An Unusual Etiology of Lemierre-Like Syndrome: Preseptal Cellulitis due to Methicillin-Resistant Staphylococcus aureus.

Lemierre's syndrome (LS) is a rare and potentially fatal condition that predominantly affects young adults with oropharyngeal infection. Fusobacterium necrophorum is the usual etiology and classically causes internal jugular vein septic thrombophlebitis, frequently complicated by septic emboli to several organs (most classically to the lungs). Lemierre-like syndrome (LLS) describes the same constellation of symptoms and pathophysiology as Lemierre's syndrome; however, Fusobacterium spp. are not the cause, and the source of infection may be nonoropharyngeal. We present a case with an unusual etiology of LLS: a patient with untreated preseptal cellulitis and associated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in the setting of injection drug use. Physical exam revealed tachypnea and rhonchi with severe periorbital and bilateral eyelid edema. Imaging demonstrated bilateral preseptal and orbital cellulitis with thrombosis of both internal jugular veins and bilateral pulmonary cavitary lesions consistent with septic pulmonary emboli. She was managed with anticoagulation and parenteral antibiotics. To our knowledge, this is the first case of LLS originating from preseptal cellulitis without evidence of preceding pharyngitis. While facial and orbital infections are rare etiologies of LLS, the potentially devastating sequelae of LLS warrant its inclusion in differential diagnoses.

Survey of Adherence with COVID-19 Prevention Behaviors During the 2020 Thanksgiving and Winter Holidays Among Members of the COVID-19 Community Research Partnership.

Prevention behaviors represent important public health tools to limit spread of SARS-CoV-2. Adherence with recommended public health prevention behaviors among 20000 + members of a COVID-19 syndromic surveillance cohort from the mid-Atlantic and southeastern United States was assessed via electronic survey following the 2020 Thanksgiving and winter holiday (WH) seasons. Respondents were predominantly non-Hispanic Whites (90%), female (60%), and ≥ 50 years old (59%). Non-household members (NHM) were present at 47.1% of Thanksgiving gatherings and 69.3% of WH gatherings. Women were more likely than men to gather with NHM (p < 0.0001). Attending gatherings with NHM decreased with older age (Thanksgiving: 60.0% of participants aged < 30 years to 36.3% aged ≥ 70 years [p-trend < 0.0001]; WH: 81.6% of those < 30 years to 61.0% of those ≥ 70 years [p-trend < 0.0001]). Non-Hispanic Whites were more likely to gather with NHM than were Hispanics or non-Hispanic Blacks (p < 0.0001). Mask wearing, reported by 37.3% at Thanksgiving and 41.9% during the WH, was more common among older participants, non-Hispanic Blacks, and Hispanics when gatherings included NHM. In this survey, most people did not fully adhere to recommended public health safety behaviors when attending holiday gatherings. It remains unknown to what extent failure to observe these recommendations may have contributed to the COVID-19 surges observed following Thanksgiving and the winter holidays in the United States.

Changing Attitudes toward the COVID-19 Vaccine among North Carolina Participants in the COVID-19 Community Research Partnership.

Coronavirus Disease-2019 (COVID-19) vaccine acceptance is variable. We surveyed participants in the COVID-19 Community Research Partnership from 17 December 2020 to 13 January 2021 to assess vaccine receptiveness. Vaccine uptake was then monitored until 15 May 2021; 20,232 participants responded to the receptiveness survey with vaccination status accessed in 18,874 participants via daily follow-up surveys (participants not completing daily surveys ≥30 days to 15 May 2021, were excluded). In the initial survey, 4802 (23.8%) were vaccine hesitant. Hesitancy was most apparent in women (Adjusted RR 0.93, p < 0.001), Black Americans (Adjusted RR 1.39, 1.41, 1.31 to non-Hispanic Whites, Other, and Hispanic or Latino, respectively p < 0.001), healthcare workers (Adjusted RR 0.93, p < 0.001), suburbanites (ref. Urban Adjusted RR 0.85, 0.90 to urban and rural dwellers, respectively, p < 0.01), and those previously diagnosed with COVID-19 (RR 1.20, p < 0.01). Those <50 years were also less accepting of vaccination. Subsequent vaccine uptake was 99% in non-hesitant participants. For those who were unsure, preferred not to answer, or answered "no", vaccination rates were 80% (Adjusted RR 0.86, p < 0.0001), 78% (Adjusted RR 0.83, p < 0.0001), and 52.7% (Adjusted RR 0.65, p < 0.0001), respectively. These findings suggest that initial intent did not correlate with vaccine uptake in our cohort.

Impact of Chronic Hepatitis C virus co-infection on outcomes of infective endocarditis in people who inject drugs.

Injection drug use (IDU) is a risk factor for infective endocarditis (IE) and hepatitis C virus (HCV) infection. This retrospective cohort study assessed HCV's impact on outcomes of adult people who inject drugs (PWID). Those admitted due to IE using modified Duke criteria from January 2012 through May 2018 were identified. The cohort was divided into HCV seropositive and seronegative groups. The seropositive group was further stratified according to HCV viremia. Complications and mortality during the IE hospitalization, at 10 weeks, and 1 year were compared across groups. Clinical factors were similar between the cohorts, except patients without viremia (29, 81%) required more ICU admissions than with viremia (30, 60%) (P < 0.05). There was no difference in mortality at all time periods between the groups. Although several factors affect mortality in PWID with IE, neither HCV antibody positivity nor viremia appear to increase the risk for complications or death.

Vitreous and Chorioretinal Lesions in People Who Inject Drugs and Are Hospitalized with Bloodstream and Related Infections.

PURPOSE: To determine the prevalence of and to characterize vitreous and chorioretinal lesions, to identify causative organisms, and to correlate symptoms with ophthalmic involvement in people who inject drugs and are hospitalized with bloodstream infection (BSI), related metastatic foci of infection (MFI), or both. DESIGN: An academic hospital-based cross-sectional study. PARTICIPANTS: Patients admitted with BSI or MFI related to injection drug use (IDU). METHODS: Patients underwent a complete eye examination within 72 hours of enrollment. Characteristics including gender; age; race; injection drug of choice (DOC); presence of coinfection with hepatitis B, hepatitis C, or human immunodeficiency virus; pathogen causing systemic infection and type of infection; and history of prior infection related to IDU were recorded. MAIN OUTCOME MEASURES: Presence of vitreous or chorioretinal findings, or both. RESULTS: Ninety-one unique patients with 96 separate hospitalizations for systemic infection were enrolled from March 28, 2018, through March 30, 2020. Vitreous or chorioretinal involvement was identified in 16 of 96 patients (16.7%). The most common ocular findings were intraretinal or white-centered hemorrhage in 9 of 96 patients, chorioretinal infiltrate in 8 of 96 patients, endophthalmitis in 5 of 96 patients, and cotton wool spots in 3 of 96 patients. Of the patients with ocular involvement, only 7 of 16 patients (44%) were symptomatic, and 5 of these were patients with endophthalmitis; the others showed chorioretinal infiltrates or intraretinal or white-centered hemorrhage and cotton wool spots. Staphylococcus aureus was the most common causative pathogen in patients with and without ocular findings. Presence of ocular symptoms, worse visual acuity, and injection DOC of methamphetamine were correlated with the presence of ocular findings. CONCLUSIONS: Patients without ocular symptoms with systemic infections related to IDU may have chorioretinal findings. Further study is needed to characterize better the epidemiologic features of these infections and to identify risk factors for ocular involvement in people who inject drugs.

Prostatic abscess: clinical features, management, and outcomes of a "Stealth" infection: retrospective case series and review of the literature.

Prostatic abscess (PA) is uncommon and may be difficult to distinguish from acute prostatitis which often leads to delayed or missed diagnoses. Although gram-negative bacilli are the traditional etiology of PA, Staphylococcus aureus is an emerging cause. The goals of this study were to characterize the current clinical features, microbiology, management, and outcomes of PA at a US academic center. A retrospective review of adult patients hospitalized with an ICD-9/10 diagnosis of PA between January 2013 and July 2018 was conducted. Inclusion criteria included age ≥18 years, a compatible genitourinary (GU) infection syndrome, and imaging consistent with PA. Relevant data were extracted and analyzed by univariate analysis as appropriate. Twenty-two patients with PA were identified with median age 57 years. Five patients (23%) were immunosuppressed and 11 (50%) had diabetes. No patient had prior PA but 3 had past prostatitis. Only 1 patient had recent GU instrumentation and none had indwelling urinary catheters. The most common presenting symptoms were fever (59%), dysuria (45%), and urinary retention (32%). Only 7 out of 18 (39%) patients had prostate tenderness on exam and none had fluctuance. As demonstrated by computed tomography, PAs were multifocal in 8 (36%) patients and 16 (73%) had PAs >2 cm in diameter. The median abscess size was 3.2 cm. S. aureus was isolated in 60% of positive urine cultures and 78% of positive blood cultures; 46% were methicillin-resistant. Nine patients (41%) received antibiotics alone whereas 13 (59%) required antibiotics plus drainage. The median duration of antimicrobial therapy was 34.5 days. Four week mortality was 9%. When comparing S. aureus PA to other causes, S. aureus patients tended to have higher fevers, more often had diabetes, and received longer durations of antibiotic therapy (median 35 days vs 31 days, P = 0.04) but age, abscess size, and mortality did not differ. PA is relatively uncommon and often clinically unsuspected. Imaging may be critical to accurate diagnosis. Optimal management usually requires antibiotics and sometimes drainage depending on abscess size. We found a significant proportion of cases due to S. aureus which might be relevant when deciding empiric antimicrobial therapy.

Infective Endocarditis Guidelines: The Challenges of Adherence-A Survey of Infectious Diseases Clinicians.

BACKGROUND: Guidelines exist to aid clinicians in managing patients with infective endocarditis (IE), but the degree of adherence with guidelines by Infectious Disease (ID) physicians is largely unknown. METHODS: An electronic survey assessing adherence with selected IE guidelines was emailed to 1409 adult ID physician members of the Infectious Diseases Society of America's Emerging Infections Network. RESULTS: Five hundred fifty-seven physicians who managed IE responded. Twenty percent indicated that ID was not consulted on every case of IE at their hospitals, and 13% did not recommend transthoracic echocardiography (TTE) for all IE cases. The duration of antimicrobial therapy was timed from the first day of negative blood cultures by 91% of respondents. Thirty-four percent of clinicians did not utilize an aminoglycoside for staphylococcal prosthetic valve IE (PVE). Double ß-lactam therapy was "usually" or "almost always" employed by 83% of respondents for enterococcal IE. For patients with active IE who underwent valve replacement and manifested positive surgical cultures, 6 weeks of postoperative antibiotics was recommended by 86% of clinicians. CONCLUSIONS: The finding that adherence was <90% with core guideline recommendations that all patients with suspected IE be seen by ID and that all patients undergo TTE is noteworthy. Aminoglycoside therapy of IE appears to be declining, with double ß-lactam regimens emerging as the preferred treatment for enterococcal IE. The duration of postoperative antimicrobial therapy for patients undergoing valve replacement during acute IE is poorly defined and represents an area for which additional evidence is needed.

Transcranial Doppler Emboli Monitoring for Infective Endocarditis.

BACKGROUND AND PURPOSE: Ischemic stroke can occur in 20-55% of patients with infective endocarditis (IE) with 75% occurring during the first 2 weeks of treatment. CT or MRI brain can diagnose the sequelae of stroke but transcranial Doppler (TCD) can document active embolization. We undertook a retrospective review of our patient cohort and a systematic review of literature to assess the role of TCD in early diagnosis and management of ischemic stroke in IE. METHODS: Retrospective chart review and literature review. RESULTS: We found 89 patients with stroke caused by IE at our institution from December 2011 to April 2018. TCDs were obtained on 26 patients; 16 were abnormal for cerebrovascular abnormalities. Only 4 patients had 30-minute emboli monitoring performed, of which one revealed emboli. We found 3 studies investigating the role of TCDs in IE that showed promise in its use as a predictive tool in stroke risk stratification. CONCLUSIONS: Presence of embolization in the form of high-intensity transient signals (HITS) detected on TCDs can be used for early diagnosis of IE, assessing efficacy of antibiotic therapy, and stratification of stroke risk in IE. This can aid further research into testing preventative interventions for reducing stroke burden in IE such as earlier valvular surgery or vacuum-assisted vegetation extraction.

Ehrlichiosis in a recent kidney transplant recipient: The repellent that did not repel! A case report and literature review of ehrlichiosis in solid organ transplant patients.

Ehrlichiosis has been infrequently reported in immunosuppressed patients such as solid organ transplants (SOT). We report a case of Ehrlichia chaffeensis infection in an immunosuppressed woman four months after deceased donor kidney transplantation. The diagnosis was confirmed by PCR testing in serum, and the patient responded promptly to treatment with doxycycline. To supplement our Case Report, a literature review encompassing 1995 to present was also performed using PubMed as the search vehicle. Search terms that were utilized include: ehrlichiosis, HME, E chaffeensis, kidney transplant(ation), renal transplant(ation), solid organ transplant(ation), and immunosuppression. The diagnosis of ehrlichiosis can be challenging in SOT patients since ehrlichiosis is not a classic opportunistic infection in SOT. Transplant physicians must have a high clinical suspicion for the diagnosis in patients with an acute febrile illness accompanied by headache, worsening cytopenias, and transaminitis who live in endemic areas, especially if they have tick exposure.

Left-sided infective endocarditis in persons who inject drugs.

PURPOSE: The purpose of this study was to describe left-sided infective endocarditis (LSIE) in persons who inject drugs (PWID) and compare that group to PWID with non-LSIE and to non-PWID with LSIE. METHODS: Retrospective single-center study of adult IE patients from 2011 to 2018. RESULTS: Of the 333 patients in our cohort, 54 were PWID with LSIE, 75 were PWID with non-LSIE, and 204 were non-PWID with LSIE. When comparing LSIE vs non-LSIE in PWID, the LSIE group was older (median age 35 vs 28.5, p < 0.01), had fewer S. aureus infections (59% vs 92%, p < 0.01), was more likely to have cardiac surgery (31% vs 13%, p < 0.01), and had a higher 10-week mortality (22% vs 5%, p < 0.01). When comparing PWID with LSIE to non-PWID with LSIE, the PWID group were younger (median age 35 vs 46, p < 0.01); had more frequent multi-valve involvement (33% vs 19%, p = 0.04), Staphylococcus aureus infections (54% vs 27%, p < 0.01), and previous IE (24% vs 8%, p < 0.01); and experienced more strokes (54% vs 31%, p < 0.01). Ten-week mortality was similar for LSIE in both PWID and non-PWID (24% vs 20%, p = 0.47). CONCLUSIONS: LSIE in PWID is not uncommon. Compared to non-LSIE in PWID, valve surgery is more common and mortality is higher. For reasons that are unclear, stroke is more frequent in LSIE in PWID than in non-PWID with LSIE but mortality is no different.

The Effect of Preexisting Anticoagulation on Cerebrovascular Events in Left-Sided Infective Endocarditis.

BACKGROUND: Stroke is a frequent complication of infective endocarditis, especially infection involving left-sided valves. Management of anticoagulation in left-sided infective endocarditis is controversial as it is unclear whether anticoagulation impacts stroke and bleeding risk in patients with this condition. The objective of this study was to evaluate the effect of anticoagulation on stroke occurrence and bleeding complications in patients with left-sided infective endocarditis. METHODS: Patients admitted to a tertiary academic hospital with left-sided infective endocarditis between December 2011 and April 2018 were identified. Patients were stratified based on receipt of therapeutic anticoagulation prior to admission. The primary outcome measure was the rate of radiographically confirmed stroke at 10 weeks. RESULTS: Two-hundred and fifty-eight consecutive patients with left-sided infective endocarditis were identified. Patients receiving anticoagulation (n = 50) were older (median age 63 vs 52; P = .02), were more likely to have a history of atrial fibrillation (22% vs 8.2%; P < .01), more often had prosthetic valves (38% vs 13.9%; P < .01), and had a lower incidence of mitral valve involvement (40% vs 62%; P < .01), compared with patients not receiving anticoagulation. There was no significant difference in the rate of stroke, cerebrovascular hemorrhage, or mortality at 10 weeks between the two cohorts. CONCLUSIONS: Preexisting anticoagulation did not appear to have an effect on stroke, cerebrovascular hemorrhage, or mortality in patients with left-sided infective endocarditis at 10 weeks. Continuation of anticoagulation in patients with a definitive preexisting indication should be considered in patients with left-sided infective endocarditis in the absence of other contraindications.

Practice Patterns of Pneumocystis Pneumonia Prophylaxis in Connective Tissue Diseases: A Survey of Infectious Disease Physicians.

BACKGROUND: Immunosuppressive therapy for connective tissue diseases (CTDs) increases risk for opportunistic infections including Pneumocystis pneumonia (PCP). High mortality rates are reported in CTD patients with PCP, which suggests a potential need for prophylaxis, but indications remain poorly defined. Wide variations in the use of PCP prophylaxis among rheumatologists have been documented. This study evaluated PCP prophylaxis patterns for CTD patients among infectious disease (ID) physicians. METHODS: An electronic survey was emailed to 1264 adult ID physicians who are members of the Infectious Diseases Society of America Emerging Infections Network. RESULTS: Six hundred thirty-one physicians responded to the survey. Respondents to the survey were more likely to work in academics (P = .02) and be early (<5 years) or late (≥25 years) in their careers (P = .0002). Forty-three percent (n = 269) made no recommendations for PCP prophylaxis in non-HIV patients. Of the 362 respondents who did make such recommendations, the greatest consensus for disease-based prophylaxis was for granulomatosis with polyangiitis (53%). For therapy-based prophylaxis, corticosteroids ≥20 mg/d was the most frequently cited indication (87%). Surrogate laboratory markers to aid in decisions about prophylaxis were not routinely used (21%). Although the majority recommended discontinuation of PCP prophylaxis with tapering of corticosteroids (65%), there was variability in the specific dose. Eighty-nine percent of respondents felt that guidelines about PCP prophylaxis would be helpful. CONCLUSIONS: There is little consensus about PCP prophylaxis in CTDs among ID physicians. Guidelines for PCP prophylaxis would be helpful when caring for these complex patients.

Cardiovascular implantable electronic device infections due to enterococcal species: Clinical features, management, and outcomes.

BACKGROUND: Enterococcal cardiovascular implantable electronic device (CIED) infections are not well characterized. METHODS: Data from the Multicenter Electrophysiologic Device Infection Cohort, a prospective study of CIED infections, were used for descriptive analysis of adults with enterococcal CIED infections. RESULTS: Of 433 patients, 21 (4.8%) had enterococcal CIED infection. Median age was 71 years. Twelve patients (57%) had permanent pacemakers, five (24%) implantable cardioverter defibrillators, and four (19%) biventricular devices. Median time from last procedure to infection was 570 days. CIED-related bloodstream infections occurred in three patients (14%) and 18 (86%) had infective endocarditis (IE), 14 (78%) of which were definite by the modified Duke criteria. IE cases were classified as follows: valvular IE, four; lead IE, eight; both valve and lead IE, six. Vegetations were demonstrated by transesophageal echocardiography in 17 patients (81%). Blood cultures were positive in 19/19 patients with confirmed results. The most common antimicrobial regimen was penicillin plus an aminoglycoside (33%). Antibiotics were given for a median of 43 days. Only 14 patients (67%) underwent device removal. There was one death during the index hospitalization with four additional deaths within 6 months (overall mortality 24%). There were no relapses. CONCLUSIONS: Enterococci caused 4.8% of CIED infections in our cohort. Based on the late onset after device placement or manipulation, most infections were likely hematogenous in origin. IE was the most common infection syndrome. Only 67% of patients underwent device removal. At 6 months follow-up, no CIED infection relapses had occurred, but overall mortality was 24%.

Repeat Infective Endocarditis in Persons Who Inject Drugs: "Take Another Little Piece of my Heart".

BACKGROUND: Injection drug use (IDU) is a major risk factor for infective endocarditis (IE). Few data exist on repeat IE (rIE) in persons who inject drugs (PWID). METHODS: Patients ≥18 years old seen at Wake Forest Baptist Medical Center from 2004 to 2017 who met Duke criteria for IE and who self-reported IDU in the 3 months before admission were identified. The subset of PWID who developed rIE, defined as another episode of IE at least 10 weeks after diagnosis of the first episode, was then reviewed. RESULTS: Of the 87 PWID who survived their first episode of IE, 22 (25.3%) experienced rIE and 77.3% had rIE within a year of the first episode. All patients who experienced rIE resumed IDU between episodes of IE. Of the patients with rIE, 54.5% had an infection caused by S. aureus and 22.7% required surgical intervention. Mortality at 1 year was 36.3%. Compared with their first IE episode, patients with rIE had fewer S. aureus infections (P = .01). Compared with PWID who experienced single-episode IE, intravenous prescription opioid use (P = .01), surgery (P < .01), tricuspid valve involvement (P = .02), and polymicrobial infection (P = .03) occurred more often during first episodes of IE in individuals who then developed rIE. CONCLUSIONS: rIE is common among IDU-related IE and confers a high 1-year mortality rate. The microbiology of rIE is varied, with S. aureus being less frequently isolated. More studies on modification of social and clinical risk factors are needed to prevent rIE.

Infectious Scleritis: What the ID Clinician Should Know.

Scleritis is an inflammatory process involving the outer coating of the globe which is characterized by focal or diffuse hyperemia, moderate to severe pain, and frequent impairment of vision. Most cases of scleritis are autoimmune in nature and are managed with topical and/or systemic corticosteroids. Infectious scleritis is a less common entity, occurring in 5%-10% of cases, and requiring directed antimicrobial therapy. We present a case of Nocardia farcinica anterior nodular scleritis diagnosed via positive culture of an excisional biopsy of a scleral nodule. The patient improved after combined surgical and medical therapy with amoxicillin-clavulanate and moxifloxacin for 12 months. Based on a literature review, a summary of reported cases of infectious scleritis is provided, and guidelines pertaining to diagnosis and management are offered.

Impact of Abandoned Leads on Cardiovascular Implantable Electronic Device Infections: A Propensity Matched Analysis of MEDIC (Multicenter Electrophysiologic Device Infection Cohort).

OBJECTIVES: This study sought to evaluate the impact of abandoned cardiovascular implantable electronic device (CIED) leads on the presentation and management of device-related infections. BACKGROUND: Device infection is a serious consequence of CIEDs and necessitates removal of all hardware for attempted cure. The merits of extracting or retaining presumed sterile but nonfunctioning leads is a subject of ongoing debate. METHODS: The MEDIC (Multicenter Electrophysiologic Device Infection Cohort) prospectively enrolled patients with CIED infections at 10 institutions in the United States and abroad between January 1, 2009, and December 31, 2012. Within a propensity-matched cohort, relevant clinical information was compared between patients who had 1 or more abandoned leads at the time of infection and those who had none. RESULTS: Matching produced a cohort of 264 patients, including 176 with no abandoned leads and 88 with abandoned leads. The groups were balanced with respect to Charlson comorbidity index, oldest lead age, device type, sex, and race. At the time of admission, those with abandoned leads were less likely to demonstrate systemic signs of infection, including leukocytosis (p = 0.023) and positive blood cultures (p = 0.005). Conversely, patients with abandoned leads were more likely to demonstrate local signs of infections, including skin erosion (p = 0.031) and positive pocket cultures (p = 0.015). In addition, patients with abandoned leads were more likely to require laser extraction (p = 0.010). CONCLUSIONS: The results of a large prospective registry of CIED infections demonstrated that patients with abandoned leads may present with different signs, symptoms, and microbiological findings and require laser extraction more than those without abandoned leads.

Attempted salvage of infected cardiovascular implantable electronic devices: Are there clinical factors that predict success?

BACKGROUND: Published guidelines mandate complete device removal in cases of cardiovascular implantable electronic device (CIED) infection. Clinical predictors of successful salvage of infected CIEDs have not been defined. METHODS: Data from the Multicenter Electrophysiologic Device Infection Collaboration, a prospective, observational, multinational cohort study of CIED infection, were used to investigate whether clinical predictors of successful salvage of infected devices could be identified. RESULTS: Of 433 adult patients with CIED infections, 306 (71%) underwent immediate device explantation. Medical management with device retention and antimicrobial therapy was initially attempted in 127 patients (29%). "Early failure" of attempted salvage occurred in 74 patients (58%) who subsequently underwent device explantation during the index hospitalization. The remaining 53 patients (42%) in the attempted salvage group retained their CIED. Twenty-six (49%) had resolution of CIED infection (successful salvage group) whereas 27 patients (51%) experienced "late" salvage failure. Upon comparing the salvage failure group, early and late (N = 101), to the group experiencing successful salvage of an infected CIED (N = 26), no clinical or laboratory predictors of successful salvage were identified. However, by univariate analysis, coagulase-negative staphylococci as infecting pathogens (P = 0.0439) and the presence of a lead vegetation (P = 0.024) were associated with overall failed salvage. CONCLUSIONS: In patients with definite CIED infections, clinical and laboratory variables cannot predict successful device salvage. Until new data are forthcoming, device explantation should remain a mandatory and early management intervention in patients with CIED infection in keeping with existing expert guidelines unless medical contraindications exist or patients refuse device removal.

Pneumocystis Pneumonia and the Rheumatologist: Which Patients Are At Risk and How Can PCP Be Prevented?

PURPOSE OF REVIEW: Immunosuppressive therapy for connective tissue diseases (CTDs) is steadily becoming more intense. The resultant impairment in cell-mediated immunity has been accompanied by an increasing risk for opportunistic infection (OI). Pneumocystis pneumonia (PCP) has been recognized as an OI in patients with CTDs, but specific risk factors and precise indications for PCP prophylaxis remain poorly defined. This review was undertaken to update information on the risk of PCP in patients with CTDs and to examine current guidelines for PCP prophylaxis in this population. RECENT FINDINGS: Data on the occurrence of PCP and indications for prophylaxis in patients with CTDs is sparse. Large systematic reviews did not incorporate patients with CTD secondary to the lack of randomized control trials. Upon reviewing guidelines published since 2015, prophylaxis for PCP is recommended only for patients with ANCA-positive vasculitis, specifically granulomatosis with polyangiitis (GPA), who are undergoing intense induction therapy. Evidence-based recommendations for the prophylaxis of PCP in patients with CTDs cannot be provided. There is expert consensus that PCP prophylaxis is warranted in patients with GPA undergoing induction therapy. Prophylaxis should perhaps also be considered for other CTD patients who are receiving similar intense immunosuppressive therapy especially if they are lymphopenic or have a low CD4 count.

Hemolytic anemia in two patients with glioblastoma multiforme: A possible interaction between vorinostat and dapsone.

Patients undergoing treatment for glioblastoma multiforme are routinely placed on prophylactic treatment for Pneumocystis jirovecii pneumonia because of significant therapy-induced lymphopenia. In patients with sulfa allergies, dapsone prophylaxis is often used due to its efficacy, long half-life, cost effectiveness, and general safety at low doses. However, dapsone may uncommonly induce a hemolytic anemia, particularly in patients deficient of glucose-6-phosphate dehydrogenase. This hemolysis is thought to be a result of oxidative stress on red blood cells induced by dapsone metabolites which produce reactive oxygen species that disrupt the red blood cell membrane and promote splenic sequestration. A single case report of dapsone-induced hemolytic anemia in a patient with glioblastoma multiforme has been reported. We present two patients with glioblastoma multiforme who developed severe hemolytic anemia shortly after initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor, while on prophylactic dapsone. There are several potential mechanisms by which histone deacetylase inhibition may alter dapsone metabolism including changes in hepatic acetylation or N-glucuronidation leading to an increase in the bioavailability of dapsone's hematotoxic metabolites. In addition, vorinostat may lead to increased hemolysis through inhibition of heat shock protein-90, a chaperone protein that maintains the integrity of the red blood cell membrane cytoskeleton. The potential interaction between dapsone and vorinostat may have important clinical implications as more than 10 clinical trials evaluating drug combinations with vorinostat in patients with malignant glioma are either ongoing or planned in North America.