Superbugs in the coming new decade; multidrug resistance and prospects for treatment of Staphylococcus aureus, Enterococcus spp. and Pseudomonas aeruginosa in 2010
Introduction
At the beginning of the 21st century, clinicians are faced with an increasing number of immunodeficient patients with advanced surgery, malignant diseases, prolonged stays in intensive care units and long-term care facilities. The average age of hospitalized patients is growing at least in Western part of the world. Many of those patients develop infections with pathogens presenting variable resistance traits but often with a quite high level of natural resistance. Concomitantly, patients are treated with ever broad-spectrum antibiotic molecules that enhance blind selection of multidrug resistance (MDR) isolates. Therefore, MDR bacteria are observed in frequent human pathogens such as in Staphylococcus aureus, Enterococcus faecium and P. aeruginosa. Pandrug resistance has been already observed for most of those bacterial species. They may become an unmet medical needs in antibacterial therapy in a near future, occurring to a large extent, mostly but not only in hospital settings.
Section snippets
Methicillin-resistant S. aureus and glycopeptide-resistant S. aureus
Though most of the S. aureus isolates were susceptible to penicillin G in the 1940s, virtually all S. aureus isolates are now at least resistant to penicillins such as aminopenicillins and ureido-penicillins due to expression of narrow-spectrum penicillinases [1]. The first cases of methicillin-resistant S. aureus (MRSA) infections were reported from the UK in 1961 and MRSA became a major problem in hospital settings worldwide in the 1980s [1].
They represent now an installed resistance pattern
Vancomycin and multidrug resistant enterococci
During the 1990s a dramatic increase of VRE infections was reported mostly in the ICUs in the USA (30% in 2006) [17]. The majority of those isolates are E. faecium whereas most of the E. faecalis isolates remain susceptible to glycopeptides in the same country.
The worldwide epidemiology of VRE spread and expression is heterogeneous [17, 18, 19]. Until recently, VREs were rare in hospitals in Europe. However, as exemplified by a VanA-type (+) E. faecium outbreak beginning in 2003 at the Bicetre
Multidrug resistance in P. aeruginosa
Multidrug resistance in P. aeruginosa is steadily increasing also worldwide [22]. Although definitions of multidrug resistance are variable, they often involve resistance to fluoroquinolones, expanded-spectrum cephalosporins, carbapenems, and aminoglycosides. As an example a progressive increase in multidrug-resistant P. aeruginosa (resistance to ≥3 antibiotics) was observed from 7.1% in 2001 to 9.9% in 2003 in the US [22, 23•]. There is no reason why such an increase of multidrug resistance in
Conclusion
The shrinking pool of large pharmaceutical industries willing to invest in antibacterial research lead to paucity of novel molecules especially against Gram-negatives [41]. We believe in an increasing identification of hospital-acquired outbreaks worldwide due to MDR and pandrug-resistant Gram-negatives such as P. aeruginosa and Acinetobacter baumannii. These species that are widely disseminated in the environment are prone to acquire from environmental species novel resistance determinants and
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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