Uete T, Matsuo K
Department of Clinical Investigation, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka.
Jpn J Antibiot. 1993 Mar;46(3):205-21.
In vitro antimicrobial susceptibility tests can play an essential role in clinical management of infectious diseases, and in vitro MIC break point is important in choice of antibiotic. Standardization of method for measuring MIC is necessary, if break points are to be fixed internationally. However, it is difficult to settle on uniform international break points, since standard doses of antibiotics and the preferred routes of administration differ in different parts of the world. With respect to in vitro MIC break points, the NCCLS system is used in the U.S.A., and in Japan, Showa disc system and the NCCLS system are both used. In Europe 6 different systems are utilized (BSAC, DIN, SFM, SIR, NCCLS, and WRG). There is a certain degree of similarity between different concentration values used to define break points in these systems. In general, however, the BSAC and DIN systems recommend lower break points and the NCCLS and SFM systems higher break points. The MIC values of the break points, +3 and +2 categories of Showa 4 category classification system (+3, +2, +, -) used in Japan, are similar to those of the BSAC system. Higher ratio of positive responses to bactericidal antibiotic therapies have been reported when ratios of peak concentrations of drugs in plasma/in vitro MIC are increased, and maximum responses are obtained when the ratio reaches about 8 in cases with aminoglycosides and beta-lactams. In neutropenic compromised patients, drug concentrations with ratios higher than 8 to 10 may be required to treat infections. Drug availabilities are different depending on drugs and sites of infections. Susceptibility patterns to antibiotics are also quite different with different organisms. From the evidence presented above, a multiple (at least 2, low and high) sensitivity MIC break point system appears to be more appropriate than a single sensitivity MIC break point system to cope with various infections. Multiplicity of break points should depend on types of organisms, antibiotic availabilities at sites of infections, and specific factors in patients. Pharmacokinetic data on antibiotics must be more precisely taken into account with respect to the diversity of dosages, and especially effective antibiotic concentrations at sites of infections.
体外抗菌药敏试验在传染病临床管理中可发挥重要作用,体外最低抑菌浓度(MIC)折点在抗生素选择中很重要。若要在国际上确定折点,测量MIC的方法标准化是必要的。然而,由于世界不同地区抗生素的标准剂量和首选给药途径不同,很难确定统一的国际折点。关于体外MIC折点,美国使用NCCLS系统,在日本,昭和纸片系统和NCCLS系统都被使用。在欧洲,使用6种不同的系统(BSAC、DIN、SFM、SIR、NCCLS和WRG)。这些系统中用于定义折点的不同浓度值之间存在一定程度的相似性。然而,一般来说,BSAC和DIN系统推荐较低的折点,而NCCLS和SFM系统推荐较高的折点。日本使用的昭和4类分类系统(+3、+2、+、-)中,折点的MIC值、+3和+2类别与BSAC系统相似。据报道,当血浆中药物峰值浓度与体外MIC的比值增加时,杀菌性抗生素治疗的阳性反应率会更高,在氨基糖苷类和β-内酰胺类药物的情况下,当该比值达到约8时可获得最大反应。在中性粒细胞减少的免疫受损患者中,可能需要高于8至10的比值的药物浓度来治疗感染。药物的可用性因药物和感染部位而异。不同生物体对抗生素的敏感性模式也有很大差异。根据上述证据,多重(至少2个,低和高)敏感性MIC折点系统似乎比单一敏感性MIC折点系统更适合应对各种感染。折点的多样性应取决于生物体的类型、感染部位的抗生素可用性以及患者的具体因素。必须更精确地考虑抗生素的药代动力学数据,以应对剂量的多样性,特别是感染部位的有效抗生素浓度。