Superbug Intro

There has been a large number of bacteria bequeathed with the title of "superbug" - usually by the press - in recent times. These include - not in any order of importance - MRSA, VRE, penicillin-resistant Streptococcus pneumoniae, multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, ESBL (extended-spectrum beta-lactamase)-producing Escherichia coli and Klebsiella pneumoniae, KPC (Klebsiella pneumoniae carbapenemase)-producing K. pneumoniae and E. coli, and lately, NDM-1 (New Delhi metallo-beta-lactamase)-producing K. pneumoniae. The term "superbug" connotes antibiotic resistance rather than hyper-virulence, a common public misconception. Some isolates of Acinetobacter baumannii are resistant to all known antibiotics, but this is a relatively weak opportunistic pathogen, largely incapable of causing infections in healthy individuals (although fulminant infections continue to occur in ICU patients, burns patients, or hospitalized patients with various tubes sticking in and out of them). On the other hand, the pneumococcus - while not particularly antibiotic resistant - can infect and kill individuals of all ages and health states (and therefore the critical importance of vaccination in childhood or when immunocompromised).

Generally, when a bacterium first develops resistance to an antibiotic, a fitness cost is imposed on the organism that comes from maintaining a new and additional "process" (that may well be alien to the bacterium - many of the antibiotic resistance genes found in bacteria capable of causing human disease are actually horizontally transferred to them from other bacterial species that may not be pathogenic). One inexact analogy would be the slowing down of your computer (especially if old) when you are running several applications at the same time. The bacterium then seems to be less capable of causing infections, a phenomenon observed with organisms like MRSA or multidrug-resistant tuberculosis when these first appeared. However, this fitness cost is not by any means static: after a period of time, the bacterium generally adapts to this and resumes "normal function" when causing infections.

As an example, when MRSA first appeared in the 1960's, physicians and scientists observed that infections only took place in the hospital setting among immunocompromised patients, and the organism disappeared after discharge from the hospital (this may take up to a year, however), replaced by other staphylococci from the community. For the longest time, this was held to be true until community-associated MRSA appeared in the late '80s and '90s. It took a long time for the scientific and medical community to actually believe that MRSA can cause infections in healthy individuals outside the hospital setting - something that most young doctors today may find hard to imagine, particularly with what we know about evolution. How did the organism evolve to do this? By replacing larger and "clunkier" methicillin resistance gene cassettes with more streamlined and smaller versions, and by assembling heterogeneous cell walls made with a variety of penicillin-binding proteins rather than homogeneous cell walls comprising mostly of the alien PBP-2' that confers methicillin resistance. Such changes enabled CA-MRSA to compete successfully with other staphylococci in the community setting, and to cause infections even in healthy individuals, resulting in outbreaks in almost all continents worldwide.

Next up: NDM-1 and why this is (IMHO) the most important antibiotic resistance phenomenon to have emerged after MRSA. Or you can look it up on Wikipedia.