automatically except in the presence of IE, infection of vascular tunnel, suppurative
thrombophlebitis or infection by certain pathogens (Corynebacterium JK,Pseudomonasspp.,
fungi,S. aureusor mycobacteria) (205). Intraluminal infusions of antibiotics have a cure rate of
30% to 50% against sensitive organisms. Whether the use of thrombolytic agents to dissolve the
fibrin sheath of the catheter improves outcomes has not been established (206).
Vascular catheters that are colonized withS. aureusmay be associated with development
ofS. aureusBSI after their removal. These catheters had no evidence ofS. aureusBSI up to
24 hours post-removal. Twenty-four percent subsequently developedS. aureusbacteremia. The
median duration for its development after catheter removal was three days with a range of 2 to
25 days. It appears that the length of placement of the line was a significant risk factor.
Administration of an appropriate antibiotic within 24 hours of the catheter’s removal reduced
the rate of subsequent bacteremia by 83% (207). The delayed appearance of the BSI is probably
related to the development of endotheliosis before the extraction of the catheter.
BSI that persists after three days of therapy with an appropriate antibiotic therapy is an
independent risk factor for IE as well as for death (208).
ANTIBIOTIC THERAPY
There are many challenges to sterilizing an infected thrombus. Among these are: (i) the
overwhelming density of organisms (10 to 100 billion bacteria/gm of tissue); (ii) the decreased
metabolic and replicative activity of the organisms, residing within the vegetation, that results
in their being less sensitive to the action of most antibiotics and (iii) the decreased penetration
of antibiotics into the platelet/fibrin thrombus. In addition, both the mobility and phagocytic
function of white cells is impaired within the fibrin rich vegetation (209–211).
Table 14 presents the basic principles of antibiotic therapy of IE. It is estimated that, in a
case ofEscherichia coliIE, 220 times the minimum bactericidal concentration (MBC) of
ceftriaxone is required to sterilize the vegetation (209). Determining the bactericidal titer
should be applied only to those patients who are not responding well to therapy or who are
infected by an unusual organism.
A maximum daily temperature of greater than 37 8 C after 10 days of treatment should be
of concern to the clinician. It may represent a relatively resistant pathogen, extracardiac
infection, pulmonary or systemic emboli, drug fever, Clostridium difficilecolitis, or an infected
intravenous site (212). If the invading organism is sensitive to the administered antibiotic, a
thorough search for an extracardiac site should be conducted. Mycotic aneurysms are probably
the most difficult source to detect. If the TTE is not helpful, then a TEE should be performed
(213,214). Sterile recurrent emboli are usually due to immunological processes and do not
necessarily represent antibiotic failure (215). Mortality rates are dependent on the nature of the
Table 14 Basic Principles of Antibiotic Therapy of the Infective Endocarditis
The necessity of using bactericidal antibiotics because of the “hostile” environment of the infected vegetationa.
The MIC and MBC of the administered antibiotic against the isolated pathogen needs to be determined in order
to insure adequate dosing of the agent.
Generally, intermittent dosing of an antibiotic provides superior penetration of the thrombus as compared to a
continuous infusion. Its penetration into tissue is directly related to its peak level in serum.
All patients with IE should be treated in a health care facility for the first 1–2 wk to monitor their hemodynamic
stability.
In cases of potential acute infective endocarditis, antibiotic therapy should be started immediately after three to five
sets blood cultures have been drawn. Preferably all of them should be obtained within 1 to 2 hr so as to allow the
expeditious commencement of antibiotic therapy. The selection of antibiotic/antibiotics to needs to be made
empirically on the basis of physical examination and clinical history.
In cases of potential subacute infective endocarditis, antibiotic treatment should not be started until the final culture
and sensitivity data are available. A delay of 1 to 2 wk in doing so does not adversely affect the final outcome.
The usual duration of therapy ranges from 4–6 wk. A 4-wk course is appropriate for an uncomplicated case of
native valve endocarditis. A shorter course of two weeks may be appropriate in certain cases (see text). Six
weeks required for the treatment of prosthetic valve endocarditis and in those infections with large vegetations
such as associated with infection by members of the HACEK family.
aLinezolid and quintristin/dalfopristin appear to be exceptions to this principle.
Source: From Ref. 222.
240 Brusch