Vitreous and Chorioretinal Lesions in People Who Inject Drugs and Are Hospitalized with Bloodstream and Related Infections.

PURPOSE: To determine the prevalence of and to characterize vitreous and chorioretinal lesions, to identify causative organisms, and to correlate symptoms with ophthalmic involvement in people who inject drugs and are hospitalized with bloodstream infection (BSI), related metastatic foci of infection (MFI), or both. DESIGN: An academic hospital-based cross-sectional study. PARTICIPANTS: Patients admitted with BSI or MFI related to injection drug use (IDU). METHODS: Patients underwent a complete eye examination within 72 hours of enrollment. Characteristics including gender; age; race; injection drug of choice (DOC); presence of coinfection with hepatitis B, hepatitis C, or human immunodeficiency virus; pathogen causing systemic infection and type of infection; and history of prior infection related to IDU were recorded. MAIN OUTCOME MEASURES: Presence of vitreous or chorioretinal findings, or both. RESULTS: Ninety-one unique patients with 96 separate hospitalizations for systemic infection were enrolled from March 28, 2018, through March 30, 2020. Vitreous or chorioretinal involvement was identified in 16 of 96 patients (16.7%). The most common ocular findings were intraretinal or white-centered hemorrhage in 9 of 96 patients, chorioretinal infiltrate in 8 of 96 patients, endophthalmitis in 5 of 96 patients, and cotton wool spots in 3 of 96 patients. Of the patients with ocular involvement, only 7 of 16 patients (44%) were symptomatic, and 5 of these were patients with endophthalmitis; the others showed chorioretinal infiltrates or intraretinal or white-centered hemorrhage and cotton wool spots. Staphylococcus aureus was the most common causative pathogen in patients with and without ocular findings. Presence of ocular symptoms, worse visual acuity, and injection DOC of methamphetamine were correlated with the presence of ocular findings. CONCLUSIONS: Patients without ocular symptoms with systemic infections related to IDU may have chorioretinal findings. Further study is needed to characterize better the epidemiologic features of these infections and to identify risk factors for ocular involvement in people who inject drugs.

Transcranial Doppler Emboli Monitoring for Infective Endocarditis.

BACKGROUND AND PURPOSE: Ischemic stroke can occur in 20-55% of patients with infective endocarditis (IE) with 75% occurring during the first 2 weeks of treatment. CT or MRI brain can diagnose the sequelae of stroke but transcranial Doppler (TCD) can document active embolization. We undertook a retrospective review of our patient cohort and a systematic review of literature to assess the role of TCD in early diagnosis and management of ischemic stroke in IE. METHODS: Retrospective chart review and literature review. RESULTS: We found 89 patients with stroke caused by IE at our institution from December 2011 to April 2018. TCDs were obtained on 26 patients; 16 were abnormal for cerebrovascular abnormalities. Only 4 patients had 30-minute emboli monitoring performed, of which one revealed emboli. We found 3 studies investigating the role of TCDs in IE that showed promise in its use as a predictive tool in stroke risk stratification. CONCLUSIONS: Presence of embolization in the form of high-intensity transient signals (HITS) detected on TCDs can be used for early diagnosis of IE, assessing efficacy of antibiotic therapy, and stratification of stroke risk in IE. This can aid further research into testing preventative interventions for reducing stroke burden in IE such as earlier valvular surgery or vacuum-assisted vegetation extraction.

Left-sided infective endocarditis in persons who inject drugs.

PURPOSE: The purpose of this study was to describe left-sided infective endocarditis (LSIE) in persons who inject drugs (PWID) and compare that group to PWID with non-LSIE and to non-PWID with LSIE. METHODS: Retrospective single-center study of adult IE patients from 2011 to 2018. RESULTS: Of the 333 patients in our cohort, 54 were PWID with LSIE, 75 were PWID with non-LSIE, and 204 were non-PWID with LSIE. When comparing LSIE vs non-LSIE in PWID, the LSIE group was older (median age 35 vs 28.5, p < 0.01), had fewer S. aureus infections (59% vs 92%, p < 0.01), was more likely to have cardiac surgery (31% vs 13%, p < 0.01), and had a higher 10-week mortality (22% vs 5%, p < 0.01). When comparing PWID with LSIE to non-PWID with LSIE, the PWID group were younger (median age 35 vs 46, p < 0.01); had more frequent multi-valve involvement (33% vs 19%, p = 0.04), Staphylococcus aureus infections (54% vs 27%, p < 0.01), and previous IE (24% vs 8%, p < 0.01); and experienced more strokes (54% vs 31%, p < 0.01). Ten-week mortality was similar for LSIE in both PWID and non-PWID (24% vs 20%, p = 0.47). CONCLUSIONS: LSIE in PWID is not uncommon. Compared to non-LSIE in PWID, valve surgery is more common and mortality is higher. For reasons that are unclear, stroke is more frequent in LSIE in PWID than in non-PWID with LSIE but mortality is no different.

Practice Patterns of Pneumocystis Pneumonia Prophylaxis in Connective Tissue Diseases: A Survey of Infectious Disease Physicians.

BACKGROUND: Immunosuppressive therapy for connective tissue diseases (CTDs) increases risk for opportunistic infections including Pneumocystis pneumonia (PCP). High mortality rates are reported in CTD patients with PCP, which suggests a potential need for prophylaxis, but indications remain poorly defined. Wide variations in the use of PCP prophylaxis among rheumatologists have been documented. This study evaluated PCP prophylaxis patterns for CTD patients among infectious disease (ID) physicians. METHODS: An electronic survey was emailed to 1264 adult ID physicians who are members of the Infectious Diseases Society of America Emerging Infections Network. RESULTS: Six hundred thirty-one physicians responded to the survey. Respondents to the survey were more likely to work in academics (P = .02) and be early (<5 years) or late (≥25 years) in their careers (P = .0002). Forty-three percent (n = 269) made no recommendations for PCP prophylaxis in non-HIV patients. Of the 362 respondents who did make such recommendations, the greatest consensus for disease-based prophylaxis was for granulomatosis with polyangiitis (53%). For therapy-based prophylaxis, corticosteroids ≥20 mg/d was the most frequently cited indication (87%). Surrogate laboratory markers to aid in decisions about prophylaxis were not routinely used (21%). Although the majority recommended discontinuation of PCP prophylaxis with tapering of corticosteroids (65%), there was variability in the specific dose. Eighty-nine percent of respondents felt that guidelines about PCP prophylaxis would be helpful. CONCLUSIONS: There is little consensus about PCP prophylaxis in CTDs among ID physicians. Guidelines for PCP prophylaxis would be helpful when caring for these complex patients.

Repeat Infective Endocarditis in Persons Who Inject Drugs: "Take Another Little Piece of my Heart".

BACKGROUND: Injection drug use (IDU) is a major risk factor for infective endocarditis (IE). Few data exist on repeat IE (rIE) in persons who inject drugs (PWID). METHODS: Patients ≥18 years old seen at Wake Forest Baptist Medical Center from 2004 to 2017 who met Duke criteria for IE and who self-reported IDU in the 3 months before admission were identified. The subset of PWID who developed rIE, defined as another episode of IE at least 10 weeks after diagnosis of the first episode, was then reviewed. RESULTS: Of the 87 PWID who survived their first episode of IE, 22 (25.3%) experienced rIE and 77.3% had rIE within a year of the first episode. All patients who experienced rIE resumed IDU between episodes of IE. Of the patients with rIE, 54.5% had an infection caused by S. aureus and 22.7% required surgical intervention. Mortality at 1 year was 36.3%. Compared with their first IE episode, patients with rIE had fewer S. aureus infections (P = .01). Compared with PWID who experienced single-episode IE, intravenous prescription opioid use (P = .01), surgery (P < .01), tricuspid valve involvement (P = .02), and polymicrobial infection (P = .03) occurred more often during first episodes of IE in individuals who then developed rIE. CONCLUSIONS: rIE is common among IDU-related IE and confers a high 1-year mortality rate. The microbiology of rIE is varied, with S. aureus being less frequently isolated. More studies on modification of social and clinical risk factors are needed to prevent rIE.

Infectious Scleritis: What the ID Clinician Should Know.

Scleritis is an inflammatory process involving the outer coating of the globe which is characterized by focal or diffuse hyperemia, moderate to severe pain, and frequent impairment of vision. Most cases of scleritis are autoimmune in nature and are managed with topical and/or systemic corticosteroids. Infectious scleritis is a less common entity, occurring in 5%-10% of cases, and requiring directed antimicrobial therapy. We present a case of Nocardia farcinica anterior nodular scleritis diagnosed via positive culture of an excisional biopsy of a scleral nodule. The patient improved after combined surgical and medical therapy with amoxicillin-clavulanate and moxifloxacin for 12 months. Based on a literature review, a summary of reported cases of infectious scleritis is provided, and guidelines pertaining to diagnosis and management are offered.

Pneumocystis Pneumonia and the Rheumatologist: Which Patients Are At Risk and How Can PCP Be Prevented?

PURPOSE OF REVIEW: Immunosuppressive therapy for connective tissue diseases (CTDs) is steadily becoming more intense. The resultant impairment in cell-mediated immunity has been accompanied by an increasing risk for opportunistic infection (OI). Pneumocystis pneumonia (PCP) has been recognized as an OI in patients with CTDs, but specific risk factors and precise indications for PCP prophylaxis remain poorly defined. This review was undertaken to update information on the risk of PCP in patients with CTDs and to examine current guidelines for PCP prophylaxis in this population. RECENT FINDINGS: Data on the occurrence of PCP and indications for prophylaxis in patients with CTDs is sparse. Large systematic reviews did not incorporate patients with CTD secondary to the lack of randomized control trials. Upon reviewing guidelines published since 2015, prophylaxis for PCP is recommended only for patients with ANCA-positive vasculitis, specifically granulomatosis with polyangiitis (GPA), who are undergoing intense induction therapy. Evidence-based recommendations for the prophylaxis of PCP in patients with CTDs cannot be provided. There is expert consensus that PCP prophylaxis is warranted in patients with GPA undergoing induction therapy. Prophylaxis should perhaps also be considered for other CTD patients who are receiving similar intense immunosuppressive therapy especially if they are lymphopenic or have a low CD4 count.

Hemolytic anemia in two patients with glioblastoma multiforme: A possible interaction between vorinostat and dapsone.

Patients undergoing treatment for glioblastoma multiforme are routinely placed on prophylactic treatment for Pneumocystis jirovecii pneumonia because of significant therapy-induced lymphopenia. In patients with sulfa allergies, dapsone prophylaxis is often used due to its efficacy, long half-life, cost effectiveness, and general safety at low doses. However, dapsone may uncommonly induce a hemolytic anemia, particularly in patients deficient of glucose-6-phosphate dehydrogenase. This hemolysis is thought to be a result of oxidative stress on red blood cells induced by dapsone metabolites which produce reactive oxygen species that disrupt the red blood cell membrane and promote splenic sequestration. A single case report of dapsone-induced hemolytic anemia in a patient with glioblastoma multiforme has been reported. We present two patients with glioblastoma multiforme who developed severe hemolytic anemia shortly after initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor, while on prophylactic dapsone. There are several potential mechanisms by which histone deacetylase inhibition may alter dapsone metabolism including changes in hepatic acetylation or N-glucuronidation leading to an increase in the bioavailability of dapsone's hematotoxic metabolites. In addition, vorinostat may lead to increased hemolysis through inhibition of heat shock protein-90, a chaperone protein that maintains the integrity of the red blood cell membrane cytoskeleton. The potential interaction between dapsone and vorinostat may have important clinical implications as more than 10 clinical trials evaluating drug combinations with vorinostat in patients with malignant glioma are either ongoing or planned in North America.

Ciprofloxacin plus piperacillin compared with tobramycin plus piperacillin as empirical therapy in febrile neutropenic patients. A randomized, double-blind trial.

BACKGROUND: Therapy with an aminoglycoside and a beta-lactam remains common empirical therapy for febrile neutropenic patients. Concerns of aminoglycoside-induced ototoxicity and nephrotoxicity have led to studies of alternate regimens. OBJECTIVE: To determine whether ciprofloxacin-piperacillin is equivalent to tobramycin-piperacillin as empirical therapy for neutropenic fever. DESIGN: Randomized, double-blind multicenter trial. SETTING: Seven U.S. university-affiliated hospitals and one private research center. PATIENTS: Febrile (temperature >/= 38 degrees C), neutropenic (neutrophil level < 1 x 10(9) cells/L) hospitalized patients who had leukemia, lymphoma, or solid tumors, or were undergoing bone marrow transplantation. INTERVENTIONS: Patients received piperacillin, 50 mg/kg of body weight intravenously every 4 hours, and ciprofloxacin, 400 mg intravenously every 8 hours, or tobramycin, 2 mg/kg intravenously every 8 hours. MEASUREMENTS: Success was defined as resolution of infection and previously positive cultures without the need to give additional antimicrobial agents. RESULTS: 543 febrile episodes were evaluated, of which 471 were clinically evaluable (234 in the ciprofloxacin-piperacillin group and 237 in the tobramycin-piperacillin group). Success rates in the ciprofloxacin-piperacillin group (63 of 234 febrile episodes) and tobramycin-piperacillin group (52 of 237 episodes) were similar (27% vs. 22%, respectively; difference, 5.0 percentage points [95% CI, -2.3 to 12.8 percentage points]), as was survival (96.2% of patients receiving ciprofloxacin-piperacillin versus 94.1% of patients receiving tobramycin-piperacillin; difference, 2.1 percentage points [CI, -2.2 to 6.4 percentage points]). Additions to the initial antimicrobial regimen were the most common reason for treatment failure in both groups (accounting for 67% of failures in the ciprofloxacin-piperacillin group and 72% in the tobramycin-piperacillin group; difference, 5.0 percentage points [CI, -13.8 to 3.7 percentage points]). Fevers resolved faster in patients receiving ciprofloxacin-piperacillin than in patients receiving tobramycin-piperacillin (mean, 5 vs. 6 days) (P = 0.005). No significant differences in adverse events or toxicity were noted (P = 0.083). CONCLUSION: Ciprofloxacin-piperacillin is as safe and effective as tobramycin-piperacillin for empirical therapy of neutropenic fever.