Elsevier

Vaccine

Volume 29, Issue 33, 26 July 2011, Pages 5544-5549
Vaccine

Bacterial etiology and serotypes of acute otitis media in Mexican children

https://doi.org/10.1016/j.vaccine.2011.04.128Get rights and content

Abstract

Streptococcus pneumoniae and Haemophilus influenzae have been consistently reported to be the two major bacterial pathogens responsible for acute otitis media (AOM), mainly from studies in the US and Europe. However, data on bacterial pathogens causing AOM in Latin America are limited. Understanding the relative importance of these pathogens in a specific setting, the serotype distribution, and their antibiotic susceptibility levels is important to provide local vaccine and treatment recommendations. We therefore conducted a prospective, multi-center, tympanocentesis-based epidemiological study of Mexican children three months to less than five years of age. Fifty percent of episodes were in children who had received at least one dose of PCV7. Overall, 64% of samples were culture positive for bacterial pathogens. H. influenzae and S. pneumoniae were the leading causes of bacterial AOM, detected in 34% and 29% of AOM episodes, respectively. The most commonly isolated S. pneumoniae serotypes were 19A, 19F and 23F. All H. influenzae isolates were identified as non-typeable. Seventy-four percent of S. pneumoniae were susceptible to penicillin, while 97% were susceptible to amoxicillin/clavulanate. All H. influenzae samples were susceptible to amoxicillin/clavulanate and cefotaxime, 95% to cefuroxime and 75% to ampicillin. Both S. pneumoniae and non-typable H. influenzae represent important targets for vaccination strategies to reduce AOM 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

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