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John S Bradley

Publications and source records attributed to John S Bradley.

At least 19 recordsLinked to original sources
PubMed2007

Population pharmacokinetic model for gatifloxacin in pediatric patients.

The broad spectrum of antimicrobial activity, oral bioavailability, extensive tissue distribution, and once-daily intravenous or oral dosing of gatifloxacin, an expanded-spectrum 8-methoxy fluoroquinolone, make it a potentially useful agent for the treatment of pediatric infections. A population pharmacokinetic model was developed to describe the pharmacokinetics of gatifloxacin in children. Data for analysis were obtained from a single-dose safety/pharmacokinetic study utilizing intensive blood sampling in patients aged 6 months to 16 years. Each subject received a single oral dose of gatifloxacin as a suspension, at doses of 5, 10, or 15 mg/kg of body weight. A total of 845 samples were obtained from 82 patients. A one-compartment model with first-order absorption and elimination was the most appropriate to describe the gatifloxacin concentrations. Covariate analysis using forward selection and backward elimination found that apparent clearance was related to body surface area, and apparent volume of distribution was related to body weight. No effect of age on drug clearance could be identified once clearance was corrected for body surface area. Based on pharmacokinetic simulations, the 10-mg/kg (maximum, 400 mg) once-daily dose of gatifloxacin is expected to provide drug exposure similar to that in healthy adults. The population pharmacokinetic model described herein will be used for Bayesian analyses of sparse pharmacokinetic sampling in phase II/III clinical trials and for Monte Carlo simulation experiments. The success of this strategy provides a model for future pediatric drug development programs.

Administration, Oral↗
PubMed2006

Multicentre surveillance of the prevalence and molecular epidemiology of macrolide resistance among pharyngeal isolates of group A streptococci in the USA.

OBJECTIVES: Rates of macrolide resistance in group A streptococci (GAS) were reported to be low in the US in the 1990s. However, we documented an unexpectedly high rate of macrolide resistance among GAS in Pittsburgh, PA, in 2001 and 2002. In an effort to define the current prevalence of macrolide-resistant GAS in the US, a multicentre surveillance project was initiated. METHODS: Between October 2002 and May 2003, 50 pharyngeal GAS isolates per month were requested from each of the nine participating sites representing a wide geographical distribution. Standard susceptibility testing was performed and the macrolide resistance phenotype was assessed using double-disc diffusion testing. Monthly and annual rates of macrolide resistance were calculated for each site. An adjusted overall rate of macrolide resistance was determined to account for differences in the numbers of GAS isolates sent from each centre. RESULTS: Overall, 171 of the 2797 collected isolates of GAS (6.1%) were resistant to erythromycin. The adjusted overall resistance rate was 5.2%. Rates of macrolide resistance varied by site (range 3.0-8.7%) and also by month (<2% to >10%). The M phenotype of macrolide resistance accounted for >60% of all macrolide-resistant isolates recovered in this study. CONCLUSIONS: These data suggest an increasing prevalence and broad geographical distribution of macrolide-resistant GAS in the US, indicating the need for ongoing local and national longitudinal surveillance to define the extent of this problem.

Anti-Bacterial Agents↗
PubMed2005

General method of preparation of mesoporous M/Si3N4 nano-composites via a non-aqueous sol-gel route.

We report a general method for the preparation of transition-metal silicon nitride nanocomposites; for example, mesoporous Pd-Si3N4 nanocomposite materials with high surface area were prepared by pyrolysis of a silicon palladium imide-chloride complex which was synthesized by reaction of silicon diimide gel with palladium chloride. These porous nanocomposites catalyse organic reactions.

Journal Article↗
PubMed2005

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.

Acute Disease↗
PubMed2005

Prediction of neurologic sequelae in childhood tuberculous meningitis: a review of 20 cases and proposal of a novel scoring system.

BACKGROUND: Despite effective antituberculous medications, the mortality and morbidity remain high in children with tuberculous meningitis (TBM). The traditional clinical staging for TBM developed by Lincoln et al in 1960 has been widely used to predict long term neurologic sequelae (NS). In the current era of critical care medicine and corticosteroid therapy, a new scoring system is needed to predict NS more accurately in children with TBM. METHODS: We reviewed all available cases of TBM in San Diego, CA, during 1991-2001 retrospectively, and we developed a novel scoring system to predict NS in children with TBM. We assessed a tuberculous meningitis acute neurologic (TBAN) score at day 0 and on day 3 of hospitalization, to compare children who subsequently developed severe NS with those who did not. RESULTS: Among 20 children with TBM, 7 children developed severe NS and 1 child died during hospitalization. The TBAN score was higher on day 0 in those with severe NS (5.5 versus 2.0, P = 0.09), and the difference became statistically significant by day 3 of hospitalization (5.5 versus 0.0, P = 0.02). Sensitivity and specificity of the TBAN score (> or =4) on day 0 (75 and 92%) and day 3 (88 and 100%) to predict severe NS were superior to the traditional clinical staging system on day 0 (63 and 58%). CONCLUSIONS: The TBAN score is an objective marker for predicting severe NS in children with TBM.

Adolescent↗
PubMed2005

Newer antistaphylococcal agents.

PURPOSE OF REVIEW: As antibiotic resistance in staphylococci continues to evolve, the ability to treat infections in children with confidence using first-generation cephalosporins, penicillins, and macrolides is decreasing. Knowledge of the local trends in resistance is important in making decisions of empiric antibiotic therapy. The antibiotic resistance pattern for the child's pathogen should be assessed whenever possible, to allow the practitioner to properly judge the risks and benefits of alternative antibiotic agents, should they be required for definitive therapy. RECENT FINDINGS: Options for therapy of most methicillin-resistant and macrolide-resistant community-acquired strains of Staphylococcus aureus include vancomycin, linezolid, and, in communities with a high proportion of susceptible strains, clindamycin. Daptomycin, a lipopeptide antibiotic with activity against virtually all strains of S. aureus, was recently approved by the United States Food and Drug Administration for adults. Second-generation glycopeptide antibiotics similar to vancomycin are in clinical trials in adults, including dalbavancin and oritavancin. Several new compounds, including cephalosporins active against methicillin-resistant S. aureus, are in preclinical development as well. SUMMARY: The recent worldwide emergence and rapid spread of community-acquired methicillin-resistant S. aureus has prompted a change in the approach to therapy of staphylococcal infections in both the outpatient clinic and the hospital. Newer agents active against methicillin-resistant S. aureus such as linezolid have been recently approved for children and other agents recently approved for adults are under investigation in children. Older agents for which relatively few data from prospective, controlled, comparative studies exist in the treatment of staphylococcal infections may also offer effective and less costly options for therapy.

Acetamides↗
PubMed2005

Defining pneumonia in critically ill infants and children.

OBJECTIVE: To define pneumonia in critically ill children in the intensive care unit setting for surveillance of infection and for the design, conduct, and evaluation of clinical trials in the prevention and therapy of lower respiratory tract infections in this population. DESIGN: Summary of the literature with review and consensus by experts in the field. RESULTS: A variety of diagnostic criteria from the medical literature, professional societies, and governmental health agencies and regulators were identified. Very few of these diagnostic criteria have been validated for use in children. We propose definitions for definite, possible, and probable pneumonia that build on identified definitions in the literature and use combinations of symptoms, signs, and laboratory criteria. Gaps in knowledge were identified. CONCLUSIONS: Although pneumonia is one of the most common diagnoses in critically ill children, there have been few studies validating diagnostic criteria. Definitions for definite, probable, and possible community-acquired pneumonia and nosocomial pneumonia were achieved by consensus of experts based on guidelines from governmental agencies, professional organizations, and published literature. Future research should determine the utility of these definitions in the critically ill child and adapt them accordingly.

Adolescent↗
PubMed2005

Using listening difficulty ratings of conditions for speech communication in rooms.

The use of listening difficulty ratings of speech communication in rooms is explored because, in common situations, word recognition scores do not discriminate well among conditions that are near to acceptable. In particular, the benefits of early reflections of speech sounds on listening difficulty were investigated and compared to the known benefits to word intelligibility scores. Listening tests were used to assess word intelligibility and perceived listening difficulty of speech in simulated sound fields. The experiments were conducted in three types of sound fields with constant levels of ambient noise: only direct sound, direct sound with early reflections, and direct sound with early reflections and reverberation. The results demonstrate that (1) listening difficulty can better discriminate among these conditions than can word recognition scores; (2) added early reflections increase the effective signal-to-noise ratio equivalent to the added energy in the conditions without reverberation; (3) the benefit of early reflections on difficulty scores is greater than expected from the simple increase in early arriving speech energy with reverberation; (4) word intelligibility tests are most appropriate for conditions with signal-to-noise (S/N) ratios less than 0 dBA, and where S/N is between 0 and 15-dBA S/N, listening difficulty is a more appropriate evaluation tool.

Adult↗
PubMed2005

Pharmacokinetics of gatifloxacin in infants and children.

Gatifloxacin is an 8-methoxy fluoroquinolone effective against a broad spectrum of pathogens common in pediatric infections. The safety and pharmacokinetics of a single dose of gatifloxacin were studied in pediatric patients from 6 months to 16 years of age. Seventy-six pediatric patients (average age, 6.7 +/- 5.0 years) were administered a single oral dose of gatifloxacin suspension (5, 10, or 15 mg/kg of body weight; 600-mg maximum) in a dose-escalating manner. Subjects were stratified by age into 4 groups. An additional 12 children, greater than 6 years of age, received gatifloxacin as the tablet formulation at a dose of approximately 10 mg/kg. Gatifloxacin's apparent clearance and half-life were 5.5 +/- 2.1 ml/min/kg and 5.1 +/- 1.4 h. The maximum concentration of drug in plasma and area under the concentration-time curve (AUC) increased in a manner approximately proportional to the dose. At the 10-mg/kg dose, the bioavailability was similar between the suspension and tablet formulation. The apparent oral clearance of gatifloxacin, normalized for body weight, exhibited a small but statistically significant decrease with increasing age. In all subjects receiving gatifloxacin at 10 mg/kg, the AUC exceeded 20 microg . h/ml (estimated free AUC/MIC ratio of > or =34 for MIC of < or =0.5 microg/ml). These data suggest that gatifloxacin at a dose of 10 mg/kg every 24 h will achieve therapeutic concentrations in plasma in infants and children.

Adolescent↗
PubMed2005

Levofloxacin pharmacokinetics in children.

Levofloxacin is a broad-spectrum fluoroquinolone antibiotic with activity against many pathogens that cause bacterial infections in children, including penicillin-resistant pneumococci. To provide dosing guidance for children, 3 single-dose, multicenter pharmacokinetic studies were conducted in 85 children in 5 age groups: 6 months to <2 years, 2 to <5 years, 5 to <10 years, 10 to <12 years, and 12 to 16 years. Each child received a single 7-mg/kg dose of levofloxacin (not to exceed 500 mg) intravenously or orally. Plasma and urine samples were collected through 24 hours after dose. Pharmacokinetic parameters were estimated and compared among the 5 age groups and to previously collected adult data. Levofloxacin absorption (as indicated by C(max) and t(max)) and distribution in children are not age dependent and are comparable to those in adults. Levofloxacin elimination (reflected by t1/2 and clearance), however, is age dependent. Children younger than 5 years of age clear levofloxacin nearly twice as fast (intravenous dose, 0.32+/-0.08 L/h/kg; oral dose, 0.28+/-0.05 L/h/kg) as adults and, as a result, have the total systemic exposure (area under the plasma drug concentration-time curve) approximately one half that of adults. The levofloxacin area under the plasma drug concentration-time curve (dose normalized) in children receiving a single dose of the oral liquid formulation is comparable to that in children receiving the intravenous formulation. To provide compatible levofloxacin exposures associated with clinical effectiveness and safety in adults, children > or =5 years need a daily dose of 10 mg/kg, whereas children 6 months to <5 years should receive 10 mg/kg every 12 hours.

Administration, Oral↗
PubMed2005

Pharmacodynamics and the prediction of efficacy in short-course antibiotic therapy: pediatric studies to validate the model.

Short-course antibiotic therapy for specific pediatric infections allows the clinician to minimize toxicities related to antibiotic exposure, to limit antibiotic resistance, and to improve compliance and cost without compromising microbiologic efficacy. Future studies of short-course therapy in children should address the pharmacokinetics of antibiotic exposure to the pathogen at the site of infection, the pharmacodynamics of pathogen eradication, and the many host factors involved in clinical and microbiologic outcomes. By using a mathematic model that integrates all important variables, one may be able to predict the probability of a cure with short-course therapy for each pathogen, antibiotic, site of infection, and host interaction.

Anti-Bacterial Agents↗
PubMed2004

Pneumococcal endocarditis in children.

Endocarditis due to Streptococcus pneumoniae is unusual in children, accounting for 3%-7% of all cases of childhood endocarditis. The US Pediatric Multicenter Pneumococcal Surveillance Group has prospectively identified patients with invasive disease at 8 children's hospitals. During the period of 1 September 1993 through 28 February 2003, a total of 11 children with pneumococcal endocarditis were seen. Seven (64%) were 3-36 months old; 8 (73%) were boys. Ten (91%) had preexisting structural heart disease; 5 had undergone previous heart surgery. Concomitant sites of infection were noted in 6 patients (55%), including 3 patients with meningitis. One patient (9%) died during hospitalization, and 5 others (45%) experienced serious complications. Only 2 patients remained hospitalized for their entire course of parenteral antibiotic therapy. Eight of 10 pneumococcal isolates tested were vaccine or vaccine-related serotypes included in the currently licensed 7-valent conjugated pneumococcal vaccine. Pneumococcal endocarditis in children is unusual but often has serious complications.

Adolescent↗
PubMed2004

Prevalence of antimicrobial resistance in bacteria isolated from central nervous system specimens as reported by U.S. hospital laboratories from 2000 to 2002.

BACKGROUND: Bacterial infections of the central nervous system, especially acute infections such as bacterial meningitis require immediate, invariably empiric antibiotic therapy. The widespread emergence of resistance among bacterial species is a cause for concern. Current antibacterial susceptibility data among central nervous system (CNS) pathogens is important to define current prevalence of resistance. METHODS: Antimicrobial susceptibility of pathogens isolated from CNS specimens was analyzed using The Surveillance Database (TSN) USA Database which gathers routine antibiotic susceptibility data from >300 US hospital laboratories. A total of 6029 organisms derived from CNS specimen sources during 2000-2002, were isolated and susceptibility tested. RESULTS: Staphylococcus aureus (23.7%) and Streptococcus pneumoniae (11.0%) were the most common gram-positive pathogens. Gram-negative species comprised approximately 25% of isolates. The modal patient age was 1 or <1 year for most organisms. Prevalence of MRSA among S. aureus from cerebrospinal fluid (CSF) and brain abscesses were 29.9-32.9%. Penicillin resistance rates were 16.6% for S. pneumoniae, 5.3% for viridans group streptococci, and 0% for S. agalactiae. For CSF isolates, ceftriaxone resistance was S. pneumoniae (3.5%), E. coli (0.6%), Klebsiella pneumoniae (2.8%), Serratia marcescens (5.6%), Enterobacter cloacae (25.0%), Haemophilus influenzae (0%). Listeria monocytogenes and N. meningitidis are not routinely susceptibility tested. CONCLUSIONS: Resistance is commonly detected, albeit still at relatively low levels for key drugs classes such as third-generation cephalosporins. This data demonstrates the need to consider predominant resistance phenotypes when choosing empiric therapies to treat CNS infections.

Journal Article↗