Multicenter Evaluation of the Xpert MRSA NxG Assay for Detection of Methicillin-Resistant Staphylococcus aureus in Nasal Swabs.

Health care-associated methicillin-resistant Staphylococcus aureus (MRSA) infections are a burden on the health care system. Clinical laboratories play a key role in reducing this burden, as the timely identification of MRSA colonization or infection facilitates infection control practices that are effective at limiting invasive MRSA infections. The Xpert MRSA NxG assay recently received FDA clearance for the direct detection of MRSA from nasal swabs. This multicenter study evaluated the clinical performance characteristics of the Xpert MRSA NxG assay with prospectively collected rayon nasal swabs (n = 1,103) and flocked swab (ESwab) nasal specimens (n = 846). Culture-based identification methods and antimicrobial susceptibility testing were used as the reference standards for comparison. According to the reference method, the positivity rates for MRSA in the population evaluated were 11.1% (122/1,103) for rayon swabs and 11.6% (98/846) for flocked swabs. The overall sensitivity and specificity of the rayon swabs were 91.0% (95% confidence interval [CI], 84.6 to 94.9%) and 96.9% (95% CI, 95.7 to 97.8%), respectively, across eight testing sites. The flocked swab specimens were 92.9% sensitive (95% CI, 86.0 to 96.5%) and 97.6% specific (95% CI, 96.2 to 98.5%) for MRSA detection across six testing sites. The sensitivity and specificity of the combined flocked and rayon swab data were 91.8% (95% CI, 87.4 to 94.8%) and 97.2% (95% CI, 96.3 to 97.9%), respectively. The positive predictive value (PPV) for rayon swabs was 78.7%, versus 83.5% for ESwabs. The negative predictive values (NPVs) for rayon swabs and ESwab specimens were 98.9% and 99.1%, respectively. In conclusion, the Xpert MRSA NxG assay is a sensitive and specific assay for the direct detection of MRSA from nasal swab specimens.

Herpes simplex virus encephalitis during treatment with etanercept.

Tumor necrosis factor alpha (TNF-α) inhibitors are widely used for the treatment of various inflammatory conditions. They are associated with an increased risk for infections. We report a case of herpes simplex virus type 1 (HSV-1) encephalitis in a patient receiving etanercept and review the literature on TNF-α and TNF-α inhibitors, and their importance in the pathophysiology of herpes simplex encephalitis.

Atrial-esophageal fistula after atrial radiofrequency catheter ablation.

Atrial-esophageal fistula is a rare but often fatal complication of catheter radiofrequency ablation. Patients occasionally have bacteremia and have been misdiagnosed with endocarditis. Infectious diseases specialists are often consulted and need to be aware of this complication. We report a case of atrial-esophageal fistula after radiofrequency ablation that illustrates the salient features of this illness.

Characteristics and Severity of Disease among 100 Cases of Imported Malaria Seen at a U.S. University Hospital, 2000-2017.

Malaria acquired in endemic areas poses a substantial risk to travelers arriving in or returning to the United States. Timely diagnosis and recognition of severe illness are crucial; however, many U.S.-based clinicians lack familiarity with this disease. We conducted a retrospective review of 100 cases of malaria in adults seen at a single urban university hospital during 2000-2017. Descriptive and analytical statistics were calculated, including logistic regression modeling case severity. Most of the patients presented with Plasmodium falciparum (76%), most commonly after travel from sub-Saharan Africa (94%). Prior malaria experience was common (50%), but adherence to a prophylactic regimen was exceedingly rare (4%). Twenty-one patients had severe malaria, including 10 with cerebral malaria. Severity was predicted by high parasitemia, bandemia, hypoglycemia, and hypotension at the time of presentation. In 24 patients, the initial treatment regimen was changed, usually because of the appearance of clinical deterioration or drug toxicity. One patient required intravenous artesunate. All patients survived, although one suffered fetal loss. Among 30 patients initially evaluated at other institutions, 43% had been treated for an alternative diagnosis. The most common reasons for transfer of patients to our hospital were inadequate facilities and lack of expertise with malaria. There needs to be increased awareness among U.S.-based travelers and clinicians regarding malaria as a potentially lethal condition, emphasizing the use of appropriate prophylaxis. Our simple model of disease severity could serve frontline physicians when deciding which patients should be admitted to the intensive care unit or transferred for higher level care.

Sexually Transmitted Infections Among HIV-Infected Individuals in the District of Columbia and Estimated HIV Transmission Risk: Data From the DC Cohort.

BACKGROUND: Washington, DC, has one of the highest rates of HIV infection in the United States. Sexual intercourse is the leading mode of HIV transmission, and sexually transmitted infections (STIs) are a risk factor for HIV acquisition and transmission. METHODS: We evaluated the incidence and demographic factors associated with chlamydia, gonorrhea, and syphilis among HIV-infected persons enrolled at 13 DC Cohort sites from 2011 to 2015. Using Poisson regression, we assessed covariates of risk for incident STIs. We also examined HIV viral loads (VLs) at the time of STI diagnosis as a proxy for HIV transmission risk. RESULTS: Six point seven percent (451/6672) developed an incident STI during a median follow-up of 32.5 months (4% chlamydia, 3% gonorrhea, 2% syphilis); 30% of participants had 2 or more STI episodes. The incidence rate of any STIs was 3.8 cases per 100 person-years (95% confidence interval [CI], 3.5-4.1); age 18-34 years, 10.8 (95% CI, 9.7-12.0); transgender women, 9.9 (95% CI, 6.9-14.0); Hispanics, 9.2 (95% CI, 7.2-11.8); and men who have sex with men (MSM), 7.7 (95% CI, 7.1-8.4). Multivariate Poisson regression showed younger age, Hispanic ethnicity, MSM risk, and higher nadir CD4 counts to be strongly associated with STIs. Among those with an STI, 41.8% had a detectable VL within 1 month of STI diagnosis, and 14.6% had a VL ≥1500 copies/mL. CONCLUSIONS: STIs are highly prevalent among HIV-infected persons receiving care in DC. HIV transmission risk is considerable at the time of STI diagnosis. Interventions toward risk reduction, antiretroviral therapy adherence, and HIV virologic suppression are critical at the time of STI evaluation.

Prevalence and trends in transmitted and acquired antiretroviral drug resistance, Washington, DC, 1999-2014.

BACKGROUND: Drug resistance limits options for antiretroviral therapy (ART) and results in poorer health outcomes among HIV-infected persons. We sought to characterize resistance patterns and to identify predictors of resistance in Washington, DC. METHODS: We analyzed resistance in the DC Cohort, a longitudinal study of HIV-infected persons in care in Washington, DC. We measured cumulative drug resistance (CDR) among participants with any genotype between 1999 and 2014 (n = 3411), transmitted drug resistance (TDR) in ART-naïve persons (n = 1503), and acquired drug resistance (ADR) in persons with genotypes before and after ART initiation (n = 309). Using logistic regression, we assessed associations between patient characteristics and transmitted resistance to any antiretroviral. RESULTS: Prevalence of TDR was 20.5%, of ADR 40.5%, and of CDR 45.1% in the respective analysis groups. From 2004 to 2013, TDR prevalence decreased for nucleoside and nucleotide analogue reverse transcriptase inhibitors (15.0 to 5.5%; p = 0.0003) and increased for integrase strand transfer inhibitors (INSTIs) (0.0-1.4%; p = 0.04). In multivariable analysis, TDR was not associated with age, race/ethnicity, HIV risk group, or years from HIV diagnosis. CONCLUSIONS: In this urban cohort of HIV-infected persons, almost half of participants tested had evidence of CDR; and resistance to INSTIs was increasing. If this trend continues, inclusion of the integrase-encoding region in baseline genotype testing should be strongly considered.

A cost-effective interdisciplinary approach to microbiologic send-out test use.

CONTEXT: Use of reference laboratories for selected laboratory testing (send-out tests) represents a significant source of laboratory costs. As the use of more complex molecular analyses becomes common in the United States, strategies to reduce costs in the clinical laboratory must evolve in order to provide high-value, cost-effective medicine. OBJECTIVE: To report a strategy that employs clinical pathology house staff and key hospital clinicians in the effective use of microbiologic send-out testing. DESIGN: The George Washington University Hospital is a 370-bed academic hospital in Washington, DC. In 2012 all requisitions for microbiologic send-out tests were screened by the clinical pathology house staff prior to final dispensation. Tests with questionable utility were brought to the attention of ordering clinicians through the use of interdisciplinary rounds and direct face-to-face consultation. RESULTS: Screening resulted in a cancellation rate of 38% of send-out tests, with proportional cost savings. Nucleic acid tests represented most of the tests screened and the largest percentage of cost saved through screening. Following consultation, requested send-out tests were most often canceled because of a lack of clinical indication. CONCLUSIONS: Direct face-to-face consultation with ordering physicians is an effective, interdisciplinary approach to managing the use of send-out testing in the microbiology laboratory.

HIV infection induces structural and functional changes in high density lipoproteins.

BACKGROUND AND AIMS: Coronary artery disease is a growing clinical problem in HIV-infected subjects. The increased risk of coronary events in this population has been linked to low levels of HDL, but the effects of HIV infection and anti-retroviral treatment (ART) on HDL structure and function remain unknown. Here, we aimed to determine the composition and function of HDL particles isolated from ART-naive and ART-positive HIV-infected patients. METHODS AND RESULTS: Proteomic profiling revealed decreased levels of paraoxonase (PON) 1 and PON 3 in HDL from HIV patients relative to HDL from uninfected controls (p < 0.0001), and PON activity of HDL from control group (0.13 ± 0.01 U/µl) was significantly higher than PON activity of HDL from HIV-infected untreated subjects (0.12 ± 0.01 U/µl, p = 0.0035), subjects treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy (0.11 ± 0.01 U/µl, p < 0.0001), subjects treated with protease inhibitor (PI)-based therapy with detectable viral load (0.11 ± 0.01 U/µl, p < 0.0001), and PI-treated patients with undetectable viral load (0.12 ± 0.01 U/µl, p = 0.0164). Lipidomic profiling uncovered a negative correlation between CD4 T cell counts and particle sphingomyelin, lyso-phosphatidylcholine and ether-linked phosphatidylserine content in the ART-naive (R(2) = 0.2611, p < 0.05; R(2) = 0.2722, p < 0.05; and R(2) = 0.3977, p < 0.05, respectively) but not treated HIV-infected subjects. Functional analysis demonstrated a negative correlation between cholesterol efflux capacity of HDL and viral load in the ART-naive HIV-infected group (R(2) = 0.26, p = 0.026). CONCLUSIONS: Taken together, these results indicate that HIV infection associates with a number of both protein and lipid compositional changes in HDL particles. Moreover, HIV infection affects cholesterol efflux function of HDL, thus contributing to an increased risk of atherosclerosis in this patient population.

Effect of delavirdine on plasma lipids and lipoproteins in patients receiving antiretroviral therapy.

Plasma lipid and lipoprotein levels were measured at baseline and after 8 weeks of highly active antiretroviral therapy among patients receiving delavirdine with or without a protease inhibitor (PI). In patients receiving nucleoside reverse transcriptase inhibitors (NRTI) plus delavirdine, there was a statistically significant increase in cholesterol and HDL levels, whereas those receiving NRTI plus a PI had no significant change in their HDL levels. When delavirdine was combined with a PI, there was a more dramatic increase in both cholesterol and HDL concentrations.

Compact quadruple therapy with the lamivudine/zidovudine combination tablet plus abacavir and efavirenz, followed by the lamivudine/zidovudine/abacavir triple nucleoside tablet plus efavirenz in treatment-naïve HIV-infected adults.

PURPOSE: To assess efficacy, safety, and adherence with compact quadruple therapy comprising one lamivudine 150-mg/zidovudine 300-mg tablet (COM) twice daily + one abacavir (ABC) 300-mg tablet twice daily + three efavirenz (EFV) 200-mg capsules at bedtime for 24 weeks, followed by one lamivudine 150-mg/zidovudine 300-mg/ABC 300-mg triple nucleoside tablet (TZV) twice daily + three EFV 200-mg capsules at bedtime for 24 weeks. METHOD: A pilot 48-week, prospective, open-label trial in which 38 antiretroviral-naïve HIV-infected adults (baseline median HIV-1 RNA 5.1 log(10) copies/mL, CD4+ cell count 285/microL) received the above treatment and were monitored regularly with respect to plasma HIV-1 RNA levels, CD4+ cell counts, T-cell receptor excision circles (TRECs), adherence, and adverse events. RESULTS: At Week 48, intent-to-treat, switch-included analysis showed plasma HIV-1 RNA levels <400 copies/mL in 100% (29/29) of patients and <50 copies/mL in 93% (27/29); 59% of patients who achieved <50 copies/mL had <3 copies/mL (16/27). Similar virologic suppression was observed in patients with baseline HIV-1 RNA above or below 100000 copies/mL. HIV-1 RNA and CD4+ cell counts changed from baseline by a median of -3.4 log(10) copies/mL and +172 cells/microL, respectively. One virologic failure occurred at Week 16. Median TRECs/100000 peripheral blood lymphocytes increased 6-fold between baseline and Week 48. Median adherence rates were consistently 100% by self-report and 94% by pill count. Grade 2-4 treatment-related adverse events included dreams (16%), nausea (13%), decreased white cells (8%), dizziness (8%), sleep disorders (8%), and malaise and fatigue (8%). A suspected ABC hypersensitivity reaction occurred in 8% (3/38) of patients. CONCLUSION: COM/ABC/EFV or TZV/EFV produced potent, durable virologic suppression and immunologic benefits, was associated with high adherence rates, and was generally well tolerated.