Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine administered to older infants and children naïve to pneumococcal vaccination.

BACKGROUND: Streptococcus pneumoniae infections are a major cause of morbidity and mortality in children <5 years old worldwide. To increase serotype coverage globally, a 13-valent pneumococcal conjugate vaccine (PCV13) has been developed and approved in many countries worldwide. OBJECTIVE: Assess the safety and immunogenicity of PCV13 in healthy older infants and children naïve to previous pneumococcal vaccination. METHODS: This was a phase 3, open-label, multicenter study conducted in Polish children (N=354) who were vaccinated according to 3 age-appropriate catch-up schedules: Group 1 (aged 7 to <12 months) received two PCV13 doses with a booster at 12-16 months of age; Group 2 (aged 12 to <24 months) received two vaccine doses only; and Group 3 (aged 24 to <72 months) received a single dose of PCV13. Statistical analyses were descriptive. The proportion of immunological "responders" achieving serotype-specific antipneumococcal polysaccharide concentrations ≥0.35µg/mL, 1-month after the last dose of vaccine, was determined for each vaccine serotype. In addition, antipolysaccharide immunoglobulin (Ig) G geometric mean concentrations (GMCs) were calculated. Safety assessments included systemic and local reactions, and adverse events. RESULTS: The proportion of immunological responders was ≥88% across groups for all serotypes. Antipolysaccharide IgG GMCs were generally similar across groups. Each schedule elicited immune response levels against all 13 serotypes comparable to or greater than levels previously reported in infants after a 3-dose series. The 3 catch-up schedules had similar tolerability and safety profiles; a trend was present towards greater local tenderness with increasing age and subsequent dose administration. CONCLUSIONS: Immunological responses and safety results support the use of PCV13 for catch-up schedules in older infants and children naïve to pneumococcal vaccination.

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in Mexico.

OBJECTIVE: To assess the safety and immune responses induced by a 13-valent pneumococcal conjugate vaccine (PCV13) after immunization of infants in Mexico. METHODS: PCV13 was given with other routine childhood vaccinations to 225 infants in Mexico at ages 2, 4, 6, and 12 months. RESULTS: The proportions of subjects achieving immunoglobulin G (IgG) concentrations ≥0.35 µg/mL after the infant series and toddler dose were ≥93.1% and ≥96.7%, respectively, for all 13 serotypes. The serotype-specific pneumococcal IgG geometric mean concentrations after the infant series and toddler dose ranged from 1.18 to 9.13 µg/mL and from 1.62 to 15.41 µg/mL, respectively. The most common local reaction and systemic event after each dose were tenderness and irritability, respectively. Most fever was mild; no fever >40.0°C (i.e., severe) was reported. One subject withdrew because of Kawasaki disease 5 days after the first dose of vaccines, but this condition was not considered related to PCV13. CONCLUSIONS: Overall, PCV13 administered with routine pediatric vaccines was immunogenic and safe in healthy infants in Mexico.

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in Mexico / Inmunogenia y seguridad de la vacuna antineumocócica conjugada 13 valente en México

OBJECTIVE: To assess the safety and immune responses induced by a 13-valent pneumococcal conjugate vaccine (PCV13) after immunization of infants in Mexico. METHODS: PCV13 was given with other routine childhood vaccinations to 225 infants in Mexico at ages 2, 4, 6, and 12 months. RESULTS: The proportions of subjects achieving immunoglobulin G (IgG) concentrations ≥0.35 µg/mL after the infant series and toddler dose were ≥93.1% and ≥96.7%, respectively, for all 13 serotypes. The serotype-specific pneumococcal IgG geometric mean concentrations after the infant series and toddler dose ranged from 1.18 to 9.13 µg/mL and from 1.62 to 15.41 µg/mL, respectively. The most common local reaction and systemic event after each dose were tenderness and irritability, respectively. Most fever was mild; no fever >40.0°C (i.e., severe) was reported. One subject withdrew because of Kawasaki disease 5 days after the first dose of vaccines, but this condition was not considered related to PCV13. CONCLUSIONS: Overall, PCV13 administered with routine pediatric vaccines was immunogenic and safe in healthy infants in Mexico.

OBJETIVO: Evaluar la seguridad y la respuesta inmunitaria inducida por una vacuna antineumocócica conjugada 13 valente (PCV13) tras la vacunación de lactantes en México. MÉTODOS: Se administró la PCV13, junto con otras vacunas habituales de la niñez, a 225 lactantes a los 2, 4, 6 y 12 meses de edad en México. RESULTADOS: Las proporciones de lactantes que alcanzaron concentraciones de inmunoglobulina G (IgG) iguales o superiores a 0,35 µg/ml después de las tres primeras dosis (serie del lactante) y tras la cuarta (dosis del inicio de la deambulación) fueron de ≥ 93,1% y ≥ 96,7%, respectivamente, para los 13 serotipos. Las medias geométricas de las concentraciones de IgG antineumocócica específica de serotipo después de las tres primeras dosis y tras la cuarta variaron de 1,18 a 9,13 µg/ml, y de 1,62 a 15,41 µg/ml, respectivamente. Las reacciones local y sistémica más frecuentes después de cada dosis fueron respectivamente el dolor en el punto de inyección y la irritabilidad. En la mayor parte de los casos, la fiebre fue de carácter leve; no se notificó ningún caso de fiebre de más de 40,0 °C (fiebre grave). Un lactante fue excluido del estudio como consecuencia de la aparición de una enfermedad de Kawasaki cinco días después de la primera dosis de la vacuna, aunque se consideró que este proceso no estaba relacionado con la PCV13. CONCLUSIONES: En términos generales, la PCV13, administrada conjuntamente con las vacunas pediátricas habituales, se mostró inmunógena e inocua en lactantes sanos de México.

Tigecycline versus levofloxacin in hospitalized patients with community-acquired pneumonia: an analysis of risk factors.

INTRODUCTION: This study was conducted to evaluate the efficacy of tigecycline (TGC) versus levofloxacin (LEV) in hospitalized patients with community-acquired pneumonia (CAP) using pooled data and to perform exploratory analyses of risk factors associated with poor outcome. MATERIALS AND METHODOLOGY: Pooled analyses of 2 phase 3 studies in patients randomized to intravenous (IV) TGC (100 mg, then 50 mg q12h) or IV LEV (500 mg q24h or q12h). Clinical responses at test of cure visit for the clinically evaluable (CE) and clinical modified intention to treat populations were assessed for patients with risk factors including aged ≥65 years, prior antibiotic failure, bacteremia, multilobar disease, chronic obstructive pulmonary disease, alcohol abuse, altered mental status, hypoxemia, renal insufficiency, diabetes mellitus, white blood cell count >30 x 10(9)/L or <4 x 10(9)/L, CURB-65 score ≥2, Fine score category of III to V and at least 2 clinical instability criteria on physical examination. RESULTS: In the CE population of 574 patients, overall cure rates were similar: TGC (253/282, 89.7%); LEV (252/292, 86.3%). For all but one risk factor, cure rates for TGC were similar to or higher than those for LEV. For individual risk factors, the greatest difference between treatment groups was observed in patients with diabetes mellitus (difference of 22.9 for TGC versus LEV; 95% confidence interval, 4.8 - 39.9). CONCLUSIONS: TGC achieved cure rates similar to those of LEV in hospitalized patients with CAP. For patients with risk factors, TGC provided generally favorable clinical outcomes.

The 13-valent pneumococcal conjugate vaccine for invasive pneumococcal disease in Alaska native children: results of a clinical trial.

BACKGROUND: During 1996 to 2000, Alaska Native children aged <5 years from Yukon Kuskokwim Delta (YKD) had invasive pneumococcal disease (IPD) rates 10-fold higher than non-Alaska Native children (547/100,000/yr versus 56/100,000/yr). After 7-valent pneumococcal conjugate vaccine (PCV7) introduction, IPD rates decreased to 148 per 100,000 during 2001 to 2004, increasing to 426 per 100,000 during 2005 to 2007 due to non-vaccine serotype disease. In 2009, we evaluated safety, immunogenicity and impact of 13-valent PCV (PCV13) in YKD children. METHODS: In a prelicensure open-label clinical trial, eligible YKD children aged <5 years were offered PCV13 as appropriate for age and prior PCV7 history. PCV13 impact was assessed using existing Alaska-wide IPD surveillance. Serotype-specific anti-pneumococcal IgG levels were measured postinfant series and posttoddler dose in a subset of subjects. Adverse events and serious adverse events were collected in all; local reactions and systemic events were collected in toddlers. All YKD children were offered licensed PCV13 when it became available. RESULTS: Three hundred seventy-two subjects received PCV13 during the clinical trial and 3342 postlicensure (April 2010 to August 2011). Adverse events were typically mild, or generally consistent with common childhood illnesses. IgG levels following PCV13 were similar to other populations. In YKD children aged <5 years, 52 IPD cases (31 PCV13-serotype) occurred during 2005 to 2008 (399.0/100,000/yr) versus 9 (7 PCV13-serotype) during January 2009 to August 2011 (106.7/100,000/yr; P < 0.001). No PCV13-serotype cases occurred among PCV13 recipients (3680 person follow-up years). CONCLUSIONS: PCV13-serotype IPD incidence declined significantly after PCV13 introduction. Although non-PCV13-serotype IPD also declined significantly, absence of PCV13-serotype IPD in children who received PCV13 suggests a protective vaccine effect.

13-valent pneumococcal conjugate vaccine given with meningococcal C-tetanus toxoid conjugate and other routine pediatric vaccinations: immunogenicity and safety.

BACKGROUND: As multiple vaccines are administered concomitantly during routine pediatric immunizations, it is important to ascertain the potential interference of any new vaccine on the immune response to the concomitantly administered vaccines. Immune responses to meningococcal serogroup C-tetanus toxoid conjugate vaccine (MnCC-TT) and the diphtheria and tetanus antigens in routine pediatric vaccines (diphtheria, tetanus, acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenza type b [DTaP-HBV-IPV/Hib] and DTaP-IPV+Hib) when given concomitantly with the 13-valent pneumococcal conjugate vaccine (PCV13) were compared with responses when given with PCV7. In addition, the immunogenicity and safety of PCV13 were assessed. METHODS: Healthy infants were randomized to receive PCV13 or PCV7 (ages 2, 4, 6 and 15 months), concomitant with MnCC-TT (2, 4 and 15 months), DTaP-HBV-IPV/Hib (2, 4 and 6 months), and DTaP-IPV+Hib (15 months). RESULTS: Immune responses to MnCC-TT and to the diphtheria and tetanus antigens administered with PCV13 were noninferior to the responses observed when the vaccines were administered with PCV7; ≥96.6 (postinfant) and ≥99.4% (posttoddler) subjects achieved prespecified immune response levels to each antigen in each group. After the infant series, ≥93.0% of subjects receiving PCV13 achieved pneumococcal anticapsular immunoglobulin G concentrations ≥0.35 µg/mL for all serotypes except serotype 3 (86.2%), increasing to 98.1-100% for most serotypes (serotype 3: 93.6%) after the toddler dose. Local and systemic reactions were similar between groups. CONCLUSIONS: Immune responses to MnCC-TT, and other childhood vaccines (DTaP-HBV-IPV/Hib, DTaP-IPV+Hib) were noninferior when concomitantly administered with PCV13 compared with PCV7. PCV13 does not interfere with MnCC-TT. PCV13 is highly immunogenic with a favorable safety profile.

Phase 3 trial evaluating the immunogenicity, safety, and tolerability of manufacturing scale 13-valent pneumococcal conjugate vaccine.

13-valent pneumococcal conjugate vaccine (PCV13) includes polysaccharide conjugates from six pneumococcal serotypes in addition to those in the licensed 7-valent vaccine, thereby offering expanded protection against pneumococcal disease. The phase 3 trial reported here was conducted per a regulatory requirement to evaluate the immunogenicity, safety, and tolerability of two lots of the final PCV13 formulation that differed with respect to production scale but not the manufacturing process. The anti-pneumococcal polysaccharide immunogenicity and safety/tolerability were found to be similar between the two PCV13 vaccine lots.