Antibiotics for CAP: Narrow-Spectrum on the Rise

Abstract

Source: Lipsett SC, Hall M, Ambroggio L, et al. Antibiotic choice and clinical outcomes in ambulatory children with community-acquired pneumonia. J Pediatr. 2021;229:207-215.E1; doi./10.1016/j.jpeds.2020.10.005Investigators from multiple institutions conducted a retrospective cohort study to assess antibiotic-prescribing patterns and clinical outcomes among children diagnosed with community-acquired pneumonia (CAP). Children were eligible if they were 1-18 years old, had an outpatient claim in the MarketScan Medicaid Database from 2010–2016 with a diagnosis of CAP, and had a prescription filled for an oral antibiotic within a day after the index visit. Patient age, visit setting (ED or outpatient clinic), visit during influenza season, asthma history, and presence of chronic conditions were obtained from the Medicaid database.The primary exposure was antibiotic type, categorized as narrow-spectrum (eg, aminopenicillins), broad-spectrum (eg, amoxicillin/clavulanate, cephalosporins), macrolide monotherapy (eg, azithromycin), narrow-spectrum agents in combination with a macrolide, and broad-spectrum agents in combination with a macrolide. The primary outcome was a claim for hospitalization for any reason 2-7 days after the index visit. A secondary outcome was severe pneumonia, defined as ICU admission, a chest drainage procedure, or death occurring 2-7 days after the index visit. Investigators used multivariable logistic regression to assess the odds of each outcome based on antibiotic type adjusted for age, number of chronic conditions, visit setting, visit during influenza seasons, and asthma co-diagnosis during the index visit. A sub-analysis was conducted excluding children with asthma, given the potential benefit of macrolides to them.There were 252,177 children included in analysis. Overall, macrolide monotherapy was prescribed in 43.2%, narrow-spectrum antibiotics in 26.1%, and broad-spectrum antibiotics in 24.7%. Macrolide use decreased over time (45.8% in 2010 to 40.5% in 2016; P <0.001) while narrow-spectrum antibiotic prescribing increased (20.1% in 2010 to 31.8% in 2016; P <0.001).A total of 1,488 children (0.69%) were hospitalized, and 117 (0.05%) developed severe pneumonia. Compared to children who received narrow-spectrum antibiotics, hospitalization was significantly higher among children who received broad-spectrum antibiotics and lower among children who received macrolide monotherapy. The absolute difference in hospitalization rate between children on narrow-spectrum and macrolide monotherapy was small, however (0.6% vs 0.4%, respectively). The odds of developing severe pneumonia were lower in children receiving macrolide monotherapy compared to those who received narrow-spectrum antibiotics, though this difference became statistically insignificant when excluding participants with asthma.The investigators conclude that macrolides are the most commonly prescribed antibiotic for CAP despite national guidelines emphasizing the use of narrow-spectrum antibiotics.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The current investigators assessed adherence to the 2011 clinical practice guideline-recommended antibiotic therapies for children with CAP.1 Amoxicillin is recommended as first-line antibiotic therapy for previously healthy, appropriately immunized infants, preschool children, school-aged children, and adolescents with mild to moderate CAP suspected to be of bacterial origin. Macrolides are recommended primarily for school-aged children and adolescents when an atypical pathogen (eg, Mycoplasma pneumoniae) is suspected.1 Alternative antibiotic recommendations are provided for those with penicillin allergy.Immunization status and penicillin allergy were not assessed in the current study. Focusing on children 1-4 years of age, 34% received amoxicillin. Lack of receipt of age-appropriate immunizations for Streptococcus pneumoniae, the most common bacterial cause of CAP in this age group,1-2 and penicillin allergy probably did not fully account for receipt of antibiotics other than aminopenicillins. About 33% received macrolide monotherapy despite concerns that 20% to 40% of S. pneumoniae isolates are resistant to macrolides3 and atypical pathogens are uncommon causes of CAP in children <5 years.4 Over the study period, there was an 18% increase in narrow-spectrum antibiotic prescribing in the 1-4 years group, but improvement is still needed, especially among children enrolled in Medicaid.Compared to children who received narrow-spectrum antibiotics, hospitalization was significantly higher among children who received broad-spectrum antibiotics, although the absolute difference was small. This finding is not intuitive, and therefore potential explanations need to be considered. Clinicians may have chosen broad-spectrum antibiotics initially for children they believed to be at higher risk of needing later hospitalization. Another point to consider is that certain broad-spectrum antibiotics (eg, second-and third-generation oral cephalosporins) provide adequate activity against only 60% to 70% of isolated strains of S. pneumoniae.1 Hence, they may be less effective than narrow-spectrum, high-dose amoxicillin if the child has CAP due to pneumococcus. The “take home” message was that initial use of broad-spectrum antibiotics did not prevent hospitalizations.Although macrolides are commonly prescribed, most children with CAP improve with narrow-spectrum oral amoxicillin (for outpatients) or IV ampicillin (for inpatients). (See AAP Grand Rounds. 2019;41[6]:65.)5Given the vagaries of diagnosis of pneumonia vs no pneumonia and the lack of definitive identification of a pathogen in the vast majority of cases, it is not surprising that the results of this study do not support current guideline recommendations for management of CAP.