S 12

ANTIBIOTIC RESISTANCE TODAY: A PERSONAL ASSESSMENT

P.C. Appelbaum
Hershey Medical Center, Hershey, Pennsylvania, USA

Resistance of major human pathogens to commonly used antimicrobials is on the increase. This review will focus on three organisms:
1) Streptococcus pneumoniae resistant to ß-lactams and other antibiotics has become a problem worldwide, with the highest resistance rates reported from Korea, Hong Kong, Japan, and Central and Eastern Europe (mainly Romania, Slovakia, Bulgaria and Croatia), France and Spain. ß-lactam resistance in this organism is caused by stepwise mutations in penicillin-binding proteins. Macrolide resistance (which usually accompanies high-level penicillin resistance) results from erm(B) (adenine dimethylase) and mef(efflux) genes, and alterations in ribosomal proteins L4, L22 and 23S rRNA. Quinolone resistance in the pneumococcus (which has been described in Hungary, Croatia, Canada and Hong Kong) is due to alterations in the QRDR of type II topoisomerase enzymes, usually coded for by par(C) and gyr(A) genes.
2) The mechanism of ß-lactam resistance in Haemophilus influenzae is usually ß-lactamase production; BLNAR strains are currently very rare indeed in Europe and the US, but common in Japan. Until recently, macrolide resistance mechanisms had not been described in this organism. We have recently reported a macrolide efflux mechanism in approximately 95% of these strains: the other 5% comprise hypersusceptible strains which are truly macrolide susceptible and do not possess the efflux mechanism and hyperresistant strains with high macrolide MICs which have both efflux and L4, L22 and/or 23S rRNA ribosomal protein mutations. In view of these findings, macrolide susceptibility breakpoints in H. influenzae require reevaluation.
3) We have recently isolated the second vancomycin resistant Staphylococcus aureus, carrying a van(A) gene. This strain is highly resistant to ß-lactams, macrolides, quinolones and aminoglycosides but susceptible to linezolid, cotrimoxazole and rifampicin. The van(A) gene is plasmid borne. Bacterial resistance to antibiotics can only increase and spread and must be counteracted by judicious antibiotic usage as well as strict measures to counteract cross infection.

S 13

EPIDEMIOLOGY OF STREPTOCOCCAL INFECTIONS IN EUROPE

R.R. Reinert
RWTH Aachen, Germany

Streptococcal disease is a major cause of morbidity and mortality, especially among children and elderly people.
Streptococcus pyogenes is responsible for the majority of cases of pharyngitis in children and adolescents and can also cause severe life-threatening diseases, such as necrotizing fasciitis and toxic shock syndrome. Streptococcus pneumoniae continues to be a significant cause for serious infections such as bacteraemia, and meningitis and for community-acquired respiratory tract infections and otitis media. The worldwide increase in antibiotic resistance in these species has become a serious infectious disease problem within the last twenty years. Prior to the early 1990s, penicillin resistance remained uncommon among clinical isolates of S. pneumoniae in Northern European countries despite the emergence of this problem in many parts of Europe, e.g. Hungary, Spain, and France. Decreased susceptibility to macrolides in S. pyogenes and in S. pneumoniae is now widespread in many European countries including Germany and Austria.
In Germany, a nation-wide study of invasive pneumococcal disease (IPD) among children < 16 years of age was started in 1997. Until 2002 2,208 cases were reported by the laboratories and hospitals. Capsular typing was carried out for 892 isolates and showed serotypes 14 (24.1%), 1 (8%), 18C (7.4%), 19F (7.4%), 23F (7.1%), and 6B (5.9%) to be the most prevalent. The percentage of cases per age group covered by the 7-valent pneumococcal conjugate vaccine including the potentially cross-protective serotype 6A was 69.5% (age group 6-11 months), 76.8% (1 year) and 74.6% (2-4 years). Epidemiological data on pneumococcal infections is now available for some European countries. Incidence of IPD is highest in the first two years of life. The mortality rate is highest in meningitis ranging from 7-27% and sequelae, either neurological or auditory, remain in about 30% of survivors. Therefore, the prevention of infections by vaccination of children with the 7-valent pneumococcal vaccine is an important goal. For adults a 23-valent vaccine is available, which is increasingly used in many European countries.