A Review of Recommended Antibiotic Therapies with Impact on Outcomes in Acute Otitis Media and Acute Bacterial Sinusitis

REPORTS A Review of Recommended Antibiotic Therapies With Impact on Outcomes in Acute Otitis Media and Acute Bacterial Sinusitis Michael E. Pichichero, MD, and Diana I. Brixner, RPh, PhD cute otitis media (AOM) and acute efficacy and adherence in the treatment of bacterial sinusitis (ABS) manage- AOM and ABS. A ment is becoming increasingly com- plex, with continual changes in the Direct and Indirect Costs pathogens responsible for these conditions. of AOM and ABS Treatment involves the selection of an effi- The total costs of both AOM and ABS can cacious agent displaying a favorable adher- be high. Direct AOM and ABS costs are typ- ence profile. Although antibiotic efficacy is ically based on medication use and physi- critical to treatment successes, therapy cian visits. Annual estimates of direct AOM adherence is arguably of equal importance, costs range from $1.96 billion to $4.1 bil- because failure to adhere to even the most lion,2,3 whereas direct sinusitis costs (as a effective therapy can ultimately lead to clin- primary diagnosis) are estimated at $1.8 bil- ical failure and undermine treatment efforts. lion.4 However, direct costs represent only a The dual importance of efficacy and adher- portion of the total economic burden of ill- ence requires additional consideration when ness. Indirect costs can include the expense treating pediatric infections. Managed care of care for sick children, transportation organizations (MCOs) are increasingly costs, the value of work time lost, baby-sit- aware that a balance is needed when weigh- ting fees, ancillary medication costs, and ing efficacy and adherence issues with expenditures for treatment of adverse antibiotics. In one study, a health mainte- effects.5 Indirect costs are estimated at $1.02 nance organization initiated a guideline billion for AOM2 and $1.6 billion for ABS.4 compliance education and provider-report- These significant indirect costs emphasize ing pathway program among 900 physicians, that AOM and ABS impose a considerable nurse practitioners, and physician assistants economic burden for the patient, family, or in Rochester, NY, resulting in increased employer who is purchasing health insur- quality of care and a reduction in pharmacy ance coverage in part or in full. costs.1 More health plans should use provider Impact of Treatment Failures and patient education strategies to improve Treatment failure can lead to persistent or provider compliance to national guidelines. recurrent infection, which in turn leads to Formulary redevelopment can improve care an increase in overall cost of care.6 Poor effi- if efforts are made to evaluate emerging cacy is in part responsible for persistent and disease management issues, including the recurrent infections, with prior antibiotic shifting microbiology of the organisms im- use increasing the likelihood of treatment plicated in AOM and ABS, medication costs, and the evaluation of products with the We would like to thank the University of the Sciences in Philadelphia for best reported adherence. The purpose of editorial assistance in the development of these articles. this paper is to present the main costs of Address Correspondence to: Michael E. Pichichero, MD, University of Rochester Medical Center, Elmwood Pediatric Group, 601 Elmwood AOM and ABS, review the impact of treat- Avenue, Box 672, Rochester, NY 14642. E-mail: michael_pichichero ment failures, and discuss the dual role of @umc.rochester.edu. S292 THE AMERICAN JOURNAL OF MANAGED CARE AUGUST 2006 A Review of Recommended Antibiotic Therapies failure by enhancing the risk of infection 7,8 Table 1. Guideline-endorsed Antibiotics from resistant organisms. An incorrect 7,17 diagnosis and poor adherence to therapy in AOM and ABS also contribute to poor treatment outcomes. Agents Primary care physicians refer and ear, nose, and throat (ENT) surgeons operate on First-line Therapy patients with persistent and recurrent infec- Amoxicillin tion.9 Consequently, improved adherence to Amoxicillin/clavulanate diagnostic criteria and appropriate antibiotic selection according to national treatment guidelines may improve the management of Second-line Therapy 6 AOM and ABS. Amoxicillin/clavulanate As discussed in the previous article, treat- Cefdinir ment success and the cost of therapy can be attributed greatly to therapy adherence.10 Cefpodoxime Adherence is influenced by factors such as Ceftriaxone tolerability, patient and caregiver prefer- Cefuroxime ence, dosing regimen/duration of therapy, palatability, and satisfaction with therapy.5,11-16 For example, tolerability and ease of AOM indicates acute otitis media; ABS, acute administration may increase adherence to bacterial sinusitis. prescribed therapy,14 and a shorter duration of therapy (ie, 5 days vs 10 days) is shown to fective against β-lactamase–producing improve therapy adherence.15 To predict the pathogens.19,20 The clinical efficacy of amox- likelihood of treatment success in AOM and icillin is well established, based on trials ABS, it is important to look at components conducted from as long as 30 years ago.17,20 of adherence for agents used to treat these Although amoxicillin is an acceptable conditions. drug for eradicating β-lactamase–negative Haemophilus influenzae, it is no better than Benefits of Judicious Treatment Selection: a placebo against β-lactamase–positive Current Therapies H influenzae.20 The release of the heptava- When selecting an agent for the treatment lent pneumococcal conjugate vaccine of AOM and ABS, the main contributors to (PCV7) in 2000 and its widespread use by favorable outcomes—efficacy and adher- 2004 gradually led to a documented shift in ence—should be examined closely. Judicious the microbiology of persistent/recurrent antibiotic selection should positively affect AOM in the pediatric population (Figure).21,22 the entire healthcare system. This merits This shift likely occurred in ABS because review of the guideline-endorsed antibiotics both diseases involve the same pathogens. (Table 1), the antibiotics not endorsed, and Even adult AOM and ABS likely have experi- the rationale for the distinction between the enced a pathogen shift because of a herd 2 groups of drugs. immunity effect of PCV7. A decrease in PNSP strains from PCV7 vaccine use alluded Guideline-endorsed Antibiotics to H influenzae as the pathogen most likely Amoxicillin. Amoxicillin is the mainstay responsible for AOM and ABS infection. H of treatment for AOM and ABS and is cur- influenzae has also become more resistant rently recommended as first-line therapy to antibiotics over the years by acquiring the in both of these conditions.17,18 Amoxicillin ability to produce β-lactamase. This shift in is effective against Streptococcus pneumo- microbiology allegedly occurring in both niae, including penicillin nonsusceptible S AOM and ABS should be considered when pneumoniae (PNSP) when administered in evaluating the antimicrobial efficacy of off-label high dosages (eg, 80-100 mg/kg amoxicillin. per day in children and 1.5 g twice daily Amoxicillin is well tolerated and has in adults). However, amoxicillin is inef- favorable taste scores in suspension for- VOL. 12, NO. 10, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S293 REPORTS cillin/clavulanate (90/6.4 mg/kg/day) has Figure. Percentage of Total Pathogens Causing shown high bacterial eradication rates for Persistent AOM and AOM Treatment Failure PNSP of 90% and 94% in 2 studies.25,26 Based That Were Streptococcus pneumoniae or on its efficacy, extra-strength amoxi- Haemophilus influenzae in Rochester, NY, cillin/clavulanate is recommended for the 1995-2003 second-line treatment of uncomplicated S pneumoniae AOM, first-line therapy for persistent/recur- H influenzae rent AOM, and first-line treatment for mild, moderate, or severe ABS.7,17,18 60 Tolerability of amoxicillin/clavulanate is problematic. In many head-to-head trials against other AOM and ABS treatments 50 (including cefdinir, cefprozil, and cefurox- s n i ime), the adverse event rate for amoxi- a r t s cillin/clavulanate exceeds that of the f 27-34 o comparator agent. In most of these stud- % 40 ies, gastrointestinal effects (such as diarrhea) are the most frequently reported adverse event of amoxicillin/clavulanate therapy. The data related to amoxicillin/clavu- 30 lanate’s palatability is also not favorable. A 1995-1997 1998-2000 2001-2003 series of 6 randomized, single-blind, Year crossover trials compared the taste and smell of oral antibiotic suspensions in chil- The change in frequency of S pneumoniae isolation was significantly lower (P = .049), and the frequency of H dren. Amoxicillin/clavulanate was consis- influenzae isolations was significantly higher over tently significantly inferior in taste and smell time (P = .021). acceptance compared with cefdinir, another AOM indicates acute otitis media. guideline-endorsed drug in both the single- and multi-center studies.35 mulation for pediatric patients.15 In- terestingly, a recent willingness-to-pay study Cefpodoxime. The third-generation ceph- in AOM patients evaluating compliance alosporin cefpodoxime is one of the recom- (defined as having no missed doses) and mended agents for AOM and ABS. Its adherence (defined as taking medication on efficacy in AOM is demonstrated in non- time) reported that amoxicillin therapy had inferiority trials versus standard-strength the poorest ratings (75% and 59%, compli- amoxicillin/clavulanate, cefaclor, cefixime, ance and adherence, respectively), signifi- and amoxicillin.36-40 In these trials, clinical

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