2019 microbiology columns - Healthcare Hygiene magazine

KPC: The Beginning of the End?

By Rodney E. Rohde, PhD, MS, SM(ASCP)CM SVCM, MBCM, FACSc

This column originally appeared in the November 2019 issue of Healthcare Hygiene magazine.

First appearing in the United States in the late 1990s, Klebsiella pneumoniae carbapenemase (KPCs)-producing bacteria have spread rapidly across hospitals and long-term care facilities in many countries. KPC-producing K. pneumoniae is by far the most commonly encountered carbapenem-resistant Enterobacteriaceae (CRE) species.

KPC-producing bacteria are a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality. With the rapid increase of infections caused by this microbe, they are now referred collectively as carbapenemase-producing Enterobacteriaceae (CPE) but one may see different acronyms – E. coli and K. pneumoniae are the primary pathogens. The type of carbapenemase enzyme detected in carbapenemase-producing Enterobacteriaceae isolates (e.g. KPC, Metallo-beta-lactamases [MBL], carbapenem-hydrolysing oxacillinase-48 [OXA-48], etc.) is a complex discussion that will not be the focus of this article. As Ambretti, et al. (2019) state, the relationship between CRE and CPE is one of broad but not complete overlapping, since most but not all CRE are CPE and vice versa. In fact, some CRE are not CPE and some CPE are not. However, these differences are important to understand with respect to diagnostics, treatment, prevention, and epidemiology.

Enterobacteriaceae, namely Escherichia coli and Klebsiella pneumoniae, are the most common human pathogens, causing infections that range from cystitis to pyelonephritis, septicemia, pneumonia, peritonitis and meningitis. The other Enterobacteriaceae causing infections in humans include Citrobacter species, Enterobacter species, Serratia marcescens, Proteus spp., and Providencia spp. These organisms persist and spread rapidly in healthcare settings by hand carriage as well as contaminated food and water. In common language, they are Enterics (gut-associated bacteria) and can be found virtually everyone, on every surface in a healthcare and community environment.

Several factors increase the risk of colonization and infection with CPE. Risk factors for CPE infection include severe underlying illness, prolonged hospital stay, the presence of invasive medical devices, and antibiotic use.

CPE infections are difficult to treat, since CPE are resistant to virtually all beta-lactam antibiotics and often contain additional mechanisms of resistance against second-line antibiotics such as aminoglycoside and fluoroquinolones. Studies have also shown emerging resistance to antibiotics of last resort (i.e., tigecycline or colistin), leaving very few therapeutic options. Certainly, we know selective pressure from colistin use is a major factor that drives resistance to this agent, as has also been shown for colistin resistance in other pathogens. It is not surprising with the surge of colistin use for CPE in hospitals during the global transmission of the agent.

Colistin resistance can emerge rather quickly once KPC-producing K. pneumoniae is utilized in healthcare and/or long-term care environments, and colistin is used to treat. Then, colistin-resistant, KPC-producing K. pneumoniae may directly colonize or infect patients who are not colonized with the colistin-susceptible counterparts, at least in the setting of ongoing selective pressure from high-level colistin use. This leads us to another set of questions. If susceptibility to colistin cannot be assumed, should clinical microbiology laboratories consider performing susceptibility testing of the isolates for colistin for all patients who receive this agent, instead of just those who are colistin experienced? In addition, from an infection prevention perspective, should patients colonized or infected with colistin-resistant strains be grouped (or isolated) from patients with colistin-susceptible strains?

CPE have been associated with adverse clinical and economic outcomes, including increased mortality, increased length of stay, delay in the institution of effective therapy, decreased functional status on discharge, and increased cost of health care. It is imperative that risk factors for infection with these organisms are clearly identified so that effective strategies can be developed to curtail the emergence and spread of these strains.

CPE and other resistant pathogens continually beg the question – have we reached the post-antibiotic era? CPE have developed the ability to become resistant to last-resort powerful antimicrobials known as carbapenems, which makes them more challenging to treat if they go on to cause infection. CPE are bacteria that are carried in the gut and are resistant to most, and sometimes all, available antibiotics.

CPE is shed in feces and transmitted by direct and indirect contact. A period of four weeks or more may elapse between that contact that results in acquisition of the organism and the time at which CPE becomes detectable in the sample. If CPE stays in the gut, it is mostly harmless. However, if it spreads to the urine or blood it can be fatal. And, for those of us who know about contamination and environmental surfaces in healthcare, this becomes especially concerning. It has been reported that more than half of all patients who develop blood stream infections with CPE die because of their infection. Many believe that of all the superbugs seen, CPE is the hardest to kill. Is this the end for antibiotics?

Rodney E. Rohde, PhD, MS, SM(ASCP)CM SVCM, MBCM, FACSc, serves as chair and professor of the Clinical Laboratory Science Program at Texas State; associate director for the Translational Health Research Initiative; as well as associate dean for research in the College of Health Professions. Follow him on Twitter @RodneyRohde / @TXST_CLS, or on his website: http://rodneyerohde.wp.txstate.edu/

HAIs: Everything Changes When It Happens to You

By Rodney E. Rohde, PhD, MS, SM(ASCP)CM SVCM, MBCM, FACSc

This column originally appeared in the November 2019 issue of Healthcare Hygiene magazine.

The Centers for Disease Control and Prevention (CDC) estimates that on any given day, 1 in 25 hospital patients get a healthcare-acquired infection (HAI). Research suggests that a growing number of HAIs are caused by pathogens that are outsmarting the antimicrobials typically used to fight them. These are known as antibiotic resistant germs, sometimes referred to as superbugs.

HAI and antimicrobial resistance (AMR), in my professional opinion, is one of the most critical public health and healthcare issues of the 21st century. They have devastating effects on physical, mental/emotional, and financial health. In addition, they cost billions of dollars in added expenses to the healthcare system. The World Health Organization (WHO) predicts that by 2050, AMR will have a $100 trillion economic impact globally as a mortality of 10 million people. If one does the math, this means that approximately one new AMR infection will occur every three seconds! At this pace, AMR/HAIs will surpass cancer as the No. 1 killer by 2050.

When I answered the phone at home one evening in late December 2007 and heard the voice of a worried woman, the genesis of an idea for my future research path began to take shape. She was concerned about her husband, she said. The retired Utah couple had traveled over the holidays and the husband, a cancer patient, developed sores on his torso. They went to the emergency room, where a doctor diagnosed a staph infection and prescribed antibiotics but ordered no lab tests. The man’s condition worsened, so he went to his family doctor. After an examination and some laboratory tests, the doctor determined that the man had methicillin-resistant Staphylococcus aureus (MRSA) — an infection that cannot be treated with most typical antibiotics. Studies show that about 1 in 3 (33 percent) people carry S. aureus bacteria in their nose, usually without any illness and approximately 5 percent of patients in U.S. hospitals carry MRSA in their nose or on their skin.

I remember it like yesterday – such a vivid reminder of the confusion, concern, and plight of these individuals dealing with such a difficult healthcare problem. The wife of the patient from Utah had some basic knowledge about MRSA from media coverage and she was very concerned about what had happened to her husband at the emergency room given his immunocompromised state because of the cancer. She just wanted to know why this had happened and whether she or anyone else they had been in contact with should be concerned about transmission.

MRSA first emerged as a serious infectious threat in the late 1960s as the bacterium developed resistance to penicillin. Vancomycin has been used as treatment for MRSA, but now even vancomycin-resistant strains are emerging. Although the Staphylococci bacteria, including MRSA, commonly colonize the skin of healthy people, often posing little to no threat, these bugs are quick to exploit any opportunity to invade wounds, nasal passageways, or mucosal membranes where they can rapidly produce infections that can become life threatening.

Fortunately, we are doing better in the war on HAIs. Progress in the latest report is based on information from the National Healthcare Safety Network (NHSN) on central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), surgical site infections (SSIs), methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections, and Clostridioides difficile events. Nationally, among acute-care hospitals between 2016 and 2017, report highlights include:

About 9% decrease in CLABSIs
About 5% decrease in CAUTIs
About 3% decrease in VAEs
No significant changes in abdominal hysterectomy SSIs
No significant changes in colon surgery SSIs
About 8% decrease in MRSA bacteremia
About 13% decrease in C. difficile infections
Concerning HAIs like MRSA, I feel particularly dedicated because of my interaction with the people I’ve interviewed and advised (including my family and friends). It is with this knowledge that I often tell my students (future medical laboratorians and nurses), family, and public that if you do nothing else when a physician or other healthcare worker prescribes you an antibiotic empirically or tells you it’s “just a regular staph infection,” be sure to demand a culture/ID and antibiotic susceptibility test. It just may save your life or that of a loved one.

We can and must be better. If not, we all fail. We fail ourselves. We fail each other. And, we especially fail those patients who need our voice and advocacy – even those who don’t know what questions to ask!

Sitting at the Intersection of Microbes and Surfaces
By Rodney E. Rohde, PhD, MS, SM(ASCP)CM SVCM, MBCM, FACSc

This column, Under the Microscope, originally appeared in the October 2019 issue of Healthcare Hygiene magazine.

It is my honor to join Healthcare Hygiene magazine as the expert columnist for “Under the Microscope.” In the coming months, this column will explore the imperatives relating to microbiology and its importance and application in the real-world healthcare environment, especially as it relates to surfaces, and the roles they play in pathogen transfer. I will also feature a monthly microbe on the growing list of deadly antimicrobial resistant microbes.

This past week, I received my weekly phone call from my parents. My dad is a retired railroad conductor who is from the #GreatestGeneration. He is one of the strongest people I know. My brother, sister and I grew up hearing him often say to us, “I don’t have time to be sick,” as he headed out on another train trip. Like many of us, our parents are our heroes.

We think of them as being invincible – until they are not.

Being a railroad conductor was a great career for my father. In my hometown of Smithville, Texas, most men wanted the job because it provided a strong and steady income for a family. It allowed my mom to be a stay at home mother who raised the three of us – also a full-time job! A railroad conductor is the boss of the train, not the engineer. Dad worked when there was still a caboose at the back of the train and I still remember the vivid stories of him telling us about “jumping on and off” of the caboose to walk the train for inspection. Unfortunately, those long walks past hundreds of railway cars meant that he was often walking at odd angles in hard rock. Well, thirty plus years of doing that wore out his knees and his ankles.

Finally, it became too much to bear and he received a medical retirement in his late 50s. A great career, yet, one that took a terrible toll on his body. Last night, dad called to let me know that one of his feet had been bothering him again. What started as a small “corn” on one of his feet opened up and started draining blood. For my father, he knows what this means, as he has had one knee replacement and multiple surgeries on both ankles to fuse bones with screws and pins.

He has now become my student with respect to trying to understand what the difference is between “regular staph infections versus #MRSA.” Dad has been in and out of the hospital the past several years receiving everything from incision and drainage procedures to full-blown surgery to remove an infected toe, tissue and bone. Likewise, he has become all too familiar with oral versus IV antibiotics from multiple classes of antimicrobials. Finally, he and mom have had long discussions with me about infection control and prevention in the healthcare and home/community setting because all #SurfacesMatter in the new post-antibiotic world of #superbugs and #antibioticresistance (#amr). It saddens me to see the confusion and sometimes surrender on their faces due to “another infection.”

While I cannot prove it, my professional opinion as an infectious disease microbiologist and medical laboratory professional leads me to believe that his problems started with the various metal components inserted into my dad’s knee and/or feet years ago – you see, ALL surfaces matter ALL the time.

Staphylococcus skin infections and the emergence of methicillin-resistant Staphylococcus aureus (MRSA) are a major health concern. Staphylococcus aureus and other species are typical normal flora for human skin. For the average person, this means that you have bacteria growing on your body and it is normal. That is what normal flora means. It grows on/in you and often can be a symbiotic (healthy) relationship. However, complications can arise if the bacteria enter the host through breaks in the skin. Whether exposure leads to infection depends on several factors: bacterial virulence; overall host status; amount of exposure or infectious dose; and the time of exposure as longer exposures increase the chance that bacteria will gain entry. Should entry occur and the host's immune system overwhelmed, symptoms can range from a minor skin infection to serious systemic infection. In some cases, severe infection can result in death.

MRSA first emerged as a serious infectious threat in the late 1960s as the bacterium developed resistance to the synthetic form of penicillin known as methicillin. In fact, even the discoverer of the miracle drug penicillin in 1928, Alexander Fleming, observed resistance to his wonder drug and warned society in the 20th century. Unfortunately, we did not listen.

Although the Staphylococci bacteria, including MRSA, commonly colonize the skin of healthy people, often posing little to no threat, these bugs are quick to exploit any opportunity to invade wounds, nasal passageways, or mucosal membranes where they can rapidly produce infections that can become life threatening. It is not surprising then, that MRSA has been the focus of intense scientific and political interest around the world and has frequently been labeled as a superbug in the popular media.

This tiny, microscopic organism is just one of many that have become resistant to commonly prescribed antibiotics. It can also remain viable for extended periods of time on different surfaces in the community and healthcare environment.
A perfect storm waiting for its next unaware victim, like my dad.

Join me in the coming months as I begin to show you what’s behind the curtain and Under the Microscope with respect to these deadly and often hidden microbes that can take a terrible toll on us and our loved ones.

Rodney E. Rohde, PhD, MS, SM(ASCP)CM SVCM, MBCM, FACSc, serves as chair and professor of the Clinical Laboratory Science Program at Texas State; associate director for the Translational Health Research Initiative; as well as associate dean for research in the College of Health Professions. He also is a member of the board of directors of the Healthcare Surfaces Institute. Follow him on Twitter @RodneyRohde /@TXST_CLS, or on his website: http://rodneyerohde.wp.txstate.edu/