Saleh, Omar Abu

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 Norovirus and serotypes (40/41) of adenoviruses are the leading cause of viral acute gastroenteritis in adults. The lack of therapeutic options can be devastating especially in the immunocompromised population. Nitazoxanide (NTZ), first designed as an antifolate anti-parasitic agent, is also known to have a broad-spectrum antiviral activity. Efficacy of NTZ in decreasing duration of symptomatic diarrhea in adults was first reported in a placebo controlled trial in 2006. Subsequent reports showed some promise as a possible therapeutic agent for viral gastroenteritis in the immunocompromised hosts. Methods Utilizing the inpatient pharmacy database we identified patients, who received NTZ for documented viral gastroenteritis, from January 1, 2008 to April 15, 2019. Chart review of cases was done to determine demographics, comorbidities, length of stay (LOS) in hospital, LOS in intensive care unit (ICU), duration of therapy, improvement in symptoms, and mortality. Results We identified 48 unique adult patients who were administered NTZ in the period under review. Of these 10 were prescribed NTZ specifically for viral gastroenteritis. 40% of the patients were females. The median age was 59 years (Interquartile Range [IR]: 47.75–69.25). Median LOS in hospital was 9.5 days (IR: 6.75–41.75). None of the patients required admission to the ICU. 4/10 patients had an active concomitant malignancy, of these 3 were receiving ongoing chemotherapy. 9/10 patients were recipients of stem cell (2) or solid-organ transplants (7). 7/10 patients were also on some form of immunosuppressive medications. Most common virus isolated was Norovirus (7/10). All patients received a standard dose of 500mg twice daily NTZ. The median duration of therapy was 7 days (range: 3–21). 6/10 patients had documented improvement in diarrhea at the end of treatment. 1/10 patients died within 30 days of diagnosis from causes unrelated to diarrheal illness (Table 1). Conclusion Our limited data set presents interesting insights into treatment of viral gastroenteritis in immunocompromised hosts, in particular transplant recipients. All of the cases identified were treated in second half of study period after January 1, 2015, signaling an increasing interest in this therapy, especially in cases with prolonged symptoms or viral shedding. Our observations indicate a need for larger studies into this application of NTZ in adult immunocompromised hosts. Disclosures All authors: No reported disclosures.

Abstract Background Mycobacterium marinum is a slow-growing, non-tuberculous mycobacterium responsible for skin and soft-tissue infections (SSTIs), tenosynovitis, and osteomyelitis (OM). We conducted a retrospective study describing the risk, clinical course, and outcome of M. marinum infection. Methods Adult patients with culture-confirmed M. marinum infections were identified from the mycology laboratory at Mayo Clinic, Rochester from January 1998 to December 2018. M. marinum infection was defined as uncomplicated (limited to SST) and complicated (tenosynovitis, OM, or disseminated). Results Forty-six cases of culture-confirmed infection with M. marinum were included (Table 1). Only 16 cases (35%) reported a water exposure and 22 (48%) involved finger and/or hand trauma. The median time to diagnosis was 3.6 months. Most patients (76%) presented with uncomplicated M. marinum infection with skin lesions mainly localized in the upper limb (Table 2). QuantiFERON and PPD were positive in 4 (8%) and 2 (4%) cases, respectively. Granulomatous inflammation and positive special stains were noted in 34 (74%) and 11 (24%) cases, respectively. Cases with complicated M. marinum infection had a longer duration of symptoms and length of treatment (P < 0.05) (Table 3). Prior to diagnosis, 63% of patients received at least one antibiotic for bacterial SSTIs. More than 50% of the patients diagnosed with M. marinum received a one drug regimen and 8% did not initiate therapy. Median treatment duration was 4.4 months. Twenty-six cases (56%) had susceptibilities performed and treatment modifications were made in 10 cases (38%). From the patients that started therapy, 73% completed therapy and 33% were lost to follow up. Cured was achieved in 87% of cases that completed therapy, 2 cases (6%) had a recurrence, and only one patient with active malignancy had a positive blood culture and died. Twelve (44%) and 10 cases (37%) were cured with one and two-drug regimens, respectively. Conclusion Most patients with M. marinum infection present as an uncomplicated infection in the upper limb. Classical exposure was only suspected in a third of the cases. Patients with complicated M. marinum infection had a prolonged duration of symptoms and lengthy treatment. Most patients were successfully treated with a one and two-drug regimen. Disclosures All authors: No reported disclosures.

Patients with febrile neutropenia (FN) often are subject to antibiotic and diagnostic test overuse. We sought to improve appropriate use of antimicrobials and diagnostic tests for patients with FN. We used a blended quality approach with Lean Six Sigma tools and iterative improvement of a clinical decision aid to guide providers through empirical antimicrobial selection and diagnostic evaluation of patients with FN during a yearlong period. We evaluated the incidence of nonadherence to best practice before, during, and after rollout of a clinical decision aid in conjunction with an educational initiative. At baseline, 71% of patients with FN had at least one critical deviation from best practice. During the project, the percentage decreased to 27.3%; 4 months after the project was completed, the percentage was 33.3% ( P = .04). A clinical decision aid can improve adherence to best practices for the empirical management of FN.

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.