Mono-and biexponential killing curves for vancomycin over a 2-to 50-p,g/ml concentration range were generated for 11 Staphylococcus aureus isolates and 12 coagulase-negative Staphylococcus species in the logarithmic phase of growth. Nonlinear least-squares regression of the initial growth rate and disappearance were not significantly different for lower or higher concentrations of vancomycin in broth.Interest in vancomycin has increased because of 3-lactam antibiotic resistance among gram-positive cocci. Recently, the disposition of and pharmacodynamic killing by vancomycin and teicoplanin have been characterized (2-5, 13, 17). Several predictive methods that propose the modification of aminoglycoside dosing models by using desired peak concentrations of 30 to 40 ,ug/ml and trough concentrations of 5 to 10 ,ug/ml have been proposed (15,22). Geraci and Hermans (11) recommended trough vancomycin concentrations of 8 to 10 ,ug/ml on the basis of an average MIC of 1 to 1.25 ,ug/ml, which has increased slightly since 1976. Carret et al.(7) described a unique application of a nonlinear regression program that is normally used for pharmacokinetic analysis. Killing curves generated from a range of ciprofloxacin concentrations were tested against Escherichia coli. The killing curves demonstrated a concentration-dependent lag phase in bacterial killing and parallel rate constants (7). The investigators (7) studied the in vitro killing of staphylococci by vancomycin in broth over a concentration range to determine whether any change in killing rate could be attributed to differences in the vancomycin concentration (1, 3, 8-10, 12, 19, 23, 24, 26, 27).Vancomycin hydrochloride (Eli Lilly & Company) was prepared as a stock solution (10 mg/ml) in phosphatebuffered saline (pH 6.0) and was frozen at -70°C in 1.5-ml aliquots. Prepared solutions were assayed every 1 to 2 weeks by using a commercial fluorescence polarization immunoassay (TDx; Abbott Laboratories, North Chicago, Ill.) (25).Staphylococcus aureus isolates were obtained from blood cultures (n = 8), respiratory secretions (n = 2), and a wound abscess (n = 1). Coagulase-negative Staphylococcus isolates were obtained from blood cultures (n = 3), abscess wound cultures (n = 4), pleural fluid culture (n = 1), urine culture (n = 1), coagulase-positive Staphylococcus saprophyticus (n = 1), and Staphylococcus epidermidis ATCC 12228 (n = 1). 50, 30,20,10,8,6,4, and 2 ,ug/ml. A growth control with no added antibiotic solution was also used. All tubes were run in duplicate.Time-kill curves were made for tubes containing bacterial suspensions and the various vancomycin concentrations incubated at 35°C. At 1, 2, 3, 4, 5, 6, 8, and 24 h postexposure, aliquots were diluted in tryptic soy broth (Difco) and plated onto blood agar plates (BBL, Cockeysville, Md.). Aliquots were made by using a clean sterile pipette tip for each tube. The number of CFU per milliliter was determined after 24 h of incubation.Killing curves were analyzed by using PKCALC, a BASIC program containing the curve...

We reviewed the current literature (1980–1990, 1991–1996) concerning drugs associated with anosmia, hyposmia, dysgeusia, parageusia, and ageusia, and the impact of these adverse effects. Case reports of patients with sudden and delayed onset of one of these disorders with evidence for implication of a drug were included. Disturbances of taste and smell among the elderly and chronically ill, including those with thermal injury, decreases interest in eating and secondarily impairs healing of wounds. Mechanisms involved with these sensory disturbances include deposition of silver sulfate in nerves after use of topical agents containing silver, altered influx of calcium and other ions, chelation or depletion of tissue‐bound zinc, disturbed bradykinin catabolism and second messenger synthesis, catabolism, and altered prostaglandin systems. Other mechanisms, particularly prolonged chemosensory disorders after early drug discontinuation, remain unknown.

Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study. Both unbound and total serum vancomycin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay. Ultrafiltrates were obtained by centrifugation at 1000 × g for ten minutes at room temperature and their assay indicated a range in protein binding from 7.9 to 71 percent. The mean protein binding (mean ±SD) was 41.95 ± 14.15 percent. No measurable adsorption of vancomycin onto the ultrafiltration membrane was noted. Orthogonal regression of unbound versus total vancomycin concentrations was described by the equation y=0.597x-0.362 with a correlation coefficient of 0.948.

Release rate constants and disappearance rate constants were determined for three atrial natriuretic peptides consisting of amino acids 1-98 (i.e., proANF 1-98), the midportion of the ANF prohormone consisting of amino acids 31-67 (i.e., proANF 31-67) and amino acids 99-126 (i.e., ANF) after right ventricular pacing at 100, 125, 150, and 180 bpm in six male mongrel dogs. Right atrial and femoral vein blood was obtained at baseline, and at 5, 12, 19, 26, 56, 86, 116, 146, and 206 minutes after right ventricular pacing. Resulting plasma concentration-time data derived parameters were compared. The disappearance rate constants for atrial and femoral venous proANF 1-98 were 0.0144 +/- 0.0087 (X +/- SD) and 0.0175 +/- 0.0075 min-1, respectively (t = 0.6158) and release rate constants were 0.1569 +/- 0.1504 and 0.0670 +/- 0.0393 min-1, respectively (t = 1.8269; P greater than .05). The proANF 31-67 disappearance rate constants were 0.0139 +/- 0.0082 and 0.0148 +/- 0.0132 min-1, respectively (t = 0.1192) and release rate constants were 0.0957 +/- 0.0414 and 0.1984 +/- 0.1762 min-1, respectively (t = 1.4812). The ANF elimination phase disappearance rate constants were 0.0663 +/- 0.0273 and 0.1116 +/- 0.0539 min-1 (t = 2.0923, P greater than .05), respectively, and the release rate constants were 0.1335 +/- 0.0532 and 0.1638 +/- 0.0520 min-1 (t = 0.7878, P greater than .05), respectively. These data indicate that proANF 1-98 and proANF 31-67 circulating beta post-distribution half-lives are approximately 45 minutes whereas beta half-life of ANF is 10 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

A 52-year-old man was admitted to a local hospital with headache, nausea, vomiting, dizziness, photophobia, and confusion after a sudden fall. Progressive changes in neurologic function were noted despite neurosurgical intervention and broad-spectrum antimicrobial coverage. Cerebral spinal fluid (CSF) culture identified Acinetobacter baumannii that was resistant to traditionally recommended therapies of amikacin and imipenem-cilastatin. The organism demonstrated minimum inhibitory concentrations of greater than 32 microg/ml and 8 microg/ml, respectively, for these two agents. Ampicillin 2 g-sulbactam 1 g every 3 hours was administered based on history of therapeutic failure of traditional dosing in our thermal injury population. Repeat CSF cultures after 12 days of ampicillin-sulbactam therapy were negative. After 35 days, the patient's A. baumannii infection was completely resolved. The patient experienced no adverse drug events or toxicity with this high-dosage regimen.