Akashdeep Singh, MD, DM
Potential Financial Conflicts of Interest: None disclosed.
Singh A.; Ampicillin plus Ceftriaxone for High-Level Aminoglycoside-Resistant Enterococcus faecalis Endocarditis. Ann Intern Med. 2008;148:243. doi: 10.7326/0003-4819-148-3-200802050-00012
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Published: Ann Intern Med. 2008;148(3):243.
TO THE EDITOR:
The antimicrobial synergism of ampicillin plus ceftriaxone to treat high-level aminoglycoside-resistant (HLAR) Enterococcus faecalis endocarditis, as shown by Gavaldà and colleagues (1), is important. However, certain basic questions need to be answered before this treatment can be incorporated into everyday practice. First, enterococci are inherently resistant to cephalosporins, including ceftriaxone. Second, ampicillin and ceftriaxone are both β-lactam antibiotics with a common mechanism of action: inhibition of synthesis of the bacterial peptidoglycan cell wall. Antimicrobial agents acting on different targets may enhance the overall antimicrobial activity. How then can there be synergism between these 2 drugs? Treatment of HLAR E. faecalis depends on precise determination of antibiotic susceptibilities, testing for bactericidal activity, ascertainment of the serum inhibitory and bactericidal titers, and monitoring of drug concentrations in the serum. Although aminoglycoside resistance is often present, these drugs can still synergize with cell-wall inhibitors, provided that the aminoglycoside's minimal inhibitory concentration is 1000 mg/L or less (2). Streptomycin is worth testing because it can be active against enterococci that are resistant to other aminoglycosides (3). The cure rate for HLAR E. faecalis in Gavaldà and colleagues' study was 52% with ampicillin plus ceftriaxone combination therapy, which does not differ from the 40% to 50% cure rate with cell-wall–susceptible agent monotherapy (4).
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