trimethoprim--sulfamethoxazole-drug-combination and Growth-Disorders

No randomised controlled trial (RCT) has examined the efficacy of cotrimoxazole (CTX) prophylaxis in HIV-exposed uninfected (HEU) infants during the breastfeeding period, in this new era of effective prevention of mother-to-child transmission (PMTCT) prophylaxis. The efficacy of CTX prophylaxis has presently been demonstrated only in HIV-infected children. The absence of proven benefits in HEU breastfed infants associated with infectious diseases justifies an RCT as proposed. Herewith lies the rationale for conducting the proposed study.. A partially blinded RCT is proposed to evaluate the efficacy of CTX prophylaxis administered from 6 weeks of age to HEU infants receiving a PMTCT regimen. A non-inferiority design will be used, randomising 1298 infants to receive CTX or not to receive CTX. Participants will be reviewed at the following time points: 6 weeks (enrolment and randomisation), 10 weeks, 14 weeks, 4 months and monthly thereafter until 12 months of age. They will be evaluated for anthropometric growth, interval illness, CTX adherence, signs and symptoms of study drug toxicity, concomitant medication use, breastfeeding status and HIV infection status. The study will compare the incidence of grade 3 and grade 4 common childhood illnesses (focusing on pneumonia and diarrhoea) and all-cause mortality until 12 months of age. In a subset of participants, we will compare grade 3 and grade 4 haemoglobin and alanine aminotransferase results as well as investigate gut integrity.. The study has ethical approval from the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC212/13).. PACTR201311000621110 and DOH-27-0614-4728; Pre-results.

Topics: Anti-Bacterial Agents; Anti-HIV Agents; Breast Feeding; Cause of Death; Diarrhea; Female; Growth Disorders; HIV; HIV Infections; Humans; Incidence; Infant; Infant Health; Infant Mortality; Infectious Disease Transmission, Vertical; Male; Morbidity; Mothers; Pneumonia; Pregnancy; Pregnancy Complications, Infectious; Research Design; Trimethoprim, Sulfamethoxazole Drug Combination

In this paper, we examined the details of severe infections, treatment efficacies, and the prognoses of 23 Japanese patients with chronic granulomatous disease (CGD). We described the mean ages at diagnosis and follow-up, which were 2.8 years (range, 0.7-10 years) and 14.9 years (range, 0.2-28.4 years), respectively. There were three deaths, two from Aspergillus pneumonia and one from liver abscess. Eighteen of the 23 patients (78%) had a complete loss of gp91phox, and three had p22-phox and one had p67phox deficiencies. Aspergillus species were found in 45% of 174 severe infections. The mean height and weight of the 20 surviving patients were -0.8 +/- 1.3SD and -1.9 +/- 1.9SD below the means for age, respectively. Short stature and underweight (below the 10th percentile of the means) for age were seen in 22% and 17% of the patients, respectively. This growth retardation reflects the severity of the disease. At 20 years of age, there was 87% survival. Ongoing prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) or antifungal drugs was given in 16 and 11 patients, respectively. Interferon-gamma (IFN-gamma) was given once a week to 14 patients. Four patients underwent hematopoietic stem cell transplantation (HSCT) and are currently well. There were infections observed in three of 21 identified related carriers of X-linked CGD. A carrier with a liver abscess had 5% normal neutrophils during the acute phase of infection, which returned to 40% normal neutrophils after recovery. The high survival rate in this hospital results from regular follow-up and prophylaxis with TMP-SMX and anti-fungal drugs beginning at the time of diagnosis, along with treatment with weekly IFN-gamma.

Topics: Adolescent; Adult; Anti-Infective Agents; Antifungal Agents; Antiviral Agents; Aspergillosis; Biomarkers; Body Height; Child; Child, Preschool; Drug Therapy, Combination; Female; Follow-Up Studies; Genetic Diseases, X-Linked; Granulomatous Disease, Chronic; Growth Disorders; Hospitals, Pediatric; Hospitals, State; Humans; Interferon-gamma; Japan; Male; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Opportunistic Infections; Phosphoproteins; Prognosis; Stem Cell Transplantation; Survival Analysis; Thinness; Trimethoprim, Sulfamethoxazole Drug Combination

A child was evaluated for growth failure at the University of California, San Diego. On two occasions the patient had renal bicarbonate wasting, acidosis, and growth failure associated with trimethoprim/sulfamethoxazole (TMP/SMZ) administration. On both occasions, the acidosis resolved and the growth rate normalized following a period without receiving TMP/SMZ. Renal tubular acidosis and growth failure may occur as a result of TMP/SMZ therapy in children.

Topics: Acidosis, Renal Tubular; Female; Growth Disorders; Humans; Infant; Otitis Media; Trimethoprim, Sulfamethoxazole Drug Combination