Advances in Infectious Diseases, 2013, 3, 219-222
http://dx.doi.org/10.4236/aid.2013.33032 Published Online September 2013 (http://www.scirp.org/journal/aid)
219
A Case of Carbapenem Resistant Non-K1/K2 Serotype
Klebsiella pneumoniae Liver Abscess
Lucy Cheng1, Leung Kristopher Siu2, Tom Chiang1,3
1Department of Medicine, Rutgers New Jersey Medical School, Newark, USA; 2Institute of Infectious Diseases and Vaccinology,
National Health Research Institutes, Miaoli, Taiwan; 3Division of Infectious Disease, Veterans Affairs New Jersey Health Care Sys-
tem, East Orange, USA.
Received July 30th, 2013; revised August 15th, 2013; accepted August 20th, 2013
Copyright © 2013 Lucy Cheng et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Klebsiella pneumoniae liver abscess (KPLA) has been described as an invasive syndrome with extrahepatic complica-
tions. The majority of KPLA is caused by capsular serotype K1 and K2 isolates. We report a case of carbapenem resis-
tant Klebsiella pneumoniae liver abscess. The patient initially presented with infected right above-the-knee amputation
and was later found with a large liver abscess. Initial antimicrobial susceptibility showed carbapenem resistant K. pneu-
moniae (CRKP). Further molecular workup revealed that the isolate was a less virulent non-K1/K2 serotype, and both
rmpA and kfu genes were negative. The lack of outer membrane porins likely contributed to the carbapenem resistance.
To our knowledge, this is a first reported case of carbapenem resistant, non-K1/K2 serotype K. pneumoniae liver ab-
scess in the United States.
Keywords: Liver Abscess; Klebsiella pneumoniae; Capsular Serotype; Carbapenem Resistance
1. Introduction
Klebsiella pneumoniae liver abscess (KPLA) has been
described as an invasive syndrome with extrahepatic
complications via hematologic spread. The hypermu-
coviscosity phenotype and capsular serotype (K1 and K2)
are the major virulence factors, along with capsular
polysaccharide synthesis regulator gene rmpA, iron che-
lator aerobactin, and iron uptake gene kfu, which have
been described to contribute to the virulence and invasive
features of K. pneumoniae [1-3]. To our knowledge, we
describe the first case of non-K1/K2 KPLA in the United
States.
2. Case Report
A 64-year-old African American man presented to the
Veterans Affairs New Jersey Healthcare System with an
infected right above-the-knee amputation (AKA). The
patient’s hospital course was complicated by poor wound
healing, wound debridement, revision of the AKA, and a
urinary tract infection with Pseudomonas aeruginosa and
Klebsiella pneumoniae, for which he was treated with
doripenem. After one and a half month of hospitalization,
the right AKA began to heal appropriately. On hospital
day 49, the patient developed transient right upper quad-
rant abdominal pain. He then developed intermittent fe-
vers ranging from 100.7˚F to 101˚F, however fever
workup including blood and urine cultures, as well as
chest X-ray were negative. The patient did not have any
further physical complaints and remained hemodynami-
cally stable.
On hospital day 57, the patient was febrile (tempera-
ture, 102˚F), with a heart rate of 121 beats per minute
and blood pressure of 155/77 mm·Hg. The physical ex-
amination was unremarkable including normal thoracic
and abdominal findings. The white cell count was 19,600
cell/μL with 90 percent neutrophils; the hemoglobin level
was 8.5 g/dL, and the platelet count was 377,000 cell/μL.
The aspartate aminotransferase and alanine aminotrans-
ferase were mildly elevated, 38 IU/L and 51 IU/L, re-
spectively. The total bilirubin level was 0.6 mg/dL. A
computerized axial tomography scan of the thorax and
abdomen showed a large loculated abscess in the right
lobe of the liver and intrahepatic biliary ductal dilatation
(Figure 1). Piperacillin-tazobactam was started empiri-
cally, and the patient underwent fine-needle aspiration of
the liver abscess and pigtail placement by interventional
radiology. Culture of the liver abscess grew carbapenem

A Case of Carbapenem Resistant Non-K1/K2 Serotype Klebsiella pneumoniae Liver Abscess 220
resistant Klebsiella pneumoniae (CRKP), which prompted
change of antibiotic therapy to tigecycline. Follow up
computerized axial tomography of the abdomen at the
end of two week treatment showed significantly dimin-
ished liver abscess. However, there was communication
between the abscess and the gallbladder. The patient un-
derwent laparoscopic cholecystectomy. He remained
asymptomatic and was discharged to a nursing home.
Antimicrobial susceptibility of the CRKP isolate was
determined by using the broth microdilution test [4], ex-
cept for that of ertapenem, which was determined by
E-test strip. MICs are as follows: ceftazidime, >128
μg/mL; ceftriaxone, 128 μg/mL; cefepime, >16 μg/mL;
ciprofloxacin, >2 μg/mL; gentamicin, 16 μg/mL; ertap-
enem, 6 μg/mL; imipenem, 1 μg/mL; and meropenem,
<1 μg/mL. Capsular serotyping of the isolate was per-
formed as previously described [5,6], and it was a
non-K1/K2 serotype. Serum bactericidal assay [7], neu-
trophil phagocytosis [8,9], and mice lethality studies
were performed. All animal care procedures and proto-
cols were approved by the Institutional Animal Care and
Use Committee of the National Health Research Institute
(NHRI-IACUC-096004-A). Susceptibility to serum kill-
ing and neutrophil phagocytosis, and LD50 ≥ 1 × 107
CFU were consistent with the less virulent non-K1/K2
serotype. The colonies were phenotypically mucoid but
string test negative.
Polymerase chain reaction (PCR) for rmpA, kfu, aero-
bactin, SHV β-lactamase, and K. pneumoniae carbap-
enemase (KPC) genes were performed as previously de-
scribed [10]. rmpA, aerobactin, and kfu genes were not
present in the isolate. SHV-11 and SHV-12 genes were
detected. The KPC gene was not detected. The outer
membrane porins (OMPs) were isolated according to the
rapid procedure of Chen et al. [11]. OMPs were extracted
with sodium lauroylsarcosinate (Sigma) and recovered
by ultracentrifugation as described previously [12]. The
OMP profiles were determined by sodium dodecyl sul-
Figure 1. Computerized axial tomography of the abdomen
showed a loculated abscess in the right lobe of the liver.
phate-polyacrylamide gel electrophoresis (SDS-PAGE)
using 12% SDS gels and were visualized by Coomassie
blue staining (Figure 2). Neither OmpK35 nor OmpK36
were present.
Pulsed-field gel electrophoresis (PFGE) and multilo-
cus sequence typing (MLST) of the CRKP isolate and
two other known KPC positive CRKP isolates from the
same institution were done as previously described
[13-17] (Figure 3). Sequence type (ST) 258 was identi-
fied in all three isolates.
3. Discussion
In the past two decades, Klebsiella pneumoniae has be-
come the primary cause of liver abscess in Southeast
Asia, including South Korea and Taiwan [18]. There is
also increasing incidence in North America with the ma-
jority of patients being of Asian descent [19,20]. KPLA
has been described as an invasive syndrome as it can
cause extrahepatic complications via hematologic spread.
The major virulence factors in KPLA are the hyper-
mucoviscosity phenotype and capsular serotype (K1 and
K2). The presence of hypermucoviscosity is confirmed
by a positive string test. Isolates of capsular serotype
K1/K2 are the most prevalent serotypes found in KPLA,
accounting for more than seventy percent of liver abscess
strains reported [1-3]. There have been several case re-
ports of confirmed K1 and K2 serotype liver abscesses in
the United States [21,22]. Due to impaired neutrophil
phagocytosis, K1/K2 serotypes are found exclusively in
disseminated cases [18]. Other virulence factors, such as
capsular polysaccharide synthesis regulator gene rmpA,
iron chelator aerobactin, and iron uptake gene kfu, have
been described to contribute to the virulence and invasive
features of K. pn eumoniae . Even though isolates of
non-K1/K2 serotypes are less virulent, the presence of
hypermucoviscosity phenotype, rmpA, aerobactin, and
kfu genes in these isolates make them capable of causing
13883 CRKP J220 M594
OmpK35
OmpK36
Figure 2. Outer membrane profiles of the case CRKP iso-
late and two other known CRKP isolates from the same
institution, J220 and M594. Lane 1, ATCC13883, is the
control strain with only intrinsic resistance to ampicillin.
Neither OmpK35 nor OmpK36 are presented in the case
isolate.

A Case of Carbapenem Resistant Non-K1/K2 Serotype Klebsiella pneumoniae Liver Abscess 221
Figure 3. Pulsed-field gel electrophoresis of the case CRKP
isolate and two other known CRKP isolates. All three iso-
lates are clonally related.
liver abscesses [1]. However, these virulent factors were
not present in the case isolate. To our knowledge, there
has not been a case of nosocomial liver abscess caused
by a non-K1/K2 serotype K. pneumoniae reported in the
United States.
Cephalosporin or combination therapy has been used
to treat KPLA. Liver abscesses caused by extended spec-
trum β-lactamase (ESBL)-producing K. pneumoniae are
uncommon [18]. Carbapenems are the antibiotic main-
stay of treatment for organisms harboring ESBLs.
However, with the emergence of CRKP and particu-
larly the epidemic in the northeastern United States,
treatment options are limited to colistin and tigecycline
[23]. Both β-lactamase genes, SHV-11 and SHV-12,
were identified in the case isolate. PFGE and MLST of
the case isolate and two known KPC positive CRKP iso-
lates from the same institution showed that the isolates
are clonally related, with all three isolates displaying
sequence type 258. The KPC gene however, was not de-
tected in the case isolate. We suspect that it may have
been lost due to plasmid instability during storage. Our
patient received two weeks of tigecycline, however his
uneventful recovery was largely due to mechanical re-
moval of the liver abscess via percutaneous drainage.
In addition to the production of carbapenemase, defi-
ciency in outer membrane porins has been proposed to
increase carbapenem resistance [24]. Most ESBL-pro-
ducing K. pneumoniae strains have only OmpK36,
whereas the majority of non-ESBL-producing K. pneu-
moniae have both OmpK35 and OmpK36. As with our
case isolate, mutant strains with double deletion of
OmpK35 and OmpK36 have been found to have in-
creased antimicrobial resistance but decreased virulence
due to weakened metabolic fitness and slowed growth
rate [24]. This most likely was attributed to the case iso-
late’s high ertapenem MIC despite being KPC negative.
Despite the low virulence of non-K1/K2 serotypes of
K. pneumoniae, they are capable of causing liver abscess
due to presence of hypermucoviscosity phenotype, rmpA,
aerobactin, and kfu genes. To our knowledge, this is the
first reported case of non-K1/K2 serotype KPLA in the
United States. Commonly associated virulence factors
were also absent in this isolate. With increasing antim-
icrobial resistance, health care providers should be aware
of the emergence of CRKP liver abscesses and use ap-
propriate antimicrobial agents when multidrug resistant
organisms are suspected.
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