Gordon E. Schutze

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.

The Home Environment and Salmonellosis in Children

Objective.  To explore the role of foods and the home environment in the development ofSalmonella infections in infants and children. Methods.  Home investigations were conducted of patients younger than 4 years of age infected with Salmonella. Cultures were obtained from foods, persons residing in the home, animals/pets/insects, and environmental sources. Like serotypes encountered in the index patients and isolates from the home underwent typing with pulsed-field gel electrophoresis. Results.  Home inspections were conducted in ∼66% of eligible homes on the average of 3.4 days after the confirmation of theSalmonella isolate. A total of 526 cultures from 50 homes were obtained from foods (120), household members (73), refrigerators (52), water (47), countertops (46), soil (42), can-openers (36), vacuum cleaners (34), animals/pets/insects (26), and others (50). Isolates with a serotype identical to those in the index patient were found in 16 homes, 3 of which included an isolate of a second serotype, and an isolate of a different serotype was recovered in 3 homes. The pulsed-field gel electrophoresis patterns of the isolates of identical serotypes from the subjects and from their environment were indistinguishable in all but 2 patients. Among isolates of the same serotype encountered in different homes, all patterns were different. The identical serotype was found in multiple locations (4), dirt surrounding front doors (4), household members (3), vacuum cleaner (1), animals/pets/insects (1), and a refrigerator shelf (1). Conclusions.  These data illustrate the importance of the childs environment in the development of salmonellosis. Clinicians should concentrate on educating the parents about the environmental spread of Salmonella. Contaminated foods in the home play a less significant role in the infection of infants and children.

Clostridium difficile Infection in Infants and Children

Infections caused by Clostridium difficile in hospitalized children are increasing. The recent publication of clinical practice guidelines for C difficile infection in adults did not address issues that are specific to children. The purpose of this policy statement is to provide the pediatrician with updated information and recommendations about C difficile infections affecting pediatric patients.

Bartonella henselae as a Cause of Prolonged Fever and Fever of Unknown Origin in Children

A prospective evaluation of 146 children with fever of unknown origin (FUO) and prolonged fever was performed from 1990 to 1996. FUO was defined as a documented daily temperature of > or = 38 degrees C for at least 14 days without diagnostic signs or symptoms. Prolonged fever was defined as fever for at least 14 days and no diagnosis at the time of referral for evaluation. An established diagnosis was made for 84 (57.5%) of 146 patients. The most common infectious disease diagnoses were Epstein-Barr virus infection (22 [15.1%] of 146), osteomyelitis (14 [9.6%] of 146), bartonellosis (7 [4.8%] of 146), and urinary tract infection (6 [4.1%] of 146). Three of seven patients with confirmed Bartonella henselae infection presented with FUO and no ultrasonographic findings compatible with hepatosplenic involvement; two patients presented with FUO and hepatosplenic involvement. The relatively common finding of acute bartonellosis in this population suggests that FUO and prolonged fever in children are other presentations of infection with B. henselae.

Acute Otitis Media Due to Penicillin-Nonsusceptible Streptococcus pneumoniae Before and After the Introduction of the Pneumococcal Conjugate Vaccine

BACKGROUND The impact of the 7-valent pneumococcal conjugate vaccine (PCV7 [Prevnar]) on penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) recovered from children with acute otitis media (AOM) is unclear. METHODS At 5 hospitals, 505 pneumococcal isolates were collected from children with AOM between 1 January 1999 and 31 December 2002. Molecular subtyping was performed on 158 isolates. RESULTS Overall, the percentage of AOM cases due to non-PCV7 serogroups (including serotype 3) increased over time (from 12% in 1999 to 32% in 2002; P < .01) and according to the number of PCV7 doses received (18% [< or = 1 dose] vs. 35% [2-4 doses]; P < .01). The percentage of cases due to vaccine-related serotypes (including serotype 19A) increased according to the number of PCV7 doses received (10% [< or = 1 dose] vs. 19% [2-4 doses]; P = .05) but not over time, whereas the percentage of cases due to serotype 19F remained unchanged both over time and according to the number of PCV7 doses received. The frequency of penicillin nonsusceptibility among PCV7 serotypes (range, 65%-75%) and non-PCV7 serogroups (range, 11%-27%) did not significantly change overall. Although no change was detected among isolates collected from children with spontaneous drainage, the percentage of pneumococci recovered at the time of myringotomy and/or tympanostomy tube placement that were nonresistant to penicillin decreased over time (from 73% in 1999 to 53% in 2002; P = .03). All of the serotype 3 strains were genetically related, whereas 88% of the isolates that were either serotype 19F or serotype 23F were related to 1 of 3 international clones. CONCLUSIONS Among children with AOM, the proportion of cases due to non-PCV7 serogroups increased, vaccine-related serotypes increased, and serotype 19F remained unchanged. Although a decrease in the proportion of cases due to PNSP occurred among children who required myringotomy and/or tympanostomy tube placement, the proportion of PNSP remained unchanged overall and among children with spontaneous drainage. Because future trends in the susceptibility patterns of pneumococcal isolates recovered from children with AOM are not easy to predict, continued surveillance is essential.

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.

Recommendations for Prevention and Control of Influenza in Children, 2012–2013

The purpose of this statement is to update recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. The key points for the upcoming 2012–2013 season are: (1) this year’s trivalent influenza vaccine contains A/California/7/2009 (H1N1)–like antigen (derived from influenza A [H1N1] pdm09 [pH1N1] virus); A/Victoria/361/2011 (H3N2)–like antigen; and B/Wisconsin/1/2010–like antigen (the influenza A [H3N2] and B antigens differ from those contained in the 2010–2011 and 2011–2012 seasonal vaccines); (2) annual universal influenza immunization is indicated; and (3) an updated dosing algorithm for administration of influenza vaccine to children 6 months through 8 years of age has been created. Pediatricians, nurses, and all health care personnel should promote influenza vaccine use and infection control measures. In addition, pediatricians should promptly identify influenza infections to enable rapid treatment, when indicated, to reduce morbidity and mortality.

Strategies for Prevention of Health Care-Associated Infections in the NICU

Health care–associated infections in the NICU result in increased morbidity and mortality, prolonged lengths of stay, and increased medical costs. Neonates are at high risk of acquiring health care–associated infections because of impaired host-defense mechanisms, limited amounts of protective endogenous flora on skin and mucosal surfaces at time of birth, reduced barrier function of their skin, use of invasive procedures and devices, and frequent exposure to broad-spectrum antibiotic agents. This clinical report reviews management and prevention of health care–associated infections in newborn infants.

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.