Referral: Mckenna On The Regulatory Limbo Of Fecal Transplants

C. difficile – Credit CDC PHIL

 

# 8324

 

Roughly 44 years ago Dr. William Nolan wrote a book called `The Making of A Surgeon’, about his internship at Bellevue Hospital in the 1950s that, quite frankly, inspired me to become an EMT, and then a Paramedic.  While dated, it still a good read, and highly recommended. 

 

But I mention it because one of the anecdotes he relates was a hysterically funny account about how he, and two other interns, concocting a `feces laced milkshake’  to try to cure a patient with intractable diarrhea, likely due to a C. Diff infection. 

 

When their resident found out what they’d done, he went ballistic, and for a time all three interns thought their careers were ended.  They waited in fear for days for the patient to die from their ill advised treatment.

 

As it turned out, the `cure’ worked, the patient was none the wiser, and the statute of limitations eventually passed and the story could be told.  Fast forward sixty years and their radical idea – of reintroducing healthy gut bacteria from a stool donor – is now on the cutting edge of medicine.

A little over a year ago, in NEJM: Effectiveness Of Fecal Transplants For C. diff, we looked at the remarkable results being obtained doing this simple procedure – a cure rate of roughly 90%..   All the more important because Clostridium difficile – or C. diff – claims tens of thousands of lives each year, and is – as the name implies – very difficult to treat.

 

More than two years ago Maryn McKenna’s wrote Fecal Transplants: They Work, the Regulations Don’t, which showed how difficult getting this simple, inexpensive and effective treatment can be in the United States due to it falling into a regulatory limbo.  Unfortunately, two years have passed, and little progress has been made in clearing the regulatory minefield. 

 

Today Maryn is back with another report, and a possible solution,  which you can read at:

 

Fecal Transplants: Treat Them Like Tissue, Not Like Drugs

• By Maryn McKenna   02.23.14  8:52 AM  

It’s been a little more than a year since the first-ever clinical trial of fecal transplants — the practice of infusing diluted donor stool into the colon of someone suffering from Clostridium difficile infection — demonstrated that the low-tech process not only works to overcome the disease’s painful, life-disrupting diarrhea, but works better than the standard treatment of antibiotics.

 

That finding confirmed what gastroenterologists had known for a while — not to mention what patients who had sought out the procedure, in the United States or in other countries, could confirm from their own experience of being rapidly and, for the most part, permanently cured.

(Continue . . . .)

NEJM: Effectiveness Of Fecal Transplants For C. diff

 

C. difficile – Credit CDC PHIL

 

UPDATE:  Just as I posted this blog, Maryn McKenna posted her take on this study, which you can read at Fecal Transplants: A Clinical Trial Confirms How Well They Work

 

# 6863

 

In December of 2011 I reviewed some of the early history of using donor feces to resolve C. difficile infections, and invited my readers to read a post by Maryn McKenna’s called Fecal Transplants: They Work, the Regulations Don’t.

 

Clostridium difficile – or C. diff – is a bacterial intestinal infection which claims tens of thousands of lives each year, and is – as the name implies – very difficult to treat.

 

Usually brought on by the use of antibiotics  - which kill off good gut bacteria along with the bad guys – C. diff can produce prolonged, and often life threatening bouts of diarrhea.

 

The idea behind a `fecal transplant’ is the re-introduction of good bacteria to afflicted patient’s gut biome.  

 

Today the NEJM has an original article showing a remarkable success rate using donor feces to resolve recurrent C. diff infections among a small group of mostly elderly patients in the Netherlands.

 

Doctors randomly selected C. diff patients to receive one of three therapies:

 

• An initial vancomycin regimen (500 mg orally four times per day for 4 days), followed by bowel lavage and subsequent infusion of a solution of donor feces through a nasoduodenal tube;
• a standard vancomycin regimen (500 mg orally four times per day for 14 days);
• or a standard vancomycin regimen with bowel lavage

The criteria for success was the resolution of diarrhea associated with C. difficile infection without relapse after 10 weeks.

 

Among patients receiving the combination vancomycin -fecal transplant treatments, 81% (n=13 of 16) saw a resolution of their C. diff diarrhea symptoms after one infusion.

 

Of the remaining three, two responded after a second infusion (total success rate 15 of 16, or 94%).

 

Success rates were more than triple that of patients who received vancomycin alone (4 of 13 patients or 31%), or vancomycin with lavage (3 of 13 patients or 23%).

 

Their conclusion:

The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin.

 

The article, with considerable detail,  is available at the NEJM.

 

Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile

Els van Nood, M.D., Anne Vrieze, M.D., Max Nieuwdorp, M.D., Ph.D., Susana Fuentes, Ph.D., Erwin G. Zoetendal, Ph.D., Willem M. de Vos, Ph.D., Caroline E. Visser, M.D., Ph.D., Ed J. Kuijper, M.D., Ph.D., Joep F.W.M. Bartelsman, M.D., Jan G.P. Tijssen, Ph.D., Peter Speelman, M.D., Ph.D., Marcel G.W. Dijkgraaf, Ph.D., and Josbert J. Keller, M.D., Ph.D.

January 16, 2013DOI: 10.1056/NEJMoa1205037

 

 

Two points I’m sure everyone is curious about.   How donors were screened, and any adverse side effects reported:

 

The authors describe the screening process this way:

Donors (<60 years of age) were volunteers who were initially screened using a questionnaire addressing risk factors for potentially transmissible diseases. Donor feces were screened for parasites (including Blastocystis hominis and Dientamoeba fragilis), C. difficile, and enteropathogenic bacteria. Blood was screened for antibodies to HIV; human T-cell lymphotropic virus types 1 and 2; hepatitis A, B, and C; cytomegalovirus; Epstein–Barr virus; Treponema pallidum; Strongyloides stercoralis; and Entamoeba histolytica. A donor pool was created, and screening was repeated every 4 months. Before donation, another questionnaire was used to screen for recent illnesses.

 

As far as adverse events were concerned:

 

Immediately after donor-feces infusion, most patients (94%) had diarrhea. In addition, cramping (31%) and belching (19%) were reported (Table 2). In all patients, these symptoms resolved within 3 hours.

During follow-up, three patients who were treated with donor feces (19%) had constipation. No other adverse events related to study treatment were reported.

 

For patients afflicted with C. diff, but who cannot get past the `ick’ factor of receiving donor feces, there may be hope on the horizon. 

 

Researchers in Ontario, Canada have developed a `synthetic stool’, containing 33 types of `good’ bacteria, they call RePOOPulate.

 

Results of limited testing (only two patients) were recently published in the open access journal Microbiome.

 

 

Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut

Elaine O Petrof^1*†, Gregory B Gloor^2†, Stephen J Vanner¹, Scott J Weese³, David Carter⁴, Michelle C Daigneault⁵, Eric M Brown⁵, Kathleen Schroeter⁵ and Emma Allen-Vercoe⁵

Conclusion

This proof-of-principle study demonstrates that a stool substitute mixture comprising a multi-species community of bacteria is capable of curing antibiotic-resistant C. difficile colitis. This benefit correlates with major changes in stool microbial profile and these changes reflect isolates from the synthetic mixture.

 

For now, fecal transplants are not FDA approved, and questions remain over the safety of using donor feces.

 

If synthetic stools products can be shown to have a Darwinian advantage over C. diff bacteria in the human gut, it would go a long ways towards eliminating any concerns over the `origins of feces’.

Bad . . . I know.  

 

But If I didn’t use that line, someone else would have.

Unnecessary Antibiotic Use & C. Difficile Infections

C. difficile – Credit CDC PHIL 

# 6842

 

We’ve more evidence today on the perils of unnecessary antibiotic usage from a study that appears in the February 2013 edition of Infection Control and Hospital Epidemiology.

While the most publicized concern over the overuse of antibiotics is the creation of resistant bacteria, it is far from being the only danger.  

 

Two years ago in The Other Reason Not To Abuse Antibiotics, we looked at the what happens to our beneficial intestinal bacteria (gut flora or microbiota) after we take a course of antibiotics, and how that might affect our health.

 

In recent years the the NIH sponsored Human Microbiome Project has spurred new research into these ubiquitous micro-organisms that reside not only in our intestines, but on our skin, in our nasal passages, oral cavities, gastrointestinal tract, and urogenital tract.

 

For all the good they do, antibiotics can indiscriminately kill off good bacteria along with the bad, and that can upset the bacterial balance in our gut.

 

When this happens, we often see the blooming of a nasty Gram-Positive bacteria called Clostridium Difficile – or C. diff – an infection which claims tens of thousands of lives each year.

 

And as the name implies, C. diff is most difficult to treat (see Referral: Maryn McKenna On Regulatory Obstacles To Fecal Transplants).

 

Today’s study, looks at the antibiotic history of patients at the Minneapolis Veterans Affairs Medical Center and found that not only are antibiotics often prescribed unnecessarily, their use substantially increased the patient’s chances of developing a C. diff infection.

 

First a link to the study, then some excerpts from the Press Release.

 

Unnecessary Antimicrobial Use in Patients with Current or Recent Clostridium difficile Infection (pp. 109-116) 

Megan K. Shaughnessy, MD; William H. Amundson, MD; Michael A. Kuskowski, PhD; Douglas D. DeCarolis, PharmD; James R. Johnson, MD; Dimitri M. Drekonja, MD, MS

DOI: 10.1086/669089

 

While the bulk of this article is behind a pay-wall, we get more details from the SHEA press release.

 

Society for Healthcare Epidemiology of America

Unnecessary antimicrobial use increases risk of recurrent infectious diarrhea

The impact of antibiotic misuse has far-reaching consequences in healthcare, including reduced efficacy of the drugs, increased prevalence of drug-resistant organisms, and increased risk of deadly infections. A new study featured in the February issue of Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America, found that many patients with Clostridium difficile infection (C. difficile) are prescribed unnecessary antibiotics, increasing their risk of recurrence of the deadly infection. The retrospective report shows that unnecessary antibiotics use is alarmingly common in this vulnerable patient population.

 

C. difficile is a bacteria that usually affects people with recent antibiotic use or hospitalization. The symptoms of C. difficile range from mild diarrhea to severe illness and death, and it is now one of the most common healthcare-associated infections. Patients with C. difficile often experience recurrent episodes of the infection, especially if they receive antibiotics again in the future.

 

Researchers at the Minneapolis Veterans Affairs Medical Center reviewed patient cases with new-onset C. difficile infection. In total, 57 percent (141) of patients with new-onset C. difficile infection received additional antimicrobials during or within 30 days after their initial C. difficile treatment, raising their risk of recurrence substantially. From this group, 77 percent received at least one dose of unnecessary antibiotic, and 26 percent of patients received unnecessary antibiotics exclusively. Common reasons noted for unnecessary antibiotic use included urinary tract infections and pneumonia (despite little-to-no evidence of either being present), inappropriate surgical prophylaxis, and asymptomatic bacteriuria.

 

"Our findings serve as a reminder to both doctors and patients to use antibiotics only when absolutely necessary, particularly in patients with a history of C. difficile," said lead researcher Megan K. Shaughnessy, MD. "Patients with C. difficile are at high-risk for recurrence, especially with additional antibiotic use. Because of this heightened risk, clinicians should be exercising increased caution with antimicrobial therapy."

 

The researchers advise that providers contemplating antimicrobial therapy should be more aware of the risk of recurrent C. difficile with antimicrobial use, patients' previous C. difficile history, and which clinical conditions require antimicrobial therapy.

 

Obviously, when you are faced with a serious bacterial infection, antibiotics are a prudent, even lifesaving form of treatment.

 

But we should not fool ourselves into believing that antibiotics are always benign, or that there are not potential consequences from taking them.

 

There is a risk-reward ratio for every drug we take.

 

For more on the importance of proper antibiotic stewardship, you may wish to revisit these earlier blogs.

 

Chan: World Faces A `Post-Antibiotic Era’

Get Smart About Antibiotics Week

IDSA: Educational Guidelines Lower Antibiotic Use

 

And for a far more complete (and eye-opening) discussion of antimicrobial resistance issues, I can think of no better primer than Maryn McKenna’s book SUPERBUG: The Fatal Menace of MRSA.

 

And Maryn’s SUPERBUG Blog, part of Wired Science Blogs, continues to provide the best day-to-day coverage of these issues.

The Flight Of The Bacterial Intruder

Credit CDC PHIL

 

 

# 6625

 

HCAIs (Health care associated Infections) or HAIs (Hospital acquired infections) constitute a major threat to life, health, and the cost of medical care in this country, and around the world. This oft quoted assessment from the CDC on the burden of Hospital Acquired Infections in the United States is from 2010.

 

A new report from CDC updates previous estimates of healthcare-associated infections. In American hospitals alone, healthcare-associated infections account for an estimated 1.7 million infections and 99,000 associated deaths each year. Of these infections:

• 32 percent of all healthcare-associated infection are urinary tract infections
• 22 percent are surgical site infections
• 15 percent are pneumonia (lung infections)
• 14 percent are bloodstream infections

 

A 2009 report The Direct Medical Costs of Healthcare-associated Infections in U.S. Hospitals and the Benefits of Prevention finds:

 

Applying two different Consumer Price Index
(CPI) adjustments to account for the rate of inflation in hospital resource prices, the overall annual direct medical costs of HAI to U.S. hospitals ranges from $28.4 to $33.8 billion (after adjusting to 2007 dollars using the CPI for all urban consumers) and $35.7 billion to $45 billion (after adjusting to 2007 dollars using the CPI for inpatient hospital services).

 

 

As you can imagine, hospitals are engaged in a perpetual battle against the spread of infection - and while progress is being made - many pathogens continue to slip past the infection control safeguards.

 

A study from the University of Leeds recently published in the Journal Building and Environment may provide a clue as to why the infection control measures being used today have failed to curb the spread of bacteria in the hospital setting.

 

 

Bioaerosol Deposition in Single and Two-Bed Hospital Rooms: A Numerical and Experimental Study

M.F. King, C.J. Noakes, P.A. Sleigh, M.A. Camargo-Valero

 

You’ll find the abstract, along with figures and tables from this article, at the link above. But the full paper is behind a pay wall. The University of Leeds website, however, has a synopsis of this research project, which is excerpted below:.

 

 

Superbugs ride air currents around hospital wards

Published Thursday 11th October 12

Hospital superbugs can float on air currents and contaminate surfaces far from infected patients’ beds, according to University of Leeds researchers.

 

The results of the study, which was funded by the Engineering and Physical Sciences Research Council (EPSRC), may explain why, despite strict cleaning regimes and hygiene controls, some hospitals still struggle to prevent bacteria moving from patient to patient.

 

It is already recognised that hospital superbugs, such as MRSA and C-difficile, can be spread through contact. Patients, visitors or even hospital staff can inadvertently touch surfaces contaminated with bacteria and then pass the infection on to others, resulting in a great stress in hospitals on keeping hands and surfaces clean.

 

But the University of Leeds research showed that coughing, sneezing or simply shaking the bedclothes can send superbugs into flight, allowing them to contaminate recently-cleaned surfaces.

 

PhD student Marco-Felipe King used a biological aerosol chamber, one of a handful in the world, to replicate conditions in one- and two-bedded hospital rooms. He released tiny aerosol droplets containing Staphyloccus aureus, a bacteria related to MRSA, from a heated mannequin simulating the heat emitted by a human body. He placed open Petri dishes where other patients’ beds, bedside tables, chairs and washbasins might be and then checked where the bacteria landed and grew.

 

The results confirmed that contamination can spread to surfaces across a ward. “The level of contamination immediately around the patient’s bed was high but you would expect that. Hospitals keep beds clean and disinfect the tables and surfaces next to beds,” said Dr Cath Noakes, from the University’s School of Civil Engineering, who supervised the work. “However, we also captured significant quantities of bacteria right across the room, up to 3.5 metres away and especially along the route of the airflows in the room.”

 

“We now need to find out whether this airborne dispersion is an important route of spreading infection,” added co-supervisor Dr Andy Sleigh.

(Continue . . .)

 

 

While we often think first of viruses when it comes to airborne transmission of illness, some types of bacteria (e.g. Legionella, Mycoplasma pneumonia, Tuberculosis) are easily aerosolized and transmitted.

 

This study is not the first to identify the airborne spread of Staphylococcus aureus, but they have developed an ingenious way to quantify it.

 

Regarding MRSA and C. Difficile the Journal of The Royal Society published a review in 2009 called:

 

Airborne transmission of disease in hospitals

I. Eames, J. W. Tang,Y. Li and P. Wilson

(EXCERPT)

MRSA can survive on surfaces or skin scales for up to 80 days and spores of Clostridium difficile may last even longer. MRSA can be transmitted in aerosol from the respiratory tract but commonly attaches to skin scales of various sizes. The distance of travel depends on the size of the scale, the larger falling to the floor within 1–2 m, the smaller travelling the entire length of the ward.

<SNIP>

Clostridium difficile spores are thought to spread in the air and can be found near a patient carrying the organism (Roberts et al. 2008). However, unlike MRSA, they are rarely isolated from air samples.

 

 

Not surprisingly, in 2010, we saw a study published in the AJIC: American Journal of Infection Control that found that the more roommates you have during a hospital stay, the greater chance you will have of contracting an HAI like MRSA or C. Diff.

 

Exposure to hospital roommates as a risk factor for health care–associated infection

Meghan Hamel, MSc, Dick Zoutman, MD, FRCPC, Chris O'Callaghan, DVM, MSc, PhD

 

The authors used this study to promote the idea  of making private (or at least, semi-private) rooms the norm in Canadian hospitals. While acknowledging that it would involve considerable up-front costs, they believe the long-term savings would be considerable.

 

All of this highlights the great challenges involved in substantially reducing the incidence of HAIs in our health care facilities.

 

Solutions must not only include stringent hand hygiene and improved cleaning methods, but engineering solutions as well.

 

For more on the prevention of Hospital Acquired Infections you may wish to visit the CDC’s HAI PAGE.

 

 

Or revisit some of these earlier blogs on hospital acquired infections.

 

HPA: Healthcare-Associated Infection (HCAI) Survey

A Barrier To Good Hand Hygiene

Study: Hospital Uniforms And Bacteria

Study: HAIs, Universal Surveillance, & MRSA

 

And finally, the subject of HAIs is often addressed by Maryn McKenna on her excellent Superbug Blog, and was a major focus of her book SUPERBUG: The Fatal Menace Of MRSA.

 

Both are highly recommended.

Referral: Maryn McKenna On Regulatory Obstacles To Fecal Transplants

 

 

 

# 5999

 

Maryn has a fascinating article this morning on her Superbug Blog on the regulatory obstacles that are hindering what appears to be a safe, cheap, and extremely effective cure for often intractable and devastating C. diff infections; Fecal Transplants.

 

First a link to Maryn’s article (which goes along with a series she is writing for Scientific American), and then I’ll return with a brief anecdote.

 

 

Fecal Transplants: They Work, the Regulations Don’t

• By Maryn McKenna December 9, 2011 

 

 

A little over 40 years ago (1970 to be precise), I read a book that had a profound effect on my future. It was Dr. William Nolen’s The Making of A Surgeon, which recounted his surgical internship at Bellevue Hospital during the 1950s.

 

It is what inspired me to become a paramedic.

 

One of the stories he relates in this book was of a patient in the surgical ward suffering from uncontrollable diarrhea due to what was likely C. diff, who was at genuine risk of dying.

 

Nolen and two other interns were at wit’s end, trying to treat this person, until one of them reasoned that if they could introduce good bacteria from a healthy patient into this patient's gut, they might effect a cure.

 

What followed next essentially involved chocolate milk, a `secret ingredient’, a lot of stirring, and no informed consent.

 

When their resident found out what they’d done, he went ballistic, and for a time all three interns thought their careers were ended.  They waited in fear for days for the patient to die from their ill advised treatment.

 

As it turned out, the `cure’ worked.

 

Although the delivery method (and donor screening) used by Nolen and his cohorts needed substantial upgrades, it is a bit amazing that 60 years later this technique hasn’t become routine.

 

While it is a bit dated, I highly recommend Dr. Nolen’s book to anyone who has an interest in the hectic, and often hilarious, learning curve of medical interns.

CMAJ: Hand Sanitizers May Be `Suboptimal’ For Preventing Norovirus

 

 

Photo Credit – CDC

 

# 5747

 

While dispensers of alcohol-based hand sanitizers have become ubiquitous in many health care facilities over the past few years, there remain serious questions over just how effective they may be in killing some particularly hearty pathogens.

 

In recent years it has become apparent that alcohol based hand cleansers are not effective at killing the spores of the Clostridium difficile bacteria, and so the CDC offers this advice:

 

How can Clostridium difficile infection be prevented in hospitals and other healthcare settings?

• Use gloves when entering patients’ rooms and during patient care.
• Perform Hand Hygiene after removing gloves.
• Because alcohol does not kill Clostridium difficile  spores, use of soap and water is more efficacious than alcohol-based hand rubs. However, early experimental data suggest that, even using soap and water, the removal of C. diffile spores is more challenging than the removal or inactivation of other common pathogens.
• Preventing contamination of the hands via glove use remains the cornerstone for preventing Clostridium difficile transmission via the hands of healthcare workers; any theoretical benefit from instituting soap and water must be balanced against the potential for decreased compliance resulting from a more complex hand hygiene message.

 

And more recently, we’ve seen increased evidence that these handy hand sanitizers may be `suboptimal’ at killing some nonenveloped viruses (including norovirus), as well.

 

In March of this year, the CDC’s MMWR published a lengthy report that called into question the efficacy of alcohol based products against norovirus:

 

Updated Norovirus Outbreak Management and Disease Prevention Guidelines

(Excerpt)

Overall, studies suggest that proper hand washing with soap and running water for at least 20 seconds is the most effective way to reduce norovirus contamination on the hands, whereas hand sanitizers might serve as an effective adjunct in between proper handwashings but should not be considered a substitute for soap and water handwashing.

 

Today, the CMAJ has an early release news item that summarizes the findings of a couple of recent studies that showed that health care facilities that relied more heavily on alcohol-based sanitizers were more apt to experience outbreaks of norovirus.

 

 

Hand sanitizers may increase norovirus risk

August 10, 2011

 

Alcohol-based hand sanitizers may not be the panacea for hand hygiene they were once supposed, as mounting research indicates they may not be effective substitutes for soap and water, and in some cases may actually increase the risk for outbreaks of highly contagious viruses in health care settings.

 

Public health experts, however, say more rigorous investigations will be necessary to trump the convenience of using hand sanitizers, among other benefits, or substantially alter existing recommendations that strongly encourage their use by health care professionals.

(Continue . . . )

 

You can read the abstract to one of these studies in the May 2011 edition of the  AJIC.

 

Use of alcohol-based hand sanitizers as a risk factor for norovirus outbreaks in long-term care facilities in northern New England: December 2006 to March 2007

 

David D. Blaney, MD, MPH , Elizabeth R. Daly, MPH , Kathryn B. Kirkland, MD ,Jon Eric Tongren, PhD, MSPH , Patsy Tassler Kelso, PhD , Elizabeth A. Talbot, MD

 

Lead author Dr. David Blaney of CDC’s  Epidemic Intelligence Service is quoted in the CMAJ article as saying that alcohol-based hand sanitizers might be, “suboptimal in controlling the spread of noroviruses.”

 

For now, the efficacy of alcohol based hand sanitizers against norovirus remains controversial at best. More, and better studies will be needed before any firm conclusions can be drawn.

 

None of this is to suggest that hand sanitizers are without value.

 

They are fast and easy - which promotes their frequent use - and when used properly they appear effective against a wide variety of bacteria and enveloped viruses, including colds and influenzas.

 

 

But when dealing with a norovirus outbreak, for now the best policy appears to be washing your hands thoroughly with soap and water.

IDSA: Educational Guidelines Lower Antibiotic Use

 

 

 

Photo Credit – CDC

 

# 5715

 

From the IDSA (Infectious Diseases Society of America) today, a major report on the reduction in outpatient antibiotic use in Quebec since an educational campaign, directed primarily at pharmacists and physicians, was begun in 2005.

 

On a per capita basis, outpatient use of antibiotics has declined by 4.2% in Quebec, while increasing by 6.5% across the rest of Canada.

 

The latest version of these guidelines are available at the Le conseil du médicament website.

 

 

 

This study appears in today’s online edition of Clinical Infectious Diseases. The press release (below) provides details.

 

Simple guidelines decreased unnecessary antibiotic use in Quebec, Canada

Infectious Diseases Society of America

[EMBARGOED FOR JULY 26, 2011] Antibiotic overuse and resistance have emerged as major threats during the past two decades. Following an outbreak of Clostridium difficile infections, which often result from antibiotic use, health care professionals in Quebec, Canada targeted physicians and pharmacists with an education campaign that reduced outpatient antibiotic use, according to a study published in Clinical Infectious Diseases and now available online.

 

The Quebec Minister of Health and the Quebec Medication Council collaborated with designated physicians and pharmacists to develop guidelines to improve prescribing practices. First issued in January 2005, the guidelines emphasized proper antibiotic use, including not prescribing antibiotics when viral infections were suspected and selecting the shortest possible duration of treatment. Approximately 30,000 printed copies of the original recommendations were distributed to all physicians and pharmacists in Quebec. An additional 193,500 copies were downloaded from the Medication Council's website. (The current versions of the guidelines are available online: LINK.)

 

During the year after the guidelines were initially distributed, the number of outpatient antibiotic prescriptions in Quebec decreased 4.2 percent. In other Canadian provinces, the number of these prescriptions increased 6.5 percent during the same period.

 

According to study author Karl Weiss, MD, of the University of Montreal, "It is possible to decrease antibiotic consumption when physicians, pharmacists, state governments, etc., are working together for a common goal. This is the key to success: having everybody involved and speaking with a common voice."

 

Dr. Weiss added, "Simple, short, easy-to-use guidelines have an impact on physicians when they are readily available. The web is an increasingly important tool to reach our audience and should now be used as such in the future. With handheld electronic devices available for all health care professionals, these downloadable guidelines can be accessed and used at any time and any circumstance."

 

The paper may be accessed at the following link.

 

Impact of a Multipronged Education Strategy on Antibiotic Prescribing in Quebec, Canada

Karl Weiss, Re´gis Blais, Anne Fortin,  Sonia Lantin, and Michel Gaudet

Department of Infectious Diseases and Microbiology, Faculty of Medicine, University of Montreal, Montreal, Canada;Department of Health Administration, Faculty of Medicine, University of Montreal, Montreal, Canada; and Conseil du Me´dicament du Que´bec, INESSS, Que´bec City,Canada

The Other Reason Not To Abuse Antibiotics

 

 

 

# 5506

 

 

We hear a lot about the dangers of overusing, or misusing antibiotics; primarily concerns over the rise of antibiotic resistant bacteria.

 

 

 

This year’s World Health Day focused on antimicrobial resistance (see WHO Unveils 6-Point Plan To Preserve Antibiotic Effectiveness and World Health Day 2011), and a day hardly goes by when we don’t hear about the dangers of drug resistant staph, MRSA, NDM-1, or other Carbapenemases.

 

Each year tens of thousands of people succumb to resistant bacteria, and many researchers fear the day may be coming when our arsenal of antibiotics will be rendered useless.

 

Yet despite these dire warnings most people still expect their doctors to prescribe a course of antibiotics – even for viral illnesses which they won’t cure – because, well . . .  it couldn’t hurt.   Right?

 

Wrong.

 

Antibiotics, like any other medicine, are double-edged swords.  They save lives, and have rightfully been called miracle drugs, but they can also cause serious side effects.

Some are well known, such as anaphylaxis (a serious, often life threatening allergic reaction).  Others, like antibiotic-associated (C. difficile) colitis are probably less well appreciated by the public, despite the terrible toll this condition takes each year.

While C. diff can occasionally occur in people not on antibiotics, most of the 3 million Americans who fall victim every year are taking `miracle’ drugs like ampicillin, amoxicillin, cephalosporins, penicillin, and erythromycin.

 

And C. diff infection is associated with nearly 30,000 deaths each year in the United States alone.

 

But even less well known, and frankly, just now beginning to be explored, is what happens to our beneficial intestinal bacteria (gut flora or microbiota) after we take a course of antibiotics, and how that might affect our health.

 

Our intestines are home to thousands of different types of flora, including bacteria, yeasts, and protozoa.  

 

While we don’t know all of the ways these microbiota contribute to human health, they are known to aid digestion and breakdown certain nutrients, to help produce various types of vitamins, and to have some role in our immune system.

 

And when you take antibiotics – even short courses – you can alter the normal ratio of these beneficial flora, and the evidence is growing that doing so can adversely affect your health.

 

Last year, Les Dethlefsen and David A. Relman, both researchers at the Department of Microbiology and Immunology and Department of Medicine, Stanford University School of Medicine, published a report in PNAS that looked at the adverse effects of antibiotics on gut flora.

 

Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation

 

While a limited study, these researchers examined the distal gut microbiota of three individuals over 10 months during which they received two courses of the antibiotic ciprofloxacin.  

 

Their primary findings (from the abstract):

 

• The effect of ciprofloxacin on the gut microbiota was profound and rapid, with a loss of diversity and a shift in community composition occurring within 3–4 d of drug initiation. By 1 wk after the end of each course, communities began to return to their initial state, but the return was often incomplete.

• Antibiotic perturbation may cause a shift to an alternative stable state, the full consequences of which remain unknown.

 

 

In November of 2010, Jernberg C, Löfmark S, Edlund C, Jansson JK. of the Department of Bacteriology, Swedish Institute for Infectious Disease Control published in the Journal Microbiology.

 

Microbiology. 2010 Nov;156(Pt 11):3216-23. Epub 2010 Aug 12.

Long-term impacts of antibiotic exposure on the human intestinal microbiota

Although it is known that antibiotics have short-term impacts on the human microbiome, recent evidence demonstrates that some impacts remain for extended periods of time. In addition, antibiotic resistant strains can persist in the human host environment in the absence of selective pressure.

 

Both molecular-based and cultivation-based approaches have revealed ecological disturbances in the microbiota after antibiotic administration; in particular for specific members of the bacterial community that are susceptible or alternatively resistant to the antibiotic in question.

 

A disturbing consequence of antibiotic treatment has been the long-term persistence of antibiotic resistance genes, for example in the human gut. These data warrant use of prudence in the administration of antibiotics that could aggravate the growing battle with emerging antibiotic resistant pathogenic strains.

 

 

All of which serves as prelude to a new study, just published in the journal Antimicrobial Agents and Chemotherapy.

 

0066-4804/11/$12.00+0     doi:10.1128/AAC.01664-10

Effect of Antibiotic Treatment on the Intestinal Metabolome

L. Caetano M. Antunes, Jun Han, Rosana B. R. Ferreira, Petra Loli, Christoph H. Borchers, and B. Brett Finlay

 

 

For details we turn to the press release from the American Society for Microbiology.

 

Antibiotics Disrupt Gut Ecology, Metabolism

Humans carry several pounds of microbes in our gastro-intestinal tracts. Recent research suggests that this microbial ecosystem plays a variety of critical roles in our health. Now, working in a mouse model, researchers from Canada describe many of the interactions between the intestinal microbiota and host, and show that antibiotics profoundly disrupt intestinal homeostasis. The research is published in the April 2011 issue of the journal Antimicrobial Agents and Chemotherapy.

"Intestinal microbes help us digest our food, provide us with vitamins that we cannot make on our own, and protect us from microbes that make us sick, amongst other things," says L Caetano M. Antunes of the University of British Columbia, a researcher on the study. In this study, the investigators used powerful mass spectrometry techniques to detect, identify, and quantify more than two thousand molecules which they extracted from mouse feces. They then administered antibiotics to the mice, to kill off most of their gut microbiota, and analyzed the feces anew.

The second round of mass spectroscopy revealed a very different metabolic landscape. The levels of 87 percent of the molecules detected had been shifted up or down by factors ranging from 2-fold to 10,000-fold.

The most profoundly altered pathways involved steroid hormones, eicosanoid hormones, sugar, fatty acid, and bile acid. "These hormones have very important functions in our health," says Antunes. "They control our immune system, reproductive functions, mineral balance, sugar metabolism, and many other important aspects of human metabolism."

The findings have two important implications, says Antunes. "First, our work shows that the unnecessary use of antibiotics has deleterious effects on human health that were previously unappreciated. Also, the fact that our gut microbes control these important molecules raises the possibility that manipulating these microbes could be used to modulate diseases that have hormonal or metabolic origins (such as inmmunodeficiency, depression, diabetes and others). However, further studies will be required to understand exactly how our microbial partners function to modulate human physiology, and to devise ways of using this information to improve human health."

(L.C.M. Antunes, J. Han, R.B.R. Ferreira, P. Lolic, C.H. Borchers, and B.B. Finlay, 2011. Effect of antibiotic treatment on the intestinal metabolome. Antim. Agents Chemother. 55:1494-1503.)

 

 

While research results obtained from mice cannot always be depended upon to translate directly to human physiology, there is a growing body of evidence linking adverse (perhaps even long-term) health effects to the use of antibiotics.

 

Obviously, when you are faced with a serious bacterial infection, antibiotics are a prudent, even lifesaving form of treatment.

 

But we should not fool ourselves into believing that antibiotics are always benign, or that there are not potential consequences from taking them.

 

There is a risk-reward ratio for every drug we take.

 

Even aspirin and NSAIDs – sold over the counter – contribute to thousands of hospitalizations and deaths each year.

 

Which is why taking medicines – any medicine – without a good reason can come back and bite you. 

 

We are just now beginning to appreciate the potential side effects of antibiotic usage. Five years from now, hopefully, we’ll know a lot more.

 

But the evidence continues to mount that taking antibiotics inappropriately is an exceedingly bad idea.

 

Not only for the community around us, but for the community inside us, as well.

Referral: McKenna On C. Diff

 

 

# 4963

 

 

While I’ve been immersed in writing two earlier blogs this morning, our favorite `scary disease girl’ Maryn McKenna has served up a terrific piece on Clostridium difficile – or C. Diff as it is commonly called – as a potential food borne illness.

 

I’ll simply step out of the way, suggest you skip breakfast, and direct you to:

 

C. diff: Blame hospitals? Or food?

• By Maryn McKenna