The extensive use of antibiotics has led to the development of multi-drug resistant organisms (MDROs), limiting the action of drugs previously considered to be highly active.
Infections involving multi-drug resistant bacteria are a major concern for most hospitals and healthcare facilities, since they contribute to an increase in morbidity and mortality compared to the underlying diseases alone. They also impact length of stay and related healthcare costs.
The main MDROs related to antimicrobial resistance are Methicillin-Resistant Staphylococcus aureus (MRSA), Extended Spectrum Beta-Lactamase (ESBL) enterobacteria, Vancomycin Resistant Enterococci (VRE) and Clostridium difficile.
Extended Spectrum Beta-Lactamase (ESBL) enterobacteria
ESBLs are enzymes that have developed resistance to many antibiotics in the β-Lactam family. These enzymes are most commonly produced by two bacteria - Escherichia coli (E.coli) and Klebsiella pneumoniae and are widespread in both hospital and community settings. An estimated 20% of K. pneumoniae infections and 31% of Enterobacter spp infections in intensive care units in the United States now involve strains not susceptible to third-generation cephalosporins.2
Enzymes that confer resistance to extended spectrum cephalosporin and carbapenem antibiotics have over the years developed into what are known as carbapenemases. They are ESBLs with versatile hydrolytic capacities that inactivate β-Lactam antibiotics, such as penicillin, cephalosporin, monobactam, and carbapenems.
The increasing use of carbapenems due to the spread of ESBLs is creating a vicious cycle, increasing the development of carbapenemase-producing bacteria resistant to the antibiotic.
Carbapenems are powerful, broad-spectrum antibiotics , which are often considered to be the last line of defence against multi-resistant strains of bacteria, such as E. coli and K. pneumoniae.
Klebsiella pneumoniae Carbapenemase (KPC) is the most prevalent resistance enzyme to date, showing resistance to all the β-Lactams, including previously effective carbapenems (imipenem, meropenem, ertapenem and doripenem) used when other antibiotics failed. K. pneumoniae is a common hospital-acquired pathogen, causing urinary tract infections, nosocomial pneumonia, and intra-abdominal infections. The spread of KPC-producing K. pneumoniae is worrying, since this species is one of the leading causes of nosocomial infections in severely ill patients.3
New Delhi Metallo beta-lactamase 1 (NDM-1) is the newest carbapenemase to emerge.4 The NDM-1 gene produces an enzyme which makes bacteria resistant to most antibiotics (including carbapenems ), except tigecycline and colistin. The NDM-1 type of plasmidic resistance means it can easily spread from one strain of bacteria to another, particularly in patients receiving antibiotic treatment. The fact that NDM-1 is found in E. coli - a typical community-acquired bacteria and the most frequent cause of urinary tract infections - may further accelerate the spread of NDM-1 resistant strains.
Staphylococcus aureus (MRSA)
In this decade, there has been a continuous increase in the incidence of MRSA in Europe and the United States. In the United States, current MRSA rates exceed 50% of all Staphylococcus aureus infections and stand at close to 90% in some Asian countries.
MRSA is now resistant to a number of antibiotics, including methicillin and other more common antibiotics such as oxacillin, penicillin and amoxicillin.
In some countries, over 60% of S. aureus cases in hospital intensive care units are now resistant to these first-line antibiotics.1
Vancomycin Resistant Enterococci (VRE)
In certain countries (particularly in the US), enteroccocci have become resistant to vancomycin, an antibiotic often used to treat enterococcal infections. Data reported to the CDC for the US during 2004 showed that VRE caused about 1 of every 3 infections in hospital intensive care units.
The incidence and severity of Clostridium difficile have increased significantly over the past 10 years, since a strain of this bacterium originating in North America acquired a new virulence. With the ability to produce greater quantities of toxins A and B, this new strain is more resistant to the antibiotic group known as fluoroquinolones, and has now also spread to European countries.