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The Tale Of A Proteus Down On Its Luck And Its Struggle To Beat The Odds
Tim Davis, MT (ASCP), *Angela Jackson, MT (ASCP) , Frances Williams, MT (ASCP) SM, Michelle Dillard, MHS, MT (ASCP) , James G Traylor, Jr., MD, Christopher Burdick, MD
INTRODUCTION
Carbapenems such as imipenem,
ertapenem, and meropenem are
important antimicrobial agents that are
used in serious infections (mixed
bacterial infections) when the
organisms are resistant to the primary
antibiotic of choice. Developing
resistance to the carbapenam family
can have a negative impact on the
outcome of a patient, leaving the
physician with fewer choices for
treatment. Although rare, the
emergence of resistance to this drug
class is becoming an important factor in
the clinical microbiology laboratory for
the purposes of monitoring and
reporting.
Resistance to carbapenems can occur
through enzymes that hydrolyze the
antimicrobial agent or through porin
changes of the microbe that don’t allow
the drug to enter.
Klebsiella pneumoniae carbapenemase
(KPC) is a beta-lactamase enzyme that
acts to destroy the carbapenem family
of drugs. This enzyme is encoded by
the KPC gene which can be passed
through plasmids or mutations of an
already existing beta-lactamase gene.
(Jean Patel, CDC, 2008 ASM)
The KPC gene was first detected in
Klebsiella pneumoniae, but is now
being detected in other gram negative
rods including Klebsiella oxytoca,
Enterobacter spp., E. coli, and others.
Although molecular tests using PCR
can be confirmatory, the Modified
Hodge Test can be used to quickly
identify the KPC enzyme phenotypically
with 100% sensitivity and variable
specificity. (Hindler, Janet, ASM 2008)
LAB RESULTS
CASE
A 29 y/o female with a history of diabetes
mellitus, hypothyroidism, chronic
secretory diarrhea, and occasional
abdominal pain was admitted to LSUHSCShreveport. An exploratory laporatomy
was performed for reduction of a small
bowel volvulus. Two months later an
exploratory laporatomy was performed
with a biopsy of the peripancreatin lymph
nodes and an excisional biopsy of a lower
quadrant abdominal mass. She was
diagnosed with G cell hyperplasia with
chronic diarrhea. During her hospital stay,
she also developed GI bleeds and acute
renal failure. She was on numerous
antibiotics including clindamycin, araxis,
fluconazole, linezolid, and others
eventually leading to an episode of
Clostridium difficile. Our lab identified a
unique Proteus mirabilis from a
catheterized urine that was resistant to
imipenem.
Proteus mirabilis is a gram negative rod
in the Enterobacteriacae family which is
part of the normal gut flora. Proteus
mirabilis causes 4 to 6% of community
aquired UTIs and 3 to 6% of nosocomial
infections including pyelonephritis.
Important Points*
KPC is NOT adequately detected by automated
systems (Vitek, Microscan, etc)
Screening methods (Chromagar KPC, Modified
Hodge Test) should be followed by molecular tests
Etest can sometimes be difficult to interpret
*Ronald M. Baker, MS, MT (ASCP); DOH Ann Meet
FL
Microscan Walkaway 96 SI
Patient’s Proteus mirabilis
ID: 99.99% Proteus Mirabilis Biotype
40061404
Drug
Ampicillin
Amox/K Clav
Amp/Sulbactam
Pip/Tazo
Ticar/K Clav
Cefazolin
Cephalothin
Cefuroxime
Ceftazidime
Drug
Ceftriaxone
Cefepime
Aztreonam
Imipenem
Amikacin
Genamicin
Tobramycin
Ciprofloxacin
Trimeth/Sulfa
Nitrofurantoin
MIC
4
<=8/4
<=8/4
<=16
<=16
<=8
<=8
8
<=2
MIC
<=8
<=8
<=8
>8
<=16
<=1
<=1
<=1
<=2/38
>64
Interps
S
S
S
S
S
S
S
S
S
Interps
S
S
S
R
S
S
S
S
S
R
RED FLAG – IMEPENEM RESISTANT
Is it a SWARMER??
A possibility for the unusual MIC
could be that the Proteus isolate
had a swarming phenotype.
However, as you can see on this
blood agar, it did NOT.
A Modified Hodge test
(or “clover-leaf” test) is a generic name
for a test for resistance using a fullysusceptible reference strain (lacking the
enzyme for resistance) as a background
with a streak of the test organism
towards an antibiotic disk.
KPC pos
Modified Hodge Test
for Carbapenemase
E = ertapenem disk
Streak lawn
of E.coli
KPC neg
MIC Confirmation
ATCC 25922
We confirmed the imipenem
result with an E test. The isolate
was resistant to imipenem (>16
ug/ml), but susceptible (<= 4
ug/ml) to meropenem and
ertapenem (CLSI).
Streak
organisms
disk to
edge
Streak organism
E
from disk to edge
KPC pos
Patient
Ertapenem
0.5 ug/ml
Lawn of E.coli
KPC pos
KPC neg
CONCLUSIONS
 Patient remains in hospital - out of ICU
 Currently on antibiotics for bacteremia
 Specimen has been sent to the CDC
per Dr. Patel’s request
 Specimen was resistant to imipenem,
but did not exhibit an expected KPC
drug susceptibility pattern (below)
KPC neg
Dr. Patel’s Guidelines for KPC Detection
E
E-test
Carbapenems
Proteus
Meropenem
0.032 ug/ml
If Enterobacteraciaceae “R” to
cefotaxime, ceftriaxone,
ceftazidime
Patient neg
Imipenem
> 32 ug/ml
If MIC is >/= 2 for ertapenem and/or
meropenem and/or imipenem
The Proteus mirabilis was sent to
two different reference labs for:
KPC pos
KPC neg
1. KPC PCR
2. Modified Hodge Test
Perform a Modified Hodge Test
Presumptive ID of KPC
Results: All NEGATIVE for KPC
Patient neg
After receiving a KPC positive
strain, a modified Hodge test was
performed by our lab.
“This is a very strange bug.”
– quote from
Paul H. Edelstein, MD