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.
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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