Community-acquired lobar pneumonia in children in the era of universal 7-valent pneumococcal vaccination: a review of clinical presentations and antimicrobial treatment from a Canadian pediatric hospital

Pediatric community-acquired pneumonia (CAP) is a common and potentially serious childhood infection, which often results in hospital admission. The World Health Organization has estimated that in developed countries, one in twenty children under the age of five years will have an episode of pneumonia each year, and 1 to 4 per 1000 children are admitted to hospital annually [1]. S. pneumoniae continues to be the most important pathogen in bacterial pneumonia. The 7-valent pneumococcal conjugate vaccine (Prevnar®, PCV-7) became available in Canada in 2000, and was added to the routine Ontario immunization schedule in January 2005 [2]. Introduction of the pneumococcal vaccine has been shown to decrease all-cause radiologic pneumonia admission rates by an average of 27% in children under the age of 5 years [3‐10].

The diagnostic and therapeutic approach to pneumonia in children is not standardized. The diagnosis of CAP in hospitalized children often relies on a chest radiograph showing consolidation (alveolar infiltrates) or consolidation complicated by effusion. It has been suggested that a radiographic pattern of alveolar infiltrates is most frequently associated with bacterial infection [11]. Available clinical guidelines for empiric treatment of pediatric CAP are largely based on consensus opinion [12‐14] This likely relates to low rates of pathogen identification, the spectrum of severity, and a paucity of randomized controlled trials to guide antimicrobial therapy. Without evidence-based guidelines, antimicrobial treatment of pediatric CAP has been shown to be variable in both inpatient and outpatient settings, with a tendency to overuse broad spectrum antimicrobials [15‐18].

We conducted a retrospective study of healthy children admitted to hospital with CAP (based on presentation of consolidative pneumonia and compatible clinical symptoms) to describe their clinical course and management, in the era of PCV-7 vaccination.

This study is a review of pediatric CAP (diagnosed by consolidation on initial chest radiograph and compatible clinical history) at a pediatric hospital, two years after the introduction of universal PCV-7 pneumococcal vaccination. Previous reviews have had smaller sample size, were less comprehensive, were limited to developing nations, or were completed prior to the introduction of the conjugated seven valent pneumococcal vaccine [10, 23‐25].

Since the diagnosis of CAP is often based on a compatible clinical presentation and a CXR finding of consolidation, we chose these as practical requirements for study inclusion. Our sample selection was an attempt to increase the probability of capturing and evaluating bacterial pneumonias given that consolidation is most frequently associated with bacterial infection [11, 26‐28]. The small sample size of the radiographs that were reviewed by the radiologists likely resulted in the low kappa scores. These values are comparable to published results, and acknowledge the inter-observer variability in interpretation of chest radiographs in the absence of clinical information [11, 28].

This study supports the significant continuing health care burden of children hospitalized with consolidative pneumonia in the era of PCV-7 use. [29] In this cohort, two-thirds of patients had at least one visit to a physician prior to their hospitalization and the average length of hospital stay was 4 days. One quarter of children had 3 or more CXRs, and nearly 20% had an invasive procedure done (chest tube insertion or VATS).

Our study found that patients presenting with effusion were not more likely to be younger, febrile, tachypneic or have a higher WBC count than those without effusion, underscoring the importance of chest radiography in pediatric CAP. Other authors have supported the importance of early radiologic evaluation in differentiating early complicated versus uncomplicated lobar pneumonia [25, 30]. Children with an effusion were more likely to be admitted to the intensive care unit.

Only 9 of the 117 (7.7%) patients had bacterial pathogens identified in blood or pleural fluid. Seven had Streptococcus pneumoniae (6 in blood and 1 in pleural fluid) and 1 child had Group A streptococcus isolated from pleural fluid. The incidence of bacteremia was 6%, which is comparable to a recent study evaluating children with CAP in the Emergency Department [31], but lower than bacteremic rates published previously in the literature [12, 32]. This is likely due to the fact that 42% of children in this cohort had antimicrobials prior to hospital presentation.

PCV-7 has been included in the publicly-funded routine immunization schedule in Ontario since 2005. By parental report, the majority of children had up-to-date vaccination series for age. Six of the seven S. pneumoniae serotypes identified in blood or pleural cultures were not PCV-7 serotypes, but would have been covered by PCV-13 (Prevnar13®), while one of the seven serotypes would have been covered by PCV-10 (Synflorix®).

(4/6 children with PCV-13 vaccine serotypes would have been age-eligible for immunization and therefore had infection potentially preventable with PCV-13.) The only vaccine-preventable serotype (9 V) occurred in a 16-year-old youth who would not have received PCV-7 immunization. The only bacteremic serotype in this cohort not included in the 7, 10 or 13-valent vaccines was 11A.

Current pediatric CAP guidelines and reviews recommend consideration of treatment with intravenous ampicillin or penicillin for hospitalized children, given the evidence for its comparable effectiveness to cefuroxime for more severe pneumonia. [12‐14, 33‐35]. Despite this, less than 5% of children received a penicillin as initial therapy. Only 19% of children with uncomplicated pneumonia received amoxicillin at discharge, and only 2 of the 7 patients with confirmed S. pneumoniae were discharged on amoxicillin. All S. pneumoniae isolates in this study were penicillin susceptible. (CHEO’s 2010 Antibiogram reports a 97% susceptibility of S. pneumoniae to penicillin [36].) Cephalosporins were prescribed in 96% of patients in this cohort rather than narrower-spectrum, less expensive antimicrobial agents, such as penicillin or ampicillin. We acknowledge that prior antimicrobial use may have influenced the physician’s antimicrobial choice on admission. Antimicrobial stewardship intiatives and recently published guidelines aimed at use of ampicillin or penicillin G (as opposed to broader spectrum coverage with second and third generation cephalosporins) may alter prescribing trends in the future.

Guidelines recommend empiric coverage with a macrolide in older children because Mycoplasma pneumoniae is more prevalent in this group [12‐14]. More recent data has shown that Mycoplasma pneumoniae may play a more important role in the younger age group than previously believed [26]. Further studies may alter the current recommendations regarding the use of macrolides in pediatric CAP, however macrolide use should be cautioned in areas where there is significant pneumococcal resistance to macrolides. In this study, macrolides were used frequently in the younger age group - nearly half of children under age 5 years were treated with a macrolide either in hospital or at discharge.

The limitations of the retrospective nature and design of the study did not permit verification of specific immunization status for PCV-7. Microbiological data was also not available for all patients. Our inclusion criteria of consolidative pneumonia would have excluded patients with very early pneumonias that did not have established consolidation on initial CXR. The study results however, are generalizable to healthy children who are hospitalized for consolidative pneumonia in populations where PCV-7 is routinely administered to children.

This study shows the substantial and continued morbidity associated with pneumonia in the era of universal PCV-7 vaccine coverage. Empiric antimicrobial choice is highly variable at this institution, emphasizing the need for clear evidence-based guidelines for the management of pediatric CAP.