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r 2009 John Wiley & Sons A/S

Transplant Infectious Disease . ISSN 1398 -2273

Short communication

Carbapenem-resistant Acinetobacter baumannii


infections after organ transplantation

P. Reddy,T.R. Zembower, M.G. Ison,T.A. Baker,V. Stosor. Carbapenem- P. Reddy1, T.R. Zembower1, M.G. Ison1,2,

resistant Acinetobacter baumannii infections after organ T.A. Baker2, V. Stosor1,2

transplantation. 1
Division of Infectious Diseases, and 2Division of Organ
Transpl Infect Dis 2010: 12: 87^93. All rights reserved
Transplantation, Northwestern University Feinberg School of
Medicine, Chicago, Illinois, USA

Abstract: Multi-drug resistant (MDR) gram-negative infections

among solid organ transplant (SOT) recipients have long been

associated with high morbidity and mortality. Acinetobacter baumannii

has emerged as a potent nosocomial pathogen with the recent Key words: organ transplantation; complications;

acquisition of resistance to broad-spectrum b-lactams, Acinetobacter; infections
aminoglycosides, £uoroquinolones, and most notably, carbapenems.

Despite a national rise in carbapenem-resistant A. baumannii (CRAB) Correspondence to:

infections, outcomes among SOT recipients with this emerging MDR Pavani Reddy, MD, Division of Infectious Diseases,
Northwestern University Feinberg School of Medicine, 645 N.
pathogen are largely unknown. This single-center cohort is the ¢rst to
Michigan Avenue, Suite 900, Chicago, IL 60611, USA
describe the characteristics, complications, and outcomes among
Tel: 1 1 312 695 5090
abdominal organ transplant recipients with CRAB. The current study Fax: 1 1 312 695 5088

suggests that SOT patients with CRAB su¡er from prolonged E-mail: p-reddy2@md.northwestern.edu
hospitalization, infection with other MDR organisms, allograft

dysfunction and loss, and high overall infection-related mortality. Received 17 October 2008, revised 2 April 2009, accepted for

publication 13 May 2009



DOI: 10.1111/j.1399-3062.2009.00445.x
Transpl Infect Dis 2010: 12: 87–93

Invasive bacterial infections have become a leading cause tance to broad-spectrum antibiotics including b-lactams,
of morbidity and mortality among solid organ transplant aminoglycosides, £uoroquinolones, and tetracyclines.
(SOT) recipients (1). Notably, the emergence of multi-drug Most notably, carbapenem-resistant A. baumannii (CRAB)
resistant (MDR) gram-negative bacteria among SOT recip- has emerged with the acquisition of enzymes (e.g., metallo-
ients has been associated with an increased risk of allograft b-lactamases, oxacillinases) capable of hydrolyzing imipe-
loss (2). Outcomes among transplant recipients with infec- nem. This recent rise in MDR A. baumannii infections has
tion due to extended-spectrum beta-lactamase (ESBL)- been associated with longer hospital length of stay (5) and
producing Enterobacteriaceae or MDR Pseudomonas aeru- increased patient mortality (6).
ginosa have been described previously (2, 3). Despite a national rise in carbapenem resistance among
Acinetobacter baumannii is almost exclusively a no- A. baumannii (National Nosocomial Infections Surveil-
socomial pathogen, associated with soft tissue infection, lance System, unpublished data), outcomes among SOT re-
urinary tract infection (UTI), catheter-associated blood- cipients who acquire this pathogen are largely unknown.
stream infection (BSI), and ventilator-associated pneumo- We report the clinical features and outcomes of abdominal
nia (VAP) among critically ill patients (4). Already organ transplant recipients who acquired CRAB in the
equipped with intrinsic resistance to the aminopenicillins post-transplant period.
and ¢rst- and second-generation cephalosporins, A. bau-
mannii has gained recent notoriety with its acquired resis-
Abbreviations : BSI, bloodstream infection; CRAB, carbapenem-resistant
Acinetobacter baumannii; ERCP, endoscopic retrograde cholangiopancreatography; Methods
ESBL, extended-spectrum beta-lactamase; HCV, hepatitis C virus; ICU, intensive
care unit; MDR, multi-drug resistant; MRSA, methicillin-resistant Staphylococcus
aureus; PTD, post-transplant day; SOT, solid organ transplant; UTI, urinary tract
infection; VAP, ventilator-associated pneumonia; VRE, vancomycin-resistant Northwestern Memorial Hospital (NMH) is an 825 -bed ac-
Enterococcus ademic medical center in Chicago, Illinois. From January 1,

87
Reddy et al: Acinetobacter infections after organ transplant

2004 to December 31, 2005, 794 abdominal organ trans- lished criteria were used to de¢ne clinical infection (8).
plants were performed at NMH including 172 liver, 407 kid- Summary statistics were performed using SAS software,
ney, and 57 combined liver^kidney procedures.W|thin this version 9.1 (SAS Institute). When appropriate, categorical
time frame, all patients with a positive culture for CRAB variables were compared using Fisher’s exact test.
were identi¢ed through the electronic microbiology da-
tabase. Organ recipients who acquired CRAB during the
study period were considered for analysis. Study patients
A. baumannii isolates were identi¢ed by the semi-auto-
mated VITEK 2s system (bioMe¤ rieux, Marcy l’Etoile,
France). Further standard biochemical techniques for the During the study period, 248 patients with A. baumannii
identi¢cation of Acinetobacter were performed if automated were identi¢ed. Among abdominal organ transplant recip-
results were o90% accurate. Carbapenem resistance was ients with A. baumannii (n 5 14), 6 (42.9%) acquired a
de¢ned as a minimum inhibitory concentration of imipe- carbapenem-resistant isolate. In contrast, among
nem  16 mg/mL. Routine antimicrobial susceptibility non-transplant patients with A. baumannii (n 5 234), only
testing for gentamicin, tobramycin, ampicillin^sulbactam, 32 (13.7%) patients acquired a carbapenem-resistant isolate
imipenem, ceftazidime, aztreonam, cefepime, cipro£oxa- (odds ratio 4.73, 95% con¢dence interval 1.35^16.38,
cin, and trimethoprim^sulfamethoxazole was performed P 5 0.01). Of note, case patients were accrued during a mul-
by the VITEK 2 s system. Additional susceptibility testing ti-city CRAB outbreak that occurred within the study pe-
for amikacin, piperacillin^tazobactam, minocycline, tetra- riod (9). Table 1 summarizes the important clinical,
cycline, and doxycycline was performed by the Kirby^Bau- epidemiologic, and transplant features of the 6 recipients
er disk di¡usion method and isolates were characterized as who acquired CRAB.
resistant or susceptible based on the interpretative criteria
of the Clinical Laboratory Standards Institute (7 ). Suscep-
tibility to colistin was determined by use of the E-test s Case 1
(AB Biodisk, Solna, Sweden).
During the study period, the predominant immunosup- A 61-year-old man with hepatitis B cirrhosis underwent or-
pression protocols for liver transplantation di¡ered by un- thotopic liver transplantation complicated by bile leak and
derlying disease. For hepatitis C virus (HCV) infection or ampullary stenosis early in the postoperative course. In-
hepatocellular carcinoma, the preferred regimen included terventions included re-operation and endoscopic retro-
methylprednisolone 500 mg on post-transplant day (PTD) grade cholangiopancreatography (ERCP) with biliary
0 followed by a steroid taper over 10 days. Maintenance of stent placement. After an extended intensive care unit
immunosuppression included tacrolimus (Prografs, (ICU) stay for ventilatory failure and prolonged mechanical
Fujisawa Pharmaceuticals, Deer¢eld, Illinois, USA) admin- ventilation, the patient was discharged to a subacute nurs-
istered to achieve a 12-h blood level of 8 ng/mL for deceased- ing facility. On PTD 45, the patient was re-admitted with
donor transplants or 5^8 ng/mL for living-donor trans- sepsis. He underwent ERCP, biliary traction sphincter-
plants for the initial 3 months post transplant. Other liver otomy, balloon dilation of the choledochocholedochostomy
recipients and combined organ recipients received anastamotic stricture, and biliary stent replacement.
alemtuzumab 30 mg as induction therapy and methylpred- Post-transplant course was further complicated by car-
nisolone 500 mg on PTD 0, 250 mg on PTD 1, and 125 mg on bapenem-sensitive A. baumannii urinary and respiratory
PTD 2. Tacrolimus was administered to achieve 12-h blood tract infections and subsequently, invasive pulmonary
concentrations of 8^10 ng/mL for the ¢rst 3 months post aspergillosis. On PTD 89, the patient developed CRAB
transplant. Combined organ recipients also received my- VAP. CRAB-directed antimicrobial therapy with amp-
cophenolate mofetil (Cellcepts, Roche, Nutely, New Jersey, icillin^sulbactam, amikacin, and nebulized tobramycin
USA) at target dose of 1.5^2.0 g/day. was administered. The pneumonia resolved and he was
The kidney recipient in this case series was infected with discharged on PTD 103.
HCV and received induction basiliximab 20 mg on PTD 0
and 2, methylprednisolone 500 mg on PTD 0, mycopheno- Case 2
late mofetil 1.0 g/day, and tacrolimus to achieve 12-h blood
concentrations of 8^10 ng/mL. A 66 -year-old woman with end-stage liver disease due to
Medical records were reviewed to collect data on patient non-alcoholic steatotic liver disease and hepatorenal syn-
demographics, transplant history, immunosuppressant drome underwent combined liver and kidney transplanta-
use, co-morbid conditions, and clinical presentation, com- tion. The immediate postoperative course was complicated
plications, and outcomes associated with CRAB. Estab- by a retroperitoneal hematoma and delayed renal allograft

88 Transplant Infectious Disease 2010: 12: 87^93


Reddy et al: Acinetobacter infections after organ transplant

Clinical and epidemiologic features of organ recipients colonized or infected with carbapenem-resistant Acinetobacter baumannii (CRAB)

Case

Characteristics 1 2 3 4 5 6

Transplant type Liver Kidney^liver Kidney^liver Kidney^liver Kidney^liver Kidney


Transplant Hepatitis B NASH, HRS Alcoholic Hepatitis C, Hepatic Cryptogenic FSGS
reason cirrhosis, HRS failure s/p HCC resection, HRS cirrhosis, HRS
MELD 40 26 39 44 35 N/A
Cold ischemia 6 8 8 10 6 UA
time (h)
Operative time 515 498 449 767 480 220
(min)
Age (years) 61 66 64 62 33 49
Sex Male Female Male Female Male Male
Ethnicity Caucasian Caucasian Asian Caucasian Caucasian African American
Induction IS Alemtuzumab Alemtuzumab Alemtuzumab None Alemtuzumab Basiliximab
Maintenance IS TAC, MMF TAC, MMF TAC, MMF TAC, prednisone TAC, MMF, TAC, MMF, prednisone
prednisone
Prior antibiotics Carbapenem 41 BL^BLI Carbapenem Carbapenem Carbapenem
BL^BLI cephalosporin Fluororquinolone BL^BLI
Metronidazole Metronidazole Vancomycin Vancomycin
Vancomycin Vancomycin
CRAB site PNA PNA PNA 1 BSI 1 UTI Respiratory tract PNA 1 BSI 1 UTI PNA 1 BSI 1 SSI 1 empyema
Prior infections Biliary sepsis Polymicrobial None VRE, CoNS peritonitis VRE UTI/BSI Pseudomonas aeruginosa
Acinetobacter UTI A. baumannii BSI Enterobacter BSI SSI  UTI
baumannii UTI Klebsiella PNA Ocular HSV, Stenotrophomonas Klebsiella PNA
A. baumannii PNA Klebsiella BSI maltophilia BSI Clostridium di⁄cile
Aspergillus PNA Candida S. maltophilia SSI colitis
peritonitis
Transplant Bile leak DGF DGF Delayed closure DGF DGF
complications Ampullary stenosis Hematoma Bile leak Hepatic artery ischemia Cardiac arrest Hematoma
Re-operation Allograft Ischemic Bile leak Pancytopenia Urine leak
rejection cholangiopathy Hepatic necrosis, SSI Allograft rejection
Re-operation Re-operation Nephrectomy
Re-operation
Outcome Survived Died Died Died Died Died

NASH, non-alcoholic steatotic hepatitis; HCC, hepatocellular carcinoma; HRS, hepatorenal syndrome; FSGS, focal segmental glomerulosclerosis; TAC,
tacrolimus; MMF, mycophenolate mofetil; BL, beta lactam; BLI, beta-lactamase inhibitor; PNA, pneumonia; UTI, urinary tract infection; BSI, bloodstream
infection; SSI, surgical site infection; DGF, delayed renal allograft function; N/A, not applicable; UA, unavailable; MELD, model for end-stage liver disease; IS,
immunosuppression; VRE, vancomycin-resistant Enterococcus; HSV, herpes simplex virus; 41, fourth generation; CoNS, coagulase-negative
Staphylococcus.

Table1

function secondary to acute tubular necrosis. On PTD 20, sistent ascites, prolonged lymphopenia, and renal allograft
the patient was diagnosed with a Klebsiella pneumoniae dysfunction requiring hemodialysis. Antibiotic therapy
UTI and Candida peritonitis, treated with piperacillin^ta- was administered for urinary, respiratory, and BSI due to
zobactam and £uconazole, respectively. The patient re- an ESBL-producing K. pneumoniae. The patient was re-
turned to the hospital on PTD 54 with fevers, ascites, and hospitalized on PTD 214 with K. pneumoniae, Proteus mira-
declining renal function. Over the next month, her hospital bilis, and vancomycin-resistant Enterococcus faecium (VRE)
course was marked by respiratory failure with prolonged urosepsis and hydronephrosis of the allograft necessitat-
mechanical ventilation and tracheostomy placement, per- ing nephrostomy tube placement. Renal allograft biopsy

Transplant Infectious Disease 2010: 12: 87^93 89


Reddy et al: Acinetobacter infections after organ transplant

suggested rejection. Computed tomography of the chest sistant Staphylococcus aureus (MRSA) BSI, and Escherichia
demonstrated bibasilar consolidation. Despite aggressive coli UTI. Though CRAB was isolated from a respiratory
supportive measures, the patient su¡ered from cardiopul- tract culture, there was no evidence of pneumonia. The pa-
monary arrest and anoxic brain injury, expiring on PTD tient clinically improved without CRAB-directed antimi-
219. Respiratory cultures later identi¢ed CRAB and MDR crobial therapy and was discharged in stable condition on
P. aeruginosa. PTD 125. She subsequently died at an outside hospital on
PTD 162. Her death was attributed to sepsis, but the etio-
logic agent was not identi¢ed.
Case 3

A 64 -year-old man with alcoholic cirrhosis and hepatorenal Case 5


syndrome underwent combined liver^kidney transplanta-
tion from a donation-after-cardiac-death donor complicated A 33 -year-old man with Werner syndrome, cryptogenic cir-
by postoperative heart failure, delayed renal allograft rhosis, and hepatorenal syndrome underwent combined liv-
function, and respiratory failure with prolonged mechani- er^kidney transplant complicated by delayed renal
cal ventilation and tracheostomy placement. He was dis- allograft function necessitating renal replacement therapy.
charged to a subacute nursing facility placement on PTD He also required prolonged mechanical ventilation and
14 but was re-admitted 3 days later with ischemic tracheostomy placement after periods of apnea and brady-
cholangiopathy, bile leak, and loculated peri-hepatic £uid cardic arrest. The transplant hospitalization was marked
collections, prompting ERCP and pancreatic and biliary by lymphopenia, neutropenia, and multiple infections in-
stent placements. The hospitalization was complicated by cluding VRE urosepsis, Clostridium di⁄cile colitis, and an
marked lymphopenia, hospital-acquired pneumonia, and ESBL-producing Enterobacter cloacae BSI. The patient was
UTI. CRAB was isolated in culture from both sites, and col- transferred to a subacute nursing facility on PTD 27. He
istin was administered for 10 days. Recurrent CRAB uro- was re-admitted on PTD 51 with sepsis attributed to a
sepsis was identi¢ed on PTD 38. Directed antimicrobial VRE UTI and an ESBL-producing K. pneumoniae and
therapy included piperacillin, colistin, and tigecycline for CRAB VAP. Initially, the patient improved on linezolid, imi-
14 days. The transplant ureteral stent was removed as a penem, and amikacin. However, on PTD 70, CRAB was iso-
possible source of recurrent UTI. However, the patient had lated from the blood and urine. Despite therapy with
progressive, refractory multisystem organ failure compli- tigecycline, ampicillin^sulbactam, doxycycline, and colis-
cated by acute neutropenia. Supportive care was with- tin, multisystem organ failure progressed. Multiple infec-
drawn and the patient died on PTD 52. MDR P. aeruginosa tious complications followed, including disseminated
was isolated from premortem blood cultures. herpes zoster virus infection, VRE peritonitis, recurrent
K. pneumoniae and CRAB VAP, K. pneumoniae peritonitis,
and coagulase-negative staphylococci BSI. Supportive
Case 4 measures were withdrawn; the patient died on PTD 130.
Details of this case have been reported previously (10).
A 62-year-old female with HCV cirrhosis underwent com-
bined liver^kidney transplantation after a right hepatic
lobe resection for hepatocellular carcinoma was compli- Case 6
cated by acute liver failure and hepatorenal syndrome.
The immediate post-transplant course was complicated by A 49 -year-old man with peripheral vascular disease, HCV
right heart failure, hepatic congestion precluding bile duct infection, and end-stage renal disease due to focal segmen-
anastamosis and abdominal wall closure, hepatic artery is- tal glomerulosclerosis underwent deceased-donor kidney
chemia, and hepatic necrosis. She required multiple re-op- transplant with an extended criteria donor organ and with
erations for choledochocholedochostomy, hepatic artery ureteroureteral anastamosis. The postoperative course
revision, and wound closure, debridement, and revision. was marked by delayed allograft function and renal re-
Post-transplant infectious complications included polymi- placement therapy; allograft biopsy suggested acute rejec-
crobial peritonitis with coagulase-negative staphylococci tion. The biopsy was complicated by a large hematoma that
and VRE, BSI due to carbapenem-susceptible Acinetobacter, required surgical evacuation on PTD 14. Following dis-
ocular infection with herpes simplex virus, and wound in- charge, hematoma recurrence and a P. aeruginosa surgical
fection and BSI due to Stenotrophomonas maltophilia. The site infection prompted re-admission on PTD 46. The pa-
patient was discharged to a subacute nursing facility on tient was placed on prolonged imipenem therapy. A urine
PTD 41, but several hospital admissions followed due to leak due to disruption of the ureteroureteral anastomosis
carbapenem-susceptible Acinetobacter BSI, methicillin-re- on PTD 60 led to percutaneous nephrostomy tube place-

90 Transplant Infectious Disease 2010: 12: 87^93


Reddy et al: Acinetobacter infections after organ transplant

ment. Numerous hospital admissions for UTIs and persis- graft rejection (n 5 2), and ureteral stenosis with urinary
tent abdominal wound infection followed over the next 2 leak and urinoma.
months. Delayed graft function persisted, and when a renal All 6 patients had risk factors for colonization and/or in-
biopsy on PTD 129 indicated moderate cellular rejection, fection with an MDR pathogen (11, 12). In the 30 days before
the patient received methylprednisolone. On PTD 193, CRAB identi¢cation, all were exposed to a subacute nurs-
CRAB was isolated from the abdominal wound and the ing facility and 5 (83%) patients were in the ICU. All 6 pa-
bloodstream. Tobramycin and colistin were initiated. Ulti- tients were colonized or infected with another MDR
mately, ongoing abdominal infection prompted transplant organism including MRSA, VRE, ESBL-producing Enter-
nephrectomy. Multiple infectious complications followed, obacteriaceae, or MDR P. aeruginosa. In addition, all 6 pa-
including VAP and parapneumonic empyema with MDR tients had a central venous catheter, 4 (66.7%) required
P. aeruginosa and CRAB, and cytomegalovirus syndrome. mechanical ventilation, and 3 (50%) required renal replace-
Despite aggressive antibiotic therapy, the patient died due ment therapy before CRAB acquisition. All patients re-
to sepsis on PTD 217. ceived broad-spectrum antibiotic therapy, including
anaerobic coverage. Details of antecedent antibiotic use
are noted in Table 1. Speci¢cally, carbapenem was used in
Results 4 (66.7%), cephalosporin in 1 (16.7%), vancomycin in 4
(66.7%), metronidazole in 2 (33.3%), and extended spec-
trum b-lactam/ESBL inhibitors in 3 (50%).
Our cohort included 1 deceased-donor kidney, 1 orthotopic CRAB was acquired a median of 93.5 days after trans-
liver, and 4 simultaneous liver^kidney recipients. Recipi- plantation (range 17^218 days). Most patients (83%) suf-
ents were predominantly male (66.7%) and Caucasian fered from CRAB pneumonia, and half of these recipients
(66.7%) with a median age of 61.5 years (range 35^68 subsequently developed CRAB BSI. Additional sites of
years). Cytomegalovirus donor (D)/recipient (R) serostatus CRAB infection included the urinary tract and the surgical
included 2 (33.3%) D 1 /R , 2 (33.3%) D 1 /R 1 , and 2 site. A sixth patient was colonized, but not infected, with
(33.3%) D /R 1 . Five isolates were typed; 4 (cases 2, 3, 5, the organism.
and 6) resembled the isolate involved in the citywide out- Four (80%) of 5 infected patients received antimicrobial
break. therapy for CRAB while 1 patient died before the identi¢ca-
All 6 recipients developed signi¢cant surgical and medi- tion of CRAB. Details of therapy are outlined inTable 2. All
cal post-transplant complications before the acquisition of 4 patients were treated with a multi-drug regimen: 2 pa-
CRAB. Hepatic complications included bile leak (n 5 2), tients received ampicillin^sulbactam in combination with
ampullary stenosis, ischemic cholangiopathy (n 5 2), and an aminoglycoside (1 of whom received tigecycline) while
hepatic allograft dysfunction. Complications of kidney the other 2 were treated with colistin and tigecycline alone.
transplantation included post-transplant hematoma Subsequent to CRAB acquisition, all patients had poor
(n 5 2), delayed renal allograft function (n 5 4), renal allo- outcomes. Four kidney recipients su¡ered from graft fail-

Carbapenem-resistant Acinetobacter baumannii (CRAB): site of infection, antibiotic susceptibilities, and antibiotic management

Antibiotic susceptibilities (minimum inhibitory concentration)

Case Transplant CRAB source AMP-S IMIP CIP DOXY COL TET AMIK TOB Antibiotic therapy

1 OLT PNA 1 UTI ND  16 4 ND ND ND 32 8 AMP-S 1 AMIK


2 CRT/OLT PNA  32  16 4 S ND R  64  16 Died before RX
3 CRT/OLT PNA 1 BSI 1 UTI  32  16 4 S o2 R R 8 COL,TIG, PIP, DOXY
4 CRT/OLT Respiratory tract 4  16 4 I ND R R  16 Colonization, no RX
5 CRT/OLT PNA 1 BSI 16  16 4 ND ND R 16  16 AMP-S, DOXY,TIG, AMIK
6 CRT PNA 1 BSI 1 SSI  32  16  4 S 0.5 R 4 4 COL 1 TIG

OLT, orthotopic liver transplant; CRT, deceased donor kidney transplant; PNA, pneumonia; UTI, urinary tract infection; BSI, bloodstream infection; SSI, skin
and soft tissue infection; ND, not done; S, susceptible by Kirby^Bauer; R, resistant by Kirby^Bauer; AMP-S, ampicillin^sulbactam; IMIP, imipenem; CIP,
cipro£oxacin; DOXY, doxycycline; COL, colistin;TET, tetracycline; AMIK, amikacin;TOB, tobramycin;TIG, tigecycline; PIP, piperacillin; RX, therapy.

Table 2

Transplant Infectious Disease 2010: 12: 87^93 91


Reddy et al: Acinetobacter infections after organ transplant

ure requiring renal replacement therapy and 1 liver^kidney ins, and extended spectrum b-lactam/ESBL inhibitors (11,
recipient experienced hepatic dysfunction. Renal allograft 17^19). Among 6 lung transplant recipients with MDR A.
rejection occurred in 2 recipients. The kidney recipient un- baumannii, antecedent mechanical ventilation and broad-
derwent transplant nephrectomy in an unsuccessful at- spectrum antibiotic exposure were common characteris-
tempt to control CRAB infection. Despite multi-drug tics (16).
therapy, 4 (66.7%) patients died subsequent to CRAB diag- Case patients had established risk factors for coloniza-
nosis, with CRAB a primary or contributing factor to death. tion and infection with MDR bacteria after SOT. Several
A ¢fth patient died from sepsis of unclear etiology. All studies have demonstrated that biliary complications or
deaths occurred within the ¢rst year post transplant, with the need for re-operation are associated withVRE coloniza-
median of 162 days (range 53^219 days). T|me from CRAB tion and infection after liver transplantation (20, 21). Nota-
acquisition to infection-related death among these 5 pa- bly, ischemic injury and other biliary complications
tients was a median of only 36 days (range 1^71 days). occurred among 3 liver transplant recipients in the present
study. Among renal transplant recipients, Linares et al. (2,
22) found that post-transplant urinary obstruction, post-
transplant nephrostomy, and a post-transplant hemodialy-
Discussion sis requirement are risk factors for the acquisition of anti-
biotic-resistant bacteria for kidney recipients. Four of 5
kidney recipients in the present study su¡ered from de-
MDR A. baumannii infections are associated with mortal- layed graft function and a post-transplant hemodialysis
ity rates of 16^49% among hospitalized patients (5, 6, 13). requirement, supporting these ¢ndings. Surgical interven-
However, outcomes of transplant recipients infected with tion was common among cases patients; 66.7% of patients
MDR A. baumannii infections are not well de¢ned. We re- colonized or infected with CRAB underwent re-operation
port our center’s recent experience with CRAB infections post transplantation.
among liver and/or kidney transplant recipients. Another common characteristic of this small cohort in-
Singh et al. (14) noted that liver transplant recipients in- cluded the use of alemtuzumab induction immunosuppres-
fected with an MDR organism are signi¢cantly less likely sion. Alemtuzumab results in profound and prolonged
to survive at 1 year compared to non-infected liver trans- immunosuppressive e¡ects but its association with the
plant counterparts or to those infected with susceptible development of MDR bacterial infections remains unclear
pathogens (14). Our cohort had similar poor outcomes, in- (23). Our cohort suggests that further study is required
cluding 66.7% renal allograft loss, 66.7% CRAB-related to clarify the risk of bacterial infection with this agent.
mortality, and 80% overall infection-related mortality Optimal therapies for the treatment of CRAB infections
within the ¢rst year of transplantation. In a retrospective are not well de¢ned. Among immunocompetent patients
study of Acinetobacter infections among critically ill surgi- with a sulbactam-susceptible Acinetobacter isolate, mono-
cal patients, the reported mortality in the organ transplant therapy with sulbactam was as e¡ective as imipenem in
subset (n 5 30) was 64.5%. Immunosuppression, primarily the treatment of VAP (24) and BSI (25). In the present study,
as a result of organ transplantation, was predictive of poor sulbactam therapy was only administered in conjunction
outcomes. While carbapenem resistance was prevalent in with an aminoglycoside, doxycycline and/or tigecycline
this cohort, it is unclear what proportion of the transplant (see Table 2); 1 patient survived and 1 died. Uncontrolled
recipients had MDR A. baumannii (15). Among the ¢rst to studies suggest that the use of colistin in combination with
examine this emerging pathogen in immunocompromised other antimicrobials (including cabapenems, ampicillin^
hosts, Sopirala et al. (16) found that lung transplant recipi- sulbactam, aminoglycosides, and rifampin) may have some
ents with MDR A. baumannii infection su¡er from allo- success in the treatment of VAP due to MDR A. baumannii
graft rejection (66.7%) or even death (33.3%). (26, 27 ). T|gecycline, a glycylcycline derivative of tetracy-
Risk factors for MDR A. baumannii acquisition among cline, has demonstrated success in the treatment of CRAB
immunocompetent patients are well de¢ned (11, 12). The infections (28), however, its utility in the treatment of seri-
present study suggests that such characteristics as central ous infection or BSI remains unclear (29). Patients in this
venous catheter use, prolonged ICU stay, and mechanical study who received colistin and/or tigecycline died, demon-
ventilation are also associated with CRAB acquisition and strating the need for further study of these agents in the
infection among SOT recipients. Baran et al. (11) noted that SOT population.
patients who received prior antibiotic therapy were at In summary, our experience suggests that poor allograft
5 -fold greater risk of CRAB. Not surprisingly, all patients outcomes and high mortality occur in patients who acquire
in this study were exposed to antimicrobial agents known CRAB in the early post-transplant period. In most cases,
to predispose to CRAB, such as carbapenems, cephalospor- CRAB infection was directly implicated in or at least con-

92 Transplant Infectious Disease 2010: 12: 87^93


Reddy et al: Acinetobacter infections after organ transplant

tributed to mortality.Though this report is limited by small 13. Kuo LC, Lai CC, Liao CH, et al. Multidrug-resistant Acinetobacter
cohort size and retrospective data collection, common fea- baumannii bacteremia: clinical features, antimicrobial therapy and
tures among this cohort included receipt of combined or- outcome. Clin Microbiol Infect 2007; 13 (2): 196^198.
14. Singh N, Gayowski T, Rihs JD,Wagener MM, Marino IR. Evolving
gan transplants, alemtuzumab induction, technical trends in multiple antibiotic-resistant bacteria in liver transplant
complications, and prior infection with other antimicrobi- recipients: a longitudinal study of antimicrobial susceptibility
al-resistant pathogens. Further study is required to de¢ne patterns. Liver Transplant 2001; 7 (1): 22^26.
acquisition risk factors speci¢c to organ recipients. 15. Trottier V, Namias N, Pust DG, et al. Outcomes of Acinetobacter
baumannii infection in critically ill surgical patients. Surg Infect
(Larchmt) 2007; 8 (4): 437^443.
16. Sopirala MM, Pope-Harman A, Nunley DR, Mo¡att-Bruce S, Ross P,
Acknowledgements: Martin SI. Multidrug resistant Acinetobacter baumannii pneumonia in
lung transplant recipients. J Heart LungTransplant 2008; 27 (7): 804^807.
Funding source: Northwestern University Feinberg School 17. del Mar Tomas M, Cartelle M, Pertega S, et al. Hospital outbreak
caused by a carbapenem-resistant strain of Acinetobacter baumannii:
of Medicine. patient prognosis and risk factors for colonization and infection. Clin
Potential con£icts of interest: None. Microbiol Infect 2005; 11: 540^546.
18. Kim YA, Choi JY, Kim CK, et al. Risk factors and outcomes of blood-
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