Considerations Unique to Pediatrics for Clinical Trial Design in Hospital‐Acquired Pneumonia and Ventilator‐Associated Pneumonia

Abstract

Background. A need exists for new antimicrobial agents to treat neonates, infants, and children for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by nosocomial antibiotic-resistant pathogens. Current and clear guidance on approval of new agents for all pediatric age groups is lacking. Methods. Studies on HAP and VAP in the neonatal and pediatric age groups were collected using PubMed (National Library of Medicine). Published articles were reviewed for pediatric-specific definitions of HAP and VAP, diagnostic techniques, rates of disease, risk factors, characteristics, and outcomes. Results. Definitions of HAP and VAP in neonatal and pediatric age groups vary considerably. No well-studied, sensitive, and specific microbiologic testing techniques exist. Morbidity and mortality associated with VAP in neonates, infants, and children have been documented. Conclusions. Investigation and approval of new agents for HAP and VAP in all pediatric age groups is needed. A uniform definition of HAP and VAP is required that is relevant for clinical trials and balances the risks of experimental therapy and sampling procedures for study patients with potential benefits for both the patient under investigation and the hospitalized children who may develop nosocomial pneumonia.

Health Care-Associated Infections Among Critically Ill Children in the US, 2007–2012

“…Next, some have expressed concern regarding the reliability of the NHSN VAP definition, especially among neonates, which could affect our results. 39,40 Finally, pediatric stepdown units and pediatric cardiac ICUs were excluded from our study because of small numbers, limiting our ability to generalize findings to these settings.…”

Influence of a combination of probiotics on bacterial infections in very low birthweight newborns

“…Late-onset pneumonia in newborns was defined as pneumonia occurring 48 h after admission with characteristic clinical signs and symptoms [5,39].…”

Recommended Design Features of Future Clinical Trials of Antibacterial Agents for Hospital‐Acquired Bacterial Pneumonia and Ventilator‐Associated Bacterial Pneumonia

“…The panel members at the workshop emphasized the need to use adequate and appropriate antibacterial therapy for all patients enrolled in studies of HABP and/or VABP [41, 42, 63, 98]. In general, individual antibacterial agents and specific combinations of agents, as well as dose and duration of therapy, that are recommended by the ATS and IDSA consensus guidelines on the treatment of HABP and/or VABP are appropriate for comparator drugs [40].…”

“…Complexities of pediatric studies of HABP and/or VABP are discussed further in this supplement [98], with an acknowledgment that invasive diagnostic techniques may not be widely used at study enrollment for neonates, infants, and children, requiring some degree of extrapolation of drug exposure and/or efficacy data from adult populations. Collection of adequate safety data for each pediatric age group, from extremely low birth weight premature infants to adolescents, remains an important goal for pediatric investigations.…”