New study reveals how MRSA infection can permanently harm immune function

Methicillin-resistant Staphylococcus aureus bacteria (yellow) and a dead human white blood cell.

Infections of the skin or other soft tissues by the hard-to-treat MRSA (methicillin-resistant Staphylococcus aureus) bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function.

“MRSA-induced impairment persisted long after the infection was resolved and the inflammation had stopped” – Timothy Padera

In a report published online in Science Translational Medicine, Harvard Medical School investigators based at Massachusetts General Hospital describe findings that MRSA infection impairs the ability of lymphatic vessels to pump lymphatic fluid to lymph nodes in mouse models, which may contribute to the frequent recurrences of MRSA infection experienced by patients.

“We found that MRSA produces toxins that kill the muscle cells critical to the pumping of lymph,” said senior study author Timothy Padera, HMS associate professor of radiation oncology at Mass General.

“MRSA with a genetic deficiency that lowers the amount of toxin produced does not kill lymphatic muscle cells, which both supports the role for bacterial toxins in the post-MRSA impairment of lymphatic function and may also suggest a possible treatment strategy,” he added.

Serious skin infections called cellulitis are reported in about 14 million U.S. patients annually, with as many as 30 percent caused by MRSA. Serious cases requiring intravenous antibiotics lead to 500,000 hospitalizations each year, and 50,000 of those patients will have recurrent infections that require hospital readmission within a month.

Patients with lymphedema—swelling and fluid buildup caused by damage to or blockage of the lymphatic system—are particularly prone to recurrent infections, which can exacerbate existing lymphedema. But until now, no studies have investigated the potential interactions between bacterial infections and lymphatic function.

In contrast to the cardiovascular system, in which blood is propelled through arteries and veins by the pumping of the heart, in the lymphatic system, lymphatic fluid—which carries immune cells and other important factors—is pumped along by the contraction of the lymphatic vessels, driven by lymphatic muscle cells.

Persistent Impairment

Experiments in mouse models of MRSA tissue infections revealed that the infection itself cleared within 30 days and associated inflammation was gone within 60 days. But the lymphatic vessels in MRSA-infected tissues showed abnormalities, including increased vessel diameter and weaker, less frequent contractions, that were still present 120 days after the induction of infection.

Close examination revealed that the number of lymphatic muscle cells surrounding lymphatic vessels was depleted as late as 260 days after infection.

“We had assumed that we would find results similar to our previous measures of impaired lymphatic function in inflammation that was not associated with an infection,” Padera said. “But while lymph pumping was restored after the resolution of sterile inflammation, MRSA-induced impairment persisted long after the infection was resolved and the inflammation had stopped.”

“This persistence long after bacteria have been cleared can be explained by the loss of lymphatic muscle cells,” he said.

Exposure of cultured mouse and human lymphatic or smooth muscle cells to the proteins produced by MRSA led to the death of these cells, and detailed analysis of MRSA-produced proteins identified a significant number of known pathogenic toxins.

Since expression of many MRSA toxins is controlled by a genetic element called the accessory gene regulator (agr), the team tested a mutant form of MRSA lacking the agr against several types of cultured cells and in their animal model.

The agr-mutant MRSA did not produce the muscle cell-killing proteins, and lymphatic function—including the strength and frequency of vessel contraction—was significantly better in mice infected with the mutant strain than in animals infected with a nonmutated strain.

“Our results strongly suggest that targeting the action of the agr during and after MRSA infection may preserve lymphatic muscle cells and, as a result, lymphatic function,” Padera said. “Now we need to confirm whether MRSA infection leads to impaired lymphatic function in humans and identify the specific MRSA toxins that cause the death of lymphatic muscle cells.”

Rapid Antibiotic Testing Comes of Age


Phoenix—In recent years, there has been an explosion of FDA-approved rapid diagnostic testing methodologies for infectious diseases. During an education session at the 2017 annual meeting of the American College of Clinical Pharmacy, pharmacists discussed some of the excitement surrounding the recent advances in treating the most worrisome bugs.

“Rapid diagnostic tests represents one of the few bright spots in the changing world of escalating antimicrobial resistance and stewardship,” said Katherine Perez, PharmD, BCPS-AQ ID, an infectious disease clinical specialist at Houston Methodist.

Dr. Perez pointed out that rapid identification of microorganisms and resistance is critical for targeted treatment in serious infections caused by multidrug-resistant gram-negative bacteria (GNB). Research efforts have focused on pathogens associated with increased morbidity, mortality and excessive health care costs, including influenza virus, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus species, Clostridium difficile, extended-spectrum beta-lactamase (ESBL)-producing Klebsiella species, carbapenemases, Mycobacterium tuberculosis and Candida species.


Current conventional culture-based methods to isolate and identify a pathogen, followed by susceptibility testing, can take 72 hours or more. This is concerning, Dr. Perez noted, because delaying administration of appropriate antimicrobials is associated with increased mortality rates for patients with gram-negative septicemia and septic shock (Clin Infect Dis 2013;57:S139-S170). Having the ability to detect the presence of resistant bacteria in a clinical sample in less than one hour, Dr. Perez noted, helps improve the effectiveness of antimicrobial stewardship programs.

In an ideal world, antimicrobial treatment would be prompt; appropriate; administered at an adequate dose and interval, guided by pharmacokinetic/pharmacodynamic principles; and discontinued appropriately, based on clinical response and microbiological data. All of this, Dr. Perez noted, is contingent on accurately determining a pathogen’s identification and antimicrobial susceptibility.

Various Methodologies

Emerging rapid detection methods of pathogens include a variety of technologies that vary greatly in complexity, price, speed and ability to identify single or multiple pathogens. Dr. Perez highlighted a number of rapid infectious disease diagnostics using different methodologies, including the polymerase chain reaction (PCR)-based FilmArray Blood Culture Identification panel (BioFire Diagnostics LLC). The panel tests for 24 pathogens and three antibiotic resistance genes associated with bloodstream infections. The test can accurately identify pathogens in more than nine of 10 positive blood cultures in about an hour, with only two minutes of hands-on time, she said (J Clin Microbiol 2016;54:687-698).


The advantages of PCR-based testing, she noted, include rapid results, low detection limits, specific organism detection and subtyping, not requiring growth on media, high throughput and, generally, short hands-on time for laboratory staff. Disadvantages include susceptibility to contamination, the need for dedicated laboratory space for instruments, and dependence on quality of products used, and most require initiation from positive cultures/single colonies. PCR cannot indicate viability of the pathogen detected and comes with practical limitations that can affect turnaround time.

Targeting Worrisome Bugs

Ryan Shields, PharmD, MS, associate professor of medicine in the Division of Infectious Diseases at the University of Pittsburgh, said carbapenem-resistant bugs top the list of most worrisome bugs. Carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae (CRE) are listed as critical priorities for research and development of new antibiotics by the World Health Organization. The CDC lists multidrug-resistant A. baumannii and P. aeruginosa as serious threats, and CRE as an urgent threat.


Carbapenem-resistant pathogens, Dr. Shields said, are associated with loss of our last line of defense against resistant pathogens and cross-resistance to other antibiotic classes. They are also associated with increased lengths of stay, health care expenditures and increased mortality rates among patients. “Carbapenem resistance is a major threat to public health,” he said.

A recent study concluded that antibiotic stewardship and infection prevention and control have been unable to prevent the rapid spread of resistant GNB, particularly carbapenem-resistant P. aeruginosa and other nonfermenting GNB, ESBL-producing and CRE (Intensive Care Med 2017 Jul 21. [Epub ahead of print]). Carbapenem-resistant Klebsiella pneumoniae, Dr. Perez said, is an emerging nosocomial pathogen associated with considerable mortality.

Rapid tests should detect all carbapenem-resistant organisms and distinguish carbapenemase-producing organisms from isolates that are resistant to carbapenems because of other mechanisms, Dr. Perez noted. The organisms have diverse enzyme types and considerable variation in levels of phenotypic carbapenem resistance (e.g., minimum inhibitory concentration evaluation). Non–carbapenemase-mediated carbapenem resistance complicates things.

The Rapidec Carba NP biochemical test (bioMérieux) detects any type of carbapenemase activity by monitoring the color change of a pH indicator according to hydrolysis of the substrate, imipenem. The tests are rapid, easy to read and handle, and cost-effective, and have a turnaround time of approximately one hour. They can be used for first-line screening in the absence of molecular typing, Dr. Perez said.

Table. Integrating Rapid Diagnostics Into Practice
Beta-Lactamase Bacteria Recommended Therapy
CTX-M (ESBL) Enterobacteriaceae Ertapenem (Invanz, Merck)
KPC Klebsiella pneumoniae and other enteric gram-negative organisms Colistin + tigecycline/aminoglycoside/carbapenem; ceftazidime-avibactam (Avycaz, Allergan)
NDM carbapenemases K. pneumoniae and other enteric gram-negative organisms Colistin + tigecycline; aztreonam (Azactam, Bristol-Myers Squibb) + ceftazidime-avibactam
VIM or IMP carbapenemase Pseudomonas aeruginosa Colistin + aztreonam/aminoglycoside/tigecycline
OXA beta-lactamases P. aeruginosa Colistin + high-dose carbapenem
Acinetobacter baumannii Colistin + minocycline; high-dose carbapenem
ESBL, extended-spectrum beta-lactamase Source: Katherine Perez, PharmD, BCPS-AQ ID.

Integrating Into Practice

Dr. Perez noted that the Infectious Diseases Society of America, CDC and National Quality Forum have recognized the emerging role of rapid diagnostics and biomarkers in antimicrobial stewardship programs. Molecular biology and testing can be used to improve antimicrobial stewardship interventions, assist in anti-infective escalation and de-escalation efforts, and improve clinical outcomes.

Implementation of rapid diagnostic tests may be cost-neutral or even constitute a cost savings when stewardship efforts streamline care. “Rapid diagnostic tests can reduce total hospital costs by decreasing length of stay,” Dr. Perez said.

Multiple stakeholders, including infectious disease physicians, microbiologists and laboratory pharmacists, need to create guidance for clinicians up front regarding the use of rapid infectious disease diagnostics, Dr. Perez noted. “There is a need to connect the dots among antimicrobial stewardship, rapid diagnostics and improved outcomes to make this case,” she said. “Who gets notified when an organism and a resistance marker are identified by rapid diagnostics?”

Providing Guidance

Stewardship pharmacists can provide guidance to clinicians to positively affect patient care. Some stewardship programs use automated alerts for positive blood cultures coupled with antimicrobial stewardship interventions, to ensure that a patient is prescribed effective antibiotics sooner, Dr. Perez said. Selective antibiogram reports for blood culture isolates are helpful for driving empirical choices and may be useful particularly for multidrug-resistant organisms.

“Advances in testing provide new opportunities for stewardship programs to streamline care for patients with serious infections,” she added. “Rapid diagnostic tests are game-changing for patient care moving forward.”

A CenturiesOld Chinese Herbal Medicine Could Help Us to Fight TB

As science struggles to find new chemicals to address old afflictions, one more time an ancient — and wholly natural — remedy may be the answer, in this case with fighting tuberculosis (TB), according to Science Alert. It turns out that a compound called arteminsinin, which comes from a form of wormwood, not only treats malaria, but antibiotic-resistant TB bacteria.



While the research is ongoing, it adds to the growing body of evidence that Mother Nature more often than not has the solution to common illnesses. Antibiotics are a foundational component of modern medicine, without which many of our current treatment modalities and medical procedures become exceedingly dangerous. But overuse of antibiotics has made them increasingly ineffective against serious infections.

This antibiotic-resistance has turned into a worldwide health threat of massive proportions that kills tens of thousands every year. One infection, Methicillin resistant Staphylococcus aureus (MRSA), kills more Americans each year than the combined total of emphysema, HIV/AIDS, Parkinson’s disease, and homicide. Solutions for this include improved infection prevention, more responsible use of antibiotics in human medicine, limiting use of antibiotics in agriculture, and finding innovative approaches to treat infections.

But in the wake of this crisis, a good thing has emerged: the re-discovery of natural infection-fighting methods. From garlic to cinnamon to probiotics and fermented foods, to sunlight and Manuka honey, there are positive things in nature that are turning out to be good combatants for fighting infections.

Manuka honey has even been shown to be more effective than antibiotics in the treatment of more than 250 clinical strains of bacteria as well as serious, hard-to-heal, antibiotic-resistant skin infections, including MRSA.

Antibiotics for All but Very Mild C difficile.

On October 29, the European Society of Clinical Microbiology and Infection (ESCMID) issued updated guidelines for Clostridium difficile infection (CDI), reviewing treatment options of antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, and fecal or bacterial intestinal transplantation. The new recommendations, published online October 5 in Clinical Microbiology and Infection, advise antibiotic treatment for all but very mild cases of CDI.

CDI, which is potentially fatal, is now the leading cause of healthcare-acquired infections in hospitals, having surpassed methicillin-resistant Staphylococcus aureus.

“[A]fter the recent development of new alternative drugs for the treatment of CDI (e.g. fidaxomicin) in US and Europe, there has been an increasing need for an update on the comparative effectiveness of the currently available antibiotic agents in the treatment of CDI, thereby providing evidence-based recommendations on this issue,” write Sylvia B. Debast, from the Centre for Infectious Diseases, Leiden University Medical Center The Netherlands, and colleagues from the ESCMID Committee.

The new guideline, which updates the 2009 ESCMID recommendations now used widely in clinical practice, summarizes currently available CDI treatment options and offers updated treatment recommendations on the basis of a literature search of randomized and nonrandomized trials.

The ESCMID and an international team of experts from 11 European countries developed recommendations for different patient subgroups, including initial nonsevere disease, severe CDI, first recurrence or risk for recurrent disease, multiple recurrences, and treatment of CDI when patients cannot receive oral antibiotics.

Antibiotic Recommended in Most Cases

Specific recommendations include the following:

·         For nonepidemic, nonsevere CDI clearly induced by antibiotic use, with no signs of severe colitis, it may be acceptable to stop the inducing antibiotic and observe the clinical response for 48 hours. However, patients must be monitored very closely and treated immediately for any signs of clinical deterioration.

·         Antibiotic treatment is recommended for all cases of CDI except for very mild CDI, which is actually triggered by antibiotic use. Suitable antibiotics include metronidazole, vancomycin, and fidaxomicin, a newer antibiotic that can be given by mouth.

·         For mild/moderate disease, metronidazole is recommended as oral antibiotic treatment of initial CDI (500 mg 3 times daily for 10 days).

·         Fidaxomicin may be used in all CDI patients for whom oral antibiotic treatment is appropriate. Specific indications for fidaxomicin may include first-line treatment in patients with first CDI recurrence or at risk for recurrent disease, in patients with multiple recurrences of CDI, and in patients with severe disease and nonsevere CDI.

These recommendations were based on 2 large phase 3 clinical studies that compared 400 mg/day oral fidaxomicin with 500 mg/day oral vancomycin, the standard of care. The rate of CDI recurrence was lower with fidaxomicin, but the cure rate was similar for both treatments.

·         For severe CDI, suitable oral antibiotic regimens are vancomycin 125 mg 4 times daily (may be increased to 500 mg 4 times daily) for 10 days, or fidaxomicin 200 mg twice daily for 10 days.

·         In life-threatening CDI, there is no evidence supporting the use of fidaxomicin.

·         In severe CDI or life-threatening disease, the use of oral metronidazole is strongly discouraged.

·         For multiple recurrent CDI, fecal transplantation is strongly recommended.

·         Total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended for CDI with colonic perforation and/or systemic inflammation and deteriorating clinical condition despite antibiotic treatment.

·         Additional measures for CDI management include discontinuing unnecessary antimicrobial therapy, adequate fluid and electrolyte replacement, avoiding antimotility medications, and reviewing proton pump inhibitor use.

‘We’ve reached the end of antibiotics’

‘We’ve reached the end of antibiotics‘: Top CDC expert declares that ‘miracle drugs’ that have saved millions are no match against ‘superbugs’ because people have overmedicated themselves

A high-ranking official with the Centers for Disease Control and Prevention has declared in an interview with PBS that the age of antibiotics has come to an end.

‘For a long time, there have been newspaper stories and covers of magazines that talked about “The end of antibiotics, question mark?”‘ said Dr Arjun Srinivasan. ‘Well, now I would say you can change the title to “The end of antibiotics, period.”’

Nightmare superbug: Srinivasan said that about 10 years ago, he began seeing outbreaks of different kinds of MRSA infections, which previously had been limited to hospitals, in schools and gyms

The associate director of the CDC sat down with Frontline over the summer for a lengthy interview about the growing problem of antibacterial resistance.

Srinivasan, who is also featured in a Frontline report called ‘Hunting the Nightmare Bacteria,’ which aired Tuesday, said that both humans and livestock have been overmedicated to such a degree that bacteria are now resistant to antibiotics.

‘We’re in the post-antibiotic era,’ he said. ‘There are patients for whom we have no therapy, and we are literally in a position of having a patient in a bed who has an infection, something that five years ago even we could have treated, but now we can’t.’.

Dr Srinivasan offered an example of this notion, citing the recent case of three Tampa Bay Buccaneers players who made headlines after reportedly contracting potentially deadly MRSA infections, which until recently were largely restricted to hospitals.

About 10 years ago, however, the CDC official began seeing outbreaks of different kinds of MRSA infections in schools and gyms.

‘In hospitals, when you see MRSA infections, you oftentimes see that in patients who have a catheter in their blood, and that creates an opportunity for MRSA to get into their bloodstream,’ he said.

Nightmare superbug: Srinivasan said that about 10 years ago, he began seeing outbreaks of different kinds of MRSA infections, which previously had been limited to hospitals, in schools and gyms

‘In the community, it was causing a very different type of infection. It was causing a lot of very, very serious and painful infections of the skin, which was completely different from what we would see in health care.’

With bacteria constantly evolving and developing resistance to conventional antibiotics, doctors have been forced to ‘reach back into the archives’ and ‘dust off’ older, more dangerous cures like colistin.

‘It’s very toxic,’ said Srinivasan. ‘We don’t like to use it. It damages the kidneys. But we’re forced to use it in a lot of instances.’

The expert went on, saying that the discovery of antibiotics in 1928 by Professor Alexander Fleming revolutionized medicine, allowing doctors to treat hundreds of millions of people suffering from illnesses that had been considered terminal for centuries.


Antibiotics also paved the way for successful organ transplants, chemotherapy, stem cell and bone marrow transplantations – all the procedures that weaken the immune system and make the body susceptible to infections.

However, the CDC director explained that people have fueled the fire of bacterial resistance through rampant overuse and misuse of antibiotics.

‘These drugs are miracle drugs, these antibiotics that we have, but we haven’t taken good care of them over the 50 years that we’ve had them,’ he told Frontline.

Srinivasan added that pharmaceutical companies are at least partially to blame for this problem, saying that they have neglected the development of new and more sophisticated antibiotics that could keep up with bacterial resistance because ‘there’s not much money to be made’ in this field.

CDC Reveals Disturbing Truth about Factory Farms and Superbugs..

Story at-a-glance

  • Agricultural usage accounts for about 80 percent of all antibiotic use in the US, so it’s a MAJOR source of human antibiotic consumption
  • According to a new CDC report, antibiotics used in livestock plays a role in antibiotic resistance and “should be phased out”; 22 percent of antibiotic-resistant illness in humans is in fact linked to food
  • MRSA infection has been rapidly increasing among people outside hospital settings as well. Increasing evidence points to factory-scale hog facilities as a source
  • Previous research suggests you have a 50/50 chance of buying meat tainted with drug-resistant bacteria when you buy meat from your local grocery store
  • Excessive exposure to antibiotics—which includes regularly eating antibiotic-laced CAFO meats—also takes a heavy toll on your gastrointestinal health. This in turn can predispose you to virtually any disease.
  • Antibiotics

According to the European Centre for Disease Prevention and Control (ECDC), antibiotic resistance is a major threat to public health worldwide, and the primary cause for this man-made epidemic is the widespread misuse of antibiotics.1

Antibiotic overuse occurs not just in medicine, but also in food production. In fact, agricultural usage accounts for about 80 percent of all antibiotic use in the US,2 so it’s a MAJOR source of human antibiotic consumption.

According to a 2009 report3 by the US Food and Drug Administration (FDA) on this subject, factory farms used a whopping 29 million pounds of antibiotics that year alone.

Animals are often fed antibiotics at low doses for disease prevention and growth promotion, and those antibiotics are transferred to you via meat, and even through the animal manure that is used as crop fertilizer.

Antibiotics are also used to compensate for the crowded, unsanitary living conditions associated with large-scale confined animal feeding operations (CAFOs).

CDC Confirms Link Between CAFOs and Superbugs

Now, the US Center for Disease Control and Prevention4 (CDC) has finally come out saying that yes, antibiotics used in livestock plays a role in antibiotic resistance and “should be phased out.” According to the CDC’s report,5 22 percent of antibiotic-resistant illness in humans is in fact linked to food. As reported by the featured article:6

“The Center for Science in the Public Interest (CSPI) said that the report shows that drug-resistant hazards in the food supply pose a serious threat to public health. One-third of the 12 resistant pathogens that CDC categorized as a ‘serious’ threat to public health are found in food.”

The four drug-resistant pathogens in question are Campylobacter, which causes an estimated 310,000 infections and 28 deaths per year; Salmonella, responsible for another 100,000 infections and 38 deaths annually; along with E.coli and Shigella. To address this growing problem, the CDC’s report issues the following recommendations:

  • Avoid inappropriate antibiotic use in food animals
  • Track antibiotic use in food animals
  • Stop spread of Campylobacter among animals on farms
  • Improve food production and processing to reduce contamination
  • Educate consumers and food workers about safe food handling practices

Source:, Antibiotic Resistance Threats in the United States, 2013

MRSA Spreading Via Hog Farms?

Two drug-resistant pathogens more commonly associated with antibiotic overuse in human medicine include Clostridium difficile and Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus (MRSA) infects more than 80,460 people and kills 11,285 people annually. Disturbingly, as discussed in a recent Mother Jones7 article, MRSA infection has been rapidly increasing among people outside hospital settings as well.

As stated in the article:

“Increasing evidence points to factory-scale hog facilities as a source. In a recent study,8 a team of researchers led by University of Iowa’s Tara Smith found MRSA in 8.5 percent of pigs on conventional farms and no pigs on antibiotic-free farms. Meanwhile, a study9, 10 just released by the journal JAMA Internal Medicine found that people who live near hog farms or places where hog manure is applied as fertilizer have a much greater risk of contracting MRSA.”

In the latter study, people with the highest exposure to manure were 38 percent more likely to contract community-associated MRSA, and 30 percent more likely to get healthcare-associated MRSA. Level of exposure was calculated based on proximity to hog farms, the size of the farms, and how much manure the farm in question used. 

Back in 2009 a University of Iowa study11 found that a full 70 percent of hogs and 64 percent of workers in industrial animal confinements tested positive for antibiotic-resistant MRSA. The study pointed out that, once MRSA is introduced, it could spread broadly to other swine and their caretakers, as well as to their families and friends.

In other parts of the world, such as the European Union, the use of antibiotics as growth promoters in animal feed has been banned for years. Yet in the US this is still a topic of debate, with industry supporters trying to downplay the inevitable fact that this irresponsible use of antibiotics is most likely posing a serious risk to human health and the environment.

As reported in 2011, you have a 50/50 chance of buying meat tainted with drug-resistant bacteria when you buy meat from your local grocery store. This shocking finding came from a study by the Translational Genomics Research Institute,12 which revealed that 47 percent of the meat and poultry samples tested contained antibiotic-resistant Staphylococcus aureus bacteria. These were samples from 80 different brands of beef, chicken, pork, and turkey from more than two dozen grocery stores scattered across the United States, in large cities from Los Angeles to Washington D.C.

The fact that antibiotic-resistant superbugs are found so widely in US meat supplies is a major red flag, a sign that we are nearing the point of no return where superbugs will continue to flourish with very little we can do to stop them. While I am not one to recommend many medications, antibiotics can be VERY useful when you need to treat a serious bacterial infection. When used properly, in the correct contexts and with responsibility, antibiotics can and do save lives that are threatened by bacterial infections. But they will only remain effective if urgent changes are made to curb the spread of antibiotic-resistant bacteria and disease… and this will only happen with a serious reduction in their use now.

Choose Your Foods Wisely

Conventional medicine certainly needs to curtail its prescriptions for antibiotics, but even if you use antibiotics judiciously you’re still exposed to great amounts of antibiotics from the foods you eat, and this is entirely unnecessary. This is one of the primary reasons why I ONLY recommend organic, grass-fed, free-range meats or organic pastured chickens, as non-medical use of antibiotics is not permitted in organic farming. They’re also far superior to CAFO-raised meats in terms ofnutritional content.

To source pure, healthful meats, your best option is to get to know a local farmer — one who uses non-toxic farming methods. If you live in an urban area, there are increasing numbers of community-supported agriculture programsavailable that offer access to healthy, locally grown foods even if you live in the heart of the city. Being able to find high-quality meat is such an important issue for me personally that I’ve made connections with sources I know provide high-quality organic grass-fed beef and free-range chicken, both of which you can find in my online store. You can eliminate the shipping charges, however, if you find a trusted farmer locally. If you live in the US, the Weston Price Foundation13 also has local chapters in most states, and many of them are connected with buying clubs in which you can easily purchase these types of foods, including grass-fed raw dairy products like milk and butter.

How CAFO Meats May Decimate Your Gut Health

Antibiotic-resistant disease is not the only danger associated with the misuse of these drugs. Excessive exposure to antibiotics—which includes regularly eating antibiotic-laced CAFO meats—also takes a heavy toll on your gastrointestinal health. This in turn can predispose you to virtually any disease. Protecting your gut health and reducing the spread of antibiotic-resistant bacteria are significant reasons for making sure you’re only eating grass-fed, organically-raised meats.

In related news, researchers at Oregon State University point out the close links between your gut health and a wide range of health issues.14 As noted in the university press release:

“Problems ranging from autoimmune disease to clinical depression and simple obesity may in fact be linked to immune dysfunction that begins with a ‘failure to communicate’ in the human gut, the scientists say. Health care of the future may include personalized diagnosis of an individual’s ‘microbiome’ to determine what prebiotics or probiotics are needed to provide balance.

Appropriate sanitation such as clean water and sewers are good. But some erroneous lessons in health care may need to be unlearned—leaving behind the fear of dirt, the love of antimicrobial cleansers, and the outdated notion that an antibiotic is always a good idea. We live in a world of ‘germs’ and many of them are good for us.

An emerging theory of disease, [Dr. Natalia] Shulzhenko said, is a disruption in the ‘crosstalk’ between the microbes in the human gut and other cells involved in the immune system and metabolic processes. ‘In a healthy person, these microbes in the gut stimulate the immune system as needed, and it in turn talks back,’ Shulzhenko said. ‘There’s an increasing disruption of these microbes from modern lifestyle, diet, overuse of antibiotics and other issues. With that disruption, the conversation is breaking down.’”

The widespread deterioration of people’s gut health can be traced back to the change in our modern diet. This includes the introduction of meats from unnaturally-raised livestock, fed genetically engineered corn and soy along with a mixture of antibiotics and other drugs. But another important dietary factor is the shunning of traditionally fermented foods, which are naturally high in the beneficial bacteria necessary for optimal gut health. Mounting research shows that beneficial bacteria in your gut is likely to have significant benefits to your health and may be essential for:

  • Protection against over-growth of other microorganisms that could cause disease
  • Digestion of food and absorption of nutrients and certain carbohydrates
  • Producing vitamins, absorbing minerals, and eliminating toxins
  • Preventing allergies
  • Maintaining natural defenses

Numerous studies have also shown that your gut flora plays a role in:

  • Mood, psychological health, and behavior
  • Celiac disease
  • Diabetes
  • Weight gain and obesity
  • Metabolic syndrome

Nurturing Your Gut Flora Is One of the Foundations of Optimal Health

Besides antibiotics, your gut bacteria are also vulnerable to factors such as chlorinated water, antibacterial soaps, pollution, and agricultural chemicals—especially glyphosate, which, incidentally, is the most widely used herbicide in the world. To protect your gut health, it’s important to avoid processed, refined foods in your diet and to regularly reseed your gut with good bacteria by eating non-pasteurized, traditionally fermented foods, such as fermented vegetables, or taking a high-quality probiotic supplement.

One of the reasons why fermented foods are so beneficial is because they contain a wide variety of different beneficial bacteria. Also, if fermented with a probiotics starter culture, the amount of healthy bacteria in a serving of fermented vegetables can far exceed the amount you’ll find in commercial probiotics supplements, making it a very cost-effective alternative. Ideally, you want to eat a variety of fermented foods to maximize the variety of bacteria you’re consuming. Healthy options include:

Lassi (an Indian yogurt drink, traditionally enjoyed before dinner) Various pickled fermentations of cabbage (sauerkraut), turnips, eggplant, cucumbers, onions, squash, and carrots Tempeh
Traditionally fermented raw milk such as kefir or yogurt, but NOT commercial versions, which typically do not have live cultures and are loaded with sugars that feed pathogenic bacteria Natto (fermented soy) Kim chee


When choosing fermented foods, steer clear of pasteurized versions, as pasteurization will destroy many of the naturally occurring probiotics. This includes most of the “probiotic” yogurts you find in every grocery store these days; since they’re pasteurized, they will be associated with all of the problems of pasteurized milk products. They also typically contain added sugars, high-fructose corn syrup, artificial coloring, and artificial sweeteners, all of which will only worsen your health.

When you first start out, you’ll want to start small, adding as little as half a tablespoon of fermented vegetables to each meal, and gradually working your way up to about a quarter to half a cup (2 to 4 oz) of fermented vegetables or other cultured food with one to three meals per day. Since cultured foods are efficient detoxifiers, you may experience detox symptoms, or a “healing crisis,” if you introduce too many at once. That said, three very positive changes occur when your good-to-bad intestinal bacteria ratio is brought back into balance:

  • Digestive problems diminish or disappear
  • Your immune system de-stresses and is better equipped to fight off disease of all kinds, contributing to a longer and healthier life
  • Your body begins to use all the good food and nutritional supplements you feed it

8 Ways to Deal With Antibiotic Resistance.

Antibiotic Resistance: Why the Urgency?

Antibiotic resistance has been declared a crisis by the World Health Organization, the Centers for Disease Control and Prevention (CDC), the Institute of Medicine, the Infectious Diseases Society of America, and virtually all other relevant organizations.

Contributing to this urgency are the following facts:

 Pharmaceutical companies are no longer developing new antibiotics because they “can’t break even.” The last new antibiotic class for gram-negative bacteria was the quinolones, developed 4 decades ago.

 Antibiotic abuse in the United States is widespread. We have only 4.6% of the global population but we have 46% of the global antibiotic market.[1]

 Our prevention record is dismal. A patient entering a US hospital is 40 times more likely to acquire methicillin-resistant Staphylococcus aureus (MRSA) bacteremia than a patient entering a hospital in The Netherlands.[2]

What Are the Solutions for Antibiotic Resistance?

1. Collect Data

The European Union has detailed, 15-year data on antibiotic use by drug, and resistance data by microbe, covering 26 countries.[3] They know what and where the problems are. For example, Greece has the highest per capita use of antibiotics, and The Netherlands has among the lowest. The proportion of Klebsiella isolates that are carbapenemase-producing in Greece is 38%, and in The Netherlands it is 0.2%. The proportion of S aureusisolates that are methicillin-resistant is 58% in Greece and 1.6% in The Netherlands.[3] These data are strong testimony supporting the acknowledged association between antibiotic abuse and resistance, and they identify areas of great need for corrective intervention. In the United States, we have no comparable data.

2. Stop Antibiotic Use on the Farm

A full 80% of antibiotic use in the United States is for growth promotion and disease prevention in farm animals.[4] Resistant bacteria and resistance genes can be traced from the chickens to the chicken meat in grocery stores and, finally, to blood cultures in patients (The “farm to fork” phenomenon).[5] The practice of antibiotics for growth promotion on the farm was stopped in Denmark many years ago, with no apparent economic or animal health consequences.[6]

3. Practice Antibiotic Stewardship

Antibiotic stewardship has many elements:

 Use a procalcitonin level as a biomarker for infection to avoid unnecessary antibiotic use, as has been shown to be successful in nearly every well-controlled trial.[7]

 Short courses of antibiotics are virtually always effective in well-controlled trials.[3,8]

 Switch antibiotics from intravenous (IV) to oral formulations to hasten discharge and reduce risks associated with IV catheters. This switch is easily done with many antibiotics (linezolid, metronidazole, fluoroquinolones, some cephalosporins, fluconazole, etc).

 Use colistin carefully. Colistin, available since 1961, is increasingly needed but is saddled with dosing errors because the recommendations in the package insert are wrong.[9]

 Avoid antibiotic redundancy, as illustrated by the report that 23% of 782,821 patients were given metronidazole on top of another agent for anaerobic bacteria.[10]

4. Reduce Inappropriate Antibiotic Use in Outpatients

The abuse of antibiotics is well known and in large part reflects consumer demand because the patient expects to walk out of the clinic with a prescription for that viral respiratory tract infection. A Cochrane review of all methods to reduce antibiotic abuse in the clinic concluded that the “3-day prescription” was the only method with documented success.[11] This means telling the patients with “sinusitis” that they probably have a viral infection that is likely to get better within 3 days, and providing a prescription that is dated 3 days later for use if the patient is not better or is getting worse at that time.

Public campaigns can work but they are costly. France conducted a national campaign to convince patients and providers to do better, with a target of a 25% reduction in antibiotic prescriptions in the entire country. They achieved a 26% reduction![12] We also need to communicate better via modern technologies such as Twitter. For example, a tweet that proclaimed “Finally over my cold, thank God for Z-pack” had 850,375 followers.[13] We need to do better in social networking arenas to reach that audience.

Information from the microbiome could be particularly important. This is in very early development, but initial studies show that antibiotics such as ciprofloxacin, commonly prescribed for 1 week, have a profound and sometimes lasting effect on the colonic microbiome. Furthermore, excessive antibiotics in childhood have been associated strongly with subsequent obesity and inflammatory bowel disease.[14]

Despite these concerns, we need to be careful with an anti-antibiotic campaign that goes too far, because antibiotics are great drugs when indicated.[15]

5. Adopt Rapid Diagnostic Tests

Molecular methods are coming fast. We now have a polymerase chain reaction test for the detection of MRSA, vancomycin-resistant EnterococcusNeisseria gonorrhoeaeChlamydia trachomatis, group B Streptococcus, tuberculosis, Candida albicans, and many others.[16] Coming soon are tests that will detect practically every bacterium as well as other pathogens, making an etiologic diagnosis to facilitate antibiotic decision-making within 1-2 hours of collecting the culture. Interpretation will be tricky, however, because many specimens will need quantitation and there will be a predictable need for substantial stewardship.

6. Develop New Drugs

“Big pharma” previously developed new antibiotics in response to the continuing development of resistance. They no longer do this because they cannot regain their investment as a result of idiosyncrasies of short-term use, low price standards, and the antiquated model of the US Food and Drug Administration (FDA).[17] Does anyone think that it would be possible to conduct a 2000-patient study with, for example, pneumonia caused by multidrug-resistant bacteria?

We need a novel method to deal with antibiotic development and its related costs. Possibilities include:

 A public-private partnership such as the combined resources of the Bill & Melinda Gates Foundation, Janssen Pharmaceuticals, and the TB Alliance, which has now produced bedaquiline, the first new FDA-approved drug for tuberculosis in the past 40 years [18];

 Federal support for this effort, such as use of Biomedical Advanced Research and Development Authority (BARDA) funds that originally targeted only bioterrorism; and

 The need for a novel system for testing drugs and diagnostics, such as the new National Institutes of Health-funded Antibiotic Resistance Network.

7. Integrate Antibiotic Resistance Initiatives Into Healthcare Reform

We need convincing evidence of the benefit of infection-prevention initiatives in the context of healthcare reform, with the goal of saving both lives and money. An example of success with this strategy is the “5-step plan to prevent central line bacteremia.”[19] The plan was logical, but it needed verification. It was tested in 103 intensive care units in Michigan, with the anticipated impressive results. Subsequently the plan was introduced in the CDC network, with the study authors’ conclusion that “If every hospital did this, it would annually save 27,000 lives and $1.8 billion.”[20]

Healthcare reform priorities are ripe for similar prevention methods, including MRSA bacteremia, Clostridium difficile infection, surgical-site infection, and catheter-associated urinary tract infections. Caution must be used to prevent “gaming the system,” however, as illustrated by the experience with central line bacteremia. When financial penalties were instituted, national rates of central line bacteremia declined by 25% within 1 week![21]

8. Create a Plan for the United States

We need a comprehensive plan for the United States that includes some or all of the points listed above. The European Union has a plan with identified priorities to address antibiotic resistance, supported by funding of $220 million per year.[22] It is humbling that although we recognize the crisis of antibiotic resistance and our role in producing it, the United States has no comparable plan in place for resolving it



a si� ia`K� `� ter change from baseline in respiratory rate, which decreased by 3.5 breaths per minute vs. a decrease of 2.8 breaths per minute in the midazolam group (P = 0.04). There were no significant differences in the overall blood pressure score—which compares intra-procedure SBP with pre-procedure SBP—in the midazolam group compared with the diazepam group (P = 0.38). The time to nadir SBP following sedative administration was also similar between the two groups (44 vs. 47 min for the midazolam and diazepam groups, respectively; P = 0.46).


We also compared outcomes in patients on PI-based ART vs. non-PI-based ART. There were no significant differences between these groups in terms of age, sex, liver disease, baseline SBP, or concomitant use of CYP 3A4 inhibitors, chronic opioids or chronic benzodiazepines. There were no significant differences between the four treatment groups (PI/midazolam; PI/diazepam; non-PI/midazolam; non-PI/diazepam) in the outcomes of lowest SBP, heart rate, nadir oxygen saturation, nadir respiratory rate, consciousness score < 2, sedation duration, or newly abnormal change in cardiac rhythm.

Multivariate Analysis

We performed multivariate analysis for four discrete outcomes – attainment of consciousness score < 2, sedation duration, nadir SBP, and cardiac rhythm score – adjusting for possible confounders based on clinical relevance and significance in univariate analysis. In adjusted analyses, we found that midazolam use (vs.diazepam use) was significantly associated with a consciousness score < 2 (odds ratio = 3.80; 95% confidence interval 1.33; 10.88) but not with cardiac rhythm score, nadir SBP, or sedation duration (data not shown).


Most endoscopic procedures are performed with the patient under moderate (‘conscious’) sedation, during which the patient is able to respond purposefully to verbal or tactile stimulation.[5] Adequate sedation can both facilitate successful completion of the procedure and increase patient tolerability by decreasing anxiety and pain.

In this retrospective analysis of 136 adult HIV-positive patients on ART who underwent a colonoscopy, we assessed the safety of midazolam vs. diazepam based on multiple physiological outcomes. We found that the patients in our cohort safely received midazolam-based sedation, with comparable haemodynamic, cardiac, and respiratory outcomes compared with patients who received diazepam. We did observe a difference in consciousness score between the midazolam and diazepam groups, consistent with the known interaction between midazolam and ART. However, no patient suffered an outcome indicative of over-sedation, such as requirement for reversal of sedation, hospitalization or unresponsiveness. It is notable that more patients in the diazepam group compared with the midazolam group (26% vs. 9%, respectively) were awake and oriented during the procedure. Had patients in the diazepam group been given more diazepam to achieve a level of moderate sedation, it is likely that the duration of sedation would have been longer in the diazepam group.

Concerns regarding the safety of midazolam use in HIV-positive patients on ART arise from the possibility of drug interactions resulting in increased levels of midazolam.[6–8] Metabolism of midazolam is almost entirely dependent on hydroxylation by CYP 3A4.[2] Guidelines indicate that iv midazolam can be co-administered with ART with close clinical monitoring.[9–11] In addition, it has been demonstrated in a number of small studies that, with careful titration, drugs such as fentanyl, meperidine and midazolam, can be administered safely for short-term procedures in HIV-positive patients on ART.[12–15]

Previous studies investigating the clinical impact of co-administration of midazolam and ART have yielded conflicting results. In a cohort of 143 ambulatory patients undergoing bronchoscopy and receiving midazolam (total doses ranged from 2 to 15 mg; average 7.5 mg), no patient suffered an adverse outcome or required intubation.[16] By contrast, in a recent study of 241 HIV-positive in-patients who received iv midazolam prior to bronchoscopy,[17] the incidence of prolonged sedation (defined as > 90 minutes) was 9.8% in patients receiving PIs compared with 1.58% in those not taking ART. One possible reason for the difference between these findings and our results is the fact that the previous cohort consisted of in-patients, in whom concomitant comorbidities may have predisposed patients to complications from sedation; indeed, 10% of the patients in the PI group had pre-existing respiratory distress or altered mental status prior to the procedure and 29% were diagnosed with Pneumocystis jirovecii pneumonia. By contrast, we examined only ambulatory patients and compared outcomes between patients on ART receiving iv midazolam and those receiving iv diazepam. It is important to acknowledge that the risks of iv midazolam may differ by procedure and the presence of medical comorbidities.

In our institution, based on pharmacokinetic principles and available evidence, we generally do not empirically reduce the dose of midazolam for HIV-positive patients undergoing procedural sedation. Peak benzodiazepine concentrations after a single dose or multiple doses over a very short period of time (e.g. 20 minutes) are not affected by drug half-life or clearance. Furthermore, in the context of short-term use, the recovery time for benzodiazepines is mainly dependent on redistribution kinetics rather than half-life.

Limitations of this study include its retrospective design and the limited sample size. To address the possibility of confounding, we conducted a multivariable analysis adjusting for variables such as age, sex, liver disease, and concomitant medications including CYP 3A4 inhibitors and chronic opioid use. We also examined outcomes in four different subgroups – midazolam- and diazepam-based sedation with and without concomitant PIs – and could not detect an association between the treatment groups and any of the outcomes. An additional limitation is that our institutional endoscopic anaesthesia scoring system may not be sensitive enough to detect the optimal level of sedation.

In conclusion, we demonstrated that HIV-positive out-patients undergoing colonoscopy who received iv midazolam for procedural sedation had similar clinical outcomes to those who received diazepam. Based on these findings, we conclude that the use of iv midazolam can be considered for HIV-positive patients on ART with close clinical monitoring. These findings should be confirmed in prospective studies or in a randomized controlled trial.



First case of infection with vancomycin-resistant Staphylococcus aureus in Europe.

Although vancomycin is often prescribed for the treatment of meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S aureus (VRSA) infections remain rare, with only few cases confirmed worldwide—mostly in the USA.1Here, we report the isolation and preliminary characterisation of the first VRSA strain in Europe isolated from a patient in Portugal.

A 74-year-old woman with diabetes mellitus, chronic renal failure requiring haemodialysis, and peripheral vascular disease conditioning critical limb ischaemia underwent endovascular revascularisation and amputation of two gangrenous toes. Previous cultures of the wound amputation site revealed Pseudomonas aeruginosa and vancomycin-susceptible MRSA, for which she was treated with vancomycin and amikacin. In May, 2013, a meticillin-resistant VRSA strain was isolated from pus of the toe amputation wound. The minimum inhibitory concentrations for vancomycin and teicoplanin were >256 μg/mL and 24 μg/mL, respectively. Vitek 2 and MicroScan systems both detected VRSA. MALDI-TOF analyses confirmed the identification of S aureus. Vancomycin-resistant Enterococcus faecalis (VRE) and P aeruginosa were also isolated from the same wound.

The strain was sequence type ST105, SCCmec type II, and harboured the mecA and vanA genes, the latter was also identified in the VRE. The genetic background of the strain is similar to that of VRSA isolated in the USA.2 However, we have not identified an epidemiological link with the USA of the patient or health-care providers, and the concomitant isolation of VRE suggests a possible source for the vanA gene,3 supporting an independent acquisition of the vancomycin-resistance determinant. The VRSA was resistant to erythromycin, clindamycin, gentamicin, and ciprofloxacin, and susceptible to co-trimoxazole, tetracycline, tygecycline, linezolid, daptomycin, quinupristin/dalfopristin, fusidic acid, cloramphenicol, rifampicin, and mupirocin.

Precautions were reinforced. The patient is clinically well, and is being treated with daptomycin, rifampicin, and amikacin, and aggressive wound care. An epidemiological investigation is ongoing, but so far transmission of VRSA from this patient to contacts at home, other patients or health-care workers from the dialysis unit was not detected.

The identification of VRSA is particularly worrying since Portugal is a country with one of the highest prevalences of MRSA and VRE in Europe.4

In all cases of VRSA detected so far there was no spread of the strain. However, the potential sustained use of vancomycin, and the circulation of strains capable of receiving elements carrying vancomycin-resistance determinants5 raise the possibility of further selection of VRSA. To prevent the emergence and dissemination of these strains, adherence to infection control recommendations, antibiotic stewardship, and surveillance are essential.

JM-C has received research grants and honoraria for serving on the speakers bureaus of Pfizer, Novartis and Gilead. MR has received honoraria for serving on speakers bureau of Pfizer. The other authors declare that they have no conflicts of interest.

Source: Lancet

Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: systematic review and meta-analysis.


Objective To evaluate studies assessing the effectiveness of a bundle of nasal decolonization and glycopeptide prophylaxis for preventing surgical site infections caused by Gram positive bacteria among patients undergoing cardiac operations or total joint replacement procedures.

Design Systematic review and meta-analysis.

Data sources PubMed (1995 to 2011), the Cochrane database of systematic reviews, CINAHL, Embase, and were searched to identify relevant studies. Pertinent journals and conference abstracts were hand searched. Study authors were contacted if more data were needed.

Eligibility criteria Randomized controlled trials, quasi-experimental studies, and cohort studies that assessed nasal decolonization or glycopeptide prophylaxis, or both, for preventing Gram positive surgical site infections compared with standard care.

Participants Patients undergoing cardiac operations or total joint replacement procedures.

Data extraction and study appraisal Two authors independently extracted data from each paper and a random effects model was used to obtain summary estimates. Risk of bias was assessed using the Downs and Black or the Cochrane scales. Heterogeneity was assessed using the Cochran Q and I2 statistics.

Results 39 studies were included. Pooled effects of 17 studies showed that nasal decolonization had a significantly protective effect against surgical site infections associated with Staphylococcus aureus (pooled relative risk 0.39, 95% confidence interval 0.31 to 0.50) when all patients underwent decolonization (0.40, 0.29 to 0.55) and when only S aureus carriers underwent decolonization (0.36, 0.22 to 0.57). Pooled effects of 15 prophylaxis studies showed that glycopeptide prophylaxis was significantly protective against surgical site infections related to methicillin (meticillin) resistant S aureus (MRSA) compared with prophylaxis using β lactam antibiotics (0.40, 0.20 to 0.80), and a non-significant risk factor for methicillin susceptible S aureus infections (1.47, 0.91 to 2.38). Seven studies assessed a bundle including decolonization and glycopeptide prophylaxis for only patients colonized with MRSA and found a significantly protective effect against surgical site infections with Gram positive bacteria (0.41, 0.30 to 0.56).

Conclusions Surgical programs that implement a bundled intervention including both nasal decolonization and glycopeptide prophylaxis for MRSA carriers may decrease rates of surgical site infections caused by S aureus or other Gram positive bacteria.


Although multiple studies have assessed the efficacy of interventions to prevent surgical site infections caused by Gram positive bacteria, these interventions are not uniformly applied to surgical patients. Our results showed that nasal decolonization was associated with decreased rates of Gram positive surgical site infections andStaphylococcus aureus surgical site infections among patients undergoing cardiac or orthopedic surgical procedures. However, these results remained statistically significant for S aureus surgical site infections, though not all Gram positive surgical site infections, when the meta-analysis was limited to randomized controlled trials. Additionally, a bundle that included nasal decolonization and glycopeptide prophylaxis for patients who carried methicillin (meticillin) resistant S aureus (MRSA) was associated with significantly decreased rates of surgical site infections caused by Gram positive bacteria and by S aureus.

We also found that routine use of prophylactic glycopeptides protected against MRSA infections but not against all Gram positive surgical site infections. Additionally, dual prophylaxis with a glycopeptide and another antimicrobial agent seemed to be more protective against Gram positive surgical site infections than prophylaxis with glycopeptides alone. This finding is consistent with studies of methicillin susceptible S aureus (MSSA) bacteremia, which found that vancomycin is less effective than a β lactam antibiotic for treating MSSA infections.63 64 These results are similar to the conclusions of a recent review article, which stated that vancomycin is not recommended for preoperative prophylaxis but may be considered as a component of an MRSA bundle to prevent surgical site infections.65

Our meta-analyses were the first to assess a bundle that included nasal decolonization and targeted glycopeptide prophylaxis for MRSA carriers. Other meta-analyses have assessed nasal decolonization or glycopeptide prophylaxis alone,66 67 68 and our results confirm the findings of the previous studies and extend these by including the results of recent studies. Future meta-analyses should assess other outcomes associated with these interventions. These outcomes could include duration of hospital stay since one group of researchers found that the mean duration of hospital stay was significantly shorter in those randomized to mupirocin and chorhexidine gluconate rather than to placebo.27 Future meta-analyses should also confirm our preliminary findings that these interventions do not open a niche for pathogens other than S aureusto fill, and should also analyze other patient populations such as those requiring trauma surgery to determine if these findings are generalizable to other surgical specialties.

Nasal decolonization protected against S aureus surgical site infections when all patients were decolonized and when only S aureus carriers were decolonized. Routine nasal decolonization of all surgical patients may be easier to implement and more cost effective than using cultures or polymerase chain reaction testing to screen patients preoperatively.69 None the less, it may be prudent to reserve mupirocin decolonization for patients who carry S aureus to prevent widespread mupirocin resistance.70Similarly, it may be prudent to do further research on targeted prophylaxis with vancomycin before including this bundle in clinical practice. Of note, the pooled relative risks assessing Gram positive surgical site infections were identical for both the decolonization studies and the bundle studies. Thus high quality studies such as cluster randomized trials are still needed to determine whether adding glycopeptide prophylaxis to nasal decolonization will further decrease the incidence of Gram positive surgical site infections.

In our sensitivity analyses we found that nasal decolonization was associated with a 1% risk difference and the bundle was associated with a 0.5% risk difference in Gram positive surgical site infections. Although these differences seem small, they are clinically significant considering that cardiac and orthopedic operations are common and surgical site infections are associated with considerable morbidity. Each year, approximately 300 000 cardiac operations and approximately 900 000 total joint arthroplasties are done in the United States alone.71 Thus these interventions could prevent 6000 to 12 000 surgical site infections per year in the United States and even more worldwide.

Limitations of this study

Our study has some limitations. Firstly, meta-analyses are only as valid as the studies that contribute to the pooled risk ratio. We included many studies that were simple before and after quasi-experimental studies. Additionally, none of the included studies adjusted statistically for potential confounders, thus confounding may be problem, especially among the observational studies. To mitigate this limitation, we performed subset analyses on the results of only randomized controlled trials. Secondly, we did not include studies that did not report or could not provide specific data on Gram positive infections, thus we may have excluded important decolonization and prophylaxis studies. However, nine of 15 contacted investigators submitted additional data for inclusion in the analyses. Thirdly, studies of the association between interventions and Gram positive surgical site infections were heterogeneous, and thus some of the meta-analysis results should be interpreted with caution. Once these studies were stratified by potential sources of heterogeneity, the stratified subsets were homogeneous. For example, nasal decolonization aims to decrease the incidence of endogenous S aureus surgical site infections. The association between nasal decolonization and Gram positive surgical site infections may have been different for studies in which S aureus caused most Gram positive surgical site infections compared with studies in which surgical site infections due to other Gram positive pathogens were common. Thus we limited heterogeneity by doing subset analyses that separated studies focusing on S aureus surgical site infections from those focusing on all Gram positive surgical site infections.


Surgical site infections caused by Gram positive bacteria may be prevented by decolonizing patients who carry S aureus in their nares and potentially by adding a glycopeptide to the usual prophylaxis using β lactam antibiotics for MRSA carriers. High quality randomized controlled trials or cluster randomized trials should be performed to further assess this bundle.

What is already known on this topic

  • Surgical site infections (SSIs) are potentially preventable adverse events of cardiac and orthopedic operations
  • SSIs significantly increase hospital length of stay, readmission rates, healthcare costs, and mortality rates
  • Clinicians and researchers have debated whether nasal decolonization or glycopeptide antibiotic prophylaxis reduce SSIs caused by Gram positive bacteria
  • Among patients undergoing cardiac or orthopedic surgery:
  • Nasal decolonization with mupirocin ointment was protective against Gram positive SSIs
  • Preoperative prophylaxis with anti-methicillin (meticillin) resistant Staphylococcus aureus (MRSA) antibiotics when given to all patients was not protective against Gram positive SSIs
  • A bundle that included nasal decolonization and anti-MRSA prophylaxis for MRSA carriers was significantly protective against Gram positive SSIs

What this study adds


  • Among patients undergoing cardiac or orthopedic surgery:
  • Nasal decolonization with mupirocin ointment was protective against Gram positive SSIs
  • Preoperative prophylaxis with anti-methicillin (meticillin) resistant Staphylococcus aureus (MRSA) antibiotics when given to all patients was not protective against Gram positive SSIs
  • A bundle that included nasal decolonization and anti-MRSA prophylaxis for MRSA carriers was significantly protective against Gram positive SSIs

Source: BMJ



Targeted versus Universal Decolonization to Prevent ICU Infection.


Both targeted decolonization and universal decolonization of patients in intensive care units (ICUs) are candidate strategies to prevent health care–associated infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA).


We conducted a pragmatic, cluster-randomized trial. Hospitals were randomly assigned to one of three strategies, with all adult ICUs in a given hospital assigned to the same strategy. Group 1 implemented MRSA screening and isolation; group 2, targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers); and group 3, universal decolonization (i.e., no screening, and decolonization of all patients). Proportional-hazards models were used to assess differences in infection reductions across the study groups, with clustering according to hospital.


A total of 43 hospitals (including 74 ICUs and 74,256 patients during the intervention period) underwent randomization. In the intervention period versus the baseline period, modeled hazard ratios for MRSA clinical isolates were 0.92 for screening and isolation (crude rate, 3.2 vs. 3.4 isolates per 1000 days), 0.75 for targeted decolonization (3.2 vs. 4.3 isolates per 1000 days), and 0.63 for universal decolonization (2.1 vs. 3.4 isolates per 1000 days) (P=0.01 for test of all groups being equal). In the intervention versus baseline periods, hazard ratios for bloodstream infection with any pathogen in the three groups were 0.99 (crude rate, 4.1 vs. 4.2 infections per 1000 days), 0.78 (3.7 vs. 4.8 infections per 1000 days), and 0.56 (3.6 vs. 6.1 infections per 1000 days), respectively (P<0.001 for test of all groups being equal). Universal decolonization resulted in a significantly greater reduction in the rate of all bloodstream infections than either targeted decolonization or screening and isolation. One bloodstream infection was prevented per 54 patients who underwent decolonization. The reductions in rates of MRSA bloodstream infection were similar to those of all bloodstream infections, but the difference was not significant. Adverse events, which occurred in 7 patients, were mild and related to chlorhexidine.


In routine ICU practice, universal decolonization was more effective than targeted decolonization or screening and isolation in reducing rates of MRSA clinical isolates and bloodstream infection from any pathogen.

Source: NEJM