Uncategorized

Community Acquired MRSA (a primer).

By Chris Rangel MD ⋅ December 4, 2005 ⋅  Email this post ⋅  Print this post ⋅ Post a comment

MRSA costly but not worse than usual bacteria.

Methicillin-resistant staphylococcus aureus (MRSA) is simply a slightly altered form of the extremely common skin bacteria Staphylococcus aureus. Throughout the ages “Staph” has been responsible for huge numbers of serious skin infections (i.e. battle wound infections). It truly is a horrible killer, potentially causing skin abscesses and less commonly causing necrotizing fasciitis (so called “flesh eating”) and if it spreads to the blood it can cause endocarditis, sepsis, deep tissue abscesses, bone and joint infections, and toxic shock.

Before the advent of antibiotics, serious or invasive Staph infections had very high morbidity and mortality rates (80% died). After the introduction of penicillin in the 1940’s the death rates from Staph infections dropped dramatically (to 25-30%) but penicillin resistant Staph strains began to appear. Several different classes of antibiotics were developed in response so that even today, bacteria resistant to penicillin type antibiotics (beta-lactams) are almost always susceptible to several other classes of antibiotics.

The exception to this rule has been MRSA. This bug tends to be not only resistant to methicillin (a type of penicillin) but also to almost all other classes of antibiotics with the exception of vancomycin (the mainstay of MRSA treatment). MRSA first appeared in the 1940s but only started to become a significant problem in the last 20 years and until the last few years MRSA was almost exclusively seen as a hospital acquired infection (mostly in critically ill patients or those with multiple other co-morbidities).

Hospital acquired MRSA is known to be able to spread directly to the community when infected hospital patients or those who become carriers are discharged home but an increasing number of MRSA infections are being seen in patients who have no known risk factors (recent hospitalization, health care workers, nursing home exposure, recent antibiotic use). This “community acquired” MRSA as caused quite a stir in the medical community and in the media who (as per par for the course) are giving it amusingly hysterical names like “super bug“, “killer Staph“, “flesh eating bacteria“, and “Mersa” (a bizarre attempt to create a name out of the abbreviation for MRSA). One reporter even went so far as to declair MRSA to be untreatable by any antibiotic (not true).

But the reality is that there is nothing “super” about MRSA the superbug. Such lay media hyping implies that MRSA is more virulent (i.e. more harmful) than it’s more common cousin Methicillin sensitive Staphylococcus Areus (MSSA). However, MSSA is perfectly capable of killing and eating flesh just as well as MRSA and in fact does so with vigor, killing and harming thousands each year despite being totally susceptible to antibiotics.

The wrinkle with MRSA is almost exclusively in its antibiotic resistance patterns. It is not at all clear whether MRSA is actually more virulent or more lethal than MSSA. While there is some evidence for worse outcomes with hospital acquired MRSA, other studies have found no differences and others have suggested that the increased risk of death from hospital acquired MRSA infection is related more to factors like the severity of illness and lengths of stay. I.e. severely ill patients are at higher risk of developing a Staph blood infection and this is more likely to be MRSA the longer that they remain in the hospital. In addition, the rapid spread of an MRSA isolate within a hospital setting appears to be directly related to the use of broad-spectrum antibiotics in susceptible patients rather then to any increased virility of MRSA itself.

There is even less data on the virulence of community acquired (CA) MRSA compared to regular ‘ol MSSA. What is known about CA-MRSA is that it appears to be significantly different then its hospital acquired (HA) counterpart. For example, there are four different variations of the gene sequence that codes for antibiotic resistance in MRSA bacteria (called the staphylococcal cassette chromosome or SCCmec if you really wanted to know). While HA-MRSA isolates can be types I, II, or III, 99% of CA-MRSA is of type IV! This suggests that rather then being a case of MRSA spreading from its breeding grounds in the hospital out to the community, CA-MRSA is an entirely new animal. This explains why most patients with CA-MRSA do not have any of the usual risk factors for MRSA that hospitalized patients do.

CA-MRSA patients tend to have skin MRSA infections rather than blood born or invasive infections like their hospital counterparts but serious CA-MRSA can and do occur. CA-MRSA while being resistant to penicillin antibiotics continue to be susceptible to other drugs including trimethoprim–sulfamethoxazole (Bactrim), doxycycline, and clindamycin (however, controled clinical outcome data is missing on the treatment of MRSA with these antibiotics). These patterns are very unlike HA-MRSA.

If CA-MRSA didn’t come from the hospitals and nursing homes then where did it come from? On this there is far less data and mostly speculation. From an epidemiological standpoint, the emergence of CA-MRSA appears to be very similar to the initial emergence of beta-lactam resistance way back when penicillin antibiotics first came out. The implication is that the emergence of CA-MRSA, like that of prior resistant bugs, is due to the heavy use of antibiotics to treat infections in the outpatient population. But the problem with this theory is that it does not explain why it took so long for CA-MRSA to develop unless a certain critical point was finally reached with the numbers of outpatient infections and the heavy use of antibiotics.

The main difference in the last few years appears not to be with the severity of Staph infections acquired in the community but with what percentages of those are caused by MRSA rather then MSSA. Starting in the 1990s, CA-MRSA accounted for up to 12-29% of all community associated Staph infections and that rate appears to be increasing (although the numbers appear to be larger in community populations with higher rates of homeless and IV drug abusers who are at higher risk of skin infections). According to a recent study in the New England Journal other risk factors for CA-MRSA infection included patients with chronic health conditions, being treated with an antibiotic within the prior year, crowed living conditions (more than one person per bedroom), and a visit to a physician’s office within the previous year (though this may reflect the existence of chronic medical conditions necessitating a visit to a doc rather then implying that CA-MRSA is acquired from exposure to a physician’s office).

Not only is there little current evidence that CA-MRSA is more virulent than MSSA but the same New England Journal study found that even though up to 73% of CA-MRSA infections were initially treated (empirically) with a non-MRSA effective antibiotic, this did not adversely affect clinical outcomes in these patients. I.e. patients with skin CA-MRSA infections initially treated with an antibiotic not effective against MRSA did not have an increased rate of follow up visits to a physician, “subsequent incision and drainage, or subsequent change in antimicrobial therapy.” This seemingly paradoxical result may be explained partly by the fact that many infections initially identified as CA-MRSA are actually borderline oxacillin-resistant S. aureus (BORSA) which is still sensitive to many penicillin antibiotics. Then again, this is the subject of much speculation.

CA-MRSA may not be worse than CA-MSSA infections but one thing is very clear. The costs of treating these infections in the coming years is going to skyrocket. The main treatment of MRSA for years has been vancomycin which must be given in IV form and this requires expensive monitoring in a hospital setting or via home nursing care. Recently several new oral medications have been developed for MRSA infections but they are ridiculously expensive. For example, linezolid (belonging to a class of antimicrobials called oxazolidinones that inhibit bacterial protein synthesis) has been approved at 400-600 mg every 12 hours for 10-14 days. A ten day supply of 600 mg tables costs over $1,000! Compare this to the penicillin amoxicillin which is used to treat relatively minor MSSA infections. A 14 day course of 875 mg of amoxicillin given twice a day is less than $30!!!! Hold on to your wallets!

The only thing “super” about CA-MRSA appears to be its impact on health care costs. Community acquired Staphylococcal infections regardless of whether they are multi drug resistant or not are potentially serious infections. Though many CA-MRSA infections may potentially be effectively treated with traditional antibiotics, medical-legal considerations will force most physicians to treat any MRSA infection with the more expensive MRSA effective antibiotics. Since we are unlikely to curtail the heavy use of antibiotics for just about every minor outpatient complaint we might as well get used to a protracted war between increasingly antibiotic resistant bacteria and the race to develop newer antibiotics to combat them.