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Biomedical subjects

M I Marks

Publications and source records attributed to M I Marks.

At least 19 recordsLinked to original sources

Cefepime. Pharmacokinetics and clinical response in patients with cystic fibrosis.

OBJECTIVE: To measure first-dose and steady-state plasma, urine, and sputum concentrations of cefepime and make preliminary assessments of the clinical efficacy of cefepime in patients with cystic fibrosis. DESIGN: Open noncomparative clinical trial. SETTING: Memorial Miller Children's Hospital of Long Beach, Calif. PARTICIPANTS: Twelve patients, aged 4 to 41 years, with a confirmed diagnosis of cystic fibrosis and chronic bronchopulmonary infections. INTERVENTIONS: Patients received cefepime at 50 mg/kg per dose (maximum dose, 2 g per dose) given intravenously every 8 hours. Clinical evaluations, pulmonary function tests, quantitative sputum cultures, and sensitivity testing were performed before, at the end of, and 2 weeks after therapy. MEASUREMENTS AND MAIN RESULTS: Mean (+/- SD) peak plasma concentrations after the first dose were 148.2 (36.6) mg/L; the following other values were included: half-life, 1.59 (0.46) hours; area under the curve, 292 (94) microgram/h per milliliter; total-body clearance, 3.01 (1.46) mL/min per kilogram; volume of distribution at steady state, 0.32 (0.10) L/kg; and percent of dose recovered in urine, 52% (27%). Steady-state and first-dose values were similar. Trough levels varied from 6.4 to 7.2 mg/L. Mean (+/- SD) sputum concentrations at steady state varied from 6.3 (5.4) to 4.8 (2.3) mg/L. At completion of therapy, nine of 10 patients' conditions were improved as indicated by clinical scores (greater than 10 points), forced vital capacity (greater than 10%), and a greater than or equal to 1 log decrease in sputum bacterial concentration. Cefepime was well tolerated in 10 patients, but rash and light-headedness developed in two patients. Pseudomonas aeruginosa minimum inhibitory concentration90 increased from the start (64 mg/L) to the end of therapy (256 mg/L) and was unchanged 2 weeks later. CONCLUSION: Based on these data and the potential advantage of a single agent for the treatment of mixed infections (Staphylococcus aureus and P aeruginosa), comparative clinical trials of cefepime and standard therapy for bronchopulmonary exacerbations in patients with cystic fibrosis appear to be warranted.

Adolescent

Vitamin A levels in children with measles in Long Beach, California.

Studies from Africa suggest that vitamin A supplementation may reduce morbidity and mortality rates associated with measles among poorly nourished children. We studied 20 children with measles in Long Beach, Calif., and found that 50% (95% confidence interval; 28% to 72%) were vitamin A deficient. This frequency among presumably well nourished American children supports evaluation of vitamin A status as a part of acute management of measles in the United States.

California

Measles.

Measles has become epidemic over most of the world, with an important increase in the number of cases and associated morbidity and mortality in the United States since 1986. The two major factors responsible for this rise in the number of cases are, first, the increase in unvaccinated preschool-age children and, second, vaccine nonresponders (approximately 5%). The highest attack rate occurred in teenagers (15 to 19 years old) and in nine states (82% of cases). This situation has prompted revised immunization recommendations for those counties reporting more than five cases of measles among preschool-age children during each of the previous 5 years. In these counties, a first dose with monovalent measles vaccine is recommended at 9 months of age, followed by a second dose with measles, mumps, and rubella vaccine at 15 months of age, and revaccination of all children at the time of school entry. Recent publications regarding the use of vitamin A and certain antiviral agents are encouraging and are discussed in the manuscript. All cases of measles should be reported and investigated promptly. A good outbreak-control program will depend on the rapid recognition of the disease, a team approach, and prompt vaccination or IgG administration to susceptible persons.

Adolescent

In-vitro activity of cefprozil (BMY 28100) and loracarbef (LY 163892) against pathogens obtained from middle ear fluid.

We compared the in-vitro activities of cefprozil, a novel oral cephalosporin, and of loracarbef, a new oral carbacephem, with other agents against middle ear fluid isolates obtained from children with acute otitis media. These included Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis. Cefprozil activity (MIC50 and MIC90) against S. pneumoniae was 0.25 and 0.50 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 2 and 2 mg/l. Loracarbef activity (MIC50 and MIC90) against S. pneumoniae was 1 and 2 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 1 and 8 mg/l. Cefprozil was four-fold more active against S. pneumoniae than loracarbef but similar to amoxycillin, amoxycillin/clavulanate, cefaclor, cefixime, cefuroxime and trimethoprim/sulfamethoxazole (TMP/SMX). Against H. influenzae, cefprozil was similar to loracarbef and other agents through less active than TMP/SMX and cefixime. Against B. catarrhalis, cefprozil was four-fold more active than loracarbef, cefaclor and cefixime but similar to the comparative antibiotics. Cefprozil and loracarbef activities were unaffected at pH 6 and 8 or in the presence of human serum, but there was a major diminution of activity for both agents at pH 5 and at inoculum sizes greater than or equal to 10(7) cfu/ml. Cefoprozil and loracarbef have consistent activity against middle ear pathogens and further pharmacokinetic and clinical studies appear warranted.

Acute Disease

Bacterial meningitis--an update.

This report emphasizes new clinical information about bacterial meningitis in infants and children. Important elements of diagnosis include examination for the presence of shock and increased intracranial pressure. In such cases, initial treatment should focus on appropriate fluid therapy, administration of oxygen, reduction of intracranial pressure and use of corticosteroids. Currently, antibiotics of choice include ampicillin plus either cefotaxime or ceftriaxone in young infants, and one of these cephalosporins in older patients (beyond 3 months of age). Shorter durations of therapy (5 to 7 days for meningococcus, 7 days for haemophilus and 7-10 days for pneumococcus) are now commonly employed. In many centers, dexamethasone is started before the first dose of antibiotic and continued for 4 days to reduce neurologic and audiologic sequelae. Future trends will include studies of endotoxin neutralizers and non-steroidal anti-inflammatory drugs to reduce further tissue injury in meningitis. Prevention of meningitis is the ultimate goal. Since Haemophilus influenzae vaccination can now begin at 2 months, this approach may bring important results soon.

Anti-Bacterial Agents

Invasive Haemophilus influenzae type B infections: a continuing challenge.

Invasive Haemophilus influenzae type b infections are a major cause of severe infections in children between 2 months and 5 years of age. Meningitis, arthritis, pneumonia, cellulitis, osteomyelitis, and epiglottitis affect approximately 25,000 patients annually and are a major cause of mortality and morbidity in children. H. influenzae type b clinical syndromes, diagnostic methods, epidemiology, immunity, and treatment are discussed in this review. Although potent antibiotics have long been available for treatment, mortality and morbidity rates have not declined substantially in the last 15 years. Prevention of disease is therefore a continuous medical challenge. Secondary cases can be prevented by identification of the high-risk groups and the application of appropriate techniques, including antimicrobial prophylaxis. Primary prevention is the major goal of current research. H. influenzae type b vaccines currently are available for protection of infants 18 months of age and older. Prevention of primary and secondary disease and future developments, including new vaccine strategies, are stressed.

Anti-Bacterial Agents

Comparative in vitro activity of a new quinolone, fleroxacin, against respiratory pathogens from patients with cystic fibrosis.

We evaluated fleroxacin, a newer fluoroquinolone, against isolates from sputum from patients with cystic fibrosis. These isolates included rough and mucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. Selected isolates were tested by the broth microdilution method to examine the influence of various pHs, inoculum sizes, and biological fluids (serum or sputum from patients with cystic fibrosis). Fleroxacin MICs for 50 and 90% of isolates of P. aeruginosa were 2.0 and 4 micrograms/ml, those for P. cepacia were 2 and 16 micrograms/ml, those for S. aureus were 0.5 and 1 microgram/ml, those for H. influenzae were 0.06 and 0.06 micrograms/ml, and those for E. coli were 0.01 and 0.03 micrograms/ml, respectively. Fleroxacin activity against mucoid P. aeruginosa was similar to the activities of enoxacin and ofloxacin but eightfold lower than that of ciprofloxacin. It was twofold more active than norfloxacin and enoxacin but was twofold less active than ciprofloxacin, ofloxacin, and nafcillin against S. aureus. Fleroxacin inhibitory activity against P. cepacia was two- to fourfold lower than that of ciprofloxacin but eightfold greater than those of the other quinolones tested. Alterations in pH, diluent, and inoculum size did not significantly affect fleroxacin activity. These results, combined with available pharmacokinetic and tissue distribution data, support the need for clinical evaluation of fleroxacin in pulmonary infections in patients with cystic fibrosis.

Anti-Bacterial Agents

In vitro activity of tosufloxacin, a new quinolone, against respiratory pathogens derived from cystic fibrosis sputum.

By using broth microdilution methods, the in vitro activity of tosufloxacin (A-64730), a new quinolone, was compared with those of other agents, including five quinolones, against geographically diverse cystic fibrosis sputum isolates obtained from 26 cystic fibrosis centers in the United States. These included Pseudomonas aeruginosa, conventional as well as especially resistant (ceftazidime, aztreonam, gentamicin, and/or tobramycin) isolates: Escherichia coli; Pseudomonas cepacia; Staphylococcus aureus; and Haemophilus influenzae. Tosufloxacin MICs for 50 and 90% of isolates of standard P. aeruginosa were 0.5 and 2.0 mg/liter, for resistant P. aeruginosa they were 4.0 and greater than 16.0 mg/liter, for E. coli they were less than or equal to 0.016 mg/liter, for P. cepacia they were 4.0 and 8.0 mg/liter, for S. aureus they were 0.063 and 0.063 mg/liter, and for H. influenzae they were less than or equal to 0.016 and 0.032 mg/liter, respectively. Tosufloxacin activities against standard and resistant strains of P. aeruginosa were similar to those of comparative quinolones. Against E. coli, tosufloxacin activity was similar to those of other quinolones. Against S. aureus, tosufloxacin activity was similar to those of trimethoprim-sulfamethoxazole and cephalexin, but tosufloxacin was more active than other agents. Against H. influenzae, tosufloxacin activity was similar to those of other quinolones. There was minor diminution of activity at pH 8.2 but major diminution of activity at pH 5.2 and at inoculum sizes of greater than or equal to 10(7) CFU/ml. Activity was unaffected by sputum but was enhanced by serum and by the omission of cation supplementation. Tosufloxacin has consistent activity against common cystic fibrosis pathogens. Its high degree of activity against S. aureus with activity maintained against P. aeruginosa and other gram-negative bacteria of interest suggests that further in vitro studies and assessment of activity in in vivo models of cystic fibrosis pulmonary infections are warranted.

4-Quinolones

Meningococcal meningitis in children.

Forty-four cases of meningococcal meningitis in children at one hospital between 1971 and 1975 inclusive were studied to document the course and complications of this disease in children in the current therapeutic era. The mortality was 5%. Of the 41 survivors 76% were healthy 1 to 5 years after the episode of meningitis. Permanent severe sequelae (facial palsy, optic atrophy and ptosis) were seen in three (7%) of the survivors, and mild hearing loss, hyperactivity and nervousness were noted in seven (17%). Electroencephalography was not useful in determining management or prognosis. Both the mortality and the frequency of early and late complications among the survivors were lower than those reported from earlier studies.

Adolescent

Penicillin-insensitive pneumococci. Case report and review.

Infections due to pneumococci with decreased susceptibility (or resistance) to penicillin have been infrequently recognized. Our experience and that of others suggest that (1) penicillin susceptibility testing of significant pneumococcal isolates should become routine; (2) penicillin may not be adequate therapy for CNS infections due to pneumococci whose penicillin minimal inhibitory concentration is greater than 0.1 microgram/ml; and (3) long-term penicillin "prophylaxis" may be inappropriate in the splenectomized patient in areas where these organisms are prevalent.

Child