Asma M Al-Jasser

BN Kim

C Hogenauer

D Boyeldieu

Fahad I Al-Mohareb

Hazza A Al-Zahrani

J Haddad

JA Korvick

JT Watson

K Hori

Khalid A Al-Anazi

LM Tang

Naem Chaudhri

P Berthelot

RD Lin

S Nathisuwan

SW Wu

U Ransjo

Y Kashiwagi

YC Sardan

English

PubMed

Springer - Publisher Connector

Klebsiella oxytoca bacteremia causing septic shock in recipients of hematopoietic stem cell transplant: Two case reports

Crossref

BioMed CentralCases Journal
ssOpen AcceCase Report
Klebsiella oxytoca bacteremia causing septic shock in recipients of 
hematopoietic stem cell transplant: Two case reports
Khalid A Al-Anazi*1, Asma M Al-Jasser2, Hazza A Al-Zahrani1, 
Naem Chaudhri1 and Fahad I Al-Mohareb1
Address: 1Section of Adult Hematology and Hematopoietic, Stem Cell Transplant, King Faisal Cancer Centre, King Faisal Specialist Hospital and 
Research Centre, P.O. Box: 3345, Riyadh 11211, Saudi Arabia and 2Section of Microbiology, Department of Pathology, Armed Forces Hospital, 
Box: X-966, P.O. Box: 7897, Riyadh 11159, Saudi Arabia
Email: Khalid A Al-Anazi* - kaa_alanazi@yahoo.com; Asma M Al-Jasser - asjass2002@yahoo.com; Hazza A Al-
Zahrani - halzahrani@kfshrc.edu.sa ; Naem Chaudhri - chaudhri@kfshrc.edu.sa; Fahad I Al-Mohareb - fmohareb@kfshrc.edu.sa
* Corresponding author    
Abstract
Background: Klebsiella oxytoca can cause various infectious complications in healthy as well as in
immunocompromised individuals.
Case Presentations: Case 1: A 49 year old female with multiple myeloma received an autologous
hematopoietic stem cell transplant in October 2005. Eight days following her autograft she
developed septic shock caused by Klebsiella oxytoca bacteremia which was successfully treated
with intravenous meropenem and gentamicin. Case 2: A 29 year old female with sickle cell anemia
and severe aplastic anemia underwent an allogeneic hematopoietic stem cell transplant in July 2005.
Seven months following her unsuccessful allograft, she developed septic shock due to Klebsiella
oxytoca bacteremia caused by a urinary tract infection. The septic episode was successfully
managed with intravenous meropenem and gentamicin. Both patients were treated at King Faisal
Specialist Hospital and Research Centre in Riyadh, Saudi Arabia. To our knowledge, they are the
first reports of Klebsiella oxytoca bacteremias and septic shocks in hematopoietic stem cell
transplant recipients.
Conclusion: Klebsiella oxytoca should be considered as a possible cause of severe infections in
recipients of various forms of hematopoietic stem cell transplantation. However, these infections
may be complicated by bacteremias, septic shocks, systemic dysfunctions and even deaths if not
managed promptly and appropriately.
Introduction
Klebsiella species are the second most frequent cause of
gram-negative bacteremia [1]. Since the early 1980s, Kleb-
siella oxytoca (K. oxytoca) isolates have been recognized
as clinically significant [2]. The isolation of this organism
from clinical specimens is an indication for therapy [2].
Extended spectrum beta lactamase (ESBL) production by
K. oxytoca causes bacterial resistance to B-lactam antibiot-
ics and contributes to therapeutic problems [2,3]. The
organism is usually resistant to the oxyimino B-lactams
such as cefotaxime, ceftazidime and the monobactam
aztreonam [2]. In patients with Klebsiella bacterermia,
monotherapy with an antibiotic that is active in-vitro
against Klebsiella eg a beta-lactam or an aminoglycoside
Published: 18 September 2008
Cases Journal 2008, 1:160 doi:10.1186/1757-1626-1-160
Received: 8 July 2008
Accepted: 18 September 2008
This article is available from: http://www.casesjournal.com/content/1/1/160
© 2008 Al-Anazi et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 4
(page number not for citation purposes)
Cases Journal 2008, 1:160 http://www.casesjournal.com/content/1/1/160is a sufficient treatment for hemodynamically stable
patients but in severely ill patients having hypotension, an
antibiotic combination therapy with a beta-lactam and an
aminoglycoside is usually preferred [1].
Case presentations
Case 1
A 49 year old Saudi female was diagnosed to have multi-
ple myeloma (MM), IgG kappa, at King Faisal Specialist
Hospital and Research Centre (KFSH&RC) in Riyadh in
April 2005. She presented with: fatigue; bony pains; ane-
mia; hypercalcemia; high total protein, Ig G level, beta-2
microglobulin and erythrocytic sedimentation rate; 40%
plasma cells in the bone marrow and diffuse lytic lesions.
After receiving 4 courses of VAD chemotherapy (vincris-
tine, doxorubicin and dexamethasone), her disease
became under control. In September 2005, she underwent
an autologous peripheral blood stem cell collection in
preparation for an autologous hematopoietic stem cell
transplant (HSCT). On admission to the HSCT unit, the
patient was asymptomatic and her physical examination
did not reveal any abnormality. Investigations showed:
CBC: WBC: 4.4 × 109/L (neutrophilis: 2.64), Hb 92 g/L
and PLT: 419 × 109/L. The renal, hepatic and coagulation
profiles were all within normal limits and a repeat bone
marrow biopsy showed 4% plasma cells. The patient was
conditioned with high dose IV melphalan and she
received acyclovir, fluconazole and trimethoprim-sul-
phamethoxazole (TMP/SMZ) as infection prophylaxis.
On 5/10/2005, the patient received her autograft without
any complications. In the early post-HSCT period, she
developed: grade II mucositis treated with IV morphine
infusion and Clostridiun difficile colitis treated with met-
ronidazole. On 13/10/2005; the patient became febrile so
septic screens were taken and she was empirically com-
menced IV piperacillin-tazobactam 4.5 grams thrice daily
and IV gentamicin 2 mg/kg twice daily. On 14/10/05, she
started to have high fever and rigors and her BP dropped
to 85/40 mm Hg. However, she had no other complaints
and physical examination did not reveal any focus of
infection. The septic screens were repeated and the IV
tazobactam-piperacillin was replaced by IV meropenem 1
gram thrice daily. Few hours later, the patient started to
improve clinically and her BP became stable. The central
blood cultures taken on 13/10/05 grew K. oxytoca sensi-
tive to augmentin, cefazolin, ceftiaxone, gentamicin and
meropenem. The peripheral blood cultures as well as the
urine, the throat and the stool cultures were negative. As
the patient maintained her hemodynamic stability, she
was continued on meropenem and gentamicin. She
engrafted her leucocytes on day +14 and her platelets on
day + 12 HSCT. After the recovery of her blood counts and
the control of her septic episode, the IV antibiotics were
replaced by oral cefuroxime. On 23/10/2005, the patient
was having no complaints and her repeated physical
examination revealed no abnormality. The blood indices,
the renal and hepatic profiles were normal. She was sent
home on: cefuroxime 500 mg orally twice daily for 4 days
in addition to prophylactic TMP/SMZ, acyclovir and flu-
conazole till day +30 HSCT. Thereafter the patient had
regular follow up at the HSCT outpatient clinic and no
major complication was encountered.
Case 2
A 29 year old Saudi female with clinically mild sickle cell
disease, requiring infrequent blood transfusions and mild
analgesia but no iron chelating agents, was diagnosed to
have severe aplastic anemia (SAA) at KFSH&RC in Riyadh
in late December 2005. She presented with mucosal
bleeding, anemic manifestation, pancytopenia and
severely hypocellular bone marrow without blasts or
abnormal cells. Screens for fanconi anemia and paroxys-
mal nocturnal hemoglobinuria were negative. Hepatitis
serology and viral screens including parvovirus B-19 were
also negative. After failing to respond to a course of anti-
thymocyte globulin, cyclosporine-A and prednisone and
finding a healthy and an HLA-identical sibling donor, the
patient was planned for an allogeneic HSCT. She was con-
ditioned with cyclophosphmide and fludarabine. She
received methotrexate and cyclosporine-A as graft versus
host disease (GVHD) prophylaxis and fluconazole, acy-
clovir and penicillin as infection prophylaxis. She received
her allograft on 11/7/2005. Unfortunately she had no
engraftment so she remained pancytopenic and she was
continued on G-CSF in addition to platelet and packed
red cell transfusions. She was given various antimicrobials
for the repeated infections encountered. On 15/2/2006,
the patient was readmitted with fever, rigors, dysuria, diz-
ziness and fatigue for 2 days. Physical examination
showed: temperature: 39.4°C, BP: 80/40 mmHg and
pulse rate 112/minute. She was looking unwell and pale.
Her chest was clear. There was bilateral loin tenderness
but no palpable abdominal organomegaly. The cardiovas-
cular and neurological examinations were normal. After
taking blood cultures and septic screens, the patient was
commenced on: IV fluids at 150 cc/hour, IV meropenem:
1 gram thrice daily and IV gentamicin 2 mg/kg twice daily
in addition to GCSF and blood product transfusion sup-
port. Few hours later, the patient started to improve; the
pyrexia and the rigors subsided and the BP started to sta-
bilize. Thereafter the patient maintained her hemody-
namic stability. The central and the peripheral blood
cultures as well as the urine cultures taken on 15/2/2006
grew: K. oxytoca sensitive to: augmentin, cefazolin, gen-
tamicin and meropenem but resistant to amoxycillin. On
16/9/2006, the patient was asymptomatic, afebrile, her BP
was normal and her repeated physical assessment showed
no more loin tenderness. Six days after the septic shock,
the IV gentamicin was stopped but the IV meropenem was
continued for a total duration of 2 weeks. Later on, thePage 2 of 4
(page number not for citation purposes)
Cases Journal 2008, 1:160 http://www.casesjournal.com/content/1/1/160patient remained pancytopenic but clinically and hemo-
dynamically stable. On 22/2/2006, the patient received a
booster dose of peripheral blood stem cells from the same
donor, which did not have any positive impact on her
bone marrow function. On 5/3/2006, the patient was dis-
charged on: prophylactic ciprofloxacin, fluconazole and
acyclovir in addition to pentamidine nebulizer 300 mg
once/month. Thereafter, she continued to be pancyto-
penic and to have regular follow up at the HSCT outpa-
tient clinic.
Discussion
Infections caused by K. oxytoca occur in healthy individu-
als, newborn babies and immunocompromised hosts
such as patients with diabetes mellitus, solid tumours and
leukemia [4-13]. These infections may be encountered in
patients having: neurosurgical procedures, prostatecto-
mies, colonoscopies, intravascular catheters, platelet
transfusions, urinary tract infections and pre-existing viral
or antibiotic induced colitis [4-7]. K. oxytoca can cause
systemic infections such as meningitis, adrenal hemor-
rhage, hemorrhagic colitis and septic shock [4-8]. Out-
breaks of K. oxytoca infections have been reported in:
newborn babies following colonization of their digestive
tracts, oncology patients following contamination of
intravenous fluids and in cardiac patients following con-
tamination of invasive blood pressure monitoring devices
[11-13].
Bacteremia caused by K. oxytoca can be nosocomial or
community-acquired [4-6,8-14]. It is usually associated
with polymicrobial bacteremias and occurs in patients
with certain underlying conditions eg hepatobiliary or
pancreatic disorders, neoplastic disorders and diabetes
mellitus [14,15]. The clinical manifestations of K. oxytoca
infections are very variable and may include: biliary tract
infections, primary bacteremias, intravascular device-
associated infections, urinary tract infections, skin and
soft tissue infections and peritonitis [14,15]. These infec-
tions may be complicated by: bacteremia and septic
shock, disseminated intravascular coagulation and death
[5,14,15]. The mortality rates range between 9 and 24%
[14,15]. Poor prognosis and fatal outcomes are associated
with: septic shock, deterioration of mental status, pol-
ymicrobial bacteremias and having certain underlying
conditions such as solid tumours [14,15]. In K. oxytoca
infections, surgical intervention, which may occasionally
be required, has been shown to have a beneficial protec-
tive role [14]. Previous antibiotic therapy is strongly asso-
ciated with resistance to the extended-spectrum
cephalosporins [14]. In patients with K. oxytoca bactere-
mia, 86% of the strains have been found to be susceptible
to cefazolin and almost all the strains have been found to
be susceptible to: ampicillin-sulbactam, aminoglycosides,
cefmetazole, quinolones and carbapenems [15].
ESBLs are extremely broad spectrum B-lactamase enzymes
that are found in a variety of enterobacteriaceae. When
producing these enzymes, the organisms become highly
effective at inactivating various B-lactam antibiotics. The
most common ESBL producing organisms are: E. coli, K.
pneumoniae and K. oxytoca [3]. ESBL producing bacteriae
are frequently resistant to many classes of antibiotics
including aminoglycosides and flouroquinolones thus
resulting in infections that are difficult to treat [2,3]. Pip-
eracillin-tazobactam and cefepime should not be rou-
tinely administered for the treatment of ESBL producers.
However, carbapenems are considered the treatment of
choice for patients infected with ESBL producing patho-
gens [3].
The first patient presented had MM and she received an
autologous HSCT after the control of her disease in an
attempt to cure the myeloma. Despite giving IV gen-
tamicin and piperacillin-tazobactam to control her febrile
neutropenic episode, she developed the septic shock one
day later. There was no clinical focus for the infection
although it coincided with an episode of colitis treated
with metronidazole. Few hours after shifting to IV mero-
penem, her septic shock became under control. The sec-
ond patient had recurrent infections as she remained
pancytopenic following the failure of her allogeneic
HSCT. The urinary tract infection was the cause of her K.
oxytoca bacteremia. As the patient presented to the HSCT
clinic with clinical evidence of septicemia (fever, rigors
and hypotension), she was immediately commenced on
IV meropenem and gentamicin which controlled her sep-
tic shock within few hours. In both patients, the organ-
isms were not ESBL producers and the septic episodes
were successfully managed in the HSCT unit without
resorting to higher levels of care or even inotropic sup-
port.
Conclusion
K. oxytoca can cause serious infections, bacteremias and
septic shocks in immunocompromised individuals
including recipients of various forms of HSCT. Careful
clinical assessment, taking enough investigations and
administration of appropriate antimicrobial therapy are
essential not only to control these infections but also to
prevent further complications.
Abbreviations
K.oxytoca: klebsiella oxytoca; MM: multiple myeloma;
SAA: severe aplastic anemia; HSCT: hematopoietic stem
cell transplantation.
Competing interests
The authors declare that they have no competing interests.Page 3 of 4
(page number not for citation purposes)
Cases Journal 2008, 1:160 http://www.casesjournal.com/content/1/1/160Publish with BioMed Central   and  every 
scientist can read your work free of charge
"BioMed Central will be the most significant development for 
disseminating the results of biomedical research in our lifetime."
Sir Paul Nurse, Cancer Research UK
Your research papers will be:
available free of charge to the entire biomedical community
peer reviewed and published immediately upon acceptance
cited in PubMed and archived on PubMed Central 
yours — you keep the copyright
Submit your manuscript here:
http://www.biomedcentral.com/info/publishing_adv.asp
BioMedcentral
Authors' contributions
All authors participated, from clinical and laboratory
points of view, in the management of the patients pre-
sented.
Consent
Written consents were obtained from both patients for
publication of these case reports.
Acknowledgements
We are grateful to all medical, nursing and technical staff, at King Faisal Spe-
cialist Hospital and Research Centre in Riyadh, Saudi Arabia, who partici-
pated in the management of the patients presented.
References
1. Korvick JA, Bryan CS, Farber B, Beam TR, Schenfeld L, Muder RR,
Weinbaum D, Lumish R, Gerding DN, Wagener MM: Prospective
observational study of Klebsiella bacteremia in 230 patients:
outcome for antibiotic combinations versus monotherapy.
Antimicrob Agents Chemother 1992, 36(12):2639-2644.
2. Wu SW, Dornbusch K, Goransson E, Ransjo U, Kornvall G: Charac-
terization of Klebsiella oxytoca septicemia isolates resistant
to aztreonam and cefuroxime.  J Antimicrob Chemother 1991,
28(3):389-397.
3. Nathisuwan S, Burgess DS, Lewis JS II: Extended-spectrum B-
lactamases: epidemiology, detection and treatment.  Pharma-
cotherapy 2001, 21(8):920-928.
4. Tang LM, Chen ST: Klebsiella oxytoca meningitis: frequent
association with neurosurgical procedures.  Infection 1995,
23(3):163-167.
5. Hori K, Yasoshima H, Yamada A, Sakurai K, Ohkubo E, Kubota A,
Uematsu K, Sasio H, Mizokami Y, Shimoyama T: Adrenal hemor-
rhage associated with Klebsiella oxytoca bacteremia.  Intern
Med 1998, 37(11):990-994.
6. Haddad J, Marcato N, Cassan P: Septic shock caused by Klebsiella
oxytoca after colonoscopy.  Gastroenterol Clin Biol 1994,
18(2):181-182.
7. Kashiwagi Y, Sato S, Nakamura M, Kuboshima S, Numabe H,
Kawashima H, Takekuma K, Hoshika A, Matsumoto T: Klebsiella
oxytoca septicemia complicating rota virus-associated acute
diarrhea.  Pediatr Infect Dis J 2007, 26(2):191-192.
8. Boyeldieu D, Vu-Thien H, Dollfus C, Bounetta M, Ballerini P, Gerota
I, Moissenet D, Landman J, Tourniaire B, Leverger G: Klebsiella oxy-
toca septicemia following platelet transfusion.  Pathol Biol
(Paris) 1999, 47(5):405-407.
9. Sardan YC, Zarakolu P, Altun B, Yildirim A, Yildirim G, Hascelik G,
Uzuno O: A cluster of nosocomial Klebsiella oxytoca blood-
stream infection in a university hospital.  Infect Control Hosp Epi-
demiol 2004, 25(10):878-882.
10. Hogenauer C, Langer C, Beuber C, Lippe IT, Schicho R, Gorkiewicz
G, Krause R, Gerstgrasser N, Krejs GJ, Hinterleitner TA: Klebsiella
oxytoca as a causative organism of antibiotic-associated
hemorrhagic colitis.  N Engl J Med 2006, 355(23):2418-2426.
11. Berthelot P, Grattard F, Patural H, Ros A, Jelassi-Saoudin H, Pozzetto
B, Teyssier G, Lucht F: Nosocomial colonization of premature
babies with Klebsiella oxytoca. Probable role of enteral feed-
ing procedure in transmission and control of the outbreak
with the use of gloves.  Infect Control Hosp Epidemiol 2001,
22(3):148-151.
12. Ransjo U, GooD Z, Jalakas K, Kuhn I, Siggelkow I, Aberg B, Anjou E:
An outbreak of Klebsiella oxytoca septicemia associated
with the use of invasive pressure monitoring equipment.  Acta
Anaesthesiol Scand 1992, 36(3):289-291.
13. Watson JT, Jones RC, Siston AM, Fernandez JR, Martin K, Beck E,
Sokalski S, Jensen BJ, Arduino MJ, Srinivasan A, Gerber SI: Outbreak
of catheter associated Klebsiella oxytoca and Enterobacter
cloacae bloodstream infections in an oncology chemother-
apy center.  Arch Intern Med 2005, 165(22):2639-2643.
14. Kim BN, Ryu J, Kim YS, Woo JH: Retrospective analysis of clini-
cal and microbiological aspects of Klebsiella oxytoca bacter-
emia over a 10 year period.  Eur J Clin Microbial Infect Dis 2002,
21(6):419-426.
15. Lin RD, Hsueh PR, Chang SC, Chen YC, Hsieh WC, Luh KT: Bacter-
emia due to Klebsiella oxytoca: clinical features of patients
and antimicrobial susceptibilities of the isolates.  Clin Infect Dis
1997, 24(6):1217-1222.Page 4 of 4
(page number not for citation purposes)


Anjou E: An outbreak of Klebsiella oxytoca septicemia associated with the use of invasive pressure monitoring equipment. Acta Anaesthesiol Scand

Cassan P: Septic shock caused by Klebsiella oxytoca after colonoscopy. Gastroenterol Clin Biol

Characterization of Klebsiella oxytoca septicemia isolates resistant to aztreonam and cefuroxime.

F: Nosocomial colonization of premature babies with Klebsiella oxytoca. Probable role of enteral feeding procedure in transmission and control of the outbreak with the use of gloves. Infect Control Hosp Epidemiol

Hinterleitner TA: Klebsiella oxytoca as a causative organism of antibiotic-associated hemorrhagic colitis.

Hoshika A, Matsumoto T: Klebsiella oxytoca septicemia complicating rota virus-associated acute diarrhea. Pediatr Infect Dis J

Leverger G: Klebsiella oxytoca septicemia following platelet transfusion. Pathol Biol (Paris)

Lewis JS II: Extended-spectrum Blactamases: epidemiology, detection and treatment. Pharmacotherapy

Luh KT: Bacteremia due to Klebsiella oxytoca: clinical features of patients and antimicrobial susceptibilities of the isolates. Clin Infect Dis

MM: Prospective observational study of Klebsiella bacteremia in 230 patients: outcome for antibiotic combinations versus monotherapy. Antimicrob Agents Chemother

Outbreak of catheter associated Klebsiella oxytoca and Enterobacter cloacae bloodstream infections in an oncology chemotherapy center. Arch Intern Med

Shimoyama T: Adrenal hemorrhage associated with Klebsiella oxytoca bacteremia. Intern Med

ST: Klebsiella oxytoca meningitis: frequent association with neurosurgical procedures. Infection

Uzuno O: A cluster of nosocomial Klebsiella oxytoca bloodstream infection in a university hospital. Infect Control Hosp Epidemiol

Woo JH: Retrospective analysis of clinical and microbiological aspects of Klebsiella oxytoca bacteremia over a 10 year period.

file:///data/remote/core/dit/data/Springer-OA/pdf/116/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjExODYvMTc1Ny0xNjI2LTEtMTYwLnBkZg==.pdf

Klebsiella oxytoca bacteremia causing septic shock in recipients of hematopoietic stem cell transplant: Two case reports

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

Crossref

Springer - Publisher Connector