Drivers of antibiotic prescribing in children and adolescents with febrile lower respiratory tract infections

Abstract

Background: Knowledge of key drivers for antibiotic prescribing in pediatric lower respiratory tract infection (LRTI) could support rational antibiotic use. Thus, we aimed to determine the impact of clinical and laboratory factors on antibiotic prescribing in children and adolescents with febrile LRTI.

Methods: Pediatric patients from the standard care control group of a randomized controlled trial (ProPAED) investigating procalcitonin guided antibiotic treatment in febrile LRTI were included in a multivariate logistic regression analysis to evaluate the impact of laboratory and clinical factors on antibiotic prescribing.

Results: The standard care control group of the ProPAED study comprised 165 LRTI patients (median age: 2.7 years, range: 0.1-16), out of which 88 (55%) received antibiotic treatment. Factors significantly associated with antibiotic prescribing in patients with complete clinical and laboratory documentation (n = 158) were C-reactive protein (OR 5.8 for a 10-fold increase, 95%CI 2.2-14.9), white blood count beyond age-dependent reference range (OR 3.9, 95%CI 1.4-11.4), body temperature (OR 1.7 for an increase by 1°C, 95%CI 1.02-2.68), and pleuritic pain (OR 2.8, 95%CI 1.1-7.6). Dyspnea (OR 0.3, 95%CI 0.1-0.7) and wheezing (OR 0.3, 95%CI 0.13-0.95) were inversely associated with antibiotic prescribing.

Conclusion: Laboratory markers were strong drivers of antibiotic prescribing in children with febrile lower respiratory tract infections, in spite of their known poor prediction of antibiotic need. Building on current guidelines for antibiotic treatment in children with febrile LRTI, a reliable decision algorithm for safe antibiotic withholding considering the laboratory and clinical factors evaluated in this study has the potential to further reduce antibiotic prescribing.

Fig 1. Associations of laboratory and clinical factors with antibiotic prescribing.

Odds ratio estimates with 95% confidence intervals (95%CI) from univariate and multivariate logistic regression analysis. Open circles and dashed lines: univariate OR and 95%CI; variables are presented in decreasing order of strength of association with antibiotic prescription (p-value, details: see Table 2), grey circles indicate a non-significant association (p-value ≥ 0.05), the OR estimate for pleural rub (OR>>10 with 95%CI ranging from 0-infinity, Table 1) is not illustrated. Black dots and solid lines: multivariate OR with 95%CI of variables remaining after backward deletion of non-significant variables. Vertical line: OR = 1 indicating no association with antibiotic prescription, ORs > 1 indicate an association with increased antibiotic prescription, ORs < 1 indicate an association with reduced antibiotic use. CRP: C-reactive protein. WBC: White blood cell count. Vacc.: Vaccine. RSV: Respiratory syncytial virus. HR: Heart rate. Hib: Haemophilus influenzae type b.

Fig 2. Sensitivities and specificities for associations with antibiotic prescribing.

Illustration of sensitivities and specificities (dots) with 95% confidence intervals (crosses) of each single variable for antibiotic prescription. Left panel: dichotomous variables. Right panel: For continuous variables the range of sensitivities and specificities for all possible thresholds is illustrated (gray receiver operating characteristic curves), as well as the sensitivity and specificity associated with the best threshold estimates. Best threshold estimates (95%CI) were: CRP: 26 (12–55) mg/L, age: 2.1 (1.1–4.8) years, temperature: 38.6 (37.3–38.9) °C, preceding fever: 2.5 (1.5–5.5) days. CRP: C-reactive protein. RSV: Respiratory syncytial virus. WBC: White blood cell count.