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Biomedical subjects

B R Meyers

Publications and source records attributed to B R Meyers.

At least 19 recordsLinked to original sources

Pharmacokinetics of ampicillin-sulbactam in healthy elderly and young volunteers.

The pharmacokinetics of ampicillin-sulbactam in elderly subjects (65 to 85 years; group 3, n = 8), compared with those in middle-aged (41 to 64 years; group 2, n = 8) and younger (20 to 40 years; group 1, n = 8) subjects, were investigated. A single 2-g dose of ampicillin combined with 1 g of sulbactam in 60 ml of intravenous solution was administered to each subject over a 30-min period. Blood and urine samples were taken at baseline and serially over an 8.5-h period following the infusion. Ampicillin and sulbactam concentrations were assayed by high-performance liquid chromatography on a reversed-phase C-8 column. The mean levels in serum of both ampicillin and sulbactam were significantly higher for samples from group 3: for ampicillin from 1 through 8.5 h, and for sulbactam for the same time interval except at 5.5 h (P less than or equal to 0.05). The mean urinary excretion of both ampicillin and sulbactam was lowest, and urinary concentrations were highest in group 3. The areas under the serum drug concentration-time curve, the half-lives, and the maximum concentrations in serum were greatest, while the total clearance was lowest, for group 3 for both ampicillin and sulbactam. These results are consistent with a prolongation of antimicrobial activity of ampicillin-sulbactam in the elderly compared with that in younger subjects.

Adult

Bloodstream infections in the elderly.

PURPOSE: Bacteremia in the elderly is associated with a different clinical course and a higher mortality rate when compared with that in younger age groups. In order to examine these issues in the aged, we reviewed the clinical course and factors involved in the outcome of 100 episodes of bloodstream infections in patients over 65 years of age. PATIENTS AND METHODS: The hospital records of all patients over 65 years of age at The Mount Sinai Hospital with a positive blood culture result during the period October 1984 to October 1986 were reviewed. Place of residence before hospital admission, site of acquisition of infection, source of bloodstream infection, and microorganism were analyzed. Antimicrobial therapy was defined as appropriate if initial therapy included one agent to which the isolate was sensitive, or inappropriate if the isolate was resistant. The following factors affecting survival were analyzed: age, sex, underlying diseases, clinical parameters on admission, white blood cell count, mental status, source of infection, microorganism isolated, antibiotic toxicity, and appropriate versus inappropriate antibiotic therapy. RESULTS: Most patients were female (63 percent), were febrile (90 percent), had an altered mental status (52 percent), and had a neutrophilic response (61 percent). Eighty-three percent of patients were admitted from the community (home), 14 percent were from long-term-care facilities, and 3 percent were transferred from other hospitals. Fifty percent of infections were nosocomial, and 44 percent were community (home and nursing home)-acquired. Gram-negative organisms accounted for 60 percent of isolates, with Escherichia coli (22 percent) and Klebsiella species (11 percent) predominating; 30 percent were gram-positive organisms, with Staphylococcus aureus (13 percent) and Streptococcus faecalis (10 percent) the most common. The overall survival was 60 percent; the survival rate was 65.8 percent for community-acquired (home) bacteremia, 75 percent for nursing home-acquired bacteremia, and 52.8 percent for hospital-acquired bacteremia. Survival for gram-negative isolates was 65 percent, versus 51.7 percent for gram-positive isolates. Survival was greatest in patients whose source of bacteremia was either the genitourinary tract (70 percent) or an intravascular device (78 percent) and poorest in patients with lower respiratory tract source (42 percent); all three patients with endocarditis died. Increased survival was observed in patients treated with appropriate antimicrobial agents regardless of age, source of infection, or bloodstream isolates.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged

Clinical pharmacokinetics of antibacterial drugs in the elderly. Implications for selection and dosage.

A review of the clinical pharmacokinetics of antibiotics in the healthy elderly reveals that for most compounds a decrease occurs in renal clearance (associated with age-related decreases in renal function), as well as a prolonged half-life and increased area under the plasma concentration-time curve. These changes are amplified in the sick infected elderly. It is important that the treating physician be aware of the potential side-effects of antimicrobial agents, and whenever possible choose those which are associated with the least adverse effects. Individual patient variability, including underlying diseases and other prescribed medications, must be taken into account when dosage is selected. beta-Lactam compounds have a remarkable safety record: specifically in the elderly, their therapeutic/toxic ratio is much higher than that observed with aminoglycosides. Regimens for this class of drugs in the elderly should maintain antibiotic concentrations above the minimum inhibitory concentrations for maximum efficacy. In the treatment of elderly patients, it is suggested that dosage and interval be based on estimated or measured creatinine clearance. Usually, for drugs that are excreted primarily by the kidney (i.e. amino-glycosides, beta-lactams and quinolones), dosage intervals must be increased when there is an associated fall in creatinine clearance. The pharmacokinetic parameters suggest that as an alternative to increasing dosage interval the usual dose may be decreased, but further studies are necessary for confirmation.

Aged

Central nervous system infections in the elderly.

Review of records of patients aged 65 years and older admitted to The Mount Sinai Hospital, New York, NY, during the period from 1970 through 1985 revealed 57 episodes of central nervous system infections, including 50 meningitides, 5 brain abscesses, 1 subdural empyema, and 1 epidural abscess. Predisposing conditions were present in 17 patients with meningitis, and concurrent infections occurred in 19 patients. Streptococcus pneumoniae accounted for 43% of all isolates; 25% were gram-negative organisms. Of the patients in this sample, fever was present in 100%, meningismus was present in 58%, and change in mental status was present in 86%. Sixty-five percent of patients with meningitis survived; increased mortality was associated with altered mental status, inappropriate initial antibiotic therapy, and hypoglycorrhachia. Delay in diagnosis, underlying disease, and bacteremia did not significantly alter outcome. All patients with focal infections presented with localizing signs and all survived.

Aged

Infectious diseases in the elderly: an overview.

The elderly represent the fastest growing portion of the population. Aspects of the normal aging process combined with chronic diseases place the elderly at increased risk for infection. This overview will discuss the most common infectious diseases in the elderly and some approaches to the prevention and treatment of these infections.

Aged

Use of antimicrobial agents in a university teaching hospital. Evolution of a comprehensive control program.

A comprehensive control program for utilization of anti-microbial agents in a large tertiary university teaching hospital regulates both dosage and duration of therapy and requires the prior approval of an infectious disease specialist for utilization of restricted antimicrobial agents. Benefits of the program include more cost-effective antimicrobial therapy and increased physician education in the use of these drugs. Gross savings in pharmacy costs for antibiotics during the first year of the program (1985) amounted to +483,032 for an average monthly savings of +40,252. Gross savings for 1986 were +211,786 with monthly savings of +17,648. The control of the use of one agent may lead to overuse of another agent. Antimicrobial prescribing patterns of physicians are quickly influenced by changing regulations of the program. An ongoing surveillance and review program of in-hospital utilization of antimicrobial agents is necessary to maintain effective and flexible controls.

Administration, Oral

Malignant external otitis. Comparison of monotherapy vs combination therapy.

Twenty patients with adult-onset diabetes mellitus and malignant external otitis (MEO) were treated at the Mount Sinai Medical Center, New York, over a seven-year period (August 1976 to October 1983). A retrospective analysis compared patients who received an antipseudomonal cephalosporin as monotherapy (group A) with those who received conventional antipseudomonal therapy (group B). Pseudomonas aeruginosa was isolated in all patients. Differences (group B less than group A) included insulin dependence, underlying vascular disease, total number of cranial nerve palsies or paresis, and surgical procedures. The overall clinical outcome was similar in both groups; 64% of patients in group A (7/11) and 70% in group B (7/10) were cured at a follow-up period of five to 57 months. A more favorable outcome was found in patients with less extensive infection in both groups. Monotherapy compared favorably with conventional antipseudomonal therapy for the treatment of patients with MEO and moderate infection.

Aged

Pharmacokinetic properties of mezlocillin in ambulatory elderly subjects.

Twelve healthy ambulatory elderly subjects (mean age, 73-78 years) randomly received either a 4-g or 5-g dose of mezlocillin intravenously. One week later the regimen was repeated and patients crossed over to the other dose. Peak serum concentrations were 165 mg/L and 281 mg/L for the 4-g and 5-g doses, respectively. For both doses, differences in t1/2 beta (1.32 hr vs 1.13 hr), AUC (275 mg.hr/L vs 403 mg.hr/L), CL (207 mL/min vs 174 mL/min), CLR (59 mL/min vs 45 mL/min), CLNR (152 mL/min vs 130 mL/min) were not statistically significant. The differences in Varea (22.4L vs 168.8L, P less than or equal to .01) and Cmax (216.6 mg/L vs 317 mg/L, P less than or equal to .05) were statistically significant. Comparison with pharmacokinetic parameters obtained in younger subjects following the 5-g dose reveals that in the elderly the AUC, Varea, and CLNR are higher whereas the CL and CLR are lower. The elderly demonstrated an increase in nonrenal clearance compared with young subjects that is not fully compensatory. The increased AUC in the elderly group suggests that clinical studies examining mezlocillin doses and dose intervals in the treatment of serious infections are warranted in infected elderly patients.

Aged

Pharmacokinetics of cefoperazone in ambulatory elderly volunteers compared with young adults.

Two groups of 10 healthy ambulatory subjects, i.e., a group of 10 persons less than or equal to 30 years of age (mean age, 27.6 years) and a group of 10 persons greater than or equal to 65 years of age (mean age, 70 years), were randomized in a single-trial crossover design to receive 1 and 2 g of cefoperazone with a 1-week washout between doses. The elderly subjects had both decreased estimated creatinine clearances and decreased albumin concentrations in serum. Cefoperazone concentrations in serum of elderly persons were significantly higher at each interval from 30 min to 6 h for the 2-g dose. Compared with that in younger persons, the total clearance in elderly subjects was significantly lower for both the 1- and 2-g doses, the renal clearance was significantly lower for the 2-g dose, and the area under the curve was significantly higher for the 2-g dose in the elderly persons. The half-life at beta phase was higher in the elderly persons at both the 1- and 2-g doses but not significantly so. Changes in total clearance and area under the curve and higher levels in serum in the elderly persons suggest a longer duration of antimicrobial activity in this age group.

Adult

Pulmonary toxoplasmosis in AIDS.

In contrast to toxoplasmosis in non-AIDS immunocompromised hosts, AIDS patients rarely have been reported to be infected at extra-CNS sites. We report the case of a 45-year-old homosexual male with AIDS who presented with pneumonitis caused by Toxoplasma gondii following a previous illness consistent with CNS toxoplasmosis.

Acquired Immunodeficiency Syndrome

Pharmacokinetics of mezlocillin in patients with hepatobiliary dysfunction.

The pharmacokinetics of mezlocillin were investigated in 26 patients with alcoholic liver disease. Serum concentrations of mezlocillin were measured following intravenous administration of 3 g doses over 30 min. The mean peak serum concentration (+/- standard deviation) of mezlocillin at the end of infusion was 138.8 +/- 55.7 mg/l and the mean terminal half-life (T 1/2 beta) was 2.10 +/- 0.9 h. The 24 h urinary recovery of mezlocillin was 35.4 +/- 12.4% of the administered dose. Serum clearance was found to be inversely correlated with alkaline phosphatase and with total bilirubin. The T 1/2 beta was related to the following clinical measurements: age, SGOT and prothrombin time. This relationship suggests it may be prudent to adjust the dosage and the dosage interval of mezlocillin in patients with hepatobiliary dysfunction.

Adult

Comparative toxicities of third-generation cephalosporins.

Data on the adverse effects experienced by 2,539 patients who received ceftazidime were compared with adverse effects reported with cefoperazone, cefotaxime, ceftizoxime, and moxalactam. There were 216 such reactions among the ceftazidime-treated patients; 158 patients (6.2 percent) had reactions that were possibly or probably drug-related. The clinical and laboratory safety profile of ceftazidime in regard to renal, hepatic, hematopoietic, and hemostatic parameters compared favorably with that of other third-generation cephalosporins. An increased serum creatinine level was observed in 0.8 percent of ceftazidime-treated patients, an increased blood urea nitrogen level in 1.6 percent, hepatic abnormalities in approximately 6 percent, diarrhea in 1.3 percent, pseudomembranous colitis in 0.12 percent, increased prothrombin time in 0.5 percent, and clinical bleeding in none. The incidence of colonization (3.8 percent) and superinfections (3 percent) associated with ceftazidime therapy was comparable to rates with other agents in this class.

Adolescent

Comparative in vitro activity of coumermycin against methicillin-resistant Staphylococcus aureus.

Coumermycin was the most active agent in vitro against methicillin-resistant Staphylococcus aureus when compared with fusidic acid, imipenem, rifampin, trimethoprim-sulfamethoxazole, and vancomycin. The MICs of coumermycin ranged from 0.002 to greater than 4 micrograms/ml and from 0.5 to greater than 4 micrograms/ml for inocula of 10(4) and 10(6) CFU/ml, respectively. The combination of coumermycin with either cephalothin or ciprofloxacin showed some synergy; antagonism was found with gentamicin.

Aminocoumarins

Bacterial sinusitis.

Sinusitis may occur secondary to infectious agents, allergens, or pollutants. Bacteriologic studies carried out from sinus punctures revealed that Streptococcus pneumoniae and Hemophilus influenzae are the most common bacterial pathogens isolated. Staphylococcus aureus and Streptococcus pyogenes are not uncommon pathogens. Complications of sinusitis, including orbital cellulitis, usually are due to infection with Staphylococcus aureus and H influenzae. The recent increase in certain areas of the country of beta-lactamase-producing strains of H influenzae is noted. When the etiology remains to be determined in the patient with acute bacterial sinusitis, initial therapy with an oral cephalosporin seems warranted.

Acute Disease

Pharmacokinetics of amdinocillin in healthy adults.

The pharmacokinetics of amdinocillin (mecillinam) were determined in 10 healthy volunteers. Single doses of 10 and 15 mg/kg of body weight were administered intravenously and intramuscularly in a crossover study. Plasma concentrations of amdinocillin were determined by microbiological assay. Mean peak plasma concentrations were 49 and 87 micrograms/ml after intravenous doses of 10 and 15 mg/kg, respectively. The terminal half-life value of 0.89 h was similar for both doses. After intramuscular injections, the mean concentration of drug in plasma was 26.2 micrograms/ml for the 10-mg/kg dose and 29.6 micrograms/ml for the 15-mg/kg dose, with terminal half-lives of 0.96 and 0.86 h, respectively. The mean apparent volumes of distribution at steady state were 18 and 16 liters/100 kg for the intravenous doses of 10 and 15 mg/kg, respectively. Drug concentrations in plasma at 4 h were above the minimal inhibitory concentrations for gram-negative organisms categorized as susceptible to this drug.

Adult