ANTIBACTERIAL EFFICACY OF NISIN AGAINST MULTIDRUG-RESISTANT GRAM-POSITIVE PATHOGENS

The rapid spread of multidrug-resistant bacterial pathogens necessitat es the search for alternative antibacterial agents. We examined the ef ficacy of the antibiotic nisin against 56 multidrug-resistant isolates of Streptococcus pneumoniae, 33 Staphylococcus aureus and 29 vancomyc in-resistant Enterococcus faecium and Enterococcus faecalis isolates. The test strains represented a large variety of clonal types las deter mined by a combination of DNA fingerprints) isolated from a variety of geographic sources, and included some of the major internationally-sp read multiresistant epidemic clones of S. pneumoniae and methicillin-r esistant S. aureus (MRSA), MRSA strains resistant to over 16 generical ly distinct antibacterial agents, and enterococcal strains resistant t o all currently available chemotherapeutic agents including glycopepti des, In the overwhelming majority of cases, treatment of growing cultu res with nisin at 1 mg/L (S. pneumoniae) or 10-20 mg/L (in MRSA and en terococci) caused extensive (10(3)- to 10(4)-fold) loss of viable titr e accompanied by various degrees of loss in the optical density of the cultures, which was most extensive in pneumococci (>90%) and least ex tensive (40-50%) in enterococci, Nevertheless, extensive variation in rates of nisin-induced autolysis was observed in each bacterial specie s. Serial exposure of a penicillin-susceptible strain of S. pneumoniae to nisin (1 mg/L) in liquid culture resulted in the rapid appearance of stable nisin-resistant mutants in which the MIC increased from 0.4 to 6.4 mg/L and the resistance trait was transferable by genetic trans formation.