group is the most frequent cause of gram-negative endocarditis. They usually produce
subacute disease that is notable for its massive arterial emboli (40).
TheEnterobacteriaceaehave demonstrated their ability to resist the entire group ofb-lactam
antibiotics by their production of extended spectrumb-lactamases (ESBL). ESBL’s enable these
gram-negative to resist the penicillins, cephalosporins, and monobactams (41). Identification of
such organisms is unreliable in many clinical laboratories. An international survey ofKlebsiella
pneumoniaebacteremia in CCU revealed that 43% of isolates produced ESBLs (14). Although this
rate may be lower in North America, the possibility of an ESBL-producing organism must
always be considered in the CCU patient with gram-negative BSI/IE (42).
Multidrug resistant (MDR), Acinetobacter baumannii infections are emerging as an
important health-care associated pathogens in CCUs will. Most often, these infections are
ventilator or intravascular catheter associated (43). What makes their treatment so difficult is
the multiplicity of their defensive mechanisms that make them resistant to many classes of
antibiotics. These factors include ESBLs, efflux pumps, altered penicillin binding proteins and
mutations of DNA gyrase and topisomerase IV.
Polymicrobial IE most often occurs in patients with IVDA IE and in those who have
undergone cardiac surgery. The most frequently isolated organisms are P. aeruginosa,
Streptococcus faecalis,S. aureus, and CoNS. The mortality rate this type of IE is generally
twice that of those infected by a single organism (44) Fungal IE has risen by 270% over the last
30 years. Most of this increase is seen individuals cared for in CCUs as well as in those who
have undergone cardiac surgery (45).
Fungi cause 1 % of total cases of IE, 5% of IVDA IE, and 13% and 5% of early and late
PVE, respectively. Risk factors for its development include exposure to broad-spectrum
antibiotics and to cytotoxic agents (46).Candidaspp. are the most frequent causes of fungal IE.
Two-thirds are identified asCandida albicans. This organism is also the most frequently
recovered from catheter associated IE, especially those devices employed in hyperalimenta-
tion. The remainder of fungal IE usually is caused byAspergillusspp., most commonly
Aspergillus fumigatus. Fungal IVDA is usually caused byCandida(C. albicans,C. parapsilosis,or
C. tropicalis). They enter the bloodstream from the injection site directly or from contamination
of the drug paraphernalia (38). In non-IVDA, IE the gastrointestinal tract or intravascular
catheters are the most common sites of entry. Contaminated operating room air is the most
common source ofAspergillusPVE (47,48).
Approximately 5% of cases of IE have persistently negative blood cultures, culture
negative IE (CNIE). This rate may be higher in some areas in the world in which hard to grow
organisms, such asCoxiella burnetti, are fairly common. Automated blood culture systems are
able to readily retrieve organisms that previously had been considered to be fastidious
(HACEK group, fungi) Table 3 presents the current causes of CNIE.
In the United States, prior antibiotic usage is the most common cause of CNIE (67% of
cases). This is especially true for patients in the CCU. In the author’s experience, the
injudicious or “knee-jerk” use of broad-spectrum antibiotics in the CCU without full workup
of the cause of fever can suppress bacterial growth at the surface but not eradicate it within the
valvular thrombus. This can produce the state of “muted IE.” These delays in the diagnosis
Table 3 Causes of Culture Negative IE
Causes Comments
Prior antibiotic use Most frequent cause, at least 35%–79% of cases
Sequestration of infection within the thrombus Surface sterilization phenomena
Fastidious organisms Fungi, Q-fever,Tropheryma whipplei,Brucellaspp.,
Rickettsiae,Chlamydiae,Legionella
Right-sided endocarditis Nonvirulent organisms are filtered out by the lungs
Bacteria free stage Untreated infection for>3mo
Mural IE in VSD –
infection related to pacemaker wires –
Abbreviations: IE, infective endocarditis; VSD, ventricular septal defect.
Source: From Ref. 49.
222 Brusch