Joan Gavaldá, MD, PhD; Oscar Len, MD; Benito Almirante, MD; Albert Pahissa, MD
Potential Financial Conflicts of Interest: None disclosed.
Gavaldá J, Len O, Almirante B, Pahissa A. Ampicillin plus Ceftriaxone for High-Level Aminoglycoside-Resistant Enterococcus faecalis Endocarditis. Ann Intern Med. 2008;148:243. doi: 10.7326/0003-4819-148-3-200802050-00013
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Published: Ann Intern Med. 2008;148(3):243.
We read with interest the letter by Dr. Singh regarding our article. First, we would like to clarify that the cure rate for HLAR E. faecalis endocarditis was 71.4%, far greater than the best cure rate reached with a cell-wall–susceptible agent alone or in combination with other therapy. After careful review of our article, we found no figure or data that could lead to this confusion. Second, Dr. Singh's question about the synergic effect of ampicillin plus ceftriaxone was evaluated in vitro by Mainardi and colleagues (1) and by our group in different studies in the experimental endocarditis model (2, 3). Mainardi and colleagues (1) used amoxicillin and cefotaxime and proposed that, at low amoxicillin concentrations, the low-molecular-weight penicillin-binding proteins (PBPs) 4 and 5 would be partially saturated, but the nonessential PBPs 2 and 3 could participate in building the cell wall. The combination with cefotaxime would totally saturate PBPs 2 and 3, producing the bactericidal synergistic effect. Thereafter, our group showed that the combination of ampicillin plus ceftriaxone was as effective as ampicillin plus gentamicin for the treatment of experimental endocarditis due to non-HLAR E. faecalis(2) and more effective than ampicillin alone in experimental endocarditis due to HLAR E. faecalis(3). Third, although we agree with Dr. Singh about the possible usefulness of the combination of ampicillin plus gentamicin if the aminoglycoside's mean inhibitory concentration is between 500 and 1000 mg/L, this may be only theoretical. Judging by the results of our study, the combination of ampicillin plus ceftriaxone would be more successful.
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