Sepsis remains among the most common complications from infectious diseases worldwide. The morbidity and mortality rates associated with sepsis range from 20% to 50%. The advances in care for patients with an immunocompromised status have been remarkable over the last 2 decades, but sepsis continues to be a major cause of death in this population Immunocompromised patients who are recipients of a solid organ or hematopoietic stem cell transplant are living longer with a better quality of life. However, some of these patients need lifelong treatment with immunosuppressive medications to maintain their transplant status. A consequence of the need for this permanent immunosuppression is the high risk of opportunistic, community, and hospital-acquired infections, all of which can lead to sepsis. In addition, the detection of serious infections may be more challenging owing to patients’ lower ability to mount the clinical symptoms that usually accompany sepsis. This article provides an update on the current knowledge of sepsis in immunocompromised patients without human immunodeficiency virus. It reviews the most pertinent causes of sepsis in this population, and addresses the specific diagnostic and therapeutic challenges in neutropenia and solid organ and hematopoietic stem cell transplantation.

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BackgroundIn 2016, our academic medical center implemented the BioFire® FilmArray® Meningitis/Encephalitis Panel (MEP), which detects 14 viral, bacterial, and fungal pathogens. Institutional guidelines recommended the test be used in nonimmunocompromised patients age ≥2 years only if the cerebrospinal fluid (CSF) white blood cell (WBC) count was >10 cells/mm3.MethodsWe reviewed all MEP performed at our institution over 2 years (January 1, 2017 to December 31, 2018). We collected CSF WBC count, protein, and glucose; MEP results; CSF culture results; and demographics. We excluded children age <2 years, immunocompromised patients, those without a CSF WBC count, and duplicate tests during the same illness.ResultsOf 453 patients, 311 met inclusion criteria. The median age was 51, 51% male. Median CSF indices: WBC/mm3 = 4, protein = 57 mg/dL, glucose = 66 mg/dL. MEP positivity rate = 12% (37/311): viruses (29/37), bacteria (7/37), and fungi (1/37). Positive bacterial/fungal MEP results compared with CSF culture are summarized in Table 1. No clinically significant discordant negative MEP results occurred compared with CSF culture, cryptococcal antigen, or other viral PCR testing. Of the 311 patients, 184 (59%) had ≤10 CSF WBC/mm3. Of these, 4 had positive MEP results: 1 enterovirus, 1 human herpes virus 6 (HHV-6) and 2 varicella zoster virus (VZV). The HHV-6 was judged clinically insignificant. The 2 VZV cases had concomitant shingles and were already on acyclovir. No clinically significant MEP results occurred in 110/311 (35%) patients with ≤ 2 CSF WBC/mm3.ConclusionIn nonimmunocompromised patients, age ≥ 2, with ≤ 10 CSF WBC/mm3 on lumbar puncture, positive MEP results were rare and the clinical significance of the 4 positives was debatable. A hard-stop restriction in this setting could have reduced overall use by up to 59% and resulted in significant cost savings. Lower CSF WBC/mm3 cut-offs could be considered and still improve MEP utilization. Disclosures All Authors: No reported Disclosures.

BackgroundAdherence to the Infectious Diseases Society of America (IDSA) guidelines for the treatment of diabetic foot infections (DFIs) has been associated with improved outcomes. Yet, compliance with these guidelines has been reported to be low. We initiated a quality improvement project aimed at improving guideline adherence for DFI management. Baseline results are reported here.MethodsWe reviewed all hospitalized primary DFIs newly initiated on antibiotics over 1 year (July 2014–June 2015). We collected demographics, DFI severity per IDSA guidelines, antibiotic use, and microbiology data. Guideline adherence for culturing and empiric antibiotic choice (based on severity) was assessed per IDSA guidelines. We then created an institutional guideline and electronic order set with built-in clinical decision support. Educational lectures on DFI best practices were given to providers who commonly treat DFIs.ResultsOne hundred seventy-seven DFI admissions were identified: 40% severe (n = 70), 47% moderate (n = 84), 8% mild (n = 14), and 5% with no evidence of infection (n = 9). Demographics: mean age 58 years; 68% male, mean HgbA1c 8.6%, length of stay 6.9 days, 3-year mortality 13%. Empiric antibiotic regimens were judged inappropriate in 36% (64/177) of cases. The most common reason for inappropriate antibiotic use was unnecessary coverage for Pseudomonas aeruginosa in 50% (54/107) of nonsevere cases. In 28% (39/140) of cases with an ulcer, wound or skin breakdown, a superficial swab culture was obtained which is inappropriate. Only 33.3% (n = 56) had a deep tissue culture obtained. In patients with deep tissue cultures, methicillin-resistant Staphylococcus aureus (MRSA) was found in 11% (6/56) of cases but covered for empirically in 88% (50/56). Pseudomonas was found in 2% (1/56) of cases but covered for empirically in 73% (41/56).ConclusionMRSA and Pseudomonas are uncommon DFI pathogens yet are frequently treated empirically. Inappropriate antibiotic use is often due to empiric coverage for Pseudomonas in nonsevere DFIs where it is a rare pathogen. Culture practices are also less than ideal with frequent superficial swabs and underutilization of deep cultures. Institutional guidelines were developed to specifically address these issues and data collection of the impact of this project is in process.Disclosures S. Bergman, Merck: Grant Investigator, Grant recipient. T. Vanschooneveld, Merck: Grant Investigator, Grant recipient.

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