Search

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.

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.

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.]

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 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.

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 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.

Despite recent advances in diagnostics and treatments, infective endocarditis is still associated with substantial morbidity and mortality. Even prolonged courses of broad-spectrum antimicrobials often fail to eradicate the infection, making surgical intervention necessary in many cases. In this review, we present recent advances in molecular microbiology techniques that have uncovered a plausible explanation for this resistance to treatment: the recently discovered social behavior of some microbes, in which colonies form a nearly impenetrable barrier around themselves called a biofilm. These biofilm structures isolate the colony from the body׳s immune response and antimicrobial drugs. We also present current thinking about possible ways biofilms can be destroyed.

Splenic abscess is an uncommon but serious complication of infective endocarditis (IE). The timing of surgical management of splenic abscess can be challenging when valve surgery is required. The American Heart Association (AHA) and the European Society of Cardiology (ESC) currently recommends splenectomy before valve replacement due to fear of reinfection of the heart valve; however, published data to support this recommendation are limited. In this series, we report outcomes for 5 patients with IE and splenic abscess who underwent valve replacement first, followed by splenectomy at a median of 19 days (range: 10-77 days) after valve surgery, with no recurrent infection of the new valve. Our experience and review of the available literature provide reassurance for splenectomy after valve surgery for IE.

Background Outpatient parenteral antimicrobial therapy (OPAT) can be managed by specialists in infectious diseases (ID) or by other physicians. Better management of OPAT can reduce the likelihood of readmission or emergency department (ED) use. The relative success of ID specialists and other physicians in managing OPAT has received little study. Methods We analyzed a national database of insurance claims for privately insured individuals under age 65, locating inpatient acute-care stays in 2013 and 2014 that were followed by OPAT. Through propensity scoring, patients who received outpatient ID intervention (ID-led OPAT) were matched 1-to-1 with those who did not (Other OPAT). We estimated regression models of hospital and ED admissions and of total healthcare payments over the first 30 days after discharge. Results The final analytic sample of 8200 observations was well balanced on clinical and demographic characteristics. Soft-tissue infection and osteomyelitis were the most common infections in the index event, each affecting more than 40% of individuals. Relative to those with Other OPAT, people with ID-led OPAT had lower odds of an ED admission (odds ratio [OR] 0.449, 95% confidence interval [CI] 0.311-0.645) or hospitalization (OR 0.661, 95% CI 0.557-0.791) over 30 days, and they accumulated $1488 less in total healthcare payments (95% CI -2 688.56--266.58). Conclusions Among privately insured individuals below age 65, ID consultations during OPAT are associated with large and significant reductions in the rates of ED admission and hospital admission in the 30 days after index events, as well as lower total healthcare spending.

Valvular involvement in Lyme disease is rare. Confirmation of Borrelia species as the causative agent with polymerase chain reaction was done in a few cases in Europe and the United States. We describe a case of mitral regurgitation with a preoperative diagnosis of myxomatous mitral valve degeneration. During surgery, the surgeon suspected infective rather than degenerative etiology; the results of tissue cultures were negative. However, universal bacterial polymerase chain reaction on explanted valve tissue detected Borrelia burgdorferi DNA. If a surgeon suspects infective endocarditis at the time surgery, appropriate specimens should be sent for histopathologic analysis, culture, and polymerase chain reaction assay.

We have noticed that patients colonized with methicillin-susceptible Staphylococcus aureus (MSSA) rarely get methicillin-resistant S. aureus (MRSA) infections. The purpose of this study was to compare the odds of a Staphylococcus aureus (SA) infection being an MRSA infection in MSSA carriers, MRSA carriers and non-carriers of SA.Hospitalizations of adult patients at the Cleveland Clinic Health System from 2008 to 2015 were screened to identify those where the patient was tested for SA colonization. The first such hospitalization was identified. Among these 90 891 patients, those who had an SA infection during the hospitalization were included. SA carrier status (MRSA, MSSA, or non-carrier), was defined based on the first nasal SA test result. The association of carrier status and MRSA infection was examined.The mean (±standard deviation (SD)) age of the 1999 included patients was 61 (17) years, and 1160 (58%) were male. Thirty percent, 26%, and 44%, were MRSA carriers, MSSA carriers and non-carriers, respectively. Of the 601 SA infections in MRSA carriers (reference group), 552 (92%) were MRSA infections compared with 42 (8%) of 516 in MSSA carriers (odds ratio (OR) 0.008, 95% confidence interval (CI) 0.005-0.012, p0.0001) and 430 (49%) of 882 in non-carriers (OR 0.072, 95% CI 0.051-0.100, p 0.0001), after controlling for age, sex, hospital length of stay and calendar year.Among patients with SA infection, the odds of the infection being an MRSA infection are 125-times lower in an MSSA carrier than in an MRSA carrier.

Historically, there has been a restrictive approach toward outpatient parenteral antimicrobial therapy (OPAT) in patients with injection drug use (IDU) due to the fear that they might utilize the intravenous catheter to inject illicit substances.We tested the hypothesis that patients with current IDU on OPAT would have less favorable treatment outcomes compared to those without current IDU.In this retrospective cohort chart review study of Cleveland Clinic OPAT registry, we identified patients with current IDU by both electronic and manual review. For each patient with current IDU, we identified 3 matched controls among those on OPAT and without current IDU, by propensity score matching on age, sex, OPAT year, and OPAT diagnosis. We compared treatment failure, infection relapse, line infection, hospital readmission, number of emergency room visits, and 90-day mortality, for patients with current IDU and their matched controls.We identified 39 patients with current IDU and 117 matched controls. Most patients with current IDU (82%) were discharged to skilled nursing facilities, whereas the majority of the control group (74%) was treated at home (p0.01). There was no significant difference in the examined treatment outcomes between the 2 groups.Patients with current IDU on OPAT did not have less favorable treatment outcomes compared to those without current IDU. Although the reason for this finding could potentially be related to difference in disposition, more studies need to be done to assess safety of home disposition among these patients.

Objectives Surgical management of invasive double-valve infective endocarditis (IE) involving the intervalvular fibrosa (IVF) is a technical challenge that requires extensive debridement followed by complex reconstruction. In this study, we present the early and mid-term outcomes of the hemi-Commando procedure and aortic root replacement with reconstruction of IVF using an aortomitral allograft. Methods From 2010 to 2017, 37 patients with IE involving the IVF underwent the hemi-Commando procedure. Postoperative clinical data and echocardiograms were reviewed for the assessment of cardiac structural integrity and clinical outcomes. Results Twenty-nine (78%) cases were redo surgery and 15 (41%) were emergency surgery. Preoperatively, 70% (n = 26) of patients were admitted to the intensive care unit and 11% (n = 4) of patients were in septic shock. Ten (27%) patients had native aortic valve IE, while 27 (73%) patients had prosthetic valve IE. Hospital death occurred in 8% (n = 3) of patients due to multisystem organ failure. Postoperative echocardiogram showed no aortic regurgitation in 86% (n = 32) and mild regurgitation in 14% (n = 5) of patients, while mitral regurgitation prevalence was none/trivial in 62% (n = 23), mild in 32% (n = 12) and moderate in 5%. Intact IVF reconstruction was confirmed in all patients with no abnormal communication between the left heart chambers. One-year survival was 91%, while 3-year survival was 82%. Mid-term follow up revealed 1 death secondary to recurrent IE. Conclusions Compared to double-valve replacement with IVF reconstruction ('Commando operation'), the early and mid-term outcomes of the hemi-Commando procedure proved to be a feasible treatment option for IVF reconstruction, enabling preservation of the mitral valve and the subvalvular apparatus in high-risk patients with invasive double-valve IE.

Staphylococcus lugdunensis is a coagulase-negative organism that causes a rare but destructive form of infective endocarditis (IE). We sought to evaluate the clinical and echocardiographic profile of S. lugdunensis IE at our institution and compare it to that of Staphylococcus aureus IE.Utilizing microbiology isolates, we retrospectively reviewed cases of S. lugdunensis bacteraemia admitted to our institution between 2002 and 2011 and included cases that met the modified Duke's criteria and those with device infection. We used univariate analysis to compare the clinical and echocardiographic features and outcomes of these patients with 76 cases of S. aureus IE.We identified 15 cases of S. lugdunensis IE (10 native, two prosthetic, three device only), amongst whom five cases had underlying structural valvular heart disease. Echocardiography revealed bulky vegetations in 12, abscesses in three, perforation in four, and valve dehiscence in one case. Overall, 7/12 (58%) of valvular IE involved left-sided valves; six of these underwent successful surgical intervention. S. lugdunensis IE resulted in marked valvular destruction similar to S. aureus IE but was more likely to affect patients with prior structural valvular heart disease (42 vs. 7%, p=0.004).Unlike other coagulase-negative staphylococci, S. lugdunensis causes a rare but destructive form of IE that can involve structurally normal native valves. Echocardiographic imaging is characterized by bulky vegetations and profound valvular destruction similar to that seen with S. aureus IE, thus isolation of this organism in the blood should not be disregarded as a contaminant. Confirmation of left-sided valvular endocarditis warrants surgical intervention.

OBJECTIVES Vancomycin and daptomycin are the two most frequently prescribed parenteral antimicrobials for resistant Gram-positive bacterial infections. The purpose of this study was to compare antimicrobial adverse event rates and associated healthcare interventions and healthcare utilization in patients treated with the two antimicrobials. METHODS All patients aged ≥18 years, discharged home from Cleveland Clinic on outpatient parenteral antimicrobial therapy (OPAT) with daptomycin or vancomycin between 1 July 2007 and 30 June 2010 were screened. Logistic regression models were built to calculate propensity to be treated with daptomycin for each patient. Propensity score-matched vancomycin-treated controls were identified for each daptomycin-treated patient. Adverse event, healthcare intervention and healthcare utilization rates during OPAT were compared in the matched cohort using negative binomial regression models. RESULTS One thousand, two hundred and eighty-eight patients were identified. Three-to-one matching provided the best matching characteristics and identified 119 daptomycin-treated subjects (2518 OPAT days) and 357 vancomycin-treated controls (6649 OPAT days). The mean patient age was 56 years and the mean OPAT duration was 19 days. Antimicrobial adverse event rates for the daptomycin and vancomycin groups were 3.2 and 7.7 per 1000 OPAT days, respectively [relative risk (RR) 0.38; 95% CI 0.15-0.86; P = 0.02]. Antimicrobial intervention rates were 5.6 and 27.1 per 1000 OPAT days, respectively (RR 0.21; 95% CI 0.11-0.36; P

A 42-year-old man presented with intermittent fevers, rigors, headache, and myalgia, and now, one-sided vision loss.

Objective Right-sided infective endocarditis is increasing because of increasing prevalence of predisposing conditions, and the role and outcomes of surgery are unclear. We therefore investigated the surgical outcomes for right-sided infective endocarditis. Methods From January 2002 to January 2015, 134 adults underwent surgery for right-sided infective endocarditis. Patients were grouped according to predisposing condition. Hospital outcomes, time-related death, and reoperation for infective endocarditis were analyzed. Results A total of 127 patients (95%) had tricuspid valve and 7 patients (5%) pulmonary valve infective endocarditis; 66 patients (49%) had isolated right-sided infective endocarditis, and 68 patients (51%) had right- and left-sided infective endocarditis. Predisposing conditions included injection drug use (30%), cardiac implantable devices (26%), chronic vascular access (19%), and other/none (25%). One native tricuspid valve was excised, 76% were repaired or reconstructed, and 23% were replaced. Intensive care unit and postoperative hospital stays were similar among groups. Injection drug users had the best early survival (no hospital mortality), and patients with chronic vascular access had the worst late survival (18% at 5 years). Survival was worst for concomitant mitral valve versus isolated right-sided infective endocarditis or concomitant aortic valve infective endocarditis. Survival after tricuspid valve replacement was worse than after repair/reconstruction. Estimated glomerular filtration rate was the strongest risk factor for death, not predisposing condition. Eleven patients underwent 12 reoperations for infective endocarditis; more reoperations occurred in injection drug users (P = .03). Conclusions Overall outcomes after surgery are variable and affected by patient condition, not predisposing condition. Injection drug use carries a higher risk of reoperation for infective endocarditis. Earlier surgery may permit more valve repairs and improve outcomes. Whenever possible, tricuspid valve replacement should be avoided.

OBJECTIVES Laboratory tests are usually requested for monitoring during outpatient parenteral antimicrobial therapy (OPAT), but these recommendations are not always followed. The purpose of this study was to determine whether rehospitalization during the OPAT course is associated with the availability of these test results to the treating physician. METHODS Electronic health records (EHRs) from all patients in the Cleveland Clinic OPAT registry with start dates from 1 January to 28 February 2011 were reviewed in a retrospective cohort study. Comprehensive data on patient and OPAT characteristics were obtained for the first OPAT course per patient. Availability of laboratory test results was defined as documentation of results of at least one recommended test in the health system's EHR. Proportions of patients rehospitalized were compared for OPAT courses with test results available and non-available. Adjustments were made for patient age, hospital length of stay, anticipated OPAT duration, OPAT site and Charlson comorbidity index score. RESULTS Four hundred patients received OPAT during the study period; 60% at home, 36% in skilled nursing facilities or long-term acute care facilities and 4% in other settings. Recommended monitoring laboratory test results were available to infectious disease physicians in 291 (73%) OPAT episodes. There were 82 patient readmissions (21%) while on OPAT. In a multivariable logistic regression model, non-availability of recommended test results was independently associated with readmissions while on OPAT (adjusted OR 2.53; 95% CI 1.36-4.73). CONCLUSIONS Non-availability of recommended test results to treating physicians for patients on OPAT is associated with increased readmissions during OPAT.

Infective endocarditis (IE) occurs at a rate of approximately 0.9-6.2 per 100,000 people per year and is associated with a high morbidity and mortality despite advancements in antibiotic and surgical treatments. The general approach to the treatment of IE is initial clinical stabilization, early acquisition of blood cultures, and definitive medical and/or surgical treatment. Surgical consultation should be obtained early when indicated in order to determine the best treatment approach for each individual patient. Surgery is indicated in most cases of prosthetic valve endocarditis, Staphylococcus aureus endocarditis, fungal endocarditis, and endocarditis associated with large vegetations (≥10 mm). Initial antibiotic therapy for IE should be targeted to the culprit microorganism; however, in some cases, empiric therapy must be initiated prior to definitive culture diagnosis. Empiric antibiotics should be targeted toward the most likely pathogens, including staphylococci, streptococci, and enterococci species. Here we discuss the recommended antibiotic regimens for the most common causes of IE as indicated by the American Heart Association and European Society of Cardiology. In 2008, the ACC/AHA published guideline updates on the treatment of valvular heart disease, which included a focused update on endocarditis prophylaxis. According to the most recent guidelines, the number of patients who require antibiotic prophylaxis has decreased substantially. Treatment of IE should be targeted toward the causative microorganism and must be based on the type and location of valve involved (native, prosthetic, left or right sided), the clinical status of the patient, and the likelihood for clinical success. This requires a collaborative effort from multiple medical specialties including infectious disease specialists, cardiologists, and cardiothoracic surgeons.

Objective The rarity of invasiveness of right-sided infective endocarditis (IE) compared with left-sided has not been well recognized and evaluated. Thus, we compared invasiveness of right- versus left-sided IE in surgically treated patients. Patients and Methods From January 2002 to January 2015, 1292 patients underwent surgery for active IE, 138 right-sided and 1224 left-sided. Among patients with right-sided IE, 131 had tricuspid and 7 pulmonary valve IE; 12% had prosthetic valve endocarditis. Endocarditis-related invasiveness was based on echocardiographic and operative findings. Results Invasive disease was rare on the right side, occurring in 1 patient (0.72%; 95% confidence interval 0.02%-4.0%); rather, it was limited to valve cusps/leaflets or was superficial. In contrast, IE was invasive in 408 of 633 patients with aortic valve (AV) IE (65%), 113 of 369 with mitral valve (MV) IE (31%), and 148 of 222 with AV and MV IE (67%). Staphylococcus aureus was a more predominant organism in right-sided than left-sided IE (right 40%, AV 19%, MV 29%), yet invasion was observed almost exclusively on the left side of the heart, which was more common and more severe with AV than MV IE and more common with prosthetic valve endocarditis than native valve IE. Conclusions Rarity of right-sided invasion even when caused by S aureus suggests that invasion and development of cavities/"abscesses" in patients with IE may be driven more by chamber pressure than organism, along with other reported host–microbial interactions. The lesser invasiveness of MV compared with AV IE suggests a similar mechanism: decompression of MV annulus invasion site(s) toward the left atrium.

Objectives Propionibacterium acnes remains a rare cause of infective endocarditis (IE). It is challenging to diagnose due to the organism's fastidious nature and the indolent presentation of the disease. The purpose of this study was to describe the clinical presentation and management of P. acnes IE with an emphasis on the methods of diagnosis. Methods We identified patients from the Cleveland Clinic Infective Endocarditis Registry who were admitted from 2007 to 2015 with definite IE by Duke Criteria. Propionibacterium acnes was defined as the causative pathogen if it was identified in at least two culture specimens, or identified with at least two different modalities: blood culture, valve culture, valve sequencing or histopathological demonstration of microorganisms. Results We identified 24 cases of P. acnes IE, 23 (96%) of which were either prosthetic valve endocarditis or IE on an annuloplasty ring. Invasive disease (71%) and embolic complications (29%) were common. All but one patient underwent surgery. Propionibacterium acnes was identified in 12.5% of routine blood cultures, 75% of blood cultures with extended incubation, 55% of valve cultures, and 95% of valve sequencing specimens. In 11 of 24 patients (46%), no causative pathogen would have been identified without valve sequencing. Conclusions Propionibacterium acnes almost exclusively causes prosthetic valve endocarditis and patients often present with advanced disease. The organism may not be readily cultured, and extended cultures appear to be necessary. In patients who have undergone surgery, valve sequencing is most reliable in establishing the diagnosis.

To determine the value of surgery for infective endocarditis (IE) in patients on hemodialysis by comparing the nature and invasiveness of endocarditis in hemodialysis and nonhemodialysis patients and their hospital and long-term outcomes, and identifying risk factors for time-related mortality after surgery.From January 1997 to January 2013, 144 patients on chronic hemodialysis and 1233 nonhemodialysis patients underwent valve surgery for IE at our institution. Propensity matching identified 99 well-matched hemodialysis and nonhemodialysis patient pairs for comparison of outcomes.Staphylococcus aureus infection was more common in hemodialysis patients than in nonhemodialysis patients (42% vs 21%; P .0001), but invasive disease was similar in the 2 groups (47%; P = .3). Hospital mortality was 13% and 5-year survival was 20% for hemodialysis patients, 20% below that expected in a general hemodialysis population but 15% above that of hemodialysis patients treated nonsurgically for IE. For matched patients, hospital mortality was 13% for hemodialysis patients versus 5.1% for nonhemodialysis patients (P = .05), and survival at 1 and 5 years was 56% versus 83% and 24% versus 59%, respectively (P .004). Use of an arteriovenous graft for dialysis access (P = .01) and preoperative placement of a pacemaker (P .0001) were risk factors for late mortality in hemodialysis patients. For matched patients, freedom from reoperation was similar in the hemodialysis and nonhemodialysis groups (P .9).Intermediate-term survival after surgery for IE in hemodialysis patients is substantially worse than that in nonhemodialysis patients, but only slightly worse than that in the general hemodialysis population and substantially better than that in hemodialysis patients with IE treated nonsurgically, supporting continued surgical intervention for IE.

Context.—Endovascular infection is an uncommon but devastating manifestation of histoplasmosis, which is often diagnosed late in disease. Objectives.—To evaluate the clinical and pathologic characteristics of patients with endovascular infections caused by Histoplasma capsulatum. Design.—All cases of patients with documented endovascular histoplasmosis at a single tertiary care center in an endemic region during the period 1993–2010 were reviewed. Results.—Patients presented with a subacute febrile illness and a history of endovascular devices. All patients had positive Histoplasma serology. Routine bacterial culture results were negative for all patients. In addition to yeast forms typical of histoplasmosis, pathologic findings also revealed mycelial forms in 4 of 5 patients. Inflammation was scant. Urinary antigen detection was positive in 4 of 5 patients and Histoplasma blood culture results were positive for 3 of 5 patients. Four patients were treated with a combination of surgical and medical therapy, which consisted of amphotericin B followed by itraconazole; these 4 patients had complete resolution of symptoms and no documented relapse. One patient died before planned surgery. Conclusions.—Histoplasma capsulatum endovascular infections are clinically characterized by a subacute febrile illness with negative bacterial cultures in patients with prosthetic endografts or valves. Noninvasive diagnostics are often the initial clue to the diagnosis. Combined medical and surgical treatment is associated with survival. On histopathologic examination both mycelial and yeast forms are often observed, with absent to minimal tissue inflammatory reaction.

Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) can be reliably differentiated by flow cytometry when labeled with nucleic acid dyes. The purpose of this study was to determine if this differentiation can be achieved while labeling with a S. aureus-specific anti-staphylococcal protein A antibody instead of nucleic acid dyes. A total of 103 S. aureus isolates were incubated for 4 h at 37°C in Mueller Hinton broth with and without oxacillin, then stained with anti-staphylococcal protein A antibody, and analyzed by flow cytometry using the Micro PRO™ instrument. Dot plots (side scatter vs. fluorescence intensity) of isolates exposed to oxacillin were examined to define two gates encompassing the majority of MSSA and MRSA signal events, respectively. The ratio of signal event counts in the two gates was called the gate signal count ratio (GSCR), and its performance was evaluated using receiver operating characteristic (ROC) curves. The GSCR could differentiate MRSA from MSSA with 98% sensitivity and 100% specificity using a cut-off of 0.6868 when the two gates were defined as follows: gate 1, fluorescence intensity 2-10, side scatter 5-70; gate 2, fluorescence intensity 7-700, side scatter 70-500. MRSA and MSSA can be accurately detected and differentiated by flow cytometry after 4 h of oxacillin exposure when labeled with anti-staphylococcal protein A antibody.

Objective.To evaluate the effects of an active surveillance program for Staphylococcus aureus linked to a decolonization protocol on the incidence of healthcare-associated infection and new nasal colonization due to S. aureus.Design.Retrospective quasi-experimental study.Setting.An 18-bed medical intensive care unit at a tertiary care center in Cleveland, Ohio.Methods.From January 1, 2006, through December 31, 2007, all patients in the medical intensive care unit were screened for S. aureus nasal carriage at admission and weekly thereafter. During the preintervention period, January 1 through September 30,2006, only surveillance occurred. During the intervention period, January 1 through December 31,2007, S. aureus carriers received mupirocin intranasally. Beginning in February 2007, carriers also received Chlorhexidine gluconate baths.Results.During the preintervention period, 604 (73.7%) of 819 patients were screened for S. aureus nasal carriage, yielding 248 prevalent carriers (30.3%). During the intervention period, 752 (78.3%) of 960 patients were screened, yielding 276 carriers (28.8%). The incidence of S. aureus carriage decreased from 25 cases in 3,982 patient-days (6.28 cases per 1,000 patient-days) before intervention to 18 cases in 5,415 patient-days (3.32 cases per 1,000 patient-days) (P = .04; relative risk [RR], 0.53 [95% confidence interval {CI}, 0.28-0.97]) and from 9.57 to 4.77 cases per 1,000 at-risk patient-days (P = .02; RR, 0.50 [95% CI, 0.27-0.91]). The incidence of S. aureus hospital-acquired bloodstream infection during the 2 periods was 2.01 and 1.11 cases per 1,000 patient-days, respectively (P = .28). The incidence of S. aureus ventilator-associated pneumonia decreased from 1.51 to 0.18 cases per 1,000 patient-days (P = .03; RR, 0.12 [95% CI, 0.01-0.83]). The total incidence of S. aureus hospital-acquired infection decreased from 3.52 to 1.29 cases per 1,000 patient-days (P = .03; RR, 0.37 [95% CI, 0.14-0.90]).Conclusions.Active surveillance for S. aureus nasal carriage combined with decolonization was associated with a decreased incidence of S. aureus colonization and hospital-acquired infection.

After isoniazid and rifampin (rifampicin), the next pivotal drug class in Mycobacterium tuberculosis treatment is the fluoroquinolone class. Mutations in resistance-determining regions (RDR) of the rpoB , katG , and gyrA genes occur with frequencies of 97%, 50%, and 85% among M. tuberculosis isolates resistant to rifampin, isoniazid, and fluoroquinolones, respectively. Sequences are highly conserved, and certain mutations correlate well with phenotypic resistance. We developed a pyrosequencing assay to determine M. tuberculosis genotypic resistance to rifampin, isoniazid, and fluoroquinolones. We characterized 102 M. tuberculosis clinical isolates from the Philippines for susceptibility to rifampin, isoniazid, and ofloxacin by using the conventional submerged-disk proportion method and validated our pyrosequencing assay using these isolates. DNA was extracted and amplified by using PCR primers directed toward the RDR of the rpoB , katG , and gyrA genes, and pyrosequencing was performed on the extracts. The M. tuberculosis H37Rv strain (ATCC 25618) was used as the reference strain. The sensitivities and specificities of pyrosequencing were 96.7% and 97.3%, 63.8% and 100%, and 70.0% and 100% for the detection of resistance to rifampin, isoniazid, and ofloxacin, respectively. Pyrosequencing is thus a rapid and accurate method for detecting M. tuberculosis resistance to these three drugs.

Background Many clinical scenarios have been encountered by patients who developed histoplasmosis after receiving a solid organ transplant at a large transplant center in an endemic area. Methods Cases of posttransplantation histoplasmosis were identified by use of multiple methods, including reviews of microbiology test results, transplant databases, and billing codes. Data were obtained retrospectively. Descriptive statistics were used. Results During the 1997-2007 study period, 3436 patients received a solid organ transplant, and 38 patients were identified as having posttransplantation histoplasmosis. Of these 38 patients, 9 were excluded from our study because the diagnosis was solely clinical. Of the remaining 29 patients, 14 had posttransplantation histoplasmosis (incidence, 1 case per 1000 person-years); 14 showed histologic evidence of histoplasmosis in the recipient or donor tissue, which was encountered unexpectedly at the time of transplantation; and 1 had histoplasmosis before receiving the transplant. Of the 14 patients who developed histoplasmosis after transplantation, 5 were heart transplant recipients, 3 were lung transplant recipients, 3 were kidney transplant recipients, 1 was a liver transplant recipient, 1 was a pancreas transplant recipient, and 1 was a kidney-pancreas transplant recipient. The median time from transplantation to diagnosis was 17 months (interquartile range, 8.1-46 months), and the median time from onset of symptoms to diagnosis 3 weeks (interquartile range, 1.9-6.5 weeks). All recipients had disseminated disease. The most common treatment was amphotericin B and itraconazole. All were cured, or still on treatment, but symptom-free. Of the 14 patients who had an explanted organ or donor tissue that showed histologic evidence of histoplasmosis, 13 (93%) were lung transplant recipients, and 1 (7%) was a liver transplant recipient. None of these patients developed active histoplasmosis, but all received prophylactic treatment. Finally, 1 patient had histoplasmosis before transplantation; he was treated with itraconazole 3 months before and after transplantation, and he did well. Conclusions In conclusion, posttransplantation histoplasmosis is rare (1 case per 1000 transplant-person-years; 95% confidence interval, 0.6-1.7), even in endemic areas. Prognosis is good but requires protracted therapy. Patients with latent infection did not develop posttransplantation histoplasmosis when prophylaxis was used.

Objectives The need for indwelling vascular access for outpatient parenteral antimicrobial therapy (OPAT) places patients at risk of vascular access complications. The purpose of this study was to describe vascular access complications during OPAT at home, and identify factors associated with their occurrence. Methods All OPAT courses carried out at home for patients at Cleveland Clinic in 2013 were identified from the institution's OPAT registry. The first OPAT course per patient was included. Vascular access complications that occurred during the treatment course were abstracted from the electronic medical record. Only complications that triggered a clinical intervention were included. Results The 1461 included OPAT courses encompassed 33,579 OPAT days of treatment. One-hundred-and-forty-four vascular access complications occurred in 131 OPAT courses (9% of OPAT courses, 4.29 complications per 1000 OPAT days). The most common complication was occlusion (53% of all complications). Hickman catheters [incidence rate ratio (IRR) 0.20, 95% CI 0.03-0.63] and indwelling ports (IRR 0.25, 95% CI 0.04-0.78) were associated with lower complication rates than peripherally inserted central catheters, as was increasing age (IRR 0.99, 95% CI 0.98-1.00). Log OPAT duration (IRR 1.60, 95% CI 1.28-2.03), female sex (IRR 1.62, 95% CI 1.16-2.28) and injection drug use (IRR 3.32, 1.16-7.46) were associated with increased risk of vascular access complications. Conclusions Nine percent of OPAT courses at home have at least one vascular access complication requiring clinical intervention. Longer OPAT duration, younger age, female sex and injection drug use are associated with increased risk of vascular access complications.

Background Infective endocarditis (IE) requiring surgical intervention in patients who actively inject drugs poses treatment challenges. Decisions regarding the need for operation are affected by concern for relapse of IE from ongoing injection drug use (IDU). The purpose of this study was to evaluate the effect of active IDU on outcomes after operation for IE. Methods All patients with IE surgically treated at Cleveland Clinic from July 1, 2007 to July 1, 2012 were identified from the Cleveland Clinic Infective Endocarditis Registry and the Cardiovascular Information Registry. Of 536 patients operated on for IE during the study period, 41 (8%) actively injected drugs. The primary outcome of the study was death or reoperation for IE. Results Patients who injected drugs had poorer survival free of reoperation, and the risk of events varied with time. In a multivariable Cox proportional hazards model, using time-dependent covariates, IDU was associated with a higher hazard of death or reoperation between 90 and 180 days (hazard ratio [HR], 9.8; 95% confidence interval [CI], 2.7–35.3) but not before 90 days (HR, 0.38; 95% CI, 0.05–3.1) or after 180 days (HR, 1.8; 95% CI, 0.8–3.8). Among patients who injected drugs, reoperation and death contributed equally to the outcome, whereas among patients who did not inject drugs, reoperation for IE was far less common. Conclusions Between 3 and 6 months after operation for IE, patients who inject drugs have a hazard of death or reoperation that is about 10 times that of patients who do not inject drugs. Before and after, the HRs are much smaller and not statistically significant.