Endocarditis: Changes in Patients and Treatment

Abstracts & Commentary

Synopsis: HIV infection and injection drug use remain major risks for endocarditis; two weeks of right-sided Staphylococcal endocarditis with cloxacillin alone is effective.

Sources: Siddiq S, et al. Endocarditis in an urban hospital in the 1990s. Arch Intern Med 1996;15:2454-2458; Ribera E, et al. Effectiveness of cloxacillin with and without gentamicin in short-term therapy for right-sided Staphylococcus aureus endocarditis: A randomized, controlled trial. Ann Intern Med 1996;125:969-973.

Siddiq and coworkers in hartford reported 182 cases of endocarditis in 159 patients in two inner city hospitals in Hartford between January 1990 and July 1993. They confirmed an increasing trend of drug addiction as a predisposing factor but found a surprising 67% of patients to be known drug abusers and that 80% of those were HIV-positive. Almost half of their cases were right-sided (49 involved the tricuspid valve), with only a quarter of the cases having known underlying heart disease. The preponderant organism was Staphylococcus aureus (57% of the cases), with Streptococcus viridans being second (31%). Tricuspid valve infections were almost all S. aureus. Transesophageal echocardiology identified vegetations in 34 of 36 cases, 16 of which had negative transthoracic studies. Vegetations larger than 20 mm were correlated with embolic complications, but the motility of the vegetations was not. There was a relative lack of microvascular physical findings. Prosthetic valve infections were associated with a 25% mortality rate.

Ribera et al confined their investigations to right-sided endocarditis due to methicillin-sensitive S. aureus infections. They randomized therapy between a 14-day course of intravenous cloxacillin (2 g every 4 hours) or two weeks of cloxacillin plus an initial seven days of gentamicin (1 mg/kg q 8 h). They evaluated 90 patients, 74 of which qualified for a study and were randomized openly. At the end of two weeks, 92% of the cloxacillin alone and 94% of the combination group were cured. In the cloxacillin alone group, there was one death and three cases for which treatment was prolonged because of a poor clinical response. In the combination group, there were two deaths, two prolonged treatments, and one relapse. They failed to find a statistically significant difference in outcome among these patients but did notice a slightly reduced duration of fever and increased incidence of renal toxicity in the combination group. The authors advocate a two-week course of cloxacillin alone for uncomplicated right-sided S. aureus endocarditis and question the added value of gentamicin.

COMMENT BY ALAN D. TICE, MD

These studies reflect an increasing incidence of right-sided S. aureus endocarditis due to intravenous drug abuse as well as an attempt to further reduce the cost of therapy by shortening the course and simplifying therapy. Hartford obviously has a problem with drug abuse and secondary drug-related HIV infections as well as endocarditis. Their figures are consistent with estimates of two cases of endocarditis per 1000 intravenous drug abusers per year.1 More than half of their cases of endocarditis are related to intravenous drug abuse. They point out the problems in recognizing and treating IV drug-related endocarditis, with the lack of the classic microvascular phenomenon, and the need to consider transesophageal echocardiology. There were also the confounding factors of compliance (15% of their patients left the hospital against medical advice) and complicating HIV infection, as well as the high mortality rate from prosthetic valves and infections.

The study in Spain is interesting and suggests that a two-week course of cloxacillin alone therapy is sufficient for uncomplicated right-sided endocarditis. With the pressures of managed care, this approach sounds attractive. Unfortunately, many of the cases of right-sided S. aureus endocarditis are complicated with persistent lung abscesses. The number of cases in the study is not sufficient to exclude the possibility of a faster response, although an increased toxicity, with the addition of an aminoglycoside.

The authors used gentamicin for only a week and used an every eight-hour regimen with a relatively low dose. This is different from the prior studies that used a twice-daily regimen of aminoglycocides. Once-daily dosing of gentamicin also seems more appropriate these days. The potential value of a once-daily regimen for two weeks is unclear.

Outpatient treatment of endocarditis is another approach at saving money, but in general, intravenous drug abusers are not sent home with a reliable vascular access and often do not have a stable enough home situation to assure completion of therapy. Skilled nursing facilities offer a less costly alternative to hospital care, although the physician involvement cannot be as great as in the hospital and patients may present management problems for the nursing staff.

The challenges of endocarditis will likely increase with the frequency of classic cases continuing to decline along with a growing number of cases with significant social and economic challenges. How short a course of therapy can safely be given from an outcomes and legal perspective remains to be determined.

Reference

1. Graves MK, Soto L. Left-sided endocarditis in parenteral drug abuser: Recent experience at a large community hospital. South Med J 1992;85:378-380.