Bacterial Community Pneumonia and Its Treatment in Children

Community Pneumonia in the Pediatric Population

The annual incidence of community-acquired pneumonia (CAP) in Europe is approximately 15 cases per 10,000 children over age 5 and about 25–35 cases in children under 5, depending on data collection methodology. The highest incidence of CAP is recorded in the population under 2 years of age [1]. CAP is a major cause of mortality worldwide in children under 5.

In most hospitalized children, the disease is caused by a viral infection, with a smaller proportion of cases being bacterial in origin. While in adults, the primary pathogen causing CAP is Streptococcus pneumoniae, the bacterial etiology in children is slightly different. In newborns, the main pathogens are group B streptococci and gram-negative enterobacteria acquired from the mother during birth. S. pneumoniae, Haemophilus influenzae, S. pyogenes, Staphylococcus aureus, and Moraxella catarrhalis are gaining importance in subsequent periods. In children over 5 years old, atypical pathogens such as Mycoplasma pneumoniae and Chlamydophila pneumoniae also play a role.

Therapeutic Options

Antibiotic treatment in children with CAP usually starts empirically. The chosen regimen should have good activity against the most likely causative pathogens without unnecessary broad-spectrum effects to avoid the development of resistant strains. Whenever possible, therapy should be guided rationally based on the results of cultures and sensitivity tests [2], especially considering the rise in penicillin-resistant strains of S. pneumoniae over the last three decades. These strains also show lower sensitivity to most other beta-lactam antibiotics.

Specific clinical recommendations for treatment vary by country. In the Czech Republic, amoxicillin is recommended as the first-line therapy for CAP in children. In cases of suspected atypical pneumonia or penicillin hypersensitivity, clarithromycin, and sometimes spiramycin, is used. Doxycycline also has good efficacy for atypical infections, but its use in the pediatric population must be carefully considered due to dental side effects (tooth discoloration, enamel hypoplasia). It should only be used in children under 8 in severe and life-threatening infections. Between ages 8 and 12, tooth enamel issues are rare but doxycycline should still be reserved for cases where other antibiotics are unlikely to be effective or are contraindicated. For moderate CAP with suspected atypical pneumonia, a combination of amoxicillin and doxycycline is used (for children under 40kg, clarithromycin or spiramycin is preferred with amoxicillin) [3].

Given the potential challenges of treating CAP in children, including infections with penicillin-resistant or ceftriaxone-resistant S. pneumoniae strains or complicated polymicrobial infections, alternatives effective against a broad spectrum of potential pathogens should be considered.

Ceftaroline Fosamil in the Pediatric Population

Ceftaroline fosamil is an intravenous cephalosporin with broad-spectrum activity against both gram-positive and gram-negative pathogens, including methicillin-resistant S. aureus and multidrug-resistant strains of S. pneumoniae. In the EU, it is indicated for the treatment of community-acquired pneumonia and complicated skin and soft tissue infections in children from birth [4]. In phase II/III–IV clinical trials, it demonstrated comparable clinical efficacy to standard treatment in children aged from 2 months to 18 years, with a safety profile consistent with studies conducted in adults [5, 6] and typical of cephalosporins. Its safety in newborns and infants aged 7–60 days was confirmed in a phase II clinical study in children with late-onset sepsis [7].

Conclusion

Available evidence suggests that ceftaroline fosamil could be beneficial in the hospital treatment of CAP in the pediatric population. Data from ongoing clinical studies and observations from routine clinical practice will further refine our understanding of this antibiotic's efficacy and safety profile in pediatric patients.

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Sources:
1. Senstad A. C., Surén P., Brauteset L. et al. Community-acquired pneumonia (CAP) in children in Oslo, Norway. Acta Paediatr 2009; 98 (2): 332−336, doi: 10.1111/j.1651-2227.2008.01088.x.
2. Esposito S., Carrothers T. J., Riccobene T. et al. Ceftaroline fosamil for treatment of pediatric complicated skin and soft tissue infections and community-acquired pneumonia. Paediatr Drugs 2021; 23 (6): 615, doi: 10.1007/s40272-021-00474-y.
3. Žemličková H., Nyč O., Prokeš M. et al. Komunitní pneumonie. Doporučení. SZÚ, 2022. Available at: www.antibiotickarezistence.cz/clanky_odbornici/komunitni-pneumonie
4. SPC Zinforo. Available at: www.ema.europa.eu/en/documents/product-information/zinforo-epar-product-information_cs.pdf
5. Cannavino C. R., Nemeth A., Korczowski B. et al. A randomized, prospective study of pediatric patients with community-acquired pneumonia treated with ceftaroline versus ceftriaxone. Pediatr Infect Dis J 2016; 35 (7): 752−759, doi: 10.1097/INF.0000000000001159.
6. Blumer J. L., Ghonghadze T., Cannavino C. et al. A multicenter, randomized, observer-blinded, active-controlled study evaluating the safety and effectiveness of ceftaroline compared with ceftriaxone plus vancomycin in pediatric patients with complicated community-acquired bacterial pneumonia. Pediatr Infect Dis J 2016; 35 (7): 760−766, doi: 10.1097/INF.0000000000001160.
7. Bradley J. S., Stone G. G., Chan P. L. S. et al. Phase 2 study of the safety, pharmacokinetics and efficacy of ceftaroline fosamil in neonates and very young infants with late-onset sepsis. Pediatr Infect Dis J 2020; 39 (5): 411−418, doi: 10.1097/INF.0000000000002607.