Therapy Analysis - Antibiotic-resistance: fighting the superbugs
A new threat
...Incidence of MRSA is increasing. A 2007 report by the US Centers for Disease Control and Prevention (CDC) estimated that the number of MRSA cases nationwide had more than doubled from 127,000 in 1999 to 278,000 in 2005, with over 17,000 attributable deaths. Similarly, the UK Office for National Statistics reported 1,629 MRSA-related deaths in England and Wales, compared to just 51 in 1993....Despite early promise, the success of antibiotics in the treatment of bacterial infections was to be short-lived. Since the development of the first antibiotics, resistant strains of bacteria, in particular Staphylococcus aureus, have become an increasing obstacle to the successful use of antibiotics. When penicillin was first introduced in 1943, resistant S. aureus infections were almost unheard of. However, in 1947, a resistant strain was identified. By 1950, around 40% of nosocomial S. aureus infections were penicillinresistant, and this figure rose to around 80% by 1960. Penicillin resistance in S. aureus is mediated by ß-lactamase. This enzyme, produced by the bacterium, hydrolyses the ß- lactam ring of the penicillin structure, rendering it inactive. In the face of increased penicillin resistance, meticillin, a narrow spectrum ß-lactam antibiotic became the first-line choice in the treatment of S. aureus infections. Like penicillin, meticillin acts by disrupting bacterial cell wall synthesis. The presence of an ortho-dimethoxyphenyl group attached to the penicillin nucleus made meticillin relatively resistant to cleavage by ß-lactamase through steric hindrance and therefore effective against penicillin-resistant bacteria.
However, in 1961 a strain of S. aureus resistant to meticillin was identified in the UK. This strain, which has since become known as meticillin-resistant Staphylococcus aureus (MRSA) acquired the ability to be resistant to treatment with all ß- lactam antibiotics, including meticillin, oxacillin, nafcillin and dicloxacillin. MRSA is present on the skin and nasal passages of 1 in 3 people, without becoming pathogenic. However, if MRSA enters the body, it is able to cause infection. MRSA infections commonly occur in the hospital setting, often in immunocompromised patients, or those with open surgical wounds, ulcers or intravenous catheters. The symptoms depend on the type of infection, but can include boils, abscesses, styes and carbuncles, as well as skin infections such as cellulitis and impetigo. More serious MRSA infections include septicaemia, septic shock, infective endocarditis and pneumonia.
Incidence of MRSA is increasing. A 2007 report by the US Centers for Disease Control and Prevention (CDC) estimated that the number of MRSA cases nationwide had more than doubled from 127,000 in 1999 to 278,000 in 2005, with over 17,000 attributable deaths. Similarly, the UK Office for National Statistics reported 1,629 MRSA-related deaths in England and Wales, compared to just 51 in 1993. The emergence of MRSA has meant that the glycopeptide antibiotic vancomycin became the drug of choice for treating MRSA. However, strains of MRSA which are resistant to vancomycin have recently emerged. While not as prevalent as MRSA, VRSA may pose a problem for the future of antibiotic therapy.
In 1986, another common antibiotic-resistant bacterium was identified (vancomycin-resistant enterococcus (VRE)). Enterococci are bacteria commonly found in the faeces of humans, and are commonly responsible for urinary tract and wound infections. Until recently, enterococcus infections were readily treatable with antibiotics.
Clostridium difficile is a Gram positive bacillus. First described in 1935, it is so-named due to the difficulty in culturing the bacteria on culture medium. A commensal bacterium of the gut, C. diff. does not usually present a disease risk. However, use of broad-spectrum antibiotics can lead to a disruption of the gut flora, giving rise to conditions such as antibiotic-associated diarrhoea, caused by overgrowth of C. diff. The bacterium is also resistant to most antibiotics, and forms heatresistant spores which are able to tolerate extreme temperatures. Therefore, C. diff has become a problem in the hospital environment, and even commonly-used hospital disinfectants can fail to kill the bacterium. Merely 60 years after the commercial availablilty of antibiotics, antibiotic-resistant bacteria represent a significant chink in our protection against infection.
