Cefprozil versus Amoxicillin/Clavulanate for the Treatment of Acute Otitis Media in Children: Meta-Analysis of Efficacy and Safety

Rafael Bolaños-Díaz, María Calderón-Cahua

Unidad de Análisis y Generación de Evidencias en Salud Pública (UNAGESP), Instituto Nacional de Salud, Lima, Perú.
Universidad Peruana Cayetano Heredia (UPCH), Lima, Perú.

DOI: 10.4236/pp.2014.54046                

Abstract

Introduction: The efficacy of amoxicillin combined with clavulanic acid in Acute Otitis Media (AOM) is not debatable, but studies report a high frequency of gastrointestinal adverse effects related to this intervention. In this scenario, several studies about the antibiotic cefprozil report that it has the same efficacy as amoxicillin/clavulanate for the treatment of AOM with significantly fewer side effects. The aim of our study was to compare the efficacy and safety of both treatments in AOM. Methodology: We searched for clinical trials and systematic reviews with or without meta-analyses in the Cochrane Group Register and the MEDLINE database up to November 2013, comparing the two interventions mentioned. Results were expressed as a rate of treatment failures or favorable response rates (clinical and microbiological in both cases), and as the rate of adverse events. The analysis was carried out considering the fixed and random effects models. The significance level used in the test for heterogeneity was 0.05. Funnel plot was used to search for publication bias. Results: 7 clinical trials were included in the analysis and no significant difference was found for both interventions regarding clinical and bacteriological response (RR = 1.02, 95% CI, 0.97-1.06, p = 0.780 and RR = 1.02, 95% CI, 0.99-1.07, p = 0.228, respectively). However, a significant difference was found in the comparison of adverse effects, showing that amoxicillin/clavulanate has a significantly higher risk of developing side effects than cefprozil (RR = 0.52, 95% CI, 0.45-0.59, p = 0.000). Conclusion: Both treatments demonstrated equal clinical and microbiological efficacy. However, the use of cefprozil is significantly associated with a lower risk of adverse effects.

Keywords

Cefprozil; Amoxicillin/Clavulanate; Acute Otitis Media

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	McCaig, L.F. and Hughes, J.M. (1995) Trends in Antimicrobial Drug Prescribing among Office-Based Physicians in the United States. JAMA, 273, 214-219. http://dx.doi.org/10.1001/jama.1995.03520270048030
[2]	McCaig, L.F., Besser, R.E. and Hughes, J.M. (2003) Antimicrobial Drug Prescription in Ambulatory Care Settings, United States, 1992-2000. Emerging Infectious Disease, 9, 432-437. http://dx.doi.org/10.3201/eid0904.020268
[3]	Marom, T., Tan, A., Wilkinson, G.S., Pierson, K.S., Freeman, J.L. and Chonmaitree, T. (2013) Trends in Otitis Media-Related Health Care Use in the United States, 2001-2011. JAMA Pediatrics, 168, 68-75. http://dx.doi.org/10.1001/jamapediatrics.2013.3924
[4]	Stool, S.E. and Field, M.J. (1989) The Impact of Otitis Media. The Pediatric Infectious Disease Journal, 8, S11-S14. http://dx.doi.org/10.1097/00006454-198901001-00006
[5]	Marom, T., Nokso-Koivisto, J. and Chonmaitree, T. (2012) Viral-Bacterial Interactions in Acute Otitis Media. Current Allergy and Asthma Reports, 12, 551-558. http://dx.doi.org/10.1007/s11882-012-0303-2
[6]	Faden, H., Duffy, L., Wasielewski, R., Wolf, J., Krystofik, D. and Tung, J. (1997) Relationship between Nasopharyngeal Colonization and the Development of Otitis Media in Children. Journal of Infectious Diseases, 175, 1440-1445. http://dx.doi.org/10.1086/516477
[7]	Posfay-Barbe, K.M. (2012) Infections in Pediatrics: Old and New Diseases. Swiss Medical Weekly, 142, w13654.
[8]	Harmes, K.M., Blackwood, R.A., Burrows, H.L., Cooke, J.M., Harrison, R.V. and Passamani, P.P. (2013) Otitis Media: Diagnosis and Treatment. American Family Physician, 88, 435-440.
[9]	Lieberthal, A.S., Carroll, A.E., Chonmaitree, T., Ganiats, T.G., Hoberman, A., Jackson, M.A., Joffe, M.D., et al. (2013) The Diagnosis and Management of Acute Otitis Media. Pediatrics, 131, e964-e999. http://dx.doi.org/10.1542/peds.2012-3488
[10]	Ball, P. (1994) Efficacy and Safety of Cefprozil versus Other Beta-Lactam Antibiotics in the Treatment of Lower Respiratory Tract Infections. European Journal of Clinical Microbiology & Infectious Diseases, 13, 851-856. http://dx.doi.org/10.1007/BF02111352
[11]	Arguedas, A.G., Zaleska, M., Stutman, H.M., Blumer, J.L. and Hains, C.S. (1991) Comparative Trial of Cefprozil vs. Amoxicillin Clavulanate Potassium in the Treatment of Children with Acute Otitis Media with Effusion. Pediatric Infectious Disease Journal, 10, 375-380. http://dx.doi.org/10.1097/00006454-199105000-00006
[12]	Stutman, H.R. and Arguedas, A.G. (1992) Comparison of Cefprozil with Other Antibiotic Regimens in the Treatment of Children with Acute Otitis Media. Clinical Infectious Diseases, 14, S204-S208. http://dx.doi.org/10.1093/clinids/14.Supplement_2.S204
[13]	Kafetzis, D.A. (1994) Multi-Investigator Evaluation of the Efficacy and Safety of Cefprozil, Amoxicillin-Clavulanate, Cefixime and Cefaclor in the Treatment of Acute Otitis Media. European Journal of Clinical Microbiology & Infectious Diseases, 13, 857-865. http://dx.doi.org/10.1007/BF02111353
[14]	Pichichero, M.E. and Casey, J.R. (2005) Acute Otitis Media: Making Sense of Recent Guidelines on Antimicrobial Treatment. Journal of Family Practice, 54, 313-322.
[15]	Brook, I. and Foote Jr., P.A. (2004) Effect of Antimicrobial Therapy with Amoxicillin and Cefprozil on Bacterial Interference and Beta-Lactamase Production in the Adenoids. Annals of Otology, Rhinology, and Laryngology, 113, 902-905.
[16]	Hedrick, J.A., Sher, L.D., Schwartz, R.H. and Pierce, P. (2001) Cefprozil versus High-Dose Amoxicillin/Clavulanate in Children with Acute Otitis Media. Clinical Therapeutics, 23, 193-204. http://dx.doi.org/10.1016/S0149-2918(01)80002-3
[17]	Powers, J.L., Gooch 3rd, W.M. and Oddo, L.P. (2000) Comparison of the Palatability of the Oral Suspension of Cefdinir vs. Amoxicillin/Clavulanate Potassium, Cefprozil and Azithromycin in Pediatric Patients. Pediatric Infectious Disease Journal, 19, S174-S180. http://dx.doi.org/10.1097/00006454-200012001-00008
[18]	Quach, C., Collet, J.P. and LeLorier, J. (2005) Effectiveness of Amoxicillin, Azithromycin, Cefprozil and Clarithromycin in the Treatment of Acute Otitis Media in Children: A Population-Based Study. Pharmacoepidemiology and Drug Safety, 14, 163-170. http://dx.doi.org/10.1002/pds.991
[19]	Moher, D., Jadad, A.R., Nichol, G., Penman, M., Tugwell, P. and Walsh, S. (1995) Assessing the Quality of Randomized Controlled Trials: An Annotated Bibliography of Scales and Check-Lists. Controlled Clinical Trials, 16, 62-73. http://dx.doi.org/10.1016/0197-2456(94)00031-W
[20]	Gehanno, P., Berche, P., Boucot, I., Lambert-Zechovskvy, N., Bingen, E., Gres, J.J. and Rollin, C. (1994) Comparative Efficacy and Safety of Cefprozil and Amoxycillin/Clavulanate in the Treatment of Acute Otitis Media in Children. Journal of Antimicrobial Chemotherapy, 33, 1209-1218. http://dx.doi.org/10.1093/jac/33.6.1209
[21]	Barriere, S.L. (1992) Pharmacology and Pharmacokinetics of Cefprozil. Clinical Infectious Diseases, 14, S184-S188. http://dx.doi.org/10.1093/clinids/14.Supplement_2.S184
[22]	Barriere, S.L. (1993) Review of in Vitro Activity, Pharmacokinetic Characteristics, Safety, and Clinical Efficacy of Cefprozil, a New Oral Cephalosporin. Annals of Pharmacotherapy, 27, 1082-1089.
[23]	Kafetzis, D.A., Astra, H. and Mitropoulos, L. (1997) Five-Day versus Ten-Day Treatment of Acute Otitis Media with Cefprozil. European Journal of Clinical Microbiology and Infectious Diseases, 16, 283-286. http://dx.doi.org/10.1007/BF01695632
[24]	Gupta, N., Bagga, V., Parmar, B.J., Kar, K., Mukherjee, A., Mehta, S. and Moharana, A.K. (2004) Efficacy and Tolerability Assessment of Cefprozil in Children with Acute Otitis Media. Indian Journal of Pediatrics, 71, 319-324. http://dx.doi.org/10.1007/BF02724098
[25]	Brook, I., Aronovitz, G.H. and Pichichero, M.E. (2001) Open-Label, Parallel-Group, Multicenter, Randomized Study of Cefprozil versus Erythromycin in Children with Group A Streptococcal Pharyngitis/Tonsillitis. Clinical Therapeutics, 23, 1889-1900. http://dx.doi.org/10.1016/S0149-2918(00)89084-0
[26]	Brook, I. and Foote, P.A. (1997) Effect of Penicillin or Cefprozil Therapy on Tonsillar Flora. Journal of Antimicrobial Chemotherapy, 40, 725-728. http://dx.doi.org/10.1093/jac/40.5.725
[27]	Gupta, N., Mukherjee, A. and Moharana, A.K. (2004) Pediatric Tonsillopharyngitis—An Evaluation of Cefprozil in Indian Patients. Indian Journal of Pediatrics, 71, 601-605. http://dx.doi.org/10.1007/BF02724119
[28]	Barbhaiya, R.H., Shukla, U.A., Gleason, C.R., Shyu, W.C., Wilber, R.B. and Pittman, K.A. (1990) Comparison of Cefprozil and Cefaclor Pharmacokinetics and Tissue Penetration. Antimicrobial Agents and Chemotherapy, 34, 1204-1209. http://dx.doi.org/10.1128/AAC.34.6.1204
[29]	Wilber, R.B., Doyle, C.A., Durham, S.J., Conetta, B.J., DeGraw, S.S. and Leigh, A. (1992) Safety Profile of Cefprozil. Clinical Infectious Diseases, 14, S264-S271. http://dx.doi.org/10.1093/clinids/14.Supplement_2.S264
[30]	Wiseman, L.R. and Benfield, P. (1993) Cefprozil. A Review of Its Antibacterial Activity, Pharmacokinetic Properties, and Therapeutic Potential. Drugs, 45, 295-317. http://dx.doi.org/10.2165/00003495-199345020-00008
[31]	Nicolau, D.P., Sutherland, C.A., Arguedas, A.G., Dagan, R. and Pichichero, M.E. (2007) Pharmacokinetics of Cefprozil in Plasma and Middle Ear Fluid: In Children Undergoing Treatment for Acute Otitis Media. Pediatric Drugs, 9, 119-123. http://dx.doi.org/10.2165/00148581-200709020-00005