ORIGINAL ARTICLE The Role of pneumoniae in Children With Chronic Sinusitis

Anthony Cultrara, MD; Nira A. Goldstein, MD; Alexander Ovchinsky, MD; Tamara Reznik, BS; Patricia M. Roblin, MS; Margaret R. Hammerschlag, MD

Background: Chlamydia pneumoniae infection is a fre- Results: Specimens were obtained from 20 children quent cause of lower respiratory disease in both adults (14 boys and 6 girls) aged 3 through 16 years. Thirteen and children. However, its role in upper respiratory dis- bilateral endoscopic ethmoidectomies with maxillary an- ease, including sinusitis, is less clear. trostomies, 10 adenoidectomies, and 3 bilateral maxil- lary sinus lavages were performed. Chlamydia pneumo- Objective: To determine the role of infection with C pneu- niae was isolated from the nasopharyngeal swab and moniae in chronic sinusitis in children. adenoid tissue of 1 child (aged 6 years); however, his middle meatal swabs and maxillary sinus aspirates were Design: Prospective collection of specimens. negative. After 10 days of treatment with clarithromy- cin, repeat nasopharyngeal cultures were negative for C Setting: Tertiary care academic medical center. pneumoniae.

Participants: Children with clinical and radiologic evi- Conclusions: With the use of sensitive culture meth- dence of chronic sinusitis unresponsive to medical man- ods, C pneumoniae was not isolated from sinus speci- agement undergoing adenoidectomy, maxillary sinus la- mens of children enrolled in this study. This prelimi- vage, or endoscopic sinus surgery for treatment. nary study suggests that C pneumoniae does not play a significant role in chronic sinusitis in children. Intervention: Nasopharyngeal and middle meatal swabs and portions of surgical specimens were obtained and cul- tured for C pneumoniae. Arch Otolaryngol Head Neck Surg. 2003;129:1094-1097

T IS ESTIMATED that between cedures including middle meatal culture 5% and 10% of upper respira- and maxillary sinus aspirations and irri- tory tract in children gations may also be performed as a first- progress to acute sinusitis, with line surgical therapy depending on the af- even fewer cases progressing to fected sinuses and preferences of the chronicI sinusitis.1 Chronic sinusitis is de- surgeon. Children who do not respond to fined as persistent symptoms of nasal con- first-line surgical treatment may require gestion, rhinorrhea, cough, or facial pain endoscopic ethmoidectomies with middle or headache lasting more than 3 months, meatal antrostomies to provide adequate or 6 episodes per year of recurrent acute drainage pathways for the ethmoid and sinusitis each lasting at least 10 days with maxillary sinuses.3,4 persistent changes on computed tomog- The predominant respon- raphy 4 weeks after medical therapy with- sible for chronic sinusitis are Streptococ- From the Departments of out an intervening acute infection.2 Chil- cus pneumoniae, Haemophilus influenzae, Otolaryngology (Drs Cultrara, dren who do not respond to appropriate Moraxella catarrhalis, Staphylococcus au- Goldstein, and Ovchinsky) and medical therapy, usually consisting of 3 to reus, ␣-hemolytic streptococcus, and oc- Pediatrics–Division of 6 weeks of broad-spectrum antibiotics and casionally anaerobes.6,7 Chlamydia pneu- Infectious Diseases (Mss Reznik possibly intranasal corticosteroids, nasal moniae, an obligate intracellular bacterial and Roblin and saline irrigations, decongestants, and al- parasite, is emerging as a frequent cause Dr Hammerschlag), State lergy management, are often referred for of lower and upper respiratory disease in University of New York 3 Downstate Medical Center, surgery. First-line surgical management both children and adults. Although it has Brooklyn. The authors have no usually consists of an adenoidectomy to been isolated from 1 adult patient with relevant financial interest in remove the adenoid pad as a source of bac- acute sinusitis,8 its role in pediatric acute this article. terial contamination to the sinuses.4,5 Pro- and chronic sinusitis is unknown. Our spe-

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 129, OCT 2003 WWW.ARCHOTO.COM 1094

©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 cific aim was to collect specimens from pediatric pa- tients undergoing surgical treatment for refractory chronic Table 1. Patient Demographics and Surgical Procedures sinusitis and, by using sensitive culture techniques, to determine the role of C pneumoniae in pediatric chronic Characteristic Finding sinusitis. Age, y Mean ± SD 8.3 ± 3.6 METHODS Range 3-16 Sex, No. (%) Children aged 2 through 18 years who were scheduled for sur- Male 14 (70) gical intervention for treatment of chronic sinusitis were re- Female 6 (30) cruited from the private practice of 3 pediatric otolaryngolo- Race, No. (%) gists and the otolaryngology clinics of the Long Island College White 16 (80) Hospital and the University Hospital of Brooklyn, Brooklyn, NY, African American 2 (10) from June 1, 2000, to August 31, 2001. All children enrolled were Hispanic 2 (10) scheduled independent of this study for one or more of the fol- Surgical procedures, No. lowing surgical procedures: adenoidectomy, unilateral or bilat- Bilateral endoscopic ethmoidectomies 10 with maxillary antrostomies eral maxillary sinus lavage, and unilateral or bilateral endo- Bilateral endoscopic ethmoidectomies 3 scopic ethmoidectomy with middle meatal antrostomy. The with maxillary antrostomies with adenoidectomy routine practice of our department is to recommend surgery for Adenoidectomy 4 children with symptoms of chronic sinusitis for at least 3 months Adenoidectomy with bilateral maxillary lavage 3 despite appropriate medical therapy. All children had a sinus ra- diograph or paranasal sinus computed tomographic scan dem- onstrating mucosal thickening of at least 4 mm, opacification, or an air-fluid level in at least 1 maxillary or ethmoid sinus. Pa- This study was approved by the institutional review boards tients with known immunodeficiencies, cystic fibrosis, congen- at the State University of New York Downstate Medical Cen- ital syndromes, intracranial and/or intraorbital sinus complica- ter, Brooklyn, and the Long Island College Hospital. For each tions, and those who received macrolide antibiotic treatment patient, a written informed consent was obtained from parent within 2 weeks of surgery were excluded from the study. or legal guardian before participation in the study. Surgical procedures were performed with the patient un- der general anesthesia. All patients underwent unilateral or bi- lateral endoscopically guided middle meatal swabs, depending RESULTS on the extent of disease. A nasopharyngeal swab was also per- formed either under visualization with the nasal endoscope or Twenty children, aged 3 through 16 years, whose demo- under direct visualization before adenoidectomy. Vogan et al9 graphics are presented in Table 1, entered and com- demonstrated a 90% correlation between bacterial pathogens iso- pleted the study. Thirteen bilateral endoscopic ethmoid- lated by endoscopically guided middle meatal swabs and max- ectomies with maxillary antrostomies, 10 adenoidectomies, illary sinus aspirations. Previous studies have also demon- and 3 bilateral maxillary sinus lavages were performed. strated a high correlation between adenoid and sinonasal bacterial 5 Seven children underwent simultaneous bilateral myrin- pathogens. Cultures for C pneumoniae were collected with wire- gotomy and tube insertion for treatment of otitis media shafted Dacron swabs (Dacroswab; Spectrum Laboratories, Los with effusion, and 2 children underwent tonsillectomy for Angeles, Calif). Specimens obtained from adenoidectomy, max- illary sinus lavage, and endoscopic ethmoidectomy were also sent treatment of recurrent . A total of 97 C pneumo- for C pneumoniae culture. Aerobic and anaerobic cultures were niae cultures were obtained; however, cultures were in- obtained from all maxillary sinus lavages and from selected other advertently not obtained from the nasopharyngeal and sites at the discretion of the attending surgeon. middle meatal swabs of one child and the middle meatal Cultures for aerobes and anaerobes were performed by stan- swabs from another child (Table 2). dard techniques. Swabs for C pneumoniae culture were im- Chlamydia pneumoniae was isolated from the naso- mersed in 2 mL of transport medium containing a sucrose phos- pharyngeal swab and adenoid tissue of 1 child (aged 6 phate buffer with 20% fetal calf serum, 10 µg of gentamicin years); however, his middle meatal swabs and maxillary sulfate per milliliter, 10 µg of vancomycin hydrochloride per sinus aspirates were negative for C pneumoniae. Hae- milliliter, and 1 µg of amphotericin B per milliliter. The speci- mophilus influenzae and S aureus were isolated from aero- mens were refrigerated for up to 24 hours or frozen at −70° if not cultured within that period. Cultures for C pneumoniae were bic cultures of his maxillary lavage. He was initially treated performed in cycloheximide-treated HEp-2 cells grown in 96- postoperatively with a combination of amoxicillin and well microtiter plates.10 All specimens were passed once, and clavulanate potassium. After the C pneumoniae culture culture confirmation was accomplished by fluorescent anti- results were obtained, he was treated with 10 days of cla- body staining with a species-specific monoclonal antibody rithromycin. After treatment, repeat nasopharyngeal cul- (Washington Research Foundation, Seattle). The culture tures were negative for C pneumoniae. This child clini- method has been demonstrated to be highly sensitive for de- cally improved after his surgery in June 2000, but he was 10,11 tecting C pneumoniae in respiratory specimens. treated with antibiotics for 3 episodes of acute sinusitis Patients who had any specimen positive for C pneumoniae during the winter after his surgery and still required daily were offered antimicrobial treatment with , intranasal corticosteroids and saline irrigations with a na- erythromycin, or . A follow-up culture for C pneumoniae from the nasopharynx or middle meatus was per- sal wash (Rinoflow; Mefar, Bovezzo, Italy, distributed by formed, with the use of the above culture techniques, at 4 weeks Respironics, Inc, Murrysville, Pa) during the winter. after therapy in the office, only if one of these sites was initially Chlamydia pneumoniae was not found in any of the culture positive for C pneumoniae. Further therapy was dictated sinus specimens obtained from the 20 children in this by the patient’s clinical course and follow-up culture findings. study. On the basis of our small sample size, the preva-

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 129, OCT 2003 WWW.ARCHOTO.COM 1095

©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Table 2. Total Specimens Collected for Culture*

Patient Nasopharynx Right Middle Left Middle Right Left Right Left No. Swab Meatal Swab Meatal Swab Adenoid Maxillary Lavage Maxillary Lavage Sinus Specimen Sinus Specimen 1X X XX 2+ X X+ X X 3X X X X X 4 XX 5X XX 6X X X X X 7X X XX 8X X X X X 9X X XX 10 X X X X X 11 X X X X X 12 X X X X X 13 X X X X X 14 X X X X X X 15 X X X X X 16 X X X X X X 17 X X X X X X 18 X X X X 19 X X X X X X 20 X X X X X X Total No. 19 18 18 10 3 3 13 13

*X indicates specimen collected; +, positive culture for Chlamydia pneumoniae.

lence of C pneumoniae was calculated to be between 0% dia; however, only 2 of these children were infected with and 13.9% by means of an exact 95% binomial confi- C pneumoniae alone. Ogawa et al19 cultured C pneumoniae dence interval.12 from the middle ear aspirates of 14% of patients with oti- Aerobic and anaerobic cultures were obtained from tis media with effusion. However, Goo et al,20 using poly- 5 maxillary sinus lavages and 1 middle meatal swab. Staphy- merase chain reaction, did not identify C pneumoniae DNA lococcus aureus alone was isolated from 2 maxillary sinus in any of the middle ear fluids from the 75 patients with lavages and 1 middle meatal swab (2 patients), H influen- otitis media with effusion. Although Grayston et al13 dem- zae and S aureus were isolated from 1 maxillary sinus la- onstrated evidence of sinusitis in 12% of their patients with vage (the child with the positive C pneumoniae cultures), and 7% of those with caused by and Pasteurella multocida and Streptococcus viridans were C pneumoniae, C pneumoniae has been identified from the isolated from 2 maxillary sinus lavages (1 patient). Al- maxillary sinus of only 1 adult with acute sinusitis in Ja- though only a limited number of specimens were ob- pan.8 Thus far, there have been no attempts to identify tained, the culture results agree with previous studies of C pneumoniae in pediatric patients with chronic sinusitis. the usual pathogens of pediatric chronic sinusitis. Our study examined 36 surgical specimens and 61 culture swabs for the presence of C pneumoniae in 20 chil- COMMENT dren with chronic sinusitis. Cell culture for detection of C pneumoniae is considered to be the gold standard for Chlamydia pneumoniae has been implicated as an impor- detection of C pneumoniae infection21; therefore, this tech- tant cause of bronchitis, pneumonia, and other respira- nique was used for C pneumoniae diagnosis for this study. tory tract infections.13,14 The proportion of community- Chlamydia pneumoniae was isolated from the nasophar- acquired associated with C pneumoniae ynx and adenoid tissue of only 1 boy who underwent an infection ranges from 6% to 28%, depending on the popu- adenoidectomy and bilateral maxillary sinus lavage. Cul- lation studied and the methods used.13,15-17 However, the tures of his middle meatal swabs and maxillary sinus as- role of C pneumoniae in upper respiratory infections is not pirates were negative for C pneumoniae. Aerobic cul- as well established. and bronchitis were seen tures from his sinus lavage tested positive for H influenzae in 1% and 5%, respectively, of college students with C pneu- and S aureus, which are known to play a significant role moniae infection presenting with these complaints.15,17 Se- in pediatric sinusitis. rologic surveys have documented the prevalence of anti- Because of the absence of C pneumoniae and the pres- body to C pneumoniae beginning in school-aged children ence of the more conventional pathogens cultured from and reaching 30% to 45% by adolescence; however, most the maxillary sinus lavages, the C pneumoniae present in infections are thought to be mild or asymptomatic.14,16 In the nasopharynx and adenoid was unlikely the primary addition, poorly correlates with culture, espe- pathogen responsible for this child’s chronic sinusitis. cially in children, where greater than 50% to 70% of chil- Studies have shown that C pneumoniae is able to estab- dren with culture-documented C pneumoniae infection were lish asymptomatic or in patients, as seronegative.14,16 Block et al18 cultured C pneumoniae from it has been isolated from the nasopharynx of 5% of healthy 8% of middle ear aspirates of children with acute otitis me- children and adults.13,15,22 Chlamydia pneumoniae may have

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 129, OCT 2003 WWW.ARCHOTO.COM 1096

©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 been a cofactor in the development of sinusitis in this 3. Manning SC. Pediatric sinusitis. Otolaryngol Clin North Am. 1993;26:623-638. child. The may have caused local inflamma- 4. Gross CW. The diagnosis and management of sinusitis in children: surgical man- agement: an otolaryngologist’s perspective. Pediatr Infect Dis. 1985;4(6suppl): tion, enabling other pathogens to invade. Coinfections S67-S72. with other organisms, including Mycoplasma pneumo- 5. Lee D, Rosenfeld RM. Adenoid bacteriology and sinonasal symptoms in chil- niae and , have been reported dren. Otolaryngol Head Neck Surg. 1997;116:301-307. in children with pneumonia caused by C pneumoniae.16 6. Muntz HR, Lusk RP. Bacteriology of the ethmoid bullae in children with chronic sinusitis. Arch Otolaryngol Head Neck Surg. 1991;117:179-181. There are no data on the role of other atypical respira- 7. Orobello PW Jr, Park RI, Belcher LJ, et al. Microbiology of chronic sinusitis in tory pathogens such as M pneumoniae in chronic sinus- children. Arch Otolaryngol Head Neck Surg. 1991;117:980-983. itis, and identification of that organism requires special- 8. Hashigucci K, Ogawa H, Suzuki T, Kazuyama Y. Isolation of Chlamydia pneumo- ized methods that are not widely available. niae from the maxillary sinus of a patient with purulent sinusitis. Clin Infect Dis. This is the first report, to our knowledge, of the iso- 1992;15:570-571. 9. Vogan JC, Bolger WE, Keyes AS. Endoscopically guided sinonasal cultures: a lation of C pneumoniae from the adenoid core. Previous direct comparison with maxillary sinus aspirate cultures. Otolaryngol Head Neck studies of upper and lower respiratory tract disease have Surg. 2000;122:370-373. predominantly used nasopharyngeal or throat swabs. The 10. Roblin PM, Dumormay W, Hammerschlag MR. Use of HEp-2 cells for improved failure to isolate C pneumoniae from any of the other chil- isolation and passage of Chlamydia pneumoniae. J Clin Microbiol. 1992;30:1968- 1971. dren, however, suggests that the organism is not a sig- 11. Gaydos CA, Roblin PM, Hammerschlag MR, et al. Diagnostic utility of PCR-EIA, nificant pathogen in pediatric chronic sinusitis. culture and serology for detection of Chlamydia pneumoniae in symptomatic and asymptomatic patients. J Clin Microbiol. 1994;32:903-905. Submitted for publication April 25, 2002; final revision re- 12. Mehta C, Patel N. StatXact Statistical Software for Exact Nonparametric Infer- ceived November 5, 2002; accepted January 24, 2003. ence: User Manual. Version 2. Cambridge, Mass: CYTEL Software Corp; 1991. 13. Grayston JT, Campbell LA, Kuo CC, et al. A new respiratory tract pathogen: Chla- This study was supported by a research grant from Ab- mydia pneumoniae strain, TWAR. J Infect Dis. 1990;161:618-625. bott Laboratories, North Chicago, Ill. 14. Emre U, Roblin PM, Gelling M, et al. The association of Chlamydia pneumoniae This study was presented as a poster at the 17th An- infection and reactive airway disease in children. Arch Pediatr Adolesc Med. 1994; nual Meeting of the American Society of Pediatric Otolar- 148:727-732. 15. Hyman CL, Augenbraun MH, Roblin PM, Schachter J, Hammerschlag MR. Asymp- yngology; May 13-14, 2002; Boca Raton, Fla. tomatic respiratory tract infection with Chlamydia pneumoniae TWAR. J Clin Mi- We thank Richard M. Rosenfeld, MD, MPH, and Ari J. crobiol. 1991;29:2082-2083. Goldsmith, MD, for contributing patients to the study and 16. Block S, Hedrick J, Hammerschlag MR, Cassell GH, Craft JC. Mycoplasma pneu- for assistance with the collection of specimens. We also thank moniae and Chlamydia pneumoniae in pediatric community-acquired pneumo- J. Hardy-Stashin, PhD, of the Department of Histology of nia: comparative safety and efficacy of clarithromycin vs erythromycin ethylsuc- cinate. Pediatr Infect Dis J. 1995;14:471-477. the Long Island College Hospital, Brooklyn, for the use of 17. Thom DH, Grayston JT, Wang SP, Kuo CC, Altman J. Chlamydia pneumoniae her −70°C freezer for specimen storage. strain TWAR, Mycoplasma pneumoniae, and viral infections in acute respiratory Corresponding author: Anthony Cultrara, MD, De- disease in a university student health clinic population. Am J Epidemiol. 1990; partment of Otolaryngology, State University of New York 132:248-256. Downstate Medical Center, 450 Clarkson Ave, Campus Box 18. Block SL, Hammerschlag MR, Hendrick J, et al. Chlamydia pneumoniae in acute otitis media. Pediatr Infect Dis J. 1997;16:858-862. 126, Brooklyn, NY 11203 (e-mail: [email protected]). 19. Ogawa H, Hashiguchi K, Kazuyama Y. Recovery of Chlamydia pneumoniae in six patients with otitis media with effusion. J Laryngol Otol. 1992;106:490-492. REFERENCES 20. Goo YA, Hori MK, Voorhies JH, Kuo C, Wang S, Campbell LA. Failure to detect Chlamydia pneumoniae in ear fluids from children with otitis media. Pediatr In- fect Dis J. 1995;14:1000-1001. 1. Wald ER, Guerra N, Byers C. Upper respiratory tract infections in young chil- 21. Hammerschlag MR. The role of Chlamydia in upper respiratory tract infections. dren: duration of and frequency of complications. Pediatrics. 1991;87:129-133. Curr Infect Dis Rep. 2000;2:115-120. 2. Lund VJ, Kennedy DW. Quantification for staging sinusitis. Ann Otol Rhinol Laryn- 22. Gnarpe J, Gnarpe H, Sundelof B. Endemic prevalence of Chlamydia pneumoniae gol Suppl. 1995;167:17-21. in subjectively healthy persons. Scand J Infect Dis. 1991;23:387-388.

(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 129, OCT 2003 WWW.ARCHOTO.COM 1097

©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021