Cardiac infections in the immunosuppressed patient.

This article presents the various manifestations of cardiac infections found in the immunosuppressed host. Emphasis is placed on the correlation between specific impairments of host defenses and the occurrence of certain types of pathogens. The effect of immunosuppression on the clinical manifestations of these infections is discussed. Finally, appropriate diagnostic modalities are presented for the major types of infections.

Fever of unknown origin.

The evaluation of an FUO is a significant test of all a physician's clinical skills. The ultimate goal of the physician is to reach a diagnosis and to cure the patient in the best possible situation. Despite such pressure both externally and self-imposed, a physician needs to meticulously follow the patient and logically pursue the available diagnostic tests. To "shotgun" the process, except in the most urgent situation, is to ultimately create more frustration, confusion, and despair among the physician and his patient.

A circulating anticoagulant in lepromatous leprosy.

We observed a patient with lepromatous leprosy and a circulating anticoagulant. Intrinsic pathway inhibition was demonstrated by prolongation of the activated partial thromboplastin time. Extrinsic pathway inhibition was demonstrated by prolongation of the prothrombin time when performed with diluted thromboplastin. A plasma co-factor was required for inhibition. Immunoadsorption with specific antisera and Sephadex G-200 fractionation suggested that the anticoagulant was an IgM immunoglobulin. The similarities between this patient's anticoagulant and those associated with other disease states are discussed.

Positive differential heterophile antibody test. Persistence in a symptomatic patient.

A patient who had documented mononucleosis in June 1971 has been persistently symptomatic since that time, with easy fatigability and weight loss. He has also had a positive differential heterophile antibody test for mononucleosis for 14 months. Although no evidence for active Estein-Barr virus (EBV) infection was discovered, the possibility of a chronic EBV infection is discussed.

Significant reduction in the incidence of phlebitis with buffered versus unbuffered cephalothin.

Cephalothin (1 g every 2 h), buffered cephalothin, and diluent alone (5% dextrose in water) were each administered for 4 days intravenously to 12 volunteers in a double-blind crossover study. The incidence of phlebitis with buffered cephalothin was significantly lower than that with unbuffered drug (P < 0.01) and almost identical to the incidence with diluent alone.

Bactericidal activity and pharmacology of flucloxacillin.

Flucloxacillin, a recent addition to the group of isoxazolyl penicillins, was studied in vitro and in normal volunteers. The bactericidal activity of the drug against most strains of gram-positive bacteria including penicillin-resistant Staphylococcus aureus was similar to that of oxacillin and approximately fourfold greater than that of cloxacillin. Each of the three penicillins was administered orally to a group of ten volunteers for eight days in a dose of 500 mg four times a day. The mean concentrations of flucloxacillin in the serum were two- to sixfold higher than those of the other two agents on the first, fourth and eighth days of therapy. The percentage of flucloxacillin bound by serum protein was 94.6 per cent; for cloxacillin and oxacillin the values were 93.5 and 91.5 per cent, respectively. Using these data, the concentrations of free flucloxacillin in serum were found to be twice as high as those of cloxacillin and oxacillin. These findings suggest that, when administered orally, this new agent may offer some therapeutic advantage over oxacillin and cloxacillin.

Effect of probenecid on penetration of oxacillin into fibrin clots in vitro.

Probenecid significantly enhanced the in vitro penetration of oxacillin into fibrin clots suspended in rabbit serum or normal saline.

Pharmacokinetics of lincomycin and clindamycin phosphate in a canine model.

Linomycin and clindamycin phosphate were studed in a canine model in which acute biliary obstruction was produced during iv infusion of antibiotic. Hepatic and renal extraction, bilary and renal excretion, and concentrations in liver and kidney were measured. Total and nonesterified clindamycin were assayed. The antibiotics were taken up by the liver at similar rates; however; the rates of excretion and concentration in bile were significantly higher for lincomycin than for clindamycin. Biliary obstruction did not affect the concentration of either antibiotic in canalicular bile. Lincomycin was extracted by the kidneys and excreted into urine at a much higher rate than was clindamycin. Concentrations of nonesterified clindamycin in the hepatic vein were higher than those in the portal vein, an observation suggesting metabolic activation within the liver. This relation was reversed by bilary obstructon. The results in this canine model indicate a greater role for the kedney in the disposition of lincomycin than in that of clindamycin, major differences between the rates of biliary excretion of the two agents, and a probable change in the metabolism of clindamycin procued by acute bilary obstruction.

Effect of diuretics on urinary excretion of cephalothin in humans.

Diuretics and antibiotics are frequently used concomitantly. The possibility of drug interactions led us to study the effects of several diuretics on the renal elimination of cephalothin. Five healthy volunteers received a constant infusion of 500 mg of sodium cephalothin per h for 9 h on 4 consecutive days. Each day, after the third hour of infusion, the subjects were given one of the following in varying order: (i) furosemide (1 mg/kg, intravenous), (ii) mercaptomerin (250 mg, intramuscular), (iii) mannitol (25 g, intravenous), or (iv) no diuretic (control day). Fluid losses were replaced hourly. Serum and complete urine collections were obtained each hour and assayed for creatinine and cephalothin (bioassay). Clearances (milliliter per minute) and urinary excretions (milligram per hour) of cephalothin did not differ either when the diuretic day values were compared with control day, or when pre- and postdiuretic results on the same day were compared. Creatinine clearances were not affected by diuretics except for a transient rise after furosemide.

Bactericidal activity and pharmacology of cefazolin.

The in vitro bactericidal activity of cefazolin was found to be similar to that of cephaloridine and cephalothin but slightly greater than that of cephalexin against a majority of 233 strains of gram-positive and gram-negative organisms. Cefazolin, however, was two- to eightfold more active than the other two drugs against Escherichia coli and klebsiella. The mean peak concentrations in the serum in 10 normal subjects 1 h after intramuscular injections of 1,000, 500, and 250 mg of cefazolin were 38.8, 18.6, and 12.2 mug/ml, respectively. The antibiotic could still be detected at 8 h. Peak values for a given dose of cephaloridine were comparable. However, blood levels of cefazolin were regularly higher than those of cephaloridine over the first 8 h. The mean half-life of cefazolin in the serum was 2 h, whereas that of cephaloridine was 1.4 h. The degree of serum protein-binding was strikingly higher for cefazolin (81%) than for cephaloridine (24%), suggesting that the antibacterial activity of the former in serum might be less than that of cephaloridine after equal doses. This proved to be the case when the bacterial activity of blood drawn 1, 4, and 8 h after injection of the two drugs was examined.

Cross-resistance of Pseudomonas to gentamicin and tobramycin.

Clinical isolates of gentamicin-resistant organisms were found to be resistant to tobramycin, a new aminoglycoside antibiotic.