[In vitro MIC break point for appropriate clinical use of antibiotic]

Abstract

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.