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Biomedical subjects

C W Norden

Publications and source records attributed to C W Norden.

At least 19 recordsLinked to original sources

Pharmacokinetics of cephradine administered intravenously and orally to young and elderly subjects.

The pharmacokinetics of IV and oral cephradine in healthy young male and female volunteers (ages 19 to 25, n = 10) were compared to those of older individuals (ages 65 to 81, n = 9). Subjects received 1 gram of cephradine by a 5-minute intravenous (IV) infusion followed the next day by a 1-gram oral dose. Serial serum and urine samples collected over a period of 12 hours after the dose were analyzed for cephradine concentration by a microbiologic assay. After IV administration, mean serum cephradine concentrations in the elderly group were significantly higher at both 6 hours (1.52 +/- 0.41 mcg/mL) and 8 hours (0.73 +/- 0.22 mcg/mL) than in the young group at 6 hours (0.43 +/- 0.11 mcg/mL). Total systemic clearance was significantly lower (2.64 +/- 0.34 vs. 4.81 +/- 0.59 ml/min/kg) and the elimination half-life was significantly longer (1.71 +/- 0.20 vs 1.12 +/- 0.13 hours) in the elderly group (P = .0001). Systemic cephradine clearance correlated positively with creatinine clearance (r2 = 0.34, P = .0110) and negatively with age (r2 = 0.79, P = .0052). The mean volume of distribution was not significantly different between the two groups. Mean renal clearance was significantly lower in the elderly group (P = .0001), but more than 80% of the dose was excreted in the urine within 6 hours in both groups. After oral administration, the mean peak concentration and time to peak concentration did not differ between groups. The relative oral bioavailability was approximately 94% in both groups. The mean serum concentrations in the elderly were higher at both 6 and 8 hours than in the young group at 6 hours. There were no differences in pharmacokinetic parameters between male and female subjects. Because of reduced cephradine clearance secondary to an age-related decline in renal function, administration of cephradine every 8 hours, rather than every 6 hours, may be sufficient in elderly patients.

Administration, Oral

Treatment of experimental chronic osteomyelitis due to Staphylococcus aureus with ampicillin/sulbactam.

Ampicillin/sulbactam was used for the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Treatment with 200 mg/kg (ampicillin) three times a day sterilized 40% of infected rabbit bones. The results of 4 weeks of treatment with ampicillin/sulbactam for chronic experimental staphylococcal osteomyelitis were comparable to those obtained previously with cephalothin and with oxacillin in previous studies and were not as good as those with clindamycin alone or combination therapy that included rifampin.

Ampicillin

Fatal adult respiratory distress syndrome in a patient with Lyme disease.

A dry cough, fever, generalized maculopapular rash, and myositis developed in a 67-year-old woman; she also had markedly abnormal liver function test results. Serologic tests proved that she had an infection of recent onset with Borrelia burgdorferi, the agent that causes Lyme disease. During a two-month course of illness, her condition remained refractory to treatment with antibiotics, salicylates, and steroids. Ultimately, fatal adult respiratory distress syndrome developed; this was believed to be secondary to Lyme disease.

Aged

Value of needle aspiration in bacteriologic diagnosis of cellulitis in adults.

We prospectively studied 30 adult patients with cellulitis, including many who were hospitalized with significant underlying medical problems. Needle aspiration of both central and leading edge areas of their lesions was performed in an attempt to establish a bacteriologic diagnosis. Potential pathogens were isolated by this technique in only 10% of the patients. Neither site of aspiration was clearly superior in terms of culture yield. Because aspirate Gram stains and cultures so rarely provided useful bacteriologic information, they were seldom helpful in guiding antibiotic selection or in influencing the outcome of treatment in most patients. However, clinical information, as well as results of primary lesion cultures when obtainable, may be used to successfully select therapy in most cases of adult cellulitis. On the basis of our results, needle aspiration may not be justified as a routine diagnostic procedure for all adults with cellulitis, though it may still be useful in selected patients.

Adolescent

In vitro activity of BMY-28100, a new oral cephalosporin.

BMY-28100 is a new orally absorbed cephalosporin whose in vitro activity was compared with that of cefaclor. BMY-28100 was more active against Staphylococcus aureus and Haemophilus influenzae than was cefaclor. In addition, there was only a small rise in MIC50 and MIC90 values for BMY-28100 when the inoculum size was increased 100- or 10,000-fold. In contrast, MIC50 and MIC90 values increased significantly for cefaclor with similar increases in inoculum size. These data suggest that BMY-28100 may be a promising agent to test for oral administration in infections caused by S. aureus and H. influenzae.

Cefaclor

In vitro activity of BMY-28142, a new cephalosporin.

BMY-28142 was compared in vitro with ceftazidime, cefotaxime and cefoperazone and was found to be more active against Pseudomonas aeruginosa and Staphylococcus aureus. Essentially no effect of increasing inoculum size 100-fold was seen-on MICs with BMY-28142 or ceftazidime; some effect was noted with cefotaxime and cefoperazone.

Bacteria

Chronic osteomyelitis caused by Staphylococcus aureus: controlled clinical trial of nafcillin therapy and nafcillin-rifampin therapy.

A controlled trial of treatment of chronic osteomyelitis caused by Staphylococcus aureus compared nafcillin alone with nafcillin plus rifampin for a six-week period. Treatment was well tolerated, the only adverse effect being mild neutropenia in four of 18 patients; no toxicity was observed from rifampin. Eight of ten patients in the combined treatment group had a favorable clinical response (with follow-up of two to four years) as compared to four of eight in the nafcillin group (P = .2). Despite the failure to show a statistically significant advantage of rifampin plus nafcillin, we conclude that the combination, along with appropriate surgery, should be considered for patients with chronic staphylococcal osteomyelitis.

Administration, Oral

Ciprofloxacin as therapy for experimental osteomyelitis caused by Pseudomonas aeruginosa.

Ciprofloxacin, a new carboxyquinoline antimicrobial agent, was compared with tobramycin in the treatment of chronic osteomyelitis due to Pseudomonas aeruginosa in rabbits. Treatment with tobramycin for four weeks was ineffective (94% had positive bone cultures). In contrast, ciprofloxacin administered for four weeks sterilized the bones of all but one (94%) of 18 treated rabbits. Treatment with ciprofloxacin for two weeks was less effective than treatment for four weeks but was more effective than either treatment with tobramycin or no therapy. Two of 10 isolates from rabbits treated with ciprofloxacin for two weeks were susceptible to MICs of ciprofloxacin that were 16- and fourfold greater than the MIC for the parent strain; the other eight isolates remained sensitive to ciprofloxacin with MICs equivalent to that of the parent strain.

Animals

Comparison of techniques for measurement of in vitro antibiotic synergism.

The methods and criteria for testing for synergy were compared with use of 22 strains of Klebsiella pneumoniae and a combination of cephalothin and gentamicin. With the checkerboard technique, the frequency of synergy varied depending on the criterion employed. When the rate of killing of bacteria by antibiotics was measured, results varied depending on the size of inoculum. When the checkerboard and killing-curve techniques were compared, there was poor correlation in terms of the frequency of strains showing synergy. Because clinical observations suggest that treatment of serious infections with combinations of antibiotics found to be synergistic in vitro may enhance survival, standardization of the methods and criteria used to test for synergy should be undertaken.

Anti-Bacterial Agents

Use of quantitative bacteriologic techniques to diagnose catheter-related sepsis.

A case of polymicrobial sepsis occurred in a patient who had a permanent indwelling hyperalimentation catheter. Because it was undesirable to remove the catheter, quantitative bacteriologic techniques were used to determine whether the catheter was the source of sepsis. Blood drawn from a peripheral vein had 25 colonies per milliliter whereas blood drawn through the catheter had more than 10,000 colonies per milliliter. On the basis of these results, the catheter was removed. The catheter tip was found to be infected with the same organisms that were present in the blood. Quantitative bacteriologic techniques may prove useful in diagnosing catheter-related sepsis when it is undesirable to remove the catheter.

Adult

Experimental osteomyelitis. V. Therapeutic trials with oxacillin and sisomicin alone and in combination.

Oxacillin was used alone and in combination with sisomicin in the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Within diseased bone, levels of oxacillin and sisomicin remained higher than the minimal inhibitory concentration for 2 and 6 hr, respectively, after injection of 50 mg of oxacillin/kg and 10 mg of sisomicin/kg. Treatment with 50 mg of oxacillin/kg four times daily or 50 mg/kg every 4 hr around the clock for 28 days sterilized 30% of the rabbit bones. Sisomicin (10 mg/kg) injected twice daily for 28 days sterilized only 5% of the rabbit bones. In contrast, treatment with the combination of oxacillin and sisomicin for either 14 or 28 days was significantly more effective, sterilizing 78% and 85%, respectively, of the bones of treated animals. S. Aureus isolated from bones of animals treated with sisomicin alone contained aminoglycoside-resistant microcolonies. Resistant microcolonies were not recovered from animals treated with oxacillin or with the combination of oxacillin plus sisomicin. In vitro studies of bacterial killing by each antibiotic alone and in combination showed more bacterial killing with the combination than with either agent alone; in vitro the combination prevented emergence of resistant microcolonies. Combination antibiotic therapy appears to be more effective in treatment of experimental osteomyelitis due to S. aureus than therapy with a single agent.

Animals