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首页> 外文期刊>Chemotherapy: International Journal of Experimental and Clinical Chemotherapy >Selection of Klebsiella pneumoniae mutants with high-level cefotaxime resistance during growth in serum containing therapeutic concentrations of cefotaxime.
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Selection of Klebsiella pneumoniae mutants with high-level cefotaxime resistance during growth in serum containing therapeutic concentrations of cefotaxime.

机译：在含有治疗浓度的头孢噻肟的血清中生长期间具有高头孢噻肟抗性的肺炎克雷伯氏菌突变体的选择。

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BACKGROUND: In a previous investigation of the genetic characterization of extended-spectrum beta-lactamases (ESBLs) in Klebsiella pneumoniae from Zagreb, Croatia, 20 strains were found to produce SHV-2 beta-lactamase. Those strains displayed varying degrees of beta-lactam resistance and a wide range of beta-lactamase activity. We concluded that more resistant isolates were hyperproducers of SHV-2 beta-lactamase. METHODS: In this investigation, we tried to develop hyperproducing variants from 8 low-level SHV-2 beta-lactamase-producing Klebsiella strains by subculturing them in serum containing therapeutic concentrations of cefotaxime (CTX). RESULTS: In most cases, there was a moderate increase in CTX resistance (twofold to threefold), except in one strain which displayed a 16-fold increase in the minimum inhibitory concentration (MIC) of CTX after incubation in the serum. That strain showed a marked increase in enzyme activity as well. The strains with a moderate increase in CTX MIC did not produce more enzyme after exposure to the serum, except for one strain which had a threefold rise in beta-lactamase activity after exposure to serum. CONCLUSIONS: In this investigation, it was established that the mutants with high-level CTX resistance developed very quickly in the biological fluids containing therapeutic concentrations of CTX. It is reasonable to expect that a similar process occurs in patients infected with an ESBL-producing K. pneumoniae strain during antibiotic treatment. Since most of the high-level CTX-resistant mutants did not have a marked rise in beta-lactamase activity after exposure to serum, it is possible that the elevated resistance was due to some other mechanism, such as reduced penicillin-binding protein affinity, changes in outer membrane proteins or efflux by multidrug efflux pumps. Copyright 2002 S. Karger AG, Basel
机译：背景：在先前对克罗地亚萨格勒布的肺炎克雷伯菌的广谱β-内酰胺酶（ESBLs）的遗传学表征研究中，发现了20株产生SHV-2β-内酰胺酶。这些菌株显示出不同程度的β-内酰胺抗性和广泛的β-内酰胺酶活性。我们得出的结论是，更多的耐药菌株是SHV-2β-内酰胺酶的高产菌。方法：在这项调查中，我们试图通过在含有治疗浓度的头孢噻肟（CTX）的血清中进行亚培养，从8株产生低水平SHV-2β-内酰胺酶的克雷伯菌中分离出高产变异体。结果：在大多数情况下，CTX耐药性有中等程度的增加（两倍至三倍），除了一种菌株在血清中孵育后CTX的最低抑菌浓度（MIC）升高了16倍。该菌株也显示出酶活性的显着增加。 CTX MIC中等增加的菌株在暴露于血清后不会产生更多的酶，除了一种菌株在暴露于血清后其β-内酰胺酶活性增加了三倍。结论：在这项研究中，已确定具有高水平CTX耐药性的突变体在含有治疗浓度CTX的生物体液中发展很快。可以合理预期在抗生素治疗期间，感染ESBL的肺炎克雷伯菌菌株的患者也会发生类似的过程。由于大多数高水平抗CTX突变体在暴露于血清后，β-内酰胺酶活性均未显着升高，因此耐药性升高可能是由于某些其他机制所致，例如青霉素结合蛋白亲和力降低，多药外排泵改变外膜蛋白质或外排。版权所有2002 S. Karger AG，巴塞尔

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