Carrizosa J, Levison M E
Antimicrob Agents Chemother. 1981 Sep;20(3):405-9. doi: 10.1128/AAC.20.3.405.
Minimal concentrations of aminoglycoside that could produce a synergistic effect with penicillin were investigated in broth cultures containing 10(8) enterococci per ml, in vitro in vegetations infected with ca. 10(8) enterococci per g, and in vivo in an experimental model of enterococcal endocarditis. Penicillin G plus gentamicin (1.5 or 0.75 microgram/ml) sterilized a broth culture of a streptomycin-resistant strain (E1) at 48 h. In contrast, penicillin G plus gentamicin (1.5 or 0.75 microgram/ml) sterilized only 2 of 15 in vitro vegetations at 5 days. Similarly, doses of gentamicin that resulted in peak serum levels of 1.5 microgram/ml failed after 10 days of therapy with penicillin G plus gentamicin to sterilize in vivo vegetations infected with E1, and doses of gentamicin that resulted in peak serum levels of about 8 micrograms/ml sterilized four of six vegetations. Similar results were obtained with a streptomycin-susceptible strain. These studies indicated that the rate of bactericidal activity in broth cultures is greater than the bacteriological response in infected vegetations and that aminoglycoside concentrations that appear efficacious on the basis of synergy studies in broth cultures may not be satisfactory clinically.
在每毫升含有10⁸肠球菌的肉汤培养物中、在每克感染约10⁸肠球菌的赘生物中以及在肠球菌性心内膜炎的实验模型中，研究了可与青霉素产生协同作用的最低氨基糖苷类浓度。青霉素G加庆大霉素（1.5或0.75微克/毫升）在48小时时使一株耐链霉素菌株（E1）的肉汤培养物无菌生长。相比之下，青霉素G加庆大霉素（1.5或0.75微克/毫升）在5天时仅使15个体外赘生物中的2个无菌生长。同样，在青霉素G加庆大霉素治疗10天后，导致血清峰值水平为1.5微克/毫升的庆大霉素剂量未能使感染E1的体内赘生物无菌生长，而导致血清峰值水平约为8微克/毫升的庆大霉素剂量使6个赘生物中的4个无菌生长。用一株对链霉素敏感的菌株也得到了类似结果。这些研究表明，肉汤培养物中的杀菌活性速率大于感染赘生物中的细菌学反应速率，并且基于肉汤培养物中的协同研究看似有效的氨基糖苷类浓度在临床上可能并不令人满意。
