Challener, Douglas W.

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 Background Sepsis frequently leads to acute kidney injury. In severe cases, patients may require continuous renal replacement therapy (CRRT) which involves placement of a dialysis catheter and an extracorporeal blood filtration circuit. CRRT is commonly considered to “mask” fever, though this phenomenon has not been investigated. Methods We queried an institutional database of all patients on CRRT from 2007 to 2015 for inpatient temperature data and antibiotic administration records. Receipts of piperacillin–tazobactam, a carbapenem, or a third or fourth-generation cephalosporin, indicating a serious infection, were considered intervention arm. We analyzed temperatures recorded in the intensive care unit before, during, and after CRRT. Patients were divided into groups that did not receive antibiotics as well as those who did. Temperature data were Winsorized to correct for outliers. We also performed descriptive statistics for each group. Results There were 237,988 temperature readings for 1,568 ICU patients on CRRT. 1,153 patients received broad-spectrum antibiotics in ICU. In patients who received antibiotics in ICU and were presumed to have an infection, the mean temperature was 37.2°C prior to initiation of CRRT, 36.8°C while on CRRT, and 37.2°C following discontinuation of CRRT. In the 415 patients who did not receive IV antibiotics, the mean temperature was 36.9°C prior to initiation of CRRT, 36.6°C while on CRRT, and 37.0°C following discontinuation of CRRT. During each of the periods before, during, and after CRRT, patients who received antibiotics had significantly higher temperatures than those who did not (P < 0.001). Patients receiving antibiotics were generally younger (mean 60 years vs. 64 years, P < 0.001), had longer ICU stays (mean 29 days vs. 12 days, P < 0.001) and spent more time being ventilated (mean 23 days vs. 7 days, P < 0.001). The mean SOFA score on day one was similar (mean 11.1 in the antibiotic group and 10.5 in the other group). Conclusion This investigation suggests that patients have slightly lower temperatures while on CRRT, by on average less than half a degree. A similar effect is seen in both patients with infections as well as those without. Further work will be needed to determine what constitutes a true febrile response in this population. Disclosures All authors: No reported disclosures.

AbstractHistoplasma capsulatum is an endemic fungus that most oftenly causes a self‐limiting illness but can result in severe infections in immunocompromised patients including pulmonary or extra‐pulmonary disease. Rarely it can also cause a chronic progressive infection of the larynx. Herein, we report a case of laryngeal histoplasmosis in a kidney transplant patient who presented with progressive symptoms of several weeks of hoarseness, dysphagia and odynophagia. Laryngoscopic examination revealed thick plaques in the oropharynx with surrounding hyper‐erythema and histopathology showed numerous intracellular yeasts forms consistent with H capsulatum. Patient was initiated on treatment with itraconazole. Infection of the larynx due to H capsulatum is highly uncommon and therefore can result in an inappropriate or delayed diagnosis. A review of literature showed four previously reported cases of laryngeal histoplasmosis in patients with solid organ transplant. This is the first case series of laryngeal histoplasmosis in transplant recipients.

AbstractA 51‐year‐old woman from Wisconsin with past medical history of kidney transplantation from her sibling 8 weeks prior, presented with symptoms of shortness of breath, cough, and a new skin rash over a 2‐week period.