Lawrence R. Freedman

Chronic Pyelonephritis at Autopsy

Excerpt About 6 years ago, an analysis of the frequency with which chronic pyelonephritis*was diagnosed at autopsy showed that males were affected about as frequently as females (2). These data wer...

Damage to the Aortic Valve as a Cause of Death in Bacterial Endocarditis

Excerpt The most common cause of death in patients with bacterial endocarditis is heart failure (1). Bacteriologic cure is generally easily achieved with antibiotics, and complications such as rena...

Outcome of Treatment

Despite the availability of chemotherapeutic agents capable of sterilizing endocardial vegetations, infective endocarditis (IE) remains a disease with a high mortality. How high depends on the location of the infection, the nature of the infecting microorganism, and the expertness with which the major cause of death, valve destruction, is recognized and treated surgically.

Host Defense Mechanisms

Very little is known about the mechanisms of host defense in intravascular infections. Considerable emphasis is put on the ineffectiveness of conventional mechanisms: the lack of a lytic effect of antibody and complement on the gram-positive cocci responsible for the vast majority of infections and the inability of polymorphonuclear leukocytes (PMN) to penetrate the fibrin barrier surrounding developing bacterial colonies. These two factors, in addition to the diminished metabolic activity of colonies located deep in the vegetations (with the consequence that they would be theoretically less susceptible to the action of antibiotics, such as penicillin), serve as the theoretical basis for the empirical clinical reality that it takes long-term treatment with bactericidal antibiotics to cure intravascular infections.

The Nonbacterial Thrombotic Vegetation

The normal endothelial surface is highly resistant to microbial infection, since bacteremia in normal man and animals rarely results in the establishment of intravascular infection. Rickettsial infection is probably the outstanding exception to this statement, since in these infections it would appear that normal endothelial cells are regularly colonized.(1) Vibrio fetus infection is often associated with a septic thrombophlebitis, but the pathogenesis of these lesions is not well understood.(2)

Prophylaxis of Intravascular Infection

There is considerable debate concerning the indications for administering antibiotics with the goal of preventing IE. There is also uncertainty as to how much of which antibiotics should be administered in those instances where it is evident that prophylaxis should be given.

Complications of Treatment

The complications of correct treatment of intravascular infections are those that one would expect with long-term high-dose antibiotic therapy. The physician must be particularly alert to the development of vestibular disturbances (20–30% of patients treated with recommended regimen for enterococcal endocarditis) due to streptomycin therapy and to discontinue streptomycin after 4 weeks when this is detected.

The Pathogenesis of Intravascular Infection

Intravascular infection is the name applied to microbial proliferation within a platelet-fibrin vegetation located within the circulatory system. The initiation of such an infection depends, in all likelihood, upon the prior establishment of a susceptible, nonbacterial thrombotic vegetation (NBTV) and dissemination via the bloodstream of microorganisms of a sort, and in a number sufficient, to attach to and multiply within the interstices of the vegetation. This sequence of events was well established 50 years ago.(1)

Establishment of Intravascular Infection

Infection of susceptible intracardiac vegetations comes about by the deposition of bacteria circulating in the bloodstream on the surface of the vegetations. This mechanism is easily demonstrable in animals, and there is no evidence to support the older suggestion that bacteria arrive in the vegetations by way of the blood supply to the valve or endocardium. Studies of the early vegetations show clearly that colonization takes place from the edge of the vegetations. With the passage of time, older colonies, often containing microbial debris with metabolically less active forms, are found at the base of the vegetations.(1–3)

Indices of Effectiveness of Treatment

Evidence of clinical improvement after the institution of effective antibiotic treatment is usually not dramatic. Patients may have prompt normalization of temperature, in which case they might feel very much better quickly. On the other hand, although fever usually does subside within 2–4 days, this subsidence is gradual, and dramatic response is not the rule. Persistence of fever may indicate ineffective antibiotic therapy or a drug reaction. In some patients, persistent low-grade fever will continue as long as the patient receives antibiotics. Reappearance of fever after an afebrile interval may indicate embolization (pulmonary or arterial), infectious complications of prolonged intravenous therapy, reseeding of the bloodstream from a peripheral abscess, or drug reaction. Rarely, persistence of fever may be an indication of the presence of concomitant underlying disease such as lymphoma or myxoma.