Iwata S, Kawahara K, Isohata E, Kin Y, Yokota T, Kusumoto Y, Sato Y, Akita H, Oikawa T, Sunakawa K
Department of Pediatrics, Kasumigaura National Hospital.
Jpn J Antibiot. 1992 Oct;45(10):1385-402.
Meropenem (MEPM, SM-7338), a novel parenteral carbapenem antibiotic, was examined for its effect on intestinal flora in children. Seven children with infectious diseases (3 male and 4 female children of age's ranging from 4 months to 8 years and 9 months weighing from 7.3 to 23.0 kg) were treated with MEPM at doses ranging 10.3 to 40.5 mg/kg 3 or 4 times a day for 6 to 12 days. Before, during and after the treatment, identities and numbers of various bacteria contained in 1 g of feces were determined and fecal beta-lactamase activity and Clostridium difficile D-1 antigen were also assayed. Changes in fecal flora during MEPM treatment was somewhat different depending on cases. Regarding Enterobacteriaceae among aerobes, all of 7 cases exhibited moderate or pronounced reductions in Escherichia coli. Some of the cases exhibited the tendency to increase in Klebsiella oxytoca. Enterobacter cloacae and Citrobacter freundii. E. coli which was reduced during the treatment increased rapidly after the treatment in 5 out of 7 cases, and the initial bacterial counts were restored. Diverse strains were observed within the genus Enterococcus, while the overall bacterial counts of this genus exhibited the tendency to increase during the treatment. As a result, no significant change in total aerobe count was observed in any case except 1 case where Enterococcus count was somewhat reduced. Among anaerobes, major bacteria such as Bacteroides, Bifidobacterium, Eubacterium and Peptococcaceae exhibited tendencies to decrease in some cases during the antibiotic treatment. Two infants and 1 child exhibited significant decreases in total anaerobe counts. In most of the cases, such changes in major anaerobes were transient and bacterial counts recovered to their initial values rapidly after completion of the treatment. In no cases, glucose non-fermentative Gram-negative bacilli or fungus became predominant. Although C. difficile D-1 antigen was observed in 4 cases, its changes had no relationship with characteristics of feces. C. difficile was not detected in any of the cases. MEPM was detected in feces in 4 cases being treatment, in concentrations ranging from 0.35 to 66.0 micrograms/g. Fecal MEPM levels were very low except in 1 case in which beta-lactamase was negative. From these results, effects of MEPM on intestinal flora in children were relatively minor compared to other new beta-lactam drugs. However, a care should be taken to minimize diarrhea and bacterial turnover when a prolonged use of the antibiotic, was practiced because of potential significant effects on intestinal flora.
美罗培南(MEPM,SM - 7338)是一种新型的胃肠外碳青霉烯类抗生素,对其在儿童肠道菌群中的作用进行了研究。7名患有传染病的儿童(3名男性和4名女性,年龄从4个月至8岁9个月,体重7.3至23.0千克)接受了美罗培南治疗,剂量为10.3至40.5毫克/千克,每天3或4次,持续6至12天。在治疗前、治疗期间和治疗后,测定了1克粪便中所含各种细菌的种类和数量,还检测了粪便β - 内酰胺酶活性和艰难梭菌D - 1抗原。美罗培南治疗期间粪便菌群的变化因病例而异。关于需氧菌中的肠杆菌科,7例患者的大肠杆菌均有中度或明显减少。部分病例中,产酸克雷伯菌、阴沟肠杆菌和弗氏柠檬酸杆菌有增加趋势。治疗期间减少的大肠杆菌在7例中有5例在治疗后迅速增加,初始细菌计数得以恢复。肠球菌属内观察到多种菌株,该属细菌总数在治疗期间有增加趋势。结果,除1例肠球菌计数有所减少外,其他病例的需氧菌总数均未观察到显著变化。在厌氧菌中,一些病例在抗生素治疗期间,拟杆菌、双歧杆菌、真杆菌和消化球菌科等主要细菌有减少趋势。2名婴儿和1名儿童的厌氧菌总数显著减少。在大多数病例中,主要厌氧菌的这种变化是短暂的,治疗结束后细菌计数迅速恢复到初始值。在任何病例中,葡萄糖非发酵革兰氏阴性杆菌或真菌均未占主导地位。虽然4例中观察到艰难梭菌D - 1抗原,但其变化与粪便特征无关。所有病例中均未检测到艰难梭菌。4例正在接受治疗的患者粪便中检测到美罗培南,浓度范围为0.35至66.0微克/克。除1例β - 内酰胺酶阴性的病例外,粪便中美罗培南水平非常低。从这些结果来看,与其他新型β - 内酰胺类药物相比,美罗培南对儿童肠道菌群的影响相对较小。然而,由于可能对肠道菌群有显著影响,在长期使用抗生素时应注意尽量减少腹泻和细菌更替。