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Comparison of amoxicillin and azithromycin in the prevention of recurrent acute otitis media
International Journal of Pediatric Otorhinolaryngology 58 (2001) 47 – 51 www.elsevier.com/locate/ijporl
Comparison of amoxicillin and azithromycin in the prevention of recurrent acute otitis media J.I. De Diego a,*, M.P. Prim a, C. Alfonso a, N. Sastre b, I. Rabanal a, J. Gavilan a a
Department of Otorhinolaryngology, ‘La Paz’ Hospital, Autonomous Uni6ersity, Madrid, Spain b Department of Research, ‘La Paz’ Hospital, Autonomous Uni6ersity, Madrid, Spain
Received 27 May 2000; received in revised form 03 November 2000; accepted 04 November 2000
Abstract Objecti6e: To compare the outcome of patients with recurrent acute otitis media (AOM) treated either with amoxicillin or with azithromycin. Methods: This prospective, controlled, and randomized study, compares the outcome of 71 patients with recurrent AOM treated with azithromycin (31 patients) or amoxicillin (40 patients) for the prevention of AOM. azithromycin was given at a dose of 10 mg/kg once a week, whereas amoxicillin was administered daily as a single intake of one third of the therapeutic dosage (20 mg/kg per day). All treatments were prescribed for 3 months. Both groups were homogeneous with regard to the currently accepted predisposing factors of recurrent AOM. Mean age of children was 35.3 months, and average follow-up was 11.5 months. The treatment was considered effective when the number of episodes of AOM dropped to less than 50% after the prophylaxis. Results: Patients in the azithromycin group had a clinical response to prophylaxis (80.6%) comparable to those treated with amoxicillin (89.5%) (P=0.300). The incidence of adverse effects was similar in both groups. Conclusion: According to these results, a prophylaxis with azithromycin is as useful as amoxicillin to prevent recurrent AOM. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Recurrent otitis media; Prophylaxis; Amoxicillin; Azithromycin
1. Introduction Many children have repeated episodes of acute otitis media (AOM) during the first years of life. Prevention (specially in severely affected children) * Corresponding author. Present address: C/Arzobispo Morcillo 12, 1°C 28029, Madrid, Spain. E-mail address: [email protected] (J.I. De Diego).
is desirable to avoid short and long-term sequelae. Among the various approaches that have been proposed for these clinical situations (antimicrobial prophylaxis, immunoprophylaxis, surgery, and control of environmental risk factors), antimicrobial prophylaxis has been considered the first option because of its compliance and effectiveness in reducing the number of new episodes of AOM [1–5]. Although the incidence of side effects of the daily protocols used nowadays is
0165-5876/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 5 - 5 8 7 6 ( 0 0 ) 0 0 4 6 5 - 1
48
J.I. De Diego et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 47–51
low, some parents are reticent to treat their children with daily doses of antibiotics through several months [2]. Thus, agents with comparable efficacy and more comfortable dosage should be assessed to obtain increased acceptance and compliance. The purpose of this study is to compare the effectiveness of azithromycin administered once-aweek with a conventional protocol of daily amoxicillin, in the prevention of recurrent AOM in children.
All data were statistically analyzed on an INVES PENTIUM computer using the BMDP statistical package (Statistical Software 7.0, 1993). The x2 test was used for qualitative variables. The Student’s t-test was employed for quantitative variables. Comparison of treatment’s results between both groups was performed by means of independent samples test. All statistical tests were considered bilateral and received the same level of significance of 0.05.
2. Material and methods In order to compare the effectiveness of azithromycin and amoxicillin in children with recurrent AOM a study with a prospective, controlled and randomized design was performed between January 1998 and May 1999. Recurrent AOM was defined as three or more episodes in the previous 6 months [4]. Each patient was randomly assigned to one treatment group (by a random distribution scheme developed before the start of the study). In each group of patients the following epidemiologic characteristics were registered: age, family history of recurrent AOM, history of prematurity, history of alergies, use of day care, household smokers, coincidence with dental eruption, history of upper respiratory related symptoms (snoring, mouth breathing, and recurrent tonsillitis), age at first AOM, season enrolled, and feeding (type — maternal or bottle and position). Patients in the azithromycin group received 10 mg/kg once a week. Amoxicillin was administered at one third of the therapeutic dose (20 mg/kg per day) daily. A 50% or more reduction of the number of episodes of AOM was used to evaluate the usefulness of the prophylaxis. All subjects were followed monthly. Patients with a new episode of AOM between visits were usually treated with the same agent of the chemoprophylaxis at therapeutic doses (10 mg/kg per day once daily during 3 days in the azithromycin children, and 20 mg/kg per day three times daily during 10 days in amoxicillin patients). The drug compliance was measured by asking parents about this question.
3. Results Seventy-one patients fulfilled the inclusion criteria and entered the study. Thirty-nine patients were male (54.9%) and 32 female (45.1%). Age ranged from 9 to 120 months (mean: 35.3 months). Two patients in the amoxicillin group could not complete the assigned treatment (one for gastrointestinal side effects and the another one for lack of compliance), leaving a total of 69 patients. Among the 69 patients who completed the study, 31 received azithromycin and 38 amoxicillin. The number of episodes per 6 months previous the onset of the chemoprophylaxis is showed in Table 1. Mean follow-up was 11.5 months (range: 6–27 months). In the azithromycin children, 22 patients were smaller than 35 months (71.0%). Likewise, 28 amoxicillin subjects (73.6%) had less than this age (Table 2). Table 1 Number of episodes of AOMa in the 6 months before the study (n =69) Number
Frequency
Percent (%)
Three Four Five Six Seven Nine Ten Twelve
26 17 6 10 4 1 2 3
37.7 24.6 8.7 14.5 5.8 1.5 2.9 4.3
a
AOM, acute otitis media.
J.I. De Diego et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 47–51 Table 2 Age of onset of the prophylaxis in each treatment group AGE (months)
Azithromycin (n = 31) n (%)
Amoxicillin (n= 38) n (%)
1–11 12–23 24–35 \35
1 7 14 9
3 9 16 10
(3.2) (22.6) (45.2) (29.0)
49
4. Discussion The main goal of the antimicrobial prophylaxis of recurrent AOM is to minimize the amount of microorganisms in the upper aerodigestive tract. Effectiveness of various therapeutic protocols has been extensively demonstrated [1–6], and the most widely used alternative to antimicrobial prophylaxis, which is the insertion of ventilation tubes has its own drawbacks and should be used cautiously [2]. However, some controversies still remain concerning the increase of beta-lactamase producing bacterias, and the appearance of resistant strains of bacteria. In our study, microbiologic controls by means of nasopharyngeal cultures were not considered for two reasons: 1. several studies have already demonstrated the lack of association between chemoprophylaxis and the appearance of resistant strains [2,5,6].
(7.8) (23.7) (42.1) (26.4)
Both treatment groups were homogeneus with regard to all epidemiologic characteristics studied (Table 2 and Table 3). In the azithromycin group, 25 patients (80.6%) experienced a reduction of more than 50% in the number of episodes of AOM. In the amoxicillin group good response to treatment was obtained in 34 subjects (89.5%). These differences are not statistically significant (P= 0.300).
Table 3 Epidemiologic characteristics CHARACTERISTICS
Azithromycin (n= 31) n (%)
Amoxicillin (n = 38) n (%)
Sex (male) Family history of recurrent AOMa History of prematurity History of alergies Use of day care Household smokers Coincidence with dental eruption History of snoring Mouth breathing Season enrolled Winter Spring Summer Autumn Bottle feeding Feeding while supine Age (months) Number of infections in the tonsils Age of first AOM (months)
117 (54.8) 15 (48.4)
21 (55.3) 24 (63.1)
– –
– –
0.582 0.162
3 2 30 24 11
– – – – –
– – – – –
0.597 0.245 0.235 0.751 0.245
a b
AOM, acute otitis media. SD, standard deviation.
2 4 21 22 12
(6.5) (12.9) (67.7) (70.9) (38.7)
12 (38.7) 11 (35.5) 15 9 2 5 8 1 – – –
(48.4) (29.0) (6.5) (16.1) (25.8) (3.2)
(7.9) (5.3) (78.9) (63.1) (28.9)
7 (18.4) 7 (18.4) 16 9 4 9 8 4 – – –
(42.1) (23.7) (10.5) (23.7) (21.0) (10.5)
Azithromycin (n = 31) Mean–SDb
Amoxicillin (n =38) Mean–SD
P
– – – – – – – – – 34.5–17.0 0.3–1.3
– – – – – – – – – 35.8–22.8 0.2–0.6
0.124 0.255
0.874 0.245 0.794 0.542
14.2–10.8
20.0–17.3
0.105
0.286
50
J.I. De Diego et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 47–51
2. the reliability of the nasopharyngeal cultures is poor in many cases: placement of a curette into the nasopharynx, near the eustachian tube to obtain the most probable germens that produces AOM, is very difficult even in the most cooperative child. Diverse epidemiologic factors have been slightly associated with a high incidence of otitis in children during the first years of life. These include: sex, season, day care centers, familial history of AOM, household smokers, history of prematurity, and no breast feeding [7 – 17]. The large number of epidemiologic factors that may have an impact on recurrent AOM emphasizes the need to design adequate studies. This prospective, randomized, and controlled study was designed to avoid bias in the selection of patients for the treatment’s groups and to obtain an useful clinical information. Homogenicity for all variables linked with recurrent AOM in children is very difficult [7 – 17], but is the only method to obtain results with adequate reliability. In our study, both groups of treatment were homogeneous according all reported factors in the current literature associated with this disease [7 – 17]. However, in the only previously published paper about this topic (efficacy of amoxicillin versus azithromycin), only 4 predisposing factors (age, sex, season of entry, and day-care-attendance) are considered to study the homogenicity between groups [5]. With respect to the statistical requeriments, more than 30 patients included in each treatment group is sufficient to allow the use of parametric tests for data analysis. According to our results, and those in a previous study [5], azithromycin is a valid alternative to amoxicillin in the treatment of recurrent AOM. Azithromycin could be the first choice in children for whom compliance could be difficult, in patients alergic to beta-lactamic, or when bacterias resistant to amoxicillin and sensitive to new macrolides are prevalent in the population [5]. Azithromycin offers the advantage of allowing more compliance of treatment with more confortable regimen. In fact, failure of compliance in this study occured only in the amoxicillin group, with 100% of azithromycin patients completing the protocol. This has been also mentioned by other
authors who find that weekly protocols of azithromycin produce more satisfaction in the parents [5]. 5. Conclusion Azithromycin can be used in the prophylaxis of recurrent AOM in children. No significant difference could be detected among treatment groups. Thus, on the basis of our study, azithromycin has a comparable usefulness than amoxicillin in prevention of recurrent AOM. References [1] C. Gonzalez, J.E. Arnold, E.A. Woody, J.B. Erdhart, R.S. Pratt, A. Getts, et al., Prevention of recurrent acute otitis media: chemoprophylaxis versus tympanostomy tubes, Laryngoscope 96 (1986) 1330– 1334. [2] M.L. Casselbrant, P.H. Kaleida, H.E. Rockette, J.L. Paradise, C.D. Bluestone, M. Kurs-Lasky, et al., Efficacy of antimicrobial prophylaxis and of tympanostomy tube insertion for prevention of recurrent acute otitis media: results of a randomized clinical trial, Pediatr. Infect. Dis. J. 11 (1992) 278– 286. [3] R.L. Williams, T.C. Chalmers, K.C. Stange, F.T. Chalmers, S.J. Bowlin, Use of antibiotics in preventing recurrent acute otitis media and in treating otitis media with effusion, J. Am. Med. Assoc. 270 (1993) 1344– 1351. [4] M.L. Casselbrant, E.M. Mandel, Acute and chronic otitis media, in: A.J. Hotaling, J.A. Stankiewicz (Eds.), Pediatric Otolaryngology for the General Otolaryngologist, Igaku-Shoin Medical Publishers, New York– Tokyo, 1996. [5] P. Marchisio, N. Principi, E. Sala, L. Lanzoni, S. Sorella, A. Massimini, Comparative study of once-weekly azithromycin and once-daily amoxicillin treatments in prevention of recurrent acute otitis media in children, Antimicrob. Agents Chemother. 40 (1996) 2732– 2736. [6] S.R. Berman, R. Nuss, C. Roark, C. Huber-Navin, K. Grose, M. Herrera, Effectiveness of continous vs. intermittent amoxicillin to prevent episodes of otitis media, Pediatr. Infect. Dis. J. 11 (1992) 63 – 67. [7] D.W. Teele, J.O. Klein, B.A. Rosner, The Greater Boston otitis media study group. Epidemiology of otitis media during the first seven years of life in children in Greater Boston: a prospective, cohort study, J. Infect. Dis. 160 (1989) 83 – 94. [8] Solomon NE, Harris LJ. Otitis media in children. Assessing the quality of medical care using short-term outcome measures. Quality of medical care assessment using outcome measures: eight disease.specific applications. Santa Monica, CA, Rand Corp., 1976.
J.I. De Diego et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 47–51 [9] D.W. Teele, J.O. Klein, B.A. Rosner, Otitis media with effusion during the first three years of life and development of speech and language, Pediatrics 74 (1984) 282– 287. [10] E.R. Wald, N. Guerra, C. Byers, Frequency and severity of infections in day care: three-year follow-up, J. Pediatr. 118 (1991) 509– 514. [11] R.A. Etzel, E.N. Pattishall, N.J. Haley, R.H. Fletcher, F.W. Hendersar, Passive smoking and middle ear effusion among children in day care, Pediatrics 90 (1992) 228–232. [12] W.H. Kitchen, G.W. Ford, D.W. Doyle, A.L. Richards, E.A. Kelly, Health and hospital readmissions of very-lowbirth-weight and normal-birth-weight children, Am. J. Dis. Child 144 (1990) 213–218. [13] O.P. Alho, M. Koivu, A.L. Hartikainen-Sorri, M. Sorri, O. Kilkkn, D. Rantekallio, Is a child’s history of acute otitis media and respiratory infection already determined
[14]
[15]
[16]
[17]
.
51
in the antenatal and perinatal period?, Int. J. Pediatr. Otorhinolaryngol. 19 (1990) 129– 137. B. Duncan, J. Ey, C.J. Holberg, A.L. Wright, F.D. Martı´nez, L.M. Taussing, Exclusive breast-feeding for at least 4 months protects against otitis media, Pediatrics 91 (1993) 867– 872. K.A. Daly, J.E. Brown, B.R. Lindgren, M.H. Meland, C.T. Le, G.S. Giebink, Epidemiology of otitis media onset by six months of age, Pediatrics 103 (1999) 1158– 1166. P. Homoe, R.B. Christensen, P. Bretlau, Acute otitis media and sociomedical risk factors among unselected children in Greenland, Int. J. Pediatr. Otorhinolaryngol. 49 (1999) 37 – 52. O.C. Ilicali, N. Keles, K. Deger, I. Savas, Relationship of passive cigarette smoking to otitis media, Arch. Otolaryngol. Head Neck Surg. 125 (1999) 758– 762.
Comparison of amoxicillin and azithromycin in the prevention of recurrent acute otitis media J.I. De Diego a,*, M.P. Prim a, C. Alfonso a, N. Sastre b, I. Rabanal a, J. Gavilan a a
Department of Otorhinolaryngology, ‘La Paz’ Hospital, Autonomous Uni6ersity, Madrid, Spain b Department of Research, ‘La Paz’ Hospital, Autonomous Uni6ersity, Madrid, Spain
Received 27 May 2000; received in revised form 03 November 2000; accepted 04 November 2000
Abstract Objecti6e: To compare the outcome of patients with recurrent acute otitis media (AOM) treated either with amoxicillin or with azithromycin. Methods: This prospective, controlled, and randomized study, compares the outcome of 71 patients with recurrent AOM treated with azithromycin (31 patients) or amoxicillin (40 patients) for the prevention of AOM. azithromycin was given at a dose of 10 mg/kg once a week, whereas amoxicillin was administered daily as a single intake of one third of the therapeutic dosage (20 mg/kg per day). All treatments were prescribed for 3 months. Both groups were homogeneous with regard to the currently accepted predisposing factors of recurrent AOM. Mean age of children was 35.3 months, and average follow-up was 11.5 months. The treatment was considered effective when the number of episodes of AOM dropped to less than 50% after the prophylaxis. Results: Patients in the azithromycin group had a clinical response to prophylaxis (80.6%) comparable to those treated with amoxicillin (89.5%) (P=0.300). The incidence of adverse effects was similar in both groups. Conclusion: According to these results, a prophylaxis with azithromycin is as useful as amoxicillin to prevent recurrent AOM. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Recurrent otitis media; Prophylaxis; Amoxicillin; Azithromycin
1. Introduction Many children have repeated episodes of acute otitis media (AOM) during the first years of life. Prevention (specially in severely affected children) * Corresponding author. Present address: C/Arzobispo Morcillo 12, 1°C 28029, Madrid, Spain. E-mail address: [email protected] (J.I. De Diego).
is desirable to avoid short and long-term sequelae. Among the various approaches that have been proposed for these clinical situations (antimicrobial prophylaxis, immunoprophylaxis, surgery, and control of environmental risk factors), antimicrobial prophylaxis has been considered the first option because of its compliance and effectiveness in reducing the number of new episodes of AOM [1–5]. Although the incidence of side effects of the daily protocols used nowadays is
0165-5876/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 5 - 5 8 7 6 ( 0 0 ) 0 0 4 6 5 - 1
48
J.I. De Diego et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 47–51
low, some parents are reticent to treat their children with daily doses of antibiotics through several months [2]. Thus, agents with comparable efficacy and more comfortable dosage should be assessed to obtain increased acceptance and compliance. The purpose of this study is to compare the effectiveness of azithromycin administered once-aweek with a conventional protocol of daily amoxicillin, in the prevention of recurrent AOM in children.
All data were statistically analyzed on an INVES PENTIUM computer using the BMDP statistical package (Statistical Software 7.0, 1993). The x2 test was used for qualitative variables. The Student’s t-test was employed for quantitative variables. Comparison of treatment’s results between both groups was performed by means of independent samples test. All statistical tests were considered bilateral and received the same level of significance of 0.05.
2. Material and methods In order to compare the effectiveness of azithromycin and amoxicillin in children with recurrent AOM a study with a prospective, controlled and randomized design was performed between January 1998 and May 1999. Recurrent AOM was defined as three or more episodes in the previous 6 months [4]. Each patient was randomly assigned to one treatment group (by a random distribution scheme developed before the start of the study). In each group of patients the following epidemiologic characteristics were registered: age, family history of recurrent AOM, history of prematurity, history of alergies, use of day care, household smokers, coincidence with dental eruption, history of upper respiratory related symptoms (snoring, mouth breathing, and recurrent tonsillitis), age at first AOM, season enrolled, and feeding (type — maternal or bottle and position). Patients in the azithromycin group received 10 mg/kg once a week. Amoxicillin was administered at one third of the therapeutic dose (20 mg/kg per day) daily. A 50% or more reduction of the number of episodes of AOM was used to evaluate the usefulness of the prophylaxis. All subjects were followed monthly. Patients with a new episode of AOM between visits were usually treated with the same agent of the chemoprophylaxis at therapeutic doses (10 mg/kg per day once daily during 3 days in the azithromycin children, and 20 mg/kg per day three times daily during 10 days in amoxicillin patients). The drug compliance was measured by asking parents about this question.
3. Results Seventy-one patients fulfilled the inclusion criteria and entered the study. Thirty-nine patients were male (54.9%) and 32 female (45.1%). Age ranged from 9 to 120 months (mean: 35.3 months). Two patients in the amoxicillin group could not complete the assigned treatment (one for gastrointestinal side effects and the another one for lack of compliance), leaving a total of 69 patients. Among the 69 patients who completed the study, 31 received azithromycin and 38 amoxicillin. The number of episodes per 6 months previous the onset of the chemoprophylaxis is showed in Table 1. Mean follow-up was 11.5 months (range: 6–27 months). In the azithromycin children, 22 patients were smaller than 35 months (71.0%). Likewise, 28 amoxicillin subjects (73.6%) had less than this age (Table 2). Table 1 Number of episodes of AOMa in the 6 months before the study (n =69) Number
Frequency
Percent (%)
Three Four Five Six Seven Nine Ten Twelve
26 17 6 10 4 1 2 3
37.7 24.6 8.7 14.5 5.8 1.5 2.9 4.3
a
AOM, acute otitis media.
J.I. De Diego et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 47–51 Table 2 Age of onset of the prophylaxis in each treatment group AGE (months)
Azithromycin (n = 31) n (%)
Amoxicillin (n= 38) n (%)
1–11 12–23 24–35 \35
1 7 14 9
3 9 16 10
(3.2) (22.6) (45.2) (29.0)
49
4. Discussion The main goal of the antimicrobial prophylaxis of recurrent AOM is to minimize the amount of microorganisms in the upper aerodigestive tract. Effectiveness of various therapeutic protocols has been extensively demonstrated [1–6], and the most widely used alternative to antimicrobial prophylaxis, which is the insertion of ventilation tubes has its own drawbacks and should be used cautiously [2]. However, some controversies still remain concerning the increase of beta-lactamase producing bacterias, and the appearance of resistant strains of bacteria. In our study, microbiologic controls by means of nasopharyngeal cultures were not considered for two reasons: 1. several studies have already demonstrated the lack of association between chemoprophylaxis and the appearance of resistant strains [2,5,6].
(7.8) (23.7) (42.1) (26.4)
Both treatment groups were homogeneus with regard to all epidemiologic characteristics studied (Table 2 and Table 3). In the azithromycin group, 25 patients (80.6%) experienced a reduction of more than 50% in the number of episodes of AOM. In the amoxicillin group good response to treatment was obtained in 34 subjects (89.5%). These differences are not statistically significant (P= 0.300).
Table 3 Epidemiologic characteristics CHARACTERISTICS
Azithromycin (n= 31) n (%)
Amoxicillin (n = 38) n (%)
Sex (male) Family history of recurrent AOMa History of prematurity History of alergies Use of day care Household smokers Coincidence with dental eruption History of snoring Mouth breathing Season enrolled Winter Spring Summer Autumn Bottle feeding Feeding while supine Age (months) Number of infections in the tonsils Age of first AOM (months)
117 (54.8) 15 (48.4)
21 (55.3) 24 (63.1)
– –
– –
0.582 0.162
3 2 30 24 11
– – – – –
– – – – –
0.597 0.245 0.235 0.751 0.245
a b
AOM, acute otitis media. SD, standard deviation.
2 4 21 22 12
(6.5) (12.9) (67.7) (70.9) (38.7)
12 (38.7) 11 (35.5) 15 9 2 5 8 1 – – –
(48.4) (29.0) (6.5) (16.1) (25.8) (3.2)
(7.9) (5.3) (78.9) (63.1) (28.9)
7 (18.4) 7 (18.4) 16 9 4 9 8 4 – – –
(42.1) (23.7) (10.5) (23.7) (21.0) (10.5)
Azithromycin (n = 31) Mean–SDb
Amoxicillin (n =38) Mean–SD
P
– – – – – – – – – 34.5–17.0 0.3–1.3
– – – – – – – – – 35.8–22.8 0.2–0.6
0.124 0.255
0.874 0.245 0.794 0.542
14.2–10.8
20.0–17.3
0.105
0.286
50
J.I. De Diego et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 47–51
2. the reliability of the nasopharyngeal cultures is poor in many cases: placement of a curette into the nasopharynx, near the eustachian tube to obtain the most probable germens that produces AOM, is very difficult even in the most cooperative child. Diverse epidemiologic factors have been slightly associated with a high incidence of otitis in children during the first years of life. These include: sex, season, day care centers, familial history of AOM, household smokers, history of prematurity, and no breast feeding [7 – 17]. The large number of epidemiologic factors that may have an impact on recurrent AOM emphasizes the need to design adequate studies. This prospective, randomized, and controlled study was designed to avoid bias in the selection of patients for the treatment’s groups and to obtain an useful clinical information. Homogenicity for all variables linked with recurrent AOM in children is very difficult [7 – 17], but is the only method to obtain results with adequate reliability. In our study, both groups of treatment were homogeneous according all reported factors in the current literature associated with this disease [7 – 17]. However, in the only previously published paper about this topic (efficacy of amoxicillin versus azithromycin), only 4 predisposing factors (age, sex, season of entry, and day-care-attendance) are considered to study the homogenicity between groups [5]. With respect to the statistical requeriments, more than 30 patients included in each treatment group is sufficient to allow the use of parametric tests for data analysis. According to our results, and those in a previous study [5], azithromycin is a valid alternative to amoxicillin in the treatment of recurrent AOM. Azithromycin could be the first choice in children for whom compliance could be difficult, in patients alergic to beta-lactamic, or when bacterias resistant to amoxicillin and sensitive to new macrolides are prevalent in the population [5]. Azithromycin offers the advantage of allowing more compliance of treatment with more confortable regimen. In fact, failure of compliance in this study occured only in the amoxicillin group, with 100% of azithromycin patients completing the protocol. This has been also mentioned by other
authors who find that weekly protocols of azithromycin produce more satisfaction in the parents [5]. 5. Conclusion Azithromycin can be used in the prophylaxis of recurrent AOM in children. No significant difference could be detected among treatment groups. Thus, on the basis of our study, azithromycin has a comparable usefulness than amoxicillin in prevention of recurrent AOM. References [1] C. Gonzalez, J.E. Arnold, E.A. Woody, J.B. Erdhart, R.S. Pratt, A. Getts, et al., Prevention of recurrent acute otitis media: chemoprophylaxis versus tympanostomy tubes, Laryngoscope 96 (1986) 1330– 1334. [2] M.L. Casselbrant, P.H. Kaleida, H.E. Rockette, J.L. Paradise, C.D. Bluestone, M. Kurs-Lasky, et al., Efficacy of antimicrobial prophylaxis and of tympanostomy tube insertion for prevention of recurrent acute otitis media: results of a randomized clinical trial, Pediatr. Infect. Dis. J. 11 (1992) 278– 286. [3] R.L. Williams, T.C. Chalmers, K.C. Stange, F.T. Chalmers, S.J. Bowlin, Use of antibiotics in preventing recurrent acute otitis media and in treating otitis media with effusion, J. Am. Med. Assoc. 270 (1993) 1344– 1351. [4] M.L. Casselbrant, E.M. Mandel, Acute and chronic otitis media, in: A.J. Hotaling, J.A. Stankiewicz (Eds.), Pediatric Otolaryngology for the General Otolaryngologist, Igaku-Shoin Medical Publishers, New York– Tokyo, 1996. [5] P. Marchisio, N. Principi, E. Sala, L. Lanzoni, S. Sorella, A. Massimini, Comparative study of once-weekly azithromycin and once-daily amoxicillin treatments in prevention of recurrent acute otitis media in children, Antimicrob. Agents Chemother. 40 (1996) 2732– 2736. [6] S.R. Berman, R. Nuss, C. Roark, C. Huber-Navin, K. Grose, M. Herrera, Effectiveness of continous vs. intermittent amoxicillin to prevent episodes of otitis media, Pediatr. Infect. Dis. J. 11 (1992) 63 – 67. [7] D.W. Teele, J.O. Klein, B.A. Rosner, The Greater Boston otitis media study group. Epidemiology of otitis media during the first seven years of life in children in Greater Boston: a prospective, cohort study, J. Infect. Dis. 160 (1989) 83 – 94. [8] Solomon NE, Harris LJ. Otitis media in children. Assessing the quality of medical care using short-term outcome measures. Quality of medical care assessment using outcome measures: eight disease.specific applications. Santa Monica, CA, Rand Corp., 1976.
J.I. De Diego et al. / Int. J. Pediatr. Otorhinolaryngol. 58 (2001) 47–51 [9] D.W. Teele, J.O. Klein, B.A. Rosner, Otitis media with effusion during the first three years of life and development of speech and language, Pediatrics 74 (1984) 282– 287. [10] E.R. Wald, N. Guerra, C. Byers, Frequency and severity of infections in day care: three-year follow-up, J. Pediatr. 118 (1991) 509– 514. [11] R.A. Etzel, E.N. Pattishall, N.J. Haley, R.H. Fletcher, F.W. Hendersar, Passive smoking and middle ear effusion among children in day care, Pediatrics 90 (1992) 228–232. [12] W.H. Kitchen, G.W. Ford, D.W. Doyle, A.L. Richards, E.A. Kelly, Health and hospital readmissions of very-lowbirth-weight and normal-birth-weight children, Am. J. Dis. Child 144 (1990) 213–218. [13] O.P. Alho, M. Koivu, A.L. Hartikainen-Sorri, M. Sorri, O. Kilkkn, D. Rantekallio, Is a child’s history of acute otitis media and respiratory infection already determined
[14]
[15]
[16]
[17]
.
51
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