Hello Elliot,

The choice of antibiotic chemotherapy for MRSA infections depend on the extent of the infection, the site, how far progressed, the health of the patient and contraindications (clashes) with other medications being taken by the patient. There is no “one shoes fits all” when it comes to such treatment, although there are standardised responses to acute situations where very little information may be available. Without writing an epic amount on the subject, I will just try to give you a basic overview of some of the issues regarding generalised MRSA treatment and why, despite treatment, morbidity and mortality is observed.

Time is of the essence in cases of MRSA infection, particularly as these infections are frequently nosocomial (occurring in hospitalised patients) who may already have a weakened immune system or be otherwise systemically stressed. Delayed treatment, i.e. greater than 45 hours, results in significant morbidity and mortality requiring prolonged treatment and consequently extended hospital stay (Lodise et al., 2003). This also leads to a greater potential for complications associated with the chemotherapy. There are particular complications with community-acquired infection, particularly as the infection may have progressed significantly before the patient presents with acute symptoms; in addition, community acquired MRSA presents some unique pathogenic properties that nosocomial strains generally do not.

I refer to an article here by Dr Mark Enright, which is a good and brief potted history of MRSA.

The trouble with asking “why do people still die from MRSA?” is that as far as many of us in the field are concerned, MRSA is not so much a “superbug” as a weak pathogen; an opportunist. Being resistant to multiple antibiotics may be intimidating, but makes it no more able to kill you than methicillin-sensitive S. aureus (MSSA). Both can readily colonise the body, particularly in the nares of the nose, but rarely cause infection in healthy people.

MRSA typically affects those people who are in a weakened state with compromised immune systems who are already hospitalised. MRSA infections vary from low grade cellulitis to bacteraemia, dependent on the route of access to the body and the status of the patient. Thus in the most serious of cases (bacteraemia or endocarditis) the question arises as to whether the patients die from MRSA, or happen to die with it. This is quite a political hot potato at the moment as national statistics and infection control targets are sustaining much scrutiny at the moment.

When MRSA infection is diagnosed, treatment should be with an antibiotic of known in vivo efficacy, such as daptomycin, linezolid, quinupristin/dalfopristin, minocycline, or vancomycin (Cunha, 2005). All antibiotics will have side affects, even the relatively low dose, low (relative) toxicity ones prescribed by your general practitioner. The most typical of these is antibiotic associated diarrhoea (AAD), essentially caused as the result of destroying the incumbent bacterial flora in your gut. This upsets the natural balance of good and bad bacteria leading to proliferation of species to which your body reacts with watery bowel movements.

In more serious cases conditions such as pseudomembranous colitis (severe inflammation of the colon) principally caused by Clostridium difficile infection. C. difficile is receiving much press recently as multi- drug resistant forms are becoming endemic in hospitals (which is where you're most likely to become colonised by this organism) and present a similar risk as MRSA itself to the very ill and immuno-compromised (fact sheet here) .

In serious MRSA infections, many of the drugs used cannot be absorbed through the gut so are given intra-venously (IV) and are themselves a more potent class of drugs. Many of them are nephrotoxic (toxic to the kidneys) and some such as vancomycin and gentamicin are ototoxic too; prolonged treatment resulting in hearing loss (more information on vancomycin toxicity). With these antibiotics regular blood serum tests are required to ensure the therapeutic dose is maintained, and more importantly, is not exceeded.

As mentioned, patients with weak immune systems and compromised defences (such as a surgical wound) are susceptible to S. aureus infections, which includes MRSA if it is prevalent; MRSA has quite an arsenal of pathogenicity factors it can bring to bear in such circumstances. A straight forward account of Staphylococcal physiology can be found at Todars Online textbook. Under different circumstances, the effect of Staphylococcal toxins can be rapid and it can be devastating resulting in morbidity or death.

In particular a recent occurrence of a particularly potent strain of S. aureus has been in the news. This community-acquired strain, producing the potent toxic Panton- Valentine Leukocidin (PVL) (further information here) can kill healthy people with alarming speed. Although thankfully rare, there are worries that this toxin could be spread to the nosocomial strains of MRSA, thus rendering them far more lethal.

So you can see that survival from an MRSA infection depends on who you are, your age, how healthy you are, whether you are immuno-compromised, whether you have a surgical wound, how long you wait to seek medical advice and finally on the potency of the MRSA strain. It is a complex interplay of bacterial virulence factors and host factors. The numbers of people dying from MRSA is unacceptable and largely preventable by adequate handwashing, appropriate pre-screening before operations with isolation wards and treatment programmes for those colonised (just harmlessly carrying); however, it must be remembered that most of those who do die are already very weak and in many people, the potency of the antibiotics required to treat the infection can be as debilitating as the infection itself.

Hope this helps,