Kern W V, Andriof E, Oethinger M, Kern P, Hacker J, Marre R
Section of Infectious Diseases and Clinical Immunology, University Hospital and Medical Center, Germany.
Antimicrob Agents Chemother. 1994 Apr;38(4):681-7. doi: 10.1128/AAC.38.4.681.
Prophylactic treatment with fluoroquinolones of patients with profound neutropenia has been found to be useful for preventing gram-negative bacteremia and has become a standard preventive-therapy strategy in many cancer centers, but the development of bacterial resistance is a cause of concern. During the past few years, we have observed an increasing number of patients with leukemia from whom fluoroquinolone-resistant strains of Escherichia coli were isolated. The increase was significant in this patient population, and among patients with other underlying diseases, the rates of isolation of such strains per number of discharges were significantly lower and did not increase. Most of the leukemia case patients (16 of 19) had been pretreated with an oral quinolone (ofloxacin), with cumulative doses until the first isolation of a resistant E. coli strain ranging from 0 to 97.8 g (median, 14.4 g). Repeated isolation of such strains was seen in 8 of 17 patients during a follow-up period of > or = 4 weeks and in 1 of 6 patients during a follow-up period of > or = 16 weeks. Ten patients developed bacteremia (mortality, 1 of 10). On the basis of the number of patients with leukemia admitted to the hematology-oncology service, the incidence of bacteremia caused by fluoroquinolone-resistant E. coli increased from < 0.5% in 1988-1989 and 0.8% in 1990-1991 to 4.5% in 1992-1993 (P < 0.01). MICs for nine isolates obtained from cultures of blood from different patients ranged between 8 and 16 microgram/ml (ciprofloxacin and PD 131628), 8 and 32 microgram/ml (ofloxacin and BAY Y 3118), and 16 and 32 microgram/ml (sparfloxacin) and indicated resistance to trimethoprim-sulfamethoxazole, ampicillin, doxycycline, and chloramphenicol. Of nine isolates obtained from cultures of blood from different patients and that were subjected to genomic DNA typing by pulsed-field gel electrophoresis of XbaI digests, seven were typeable. Among these, four different genotypes were identified, suggesting both the independent development and the horizontal spread of resistant clones of E. coli.
已发现对严重中性粒细胞减少症患者进行氟喹诺酮预防性治疗有助于预防革兰阴性菌血症,并且在许多癌症中心已成为标准的预防性治疗策略,但细菌耐药性的产生令人担忧。在过去几年中,我们观察到越来越多的白血病患者分离出对氟喹诺酮耐药的大肠杆菌菌株。在该患者群体中这种增加很显著,而在患有其他基础疾病的患者中,此类菌株的分离率相对于出院人数显著较低且没有增加。大多数白血病病例患者(19例中的16例)曾接受过口服喹诺酮(氧氟沙星)治疗,直到首次分离出耐药大肠杆菌菌株时的累积剂量为0至97.8克(中位数为14.4克)。在随访期≥4周的17例患者中有8例以及在随访期≥16周的6例患者中有1例再次分离出此类菌株。10例患者发生了菌血症(死亡率为10例中的1例)。根据血液学 - 肿瘤学服务部门收治的白血病患者数量,由对氟喹诺酮耐药的大肠杆菌引起的菌血症发生率从1988 - 1989年的<0.5%和1990 - 1991年的0.8%增加到1992 - 1993年的4.5%(P<0.01)。从不同患者血液培养物中获得的9株分离菌对环丙沙星和PD 131628的最低抑菌浓度(MIC)在8至16微克/毫升之间,对氧氟沙星和BAY Y 3118的MIC在8至32微克/毫升之间,对司帕沙星的MIC在16至32微克/毫升之间,并且显示对甲氧苄啶 - 磺胺甲恶唑、氨苄西林、强力霉素和氯霉素耐药。从不同患者血液培养物中获得并通过XbaI酶切脉冲场凝胶电泳进行基因组DNA分型的9株分离菌中,7株可分型。其中,鉴定出4种不同的基因型,提示大肠杆菌耐药克隆既有独立产生也有水平传播。