Adenovirus as a Potential Bacterial Mimicker in Hospitalized Children: Clinical Phenotype, Inflammatory Response and Antibiotic Prescribing in a Two-Year Cohort from Southern Italy

Background: Adenovirus infection in children is frequently accompanied by marked systemic inflammation that may overlap with laboratory features traditionally associated with bacterial infection, potentially contributing to antibiotic prescribing. We aimed to characterize the clinical and inflammatory phenotype of hospitalized pediatric adenovirus infection and to investigate the association between inflammatory markers and antibiotic prescribing. Methods: We conducted a retrospective observational study of 111 consecutive children hospitalized with polymerase chain reaction (PCR)-confirmed adenovirus infection between 10 February 2024 and 31 December 2025. Clinical characteristics were described in a detailed 2025 subcohort (n = 60). The 2025 adenovirus cohort was compared with a contemporaneous cohort of children hospitalized with other PCR-confirmed respiratory viral infections (n = 93) and with a previously published Italian cohort (n = 100). Multivariable logistic regression analyses were performed to identify factors independently associated with overall and parenteral antibiotic therapy. Results: The overall cohort had a median age of 22 months (interquartile range [IQR], 14.0–35.5), a median CRP concentration of 63.0 mg/L (IQR, 32.8–117.4), and an antibiotic prescribing rate of 52.3%. Compared with children hospitalized for other respiratory viral infections, those with adenovirus exhibited significantly higher white blood cell counts, absolute neutrophil counts, and CRP concentrations (all p ≤ 0.006), whereas overall antibiotic prescribing was similar (48.3% vs. 51.6%; p = 0.690). Increasing CRP concentrations were independently associated with antibiotic therapy: for each doubling of CRP + 1, the adjusted odds of receiving any antibiotic increased by 58% (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.23–2.03; p < 0.001), whereas the odds of receiving parenteral antibiotic therapy increased by 43% (aOR, 1.43; 95% CI, 1.13–1.82; p = 0.003). After adjustment for CRP concentration, age, and sex, adenovirus detection was associated with lower odds of receiving any antibiotic therapy compared with other respiratory viral infections (aOR, 0.31; 95% CI, 0.13–0.75; p = 0.010), whereas no statistically significant association was observed with parenteral antibiotic therapy. Conclusions: Hospitalized children with adenovirus detection exhibited a pronounced inflammatory response compared with children hospitalized with other respiratory viral infections, despite less frequent oxygen therapy and a shorter median hospital stay. Higher CRP concentrations were associated with increased adjusted odds of antibiotic prescribing, whereas adenovirus detection was associated with lower adjusted odds of receiving any antibiotic therapy. These findings underscore the importance of interpreting inflammatory biomarkers within the broader clinical context and support careful antimicrobial prescribing without compromising vigilance for bacterial infection.