Comparative efficacy of ampicillin and media
trimethoprim-sulfamethoxazole in otitis
G.G. Cameron,* md; A.C. Pomahac,** md; M.T. Johnston^
Summary: Seventy-nine children with acute otitis media were the subjects in a study designed to compare the effectiveness of ampicillin and trimethoprim-sulfamethoxazole in this infection. They received either of these two agents according to a double-blind randomized procedure that also took the child's weight into account. No significant difference was found in the clinical outcome between the two treatment regimens. Undesirable side effects from TMP-SMX were notably few. Comparaison entre la penicilline et le trimethoprime-sulfamethoxazole dans le traitement des
Resume:
infections de I'oreille, du nez et de la gorge Chez des malades adultes souffrant d'infections actives de I'oreille, du nez et de la gorge, nous avons entrepris des essais comparatifs entre la penicilline et I'association trimethoprime-sulfamethoxazole (TMP-SMX) par la methode du double anonymat. II en ressort que le TMP-SMX a permis d'obtenir une amelioration clinique semblable que la penicilline, mais que le premier medicament couvrait un spectre plus etendu que la penicilline, au point de vue de I'elimination des organismes pathogenes. Nous exposons enfin les difficultes rencontrees pour obtenir des cultures positives qui refletaient fidelement I'etat clinique.
In clinical practice the problem of middle ear infections, especially in children, is a common one. The differentiation of a simple catarrhal otitis media from a suppurative otitis media requiring antimicrobial therapy is by no means easy. Some investigators believe that as many as three quarters of these infections are caused by common upper respiratory tract bacterial pathogens.1 Traditionally, the broad-spectrum agent ampicillin has been employed in treating otitis media in children less than 4 years of age because Hemophilus influenzae is most often the causative organism in this age group/ The synergy of the folic acid antagonist trimethoprim with sulfonamides has been exploited for many years to combat infectious disease in all regions of the body.3*8 The combination of sulfamethoxazole and trimethoprim (TMP-SMX) has been found to be bactericidal against all the middle ear pathogens H. influenzae, D. pneumoniae, staphylococci and streptococ¬ ci 4,5,8 Therefore one would expect acute otitis media to respond well to treatment with this agent. Moreover, it has been shown to be safe for administration to the pediatric age group.6
md
The present study was conducted to assess the effectiveness of TMP-SMX as compared with ampicillin when employed in short-term treatment regimens for otitis media in children.
Materials and methods We reviewed all clinical cases of otitis media seen by us in practices during the fall and winter of 1971 through 1974. The patient population was limited to children of low (15 to 25 kg) and high (25 to 50 kg) weight manifesting the signs and symptoms of fever, deep throbbing pain in the ear and hearing loss. Usually otoscopy would reveal a dull, bulging, fiery-red eardrum and there would be pain on pressure over the mastoid antrum. Tuning fork tests showed the expected conductive hearing loss in the affected ear. Excluded from the study were children with known penicillin or sulfonamide allergy, children otherwise in ill health, as well as children under treatment with antimicrobials or nasal decongestants when first seen. At the initial examination careful attention was paid to the presence of variables such as previous episodes of middle ear infection, an allergic background in the affected child, and perforation of the tympanic membrane. Appropriate cultures were taken wherever possible from the pharynx and/or external auditory canal. Patients in the low-weight group were given one capsule every 8 hours of either ampicillin, 250 mg, or TMP-SMX,40/200 mg. Those in the high-weight group received two capsules every 8 hours of either ampicillin, 167 mg per capsule, or TMP-SMX, 26/66 mg per capsule. The particular agent was assigned on a random basis using a double-blind technique. After 1 week of continuous therapy the children were re-examined. The evolution of the disease was assessed as to alleviation of the symptoms and objective clearing of the drum inflammation and hearing loss. These were classified as "no change"; "minimum change", meaning partial improvement of the drum inflammation and an absence of systemic signs of illness but usually with residual hearing loss; or "maximum change", meaning complete clearing of all localized signs of otitis in a child with no subjective complaints. Data of all patients successfully completing a 7-day course of our
Teble I.Therepeutic outcome in individuel
ears
High-weight group
treeted
Low-weight group
Family medicine unit, Queen Elizabeth Hospital, Montreal Medical director of student health services, University of Lethbridge, Lethbridge, Alta.
*
**
tMoncton Medical Clinic, Moncton, NB
Reprint requests to: Dr. G.G. Cameron, Queen Elizabeth Hospital, Montreal, Que. H4A 3L6 CMA JOURNAL/JUNE
14, 1975/VOL. 112 87S
the medication were included in the statistical analysis. The data from all investigators were pooled and all affected ears were considered separately. A chi-square analysis and a t-test were used to compare the two treatment regimens in each of the high- and low-weight groups. For the t-test, scores were assigned (no change = 0, minimum improvement = 1, maximum improvement = 2) to therapeutic outcomes, assuming that the same quantitative interval separates "no change" from "minimum improvement" and "minimum improvement" from "maximum improvement". Results Eighty-seven patients with clinical otitis media were treated. Eight of these patients failed to complete the therapy, five because of poor compliance for obscure reasons, and three because of gastrointestinal upset. Of the latter group, two were taking ampicillin and one was taking TMP-SMX. Comparison of the results achieved in both groups with the ampicillin and TMP-SMX is shown in Table I. Statistically, at a probability value of 0.05, there were no significant differences in the therapeutic outcome between the two treatment regimens in either the low- or high-weight groups. Table II analyses the cases in which it was possible to obtain a positive culture from either the nasopharynx secretions or pus obtained from the middle ear. The majority of pathogens isolated were hemolytic streptococci, Diplococcus pneumoniae and Hemophilus influenzae. In one case a Pseudomonas species was found; this opportunistic organism is usually not common in middle ear infections, except in chronic cases in which perforation of the drum has been established for long periods of time. Table Il-Pathogens isolated from nasopharyngeal swabs or suppurative material from middle ear
No. present
Ampicillin
Hemolytic streptococci
9
4
5
D. pneumoniae H. influenzae Pseudomonas species
3 2 1
1 2 -
2 1
CMA JOURNAL/JUNE 14, 1975/VOL. 112
Discussion The results of our study indicate that the combination trimethoprim-sulfamethoxazole should be included among the antimicrobial drugs effective in clinical middle ear infections in children. In both the high-weight and low-weight groups, TN4P-SMX and ampicillin were equally efficacious in treating otitis media. Attempts to identify the etiologic agents in acute otitis media do not always meet with success, and the debate over viral v. bacterial causation goes on. The practitioner, when confronted by the small child with a low-grade fever, a shrill cry and a red, angry ear drum, makes his clinical decisions usually without the benefit of a complete bacteriologic work-up. This trial takes a further step in showing that TMP-SMX shares with ampicillin a proved clinical effectiveness combined with a low incidence of side effects when used to combat the common pathogens causing otitis media in children. References
Successful antibiotic
88S
Both medications were efficacious in all patients from whom cultures were obtained, even in the one in whom Pseudomonas was present and who received TMP-SMX. Spontaneous perforation of the drum and/or the need for myringotomy were not observed in any patients, reflecting perhaps the early diagnosis and treatment the public has come to expect for ear infections. In the patients who completed the therapy, adverse effects were observed in four in the ampicillin group: a transitory rash in one patient and gastrointestinal upset in three others. Of the TMP-SMX patients, one complained of dry skin and in four, mild nausea or vomiting was noted. In none of these cases was the side effect judged important enough to warrant discontinuation of the medication.
TMP-SMX
I. LAXDAL QE, BLAKE RM, CARTMILL T, et al: Etiology of acute otitis media in infants and children. Can Med Assoc J 94: 159, 1966
2. FERGUSON CF, KENDIG E: Pediatric Otolaryngology. Toronto,
Saunders, 1972 3. BRUMFITT W, PURSELL R: Trimethoprim-sulfamethoxazole: the present position. J Infect Dis 128 (suppl): 778, 1973 4. BUSHBY, SRM: Trimethoprim-sulfamethoxazole: in vitro microbiological aspects. Ibid. p 442 5. LAXDAL QE: My child has an earache. Can Fain Physician 20: 65, 1974 6. LEWIN EB, KLEIN JO, FINLAND M: Trimethoprim-sulfamethoxazole: absorption, excretion and toxicity in six children. J Infect Dis 128 (suppl): 618, 1973 7. MALLETT E, MUSSELWHITE D: The use of Septrin in the treatment of upper respiratory tract infections. Practitioner 205: 807, 1970 8. HERNALSTEEN L: Comparison of two anti-infective treatments in otorhinolaryngology. Presented at the 5th International Congress on Infectious Diseases, Vienna, 1970
trimethoprim-sulfamethoxazole in otitis
G.G. Cameron,* md; A.C. Pomahac,** md; M.T. Johnston^
Summary: Seventy-nine children with acute otitis media were the subjects in a study designed to compare the effectiveness of ampicillin and trimethoprim-sulfamethoxazole in this infection. They received either of these two agents according to a double-blind randomized procedure that also took the child's weight into account. No significant difference was found in the clinical outcome between the two treatment regimens. Undesirable side effects from TMP-SMX were notably few. Comparaison entre la penicilline et le trimethoprime-sulfamethoxazole dans le traitement des
Resume:
infections de I'oreille, du nez et de la gorge Chez des malades adultes souffrant d'infections actives de I'oreille, du nez et de la gorge, nous avons entrepris des essais comparatifs entre la penicilline et I'association trimethoprime-sulfamethoxazole (TMP-SMX) par la methode du double anonymat. II en ressort que le TMP-SMX a permis d'obtenir une amelioration clinique semblable que la penicilline, mais que le premier medicament couvrait un spectre plus etendu que la penicilline, au point de vue de I'elimination des organismes pathogenes. Nous exposons enfin les difficultes rencontrees pour obtenir des cultures positives qui refletaient fidelement I'etat clinique.
In clinical practice the problem of middle ear infections, especially in children, is a common one. The differentiation of a simple catarrhal otitis media from a suppurative otitis media requiring antimicrobial therapy is by no means easy. Some investigators believe that as many as three quarters of these infections are caused by common upper respiratory tract bacterial pathogens.1 Traditionally, the broad-spectrum agent ampicillin has been employed in treating otitis media in children less than 4 years of age because Hemophilus influenzae is most often the causative organism in this age group/ The synergy of the folic acid antagonist trimethoprim with sulfonamides has been exploited for many years to combat infectious disease in all regions of the body.3*8 The combination of sulfamethoxazole and trimethoprim (TMP-SMX) has been found to be bactericidal against all the middle ear pathogens H. influenzae, D. pneumoniae, staphylococci and streptococ¬ ci 4,5,8 Therefore one would expect acute otitis media to respond well to treatment with this agent. Moreover, it has been shown to be safe for administration to the pediatric age group.6
md
The present study was conducted to assess the effectiveness of TMP-SMX as compared with ampicillin when employed in short-term treatment regimens for otitis media in children.
Materials and methods We reviewed all clinical cases of otitis media seen by us in practices during the fall and winter of 1971 through 1974. The patient population was limited to children of low (15 to 25 kg) and high (25 to 50 kg) weight manifesting the signs and symptoms of fever, deep throbbing pain in the ear and hearing loss. Usually otoscopy would reveal a dull, bulging, fiery-red eardrum and there would be pain on pressure over the mastoid antrum. Tuning fork tests showed the expected conductive hearing loss in the affected ear. Excluded from the study were children with known penicillin or sulfonamide allergy, children otherwise in ill health, as well as children under treatment with antimicrobials or nasal decongestants when first seen. At the initial examination careful attention was paid to the presence of variables such as previous episodes of middle ear infection, an allergic background in the affected child, and perforation of the tympanic membrane. Appropriate cultures were taken wherever possible from the pharynx and/or external auditory canal. Patients in the low-weight group were given one capsule every 8 hours of either ampicillin, 250 mg, or TMP-SMX,40/200 mg. Those in the high-weight group received two capsules every 8 hours of either ampicillin, 167 mg per capsule, or TMP-SMX, 26/66 mg per capsule. The particular agent was assigned on a random basis using a double-blind technique. After 1 week of continuous therapy the children were re-examined. The evolution of the disease was assessed as to alleviation of the symptoms and objective clearing of the drum inflammation and hearing loss. These were classified as "no change"; "minimum change", meaning partial improvement of the drum inflammation and an absence of systemic signs of illness but usually with residual hearing loss; or "maximum change", meaning complete clearing of all localized signs of otitis in a child with no subjective complaints. Data of all patients successfully completing a 7-day course of our
Teble I.Therepeutic outcome in individuel
ears
High-weight group
treeted
Low-weight group
Family medicine unit, Queen Elizabeth Hospital, Montreal Medical director of student health services, University of Lethbridge, Lethbridge, Alta.
*
**
tMoncton Medical Clinic, Moncton, NB
Reprint requests to: Dr. G.G. Cameron, Queen Elizabeth Hospital, Montreal, Que. H4A 3L6 CMA JOURNAL/JUNE
14, 1975/VOL. 112 87S
the medication were included in the statistical analysis. The data from all investigators were pooled and all affected ears were considered separately. A chi-square analysis and a t-test were used to compare the two treatment regimens in each of the high- and low-weight groups. For the t-test, scores were assigned (no change = 0, minimum improvement = 1, maximum improvement = 2) to therapeutic outcomes, assuming that the same quantitative interval separates "no change" from "minimum improvement" and "minimum improvement" from "maximum improvement". Results Eighty-seven patients with clinical otitis media were treated. Eight of these patients failed to complete the therapy, five because of poor compliance for obscure reasons, and three because of gastrointestinal upset. Of the latter group, two were taking ampicillin and one was taking TMP-SMX. Comparison of the results achieved in both groups with the ampicillin and TMP-SMX is shown in Table I. Statistically, at a probability value of 0.05, there were no significant differences in the therapeutic outcome between the two treatment regimens in either the low- or high-weight groups. Table II analyses the cases in which it was possible to obtain a positive culture from either the nasopharynx secretions or pus obtained from the middle ear. The majority of pathogens isolated were hemolytic streptococci, Diplococcus pneumoniae and Hemophilus influenzae. In one case a Pseudomonas species was found; this opportunistic organism is usually not common in middle ear infections, except in chronic cases in which perforation of the drum has been established for long periods of time. Table Il-Pathogens isolated from nasopharyngeal swabs or suppurative material from middle ear
No. present
Ampicillin
Hemolytic streptococci
9
4
5
D. pneumoniae H. influenzae Pseudomonas species
3 2 1
1 2 -
2 1
CMA JOURNAL/JUNE 14, 1975/VOL. 112
Discussion The results of our study indicate that the combination trimethoprim-sulfamethoxazole should be included among the antimicrobial drugs effective in clinical middle ear infections in children. In both the high-weight and low-weight groups, TN4P-SMX and ampicillin were equally efficacious in treating otitis media. Attempts to identify the etiologic agents in acute otitis media do not always meet with success, and the debate over viral v. bacterial causation goes on. The practitioner, when confronted by the small child with a low-grade fever, a shrill cry and a red, angry ear drum, makes his clinical decisions usually without the benefit of a complete bacteriologic work-up. This trial takes a further step in showing that TMP-SMX shares with ampicillin a proved clinical effectiveness combined with a low incidence of side effects when used to combat the common pathogens causing otitis media in children. References
Successful antibiotic
88S
Both medications were efficacious in all patients from whom cultures were obtained, even in the one in whom Pseudomonas was present and who received TMP-SMX. Spontaneous perforation of the drum and/or the need for myringotomy were not observed in any patients, reflecting perhaps the early diagnosis and treatment the public has come to expect for ear infections. In the patients who completed the therapy, adverse effects were observed in four in the ampicillin group: a transitory rash in one patient and gastrointestinal upset in three others. Of the TMP-SMX patients, one complained of dry skin and in four, mild nausea or vomiting was noted. In none of these cases was the side effect judged important enough to warrant discontinuation of the medication.
TMP-SMX
I. LAXDAL QE, BLAKE RM, CARTMILL T, et al: Etiology of acute otitis media in infants and children. Can Med Assoc J 94: 159, 1966
2. FERGUSON CF, KENDIG E: Pediatric Otolaryngology. Toronto,
Saunders, 1972 3. BRUMFITT W, PURSELL R: Trimethoprim-sulfamethoxazole: the present position. J Infect Dis 128 (suppl): 778, 1973 4. BUSHBY, SRM: Trimethoprim-sulfamethoxazole: in vitro microbiological aspects. Ibid. p 442 5. LAXDAL QE: My child has an earache. Can Fain Physician 20: 65, 1974 6. LEWIN EB, KLEIN JO, FINLAND M: Trimethoprim-sulfamethoxazole: absorption, excretion and toxicity in six children. J Infect Dis 128 (suppl): 618, 1973 7. MALLETT E, MUSSELWHITE D: The use of Septrin in the treatment of upper respiratory tract infections. Practitioner 205: 807, 1970 8. HERNALSTEEN L: Comparison of two anti-infective treatments in otorhinolaryngology. Presented at the 5th International Congress on Infectious Diseases, Vienna, 1970
