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Biomedical subjects

M I Marks

Publications and source records attributed to M I Marks.

At least 55 records · Page 3Linked to original sources
PubMed1986

Aztreonam therapy for serious gram-negative infections in children.

Fifty-nine children were enrolled in an open trial of aztreonam, a monocyclic beta-lactam, therapy for serious gram-negative infections. Thirty-six infections were microbiologically evaluable and received five or more days of therapy. Patients' ages ranged from 3 days to 12 years, and diagnoses included pyelonephritis or cystitis (20), deep soft tissue or joint infection (seven), septicemia (four), pneumonia (three), peritonitis, and epiglottitis. Causative bacteria included Escherichia coli and other Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus influenzae. The standard regimen was 30 mg/kg every six or eight hours intravenously. All isolates were aztreonam-susceptible and were eradicated during therapy. Two patients had microbiologic relapses: a patient with Salmonella choleraesuis meningitis who was initially treated for only ten days and a patient with E coli pyelonephritis. Clinical cure was achieved in 31 of 36 children. Pharmacokinetic studies performed in six children demonstrated no difference in serum concentrations or pharmacokinetic variables between day 1 and day 7 of therapy. Although several patients had transient eosinophilia (eight), elevated levels of aminotransferase (seven), or thrombocytosis (ten), no clinically significant adverse effects were noted. In this initial, uncontrolled study, aztreonam was effective and safe in the treatment of a variety of serious gram-negative infections in children.

Aztreonam↗
PubMed1986

Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial.

In a multicenter randomized trial, 107 children with bacterial meningitis were initially given either cefuroxime or ampicillin plus chloramphenicol. Patients were alternately assigned to 7- or 10-day courses of the designated antimicrobial regimen. CSF isolates included Haemophilus influenzae type b (89, of which 25% were beta-lactamase positive), Streptococcus pneumoniae, and Neisseria meningitidis. Although mean CSF bactericidal titers against Haemophilus isolates were 1:6 in each treatment group, H. influenzae was cultured from CSF in four of 39 patients receiving cefuroxime, 24 to 48 hours after initiation of therapy, compared with none of 40 patients given ampicillin plus chloramphenicol (P = 0.11). Clinical cure rates were similar (95%); one death occurred in each group. One child given cefuroxime had persistent meningitis after 5 days of therapy, and mastoiditis with secondary bacteremia developed in one on day 10. Three patients had relapse or reinfection. One patient who received cefuroxime for 10 days had a relapse of epiglottitis 17 days later, and of the patients given ampicillin plus chloramphenicol, one had a relapse of meningitis 1 week after 7 days of therapy, and bacteremia developed in one 42 days after completion of 10 days of therapy. No increase in either in-hospital complications or relapses occurred with a 7-day treatment course. Proof of the equivalence of the antibiotic regimens and the efficacy of 7-day courses of treatment, as well as the consequences of delayed CSF sterilization, will require additional investigation.

Adolescent↗
PubMed1986

Comparative analysis of Haemophilus influenzae type b and Escherichia coli J5 lipopolysaccharides.

Haemophilus influenzae type b (HIB) and Escherichia coli J5 (J5) lipopolysaccharides (LPS) were examined to explore the basis of previously observed cross-protection. HIB-LPS and J5-LPS contained ketodeoxyoctonate, glucose, glucoheptose and glucosamine as common carbohydrate moieties, and laurate, myristate, beta-hydroxymyristate and palmitate as common fatty acids, although in different ratios. J5-LPS was five times more lethal than HIB-LPS for chick embryos. Weak serological cross-reactivity was observed by haemagglutination and two-dimensional immunoelectrophoresis. No significant cross-reactivity was demonstrated by enzyme-linked immunosorbent or toxicity-neutralisation assays. The cross-reactivity observed between HIB-LPS and J5-LPS was probably due to common components in the core glycolipid.

Animals↗
PubMed1986

Pharmacokinetics of single-dose oral ciprofloxacin in patients undergoing chronic ambulatory peritoneal dialysis.

The prevention and treatment of peritonitis in patients undergoing peritoneal dialysis is often complicated by several factors, including nephrotoxicity, requirement for hospitalization, parenteral antibiotic therapy, and infection caused by resistant microorganisms. Ciprofloxacin, a new carboxyquinolone derivative, may offer the advantages of oral administration, a broad spectrum of antibacterial activity, and safety for the management of these patients. The pharmacokinetics of ciprofloxacin in serum and peritoneal fluid of eight adult patients undergoing chronic ambulatory peritoneal dialysis (CAPD) were investigated. Each patient ingested a single 750-mg dose of ciprofloxacin, and drug concentrations were measured by high-pressure liquid chromatography in serum and peritoneal fluid for 48 h after the dose. Serum concentrations reached a mean peak of 3.6 micrograms/ml 1 to 2 h after the oral dose. The mean terminal serum half-life was 16.8 h, and the mean peritoneal fluid/serum concentration ratio was 0.64. The mean peak ciprofloxacin concentration in peritoneal fluid was 1.3 micrograms/ml, and the bioactivity of the drug in peritoneal fluid was confirmed. These data indicated that therapeutic concentrations of ciprofloxacin against bacterial pathogens commonly associated with peritonitis in CAPD patients may be achievable in the peritoneal fluid after oral administration to patients undergoing CAPD. In addition, the pharmacokinetic data provide guidelines for further clinical studies of oral ciprofloxacin in CAPD patients.

Adult↗
PubMed1986

Single-dose pharmacokinetics of imipenem-cilastatin in pediatric patients.

The single-dose pharmacokinetics of two dosages of imipenem-cilastatin (1:1), 10 and 25 mg/kg, were studied in ten children. Plasma concentrations, half-lives, and areas under the curve of both imipenem and cilastatin was significantly greater at the 25 mg/kg dosage but the half-lives and clearances of the two drugs were similar to each other only at the larger dose. After a 25 mg/kg dose, the mean peak and trough (6 hr) plasma concentrations of imipenem were 78.8 and 0.68 micrograms/ml, respectively, and the half-lives of imipenem and cilastatin were 1.12 and 0.97 hr, respectively. Urinary excretion of imipenem was 43-47% during the 6 hr following administration of either dosage. No clinical or laboratory toxicity was noted. A 25 mg/kg dose of imipenem-cilastatin maintains serum concentrations of imipenem above the minimum inhibitory concentration (MIC) of potential pathogens for 4-6 hr and seems appropriate for multiple-dose studies. Our data suggest that a minimum dosage, greater than 10 mg/kg, of cilastatin may be required to prolong the half-life of imipenem to adult values.

Child↗
PubMed1985

Age-related prevalence of human serum IgG and IgM antibody to the core glycolipid of Escherichia coli strain J5, as measured by ELISA.

Administration of antibody to Escherichia coli strain J5 reduces mortality in patients with gram-negative septic shock. Limited evidence suggests that this antibody is present in the serum of healthy individuals and deficient in persons with malignancy; however, the age-related prevalence of serum antibody to strain J5 in normal subjects is unknown. We developed an ELISA method to measure IgG and IgM antibody to purified J5 lipopolysaccharide (LPS) in sera from 33 maternal-newborn cord pairs, 40 neonates, and 253 individuals aged from one day to twenty years. Reciprocal geometric mean titers for serum antibody to strain J5 LPS were as follows: maternal-IgG, 12.3; IgM, 174; one month old or less-IgG, 8.3; IgM, 5.6; one to 24 months old-IgG, 10.5; IgM, 44.7; greater than 24 months old -IgG, 16.2; IgM, 200. We conclude that human serum antibody to J5 LPS is predominantly IgM and that it is usually present by two years of age. The ELISA method should provide a valuable tool in studying the relation of core glycolipid antibody to immunity and therapy of gram-negative bacterial infections.

Adolescent↗
PubMed1985

Low frequency of bacterial resistance to enoxacin in vitro and in experimental pneumonia.

The tendency for bacteria to develop resistance to enoxacin (Cl-919, AT-2266), a new oxyquinolone derivative, was investigated in vitro and in vivo. The mutation frequencies of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Salmonella sp., and Haemophilus influenzae to enoxacin, norfloxacin, nalidixic acid, tobramycin, cephalexin, cefotaxime, ampicillin, azlocillin, oxacillin, and ticarcillin were determined by plating large numbers of organisms onto antibiotic-containing agar. Enoxacin resistance developed infrequently. For example, the mutation frequency of Ps. aeruginosa in the presence of enoxacin was 1 in 2.8 X 10(9) cells as compared to 1 in 1.1 X 10(6) for nalidixic acid. The increase in MIC after serial transfer through increasing concentrations of enoxacin ranged from 8-fold for Ps. aeruginosa and Staph. aureus to 256-fold for H. influenzae. Rats with chronic Ps. aeruginosa pneumonia were given subtherapeutic doses of enoxacin daily for ten weeks. Two rats were sacrificed weekly and the homogenized lungs were cultured on agar containing 5 mg/l of enoxacin and on antibiotic-free agar. No organisms resistant to 5 mg/l of enoxacin were recovered. No increase in the minimum inhibitory concentration of enoxacin for the infecting organism was seen.

Animals↗
PubMed1985

In vitro antibacterial activities of antibiotics against Pseudomonas aeruginosa in peritoneal dialysis fluid.

Intraperitoneal antibiotics are used to treat Pseudomonas aeruginosa peritonitis, a serious complication of continuous ambulatory peritoneal dialysis. However, P. aeruginosa killing is often inefficient despite low MBCs. Broth dilution MIC/MBC and time kill curves of tobramycin, amikacin, netilmicin, azlocillin, piperacillin, ceftazidime, cefsulodin, and ciprofloxacin were determined in peritoneal dialysis fluid (PDF), buffered PDF, fluid recovered from patients on continuous ambulatory peritoneal dialysis (RPF), and cation-supplemented Mueller-Hinton broth. MBCs of all antibiotics were 8 to 16 times greater in PDF and RPF than in Mueller-Hinton broth or buffered PDF. Use of the time kill curve technique and Mueller-Hinton broth showed that aminoglycosides killed greater than or equal to 99.9% of P. aeruginosa at 1 h, ciprofloxacin killed greater than or equal to 99.9% at 2 h, and beta-lactams killed greater than or equal to 99.9% at 6 h. In contrast, killing was not demonstrated in PDF by any drug at 6 h and by aminoglycosides only at 24 h. Bactericidal activity was optimal in RPF for ciprofloxacin at 1 h and for aminoglycosides at 2 h; bactericidal activity was not demonstrated in RPF with any beta-lactam (no kill by penicillins; less than 99% kill by cephalosporins). Slow bacterial growth, increased protein binding, and glucose concentrations and other inhibitors may interfere with beta-lactam activity in RPF. These considerations and reported clinical failures and toxicity of aminoglycoside therapy warrant further study of quinolones and drug combinations in P. aeruginosa peritonitis.

Anti-Bacterial Agents↗
PubMed1985

In vitro activity of BMY-28142 against pediatric pathogens, including isolates from cystic fibrosis sputum.

The antibacterial activity of BMY-28142, a new aminothiazole cephalosporin, was measured by standardized broth microdilution and agar dilution methods against 450 gram-positive and gram-negative bacteria isolated from pediatric infections, including acute pulmonary exacerbations of cystic fibrosis. BMY-28142 activity was compared with that of aminoglycosides, beta-lactams, chloramphenicol, trimethoprim-sulfamethoxazole, vancomycin, and clindamycin. The activity of BMY-28142 in combination with other antimicrobial agents against Pseudomonas aeruginosa was also determined. Furthermore, the effects of inoculum and pH on BMY-28142 activity were evaluated. BMY-21842 was active against most of the gram-positive and gram-negative isolates, with the exception of methicillin-resistant Staphylococcus aureus and Pseudomonas cepacia. The combination of BMY-28142 with tobramycin was often synergistic, and combinations of BMY-28142 with either polymyxin B or imipenem were usually antagonistic. BMY-28142 antibacterial activity could be adversely affected at extremes of medium pH and by high inoculum densities.

Bacteria↗
PubMed1985

Penetration of latamoxef, cefoperazone and piperacillin into the sputum of patients with cystic fibrosis.

Concentrations of latamoxef, cefoperazone and piperacillin, administered intravenously, were measured in serum and sputum of cystic fibrosis patients with recurrent pulmonary infections, chronically colonized with Pseudomonas aeruginosa. Serum pharmacokinetic data were consistent with prior reports. Peak sputum to peak serum concentrations were approximately 3% for each antimicrobial. However, the more prolonged sputum concentrations of piperacillin were reflected in greater areas under the sputum concentration-time curve and a longer duration above the MIC50 of tested P. aeruginosa strains for that drug.

Adolescent↗
PubMed1985

Synergistic antiviral effects of acyclovir and vidarabine on herpes simplex infection in newborn mice.

277 5-7-day-old white Swiss mice were infected intranasally with Herpes simplex virus type 2 (HSV2) to mimic disseminated herpetic infection in human newborns. The antiviral efficacy of acyclovir, vidarabine and specific antiserum (SAS) alone and in combination was assessed. A significant increase in survival rate (52%) was observed with the combination of acyclovir (80 mg/kg/day) and vidarabine (125 mg/kg/day) compared to either compound (24 and 6%, respectively) when therapy was begun 30 h after infection and continued daily for the next 4 days. Combinations of acyclovir, vidarabine and SAS had less protective effect (8%) than acyclovir with SAS (32%) or vidarabine with SAS (12%). No improvement was observed in survival rate of HSV2-infected mice treated with SAS as compared with controls (0% and 5%, respectively). These results suggest the enhanced antiherpes effect in newborn mice is due to synergism of acyclovir and vidarabine, a combination deserving further evaluation for the treatment of HSV2 infections in humans.

Acyclovir↗
PubMed1985

In vitro activity of ciprofloxacin against pediatric pathogens.

We tested ciprofloxacin, a new quinoline derivative, against 783 gram-positive and gram-negative bacteria utilizing either standardized microbroth or agar dilution methods. Ciprofloxacin activity was compared to that of cephalosporins, enoxacin, norfloxacin, ampicillin, chloramphenicol, tobramycin, ticarcillin, erythromycin and trimethoprim/sulfamethoxazole. MIC90 values (range) in micrograms/ml were: Pseudomonas aeruginosa = 1 (less than or equal to 0.015-8); Staphylococcus spp. = 0.12 (less than or equal to 0.015-1); Enterobacteriaceae = 0.03 (less than or equal to 0.015-1); Haemophilus influenzae = 0.015 (less than or equal to 0.004-0.03); Streptococcus faecalis = 2 (0.5-4). The MIC90 of ciprofloxacin for 98 tobramycin-resistant isolates was 2.0 micrograms/ml. Ciprofloxacin was stable at temperatures of 35, 22, 4, -20 and -70 degrees C for up to 15 weeks. Varying the inoculum from 10(3) to 10(7) colony forming units per ml or the pH from 6-9 resulted in no increase in the MIC. Of the new quinoline derivatives tested, ciprofloxacin demonstrated consistently superior antibacterial activity. Ciprofloxacin may be particularly effective for oral administration in infections requiring prolonged antibiotic therapy, such as bone, joint, and complicated soft tissue infections, and in pulmonary infections in patients with cystic fibrosis.

Anti-Bacterial Agents↗
PubMed1985

Potential of moxalactam and other new antimicrobial agents for bilirubin-albumin displacement in neonates.

The effects of several novel antibiotics on in vitro binding of bilirubin to human serum albumin were investigated. At physiologic bilirubin-albumin ratios and pH values, aztreonam, imipenem, azlocillin, enoxacin and ciprofloxacin did not compete with bilirubin at drug concentrations less than 900 micrograms/mL. Cefoperazone caused an apparent increase in unbound bilirubin only at concentrations greater than 35 microM (330 micrograms/mL). Moxalactam, however, caused a linear increase in unbound bilirubin, greater than that seen with sulfisoxazole, over the entire range of antibiotic concentrations. These results may have implications for the use of these newer antimicrobial agents in neonatal infections.

Anti-Bacterial Agents↗