Jeffrey M. Bender

Pneumococcal Necrotizing Pneumonia in Utah: Does Serotype Matter?

BACKGROUND Streptococcus pneumoniae is the most common cause of bacterial pneumonia in children. Despite the use of the 7-valent pneumococcal conjugate vaccine, the incidence of pneumococcal necrotizing pneumonia (PNP) has been increasing. Our objectives were to describe temporal trends in PNP and to evaluate pneumococcal serotypes associated with PNP in Utah. METHODS We performed a retrospective review of all children <18 years of age who were cared for at a tertiary care childrens hospital and who had blood, lung tissue, broncheoalveolar lavage, or pleural fluid cultures that grew S. pneumoniae, as well as radiographic evidence of pneumonia, from January 1997 through March 2006. All S. pneumoniae isolates were typed. RESULTS A total of 124 children with pneumococcal pneumonia were identified, and 33 (27%) of these children had radiographic evidence of PNP. During the period 1997-2000, 5 (13%) of 39 cases of culture-confirmed pneumococcal pneumonia were associated with PNP. In contrast, during the period 2001-2006, 28 (33%) of 85 pneumococcal pneumonia cases were complicated by PNP (odds ratio, 3.34; 95% confidence interval, 1.11-12.03). Non-7-valent pneumococcal conjugate vaccine serotypes comprised 49% of the isolates during 1997-2000 and 88% of isolates during 2001-2006 (odds ratio, 7.89; 95% confidence interval, 2.91-21.90). Pneumonia due to serotype 3 was most often associated with PNP. Eleven (79%) of 14 cases of serotype 3-associated pneumonia were associated with PNP. When compared with all other serotypes, serotype 3 was strongly associated with necrosis (odds ratio, 14.67; 95% confidence interval, 3.39-86.25). CONCLUSIONS PNP is a serious and increasingly common complication of S. pneumoniae pneumonia in Utah. Infection with serotype 3 is associated with an increased risk of developing PNP. The increase in the incidence of infection due to nonvaccine serotypes reported worldwide and the changing epidemiology of invasive pneumococcal disease should be considered when developing vaccine strategies.

Association Between Breast Milk Bacterial Communities and Establishment and Development of the Infant Gut Microbiome

Importance Establishment of the infant microbiome has lifelong implications on health and immunity. Gut microbiota of breastfed compared with nonbreastfed individuals differ during infancy as well as into adulthood. Breast milk contains a diverse population of bacteria, but little is known about the vertical transfer of bacteria from mother to infant by breastfeeding. Objective To determine the association between the maternal breast milk and areolar skin and infant gut bacterial communities. Design, Setting, and Participants In a prospective, longitudinal study, bacterial composition was identified with sequencing of the 16S ribosomal RNA gene in breast milk, areolar skin, and infant stool samples of 107 healthy mother-infant pairs. The study was conducted in Los Angeles, California, and St Petersburg, Florida, between January 1, 2010, and February 28, 2015. Exposures Amount and duration of daily breastfeeding and timing of solid food introduction. Main Outcomes and Measures Bacterial composition in maternal breast milk, areolar skin, and infant stool by sequencing of the 16S ribosomal RNA gene. Results In the 107 healthy mother and infant pairs (median age at the time of specimen collection, 40 days; range, 1-331 days), 52 (43.0%) of the infants were male. Bacterial communities were distinct in milk, areolar skin, and stool, differing in both composition and diversity. The infant gut microbial communities were more closely related to an infant’s mother’s milk and skin compared with a random mother (mean difference in Bray-Curtis distances, 0.012 and 0.014, respectively; P < .001 for both). Source tracking analysis was used to estimate the contribution of the breast milk and areolar skin microbiomes to the infant gut microbiome. During the first 30 days of life, infants who breastfed to obtain 75% or more of their daily milk intake received a mean (SD) of 27.7% (15.2%) of the bacteria from breast milk and 10.3% (6.0%) from areolar skin. Bacterial diversity (Faith phylogenetic diversity, P = .003) and composition changes were associated with the proportion of daily breast milk intake in a dose-dependent manner, even after the introduction of solid foods. Conclusions and Relevance The results of this study indicate that bacteria in mother’s breast milk seed the infant gut, underscoring the importance of breastfeeding in the development of the infant gut microbiome.

Increasing incidence of invasive Haemophilus influenzae disease in adults, Utah, USA.

TOC Summary: The infection disproportionately affected patients >65 years of age.

Parapneumonic empyema deaths during past century, Utah.

Vaccine strategies and antimicrobial drug stockpiling to control empyema will increase preparedness as we prepare for the next influenza pandemic.

Streptococcus pneumoniae-associated hemolytic uremic syndrome among children in North America.

Background: To better characterize Streptococcus pneumoniae-associated hemolytic-uremic syndrome (SP-HUS), we report the largest series of SP-HUS among children in North America. Methods: We surveyed pediatric members of the Emerging Infections Network to identify SP-HUS cases. Respondents contributed clinical and laboratory features of these pediatric cases. Results: A total of 37 cases occurring between 1997 and 2009 were submitted. Of them, 33 cases (89%) were culture-confirmed and 4 (11%) were diagnosed clinically. The median patient age was 2 years, and 28 (76%) patients had completed their heptavalent pneumococcal conjugate vaccination (PCV7) series. Most patients presented with pneumonia (84%) and bacteremia (78%), whereas other clinical manifestations such as pericardial effusion (14%) and meningitis (11%) were less common. Of 29 patients, with bacteremia 6 (21%) had S. pneumoniae concurrently isolated from cerebrospinal fluid or pleural fluid. Severe illness was common with 35 (95%) patients requiring admission to the intensive care unit, over half requiring mechanical ventilation and chest tube placement or video-assisted thoracoscopic surgery, and 27 (73%) requiring dialysis during hospitalization. Among 30 patients with follow-up of 6 months, 7 (23%) remained dialysis dependent, 3 (10%) had undergone renal transplantation, 4 (13%) had neurologic sequelae, and 1 (3%) died. Among 24 serotyped isolates, 96% were non-PCV7 serotypes, most commonly 19A (50%), 92% are included in PCV13, and 10% were penicillin nonsusceptible (minimal inhibitory concentration >2 &mgr;g/mL). Conclusions: North American children with SP-HUS had severe clinical manifestations and significant morbidity. In this series, nearly all cases were caused by serotypes that are not in PCV7 but are included in PCV13.

Influenza virus infection in infants less than three months of age.

Objective: We evaluated the presentation, outcomes, and the risk of serious bacterial infection (SBI) in infants <3 months old with influenza virus infection. Patients and Methods: We identified demographic, hospitalization, and microbiologic data from computerized medical records for all infants and children <24 months of age, with laboratory confirmed influenza infection cared for at a tertiary care childrens hospital during 4 winter seasons (2004–2008). We compared those <3 months of age with older groups. Results: We identified 833 children <24 months of age with laboratory-confirmed influenza. Of those, 218 were <3 months old. Influenza accounted for 3.6% of all evaluations of febrile infants and 12% of febrile infant encounters during winter. Infants <3 months of age were less likely to have a high risk chronic medical condition, but were more likely to be hospitalized than children 3 to <24 months old (P < 0.005). Infants <3 months with influenza had fewer prolonged hospital stays than those 3 to <6 months old [P = 0.056; OR: 0.5 (0.24–1.0)] and 6 to <12 months old [P = 0.011; OR: 0.43 (0.24–0.83)]. Five (2.3%) infants <3 months old had SBI. Conclusions: Infants <3 months of age with influenza virus infection often present with fever alone. Although they are more likely to be hospitalized than those 3 to <24 months old, hospital stays are short and outcomes generally good. Infants with influenza virus infection have a low risk of concomitant SBI.

The Changing Epidemiology of Invasive Pneumococcal Disease at a Tertiary Children's Hospital Through the 7-valent Pneumococcal Conjugate Vaccine Era A Case for Continuous Surveillance

Background: In 2000, a 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among US children. Many sites have since reported changes in invasive pneumococcal disease (IPD). We recognized an opportunity to describe the changes in epidemiology, clinical syndromes, and serotype distribution during a 14-year period including 4 years before vaccine introduction and spanning the entire PCV7 era. Methods: Cases were defined as children <18 years of age who were cared for at Primary Childrens Medical Center for culture-confirmed IPD. We defined the prevaccine period as the time frame spanning from 1997 to 2000 and the postvaccine period from 2001 to 2010. Demographics, clinical data, and outcomes were collected through electronic query and chart review. Streptococcus pneumoniae serotyping was performed using the capsular swelling method. Results: The median age of children with IPD increased from 19 months during the prevaccine period to 27 months during postvaccine period (P = 0.02), with a larger proportion of IPD among children older than 5 years. The proportion of IPD associated with pneumonia increased substantially from 29% to 50% (P < 0.001). This increase was primarily attributable to an increase in complicated pneumonia (17% to 33%, P < 0.001). Nonvaccine serotypes 7F, 19A, 22F, and 3 emerged as the dominant serotypes in the postvaccine period. In children with IPD who were younger than 5 years, for whom vaccine is recommended, 67% of the cases were caused by serotypes in 13-valent PCV during 2005 to 2010. Conclusions: After PCV7 was introduced, significant changes in IPD were noted. One-third of IPD occurred in children older than 5 years, who were outside the age-group for which PCV is recommended. Continued surveillance is warranted to identify further evolution of the epidemiology, clinical syndromes, and serotype distribution of S. pneumoniae after 13-valent PCV licensure.

Epidemiology of Streptococcus pneumoniae-induced hemolytic uremic syndrome in Utah children.

Background: Hemolytic uremic syndrome (HUS) is an uncommon complication of invasive pneumococcal disease (IPD) in children. Few studies examine the Streptococcus pneumoniae serotypes associated with HUS. Our objective was to describe the epidemiology of S. pneumoniae-related HUS (SP-HUS) and the serotypes associated with HUS in Utah children. Methods: We reviewed separate longitudinal databases of HUS and IPD. These included all children <18 years cared for at Primary Childrens Medical Center, Salt Lake City, UT, with IPD from 1997 to 2008 and all children in Utah with HUS since 1971. Results: We identified 435 Utah children with culture-confirmed IPD (1997–2008) and 460 with HUS (1971–2008). There were no reported cases of SP-HUS before 1997. With the introduction of pneumococcal conjugate vaccine (PCV-7) in 2000, the percentage of IPD complicated by SP-HUS has increased from 0.3% to 5.6% (P < 0.001). Pneumonia (P = 0.051) and empyema (P = 0.012) were associated with the development of SP-HUS compared with IPD without SP-HUS. Children with SP-HUS also required ICU care and had longer stays than those with IPD alone. Only serotype 3 appeared associated with SP-HUS (P = 0.067). Conclusions: We identified an increasing incidence of SP-HUS in Utah children. SP-HUS is a serious complication of IPD associated most frequently with pneumonia and empyema because of serotypes not included in the PCV-7, particularly serotype 3.

Invasive Haemophilus influenzae Disease in Utah Children: An 11-Year Population-Based Study in the Era of Conjugate Vaccine

BACKGROUND The incidence of invasive Haemophilus influenzae infection decreased dramatically since the introduction of the H. influenzae serotype b (Hib) conjugate vaccine. H. influenzae invasive disease continues to occur and cause significant morbidity and mortality in children aged <5 years. We aimed to report the epidemiology and serotypes of invasive H. influenzae disease in children from Utah in the post-Hib vaccine era. METHODS We identified all cases of invasive H. influenzae disease, defined as H. influenzae isolated from a sterile site, during the period 1998-2008 among children aged <18 years who were living in Utah. RESULTS We identified 91 cases of invasive H. influenzae disease in children. Children aged <5 years accounted for 78 cases (86%). H. influenzae serotype a (Hia) was the most common serotype (22 cases), representing 28% of all cases of invasive disease among children aged <5 years. The majority (15 cases [93%]) of Hib disease cases occurred among children aged <5 years and accounted for 18% of all cases of H. influenzae invasive disease in this age group. The mean incidence of Hia disease increased from 0.8 cases per 100,000 child-years in 1998 to 2.6 cases per 100,000 child-years in 2008. The incidence of Hib disease among children aged <5 years remained steady at 0.5 cases per 100,000 child-years. Bacteremia accounted for 61% of all cases of invasive disease. One-half (13 of 26) of cases of H. influenzae meningitis were due to Hia. CONCLUSIONS H. influenzae continues to cause invasive disease in Utah children. Hia is the primary cause of the overall increased incidence of invasive H. influenzae disease and leads to disease similar to Hib. Isolated cases of Hib disease demonstrate a continued reservoir. The success of the Hib conjugate vaccine may therefore be vulnerable to vaccine shortages and refusal of vaccination.

Culture-Negative Intracerebral Abscesses in Children and Adolescents from Streptococcus anginosus Group Infection: A Case Series

We report the use of 16S ribosomal RNA gene amplification and sequencing to diagnose culture-negative intracerebral abscesses in younger patients. These 3 cases demonstrate the optimal application of gene sequencing from direct specimens for patients with negative culture results compromised by antibacterial therapy but histories highly suggestive of acute bacterial infection.