increasing prevalence of isolates ofS. aureusfor whom the MIC of vancomycin is greater than
4 mg/mL (242). In addition, it appears that the penetration of vancomycin into target tissues is
decreased especially in diabetics (243). Similar concerns exist regarding the efficacy of
vancomycin in treating MRSA infections (244). Until sensitivities are known, it is advisable to
use high does vancomycin to achieve a trough level of greater than 15mg/mL (245).
Over the last decade, several antibiotics have come on the market to meet the increasing
challenge of severe infections due to resistant gram-positive agents (Table 18). The potential for
increasing vancomycin toxicity at higher dose levels is an added to reason to consider these
agents as both empiric and definitive treatment. Linezolid appears to be superior to
vancomycin for many types of MRSA infections including IE (246–248). Therapeutic failures
of this agent in treating IE have been documented. Some are due to inadequate serum levels as
well as possibly due to the bacteriostatic quality of the drug (249). Linezolid administration is
associated with significant hematological side effects including anemia and thrombocytopenia.
These are usually reversible upon cessation of treatment. However, the neuropathy occurs at
an increasing rate the longer medication is administered. It often is irreversible or partially
reversible. This limits its safety period to no more than four to six weeks. The risk of the
serotonin syndrome with concurrent SSRI and linezolid therapy does occur. However, the
risk–benefit analysis often favors starting linezolid in these patients because of shortcomings of
vancomycin. Optic neuritis is an idiosyncratic reaction that can occur at any time. Linezolid’s
advantages are that it is extremely well absorbed orally and lends itself to transition therapy. In
one series of patients with complicated gram-positive IE who required to mediate cardiac
surgery, patients were successfully switched early and successfully to oral linezolid therapy in
finish a four- to six-week course of antibiotic (250). The author has had similar success in
treating susceptible gram-positive IE in nonsurgical patients.
Daptomycin is a bactericidal drug that has had a good amount of success in treating
MSSA and MRSA IE (251). Myositis is a significant side effect especially at higher doses.
Resistance to the drug is on the increase. This occurs in association with changes in surface
charge, membrane phospholipids, and drug binding ofS. aureus(252). It appears that prior
vancomycin therapy promotes resistance to daptomycin. This is probably due to the decreased
penetration of daptomycin secondary to an increase in the thickness of the cell wall of
S. aureus(253).
Tigecycline is another of the alternative agents for resistant gram-positive organisms. It
has relatively few side effects. Experience with this compound is still limited (254). Tables 18,
19, and 20 summarize the antibiotic treatment of staphylococcal IE.
Tables 21, 22, and 23 present the antibiotic regimens for the treatment of other types of
the IE that were in the may be encountered in CCU.
FUNGAL ENDOCARDITIS
Combined medical and surgical treatment is necessary for cure of the vast majority of fungal
valvular infections. Amphotericin B has been the mainstay of medical therapy of fungal IE (47).
Table 20 Therapy for Coagulase-Negative Staphylococcal Infection of Prosthetic Valves or Other Prosthetic
Materiala,b
Antibiotic Dosage regimen
Vancomycin 15 mg/kg q12h for 6 wk
and
Rifampin 300 mg PO q8h for 6 wk
and
Gentamicin 3mg/kg q24h IV as a single dose or in divided doses q12h for 2 wk
a80% of isolates recovered within the first year after valve replacement are resistant to theb-lactam antibiotics.
After this period, 30% are resistant. Sensitivity to the penicillins must be confirmed because standard sensitivity
testing may not detect resistance. If the isolate is sensitive, oxacillin or cefazolin may be substituted.
bIf the organism is resistant to the aminoglycosides, a quinolone, to which it is proven sensitive, should be
substituted.
Source: From Ref. 222.
Infective Endocarditis and Its Mimics in Critical Care 245