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Biomedical subjects

J S Tan

Publications and source records attributed to J S Tan.

At least 73 records · Page 4Linked to original sources

Canine model for the simultaneous measurement of antibiotic levels in tissues and bacterial killing rate.

Antibiotic levels in serum are commonly used to guide antibiotic therapy. The antibiotic levels in interstitial fluid are a more accurate reflection of the efficacy of antibiotic penetration into the tissues. Although there are experimental models for determining interstitial fluid levels, there is no model for measuring the in vivo killing of bacteria, which is the endpoint of antibiotic therapy. We developed an accurate, reliable animal model which allows measurement of the in vivo killing of bacteria along with a determination of antibiotic levels in tissues. Modified Sykes-Moore chambers were applied to the dissected external oblique muscle of 14 dogs. The chambers were inoculated with clinical isolates of Staphylococcus aureus or Escherichia coli. The dogs were treated with cefoxitin or gentamicin. Quantitative cultures were performed, and the antibiotic levels in interstitial fluid were determined.

Animals↗

Timentin versus piperacillin in the therapy of serious urinary tract infections.

In a comparative study, 47 patients received Timentin, a combination of ticarcillin plus clavulanic acid, or piperacillin to treat serious urinary tract infections. Thirty-nine infections in 38 patients were clinically evaluable (21 in the Timentin-treated group and 18 in the piperacillin-treated group). These included pyelonephritis (10 in the Timentin-treated group and five in the piperacillin-treated group), bladder infections with sepsis (11 in the Timentin-treated group and 11 in the piperacillin-treated group) and bladder infections without fever (two in the piperacillin-treated group). The addition of clavulanic acid to ticarcillin greatly enhanced the susceptibility of five of the 28 evaluable pathogens in the Timentin-treated group (two Escherichia coli isolates, two Staphylococcus aureus isolates, and one Klebsiella pneumoniae isolate). The minimal inhibitory concentrations at which 50 and 90 percent of the bacterial growth was inhibited were 4 and 64 micrograms/ml, respectively, for Timentin, and 4 and 32 micrograms/ml, respectively, for piperacillin. All evaluable patients had a satisfactory symptomatic response at the end of the trial. Of 28 evaluable pathogens treated with Timentin, 18 were eradicated up through the one-week post-therapy evaluation period; of 27 evaluable pathogens treated with piperacillin, 18 were eradicated up through the same time period. Eradicated pathogens included E. coli (six of 13 in the Timentin-treated group and six of 11 in the piperacillin-treated group), other Enterobacteriaceae (three of three in the Timentin-treated group and eight of 10 in the piperacillin-treated group), Pseudomonas aeruginosa (two of four in the piperacillin-treated group), enterococcus (two of three in the Timentin-treated group and two of two in the piperacillin-treated group), staphylococcal species (four of five in the Timentin-treated group), and other organisms (three of four in the Timentin-treated group). Resistance did not develop in any of the persisting pathogens. Adverse effects thought possibly to be related to the study drugs were minimal and included rash in one Timentin-treated patient and diarrhea in another.

Adult↗

Comparison of ticarcillin plus clavulanic acid with cefoxitin in the treatment of female pelvic infection.

Ninety-three female patients with post-cesarean endometritis, post-hysterectomy pelvic cellulitis, and other miscellaneous moderately severe pelvic soft-tissue infections were treated in a randomized fashion with either ticarcillin plus clavulanic acid or cefoxitin. Of the 47 patients treated with ticarcillin plus clavulanic acid, 38 had clinical cures, four showed improvement, therapy failed in three, and two were nonevaluable, for a failure rate of 6.7 percent. Of the 46 patients treated with cefoxitin, 33 had clinical cures, five showed improvement, therapy failed in seven, and one was nonevaluable, for a failure rate of 15.6 percent. Bacteriologically, the addition of clavulanic acid to ticarcillin was found to broaden the antibacterial spectrum to include some Escherichia coli, most Klebsiella, many coagulase-negative staphylococci, and all isolates of Staphylococcus aureus. Adverse reactions were few, with only one patient having therapy with cefoxitin discontinued because of side effects. It is concluded that ticarcillin plus clavulanic acid is quite suitable for antibiotic therapy of female pelvic soft-tissue infection, based on the (expanded) coverage of both aerobic and anaerobic bacterial species.

Adolescent↗

Cefmenoxime versus cefoxitin in the treatment of serious bacterial infections.

A comparative study was conducted using cefmenoxime, a new extended spectrum cephalosporin, versus cefoxitin. Entry into the study was based on a computer-generated randomization (two cefmenoxime to one cefoxitin). An intravenous dose of cefmenoxime (0.5 to 1 g every six hours) or cefoxitin (1 to 2 g every six hours) was administered to patients suspected of having serious bacterial infections. Six patients had urinary tract infections. Four who received cefmenoxime, including two with positive blood cultures, had eradication of bacteremia. One of the two who received cefoxitin had significant bacteriuria, and the urine was clear after treatment. Twenty-four patients were treated for lower respiratory tract infections. All 15 patients who received cefmenoxime had clinical and bacteriologic cures. Two of the nine patients who received cefoxitin continued to have the pathogens at the end of the treatment period. Both patients had a neoplasm of the lung. All 11 patients who had soft tissue infections (nine of whom received cefmenoxime) responded well. Both antibiotics were well tolerated.

Bacterial Infections↗

Antibiotic prophylaxis in high-risk biliary operations: multicenter trial of single preoperative ceftriaxone versus multidose cefazolin.

A prospective, double-blind trial of a single preoperative dose of ceftriaxone, a new long-acting cephalosporin, versus one preoperative and three postoperative doses of cefazolin was carried out in 81 patients at high risk of infection after biliary surgery. Indications for antibiotic prophylaxis included recent or ongoing cholecystitis (52 patients), common duct stones (14 patients), common duct obstruction (3 patients), and age greater than 70 years (22 patients). Intraoperative bile cultures were positive in 7 of 41 patients (17.1 percent) given ceftriaxone and 12 of 40 patients (30 percent) given cefazolin, but there were no wound infections in either group. Neither regimen was associated with significant antibiotic resistance. Side effects, such as proteinuria and elevated liver transaminases and alkaline phosphatase levels, were transient and not definitely related to the antibiotics. We conclude that a single preoperative dose of ceftriaxone is as effective as multiple perioperative doses of cefazolin in the prophylaxis of infection associated with biliary tract surgery.

Adolescent↗

Diffusibility of the newer cephalosporins into human interstitial fluids.

A skin window technique was used to investigate the ability of three of the newer cephalosporins, moxalactam, cefoperazone, and ceftriaxone, to enter the interstitial fluid of normal, healthy volunteers. Intravenous and intramuscular routes of delivery were compared. The method of delivery did not greatly affect diffusibility with moxalactam and ceftriaxone. Intravenous infusion resulted in greater diffusibility with cefoperazone than did intramuscular injection. Cefoperazone demonstrated the lowest diffusibility of the three test drugs. Ceftriaxone, administered at one-half the dose of cefoperazone and moxalactam, demonstrated the greatest ability to diffuse into interstitial fluid despite its high level of binding to plasma protein. The better diffusibility of ceftriaxone may be explained by a persistently high concentration gradient provided by its long serum half-life. Overall, the results support the concept of the concentration gradient as an important determinant of antibiotic activity.

Adolescent↗

Timentin versus piperacillin or moxalactam in the therapy of acute bacterial infections.

In a randomized comparative study, 116 patients with acute bacterial infections were treated with timentin (ticarcillin plus clavulanic acid) or a comparative agent (piperacillin for respiratory or urinary tract infections, and moxalactam for soft tissue infections). There were 91 clinically evaluated infections (timentin, 46; piperacillin, 29; moxalactam, 16). Twelve patients were bacteremic. A satisfactory clinical response occurred in all 46 patients treated with timentin and in 42 of the 45 treated with a comparative agent. Two clinical failures were due to superinfection (a Staphylococcus aureus pneumonia in the piperacillin group and an enterococcal skin infection in the moxalactam group), and one clinical failure was due to a primary S. aureus skin infection (moxalactam group). One wound isolate of Pseudomonas aeruginosa developed resistance to timentin during therapy (despite clinical improvement). Adverse reactions were uncommon but did include one patient treated with timentin who developed unexplained hallucinations.

Acute Disease↗

High-pressure liquid chromatographic method for analysis of cephalosporins.

A high-pressure liquid chromatographic method is described for the analysis of a wide range of cephalosporin congeners, using only three reagents for extraction and drug analysis. Plasma was treated with cold methanol-0.1 M sodium acetate to precipitate protein. Cephalosporins were resolved on a C-18 reverse-phase column, utilizing a mobile phase of various percentages of 0.01 M sodium acetate and acetonitrile-methanol. Compounds analyzed included cephalexin, cefamandole, cephalothin, cefotaxime, cefazolin, cephaloridine, cefoxitin, cefaclor, cephapirin, and cefoperazone. Each antibiotic demonstrated excellent linearity throughout the therapeutic range. The method of standard additions revealed recoveries of 93 to 101%, with detection limits ranging from 0.2 to 1.0 micrograms/ml for these drugs. Retention times ranged from 4 to 6 min. This method offers a rapid and simple means by which this group of cephalosporins may be reliably quantitated.

Cephalosporins↗

Clinical evaluation of ceftriaxone.

Seventy-seven patients with acute bacterial infections were treated with ceftriaxone (1 gm administered intravenously every 12 hours). The 58 patients evaluable for efficacy had 60 infections, including 39 of the respiratory tract, 14 of the urinary tract, and seven of soft tissue. Five patients were bacteremic. The mean duration of ceftriaxone treatment was eight days for patients with respiratory and urinary tract infections and 13 days for patients with other types of infections. A satisfactory clinical response occurred in 56 (93%) of the infections. Eighty-four (94%) of the 89 pretherapy pathogens were bacteriologically eradicated. Included were all 19 isolates of Haemophilus influenzae, all 15 of Streptococcus pneumoniae, all 12 of Escherichia coli, 22 of the 23 isolates of other Enterobacteriaceae species, three of five isolates of Pseudomonas aeruginosa, and three of four isolates of Staphylococcus aureus. Two cases of superinfection (one with bacteremia) occurred with P aeruginosa. There were two cases each of reinfection and colonization with Streptococcus faecalis. One patient developed manifestations of culture-documented S pneumoniae meningitis eight hours after the first dose was administered. Peak and trough plasma levels of ceftriaxone were 142 and 64 micrograms/ml. Ceftriaxone achieved therapeutic levels in infected cerebrospinal fluid and in the abscess fluid of selected patients. Adverse effects, which were mild, included diarrhea in 4% of the patients and elevated transaminase levels in 10%.

Adult↗

Amdinocillin plus cefoxitin versus cefoxitin alone in therapy of mixed soft tissue infections (including diabetic foot infections).

In a randomized comparative trial, 45 patients were treated with amdinocillin plus cefoxitin or cefoxitin alone for bacterial soft tissue infections. Most patients were diabetic and had polymicrobial foot infections. The combination of amdinocillin plus cefoxitin was active in vitro against 71 percent of the isolates obtained before therapy as compared with 65 percent for cefoxitin alone. The combination demonstrated synergy for 29 percent of the isolates tested. A satisfactory clinical response occurred in 90 percent and 71 percent of patients treated with the combination regimen and cefoxitin, respectively, (p greater than 0.1). An increase in serum creatinine thought to be due to interstitial nephritis occurred in one patient treated with the combination regimen. The combination of amdinocillin and cefoxitin was effective in mixed soft tissue infections including diabetic foot infections.

Adult↗

Cefoperazone versus cefamandole in the treatment of acute bacterial lower respiratory tract infections.

In a randomized comparative study, 113 patients were treated with cefoperazone or cefamandole for acute bacterial lower respiratory tract infections. Most patients had Streptococcus pneumoniae or Haemophilus influenzae infections, although five patients in the cefoperazone group had infections caused by other Gram-negative bacilli (two with Pseudomonas aeruginosa). The clinical responses and adverse effects were not significantly different between the two treatment groups. Satisfactory clinical responses occurred in 36/39 (92%) of evaluable patients in the cefoperazone group and 33/34 (97%) of evaluable patients treated with cefamandole. Two failures in the cefoperazone group were secondary to superinfection (Acinetobacter and Ps. aeruginosa). Bacteriological and symptomatic failure occurred in one patient with Ps. aeruginosa lung abscess treated with cefoperazone and in one patient with a polymicrobial empyema treated with cefamandole. The results of this study indicate that cefoperazone is safe and effective in the therapy of acute bacterial lower respiratory tract infections.

Acute Disease↗