Natalie Neu

Epidemiology of candidemia at a Children's hospital, 2002 to 2006.

Background: There are few recent studies evaluating trends in the epidemiology of candidemia including changes in species or utilization of antifungal agents in children. Methods: We performed a retrospective case series of candidemia at our childrens hospital from 2002 to 2006. Our objectives were to study trends in the rates of candidemia, demographic characteristics, Candida species, antifungal susceptibility, and antifungal utilization. These data were obtained from the electronic medical records. Results: There were 203 episodes of candidemia in 154 subjects. During the study period, the average rate of candidemia was 5.52 per 1000 patient-discharges and did not change throughout the study. The mean and median ages of subjects were 3 years versus 9 months, respectively, and 38% were less than 3 months of age. Gastrointestinal disorders were a common comorbid condition (33%), especially for subjects with multiple episodes of candidemia. Overall, Candida parapsilosis and Candida albicans caused 43% and 26% of episodes, respectively, and candidemia caused by Candida glabrata (5.3%–23%) and Candida krusei (0%–8.5%) increased during the study. Ninety-eight percent of C. albicans and C. parapsilosis isolates remained susceptible to all antifungal drugs. From 2003–2006, the use of antifungal agents increased from 79 days to 150 days per 1000 hospital-days. Conclusions: While antifungal use at our hospital increased, candidemia rates remained stable. C. parapsilosis was the most common species but other non–C. albicans species increased during the study period. Local epidemiology should be monitored in pediatric populations for potential impact on management strategies.

Effect of Fluconazole Prophylaxis on Candidiasis and Mortality in Premature Infants: A Randomized Clinical Trial

IMPORTANCE Invasive candidiasis in premature infants causes death and neurodevelopmental impairment. Fluconazole prophylaxis reduces candidiasis, but its effect on mortality and the safety of fluconazole are unknown. OBJECTIVE To evaluate the efficacy and safety of fluconazole in preventing death or invasive candidiasis in extremely low-birth-weight infants. DESIGN, SETTING, AND PATIENTS This study was a randomized, blinded, placebo-controlled trial of fluconazole in premature infants. Infants weighing less than 750 g at birth (N = 361) from 32 neonatal intensive care units (NICUs) in the United States were randomly assigned to receive either fluconazole or placebo twice weekly for 42 days. Surviving infants were evaluated at 18 to 22 months corrected age for neurodevelopmental outcomes. The study was conducted between November 2008 and February 2013. INTERVENTIONS Fluconazole (6 mg/kg of body weight) or placebo. MAIN OUTCOMES AND MEASURES The primary end point was a composite of death or definite or probable invasive candidiasis prior to study day 49 (1 week after completion of study drug). Secondary and safety outcomes included invasive candidiasis, liver function, bacterial infection, length of stay, intracranial hemorrhage, periventricular leukomalacia, chronic lung disease, patent ductus arteriosus requiring surgery, retinopathy of prematurity requiring surgery, necrotizing enterocolitis, spontaneous intestinal perforation, and neurodevelopmental outcomes-defined as a Bayley-III cognition composite score of less than 70, blindness, deafness, or cerebral palsy at 18 to 22 months corrected age. RESULTS Among infants receiving fluconazole, the composite primary end point of death or invasive candidiasis was 16% (95% CI, 11%-22%) vs 21% in the placebo group (95% CI, 15%-28%; odds ratio, 0.73 [95% CI, 0.43-1.23]; P = .24; treatment difference, -5% [95% CI, -13% to 3%]). Invasive candidiasis occurred less frequently in the fluconazole group (3% [95% CI, 1%-6%]) vs the placebo group (9% [95% CI, 5%-14%]; P = .02; treatment difference, -6% [95% CI, -11% to -1%]). The cumulative incidences of other secondary outcomes were not statistically different between groups. Neurodevelopmental impairment did not differ between the groups (fluconazole, 31% [95% CI, 21%-41%] vs placebo, 27% [95% CI, 18%-37%]; P = .60; treatment difference, 4% [95% CI, -10% to 17%]). CONCLUSIONS AND RELEVANCE Among infants with a birth weight of less than 750 g, 42 days of fluconazole prophylaxis compared with placebo did not result in a lower incidence of the composite of death or invasive candidiasis. These findings do not support the universal use of prophylactic fluconazole in extremely low-birth-weight infants. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00734539.

Effectiveness of Varicella Vaccine in Children Infected with HIV

Although varicella vaccine is given to clinically stable human immunodeficiency virus (HIV)-infected children, its effectiveness is unknown. We assessed its effectiveness by reviewing the medical records of closely monitored HIV-infected children, including those receiving highly active antiretroviral therapy (HAART) between 1989 and 2007. Varicella immunization and development of varicella or herpes zoster were noted. Effectiveness was calculated by subtracting from 1 the rate ratios for the incidence rates of varicella or herpes zoster in vaccinated versus unvaccinated children. The effectiveness of the vaccine was 82% (95% confidence interval [CI], 24%-99%; P = .01) against varicella and was 100% (95% CI, 67%-100%; P < .001) against herpes zoster. When the analysis was controlled for receipt of HAART, vaccination remained highly protective against herpes zoster.

Lower peak bone mass and abnormal trabecular and cortical microarchitecture in young men infected with HIV early in life.

Introduction:HIV infection and antiretroviral therapy (ART) early in life may interfere with acquisition of peak bone mass, thereby increasing fracture risk in adulthood. Methods:We conducted a cross-sectional study of dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) in 30 HIV-infected African–American or Hispanic Tanner stage 5 men aged 20–25 on ART (15 perinatally infected and 15 infected during adolescence) and 15 HIV-uninfected controls. Results:HIV-infected men were similar in age and BMI, but were more likely to be African–American (P = 0.01) than uninfected men. DXA-derived areal bone mineral density (aBMD) Z-scores were 0.4–1.2 lower in HIV-infected men at the spine, hip, and radius (all P < 0.05). At the radius and tibia, total and trabecular volumetric BMD (vBMD), and cortical and trabecular thickness were between 6 and 19% lower in HIV-infected than uninfected men (P <0.05). HIV-infected men had dramatic deficiencies in plate-related parameters by individual trabeculae segmentation (ITS) analyses and 14–17% lower bone stiffness by finite element analysis. Differences in most HR-pQCT parameters remained significant after adjustment for race/ethnicity. No DXA or HR-pQCT parameters differed between men infected perinatally or during adolescence. Conclusion:At an age by which young men have typically acquired peak bone mass, HIV-infected men on ART have lower BMD, markedly abnormal trabecular plate and cortical microarchitecture, and decreased whole bone stiffness, whether infected perinatally or during adolescence. Reduced bone strength in young adults infected with HIV early in life may place them at higher risk for fractures as they age.

Activity of A-56268 compared with that of erythromycin and other oral agents against aerobic and anaerobic bacteria.

A-56268 was compared with erythromycin, roxithromycin (RU 28965), and perorally administered antimicrobial agents. Its in vitro activity was similar to that of erythromycin and slightly greater than that of roxithromycin, with beta-hemolytic streptococci and Streptococcus pneumoniae inhibited by less than 2 micrograms of A-56268 per ml (50% inhibited by 0.06 microgram/ml). Streptococcus pyogenes, S. agalactiae, S. Pneumoniae, and S. faecalis resistant to erythromycin were resistant to A-56268, and 4 micrograms/ml inhibited 90% of Haemophilus influenzae isolates.

Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir

Objectives:Therapeutic HIV vaccinations may alter the size of the resting memory CD4+ T-cell latent HIV reservoir as HIV establishes latency when memory responses are formed, including those toward HIV. Alternatively, latently infected CD4+ T cells maybe killed, while exiting the reservoir upon activation. Methods:The effect of therapeutic immunization with modified vaccinia Ankara and Fowlpox-based HIV vaccines on the latent reservoir was examined in 19 young adults who were receiving effective antiretroviral therapy. Correlations between size of the reservoir [measured in infectious units per million (IUPM)] resting CD4+ T cells and HIV-specific immune responses, including immune activation were examined. Decay of the reservoir was assessed using random-effects model. Results:A modest transient decrease in the size of the reservoir was observed at week 40 [mean −0.31 log10 IUPM (95% confidence interval: −0.60 to −0.03; P = 0.03] following HIV vaccinations. The estimated half-life (T1/2) of the reservoir during the 40 weeks following vaccination was 9.8 months and statistically different from zero (P = 0.02), but 35.3 months and not different from zero (P = 0.21) over 72 weeks of study. Latent reservoir size at baseline was not correlated with HIV-specific CD4+, CD8+ responses or immune activation, but became correlated with CD4+ IFN&ggr; (r = 0.54, P = 0.02) and IL-2 responses at 6 weeks after immunization (r = 0.48, P = 0.04). Conclusion:Therapeutic HIV vaccinations led to a transient increase in decay of latently infected CD4+ T cells. Further studies of therapeutic HIV vaccines may provide important insights into facilitating decay of the latent reservoir.

HIV Testing Preferences Among Young Men of Color Who Have Sex With Men

OBJECTIVES We assessed awareness of and preferences for rapid HIV testing among young, urban men of color who have sex with men and are engaged in high-risk behaviors for HIV. METHODS A cross-sectional survey was conducted in New York City among 177 young men who have sex with men (MSM). RESULTS Among the 85% of the participants who had previously undergone HIV testing, 43% reported rapid testing at their most recent test. In terms of future tests, 64% would seek rapid testing, as compared with 36% who preferred traditional testing. Those who preferred rapid testing were significantly more likely to have attended at least some college, to have discussed HIV testing with a sexual partner, to be aware of rapid testing, and to have had a previous HIV test. CONCLUSIONS In general, young MSM of color seem aware of rapid testing. However, our results indicate the need to carefully consider the unique needs of those who are particularly disenfranchised or engaged in high-risk behaviors and who may need concerted efforts around HIV counseling and testing. Likewise, our findings point to a need for more effective education and social marketing strategies.

Postexposure prophylaxis for HIV in children and adolescents after sexual assault: a prospective observational study in an urban medical center.

Background: We sought to evaluate the tolerability and feasibility of establishing an HIV postexposure prophylaxis (PEP) program at our hospital using the guidelines for children and adolescents after sexual assault. Methods: This study was a prospective, nonrandomized observational study conducted from March 1999 until September 2002. Subjects (age <19 years) who presented to a pediatric emergency room within 72 hours of a sexual assault were eligible for enrollment. A 28-day PEP regimen of zidovudine and lamivudine was given. Results: In all, 70 adolescents were evaluated and 33 (31 females and 2 males) were enrolled. The mean age of enrolled subjects was 15 years, 61% were Hispanic, 30% black, and 79% presented to the emergency room within 24 hours of assault. Vaginal exposure was the most common site of penetration (64% [21 of 33]), but 18% (6 of 33) reported anal penetration. Only 9 subjects (27%) took ≥90% of all the medications. All subjects who returned for follow up tested HIV-negative. Adverse events occurred in 48% (16 of 33) of subjects; the most common events were abdominal pain, nausea, or vomiting. Conclusion: Poor adherence to medications and visits is a significant problem in PEP programs for sexually assaulted children and adolescents.

Microbiological activity of ceftolozane/tazobactam, ceftazidime, meropenem, and piperacillin/tazobactam against Pseudomonas aeruginosa isolated from children with cystic fibrosis

The activity of ceftolozane/tazobactam was tested against 50 nonduplicate Pseudomonas aeruginosa from 18 cystic fibrosis children collected in 2012-2014. These isolates were multidrug resistant with susceptibility to meropenem, ceftazidime, and piperacillin/tazobactam of 46%, 58%, and 50%, respectively. Ceftolozane/tazobactam was the most active with MIC50, MIC90, and percent susceptibility of 2mg/L, 8 mg/L, and 86%.

Health Literacy and Adherence to Antiretroviral Therapy Among HIV-Infected Youth

&NA; Health literacy has been associated with adherence to antiretroviral therapy (ART) in HIV‐infected adults, but this association has not been demonstrated in HIV‐infected adolescents. Using an expanded health literacy model, we examined the relationship between health literacy, functional literacy, beliefs about ART, media use, and adherence to ART. A convenience sample of HIV‐infected adolescents (n = 50) was recruited for this cross‐sectional study. The primary outcome of adherence was measured with 3‐day self‐reports. Health literacy as measured by the Test of Functional Health Literacy in Adults (TOFHLA) was not predictive of adherence (p = .15). Participants with higher positive outcome expectancy scores regarding ART were more likely to report 100% adherence, and participants with below‐grade‐level reading were less likely to report 100% adherence (p < .05). Our findings highlight the importance of assessing both health beliefs and reading skills as part of adherence support for HIV‐infected youth.