Heikkilä E, Renkonen O V, Sunila R, Uurasmaa P, Huovinen P
Department of Medical Microbiology, University of Turku, Finland.
J Antimicrob Chemother. 1990 Feb;25(2):275-83. doi: 10.1093/jac/25.2.275.
Trimethoprim (TMP), either alone or in combination with sulphonamides, is commonly used for treating urinary tract infections. In Finland, TMP alone has been in clinical use since 1973. TMP resistance in the major outpatient urinary tract pathogen, Escherichia coli, increased during 1978-1988 from 5% to 16% in the Turku area, during 1980-1988 from 3% to 19% in the Helsinki area and also during 1980-1988 from 3% to 14% in the Rovaniemi area. The majority (91%) of TMP-resistant strains were highly-resistant to TMP (MIC greater than or equal to 1024 mg/l). The most common (57%) TMP resistance gene, detected by DNA hybridization, was the type I dihydrofolate (DHFR) gene. The type II DHFR genes were found in less than 3% of the strains studied. No positive hybridizations were detected with the type III DHFR probe, and only a few positive hybridizations were found with the type V DHFR probe. Forty percent of the isolates did not hybridize with any of the DHFR probes used, suggesting additional unknown resistance mechanisms responsible for the high-level TMP resistance. These unknown TMP resistance mechanisms, together with the type I DHFR-mediated resistance, were responsible for the increase of TMP resistance among the E. coli strains studied.
甲氧苄啶（TMP）单独使用或与磺胺类药物联合使用，常用于治疗尿路感染。在芬兰，自1973年起TMP就已单独用于临床。在主要的门诊尿路感染病原体大肠埃希菌中，1978 - 1988年图尔库地区的TMP耐药率从5%增至16%，1980 - 1988年赫尔辛基地区从3%增至19%，1980 - 1988年罗瓦涅米地区也从3%增至14%。大多数（91%）对TMP耐药的菌株对TMP高度耐药（最低抑菌浓度大于或等于1024 mg/l）。通过DNA杂交检测到的最常见（57%）的TMP耐药基因是I型二氢叶酸还原酶（DHFR）基因。在所研究的菌株中，II型DHFR基因的发现率低于3%。用III型DHFR探针未检测到阳性杂交信号，用V型DHFR探针仅发现少数阳性杂交信号。40%的分离株与所使用的任何DHFR探针均未杂交，这表明存在其他未知的耐药机制导致高水平的TMP耐药。这些未知的TMP耐药机制与I型DHFR介导的耐药一起，导致了所研究的大肠埃希菌菌株中TMP耐药性的增加。
