Equivalent efficacy and reduced occurrence of diarrhea from a new formulation of amoxicillin/clavulanate potassium (Augmentin®) for treatment of acute otitis media in children

Hoberman, Alejandro; Paradise, Jack L.; Burch, Daniel J.; Valinski, Wendy; Hedrick, James; Aronovitz, Gerson; Drehobl, Margaret; Rogers, Jeffrey

doi:10.1097/00006454-199705000-00002

Cited by 115 publications

(54 citation statements)

References 28 publications

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“…Our patients were considerably younger than those in most studies (all were Ͻ36 months of age; median age, 9 months), while in many published studies the upper age limit was Ͼ10 years, with a median of about 4 to 5 years. Higher clinical failure rates among patients younger than 2 years of age compared to those among older children have repeatedly been observed (22,42). Furthermore, our study group consisted of patients with more severe disease than those usually enrolled in most other studies: 58% had bilateral AOM, and 65% had recurrent AOM (with 30% having more than three previous episodes of AOM).…”

Section: Discussionmentioning

confidence: 99%

Bacteriologic Efficacies of Oral Azithromycin and Oral Cefaclor in Treatment of Acute Otitis Media in Infants and Young Children

Dagan

Leibovitz

Fliss³

et al. 2000

Antimicrob Agents Chemother

125

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A prospective, open-label, randomized study was conducted in order to determine the bacteriologic efficacies of cefaclor and azithromycin in acute otitis media (AOM). Tympanocentesis was performed on entry into the study and 3 to 4 days after initiation of treatment. Bacteriologic failure after 3 to 4 days of treatment with both drugs occurred in a high proportion of culture-positive patients, especially in those in whom AOM was caused by Haemophilus influenzae (16 of 33 [53%] of those treated with azithromycin and 13 of 34 [52%] of those treated with cefaclor). Although a clear correlation of the persistence of the pathogen with increased MICs of the respective drugs could be demonstrated for Streptococcus pneumoniae, no such correlation was found for H. influenzae. It is proposed that susceptibility breakpoints for H. influenzae should be considerably lower than the current ones for both cefaclor and azithromycin for AOM caused by H. influenzae.By definition, the goal of antibiotics in the treatment of acute otitis media (AOM) is eradication of the causative organism from the middle-ear fluid. In order to reach this goal, two conditions must be met: (i) the drug should be active against the causative organisms, and (ii) the drug should reach the middle-ear fluid and maintain a sufficient concentration long enough to allow bacterial inhibition and eventual killing (11). Although these two conditions can be tested in animal models, the ultimate challenge is the eradication of the pathogens from humans and, more specifically, from infants and young children, since they constitute the majority of patients with AOM.Unfortunately, the pharmacodynamic profiles of antimicrobial drugs (i.e., the relationship between concentrations at the site of infection over time and the antimicrobial effect) may not always be determined with accuracy in infants and young children, for obvious reasons. Thus, eradication of the pathogens must be studied in infants and children with AOM. Pathogen eradication can be assessed by performing trials in which a middle-ear fluid sample for culture is obtained immediately before antibiotic administration and a second one is obtained during the course of treatment (35). Howie and Ploussard (23) were the first to introduce this method and named it the "in vivo sensitivity test." The advantage of this method is that, with relatively few enrolled subjects, it can discriminate the effects of different drugs and predict clinical efficacy (13, 14, 23-26, 34, 35).The recent increase in the prevalence of antibiotic-resistant Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis has important implications for the treatment of AOM and poses a challenge to clinicians (5,7,13,18,21,25,28,33,48,49 1996). We recently demonstrated that in patients with AOM caused by S. pneumoniae isolates not susceptible to ␤-lactam antibiotics, the bacteriologic outcome was unsatisfactory in patients treated with various ␤-lactam antibiotics 13, 14, 32; Leibovitz et al., 36th ICAAC). The introductio...

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Section: Discussionmentioning

confidence: 99%

Bacteriologic Efficacies of Oral Azithromycin and Oral Cefaclor in Treatment of Acute Otitis Media in Infants and Young Children

Dagan

Leibovitz

Fliss³

et al. 2000

Antimicrob Agents Chemother

125

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“…145,151 In children who have taken amoxicillin in the previous 30 days, those with concurrent conjunctivitis, or those for whom coverage for β-lactamasepositive H influenzae and M catarrhalis is desired, therapy should be initiated with high-dose amoxicillin-clavulanate (90 mg/kg/day of amoxicillin, with 6.4 mg/kg/day of clavulanate, a ratio of amoxicillin to clavulanate of 14:1, given in 2 divided doses, which is less likely to cause diarrhea than other amoxicillinclavulanate preparations). 162 Alternative initial antibiotics include cefdinir (14 mg/kg per day in 1 or 2 doses), cefuroxime (30 mg/kg per day in 2 divided doses), cefpodoxime (10 mg/kg per day in 2 divided doses), or ceftriaxone (50 mg/kg, administered intramuscularly). It is important to note that alternative antibiotics vary in their efficacy against AOM pathogens.…”

Section: Microbiologymentioning

confidence: 99%

“…Several studies favor standard 10-day therapy over shorter courses for children younger than 2 years. 162,[190][191][192][193][194] Thus, for children younger than 2 years and children with severe symptoms, a standard 10-day course is recommended. A 7-day course of oral antibiotic appears to be equally effective in children 2 to 5 years of age with mild or moderate AOM.…”

Section: Duration Of Therapymentioning

confidence: 99%

The Diagnosis and Management of Acute Otitis Media

Tunkel

Rosenfeld²,

Sevilla³

et al. 2013

Pediatrics

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1,064

872

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This evidence-based clinical practice guideline is a revision of the 2004 acute otitis media (AOM) guideline from the American Academy of Pediatrics (AAP) and American Academy of Family Physicians. It provides recommendations to primary care clinicians for the management of children from 6 months through 12 years of age with uncomplicated AOM.In 2009, the AAP convened a committee composed of primary care physicians and experts in the fields of pediatrics, family practice, otolaryngology, epidemiology, infectious disease, emergency medicine, and guideline methodology. The subcommittee partnered with the Agency for Healthcare Research and Quality and the Southern California Evidence-Based Practice Center to develop a comprehensive review of the new literature related to AOM since the initial evidence report of 2000. The resulting evidence report and other sources of data were used to formulate the practice guideline recommendations.The focus of this practice guideline is the appropriate diagnosis and initial treatment of a child presenting with AOM. The guideline provides a specific, stringent definition of AOM. It addresses pain management, initial observation versus antibiotic treatment, appropriate choices of antibiotic agents, and preventive measures. It also addresses recurrent AOM, which was not included in the 2004 guideline. Decisions were made on the basis of a systematic grading of the quality of evidence and benefit-harm relationships.The practice guideline underwent comprehensive peer review before formal approval by the AAP.This clinical practice guideline is not intended as a sole source of guidance in the management of children with AOM. Rather, it is intended to assist primary care clinicians by providing a framework for clinical decision-making. It is not intended to replace clinical judgment or establish a protocol for all children with this condition. These recommendations may not provide the only appropriate approach to the management of this problem. Pediatrics 2013;131:e964-e999

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“…Formulations of A/C have used various ratios of the two components, ranging from 4:1 to 14:1 (5,6). Over time, the trend has been to reduce the total dose of clavulanate in order to lower the incidence of diarrhea and, in the latest formulation, to increase the dose of amoxicillin to improve efficacy against nonsusceptible S. pneumoniae, while maintaining the dose of clavulanate to preserve efficacy against H. influenzae and M. catarrhalis (7).…”

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confidence: 99%

Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media

Hoberman

Paradise

Rockette

et al. 2017

Antimicrob Agents Chemother

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Amoxicillin-clavulanate (A/C) is currently the most effective oral antimicrobial in treating children with acute otitis media (AOM), but the standard dosage of 90 mg amoxicillin/6.4 mg clavulanate/kg of body weight/day commonly causes diarrhea. We examined whether an A/C formulation containing lower concentrations of clavulanate would result in less diarrhea while maintaining plasma levels of amoxicillin and clavulanate adequate to eradicate middle-ear pathogens and to achieve clinical success. We conducted an open-label study in children with AOM who were 6 to 23 months of age. In phase 1, we treated 40 children with a reduced-clavulanate A/C formulation providing 90 mg amoxicillin/3.2 mg clavulanate/kg/day for 10 days. In phase 2, we treated 72 children with the same formulation at a dosage of 80 mg amoxicillin/2.85 mg clavulanate/kg/day for 10 days. We compared the rates of protocoldefined diarrhea (PDD), diaper dermatitis, and AOM clinical response in these children with rates we had reported in children who received the standard A/C regimen, and we obtained plasma levels of amoxicillin and clavulanate at various time points. Outcomes in phase 1 children and in children who had received the standard regimen did not differ significantly. Rates of PDD in children receiving phase 2 and standard regimens were 17% and 26%, respectively (P ϭ 0.10). The corresponding rates of diaper dermatitis were 21% and 33% (P ϭ 0.04) and of AOM treatment failure were 12% and 16% (P ϭ 0.44). Symptomatic responses did not differ significantly between regimens; both gave clavulanate levels sufficient to inhibit ␤-lactamase activity. In young children with AOM, clavulanate dosages lower than those currently used may be associated with fewer side effects without reducing clinical efficacy. (This study has been registered at ClinicalTrials.gov under registration no. NCT02630992.) KEYWORDS acute otitis media, amoxicillin-clavulanate, antimicrobial treatment N ext to the common cold, acute otitis media (AOM) is the most frequently diagnosed illness in children in the United States (1) and the most commonly cited indication for antimicrobial treatment (2). Findings of two recent placebo-controlled trials support routine antimicrobial treatment of AOM in very young children. In those trials, affected children under 3 years of age who received antimicrobial treatment for 7 or 10 days experienced more-favorable outcomes than those who received placebo (3, 4). In both studies, amoxicillin-clavulanate was used as the active treatment-albeit in different dosing regimens-because it had been previously shown to have the highest rates of eradication of AOM pathogens, with high resultant rates of clinical cure. The efficacy of A/C is attributable in part to inactivation, by the clavulanate

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Equivalent efficacy and reduced occurrence of diarrhea from a new formulation of amoxicillin/clavulanate potassium (Augmentin®) for treatment of acute otitis media in children

Cited by 115 publications

References 28 publications

Bacteriologic Efficacies of Oral Azithromycin and Oral Cefaclor in Treatment of Acute Otitis Media in Infants and Young Children

Bacteriologic Efficacies of Oral Azithromycin and Oral Cefaclor in Treatment of Acute Otitis Media in Infants and Young Children

The Diagnosis and Management of Acute Otitis Media

Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media

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