- Email: [email protected]
Relationship between clinical signs and symptoms and nasopharyngeal flora in acute otitis media
Research Notes 679
8. Vogiatzakis E, Stefanou S, Skrobelou A, Anagnostou S, Marinis E, Matsiota-Bernard P. Molecular markers for the investigation of Mycobacterium gordonae epidemics. J Hosp Infect 1998; 38: 217–222. 9. Zhang Y, Rajagopalan M, Brown BA, Wallace RJ. Randomly amplified polymorphic DNA PCR for comparison of Mycobacterium abscessus strains from nosocomial outbreaks. J Clin Microbiol 1997; 35: 3132–3139. 10. Martı´n Casabona N, Rossello´ Urgell J. Micobacterias ambientales en Espan˜a: Aislamientos durante el periodo 1976–96. Med Clı´n (Barcelona) 2000; 115: 663–670. 11. Gebo KA, Srinivasian A, Perl TM, Ross T, Groth A, Merz WG. Pseudo-outbreak of Mycobacterium fortuitum on a human immunodeficiency virus ward: transient respiratory tract colonization from a contaminated ice machine. Clin Infect Dis 2002; 35: 32–38. 12. LaBombardi VJ, O’Brien AM, Kislak JW. Pseudo-outbreak of Mycobacterium fortuitum due to contaminated ice machines. Am J Infect Control 2002; 30: 184–186. 13. Ashford DA, Kellerman S, Yakrus M et al. Pseudo-outbreak of septicemia due to rapidly growing mycobacteria associated with extrinsic contamination of culture supplement. J Clin Microbiol 1997; 35: 2040–2042. 14. Wurtz R, Demarais P, Trainor W et al. Specimen contamination in mycobacteriology laboratory detected by pseudo-outbreak of multidrug-resistant tuberculosis: analysis by routine epidemiology and confirmation by molecular technique. J Clin Microbiol 1996; 34: 1017–1019. 15. Meunier J-R, Grimont PAD. Factors affecting reproducibility of random amplified polymorphic DNA fingerprinting. Res Microbiol 1993; 144: 373–379.
RESEARCH NOTE Relationship between clinical signs and symptoms and nasopharyngeal flora in acute otitis media R. Cohen1, C. Levy2, V. Hentgen3, M. Boucherat2, F. de La Rocque2, P. d’Athis4 and E. Bingen5 1
Service de Microbiologie, Centre Hospitalier Intercommunal Cre´teil, Cre´teil, 2Association Clinique et The´rapeutique Infantile du Val de Marne, Saint Maur, 3Service de Pe´diatrie, Hoˆpital de Versailles, De´partement de Biostatistique, Versailles, 4Centre Hospitalier Universitaire Dijon, Dijon, 5Service de Microbiologie, Hoˆpital Robert Debre´, Paris, France Corresponding author and reprint requests: R. Cohen, De´partement de Microbiologie, Centre Hospitalier Intercommunal de Cre´teil, 40 avenue de Verdun, 94 000 Cre´teil, France E-mail: [email protected]
ABSTRACT Possible links between the clinical signs and symptoms of acute otitis media and the composition of the nasopharyngeal flora were investigated by reviewing the files of 1807 children enrolled in four randomised, multicentre trials. A standard protocol was used, nasopharyngeal samples were cultured, and signs and symptoms were recorded. Carriage of Haemophilus influenzae was associated positively with conjunctivitis (OR 4.83, 95% CI 3.76–6.20) and negatively with fever (OR 0.69, 95% CI 0.56–0.86). Carriage of pneumococci was associated positively with fever (OR 1.32, 95% CI 1.08–1.63) and negatively with conjunctivitis (OR 0.50, 95% CI 0.40–0.63). Keywords Acute otitis media, children, Haemophilus influenza, nasopharyngeal flora, Streptococcus pneumoniae Original Submission: 4 October 2005; Revised Submission: 22 November 2005; Accepted: 14 December 2005
Clin Microbiol Infect 2006; 12: 679–682 10.1111/j.1469-0691.2006.01483.x Various bacteria and viruses have been documented as pathogens in cases of acute otitis media (AOM). Previous reports suggest that the clinical characteristics of AOM may help to predict the bacterial pathogen(s) present in middle ear fluid. In particular, Streptococcus pneumoniae is associated with higher fever, more severe earache, and more frequent sequelae and complications, while Haemophilus influenzae is associated with less severe AOM and with conjunctivitis [1–4]. As the onset of bacterial AOM appears to require initial nasopharyngeal colonisation by the homologous strain, the present study investigated the composition of the nasopharyngeal flora of AOM patients according to their demographical characteristics and clinical signs and symptoms [5]. Using a standardised protocol, four successive randomised trials were used to compare several antibiotic regimens for the treatment of AOM. The methods have been described in detail elsewhere [6–8] and the protocols were approved by the Saint Germain en Laye Hospital Ethics Committee. Written informed consent was obtained from parents or guardians. The study populations comprised children of both genders, aged from 4 months to 4 years, with newly diagnosed AOM. Diagnostic criteria for AOM included the
2006 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 12, 672–694
680 Clinical Microbiology and Infection, Volume 12 Number 7, July 2006
Paradise algorithm for acute suppurative otitis media (effusion plus marked redness or marked bulging, or moderate redness and bulging) associated with fever and ⁄ or otalgia and ⁄ or irritability [9]. Patients were not eligible if they had received antibiotic treatment within the 7 days preceding enrolment. Upon inclusion, the patients were sampled to identify bacterial pathogens colonising the nasopharyngeal niche. Nasopharyngeal specimens were taken with cotton-tipped wire swabs and transported to a central bacteriology laboratory on selective transport medium at ambient temperature. All specimens were cultured aerobically on blood and chocolate agar in air with CO2 10% v ⁄ v. A second blood agar plate was incubated anaerobically. Isolates were identified using standard microbiological methods [8]. Information gathered at study entry included gender, age, history of day care and AOM, and clinical symptoms and signs of AOM (thoroughly documented in the four trials). Data were analysed using Statview II (SAS Inc., Chicago, IL, USA) to compare frequencies and perform chisquare tests, and Intercooled STATA 8 (Stata Corp.,
College Station, TX, USA) to perform multivariate analyses. The influence of attendance at a day care centre (DCC), conjunctivitis, fever, otalgia or irritability, history of AOM, gender, year, season and age on nasopharyngeal colonisation were analysed with logistic regression models. Between October 1993 and June 2000, 1807 children with AOM were enrolled in four studies conducted by 83 French paediatricians who had been trained to conduct clinical trials involving AOM. In total, 53.7% of the children were boys; 89.3% were aged < 24 months (median age 12.8 months, mean 14.6 ± 7.6 months); 436 (24.1%) children attended a DCC, 530 (29.4%) were cared for by childminders and 841 (46.5%) were kept at home. Fever (> 38C; median 38.5C, mean 38.6 ± 0.6C) was recorded in 1217 (67.3%) cases, earache or irritability in 1304 (83%) cases, and conjunctivitis in 436 (24.1%) cases. Table 1 shows the carriage rates of S. pneumoniae, H. influenzae and Moraxella catarrhalis, grouped according to demographical and clinical characteristics. At least one of these pathogens was isolated from the nasopharyngeal niche of 1607 patients; 661 patients carried only one
S. pneumoniae
H. influenzae
M. catarrhalis
n (%)
n (%)
n (%)
Overall population (n = 1807)
1047 (57.9)
849 (46.9)
939 (51.9)
Otitis-prone children Yes (n = 212) No (n = 1593) p OR (95% CI)
124 (58.5) 923 (57.9) 0.9 1.01 (0.75–1.37)
111 (52.3) 738 (46.3) 0.09 1.11 (0.81–1.50)
114 (53.8) 769 (51.7) 0.1 0.96 (0.72–1.29)
Day care DCC (n = 436) Childminder (n = 530) Home (n = 841) p OR (95% CI)
298 (68.3) 288 (54.3) 461 (54.8) < 0.0001 2.02 (1.58–2.58)
261 (59.9) 226 (42.6) 362 (43.1) < 0.0001 1.73 (1.36–2.21)
264 (60.5) 264 (49.8) 411 (48.9) 0.0002 1.45 (1.15–1.83)
Fever ‡ 38.5C (n = 671) ‡ 38C and £ 38.4C (n = 545) No (n = 591) p OR (95% CI)
434 (64.7) 308 (56.5) 305 (51.6) < 0.0001 1.32 (1.08–1.63)
277 (41.3) 252 (46.2) 320 (54.1) < 0.0001 0.69 (0.56–0.86)
371 285 283 0.03 1.16
Otalgia or irritability Yes (n = 1304) No (n = 267) p OR (95% CI)
740 (56.7) 156 (58.4) 0.6 0.94 (0.85–1.04)
614 (47.1) 122 (45.7) 0.7 0.96 (0.87–1.06)
645 (49.5) 150 (56.2) 0.04 0.86 (0.79–0.95)
Conjunctivitis Yes (n = 436) No (n = 1371) p OR (95% CI)
203 (46.6) 844 (61.6) < 0.0001 0.50 (0.40–0.63)
330 (75.7) 519 (37.8) < 0.0001 4.83 (3.76–6.20)
220 (50.5) 719 (52.4) 0.5 0.92 (0.74–1.15)
Table 1. Carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis according to clinical characteristics
(55.3) (52.3) (47.9) (0.95–1.43)
a
a
Not determined for 236 children. DCC, day care centre.
2006 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 12, 672–694
Research Notes 681
species, 668 patients carried two species, and 278 patients carried three species. Logistic regression analysis showed that pneumococcal carriage was associated positively with fever (OR 1.32, 95% CI 1.08–1.63) and DCC attendance (OR 2.02, 95% CI 1.58–2.58), and negatively with conjunctivitis (OR 0.50, 95% CI 0.40–0.63). Carriage of H. influenzae was associated positively with conjunctivitis (OR 4.83, 95% CI 3.76–6.20) and DCC attendance (OR 1.73, 95% CI 1.36–2.21), and negatively with fever (OR 0.69, 95% CI 0.56–0.86). Carriage of M. catarrhalis was associated positively with DCC attendance (OR 1.45, 95% CI 1.15–1.83), and negatively with otalgia and irritability (OR 0.86, 95% CI 0.79–0.95). Multiple carriage was more frequent among patients attending a DCC (OR 2.36, CI 1.86–2.99) and among patients with conjunctivitis (OR 1.31, 95% CI 1.05–1.65). The microbial ecology of the nasopharyngeal niche is highly complex. Colonisation rates vary throughout the world and are influenced by environmental factors such as DCC attendance. In a previous study, acute respiratory illness, and particularly AOM, increased the rate of colonisation by AOM-causing bacteria [10]. The correlations found in the present study are in keeping with the results of studies based on middle ear fluid culture [1–3]. Only one study failed to show a correlation between clinical symptoms and the bacteriological aetiology of AOM [11]. To our knowledge, the present study is the first to show a significant link between the composition of the nasopharyngeal flora and the characteristics of patients with AOM. Nasopharyngeal samples were used because they are easy to obtain, painless, non-traumatic, and also because they have considerable epidemiological value, particularly for monitoring antibiotic resistance among bacterial species involved in AOM. However, because the causative bacteria of AOM often grow alongside other organisms in nasopharyngeal cultures, this type of sample has poor positive predictive value for the causative agent and is not recommended in clinical practice [5,12]. Colonisation by potential pathogens is generally symptomless, but can act as a springboard for local or even systemic infection. Indirectly, the present results support the view that the onset of AOM requires initial nasopharyngeal colonisation by the homologous species [13,14]. Populations with high rates of S. pneumoniae or H. influenzae carriage are particularly valuable for
studying the impact of vaccination programmes and antibiotic treatment. The present results suggest that enrolment of AOM patients with fever, but not conjunctivitis, could reduce the number of subjects needed to demonstrate the impact of pneumococcal conjugate vaccines or antibiotics on carriage of S. pneumoniae. Likewise, studies of the impact of future vaccines against non-typeable H. influenzae in the nasopharyngeal flora should focus on AOM patients with conjunctivitis but not fever. REFERENCES 1. Howie VM, Ploussard JH, Lester RL. Otitis media: a clinical and bacteriological correlation. Pediatrics 1970; 45: 29– 35. 2. Palmu AA, Herva E, Savolainen H, Karma P, Makela PH, Kilpi TM. Association of clinical signs and symptoms with bacterial findings in acute otitis media. Clin Infect Dis 2004; 38: 234–242. 3. Rodriguez WJ, Schwartz RH. Streptococcus pneumoniae causes otitis media with higher fever and more redness of tympanic membranes than Haemophilus influenzae or Moraxella catarrhalis. Pediatr Infect Dis J 1999; 18: 942–944. 4. Bodor FF. Conjunctivitis-otitis syndrome. Pediatrics 1982; 69: 695–698. 5. Faden H, Stanievich J, Brodsky L, Bernstein J, Ogra PL. Changes in nasopharyngeal flora during otitis media of childhood. Pediatr Infect Dis J 1990; 9: 623–626. 6. Cohen R, de La Rocque F, Boucherat M et al. A randomised trial of cefpodoxime-proxetil 5 days vs. amoxicillinclavulanate 8 days in children with acute otitis media. Me´d Mal Infect 1997; 27: 596–602. 7. Cohen R, Levy C, Boucherat M, Langue J, de La Rocque F. A multicentre, randomised, double-blind trial of five vs. 10 days of antibiotic therapy for acute otitis media in young children. J Pediatr 1998; 133: 634–639. 8. Cohen R, Levy C, Boucherat M et al. Five vs. 10 days of antibiotic therapy for acute otitis media in young children. Pediatr Infect Dis J 2000; 19: 458–463. 9. Paradise JL. On classifying otitis media as suppurative or non-suppurative, with a suggested clinical schema. J Pediatr 1987; 111: 948–951. 10. Cohen R, Varon E. Change in nasopharyngeal flora without antibiotics. Lett Infect 2001; 16: 4–8. 11. Leibovitz ESR, Piglansky L, Raiz S, Press J, Leiberman A, Dagan R. Can acute otitis media caused by Haemophilus influenzae be distinguished from that caused by Streptococcus pneumoniae? Pediatr Infect Dis J 2003; 22: 509–515. 12. Gehanno P, Lenoir G, Barry B, Bons J, Boucot I, Berche P. Evaluation of nasopharyngeal cultures for bacteriologic assessment of acute otitis media in children. Pediatr Infect Dis J 1996; 15: 329–332. 13. Faden H, Duffy L, Wasielewski R, Wolf J, Krystofik D, Tung Y. Relationship between nasopharyngeal colonisation and the development of otitis media in children. Tonawanda ⁄ Williamsville Paediatrics. J Infect Dis 1997; 175: 1440–1445.
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682 Clinical Microbiology and Infection, Volume 12 Number 7, July 2006
14. Gray BM, Converse GM, Dillon HC. Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J Infect Dis 1980; 142: 923–933.
Original Submission: 20 September 2005; Revised Submission: 12 November 2005; Accepted: 14 December 2005
Clin Microbiol Infect 2006; 12: 682–684 10.1111/j.1469-0691.2006.01484.x
RESEARCH NOTE Usefulness of pneumococcal antigen detection in pleural fluid samples by immunochromatographic assay for diagnosis of pneumococcal pneumonia F. Andreo1, J. Domı´nguez2, J. Ruiz-Manzano3, C. Prat2, S. Blanco2, L. Lores1, M. D. Sa´nchez2, I. Latorre2, M. Gime´nez2 and V. Ausina2 1
Servei de Pneumologia, Hospital de Sant Boi, Servei de Microbiologia, 3Servei de Pneumologia, Hospital Universitari Germans Trias i Pujol, Facultat de Medicina, Universitat Auto`noma de Barcelona, Barcelona, Spain
2
ABSTRACT This study investigated the utility of an immunochromatographic test (ICT) for the detection of Streptococcus pneumoniae antigens in pleural fluid. Antigen was detected in 15 of 19 (79%) patients with pneumococcal pneumonia. The ICT was always negative in patients with non-pneumococcal pneumonia, but was positive in three cases with a non-infectious aetiology. In patients with pneumonia for which no pathogen was identified, antigen was detected in one of 24 pleural fluids tested. The ICT can be a valuable tool for the management of pneumonia because it can detect pneumococcal antigen in pleural effusion samples. Keywords Antigen detection, immunochromatographic test, pleural fluid, pneumococcal pneumonia, Streptococcus pneumoniae
Corresponding author and reprint requests: J. Domı´nguez, Servei de Microbiologia, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s ⁄ n, 08916 Badalona, Barcelona, Spain E-mail: [email protected]
Community-acquired pneumonia is a significant cause of morbidity and mortality, with the most common aetiological agent in virtually all studies being Streptococcus pneumoniae [1,2]. A definite diagnosis of pneumococcal pneumonia requires the isolation of S. pneumoniae from blood, pleural fluid effusions, trans-tracheal aspirate, trans-thoracic aspirate or samples obtained by protected brush. However, blood and pleural fluid cultures are positive in only 30% of cases, and invasive samples are not routinely or indiscriminately performed because they require trained personnel and may have adverse effects. According to the guidelines of the Infectious Diseases Society of America [1] and the American Thoracic Society [2], any significant pleural effusion should be sampled to rule out the possibility of empyema or complicated parapneumonic effusion. Pleural fluid examination should include Gram’s stain and bacterial culture. However, the diagnostic accuracy of these techniques may be reduced by various factors, including preceding antibiotic therapy. A rapid and accurate detection method for pneumococcal antigen in pleural fluid effusions would therefore be most useful. Polysaccharide capsular antigen detection methods, i.e., agglutination tests and counter-immunoelectrophoresis (CIE), have been used for antigen detection in respiratory and other samples [3], including pleural effusions [4]. An immunochromatographic test (ICT) (NOW Streptococcus pneumoniae Antigen Test; Binax, Portland, ME, USA) has been developed to detect C polysaccharide antigen (PnC) in urine samples [5,6]. The aim of the present study was to determine the utility of the ICT for the detection of S. pneumoniae-specific antigens in pleural effusions. In total, 91 pleural fluid samples were included in the study. Patients and samples were classified into four groups: group 1 included 19 parapneumonic pleural fluids from 16 patients (nine male and seven female; mean age 54.26 years, range 18–91 years) who were diagnosed with pneumococcal pneumonia; group 2 included seven parapneumonic pleural effusions from six patients
2006 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 12, 672–694
8. Vogiatzakis E, Stefanou S, Skrobelou A, Anagnostou S, Marinis E, Matsiota-Bernard P. Molecular markers for the investigation of Mycobacterium gordonae epidemics. J Hosp Infect 1998; 38: 217–222. 9. Zhang Y, Rajagopalan M, Brown BA, Wallace RJ. Randomly amplified polymorphic DNA PCR for comparison of Mycobacterium abscessus strains from nosocomial outbreaks. J Clin Microbiol 1997; 35: 3132–3139. 10. Martı´n Casabona N, Rossello´ Urgell J. Micobacterias ambientales en Espan˜a: Aislamientos durante el periodo 1976–96. Med Clı´n (Barcelona) 2000; 115: 663–670. 11. Gebo KA, Srinivasian A, Perl TM, Ross T, Groth A, Merz WG. Pseudo-outbreak of Mycobacterium fortuitum on a human immunodeficiency virus ward: transient respiratory tract colonization from a contaminated ice machine. Clin Infect Dis 2002; 35: 32–38. 12. LaBombardi VJ, O’Brien AM, Kislak JW. Pseudo-outbreak of Mycobacterium fortuitum due to contaminated ice machines. Am J Infect Control 2002; 30: 184–186. 13. Ashford DA, Kellerman S, Yakrus M et al. Pseudo-outbreak of septicemia due to rapidly growing mycobacteria associated with extrinsic contamination of culture supplement. J Clin Microbiol 1997; 35: 2040–2042. 14. Wurtz R, Demarais P, Trainor W et al. Specimen contamination in mycobacteriology laboratory detected by pseudo-outbreak of multidrug-resistant tuberculosis: analysis by routine epidemiology and confirmation by molecular technique. J Clin Microbiol 1996; 34: 1017–1019. 15. Meunier J-R, Grimont PAD. Factors affecting reproducibility of random amplified polymorphic DNA fingerprinting. Res Microbiol 1993; 144: 373–379.
RESEARCH NOTE Relationship between clinical signs and symptoms and nasopharyngeal flora in acute otitis media R. Cohen1, C. Levy2, V. Hentgen3, M. Boucherat2, F. de La Rocque2, P. d’Athis4 and E. Bingen5 1
Service de Microbiologie, Centre Hospitalier Intercommunal Cre´teil, Cre´teil, 2Association Clinique et The´rapeutique Infantile du Val de Marne, Saint Maur, 3Service de Pe´diatrie, Hoˆpital de Versailles, De´partement de Biostatistique, Versailles, 4Centre Hospitalier Universitaire Dijon, Dijon, 5Service de Microbiologie, Hoˆpital Robert Debre´, Paris, France Corresponding author and reprint requests: R. Cohen, De´partement de Microbiologie, Centre Hospitalier Intercommunal de Cre´teil, 40 avenue de Verdun, 94 000 Cre´teil, France E-mail: [email protected]
ABSTRACT Possible links between the clinical signs and symptoms of acute otitis media and the composition of the nasopharyngeal flora were investigated by reviewing the files of 1807 children enrolled in four randomised, multicentre trials. A standard protocol was used, nasopharyngeal samples were cultured, and signs and symptoms were recorded. Carriage of Haemophilus influenzae was associated positively with conjunctivitis (OR 4.83, 95% CI 3.76–6.20) and negatively with fever (OR 0.69, 95% CI 0.56–0.86). Carriage of pneumococci was associated positively with fever (OR 1.32, 95% CI 1.08–1.63) and negatively with conjunctivitis (OR 0.50, 95% CI 0.40–0.63). Keywords Acute otitis media, children, Haemophilus influenza, nasopharyngeal flora, Streptococcus pneumoniae Original Submission: 4 October 2005; Revised Submission: 22 November 2005; Accepted: 14 December 2005
Clin Microbiol Infect 2006; 12: 679–682 10.1111/j.1469-0691.2006.01483.x Various bacteria and viruses have been documented as pathogens in cases of acute otitis media (AOM). Previous reports suggest that the clinical characteristics of AOM may help to predict the bacterial pathogen(s) present in middle ear fluid. In particular, Streptococcus pneumoniae is associated with higher fever, more severe earache, and more frequent sequelae and complications, while Haemophilus influenzae is associated with less severe AOM and with conjunctivitis [1–4]. As the onset of bacterial AOM appears to require initial nasopharyngeal colonisation by the homologous strain, the present study investigated the composition of the nasopharyngeal flora of AOM patients according to their demographical characteristics and clinical signs and symptoms [5]. Using a standardised protocol, four successive randomised trials were used to compare several antibiotic regimens for the treatment of AOM. The methods have been described in detail elsewhere [6–8] and the protocols were approved by the Saint Germain en Laye Hospital Ethics Committee. Written informed consent was obtained from parents or guardians. The study populations comprised children of both genders, aged from 4 months to 4 years, with newly diagnosed AOM. Diagnostic criteria for AOM included the
2006 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 12, 672–694
680 Clinical Microbiology and Infection, Volume 12 Number 7, July 2006
Paradise algorithm for acute suppurative otitis media (effusion plus marked redness or marked bulging, or moderate redness and bulging) associated with fever and ⁄ or otalgia and ⁄ or irritability [9]. Patients were not eligible if they had received antibiotic treatment within the 7 days preceding enrolment. Upon inclusion, the patients were sampled to identify bacterial pathogens colonising the nasopharyngeal niche. Nasopharyngeal specimens were taken with cotton-tipped wire swabs and transported to a central bacteriology laboratory on selective transport medium at ambient temperature. All specimens were cultured aerobically on blood and chocolate agar in air with CO2 10% v ⁄ v. A second blood agar plate was incubated anaerobically. Isolates were identified using standard microbiological methods [8]. Information gathered at study entry included gender, age, history of day care and AOM, and clinical symptoms and signs of AOM (thoroughly documented in the four trials). Data were analysed using Statview II (SAS Inc., Chicago, IL, USA) to compare frequencies and perform chisquare tests, and Intercooled STATA 8 (Stata Corp.,
College Station, TX, USA) to perform multivariate analyses. The influence of attendance at a day care centre (DCC), conjunctivitis, fever, otalgia or irritability, history of AOM, gender, year, season and age on nasopharyngeal colonisation were analysed with logistic regression models. Between October 1993 and June 2000, 1807 children with AOM were enrolled in four studies conducted by 83 French paediatricians who had been trained to conduct clinical trials involving AOM. In total, 53.7% of the children were boys; 89.3% were aged < 24 months (median age 12.8 months, mean 14.6 ± 7.6 months); 436 (24.1%) children attended a DCC, 530 (29.4%) were cared for by childminders and 841 (46.5%) were kept at home. Fever (> 38C; median 38.5C, mean 38.6 ± 0.6C) was recorded in 1217 (67.3%) cases, earache or irritability in 1304 (83%) cases, and conjunctivitis in 436 (24.1%) cases. Table 1 shows the carriage rates of S. pneumoniae, H. influenzae and Moraxella catarrhalis, grouped according to demographical and clinical characteristics. At least one of these pathogens was isolated from the nasopharyngeal niche of 1607 patients; 661 patients carried only one
S. pneumoniae
H. influenzae
M. catarrhalis
n (%)
n (%)
n (%)
Overall population (n = 1807)
1047 (57.9)
849 (46.9)
939 (51.9)
Otitis-prone children Yes (n = 212) No (n = 1593) p OR (95% CI)
124 (58.5) 923 (57.9) 0.9 1.01 (0.75–1.37)
111 (52.3) 738 (46.3) 0.09 1.11 (0.81–1.50)
114 (53.8) 769 (51.7) 0.1 0.96 (0.72–1.29)
Day care DCC (n = 436) Childminder (n = 530) Home (n = 841) p OR (95% CI)
298 (68.3) 288 (54.3) 461 (54.8) < 0.0001 2.02 (1.58–2.58)
261 (59.9) 226 (42.6) 362 (43.1) < 0.0001 1.73 (1.36–2.21)
264 (60.5) 264 (49.8) 411 (48.9) 0.0002 1.45 (1.15–1.83)
Fever ‡ 38.5C (n = 671) ‡ 38C and £ 38.4C (n = 545) No (n = 591) p OR (95% CI)
434 (64.7) 308 (56.5) 305 (51.6) < 0.0001 1.32 (1.08–1.63)
277 (41.3) 252 (46.2) 320 (54.1) < 0.0001 0.69 (0.56–0.86)
371 285 283 0.03 1.16
Otalgia or irritability Yes (n = 1304) No (n = 267) p OR (95% CI)
740 (56.7) 156 (58.4) 0.6 0.94 (0.85–1.04)
614 (47.1) 122 (45.7) 0.7 0.96 (0.87–1.06)
645 (49.5) 150 (56.2) 0.04 0.86 (0.79–0.95)
Conjunctivitis Yes (n = 436) No (n = 1371) p OR (95% CI)
203 (46.6) 844 (61.6) < 0.0001 0.50 (0.40–0.63)
330 (75.7) 519 (37.8) < 0.0001 4.83 (3.76–6.20)
220 (50.5) 719 (52.4) 0.5 0.92 (0.74–1.15)
Table 1. Carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis according to clinical characteristics
(55.3) (52.3) (47.9) (0.95–1.43)
a
a
Not determined for 236 children. DCC, day care centre.
2006 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 12, 672–694
Research Notes 681
species, 668 patients carried two species, and 278 patients carried three species. Logistic regression analysis showed that pneumococcal carriage was associated positively with fever (OR 1.32, 95% CI 1.08–1.63) and DCC attendance (OR 2.02, 95% CI 1.58–2.58), and negatively with conjunctivitis (OR 0.50, 95% CI 0.40–0.63). Carriage of H. influenzae was associated positively with conjunctivitis (OR 4.83, 95% CI 3.76–6.20) and DCC attendance (OR 1.73, 95% CI 1.36–2.21), and negatively with fever (OR 0.69, 95% CI 0.56–0.86). Carriage of M. catarrhalis was associated positively with DCC attendance (OR 1.45, 95% CI 1.15–1.83), and negatively with otalgia and irritability (OR 0.86, 95% CI 0.79–0.95). Multiple carriage was more frequent among patients attending a DCC (OR 2.36, CI 1.86–2.99) and among patients with conjunctivitis (OR 1.31, 95% CI 1.05–1.65). The microbial ecology of the nasopharyngeal niche is highly complex. Colonisation rates vary throughout the world and are influenced by environmental factors such as DCC attendance. In a previous study, acute respiratory illness, and particularly AOM, increased the rate of colonisation by AOM-causing bacteria [10]. The correlations found in the present study are in keeping with the results of studies based on middle ear fluid culture [1–3]. Only one study failed to show a correlation between clinical symptoms and the bacteriological aetiology of AOM [11]. To our knowledge, the present study is the first to show a significant link between the composition of the nasopharyngeal flora and the characteristics of patients with AOM. Nasopharyngeal samples were used because they are easy to obtain, painless, non-traumatic, and also because they have considerable epidemiological value, particularly for monitoring antibiotic resistance among bacterial species involved in AOM. However, because the causative bacteria of AOM often grow alongside other organisms in nasopharyngeal cultures, this type of sample has poor positive predictive value for the causative agent and is not recommended in clinical practice [5,12]. Colonisation by potential pathogens is generally symptomless, but can act as a springboard for local or even systemic infection. Indirectly, the present results support the view that the onset of AOM requires initial nasopharyngeal colonisation by the homologous species [13,14]. Populations with high rates of S. pneumoniae or H. influenzae carriage are particularly valuable for
studying the impact of vaccination programmes and antibiotic treatment. The present results suggest that enrolment of AOM patients with fever, but not conjunctivitis, could reduce the number of subjects needed to demonstrate the impact of pneumococcal conjugate vaccines or antibiotics on carriage of S. pneumoniae. Likewise, studies of the impact of future vaccines against non-typeable H. influenzae in the nasopharyngeal flora should focus on AOM patients with conjunctivitis but not fever. REFERENCES 1. Howie VM, Ploussard JH, Lester RL. Otitis media: a clinical and bacteriological correlation. Pediatrics 1970; 45: 29– 35. 2. Palmu AA, Herva E, Savolainen H, Karma P, Makela PH, Kilpi TM. Association of clinical signs and symptoms with bacterial findings in acute otitis media. Clin Infect Dis 2004; 38: 234–242. 3. Rodriguez WJ, Schwartz RH. Streptococcus pneumoniae causes otitis media with higher fever and more redness of tympanic membranes than Haemophilus influenzae or Moraxella catarrhalis. Pediatr Infect Dis J 1999; 18: 942–944. 4. Bodor FF. Conjunctivitis-otitis syndrome. Pediatrics 1982; 69: 695–698. 5. Faden H, Stanievich J, Brodsky L, Bernstein J, Ogra PL. Changes in nasopharyngeal flora during otitis media of childhood. Pediatr Infect Dis J 1990; 9: 623–626. 6. Cohen R, de La Rocque F, Boucherat M et al. A randomised trial of cefpodoxime-proxetil 5 days vs. amoxicillinclavulanate 8 days in children with acute otitis media. Me´d Mal Infect 1997; 27: 596–602. 7. Cohen R, Levy C, Boucherat M, Langue J, de La Rocque F. A multicentre, randomised, double-blind trial of five vs. 10 days of antibiotic therapy for acute otitis media in young children. J Pediatr 1998; 133: 634–639. 8. Cohen R, Levy C, Boucherat M et al. Five vs. 10 days of antibiotic therapy for acute otitis media in young children. Pediatr Infect Dis J 2000; 19: 458–463. 9. Paradise JL. On classifying otitis media as suppurative or non-suppurative, with a suggested clinical schema. J Pediatr 1987; 111: 948–951. 10. Cohen R, Varon E. Change in nasopharyngeal flora without antibiotics. Lett Infect 2001; 16: 4–8. 11. Leibovitz ESR, Piglansky L, Raiz S, Press J, Leiberman A, Dagan R. Can acute otitis media caused by Haemophilus influenzae be distinguished from that caused by Streptococcus pneumoniae? Pediatr Infect Dis J 2003; 22: 509–515. 12. Gehanno P, Lenoir G, Barry B, Bons J, Boucot I, Berche P. Evaluation of nasopharyngeal cultures for bacteriologic assessment of acute otitis media in children. Pediatr Infect Dis J 1996; 15: 329–332. 13. Faden H, Duffy L, Wasielewski R, Wolf J, Krystofik D, Tung Y. Relationship between nasopharyngeal colonisation and the development of otitis media in children. Tonawanda ⁄ Williamsville Paediatrics. J Infect Dis 1997; 175: 1440–1445.
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682 Clinical Microbiology and Infection, Volume 12 Number 7, July 2006
14. Gray BM, Converse GM, Dillon HC. Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J Infect Dis 1980; 142: 923–933.
Original Submission: 20 September 2005; Revised Submission: 12 November 2005; Accepted: 14 December 2005
Clin Microbiol Infect 2006; 12: 682–684 10.1111/j.1469-0691.2006.01484.x
RESEARCH NOTE Usefulness of pneumococcal antigen detection in pleural fluid samples by immunochromatographic assay for diagnosis of pneumococcal pneumonia F. Andreo1, J. Domı´nguez2, J. Ruiz-Manzano3, C. Prat2, S. Blanco2, L. Lores1, M. D. Sa´nchez2, I. Latorre2, M. Gime´nez2 and V. Ausina2 1
Servei de Pneumologia, Hospital de Sant Boi, Servei de Microbiologia, 3Servei de Pneumologia, Hospital Universitari Germans Trias i Pujol, Facultat de Medicina, Universitat Auto`noma de Barcelona, Barcelona, Spain
2
ABSTRACT This study investigated the utility of an immunochromatographic test (ICT) for the detection of Streptococcus pneumoniae antigens in pleural fluid. Antigen was detected in 15 of 19 (79%) patients with pneumococcal pneumonia. The ICT was always negative in patients with non-pneumococcal pneumonia, but was positive in three cases with a non-infectious aetiology. In patients with pneumonia for which no pathogen was identified, antigen was detected in one of 24 pleural fluids tested. The ICT can be a valuable tool for the management of pneumonia because it can detect pneumococcal antigen in pleural effusion samples. Keywords Antigen detection, immunochromatographic test, pleural fluid, pneumococcal pneumonia, Streptococcus pneumoniae
Corresponding author and reprint requests: J. Domı´nguez, Servei de Microbiologia, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s ⁄ n, 08916 Badalona, Barcelona, Spain E-mail: [email protected]
Community-acquired pneumonia is a significant cause of morbidity and mortality, with the most common aetiological agent in virtually all studies being Streptococcus pneumoniae [1,2]. A definite diagnosis of pneumococcal pneumonia requires the isolation of S. pneumoniae from blood, pleural fluid effusions, trans-tracheal aspirate, trans-thoracic aspirate or samples obtained by protected brush. However, blood and pleural fluid cultures are positive in only 30% of cases, and invasive samples are not routinely or indiscriminately performed because they require trained personnel and may have adverse effects. According to the guidelines of the Infectious Diseases Society of America [1] and the American Thoracic Society [2], any significant pleural effusion should be sampled to rule out the possibility of empyema or complicated parapneumonic effusion. Pleural fluid examination should include Gram’s stain and bacterial culture. However, the diagnostic accuracy of these techniques may be reduced by various factors, including preceding antibiotic therapy. A rapid and accurate detection method for pneumococcal antigen in pleural fluid effusions would therefore be most useful. Polysaccharide capsular antigen detection methods, i.e., agglutination tests and counter-immunoelectrophoresis (CIE), have been used for antigen detection in respiratory and other samples [3], including pleural effusions [4]. An immunochromatographic test (ICT) (NOW Streptococcus pneumoniae Antigen Test; Binax, Portland, ME, USA) has been developed to detect C polysaccharide antigen (PnC) in urine samples [5,6]. The aim of the present study was to determine the utility of the ICT for the detection of S. pneumoniae-specific antigens in pleural effusions. In total, 91 pleural fluid samples were included in the study. Patients and samples were classified into four groups: group 1 included 19 parapneumonic pleural fluids from 16 patients (nine male and seven female; mean age 54.26 years, range 18–91 years) who were diagnosed with pneumococcal pneumonia; group 2 included seven parapneumonic pleural effusions from six patients
2006 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 12, 672–694