Two major objectives must be achieved to treat IE effectively. The infecting micro-organism in the vegetation must be eradicated. Also, invasive, destructive intracardiac and focal extracardiac complications of infection must be resolved if morbidity and mortality are to be minimized. The second objective often exceeds the capacity of effective antimicrobial therapy and requires cardiac or other surgical intervention.
Bacteria in vegetations multiply to population densities approaching 10 9 to 10 10 organisms per gram of tissue, become metabolically dormant, and are difficult to eradicate. Optimal therapy should use bactericidal antibiotics or antibiotic combinations rather than bacteriostatic agents.Additionally, antibiotics reach the central area of avascular vegetations by passive diffusion. To reach effective antibiotic concentrations in vegetations, high serum concentration must be achieved, and penetration by some agents is limited even then. Parenteral antimicrobial therapy is used whenever feasible in order to achieve suitable serum antibiotic concentrations and to avoid the potentially erratic absorption or orally administered therapy. Treatment is continued for prolonged period to ensure eradication of dormant microorganisms.
In selecting antimicrobial therapy for patients with IE, one must consider the ability of potential agents to kill the causative organism as well as the MIC (minimum inhibitory concentration) and minimum bactericidal concentration (MBC) of these antibiotics for the organism. The MIC is the lowest concentration that inhibits growth, and MBC is the lowest concentration that decreases a standard inoculum of organisms 99.9 per cent during 24 hours. For the vast majority of streptococci and staphylococci, the MIC and MBC of penicillins, cephalosporins, or vancomycin are the same or differ by only a factor of two to four. Organisms for which the MBC for these antibiotics is 10 fold or greater than the MIC are occasionally encountered. This phenomenon has been termed tolerance. Most of the tolerant strains are simply killed more slowly than non tolerant strains and with prolonged incubation (48 hours) their MICs and MBCs are similar. Enterococci can be killed by the combined activity of selected penicillins or vancomycin and an aminoglycoside. This enhanced antibiotic activity of the combination against enterococci, if of sufficient magnitude, is called synergy or a synergistic bactericidal effect.A synergistic bactericidal effect is required for optimal therapy of enterococcal endocarditis and has
been used to achieve more effective therapy or effective short-course therapy of IE caused by other organisms.
The regimens recommended for the treatment of IE caused by specific organisms are designed to provide high concentrations of antibiotics in serum, also deep in vegetations. Concentrations that exceed the organism’s MIC throughout most, if not routinely measured, but currently recommended antimicrobial regimens are based on these values for specific organisms. With the exception of staphylococcal endocarditis, the antimicrobial regimens recommended for the treatment of NVE and PVE are similar, although more prolonged treatment is often advised for PVE.
Antimicrobial Therapy For Specific Organisms
1) Treatment for Native Valve Endocarditis Due to Penicillin-Susceptible Viridans Streptococci and Streptococcus Bovis (Minimum Inhibitory Concentration < 0.1μg/ml).
2)Treatment for Native Valve Endocarditis Due to Strains of Viridans Streptococci and Streptococcus Bovis, Relatively Resistant to Penicillin G (Minimum Inhibitory Concentration >0.1μg/ml and <0.5μg/ml.
3) Standard Therapy for Endocarditis Due to Enterococci
Bacteria in vegetations multiply to population densities approaching 10 9 to 10 10 organisms per gram of tissue, become metabolically dormant, and are difficult to eradicate. Optimal therapy should use bactericidal antibiotics or antibiotic combinations rather than bacteriostatic agents.Additionally, antibiotics reach the central area of avascular vegetations by passive diffusion. To reach effective antibiotic concentrations in vegetations, high serum concentration must be achieved, and penetration by some agents is limited even then. Parenteral antimicrobial therapy is used whenever feasible in order to achieve suitable serum antibiotic concentrations and to avoid the potentially erratic absorption or orally administered therapy. Treatment is continued for prolonged period to ensure eradication of dormant microorganisms.
In selecting antimicrobial therapy for patients with IE, one must consider the ability of potential agents to kill the causative organism as well as the MIC (minimum inhibitory concentration) and minimum bactericidal concentration (MBC) of these antibiotics for the organism. The MIC is the lowest concentration that inhibits growth, and MBC is the lowest concentration that decreases a standard inoculum of organisms 99.9 per cent during 24 hours. For the vast majority of streptococci and staphylococci, the MIC and MBC of penicillins, cephalosporins, or vancomycin are the same or differ by only a factor of two to four. Organisms for which the MBC for these antibiotics is 10 fold or greater than the MIC are occasionally encountered. This phenomenon has been termed tolerance. Most of the tolerant strains are simply killed more slowly than non tolerant strains and with prolonged incubation (48 hours) their MICs and MBCs are similar. Enterococci can be killed by the combined activity of selected penicillins or vancomycin and an aminoglycoside. This enhanced antibiotic activity of the combination against enterococci, if of sufficient magnitude, is called synergy or a synergistic bactericidal effect.A synergistic bactericidal effect is required for optimal therapy of enterococcal endocarditis and has
been used to achieve more effective therapy or effective short-course therapy of IE caused by other organisms.
The regimens recommended for the treatment of IE caused by specific organisms are designed to provide high concentrations of antibiotics in serum, also deep in vegetations. Concentrations that exceed the organism’s MIC throughout most, if not routinely measured, but currently recommended antimicrobial regimens are based on these values for specific organisms. With the exception of staphylococcal endocarditis, the antimicrobial regimens recommended for the treatment of NVE and PVE are similar, although more prolonged treatment is often advised for PVE.
Antimicrobial Therapy For Specific Organisms
1) Treatment for Native Valve Endocarditis Due to Penicillin-Susceptible Viridans Streptococci and Streptococcus Bovis (Minimum Inhibitory Concentration < 0.1μg/ml).
2)Treatment for Native Valve Endocarditis Due to Strains of Viridans Streptococci and Streptococcus Bovis, Relatively Resistant to Penicillin G (Minimum Inhibitory Concentration >0.1μg/ml and <0.5μg/ml.
3) Standard Therapy for Endocarditis Due to Enterococci
All enterococci causing endocarditis must be tested for antimicrobial susceptibility in order to select optimal therapy. These regimens are for treatment of endocarditis caused by enterococci that are susceptible to vancomycin or ampicillin and not highly resistant to gentamicin.These may also be used for treatment of endocarditis caused by penicillin-resistant(MIC > 0.5) viridans streptococci and nutritionally variant spreptococci (S.defectivus, S. adjacens), or enterococcal PVE.Cephalosporins are not alternatives to penicillin/ampicillin in penicillin-allergic patients.4)Treatment for Staphylococcal Endocarditis in the Absence of Prosthetic Material
5)Treatment of Staphylococcal Endocarditis in the Presence of a Prosthetic Valve or other Prosthetic Material
7)Culture-Negative Endocarditis
Special studies to diagnose IE caused by fastidious bacteria and other organisms must be performed (serological studies). Thereafter, unless clinical or epidemiologic clues suggest an etiological diagnosis, the recommended treatment for culture negative NVE is ampicillin plus gentamicin (standard regimen for enterococcal endocarditis, because in the absence of confounding antibiotic therapy enterococci and staphylococci are unlikely causes of culture-negative NVE, ceftriaxone could be used in this regimen instead of ampicillin. For patients with culture-negative PVE, vancomycin is added to this regimen.
Monitoring Therapy for Endocarditis
Within a week after initiation of effective antimicrobial therapy, almost 75 per cent of patients with IE, including those with PVE, are afebrile and 90 per cent have defervesced by the end of the second week of treatment. Persistence or recurrence of fever more than 7 to 10 days after initiation of antibiotic therapy identified patients with increased morality rate and with complications of infection or therapy.
Patients must be carefully monitored during therapy and for several months thereafter. Failure of antimicrobial therapy, myocardial or metastatic abscess, emboli, hypersensitivity to antimicrobial agents, and other complications of therapy (catheter-related infection,thrombophlebitis) or intercurrent illness may be manifested by persistent or recurrent fever. Drug reactions have accounted for fever in 17 to 28 per cent of these patients. In 33 to 45 per cent of patients, persistent fever was associated with significant intracardiac complications,many of which require surgical intervention.
Renal function should be monitored in patients receiving vancomycin or aminoglycosides, and the complete blood counts should be checked at least weekly in patients receiving high dose beta-lactam antibiotics or vancomycin.
Natural History of Vegetations
• On repeat echo, 3 weeks to 3 months after initiation of ultimately effective antibiotic therapy, 29 per cent disappear, 59 per cent were unchanged, 24 per cent were smaller, and 17 per cent were larger.
• In the absence of severe valvular regurgitation or ongoing clinical symptoms, such persistence does not correlate with late complications.
• In contrast, increase in vegetation size by echocardiography over the course of therapy may identify a subset of patients with a higher rate of complications, independently of the presence of persistent bacteremia or overt clinical stigmata of IE.
Special studies to diagnose IE caused by fastidious bacteria and other organisms must be performed (serological studies). Thereafter, unless clinical or epidemiologic clues suggest an etiological diagnosis, the recommended treatment for culture negative NVE is ampicillin plus gentamicin (standard regimen for enterococcal endocarditis, because in the absence of confounding antibiotic therapy enterococci and staphylococci are unlikely causes of culture-negative NVE, ceftriaxone could be used in this regimen instead of ampicillin. For patients with culture-negative PVE, vancomycin is added to this regimen.
Monitoring Therapy for Endocarditis
Within a week after initiation of effective antimicrobial therapy, almost 75 per cent of patients with IE, including those with PVE, are afebrile and 90 per cent have defervesced by the end of the second week of treatment. Persistence or recurrence of fever more than 7 to 10 days after initiation of antibiotic therapy identified patients with increased morality rate and with complications of infection or therapy.
Patients must be carefully monitored during therapy and for several months thereafter. Failure of antimicrobial therapy, myocardial or metastatic abscess, emboli, hypersensitivity to antimicrobial agents, and other complications of therapy (catheter-related infection,thrombophlebitis) or intercurrent illness may be manifested by persistent or recurrent fever. Drug reactions have accounted for fever in 17 to 28 per cent of these patients. In 33 to 45 per cent of patients, persistent fever was associated with significant intracardiac complications,many of which require surgical intervention.
Renal function should be monitored in patients receiving vancomycin or aminoglycosides, and the complete blood counts should be checked at least weekly in patients receiving high dose beta-lactam antibiotics or vancomycin.
Natural History of Vegetations
• On repeat echo, 3 weeks to 3 months after initiation of ultimately effective antibiotic therapy, 29 per cent disappear, 59 per cent were unchanged, 24 per cent were smaller, and 17 per cent were larger.
• In the absence of severe valvular regurgitation or ongoing clinical symptoms, such persistence does not correlate with late complications.
• In contrast, increase in vegetation size by echocardiography over the course of therapy may identify a subset of patients with a higher rate of complications, independently of the presence of persistent bacteremia or overt clinical stigmata of IE.
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