Although I may give a more complete scientific explanation in a future post, I just wanted to pique your interest so that you can do some reading and exploration on your own about this major threat.  In the most basic terms, ESBLs are enzymes that inactivate most current beta-lactam antibiotics including cephalosporins and penicillins.  The most common organism in which the ESBLs are found seem to be E. coli and Proteus mirabilis.  Many of us of a certain generation remember a time when these organisms were so susceptible to antibiotics that you could pretty much choose any drug with basic gram negative activity and it would be effective.  Now, there are isolates of these organism resistant to most commonly used antibiotics and only susceptible to traditionally thought of “big guns” such as carbapenems, and tigecylcine.  And, don’t think these are only found in urinary tract infections, bacteremia, pneumonia or other severe hospital based infections, I have seen them in diabetic foot infections on a number of occasions.

As the name implies, KPCs are enzymes that not only inhibit the previously mentioned antibiotics but also one of the remaining choices effective for ESBLs…carbapenems.  Needless to say, this makes these organisms extremely difficult to treat.  Tigecycline resistance has been reported.  In severe, life threatening infections caused by KPC containing organism the “last ditch” treatment has become either polymyxin-B or colistin.  These are nasty drugs with rather significant adverse event profiles, mostly renal toxicity.  The problem is that, as recently as the past month or two there have been reports of both polymyxin and colistin resistant strains reported in the literature leaving, essentially, no good treatment.  This is why the physician interviewed for the GMA story reported 40%+ mortality related to this organism.  To date the vast majority of these cases are occurring in debilitated hospitalized patients but, the very first KPC in our hospital occurred in a patient I was seeing with a diabetic foot infection. 

 The “MDRO of MDROs” has to be those containing the NDM-1 gene.  This gene was first reported in 2008 in Sweden in a patient hospitalized in India and has a greater ability to rapidly spread to other bacteria than does KPC.  This has become a huge issue in Asia and Europe but has now also spread to the US with, at last count, I believe 4 reported cases.  All patients had some relationship to the Indian subcontinent either having come from there or visited as a tourist.  These bacteria have a similar antimicrobial susceptibility pattern as the KPCs but tend to develop resistance more rapidly.  In the February 2011 issue of Clinical Infectious Diseases an Editorial Commentary says it all just by its’ title “New Delhi Metallo-β-lactamase and Multidrug Resistance: A Global SOS?  http://cid.oxfordjournals.org/content/52/4/485.extract.  To only make matters worse, as recently as last week I saw the first report of an Acinetobacter with a brand new variant, the NDM-2 gene http://jac.oxfordjournals.org/cgi/content/abstract/dkr135v1.   

Unfortunately, there is not a lot of promise for new antibiotic development to fight these MDROs.  The Pharma industry does not make its money on new antibiotic development as most of these drugs are only given for a short period of time in contrast to therapies for hypertension, GERD and cholesterol. To this end the Infectious Diseases Society of America has developed the “Bad Bugs Need Drugs, 10 by 20” campaign  (http://idsociety.org/10×20.htm) a collaboration between the IDSA, Industry and the Government to developed 10 new antibiotics by 2020. I urge all of the readership to check out this website and others to educate yourselves on the risks and dangers these new organisms cause.

- Interesting question as I just received a memo from the dental school at the University asking my preferences regarding antibiotic prophylaxis with implant (hardware) patients and dental surgery. The letter outlined the 2003 decision with the ADA and AAOS as well as followup decisions by both organizations. My take is that one has no choice but to recomend AP due to the medical-legal questions. There is little evidence suggesting it is required but one has to take this time honored procedure into consideration.  This is an interesting point.  Originally, the ADA and AAOS actually came out in a joint statement and concluded that it was NOT routinely needed to prophylax a patient for dental work even if they have a prosthetic joint unless the patient was undergoing a “high risk” dental procedure. As recently as Nov 2009 they changed their position to recommend prophy in these patients prior to any dental procedure!  As you will see below, this is not supported by science. As to the medico-legal issue, there is no question that this does come into play, unfortunately, when making medical decisions.  I think it is time (call be an idealist) we should practice medicine based on science and not fear of repercussions.

- No to both unless prior infection. Actually, this is the “correct” answer based on the paper I will share with you below.

- Related question: 30 yo F w/ Mitral Valve Prolapse. Need ABX prophy for foot or ankle surgery w/ or wo/ implants? Absolutely NONE!  The American Heart Association guidelines for prophylaxis against endocarditis are clear on this point (I think I see another blog post idea).  In 2007 they backed off many recommendations for prophy and now only recommend it when surgically manipulating an actual infection (abscess, cellulitis, etc) in a patient with a “high risk” for infective endocarditis.  These high risks are mostly prosthetic heart valves and other major cardiac conditions and do NOT include MVP. Clean elective surgery through surgically prepared skin has not required prophy since their 1997 Guidelines.

- No to both of these questions. If they had a tooth abscess then I may consider. As far as I know they don’t have people with foot/knee/hip implants take abx everytime they brush their teeth. I Think in the case of bunion surgery on a patient with a known knee prosthesis that preop Ancef is enough. Great point! The issue is the development of bacteremia.  This occurs every time someone brushes their teeth, flosses, eats hard food. You don’t prophy with each of these activities so there is no reason to do it for surgery.  Only when an infection is being manipulated should it be considered.

- In the first scenario, if the patient is immunocompromised in any way, I would advise a cephalosporin. Good suggestion.  Interesting “immunocompromise” of the patient does not seem to come up in any guideline.  I don’t know why.

- In the second scenario, since the joint implant is less than 2 years old, I would recommended prophylactic antibiotics.  Excellent point!  The 2 year rule has been around for a while.  It is presumed that if the implant is in place less than 2 years there is a higher risk of it getting infected.  I am not really certain where that comes from or the validity of it. My only issue would be that if you are not manipulating and infection and are doing your bunion surgery through surgically prepared skin, there should be no bacteremia and no reason to give prophy…just like if it was for endocarditis.

I want to thank those who took the time to respond.  I really enjoyed reading, and thinking about your comments. 

Now here is why I brought it up in the first place:  In the January 1, 2010 issue of Clinical Infectious Diseases there is a study by Berbari et.al. out of the Mayo Clinic entitled “Dental Procedures as Risk Factors for Prosthetic Hip or Knee Infection: A Hospital-Based Prospective Case-Control Study.  (PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19951109 ) .  This elegantly done study looked at 339 patients admitted with prosthetic joint infections (PJI) vs. 339 admissions of patients with non infected prosthetic joints.  They examined dozens of parameters including; the type of dental procedure, time from implant to the dental procedure, time from dental procedure to current admission, operative factors, diabetes, immunocompromise, organisms recovered and many others.  I think it is important for you to read verbatim what they stated in the Results and Conclusion parts of their Abstract:

RESULTS: A total of 339 case patients and 339 control subjects were enrolled in the study. There was no increased risk of prosthetic hip or knee infection for patients undergoing a high-risk or low-risk dental procedure who were not administered antibiotic prophylaxis (adjusted odds ratio [OR], 0.8; 95% confidence interval [CI], 0.4-1.6), compared with the risk for patients not undergoing a dental procedure (adjusted OR, 0.6; 95% CI, 0.4-1.1) respectively. Antibiotic prophylaxis in high-risk or low-risk dental procedures did not decrease the risk of subsequent total hip or knee infection (adjusted OR, 0.9 [95% CI, 0.5-1.6] and 1.2 [95% CI, 0.7-2.2], respectively).

CONCLUSIONS: Dental procedures were not risk factors for subsequent total hip or knee infection. The use of antibiotic prophylaxis prior to dental procedures did not decrease the risk of subsequent total hip or knee infection.

They go on to question the recent AAOS recommendations since they were seemingly not based on any science.  They recognize in the manuscript: “Although the adverse risk of antibiotic prophylaxis in the individual patient may seem remote and unlikely, the risk to the overall population with a joint arthroplasty and to society at large seems prohibitive”.  I believe that this is something we forget when making decisions on our individual patients.  We do thing, like give possibly unnecessary antibiotics to “cover ourselves” from medico-legal concerns and because, frankly, it probably will not hurt that one patient.  But when you multiply your actions times thousands of practitioners thinking the same thing, times the 10s of thousands of patients being treated we start to have an impact on the global microbiota. 

I urge my readers to seek out this article since there are lots of other interesting points that are made and I don’t have the space to go into with this post.