Effects of highly active antiretroviral therapy (HAART) on cholesterol in HIV-1 infected children: a retrospective cohort study.

OBJECTIVE: To determine the extent to which different highly active antiretroviral therapy (HAART) regimens pose risks for hypercholesterolemia in children with perinatal HIV-1. METHODS: A single center, retrospective cohort study examined different HAART regimens and total cholesterol (TC) levels. The primary outcomes were TC levels > 180, > 200 mg/dl. HAART was defined as multiple nucleoside analog reverse transcriptase inhibitors (NRTI), NRTI and protease inhibitor (PI) combinations (NRTI/PI), and NRTI and non-nucleoside analog reverse transcriptase inhibitor (NNRTI) combinations (NRTI/NNRTI). Controls were HIV-1 infected children while on no medications (No MED). Univariate and multivariable Cox regression models generated hazard ratios for each of the primary outcomes with duration of therapy in the model. RESULTS: Of the 178 HIV-1 infected children eligible for study, 72.4% had TC > 180 mg/dl, 53.4% had TC > 200 mg/dl. For TC > 200, the multivariable analysis showed increased risk with NRTI/NNRTI (HR: 1.86, 95%CI: 1.34-2.19) and NRTI/PI (HR: 3.45, 95%CI: 2.65-4.51) when compared to No MED. Compared to NRTI/NNRTI, NRTI/PI increased the risk for TC > 200 mg/dl (HR: 1.86, 95%CI: 1.45-2.39) in the multivariable model. CONCLUSIONS: In vertically acquired HIV-1 infected children, HAART elevates the risk of hypercholesterolemia. NRTI/PI increased risk of TC levels threefold, while NRTI/NNRTI increased risk twofold over No MED.

Fluoroquinolone resistance in pediatric bloodstream infections because of Escherichia coli and Klebsiella species.

In pediatric bloodstream infections with fluoroquinolone (FQ)-resistant Escherichia coli and Klebsielia species, we noted an association between FQ resistance and extended-spectrum beta-lactamase (ESBL) production (OR, 12; 95% CI: 2.28-83.8). A case control study revealed no significant risk factors (including prior antibiotic use) for FQ resistance among ESBL E coli and Klebsiella species (ESBL-EK).

Outcome of Escherichia coli and/or Klebsiella bloodstream infection in children with central venous catheters.

We conducted a retrospective cohort study of children with catheter-associated bloodstream infections (BSIs) due to Escherichia coli and/or Klebsiella. Risk factors for poor outcome (ie, death or recurrence of infection) were receipt of mechanical ventilation (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 1.39-16.30]) and receipt of total parenteral nutrition (aOR, 3.5 [95% CI, 1.1-10.8]). A significant proportion of children with catheter-associated BSI were treated successfully without catheter removal.

Zygomycosis in children: a systematic review and analysis of reported cases.

BACKGROUND: Zygomycosis has emerged as an increasingly important infection with a high mortality especially in immunocompromised patients. No comprehensive analysis of pediatric zygomycosis cases has been published to date. METHODS: We used a PUBMED search for English publications of pediatric (0-18 years) zygomycosis cases and references from major books as well as single case reports or case series. Individual references were reviewed for additional cases. Data were entered into Filemaker-pro database and analyzed by logistic regression analysis. RESULTS: One hundred fifty-seven cases (64% male) were found with median age 5 years (range, 0.16-13). Underlying conditions included neutropenia (18%), prematurity (17%), diabetes mellitus (15%), ketoacidosis (10%), and no apparent underlying condition (14%). The most common patterns of zygomycosis were cutaneous (27%), gastrointestinal (21%), rhinocerebral (18%), and pulmonary (16%). Among 77 culture-confirmed cases, Rhizopus spp. (44%) and Mucor spp. (15%) were most commonly identified. Of 81 patients who were given antifungal therapy, 73% received an amphotericin B formulation only. The remaining patients received mostly amphotericin B in combination with other antifungal agents. Mortality in patients without antifungal therapy was higher than in those with therapy (88% versus 36%, P < 0.0001). Ninety-two (59%) patients underwent surgery. Cerebral, gastrointestinal, disseminated and cutaneous zygomycosis were associated with mortality rates of 100, 100, 88, and 0%, respectively. Independent risk factors for death were disseminated infection (OR: 7.18; 95% CI: 3.02-36.59) and age <1 year (OR: 3.85; 95% CI: 1.05-7.43). Antifungal therapy and particularly surgery reduced risk of death by 92% (OR: 0.07; 95% CI: 0.04-0.25) and 84% (OR: 0.16; 95% CI: 0.09-0.61), respectively. CONCLUSIONS: Zygomycosis is a life-threatening infection in children with neutropenia, diabetes mellitus, and prematurity as common predisposing factors, and there is high mortality in untreated disease, disseminated infection, and age <1 year. Amphotericin B and surgery significantly improve outcome.

Complications of central venous catheters used for the treatment of acute hematogenous osteomyelitis.

OBJECTIVE: To determine the complications and risk factors for complications associated with using central venous catheters (CVCs) for the treatment of acute hematogenous osteomyelitis (AHO). METHODS: We conducted a retrospective cohort study of all patients admitted to the Children's Hospital of Philadelphia between January 1, 2000, and December 31, 2003, with a diagnosis of AHO. RESULTS: Eighty patients with AHO met inclusion criteria. The median age was 5 years, and 66% of the patients were male. The most commonly affected bones were the femur (25%), tibia (20%), and pelvis (16%). Staphylococcus aureus was the most common organism identified from cultures of bone (67%) and blood (30%). Seventy-five patients (94%) received >2 weeks of intravenous (IV) antibiotic therapy via a CVC and 5 (6%) received <2 weeks of IV antibiotic therapy before conversion to oral therapy for a median of 25 days. None of the patients who switched to oral therapy within 2 weeks was rehospitalized or returned to the emergency department. Of the 75 patients who received >2 weeks of IV therapy, 41% had > or =1 CVC-associated complication. Seventeen patients (23%) had a CVC malfunction or displacement, 8 (11%) had a catheter-associated bloodstream infection, 8 (11%) had fever with negative blood culture results, and 4 (5%) had a local skin infection at the site of catheter insertion. Older age was protective against the development of a CVC-associated complication, whereas the lowest median household income was associated with development of a CVC-associated complication. CONCLUSIONS: Interventions to reduce CVC-associated complications should be developed and evaluated, particularly for young children and those from families with low household incomes. Clinical trials are needed to evaluate the safety and efficacy of oral antibiotic therapy after a short course of IV therapy as an alternative to prolonged IV therapy.

Clinical and molecular epidemiology of community-acquired methicillin-resistant Staphylococcus aureus infections among children with risk factors for health care-associated infection: 2001-2003.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has recently emerged as a common cause of infection in children in many parts of the world. The epidemiology of community-acquired MRSA (CA-MRSA) among healthy children has been recently described. However, little is known about CA-MRSA in children with underlying medical conditions. OBJECTIVE: To compare the clinical and molecular epidemiology of CA-MRSA in children with and without risk factors for health care-associated infections (RF-HAI). METHODS: We conducted a 3-year retrospective cohort study of children with CA-MRSA infection. RF-HAI, including hospitalization within the past year, indwelling medical devices or chronic medical condition, were identified by chart review. Genetic relatedness of CA-MRSA strains was assessed by pulsed field gel electrophoresis. Polymerase chain reaction was used to detect Panton-Valentine leukocidin and determine staphylococcal chromosomal cassette carrying the mecA methicillin-resistant gene (SCCmec) type. RESULTS: We identified 446 episodes of community-acquired S. aureus infections, of which 134 (30%) were caused by MRSA. During the 3-year study period, the proportion of S. aureus infections caused by MRSA rose from 15% (12 of 80) to 40% (93 of 235) (P < 0.001) with the increase noted predominately in children with skin and soft tissue infections. RF-HAI were identified in 56 (42%) patients with CA-MRSA. Among subjects with CA-MRSA, children with RF-HAI were more likely to have had an invasive infection than healthy children (32% versus 5%; P < 0.001). CA-MRSA isolates from children with RF-HAI were similar to those without RF-HAI; all laboratory-retained CA-MRSA isolates harbored the SCCmec type IV cassette, and almost all isolates were susceptible to trimethoprim-sulfamethoxazole and clindamycin. However, pulsed field gel electrophoresis revealed greater molecular diversity among CA-MRSA isolates recovered from children with RF-HAI compared with those from otherwise healthy children (P = 0.001). Additionally CA-MRSA isolates from children with RF-HAI were less likely to contain sequences for Panton-Valentine leukocidin (P < 0.001) and more likely to be resistant to 3 or more classes of antibiotics (P = 0.033). CONCLUSION: CA-MRSA strains recovered from children with RF-HAI were phenotypically similar to those recovered from healthy children The absence of SCCmec type II or III MRSA among children with RF-HAI suggests that CA-MRSA strains might have become endemic within pediatric health care facilities.

Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the United States, 2000.

OBJECTIVE: Invasive aspergillosis (IA) is the most common filamentous fungal infection observed in immunocompromised patients. The incidence of invasive aspergillosis has increased significantly in recent decades in parallel with the increasing number and improved survival of immunocompromised patients. IA in adults has been well characterized; however, only a few small studies of IA in children have been reported. Therefore, the objective of this study was to describe the incidence and outcomes of children with IA. METHODS: We performed a retrospective cohort study using the 2000 Kids Inpatient Database, a national database of hospital inpatient stays during 2000. IA was defined as aspergillosis that occurred in a child with malignancy (solid tumor, leukemia, or lymphoma), hematologic/immunologic deficiency, or transplant (bone marrow or solid organ). Discharge weighting was applied to the data to obtain nationally representative estimates of disease. RESULTS: During 2000, there were an estimated 666 pediatric cases of IA among 152,231 immunocompromised children, yielding an annual incidence of 437/100,000 (0.4%) among hospitalized immunocompromised children. Children with malignancy accounted for the majority (74%) of cases of IA. The highest incidence of IA was seen in children who had undergone allogeneic bone marrow transplantation (4.5%) and those with acute myelogenous leukemia (4%). The overall in-hospital mortality of immunocompromised children with IA was 18%. Children with malignancy and IA were at higher risk for death than children with malignancy and without IA. Pediatric patients with IA had a significantly longer median length of hospital stay (16 days) than immunocompromised children without IA (3 days). The median total hospital charges for patients with IA were $49309 compared with immunocompromised children without IA ($9035). CONCLUSIONS: The impact of IA on increases in mortality, length of hospital stay, and the burden of cost in the hospital setting underscores the need for improved means of diagnosis, prevention, and treatment of IA in immunocompromised children.

Hospitalizations for endemic mycoses: a population-based national study.

We performed a retrospective cohort study, using the 2002 Nationwide Inpatient Sample, a national database of hospital inpatient stays, to describe the incidence and epidemiology of endemic mycoses requiring hospitalization. An estimated 332 pediatric and 6003 adult patients with endemic mycoses required hospitalization (4.6 and 28.7 cases per 1 million children and adults, respectively). Crude mortality rates were 5% and 7% among children and adults, respectively.

The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis.

BACKGROUND: Candida species are the fourth most common cause of bloodstream infection and are the leading cause of invasive fungal infection among hospitalized patients in the United States. However, the frequency and outcomes attributable to the infection are uncertain. This retrospective study set out to estimate the incidence of candidemia in hospitalized adults and children in the United States and to determine attributable mortality, length of hospital stay, and hospital charges related to candidemia. METHODS: We used the Nationwide Inpatient Sample 2000 for adult patients and the Kids' Inpatient Database 2000 for pediatric patients. We matched candidemia-exposed and candidemia-unexposed patients by the propensity scores for the probability of candidemia exposure, which were derived from patient characteristics. Attributable outcomes were calculated as the differences in estimates of outcomes between propensity score-matched patients with and without candidemia. RESULTS: In the United States in 2000, candidemia was diagnosed in an estimated 1118 hospital admissions of pediatric patients and 8949 hospital admissions of adult patients, yielding a frequency of 43 cases per 100,000 pediatric admissions (95% confidence interval [CI], 35-52 cases per 100,000 pediatric admissions) and 30 cases per 100,000 adult admissions (95% CI, 26-34 cases per 100,000 adult admissions). In pediatric patients, candidemia was associated with a 10.0% increase in mortality (95% CI, 6.2%-13.8%), a mean 21.1-day increase in length of stay (95% CI, 14.4-27.8 days), and a mean increase in total per-patient hospital charges of 92,266 dollars (95% CI, 65,058 dollars-119,474 dollars). In adult patients, candidemia was associated with a 14.5% increase in mortality (95% CI, 12.1%-16.9%), a mean 10.1-day increase in length of stay (95% CI, 8.9-11.3 days), and a mean increase in hospital charges of 39,331 dollars (95% CI, 33,604 dollars-45,602 dollars). CONCLUSION: The impact of candidemia on excess mortality, increased length of stay, and the burden of cost of hospitalization underscores the need for improved means of prevention and treatment of candidemia in adults and children.

Epidemiology and outcome of zygomycosis: a review of 929 reported cases.

BACKGROUND: Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. METHODS: We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. RESULTS: The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 [66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). CONCLUSIONS: Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.

Risk factors for mortality in children with candidemia.

We performed a retrospective cohort study of hospitalized children with positive blood cultures for Candida species. Independent risk factors for mortality by multivariable analysis were location in the pediatric intensive care unit at the time of infection (hazard ratio, 6.3; 95% confidence interval, 1.6-24.3) and the presence of an arterial catheter (hazard ratio, 2.4; 95% confidence interval, 1.1-5.8). Our findings help identify a group of pediatric patients that should be targeted for future interventions to prevent and treat candidemia.

Hormonal contraceptive use and the effectiveness of highly active antiretroviral therapy.

The role of hormonal contraceptive use in the effectiveness of highly active antiretroviral therapy (HAART) was examined among participants in the Women's Interagency HIV Study who were followed from HAART initiation to 2001. Propensity score selection was used to match 77 hormonal contraceptive users with 77 nonusers on age, race, and pre-HAART CD4-positive T-lymphocyte (CD4+ cell) count and viral load. The authors compared hormonal contraceptive users and nonusers with regard to the CD4+ cell count and viral load responses to HAART upon initiation. Proportional hazards analyses were used to assess the effect of hormonal contraceptive use on times to increases in CD4+ cell count of 50 cells/mm(3) and 100 cells/mm(3) and achievement of an undetectable viral load. There were no statistically significant differences in CD4+ cell counts and log viral load responses by hormone use after HAART initiation, except in log viral load at the third visit after initiation (p = 0.047). Time-dependent hormonal contraceptive use was not a statistically significant predictor of achieving increases in CD4+ cell count of 50 cells/mm(3) and 100 cells/mm(3) or an undetectable viral load (p = 0.517, p = 0.751, and p = 0.218, respectively) after HAART initiation. In conclusion, the authors did not find substantial evidence that use of hormonal contraceptives strongly affected responses to HAART.

Risk factors for and outcomes of bloodstream infection caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in children.

OBJECTIVE: The increasing prevalence of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) has become a growing concern in the hospitalized patient population. Previous studies on risk factors for infection with ESBL-EK have mainly focused on adult populations, and these findings may not be relevant among the pediatric population that experiences a unique set of health care exposures and underlying conditions. The objective of this study was to define the risk factors and outcomes associated with ESBL-EK bloodstream infections in children. METHODS: We conducted a nested case-control study using data from the Children's Hospital of Philadelphia from May 1, 1999, to September 30, 2003. Eligible patients were identified from the hospital database of microbiology laboratory records. All patients with ESBL-EK bloodstream infections were compared to a random sample of patients with non-ESBL-EK bloodstream infections. Risk factors analyzed included prior antimicrobial use, comorbid conditions, and demographic characteristics. Pulsed-field gel electrophoresis was performed to determine genetic relatedness of the ESBL-EK isolates. RESULTS: Thirty-five cases and 105 control subjects were included in the study. The median age among the cases was 2 years (interquartile range: 0-11), compared with 1 year (interquartile range: 0-8) among control subjects. Patients with ESBL-EK infections were 5.8 times (95% confidence interval: 1.9-17.7) more likely to have had exposure to an extended-spectrum cephalosporin in the 30 days before infection than those with non-ESBL-EK infections. Other independent predictors of ESBL-EK infection were being female, infection with a Klebsiella species, and steroid use in the 30 days before infection. All ESBL-EK isolates were susceptible to carbapenem antibiotics. Pulsed-field gel electrophoresis analysis revealed that the ESBL-EK isolates were polyclonal. Although a substantially higher proportion of children with ESBL-EK died (in-hospital mortality: 36% vs 13%), this difference was not statistically significant. CONCLUSIONS: Receipt of extended-spectrum cephalosporins in the 30 days before infection by an Escherichia coli or Klebsiella species is significantly associated with having an ESBL-EK infection in hospitalized children. Curtailed use of cephalosporins among high-risk groups may reduce the occurrence of ESBL-EK infections. Future studies on identifying high-risk children and investigating the impact of curtailed third-generation cephalosporin use to limit additional emergence of ESBL-EK infections should be undertaken.