Susan E. Pacheco

Clinical experience with linezolid for the treatment of Nocardia infection

Linezolid is an oxazolidinone that has activity against most gram-positive bacteria, including in vitro activity against all Nocardia species and strains. We describe 6 clinical cases of nocardiosis that were successfully treated with linezolid. Two patients had underlying X-linked chronic granulomatous disease, and 2 patients were receiving chronic corticosteroid therapy. Four of 6 patients had disseminated disease, and 2 of these 4 patients had multiple brain abscesses. Four patients primarily received monotherapy; for the fifth patient, linezolid was added to a failing multiple-drug regimen, and, for the sixth patient, it was used as part of combination therapy. All 6 patients were successfully treated, although 1 patient had a presumed relapse of central nervous system infection after premature discontinuation of the drug. Linezolid appears to be an effective alternative for the treatment of nocardiosis.

Recombinant Norwalk Virus-Like Particles Administered Intranasally to Mice Induce Systemic and Mucosal (Fecal and Vaginal) Immune Responses

ABSTRACT Recombinant Norwalk virus-like particles (rNV VLPs) were administered to BALB/c mice by the intranasal (i.n.) route to evaluate the induction of mucosal antibody responses. The results were compared to systemic and mucosal responses observed in new and previous studies (J. M. Ball, M. E. Hardy, R. L. Atmar, M. E. Connor, and M. K. Estes, J. Virol. 72:1345–1353, 1998) after oral administration of rNV VLPs. Immunizations were given in the presence or absence of a mucosal adjuvant, mutant Escherichia coliheat-labile toxin LT(R192G). rNV-specific immunoglobulin G (IgG) and fecal IgA were evaluated by enzyme-linked immunosorbent assay. The i.n. delivery of rNV VLPs was more effective than the oral route at inducing serum IgG and fecal IgA responses to low doses of rNV particles. Vaginal responses of female mice given VLPs by the i.n. and oral routes were also examined. All mice that received two immunizations with low doses i.n. (10 or 25 μg) of rNV VLPs and the majority of mice that received two high doses orally (200 μg) in the absence of adjuvant had rNV-specific serum IgG, fecal, and vaginal responses. Additional experiments evaluated whether rNV VLPs can function as a mucosal adjuvant by evaluating the immune responses to two soluble proteins, keyhole limpet hemocyanin and chicken egg albumin. Under the conditions tested, rNV VLPs did not enhance the serum IgG or fecal IgA response to these soluble proteins when coadministered by the i.n. or oral route. Low doses of nonreplicating rNV VLPs are immunogenic when administered i.n. in the absence of adjuvant, and addition of adjuvant enhanced the magnitude and duration of these responses. Recombinant NV VLPs represent a candidate mucosal vaccine for NV infections in humans.

Effect of Perinatal Antiretroviral Drug Exposure on Hematologic Values in HIV-Uninfected Children: An Analysis of the Women and Infants Transmission Study

BACKGROUND With the increasing use of antiretroviral (ARV) drugs to prevent mother-to-child transmission of human immunodeficiency virus (HIV), large numbers of infants are exposed, with possible consequent toxicity. METHODS Hematologic values in 1820 uninfected HIV- and ARV-exposed children were compared with those in 351 ARV-unexposed children from the Women and Infants Transmission Study. Hemoglobin concentrations and platelet, neutrophil, lymphocyte, and CD4+ and CD8+ cell counts were analyzed at birth and ages 2, 6, 12, 18, and 24 months. Multivariate analysis was conducted age 0-2 and 6-24 months, with adjustment for multiple cofactors. RESULTS Hemoglobin concentrations and neutrophil, lymphocyte, and CD4+ cell counts were significantly lower at age 0-2 months in infants exposed to ARV drugs than in those who were not. At 6-24 months, differences in hemoglobin concentrations and neutrophil counts were no longer significant, whereas differences in platelet, lymphocyte, and CD4+ cell counts persisted and CD8+ cell counts became significantly lower. In comparison with ARV monotherapy, combination therapy was associated with larger decreases in neutrophil, lymphocyte, and CD8+ cell counts at age 0-2 months but with only differences in CD8+ cell counts at age 6-24 months. Clinically significant abnormalities were rare and did not differ by exposure to ARV drugs. CONCLUSION Infants exposed to ARV drugs have small but significant differences in several hematologic parameters for the first 24 months of life. These results indicate the need for long-term follow-up of uninfected infants with ARV exposure.

Effect of an Enhanced Medical Home on Serious Illness and Cost of Care Among High-Risk Children With Chronic Illness A Randomized Clinical Trial

IMPORTANCE Patient-centered medical homes have not been shown to reduce adverse outcomes or costs in adults or children with chronic illness. OBJECTIVE To assess whether an enhanced medical home providing comprehensive care prevents serious illness (death, intensive care unit [ICU] admission, or hospital stay >7 days) and/or reduces costs among children with chronic illness. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of high-risk children with chronic illness (≥3 emergency department visits, ≥2 hospitalizations, or ≥1 pediatric ICU admissions during previous year, and >50% estimated risk for hospitalization) treated at a high-risk clinic at the University of Texas, Houston, and randomized to comprehensive care (n = 105) or usual care (n = 96). Enrollment was between March 2011 and February 2013 (when predefined stopping rules for benefit were met) and outcome evaluations continued through August 31, 2013. INTERVENTIONS Comprehensive care included treatment from primary care clinicians and specialists in the same clinic with multiple features to promote prompt effective care. Usual care was provided locally in private offices or faculty-supervised clinics without modification. MAIN OUTCOMES AND MEASURES Primary outcome: children with a serious illness (death, ICU admission, or hospital stay >7 days), costs (health system perspective). Secondary outcomes: individual serious illnesses, medical services, Medicaid payments, and medical school revenues and costs. RESULTS In an intent-to-treat analysis, comprehensive care decreased both the rate of children with a serious illness (10 per 100 child-years vs 22 for usual care; rate ratio [RR], 0.45 [95% CI, 0.28-0.73]), and total hospital and clinic costs (

Changes in intestinal Toll-like receptors and cytokines precede histological injury in a rat model of necrotizing enterocolitis

16,523 vs

Hepatitis C Virus Coinfection and HIV Load, CD4+ Cell Percentage, and Clinical Progression to AIDS or Death among HIV-Infected Women: Women and Infants Transmission Study

26,781 per child-year, respectively; cost ratio, 0.58 [95% CI, 0.38-0.88]). In analyses of net monetary benefit, the probability that comprehensive care was cost neutral or cost saving was 97%. Comprehensive care reduced (per 100 child-years) serious illnesses (16 vs 44 for usual care; RR, 0.33 [95% CI, 0.17-0.66]), emergency department visits (90 vs 190; RR, 0.48 [95% CI, 0.34-0.67]), hospitalizations (69 vs 131; RR, 0.51 [95% CI, 0.33-0.77]), pediatric ICU admissions (9 vs 26; RR, 0.35 [95% CI, 0.18-0.70]), and number of days in a hospital (276 vs 635; RR, 0.36 [95% CI, 0.19-0.67]). Medicaid payments were reduced by

Laboratory Aspects of Immunology

6243 (95% CI,

Intranasal Immunization with HIV Reverse Transcriptase: Effect of Dose in the Induction of Helper T Cell Type 1 and 2 Immunity

1302-

Global Climate Change and Children's Health.

11,678) per child-year. Medical school losses (costs minus revenues) increased by

Dysanaptic growth of lung and airway in children with post-infectious bronchiolitis obliterans.

6018 (95% CI,