Medical management of chronic suppurative otitis media without cholesteatoma in children D. M. Fliss, MD, R. D a g a n , MD, Z. Houri, MD, a n d A, L e i b e r m a n , MD From the Department of Otolaryngology, the Pediatric Infectious DiseasesUnit, and the Division of Pediatrics, Soroka University Medical Center and the Faculty of Health Sciences, BenGurion University of the Negev,. Beer-Sheva, Israel To determine whether systemic administration of antibiotics may eliminate or reduce the n e e d for t y m p a n o m a s t o i d surgery in chronic suppurative otitis media without cholesteatoma, we undertook a randomized, prospective study c o m p a r i n g three regimens: (1) daily suction and d6bridement, with intravenous administration of mezlocillin until 3 days after the discharge stopped, (2) daily suction and d6bridement, with intravenous use of ceftazidime until 3 days after the discharge, stopped, and (3) daily suction and d 6 b r i d e m e n t without antibiotics. No t o p i c a l antimicrobial agents were used during the study. Fifty-one patients were included, and 48 children c o m p l e t e d the study. The duration of discharge from the ear before treatment was 2 to 123 months (median 20 months). In 26 patients (51%), the disease was bilateral. A e r o b i c cultures, o b t a i n e d with the Alden-Senturia middle ear aspirator, y i e l d e d Pseudomonas aeruginosa in 98%, enteric gram-negative bacilli in 33%, s t a p h y l o c o c c i in 25%, a n d Haemophilus influenzae in 12%. The first 33 patients were randomly assigned to o n e of the three regimens. In the 21 patients treated with suction and antibiotics (either mezlocillin or ceftazidime), the discharge s t o p p e d completely, versus in only I (8%) of 12 patients in the suction-only regimen (p 14 days. Amoxicillin prophylaxis was administered to 27 (56%) of the patients after c o m p l e t i o n of therapy. All patients were followed for 6 months. Drainage recurred in 12 (25%) patients during the first 3 months after the study. The recurrence rate was not a f f e c t e d by the antibiotic regimen, the patient's age, the duration of d r a i n a g e before initiation of antibiotic therapy, or prophylaxis. We c o n c l u d e that intravenous wide-spectrum antibiotic therapy in conjunction with daily suction and d ~ b r i d e m e n t is efficacious for the treatment of chronic suppurative otitis media without cholesteatoma. (J PEDIATR1990;116: 991-6)
Chronic suppurative otitis media without cholesteatoma is associated with chronic ear discharge that persists beyond Submitted for publication Aug. 21, 1989; accepted Jan. 3, 1990. Reprint requests: Ron Dagan MD, Director, Peiliatric Infectious Disease Unit, Soroka University Medical Center, P. O. Box 151, Beer-Sheva, Israel. 9/25/19195
6 weeks because of a nonintact tympanic membrane.I, 2 Although considered by some authors a "safe," "benign," or "limited" disease, 3, 4 chronic suppurative otitis media may lead to deterioration of conductive hearing as a result of ossicular chain damage, 5 sensorineural hearing loss, 6, 7 or, less frequently, a potentially lethal intracranial spread of the infection. 8-10 Until recently the standard medical management of
991
992
Fliss et al.
The Journal o f Pediatrics June 1990
T a b l e I. Organisms isolated from 77 ears of 51 patients with chronic suppurative otitis media, before initiation of antibiotic therapy Patients Organisms Pseudomonas P. aeruginosa Pseudomonas spp
Enteric gram-negative E. coli Enterobacter spp Proteus mirabilis
Others Staphylococcus S. aureus S. epidermidis H. influenzae*
Others
No.
%
51
100
50 l 17
33
6
5 4
2 13 11 2 6
5
25
12 10
*Untypable.
chronic suppurative otitis media without cholesteatoma consisted of aural toilet, oral or topical administration of antibiotics with or without steroids, or local insufflation of antiseptic powders, g, 11-17Such regimens did not alter the natural course of the disease, lg and cautions concerning the potential ototoxie effects of the topically applied agents have been expressed. 19-21 The standard treatment for cases unresponsive to the conservative treatment has been tympanomastoid s u r g e r y y but Kenna et al. 23 recently suggested that broad-spectrum, systemically administered antibiotics may be efficacious in the treatment of chronic suppurative otitis media without cholesteatoma. Because P s e u d o m o n a s aeruginoa is often isolated from the middle ear, it was recommended that parenterally administered antibiotics with antipseudomonal activity be used, followed by oral prophylactic antibiotic therapy to prevent recurrence. 24-26 This prospective, comparative, randomized study was conducted to determine (1) the efficacy of medical management of chronic suppurative otitis media without eholesteatoma with antibiotics active against P. aeruginosa, (2) the recurrence rate of chronic discharge after therapy, and (3) the need for antibiotic prophylaxis to prevent recurrence of Chronic discharge after therapy~ METHODS The patients were identified at the Soroka University Medical Center Otolaryngology Outpatient Clinic. Eligibility criteria were as follows: (1) age 3 months to 16 years, (2) continuous otorrhea through a tympanic membrane perforation or a ventilation tube for at least 2 months, (3)
failure of at least one complete conventional oral antibiotic course, and (4) no topical or systemic antibiotics during the week before enrollment. Children were excluded from the study if one of the following findings was present: (1) "a" foreign body in the external canal, (2) evidence of cholesteatoma, (3) evidence of intracranial or intratemporal complications, (4)known hypersensitivity to/3-1aetam antibiotics, and (5) the presence of an underlying serious condition such as immunodeficiency, malignancy, or cystic fibrosis. The study was approved by the Soroka Medical Center Ethical Committee. After verbal consent was obtained, all children were seen daily for 7 days in the otolaryngology outpatient clinic before initiation of antibiotic therapy, and the following procedures were performed: (1) A complete physical examination was performed by a pediatrician, and an otomicroscopic evaluation was made by an otolaryngologist. (2) Discharge and debris were removed from the external meatus, and aspirate obtained from the middle ear through the tympanic perforation by an Alden-Senturia middle ear aspirator 12 was introduced into Amies transport medium without charcoal (Exogen, from Clydebank Industrial Estate, Clydebank, Scotland). The swabs were immediately sent to the bacteriology laboratory. In addition, granulation tissue or polypoid formations were removed and sent for histopathologic examination. (3) A pure-tone audiogram was obtained on entry. Brain-stem audiometry was performed in children younger than 8 months of age. (4) Mastoid radiography was performed, in addition to laboratory examinations, including leukocyte count with a differential count and determination of serum electrolyte, urea, and creatinine values. (5) Finally, serum complement (CHs0, C3, C4) and serum immunoglobulindeterminations were made. All bacteriologic specimens were inoculated within less than 24 hours onto chocolate agar and 5% sheep blood agar thioglycolate medium at 37 ~ C in a carbon dioxide incubator. All patients had daily suction and d6bridement for 7 days before the initiation of antibiotic therapy. If otorrhea persisted after the first week, the patients were hospitalized and then randomly assigned to one of three treatment groups: Group 1 received daily suction and d6bridement with mezlocillin, 200 mg/kg given intravenously in three divided doses (maximum of 6.0 daily). Group 2 received daily suction and d6bridement withceftazidime, 150 mg/kg given intravenously in three divided doses (maximum of 3.0 gm daily). Both groups 1 and 2 received antibiotics until 3 days after complete cessation of discharge, except that it was decided not to treat the patients for more than 3 weeks. Group 3 received daily suction and d6bridement without
Volume 116 Number 6
antibiotics. If the discharge continued after an additional 7 days (for a total of 14 days), ceftazidime was added. No topical antimicrobial agents were used throughout the study. Ventilation tubes were placed at the end of every successful treatment if the tympanic membrane spontaneously closed. The first 19 patients were discharged from the hospital without antibiotic prophylaxis. However, when it was brought to our attention that the suggested treatment included antibiotic prophylaxisy we decided to administer to the remainder of the children a daily prophylactic single dose of amoxicillin (20 mg/kg; maximum 750 mg) for at least 2 months and to compare the recurrence rate between the patients who received prophylaxis and those who did not. All patients were reexamined at 3 days, 7 days, and 21 days and at 2, 3, and 6 months after discharge from the hospital to determine whether spontaneous closure of the perforation or recurrence of otorrhea, polyps, or granulation had occurred. In case of recurrence without cholesteatoma, we suggested a second course of intravenous antibiotic therapy. If a second course of antibiotic treatment failed, tympanomastoid surgery was proposed to the parents. Statistical analysis. The difference between the treatment groups was evaluated by cbi-square test, Fisher Exact Test, or Student t test as appropriate. A p value of 14 Days (%)
Mezlocillin (n = 17)
Ceftazidime (n = 19)
19-108 37
13-147 44
6-64 22 59
2-123 18 53
47
37
100
100
4-18 11.8 + 3.6 29
9-18 12.4 __+3.4 21
100% of the cases, followed by enteric gram-negative bacilli (33%), stapylococci (mainly Staphylococcus aureus) in 25% of cases, and Haemophilus influenzae in 12% of cases. When both ears had chronic discharge, culture results did not differ between the two ears. The sex, age, and duration of otorrhea before the initiation of therapy did not show any association with the microorganism isolated from the middle ear. The microorganisms were equally susceptible to mezlocillin and ceftazidime, except for S. aureus, which was resistant to mezlocillin but susceptible to ceftazidime. Treatment. The first 33 patients were randomly assigned, as described previously, to one of three groups (suction only, suction and mezlocillin, or suction and ceftazidime). No difference was observed among the groups for age, duration of drainage before treatment, proportion of children with bilateral discharge, or presence of granulation tissue and polyps. In all 10 patients treated with mizlocillin and suction, and in all 11 patients treated with ceftazidime and suction, the discharge stopped completely (mean duration 11.3 + 5.3 and 12.5 +_5.5 days, respectively), whereas the discharge stopped in only 1 (8%) of 12 patients in whom only suction was performed (p
Chronic suppurative otitis media without cholesteatoma is associated with chronic ear discharge that persists beyond Submitted for publication Aug. 21, 1989; accepted Jan. 3, 1990. Reprint requests: Ron Dagan MD, Director, Peiliatric Infectious Disease Unit, Soroka University Medical Center, P. O. Box 151, Beer-Sheva, Israel. 9/25/19195
6 weeks because of a nonintact tympanic membrane.I, 2 Although considered by some authors a "safe," "benign," or "limited" disease, 3, 4 chronic suppurative otitis media may lead to deterioration of conductive hearing as a result of ossicular chain damage, 5 sensorineural hearing loss, 6, 7 or, less frequently, a potentially lethal intracranial spread of the infection. 8-10 Until recently the standard medical management of
991
992
Fliss et al.
The Journal o f Pediatrics June 1990
T a b l e I. Organisms isolated from 77 ears of 51 patients with chronic suppurative otitis media, before initiation of antibiotic therapy Patients Organisms Pseudomonas P. aeruginosa Pseudomonas spp
Enteric gram-negative E. coli Enterobacter spp Proteus mirabilis
Others Staphylococcus S. aureus S. epidermidis H. influenzae*
Others
No.
%
51
100
50 l 17
33
6
5 4
2 13 11 2 6
5
25
12 10
*Untypable.
chronic suppurative otitis media without cholesteatoma consisted of aural toilet, oral or topical administration of antibiotics with or without steroids, or local insufflation of antiseptic powders, g, 11-17Such regimens did not alter the natural course of the disease, lg and cautions concerning the potential ototoxie effects of the topically applied agents have been expressed. 19-21 The standard treatment for cases unresponsive to the conservative treatment has been tympanomastoid s u r g e r y y but Kenna et al. 23 recently suggested that broad-spectrum, systemically administered antibiotics may be efficacious in the treatment of chronic suppurative otitis media without cholesteatoma. Because P s e u d o m o n a s aeruginoa is often isolated from the middle ear, it was recommended that parenterally administered antibiotics with antipseudomonal activity be used, followed by oral prophylactic antibiotic therapy to prevent recurrence. 24-26 This prospective, comparative, randomized study was conducted to determine (1) the efficacy of medical management of chronic suppurative otitis media without eholesteatoma with antibiotics active against P. aeruginosa, (2) the recurrence rate of chronic discharge after therapy, and (3) the need for antibiotic prophylaxis to prevent recurrence of Chronic discharge after therapy~ METHODS The patients were identified at the Soroka University Medical Center Otolaryngology Outpatient Clinic. Eligibility criteria were as follows: (1) age 3 months to 16 years, (2) continuous otorrhea through a tympanic membrane perforation or a ventilation tube for at least 2 months, (3)
failure of at least one complete conventional oral antibiotic course, and (4) no topical or systemic antibiotics during the week before enrollment. Children were excluded from the study if one of the following findings was present: (1) "a" foreign body in the external canal, (2) evidence of cholesteatoma, (3) evidence of intracranial or intratemporal complications, (4)known hypersensitivity to/3-1aetam antibiotics, and (5) the presence of an underlying serious condition such as immunodeficiency, malignancy, or cystic fibrosis. The study was approved by the Soroka Medical Center Ethical Committee. After verbal consent was obtained, all children were seen daily for 7 days in the otolaryngology outpatient clinic before initiation of antibiotic therapy, and the following procedures were performed: (1) A complete physical examination was performed by a pediatrician, and an otomicroscopic evaluation was made by an otolaryngologist. (2) Discharge and debris were removed from the external meatus, and aspirate obtained from the middle ear through the tympanic perforation by an Alden-Senturia middle ear aspirator 12 was introduced into Amies transport medium without charcoal (Exogen, from Clydebank Industrial Estate, Clydebank, Scotland). The swabs were immediately sent to the bacteriology laboratory. In addition, granulation tissue or polypoid formations were removed and sent for histopathologic examination. (3) A pure-tone audiogram was obtained on entry. Brain-stem audiometry was performed in children younger than 8 months of age. (4) Mastoid radiography was performed, in addition to laboratory examinations, including leukocyte count with a differential count and determination of serum electrolyte, urea, and creatinine values. (5) Finally, serum complement (CHs0, C3, C4) and serum immunoglobulindeterminations were made. All bacteriologic specimens were inoculated within less than 24 hours onto chocolate agar and 5% sheep blood agar thioglycolate medium at 37 ~ C in a carbon dioxide incubator. All patients had daily suction and d6bridement for 7 days before the initiation of antibiotic therapy. If otorrhea persisted after the first week, the patients were hospitalized and then randomly assigned to one of three treatment groups: Group 1 received daily suction and d6bridement with mezlocillin, 200 mg/kg given intravenously in three divided doses (maximum of 6.0 daily). Group 2 received daily suction and d6bridement withceftazidime, 150 mg/kg given intravenously in three divided doses (maximum of 3.0 gm daily). Both groups 1 and 2 received antibiotics until 3 days after complete cessation of discharge, except that it was decided not to treat the patients for more than 3 weeks. Group 3 received daily suction and d6bridement without
Volume 116 Number 6
antibiotics. If the discharge continued after an additional 7 days (for a total of 14 days), ceftazidime was added. No topical antimicrobial agents were used throughout the study. Ventilation tubes were placed at the end of every successful treatment if the tympanic membrane spontaneously closed. The first 19 patients were discharged from the hospital without antibiotic prophylaxis. However, when it was brought to our attention that the suggested treatment included antibiotic prophylaxisy we decided to administer to the remainder of the children a daily prophylactic single dose of amoxicillin (20 mg/kg; maximum 750 mg) for at least 2 months and to compare the recurrence rate between the patients who received prophylaxis and those who did not. All patients were reexamined at 3 days, 7 days, and 21 days and at 2, 3, and 6 months after discharge from the hospital to determine whether spontaneous closure of the perforation or recurrence of otorrhea, polyps, or granulation had occurred. In case of recurrence without cholesteatoma, we suggested a second course of intravenous antibiotic therapy. If a second course of antibiotic treatment failed, tympanomastoid surgery was proposed to the parents. Statistical analysis. The difference between the treatment groups was evaluated by cbi-square test, Fisher Exact Test, or Student t test as appropriate. A p value of 14 Days (%)
Mezlocillin (n = 17)
Ceftazidime (n = 19)
19-108 37
13-147 44
6-64 22 59
2-123 18 53
47
37
100
100
4-18 11.8 + 3.6 29
9-18 12.4 __+3.4 21
100% of the cases, followed by enteric gram-negative bacilli (33%), stapylococci (mainly Staphylococcus aureus) in 25% of cases, and Haemophilus influenzae in 12% of cases. When both ears had chronic discharge, culture results did not differ between the two ears. The sex, age, and duration of otorrhea before the initiation of therapy did not show any association with the microorganism isolated from the middle ear. The microorganisms were equally susceptible to mezlocillin and ceftazidime, except for S. aureus, which was resistant to mezlocillin but susceptible to ceftazidime. Treatment. The first 33 patients were randomly assigned, as described previously, to one of three groups (suction only, suction and mezlocillin, or suction and ceftazidime). No difference was observed among the groups for age, duration of drainage before treatment, proportion of children with bilateral discharge, or presence of granulation tissue and polyps. In all 10 patients treated with mizlocillin and suction, and in all 11 patients treated with ceftazidime and suction, the discharge stopped completely (mean duration 11.3 + 5.3 and 12.5 +_5.5 days, respectively), whereas the discharge stopped in only 1 (8%) of 12 patients in whom only suction was performed (p
