S 15

DYNAMICS OF EPIDEMIC MRSA

W. Witte, C. Cuny and C. Braulke
Wernigerode, Germany

From 1991 to 1994, three clonal groups of MRSA with epidemic interhospital spread were predominant in Germany: the Northern German Epidemic MRSA (corresponding to the Iberic clone widely spread in several European countries), the Southern German MRSA (corresponding to epidemic strains from Belgium, Slovenia, Bulgaria, and UK [EMRSA]), and the Hannover area MRSA. These groups exhibited a broad pattern of multiresistance including aac6’-aph2”-based aminoglycosid resistance. After 1995, the prevalence of these clonal groups declined from 20 to 30% for each to about 3-1%, whereas that of newly emerging groups with less broad multiresistance as A: the Berlin epidemic strain with mecA, grlA (also in Sweden and in Belgium);
B: the Barnim epidemic strain with mecA, ermC, grlA (identical to EMRSA15 from UK, also occurring in Sweden); and C: the Rhine-Hesse epidemic strain with mecA, ermC (also in Belgium and Finland) has increased (A: 1994-11%, 2000-26.7%;
B: until 1996-0, 2000-19.8 %; C: until 1998-0, 2000-6%). Besides an outbreak of GISA belonging to North German Epidemic MRSA, one of the other epidemic MRSA had exhibited this phenotype or acquired resistance to quinupristin-dalfopristin and to linezolid. Increasing spread of newly emerging epidemic MRSA with less broad resistance patterns has led to decrease in MRSA of resistance to gentamicin (now 4.1%), to oxytetracycline (now 9.2%), to rifampicin (now 4.1%), and to trimethoprim (now 9.7%). Epidemic MRSA prevalent in Central Europe obviously have also been disseminated in other European countries.

S 16

NEW APPROACHES TO THE THERAPY GRAM + INFECTIONS

R.C. Moellering
Herrman L. Blumgart, Professor of Medicine, Harvard Medical School
Physician-in-Chief and Chairman, Department of Medicine
Beth Israel Deaconess Medical Center, Boston, Massachusetts USA

Despite the discovery and clinical use of a number of effective antimicrobial agents, infections due to gram-positive bacteria remain major clinical problems throughout the world. A great deal (but not all) of the difficulty in treating these infections is related to growing resistance to antimicrobial agents among these bacteria. Several new antimicrobial agents have been developed specifically to combat problems in resistance. These include quinupristin/dalfopristin, linezolid, telithromycin, and several new fluoroquinolones with expanded activity against gram-positive bacteria. In addition, there are a number of promising antimicrobial agents with excellent activity against gram-positive bacteria in phase III clinical development. These include daptomycin, oritavancin, dalbavancin, and tigecycline. The attempts to combat resistant gram-positive bacteria, however, do not stop here and there are also some promising new antimicrobial agents in phase I/II clinical development including LBM415, a novel peptide deformylase inhibitor, several new glycopeptides, as well as cephalosporins and fluoroquinolones with enhanced activity against methicillin-resistant staphylococci. Despite all of this activity, however, there remain a number of important unaddressed issues. These include the fact that many of the agents currently being developed are bacteriostatic, rather than bactericidal. Moreover, acute, early deaths continue to occur despite effective antimicrobial therapy because of the virulence of some of these bacteria. None of the currently available agents is particularly effective against bacteria that are slowly growing or in lag phase of growth and the activity of these agents is markedly diminished in the presence of biofilm, which commonly is produced by these organisms in vivo. Finally, new mechanisms of resistance continue to emerge. Thus, novel approaches are badly needed. Among these are strategies to inhibit quorum sensing and other virulence pathways. In addition, the development of drugs active on bacteria growing in biofilm is important as is the development of agents which inhibit biofilm formation. The use of antisense nucleotides may yet have promise. The full potential for vaccines has yet to be fulfilled, either. Thus, despite development of a number of new antimicrobial agents, and the presence of promising agents in the pipeline, significant challenges remain.