Volume 2, Issue 1 , Pages 9-13, March 2007
Nontuberculous mycobacterial sinusitis in children with cystic fibrosis☆
Article Outline
Summary
Objective
Only 13 cases of nontuberculous mycobacterial (NTM) sinusitis have been reported in the literature, the majority in patients with AIDS. We report three pediatric patients routinely followed at our cystic fibrosis (CF) center with sinus cultures positive for NTM.
Methods
Case report and review of the literature.
Results
One patient had positive NTM sinus cultures after a sinus procedure and was then noted to have NTM on sputum cultures. The second patient was noted to have NTM on bronchoscopy and then underwent sinus cultures demonstrating the same organism. The third patient had NTM in the sinuses on routine endoscopic sinus surgery and is still undergoing further evaluation.
Conclusions
Questions arise as to whether disease in the lungs is affected by a reservoir in the sinuses and should sinus cultures and debridement be performed in all cases of NTM lung disease in CF patients. Since NTM has been increasing in prevalence in sputum cultures in the CF population, its existence in the sinuses should be considered when these patients present with sinus disease.
Keywords: Nontuberculous mycobacterium, Acid-fast bacilli, Atypical sinusitis, Mycobacterium abscessus, Cystic fibrosis, Pediatric sinusitis
1. Introduction
There have been only 13 reported cases of atypical or nontuberculous mycobacteria (NTM) isolated from the paranasal sinuses [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12] (Table 1). The majority of these have been in immunocompromised patients, particularly in AIDS, with many of these patients dying shortly after infection. Only two pediatric patients have been reported with NTM sinusitis and none with cystic fibrosis (CF) [6], [10]. However, it has recently been recognized that NTM are becoming increasingly prevalent in the cystic fibrosis population, particularly as a pathogen in lung disease [13], [14], [15], [16], [17]. The NTM most commonly recovered in sputum samples have been Mycobacterium avium complex and Mycobacterium abscessus, accounting for 88% of NTM in a study of 986 patients [13]. We report three children with NTM sinusitis; all of whom have typical gastrointestinal and pulmonary disease associated with CF.
Table 1. Reported cases of nontuberculous mycobacterial sinusitis
| Author/year | Organism | Location | Age/sex | Comorbities | Treatment | Follow-up |
|---|---|---|---|---|---|---|
| Eron et al. in 1981 [1] | M. chelonei | Maxillary | 47/female | Diabetes | Multiple endoscopic and external sinus procedures and IV/IM/PO antibiotics | Not reported |
| Zurlo et al. in 1992 [2] | M. avium complex | Not reported | Not reported | AIDS | Not reported | Not reported |
| Li et al. in 1994 [3] | M. kansasii | Ethmoid | 29/female | AIDS | Endoscopic sinus surgery and 2 week course of IV antibiotics, 5 month course of PO antituberculosis medications | Died 8 months later of pneumonia |
| Naguib et al. in 1994 [4] | M. kansasii | Maxillary or ethmoid | 43/male | AIDS | Endoscopic sinus surgery ×2, antituberculosis medications and PO antibiotics | Died 2 months later of toxoplasmosis |
| Naguib et al. in 1994 [4] | M. kansasii and M. avium complex | Frontal | 33/male | AIDS | Frontal osteomyelitis/abscess treated with I&D and IV amikacin/cefoxitin and then antituberculosis medications | Died 9 months later due to AIDS complications |
| Tsi et al. in 1994 [5] | M. avium complex | Not reported | Not reported | AIDS | Not reported | Not reported |
| Sussman in 1995 [6] | M. avium complex | Maxillary or ethmoid | “Child”/female | AIDS | Endoscopic sinus surgery, clarithromycin, and antituberculosis medications | Died 2 months later due to disseminated MAC |
| Upadhyay et al. in 1995 [7] | M. kansasii | Not reported | Not reported | AIDS | Endoscopic sinus surgery, antibiotics | Not reported |
| Cibrian et al. in 1996 [8] | M. avium complex | Not reported | 24/male | AIDS | Endoscopic sinus surgery, antibiotics, and antituberculosis medications | Not reported |
| Ferguson et al. in 1997 [9] | M. avium complex | Maxillary or ethmoid | 38/male | AIDS | Endoscopic sinus surgery and amikacin, rifampin, and clarithromycin for 1 month | Died 3 weeks after treatment |
| Weiss et al. in 1997 [10] | M. avium complex | Frontal | 13/female | None | Endoscopic and external sinus drainage secondary to subperiosteal abscess and then IV antibiotics | Well at 5 month follow-up, no repeat cultures performed |
| Spring and Miller in 1999 [11] | M. chelonae | Maxillary | 36/female | None | Multiple endoscopic and external sinus procedures, radical orbital sparing maxillectomy, prolonged IV antibiotics, IV gamma globulin | Asymptomatic at unspecified time interval, no repeat cultures obtained |
| Mra et al. in 2002 [12] | M. avium complex | Sphenoid | 56/female | None | Presented with cavernous sinus thrombosis, treated with antibiotics and heparin for greater than 1 month | Residual dysfunction of eye movement, no repeat cultures obtained |
2. Methods
Three cases of NTM isolated from the paranasal sinuses were reviewed. All patients had cultures taken via suction trap from the maxillary sinus. In two cases this was from the natural ostium and in one instance (case 2) from an inferior meatal puncture with a needle and lavage of the sinus. Bronchial cultures were carried out during bronchoscopy by bronchial lavage.
2.1. Case 1
A 10-year-old female was diagnosed with cystic fibrosis at birth due to meconium ileus and was noted to be homozygous for deltaF508. She has a history of Staphylococcus aureus on sputum cultures and had a prolonged history of recurrent sinusitis and frontal headaches. A sinus CT revealed extensive sinus disease and polyposis. Bilateral nasal polypectomies, maxillary antrostomies, and total ethmoidectomies were performed. The acid fast bacilli (AFB) smear from the maxillary sinus revealed moderate acid fast bacilli and culture revealed a rapid-growing mycobacterium typed as Mycobacterium chelonae–abscessus complex sensitive to cefoxitin. A bronchial lavage was performed and although the AFB smear was negative the culture was positive for M. chelonae–abscessus complex. The child was stable from a pulmonary standpoint and the decision was made to hold off on additional treatment. The patient has continued with stable pulmonary function tests and without radiographical or clinical evidence of mycobacterium infection 1 year later, though has yet to be recultured.
2.2. Case 2
A 7-year-old female was diagnosed with cystic fibrosis at 18 months due to recurrent pneumonia and diarrhea. She has two positive sweat tests and is homozygous for deltaF508. Cultures have shown that she is not colonized with Pseudomonas aeruginosa. She underwent bronchoscopy to obtain cultures as she had recurrent pneumonias with only a fair response to conventional antibiotics. Broncho-alveolar lavage cultures revealed moderate acid fast bacilli on AFB smear and M. chelonae–abscessus complex on culture. A sinus CT was ordered as part of further work-up which demonstrated moderately diffuse sinus mucosal thickening (Fig. 1). The patient was then referred to otolaryngology for evaluation. Sinus cultures were performed in the operating room revealing acid fast bacilli on AFB smear and M. chelonae–abscessus complex on culture of the maxillary sinus. Clinically and radiographically the patient persisted with lung disease and was put on a 4 month course of IV cefoxitin and amikacin along with oral clarithromycin. She is improved clinically 3 months after treatment with normal spirometry and remains on oral antibiotics but has not yet been recultured.
Fig. 1.
Preoperative coronal CT scan from patient in case 3.
2.3. Case 3
An 8-year-old male was diagnosed with cystic fibrosis at the age of 2 months with a history of significant respiratory distress and Pseudomonas pneumonia. He has two positive sweat tests and has cultured P. aeruginosa intermittently since that time. He was followed at the otolaryngology office for recurrent sinusitis, polyposis, and headaches and had two previous sinus procedures. A sinus CT revealed essentially complete opacification of bilateral maxillary, ethmoid, and sphenoid sinuses with bowing of the medial maxillary sinus walls (Fig. 2). An endoscopic sinus surgery was performed using image-guidance, removing disease from all the aforementioned sinuses (Fig. 3). AFB smear was negative but culture revealed M. avium complex by genetic probe. The patient received a 1 month course of oral antibiotics and is awaiting sputum cultures for determination of further management. He remains clinically well with stable lung function and free of sinus disease at this time.
Fig. 2.
Preoperative coronal CT scan from patient in case 2.
Fig. 3.
Endoscopic view of left middle meatal polyp in patient in case 3.
3. Discussion
Nontuberculous mycobacteria is increasingly recognized as a pathogen in the CF population [13], [14], [15], [16], [17]. The largest prospective study, a multicenter study published in 2002 by Olivier et al., reported a prevalence of 13% of NTM from sputum samples of 986 CF patients older than 10 years [13]. M. abscessus, the second most frequently isolated mycobacteria in the study, is particularly worrisome as this rapid-grower, Runyon IV mycobacterium is not only a virulent organism, often causing severe lung disease, but is susceptible to only a small number of medications [14].
Prior to 1992, M. abscessus was classified as a subset of M. chelonae but since then has gained species status. This is important as M. chelonae usually produces disseminated skin disease in the setting of steroid therapy while M. abscessus is more likely to be a virulent organism and may cause disease without immunosuppression [18]. Although our lab did not subdivide these organisms and reported them as M. chelonae–abscessus complex, it is our belief that both patients 1 and 2 were infected with M. abscessus and not M. chelonae based on the much greater incidence of M. abscessus in cystic fibrosis patients, its increased propensity to cause respiratory disease, and the increased likelihood of being sensitive to cefoxitin, a characteristic more common with M. abscessus [15].
It has been reported that M. abscessus is uniformly resistant to standard antituberculosis drugs and susceptible to only parenteral antibiotics and newer oral macrolides [15]. This was supported by an analysis by Griffith et al., who studied 120 patients with M. abscessus isolated from the lungs and reported that although many subjects can improve clinically with short courses (2–4 weeks) of antibiotic therapy (cefoxitin, amikacin, and imipenem), they relapse when not receiving therapy. They further remarked that they had no documented instances of permanent sputum conversion to culture-negative and symptomatic improvement utilizing parenteral antibiotics alone for M. abscessus. Overall, they found that only surgical resection of localized disease has proven effective for long term sputum conversion [19]. Cullen et al. came to the similar conclusion that eradication of M. abscessus with antimicrobial agents alone is unlikely [15].
Despite this information, the role of therapy remains controversial for the culture positive patient. In a study by Quittell it was recommended that CF patients should be treated for NTM positive sputum cultures with multiple antibiotics, if they meet American Thoracic Society guidelines, continuing for at least 12 months after AFB cultures become negative [17]. Others feel that the role of treatment is unclear as it is difficult to determine if patients are colonized or have actual disease, thus questioning the significance and clinical course of NTM positive sputum cultures [15], [16].
In addition to treatment of the lung disease, the question about the significance of sinus colonization remains. It is possible that the sinuses may serve as a reservoir for the lung disease and elimination of the disease in the sinuses may have a positive impact on the patients’ overall prognosis. This has prompted us to investigate our patients further by culturing them both in the lungs and sinuses in the near future.
4. Conclusions
Based on our cases and the recent literature, we recommend that all cystic fibrosis patients undergoing sinus surgery be smeared and cultured for acid-fast bacilli. If the cultures come out positive, sputum samples should be obtained and treatment planning determined along with pulmonary and infectious disease specialists. As NTM sinusitis becomes a more recognized entity, the optimal management and relationship with concurrent lung disease will have to be addressed.
References
- Mycobacterium chelonei infects the maxillary sinus. Va Med. 1981;108:335–338
- Sinusitis in HIV-1 infection. Am. J. Med. 1992;93:157–162
- Mycobacterium kansasii sinusitis in a patient with AIDS. Clin. Infect. Dis. 1994;19:792–793
- . Paranasal sinus infection due to atypical mycobacteria in two patients with AIDS. Clin. Infect. Dis. 1994;19:789–791
- Sinusitis en infeccion por VIH. Acta Otorrinolaringol. Esp. 1994;45:301–302
- . Sinusitis caused by Mycobacterium avium-intracellulare in a patient with human immunodeficiency virus. Pediatr. Infect. Dis. J. 1995;14:716
- Bacteriology of sinusitis in human immunodeficiency virus-positive patients: implications for management. Laryngoscope. 1995;105:1058–1060
- Sinusitis por Mycobacterium avium-M intracellulare en paciente con infeccion por HIV. Enferm. Infecc. Microbiol. Clin. 1996;14:401–402
- . Mycobacterium avium complex infection of the paranasal sinuses. Otolaryngol. Head Neck Surg. 1997;117:S160–S162
- . Nontuberculous mycobacterial infection of the frontal sinus in a child. Otolaryngol. Head Neck Surg. 1997;116:110–112
- . Initial report of primary sinusitis caused by an atypical pathogen (Mycobacterium chelonae) in an immunocompetent adult. Ear Nose Throat J. 1999;78:358–359362–364
- . Infectious and neoplastic disease of the sphenoid. Rhinology. 2002;34–40
- Nontuberculous mycobacteria I: multicenter prevalence study in cystic fibrosis. Am. J. Respir. Crit. Care Med. 2003;167:828–834
- Mycobacterium abscessus and children with cystic fibrosis. Emerg. Infect. Dis. 2003;9:1587–1591
- Mycobacterium abscessus infection in cystic fibrosis colonization or infection?. Am. J. Respir. Crit. Care Med. 2000;161:641–645
- . The natural history of nontuberculous mycobacteria in patients with cystic fibrosis. Paediatr. Respir. Rev. 2004;5:S213–S216
- . Management of non-tuberculous mycobacteria in patients with cystic fibrosis. Paediatr. Respir. Rev. 2004;5:S217–S219
- . Mycobacterium chelonae vs abscessus. Ped. Infect. Dis. J. 1997;16:829
- . Clinical features of pulmonary disease caused by rapidly growing mycobacteria An analysis of 154 patients. Am. Rev. Respir. Dis. 1993;147:1271–1278
☆ Presented as a poster presentation at the spring meeting of the American Rhinologic Society, May 2005.
PII: S1871-4048(06)00093-1
doi:10.1016/j.pedex.2006.10.002
© 2006 Elsevier Ireland Ltd. All rights reserved.
Volume 2, Issue 1 , Pages 9-13, March 2007
