Bush K, Flamm R K, Ohringer S, Singer S B, Summerill R, Bonner D P
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08540.
Antimicrob Agents Chemother. 1991 Nov;35(11):2203-8. doi: 10.1128/AAC.35.11.2203.
An isolate of Serratia marcescens that produced both an inducible chromosomal and a plasmid-mediated TEM-1 beta-lactamase was resistant to ampicillin and amoxicillin and also demonstrated decreased susceptibility to extended-spectrum beta-lactam antibiotics (ESBAs). Clavulanic acid did not lower the MICs of the ESBAs, but it decreased the MICs of the penicillins. The TEM-1-producing plasmid was transferred to a more susceptible S. marcescens strain that produced a well-characterized inducible chromosomal beta-lactamase. The MICs of the ESBAs remained at a low level for the transconjugant. Ampicillin and amoxicillin which were good substrates for the plasmid-mediated enzyme, were not well hydrolyzed by the chromosomal enzymes; the ESBAs were hydrolyzed slowly by all the enzymes. When each of the S. marcescens strains was grown with these beta-lactam antibiotics, at least modest increases in chromosomal beta-lactamase activity were observed. When organisms were grown in the presence of clavulanic acid and an ESBA, no enhanced induction was observed. The increases in the MICs of the ESBAs observed for the initial clinical isolate may have been due to a combination of low inducibility, slow hydrolysis, and differences in permeability between the S. marcescens isolates. When clavulanic acid and a penicillin were added to strains that produced both a plasmid-mediated TEM and a chromosomal beta-lactamase, much higher levels of chromosomal beta-lactamase activity were present than were observed in cultures induced by the penicillin alone. This was due to the higher levels of penicillin that were available for induction as a result of inhibition of the TEM enzyme by clavulanate.
一株产诱导型染色体β-内酰胺酶和质粒介导的TEM-1β-内酰胺酶的粘质沙雷氏菌对氨苄西林和阿莫西林耐药，对超广谱β-内酰胺类抗生素（ESBAs）的敏感性也降低。克拉维酸未降低ESBAs的最低抑菌浓度（MICs），但降低了青霉素类的MICs。产TEM-1的质粒被转移到一株更敏感的、产特征明确的诱导型染色体β-内酰胺酶的粘质沙雷氏菌菌株。转接合子对ESBAs的MICs仍处于低水平。作为质粒介导酶良好底物的氨苄西林和阿莫西林，未被染色体酶充分水解；ESBAs被所有酶缓慢水解。当每种粘质沙雷氏菌菌株与这些β-内酰胺类抗生素一起培养时，观察到染色体β-内酰胺酶活性至少有适度增加。当生物体在克拉维酸和一种ESBA存在下生长时，未观察到增强的诱导作用。最初临床分离株中观察到的ESBAs的MICs增加可能是由于诱导性低、水解缓慢以及粘质沙雷氏菌分离株之间通透性差异共同作用的结果。当向同时产质粒介导的TEM和染色体β-内酰胺酶的菌株中添加克拉维酸和青霉素时，染色体β-内酰胺酶活性水平比单独用青霉素诱导的培养物中观察到的要高得多。这是由于克拉维酸盐抑制TEM酶后，有更高水平的青霉素可用于诱导。
