Superbugs in the coming new decade; multidrug resistance and prospects for treatment of Staphylococcus aureus, Enterococcus spp. and Pseudomonas aeruginosa in 2010

doi:10.1016/j.mib.2007.07.004

Current Opinion in Microbiology

Volume 10, Issue 5, October 2007, Pages 436-440

https://doi.org/10.1016/j.mib.2007.07.004 Get rights and content

New resistance problems have emerged recently among hospital and community-acquired pathogens such as in Staphylococcus aureus, Enterococcus faecium and Pseudomonas aeruginosa. Hospital-acquired and now community-acquired methicillin-resistant S. aureus are emerging worldwide whereas vancomycin-resistant S. aureus remain extremely rare. Hospital-acquired outbreaks of vancomycin-resistant enterococci and multidrug resistant Pseudomonas aeruginosa infections are increasingly reported worldwide. Whereas novel molecules are being developed for treating Gram-positive infections, difficult to non possible-to-treat pandrug-resistant P. aeruginosa infections may become a therapeutic challenge soon.

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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View full text

Superbugs in the coming new decade; multidrug resistance and prospects for treatment of Staphylococcus aureus, Enterococcus spp. and Pseudomonas aeruginosa in 2010

Introduction

Section snippets

Methicillin-resistant S. aureus and glycopeptide-resistant S. aureus

Vancomycin and multidrug resistant enterococci

Multidrug resistance in P. aeruginosa

Conclusion

References and recommended reading

Lancet Infect Dis

Am J Med

Diagn Microbiol Infect Dis

Lancet

Clin Infect Dis

Nature

Antimicrob Agents Chemother

Antimicrobial Agents Chemother

Biochem Pharmacol

MRSA—the tip of the iceberg

Clin Microbiol Infect

Controlling methicillin-resistant Staphylococcus aureus; quantifying the effects of interventions and rapid diagnostic testing

Proc Natl Acad Sci U S A

Look before you leap: active surveillance for multidrug-resistant organisms

Clin Infect Dis

Anti-MRSA β-lactams in development, with a focus on ceftobiprole: the first anti-MRSA β-lactam to demonstrate clinical efficacy

Expert Opin Investig Drugs

Dalbavancin: a new option for the treatment of gram-positive infections

Ann Pharmacother

Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles

N Engl J Med

Global distribution of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus

Emerg Infect Dis

Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus

Lancet

Transmission of methicillin-resistant Staphylococcus aureus to a microbiologist

N Engl J Med

High-level vancomycin-resistant Staphylococcus aureus isolates associated with a polymicrobial biofilm

Antimicrobial Agents Chemother

Heterologous expression of the enterococcal vanA operon in methicillin-resistant Staphylococcus aureus

Antimicrob Agents Chemother

Identification of high-risk enterococcal clonal complexes: global dispersion and antibiotic resistance

Curr Opin Microbiol

Emergence of vanA genotype vancomycin-resistant Enterococci with low or moderate levels of teicoplanin Resistance in Korea

J Clin Microbiol