In vitro Activity of Cefditoren against Middle Ear Fluid Isolates from Costa Rican Children with Otitis Media.

Otitis media (OM) is one of the most common infections in children, Streptococcus pneumoniae and nontypable Haemophilus influenzae being the two most common pathogens isolated in the middle ear fluid (MEF) of children with OM. Cefditoren is a third-generation cephalosporin with broad-spectrum antibacterial activity, including activity against those pathogens commonly causing OM, with enhanced stability against common ß-lactamases. The main objective of this study was to evaluate the in vitro activity of cefditoren against pathogens collected from the MEF of Costa Rican children with OM between 2006 and 2011. A total of 715 samples were analyzed. Among the 89 S. pneumoniae strains that were penicillin-nonsusceptible, only 7% were cefditoren-resistant according to Spanish Regulatory Agency criteria; among the H. influenza and M. catarrhalis isolates obtained, 100 and 90% of the isolates, respectively, were cefditoren-susceptible. MIC50/90 against the 207 PCV-13 S. pneumoniae serotyped strains and the 79 serotypes not covered by PCV-13 for cefditoren were 0.03/1 and 0.03/0.12 mg/l, respectively. For both amoxicillin-susceptible and resistant H. influenzae strains, the MIC range against cefditoren was from ≤0.015 to 0.06 mg/l as well. In conclusion, the confirmation of the wide spectrum of activity of cefditoren and its intrinsic strength against resistant strains allows us to suggest that cefditoren might be included as one of the best choices among antibiotics that are widely used in empiric therapy for OM in pediatric patients.

Assessment of the safety, tolerability and kinetics of the immune response to A/H1N1v vaccine formulations with and without adjuvant in healthy pediatric subjects from 3 through 17 years of age.

BACKGROUND: The recent global A/H1N1v pandemic led to major efforts to develop effective vaccines against the novel virus, while global demand and limited production capacity focused attention on dose sparing and schedules. METHODS: An open-label phase III study of immunogenicity and safety of novel A/H1N1v vaccines included 392 Costa Rican children in two pediatric cohorts (3-8 and 9-17 years). They received two doses, of either an MF59®-adjuvanted formulation containing 7.5 µg antigen or non-adjuvanted formulations containing 15 or 30 µg antigen, three weeks apart. Immunogenicity was assessed as hemagglutination inhibition (HI) titers using the CBER licensure criteria. RESULTS: All three vaccines elicited immune responses in 9-17 year-olds meeting CBER criteria three weeks after one dose; responses were not enhanced by second dose. In 3-8 year-olds only the adjuvanted vaccine met the CBER criteria after one dose, but all three vaccines met criteria after second dose. All vaccines were well tolerated; no related Serious Adverse Events (SAE) and few severe solicited reactions were reported. MF59-adjuvanted vaccine was associated with more reports of injection site pain and tenderness and overall systemic solicited reactions, most notably in older subjects, all of which decreased after the second dose. CONCLUSION: One dose of non-adjuvanted A/H1N1v vaccine is adequate in 9-17 year-olds, but younger children require either one dose of MF59-adjuvanted vaccine or two doses of non-adjuvanted vaccine to achieve protective titers. Enhanced immunogenicity with MF59 is associated with a small increase in reactogenicity, but no safety issues.

Streptococcus pneumoniae serotype 3 among Costa Rican children with otitis media: clinical, epidemiological characteristics and antimicrobial resistance patterns.

BACKGROUND: After the introduction of the seven valent-pneumococcal conjugated vaccine into our National Immunization Program, it is important to establish and track local serotype distribution in order to evaluate its impact specially because serotype replacement phenomena has been described.To describe the clinical, epidemiological and antimicrobial resistance patterns of Costa Rican children with otitis media caused by Streptococcus pneumoniae serotype 3. METHODS: Middle ear fluid samples were obtained from Costa Rican children with otitis media who participated in various antimicrobial clinical trials between 1992 and 2007. Streptococcus pneumoniae was identified according to laboratory standard procedures. Strains were serotyped and antimicrobial susceptibility to penicillin, amoxicillin, cefuroxime, ceftriaxone, azithromycin and levofloxacin was determined by E-test. RESULTS: Throughout 1992-2007 a total of 1919 tympanocentesis were performed in children with otitis media (median age: 19 months) and yielded a total of 1208 middle ear isolates. The most common pathogens were: Streptococcus pneumoniae, 511 isolates (49%); Non-Typable Haemophilus influenzae, 386 isolates (37%); Moraxella catarrahalis, 100 isolates (9.5%); and Streptococcus pyogenes, 54 isolates (5%). Streptococcus pneumoniae serotyping was performed in 346/511 isolates (68%) recovered during years 1999-2006. The most common serotypes were 19F (101/30.0%), 14 (46/13.7%), 3 (34/10.1%), 6B (30/8.9%) and 23F (23/6.8%). Analysis performed per years showed a higher prevalence of serotype 3 Streptococcus pneumoniae during the study period 2004 and 2005. During the entire study period (1999-2006) serotype 3 was most commonly isolated in children older than 24 months (61.2% vs 40.6%;P = 0.05) and showed a lower rate of penicillin non-susceptibility (4.0% vs 18%; P = 0.003). CONCLUSION: Streptococcus pneumoniae serotype 3 is an important pathogen in Costa Rican children with otitis media, especially in children older than 24 months of age (P = 0.05). Most serotype 3 isolates were susceptible to penicillin, cephalosporins, macrolides and quinolones.

Seasonal distribution of otitis media pathogens among Costa Rican children.

BACKGROUND: Otitis media is an important cause of pediatric consultation, and knowledge of yearly pathogen distribution might improve antimicrobial selection. OBJECTIVES: To determine the seasonal pathogen and antimicrobial resistance distribution among Costa Rican children with otitis media. METHODS: Between 1999 and 2004, 952 children with otitis media, aged 3-144 months who participated in various clinical trials, were analyzed. Data obtained from this period were compared against historical data collected between 1992 and 1997. RESULTS: Five hundred sixteen (52%) children had a baseline middle ear fluid pathogen isolated. The most common pathogens were Streptococcus pneumoniae 252 (49%), Haemophilus influenzae 190 (37%), S. pyogenes 38 (7%), and Moraxella catarrhalis 36 (7%). The overall proportion of H. influenzae (24-37%; P = 0.01) and the production of beta-lactamase producing H. influenzae (2.6-7%; P = 0.02) increased from 1992-1997 to 1999-2004. There was a nonstatistically significant trend for a higher frequency of S. pneumoniae and H. influenzae isolates detected during the rainy season than during the dry season: S. pneumoniae 58% versus 42% but not significant (P = 0.1) and H. influenzae 68% versus 32% (P = 0.06), respectively. During the rainy season, penicillin-nonsusceptible S. pneumoniae was identified more frequently (38.5%) than during the dry season (18%) (P = 0.003; odds ratio: 2.94; 95% confidence interval: 1.4-6.45). Penicillin-nonsusceptible S. pneumoniae decreased from 46.5% (1999-2001) to 16% (2002-2003) and this was associated with a significant decline of a circulating 19F penicillin-resistant S. pneumoniae serotype (from 89% to 26%), respectively. CONCLUSIONS: S. pneumoniae and H. influenzae are the 2 most common pathogens producing otitis media in Costa Rican children. An increase in the number of H. influenzae and M. catarrhalis was observed in recent years. Penicillin-nonsusceptible S. pneumoniae isolates were more commonly observed during the rainy season, in which increased morbidity with respiratory pathogens is observed.

An international serotype 3 clone causing pediatric noninvasive infections in Israel, Costa Rica, and Lithuania.

BACKGROUND: Serotype 3 is known for its ability to cause invasive diseases worldwide. In the United States, after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), the prevalence of a serotype 3 clone (Netherlands-31/ST180) increased. The present study was aimed to evaluate the importance of serotype 3 clones in noninvasive infections in Israel, Costa Rica, and Lithuania. METHODS: Molecular typing and antibiotic resistance were performed on 77 serotype 3 strains recovered from pediatric noninvasive infections during 2003-2005, and on 50 carried strains from healthy carriers. RESULTS: Serotype 3 ranked second among isolates from noninvasive infections in Costa Rica and Lithuania, and seventh among the Israeli isolates. Pulsed field gel electrophoresis (PFGE) analysis revealed the presence of 1 major cluster (64/77, 83%); this cluster comprised 60/64 fully susceptible strains that corresponded to the Netherlands-31/ST180 clone, and 4/64 multidrug-resistant strains, all from Lithuania, that corresponded to ST505, a double locus variant of ST180. Two additional fully susceptible clones, ST458 (11/77, 14%) and ST1116 (2/77, 3%), were found among the Israeli and Costa Rican strains, respectively. The same PFGE clusters identified among noninvasive infections were found among 50 isolates from carriers, with the same molecular characteristics. CONCLUSIONS: Serotype 3 accounts for a large proportion of mucosal disease in children, even before the introduction of PCV7. The data presented here describe for the first time the importance of a multidrug-resistant serotype 3 clone, ST505, in noninvasive infections.

An open-label, double tympanocentesis, single-center study of trimethoprim sulfametoxasole in children with acute otitis media.

Trimethoprim sulfamethoxasole has been recommended for the treatment of acute otitis media. In this double tympanocentesis study, children aged 3 to 48 months with acute otitis media received trimethoprim sulfamethoxasole twice daily (40 mg/kg/d) for 10 days. All children had a baseline tympanocentesis and in culture-positive children, tympanocentesis was repeated at the on-therapy visit. Of 89 children enrolled, 51 (57%) were clinically and bacteriologically evaluable. Bacteriologic eradication was achieved in 80% (42 of 52) of children, and overall clinical response at the end of therapy was 78%. Clinical success was 69% for culture-positive children versus 91% for culture-negative children at baseline tympanocentesis (P = 0.03). In this study, trimethoprim sulfamethoxasole clinical response was unsatisfactory, especially among culture-'positive children.

Activity of trimethoprim-sulfamethoxazole against middle ear fluid pathogens obtained from Costa Rican children with otitis media.

For many years, trimethoprim-sulfamethoxazole (TMP-SMX) has been recommended as an alternative antimicrobial agent for the treatment of children with otitis media (OM). This study analyzed the in vitro activity of TMP-SMX against respiratory pathogens obtained from middle ear fluid of Costa Rican children 6-60 months of age with acute OM, recurrent OM, therapeutic failures and acute OM at risk for having a resistant pathogen. Between 2002 and 2003, a total of 124 middle ear fluid bacterial isolates were analyzed and compared with historic data from 1992 to 1997. A significant increase in the number of TMP-SMX Streptococcus pneumoniae (P = 0.00008)- and Haemophilus influenzae (P = 0.04)-resistant strains was observed during 2002-2003 when compared with strains from 1992-1997.

Middle ear fluid Streptococcus pneumoniae serotype distribution in Costa Rican children with otitis media.

BACKGROUND: Streptococcus pneumoniae conjugate vaccine became available in Costa Rica in 2004. Previous S. pneumoniae middle ear fluid (MEF) data obtained during the period 1999-2001 from Costa Rican children indicated that serotype 19F was the most common type (75%), but more recently other serotypes have become more prevalent. OBJECTIVES: To establish the most common S. pneumoniae serotypes present in the MEF of Costa Rican children with otitis media (OM) and to analyze serotype distribution by demographic factors, disease distribution and antimicrobial susceptibility patterns and assess the potential protection provided by the new conjugated heptavalent S. pneumoniae vaccine in Costa Rican children with OM. METHODS: During 2002 and 2003, 69 S. pneumoniae isolates were obtained from the MEF of Costa Rican children, ages 3-49 months, with OM. Serotyping was performed by the quellung reaction with antisera from Statens Serum Institute, Copenhagen, Denmark. RESULTS: The most common S. pneumoniae serotypes isolated were 19F (26.1%), 6B (14.5%), 9V (8.7%), 16F (8.7%), 14 (5.8%), 23F (5.8%), 3 (5.8%) and 6A (5.8%). Serotype distribution was similar among children younger than 24 months of age or 24 months of age or older and by disease distribution. There was a tendency towards more penicillin- and trimethoprim-sulfamethoxazole-nonsusceptible isolates among vaccine-type strains than among non-vaccine type strains. CONCLUSIONS: The serotype distribution of S. pneumoniae causing pediatric OM in Costa Rica is similar to those reported from developed countries. The current heptavalent pneumococcal conjugate vaccine covers 74% of OM episodes in Costa Rican children.

A randomized, multicenter, double blind, double dummy trial of single dose azithromycin versus high dose amoxicillin for treatment of uncomplicated acute otitis media.

BACKGROUND: High dose amoxicillin is recommended for the initial treatment of children with acute otitis media (AOM), particularly patients at risk for having drug-resistant Streptococcus pneumoniae. Single dose azithromycin (30 mg/kg) is considered an alternative agent for the treatment of AOM. OBJECTIVE: To compare the clinical efficacy and safety of single dose azithromycin with that of high dose amoxicillin among children with uncomplicated AOM. METHODS: This was a double blind, double dummy, multinational, clinical trial in which children (6-30 months of age) with AOM were randomized to treatment with single dose azithromycin (30 mg/kg) or high dose amoxicillin (90 mg/kg/d, in 2 divided doses) for 10 days. Tympanocentesis was performed at baseline and clinical responses were assessed at days 12-14 (end of therapy) and at days 25-28 (end of study). RESULTS: The study enrolled 313 patients, and 83% of the patients were < or =2 years of age. A total of 158 patients in the azithromycin group and 154 in the amoxicillin group were considered clinical modified intent-to-treat patients. A middle ear pathogen was detected for 212 patients (68%). Haemophilus influenzae was the most common pathogen (isolated for 96 patients), followed by S. pneumoniae (92 patients), Moraxella catarrhalis (23 patients) and Streptococcus pyogenes (23 patients). beta-Lactamase production was observed for 17% of H. influenzae isolates and 100% of M. catarrhalis isolates. Thirty-five (38%) S. pneumoniae isolates were penicillin-nonsusceptible and 24 (26%) isolates were macrolide-resistant. At the end of therapy, clinical success rates for azithromycin and amoxicillin were comparable for all patients (84 and 84%, respectively) and for children < or =2 years of age (82 and 82%, respectively). At the end of therapy and end of study, clinical efficacies among all microbiologic modified intent-to-treat evaluable subjects were comparable for patients treated with azithromycin (80%) and patients treated with amoxicillin (83%). The rates of treatment-related adverse events for azithromycin and amoxicillin were 20% and 29%, respectively (P = 0.064). Diarrhea was more common in the amoxicillin group than in the azithromycin group (17.5 and 8.2%, respectively) (P = 0.017). Compliance, defined as completion of > or =80% of the study medication, was higher in the azithromycin group (100%) than in the amoxicillin group (90%) (P = 0.001). CONCLUSIONS: In this study, single dose azithromycin was as effective as high dose amoxicillin for the treatment of children with AOM, whereas rates of adverse events were lower and compliance improved with the simplified single dose regimen.

Etiology and antimicrobial susceptibility of middle ear fluid pathogens in Costa Rican children with otitis media before and after the introduction of the 7-valent pneumococcal conjugate vaccine in the National Immunization Program: acute otitis media microbiology in Costa Rican children.

Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009). This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010-2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3-59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥ 2 PCV7 doses or ≥ 1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction. Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.

Single dose azithromycin for the treatment of uncomplicated otitis media.

Three clinical trials have examined the efficacy and safety of single dose azithromycin (30 mg/kg) in children with uncomplicated acute otitis media (AOM). In the first trial, a small pilot study, the clinical and microbiologic efficacy of single dose azithromycin was comparable with that of 3-day azithromycin or single dose ceftriaxone. A second, non-comparative trial confirmed the clinical and microbiologic efficacy of the single dose regimen. The third study, a large double blind, double dummy trial, demonstrated comparable clinical success rates between single dose azithromycin and 10-day standard amoxicillin/clavulanate. The incidence of drug-related adverse events in patients treated with single dose azithromycin was low in all three trials and similar to rates that have been reported for other antimicrobial agents used for the treatment of patients with AOM. In the amoxicillin/clavulanate trial, compliance with single dose azithromycin was significantly better than with the amoxicillin/clavulanate regimen (P < 0.001). We conclude that a single dose of azithromycin (30 mg/kg) is safe and effective for the treatment of uncomplicated AOM in children.

Microbiology of otitis media in Costa Rican children, 1999 through 2001.

BACKGROUND: Because of the increasing number of resistant middle ear pathogens and the impact of the new conjugate Streptococcus pneumoniae vaccine, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required. OBJECTIVE: To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media (AOM), recurrent otitis media (ROM) and therapeutic failure otitis media (FOM). METHODS: Between 1999 and 2001 middle ear fluid (MEF) was collected from 276 Costa Rican patients. S. pneumoniae serotyping and pulsed field gel electrophoresis analysis was done on available strains. RESULTS: Among the total study population, 102 were AOM patients, 98 were ROM patients and 76 were FOM patients. Overall S. pneumoniae (88 strains) was the most common pathogen isolated followed by Haemophilus influenzae (41 strains) and Streptococcus pyogenes (10 strains). H. influenzae was the most common agent in FOM patients (P = 0.015). Beta-lactamase production was observed in 3 of 41 (7%) H. influenzae strains and 3 of 3 (100%) Moraxella catarrhalis strains. Penicillin-nonsusceptible S. pneumoniae strains were more common in FOM (64%) and ROM (63%) patients than in AOM (42%) patients (P = 0.05). S. pneumoniae serotype 19F was the most prevalent serotype, mainly within one distinct clone. CONCLUSIONS: Overall S. pneumoniae serotype 19F was the most common isolate from the middle ear fluid of Costa Rican children. Beta-lactamase-negative H. influenzae was the most prevalent in the subpopulation of patients with FOM. S. pyogenes was the third most common isolate and M. catarrhalis was uncommon.

Streptococcus pneumoniae serotypes isolated from the middle ear fluid of Costa Rican children following introduction of the heptavalent pneumococcal conjugate vaccine into a limited population.

BACKGROUND: The heptavalent pneumococcal conjugate vaccine (PCV-7) was introduced in high risk children and into the private market in Costa Rica in 2004 (<5% annual birth cohort). The aim of this study was to compare the Streptococcus pneumoniae serotype (ST) distribution, antibiotic resistance patterns and potential coverage before and after partial introduction of PCV-7. METHODS: A comparison between the S. pneumoniae isolates obtained and serotyped from the middle ear fluid (MEF) of Costa Rican children with otitis media between years 1999 and 2003 (before PCV-7 usage) and those isolates obtained from 2004 to 2008. RESULTS: A total of 145 and 218 MEF S. pneumoniae were serotyped between years 1999 and 2003 and 2004 and 2008, respectively. Considering a 19F outbreak observed between years 1999 and 2003, the following statistically significant changes in serotype distribution were detected between 1999 and 2003 and 2004 and 2008: ST 3: 4.8-12.8% (P=0.01); ST 11A: 0-4.1% (P=0.01); ST 14: 3.5-21.1% (P<0.001) and ST 19F: 52.4-18.3% (P<0.05). Comparison of the two study periods demonstrated that during 2004 and 2008 a statistically significant decrease in penicillin non-susceptible serotypes (36.2-20.4% [P=0.003]) and a statistically significant increase in trimethoprim-sulfametoxazole resistant serotypes (54.9-68.5%, respectively [P=0.03]) was observed. Potential pneumococcal vaccines coverage between 1999 and 2003 and between 2004 and 2008 were: for PCV-7: 77.2-60.5%, respectively (P=0.001); for the 10-valent conjugated vaccine (PCV-10): 78.6-61.4%, respectively (P=0.0008) and for the 13-valent conjugated vaccine (PCV-13): 84.8-79.3%, respectively (P=0.2). CONCLUSIONS: Changes in the serotype distribution and antimicrobial susceptibility of MEF S. pneumoniae have been observed in Costa Rican children with OM. Because of the limited use of PCV-7 during the study period, these changes probably cannot be attributed to PCV-7 use. Between 2004 and 2008, PCV-13 offered the highest potential vaccine coverage.

Prospective epidemiologic surveillance of invasive pneumococcal disease and pneumonia in children in San José, Costa Rica.

BACKGROUND: Streptococcus pneumoniae (SP) is the leading cause of vaccine-preventable death in children <5 years of age, globally. This surveillance determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest radiograph-confirmed pneumonia (CXR+Pn); and SP serotype distribution and antimicrobial susceptibility in children in San José, Costa Rica. METHODS: This was a 2-year prospective, population-based surveillance conducted in 2007-2009 in children aged 28 days to 36 months presenting to participating healthcare centers. Eligibility criteria for study inclusion were as follows: temperature ≥ 39.0°C within 24h and/or clinical suspicion of IPD or pneumonia. RESULTS: 8801 subjects were enrolled. Median age: 14.5 months. A total of 25 children had invasive pneumococcal disease with S. pneumoniae isolated from nonduplicative cultures (22) or detected solely by PCR and a clinical picture consistent with IPD (3). Sources of positive cultures (some children had >1 positive culture) were: blood (20), pleural fluid (4), and cerebrospinal fluid (3). Of the 3 cases detected solely by PCR, 2 were from cerebrospinal fluid and 1 from pleural fluid. The overall IPD incidence rates for culture-positive only cases for children aged 28 days to <3 years was 33.7/100,000 per year for years 1 and 2 combined. Age stratification of culture-positive only subjects showed a peak during year 1 (106.8/100,000) in children 28 days to <6 months of age group, and in year 2 (45.5/100,000) in children 12 months to <24 months of age group. Most common serotypes were 14 (28.6%), followed by 3, 4, 6A, 19A, and 22F (9.5% each). Of 22 nonduplicative IPD isolates, 42.9% were penicillin- and trimethoprim/sulfamethoxazole nonsusceptible isolates. Consideration of PCR-positive cases increases the incidence of IPD for children aged 28 days to <3 years to 46.0/100,000. Overall incidence of clinical pneumonia and CXR+Pn was 1968/100,000 and 551/100,000, respectively. CONCLUSIONS: There is a considerable burden of IPD and pneumonia in children in San José. These epidemiologic data serve as a baseline to evaluate the effectiveness of the incorporation of new conjugate pneumococcal vaccines into the National Immunization Program in Costa Rican children.

Bacteriology of community-acquired invasive disease found in a multicountry prospective, population-based, epidemiological surveillance for Pneumococcus in children in Latin America.

Several bacteria cause community-acquired invasive bacterial disease in children; many are vaccine preventable. Knowledge of pathogens causing community-acquired invasive bacterial disease is important when selecting antimicrobial therapy and implementing vaccine prevention strategies. We describe bacteriology of community-acquired invasive disease observed among 31,641 blood and sterile fluid cultures from children aged 28 days to 36 months in 3 Latin American countries over 2 years.

Prevenar experience.

Streptococcus pneumoniae is one of the leading bacterial pathogens causing invasive disease and non-invasive infections at both extremes of life: in children younger than 5 years and in elderly persons of 65 years or more. Pneumococcal infections result in substantial morbidity and mortality among children under 5 years of age; it is estimated that 1,600,000 deaths occur per year in that age range alone, mostly in developing countries, thus representing a serious public health problem around the globe. Infections caused by S. pneumoniae are considered by the World Health Organization (WHO) as the number one vaccine-preventable cause of death in children younger than 5 years of age. In 2000, the first heptavalent conjugated pneumococcal vaccine (PCV7) was licensed in the United States, differing from the already available non-conjugated polysaccharide pneumococcal vaccine in its ability to induce a protective immune response in children under 2 years of age. Initial efficacy studies in the United States with PCV7 revealed a 97.4% efficacy against invasive pneumococcal disease (IPD) caused by vaccine serotypes (4, 9V, 14, 19F, 23F, 18C and 6B). PCV7 was introduced into the National Immunization Program (NIP) of various countries starting in year 2000 and, after 11 years of use, the data confirm that PCV7 introduction resulted in a major reduction of S. pneumoniae IPD, non-bacteremic pneumonia, otitis media medical visits, the need for tympanic tubes, the number of cases of otorrhea and of various antimicrobial resistant strains in children <5 years of age. Additionally, reductions in S. pneumoniae infections have been observed in unvaccinated children above 5 years of age and adults including individuals older than 65 years of age (herd effect). Effectiveness has been observed in countries using a 4-dose regimen (3 infant doses followed by a booster during the second year of life) but also in countries with modified reduced doses (2 infant doses and a booster during the second year of life or after 3 infant doses with no booster).

Single-dose extended-release azithromycin versus a 10-day regimen of amoxicillin/clavulanate for the treatment of children with acute otitis media.

OBJECTIVES: A randomized, double-blind, double-dummy, multicenter international study was conducted to assess the clinical and bacteriologic response, safety, and compliance of a single 60-mg/kg dose of azithromycin extended-release (ER) versus a 10-day regimen of amoxicillin/clavulanate 90/6.4 mg/kg per day in children with acute otitis media at high risk of persistent or recurrent middle ear infection. METHODS: Children aged 3 to 48 months were enrolled and stratified into two age groups (≤ 24 months and >24 months). Pretreatment tympanocentesis was performed at all sites and was repeated during treatment at selected sites. RESULTS: The primary endpoint, clinical response at the test-of-cure visit in the bacteriologic eligible population, was achieved in 80.5% of children in the azithromycin ER group and 84.5% of children in the amoxicillin/clavulanate group (difference-3.9%; 95% confidence interval-10.4, 2.6). Bacteriologic eradication was 82.6% in the azithromycin ER group and 92% in the amoxicillin/clavulanate group (p=0.050). Children who received amoxicillin/clavulanate had significantly higher rates of dermatitis and diarrhea, a greater burden of adverse events, and a lower rate of compliance to study drug compared to those who received azithromycin ER. CONCLUSIONS: A single 60-mg/kg dose of azithromycin ER provides near equivalent effectiveness to a 10-day regimen of amoxicillin/clavulanate 90/6.4 mg/kg per day in the treatment of children with acute otitis media.

Acute otitis media severity of symptom score in a tympanocentesis study.

We followed symptoms of children with acute otitis media (AOM), who were enrolled in a clinical trial that included a baseline tympanocentesis. We observed marked and rapid improvement in symptom scores after tympanocentesis. Although symptom scores (measured by the AOM-SOS) correlated with overall clinical assessment and bacteriologic outcome, the early effect of tympanocentesis rendered the AOM-SOS less useful as a primary outcome measure.