Telithromycin for the treatment of acute bacterial maxillary sinusitis: a review of a new antibacterial agent.

Objective: Telithromycin, the first approved ketolide antibiotic, was developed to treat community-acquired respiratory tract infections, including acute bacterial maxillary sinusitis (ABMS). A previously published study showed that a 5-day course of 800 mg telithromycin once daily is as effective as a 10-day course in the treatment of ABMS.

Materials and Methods: Data were pooled from two controlled, multinational, prospective, randomized, double-blinded ABMS trials comparing 5-day telithromycin (800 mg once daily) with 10-day amoxicillin-clavulanate (500/125 mg 3 times daily) and cefuroxime axetil (250 mg twice daily). Clinical cure and bacteriologic eradication rates were compared by means of descriptive statistics.

Results: The clinical cure rate for telithromycin was 80.9% versus 77.4% for comparators; bacteriologic eradication rate for telithromycin was 84.9% versus 81.7% for comparators. Most adverse events were mild to moderate in intensity and, most commonly, gastrointestinal in nature.

Conclusions: These results support the conclusion that 5 days of treatment with telithromycin is as safe and effective in patients with ABMS as a 10-day course of treatment with amoxicillin-clavulanate or cefuroxime axetil.

Key Words: telithromycin, sinusitis, antimicrobial, antibiotic, acute bacterial maxillary sinusitis

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Family physicians are on the front line for the diagnosis and management of respiratory tract infections. Approximately one quarter of all office and clinic visits in the United States are with family physicians, and upper respiratory tract infections are the third most common reason for such visits. (1) Sinusitis is one of the most common diagnoses in ambulatory care and is the fifth most common reason for prescription of antimicrobial drugs. (2)

The symptoms of acute bacterial maxillary sinusitis (ABMS) are well defined, and this disease can be readily differentiated from other upper respiratory conditions by clinical evaluation in the family physician's office or clinic. (3,4) ABMS most often follows a viral infection, (5) with up to 2% of viral upper respiratory infections complicated by a bacterial infection that results in ABMS. (6,7) The bacteria most often isolated from patients with ABMS are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. (7)

Treatment guidelines for management of patients with ABMS generally recommend 10 to 14 days of high-dose amoxicillin as first-line therapy, (5,8,9) but a wide range of alternatives (including other [beta]-lactams, macrolides, and fluoroquinolones) are recommended for patients with moderate symptoms, a history of recent antimicrobial therapy, [beta]-lactam allergy, or a combination of these conditions. (5)

Although 10 to 14 days of treatment with amoxicillin may be effective in many patients with ABMS, this approach has important limitations. First, pathogens responsible for ABMS may be resistant to amoxicillin as well as to other penicillins. (7) Results from US-based surveillance studies have indicated that approximately 25 to 50% of S pneumoniae have decreased susceptibility to penicillin, (10) 40.9% of sinus-specimen S pneumoniae isolates were macrolide-resistant, and 23.5% of S pneumoniae isolates showed multiple-drug resistance (resistant to three or more antimicrobial classes). (11)

Second, a long treatment regimen requiring multiple daily doses has the potential to reduce patient compliance, increase the risk for poor therapeutic outcomes, and promote the development of bacterial resistance. (12-17)

New approaches to the management of ABMS are aimed at improving clinical and microbiologic outcomes as well as reducing the risk of antimicrobial resistance. Telithromycin is the first approved member of a new class of ketolide antimicrobial agents. It is a semisynthetic derivative of erythromycin, but unlike erythromycin and other macrolides that bind only to domain V on the bacterial 23S rRNA, telithromycin inhibits protein synthesis by interacting strongly with 2 domains (domains II and V) on the bacterial 23S rRNA. (18-20)

The results of in vitro studies have demonstrated that telithromycin has high activity against all pathogens commonly associated with ABMS, including resistant strains of S pneumoniae. (21,22) It also has a terminal elimination half-life of more than 9 hours, which permits once-daily dosing, (23,24) as well as a favorable pharmacokinetic/pharmacodynamic profile with high tissue penetration at the site of infection. Favorable tissue penetration was demonstrated in an evaluation of 22 patients who underwent endoscopic endonasal surgery for nasal polyposis and were given a 3-day course of 800 mg telithromycin once daily before surgery. (25) Sinus tissue samples were taken 2, 3, 4, 5, 12, and 24 hours after the last dose was given and showed mean sinus tissue concentrations of telithromycin (measured in mg/kg) of 6.60 [+ or -] 3.48, 4.66 [+ or -] 2.45, 6.96 [+ or -] 1.58, 5.44 [+ or -] 0.97, 3.98 [+ or -] 1.93, and 1.58 [+ or -] 1.68 at the indicated time points, respectively. These data showed that a 3-day course of telithromycin (800 mg once daily) achieves high sinus tissue concentrations in excess of the minimum inhibitory concentration needed to inhibit the visible growth of 90% of a population of organism's values for key bacterial pathogens responsible for ABMS. (25) The efficacy and safety of short-course therapy with telithromycin in the treatment of ABMS has been tested in three phase III clinical studies and is the subject of this pooled analysis.

This paper introduces data that demonstrate that 5 days of telithromycin (800 mg once daily) is as effective as 10 days of telithromycin (800 mg once daily) for the management of ABMS. In addition, results of analyses of data pooled from two double-blinded, controlled studies show that 5 days of telithromycin (800 mg once daily) therapy is equivalent to 10 days of therapy with the active comparators in patients with ABMS.

Five-day versus Ten-day telithromycin in patients with ABMS

Results from a recently published, multinational, randomized, double-blinded clinical trial showed that 5 days of treatment with 800 mg telithromycin once daily is as effective as 10 days of 800 mg telithromycin once daily in patients with ABMS (26) (Table 1). Roos and colleagues (26) compared the efficacy and tolerability of 5 or 10 days of treatment with 800 mg telithromycin administered once daily to 341 patients diagnosed with ABMS on the basis of clinical signs and symptoms and with radiologically confirmed sinusitis. Because this study compared 5-day versus 10-day telithromycin and no other comparator, it is not included in the description of efficacy and safety results. Causative pathogens were isolated by pretreatment sinus puncture. Clinical cure and bacteriologic eradication (confirmed or presumed) rates were virtually identical for the patients treated for 5 days (91.1% and 90.7%, respectively) and for 10 days (91.0% and 91.3%, respectively). The 5-day course of therapy with telithromycin was not associated with an increased risk of relapse or reinfection versus the 10-day course of treatment. (26)

Active-comparator controlled studies of short-course telithromycin in patients with ABMS: pooled analysis

Material and Methods

Study designs

The active comparators in two controlled, multinational, prospective, randomized, double-blinded studies of 5-day telithromycin (800 mg once daily) in patients with ABMS were amoxicillin-clavulanate (500/125 mg 3 times daily for 10 days) or cefuroxime axetil (250 mg twice daily for 10 days) (27,28) (Table 1). Study 3002 was not included in this analysis because it did not include a comparator antibiotic. Only the results for the patients treated with telithromycin for 5 days or active-comparator antibiotics for 10 days are considered in this pooled analysis.

Patients

Adult and adolescent patients, 13 years or older, were enrolled in the two trials. (27,28) Patients were enrolled in the respective studies if they had one or two clinical symptoms (eg, purulent nasal discharge; maxillary pain at percussion or toothache; facial pain, pressure, or tightness; or nasal congestion). Patients with recurrent (more than three episodes in the previous year) or chronic sinusitis (symptoms lasting longer than 28 days) were excluded. Patients were also required to have radiologic findings of total sinus opacity, air-fluid levels (all studies), or mucosal thickening ([greater than or equal to]6 mm (27) or [greater than or equal to] 10 mm (28)). Sinusitis was rated by the investigators as mild, moderate, or severe, based on clinical and radiologic findings. The studies defined the modified intent-to-treat population (mITT) as all randomly assigned subjects with a confirmed diagnosis of infection who received one or more doses of study medication. The mITT population is used to define the subject population enrolled in the studies; the per-protocol clinical (PPc) population as clinically evaluable mITT subjects except those with a major protocol violation, and the per-protocol bacteriologic (PPb) population as PPc subjects with a causative pathogen isolated at pretherapy/entry. (27,28)

Microbiology

Sinus puncture or sinus endoscopy was carried out for selected patients. In Study 3011, only sinus endoscopy was performed in patients younger than 18 years of age (Table 1). Material obtained was used for Gram staining and culture of causative pathogens. (27,28)

Assessments

Patients were assessed at five visits: pretherapy/entry (day 1), during therapy (days 3 through 5), end of therapy (days 11 through 13), post-therapy/test of cure (TOC; days 17 through 24), and late post-therapy (days 31 through 45). (27,28)

Outcomes

All randomly assigned patients with a confirmed diagnosis of ABMS who received at least one dose of study medication were included in the mITT population. Efficacy analysis was completed in the PPc population. (27,28)

Bacteriologic

The bacteriologic effectiveness of telithromycin was determined in the PPb patients at post-therapy/TOC. Bacteriologic outcome was classified as satisfactory if the causative pathogen was presumed eradicated at post-therapy/TOC. Bacteriologic eradication was presumed in patients when a favorable clinical response was present, since repeat sinus punctures were not clinically indicated in these patients. S pneumoniae isolates from patients in the two trials were tested for their susceptibility (minimum inhibitory concentration and disk zone inhibition) to penicillin, erythromycin, and telithromycin, using the National Committee for Clinical Laboratory Standards recommended criteria and methodology. (27,28)

Safety

All patients who received at least one dose of the study medication and who had at least one safety assessment after the start of treatment were included in the safety population. Safety evaluations included physical examinations, vital signs (heart rate, temperature, respiratory rate, and blood pressure), 12-lead electrocardiograms, standard clinical laboratory tests (hematology, biochemistry, and urinalysis), and both observed and reported adverse events. Study investigators recorded the nature and severity (mild, moderate, or severe) of any adverse event, as well as the time of onset, time course of the effects, and relation to study treatment. (27,28)

Statistical analyses

A two-sided 95% confidence interval was constructed for the differences in clinical outcomes between pairs of treatments. Equivalence between treatments was demonstrated if the lower 95% confidence interval was 15% or greater, and the upper limit crossed zero. (27,28)

Results

Patients

The two trials included a total of 759 patients in the mITT population. The demographic and clinical characteristics of these patients are summarized in Table 2. Both treatment groups included a small number of adolescent (13 to 18 years of age) and elderly (65 years of age or older) patients, and the severity of current infection was matched between groups. More than 95% of patients in each group had two or more major clinical signs or symptoms of acute sinusitis (eg, facial pain, pressure, or tightness; nasal congestion; purulent nasal or postnasal discharge; hyposmia; or fever). (27,28)

Clinical efficacy

The clinical cure rate at post-therapy/TOC for the PPc population was 80.9% (271/335) for patients treated with telithromycin for 5 days versus 77.4% (175/226) for those who received 10 days of treatment with either amoxicillin-clavulanate or cefuroxime axetil. The clinical cure rates by pathogen for patients in the two groups were comparable (Table 3). (27,28)

Clinical efficacy with 5-day telithromycin in a subpopulation of PPc subjects who had severe disease (as assessed by the investigator), a long duration of symptoms ([greater than or equal to]7 d), or the presence of specific radiologic findings was similar to the clinical efficacy in the overall population (Fig. 1). The clinical cure rate for patients with severe ABMS who received 5 days of treatment with telithromycin was 81.8% (45/55) versus 77.8% (35/45) for patients treated with comparators. (29)

Bacteriologic efficacy

In the two comparative trials, the overall bacteriologic eradication rates for 5 days of treatment with telithromycin versus 10 days of therapy with comparators were 84.9% (118/139) and 81.7% (58/71), respectively (Table 4). (27,28) There was no apparent difference between the effectiveness of telithromycin and comparators against any of the pathogens commonly associated with ABMS, including resistant strains of S pneumoniae. Five days of treatment with telithromycin eradicated 7 of 9 strains of penicillin-resistant S pneumoniae, 10 of 12 strains of erythromycin-resistant S pneumoniae, and 5 of 7 strains of S pneumoniae resistant to both penicillin and erythromycin. The 10-day course of cefuroxime axetil eradicated 6 of 6 strains of S pneumoniae that were resistant to penicillin, erythromycin, or both. (28)

Safety

Overall, 5 days of treatment with telithromycin was well tolerated by the patients in these analyses. The overall rate of treatment-emergent adverse events considered by the investigator to be possibly related to study medication was 32.1% (159/496) for 5 days of treatment with telithromycin versus 34.2% (125/366) for the comparators. The most commonly reported treatment-related adverse events in these trials were diarrhea and nausea (Table 5). Eye disorders were reported in 8 (1.6%) telithromycin-treated patients: blurred vision (n = 2), nonspecific visual disturbance (n = 1), conjunctivitis (n = 3), nonspecific inflammation (n = 1), and increased lacrimation (n = 1). Five (1.4%) comparator-treated patients reported eye disorders: photophobia (n = 1), conjunctivitis (n = 1), eye pain (n = 1), eye pruritus (n = 1), and vitreous floaters (n = 1). The discontinuation rate attributed to adverse events was low. Overall, 3.6% of patients treated with telithromycin for 5 days discontinued treatment because of drug-related adverse events; 3.5% of those who received comparators discontinued treatment because of such events.

There were no treatment-related serious adverse events in the telithromycin group compared with two treatment-related serious adverse events in the comparator group. Severe treatment-related adverse events were similar between the telithromycin and comparator group (4.2% and 3.5%, respectively). There were no deaths in any of the studies. (27,28)

Discussion

The Roos study (26) demonstrated the comparable clinical and bacteriologic efficacies between 5 days of telithromycin versus 10 days of telithromycin. Subsequently, two additional studies were carried out with effective antibiotics (amoxicillin-clavulanate or cefuroxime axetil) as comparators. (27,28) The results of these analyses of data pooled from the two active-controlled studies confirmed that 5 days of telithromycin is at least as effective, both clinically and bacteriologically, as 10 days of treatment with amoxicillin-clavulanate or cefuroxime axetil in patients with suspected ABMS. In contrast to routine clinical practice and many clinical trials of antimicrobial therapy in patients with suspected ABMS, (30-32) sinus puncture was carried out whenever possible in the two studies in this analysis. The results of these studies show that 5 days of treatment with telithromycin is as clinically effective as comparator agents when treating patients infected with the pathogens most often associated with ABMS, including S pneumoniae, H influenzae, M catarrhalis, and S aureus. Importantly, available data indicate that telithromycin is effective in patients infected with penicillin-resistant, erythromycin-resistant, or both strains of S pneumoniae.

The signs and symptoms of the patients in these analyses are consistent with those listed in the guidelines for the clinical diagnosis of ABMS. (5) Thus, the patients treated in these trials were good candidates for empiric antimicrobial therapy in routine clinical practice and include those with confirmed radiographic changes, those with a long duration of symptoms ([greater than or equal to]7 days), and those assessed with severe disease. The analysis also demonstrated that telithromycin was well tolerated, with low rates of discontinuation related to adverse events. Safety and tolerability are important determinants of patient compliance and thus have the potential to positively influence clinical and microbiologic outcomes and the emergence of bacterial resistance.

Acute bacterial maxillary sinusitis is one of the most common clinical entities seen by family practitioners. Approximately 2% of adults with the common cold also have bacterial infections that would benefit from prompt antimicrobial therapy to reduce the duration of symptoms and to avoid potentially serious complications. (6,7,33) The current treatment guidelines identify clinical signs and symptoms commonly associated with ABMS to assist clinicians in recognizing patients who are likely to have ABMS and who will benefit from treatment with an appropriate antimicrobial agent. (5)

The pooling of results from multiple studies can increase assurance for practicing physicians about the effectiveness of a given treatment in large numbers of patients meeting specific inclusion criteria. The efficacy data from the two active-controlled studies of patients with ABMS demonstrate the effectiveness of 5-day telithromycin treatment in patients infected with common pathogens, including resistant strains of S pneumoniae.

Conclusion

Strategies that use the most potent antimicrobial agent with the highest probability for bacterial eradication over the shortest period of time may reduce the risk for selection of resistance and improve outcomes. The results of the analyses confirm that a short, 5-day course of treatment with once-daily telithromycin is well tolerated and has comparable clinical efficacy to 10-day therapy with either amoxicillin-clavulanate or cefuroxime axetil.

References

1. Cherry DK, Woodwell DA. National Ambulatory Medical Care Survey: 2000 summary. Adv Data 2002;328:1-32.

2. Snow V, Mottur-Pilson C, Hickner JM, Principles of appropriate antibiotic use for acute sinusitis in adults. Ann Intern Med 2001;134:495-497.

3. Lanza DC, Kennedy DW. Adult rhinosinusitis defined. Otolaryngol Head Neck Surg 1997;117:S1-S7.

4. Williams JW Jr, Simel DL, Roberts L, et al. Clinical evaluation for sinusitis: Making the diagnosis by history and physical examination. Ann Intern Med 1992;117:705-710.

5. Anon JB, Jacobs MR, Poole MD, et al. with the Sinus and Allergy Health Partnership. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg 2004;130:1-45.

6. Gwaltney JM Jr. Acute community-acquired sinusitis. Clin Infect Dis 1996;23:1209-1225.

7. Sokol W. Epidemiology of sinusitis in the primary care setting: results from the 1999-2000 respiratory surveillance program. Am J Med 2001;111(Suppl 9A):19S-24S.

8. Spector SL, Bernstein IL, Li JT, et al. Parameters for the diagnosis and management of sinusitis. J Allergy Clin Immunol 1998;102:S107-S144.

9. Brook I, Gooch WM III, Jenkins SG, et al. Medical management of acute bacterial sinusitis. Recommendations of a clinical advisory committee on pediatric and adult sinusitis. Ann Otol Rhinol Laryngol Suppl 2000;182:2-20.

10. Appelbaum PC. Resistance among Streptococcus pneumoniae: implications for drug selection. Clin Infect Dis 2002;34:1613-1620.

11. Sahm DF, Weaver MK, Flamm RK, et al. Antimicrobial susceptibility in Streptococcus pneumoniae recovered from sinus specimens: results from 2000-2003 TRUST Surveillance Studies. Paper presented at the 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, Sept 14-17, 2003 (abstract C2-924).

12. Guay DRP. Short-course antimicrobial therapy for upper respiratory tract infections. Clin Ther 2000;22:673-684.

13. Leclercq R. Overcoming antimicrobial resistance: profile of a new ketolide antibacterial, telithromycin. J Antimicrob Chemother. 2001;48(Suppl T1):9-23.

14. Adam D. Short-course antibiotic therapy for infections with a single causative pathogen. J Int Med Res 2000;28(Suppl 1):13A-24A.

15. Pechere JC. Parameters important in short antibiotic courses. J Int Med Res 2000;28(Suppl 1):3A-12A.

16. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001;23:1296-1310.

17. Schrag SJ, Pena C, Fernandez J, et al. Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: a randomized trial. JAMA 2001;286:49-56.

18. Xiong L, Shah S, Mauvais P, et al. A ketolide resistance mutation in domain II of 23S rRNA reveals the proximity of hairpin 35 to the peptidyl transferase centre. Mol Microbiol 1999;31:633-639.

19. Douthwaite S, Hansen LH, Mauvais P. Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA. Mol Microbiol 2000;36:183-193.

20. Hansen LH, Mauvais P, Douthwaite S. The macrolide-ketolide antibiotic binding site is formed by structures in domains II and V of 23S ribosomal RNA. Mol Microbiol 1999;31:623-631.

21. Felmingham D. Microbiological profile of telithromycin, the first ketolide antimicrobial. Clin Microbiol Infect. 2001;7(Suppl 3):2-10.

22. Fuchs PC, Barry AL, Brown SD. In vitro activity of telithromycin against Streptococcus pneumoniae resistant to other antibiotics, including cefotaxime. J Antimicrob Chemother 2002;49:399-401.

23. Bearden DT, Neuhauser MM, Garey KW. Telithromycin: an oral ketolide for respiratory infections. Pharmacotherapy 2001;21:1204-1222.

24. Okamoto H, Miyazaki S, Tateda K, et al. In vivo efficacy of telithromycin (HMR3647) against Streptococcus pneumoniae and Haemophilus influenzae. Antimicrob Agents Chemother 2001;45:3250-3252.

25. Klossek JM, Serrano E, Peynegre R, et al. Penetration of telithromycin (HMR 3647), a new ketolide, into sinus tissue in patients undergoing sinusectomy. In: Program and Abstracts of the 22nd Interdisciplinary Meeting on Anti-Infectious Chemotherapy; December 5-6, 2002; Paris, France. Abstract 33-C6.

26. Roos K, Brunswig-Pitschner C, Kostrica R, et al. Efficacy and tolerability of once-daily therapy with telithromycin for 5 or 10 days for the treatment of acute maxillary sinusitis. Chemotherapy 2002;48:100-108.

27. Luterman M, Tellier G, Lasko B, et al. Efficacy and tolerability of telithromycin for 5 or 10 days vs amoxicillin/clavulanic acid for 10 days in acute maxillary sinusitis. Ear Nose Throat J 2003;82:576-586.

28. Buchanan PP, Stephens TA, Leroy B. A comparison of the efficacy of telithromycin versus cefuroxime axetil in the treatment of acute bacterial maxillary sinusitis. Am J Rhinol 2003;17:369-377.

29. Tellier G, Rangaraju M, Leroy B, et al. Telithromycin is efficacious for the treatment of acute maxillary sinusitis in patients of special interest. Paper presented at the 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, Sept 14-17, 2003 (poster L-1381).

30. Rakkar S, Roberts K, Towe BF, et al. Moxifloxacin versus amoxicillin clavulanate in the treatment of acute maxillary sinusitis: a primary care experience. Int J Clin Pract 2001;55:309-315.

31. Murray JJ, Solomon E, McCluskey D, et al. Phase III, randomized, double-blind study of clarithromycin extended-release and immediate-release formulations in the treatment of adult patients with acute maxillary sinusitis. Clin Ther 2000;22:1421-1432.

32. Henry DC, Moller DJ Jr, Adelglass J, et al. Comparison of sparfloxacin and clarithromycin in the treatment of acute bacterial maxillary sinusitis. Sparfloxacin Multicenter AMS Study Group. Clin Ther 1999;21:340-352.

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Guy Tellier, MD, Stephen A. Brunton, MD, and Roomi Nusrat, MD

From Zoom International Clinical Research Group, St. Jerome, Quebec, Canada; Carolinas Medical Center, Charlotte, NC; and Aventis Pharmaceuticals, Bridgewater, NJ.

Reprint requests to Dr. Guy Tellier, Zoom International Clinical Research Group, 290 rue Montigny, Bloc F, St. Jerome, Quebec, Canada J7Z 5T3. Email: [e-mail]

Accepted April 21, 2005.

Supported by Aventis Pharmaceuticals, Bridgewater, NJ. Dr. Tellier receives research support from Aventis Pharmaceuticals. Dr. Brunton is a consultant for Aventis Pharmaceuticals and Ortho-McNeil Pharmaceuticals, and Dr. Nusrat is an employee of Aventis Pharmaceuticals.

RELATED ARTICLE: Key Points

* Telithromycin (800 mg/d) for 5 days is as effective as the same dose given for 10 days for the treatment of acute bacterial maxillary sinusitis.

* For the treatment of acute bacterial maxillary sinusitis, 800 mg/d telithromycin for 5 days is as safe and efficacious as its comparators, 500/125 mg amoxicillin-clavulanate given 3 times per day and 250 mg cefuroxime axetil given twice a day.

* Telithromycin (800 mg/d) for 5 days is a safe, clinically and bacteriologically effective treatment option for patients with acute bacterial maxillary sinusitis.

Table 1. Modified intent-to-treat patient numbers and treatment regimens
from three clinical studies of telithromycin

Study (Ref. No.)  Treatment regimen                     n

3002 (26)         Telithromycin (800 mg qd, 5 d)        167
                  Telithromycin (800 mg qd, 10 d) (a)   168
3005 (27)         Telithromycin (800 mg qd, 5 d)        201
                  Amoxicillin-clavulanate               202
                    (500/125 mg tid, 10 d)
3011 (28)         Telithromycin (800 mg qd, 5 d)        240
                  Cefuroxime axetil (250 mg bid, 10 d)  116
Combined          Telithromycin, 5 d                    608
                  Comparator, 10 d                      318

(a) Not included in pooled analysis illustrating efficacy and safety
relative to other established comparators.
qd, once daily; d, daily; tid, three times daily; bid, twice daily.

Table 2. Demographic and clinical characteristics of patients in the
modified intent-to-treat populations in the active-comparator controlled
trials (27,28)

                                           No. of patients (%)
                                    Telithromycin    Comparator (a)
                                    (800 mg for 5 d) (10 d)
                                    (n = 441)        (n = 318)

Sex
  Male                              192 (43.5)        118 (37.1)
  Female                            249 (56.5)        200 (62.9)
Mean age (yr)                        40.1              40.1
  13-18                               9 (2.1)           6 (1.9)
  > 18 to < 65                      402 (91.1)        297 (93.4)
  [greater than or equal to] 65      30 (6.8)          15 (4.7)
Ethnicity
  White                             396 (89.8)        278 (87.4)
  Black                              22 (5.0)          24 (7.6)
  Asian                              16 (3.6)          13 (4.1)
  Other                               7 (1.6)           3 (0.9)
Sinus puncture at entry             158 (35.8)         78 (24.5)
Severity of current infection (b)
  Mild                               23 (5.2)          17 (5.4)
  Moderate                          343 (77.8)        237 (74.5)
  Severe                             75 (17.0)         64 (20.1)
Duration of symptoms (d)
  0-3                                22 (5.0)          23 (7.2)
  4-6                                58 (13.1)         53 (16.7)
  [greater than or equal to] 7      361 (81.9)        242 (76.1)
Sinus radiographic findings
  Total opacity                     131 (29.7)         64 (20.1)
  Air-fluid level                   168 (38.1)        139 (43.7)
  Mucosal thickening                271 (51.1)        206 (64.8)
    [greater than or equal to]6 mm

(a) Amoxicillin-clavulanate (500/125 mg 3 times daily) and cefuroxime
axetil (250 mg twice daily).
(b) Investigator-rated.

Table 3. Clinical cure for patients in the per-protocol bacteriologic
population with4 acute bacterial maxillary sinusitis and pathogens
isolated at baseline in the active-comparator controlled trials at post-
therapy/test of cure (a),(27,28)

                          Telithromycin     Comparator
                          (800 mg for 5 d)  (for 10 d)
Causative pathogen        N     n    %      N   n   %

Streptococcus pneumoniae  31    27    87.1  16  14   87.5
Haemophilus influenzae    34    28    82.4  15  13   86.7
Moraxella catarrhalis      7     7   100.0   7   7  100.0
Staphylococcus aureus     12    11    91.7   4   3   75.0

(a) N, subjects in bacteriologic per-protocol population with causative
pathogen isolated at pretherapy/entry; n, number clinically cured.

                             Clinical Cure (% of Patients)
                             Telithromycin, active
                             controlled studies (5
                             days)                  Comparator (10 days)

Symptoms                     81.5 (229/281)         78.1 (135/173)
[greater than or equal to]7
Days
Air-Fluid Level              84.1 (106/126)         80.4 (82/102)
Total Opacity                85.7 (84/98)           76.7 (33/43)
Severe ABMS                  81.8 (45/55)           77.8 (35/45)

Clinical efficacy of treatment with a 5-day course of telithromycin
versus 10-day treatment with comparators in per-protocol clinical
patients with acute bacterial maxillary sinusitis (ABMS) as assessed by
the investigator. (29)

Note: Table made from bar graph.

Table 4. Bacteriologic eradication rates by baseline pathogen in
per-protocol bacteriologic population at post-therapy/test of cure in
active-comparator controlled trials (27,28)

                        Telithromycin (800 mg
                        for 5 d)                 Comparator (for 10 d)
Pathogen (a)            No. eradicated/          No. eradicated/
                        No. isolated (b)  %      No. isolated      %

Streptococcus
  pneumoniae                28/31          90.3      14/16         87.5
Haemophilus influenzae      28/34          82.4      13/15         86.7
Moraxella catarrhalis        7/7          100.0       7/7         100.0
Staphylococcus aureus       12/12         100.0       3/4          75.0

(a) Single and multiple pathogen infections; eradication includes both
documented and presumed eradication.
(b) Denominator was based on total number evaluable, excluding
indeterminate responses.

Table 5. Treatment-emergent adverse events considered to be possibly
related to study medication observed in 2% or greater of patients in the
safety population in active-comparator controlled trials (a),(27,28)

                                  No. of patients (%)
                              Telithromycin     Comparator
                              (800 mg for 5 d)  (for 10 d)
Adverse event                 (n = 496)         (n = 366)

Total possibly related TEAEs  159 (32.1)        125 (34.2)
Diarrhea                       64 (12.9)         67 (18.3)
Nausea                         46 (9.3)          24 (6.6)
Dizziness                      20 (4.0)           5 (1.4)
Vomiting                       10 (2.0)           8 (2.2)
Abdominal pain                 10 (2.0)           6 (1.3)

(a) TEAE, treatment-emergent adverse events.