Archive for the ‘MRSA’ Category

There's Silver in Them There Pills

Wednesday, December 25th, 2013

Like most medically-trained people (and hopefully many of the rest of us), I've been highly concerned about the rise of drug-resistant microorganisms, bacteria that can't be treated with our standard antibiotics. A recent article in The Wall Street Journal with the intriguing title "Antibiotics of the Future" offered considerable hope, but let look at some background on the subject first.

The WSJ article said that two million patients each year in the United States develop infections that doctors can't combat with our normal antibiotics; earlier in the year, the CDC in a report titled "Antibiotic Resistance Threats in the United States 2013" estimated that at least 23,000 of them die. They divide the microorganisms, all bacteria except for Candida (a fungus), into three groups: those whose threat levels are considered urgent, serious or concerning. The three in the urgent category include Clostridium difficile, which causes severe, life-threatening diarrhea, often in patients who have been hospitalized and are already on antibiotics, and leads to a quarter-million infections, 14,000 deaths and a billion dollars in medical expenses yearly. Then there are the carbapenem-resistant Enterobacteriaceae,  abbreviated as CRE (the carbapenems are powerful antibiotics considered the "drugs of last resort," used when all other old and modern antimicrobials fail or are thought to be likely to fail; Eneterobacteriaceae are bacteria that are part of the normal gut flora.)

CRE infections most often happen in patients getting treatment for other serious conditions. They may be on a respirator, have a long-term catheter in their bladder or have been on other antibiotics. One estimate says there are 9,000 CRE infections a year and they cause at least 600 deaths. Patients in intensive care units not infrequently have IV catheters placed in large veins in the neck, chest or groin to allow hospital personnel to give medications and draw blood sample for a prolonged period of time. If these get infected they can cause a bloodstream infection (sepsis is the medical term). About half of all hospital patients who get CRE that goes on to cause a bloodstream infection die.

The third infectious urgent threat level is the bacteria, Neisseria gonorrhoeae, that causes the STD gonorrhea. The CDC estimates more than 800,000 cases occur yearly in the United States and 30% of these are resistant to some antibiotic, but almost all can be treated, at this time, with a two-drug cocktail. Gonorrhea causes severe reproductive system complications and the CDC says it "disproportionally affects sexual, racial and ethnic minorities."

Then there is MRSA, methicillin-resistant Staphylococcus aureus. This bug is classified as serious, not urgent, yet there are roughly 80,000 severe MRSA cases a year and over 11,000 of these patients die. Most major MRSA cases are seen in healthcare setting among patients with weakened immune systems (e.g., those on hemodialysis or receiving cancer therapy) but less serious MRSA  can case problems in otherwise healthy people, including athletes who share towels or razors, children in day-care and members of the military in cramped quarters. Some of these infections, usually of the skin, can become severe and life-threatening.

The CDC piece, except for Candida, excludes non-bacterial diseases, but I received a reader comment a while back from a person whose website ( has a post on Deadly Viruses.  Like parasitic diseases, e.g., malaria, viruses through the ages have killed simply enormous numbers of people. Now we're facing a future when bacterial illnesses could overtake their status as the prime infectious threats to mankind.

An article in the December 23, 2013 online version of the New York Times described an increased death rate among dolphins, with many dying of viral disease. A number of them also showed evidence of antibiotic resistant bacteria, presumably from environmental contamination. Dolphins have been termed the modern equivalent of the canary in the coal mine, a biological early warning system analogous to the times when miners used to carry caged canaries while at work; if there was any methane or carbon monoxide in the mine, the canary would die before the levels of the gas reached those hazardous to humans.

The New England Journal of Medicine in January, 2013published an article titled "The Future of Antibiotics and Resistance." The lead author, Dr. Brad Spelberg, works where I did my research fellowship. He and two colleagues mention that antibiotic-resistant bacteria are considered, in a major yearly publication by the World Economic Forum  (WEF), to be a leading risk to human health.

The World Economic Forum's (WEF) 2013 publication on Global Risks analyzed fifty possibilities (e.g., economic disparity, religious fanaticism, rising greenhouse gas emissions, terrorism, water supply crises), examining their likelihood over the next decade, the impact if they actually happen and how interconnected they were to each other.  It used those to generate analyses of three major risk cases: one was on the threats to economic/environmental systems, a second on so-called 'digital wildfires" from misinformation, and  The Dangers of Hubris on Human Health, devoted to antibiotic-resistant bacteria.

In a study done in Europe, 50% of French patients experiencing a flu-like syndrome (FLS) expected their physician to prescribe an antibiotic; FLS may be caused by influenza virus or other viruses and antibiotics are not of any use against these viral diseases. The WEF piece mentioned an article reporting 98% of Chinese children seen in a Beijing pediatric hospital for common colds were given antibiotics.

Huge quantities of antibiotics are being used for animals as well.  Animals being raised for their meat are often given antibiotics as growth promoters. A 1950 article in Science News announced results from Lederle Laboratories that lacing the hog feed with trace amounts of an antibiotic could increase the yield of meat by a half. Then in 1977 the FDA sent out a notice that it would withdraw approval of non-medical use of penicillin and tetracyclines, but no hearings on the subject followed that non-binding pronouncement.

A Federal District judge finally ordered those FDA hearings in 2012, but an article online less than two weeks ago said only suggestions to the animal-growing industry have resulted. In 2009, more than 3,000,000 kilograms of antibiotics were given to US patients; in 2010, 13,000,000 kilograms were used for animals.

Back to the Wall Street Journal article: it mentions four new approaches to treatment of these deadly bugs. The two I found most intriguing were research to befuddle the bacteria by working against the signaling chemicals they use to become infectious and using silver to increase the ease with which antibiotics enter the microbes.

There's a way to go before these concepts are translated into bedside medicine, but there is more than a glimmer of hope on the horizon.


The ongoing war: superbugs versus humanity

Tuesday, June 4th, 2013

I saw an article that gave me some hope for our current bacterial and viral dilemmas; it involved a new strategy to prevent infections, rather than treating them after they've struck. I'm all for preventive medicine, both in the infectious disease arena and in medicine in general. I think we "play catch-up" all too often.

How this ICU staffer chooses to protect you from MRSA is crucial.

How this ICU staffer chooses to protect you from MRSA is crucial.

The piece was in The Wall Street Journal on May 30, 21013 with its headline,  "New Tack in Preventing Hospital Infections: Germ-Killing Soap-Ointment Treatment for all ICU Patients Shown to be More Effective than Isolating Some After Screening" The original article  was printed online in the New England Journal of Medicine on May 29, 2013 and its title was  "Targeted versus Universal Decolonization to Prevent ICU Infection."

We're mostly talking about MRSA (Methicillin-resistant Staphylococcus aureus), that strain of the familiar Staph bacteria that's been plaguing us for the last few decades, in large part as a result of unnecessary antibiotic use.

Even if antibiotics are used only for significant bacterial infections, a small proportion of the "bugs" may survive. The population of those germs who cannot be killed by the particular antibiotic can multiply and be spread to others. When antimicrobial drugs are used inappropriately used to "treat" viral infections (e.g., "flu" or the common cold) or given wholesale to food animals (beef, chicken, pigs) to promote growth), we're also likely to be find ourselves with bacteria that are resistant to those antibiotics we've previously been able to use successfully.

About 30% of us carry staph of our skin or in our nostrils (without being ill) and somewhere between 1% and 2.5% carry MRSA. Otherwise healthy people can develop infection with it as a painful skin boil, especially in rugby or football players and high school wrestlers, but also in those who are child care workers or live in crowded settings.

Since moving here in 1999 I'm personally aware of two people who started with what seemed to be very minor skin infections, but later were diagnosed with extremely serious progression of their initial disease. One died from what was eventually diagnosed as fleshing-eating Strep; the other survived, but spend a long time in intensive care with a Staph infection that spread from a bump on his arm up to his chest.

Hospitals often screen patients for MRSA and nine states now mandate such screening. But the study mentioned above attempted to see if there was a better way to avert serious infections in the intensive care setting where patients are the sickest.

MRSA growing on a culture plate.

MRSA growing on a culture plate.

Forty-three hospitals with 74 ICUs and nearly 75,000 patents were randomly assigned to one of three infection prevention strategies: the first group screened patents for MRSA and isolated those who tested positive; the second group added "decolonization," removing the bacteria by washing MRSA-positive patents with an antimicrobial (bacteria-killing) soap plus giving them a nasal antibiotic; the third group of hospitals did not screen patents, but treated every ICU patient as though they had MRSA, i.e., with the soap and the nasal antibiotic.

Universal decolonization cut the rate of positive blood cultures, a way to look at the most serious infections, by 44%. That included not only Staph, but other bacteria as well. Only seven of the research subjects had any form of adverse reaction and those were mild rashes of itching; all resolved after stopping the washing.

The Mayo Clinic webpage on MRSA discusses risk factors for hospital-associated MRSA infections (HA-MRSA) and for those that are community-associated (CA-MRSA). Just being hospitalized increases your risk as does having an invasive medical device (urinary catheter or IV line) and residing in a long-term care facility. Remember, carriers of MRSA can spread the germ, even if they are not sick from it. For CA-MRSA the risk factors include contact sport, living in crowded or unsanitary conditions and men who have homosexual relations.

The World Health Organization (WHO) has an online fact sheet on Antimicrobial resistance. Infections that fail to respond to conventional therapy result in higher medical care costs, greater length of illnesses and a higher risk of a fatal outcome.

MRSA is by no means the only germ that has developed drug resistance. WHO estimates over 630,000 cases of multi-drug resistant tuberculosis (MDR) requiring longer therapy with more drugs. Malaria, caused by one of five species of a parasite that are carried by mosquitos, has become increasingly difficult to treat because of this issue. Malaria cases in the United States have been relatively rare, about 1,200 per year while annually there are 300 million cases and one million deaths from the disease elsewhere in the world.

Most US cases have occurred in those who travel to sub-Saharan Africa, India, or Southeast Asia; That is likely to change as the expected average temperature increase of 0.4 degrees Celcius over the next eight years will likely increase our mosquito population by up to 30%, including the one mosquito species that carries the Plasmodium falciparum, the most deadly type that I've only seen when I was serving at the Air Force Regional Medical Center located on Clark AFB in the Philippines.

A recent online copy of The New York Times has an article titled, "Pressure Grows to Created Drugs for Superbugs." Health and Human Services (HHS) is going to pay $40 million to a pharmaceutical company to develop new antibiotics to combat drug resistance; they are concerned about biological agents that terrorists may utilize to cause widespread death.

But in the meantime, tens of thousands of our citizens die from inceptions, mostly hospital-acquired and caused by the current generation of antibiotic resistant germs. The FDA's director of the Center for Drug Evaluation and research was quoted as saying, "We are facing a huge crisis worldwide not having an antibiotic pipeline... but what is worse is the thought of where we will be five to 10 years from now."

A move to fast-track approval of new anti-infective drugs is being hotly debated. The Infectious Disease Society of America would support their labeling for use on only the very sickest patients.

Others are concerned that these restrictions are insufficient; that the new medicines will be used for those less-than critically ill without our knowing how the antibiotics will perform and what their advise effects may be. One director of the infectious disease society said, "The last thing we want is for a new drug to be overused."

The next twenty to fifty years will be a critical time for the germs versus humans war.