Weight-Based Antibiotic Dosing in Osteomyelitis

Abstract

Source: Kyler KE, Lee BR, Glynn EF, et al. Clinical outcome and antibiotic dosing differences by weight in children with acute osteomyelitis. Hosp Pediatr. 2021;11(10):1112-1120; doi:10.1542/hpeds.2021-005890Investigators from multiple institutions conducted a retrospective study to compare outcomes in children with acute hematogenous osteomyelitis (AHO) who had healthy weights or were overweight or obese and evaluate antibiotic dosing variability by weight category. For the study, they abstracted data from the Cerner Health Facts database, which includes diagnostic and procedure codes, demographic information, inpatient medication orders, length of hospital stay (LOS), and anthropometric measurements on patient encounters from 684 health care facilities in the US. Study participants were children 2–17 years old with a primary diagnosis of AHO (based on ICD-9 and ICD-10 codes), hospitalized between 2010 and 2017. Children were categorized as healthy weight (BMI ≥5th and <85th percentile), overweight (BMI ≥85th and <95th percentile), or obese (≥95th percentile). Primary study outcomes included AHO-related procedures and complications occurring within 6 months of the index hospitalization. Rates of these outcomes were compared for patients in different weight categories using chi-square tests. Secondary outcomes included LOS and AHO antibiotic dose, calculated as the mg/kg/day dose for commonly used drugs. Kruskal-Wallis tests were used to compare LOS and antibiotic dose in children in different weight groups.There were 755 children enrolled. The mean age of study patients was 9.4 years, and 66% were male; 455 (60.3%) were classified as healthy weight, 117 (15.5%) were overweight, and 183 (24.2%) were categorized as obese. A total of 99 (13.1%) patients had an AHO-related procedure. The common procedures in all weight categories were surgical debridement and bone abscess drainage. The rates of procedures were higher in children who were obese or overweight than in healthy weight patients (16.9%, 18.8%, and 10.1%, respectively; P = 0.009). Complications occurred in 273 (36.2%) participants, including pyogenic arthritis in 139 (18.4%), myositis in 78 (10.3%), and sepsis in 43 (5.7%). There was no significant difference in rate of complications among children in different weight categories. LOS varied significantly by weight group (median LOS 4.9 days for healthy weight, 5.8 for overweight, and 5.7 for obese patients; P = 0.03). Among the study patients, 330 (50.3%) received clindamycin, 113 (17.2%) vancomycin, 83 (12.6%) cefazolin, and 26 (3.9%) ceftriaxone. Obese children received significantly lower doses by weight than healthy-weight patients for cefazolin (P <0.05), clindamycin (P <0.05), and ceftriaxone (P ≤0.01). There was no significant difference in dose of vancomycin between those who were obese or healthy weight and no significant difference in dose between those who were overweight vs healthy weight for any antibiotic assessed.The authors conclude that obese and overweight children with AHO had longer LOS and more procedures than healthy-weight patients.Dr Winer 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.One of the enduring mantras in pediatrics is “children are not just little adults.” Yet, when learning about medication dosing, pediatricians often learn to check whether the weight-based dosing exceeds the typical adult dosing or the maximum listed. Weight-based dosing has its limitations, with increased volume of distribution and differences in clearance rates noted for younger children.1 Further complexity arises with the knowledge that lipophilic medications, including clindamycin, may need to be dosed differently in obese and overweight patients, with some recommending to use ideal or adjusted body weight for hydrophilic medications and total body weight for lipophilic medications.2The investigators of the current study found significant differences in weight-adjusted daily dosing of antibiotics for AHO. As expected, the biggest differences were in the beta-lactams, which are hydrophilic. There was a small but statistically significant decrease in weight-based clindamycin dosing in obese vs normal-weight children. There were no statistically significant weight-based dosing differences in vancomycin, despite it being a hydrophilic antibiotic and having a narrow therapeutic window. This may represent closer drug-level monitoring in obese children.3It is reassuring to see that although overweight and obese children needed more extensive initial surgical treatment and had longer average LOS, there were no differences in the rate of complications among children in the weight categories. Many of the differences seen may be due to differences in obesity-associated biologic factors and not differences in antibiotic prescribing.Differences exist in weight-based antibiotic dosing between normal-weight, overweight, and obese children with AHO. While overweight and obese children have higher rates of surgical intervention and longer LOS, these differences are not associated with increased complication rates. (See AAP Grand Rounds. 2021;46[5]:57.)4The lack of patient-specific data, such as microbiology results and illness severity, raise the possibility that it may be premature to conclude that complication rates and treatment failure do not differ between weight categories in children with AHO.