Tina Q. Tan

Three-Year Multicenter Surveillance of Pneumococcal Meningitis in Children: Clinical Characteristics, and Outcome Related to Penicillin Susceptibility and Dexamethasone Use

Objectives. To evaluate the antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from the blood and cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment, and outcome of children with meningitis caused by S pneumoniae based on antimicrobial susceptibility of isolates and the administration of dexamethasone. Design and Patients. Children with pneumococcal meningitis were identified from among a group of patients with systemic infections caused by S pneumoniae who were enrolled prospectively in the United States Pediatric Multicenter Pneumococcal Surveillance Study at eight childrens hospitals in the United States. From September 1, 1993 to August 31, 1996, 180 children with 181 episodes of pneumococcal meningitis were identified and data were collected by retrospective chart review. Outcome. Clinical and laboratory characteristics were assessed. All pneumococcal isolates were serotyped and antibiotic susceptibilities for penicillin and ceftriaxone were determined. Clinical presentation, hospital course, and outcome parameters at discharge were compared between children infected with penicillin-susceptible isolates and those with nonsusceptible isolates and for children who did and did not receive dexamethasone. Results. Fourteen (7.7%) of 180 children died; none of the fatalities were because of a documented failure of treatment caused by a resistant strain. Only 1 child, who had mastoiditis and a lymphangioma, experienced a bacteriologic failure with a penicillin-resistant (minimum inhibitory concentration = 2 μg/mL) organism. Of the 166 surviving children, 41 (25%) developed neurologic sequelae (motor deficits) and 48 (32%) of 151 children had unilateral (n = 26) or bilateral (n = 22) moderate to severe hearing loss at discharge. Overall, 12.7% and 6.6% of the pneumococcal isolates were intermediate and resistant to penicillin and 4.4% and 2.8% were intermediate and resistant to ceftriaxone, respectively. Clinical presentation, cerebrospinal fluid indices on admission, and hospital course, morbidity, and mortality rates were similar for patients infected with penicillin- or ceftriaxone-susceptible versus nonsusceptible organisms. However, the relatively small numbers of nonsusceptible isolates and the inclusion of vancomycin in the treatment regimen for the majority of the patients limit the power of this study to detect significant differences in outcome between patients infected with susceptible and nonsusceptible isolates. Nonetheless, our results show that the nonsusceptible organisms do not seem to be intrinsically more virulent. Forty children (22%) received dexamethasone (≥8 doses) initiated before or within 1 hour after the first dose of antibiotics. The incidence of any moderate or severe hearing loss was significantly higher in the dexamethasone group (46%) compared with children not receiving any dexamethasone (23%). The incidence of any neurologic deficits, including hearing loss, also was significantly higher in the dexamethasone group (55% vs 33%). However, children in the dexamethasone group more frequently required intubation and mechanical ventilation and had lower initial concentration of glucose in the cerebrospinal fluid than children who did not receive any dexamethasone. When we controlled for the confounding factor, severity of illness (intubation), the incidence of any deafness and of any neurologic sequelae, including deafness, were no longer significantly different between children who did or did not receive dexamethasone. Conclusions. Children with pneumococcal meningitis caused by penicillin- or ceftriaxone-nonsusceptible organisms and those infected by susceptible strains had similar clinical presentation and outcome. The use of dexamethasone was not associated with a beneficial effect in this retrospective and nonrandomized study. Only a well-designed, prospective, randomized, placebo-controlled study, conducted in centers where optimal supportive care can be provided, will determine the potential benefit, if any, of dexamethasone in patients with pneumococcal meningitis.

Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection

Palivizumab was licensed in June 1998 by the Food and Drug Administration for the reduction of serious lower respiratory tract infection caused by respiratory syncytial virus (RSV) in children at increased risk of severe disease. Since that time, the American Academy of Pediatrics has updated its guidance for the use of palivizumab 4 times as additional data became available to provide a better understanding of infants and young children at greatest risk of hospitalization attributable to RSV infection. The updated recommendations in this policy statement reflect new information regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effect of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates. This policy statement updates and replaces the recommendations found in the 2012 Red Book.

Early Trends for Invasive Pneumococcal Infections in Children After the Introduction of the 13-valent Pneumococcal Conjugate Vaccine

Background: The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced for routine administration to infants and children in 2010 in the United States. We have monitored clinical and microbiologic features of invasive pneumococcal infections among children before and after PCV13 use. Methods: Infants and children cared for at 8 children hospitals in the United States with culture-proven invasive infections caused by S. pneumoniae were identified in an ongoing prospective surveillance study. Demographic and clinical data were recorded on a standard case report form. Serotype and antimicrobial susceptibilities of isolates were determined. Results: Since routine PCV13 immunization in 2010, invasive pneumococcal infections decreased 42% overall and 53% for children <24 months of age in 2011 compared with the average number of cases for 2007 to 2009. PCV13 serotype isolates decreased 57% during these same time periods; 19A, 7F and 3 decreased by 58%, 54% and 68%, respectively. The number of infections caused by serotypes 1 and 6C also decreased in 2011. The most common non-PCV13 serotypes encountered in 2010 and 2011 combined were 33F, 22F, 12, 15B, 15C, 23A and 11. Bacteremia, pneumonia and mastoiditis cases decreased more than meningitis cases. Conclusions: After the introduction of PCV13, invasive pneumococcal infections decreased among 8 children hospitals compared with the 3 years before PCV13 use. Slight increases in some non-PCV13 serotype isolates were noted in 2011. Continued surveillance is necessary to determine the effectiveness of PCV13 including herd protection as well as any emerging invasive serotypes.

Serotype 19A Is the Most Common Serotype Causing Invasive Pneumococcal Infections in Children

OBJECTIVE: The purpose of this study was to monitor the clinical and microbiologic features of invasive infections caused by Streptococcus pneumoniae among children before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). DESIGN: We conducted a 15-year prospective surveillance study of all invasive pneumococcal infections in children. The sample included infants and children at 8 childrens hospitals in the United States with culture-proven invasive S pneumoniae infections. RESULTS: Since the implementation of routine PCV7 immunization in 2000, invasive infections have decreased yearly from 2001 through 2004, to a nadir of 151 infections; the rate then increased from 2005 through 2008. Compared with the pre-PCV7 era, a greater proportion of children with invasive pneumococcal infection had an underlying condition in the post-PCV7 period. Compared with the total number of annual admissions, the number of 19A isolates increased significantly from 2001 to 2008 (P < .00001). In 2007 and 2008, only 16 isolates (4%) were vaccine serotypes; 19A accounted for 46% (168 of 369) of the non-PCV7 serotypes. Thirty percent of the 19A isolates were multidrug resistant. Serotypes 1, 3, and 7F accounted for 22% of the non-PCV7 serotypes. Among children with invasive pneumococcal infections, the likelihood of a 19A serotype increased with the number of preceding PCV7 doses. CONCLUSIONS: Since 2005, the number of invasive pneumococcal infections in children has increased at 8 childrens hospitals, primarily as a result of serotype 19A isolates, one third of which were resistant to multiple antibiotics in 2007 and 2008. Continued surveillance is necessary to detect emerging serotypes after the planned introduction of 13-valent or other pneumococcal vaccines.

New Pertussis Vaccination Strategies beyond Infancy: Recommendations by the Global Pertussis Initiative

BACKGROUND The Global Pertussis Initiative, an expert scientific forum, was established to address the ongoing problems associated with pertussis disease worldwide. METHODS The group analyzed pertussis disease trends, developed recommendations to improve disease control through expanded vaccination strategies, and proposed solutions to barriers to implementation and support of research activities. RESULTS Bordetella pertussis infection is endemic and continues to be a serious problem among unvaccinated or incompletely vaccinated infants. In addition, the reported incidence of pertussis disease is increasing in adolescents and adults, who not only experience a considerable health burden themselves but also infect vulnerable infants. CONCLUSIONS Current vaccination strategies need to be reinforced. Expanded vaccination should include adding booster doses to existing childhood schedules (preschool or adolescent) and booster doses for those specific adult subgroups that have the highest risk of transmitting B. pertussis infection to infants (i.e., new parents, other contacts of newborns, and health care workers). More epidemiological studies and studies of disease transmission and the cost-effectiveness of vaccination would be valuable, and surveillance, diagnostic improvements, and educational campaigns are needed for implementation. However, as a prelude to universal adult vaccination, immediate universal adolescent vaccination should be instituted in countries in which it is economically feasible.

Six year multicenter surveillance of invasive pneumococcal infections in children.

OBJECTIVE Monitor clinical and microbiologic features including antimicrobial susceptibility of invasive pneumococcal infections among children. DESIGN A 6-year (September, 1993, through August, 1999) prospective surveillance study of all invasive pneumococcal infections in children. PATIENTS Infants and children cared for at eight childrens hospitals in the United States with culture-proved invasive pneumococcal infection. RESULTS During the 6-year period 2581 episodes of invasive pneumococcal infection occurred in 2498 children. Underlying conditions were present in 29% of the children. Of children without an underlying condition, 15% of the total infections occurred in those 25 to 60 months old. As the ages of the children advanced the proportion of cases classified as bacteremia declined, whereas the proportion classified as pneumonia increased. Also, as the ages of the children increased the proportion of isolates in serotypes/serogroups 1, 3 and 23 increased. whereas the proportion for serotype 14 diminished. During the 6 years of the study, there was a significant increase in the percentage of isolates intermediate or resistant to penicillin (P < 0.000001) or intermediate to ceftriaxone (P < 0.002). By the sixth year of the study, 37 and 11% of the isolates were nonsusceptible to penicillin or ceftriaxone, respectively. Antibiotic use in the 30 days before diagnosis of systemic pneumococcal infection occurred in 30 to 35% of the children for each of the 6 years. The overall case-fatality rate for children with systemic pneumococcal infection was 1.56%. Mortality was greatest in children >60 months old and in those with underlying conditions; mortality was not related to antibiotic susceptibility. CONCLUSIONS The percentage of pneumococcal isolates recovered from children with systemic infection which were intermediate for penicillin or ceftriaxone or resistant to penicillin increased steadily during the 6-year period. There was also a trend toward increasing rates of resistance to ceftriaxone. The age and serogroup/serotype distributions of our patients support the recommendations to consider administration of the seven valent pneumococcal conjugate vaccine for all children 24 to 59 months old, with special consideration for selected groups.

Clinical Definitions of Pertussis: Summary of a Global Pertussis Initiative Roundtable Meeting, February 2011

Existing clinical case definitions of pertussis are decades old and based largely on clinical presentation in infants and children, yet an increasing burden is borne by adolescents and adults who may manifest distinct signs/symptoms. Therefore, a “one-size-fits-all” clinical case definition is no longer appropriate. Seeking to improve pertussis diagnosis, the Global Pertussis Initiative (GPI) developed an algorithm that delineates the signs/symptoms of pertussis most common to 3 age groups: 0–3 months, 4 months to 9 years, and ≥10 years. These case definitions are based on clinical presentation alone, but do include recommendations on laboratory diagnostics. Until pertussis can be accurately diagnosed, its burden will remain underestimated, making the introduction of epidemiologically appropriate preventive strategies difficult. The proposed definitions are intended to be widely applicable and to encourage the expanded use of laboratory diagnostics. Determination of their utility and their sensitivity and/or specificity versus existing case definitions is required.

Antibiotic therapy and acute outcome of meningitis due to Streptococcus pneumoniae considered intermediately susceptible to broad-spectrum cephalosporins.

Children with meningitis due to Streptococcus pneumoniae isolates that are relatively or fully resistant to penicillin and have decreased susceptibility to broad-spectrum cephalosporins (MIC, > or = 2.0 micrograms/ml) who have failed treatment with broad-spectrum cephalosporins have been reported. The National Committee for Clinical Laboratory Standards has newly revised guidelines indicating that S. pneumoniae isolates associated with meningitis for which the MICs are > or = 0.5 micrograms/ml should be considered resistant to broad-spectrum cephalosporins. This recommendation is not clearly based on data related to clinical outcome and may be too conservative. We present data on five children who had S. pneumoniae meningitis due to isolates that were relatively or fully resistant to penicillin (MIC range, 0.125 to 4.0 micrograms/ml) and had cefotaxime or ceftriaxone MICs of 0.50 to 2.0 micrograms/ml. Their clinical courses and outcomes were comparable to those of five children with S. pneumoniae meningitis due to strains that were relatively or fully resistant to penicillin and were inhibited by cefotaxime at concentrations of < or = 0.25 micrograms/ml, as well as to those of 25 patients with S. pneumoniae meningitis due to penicillin-susceptible isolates identified during the same period. Children with meningitis due to S. pneumoniae with cefotaxime or ceftriaxone MICs of < or = 1.0 micrograms/ml may be adequately treated with these antibiotics. Further clinical data are required before solid recommendations can be made regarding cephalosporin breakpoints for S. pneumoniae.

Potential strategies to reduce the burden of pertussis.

Pertussis continues to be a significant cause of morbidity and mortality among nonimmunized young infants. Although the inception of childhood pertussis immunization programs has significantly reduced the occurrence of the disease in children, waning vaccine-induced immunity permits the disease to affect adolescents and adults, who in turn transmit the disease to unimmunized or incompletely immunized infants. The Global Pertussis Initiative brought together experts from 17 countries around the world to evaluate strategies to improve disease control. Seven strategies were considered: (1) universal adult immunization; (2) selective immunization of mothers and close family contacts of newborns; (3) selective immunization of health care workers; (4) selective immunization of child care workers; (5) universal immunization of adolescents; (6) preschool booster at 4–6 years of age; and (7) reinforcement and/or improvement of current infant and toddler immunization strategies. Because immunization programs vary widely from country to country, no single strategy is likely to be appropriate for all. Moreover it would be helpful to have additional data to support the strategies and provide a better understanding of the disease so that new approaches can be monitored effectively. However, certain steps can be taken now to reduce the incidence of pertussis.

Invasive pneumococcal infections in children with asplenia.

Background. Asplenia is associated with an increased risk of infections caused by Streptococcus pneumoniae. Overwhelming infection can be fulminate and lead to a fatal outcome. Objective. To review the epidemiology and clinical course of invasive S. pneumoniae infections in children with asplenia before the release of the conjugate pneumococcal vaccine. Methods. Children with S. pneumoniae infections from eight children’s hospitals in the US were identified prospectively from September, 1993, to August, 1999. Further demographic, medical and microbiologic information was gathered retrospectively from the charts of patients with asplenia. Results. Twenty-two asplenic patients with 26 episodes of invasive S. pneumoniae were identified. This represents 1% of the 2581 episodes of invasive S. pneumoniae infections identified in our study. Twelve had congenital asplenia (CA), and 10 had undergone surgical splenectomy. Nine of the patients with CA had associated complex congenital heart disease. The median age at first infection was 12.5 months for CA patients as compared with 69 months in children with surgical splenectomy (P < 0.001). Seventy-five percent of those eligible had received the polysaccharide pneumococcal vaccine. The most common serotypes isolated were 6B (8), 23F (7), 18C (2) and 19A (2). Antimicrobial prophylaxis had been prescribed for 82% of the study cohort. Clinical presentations of the 26 episodes included fever (22), shock (7), petechiae or purpura (7), disseminated intravascular coagulation (5) and respiratory distress (5). Clinical illness included bacteremia alone (12), meningitis alone (8), bacteremia with otitis media-sinusitis (3), bacteremia with pneumonia (2) and meningitis with osteomyelitis (1). Five of the 6 patients who died had meningitis. Three of the survivors (19%) had significant morbidity, and all of them had meningitis. Two patients had 2 episodes each, and 1 patient had 3 episodes. All but 1 of the multiple episodes was with a different serotype. Forty-six percent of isolates were nonsusceptible to penicillin, and 19% were nonsusceptible to ceftriaxone. There was no association between antimicrobial resistance and mortality. Conclusions. Invasive pneumococcal disease in patients with asplenia has a high mortality, especially in those with meningitis. Even though the new conjugate vaccine might increase protection, 19% of patients had disease caused by serotypes not included in the current heptavalent vaccine. Clinicians should continue to be aggressive in evaluating asplenic patients with unexplained fevers.