Ex vivo peripheral blood mononuclear cell response to R848 in children after supplementation with the probiotic Lactobacillus acidophilus NCFM/Bifidobacterium lactis Bi-07.

Several studies have demonstrated a decrease in upper respiratory infection (URI) frequency and severity in subjects taking probiotic supplements. We hypothesised beneficial effects of probiotics on viral URI in children are due to modulation of inflammatory innate immune responses. We tested this hypothesis, providing children with a probiotic combination of Lactobacillus acidophilus/Bidfidobacterium animalis ssp. lactis Bi-07 (NCFM/Bi-07) and measuring levels of cytokines in response to stimulation of peripheral blood mononuclear cells (PBMCs) to toll-like receptor (TLR) 7/8 agonist resiquimod (R848). In this open label study, 21 (2 dropouts) children received probiotic containing 5×109 cfu each of NCFM/(Bi-07) daily for 30 days. Whole blood was taken from each subject at study entry and 30 days for culture of PBMCs. PBMCs stimulated with resiquimod (R848) or unstimulated were incubated and a panel of immune markers was measured. There was a significant decrease in the net (stimulated-null) level of myeloid progenitor inhibitory factor 1 (MPIF-1) (mean decrease 0.1 ng/ml, 95% confidence interval 0.01-0.24, P=0.032) following probiotic supplementation. The change in immune marker levels after supplementation, when analysed together with respect to expected inflammatory/anti-inflammatory effects, was increased for interleukin (IL)-10 and decreased for MPIF-1, IL-8, interferon gamma induced protein 10, macrophage inflammatory protein 3 alpha (MIP-3α) and E-selectin (P=0.01). Adverse events were mild. In conclusion, supplementation with this probiotic combination was safe and resulted in significant modulation of PBMC limited immune response to TLR7/8 agonist R848 and in levels of MPIF-1 and MIP-3α. The anti-inflammatory effect may be one mechanism by which probiotics modulate the immune system however further study is needed.

Parental perception of children's weight in a paediatric primary care setting.

OBJECTIVE: To determine how parents of overweight children perceived their children's weight status compared with actual body mass index (BMI). METHODS: This descriptive, cross-sectional study assessed parental perception of and concern about weight, diet and physical activity of 3-12-year-olds. BMI values >or=85th and <95th percentile and >or=95th percentile were considered at risk for overweight and overweight respectively. Differences between groups were tested with chi-squared analyses or Fishers exact test as appropriate and further explored using logistic regression analysis. RESULTS: Questionnaires were completed at 612 health maintenance visits (278 girls). Overall, 15% of both boys and girls were at risk for overweight and 22% of boys and 24% of girls were overweight. Forty-nine per cent of parents recognized their overweight children as overweight. Perceptions were more often correct for parents of girls than boys (63% versus 36%, P < 0.001) and for older compared with younger children (61.7% versus 17.5%, P < 0.001). CONCLUSIONS: Parents of overweight children frequently did not perceive their children as exceeding healthy weight standards. Targeting parental perception as a point of intervention is necessary.

Short term oral cefixime therapy for treatment of bacterial conjunctivitis.

BACKGROUND: There have been few controlled studies evaluating treatment of bacterial conjunctivitis beyond the newborn period. Topical therapy of bacterial conjunctivitis achieves a clinical cure but does not prevent acute otitis media (AOM). OBJECTIVES: The aim of this study was to compare systemic antibiotic therapy (cefixime) with topical therapy with polymyxin-bacitracin for treatment of acute bacterial conjunctivitis with regard to clinical and bacteriologic cure and prevention of AOM. METHODS: This study was a randomized, double blind, placebo-controlled trial of polymyxin-bacitracin ointment and oral placebo vs. topical placebo and oral cefixime in children with presumed acute bacterial conjunctivitis. Topical therapy was administered for 7 days; oral therapy was administered for 3 days. Bacterial cultures were obtained at entry and on Day 3 of treatment. Children were examined on Days 3 and 10 or if they worsened within 15 days of entry. RESULTS: Eighty children were enrolled in the study. Bacterial cultures of the conjunctiva were positive in 70% of children: Haemophilus influenzae (53.7%); Streptococcus pneumoniae (13.8%); H. influenzae and S. pneumoniae (1.2%); and Moraxella catarrhalis (1.3%). There were 7 (17.5%) bacteriologic failures among children receiving topical antibiotic and oral placebo and 15 (37.5%) bacteriologic failures among children receiving topical placebo and oral cefixime (P = 0.07 with Yates correction). There was no difference between study groups with regard to either clinical cure or the development of AOM. Nine children (11%), 5 who received active topical therapy and 4 who received active oral drug, developed AOM either during or within 15 days of study entry. CONCLUSION: Cefixime was not more effective than topical polymyxin-bacitracin in either the eradication of conjunctival colonization with respiratory pathogens or the prevention of AOM in children with acute bacterial conjunctivitis.

Enhanced urinalysis improves identification of febrile infants ages 60 days and younger at low risk for serious bacterial illness.

OBJECTIVE: Investigators have sought to establish "low-risk" criteria to identify febrile young infants who can be observed safely without antibiotics. Previous studies have used criteria for standard urinalysis to identify suspected urinary tract infection; however, cases of urinary tract infection have been missed. Enhanced urinalysis, using hemocytometer cell count and Gram stain performed on uncentrifuged urine, has been shown to have greater sensitivity and negative predictive value than standard urinalysis. The objective of this study was to evaluate the ability of criteria that incorporate enhanced urinalysis to identify febrile young infants who are at low risk for serious bacterial illness (SBI). METHODS: Institutional guidelines were established in 1999 to evaluate in a retrospective cohort study infants who were /=38.0 degrees C. "Low-risk" criteria included 1) well appearance without focal infection (excluding otitis media); 2) no history of prematurity, illness, or previous antibiotics; 3) peripheral white blood cell count (WBC) between 5 and 15 000/mm(3); 4) absolute band count

Pneumococcal infections in children after transplantation.

Bacterial infections in recipients of bone marrow and solid-organ transplants remain a major cause of morbidity and death. The cases of 42 children who had undergone transplantation and developed an infection with Streptococcus pneumoniae were retrospectively reviewed. Thirty-four patients had 1 episode of infection, whereas 7 had 2 episodes and 1 had 3 episodes of infection. Solid-organ recipients were more likely to have recurrent invasive disease (P<.02). A total of 31 (74%) of 42 patients were on immunosuppressive therapy, and 74% had been on antimicrobial therapy within 30 days before diagnosis of S. pneumoniae infection. Only 33% of eligible patients had received a pneumococcal vaccine. Twenty-six percent of isolates recovered were not susceptible to penicillin, and 18% were not susceptible to ceftriaxone. Two patients experienced infection-related deaths; one of these had a penicillin-nonsusceptible isolate. The antimicrobial susceptibilities and outcome of infections with S. pneumoniae in patients who have undergone transplantation are similar to those in the general pediatric population.

Outcome of invasive infections outside the central nervous system caused by Streptococcus pneumoniae isolates nonsusceptible to ceftriazone in children treated with beta-lactam antibiotics.

OBJECTIVE: To determine the outcome of children treated primarily with beta-lactam antibiotics for a systemic infection outside the central nervous system (CNS) caused by isolates of Streptococcus pneumoniae nonsusceptible to ceftriaxone (MIC > or = 1.0 microg/ml). DESIGN: Retrospective review of the medical records of children identified prospectively with invasive infections outside of the CNS caused by isolates of S. pneumoniae that were not susceptible to ceftriaxone between September, 1993, and August, 1999. A subset of this group treated primarily with beta-lactam antibiotics was analyzed for outcome. PATIENTS: Infants and children with pneumococcal infections cared for at eight children's hospitals. RESULTS: Among 2,100 patients with invasive infections outside the CNS caused by S. pneumoniae, 166 had isolates not susceptible to ceftriaxone. One hundred patients treated primarily with beta-lactam antibiotics were identified. From this group 71 and 14 children had bacteremia alone or with pneumonia, respectively, caused by strains with an MIC of 1.0 microg/ml. Bacteremia or pneumonia caused by isolates with a ceftriaxone MIC > or = 2.0 microg/ml occurred in 6 and 5 children, respectively. Three children with septic arthritis and 1 with cellulitis had infections caused by strains with an MIC to ceftriaxone of 1.0 microg/ml. Most were treated with parenteral ceftriaxone, cefotaxime or cefuroxime for one or more doses followed by an oral antibiotic. All but one child were successfully treated. The failure occurred in a child with severe combined immune deficiency and bacteremia (MIC = 1.0 microg/ml) who remained febrile after a single dose of ceftriaxone followed by 12 days of cefprozil. CONCLUSION: Ceftriaxone, cefotaxime or cefuroxime are adequate to treat invasive infections outside the CNS caused by pneumococcal isolates with MICs up to 2.0 microg/ml, a concentration currently considered resistant for these antibiotics by National Committee for Clinical Laboratory Standards breakpoints.

Convalescent phase outpatient parenteral antiinfective therapy for children with complicated appendicitis.

BACKGROUND: Children with a perforated or gangrenous appendix become clinically stable after medical and/or surgical therapy but often remain in the hospital solely to complete parenteral antibiotic therapy. This prospective study investigates the outcomes when children who meet specified criteria are discharged to complete parenteral antibiotic therapy at home. METHODS: Children age 1 to 17 years with appendicitis complicated by generalized peritonitis or intraabdominal abscess were eligible to participate. Subjects whose fever was decreasing, who were able to tolerate oral liquids and for whom further parenteral antibiotic therapy was deemed necessary were discharged from the hospital to receive outpatient parenteral antiinfective therapy (OPAT) with meropenem. Therapy was administered by a family member and supervised by home care nurses. Study personnel visited the home daily to collect data on adverse events, compliance and resource utilization. Pa tients served as their own controls in models of reduced hospitalization and net cost savings. RESULTS: Discharged on average on the fourth postoperative day, 87 children received 4.5 +/- 2.1 days of OPAT. Six (7%) children were subsequently readmitted for complications including bowel obstruction (4 children), intraabdominal abscess (1 child) and pleural effusion (1 child). Another child developed a viral syndrome during OPAT. All other patients recovered uneventfully. Six (7%) children discontinued meropenem prematurely because of rash (4 patients) or diarrhea (2 patients). According to models in which each day of OPAT replaced a day of inpatient care, discharge to OPAT reduced hospitalization by 42 +/- 15% and saved a median of $2908 (10th to 90th percentile range, $1,077 to $4,707) per patient. CONCLUSION: Convalescent phase OPAT is a cost-effective alternative to continued hospitalization for children with complicated appendicitis who are clinically stable yet require further parenteral antibiotic therapy.

Acute otitis media caused by Streptococcus pneumoniae in children's hospitals between 1994 and 1997.

OBJECTIVE: To determine patterns of resistance for isolates of Streptococcus pneumoniae recovered from middle ear fluids of children from eight children's hospitals between September, 1994, and August, 1997. METHODS: Data were extracted retrospectively from the medical records of eight children's hospitals. A standardized data form was completed for each episode of pneumococcal infection. Systemic isolates (blood and pleural, synovial and spinal fluids) of S. pneumoniae were collected during the same period. All isolates of S. pneumoniae from each center were sent to a central laboratory. Susceptibility to penicillin and ceftriaxone was determined by microbroth dilution. Organisms were considered nonsusceptible to penicillin if the minimum inhibitory concentration was > or = 0.1 microg/ml and nonsusceptible to ceftriaxone if the minimum inhibitory concentration was > or = 1.0 microg/ml. RESULTS: S. pneumoniae was recovered from the middle ear fluids of 707 children from all centers during the study period. Thirty-nine (5.5%) were infections recorded at 4 centers which evaluated middle ear fluid only sporadically and were not included in this analysis. The remaining 668 infections reported by the 4 remaining participating hospitals reflect the experience of 608 children. There were 54% boys; 440 (73%) were Caucasian, 111 (18%) were African-American, 38 (6%) were Hispanic and for 19 (3%) the race was not recorded. The children ranged in age from 16 days to 13.8 years with a mean (+/-sD) of 26.0 (+/- 26.1) months. Children who received antibiotics in the 30 days before the middle ear isolate was recovered were more likely to harbor a resistant strain of S. pneumoniae than children who had not recently received an antibiotic (P < 0.001). Isolates recovered from children with spontaneous otorrhea were more likely to be susceptible to penicillin than isolates recovered during myringotomy, with or without the insertion of tympanostomy tubes (P < 0.01). There was wide variation in the susceptibility of middle ear isolates to penicillin and ceftriaxone according to geographic location; however, in every locale the middle ear isolates were less likely to be susceptible to penicillin and ceftriaxone than systemic isolates of S. pneumoniae. CONCLUSION: The prevalence of penicillin-resistant and cephalosporin-resistant S. pneumoniae in middle ear isolates derived from children cared for at four different children's hospitals was quite variable. In some locations the prevalence of resistance is still increasing, whereas in other areas the rate of resistance was at a plateau during the period of surveillance. The prevalence of isolates of S. pneumoniae susceptible to penicillin and ceftriaxone was always less common among middle ear isolates than among systemic isolates. Previous antibiotic use remains the most predictive factor for the recovery of isolates resistant to penicillin and ceftriaxone.

Bacterial meningitis in childhood at the Children's Hospital of Pittsburgh: 1988-1998.

Bacterial meningitis is an important acute infectious disease of childhood that remains a source of substantial morbidity and mortality. The impact of the Haemophilus influenzae type b (HIB) conjugate vaccines on the epidemiology of the other bacterial causes of meningitis in childhood has received little attention. The objective of this study is to report the experience at a tertiary-care children's hospital with the occurrence of bacterial meningitis before and after the licensure of the HIB conjugate vaccine. With use of International Classification of Diseases diagnostic codes for bacterial meningitis, a list of all children admitted to Children's Hospital of Pittsburgh with a primary or secondary diagnosis of meningitis due to H. influenzae, Streptococcus pneumoniae, and Neisseria meningitidis from January 1, 1988, to December 31, 1998, was constructed. Medical records were examined for basic patient demographic information including age, gender, race, bacterial etiology of meningitis, receipt of vaccine for HIB, underlying conditions, and fatalities. Two hundred twenty-one cases of bacterial meningitis caused by H. influenzae, N. meningitidis, and S. pneumoniae were identified. The age of infected children ranged from 1 month to 18 years, with a mean and median age of 38.1 months and 13 months, respectively. Fifty-two percent of the children were female, 83% were Caucasian and 16% were African-American. Before the routine use of HIB conjugate vaccine, HIB was the bacterial species responsible for the greatest proportion of cases (average of 58%/year). The absolute number of cases of bacterial meningitis attributable to HIB declined after 1991 to an average of 2.5 cases/year. The number of cases of meningitis caused by S. pneumoniae and N. meningitidis have remained relatively stable between 1988 and 1998. The case fatality rates for children with meningitis caused by H. influenzae, S. pneumoniae, and N. meningitidis were 0.0%, 9.2%, and 7.5%, respectively. Most cases of meningitis due to HIB occurred in children who had not been immunized. Three children who received the polysaccharide vaccine developed meningitis due to HIB; there were no failures of the conjugate vaccine.

Pneumococcal facial cellulitis in children.

OBJECTIVE: To review the epidemiology and clinical course of facial cellulitis attributable to Streptococcus pneumoniae in children. DESIGN: Cases were reviewed retrospectively at 8 children's hospitals in the United States for the period of September 1993 through December 1998. RESULTS: We identified 52 cases of pneumococcal facial cellulitis (45 periorbital and 7 buccal). Ninety-two percent of patients were <36 months old. Most were previously healthy; among the 6 with underlying disease were the only 2 patients with bilateral facial cellulitis. Fever (temperature: >/=100.5 degrees F) and leukocytosis (white blood cell count: >15 000/mm(3)) were noted at presentation in 78% and 82%, respectively. Two of 15 patients who underwent lumbar puncture had cerebrospinal fluid with mild pleocytosis, which was culture-negative. All patients had blood cultures positive for S pneumoniae. Serotypes 14 and 6B accounted for 53% and 27% of isolates, respectively. Overall, 16% and 4% were nonsusceptible to penicillin and ceftriaxone, respectively. Such isolates did not seem to cause disease that was either more severe or more refractory to therapy than that attributable to penicillin-susceptible isolates. Overall, the patients did well; one third were treated as outpatients. CONCLUSIONS: Pneumococcal facial cellulitis occurs primarily in young children (<36 months of age) who are at risk for pneumococcal bacteremia. They present with fever and leukocytosis. Response to therapy is generally good in those with disease attributable to penicillin-susceptible or -nonsusceptible S pneumoniae. Ninety-six percent of the serotypes causing facial cellulitis in this series are included in the heptavalent-conjugated pneumococcal vaccine recently licensed in the United States.

Pneumococcal mastoiditis in children.

OBJECTIVE: To determine the impact of antibiotic resistance on the frequency, clinical features, and management/outcome of mastoiditis attributable to Streptococcus pneumoniae. DESIGN: Retrospective review of the medical records of children with mastoiditis caused by S pneumoniae from September 1993 through December 1998. PATIENTS: Infants and children with pneumococcal mastoiditis cared for at 8 children's hospitals in the United States. RESULTS: Thirty-four children with pneumococcal mastoiditis were identified. The median age of the children was 12 months (range: 2 months-12.5 years); 28 (82%) were

Treatment of shigellosis with cefixime: two days vs. five days.

BACKGROUND: Although the recommended standard course of therapy for shigellosis is 5 days of oral ampicillin or trimethoprim-sulfamethoxazole therapy, successful outcome has been reported in adults treated with abbreviated courses of antibiotics. The purpose of this study was to compare short course (2-day) vs. 5-day therapy with cefixime for treatment of diarrheal disease caused by Shigella sonnei in children. METHODS: This was a prospective, randomized, double blind, placebo-controlled study. Patients were eligible if they were at least 6 months of age and presented to the Children's Hospital of Pittsburgh during an outbreak of diarrhea caused by S. sonnei, with (1) a history of fever and diarrhea (at least three loose or watery stools per day), (2) bloody diarrhea or (3) diarrhea and known exposure to an individual with documented shigellosis. Patients were randomized to receive either 2 days of cefixime (8 mg/kg(day) given once daily followed by 3 days of placebo or 5 days of cefixime. Telephone follow-up was performed on Days 3, 7 and 14 after enrollment. Follow-up stool cultures were obtained on Day 7 to assess bacteriologic cure. There were standardized definitions for cure, improvement, failure and relapse. RESULTS: Forty-seven patients were enrolled. Eleven were eliminated from analysis because their stool cultures were not positive for S. sonnei. There were 36 evaluable patients, 21 in the 2-day group and 15 in the 5-day group. Patients ranged in age from 6 months to 17 years. Forty-four percent of the subjects were male. Symptoms were improved or had resolved by Day 3 of therapy in all patients. There were 8 patients who experienced a clinical relapse: 5 of 21 (24%) patients in the 2-day treatment group and 3 of 15 (20%) in the 5-day group. There were 13 patients who experienced a bacteriologic failure (defined as the occurrence of a positive culture at the Day 7 follow-up visit), 11 of 20 (55%) in the 2-day group and 2 of 14 (14%) in the 5-day group (P < 0.02). CONCLUSION: Two- and 5-day treatment courses with cefixime for treatment of diarrheal disease caused by S. sonnei result in similar rates of clinical cure and clinical relapses; however, there was a higher rate of bacteriologic failure with shorter course therapy.

Cerebrospinal fluid findings in aseptic versus bacterial meningitis.

BACKGROUND: Aseptic meningitis is often reported to be characterized by a mononuclear cell predominance in the cerebrospinal fluid (CSF), whereas bacterial meningitis is characterized by a polymorphonuclear (PMN) cell predominance. In contrast, other studies suggest that PMNs can be the most prevalent cell in early aseptic meningitis followed by a shift to mononuclear cells within 24 hours. These contradictory reports may lead to uncertainty in the diagnosis and treatment of meningitis. OBJECTIVES: To assess 1) the characteristics of the CSF differential in aseptic versus bacterial meningitis, 2) the influence of duration of illness on the CSF differential, and 3) the role of the CSF differential in discriminating between aseptic versus bacterial meningitis. METHODS: A retrospective chart review was conducted of all cases of meningitis in children >30 days of age hospitalized during the peak months for enteroviral meningitis (April to October) between 1992 to 1997. Cases of aseptic meningitis were defined as having at least 20 white blood cells/mm(3) and the absence of bacterial growth on culture. Patients were excluded if they received antibiotic therapy within the previous 5 days. Cases of bacterial meningitis were defined as having a positive culture of the CSF or the presence of a CSF pleocytosis with positive cultures of the blood. CSF variables including white blood cell differential and time from the onset of symptoms to the performance of a lumbar puncture were analyzed. PMNs were considered to be predominant when the percentage of neutrophils added to juvenile forms was >50% of cells. RESULTS: One hundred fifty-eight cases of meningitis were reviewed: 138 were aseptic and 20 were bacterial. The patients ranged in age from 30 days to 18 years; 61% were male. Fifty-seven percent of cases of aseptic meningitis had a PMN predominance. The percentage of PMNs in the CSF in patients with aseptic meningitis was not statistically different for patients who had a lumbar puncture performed either within or beyond 24 hours of the onset of symptoms. Fifty-one percent of the 53 patients with aseptic meningitis and duration of illness >24 hours had a PMN predominance. The ability of a PMN predominance to differentiate between aseptic and bacterial meningitis was assessed. The sensitivity of a PMN predominance for aseptic meningitis is 57% whereas the specificity is 10%. The positive predictive value of a PMN predominance for aseptic disease is 81% but the negative predictive value is 3%. Alternative definitions of PMN predominance from 60% to 90% were not useful as a clinical indicator of bacterial disease. CONCLUSIONS: The majority of children with aseptic meningitis have a PMN predominance in the CSF. The PMN predominance is not limited to the first 24 hours of illness. Because the majority of children with a PMN predominance during enteroviral season will have aseptic disease, a PMN predominance as a sole criterion does not discriminate between aseptic and bacterial meningitis.

Treatment of urinary tract infections.

Treatment of UTI with oral antibiotics alone is generally effective, even in young children with pyelonephritis. Cefixime has a broad spectrum of activity and is suitable as an empiric agent in most cases. In patients who are unlikely to tolerate oral medications because of vomiting or who appear toxic on examination, hospitalization and initial treatment with i.v. therapy is indicated. In general, radiographic studies can be performed prior to completion of the primary course of antibiotics, and prophylactic treatment is unnecessary. Patients should receive instruction about the risk of recurrent infection and should be advised to seek medical attention when symptoms of UTI develop.

Management of rhinosinusitis in children.

The authors provide definitions for the different forms of pediatric rhinosinusitis, with an enumeration of the main symptoms and signs. They also provide the indications for CT scan examination and microbiological investigations. In addition, they emphasize the importance of concomitant systemic disease, such as allergy and immunological disorders. The adequate medical management, which is mandatory before any surgery, is considered and discussed, and the indications for surgery are provided.