Widening Differences in Acute Otitis Media Study Populations
- Reprints or correspondence: Dr Michael Pichichero, Rochester General Hospital, Research Institute, 1425 Portland Ave, Rochester, NY 14621 (Michael.pichichero{at}rochestergeneral.org).
The article “Acute Otitis Media Caused by Moraxella catarrhalis: Epidemiologic and Clinical Characteristics” in this issue of Clinical Infectious Diseases is one of many interesting papers by the Beer-Sheva, Israel, Pediatric Infectious Disease Group led by Ron Dagan and Eugene Leibovitz. These investigators are prominent authorities in acute otitis media (AOM) and nasopharynx colonization in children and continue to evaluate their extensive data. In the current article they describe results relating to the role of Moraxella catarrhalis in AOM [1], a topic recently reviewed in this journal [2].
The main findings are as follows. First, M. catarrhalis is more often observed in mixed AOM infections than as a solo pathogen, compared with Streptococcus pneumoniae and nontypable Haemophilus influenzae . Second, as a solo pathogen M. catarrhalis is isolated more often in children aged <12 months and in first episodes. Third, M. catarrhalis causes less spontaneous perforation of the tympanic membrane (suggestive of somewhat less virulence) than S. pneumoniae or nontypable H. influenzae .
A key objective of the study was to determine whether selected clinical features of M. catarrhalis AOM are less severe than AOM caused by S. pneumoniae and nontypable H. influenzae . To this end, the authors collected information on fever (an excellent objective clinical measure), vomiting (a nonspecific measure), and spontaneous perforation of the tympanic membrane. The research would have been strengthened if the authors would have systematically collected symptoms and signs of AOM when the patient presented for care, as was done by Rodriguez and Schwartz [3].
Another point to be considered is that this study occurred during a 7-year time frame. The dynamics of change due to antibiotic selection, frequency of antibiotic use, and sporadic use of pneumococcal conjugate vaccines (PCVs) in Beer-Sheva during the 7 years of sample collection is unknown, but it is likely to be different from the United States and elsewhere in the world. The differences in their observations of AOM pathogen mix from those of the United States [4-11] have become a topic of increasing conversation among AOM experts. In the United States, the use of PCV7 in children has caused marked changes in the AOM pathogen mix and organism antibiotic susceptibility [9, 10]. Dagan et al [12] have themselves recently described shifts in pneumococcal serotypes in their region (specifically including the emergence of serotype 19A) despite the absence of widespread use of PCV7, and they attributed that change to a “dramatic” increase in use of azithromycin in their area. How did this change in antibiotic prescribing affect M. catarrhalis isolations, epidemiology, and mixed infection rates?
The frequency of isolation of 2 or even 3 pathogens from the middle ear is remarkably high in the Beer-Sheva population compared with most US studies. The investigation included 14.5% of cultures from spontaneous perforations of the tympanic membrane. Culture results were included if the perforation occurred up to 7 days before enrollment. Limiting results to perforations that were <24 h old would have produced more accurate data [13]. However, this design flaw would most likely lead to increased isolation of Staphylococcus aureus and other skin flora. Our otitis media research center has found that 2.5%-7.0% of tympanocentesis cultures yield 2 otopathogens, with 3 otopathogens being rare (<1%) [5, 7, 9]. In a recent paper [11], isolation rates of 2 otopathogens from children with recurrent and difficult-to-treat AOM were reported to be 6.5% by Hoberman in Pittsburgh, Pennsylvania, and 0% by Schwartz in Vienna, Virginia; 2 pathogen isolation rates by Block et al [8] in Bardstown, Kentucky (6.7%); Pelton et al [14] in Boston, Massachusetts (1.6%); Rosenblut et al [15] in Chile (3.6%); Kilpi et al [16] in Finland (7.3%); and Arguedas et al [17] in Costa Rica (2.6%) have been similar to those in my own center. In contrast, the article by the Beer-Sheva group describes a 24.7% rate of multiple otopathogens, and 122 cases in children involved 3 otopathogens in the same ear at the same time. In an exclusively otitis-prone population, Block et al [6] had a 13% rate of 2 pathogens, Ruohola et al [18] found a rate of 19% from tympanostomy tube otorrhea, and Gehanno et al [19] found a rate of 17% among patients referred to an otolaryngologist for tympanocentesis. Thus, the high double-otopathogen rate from Beer-Sheva appears inconsistent with many US studies and similar to specific, likely more severe and more frequently infected populations, in the United States, Finland, and France. Such a result needs to be reconciled because it causes concern about the generalizability of the results from Beer-Sheva. Indeed, it may be that results from Beer-Sheva, with its unique patterns of antibiotic use and population dynamics with or without limited PCV vaccinations, should be cautiously extrapolated to countries such as the United States, as a highly PCV7 vaccinated country, with different patterns of antibiotic use and/or different population dynamics. The past 2 decades of comparability of otopathogen distribution and antibiotic susceptibility among international AOM investigator sites may be over.
This study evaluated 2 populations (Jewish and Bedouin). Dagan and Leibovitz have emphasized in the past the advantages of their study population in providing information about a “first world population” (the Jews) and a “third world population” (the Bedouins). In this current report significant differences were observed between these populations for at least 1 of the analyses, and differences in these populations exist in overall antibiotic use, azithromycin use, crowding, medical care seeking, smoking, lifestyle, access to PCV7 privately, and proportionate participation in all the trials that generated this huge database. This difference in population dynamics is an important feature to be understood.
Variations in AOM study designs can produce significant variations in outcomes for antibiotic and vaccination efficacy trials [20]. However, our otitis media research center has participated with Pichichero et al [21] and Arguedas et al [22] in several different efficacy studies during which we evaluated antibiotics using the same study design. The ability of the Beer-Sheva group to recruit study participants has constantly been exceptional and the quality of their data impeccable. Yet when the results of treatment have been compared, the differences in mixed pathogen isolation rates and outcomes in children studied from Beer-Sheva compared with our center or other centers were often clear, although masked, when combined into overall tallies of results. It seems it is neither the scientists nor the study design, but there is something different in Beer-Sheva, Israel, and that difference probably affects what they describe in this current article regarding M. catarrhalis and multiple mixed AOM pathogens.
- Received August 7, 2009.
- Accepted August 10, 2009.
- © 2009 by the Infectious Diseases Society of America
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