PEDIATRIC PHARMACOLOGY AND THERAPEUTICS
Cefixime compared with amoxicillin for treatment of acute otitis media C a n d i c e E, Johnson, MD, PhD, Susan A, Carlin, MD, Dennis M, Super, MD, MPH, James M, Rehmus, MD, David G, Roberts, MD, Norman C, Christopher, MD, Judy K, Whitweli, RN, a n d Paul A, Shurin, MD* From the Department of Pediatrics, Case Western Reserve School of Medicine, MetroHealth Medical Center, Cleveland, Ohio Cefixime was compared with amoxicillin for treatment of acute otitis media in a randomized trial. Results of tympanocentesis on day 3 to 5 of therapy were used as the major outcome. Total daily doses were 8 mg/kg of cefixime and 40 m g / k g of amoxicillin. One hundred twenty-six patients were randomly assigned to receive treatment; 64 cultures grew pathogens. Pathogens were eradicated from the middle ear after 3 to 5 days of therapy in 27 (79.4%) of 34 children given amoxicillin and 26 (86.7%) of 30 children given cefixime (p = 0.47). When Strept o c o c c u s p n e u m o n i a e cases were analyzed, bacteriologic cure occurred in 14 (93.3%) of 15 children given amoxicillin and 12 (75%) of 16 given cefixime (p = 0.333). When cases of Haemophilus influenzae infection were analyzed, significantly more cures occurred with cefixime (10/10, 100%) than amoxicillin (8/13, 62%) (p = 0.046). Pathogens associated with failure of amoxicillin therapy were 14. influenzae (five cases, two ~-lactamase-positive), $. p n e u m o n i a e (one case), and Moraxella catarrhalis (one case, ~-lactamase-positive). The four failures with cefixime therapy were all in patients infected with S. pneumoniae. Rates of rash, diarrhea, and vomiting were the same in both groups and did not necessitate stopping therapy. We conclude the following: (I) Cefixime and amoxicillin were equivalent in overall clinical and bacteriologic efficacy for otitis media. (2) Cefixime was more efficacious than amoxicillin in treating/4. influenzae otitis media and should be preferred when 14. influenzae is the suspected etiologic agent. (3) Side effects of both drugs were mild and equivalent. (J PEDIATR1991;119:117-22) Because of the increasing frequency of ~3-1actamase-producing strains of Haemophilus influenzae 1 and Moraxella (previously Branhamella) catarrhalis 2 in respiratory tract infections, there have been many recent studies of new cephalosporins that are/3-1actamase stable. Although inSupported by Lederle Laboratories, Pearl River, N.Y. Presented at the Ambulatory Pediatrics Society, Anaheim, California, May 1990 (abstract published in Am J Dis Child 1990;144:421 ). Submitted for publication Dec. 13, 1990; accepted Feb. 14, 1991. Reprint requests: Candice E. Johnson, MD, PhD, Department of Pediatrics, MetroHealth Medical Center, 3395 Scranton Rd., Cleveland, OH 44109. *Now at College of Physicians and Surgeons, Columbia University, New York, N.Y. 9/25/28733
creasing rates of resistance of H. influenzae to amoxicillin in vitro have been documented in nationwid e surveys, 1 there is little published evidence of an increased clinical or bacteriologic failure rate for amoxicillin in otitis media. We compared amoxieillin with cefixime, a new/3-1actamasestable cephalosporin, using the results of a second tymMIC
Minimum inhibitory concentration
[
panocentesis on day 3 to 5 of therapy as the major outcome; this tympanocentesis has been referred to by Howie et al. ~ as the "in vivo sensitivity test in otitis media," METHODS Patient selection. Children from 8 weeks to 13 years of age attending the MetroHealth Medical Center Pediatric 117
118
Johnson et al.
The Journal of Pediatrics July 1991
T o b l e I. Patient population in the two treatment groups
Mean age (mo) Sex (%) Male Female Race (%) White Black Ears affected (%) Unilateral Bilateral Fever (%) Present Absent Previous episodes of otitis media (%) >3 --
Cefixime compared with amoxicillin for treatment of acute otitis media C a n d i c e E, Johnson, MD, PhD, Susan A, Carlin, MD, Dennis M, Super, MD, MPH, James M, Rehmus, MD, David G, Roberts, MD, Norman C, Christopher, MD, Judy K, Whitweli, RN, a n d Paul A, Shurin, MD* From the Department of Pediatrics, Case Western Reserve School of Medicine, MetroHealth Medical Center, Cleveland, Ohio Cefixime was compared with amoxicillin for treatment of acute otitis media in a randomized trial. Results of tympanocentesis on day 3 to 5 of therapy were used as the major outcome. Total daily doses were 8 mg/kg of cefixime and 40 m g / k g of amoxicillin. One hundred twenty-six patients were randomly assigned to receive treatment; 64 cultures grew pathogens. Pathogens were eradicated from the middle ear after 3 to 5 days of therapy in 27 (79.4%) of 34 children given amoxicillin and 26 (86.7%) of 30 children given cefixime (p = 0.47). When Strept o c o c c u s p n e u m o n i a e cases were analyzed, bacteriologic cure occurred in 14 (93.3%) of 15 children given amoxicillin and 12 (75%) of 16 given cefixime (p = 0.333). When cases of Haemophilus influenzae infection were analyzed, significantly more cures occurred with cefixime (10/10, 100%) than amoxicillin (8/13, 62%) (p = 0.046). Pathogens associated with failure of amoxicillin therapy were 14. influenzae (five cases, two ~-lactamase-positive), $. p n e u m o n i a e (one case), and Moraxella catarrhalis (one case, ~-lactamase-positive). The four failures with cefixime therapy were all in patients infected with S. pneumoniae. Rates of rash, diarrhea, and vomiting were the same in both groups and did not necessitate stopping therapy. We conclude the following: (I) Cefixime and amoxicillin were equivalent in overall clinical and bacteriologic efficacy for otitis media. (2) Cefixime was more efficacious than amoxicillin in treating/4. influenzae otitis media and should be preferred when 14. influenzae is the suspected etiologic agent. (3) Side effects of both drugs were mild and equivalent. (J PEDIATR1991;119:117-22) Because of the increasing frequency of ~3-1actamase-producing strains of Haemophilus influenzae 1 and Moraxella (previously Branhamella) catarrhalis 2 in respiratory tract infections, there have been many recent studies of new cephalosporins that are/3-1actamase stable. Although inSupported by Lederle Laboratories, Pearl River, N.Y. Presented at the Ambulatory Pediatrics Society, Anaheim, California, May 1990 (abstract published in Am J Dis Child 1990;144:421 ). Submitted for publication Dec. 13, 1990; accepted Feb. 14, 1991. Reprint requests: Candice E. Johnson, MD, PhD, Department of Pediatrics, MetroHealth Medical Center, 3395 Scranton Rd., Cleveland, OH 44109. *Now at College of Physicians and Surgeons, Columbia University, New York, N.Y. 9/25/28733
creasing rates of resistance of H. influenzae to amoxicillin in vitro have been documented in nationwid e surveys, 1 there is little published evidence of an increased clinical or bacteriologic failure rate for amoxicillin in otitis media. We compared amoxieillin with cefixime, a new/3-1actamasestable cephalosporin, using the results of a second tymMIC
Minimum inhibitory concentration
[
panocentesis on day 3 to 5 of therapy as the major outcome; this tympanocentesis has been referred to by Howie et al. ~ as the "in vivo sensitivity test in otitis media," METHODS Patient selection. Children from 8 weeks to 13 years of age attending the MetroHealth Medical Center Pediatric 117
118
Johnson et al.
The Journal of Pediatrics July 1991
T o b l e I. Patient population in the two treatment groups
Mean age (mo) Sex (%) Male Female Race (%) White Black Ears affected (%) Unilateral Bilateral Fever (%) Present Absent Previous episodes of otitis media (%) >3 --
