Frank Cox

Polymicrobial infective endocarditis: An increasing clinical entity

Polymicrobial endocarditis was very uncommon until ten years ago. However, since that time, at least 21 cases were reported, and 10 patients with this mixed infection were seen at our hospital. All, except one of these infections, occurred in patients who had undergone heart surgery or abused intravenous drugs. Although, generally clinically indistinguishable from mono-microbial endocarditis, these mixed infections carried a very high mortality rate (greater than 30 per cent), and an unusually large number of the patients (greater than 50 per cent) needed heart surgery either to control the infection or to repair cardiac defects resulting from the infection. The prognosis depended on the species rather than the number of organisms isolated and on aggressive antimicrobial and surgical therapy.

Effect of Renal Failure and Dialysis on the Serum Concentration of the Aminoglycoside Amikacin

Serum and dialysate levels of amikacin were determined at appropriate intervals after a 300-mg intravenous dose as a continuous infusion in six patients with end-stage renal failure undergoing hemodialysis and in three patients on peritoneal dialysis. The mean serum half-life of amikacin was 3.75 h during (or after) hemodialysis and 29 h during (or after) peritoneal dialysis. Although not on hemodialysis in the same six patients, the serum half-life was 28 h. The results indicate that the maintenance dose of amikacin should be markedly decreased in patients with severe renal failure even if they are treated with peritoneal dialysis, and that serial serum antibiotic concentrations are essential to prevent cumulative toxicity of the drug.

Clinical Studies of Cefazolin and Comparison with Other Cephalosporins

Cefazolin, a new cephalosporin derivative, was studied in the treatment of 105 hospitalized patients with a variety of infections including endocarditis, pneumonia, and urinary and soft tissue infections, and was found to be effective in 104 patients. Cefazolin was also tested in vitro and shown to be effective against staphylococci, pneumococci, Escherichia coli, Klebsiella sp., and Proteus mirabilis by agar dilution method. It was shown to produce high serum levels when administered in a 250- to 1,000-mg intramuscular dose and was well tolerated and free from renal toxicity. Comparison of the results of this study with those from our prior studies on cephaloridine revealed equivalent antibiotic potency, good tolerance to both the agents when given intramuscularly, superior, average blood levels with cefazolin, equal clinical efficacy, and absence of renal toxicity with cefazolin (unlike cephaloridine). Similarly, the results of treatment of pneumococcal pneumonia with intramuscular cefazolin were found to be superior to those for oral cephalexin.

Effects of Renal Failure and Dialysis on Cefazolin Pharmacokinetics

Serum and urinary levels of cefazolin were determined after a 500-mg parenteral dose in eight azotemic volunteers. The mean peak serum concentration was 1.5 to 5 times the levels obtained in nonazotemic patients. The serum half-life of cefazolin was increased significantly. In patients on dialysis, the mean serum half-life of cefazolin was 4.05 h during (or after) hemodialysis, and 32.1 h during (or after) peritoneal dialysis. There was a significant decrease in cefazolin removal when dialysate flow or membrane surface area of the dialyzer were decreased. It was also shown that one circuit through the dialysis unit caused measurable decrease in cefazolin concentration. These data and previously published reports suggest: (i) the maintenance dose of cefazolin can be decreased in azotemic patients; (ii) patients on hemodialysis will require an additional half dose after dialysis because of efficient removal during hemodialysis; and (iii) patients on peritoneal dialysis do not require an extra dose.

Pseudomonas putida and Septic Arthritis

Excerpt To the editor:Pseudomonas putidais a Gram-negative, aerobic, fluorescent pseudomonad that has multitrichous flagella, does not grow at 42 °C, and is characterized by variable acid productio...

In Vitro and Clinical Studies of Cefatrizine, a New Semisynthetic Cephalosporin

Cefatrizine, a new oral semisynthetic cephalosporin, was evaluated in vitro and in the treatment of 18 patients with acute urinary tract infection, pneumonia, and soft tissue infection. In vitro, it was more active than cephalexin for gram-positive and gram-negative bacteria. It was also more active than cephalothin, cefazolin, and cephapirin against most of the gram-negative bacteria but less active against the gram-positive bacteria. Of the patients treated with cefatrizine, only one failed to respond. This patient had pneumococcal conjunctivitis and hypogammaglobulinemia and neutropenia. The mean peak serum level after multiple 6-hourly doses of 500 mg was 6.2 μg/ml. The serum levels of cefatrizine necessary for inhibition of most susceptible organisms were well within the achievable range. The drug was well tolerated, and no renal, hepatic, or hematological toxicity was detected.

Comparative biliary concentrations of cephazolin and cephalothin in patients with biliary tract disease.

The concentration of cephazolin in the serum, gall bladder bile, common duct bile, and gall bladder wall were considerably higher than cephalothin especially with IV administration and indicate that cephazolin should be a useful antibiotic in the surgical treatment of acute cholecystitis.

Antibiotic Prophylaxis — Yes or No? — Endocarditis

Antibiotic prophylaxis of subacute bacterial endocarditis before dental manipulations and other surgical procedures in patients with known heart disease has been widely used for over 25 years but its effectiveness has never been proved.(1) The basis of this practice is the observation that a small proportion of patients with endocarditis have a dental procedure before onset of the heart infection. However, among susceptible heart disease patients, the actual rate of development of endocarditis in association with operative procedures likely to produce bacteremia is extremely low. Therefore, it has not been possible to determine the value of antibiotic prophylaxis by clinical observation. Indeed, the presumed success of recommended antibiotics may be more due to inherently low infection rates than prophylaxis per se. Thus, even after administration of penicillin according to an approved regimen, cases of penicillin-sensitive endocarditis after tooth extractions are reported.(2) In our own hospital three such patients were seen in the past 20 years. An alternate explanation for the failure of antibiotic prophylaxis is that the “approved regimen was inadequate. This may relate to the basis for recommended schedules, namely, in vitro sensitivities of the organisms and serum concentrations achieved by the antibiotic. Although bacteremia is reduced, the frequency of lodgment and multiplication of bacteria on the endocardium under these conditions is not known. Since clinical observation cannot answer this dilemma, it recently was proposed by Durack and Petersdorf, (3) and also by Beeson, (4) that clinical recommendations be developed based on data derived from the prevention of bacterial endocarditis in a suitable animal model.