens that met inclusion criteria were, respectively, as follows: Centers for Disease Control and Prevention 2019 nCoV Real-Time RT-PCR Diagnostic Panel, 100% and 0%; TIB MOLBIOL/Roche z 480 Assay, 96.5% and 3.5%; Xpert Xpress SARS-CoV-2 (Cepheid), 97.6% and 2.4%; Simplexa COVID-19 Direct Kit (DiaSorin), 88.1% and 11.9%; and ID Now COVID-19 (Abbott), 83.3% and 16.7%. Conclusions The assays that included a nucleic acid extraction followed by reverse transcription polymerase chain reaction were more sensitive than assays that lacked a full extraction. Most false negatives were seen in patients with low viral loads, as extrapolated from crossing threshold values.

OBJECTIVE. The purpose of this meta-analysis was to assess the diagnostic performance of CT and MRI in detecting mycotic aneurysm, an infection of high mortality and morbidity. MATERIALS AND METHODS. The PubMed, Cochrane, and Embase databases were searched from January 1, 1980, through June 30, 2019, for diagnostic studies assessing both sensitivity and specificity of CT or MRI for detecting mycotic aneurysms, and studies were pooled by use of random-effects models and freely available meta-analysis software. RESULTS. Among 1507 articles searched, 15 studies of CT (13 studies) or MRI (five studies) for aortic and cerebral mycotic aneurysms were included. The studies evaluated 622 imaging examinations for 249 mycotic aneurysms. The pooled sensitivities and specificities of CT for all mycotic aneurysms were 0.82 (95% CI, 0.77-0.87) and 0.93 (95% CI, 0.89-0.95) and of MRI were 0.79 (95% CI, 0.61-0.91) and 0.89 (95% CI, 0.81-0.95). CT and MRI had pooled sensitivities and specificities of 0.84 (95% CI, 0.78-0.89) and 0.92 (95% CI, 0.89-0.95) for aortic and 0.71 (95% CI, 0.54-0.85) and 0.90 (95% CI, 0.83-0.95) for cerebral mycotic aneurysms. Heterogeneity and publication bias were observed in some pooled analyses. CONCLUSION. CT and MRI had moderately high sensitivities and specificities for mycotic aneurysms. Study heterogeneity, publication bias, and modest sample size were important limitations, warranting larger and higher-quality studies.

Background: Cardiac computed tomography (CT) is emerging as an adjunctive modality to echocardiography in the evaluation of infective endocarditis (IE) and surgical planning. CT studies in IE have, however, focused on its diagnostic rather than prognostic utility, the latter of which is important in high-risk diseases like IE. We evaluated the associations between cardiac CT and transesophageal echocardiography (TEE) findings and adverse outcomes after IE surgery. Methods: Of 833 consecutive patients with surgically proven IE during May 1, 2014 to May 1, 2019, at Cleveland Clinic, 155 underwent both preoperative ECG-gated contrast-enhanced CT and TEE. Multivariable analyses were performed to identify CT and TEE biomarkers that predict adverse outcomes after IE surgery, adjusting for EuroSCORE II (European System for Cardiac operative Risk Evaluation II). Results: CT and TEE were positive for IE in 123 (75.0%) and 124 (75.6%) of patients, respectively. Thirty-day mortality occurred in 3 (1.9%) patients and composite mortality or morbidities in 72 (46.5%). Pseudoaneurysm or abscess detected on TEE was the only imaging biomarker to show independent association with composite mortality or morbidities in-hospital, with odds ratio (95% CI) of 3.66 (1.76–7.59), P =0.001. There were 17 late deaths, and both pseudoaneurysm or abscess detected on CT and fistula detected on CT were the only independent predictors of total mortality during follow-up, with hazards ratios (95% CI) of 3.82 (1.25–11.7), P P =0.007, respectively. Conclusions: We identified cardiac CT and TEE features that predicted separate adverse outcomes after IE surgery. Imaging biomarkers can play important roles incremental to conventional clinical factors for risk stratification in patients undergoing IE surgery.

Background Advanced aortic valve infective endocarditis (IE) with progression and destruction beyond the valve cusps—invasive IE—is incompletely characterized. This study aimed to characterize further the invasive disease extent, location, and stage and correlate macroscopic operative findings with microscopic disease patterns and progression. Methods A total of 43 patients with invasive aortic valve IE were prospectively enrolled from August 2017 to July 2018. Of these patients, 23 (53%) had prosthetic valve IE, 2 (5%) had allograft IE, and 18 (42%) had native aortic valve IE. Surgical findings and intraoperative photography were analyzed for invasion location, extent, and stage. Surgical samples were formalin fixed and analyzed histologically. The time course of disease and management were evaluated. Results Pathogens included Staphylococcus aureus in 17 patients (40%). Invasion predominantly affected the non–left coronary commissure (76%) and was circumferential in 15 patients (35%) (14 had prosthetic valves). Extraaortic cellulitis was present in 29 patients (67%), abscess in 13 (30%), abscess cavity in 29 (67%), and pseudoaneurysm in 8 (19%); 7 (16%) had fistulas. Histopathologic examination revealed acute inflammation, abscess formation, and lysis of connective tissue but not of myocardium or elastic tissue. Median time from onset of symptoms to antibiotics was 5 days, invasion confirmation 15 days, and surgery 37 days. Patients with S aureus had a 21-day shorter time course than patients non–S aureus. New or worsening heart block developed in 8 patients. Conclusions Advanced invasive aortic valve IE demonstrates consistent gross patterns and stages correlating with histopathologic findings. Invasion results from a confluence of factors, including pathogen, time, and host immune response, and primarily affects the fibrous skeleton of the heart and expands to low-pressure regions.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of nasopharyngeal swabs (NPS) and viral transport media, necessitating the search for alternate diagnostic specimens, such as saliva. We directly compared matched saliva and NPS specimens from symptomatic patients suspected of having COVID-19. An enhanced saliva specimen (i.e., strong sniff, elicited cough, and collection of saliva/secretions) was collected without transport medium prior to collection of NPS from 224 patients with symptoms deemed consistent with COVID-19., The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of nasopharyngeal swabs (NPS) and viral transport media, necessitating the search for alternate diagnostic specimens, such as saliva. We directly compared matched saliva and NPS specimens from symptomatic patients suspected of having COVID-19. An enhanced saliva specimen (i.e., strong sniff, elicited cough, and collection of saliva/secretions) was collected without transport medium prior to collection of NPS from 224 patients with symptoms deemed consistent with COVID-19. Both specimens were tested with the CDC 2019 nCoV real-time RT-PCR diagnostic panel (4 February 2020 version), with the NPS result used as the reference standard. For the 216 patients included in the final analysis, there was 100% positive agreement (38/38 positive specimens) and 99.4% negative agreement (177/178 negative specimens). The one discrepant specimen had the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed in the saliva specimen using an alternate FDA EUA assay. The overall mean difference in cycle threshold (CT) values for the positive NPS and saliva specimens was −3.61 (95% confidence interval [CI], −5.78 to −1.44; P = 0.002). An enhanced saliva specimen performed as well as NPS for the qualitative detection of SARS-CoV-2 in symptomatic patients, although the overall mean viral load in saliva was lower.

Background Although widely accepted for adults, the safety of outpatient parenteral antimicrobial therapy (OPAT) in very old patients has not been examined. Methods Nonagenarians (age ≥90 years) discharged from the hospital on OPAT over a 5-year period were identified from the Cleveland Clinic OPAT Registry. Three matched controls ( Results Of 126 nonagenarians and 378 controls, 7 were excluded for various reasons. Among the remaining 497 subjects, 306 (62%) were male, 311 (63%) were treated for cardiovascular or osteoarticular infections, and 363 (73%) were discharged to a residential health care facility. The mean (SD) ages of nonagenarians and controls were 92 (2) and 62 (16) years, respectively. Compared with matched controls, being a nonagenarian was not associated with increased risk of OPAT-related ED visit (hazard ratio [HR], 0.77; 95% CI, 0.33–1.80; P = .55), OPAT-related readmission (HR, 0.78; 95% CI, 0.28–2.16; P = .63), adverse drug event from OPAT medications (incidence rate ratio [IRR], 1.00; 95% CI, 0.43–2.17; P = .99), or vascular access complications (IRR, 0.66; 95% CI, 0.27–1.51; P = .32). Nonagenarians had a higher risk of death overall (HR, 2.64; 95% CI, 1.52–4.58; P Conclusions Compared with younger patients, OPAT in nonagenarians is not associated with higher risk of OPAT-related complications. OPAT can be provided as safely to nonagenarians as to younger patients.

Background Infective endocarditis (IE) is a rare complication following solid organ transplant (SOT); data on the clinical features and outcomes of IE in SOT recipients in the modern era are limited. Methods We conducted a single-center retrospective cohort study of IE diagnosed from 1/2008-12/2014 in SOT recipients, who were matched by age and microorganism to cases of IE in non-SOT, to describe the clinical features and outcomes. Results There were 14 cases of IE identified in SOT recipients matched to 56 non-SOT controls. Median time from transplant to IE was 1017 days (IQR 379-1830). Compared to non-SOT patients, SOT patients were more likely to be undergoing current hemodialysis (16% vs 36%) and to possess indwelling central venous catheters within the 30 days prior to diagnosis of IE (27% vs 50%). No SOT patients had documented drug use as a risk factor for IE whereas 6 (11%) non-SOT did. Enterococcus was the most common etiologic agent and was isolated in 50% of cases; only one fungal infection was identified, a mixed infection with Candida. Thirty-day mortality was 14% in SOT patients, significantly higher versus no deaths in non-SOT (P = .037). Conclusions The present study illustrates a change in epidemiology of IE in SOT patients characterized by IE that generally occurs more than one-year post-transplant, is due to bacterial infection rather than fungus, and appears to be health care associated. Multicenter studies are merited to explore transplant-specific risk factors for IE in the special population of SOT patients.

Purpose To characterize the ophthalmic clinical and multimodal imaging findings of disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Design Observational case series. Participants Four patients (8 eyes) with disseminated M. chimaera infection. Methods Patients were evaluated with biomicroscopy, OCT and OCT angiography, fundus autofluorescence, and fluorescein and indocyanine green angiography. Main Outcome Measures Clinical and multimodal imaging findings of patients with disseminated M. chimaera infection. Results All 4 patients were white men with a mean age of 65.5 years (range, 60–75 years) who had aortic valve or root infection, or both, with M. chimaera diagnosed by culture, gene sequencing, or both. All 4 patients demonstrated bilateral choroidal lesions on funduscopy and evidence of osteomyelitis by imaging, culture analysis, or both at the time of ocular diagnosis. Indocyanine green and OCT angiography revealed numerous additional subclinical choroidal lesions and were used to track disease response to therapy. Fluorescein angiography and fundus autofluorescence were useful in determining lesion age and activity. All patients were treated with 3- or 4-drug antimycobacterial therapy. Three underwent revision of cardiothoracic surgery with removal of infected graft. One patient went on to demonstrate progressive ocular disease that was noted before each of his surgical revisions. Two patients showed improvement in ocular and systemic disease, however one of them developed a choroidal neovascular membrane. The final patient was a single encounter whose clinical and imaging findings showed longstanding inactive disease. Conclusions Ophthalmologists should be aware of the systemic and ocular findings of this rare life-threatening disease. Multimodal imaging is useful in corroborating a diagnosis of ocular M. chimaera and particularly in evaluating patient response to therapy, because choroidal activity seems to mimic systemic activity. Treating physicians should be aware of the co-occurrence of choroiditis and osteomyelitis. Choroidal neovascular membrane can also be a late complication of this disease.

The purpose of this study was to describe the distribution of streptococci causing infective endocarditis (IE). A total of 296 patients with definite IE admitted from July 2007 to December 2014 were identified, with microbial identification done by a combination of blood culture, valve culture, and valve polymerase chain reaction (PCR). The overall distribution of streptococci was 76% viridans (n = 224), 17% pyogenic (50), 6% nutritionally variant (17), and 2% anaerobic (5). Sixty-three (21%) viridans group streptococci were not identified further. The distribution of the remaining 161 viridans group streptococci was Streptococcus mitis group 61%, S. bovis group 15%, S. mutans group 13%, S. anginosus group 9%, and S. salivarius group 1%. Of the 50 pyogenic streptococci, 78% were S. agalactiae and 16% were S. dysgalactiae. PCR was significantly more sensitive than culture in identifying streptococci in excised heart valves.

Objectives Patients receiving outpatient parenteral antimicrobial therapy (OPAT) may require emergency department (ED) visits to manage complications. This study's purpose was to identify risk factors for ED visits during OPAT and risk factors for hospitalization among patients with ED visits. Methods All OPAT courses initiated between 1 January 2013 and 1 January 2017 at Cleveland Clinic were identified. The first OPAT course per patient was included. For these, ED visits within 30 days were identified. Reasons and risk factors for these visits were sought, as were risk factors for hospitalization among patients visiting the ED. Results Among 8263 patients on OPAT, 381 (4.6%) had at least one ED visit, an additional 1133 (14%) were hospitalized and an additional 50 (0.6%) died, within 30 days. One hundred and ninety-three ED visits (51%) were OPAT related. In a multivariable subdistribution proportional hazards competing risks regression model, prior ED visit (preceding year) was most strongly associated with ED visits (HR 2.29, 95% CI 1.76-2.98, P = 8.1 × 10-10). Eighty-five visits (22%) led to hospitalization. Compared with non-OPAT-related reasons, visits for vascular access complications were associated with lower odds of hospitalization (OR 0.36, 95% CI 0.14-0.83, P = 0.022) and visits for worsening infection with higher odds (OR 18.95, 95% CI 5.50-79.85, P = 1.2 × 10-7). Conclusions Compared with patients without, patients with prior ED visit have a 2.3-fold higher hazard of an ED visit within 30 days of OPAT initiation. Visits for worsening infection are much more likely to result in hospitalization than those for vascular access complications.

BACKGROUND Limited published data exist on outcomes related to heart and/or lung transplantation in human immunodeficiency virus (HIV)-infected individuals. METHODS We conducted a multicenter retrospective study of heart and lung transplantation in HIV-infected patients and describe key transplant- and HIV-related outcomes. RESULTS We identified 29 HIV-infected thoracic transplant recipients (21 heart, 7 lung, and 1 heart and/or lung) across 14 transplant centers from 2000 through 2016. Compared with an International Society for Heart and Lung Transplantation registry cohort, we demonstrated similar 1-, 3-, and 5-year patient and allograft survivals for each organ type with a median follow up of 1,064 (range, 184–3,745) days for heart and 1,540 (range, 116–3,206) days for lung recipients. At 1 year, significant rejection rates were high (62%) for heart transplant recipients (HTRs). Risk factors for rejection were inconclusive, likely because of small numbers, but may be related to cautious early immunosuppression and infrequent use of induction therapy. Pulmonary bacterial infections were high (86%) for lung transplant recipients (LTRs). Median CD4 counts changed from baseline to 1 year from 399 to 411 cells/µl for HTRs and 638 to 280 cells/µl for LTRs. Acquired immunodeficiency syndrome–related events, including infections and malignancies, were rare. Rates of severe renal dysfunction suggest a need to modify nephrotoxic anti-retrovirals and/or immunosuppressants . CONCLUSIONS HIV-infected HTRs and LTRs have similar survival rates to their HIV-uninfected counterparts. Although optimal immunosuppression is not defined, it should be at least as aggressive as that for HIV-uninfected recipients. Such data may help pave the way for the use of hearts and lungs from HIV-infected donors in HIV-infected recipients through HIV Organ Policy Equity Act protocols.

Gemella are gram-positive bacteria that rarely cause infective endocarditis (IE). This article summarizes the characteristics of a series of patients with Gemella IE. We identified cases of Gemella IE in patients aged18 years old hospitalized at Cleveland Clinic between July 1, 2007, and January 1, 2018, within the institutional review board-approved Cleveland Clinic IE Registry. Clinical features were obtained by manual chart review. Thirteen cases of Gemella IE were identified and accounted for1% of all cases of IE in the registry. Eight were native and 5 were prosthetic valve IE. All were left-sided. Sixty-nine percent had positive blood cultures for Gemella, but 31% were identified solely based on 16S rRNA polymerase chain reaction (PCR) of explanted valves with sequence identification. None had positive valve cultures. All were treated surgically and survived to hospital discharge. Gemella is a rare cause of IE, albeit likely underrecognized without utilization of valve PCR.

Background Infectious endocarditis is often complicated by conduction abnormalities at the time of presentation. Cardiac surgery is the treatment of choice for many infectious endocarditis patients, but carries an additional risk of persistent postoperative conduction abnormality. We sought to define the incidence and clinical predictors of significant postoperative conduction abnormalities necessitating permanent pacemaker implantation after cardiac surgery for infectious endocarditis. Methods All consecutive patients with infectious endocarditis who were surgically treated at Cleveland Clinic from 2007 to 2013 were identified using the Cleveland Clinic Infective Endocarditis Registry and the Cardiovascular Information Registry. Patients with a pre-existing cardiac implantable electronic device were excluded. The primary outcome was the need for permanent pacemaker placement postoperatively for atrioventricular block. Regression analysis was performed to identify risk factors for permanent pacemaker requirement. Results Among 444 infectious endocarditis patients who underwent cardiac surgery for infectious endocarditis, 57 (13%) required postoperative permanent pacemaker for atrioventricular block. Multivariable analysis identified that prolongation in preoperative PR and QRS intervals, Staphylococcus aureus as the infectious endocarditis organism, the presence of intracardiac abscess, tricuspid valve involvement, and prior valvular surgery independently predicted postoperative permanent pacemaker placement. The developed model exhibited excellent predictive ability (c-statistic 0.88) and calibration. Conclusion Infectious endocarditis cardiac surgery patients often require a postoperative permanent pacemaker. Preoperative conduction abnormality, S. aureus infection, abscess, tricuspid valve involvement, and prior valvular surgery are strong predictors of postoperative permanent pacemaker placement.

Prosthetic valve endocarditis (PVE) is a serious condition with high morbidity and mortality. This study investigated the association of surgical treatment with survival among patients with PVE.A retrospective cohort study was done of patients with PVE hospitalized over 8 years in a large referral center. Association of surgery with survival was evaluated with multivariable Cox proportional hazards regression, adjusting for propensity to be accepted for surgery, and analyzing surgery as a time-dependent covariate. Survival was also compared separately in a 1:1 propensity score-matched cohort of patients accepted for surgery and control patients consigned to nonsurgical treatment.Of 523 patients (mean [SD] age, 61 [14] years; 370 [71%] men; 393 [75%] initially accepted for surgery), 404 ultimately underwent surgery and 119 received nonsurgical treatment alone. Surgical treatment was associated with significantly lower hazard of death in the entire cohort (hazard ratio [HR] = 0.32; 95% confidence interval [CI]: 0.22-0.48; P.001) and in the 1:1 matched cohort (HR = 0.33; 95% CI: 0.19-0.57; P.001). Initial acceptance for surgery was associated with significantly lower odds of in-hospital death (odds ratio [OR] = 0.26; 95% CI: 0.11-0.59; P.001), death or readmission within 90 days (OR = 0.17; 95% CI: 0.07-0.43; P.001), and death within 1 year (OR = 0.16; 95% CI: 0.08-0.34; P.001).Surgical treatment is associated with a large survival benefit in PVE. A decision to pursue nonsurgical treatment in PVE should entail close follow-up for any development of an indication for surgery.

IMPORTANCE: Infective endocarditis is a life-threating condition with annual mortality of as much as 40% and is associated with embolic events in as many as 80% of cases. These embolic events have notable prognostic implications and have been linked to increased length of stay in intensive care units and mortality. A vegetation size greater than 10 mm has often been suggested as an optimal cutoff to estimate the risk of embolism, but the evidence is based largely on small observational studies. OBJECTIVE: To study the association of vegetation size greater than 10 mm with embolic events using meta-analytic techniques. DATA SOURCES: A computerized literature search of all publications in the PubMed and EMBASE databases from inception to May 1, 2017, was performed with search terms including varying combinations of infective endocarditis, emboli, vegetation size, pulmonary infarct, stroke, splenic emboli, renal emboli, retinal emboli, and mesenteric emboli. This search was last assessed as being up to date on May 1, 2017. STUDY SELECTION: Observational studies or randomized clinical trials that evaluated the association of vegetation size greater than 10 mm with embolic events in adult patients with infective endocarditis were included. Conference abstracts and non–English language literature were excluded. The search was conducted by 2 independent reviewers blinded to the other’s work. DATA EXTRACTION AND SYNTHESIS: Following PRISMA guidelines, the 2 reviewers independently extracted data; disputes were resolved with consensus or by a third investigator. Categorical dichotomous data were summarized across treatment arms using Mantel-Haenszel odds ratios (ORs) with 95% CIs. Heterogeneity of effects was evaluated using the Higgins I(2) statistic. RESULTS: The search yielded 21 unique studies published from 1983 to 2016 with a total of 6646 unique patients with infective endocarditis and 5116 vegetations with available dimensions. Patients with a vegetation size greater than 10 mm had increased odds of embolic events (OR, 2.28; 95% CI, 1.71-3.05; P

Infection has been associated with stroke in patients with left ventricular assist devices (LVAD); however, little data exist on the timing, type and mortality impact of infection-related stroke.Prospectively collected data of HeartMate II (N = 332) and HeartWare (N = 70) LVAD patients from a single center were reviewed. Only strokes (ischemic or hemorrhagic) that occurred within 6 weeks following a LVAD infection were considered in analyses. The association between LVAD infections (wound, pump pocket, driveline and/or bloodstream infection [BSI]), specific pathogens and ischemic and hemorrhagic strokes was evaluated using multivariable logistic regression analysis. The impact of infection-related stroke on cumulative survival was assessed using Kaplan-Meier analysis.Of 402 patients, LVAD infection occurred in 158 (39%) including BSI in 107 (27%), driveline infection in 67 (17%), wound infection in 31 (8%) and pump pocket infection in 24 (6%). LVAD infection-related stroke occurred in 20/158 (13%) patients in a median of 4 days (0-36 days) from documented infection. In multivariable analysis, ischemic stroke was associated with wound infection (aOR 9.0, 95% CI 2.4-34.0, P = 0.001) and BSI (aOR 7.7, 95% CI 0.9-66.0, P = 0.064), and hemorrhagic stroke was associated with BSI in 100% of cases (P = 0.01). There was no association with driveline or pump pocket infection. The cumulative survival rate among patients with infection-related stroke was significantly lower compared to those with LVAD infection but no stroke (log-rank P 0.001). There was a trend toward shorter stroke-free survival among patients with LVAD infection.LVAD infections, particularly BSI, are significantly associated with stroke, and infection-related stroke conferred significantly lower cumulative survival.

Cryptococcal intraocular infection is a rare disease and is usually associated with generalized systemic disease in immunocompromised patients. The diagnosis may be difficult because of the rarity of this disease and its similarities to other uveitic entities. We describe a case of culture-positive cryptococcal iridociliary granuloma diagnosed by anterior chamber tap and fine-needle aspiration biopsy in a 60-year-old immunocompetent woman with acute granulomatous uveitis. She was treated successfully with systemic amphotericin B and fluconazole and intravitreal amphotericin B, with improvement in the inflammation and visual acuity and regression of the iridociliary granuloma. We review previously reported cases of intraocular cryptococcal infection. Cryptococcal iridociliary granuloma should be considered in the differential diagnosis of an atypical iridociliary mass associated with acute uveitis.

Background Rifampin is recommended as adjunctive treatment for staphylococcal prosthetic valve endocarditis (PVE). It is unclear whether this should hold for surgically treated patients. The purpose of this study was to examine whether adjunctive rifampin treatment in addition to cell wall active antimicrobial agents in patients with surgically treated staphylococcal infective endocarditis (IE) results in better outcomes. Methods Patients operated on for staphylococcal IE from April 1, 2008, to July 1, 2014, were identified from our institution's IE registry. Rifampin treatment was defined as 3 or more days of rifampin postoperatively. Cox proportional hazards regression was used to compare a composite outcome of death or reoperation for IE relapse, between patients treated and not treated with rifampin, adjusted for propensity to be treated with rifampin, methicillin resistance, all-purpose refined diagnosis related group (APR-DRG) severity score, and APR-DRG mortality risk. Results In all, 273 patients were identified. The mean age was 56 years, 66% were male, 50% had PVE, 60% had S. aureus or S. lugdunensis infection, 89% had left side involvement, and 57% had invasive disease. Fifty-one (27%) received 3 or more days of rifampin postoperatively. Ninety-two patients died or underwent reoperation for IE relapse at a median of 205 days (interquartile range 56 to 718 days). In a multivariable model, patients treated with rifampin had a similar hazard of death or reoperation for IE relapse as those not treated (hazard ratio 0.76, 95% confidence interval 0.44 to 1.32, p value 0.34). The results were robust to varying definitions of rifampin treatment. Conclusions Among patients with surgically treated staphylococcal IE there was insufficient evidence to claim a reoperation-free survival benefit from treatment with rifampin. Rifampin should not be used as adjunctive therapy for staphylococcal IE in patients who have undergone surgical procedures for its treatment.