Healthcare Hygiene magazine December 2019 | Page 8

under the microscope By Rodney E. Rohde, PhD, MS, SM(ASCP)CM SVCM, MBCM, FACSc KPC: The Beginning of the End? F irst appearing in the United States in the late 1990s, Klebsiella pneumoniae carbapenemase (KPCs)-pro- ducing 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 as- sociated 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 carbap- enemase-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. 8 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 healthcare. 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/ december 2019 • www.healthcarehygienemagazine.com