Faculty Bibliography

Background. Currently there is conficting evidence regarding probiotics affect-ing the incidence and/or severity of Clostridium difcile infection (CDI). According to the IDSA guidelines, there are insufcient data to support the use of probiotics as primary prophylaxis of CDI. The primary objective of this study was to evaluate whether the administration of probiotics is efcacious for CDI prophylaxis in patients who are on antibiotics making them at increased risk for contracting CDI. Methods. The study is an Institutional Review Board approved retrospective cohort study looking at patients who were admitted to NYU Winthrop University Hospital and received at least one dose of antibiotics considered high-risk of inducing CDI. Patients were grouped according to concurrent probiotic use and the association between probiotic use and incident CDI was examined. A model for incident CDI adjusting for number of concurrent antibiotics, patient age, proton pump inhibitors, histamine receptor antagonists, presence of colitis, and chemotherapy was also estimated. Microbiology reports were analyzed for up to 12 weeks post initial administration of antibiotics to determine whether patient acquired CDI. If no CDI occurred during the admission or post discharge, data was censored at 12 weeks. Results. Of 2,208 patients, 1,502 (68%) were included in the interim analysis. Ninety-six out of 1,502 patients (6.39%) had CDI within 12 weeks of antibiotics initiation. One hundred thirty-fve (9%) were on probiotics during antibiotic use and 1,367 (91%) were not. Of those taking probiotics, 11.1% had an incident of CDI and of those not taking probiotics, 5.9% had an incident of CDI with a relative risk of 1.88 (1.11, 3.16) and a P = 0.02. Afer adjustment, although a positive association between probi-otics and CDI was still observed, it was not statistically signifcant (P = 0.24) Conclusion. Based on the interim analysis, probiotics were associated with a higher risk of CDI in univariate analysis, however, when adjusted for several confounding factors this association, while still positive, was no longer statistically signifcant. Further data collection is ongoing to corroborate these results

Fever of unknown origin (FUO) refers to fevers of > 101 °F that persist for > 3 weeks and remain undiagnosed after a focused inpatient or outpatient workup. FUO may be due to infectious, malignant/neoplastic, rheumatic/inflammatory, or miscellaneous disorders. The FUO category determines the focus of the diagnostic workup. In the case presented of an FUO in a young woman, there were clinical findings of both CMV infectious mononucleosis or a lymphoma, e.g., highly elevated ESR, elevated ferritin levels, and elevated ACE level, β-2 microglobulins. The indium scan showed intense splenic uptake. Lymph node biopsy, PET scan, and flow cytometry were negative for lymphoma. CMV infectious mononucleosis was the diagnosis, and she made a slow recovery.

Culture negative endocarditis (CNE) is a common concern in patients with fever, heart murmur, cardiac vegetation, and negative blood cultures. The diagnosis of CNE is not based only on negative blood cultures and a cardiac vegetation. The clinical definition of CNE is based on negative blood cultures plus the findings of culture positive infective endocarditis (IE), e.g., fever, cardiac vegetation, splenomegaly, peripheral manifestations. Because embolic splenic infarcts may occur with culture positive IE, some may assume that splenic infarcts are a sign of CNE. Previously, CNE was due to fastidious and non-culturable organisms. With current diagnostic methods, fastidious organisms grow in 2-3 days. Therefore, fastidious IE are a subset of culture positive IE, but do not represent true CNE. We describe a case of an elderly female who presented with a fever of unknown origin (FUO) and multiple splenic infarcts thought by some to represent CNE. An extensive workup for CNE pathogens was negative. The final cause of her splenic infarcts was a diffuse large B-cell lymphoma (DLBCL). Review of the literature, as well as this case, confirms that splenic infarcts are not a feature of CNE. In patients with fever, splenic infarcts, and negative blood cultures, physicians should search for an alternate explanation rather than CNE, e.g., malignancy and hypercoaguable state (lupus anticoagulant).

Current therapy of Clostridium difficile diarrhea (CDD) is problematic. Optimal treatment for CDD remains oral vancomycin, but there is little data on oral vancomycin dosing regimens. The objective of this C. difficile diarrhea study was to compare the efficacy of "high dose" vancomycin, 500 mg (PO) q6h, as sole treatment and in those who after 72 h failed to respond to conventional doses of oral vancomycin, 125-250 mg (PO) q6h. Hospitalized adults with CDD were evaluated by various oral vancomycin regimens, i.e., a conventional dose group (125-250 mg (PO) q6h), a "high dose escalation" dose group (250 mg → 500 mg (PO) q6h), and a "high dose" group (500 mg (PO) q6h). Oral vancomycin treatment groups were compared by time to improvement, i.e., decrease in >50% of watery stools/day and duration of therapy. The high dose escalation and high dose oral vancomycin groups showed the most rapid resolution of diarrhea. There was marked decrease in stools/day after "high dose" vancomycin escalation from conventional dosing, i.e., 250 mg (PO) q6h → 500 mg (PO) q6h. This study demonstrated that "high dose" escalation or initial high dose oral vancomycin, i.e., 500 mg (PO) q6h was the most efficacious regimen for CDD.

OBJECTIVE:The clinical effectiveness of tigecycline depends on appropriate use, and PK/PD (pharmacokinetic/pharmacodynamic) parameters related to dose and dosing interval. METHODS:In our 600-bed university-affiliated teaching hospital, we conducted a tigecycline efficacy review over a three-month period in 34 evaluable patients. Parameters assessed included clinical response, cure or treatment failure, once daily as q12h dosing, maintenance dosing, high dose vs. standard loading regimens, adverse effects, and the effect of infectious disease consultation on outcomes. RESULTS:colitis. Adverse effects were infrequent and limited to mild nausea/vomiting. Once daily HDT was highly effective, and the few treatment failures were related to suboptimal/split dosing regimens. CONCLUSION/CONCLUSIONS:Once daily HDT was highly effective when used to treat susceptible pathogens and when optimally dosed, i.e., 200-400 mg (IV) loading dose ×1, followed by a once daily maintenance dose of 100-200 mg (IV) q24h.

An index case of Legionnaires's disease with mediastinal adenopathy prompted us to review our recent experience with Legionnaires' disease to determine the incidence of mediastinal adenopathy of this finding in Legionnaires' disease. We reviewed the radiographic findings of 90 hospitalized adults with Legionnaires' disease from 2015 to 2017. Excluded were 11 patients with mediastinal adenopathy due to non-Legionnaires' disease causes, e.g., lymphoma. Thirty-seven of the remaining patients had both chest films and chest computed tomography (CT) scans. Of the 37 Legionnaires' disease cases, 13/37 (35%) had mediastinal adenopathy and 8/27 (24%) also had unilateral hilar adenopathy. These chest CT findings were not seen on chest films. Chest CT scans are needed to detect mediastinal adenopathy in Legionnaires' disease. Mediastinal adenopathy may be due to Legionnaires' disease or a malignancy. Some findings in Legionnaires' disease are also present in mediastinal adenopathy due to lymphomas, e.g., highly elevated erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and ferritin. Hospitalized adults with Legionnaires' disease and mediastinal adenopathy should have serial chest CT scans to monitor resolution of the mediastinal adenopathy. In hospitalized adults with otherwise unexplained persistent mediastinal adenopathy, they should be considered as being due to another etiology, e.g., lymphoma, until proven otherwise.