The temporal evolution of susceptibility to antibiotics, determined by disk diffusion, was analyzed for historical clinical L. monocytogenes strains isolated between 1926 and 1988 that originated from the collection of the NRC and the international Special Listeria Culture Collection (SLCC). Between 1926 and 1963, all L. monocytogenes strains isolated from humans in France (n = 13) or other countries (n = 51) from our collections were tested. During this period, we also tested a randomly selected set representative of all animal isolates (n = 23). For strains isolated between 1964 and 1988, we tested a randomly selected set of L. monocytogenes strains isolated from humans in France (n = 61/477 isolates) representative of each year, clinical form, and serovar.
As expected, the natural resistance preexisted marketing and use of major classes of antibiotics. However, no acquired resistance to the 23 antibiotics tested was detected for strains isolated between 1926 and 1988.
Although L. monocytogenes resistant to penicillins were not detected by disk diffusion according to the breakpoints of EUCAST, the MICs of penicillin, amoxicillin, and ampicillin were determined by Etest for a set of 436 L. monocytogenes strains isolated from humans in France between 1926 and 2007 and distributed in four successive time periods (Table ).
Evolution of median value of MICs of penicillins for clinical L. monocytogenes strains isolated in France between 1926 and 2007 according to four time periods
Statistical analysis showed a significant difference in the distribution of MICs between 1926 and 2007 according to the selected time periods (P
= 0.00001, Kruskal-Wallis test). The comparison of each period to each other showed that the MICs determined during the 1926 to 1963 and 1964 to 1988 periods differ from those observed during the 1989 to 2005 and 2006 to 2007 time periods (P
= 0.0001, Wilcoxon test). The MIC50
s of aminopenicillins for 1989 to 2007 were more than twice those for 1926 to 1988 (Table ). Moreover, the number of strains with MICs greater than 1 μg/ml has increased since 1989. Strains with an MIC of 2 μg/ml, not observed before 1988, have recently emerged. Whereas this increase in MICs has already been reported for environmental strains (7
), we observed the same increase for L. monocytogenes
strains isolated from humans in France since 1926. As has been observed for Streptococcus pneumoniae
), this MIC creeping could be explained by increased use of beta-lactams from the middle of the 20th century, accentuated in recent years. Although we do not report resistance to penicillins associated with clinical failure, the results of this study justify systematic determination of MICs of aminopenicillins for adapting dosages. According to MICs, no differences in activity between ampicillin and amoxicillin have been observed, contrary to what had been suggested in previous studies (33
Acquired resistance in L. monocytogenes from humans has no clinical consequence so far as it does not concern the first-line treatment of listeriosis. However, transfer of resistance genes from other bacteria and the recent increasing MICs of aminopenicillins underline the need for active and continuous surveillance of the susceptibility to antibiotics.