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Biomedical subjects

R J Fass

Publications and source records attributed to R J Fass.

At least 73 records · Page 4Linked to original sources

Treatment of skin and soft tissue infections with imipenem/cilastatin.

Ninety-eight adult patients with skin and soft tissue infections caused by a variety of bacterial pathogens were treated with imipenem/cilastatin (71), cefazolin (21), or moxalactam (six) at three medical centers. Favorable clinical responses were observed in 87 of the 90 evaluable cases (97 percent). Most etiologic pathogens were eradicated during treatment including five of seven which demonstrated in vitro resistance to the therapeutic agent. Strains that persisted during treatment were not associated with therapeutic failure except in one cefazolin-treated patient who was infected with Bacteroides fragilis. All three drugs were well tolerated and no specific patterns of adverse reactions were observed.

Adult↗

Comparison of the effectiveness of moxalactam and cefazolin in the prevention of infection in patients undergoing abdominal operations.

Patients undergoing elective intraabdominal operations received a three-dose prophylactic regimen of either moxalactam (83 patients) or cefazolin (98 patients) in a blinded, randomized fashion. There was a 9% overall infection rate with 6% for those in the cefazolin group (6/98), and 12% for those treated with moxalactam (10/83) (p = 0.26). Infection rates stratified by types of surgery were similar for both regimens. The drugs were well tolerated, with minimal side effects. Patients at highest risk of infection were those with obstruction of upper gastrointestinal tract and those with pancreatitis. We concluded that moxalactam was no more effective than cefazolin in preventing postoperative infections in this study population.

Abdomen↗

In vitro activity of carumonam.

The in vitro activities of carumonam and eight comparative antimicrobial agents were studied. MICs of carumonam were less than or equal to 0.5 microgram/ml for 91% of members of the family Enterobacteriaceae and less than or equal to 16 micrograms/ml for 88% of nonfermenters; gram-positive cocci and anaerobic bacteria were resistant. Combinations of carumonam with piperacillin, nafcillin, or clindamycin were usually indifferent, although synergy between carumonam and piperacillin was observed with 20 (13%) of 155 strains.

Anti-Bacterial Agents↗

Ciprofloxacin disk susceptibility tests: interpretive zone size standards for 5-microgram disks.

Evaluations of 5-microgram ciprofloxacin disk diffusion susceptibility tests were performed independently by seven different investigators. The results of the separate tests were combined to increase the number of resistant strains in the challenge set of microorganisms. Based on data with 2,652 isolates, the following interpretive breakpoints are tentatively proposed for use in ongoing clinical trials of ciprofloxacin: less than or equal to 15 mm, resistant (MIC greater than 2.0 micrograms/ml); 16 to 20 mm, intermediate (1.0 less than MIC less than or equal to 2.0 micrograms/ml); and greater than or equal to 21 mm, susceptible (MIC less than or equal to 1.0 micrograms/ml). Disk tests with Streptococcus spp. and with Pseudomonas maltophilia were not reliable; other microorganisms were accurately categorized by the disk diffusion test.

Acinetobacter↗

The quinolones.

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Gram-Negative Bacteria↗

Laboratory tests for defining bactericidal activity as predictors of antibiotic efficacy in the treatment of endocarditis due to Staphylococcus aureus in rabbits.

The validity of laboratory tests that define bactericidal activity to predict antimicrobial efficacy was studied in rabbits with endocarditis due to Staphylococcus aureus, both nafcillin-nontolerant (NT) and nafcillin-tolerant (T). Infected rabbits were treated with nafcillin, clindamycin, chloramphenicol, or no drug (control) for up to 11 days; dosage was designed so that peak antibiotic serum concentration/minimal inhibitory concentration ratios were approximately 50. During treatment, peak and trough serum concentration/minimal bactericidal concentration ratios and peak and trough titers of serum bactericidal antibacterial activity were determined. The rank order of efficacy, as defined by survival, eradication of bacteremia, and sterilization of cardiac vegetations, was nafcillin = clindamycin greater than chloramphenicol greater than control, both adjusted and unadjusted for the challenge strain of S. aureus. Bactericidal activity (observed only with nafcillin plus S. aureus NT) was associated with lower bacterial counts in vegetations at four days but was otherwise unrelated to therapeutic outcome.

Analysis of Variance↗

Comparative efficacies of mezlocillin and ampicillin alone or in combination with gentamicin in the treatment of Streptococcus faecalis endocarditis in rabbits.

The in vitro and in vivo activities of mezlocillin and ampicillin, alone and in combination with gentamicin, against Streptococcus faecalis were compared. In vitro, relative bactericidal and activities for 10 strains of S. faecalis were as follows: mezlocillin plus gentamicin greater than ampicillin plus gentamicin (P is not significant) greater than mezlocillin (P less than 0.01) greater than ampicillin (P less than 0.01) greater than gentamicin (P less than 0.01) greater than control (P less than 0.01). One of the strains was used to induce endocarditis in rabbits. Infected rabbits were treated by random selection with ampicillin, mezlocillin, ampicillin plus gentamicin, mezlocillin plus gentamicin, or saline (control) for 7 days. Among antibiotic-treated rabbits, survival rates were the same, but ampicillin was less effective than the other regimens in sterilizing both blood cultures (P less than 0.001 on day 4) and cardiac vegetations (P less than 0.05 on day 7). Differences in quantitative vegetation cultures among rabbits treated with mezlocillin, mezlocillin plus gentamicin, or ampicillin plus gentamicin and sacrificed on day 7 were not significantly different. Peak inhibitory and bactericidal antibacterial activity titers in serum determined during treatment were higher with mezlocillin (with or without gentamicin) than with ampicillin (with or without gentamicin) (P less than 0.01). Mezlocillin may be more effective than ampicillin in the treatment of S. faecalis infections in humans.

Ampicillin↗

Correlation of in vitro activities of cephalothin and ceftazidime with their efficacies in the treatment of Staphylococcus aureus endocarditis in rabbits.

Rabbits with Staphylococcus aureus endocarditis were treated with cephalothin or ceftazidime to determine whether differences in in vitro activity would result in differences in in vivo efficacy. Antibiotics were administered in doses equivalent to maximum recommended human doses, and results of laboratory tests to predict antimicrobial efficacy were determined during treatment. Cephalothin and ceftazidime MICs for the challenge strain were 0.5 and 8 micrograms/ml, respectively. MBCs were 32 and greater than 128 micrograms/ml, respectively. With peak sera, laboratory results (means) for cephalothin and ceftazidime were as follows: ratios of concentration in serum to MIC, 300 and 16; ratios of concentration in serum to MBC, 4.8 and less than 1; bacteriostatic antibacterial activity titers in serum, 1:256 and 1:16; and bactericidal antibacterial activity titers in serum, 1:16 and 1:4, respectively. Trough sera contained little or no measurable antibiotic and had no antibacterial activity. Both cephalothin and ceftazidime were efficacious in the treatment of infected rabbits. There were no statistically significant differences in efficacy as defined by survival, eradication of bacteremia, or sterilization of cardiac vegetations. Results of laboratory tests which quantitated antimicrobial activity did not correlate with efficacy, either independent of antibiotic or adjusted for antibiotic. Despite their lesser in vitro activities, the new cephalosporins may be equivalent to the older cephalosporins for treating staphylococcal infections in humans, when administered in maximum recommended doses.

Animals↗

Comparative in vitro activities of apalcillin and piperacillin against gram-negative bacilli.

The susceptibilities of 317 gram-negative bacilli to apalcillin and piperacillin were determined by standardized microdilution and disk diffusion tests. The respective percentages of strains susceptible to less than or equal to 64 micrograms of apalcillin and piperacillin per ml were as follows: members of the family Enterobacteriaceae, 90 and 88%; randomly selected Pseudomonas aeruginosa, 100 and 100%; multi-drug-resistant P. aeruginosa, 100 and 75%; and other nonfermenters and Aeromonas hydrophila, 99 and 97%. The drugs had equal activity against Enterobacteriaceae and A. hydrophila; apalcillin was more active against Pseudomonas species and Acinetobacter calcoaceticus, and piperacillin was more active against other nonfermenters. By using linear regression analysis, we found that the MICs of apalcillin and piperacillin were highly interrelated; the lines of best fit had slopes close to unity, and correlation coefficients (r) were greater than 0.90 for Enterobacteriaceae as a group and for other species individually. With disk diffusion testing, inhibition zone diameters around 100 micrograms apalcillin and 100 micrograms piperacillin disks correlated well with respective MICs for Enterobacteriaceae and P. aeruginosa (r = -0.93 to -0.96). Using an error rate-bound classification scheme, we determined breakpoints for apalcillin susceptibility and confirmed those previously established for piperacillin to be appropriate. The apalcillin disk, with modified breakpoints, could be used to predict piperacillin MICs for all organisms, but the piperacillin disk could not be used to predict apalcillin MICs for nonfermenters.

Ampicillin↗

A comparison of the effects of mezlocillin and carbenicillin on haemostasis in volunteers.

Mezlocillin and carbenicillin were administered intravenously to healthy male volunteers, for six days each, in a double-blind crossover study. Tests to detect abnormalities in haemostasis were performed before, during and after administration. Platelet aggregation studies indicated that both antibiotics interfered with platelet aggregation and secretion resulting in prolonged bleeding times. The effect was dose related and rapidly reversible after discontinuation of the antibiotics. It always occurred earlier and was more profound with carbenicillin than with mezlocillin (P = 0.008). Bleeding times greater than 15 min were observed in 17% of volunteers who received 18 g/day of mezlocillin and 83% of volunteers who received 18 g/day of carbenicillin (P less than 0.05). There were no abnormalities in the coagulation cascade. The risk of acquiring an antibiotic-induced clinical bleeding disorder is lower with mezlocillin than with carbenicillin.

Adenosine Diphosphate↗

Statistical comparison of the antibacterial activities of broad-spectrum penicillins against gram-negative bacilli.

Minimal inhibitory concentrations (MICs) or two alpha-carboxypenicillins (carbenicillin and ticarcillin) and three acylaminopenicillins (azlocillin, mezlocillin, and piperacillin) for 300 aerobic and facultative gram-negative bacilli were determined by a microdilution method and compared by parametric statistical tests. Within each group of penicillins, MICs were highly interrelated; MICs of one antibiotic were readily predictable based on knowledge of MICs of another antibiotic. Ticarcillin was consistently more active than carbenicillin by approximately one dilution step, but the relative activities of the acylaminopenicillins varied by bacterial species. The acylaminopenicillins were generally more active than the alpha-carboxypenicillins, particularly against alpha-carboxypenicillin-resistant organisms. There were exceptions, however, and antibiotic MICs in one group were not readily predictable on the basis of the knowledge of antibiotic MICs in the other group. The enhanced antibacterial potencies and spectra of the acylaminopenicillins against gram-negative bacilli make these antibiotics potentially useful therapeutic agents. It is not necessary for clinical laboratories to routinely perform susceptibility tests with all five antibiotics.

Analysis of Variance↗

In vitro activity of ciprofloxacin (Bay o 9867).

The in vitro activities of ciprofloxacin (Bay o 9867) and seven comparative antimicrobial agents against 664 aerobic and facultatively anaerobic bacterial isolates were studied. Minimal inhibitory concentrations (MICs) of ciprofloxacin were less than or equal to 2 micrograms/ml for Enterobacteriaceae, less than or equal to 8 micrograms/ml for nonfermentative gram-negative bacilli, less than or equal to 4 micrograms/ml for gram-positive cocci, less than or equal to 0.03 micrograms/ml for Aeromonas hydrophila and Pasteurella multocida, and less than or equal to 1 microgram/ml for Listeria monocytogenes. MICs for multi-drug-resistant Enterobacteriaceae and Pseudomonas aeruginosa were less than or equal to 4 micrograms/ml. Ciprofloxacin MICs were consistently 0 to 4 (usually 2 to 3) dilution steps lower than those of a related drug, norfloxacin (P less than 0.0001). For most species, they were lower than MICs of cefotaxime, aztreonam, theinamycin, mezlocillin, trimethoprim-sulfamethoxazole, and amikacin. With all eight drugs, increasing the inoculum size by 100-fold had a variable effect on MICs which was species related. Ciprofloxacin is a potent broad-spectrum new antimicrobial agent.

Anti-Bacterial Agents↗

Cefotaxime: pharmacokinetics and in vitro antibacterial activity of serum and urine in normal human volunteers.

The pharmacokinetic and antibacterial properties of cefotaxime were determined in normal adult volunteers. Single doses of 250, 500, 1,000 and 2,000 mg were evaluated following 5- and 20-min intravenous (i.v.) infusions and intramuscular (i.m.) administration. Cefotaxime was well tolerated and mean peak serum levels exceeded the minimum inhibition concentration (MIC) values for a wide spectrum of potential bacterial pathogens. Approximately 48% of the i.v. doses was excreted renally; average volume of distribution was 30% of body weight and the t 1/2 was about 1 h. Cefotaxime was rapidly absorbed following i.m. injection with maximum serum concentrations occurring at approximately 0.6 h. Serum and urine antibacterial activity reflected the concentration of cefotaxime and MIC of the bacterial pathogens tested.

Bacteria↗

Comparative in vitro activities of third-generation cephalosporins.

The in vitro susceptibilities of 823 clinical isolates to eight third-generation cephalosporin and cephalosporinlike antibiotics were studied. All eight antibiotics were more active and had broader spectrums of activity against gram-negative bacilli and anaerobes than older derivatives; however, they were less active against gram-positive cocci. Cefotaxime sodium, cefmenoxime hydrochloride, ceftriaxone disodium, and ceftizoxime sodium had similar activities. Cefoperazone sodium was more active than those drugs against Pseudomonas aeruginosa but less active against Enterobacteriaceae and Acinetobacter. Ceftazidime pentahydrate was more active against P aeruginosa but less active against gram-positive cocci. Moxalactam disodium was more active against some Enterobacteriaceae, Pseudomonas maltophilia, and Bacteroides fragilis but less active against gram-positive cocci. Thienamycin formamidide monohydrate had the broadest spectrum of activity and was the only antibiotic active against Streptococcus faecalis; the only resistant species were P maltophilia and Pseudomonas cepacia.

Cephalosporins↗