Journal of Antimicrobial Chemotherapy (1990) 26, Suppl. E, 87-91

Comparison of cefpodoxime proxetil with cefaclor in the treatment of sinusitis

"Hopital Bichat, 46 rue Henri Huchard, 75018 Paris, France; bH6pital Necker, 149 rue de sevres, 75015 Paris, France; 'Hdpital Universitaire Saint-Pierre, Bruxelles, Belgium The efficacy and tolerance of cefpodoxime proxetil were compared with those of cefaclor in a multicentre, international, prospective, double-blind, placebocontrolled study in adult outpatients suffering from acute sinusitis. At the end of treatment, cefpodoxime proxetil was more effective than cefaclor, producing complete clinical cure in 84% of cases (102/122) VJ 68% of cases (77/114) in the cefaclor group (P = 0-01). The overall clinical efficacy (cure + improvement) was similar in the two groups with 95% (116/122) satisfactory responses in the cefpodoxime proxetil group and 93% (106/114) in the cefaclor group. Bacteriological response was similar with 95% eradication in the cefpodoxime proxetil group (55/ 58) vs 91% with cefaclor (63/69).

Introduction

Acute bacterial sinusitis is a common clinical problem complicating approximately one in every 200 common colds (Wald et al., 1981). The bacterial species most frequently isolated from infected paranasal sinuses are Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis and Str.pyogenes (Hanobey et al., 1979). The signs and symptoms of bacterial infection of the sinus are non-specific and direct puncture with aspiration of the sinus cavities and bacteriological identification are not performed routinely. Treatment is therefore frequently empirical. However, aspiration must be performed in cases of acute or chronic recurring sinusitis. Endoscopic examination of the lateral nasal wall may show purulent secretions emerging from the middle meatus. Increasingly, the combination of nasal endoscopy with computerized axial tomography of the sinuses has proved ideal for the diagnosis of chronic sinusitis. Nasal endoscopy thus represents real progress in the diagnosis of this condition. However, to match this progress in terms of the treatment of sinusitis requires the development of orally administered antibiotics that will prove effective in empirical therapy. Cefpodoxime proxetil, a new oral third generation cephalosporin, has an antibacterial spectrum that includes those pathogens most often responsible for sinusitis. Cefaclor is known as a standard drug among the oral cephalosporins for the treatment of acute sinusitis in adult patients (Wald et al., 1984; Ekedahl, 1987). It was used as a comparative antibiotic in this international, multicentre, randomized double-blind, placebo controlled study to assess the efficacy and tolerance of cefpodoxime proxetil in adult sinusitis. 87 03O5-7453/9O/26EO87 + 05 $02.00/0

© 1990 The British Society for Antimicrobial Chemotherapy

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P. Gehanno", J. Depondt", B. Barry", M. Simonet* and H. Dewever"

88

P. Gehamw et aL Materials and methods

Results Two hundred and sixty-seven patients were enrolled in this study from 34 centres in Europe. Patients included were predominantly female (158/258 = 61-2%). No significant difference was observed between the two treatment groups in terms of demographic characteristics (Table I). No significant difference was observed between the two treatment groups in terms of clinical signs and radiological findings on admission. The mean duration of treatment was 9-9 days in both groups. Of the 267 patients enrolled in this study, 258 patients were evaluable for tolerance; and 236 patients were evaluable for clinical efficacy. Nine cases (four in the cefpodoxime proxetil group and five in the cefaclor group) could not be included in the analysis of tolerance; despite consent being obtained for entering the trial, they did not take any of the study medications. Twenty-two patients were excluded from the analysis of clinical efficacy (11 because of organisms resistant to cefaclor and/or cefpodoxime at pretreatment culture; and 11 for other reasons such as protocol violation or diagnostic error). Of the 236 patients evaluable for clinical efficacy, 127 were evaluable for bacteriological efficacy. At the end of treatment, cefpodoxime proxetil produced a satisfactory clinical response in 84% of cases (102/122), while 68% of cases (77/114) in the cefaclor group (P = 0-01) showed a satisfactory response. The overall clinical efficacy (satisfactory plus improved) was similar in the two groups with 95% (115/122) satisfactory or improved responses after cefpodoxime proxetil and 93% (106/114) after cefaclor. Two hundred and five pathogens were identified from sinus aspirates in 151 of 256 (59%) patients at inclusion. The distribution of these pathogens is detailed in Table II. The bacteriological response was similar with a satisfactory response in 95% in the

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Adult patients with a diagnosis of acute sinusitis suspected from clinical and radiological signs were enrolled in the study, after giving informed consent. A sample of sinus discharge was taken from the inferior meatus via a sterile catheter under local anaesthesia before treatment in all cases. The sinus fluid was cultured by standard laboratory methods. Sensitivity of significant isolates to cefaclor and cefpodoxime was determined by a disc diffusion method. The discs contained 30 /zg of each drug, and the criteria for interpretation of zone diameters were as follows: cefpodoxime, sensitive ^ 22 mm, resistant < 22 mm; cefaclor, sensitive ^ 18 mm, resistant < 18 mm. Patients were randomized to receive either cefpodoxime proxetil 200 mg bd or cefaclor 500 mg tds. In addition to the study drug, all patients received prednisolone orally (10 mg tid if < 60 kg body weight or 20 mg tid if > 60 kg) and fenoxazoline (nasal spray, tid for four days) during the trial. Other antibiotic, antipyretic or antiinflammatory drugs were prohibited. The clinical response was considered satisfactory if the infection was completely cleared with disappearance of clinical symptoms (nasal discharge and pain) and disappearance or improvement of radiological signs. The clinical response was considered improved if the clinical symptoms were improved, and unsatisfactory if the clinical features and the sinus X-ray remained unchanged or worsened. A satisfactory bacteriological response implied eradication of the causative pathogen or complete cure of a bacteriologically documented infection.

Treatment of sinusitis

89

Table L Demographic characteristics for all patients treated Characteristics

Cefpodoxime proxctil 200 ing bd

Cefaclor 500 mg tid

All patients

133

125

258

41-3 (13-4) 19-77

421 (151) 19-88

41-7 (14-2) 19-88

Sex M F

53 (39-8%) 80 (60-2%)

47 (37-6%) 78 (62-4%)

100 (38-8%) 158 (61-2%)

127 (95-5%) 6 (4-5%) 0 (0-0%)

117(93-6%) 6 (4-8%) 2 (1-6%)

244 (94-6%) 12 (4-7%) 2 (0-8%)

63-4(11-7) 44-104

63-6 (10-9) 40-101

63-5(11-3) 40-104

168-2 (8-4) 148-189

167-0 (7-7) 148-195

167-6 (81) 148-195

Race white black oriental Weight (kg) mean* range Height (cm) mean' range •Standard deviation.

cefpodoxime proxetil group (55/58) and 91% satisfactory response with cefaclor (63/69). It is interesting to note that all cases of staphylococcal sinusitis were cured in the cefpodoxime proxetil group. Eleven patients were excluded from clinical and bacteriological analysis because of a resistant pathogen. Of these, one patient had a Pseudomonas aeruginosa infection with an organism which was resistant to both cefpodoxime and cefaclor and ten patients had infections with other pathogens apparently resistant on disc sensitivity testing only to cefaclor. Considered as a proportion of the total number of bacteria isolated and considered responsible for the infection, the number of pathogens resistant to cefaclor was significantly greater than the number of pathogens resistant to cefpodoxime (P < 0-05, MacNemar test). The resistant pathogens on pretreatment culture are detailed in Table III. Nineteen adverse events, judged by the investigator as probably or possibly drugrelated (nine in the cefpodoxime proxetil group, ten in the cefaclor group) were observed in seventeen patients (nine in the cefpodoxime proxetil group, eight in the cefaclor group) and discontinuation of therapy occurred in seven cases (three in the cefpodoxime proxetil group, four in the cefaclor group). No unexpected adverse events were observed. No difference between groups in respect of haematological and biochemical changes were observed. Discussion In this series, H. influenzae was responsible for 35% of cases, a proportion similar to that in previous reports. H. influenzae is currently the main causative pathogen found in sinusitis. The frequency of reporting of this organism has increased in recent years (Scheld el al., 1986; Jousimes-Somer, Savolatinen & Yukoski, 1988). Str.pneumoniae

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Number of patients Age (years) mean range

90

P. Gehanno et aL Table EL Pathogens isolated in the prctreatment culture from sinus fluid (all patients)

Pathogens

Treatment group Cefpodoxime proxetil Cefaclor

Total

29 29 0 0

43 41 1 1

72(351%) 70 1 1

Streptococcus spp. Str. pneumoniae Str. anaerobes

23 15 0 4 4

26 17 2 2 5

49 (23-9%) 32 2 6 9

B. catarrhalis

14

12

26 (12-7%)

Staphylococcus spp. Staph. aureus Staphylococcus spp.'

12 9 3

13 11 2

25 (12-2%) 20 5

Corynebacterium spp.*

4

6

10 (4-9%)

14 4 3 1 0

9 4 2 0 1 0 1 0 1 0 0 0

23 (11-2%) 8 5

Group A, C. Streptococcus spp.'

Others Proteus spp. Klebsiella spp. Escherichia coli Serratia marcescens Moraxella spp. Neisseria meningitidis Acinetobacter spp.' Peptostreptococcus spp.' Enterobacter cloacae Ps. aeruginosa Citrobacter spp.* Number of pathogens Number of patients from whom pathogens were isolated

()

;!

96

109

205

70/132

81/124

151/256

•Not speciated.

was found in 16% of the samples, a percentage which is similar to that which has been reported in European studies (Gehanno et al., 1988; Fasquelle et al., 1989), but somewhat lower than the proportion found in the USA (Wald et al., 1984; Scheld et al., 1986). B. catarrhalis is rarely encountered in adult sinusitis (5%). In this trial, B. catarrhalis was found in 13% of cases, an isolation rate close to that previously described in Sweden during 1987. Staph. aureus was found in 12% of cases. A similar percentage has been reported in other studies (Gehanno et al., 1988). Thus, H. influenzas, Str. pneumoniae, B. catarrhalis and S. aureus together represent the majority of the organisms responsible for acute sinusitis in adul.s. One of the expected advantages of the antibacterial spectrum of cefpodoxime, as compared with cefaclor, is its potential activity against most /?-lactamase-producing bacterial species (Utsui, Inoue & Mitsuhashi, 1987; Chin & Neu, 1988; Jones & Barry, 1988). This was confirmed in the present trial with H. influenzas where six strains

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Haemophilus spp. H. influenzat H. parainfluenzae Haemophilus spp*

Treatment of sinusitis

91

Table HI. Apparently resistant pathogens (disc diffusion test) isolated before treatment. For method, see text

Pathogens

Total

— — — — 1 1

Pathogens resistant to cefaclor 2 1 1 1 2 1 1 1 1 11

Number of patients 2

!

1

resistant to cefaclor were all sensitive to cefpodoxime. In this study 20 strains of Staph. aureus were identified. From the findings in this study, as judged by clinical and radiological responses, cefpodoxime proxetil (200 mg bd) may be somewhat more effective than cefaclor 500 mg tds for ten days, in the treatment of acute sinusitis in adult out-patients. Noneradication of H. influemae occurred in five cases with cefaclor. All cases of H. influenzae were eradicated with cefpodoxime proxetil. References Chin, N. X. & Neu, H. C. (1988). In vitro activity of an oral iminomethoxy aminothiazolyl cephalosporin. Antimicrobial Agents and Chemotherapy 32, 671-7. Ekedahl, F. (1987). Akute Sinusitis bei Erwachusenen. Infection 15, 120-2. Fasquelle, D., Dumas, G., Alami, M. & Burnichon, J. (1989). Examen microbiologique des ponctions de sinus lors de sinusites. Etude retrospective de 270 ponctions et revue de la litterature. Medecwe et Maladies Infectieuses 5, 299-304. Gehanno, P., Leclercq, M., Thibault, M., Pichon, F. & Duval, J. (1988). Bacteriologie des sinusites aigues et des sinusites chroniques en 1988. Reunion Interdisciplinaire de la Chimtotherapie Anti-lnfectieuse. Paris, 1988. Hanobey, B. H., Sande, M. A., Seale, D. L. & Gwaltney, J. L. (1979). Etiology and antimicrobial therapy of acute maxillary sinusitis. Journal of Infectious Diseases 139, 197-202. Jones, R. & Barry, A. L. (1988). Antimicrobial activity and disk diffusion susceptibility testing of U-76, 253 A (R-3746), the active metabolite of the new cephalosporin ester, U-76, 252 (CS807). Antimicrobial Agents and Chemotherapy 32, 443-9. Jousimes-Somer, H. R., Savolatinen, S. & Yukoski, J. S. (1988). Bacteriological findings of acute maxillary sinusitis in young adults. Journal of Clinical Microbiology 26, 1919-25. Scheld, W. M., Sydnor, A., Farr, B., Gratz, J. C. & Gwaltney, J. M. (1986). Comparison of cyclacillin and amoxycillin for therapy of acute maxillary sinusitis. Antimicrobial Agents and Chemotherapy 30, 350-3. Utsui, Y., Inove, M. & Mitsuhashi, S. (1987). In vitro and in vivo antibacterial activities of CS807, a new oral cephalosporin. Antimicrobial Agents and Chemotherapy 31, 1085-92. Wald, E. R., Mihnoe, G. J., Bowen, A., Ledesma-Medina, J., Salamon, N. & Bluestone, C. D. (1981). Acute maxillary sinusitis in children. New England Journal of Medicine 304, 749-54. Wald, E. R., Reilly, J. S., Casselbrant, M., Ledesma-Medina, J., Milmoe, G. J., Bluestone, C. D. et al. (1984). Treatment of acute maxillary sinusitis in childhood: a comparative study of amoxycillin and cefaclor. Journal of Pediatrics 104, 297-302.

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H. influemae B. catarrhalis Ent. cloacae Citrobacter spp. Morganella morganii Pr. vulgaris Acinetobacter spp. Staph. aureus Ps. aeruginosa

Pathogens resistant to cefpodoxime

Comparison of cefpodoxime proxetil with cefaclor in the treatment of sinusitis.

The efficacy and tolerance of cefpodoxime proxetil were compared with those of cefaclor in a multicentre, international, prospective, double-blind, pl...
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