Protease inhibitor therapy in HIV-infected children.

We reviewed the short-term response to and safety of protease inhibitor (PI) therapy in HIV-infected children by performing a retrospective chart review of open-label PI containing combination therapy at two urban pediatric HIV centers. Seventy HIV-infected children received 101 PI containing antiretroviral therapy (ART) combinations. Main outcome measures were follow-up CD4 counts, viral loads, and patient or caregiver reported compliance. During follow-up, treatment with PI ART was associated with a mean maximal increase in CD4+ lymphocyte count of 454 x 10(6)/L and a mean maximal decrease in viral load of 1.76 log units. Of the 32 patients who achieved undetectable viral loads, 28 (87.5%) remained undetectable through a mean follow-up of 8.9 months. Patients who reported good compliance achieved a higher rate of response (92.6%) than those who reported poor compliance (61.5%). Of 14 changes made to a second PI because of treatment failure, 11 (78.6%) resulted in a positive response to the second regimen. Nineteen of 101 courses of PI therapy resulted in significant side effects, including renal complications in 8 of 21 patients treated with indinavir. PI ART was associated with substantial short-term improvement in immunological and virological parameters in this heavily pretreated cohort, with 40% of patients maintaining an undetectable viral load after 9 months of therapy. Patients who failed one PI regimen usually responded to a second regimen. There was a significant rate of side effects from PI treatment.

Is Clostridium difficile a pathogen in the newborn intensive care unit? A prospective evaluation.

OBJECTIVES: The purpose of this study was to investigate (1) the presence of Clostridium difficile toxin in patients in the newborn intensive care unit and (2) the association of C. difficile toxin with gastrointestinal tract symptoms in this population. STUDY DESIGN: A prospective, masked study was done in which twice-weekly stool specimens of subjects hospitalized in a newborn intensive care unit during a 4-month period were analyzed for C. difficile toxin A by enzyme immunoassay. Daily data collection included infant clinical status, stool frequency and character, presence of gastrointestinal tract symptoms, and actions taken for gastrointestinal tract symptoms. Infants hospitalized 5 or more days who had at least two stool assays comprised the study population. For data analysis, an infant with C. difficile toxin-positive status was defined as an infant with two or more toxin-positive stools. RESULTS: Of 87 infants who met study criteria, 42 (48%) had toxin-negative and 45 (52%) toxin-positive results on at least one specimen. Of the infants with toxin-positive findings, 27 (31%) had two or more positive stool assays and comprised the comparison group. The infants with toxin-positive results were smaller, less mature, and had a longer hospital stay than infants with toxin-negative results (p < 0.001). Infants with toxin-positive findings had more days per infant with frequent (> 6) stools and abnormal stools (p < 0.001). The total number of symptom days was 8.2 +/- 5.7 in infants in the toxin-positive group versus 2.2 +/- 2.2 in those in the toxin-negative group (p < 0.001). The mean number of times stools were sent for evaluation and culture was greater in infants with toxin-positive findings (p < or = 0.012) whereas there was no difference in the number of times oral feedings were withheld from infants or infants had abdominal films obtained (p > or = 0.18). CONCLUSIONS: Infants hospitalized in our newborn intensive care unit frequently had stools positive for C. difficile toxin A. When compared with infants with toxin-negative findings, infants with colonization had an increased number of days with gastrointestinal tract symptoms.

Protease inhibitor therapy in children with perinatally acquired HIV infection.

OBJECTIVE: To review the short-term response and safety of protease inhibitor therapy in HIV-infected children. DESIGN: Retrospective chart review of open-label protease inhibitor-containing combination therapy. SETTING: Two urban pediatric HIV centers. PATIENTS: Twenty-eight HIV-infected children were prescribed 30 protease inhibitor-containing antiretroviral therapy combinations. The median age at initiation of protease inhibitor antiretroviral therapy was 79 months. Patients had been on previous antiretroviral therapy for a mean of 45.5 months. RESULTS: Of the 28 children who completed at least 1 month of therapy, 26 experienced marked virologic and immunologic improvement (mean maximal decrease in viral load 1.90 log10 copies/ml; SD, 0.8; mean maximal rise in CD4+ lymphocytes of 279 x 10(6)/l; SD, 300 x 10(6)/l). Eleven patients achieved a viral nadir of < 400 copies/ml, and seven sustained this level of viral suppression for a mean of 6 months. Indinavir use was associated with a high incidence of renal side-effects, including two patients who developed interstitial nephritis. Two patients on ritonavir experienced a significant elevation of liver enzymes. CONCLUSIONS: Protease inhibitor therapy was associated with substantial short-term virologic and immunologic improvement in this primarily heavily pretreated cohort, with 25% maintaining a viral load of < 400 copies/ml after 6 months of therapy. There was a significant rate of adverse events. Pharmacokinetic and safety data are needed to guide aggressive antiretroviral therapy in HIV-infected children, and further treatment options are required for those failing or intolerant to the available protease inhibitors.

Fusarium peritonitis in a child on peritoneal dialysis: case report and review of the literature.

OBJECTIVE: To review various aspects of the management of peritonitis due to Fusarium, a soil mold which infrequently causes infections in humans. DATA SOURCES: A case of Fusarium peritonitis in a child on chronic peritoneal dialysis (PD) is presented. The child developed Fusarium peritonitis 2 weeks after an episode of bacterial peritonitis. His Tenckhoff catheter was removed, and he was maintained on hemodialysis while receiving intravenous amphotericin. Following 2 weeks of treatment with amphotericin, he was successfully returned to PD. A literature review of all previously reported cases of Fusarium peritonitis was then conducted to determine features common to infections caused by Fusarium. Emphasis was also placed on unique characteristics of the organism that may affect patient management, as well as patient characteristics that may increase the risk for infection by Fusarium. RESULTS: Fusarium may cause infection in immunosuppressed individuals, such as cancer patients or patients on chronic PD. The organism has a propensity to attach to foreign bodies such as intravascular and intraperitoneal catheters. Therefore, successful treatment of infections caused by Fusarium may require catheter removal in addition to systemic antifungal therapy. CONCLUSIONS: This report presents the first known case of Fusarium peritonitis in a child. In view of the difficulties posed by this unusual organism, optimal therapy of Fusarium peritonitis should consist of immediate catheter removal and treatment with systemic antifungal drugs.