Wednesday, October 18, 2017

Don't be lame. Get your flu shot.

I'm getting a little tired of hearing this: "I got the flu once after getting the shot, I'll never get it again." No, you didn't.

Also, at what point did your primary care provider become "government" or in the pocket of Big Pharma? The recommendation to get your flu shot if you are able is not some government conspiracy or ploy for pharmaceutical companies to make oodles of money. Guess what? Your doctor doesn't work for the government and pharmaceutical companies make more money on erectile dysfunction and high blood pressure medications than they ever will on a once-a-year vaccine. You may think it's not a big deal if you don't get your flu shot because you're reasonably healthy and it's okay if you get sick for a week. That may very well be true. But consider your grandparents, parents of a certain age, and babies and other young ones. Consider your friend or family member or acquaintance or stranger on the bus that may be immunocompromised due to cancer treatments. Cancer is BAD ENOUGH without having to worry about catching influenza from someone that just doesn't "believe in vaccination," like getting vaccinated is on the same level as believing in leprechauns. Consider what it means to miss an entire week of work. I came down with influenza last year, two weeks before my work had its flu shot event. It was awful. Body aches so intense that the weight of my own body was almost too much to bear. Fever spikes up to 103 degrees. I never want to go through that again. You shouldn't be so flippant about it. 

Here are some flu facts:

Fact: Influenza kills. Over a period of 30 years between 1976 and 2006, estimates of flu-associated deaths in the United States range from a low of about 3,000 to a high of about 49,000 people per season. During a regular flu season, around 90 percent of deaths occur in people 65 years and older. Children die too; 107 children under age 18 died from influenza during the 2016-17 season. These deaths very well could have been prevented by vaccination. A study conducted by the Centers for Disease Control and Prevention (CDC) showed that between 2010 and 2014, of 291 deaths in children 6 months to 17 years, only 26% had been vaccinated against flu before getting sick. We can do better for our kids. We can do better for our parents and grandparents.

Fact: You cannot get the flu from the flu shot. Flu shots are made either from a dead virus or with no virus at all, depending on which shot you get; it's biologically impossible for the flu shot to give you influenza.

Fact: The shot itself and what your body does to make the antibodies that protect you can cause body aches and possibly a low-grade fever. Don't be a wuss, that's not influenza.

Fact: It can take up to 2 weeks after getting the shot for your body to do what it needs to protect you. So, you could potentially have come in contact with influenza before you got the shot, or sometime in that 2-week window, and still get sick. 

Fact: The flu mist (nasal spray) is made with live virus, but one that's had its nastiness factors taken away. You may have more localized side effects like runny nose, cough, or sore throat, but the flu mist cannot give you full-blown influenza. Not possible.
         Sub-fact: The flu mist is NOT available this year and I don't know when or if it will be back. 

Fact: The "stomach flu" is not influenza. It's most likely a nasty little bugger called norovirus. I'll talk about that fresh hell another day. Stop calling it the flu.

Here's the thing. I'm not going to lie to you; the flu shot isn't perfect, it won't protect everyone and for some it won't work at all. But it is the best we have and we have to do the best we can with what we have! The recommendation is everyone age 6 months and older that is able should get their flu shot. It's the right thing to do for the herd! Plus, this year's flu season could potentially be a real doozy. We can often look to the southern hemisphere for a clue of how things will go for us. Australia is just entering their spring season and the flu season is winding down. And it was bad. Here's a news article from the country outlining the severity. 

To re-cap: Your primary care provider does actually look out for your best interests. The flu shot won't give you the flu. It will help to protect you and the people around you. Most people age 6 months and older can get the flu shot. Talk to your health care provider to make sure you are able. Do your part and get vaccinated!! Don’t be lame.

Sunday, August 6, 2017

When good bacteria go bad: Shiga toxin-producing Escherichia coli

Two young children, siblings - brother and little sister, got sick last month. The little girl sadly succumbed and passed away. Her older brother was gravely ill, fighting for his life, slowly recovered, and is now thankfully home. What could have caused this unfathomable tragedy? A strain of normally beneficial bacteria, Escherichia coli, or E. coli (E-coal-I).

E. coli is a kind of bacteria that lives in the guts of mammals, including humans, cows, sheep, and goats. Garden variety E. coli doesn't cause any harm, maybe a little gas. Sometimes it ends up in your urethra and causes a urinary tract infection. No big deal (unless it's resistant to antibiotics, but we've gone there already). Unfortunately, there also exist pathogenic E. coli. These are the strains of E. coli that can make us sick. You can think of different strains of a certain bacteria as flavors of ice cream. Vanilla, chocolate, mint chocolate chip, Rocky Road, whatever you like. It's all ice cream (E. coli), but it comes in many different flavors (strains). There are strains of E. coli that are sticky and adhere to the lining of your intestines more than others. Some of those sticky strains also can cause you to have diarrhea, and a lot of it. As your intestines become a mad torrent of watery contents, many of your normal beneficial bacteria are swept away in the tide. The E. coli strains that are more sticky are able to hang on tight. Then once the rest of your bacteria are gone, they can take over the area without any competition. There are several different groupings of pathogenic E. coli and to talk about them there's going to be a lot of long words that are hard to pronounce and lots of abbreviations. Hang on tight. First thing to note: the prefix "entero" refers to the intestine. 

Enterotoxigenic E. coli, or ETEC,
Enteropathogenic E. coli, or EPEC,
Enteroaggregative E. coli, or EAEC,
Enteroinvasive E. coli, or EIEC,
Diffusely adherent E. coli, or DAEC,
and Shiga toxin-producing E. coli, or STEC. Also known as Enterohemorrhagic (EHEC), or Verocytotoxin-producing (VTEC). 

The groups listed above all have varying abilities to stick to your intestinal wall, to resist your stomach acids, and to cause you to have diarrhea that can be bloody. STEC (S-teck) is what you hear about in the news, mostly when there is an outbreak of illness caused by contaminated food. STEC is a bad guy, a really bad, bad bacteria. STEC is what we're talking about here. 

The kind of STEC that you've probably heard of is called E. coli O157:H7, sometimes referred to as E. coli O157 or simply as O157. The "O" number refers to an antigen on the surface of the bacterial cell wall. The "H" number is an antigen on the flagella (whip-like appendages that allow the bacteria to swim around). I don't want to get too into the weeds about bacterial cell wall structures and whatnot. What's important is there is tremendous variability of "O" and "H" antigens among bacteria like E. coli and so we use them in microbiology to separate, categorize, and name. This is called serotyping. E. coli O157:H7 is a serotype of STEC. There are many other serotypes of STEC besides O157. We have O111, O26, O104, O121, and O145 to name a handful; there are a lot more. Last year there was a multi-state outbreak of STEC infections caused by O121 and O26 that was associated with consuming raw flour, like eating undercooked baked goods or pizza dough, or licking the spoon when you make cookies. In 2011, there was a massive outbreak of STEC infections caused by O104:H4 associated with eating contaminated raw fenugreek sprouts: 4,075 cases and 50 deaths in 16 countries.

Why does STEC cause so many illnesses? Why do people get so sick? STEC produces toxins called Shiga toxins, named after Dr. Kiyoshi Shiga - the doctor who discovered the bacteria responsible for dysentery. Those of you old enough, and young enough, and Minnesotan enough, to have played the game Oregon Trail may recall members of your caravan dying of dysentery on the long journey west. 
(Image: MECC)

Dysentery is a diarrheal illness caused by bacteria called Shigella which are very similar to E. coli, and produce the same kind of toxin. 80 years after the discovery of the Shiga toxin that causes dysentery, researchers discovered the toxins in certain strains of E. coli, the STECs. Shiga toxins are toxic to the kinds of cells that line the intestines, causing damage to the lining. In the grand scheme of things, having a damaged intestinal wall doesn't seem all that terrible. You'll probably have a "stomach ache" and some diarrhea, albeit bloody which is not awesome. But you'll probably get better in a few days and be back to somewhat normal. But remember I said the STECs are the really bad guys. Sometimes an infection with STEC can lead to a complication called hemolytic uremic syndrome, or HUS. 

HUS is a disease that involves the kidneys, red blood cells, and platelets (cells that clot your blood). It most often affects young children and can cause severe illness and death. The two siblings I told you about at the beginning both developed HUS. This disease can also be caused by other bacterial infections, some viruses, medications, and other reasons. HUS occurs in about 5-10% of STEC infections. 

Somehow (researchers are still working this out), the toxins get out of the intestines where they are drawn to cells that produce what are called Gb3 receptors. A receptor is defined as "a region of tissue, or a molecule in a cell membrane, that responds specifically to a particular neurotransmitter, hormone, antigen, or other substance." Which I suppose is a fancy way of saying it's like an iPhone charger port. Your charger cord (Shiga toxin) only works for an iPhone port, and only a specific version of the iPhone port. Shiga toxins are able to bind (plug in) to Gb3 receptors. Kidneys have more Gb3 receptors than any other part of your body and kids' kidneys have more Gb3 receptors than adults. This is likely why kids are more likely to develop HUS due to an STEC infection than are adults. And also why HUS leads to kidney failure in up to 70% of patients. Some patients also have neurological symptoms like altered consciousness and seizures. The processes by which HUS causes kidney failure and other organ damage are complicated and I've already gone on for quite a long time spewing technical medical jargon so I'll spare you. Wikipedia has a pretty good page on HUS, as does Medscape, if you're so inclined. 

Treatment for HUS is largely supportive and may include dialysis while the kidneys recover. Treatment of the STEC infection with antibiotics is not generally recommended; there is some evidence to suggest that the bacteria release more toxins, leading to increased risk of HUS. Other evidence shows certain antibiotics may prevent HUS. More studies are needed. What we do know is that antibiotic treatment has little effect on the duration or severity of the gastrointestinal infection symptoms.

So what can you do? 
I talked about how STEC infections end up in the news when there is an outbreak of illness associated with contaminated food. I think most people of a certain age associate O157 with undercooked hamburger because of a large outbreak associated with eating hamburgers from a popular fast food restaurant called Jack In The Box. We know that undercooked meat can make us sick and we take steps to ensure that doesn't happen. What many people don't realize, however, is that cooking meat properly does nothing to stop contamination of the side salad from using the same cutting board or utensils for handling both raw meat and vegetables. 

People may also not be aware the same bacteria that can be found in hamburger meat can also be found in other foods like raw flour, lettuce and other leafy greens, sprouts, raw (unpasteurized) milk, and pretty much anything else that has come into contact with poop contaminated with STEC. STECs are found in the guts of ruminants like goats, sheep, deer, and cattle. These animals don't have any of the Gb3 receptors we talked about earlier, so they don't show symptoms. The bacteria are just living in the gut and hitch a ride out of the body on occasion in the animal's poop. You may have noticed cattle, goats, and others don't concern themselves with hygiene the way we humans do. They just poop and walk away. Sometimes the poop is a little loose and runs down a leg or splatters on an utter; sometimes they walk in it and spread it around on their hooves. Animals in fields, barns, large-scale feed lots, and petting zoos may take a snooze on a hot day and lay down in their own feces and the poo of their pals. The bacteria in the poop get transferred to the animal's hide. Then we head to the petting zoo and give that cute little animal a hug or a pet or a scratch. And if we're a little kid, we pretty much instantly put our hand in our mouth. Animals carrying STEC may graze near a field of lettuce, or that field of lettuce may be fertilized with cattle feces that hasn't been properly composted to reduce the numbers of bacteria. Insects, birds, and rodents can pick up STEC on their feet and transfer those bacteria to a field of wheat. 

I don't want to make it seem like there isn't anything you can do. There is! Following safe food handling guidelines and hand hygiene are the best ways to protect yourself and your family.
  • Never eat raw or undercooked ground beef and cook all meat thoroughly according to guidelines
  • Dedicate one cutting board and utensils for handling meat and another for vegetables
  • Wash cutting boards, utensils, and counters after handling raw meat
  • Don't eat raw or undercooked dough
  • Wash your hands before cooking, after handling raw meat, and before you eat
  • Wash your hands and your children's hands when at a petting zoo or fair or carnival or any other place where you have encountered and touched animals and their surroundings
  • Wash your hands after handling dirty diapers and helping kids use the bathroom
  • Avoid swallowing water in lakes, streams, ponds, swimming pools, and splash pads
I hope I didn't freak you out too much. Be safe and have a happy summer!

Saturday, January 14, 2017

Pan-resistant does not mean "resistant to sauce pans"

Well this is it folks, the end of days is nigh. The Centers for Disease Control and Prevention (CDC) put out a report in the Morbidity and Mortality Weekly Report (MMWR) yesterday. "Notes from the Field: Pan-Resistant New Delhi Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae — Washoe County, Nevada, 2016" tells the tale of a particularly scary kind of bacteria. This is the kind of bacteria that is the impetus for the title of my blog, Death by UTI. New Delhi Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae is a flavor of carbapenem-resistant Enterobacteriaceae. Let's back up a step or two shall we?

Enterobacteriaceae (entero-bact-ear-E-A-C-A) are a large family of bacteria that live in the guts of mammals, including humans. You probably have heard of Escherichia coli, or E. coli right? E. coli is a member of the Enterobacteriaceae family along with K. pneumoniae and a whole host of others. They all live in the gut happily breaking down food components for their use and ours. Sometimes the byproducts of bacterial munching are not so welcome, like gas. But we all fart and that's just the way it is. These bacteria living in our guts are not out to harm us, but occasionally they wind up in areas they shouldn't. Such as the urethra and bladder where the result might be a urinary tract infection. Or the bloodstream where the result might be death. Antibiotics used to be able to readily kill these bacteria, curing infections and allowing us all to live to ripe old ages. But this family of bacteria living in our guts is very good at developing resistance to the antibiotics we throw at it. Resistance means that the bacteria have ways of living in the face of the antibiotics that intend to kill them. It's all very Hunger Games.

Carbapenem-resistant Enterobacteriaceae, or CRE, are those members of the family that are resistant to carbapenem antibiotics. The carbapenem antibiotics were introduced relatively recently for the treatment of infections caused by Enterobacteriaceae that are resistant to a bunch of other antibiotics. CRE have several different ways to resist carbapenems. They change the walls of their cells so that the antibiotic can't get in. Or they turn on pumps that flush the antibiotic back out once it has entered, like a teeny tiny sump pump. They also produce enzymes (macromolecules that accelerate chemical reactions) that break down the structure of the antibiotic rendering it useless. It's these darn enzymes that are such a worry.

A beta-lactamase is a type of enzyme (you can always recognize an enzyme by the -ase at the end of its name) that breaks down beta-lactam antibiotics such as penicillin. Specifically, bacteria release the enzyme into the space around their cells. The enzyme then cleaves the beta-lactam ring in the antibiotic's molecule, its basic structure. Once that ring is cleaved, the antibiotic molecule no longer holds its shape and is not able to bind to the bacterial cell wall. Success! For the bacteria that is. For humans, this is bad news. If the antibiotic doesn't work, the infection is less likely to go away. Your body's natural defenses will do what they can, but it might not be enough. There are many different beta-lactamase enzymes that are active against various beta-lactam antibiotics. Beta-lactamases that are active against carbapenems are called carbapenemases. These enzymes also are active against all of the older beta-lactam antibiotics. As if this weren't bad enough, here comes the super scary part: bacteria share with each other. Friendly little buggers. If one bacterium learns how to make these enzymes (meaning that they have genes that code for them) they can pass that information on to their children through their DNA. What makes these beta-lactamases, particularly the carbapenemases, so terrifying is that the genes that code for them are often located on plasmids. Plasmids are bits of DNA that are free-floating, that is to say that they aren't attached to the DNA strands. They are free to move about and transfer to other bacteria, including those that aren't even the same species. So an E. coli can share its genetic information with a K. pneumoniae or another member of the Enterobacteriaceae family. Beatrice the Biologist (who I adore with my whole heart) shows us just how happily these bacteria share their genetic info.
When you consider the bacterial stew that is the human gut, you begin to understand how troublesome this is. Bacteria are constantly bumping up against one another. Kind of like a crowded dance floor. Remember this.

New Delhi-Metallo-Beta-Lactamase, or NDM, is a kind of carbapenemase that is so-called for two reasons: 1. The first reported case of this enzyme was from an infection in a patient who had received health care in New Delhi, India and 2. This enzyme requires the metal zinc in order to do its job, hence "metallo." The first case was reported in 2009 and since then, NDM has spread across the globe and into the United States. Most of the cases in the U.S. have been patients that have lived in and/or received significant health care in areas where NDM is endemic, such as India, Pakistan, and Bangladesh. However, there have been reports of outbreaks of infection or colonization with NDM-producing CRE that have been associated with medical procedures in the U.S. like in Illinois, Colorado, and others. NDM is of particular concern because the genetic info that codes for the enzyme is located on a promiscuous plasmid, one that quite readily passes from one bacterium to another. Picture that crowded dance floor. One bacterium bumps into another: "Hey man, it's been a long time! So good to see you, how are the kids? Great. Say, you want a resistance gene? It's a good one. Yeah, you'll be resistant to so many antibiotics! Here you go pal!" Or that's how I assume it goes down.

Okay, that was a LOT of information. My apologies, but this is an extremely complicated topic. Thanks for sticking with it. Let's get back to the story at hand.

The report in yesterday's MMWR refers to a patient that developed an infection caused by a strain of NDM-producing K. pneumoniae that was "pan-resistant." That means resistant to ALL available antibiotics. Every. Single. Antibiotic. Even the really old, not-often-used-because-they-are-so-toxic antibiotics. The good news is pan-resistance is exceedingly rare in the U.S. The bad news is that we fear that it will become more common. New antibiotics don't come around often and when they do are frequently just slightly different versions of old antibiotics. For example, we are now up to the 5th generation of a particular group of antibiotics called cephalosporins because bacteria have developed resistance to the 1st, 2nd, 3rd, and 4th generations. You see, bacteria develop resistance to our "new" antibiotics as soon we start using them. It's a war that we are losing. A war that suggests we need to change tactics, but that's a story for another time.

The patient at the heart of yesterday's MMWR unfortunately lost her life. The Center for Infectious Disease Research and Policy (CIDRAP) ran a piece on this case that delves a bit deeper than the MMWR report itself. Now I need you to understand that pan-resistance is a HUGE deal and exceedingly scary. Physicians and pharmacists can attempt to treat an infection caused by such bacteria by combining different antibiotics and using higher doses in the hopes that they will be able to fight off the bacteria. This can and does work, but not always and not without serious consequences. Antibiotics are NOT benign drugs. They are medications that can have major side effects and adverse events like Clostridium difficile diarrheal infection, permanent disabling issues involving tendons, muscles, joints, nerves, and the central nervous system, and neurological problems. This patient had an infection with NDM-producing bacteria and we talked about how promiscuous the plasmid is that carries the genetic information for NDM. Once the hospital was notified of this infection the patient was placed on Contact Precautions and there were studies done to determine if transmission occurred. Had this bacteria spread to any patients that had been roommates of the case or were hospitalized on the same floor prior to Contact Precautions having been implemented? Thankfully, no transmission was found to have happened.

So what can you do?
Be mindful of antibiotics.
1. Don't demand or take antibiotics for viral infections like colds, acute bronchitis, and sore throats. Antibiotics don't work against viruses, all they do is kill off regular bacteria and leave the resistant ones behind to take over.
2. When you do have a bacterial infection and are prescribed antibiotics, take the WHOLE dose. Don't save some for another time and don't share antibiotics with friends and family.

Be aware of the risk factors for infections caused by CRE. This list is not all inclusive.
1. Hospitalizations or surgery in the last year
2. Residing in nursing homes or long-term acute care hospitals in the last year
3. Indwelling devices like urinary catheters (more of a short-term risk, unless you are chronically catheterized)
4. Exposure to antibiotics in the last year
5. Receipt of health care in an area in which CRE is endemic

It is no guarantee that if you have one of the above risk factors you will get an infection with CRE. It just means that you have a higher risk than people who don't have any of the above risk factors.

CRE and other antibiotic-resistant infections are more common in people who have significant health care exposures, but none of us are immune. The thing to remember here is that antibiotics are a shared resource. Use in one person may cause resistance only in that person's bacteria, but when that bacteria spread to someone else it becomes a much bigger problem. We are on the brink of a post-antibiotic era.

Cue the ominous music.