Bacterial etiology and serotypes of acute otitis media in Mexican children
Introduction
Acute otitis media (AOM) is the most frequent bacterial infection in children, and often the primary reason for the prescription of antibiotics by pediatricians [1], [2], [3], [4]. Based mainly on studies in the US and Europe, Streptococcus pneumoniae (S. pneumoniae) and non-typeable Haemophilus influenzae (NTHi) have been consistently reported to be the two major bacterial pathogens responsible for AOM [5], [6], [7], [8]. However, there are limited recent data on the etiology of AOM in Latin America, including Mexico. The most recent data from the region come from Costa Rica, but the representativeness of these data for the Latin American region is unclear given apparent variation in incidence, antibiotic use patterns, and serotype distribution by country in the region [9].
Understanding the pathogens involved in AOM is important not only for treatment options but also because pneumococcal conjugate vaccines have shown promise in preventing this disease. For example, randomized clinical trials with a 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar™/Prevenar™, Pfizer/Wyeth) in the US and Finland reported reductions in incidence of AOM of 6–9% [10], [11], [12], [13], while database analyses suggest approximately 20% (range 4–43%) decreases in AOM visit rates following introduction of PCV7 in universal mass vaccination programs [14]. In the recently licensed 10-valent pneumococcal H. influenzae (H. influenzae) protein D conjugate vaccine (PHiD-CV; Synflorix™, GSK Biologicals, Rixensart, Belgium), eight of the 10 pneumococcal serotypes are conjugated to the recombinant form of surface exposed protein D derived from NTHi. In a clinical trial conducted in the Czech and Slovak Republics, an 11-valent prototype vaccine that used the outer membrane protein D carrier derived from H. influenzae as a carrier showed 35% efficacy against clinical AOM, with statistically significant protection against both S. pneumoniae and H. influenzae AOM [15]. However, the potential impact of this and other vaccines cannot be estimated without comprehensive data on AOM incidence and etiology.
Antibiotic resistance of S. pneumoniae is a concern worldwide, and there is evidence of increasing antibiotic resistance for S. pneumoniae in Latin America, particularly in Mexico and the Dominican Republic [16], [17]. Resistance of S. pneumoniae in patients with AOM has been demonstrated in Mexico, with a focus on the high levels of resistance to penicillin [18], [19]. A study of respiratory infections in Mexico also found that resistance to penicillin was a reliable marker for higher probability of multidrug resistance [20]. Due to the risk of treatment failures, up-to-date information on antibiotic resistance has important clinical implications for determining the best approach for treatment of AOM.
This study aimed to characterize the bacterial etiology and serotypes of AOM cases in Mexico, determine what proportion of disease is covered by the currently licensed vaccines, and determine antibiotic susceptibility of the pathogens. In Mexico, PCV7 was introduced for high risk groups in 2006, and included in the National Immunization Program beginning in 2008. PHiD-CV was included in the National Immunization Program at the end 2010 [21].
Section snippets
Methods
This was a prospective, multi-center, epidemiological study conducted within a routine clinical setting in three centers in Durango, Mexico City and Chiapas. The study included children 3–59 months of age visiting pediatric clinics for AOM, from whom a middle ear fluid (MEF) sample was available either by tympanocentesis or spontaneous otorrhea. Unlike many tympanocentesis studies, this study mainly included sporadic cases, and did not focus on recurrent or problematic AOM. Patients identified
Results
A total of 465 children were screened at three study centers between March 11, 2008 and April 2, 2009. Acceptance to participate in the study was provided for 126 episodes of AOM, fifteen of which were eliminated for failing to meet study inclusion criteria. Three of the remaining 111 episodes were classified as treatment failures. Among all of the AOM episodes, there were 10 bilateral infections for which samples from both the left and right ears were collected, and 101 unilateral infections
Discussion
In this study, 64% of samples cultured positive for one of the pathogens under study, which was higher than the 53–58% we expected based on the literature [24], [25], especially given the context of high antibiotic use. H. influenzae and S. pneumoniae were the leading causes of bacterial AOM, and were found in similar proportions.
After the introduction of PCV7 in the US, NTHi became the most common pathogen for a period of time [7], [26], but an increase in non-PCV7 S. pneumoniae was also noted
Conclusions
In summary, this assessment of AOM etiology in Mexican children aged three months to less than five years, visiting pediatric clinics for AOM, showed that 63% of all culture-positive samples were positive for either S. pneumoniae or H. influenzae. Both S. pneumoniae and non-typable H. influenzae represent important targets for vaccination strategies to reduce AOM in Mexican children.
Acknowledgements
The authors thank Dr. Neydi Osnaya Romero, Irma A Ramirez Ruiz, Roberto Carreno, Claudia Cuevas Garcia and Edurne Gomez Roig (GlaxoSmithKline) and Margarita Hernandez-Salgado (Instituto Nacional de Salud Pública, México). They also thank Anna Dow (Freelance) for scientific writing support and Veronique Mouton (GlaxoSmithKline Biologicals) for editorial assistance and manuscript coordination.
Trademark: Prevenar/Prevnar is a trademark of Pfizer/Wyeth; Synflorix is a trademark of GlaxoSmithKline
References (38)
- et al.
Incidence, air pollution and risk factors of acute otitis media in the first year of life: a prospective study
An Pediatr (Barc)
(2004) - et al.
Acute otitis media in a pediatric primary care unit
An Pediatr (Barc)
(2004) - et al.
Understanding the link between pneumococcal serotypes and invasive disease
Vaccine
(2009) - et al.
Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study
Lancet
(2006) - et al.
Antibiotic resistance in Latin America: a cause for alarm
Vaccine
(2009) - et al.
Antimicrobial susceptibility of Streptococcus pneumoniae in Latin America: results from five years of the SENTRY Antimicrobial Surveillance Program
Clin Microbiol Infect
(2004) - et al.
Antimicrobial susceptibility patterns of Streptococcus pneumoniae in Mexico
Diagn Microbiol Infect Dis
(2004) - et al.
Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: potential implications for pneumococcal conjugate vaccines
Vaccine
(2009) - et al.
A dynamic model of pneumococcal infection in the United States: implications for prevention through vaccination
Vaccine
(2010) - et al.
Enquête épidémiologique sur l’AOM en pratique de ville
Med Enfance
(1996)
Trends in antimicrobial drug prescribing among office-based physicians in the United States
JAMA
Open label, multicenter study of gatifloxacin treatment of recurrent otitis media and acute otitis media treatment failure
Pediatr Infect Dis J
Terminology and classification
Changes in frequency and pathogens causing acute otitis media in 1995–2003
Pediatr Infect Dis J
Haemophilus influenzae: a significant pathogen in acute otitis media
Pediatr Infect Dis J
Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group
Pediatr Infect Dis J
Efficacy of a pneumococcal conjugate vaccine against acute otitis media
N Engl J Med
Impact of the pneumococcal conjugate vaccine on otitis media
Pediatr Infect Dis J
The seven-valent pneumococcal conjugate vaccine reduces tympanostomy tube placement in children
Pediatr Infect Dis J
Cited by (19)
A systematic review and meta-analysis of antimicrobial resistance in paediatric acute otitis media
2019, International Journal of Pediatric OtorhinolaryngologyCitation Excerpt :Abstracts were screened for relevance to bacteriology or antimicrobial resistance in acute otitis media in children, which identified 204 articles. The full texts and bibliographies were read, and 48 articles [17–28] [29–64], had quantitative data that could be included in the analysis (Fig. 1, Table 1). Of these, 8 were retrospective studies, 27 were prospective studies, 4 were a combination of both prospective and retrospective analysis, and 9 were drug trials.
Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean 2010–2015: A systematic review and a time series analysis
2018, VaccineCitation Excerpt :Forty-three studies reported on IPD [12,16–19,25–62], of which 26 used data from SIREVA [12,27–51] and 11 used data from other sources [52–62] (Tables 1 and S7). Eighteen publications reported on non-IPD data: six focused on AOM [33,59,63–66] and 12 on nasopharyngeal carriage [67–78] (Table 2). Among 37 studies for IPD (excluding the six SIREVA bulletins), 19 were retrospective and/or laboratory-based surveillance case series, and 18 were literature reviews or prospective/enhanced active surveillance (Table S8).
Estimación de la Relación Costo-Efectividad de las Vacunas Neumocócicas Conjugadas Prevenar-13 y Synflorix®, Utilizadas en Los Programas de Vacunación de Población Infantil Mexicana
2016, Value in Health Regional IssuesCitation Excerpt :La etiología de otitis media aguda fue estimada con base en un estudio realizado en México que reportó que un 29% de los casos fue imputable a S. pneumoniae y un 34% a HiNT [17]. La distribución de los serotipos de S. pneumoniae responsables de los cuadros de otitis media fue obtenida a partir de cuatro estudios referidos en la revisión sistemática de Bardach y cols [12] y dos más realizados por Macías Parra y cols [17] y Sierra y cols [18] en México y Colombia, respectivamente. Adicionalmente, la distribución promedio de los serotipos de S. pneumoniae causantes de la enfermedad neumocócica invasiva fue obtenida a partir de los datos reportados por el sistema de vigilancia epidemiológica denominado SIREVA II, para el período que va desde el año 2010 hasta el 2012 [19–21] (los detalles de toda esta información estan en el archivo de Datos Suplementarios).
Bacterial etiology of acute otitis media in Spain in the post-pneumococcal conjugate vaccine era
2016, Anales de PediatriaBacterial etiology of acute otitis media in the era prior to universal pneumococcal vaccination in Taiwanese children
2014, Journal of Microbiology, Immunology and InfectionCitation Excerpt :NTHi even once became the predominance pathogen in the United States.13 A later study in Mexico showed the incidence of bacterial AOM caused by S. pneumoniae elevated again and was almost equal to NTHi.18 It was suggested that this should be the result from the increasing of non-PCV7 serotypes.
The role of non-typable Haemophilus influenza in recurrent otitis media in children
2024, Egyptian Journal of Otolaryngology