A prospective study of the epidemiology of infective endocarditis (IE) in a well-defined urban population of 428,000 inhabitants during a 5-year period was carried out. All patients were treated in the same institution, and history, diagnostic procedures, and treatment were standardized. Of 233 consecutive suspected episodes of IE, 127 fulfilled the modified von Reyn criteria. After patients not living in the defined area were excluded, 99 episodes in 90 patients were analyzed in the epidemiologic part of the study. Of these, 33 episodes were definite endocarditis, verified by surgery or autopsy; 35 probable; and 31 possible endocarditis episodes. Another 34 episodes were found retrospectively and are included in the incidence calculation. The crude incidence was calculated to be 6.2/100,000 inhabitants per year, which is high compared to earlier studies. Adjusted to the population of Sweden, the incidence was 5.9/100,000 inhabitants per year. The annual incidence was higher for women, 6.6/100,000, than for men, 5.8/100,000. In the oldest age-group (80-89 years) the annual incidence was 22/100,000 in the prospective study and 30/100,000 if retrospective cases were included. Contrary to almost all other studies, we did not find a male predominance among our cases. Only 7% of patients were intravenous drug abusers, and 15% had a prosthetic valve. The most common bacteria were methicillin-susceptible Staphylococcus aureus (31%) and alpha-streptococci (28%); 12% of episodes were culture negative. The mortality from IE in the population was 1.4/100,000 inhabitants per year. A higher-than-expected incidence of IE was found, especially among older patients and women.

No abstract

Pacemaker endocarditis is a rare but serious complication. Few studies addressing its treatment have been published. Clinical characteristics and outcome were retrospectively studied in 38 patients with 44 episodes of pacemaker infective endocarditis (PMIE) in Göteborg, during 1984-2001. The male/female ratio of episodes was 27/17 and the mean age 69 y. Transthoracic echocardiography (TTE) showed vegetation in 4/22 (18%) episodes and transoesophageal echocardiography (TEE) in 22/33 (67%). Staphylococci were isolated in 66% of blood cultures. The pacemaker system (PS) was removed in 28 episodes and in 18 of these there were no signs of reinfection at follow-up. In 16 episodes the PS was not removed, and in 13 of these, signs of infection were found at follow-up. Thus, the present study of PMIE showed staphylococci to be predominant causative agents and demonstrated a high diagnostic sensitivity of TEE. According to our results, PM removal rather than conservative treatment should be considered in all cases.

Background: Long-term parenteral ␤-lactam treatment is often complicated by adverse reactions that necessitate drug withdrawal.

N-Formimidoyl thienamycin (MK0787) undergoes renal metabolism by a dipeptidase, dehydropeptidase I, located on the brush border of the proximal tubular cells. The effects of two inhibitors (MK-789 and MK-791) of dehydropeptidase I on the pharmacokinetics of N-formimidoyl thienamycin were studied in 41 healthy subjects receiving various combinations of N-formimidoyl thienamycin and MK-789 or MK-791. Both inhibitors affected the plasma kinetics of N-formimidoyl thienamycin only to a small extent. Plasma concentrations and the area under the plasma concentration curve increased about 20%'o with a proportional decrease in plasma clearance. Plasma half-life was not altered significantly. Coadministration of MK-789 or MK-791 resulted in uniform and marked increases in urinary recovery and renal clearance of N-formimidoyl thienamycin. Thus, at an Nformimidoyl thienamycin/MK-791 ratio of 1:0.25 or higher, the urinary recovery was about 72% in all subjects, whereas it varied between 7.7 and 43% when Nformimidoyl thienamycin was given alone. The ratio of the N-formimidoyl thienamycin and MK-791 doses affected response. At relatively higher doses of MK-791, significant increases of N-formimidoyl thienamycin urinary recovery, renal clearance, and urine concentrations occurred during the later part of the 10-h observation period after each administration. At a 1:1 ratio of the two drugs, the inhibition of renal metabolism of N-formimidoyl thienamycin was maintained for at least 8 h, whereas renal clearance declined as soon as 4 h after the administration of a 1:0.25 ratio. The results indicated that MK-789 and MK-791 alter the renal excretion of N-formimidoyl thienamycin from glomerular filtration plus tubular secretion to glomerular ifitration only, possibly by competitively inhibiting the penetration of N-formimidoyl thienamycin into the proximal tubular cells.The human pharmacokinetics of N-formimidoyl thienamycin (MK0787) are characterized by high plasma concentrations and rapid elimination via the kidneys (3). The urinary recovery (UR) of N-formimidoyl thienamycin varies considerably between subjects, whereas the withinsubject variation is very small (3). The were included in the studies described in this report.All subjects gave their informed written consent to participate, and the protocols for the studies were 300