Approaches to Reduce Use and Duration of Anti-MRSA Agents for Antimicrobial Stewardship Programs: A Review of Recent Literature.

Antimicrobial stewardship programs (ASPs) have the potential to effectively deescalate unnecessary methicillin-resistant Staphylococcus aureus (MRSA) coverage. This review summarizes literature published from 2014 through 2021 describing contemporary ASP methods and their resulting effectiveness at reducing anti-MRSA agent use (ie vancomycin, linezolid, daptomycin, ceftaroline, and clindamycin). This review of the literature examined the following strategies, which had reports of success in either decreasing the use or duration of anti-MRSA agents: prospective review and feedback, antibiotic timeouts, health system or department protocol changes, polymerase chain reaction (PCR) and rapid testing of patient samples. Most of the current literature continue to support most ASP interventions including antibiotic timeouts, pathways, and molecular testing including MRSA nasal PCRs and rapid diagnostic testing can be successful at reducing unnecessary anti-MRSA use.

Contemporary Treatment of Resistant Gram-Negative Infections in Pediatric Patients.

Gram-negative resistance is increasing in serious infections, including in children. There are many mechanisms of resistance, most commonly beta-lactamases. The most concerning beta-lactamases are AmpC, extended spectrum beta-lactamases, and carbapenemases. Efflux pumps and porins are also important in Pseudomonas infections. For some mechanisms of resistance, dose adjustment of antibiotics may help to overcome resistance and effectively treat infections. Therefore, it is important to consider pediatric pharmacokinetic differences when dosing antibiotics to ensure adequate concentrations are reached and maintained. These considerations important for older antibiotics and newer agents.

Impact of Direct From Blood Culture Identification of Pathogens Paired With Antimicrobial Stewardship Interventions in a Pediatric Hospital.

OBJECTIVE: Identification of organisms directly from positive blood culture by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has the potential for improved clinical outcomes through earlier organism identification and shorter time to appropriate clinical intervention. The uses of this technology in pediatric patients and its impact in this patient population have not been well described. METHODS: Direct from positive blood culture organism identification via MALDI-TOF was implemented in September 2019. A quality improvement project was performed to assess its impact on admissions for contaminant blood cultures and time to effective and optimal antimicrobials and clinical decision-making. A pre- and post-implementation retrospective review for consecutive September through February time periods, was conducted on patients with positive monomicrobial blood cultures. Statistics were evaluated using Mann-Whitney U and χ2 tests. RESULTS: One hundred nineteen patients with 131 unique blood cultures (65 in pre- and 66 in post-implementation) were identified. Time to identification was shorter, median 35.4 hours (IQR, 22.7-54.3) versus 42.3 hours (IQR, 36.5-49) in post- and pre-groups, respectively (p = 0.02). Patients were less likely to be admitted for a contaminated blood culture in the post-implementation, 26% versus 11% in the pre-implementation (p = 0.03) group. In patients treated for bacteremia, there was a shorter time to optimal therapy from Gram stain reporting in the post-implementation (median 42.7 hours [IQR, 27.2-72]) versus pre-implementation (median 60.8 hours [IQR, 42.9-80.6]) (p = 0.03). CONCLUSIONS: Direct from positive blood culture identification by MALDI-TOF decreased time to effective and optimal antimicrobials and decreased unnecessary admission in pediatric patients for contaminated blood cultures.

Comparing Vancomycin Area Under the Curve With a Pharmacist Protocol that Incorporates Trough and Maximum Doses at a Children's Hospital.

OBJECTIVE: Updated vancomycin guidelines suggest dose adjustment based on area under the curve in a 24-hour period (AUC24). This study aims to determine whether a pharmacist managed vancomycin protocol that incorporates maximum dosing paired with trough monitoring can achieve appropriate vancomycin AUC24 exposures. METHODS: A retrospective review was performed evaluating vancomycin usage from October 2018 through September 2019 at a children's hospital. Patients with less than 4 doses or lack a trough concentration were excluded. Vancomycin AUC24 were estimated using 2 calculations: 1) the Le method, incorporating age and serum creatinine, and 2) the trapezoidal method based upon population data and patient-specific trough. Target AUC24 ranges were assessed. AUC24 goals were 400 to 600 mg·hr/L, but due to known variations between calculations, a variance of 20 mg·hr/L was allowed for each end of the goal. Secondary analyses included evaluations of efficacy and toxicity. RESULTS: Two-hundred twenty-three patients were included. Initial doses were estimated to meet AUC24 goals in only 63%. After trough-based dose modification, 81% achieved a therapeutic AUC24. Using the trapezoidal method, therapeutic concentrations were found in 51% of patients based on the initial dose and 77% after dose modification. Only 6.3% of patients had kidney injury with only 1 of those patients having any calculated AUC24 > 600 mg·hr/L and none above 620 mg·hr/L. No clinical failures were identified. CONCLUSIONS: Increased initial dosing in infants and children is needed to result in AUC24 exposures recommended in the guidelines. Maximum dosing paired with trough monitoring may be an alternative to AUC24 monitoring in areas that are unable to perform AUC24 calculations. Prospective data are needed to validate these conclusions.

Advancing pediatric antimicrobial stewardship: Has pharmacodynamic dosing for gram-negative infections taken effect?

Objective: To characterize pharmacodynamic dosing strategies used at children's hospitals using a national survey. Design: Survey. Setting: Children's hospitals. Participants: Volunteer sample of antimicrobial stewardship program (ASP) respondents. Methods: A nationwide survey was conducted to gain greater insight into the current adoption of nontraditional dosing methods and monitoring of select ß-lactam and fluoroquinolone antibiotics used to treat serious gram-negative infections in pediatric populations. The survey was performed through the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative. Results: Of the 75 children's hospitals that responded, 68% of programs reported adoption of pharmacodynamically optimized dosing using prolonged ß-lactam infusions and 35% using continuous ß-lactam infusions, although use was infrequent. Factors including routine MIC monitoring and formal postgraduate training and board certification of ASP pharmacists were associated with increased utilization of pharmacodynamic dosing. In addition, 60% of programs reported using pharmacodynamically optimized ciprofloxacin and 14% reported using pharmacodynamically optimized levofloxacin. Only 20% of programs monitored ß-lactam levels; they commonly cited lack of published guidance, practitioner experience, and laboratomory support as reasons for lack of utilization. Less physician time dedicated to ASP programs was associated with lower adoption of optimized dosing. Conclusions: Use of pharmacodynamic dosing through prolonged and continuous infusions of ß-lactams have not yet been routinely adopted at children's hospitals. Further guidance from trials and literature are needed to continue to guide pediatric pharmacodynamic dosing efforts. Children's hospitals should utilize these data to compare practices and to prioritize further research and education efforts.

Multidisciplinary Guidance Regarding the Use of Immunomodulatory Therapies for Acute Coronavirus Disease 2019 in Pediatric Patients.

BACKGROUND: Immune-mediated lung injury and systemic hyperinflammation are characteristic of severe and critical coronavirus disease 2019 (COVID-19) in adults. Although the majority of severe acute respiratory syndrome coronavirus 2 infections in pediatric populations result in minimal or mild COVID-19 in the acute phase of infection, a small subset of children develop severe and even critical disease in this phase with concomitant inflammation that may benefit from immunomodulation. Therefore, guidance is needed regarding immunomodulatory therapies in the setting of acute pediatric COVID-19. This document does not provide guidance regarding the recently emergent multisystem inflammatory syndrome in children (MIS-C). METHODS: A multidisciplinary panel of pediatric subspecialty physicians and pharmacists with expertise in infectious diseases, rheumatology, hematology/oncology, and critical care medicine was convened. Guidance statements were developed based on best available evidence and expert opinion. RESULTS: The panel devised a framework for considering the use of immunomodulatory therapy based on an assessment of clinical disease severity and degree of multiorgan involvement combined with evidence of hyperinflammation. Additionally, the known rationale for consideration of each immunomodulatory approach and the associated risks and benefits was summarized. CONCLUSIONS: Immunomodulatory therapy is not recommended for the majority of pediatric patients, who typically develop mild or moderate COVID-19. For children with severe or critical illness, the use of immunomodulatory agents may be beneficial. The risks and benefits of such therapies are variable and should be evaluated on a case-by-case basis with input from appropriate specialty services. When available, the panel strongly favors immunomodulatory agent use within the context of clinical trials. The framework presented herein offers an approach to decision-making regarding immunomodulatory therapy for severe or critical pediatric COVID-19 and is informed by currently available data, while awaiting results of placebo-controlled randomized clinical trials.

Applying Pharmacodynamics and Antimicrobial Stewardship to Pediatric Preseptal and Orbital Cellulitis.

Orbital and preseptal cellulitis are most commonly caused by organisms that originate in the upper respiratory tract or from the skin. There is significant variation in antibiotics used, but ampicillin-sulbactam, ceftriaxone, metronidazole, clindamycin, amoxicillin, amoxicillin-clavulanate, cefuroxime, and vancomycin are often used in the treatment of these infections. The choice of antibiotic, however, is only one consideration. It is also important that antibiotics are dosed to optimize their pharmacodynamic target attainment. Like other serious infections, therapy can be transitioned from initial intravenous therapy to an oral regimen when there are clear signs of clinical and laboratory improvement. The total duration of therapy for these infections have also been decreasing in recent years with durations of approximately 2 weeks becoming more common, even for orbital or subperiosteal infections. Antimicrobial stewardship programs can work closely with providers who manage these infections to create pathways, choose optimal antibiotics and dosage, transition from intravenous to oral therapy, and provide shortest effective durations.

Position Paper: Pharmacists and Childhood Vaccines.

Vaccination rates of children in the United States remain below the target coverage levels identified in the Healthy People 2020 objectives. Given the success of pharmacists in providing adult vaccinations and the accessibility of pharmacists to the public, expanding pharmacists' authority to vaccinate children may improve vaccination rates of children, particularly in key disease states. This article serves as a Position Statement of the Pediatric Pharmacy Advocacy Group (PPAG), who supports the expansion of pharmacists' authority to vaccinate children. PPAG also believes that increased use of state vaccination registries by pharmacists will help improve communication and documentation of vaccines between providers. PPAG also recommends that continued education and maintaining current knowledge of vaccines and vaccine schedules are vital for pharmacist immunizers. Finally, PPAG believes that pharmacists should be advocates for childhood vaccinations.

Management of Pediatric Acute Hematogenous Osteomyelitis, Part II: A Focus on Methicillin-Resistant Staphylococcus aureus, Current and Emerging Therapies.

Methicillin-resistant Staphylococcus aureus (MRSA) has become the most prevalent cause of acute hematogenous osteomyelitis (AHO) in pediatric patients. This increase in MRSA is due to the rise in community-acquired MRSA. Therefore, it is important that clinicians are aware of the various and upcoming therapies that cover this bacterium. A literature search of the Medline database was performed from creation through January 2018. Articles chosen for the review emphasize well-established MRSA treatment options for pediatric AHO, newer therapies on the horizon, and important pharmacokinetics and pharmacodynamic concepts for treatment. Traditional therapies, including vancomycin and clindamycin, remain effective for the treatment of pediatric AHO. When these agents cannot be used, evidence in AHO has been growing for daptomycin, linezolid, and ceftaroline. Further initial pediatric data with the long-acting lipoglycopeptides show promise and in the future may provide a role in AHO treatment in children.

Management of Pediatric Acute Hematogenous Osteomyelitis, Part I: Antimicrobial Stewardship Approach and Review of Therapies for Methicillin-Susceptible Staphylococcus aureus, Streptococcus pyogenes, and Kingella kingae.

Acute hematogenous osteomyelitis (AHO), often occurring in young children, is the most frequently diagnosed type of osteomyelitis in pediatric patients. Optimizing antibiotics is essential as delays to receipt of appropriate therapy can lead to chronic osteomyelitis, as well as impairments in bone growth and development. Antimicrobial stewardship programs (ASPs) are in a key position to help improve the care of patients with AHO as they contain a pharmacist with expertise in antibiotic drug selection, optimization of dosing, and microbiologic test review. A literature search of the MEDLINE database was conducted from initiation through January 2018. Articles selected for the review focus on pathogen identification, pharmacokinetics and pharmacodynamics, efficacy and safety in children, transition from intravenous to oral therapy, duration of treatment, and antimicrobial stewardship interventions. This review will highlight the potential roles ASPs can have in improving the management of AHO in pediatric patients. These roles include the creation of clinical pathways, improving testing algorithms, antibiotic choice and dosing, intravenous to oral transitions, duration of treatment, and therapy monitoring. Overall, patients are most effectively treated by focusing treatments on age, presentation, local sensitivities, and directed therapy with pathogen identification.

Ceftazidime/Avibactam and Ceftolozane/Tazobactam: Novel Therapy for Multidrug Resistant Gram Negative Infections in Children.

The rise in Multidrug-resistant (MDR) infections has become a significant problem in both the developing countries and in the United States (U.S.). Specifically, MDR gram-negative infections are emerging, affecting not only adults but children as well. The specific gram-negative organisms that have been most concerning within the pediatric population include MDR P. aeruginosa, Enterobacteriaceae, and Acinetobacter spp. The increase in antimicrobial resistance rates is associated with various mechanisms with one of the most common being the production of beta-lactamases. Both Ceftazidime/Avibactam (CZA) and Ceftolozane/Tazobactam (C/T) are two recently approved antibiotics in the U.S. While both of these agents are inhibitors of beta-lactamase enzymes, there are differences between them that are important to understand. At this time, the data in children for these agents are extremely limited. The aim of this review is to describe the characteristics of these agents and their potential uses in pediatric patients.

Evaluation of a Second-Sign Process for Antimicrobial Prior Authorization.

BACKGROUND: A second-sign prospective restriction of select broad-spectrum antimicrobials was fully implemented in January 2015 as a pediatric antimicrobial stewardship program (ASP) initiative to help ensure the most appropriate empiric use of ceftaroline, cefepime, fidaxomicin, linezolid, and vancomycin (intravenous). The objective of this evaluation is to assess the effectiveness of a forced second-sign process in the electronic medical record as a pediatric ASP strategy. We anticipated that the second-sign process for antibiotics would increase the appropriateness of empiric antibiotic use, as defined by preapproved criteria, clinical pathways, national guidelines, and pediatric-specific infectious diseases reference texts, while not causing significant delay in the initial administration of antibiotic therapy. METHODS: This was a retrospective before and after intervention chart review conducted from July 2014 to June 2015. The study was conducted at a 187-bed, freestanding teaching children's hospital that included the following: level-1 pediatric trauma center, 18-bed pediatric intensive care unit, and 32-bed neonatal intensive care unit. RESULTS: A total of 1178 orders were identified, and 389 met inclusion criteria. The vast majority of second-sign orders were for vancomycin (92%), 61% were written for males, and the median age was 6 years old. Appropriateness of second-sign restricted antibiotic use significantly increased after second-sign implementation (84.5% to 92.9%, P = .01). The secondary outcome of time from initial order entry to medication administration was not different between the before and after groups (median time, 184.5 [interquartile range, 110.25-280.75] vs 174 [interquartile range, 104-228] minutes; P = .342). CONCLUSIONS: The use of a second-sign approval process for antimicrobial restriction can lead to increased appropriateness of antibiotic use at a pediatric hospital, without causing a delay in administration.

A Dual Case of Peritonitis and Central Nervous System Infection Caused by Nutritionally Variant Streptococcal Species.

Nutritional variant streptococci (NVS) are difficult to identify bacteria that can cause invasive infections such as endocarditis and meningitis. NVS as a cause of peritonitis has not been routinely described. This case of NVS as the etiology of peritonitis associated with previous neurosurgery and ventriculoperitoneal (VP) shunt revision demonstrates its potential role as a significant pathogen in patients with peritonitis and VP shunts. Therapy consists of vancomycin plus a second agent but since there are no standards for susceptibility testing, clinical response remains the standard for determining the efficacy of treatment. When there is central nervous system (CNS) involvement it is important to include drugs with appropriate CNS penetration.

Pharmacodynamically Guided Levofloxacin Dosing for Pediatric Community-Acquired Pneumonia.

BACKGROUND.: Oral levofloxacin is recommended as a preferred treatment for infection with Streptococcus pneumoniae with a penicillin minimum inhibitory concentration (MIC) of ≥4 µg/mL and as an alternative for infection with S pneumoniae with a penicillin MIC of ≤2 µg/mL. To investigate the current dosing recommendations and create a pharmacodynamically guided regimen, a Monte Carlo simulation was performed. METHODS.: The simulation included a previously published 1-compartment model, and incorporated a formula that takes into account age-appropriate weights for hospitalized patients. Three different dosing regimens, including community-acquired pneumonia guideline dosing, inhalational anthrax dosing, and a pharmacodynamically guided regimen, were assessed. The probability of target attainment was described as the proportion of patients who achieve an unbound-drug area under the concentration-time curve over 24 hours divided by the MIC above 33.7 µg/mL per hour. Microbiologic data from 2 stand-alone pediatric tertiary care centers were included. RESULTS.: Guideline-recommended doses of levofloxacin seem to produce suboptimal exposure in patients aged 5-14 years for pneumococci with an MIC of 1 µg/mL. Anthrax dosing was suboptimal in patients aged <5 years and in those aged >15 years. The pharmacodynamically guided regimen maintained a probability of target attainment of >90% for all age groups without producing peak concentrations higher than those previously described. None of the regimens attained the pharmacodynamic targets for a levofloxacin MIC of 2 µg/mL. CONCLUSIONS.: Current dosing recommendations were found to be suboptimal for specific age groups. A pharmacodynamically guided levofloxacin dosing regimen was determined, but it will need to be studied clinically for safety and tolerability.

Management of Pneumonia in the Pediatric Critical Care Unit: An Area for Antimicrobial Stewardship.

BACKGROUND: Pediatric pneumonia is one of the most common causes of childhood infection requiring hospitalization and is a substantial driver of antimicrobial use among hospitalized children. About 12-20% of pediatric patients hospitalized with community-acquired pneumonia (CAP) require critical care. Additionally, nosocomial pneumonias (i.e. hospital-acquired and ventilator- associated pneumonias) are responsible for 15-53% of hospital-associated infections and are the most common indication for empiric antibiotics in the pediatric intensive care unit. OBJECTIVE: Respiratory infections, especially pneumonias, are a strong area for antimicrobial stewardship program (ASP) interventions, as they have been shown to improve patient outcomes while reducing inappropriate antimicrobial use, antimicrobial resistance, and overall costs. METHOD: Optimizing the selection of appropriate antimicrobial therapies is difficult for pediatric pneumonias because of the ill-defined definitive diagnostic criteria and difficulty differentiating between viral and bacterial etiology. RESULT: The aim of this review is to highlight the role of antimicrobial stewardship efforts in the treatment of pneumonias in critically ill children by discussing the emerging role of diagnostic criteria, the etiology of disease, appropriate targeted antimicrobial selection, and the optimization of antibiotic dosing and pharmacodynamic targets.

Making a Case for Pediatric Antimicrobial Stewardship Programs.

Although antimicrobials are commonly used in children, it is important to remember that they can have a profound impact on this unique patient population. Inadvertent consequences of antiinfective use in children include antimicrobial resistance, infection caused by Clostridium difficile, increased risk of obesity, and adverse drug events. In addition, compared with adults, children have different dosing requirements, antimicrobial formulation needs, pharmacokinetics, and antimicrobial susceptibility profiles. Therefore, pediatric-specific antimicrobial stewardship efforts are needed to promote appropriate use of antimicrobials in children. The primary purposes of this review article are to provide a rationale behind pediatric-focused antimicrobial stewardship and to describe currently available evidence regarding the initiatives of pediatric antimicrobial stewardship programs (ASPs). A literature search of the Medline database was performed (from inception through March 2015). The studies included in this review focus on antimicrobial stewardship interventions in inpatient pediatric settings. Ten inpatient studies involving pediatric-focused antimicrobial stewardship interventions were identified from the published literature. Four studies used the core strategy of prospective audit with feedback; two used prior approval. The remaining four used supplemental antimicrobial stewardship strategies (guidelines, clinical pathways, and computerized decision support tools). In general, the interventions resulted in decreased antimicrobial use, reduced antimicrobial costs, and fewer prescribing errors. Children have unique medical needs related to antimicrobials and deserve focused ASP efforts. The literature regarding pediatric antimicrobial stewardship interventions is limited, but published interventions may serve as paradigms for developing pediatric ASPs as demonstrated by the general success of these interventions.

Role of tipranavir in treatment of patients with multidrug-resistant HIV.

The worldwide emergence of multidrug-resistant human immunodeficiency virus (HIV)-1 strains has the driven the development of new antiretroviral (ARV) agents. Over the past 5 years, HIV-entry and integrase inhibitor ARVs, as well as improved non-nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), have become available for treatment. It is important to assess how these new ARVs might be most judiciously used, paying close attention to viral susceptibility patterns, pharmacodynamic parameters, and the likelihood that patients will adhere to their therapy. Herein we review published material in Medline, EMBASE, and ISI for each antiretroviral agent/classes currently approved and summarize the available data on their efficacy, safety, and pharmacologic parameters. We focus on the role of tipranavir, a recently approved nonpeptidic PI, for treating HIV-infected children, adolescents, and adults with a history of multidrug-resistant HIV.

Recombinant human growth hormone in the treatment of patients with cystic fibrosis.

CONTEXT: Recombinant human growth hormone (rhGH) improves growth in patients with growth hormone deficiency or idiopathic short stature. Its role in patients with cystic fibrosis (CF) is unclear. OBJECTIVE: To review the effectiveness of rhGH in the treatment of patients with CF. METHODS: Medline and the Cochrane Central Register of Controlled Trials were searched from the earliest date through April 2010. Randomized controlled trials, observational studies, systematic reviews/meta-analyses, or case reports were included if rhGH therapy was administered to patients with CF and data on prespecified harms, intermediate outcomes, or final health outcomes were reported. When applicable, end points were pooled by using a random-effects model. The overall body of evidence was graded for each outcome as insufficient, low, moderate, or high. RESULTS: Ten unique controlled trials (n = 312) and 8 observational studies (n = 58) were included. On quantitative synthesis of controlled trials, several markers of pulmonary function, anthropometrics, and bone mineralization were significantly improved versus control. Results of single-arm observational studies for the aforementioned outcomes were generally supportive of findings in clinical trials. There is insufficient evidence to determine the effect of rhGH on intravenous antibiotic use during therapy, pulmonary exacerbations, health-related quality-of-life, bone consequences, or total mortality, but moderate evidence suggests that rhGH therapy reduces the rate of hospitalization versus control. CONCLUSIONS: rhGH improved almost all intermediate measures of pulmonary function, height, and weight in patients with CF. Improvements in bone mineral content are also promising. However, with the exception of hospitalizations, the benefits on final health outcomes cannot be directly determined at this time.

Increased clinical failures when treating acute otitis media with macrolides: a meta-analysis.

BACKGROUND: Macrolide antibiotics are often used to treat children with acute otitis media (AOM); however, the 2004 American Academy of Pediatrics (AAP) and American Academy of Family Physicians guidelines recommend against their use in patients without history of a type I allergic reaction to penicillins. OBJECTIVE: To evaluate via meta-analysis the comparative efficacy of amoxicillin or amoxicillin/clavulanate to that of macrolide antibiotics in the treatment of children with AOM. METHODS: A systematic literature search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts was conducted from the earliest available date through September 2008. We used the following MeSH and key words: amoxicillin, amoxicillin/clavulanate, Augmentin, azithromycin, ceftriaxone, clarithromycin, macrolides, AND media, otitis media, and effusion. Included studies were randomized, blinded, and controlled trials evaluating guideline-recommended antibiotics (amoxicillin or amoxicillin/clavulanate) compared to macrolide antibiotics (azithromycin or clarithromycin) in AOM in children. The primary outcome assessed was clinical failure measured between days 10 and 16 after starting antibiotic therapy. Results are reported as relative risks (RRs) with 95% confidence intervals and were calculated using a random-effects model. RESULTS: A total of 10 trials (N = 2766) evaluating children 6 months-15 years old were included in the meta-analysis. Upon meta-analysis, the use of macrolide antibiotics was associated with an increased risk of clinical failure (RR 1.31 [95% CI 1.07 to 1.60]; p = 0.008) corresponding to a number needed to harm of 32. Upon safety analysis, rates of any adverse reaction (RR 0.74 [95% CI 0.60 to 0.90]; p = 0.003) and diarrhea (RR 0.41 [95% CI 0.32 to 0.52]; p < 0.0001) were significantly lower in the macrolide group. CONCLUSIONS: The meta-analysis suggests that patients treated with macrolides for AOM may be more likely to have clinical failures. As such, it supports the current AAP AOM recommendation that macrolides be reserved for patients who can not receive amoxicillin or amoxicillin/clavulanate.