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Biomedical subjects

M I Marks

Publications and source records attributed to M I Marks.

At least 73 records · Page 4Linked to original sources

A multicenter comparison of related pharmacologic features of cephalexin and dicloxacillin given for two months to young children with cystic fibrosis.

Twenty-one cystic fibrosis patients under 3 years of age were enrolled in an open multicenter study to assess the feasibility of the study design and to compare selected pharmacologic features of cephalexin or dicloxacillin administered orally for 2 months. Patient tolerance and compliance were significantly less for dicloxacillin (p less than .01 and p less than .001, respectively). Superficial Candida infections were more common in the cephalexin group (p = 0.02), however increased stool frequency and nonspecific diaper rashes were more prevalent in patients receiving dicloxacillin (p less than .05). Staphylococcus aureus was isolated from respiratory secretions after 2 months from two dicloxacillin and no cephalexin patients. Areas under the curve and peak serum concentrations were higher for cephalexin (p less than .05 and p = .02), but antistaphylococcal activity in serum was higher for dicloxacillin (p less than .05) due to a lower mean MIC compared to cephalexin. Deep pharyngeal plus routine throat culture yielded more pathogens than either method alone. Express mail and central processing of respiratory specimens was efficient for most organisms, however there was some loss of Streptococcus pneumoniae and Haemophilus influenzae. Cephalexin was associated with better patient acceptance and compliance despite higher rates of superficial fungal infections as compared to dicloxacillin. Cephalexin, routine bacteriologic throat swabs processed locally or centrally, mail-in urine compliance assessment and a multicenter design are feasible components for a long-term prospective evaluation of antibiotic prophylaxis in patients with cystic fibrosis.

Administration, Oral↗

Hemophilus influenzae type b meningitis in infant rabbits. Pathogenesis and therapy.

A model of human Hemophilus influenzae type b meningitis was developed in infant rabbits infected intranasally. The pathogenesis and course resembled that in human beings; bacteremia was followed by meningitis with a high mortality. Pretreatment of the nasopharyngeal mucosa with 0.5% trypsin or normal saline significantly increased the rate of bacteremia. Death was age related. Intranasal challenge with type f and nontypeable H influenzae was associated with transient bacteremia. Our results suggest that factors on the respiratory tract epithelial cell surface influence colonization and infection with H influenzae type b and confirm the importance of other host and parasite factors. Intravenous aztreonam resulted in a peak CSF concentration that was 6% to 7% of the serum concentration in infected meninges but only 2% to 3% in normal meninges. Aztreonam reduced mortality in established H influenzae type b meningitis from 88% in untreated animals to 9%.

Animals↗

Bacterial meningitis in infants and children.

Bacterial meningitis of infants and children exact a major toll worldwide. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis continue to be the major causes, and efforts to reduce the incidence of this disease have had limited success. Major advances in rapid diagnosis, such as antigen detection, have occurred over the past several decades; however, Gram stain, cytologic examination and culture of the CSF remain the most reliable means of making an etiologic diagnosis. Despite shifts in bacterial susceptibilities to commonly used antibacterial agents, penicillin, ampicillin and chloramphenicol remain effective therapy for the vast majority of cases, although newer cephalosporin derivatives may be required to avoid the toxicities of chloramphenicol and to effectively treat selected bacteria that have developed resistance to these more classical antibiotics. The prognosis for bacterial meningitis in infants and children remains guarded because of late diagnosis and the severity of the disease. Major reductions in the incidence of the disease will depend on definition of high-risk populations and application of appropriate preventions.

Anti-Bacterial Agents↗

Moxalactam therapy of Haemophilus influenzae type b meningitis in children.

Thirty-four children with Haemophilus influenzae type b meningitis were given prospectively either moxalactam (200 mg/kg/day) or ampicillin (400 mg/kg/day) plus chloramphenicol (75 mg/kg/day). One patient in each group died. The mean duration of fever, clinical response, sequential cerebrospinal fluid findings, and incidence of neurologic sequelae were similar between groups. Moxalactam cerebrospinal fluid bioactivity was significantly greater than that of ampicillin or chloramphenicol throughout therapy. Neutropenia, liver enzyme abnormalities, and diarrhea were not significantly different. In eight of 11 patients given moxalactam (versus one of 14 controls) there was complete elimination of gram-negative aerobic flora in the stools by day 10 (P = 0.002); however, none acquired Clostridium difficile. Moxalactam in effective therapy for H. influenzae type b meningitis.

Ampicillin↗

In vitro antimicrobial activity of aztreonam alone and in combination against bacterial isolates from pediatric patients.

We examined 134 pediatric clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, and gram-positive cocci for susceptibility to aztreonam alone and in combination with seven other antibiotics. All 98 gram-negative isolates were susceptible to aztreonam with similar inhibitory and bactericidal activity. Combinations of aztreonam with cefoxitin, ampicillin, or clindamycin were generally indifferent or additive. Synergism was occasionally seen against enteric organisms with aztreonam plus cefoxitin or clindamycin. Combinations of tobramycin and aztreonam were synergistic (62%) against P. aeruginosa; aztreonam plus piperacillin or ticarcillin was additive. Aztreonam did not affect the activity of nafcillin against Staphylococcus aureus, or of ampicillin against species of Streptococcus group B or D. Antagonism was seen only with aztreonam plus cefoxitin against Enterobacter species, but not at clinically significant concentrations. Several combinations of antibiotics with aztreonam should be appropriate for initial therapy of infections in children without major risks of antibacterial antagonism.

Anti-Bacterial Agents↗

Single-dose pharmacokinetics of aztreonam in pediatric patients.

Single intravenous doses (30 mg/kg) of aztreonam, a novel monobactam antibiotic, were administered to 29 children from 2 days to 11 years old. Serum, urine, and, when possible, cerebrospinal fluid samples were analyzed by high-pressure liquid chromatography and microbiological methods. The concentration of aztreonam in serum 15 min after drug administration was approximately 100 micrograms/ml in all age groups. The elimination half-life varied inversely, and the clearance from serum varied directly, with age. Aztreonam pharmacokinetics in 2- to 12-year-olds were similar to those in adults. The concentration in urine was high and prolonged, with potentially therapeutic concentrations still present 12 to 24 h after infusion in all age groups. Penetration into cerebrospinal fluid averaged 17.3% in children with inflamed meninges. Standard clinical and laboratory measurements revealed no untoward reactions. The 30-mg/kg dose of aztreonam produced potentially therapeutic concentrations in serum, urine, and cerebrospinal fluid. A dosage schedule of every 6 to 8 h in older children and every 8 to 12 h in neonates is suggested for multiple-dose clinical trials.

Age Factors↗

Haemophilus influenzae infections. The impact of resistance on the use of aminopenicillins and other antimicrobials in outpatient therapy.

The clinical manifestations of Haemophilus influenzae infections and the growing problem of ampicillin-resistant strains are reviewed. Despite the fact that approximately 25 percent of H. influenzae are resistant to penicillin and ampicillin, oral aminopenicillins (ampicillin, amoxicillin, bacampicillin, and cyclacillin) are commonly used for the outpatient management of these infections. The characteristics of these drugs and the rationale for their use are discussed and compared with alternative approaches to therapy. This subject requires periodic review in consideration of the increasing prevalence of ampicillin and multiple antibiotic resistance among H. influenzae isolates.

Adult↗

Antibiotic therapy of fulminant E. coli K1 sepsis in infant rabbits.

A model of overwhelming E. coli K1 sepsis and early meningitis was developed in infant rabbits and used to compare clinical and bacteriologic efficacy of ampicillin, moxalactam, cephalothin and chloramphenicol. Intraperitoneal injection of 10(7) E. coli K1 into 1- or 2-wk-old rabbits produced a rapidly progressive infection which, if left untreated, produced bacteremia in 100% of animals, meningitis in 78%, and mortality in 100%. Therapy was initiated 4 h after ip infection at which time mean bacterial concentration (log10 CFU/ml) ranged from 4.4-4.8 in the blood and from 1.8-2.3 in the cerebral spinal fluid (CSF). Pre-treatment frequency of bacteremia (100%) and meningitis (17-23%) was similar for all experimental groups. Antibiotic concentrations in blood and CSF 2 h after a dose exceeded the E. coli minimum inhibitory concentration with the exception of CSF cephalothin, which was undetectable. Moxalactam, ampicillin, and chloramphenicol significantly reduced the incidence of bacteremia and meningitis relative to cephalothin or saline controls (P less than 0.02). Mortality rates among the former three groups were high (64-82%) but significantly less than in saline or cephalothin-treated rabbits (100%). In this neonatal model of fulminant sepsis with early meningitis, moxalactam provided no therapeutic advantage over ampicillin or chloramphenicol.

Animals↗

Leiomyoma presenting as prolonged fever, anemia, and thrombocytosis.

The manifestations of leiomyoma of the large bowel in a 2-year-old boy included prolonged fever, anemia, and thrombocytosis. This parallels the previously reported case in an adult. Awareness of these features may suggest the diagnosis in future patients, and thereby offer opportunities to study the pathogenesis of these abnormalities before surgery.

Anemia↗

Erythromycin in treatment of Campylobacter enteritis in children.

Erythromycin ethylsuccinate therapy was compared with no treatment in a randomized, prospective trial of treatment of Campylobacter enteritis in infants and children. Patients received either erythromycin ethylsuccinate (N = 15), 40 mg/kg/day every six hours, for seven days or no treatment (N = 12). The mean age (5.5 v 3.7 years), sex ratio, and mean duration of illness before admission to study (5.5 v 6.4 days) of the two groups were similar. No difference was noted in the mean days to resolution of diarrhea (3.2 v 3.8 days). However, the mean duration of bacterial shedding was shorter in the treatment group (2.0 days) compared with the group without treatment (16.8 days). Bacteriologic relapse occurred in one patient in the treatment group, and three relapses occurred in the group without treatment. Two secondary cases occurred among household contacts, one in each group.

Campylobacter Infections↗

Ceftriaxone therapy in pediatric patients.

Twenty-six children, aged 2 months to 15 years, were treated with intravenous ceftriaxone sodium, 37.5 mg/kg every 12 hours, for an average of seven days. Clinical and microbiologic cures occurred in 19 of 21 patients, from whom bacterial pathogens were cultured. Ceftriaxone was not effective in treating an 18-month-old infant with periorbital cellulitis caused by relatively resistant Staphylococcus aureus. A relapse occurred in a 2-month-old infant with meningitis caused by ceftriaxone-sensitive Salmonella. Eleven patients had transient diarrhea, superficial candidiasis developed in ten patients, and one patient experienced skin flushing during administration of the antibiotic. Transient asymptomatic laboratory abnormalities were detected in 15 patients; nine patients had elevated serum concentrations of transaminases or bilirubin, 11 had thrombocytosis, three experienced eosinophilia, and one had thrombocytopenia. Transient suppression of normal flora of the intestine occurred in 21 patients. Side effects were not serious enough to warrant discontinuing ceftriaxone therapy in any patient.

Adolescent↗