Active hospital-based surveillance of invasive pneumococcal disease and clinical pneumonia in infants and young children in two Polish counties.

INTRODUCTION: Invasive pneumococcal disease (IPD) incidence, serotype distribution, and antibiotic susceptibility of Streptococcus pneumoniae were estimated in children aged 28 days to < 60 months. MATERIAL AND METHODS: One-year prospective, hospital-based surveillance was conducted starting on February 15, 2008, at two children's hospitals serving the city and surrounding county of Poznan and Poznanski, Poland. Eligible children had fever ≥ 39.0°C or physician-suspected IPD. Blood cultures were obtained from all children, cerebrospinal fluid in suspected meningitis cases, and chest radiographs (CXRs) in suspected pneumonia cases. RESULTS: Seven of 1,581 eligible children had confirmed IPD. Estimated IPD incidence per 100,000 children was 11.89 (95% CI: 4.78-24.50) overall and 20.1 (95% CI: 6.52-46.84) in subjects aged 28 days to < 24 months. One S. pneumoniae isolate of each of the following serotypes was obtained: 6B, 14, 23A, 23F, and 33F. Two isolates were resistant to both trimethoprim-sulfamethoxazole and erythromycin. Clinical pneumonia incidence among children aged 28 days to < 24 months and 24 months to < 60 months was 3,151.3 (95% CI: 2934.7-3379.7) and 962.7 (95% CI: 861.2-10,072.9) per 100,000 children, respectively. CXR-confirmed pneumonia rates in the same groups were 1,035.7 (95% CI: 913.2-1,170.1) and 379.8 (95% CI: 317.1-451.3) per 100,000 children, respectively. CONCLUSIONS: IPD is an important cause of morbidity in Poznan and Poznanski county, Poland. Among participants aged < 5 years with fever or suspected IPD, pneumonia was the most common diagnosis and was highest in children aged < 24 months.

Long-term immune responses to pneumococcal conjugate vaccines in children previously vaccinated with 7-valent pneumococcal conjugate vaccine.

BACKGROUND: Seven-valent pneumococcal conjugate vaccine (PCV7) has reduced incidence of vaccine-serotype pneumococcal diseases. Using a single dose of 13-valent pneumoccal conjugate vaccine (PCV13), we evaluated late immune responses 10 years after vaccination with PCV7 in infancy, compared with a PCV7-naïve cohort. METHODS: In this open-label study, we administered 1 dose of PCV13 to children aged 11-14 years who had previously received PCV7 (PCV7/PCV13) or meningococcal group C conjugate vaccine (MnCC/PCV13) during infancy. We evaluated serotype-specific immunoglobulin G concentrations and opsonophagocytic activity prevaccination and 1 week and 1 month postvaccination. We recorded local reactions and systemic events for 4 days postvaccination and adverse events for 6 months. RESULTS: Seventy-four subjects received PCV13 (PCV7/PCV13, n = 38; MnCC/PCV13, n = 36). Prevaccination with PCV13, >62.9% of subjects had immunoglobulin G concentrations ≥0.35 µg/mL for all serotypes except serotype 4 (28-29%); proportions increased at 1 month postvaccination to 100% for all serotypes except serotypes 3 (PCV7/PCV13, 94.7%; MnCC/PCV13, 97.0%) and 14 (MnCC/PCV13, 97.1%). Immunoglobulin G and opsonophagocytic activity concentrations for the 7 common and 6 additional serotypes were similar in both groups prevaccination and increased in both groups from prevaccination to 1 week and 1 month postvaccination. Local reactions and fever were mild or moderate; no serious adverse events were reported. CONCLUSION: Late immune responses after a single dose of PCV13 were similar in children aged 11-14 years regardless of previous vaccination with PCV7 or MnCC. PCV13 was immunogenic, safe and well tolerated.

Pharmacokinetics and safety profile of tigecycline in children aged 8 to 11 years with selected serious infections: a multicenter, open-label, ascending-dose study.

BACKGROUND: Tigecycline, a broad-spectrum antibiotic used for treating serious bacterial infections in adults, may be suitable for pediatric use once an appropriate dosage is determined. OBJECTIVE: The aim of this study was to assess the pharmacokinetic (PK) properties, safety profile, and descriptive efficacy of tigecycline. METHODS: In this Phase II, multicenter, open-label clinical trial, children aged 8 to 11 years with community-acquired pneumonia (CAP), complicated intra-abdominal infection (cIAI), or complicated skin and skin structure infections (cSSSI) were administered tigecycline 0.75, 1, or 1.25 mg/kg. RESULTS: A total of 58 patients received ≥ 1 dose of tigecycline (31 boys; 44 white; mean age, 10 years; mean weight, 35 kg); 47 had data from samples available for PK analysis. The mean (SD) PK values were: C(max), 1899 (2954) ng/mL; T(max), 0.56 (0.18) hour; between-dose AUC, 2833 (1557) ng · h/mL; weight-normalized clearance, 0.503 (0.293) L/h/kg; and Vd(ss), 4.88 (4.84) L/kg. Overall clinical cure rates at test-of-cure were 94% (16/17), 76% (16/21), and 75% (15/20) in the 0.75-, 1-, and 1.25-mg/kg cohorts, respectively. The rates of protocol violations were higher in the 1- and 1.25-mg/kg groups, resulting in higher proportions of indeterminate clinical cure assessments relative to the 0.75-mg/kg cohort (19% and 15% vs 0%). The most frequent adverse event was nausea, which occurred in 50% of patients overall (29/58) and the prevalence of which was significantly higher in the 1.25-mg/kg group versus the 0.75-mg/kg group (65% vs 18%; P = 0.007). Pharmacodynamic simulations using MIC data from an ongoing microbiological surveillance trial predicted that a dosage of 1.2 mg/kg q12h would lead to therapeutic target attainment levels of up to 82% for the target AUC(0-24)/MIC ratios. CONCLUSION: A tigecycline dosage of ∼1.2 mg/kg q12h may represent the most appropriate dosage for subsequent evaluation in Phase III clinical trials in children aged 8 to 11 years with selected serious bacterial infections. ClinicalTrials.gov identifier: NCT00488345.

Efficacy and safety of tigecycline monotherapy compared with vancomycin-aztreonam in the treatment of complicated skin and skin structure infections in patients from India and Taiwan.

BACKGROUND: To compare the monotherapy of tigecycline with vancomycin-aztreonam in hospitalized patients from India and Taiwan with complicated skin and skin structure infections (cSSSIs). METHODS: Safety and efficacy data were analyzed for Indian (n = 86) and Taiwanese (n = 41) patients hospitalized with cSSSIs who participated in two international Phase 3, randomized, double-blind studies. RESULTS: Patients were treated for 5-14 days. Cure rates at the test-of-cure assessment (12-92 days post-therapy) were generally similar between tigecycline and vancomycin-aztreonam in the clinically evaluable populations (India, 83.3% vs. 75.8%; Taiwan, 78.6% vs. 90%) and in the clinical modified intent-to-treat populations (India, 78.6% vs. 66.7%; Taiwan, 73.3% vs. 75.0%). Nausea and vomiting occurred more frequently with tigecycline, but overall safety and tolerability were comparable between the two treatments. CONCLUSIONS: Tigecycline monotherapy is a safe and effective therapy for cSSSIs in geographically distinct populations in Asia.