Skip to main page content

• HOME
• Current Issue
• Archive
• Alerts
• About ASM
• Contact us
• Tech Support
• Journals.ASM.org

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Brook, I. Articles by Hausfeld, J. N. Search for Related Content PubMed PubMed Citation Articles by Brook, I. Articles by Hausfeld, J. N.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2005, p. 4793-4794, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4793-4794.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Recovery of Interfering Bacteria in the Nasopharynx following Antimicrobial Therapy of Acute Maxillary Sinusitis with Telithromycin or Amoxicillin-Clavulanate

Itzhak Brook and Jeffrey N. Hausfeld^*

Georgetown University School of Medicine, Washington, D.C

Received 4 June 2005/ Returned for modification 8 July 2005/ Accepted 19 August 2005

Top Abstract Text References

 
The effect on the nasopharyngeal flora of 7 days of amoxicillin-clavulanate or 5 days of 800 mg once a day was studied in 50 adults with acute sinusitis. The numbers of potential pathogens and interfering alpha-hemolytic streptococci were equally reduced after both therapies. However, the number of interfering Prevotella spp. declined more significantly after amoxicillin-clavulanate treatment.

Top Abstract Text References

 
The nasopharynx is colonized by nonpathogenic aerobic and anaerobic organisms (12), some capable of interfering with the growth of potential pathogens. Interfering organisms are less often isolated from sinusitis-prone patients than controls (5). These organisms include alpha-hemolytic streptococci (AHS) and Prevotella melaninogenica (14). Conversely, colonization by potential pathogens increases in otitis media-prone children and adults during respiratory illness (9). Interfering flora may therefore inhibit the colonization or growth of potential pathogens and prevent sinusitis (5, 12).

Administration of antimicrobials can affect the composition of the nasopharyngeal flora (10). Oral flora with interfering capability such as aerobic and anaerobic streptococci and penicillin-susceptible Prevotella spp. are generally susceptible to amoxicillin. However, over one-half of Prevotella spp. resist penicillins through the production of beta-lactamase (3) but are susceptible to amoxicillin-clavulanate (AC). In contrast these Prevotella spp. are generally less susceptible to ketolides (11).

This study compared the effects on the nasopharyngeal flora of therapy of acute maxillary sinusitis with either AC, a wide-spectrum antimicrobial effective against potential pathogens as well as aerobic and anaerobic interfering organisms, and the ketolide telithromycin (TE), which is effective against pathogenic organisms (1) but is less inhibitory towards interfering Prevotella spp. No assessment was made of the clinical response.

Fifty consecutively seen patients (31 males, age 18 to 66 years; mean age, 44 years) with acute maxillary sinusitis were studied. Symptoms lasted 10 to 30 days, none had respiratory infection for <1 month and none smoked, and they had not received antimicrobials for <6 weeks. Patients' complaints included facial pain, frontal headache, purulent nasal discharge, fever, and malaise. Plain radiographic or computed tomography studies were obtained. Sinusitis was defined radiographically as complete sinus opacity, an air-fluid level, or mucous membrane thickening of >6 mm (5).

Antimicrobials were chosen by the treating physicians according to the patients' needs. Twenty-five patients received 875 mg of AC twice a day for 7 days, and 25 received 800 mg of TE once a day for 5 days. Compliance was assessed by unused-medicine inspection. Patients who failed to take two or more dosages or failed to return their medicine bottles were excluded. The study was granted Institutional Review Board approval. Statistical analysis was done using the t test and the ²-square test with continuity correction.

Nasopharyngeal cultures were obtained with calcium alginate swabs that were immediately plated into media supportive of the growth of aerobic and anaerobic bacteria at the initial outpatient visit prior to therapy and on a follow-up 10 to 12 days later. Culture collectors and the microbiologist were blinded to the therapy. Cultures were processed for the recovery of potential pathogens and two types of organisms known to possess inhibitory activity: AHS and Prevotella spp. Inhibitory activity was tested as previously described (5) against one strain each of recent clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Processing of specimens, organism identification, and determination of beta-lactamase production were done as previously described (5, 13, 17).

Intermediate resistance to penicillin was defined as a MIC of 0.1 to 1.0 µg/ml, and high resistance was defined as a MIC of 2.0 µg/ml. MICs were determined using the CLSI (formerly NCCLS) broth microdilution method with Mueller-Hinton broth, supplemented with 5% lysed horse blood (15, 16). A final inoculum of 7 x 10⁴ to 1 x 10⁵ bacteria was used, and microtiter plates were incubated at 36.5°C in ambient air for 16 to 20 h. MIC end points were read as the lowest concentration of antimicrobial that totally inhibited macroscopically visible growth of the inoculum. Standard quality control strains (ATCC) were included in each run. Isolates were tested against penicillin G, AC, and TE. Susceptibilities were calculated based on CLSI breakpoints.

Before therapy, potential pathogens were isolated from the nasopharynges of 13 (52%) of those treated with AC and 14 (56%) treated with TE. Following therapy, the number of potential pathogens was equally reduced by both therapies. (Table 1).

View this table: [in this window] [in a new window]

TABLE 1. Potential pathogens recovered from the nasopharynges of patients treated with amoxicillin-clavulanate and telithromycin

A total of 26 interfering AHS were recovered from 22 of the AC-treated patients prior to therapy, and the number declined to 7 recovered from 7 patients after therapy (P < 0.001). A total of 28 interfering AHS were recovered from 23 of the TE-treated patients prior to therapy, and the number declined to 8 recovered from 7 patients (P < 0.001) (Table 2).

View this table: [in this window] [in a new window]

TABLE 2. Effect of antimicrobial therapy on the recovery of interfering bacteria capable of interfering with the growth of potential pathogens in patients treated with either amoxicillin-clavulanate or telithromycin for acute maxillay sinusitis

A total of 28 interfering Prevotella isolates were recovered from the 21 of the AC-treated patients prior to therapy, and the number declined to 9 recovered from 8 patients after therapy (P < 0.001). A total of 27 interfering Prevotella isolates were recovered from the 22 of the TE-treated patients prior to therapy, and the number declined to 21 recovered from 19 patients (P > 0.05). Twenty-nine of the 55 (53%) interfering Prevotella isolates produced beta-lactamase.

This study compared the effects of two types of antimicrobial therapies, AC and TE, on the nasopharyngeal flora. While both agents are effective against penicillin-susceptible or -resistant potential pathogens, S. pneumoniae, H. influenzae, and M. catarrhalis, they have selective activity against the nasopharyngeal flora. Differences were noted in the recovery of organisms with interfering capability following therapy. While the number of interfering AHS declined after therapy with either AC or TE, the number of interfering Prevotella isolates declined more significantly after AC treatment.

AC is an antimicrobial with broad-spectrum efficacy, active against AHS and penicillin-resistant Prevotella. TE, in contrast, is less effective against Bacteroides fragilis and Fusobacteria in vitro (8). Although the MICs of TE and AC against Prevotella were similar (11), these organisms seem to survive better in the nasopharyngeal flora following TE therapy compared to AC.

The presence of interfering organisms may play a role in the prevention of respiratory infections. A greater number of interfering organisms and fewer H. influenzae organisms were recovered in the adenoids of non-otitis-prone children compared to otitis-prone children (2). Interfering organisms inhibit colonization in patients and in vitro growth of pathogens (4-7, 13). The production of bacteriocin and other growth-inhibitory substances or utilization of essential nutrients may explain this phenomenon (7).

This study suggests the potential benefit of an antimicrobial that selectively spares interfering organisms while eliminating potentially pathogens. Further studies are warranted to explore the clinical implications of these findings and how quickly pathogens can recolonize the nasopharynx following therapy with various antimicrobials.

 
The authors acknowledge the laboratory support of D. Giraldo.

 
* Corresponding author. Mailing address: 4431 Albemarle St. NW, Washington, DC 20016. Phone: (301) 295-2698. Fax: (202) 244-6809. E-mail: ib6{at}georgetown.edu/.

Top Abstract Text References

 

1
1. Barry, A. L., P. C. Fuchs, and S. D. Brown. 1998. In vitro activities of the ketolide HMR 3647 against recent gram-positive clinical isolates and Haemophilus influenzae. Antimicrob. Agents Chemother. 42:2138-2140.[Abstract/Free Full Text]
2
2. Bernstein, J. M., S. Sagahtaheri-Altaie, D. M. Dryja, and J. Wactawski-Wende. 1994. Bacterial interference in nasopharyngeal bacterial flora of otitis-prone and non-otitis-prone children. Acta Otorhinolaryngol. Belg. 48:1-9.[Medline]
3
3. Brook, I., L. Calhoun, and P. Yocum. 1980. Beta-lactamase-producing isolates of Bacteroides species from children. Antimicrob. Agents Chemother. 18:164-166.[Abstract/Free Full Text]
4
4. Brook, I., and A. E. Gober. 1995. Role of bacterial interference and beta-lactamase-producing bacteria in the failure of penicillin to eradicate group A streptococcal pharyngotonsillitis. Arch. Otolaryngol. Head Neck Surg. 121:1405-1409.[Abstract/Free Full Text]
5
5. Brook, I., and A. E. Gober. 1999. Bacterial interference in the nasopharynx and nasal cavity of sinusitis prone and non-sinusitis prone children. Acta Otolaryngol. 119:832-836.[CrossRef][Medline]
6
6. Brook, I. 2001. The role of beta-lactamase producing bacteria and bacterial interference in streptococcal tonsillitis. Int. J. Antimicrob. Agents 17:439-442.[CrossRef][Medline]
7
7. Brook, I. 1999. Bacterial interference. Crit. Rev. Microbiol. 25:155-172.[CrossRef][Medline]
8
8. Credito, K. L., L. M. Ednie, M. R. Jacobs, and P. C. Appelbaum. 1999. Activity of telithromycin (HMR 3647) against anaerobic bacteria compared to those of eight other agents by time-kill methodology. Antimicrob. Agents Chemother. 43:2027-2031.[Abstract/Free Full Text]
9
9. Faden, H., M. J. Zaz, J. M. Bernstein, L. Brodsky, J. Stamievich, and P. L. Ogru. 1991. Nasopharyngeal flora in the first three years of life in normal and otitis-prone children. Ann. Otol. Rhinol. Laryngol. 100:612-615.[Medline]
10
10. Foote, P. A., Jr., and I. Brook. 1989. Penicillin and clindamycin therapy in recurrent tonsillitis. Effect of microbiol flora. Arch. Otolaryngol. Head Neck Surg. 115:856-859.
11
11. Goldstein, E. J., D. M. Citron, C. V. Merriam, Y. Warren, K. L. Tyrrel, and H. Fernandez. 2003. In vitro activities of telithromycin and 10 oral agents against aerobic and anaerobic pathogens isolated from antral puncture specimens from patients with sinusitis. Antimicrob. Agents Chemother. 47: 1963-1967.[Abstract/Free Full Text]
12
12. Mackowiak, P. A. 1982. The normal flora. N. Engl. J. Med. 307:83-93.[Medline]
13
13. Murray, P. R., E. J. Barron, J. H. Jorgenson, M. A. Pfaller, and R. H. Yolken (ed.). 2003. Manual of clinical microbiology, 8th ed. ASM Press, Washington, D.C.
14
14. Murray, P. R., and J. E. Rosenblatt. 1976. Bacterial interference by oropharyngeal and clinical isolates of anaerobic bacteria. J. Infect. Dis. 134:281-285.[Medline]
15
15. National Committee for Clinical Laboratory Standards. 2003. Methods for dilution antimicrobial tests for bacteria that grow aerobically. Approved standard M7-A6. National Committee for Clinical Laboratory Standards, Wayne, Pa.
16
16. National Committee for Clinical Laboratory Standards. 2003. Performance standards for antimicrobial susceptibility testing. Supplement tables M100-S13/M7. National Committee for Clinical Laboratory Standards, Wayne, Pa.
17
17. O'Callaghan, D. H., A. Morris, S. M. Kirby, and A. H. Shingler. 1972. Novel method for detection of beta-lactamase by using a chromogenic cephalosporin substrate. Antimicrob. Agents Chemother. 1:283-288.[Abstract/Free Full Text]

---

Antimicrobial Agents and Chemotherapy, November 2005, p. 4793-4794, Vol. 49, No. 11
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.11.4793-4794.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Brook, I. Articles by Hausfeld, J. N. Search for Related Content PubMed PubMed Citation Articles by Brook, I. Articles by Hausfeld, J. N.