CA-MRSA: a reemerging infectious disease?

July 2006

One of the more interesting conferences I have had the opportunity to participate in, thanks to my good friend and Infectious Disease News editorial board member Jim Hughes, was held in Atlanta two months ago under the auspices of SECEBT, the Southeastern Center for Emerging Biological Threats.

SECEBT is a loose consortium of CDC, southeastern state and local health departments, and academic institutions from southeastern states, and is based at Emory University. The topic was the challenges of MRSA as a community pathogen. Being of a “certain age,” my assignment was to look back at what we had learned in the 1950s and 1960s, an era in which there was rampant staphylococcal infection spreading in U.S. hospitals. Many and perhaps most IDN readers may well be unfamiliar with that era, so I think it is worth stepping back 50 years to review what happened then and what we learned then that may be relevant to present threats of CA-MRSA infection.

From 1955 to about 1965, staphylococcal infection was rampant in U.S. hospitals, caused by apparently new, virulent, and antibiotic-resistant “hospital strains.” There were rapid and dramatic increases in infections in newborns and obstetrical and surgical patients. Up to 25% of newborns developed pyodermas, and maternal breast abscesses were common. In some hospitals, 1% of postpartum women died of staphylococcal sepsis. These strains were uniformly penicillin-resistant and mostly tetracycline-resistant as well. Antibiotic treatment was limited to chloramphenicol, erythromycin and sometimes kanamycin; only erythromycin could be considered a good antistaphylococcal drug, and these strains were sometimes erythromycin-resistant as well. Penicillinase-resistant penicillins didn’t come along until 1960 or 1961.

The preferred technique of strain identification in those days was bacteriophage typing. This was done in only a few laboratories in the United States and always took two weeks or more for the results to appear. Meanwhile, antibiotic resistance patterns became a sort of de facto strain identification technique but soon proved grossly unreliable for epidemiologic purposes. The epidemic, virulent strains in that era almost all belonged to the so-called “80/81 complex,” a large group that sometimes included lysis by the 52 and 52A phages and were referred to as 80/81/52/52A strains.

On top of all that, in 1957 pandemic Asian influenza loomed, and U.S. hospitals were forced to face some serious issues. That was the era in which hospital infection control as we know it today was born, with leadership from the American Hospital Association, the American College of Surgeons, and a short time later, the CDC – then the Communicable Disease Center.

There was a large research literature on hospital-acquired staphylococcal infection, both descriptive and interventional, accumulated between 1955 and 1965. My friend and colleague, Dr. Andy Nahmias, and I published a three-part Medical Progress article in The New England Journal of Medicine in 1961 on the topic, and used an epidemiologic cycle of staphylococcal infection transmission in hospitals as a way to focus efforts to prevent transmission and subsequent staphylococcal disease. I will try to summarize the important information we learned by focusing on various points in the cycle.

• The staphylococcus itself: Even though the key studies of how chemoprophylaxis might work were carried out by Dr. John Burke in the late 1950s, it was still more than a decade later before we learned how to use targeted chemoprophylaxis in surgery effectively; that is, by having the appropriate drug on board at the time surgery begins.
• The infected host: Barrier precautions, hand-washing and, of course, effective antibiotic treatment could interrupt spread from the infected host, but personnel had to learn to use these techniques effectively. Furthermore, there needed to be continual reinforcement since it is so difficult for HCPs to appreciate an infection that has been prevented. This remains just as true today.
• The asymptomatic carrier: An astonishing number of studies of carriers were conducted, both among personnel carriers and patient carriers. Only a small proportion of carriers were effective disseminators of the staphylococci they carried, and these people were often co-infected with a respiratory virus such as an adenovirus. When this mechanism operated in infants, it produced the “cloud baby” phenomenon. Whether this mechanism operated in adults or personnel carriers was never established, but it seemed plausible then, and still does. A number of approaches to controlling nasal carriage among newborns were tried, but the one that was most reliably effective was 3% hexachlorophene washes. It then took almost a decade before we learned about the CNS toxicity of 3% hexachlorophene, especially in premature infants. Control of infant carriage also resulted in control of maternal breast abscesses.
• Airborne spread: Ultraviolet light was proven ineffective in preventing surgical wound infections. Laminar flow rooms became popular in some centers but seemed ineffective on others.
• Contaminated objects: Spread via fomites was relatively easy to interrupt with appropriate sterilization, disinfection or decontamination.
• The susceptible patient in the hospital: Long-term chemoprophylaxis was not effective, nor was “reverse isolation.” Highly protected environments, eg, “bubbles” could be partially effective, but at a terrible psychological price. Staphylococcal vaccines were tried and failed, but are still with us, some showing some promise of success.

Modes of transmission

The modes of transmission in hospitals seemed to rank as follows: contact, droplet, then airborne, but this must be considered an impression rather than an established fact.

By the mid-1960s the epidemic staphylococcal problems began to subside, and although they never really went away, it became clear that the epidemic was over.

No one knows why, even today. The options are several: Our epidemiologic controls were effective in controlling the epidemic; or alternatively, the introduction of penicillinase-resistant penicillins controlled the problem; or alternatively, this was a long-term secular change in the ecology of staphylococci and had little to do with our antibiotics or epidemiologic controls. Probably there was some truth in each point of view, but the real answer remains unknown.

A recent paper by Ashley-Robinson and colleagues from several reference laboratories in the world, including CDC, (Lancet. 2005;365:1256-1258) looked at some of these 40- to 50-year-old phage type 80/81 strains to see if they might be related to CA-MRSA as we know them today.

The answer appeared to be a guarded yes, although the data are not at all conclusive. Interestingly, all the strains from that era contained PVL, a toxin that we associate with virulence in CA-MRSA today. Have these old strains acquired methicillin-resistance and now reemerged as a community-acquired clone? Is this a biological example of “what goes around comes around?” More important, will it subside as mysteriously as the hospital-acquired strains did in the 1960s? As the old Chinese proverb says: May you live in interesting times!

Some other fascinating information was presented at the SECEBT meeting, which I’ll discuss in a subsequent column.