First ASP Jedi

25 Aug

“The Jedi are a monastic spiritual organization in the Star Wars universe. They are bound to a code of ethics, morality, principles and justice. The Jedi are trained to use the Force through passive meditation, practicing selflessness, and commitment to justice while at the same time rejecting emotions such as passion, fear, anger and hate.” (Wikipedia)


We would like to recognize our first Antimicrobial Stewardship Jedi. The success of our stewardship program would not be possible without these exemplary members of the team. Our first Jedi and intensivist often predicts and executes our stewardship suggestions before Dan and I verbally communicate them. A champion of stewardship, Dr. Lisa Huzel has always been an ally to the ASP team. She shares many qualities of a true Jedi but as an ASP Jedi she also is aware of the value as well as unintended consequences of antibiotics.

Kudos to you Dr. Huzel. The force is strong with this one.


TB Skin Test Interpretation

14 Jun

I apologize, it’s been a while since we’ve posted.  Since our last post we’ve expanded our program to cover both our critical care area as well as two acute medical wards.  Unfortunately, this doesn’t leave a lot of time to blog.  Although we have many topics we could cover and share. I am hoping to  post some of our results from our program.

I had an excellent discussion with one of our CRITCARE nurses regarding positive tuberculin skin tests (TST).   Dan suggested we use the tstin3d tool (see link below).

I tried it out for funsies.   The last time I had a TST it was negative but if it were positive today the likelihood of this being a true positive test is 34.17% (PPV).  My annual risk of TB is estimated to be 0.03%  It also provides cumulative risk of active TB until age 80 and risk of  drug induced hepatitis from INH and probability of hospitalization from hepatitis.  Very cool tool!  Thanks Dan!

Check it out ! Hope you find it helpful.

Link 3 Jul

Combating Acid Reflux May Bring Host of Ills

Thought I’d share this NY Times piece by Roni C Rabin.

An easy read discussing more downfalls, and collateral damage associated with the use of proton pump  inhibitors.

The Fecal Veneer – Part 2

18 May

So, GNB colonization of the respiratory tract is possible.  Why do these pathogens that normally like to live in the GI tract move and end up in our mouths and respiratory tracts?  An amazing review by Curtis Donsky provides the basis for this blog entry. (1).

The answer is all in the doo doo. The human colon contains as many as 1 trillion (1,000,000,000,000) bacteria per gram.  This massive reservoir of bacteria from the GI tract is the source of the “fecal veneer” on hospital surfaces and the skin of patients. The fecal veneer (or fecal patina if you’re fancy) is the theory that the world is covered in a thin layer of stool.

In our hospitalized patients, imagine a bull’s eye of bacteria from the rectum that gradually grows with decreased hygiene and is aided by iatrogenic causes. (2) This army of bacteria spreads in all directions and can eventually reach the mouth.  Fecal incontinence , diarrhea, altered mental status, and debilitation also could potentially contribute to this. Patients are touched and moved often.  We use various instruments that come in contact with the environment and the patient.  Patient’s are not able to shower, their linens aren’t changed often. You get the picture.

Add to this antibiotics, and acid suppression that can interrupt our natural colonization resistance.  Colonization resistance is our natural and diverse makeup of bacteria which prevents pathogens from taking over. Below is a figure from Donsky’s paper which is a great summary.

There are other cans where the veneer originates.  While training during rounds, a former truck driver and ID physician went on a rant that toilets were like bacterial volcanoes when flushed spewing and aerosolizing #1s and #2s into the environment.  I didn’t believe the kooky ID man.  He was right.  Lidless toilets can aerosolize C difficile and other pathogens.(3,4) Best used faecal suspensions of C diff and sampled air, and measured surface contamination.  Adding a lid to the toilet eliminated the surface contamination (luckily our ICU has lidded toilets).

This micro thin patina can’t be avoided.  Although it can’t be seen or smelled, it most definitely exists. As a patient’s length of stay increases the interactions with potentially contaminated instruments and hands of healthcare workers increases.

It’s easy to see how a patient  can be colonized now with the doo doo.  This can happen either directly (from the environment of the patient) or indirectly (by healthcare worker’s hands and equipment).   Hopefully this highlights the importance of hand hygiene and initiatives like chlorhexidine baths (5,6). Back to the cases, antibiotics were started on both patients.   We used a short course of 3 days in one of the patients.   (7).

We do a yearly boys weekend camping trip.  Showers are a luxury that aren’t afforded. By the end of the weekend I feel pretty filthy and just want a shower.  I wonder if this is what my patina feels like.

Don’t you want to sterilize your desk and wash your hands?

[1] Donskey, C. J. (2004). The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens. Clinical Infectious Diseases, 39(2), 219-226. Retrieved from

[2] Williams, L. (2012). Intensive care unit environments and the fecal patina: A simple problem? Critical Care Medicine, 40(4), 1333-1334. Retrieved from

[3] Best, E. L., Sandoe, J. A. T., & Wilcox, M. H. (2012). Potential for aerosolization of Clostridium difficile after flushing toilets: the role of toilet lids in reducing environmental contamination risk. The Journal of hospital infection, 80(1), 1-5. Retrieved from

[4] Barker, J., & Jones, M. V. (2005). The potential spread of infection caused by aerosol contamination of surfaces after flushing a domestic toilet. Journal of Applied Microbiology, 99(2), 339-347. Retrieved from

[5] Bleasdale, S. C., Trick, W. E., Gonzalez, I. M., Lyles, R. D., Hayden, M. K., & Weinstein, R. A. (2007). Effectiveness of chlorhexidine bathing to reduce catheter-associated bloodstream infections in medical intensive care unit patients. Archives of Internal Medicine, 167(19), 2073-2079. Retrieved from

[6] Climo, M. W., Sepkowitz, K. A., Zuccotti, G., Fraser, V. J., Warren, D. K., Perl, T. M., Speck, K., et al. (2009). The effect of daily bathing with chlorhexidine on the acquisition of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and healthcare-associated bloodstream infections: results of a quasi-experimental multicenter trial. Critical Care Medicine, 37(6), 1858-1865. Society of Critical Care Medicine and Lippincott Williams & Wilkins. Retrieved from

[7] Singh, N., Rogers, P., Atwood, C. W., Wagener, M. M., & Yu, V. L. (2000). Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. American Journal of Respiratory and Critical Care Medicine. Am Thoracic Soc. Retrieved from

Respiratory tract colonization with GNB Part 1

18 May

 It’s been a crazy last few months, we’ve been busy with many side projects with ASP.  Dan and I have been adding to our list of blog topics. I’m looking forward to Dan’s planned post on ‘why fluoroquinolones are evil.’

This is a 2 part post. The topic of this post comes from two recent interactions we had with our colleagues.  Two cases (two different hospitals) of suspected ICU HAP/VAP with gut/poo bacteria (Klebs + E coli).  Both patients grew these bugs from sputum cultures and the comment was made that these must be pneumonias because you can’t be colonized with poo in your respiratory tract.

A paper by Johanson et. al published in the New England Journal of Medicine in 1969[1] provides a great starting point to this discussion.  The group from Texas selected 5 groups of adults: non-hospitalized normal subjects (members of Dallas fire dept); hospital associated normal subjects (hospital staff); physically normal hospitalized patients (psych ward); moderately ill hospitalized patients (ortho); and near death (moribund) patients (critically ill medical).  They obtained oropharyngeal cultures from each of the groups.  They found that 57% of moribund patients were colonized with gram negative bacilli (GNB) and 16% of moderately ill patients (orthopedic) were colonized.  2% from the non-hospitalized normal subjects were also colonized.  This was a small study, and has its flaws.  There are other papers that explore colonization with GNBs.  (2,3,4)   It is possible to have poo bacteria in the mouth/oropharynx. 

In normal hosts >90% of GNB in the oropharynx is cleared by effective salivary flow and swallowing.  (5) Our sicker and elderly patients have impairment of these clearance mechanisms thus the increased risk of colonization by pathogenic GNBs. 

But how do GNBs get into the mouth/oropharynx to begin with? The answer is pretty wild.

[1]Johanson, W. G., Pierce, A. K., & Sanford, J. P. (1969). Changing pharyngeal bacterial flora of hospitalized patients. Emergence of gram-negative bacilli. The New England Journal of Medicine, 281(21), 1137-1140.

 [2] Garrouste-Orgeas, M., Chevret, S., Arlet, G., Marie, O., Rouveau, M., Popoff, N., & Schlemmer, B. (1997). Oropharyngeal or gastric colonization and nosocomial pneumonia in adult intensive care unit patients. A prospective study based on genomic DNA analysis. American Journal of Respiratory and Critical Care Medicine, 156(5), 1647-1655. Retrieved from

[3] Heyland, D., & Mandell, L. A. (1992). Gastric colonization by gram-negative bacilli and nosocomial pneumonia in the intensive care unit patient. Evidence for causation. Chest, 101(1), 187-193.

[4] Mackowiak, P. A., Martin, R. M., Jones, S. R., & Smith, J. W. (1978). Pharyngeal colonization by gram-negative bacilli in aspiration-prone persons. Archives of Internal Medicine, 138(8), 1224-1227.

[5] Palmer, L. B., Albulak, K., Fields, S., Filkin, A. M., Simon, S., & Smaldone, G. C. (2001). Oral clearance and pathogenic oropharyngeal colonization in the elderly. American Journal of Respiratory and Critical Care Medicine, 164(3), 464-468. Retrieved from

Antibiotics & C-diff Risk

23 Feb

During one of our interventions we suggested modifying an antibiotic regimen to use, in our opinion, a less C-diffogenic antibiotic.  This prompted us to do a literature search on the C-diffogenicity (not sure if this is a word) of various antibiotics.

Several risk factors have been identified for Clostridium difficile infection (CDI).  Culprits include, increased age, use of acid suppression therapy, and antibiotic therapy to name a few (1).   The most widely reported and well documented risk factor is antimicrobial exposure (2).  Prudent antibiotic use and antimicrobial stewardship programs have been shown to decrease nosocomial CDI (3).  That being said, we have also encountered community acquired CDI in patients without prior antibiotic exposure (4).   

The postulated pathophysiology of antibiotic associated CDI is that antibiotic exposure/use disrupts the natural microflora of the colon (killing the good and bad bugs).  This microflora provides a defence against potential pathogens (e.g.  C. difficile) by inhibiting colonization.  Once this intestinal flora is altered it may take weeks for it to return to normal levels.  (5,6).   This concept of reverting back to the normal flora has been recently challenged in an editorial published in Nature.  The author suggests that sometimes the natural flora may never fully recover.  A very interesting read (10).  This disruption is thought to either cause an overgrowth of indigenous C. difficile or allow for ingested C. difficile spores to colonize the flora (7, 8, 9).

Back to the topic of this post.  I was unable to find a nice chart outlining the C-diffogenciity of various antibiotics.  We compiled this list based on the risk ratios of different antibiotics based on two published papers and our own clinical experience (1, 11).  Unfortunately there are no published prospective randomized trials that explore this issue (that I’m aware of).  Thus, this chart is likely affected by many biases and is our opinion.  Due to the complexity of CDI and lack of prospective clinical trials it’s difficult to say that a patient will acquire CDI by using a certain antibiotic.  If we aim to treat patients with the optimal antibiotic at the shortest duration we can minimize the collateral damage associated with antibiotic use (12).

Again, this chart is for informational purposes.  Any antibiotic exposure increases the risk of CDI.

Most likely to cause C diff Less likely to cause C. diff
Quinolones (moxifloxacin, levofloxacin, ciprofloxacin) Trimethoprim/sulfamethoxazole
Cephalosporins (1st generation may have lower risk) Nitrofurantoin
Clindamycin Macrolides (e.g. azithromycin, erythromycin)
Amoxicillin/Clavulanate Penicillin + Antistaphylococcal penicillins
  Aminoglycosides (e.g. tobramycin, gentamicin)
  Tetracyclines (large confidence interval)



  1.  Dial, S., Kezouh, A., Dascal, A., Barkun, A., & Suissa, S. (2008). Patterns of antibiotic use and risk of hospital admission because of Clostridium difficile infection. CMAJ Canadian Medical Association Journal, 179(8), 767-772. Canadian Medical Association. Retrieved from
  2. Owens, R. C., Donskey, C. J., Gaynes, R. P., Loo, V. G., & Muto, C. A. (2008). Antimicrobial-associated risk factors for Clostridium difficile infection. (C J Donskey, R P Gaynes, V G Loo, & C A Muto, Eds.)Clinical Infectious Diseases, 46 Suppl 1(Suppl 1), S19-S31. Retrieved from
  3. Valiquette, L., Cossette, B., Garant, M.-P., Diab, H., & Pépin, J. (2007). Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent NAP1/027 strain. Clinical Infectious Diseases, 45 Suppl 2(Suppl 2), S112-S121. Retrieved from
  4. Kuntz, J. L., Chrischilles, E. A., Pendergast, J. F., Herwaldt, L. A., & Polgreen, P. M. (2011). Incidence of and risk factors for community-associated Clostridium difficile infection: A nested case-control study. The Journal of antimicrobial chemotherapy, 11(3), 194. BioMed Central. Retrieved from
  5. Donskey, C. J. (2004). The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens. Clinical Infectious Diseases, 39(2), 219-226. Retrieved from
  6. Gerding, D. N. (2004). Clindamycin, cephalosporins, fluoroquinolones, and Clostridium difficile-associated diarrhea: this is an antimicrobial resistance problem. Clinical Infectious Diseases. Retrieved from
  7. Wilson, K. H. (1993). The microecology of Clostridium difficile. Clinical Infectious Diseases, 16 Suppl 4(4), S214-S218. Retrieved from
  8. Chang, J. Y., Antonopoulos, D. A., Kalra, A., Tonelli, A., Khalife, W. T., Schmidt, T. M., & Young, V. B. (2008). Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. The Journal of Infectious Diseases, 197(3), 435-438. Oxford University Press. Retrieved from
  9. Rodriguez-Palacios, A., Staempfli, H. R., Duffield, T., & Weese, J. S. (2007). Clostridium difficile in Retail Ground Meat, Canada. Emerging Infectious Diseases, 13(3), 485-487. Centers for Disease Control and Prevention. Retrieved from
  10. Blaser, M. (2011). Antibiotic overuse: Stop the killing of beneficial bacteria. Nature, 476(7361), 393-394. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Retrieved from
  11. Bignardi, G. E. (1998). difficile Risk factors infection. The Journal of hospital infection, 40(1), 1-15. Elsevier. Retrieved from
  12. Stevens, V., Dumyati, G., Fine, L. S., Fisher, S. G., & Van Wijngaarden, E. (2011). Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clinical Infectious Diseases, 53(1), 42-48. Retrieved from

Proton Pump Inhibitor (PPI) Use and Clostridium difficile

21 Dec

While following one of our patients we suggested discontinuing her PPI if it was feasible.  This led to a discussion on the data linking Clostridium difficile infection (CDI) and acid suppressive agents.  Here’s our take on the issue.

“The hippies knew, acid is good, man.” Dr. Mark Crislip.

PPI use at our institution, and I’m sure many others, is widespread.   In 2009 US News reported that PPI sales in the US amounted to 13.9 billion dollars! PPIs are well tolerated and effective.  PPIs, like antibiotics however, are not without harm.

In 2007, a systematic review was published in the American Journal of Gastroenterology. (2)  The review evaluated 11 observational studies (n=126,999).  The team at McMaster found an associated between acid suppression and C. difficile infection with a combined OR of 2.05 (1.47 – 2.85). Ten of the studies showed a positive association between PPI use and CDI.

Infection & Colonization

A recent article by Loo and colleagues (3) found that proton pump inhibitor use along with use of antibiotics and older age were significant risk factors for nosocomial CDI.   The prospective study took place in six Canadian hospitals in Quebec and Ontario and involved 4,143 patients.  Of those patients 117 (2.8%) and 123 (3.0%) patients developed health care associated C. difficile infection or colonization.  Previous use of proton-pump inhibitors was associated with Clostridium difficile infection [OR 2.64 95% CI (1.71-4.09)].  The study also showed PPIs [OR 1.71 (1.15 – 2.52)] & H2 blockers [2.14 (1.24 – 3.70)] were also associated with C difficile colonization.

Dose Response

Another trial displayed that increasing levels of acid-suppressive therapy was related to increasing rates of nosocomial CDI (4).  Howell’s group analyzed data collected prospectively for ‘other reasons.’  They analyzed 101,796 hospital discharges over 5 years.  Increasing the level of acid suppression increased the risk of health care associated C difficile.  [no acid suppression=reference Odds Ratio = 1(CI), H2 blocker only OR = 1.53 (1.12 – 2.10), daily PPI OR = 1.74 (1.39 – 2.18), PPI more frequently OR = 2.36 (1.79 – 3.11)].  Although this was an observational study the findings are impressive; receiving a daily PPI was associated with a >70% increase in the odds of developing C difficile. The study essentially provides a dose-response curve for acid suppressants and CDI.  Very cool data.

 Recurrent CDI

Amy Linsky et al (5) found that proton pump inhibitor use during CDI treatment was associated with an increased risk of recurrence within 15-90 days.  Hazard ratio 1.42 [CI 1.11-1.82; P=0.008].  This retrospective cohort study used the New England VA database and reviewed 1,549 patients with findings of C difficile toxin.  The increased risk of recurrent CDI was significantly higher in patients older than 80 years.

PPIs and Neutrophils

A small open label study done on 10 healthy subjects found that omeprazole impaired production of reactive oxygen intermediates by neutrophils.   The study linked single doses of omeprazole to decreased bactericidal activity of neutrophils (6).   This provides another proposed mechanism of the association between the class of drugs and pathogen.


Based on the above data it’s likely that gastric acidity plays a major role in protecting against infection from Clostridium difficile. Studies have shown that more acidic gastric juices were more effective than less-acidic gastric juices in killing C difficile and neutralizing its toxin.  (7)  The association is likely mutlifactorial (think swiss cheese). Curbing inappropriate PPI use could vastly improve the care we provide our patients.

One of our tenets as clinicians is to first, do no harm.  There are definitely multiple patient groups that would benefit from PPI therapy: patients with upper GI bleeds, GERD, erosive esophagitis, patients on dual anti-platelet medications or NSAIDs, H. Pylori eradication, and patients at high risk of stress ulcers.   I was unable to find a consensus guideline suggesting when PPIs should and shouldn’t be used; this is part of the problem.  PPIs are very effective and easy to prescribe.  However, we should be aware of the potential collateral damage associated with their use.  There’s data suggesting PPI use is associated with increased risk of fractures, pneumonia, and Clostridium difficile (email for more references)We should attempt to use agents with the least collateral damage for the shortest duration possible.

During stewardship rounds we suggest discontinuation of PPIs or de-escalation of PPIs to H2RAs if possible.  If there’s a clear indication for PPI use it at the lowest effective dose, for the shortest duration possible. This sounds familiar doesn’t it? :)



The FDA issued a Safety Announcement last week supporting the above post.

Feb 15, 2012




  1. Thorens, J., Froehlich, F., Schwizer, W., Saraga, E., Bille, J., Gyr, K., Duroux, P., et al. (1996). Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study. Gut, 39(1), 54-59. Retrieved from
  2. Leonard, J., Marshall, J. K., & Moayyedi, P. (2007). Systematic review of the risk of enteric infection in patients taking acid suppression. American Journal of Gastroenterology, 102(9), 2047-2056; quiz 2057. Retrieved from
  3. Loo, V. G., Bourgault, A.-M., Poirier, L., Lamothe, F., Michaud, S., Turgeon, N., Toye, B., et al. (2011). Host and pathogen factors for Clostridium difficile infection and colonization. The New England Journal of Medicine, 365(18), 1693-703. Retrieved from
  4. Howell, M. D., Novack, V., Grgurich, P., Soulliard, D., Novack, L., Pencina, M., & Talmor, D. (2010). Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Archives of Internal Medicine, 170(9), 784-790. Retrieved from
  5. Linsky A, Gupta K, Lawler EV, Fonda JR, Hermos JA. (2010). Proton pump inhibitors and risk for recurrent Clostridium difficile infection.  Archives of Internal Medicine, 170(9), 772-778. Retrieved from
  6. Zedtwitz-Liebenstein, K., Wenisch, C., Patruta, S., Parschalk, B., Daxböck, F., & Graninger, W. (2002). Omeprazole treatment diminishes intra- and extracellular neutrophil reactive oxygen production and bactericidal activity. Critical Care Medicine, 30(5), 1118-1122. Retrieved from
  7. Gurian, L., Ward, T. T., & Katon, R. M. (1982). Possible foodborne transmission in a case of pseudomembranous colitis due to Clostridium difficile: influence of gastrointestinal secretions on Clostridium difficile infection. Gastroenterology. Retrieved from