James S. Tan

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.

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.

Treatment of Bacteriuria in Pregnancy

SummaryThe presence of bacteriuria during gestation increases the chance of acute pyelonephritis. Treatment of bacteriuria in pregnancy reduces subsequent development of symptomatic disease.Numerous studies have shown that single-dose therapy for asymptomatic bacteriuria is as effective as longer course of treatment. Single-dose therapy also has the advantages of improved compliance, reduced costs, and less adverse effects resulting from long term therapy.Follow-up cultures following antimicrobial treatment should be used for early detection of recurrence or relapse. If the urine culture yields no growth, a urine culture at a monthly interval will suffice. If on the other hand bacteriuria is present, a repeat course of antimicrobial therapy should be chosen based on antimicrobial susceptibility testing. A longer course of therapy, possibly with a different drug, is recommended for women with a positive follow-up urine culture. Acute cystitis may be treated with the same regimen as asymptomatic bacteriuria. When upper urinary tract infection is suspected, hospitalisation and a longer course of therapy is recommended. If the organism is susceptible to cefalexin or nitrofurantoin, postcoital prophylaxis with either agent for the remainder of the pregnancy may be beneficial.

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.

Timentin versus moxalactam in the treatment of skin and soft tissue infections.

T imentin is a combination of two beta-lactam antibiotics, ticarcillin and clavulanic acid. Clavulanic acid, a “suicide” inhibitor of beta-lactamases, enhances the spectrum of activity of ticarcillin to include beta-lactamase-producing Staphylococcus, gram-negative enteric bacteria including Klebsiella, Enterobacter, and Serratia, some strains of Pseudomonas aeruginosa, and Bacteroides species including 8. fragilis [1,2]. With this broadened spectrum of antimicrobial activity, Timentin appears to be an ideal candidate for use in the treatment of skin and soft tissue infections. In this study, we treated patients who were hospitalized for skin and soft tissue infections with either Timentin or moxalactam to evaluate the efficacy and toxicity of this new preparation.

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.

In vitro susceptibility of the Bacteroides fragilis group in community hospitals

The antimicrobial susceptibility of clinical isolates of the Bacteroides fragilis group was determined at six community hospitals (one large, greater than 600 beds; and five smaller, 96-325 beds). Imipenem was the most active beta-lactam with 100% of isolates being sensitive at 4 micrograms/ml. The percentage of isolates inhibited at 16 micrograms/ml (and 32 micrograms/ml) for the 7-alpha-methoxy antibiotics was: cefoxitin 66 (90); moxalactam 73 (85); cefotetan 68 (72); cefmetazole 40 (61). Metronidazole, chloramphenicol, and clindamycin were active against 100%, 100%, and 89% at breakpoints of 8 micrograms/ml, 8 micrograms/ml, and 4 micrograms/ml, respectively. The activity of several beta-lactams in our report differed slightly from that reported from university teaching hospitals. There were differences at many of the breakpoints for activity of some of the beta-lactam antibiotics for isolates from the large community hospital as compared with the combined isolates from the smaller community hospitals. Interestingly, the pattern was one of more resistance at the smaller community hospitals.

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. Images

Bullous Skin Lesions Associated With Yersinia Enterocolitica Septicemia

An 86-year-old woman developed large bullae on both legs during the course of septicemia due to Yersinia enterocolitica. Although erysipelas-like lesions and erythema nodosum have been known to be associated with Yersinia infections, this is the first reported case with multiple bullae.

Levels of amdinocillin in human plasma and interstitial fluid following intravenous administration

Amdinocillin levels in human plasma and interstitial fluid were studied in 12 human volunteers. The results showed that relatively high levels of amdinocillin were detected in the interstitial fluid. The fluid to plasma ratio of the area under the curve was 0.25. This is consistent with high diffusibility as seen in drugs with a low percentage of protein binding.