Baddour, Larry M.

Abstract Background Histoplasma capsulatum is an extremely rare cause of prosthetic valve endocarditis (PVE) and can present with non-specific symptoms leading to a delay in diagnosis with unfavourable outcomes. Case summary A 65-year-old male patient with a history of a bioprosthetic aortic valve replacement and non-obstructive coronary artery disease was admitted for altered mentation, failure to thrive, and a 20-pound unintentional weight loss over the past 4 months. Upon examination, he was lethargic but afebrile and haemodynamically stable. A late peaking ejection murmur was heard on exam. Skin exam was significant for embolic phenomenon involving the extremities. Inflammatory markers and serum calcium were elevated. A bedside echocardiogram showed severe obstruction across the aortic valve prosthesis. Two years prior, he had an echocardiogram with a normal functioning prosthesis. Routine blood cultures were negative and serologic screening was unrevealing. Urine Histoplasma antigen screen was positive on hospital day 3 and on hospital day 10, fungal blood cultures were positive for H. capsulatum. Unfortunately, the patient died shortly afterwards as a result of multiorgan failure from embolic manifestations of the infection. Discussion Based on our patient's findings and those of previously reported cases in the literature, H. capsulatum PVE should be strongly considered in patients from endemic areas with non-specific symptoms and negative routine blood cultures.

AbstractBackgroundEnterococcal cardiovascular implantable electronic device (CIED) infections are not well characterized.MethodsData from the Multicenter Electrophysiologic Device Infection Cohort, a prospective study of CIED infections, were used for descriptive analysis of adults with enterococcal CIED infections.ResultsOf 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.ConclusionsEnterococci 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%.

Dentists prescribe a large portion of all oral antibiotics, and these are associated with a risk of adverse drug reactions (ADRs). The aim of this study was to quantify the risk of ADRs associated with oral antibiotics commonly prescribed by dentists. NHS Digital Prescribing data and Yellow Card Drug Analysis data for 2010 to 2017 were abstracted to quantify dental antibiotic prescribing in England, and the rate and types of ADRs associated with them. During the period of study, the mean number of actively practicing dentists in England was 23,624. Amoxicillin accounted for 64.8% of dental antibiotic prescribing and had the lowest reported rate of fatal ADRs (0.1/million prescriptions) and overall ADRs (21.5/million prescriptions). Indeed, amoxicillin was respectively 6 and 3 times less likely to cause an ADR than the other penicillins, penicillin V and amoxicillin + clavulanic acid, and appears to be very safe in patients with no history of penicillin allergy. In contrast, clindamycin, which is often used in patients with penicillin allergy, had the highest rate of fatal (2.9/million prescriptions) and overall (337.3/million prescriptions) ADRs, with Clostridiodes (formerly Clostridium) difficile infections pivotal to its ADR profile. Other amoxicillin alternatives, clarithromycin and metronidazole, while significantly worse than amoxicillin, were 3 and nearly 5 times less likely to cause an ADR than clindamycin. Ranked from least to most likely to cause an ADR, antibiotics most commonly prescribed were as follows: amoxicillin < cephalosporins < erythromycin < tetracyclines < azithromycin < metronidazole < amoxicillin + clavulanic acid < clarithromycin < penicillin V < clindamycin. This study confirmed the high level of safety associated with use of amoxicillin by dentists and the significantly worse rates of fatal and nonfatal ADRs associated with other penicillins and alternatives to amoxicillin for those who are penicillin allergic. In particular, clindamycin had the highest rate of fatal and nonfatal ADRs of any of the antibiotics commonly prescribed by dentists.

Abstract Background Sonicate fluid (SF), a solution derived from vortexing and sonication of explanted cardiovascular implantable electronic devices (CIEDs), is a higher-yield specimen compared with swabs or tissues for culture-based detection of microorganisms associated with CIED infection. Despite this, SF culture fails to identify a causative organism in ~50% of cases. We aimed to evaluate the diagnostic performance of 16S ribosomal RNA gene (rRNA) polymerase chain reaction (PCR)/sequencing of SF and compare it with that of SF culture. Methods We identified 322 SF specimens from extracted CIEDs and reviewed clinical data for each patient. Subjects were classified as having or not having CIED infection. Cases were subcategorized as culture negative if no significant growth was reported from SF cultures and as culture positive if an organism was detected above predefined thresholds. 16S rRNA PCR/sequencing was performed, with the organisms identified reported according to Clinical and Laboratory Standards Institute guidelines for sequence data interpretation. Results A total of 278 SF samples corresponded to infected cases, of which 160 were culture positive and 118 culture negative. The remaining 44 were from noninfected cases, of which 2 were culture positive. Compared with SF culture, the sensitivity of 16S rRNA PCR/sequencing was higher (64% vs 57.5%, P = .003). 16S rRNA PCR/sequencing detected a potential pathogen in 28 of 118 culture-negative cases, identifying staphylococci in the majority (18/28). Conclusions 16S rRNA PCR/sequencing has higher sensitivity to detect bacteria in SF from extracted CIEDs than does SF culture.

Abstract Background Unlike enterococcal native and prosthetic valve infective endocarditis (IE), enterococcal CIED infections are not well described. Methods Data from the Multicenter Electrophysiologic Device Infection Collaboration (MEDIC), a prospective, observational, multinational cohort study of CIED infections, were used to provide a descriptive analysis of adult patients with CIED infections due to enterococcal species. Results Of 433 patients, 21 (4.8%) were diagnosed with enterococcal CIED infection. Specific data on enterococcal species and antimicrobial susceptibilities were not recorded. The mean age was 70.8 years. No patient had previous CIED infection. Twelve patients (57%) had permanent pacemakers, 5 (24%) had implantable cardioverter defibrillators, and 4 (19%) had biventricular devices. Among the 21 infections, 3 (14%) were categorized as CIED-related bloodstream infections and 18 (86%) as IE; no patient had isolated pocket infection. Of the IE cases, four were valvular IE, eight were lead IE, and six were both. Fourteen cases of IE (78%) were definite by the modified Duke criteria. Median time from last device procedure to infection was 510 days (range 37–2,952 days). The most common presenting symptom was fever (48%); five patients (24%) exhibited local signs of pocket infection. All 21 patients underwent TEE with vegetations demonstrated in 17 (81%). Blood cultures grew enterococci from all patients. The most common antimicrobial regimen was a penicillin plus aminoglycoside (38%); two patients (9.5%) received ampicillin + ceftriaxone. Antibiotics were given for a median of 43 days. Only 14 patients (67%) had complete device removal; the seven patients retaining their device were judged to be at high risk for extraction. There was one death during the index hospital stay with four additional patients dying over the 6 months after therapy (overall mortality 24%); two of the seven patients retaining their CIED died. Conclusion Enterococci caused 4.8% of all CIED infections in our cohort. Most infections appeared to be hematogenous in origin with late onset. IE was the most common infectious syndrome. A penicillin plus aminoglycoside, given for 6 weeks, was the most frequent therapy. Only 67% of patients underwent device removal. At 6 months follow-up, no relapses had occurred but overall mortality was 24%. Disclosures J. E. Peacock Jr., Pfizer, Inc.: Shareholder, Owns common stock in Pfizer which was inherited and held in a trust. M. R. Sohail, TyRx Inc.: Investigator, Research support. Medtronic Inc.: Investigator, Research support. Medtronic Inc.: Consultant, Speaker honorarium. Spectranetics: Consultant, Speaker honorarium. Boston Scientific Corp: Consultant, Speaker honorarium. L. M. Baddour, UpToDate: Collaborator, Royalty payment. J. M. Miro, Abbvie: Consultant and Grant Investigator, Consulting honoraria and Research grant. Bristol-Myers Squibb: Consultant and Grant Investigator, Consulting honoraria and Research grant. Genentech: Consultant and Grant Investigator, Consulting honoraria and Research grant. Medtronic: Consultant and Grant Investigator, Consulting honoraria and Research grant. Novartis: Consultant and Grant Investigator, Consulting honoraria and Research grant. Gilead Sciences: Consultant and Grant Investigator, Consulting honoraria and Research grant. Pfizer: Consultant and Grant Investigator, Consulting honoraria and Research grant. ViiV Healthcare: Consultant and Grant Investigator, Consulting honoraria and Research grant. A. J. Greenspon, Medtronic: Consultant, Speaker honorarium. Boston Scientific: Consultant, Speaker honorarium. St. Jude: Consultant, Speaker honorarium. R. G. Carrillo, St. Jude Medical Group: Speaker’s Bureau, Research support. Spectranetics: Consultant, Speaker honorarium. Sorin Group: Speaker’s Bureau, None. Boston Scientific Corp: Speaker’s Bureau, None. D. Z. Uslan, Medtronic: Investigator, Research support. Boston Scientific: Consultant, Speaker honorarium.

Abstract Background Nutritionally variant streptococci (NVS) are an infrequent cause of infective endocarditis (IE) and management recommendations are based on weak levels of evidence largely derived from case reports, small case series, and animal models of experimental endocarditis. Moreover, taxonomic changes have led to some confusion in designation of these organisms. Methods We retrospectively collected and analyzed data from 33 patients with NVS IE from 1970 to 2017. Only patients who met modified Duke Criteria for IE were included. Results Mean patient age was 55 years and 61% were males. The most common comorbidities included diabetes mellitus (12%), malignancy (3%), heart failure (16%), coronary artery disease (25%), and chronic liver disease (9%). Predisposing valve abnormalities included rheumatic heart disease (11%), bicuspid aortic valve (22%), transplant valvulopathy (3%), mitral valve prolapse (3%), and congenital heart disease (11%). Cultures were reported as NVS (70%), Granulicatella species (18%) and Abiotrophia species (12%). Echocardiogram findings included vegetations (67%), new regurgitation (55%), perivalvular abscess (3%), mitral valve prolapse (3%), and ruptured mitral valve chordae (3%). Both prosthetic (26%) and native valve IE (74%) was seen, and the valves involved were aortic (37%), mitral (50%) and both aortic and mitral (13%). Complications were seen in 27% of patients, including heart failure (17%), splenic infarct (11%), stroke (8%), mycotic aneurysm (3%), and glomerulonephritis (2%). In vitro susceptibility to penicillin, ceftriaxone, and vancomycin was 88%, 80%, and 100%, respectively. The majority (77%) of patients were treated with a combination of β-lactam and aminoglycoside. Median duration of treatment was 33 days. Surgery was performed in 50% of patients with no significant difference in survival between those who were treated with combined medical/surgical treatment and those treated with medical therapy alone. Overall survival at 1, 4, and 10 years was 93%, 83%, and 66%, respectively. Conclusion IE due to NVS is a rare entity and is associated with a high rate of serious complications and may involve multiple valves. Long-term, two-thirds of the patients survived more than 10 years. Disclosures All authors: No reported disclosures.