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Background. Invasive pneumococcal disease (IPD) continues to be a significant burden in children despite the implementation of two generations of conjugate vaccines. Serotype replacement by nonvaccine serotypes is reported in multiple areas around the world. This study is a continuation of previous studies and describes the incidence, serotype distribution, and antibiotic resistance pattern of Streptococcus pneumoniae serotypes causing IPD at Children's Medical Center Dallas after introduction of 13-valent pneumococcal conjugate vaccine (PCV13). Methods. Streptococcus pneumoniae isolates from normally sterile sites were collected from January 1, 1999 to June 30, 2014. Demographic and clinical information was extracted for analysis. Incidence of IPD was calculated using inpatient and emergency center admissions to Children's Medical Center of Dallas as the denominator. Isolates were serotyped and penicillin/cefotaxime susceptibilities were determined. Selected nontypeable isolates were further characterized by multilocus sequence typing. A χ2 test and the Cochran-Armitage Trend Test for trend analysis were used to evaluate change in serotype and antibiotic susceptibility patterns over time. Results. Comparison of the different study periods showed a significant reduction in the incidence of IPD in PCV13 era compared with prevaccine era and PCV7 era (P < .05). Children younger than 24 months showed the largest reduction of disease incidence. More than 40% of patients with IPD had a documented comorbidity. Cases of pneumonia continued to decrease in the PCV13 era (P < .002). The most common non-PCV13 serotypes after vaccine introduction were as follows: 23B, 6C, 23A, 9N/L, and 12. Penicillin resistance by meningitis breakpoint decreased significantly in the PCV13 era. Conclusions. After introduction of PCV13 in Dallas, incidence of IPD caused by strains contained in the vaccine and penicillin resistance continued to decrease. Serotype replacement phenomena and persistence of PCV7 serotypes were documented. Patients with comorbidities represented a large percentage of patients with IPD. Concerns for geographic variation in serotype replacement phenomena arise from the present study. [ABSTRACT FROM AUTHOR]

Background. Studies suggest that the 7-valent pneumococcal conjugate vaccine (PCV7) reduces carriage of vaccine-type (VT) Streptococcus pneumoniae (SP). We studied the effect of PCV7 on carriage of VT- and non-VT (NVT) SP, by studying the effect of PCV7 on nasopharyngeal (NP) colonization by VT and NVT SP during early childhood. Methods. At 2 months of age, 278 infants were enrolled in this study. To determine carriage of SP, NP samples were obtained before each PCV7 dose, at 9 months of age, and 2–3 months after the booster dose of vaccine. Results. The carriage of SP increased slightly, from 12% (95% confidence interval [CI], 8%–16%) of subjects at 2 months of age to 18% (95% CI, 13%–23%) at 4 months of age (P < .05. Carriage of SP remained in 24%– 30% of subjects during subsequent months. Between the 12- and 18-month visits, the carriage rate of VT SP decreased significantly, from 18% (95% CI, 13%–23%) to 9% (95% CI, 5%–13%) of subjects (P = .001) The trend of a decrease in carriage of penicillin-nonsusceptible SP, from 16% of subjects (95% CI, 11%–21%) at the 12–15-month visit to 9% (95% CI, 5%–13%) at the 15–18-month visit, was found after the booster dose of vaccine. Conclusion. The reduction of VT-SP colonization and replacement by NVT SP after the booster dose of vaccine suggests the possibility that widespread vaccination will result in replacement of pneumococci mainly by antibiotic-susceptible NVT SP. [ABSTRACT FROM AUTHOR]

This review comprises aspects of the epidemiology, microbiology, pathophysiology, clinical manifestations, diagnosis, management, prognosis, and prevention of bacterial meningitis, with emphasis on the paediatric population. The beginning of this millennium has witnessed the virtual disappearance of Haemophilus invasive disease in some countries, emergence of pneumococcal strains that are resistant to multiple antibiotics, isolation of pneumococci with tolerance to vancomycin, outbreaks and clusters of meningococcal meningitis in several geographical areas, and intense research in development of effective conjugate pneumococcal and meningococcal vaccines. Bacterial meningitis has become an uncommon disease in the developed world. Unfortunately, because of limited economic resources and poor living conditions, many developing countries are still affected by the devastating consequences of this life-threatening systemic infection. Basic and clinical research is needed to discover new antimicrobial and anti-inflammatory agents to improve outcome from disease. Novel strategies are needed to distribute and implement effective vaccines worldwide to prevent bacterial meningitis. [ABSTRACT FROM AUTHOR]

Presents a study which examined the effects of large dosages of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, nonpneumococcal alpha -hemolytic streptococci and Staphylococcus aureus in children with acute otitis media. Association of the prior use of antibiotics with carriage of resistant bacteria; Methodology; Results.

A prospective study of 154 consecutive high-risk hospitalized children with lower respiratory infections was conducted to determine the clinical utility of a pneumolysin-based polymerase chain reaction (PCR) assay compared with blood and pleural fluid cultures and serological and urinary antigen tests to determine the incidence of Streptococcus pneumoniae. Whole blood, buffy coat, or plasma samples from 67 children (44%) tested positive by PCR. Sensitivity was 100% among 11 promptly tested culture-confirmed children and specificity was 95% among control subjects. Age, prior oral antibiotic therapy, and pneumococcal nasopha-ryngeal colonization did not influence PCR results, whereas several surrogates of disease severity were associated with positive tests. Although serological and urinary antigen tests had comparable sensitivity, specificity varied among infected children, and statistical agreement among all assays was limited. These findings support the use of PCR tests to evaluate the protective efficacy of pneumococcal conjugate vaccines and to identify promptly children with pretreated or nonbacteremic pneumococcal lower respiratory infections. [ABSTRACT FROM AUTHOR]

Evaluates the effect of antibiotic therapy on nasopharyngeal colonization of Streptococcus pneumoniae and Haemophilus influenzae in children diagnosed with acute otitis media. Eradication or suppression of all strains of S. pneumoniae susceptible to penicillin by amoxicillin/clavulanate therapy; Reduction of carriage of H. influenzae by antimicrobial therapy.

Abstract. The pharmacokinetics of kanamycin and gentamicin were studied after intramuscular (IM) and intravenous (IV) (constant infusion over 20 minutes) administration in newborn infants. The serum concentrations, half-lives, area-under-the-curve values, and volumes of distribution were similar for each drug after both routes of administration. Based on these pharmacological similarities, it is likely that these aminoglycosides can be given safely and effectively as constant IV infusions to neonates in whom IM injections are not feasible. [ABSTRACT FROM AUTHOR]

Because of its greater activity against Pseudomonas and Proteus and comparable activity against other bacteria, carbenicillin has theoretical advantages over ampicillin or penicillin as initial therapy, along with an aminoglycoside antibiotic, for suspected infections in the neonate. From a previous study of carbenicillin pharmacokinetics, mathematical predictions of dosage and intervals of administration were made and tested in 55 infants from 1 to 45 days of age treated with carbenicillin and gentamicin. Clinical efficacy was compared with a randomly selected group of 55 babies treated with ampicillin and gentamicin. No deaths directly attributable to infection occurred in either group. In bacteriologically documented infections follow-up cultures indicated eradication of the pathogen. All serum specimens tested for bactericidal power against Escherichia coli or Pseudomonas had bacterial titers of 1:2 or greater. Dose response curves and daily serum specimens during subsequent days of treatment were assayed for antibiotic content. Peak serum level and serum half-life were correlated with dosage, interval, age, and weight. The proposed dosage schedule of carbenicillin for neonates is (1) 100 mg/kg initial dose; (2) 75 mg/kg subsequent doses at eight hourly intervals through 7 days of age for infants under 2,000 gm and at six hourly intervals until 4 days of age for babies weighing over 2,000 gm; (3) thereafter, 100 mg/kg every six hours for both weight groups. These dosages should assure therapeutic serum concentrations or carbenicillin when its use is desired or indicated for the neonate. Therapeutic results with carbenicillin and gentamicin were satisfactory in this study, but a larger experience is needed before the relative efficacy of this combination vis-à-vis other antibiotics commonly used for neonatal infections can be assessed. [ABSTRACT FROM AUTHOR]

Abstract. To determine the clinical importance of CSF cultures that are persistently positive for pathogens in patients treated for meningitis with the new cephalosporins, the records of 301 infants and children with bacterial meningitis enrolled prospectively in four clinical efficacy trials of cefuroxime or ceftriaxone therapy were reviewed. CSF culture results were positive for 20 patients and they were sterile at 18 to 36 hours after start of therapy for 281 patients. Seizures, subdural effusions, and hemiparesis were found significantly more often during hospitalization in those with delayed sterilization of CSF. Children with persistently positive cultures had a significantly higher incidence of neurologic abnormalities at the time of hospital discharge (45% v 19%) and at follow-up (41% v 13%) and of moderate to profound hearing impairment (35% v 15%) than did those with prompt sterilization of CSF. Repeat CSF examination is a useful prognostic indicator in infants and young children with bacterial meningitis. [ABSTRACT FROM AUTHOR]

Abstract. Thirteen children with sickle cell disease were identified as having 14 episodes of osteoarticular infection in a review of 27 years' experience. There were eight episodes of osteomyelitis or osteoarthritis and six of suppurative arthritis alone. The etiologic agents in osteomyelitis or osteoarthritis were Salmonella sp in four cases, Escherichia coli in one, Enterobacter aerogenes in one, Staphylococcus aureus in one, and Haemophilus influenzae type b in one. Five of the cases with infection limited to the joint were caused by Streptococcus pneumoniae; the sixth was caused by H influenzae type b. Fever (is greater than or equal to 38.3 Celsius) was present in all children and the temperature was in excess of 39 Celsius in 62%. The mean duration of pain before admission was 4.5 days. The initial total white blood cell count ranged from 5,200 to 29,700/micro L (mean 19,436/micro L) and the total band neutrophil count ranged from 0 to 5,103/micro L (mean 1,660/micro L). The ESR was greater than 20 mm/h in eight of the ten patients who were tested. Management consisted of antibiotic therapy in all. Needle aspiration was performed in two patients with osteomyelitis and in three with suppurative arthritis. Incision and drainage was performed in two cases of osteomyelitis and in four with suppurative arthritis. The outcome was satisfactory in all except one patient who had several complications as a consequence of femoral neck osteomyelitis. Recurrence was reported in only one patient. [ABSTRACT FROM AUTHOR]

Abstract. The clinical and laboratory features of urinary tract infections in 100 infants aged 5 days to 8 months are presented. Of the patients in the first three months of life 75% were boys, and of infants aged 3 to 8 months only 11% were boys; 95% of the infants were uncircumcised. Sepsis was documented in 31% of neonates, 21% of infants aged 1 to 2 months, 14% of those aged 2 to 3 months, and 5.5% of infants >3 months of age. Roentgenographic abnormalities of the urinary system were found in 45% of female and 7% of male infants. All infants responded promptly to antimicrobial therapy. The possible factors related to the predominance of male infants with urinary tract infections in the first three months of life are discussed. [ABSTRACT FROM AUTHOR]

Abstract. This study was designed to determine whether serum C-reactive protein (CRP) concentrations could be used to identify children with uncomplicated lower urinary tract infection who would respond favorably to short-term antibiotic therapy. A one-day or ten-day regimen of cefadroxil (30 mg/kg/day in two divided doses) was assigned randomly to 80 children who had acute urinary tract infection and CRP concentrations <28 micro g/ml (CRP-negative group). Ten days of cefadroxil therapy was used to treat 44 children with urinary tract infection and CRP values Is equal to or greater than 28 micro g/ml (CRP-positive group). The clinical and laboratory characteristics of the children in the two CRP-negative therapy groups were similar to, but different from those of children with CRP-positive infections. Recurrent infections occurred significantly more often at four to five days after completion of therapy in CRP-negative children who received one day (44.4%) compared to ten days (20%) of cefadroxil therapy (P < .05). When data from this study were combined with those from our previously published investigation of short-term antibiotic therapy in CRP-negative children, a significantly larger percentage of recurrences was documented immediately after one or four days of antibiotics (79%) compared to recurrences after the standard ten-day regimen (41%). Additionally, the total rate of recurrent infections for all children in both studies was significantly larger in those who received short-term therapy (48%) as opposed to conventional therapy (34%). These data indicate that short-term antibiotic therapy is less effective than the conventional ten-day regimen in... [ABSTRACT FROM AUTHOR]

Abstract. Clinical manifestations, diagnostic studies, and management of pyogenic sacroiliitis were reviewed in 77 pediatric patients. This infection occurs primarily in late childhood, is more common in boys, and has a subacute onset in about two thirds of cases. Recognition of the characteristic signs and symptoms of sacroiliac involvement coupled with radioisotope bone scanning substantially reduces the delay in correct diagnosis that averaged 3.9 weeks in all patients (4.8 weeks in those without and 1.7 weeks in those with bone scans performed). Joint aspiration under biplane fluoroscopic control and culture of the aspirated material is indicated in establishing the specific etiologic agent which is Staphylococcus aureus in most cases. Adequate management of pyogenic sacroiliitis consists of appropriately monitored antibiotic treatment and, if present, evacuation of pus. The use of spica cast immobilization offers no apparent beneficial effect. Indications for surgery include drainage of pus and removal of sequestered bone. With adequate management the prognosis of suppurative sacroiliitis in pediatric patients is excellent, despite persistent abnormal radiographic findings in most patients. [ABSTRACT FROM AUTHOR]

Abstract. Pharmacokinetic studies of rifampin were performed in 38 infants and children after administration of three different oral formulations. Mean peak serum concentrations of from 9 to 11.5 micro g/ml were observed one hour after a 10-mg/kg dose and the average half-life was 2.9 hours. Patients who received rifampin suspension in applesauce had smaller serum concentrations and area-under-the-curve values than did those who were given suspension alone. The mixture of rifampin powder and applesauce resulted in more variable serum levels. The concentrations of drug in tears from 18 subjects were similar to those in serum. All but one of 118 saliva specimens obtained from two to eight hours after the 10-mg/kg dose had antimicrobial activity. Of samples taken at two hours, 95% contained rifampin levels that exceeded the minimal bacterial concentration for 15 Haemophilus influenzae type b strains. Bactericidal activity against Haemophilus correlated with salivary rifampin concentrations and was detectable in virtually all specimens containing equal to or is greater than 0.8 micro g/ml. These data provide the pharmacokinetic basis for rifampin prophylaxis of close contacts of H influenzae type b disease, but are insufficient alone to recommend routine usage of rifampin for this purpose until results of additional epidemiologic studies are available. Pediatrics 66:17-21, 1980; rifampin, Haemophilus influenzae type b. [ABSTRACT FROM AUTHOR]

Abstract. The pharmacokinetics of amoxicillin and ampicillin were studied in 24 infants and children. Mean peak serum concentrations of 5.4 micro g/ml in fasting and 3.2 micro g/ml in nonfasting patients were observed after 15 mg/ kg amoxicillin doses. Area under the curve values and serum half-life values were similar in fasting and nonfasting patients. The pharmacokinetics of amoxicillin (15 mg/ kg) were compared to those of ampicillin (25 mg/kg). Peak serum concentrations, area under the curve values and half-life times were comparable for the two drugs. Amoxicillin (25 mg/kg) and ampicillin (25 mg/kg) were compared in cross-over fashion in 11 children. Serum concentrations of amoxicillin were consistently larger than those of ampicillin; the differences were of borderline significance at one and two hours and statistically significant at four and six hours after the dosage. The bioavailability of amoxicillin was twice that of ampicillin. Amoxicillin was detected in approximately half of the saliva samples studied. Although the salivary concentrations in many children exceeded the inhibitory level for most pneumococci and group A streptococci and for many non-beta lactamase-producing Haemophilus influenzae type b strains, the clinical relevance of these observations is unknown. Pediatrics 64:627-631, 1979; amoxicillin, ampicillin, pharmacokinetics, infants, children, dosages. [ABSTRACT FROM AUTHOR]

Abstract. One hundred four patients with 124 episodes of urinary tract infection were studied. Serum C-reactive protein (CRP) was determined on diagnosis of each patient. Children with a CRP equal to or greater than 30 /micro g/ml (CRP-pos) differed significantly from those with values less than 30 micro g/ml (CRP-neg) in age, clinical presentation, K type of Escherichia coli causing disease, frequency or radiographic abnormalities, and presence of antibody coating of bacteria in the urinary sediment. E coli K1 strains caused disease significantly more often in CRP-pos than in CRP-neg patients, and children with K1 infections were younger than those with non-K1 infections. The antibody-coated bacteria test was neither sensitive nor specific for localization of infection in pediatric patients. Determination of Kl antibody concentrations in serum and urine of E coli Kl-infected children provided data supporting the measurement of CRP as one means of localizing urinary tract infections. Patients with CRP-neg infections were treated as successfully with four days of antimicrobial therapy as with ten days. [ABSTRACT FROM AUTHOR]

Abstract. This article reports the results of a four-year follow-up study initiated in 1970 on the long-term effects of gentamicin and kanamycin use in newborn infants. Audiometric, vestibular, and psychometric evaluations were performed on gentamicin-treated, kanamycin-treated, and untreated, matched control infants and children. No substantial sensorineural hearing loss or vestibular dysfunction was identified in these patients that could be attributed to aminoglycoside therapy. Performances on the Illinois Test of Psycholinguistic Abilities, Beery Test of Visual Motor Integration, the Peabody Picture Vocabulary Test, and on fine and gross motor examinations were comparable for the three study groups. Pediatrics 63:443-450, 1979, newborn, kanamycin, gentamicin, ototoxicity, vestibular function, psychological testing. [ABSTRACT FROM AUTHOR]