Fida, Madiha

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

Abstract Background Polymerase chain reaction (PCR)/sequencing targeting the 16S ribosomal RNA (rRNA) gene to detect bacteria in normally sterile tissues and fluids has become increasingly popular in clinical medicine. This culture-independent technique can detect bacteria that are nonviable or difficult to cultivate using conventional methods. The clinical value of this type of testing is not well defined. We aimed to assess the diagnostic value of 16S rRNA PCR/Sanger sequencing as a clinical diagnostic assay at Mayo Clinic. Methods This is an interim analysis of the first 173 of 478 patients who had 16S rRNA PCR/Sanger sequencing done on sterile tissues or fluids at our institution from April, 2017 to November, 2018 as part of routine clinical practice. Medical records are being retrospectively reviewed, with results compared with those of culture. Results We reviewed 207 specimens from 173 patients (musculoskeletal 79%, cardiovascular 7%, central nervous system 4%, other 9%) that underwent 16S rRNA PCR/Sanger sequencing by clinical request (Table 1). In 90% of these specimens, the test was pre-planned rather than added-on. Nine specimens were excluded from analysis, as cultures were not performed. Overall concordance of culture with PCR/sequencing was 81% (160/197; P < 0.0001). Of 44 culture-positive specimens, PCR detected the same bacterium in 21 (48%) (Table 2). 45% (20/44) of those with positive cultures and 46% of those with positive PCR/sequencing results had received prior antimicrobial therapy (Table 3). PCR was negative in 139/144 specimens that were culture-negative (97%). PCR/sequencing was helpful in detecting a putative bacterial pathogen in 4 patients with negative cultures (Table 4). Conclusion Overall, 16S rRNA PCR/Sanger sequencing improved diagnostic yield compared with culture in a minority of cases. The described assay is limited by its inability to detect polymicrobial infections, a technical limitation that could possibly be addressed using massive parallel sequencing. Careful selection of cases and a save and add-on approach may be more cost-effective than upfront testing, although this was requested in a minority of cases. Disclosures Robin Patel, MD, ASM and IDSA: Other Financial or Material Support, Travel reimbursement, editor’s stipends; CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited, Shionogi: Grant/Research Support; Curetis, Specific Technologies, NextGen Diagnostics, PathoQuest, Qvella: Consultant; NBME, Up-to-Date, the Infectious Diseases Board Review Course: Honorarium recipient, Other Financial or Material Support; Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued: Other Financial or Material Support, Patents.

Abstract Babesiosis is an emerging health risk, and clinicians need to be aware of its different clinical manifestations. In our cohort of 38 patients, almost half did not recall a tick bite, and diagnosis was delayed due to the nonspecific nature of symptoms. Sixty-eight percent of patients required hospitalization, with 21% requiring intensive care unit stay. Coinfection with Lyme, anaplasma, or both Lyme and anaplasma was seen in 24%, 5%, and 8% of the patients, respectively. None of the patients in our cohort died from their disease.

Abstract Human herpesviruses 6 (HHV-6) A and B cause encephalitis in patients with hematologic malignancies, especially those undergoing allogeneic hematopoietic stem cell transplantation. In this cohort of 10 patients, persistent neurologic deficits associated with moderate to severe bilateral hippocampal atrophy were characteristic long-term findings, despite prolonged antiviral treatment.

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 Stenotrophomonas maltophilia is a hospital acquired infection that is associated with high morbidity and mortality. There has been a reported rise in S. maltophilia infections, presumed secondary to the increase in the population at risk. Methods We retrospectively reviewed all hospitalized adult patients in Mayo Clinic, MN with S. maltophilia bacteremia from January 2008 through January 2018. We analyzed patient population and described patients at risk, sources of infection, and changes in antimicrobial susceptibility profile. Results A total of 94 patients were analyzed, including 52 males, median age of 56 (46–65.75 IQR). The population included 60 infections in those with malignancies and 30 infections in transplant recipients. At presentation, 58 (61.7%) were febrile, while 54 (58.1%) presented with hemodynamic instability. Majority (70.2%) received broad-spectrum antimicrobials within 2 weeks of presentation. The most common source was catheter associated infection (n = 60), 15 cases were secondary to gastrointestinal, and 9 due to a pulmonary source. Almost half, 46 (48.9%) required ICU admission. Two patients were diagnosed with endocarditis. Most isolates, 61(64.9%), were resistant to ceftazidime, 2 (2.2%) resistant to TMP/SMX and 20 (21.5%) were resistant to levofloxacin. Exposure to a quinolone in the 30 days prior to presentation did not impact fluoroquinolone resistance. Five patients were exposed to Trimethoprim/Sulfamethoxazole (TMP/SMX) in the 30 days prior to presentation, which was associated with higher rate of TMP/SMX resistance compared with those without exposure (80% vs. 98.8%, P = 0.004). Treatment options commonly included combination therapy, and TMP/SMX was a primary agent used in the majority, 59 (62.8%). All-cause in-hospital mortality was 26.6%. All-cause mortality was lower for line associated infections (16.67%) vs. other sources (44.12%) with P = 0.0038. Conclusion S. maltophilia bacteremia should be considered in hospitalized patients with recent use of broad-spectrum antibiotics. Although TMP/SMX continues to have reliable activity, use of empiric ceftazidime pending susceptibility testing should be avoided as trend toward increasing resistance is noted. We noted a drop in TMP/SMX susceptibility in those with recent reported TMP/SMX use. Disclosures All authors: No reported disclosures.

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.