A 62-year-old man presented with fever, abdominal pain, and malaise 13 months after emergency endovascular aortic repair. Computed tomographic angiograms showed a periprosthetic fluid and gas collection, so infection was diagnosed. Open conversion was performed, involving endograft explantation and in situ aortic reconstruction. Cultures and the explanted prosthesis were positive for carbapenemase-producing Klebsiella pneumoniae, resistant to colistin. Because of the sparse data on endograft infections caused by this pathogen, we placed the patient on an empiric double-carbapenem regimen for 4 weeks. Symptomatic recovery occurred after 21 days. On the 30th day, we deployed a stent to treat a new pseudoaneurysm. Three years later, the patient had no signs of persistent or recurrent infection. We think that this is the first report of aortic endograft infection caused by colistin-resistant, carbapenemase-producing K. pneumoniae.

Endovascular aneurysm repair (EVAR) has become an alternative to aortic surgery and is often the treatment of choice for patients who have favorable anatomy.1–4  Results from EVAR can equal or exceed those of open surgery; however, EVAR's higher complication rate necessitates monitoring, in case patients need reintervention.5,6  Although one of the least frequent causes of reintervention is infection (incidence, <1% of EVAR cases),7–9  it is associated with high mortality rates for surgically and conservatively treated patients.10–15  Bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae (CPKP) are typically associated with a mortality rate of 13% to 58%, and few therapeutic options are available.16,17 

We present what we think is the first case of aortic endograft infection caused by colistin-resistant CPKP, report the therapeutic regimen and surgical course in a 62-year-old patient, and discuss the relevant medical literature.

Case Report

In September 2011, a 62-year-old man who had arterial hypertension, dyslipidemia, and paroxysmal atrial fibrillation was referred to a vascular center because of sudden-onset lumbar pain and fever. The patient underwent urgent EVAR for an inflammatory abdominal aortic aneurysm. A 31 × 14 × 145-mm Gore® Excluder® endograft (W.L. Gore & Associates, Inc.; Flagstaff, Ariz) was deployed.

After EVAR, the patient's lumbar pain promptly disappeared, but his fever persisted. Blood cultures grew methicillin-resistant Staphylococcus epidermidis, and a urine culture contained >100,000 colony-forming units of Pseudomonas aeruginosa and Serratia marcescens. Examination of the central venous catheter tip used during the EVAR procedure yielded Candida albicans. The patient underwent 50 days of specific antibiotic therapy until his fever disappeared, and then he was discharged from the hospital. During his hospitalization, a computed tomographic angiogram (CTA) showed thickening and enhancement of the aortic wall, suggesting a persistent, intense periaortic inflammatory reaction.

In November 2012, the patient was admitted to our hospital with fever (temperature, 38.8 °C), abdominal pain, and malaise. Blood tests revealed mild anemia (hemoglobin, 10.7 g/dL), leukocytosis (white blood cell count, 18.25 ×109 /L) with significant neutrophilia (neutrophils, 15.77 ×103 /μL), an elevated serum C-reactive protein level of 27.95 mg/L, and an erythrocyte sedimentation rate of 56 mm/hr. An emergency CTA showed a perigraft gas collection, consistent with endograft infection (Fig. 1).

Fig. 1

Preoperative computed tomographic angiogram shows periprosthetic fluid and gas collections associated with inflammation of the aortic wall.

Fig. 1

Preoperative computed tomographic angiogram shows periprosthetic fluid and gas collections associated with inflammation of the aortic wall.

Even in the absence of melena, an esophagogastroduodenoscopy was performed, to exclude a secondary aortoenteric fistula. Surgical conversion consisting of endograft explantation and aortic reconstruction was planned.

Surgery was performed through a median xifopubic laparotomy. The juxtarenal aortic wall was substantially inflamed, so suprarenal clamping was necessary. Renal hypothermia was achieved by selective perfusion of the renal arteries (4 °C lactated Ringer solution with 12.5 g/L of mannitol and 125 mg/L of methylprednisolone).18  The endograft (Fig. 2A) was completely removed, and infrarenal reconstruction was performed in end-to-end fashion with use of a rifampin-soaked, silver-coated Dacron bifurcated graft (Fig. 2B).

Fig. 2

Intraoperative photographs show A) evidence of graft infection and B) the completed reconstruction.

Fig. 2

Intraoperative photographs show A) evidence of graft infection and B) the completed reconstruction.

During the patient's 9-day postoperative intensive care unit stay, he had fever (temperature, 39 °C) and pneumonia. Blood cultures, bronchoalveolar-lavage fluid samples, and the explanted prosthesis were positive for colistin-resistant CPKP: the minimum inhibitory concentrations of ertapenem, meropenem, and colistin were 128, 256, and ≥16 μg/mL, respectively. In accordance with the available medical literature,17  empiric therapy with fosfomycin (3 g, 4×/d) and tigecycline (50 mg, 2×/d) was started; however, the fever and positive cultures persisted.

An experimental protocol at our hospital enabled the intravenous administration of ertapenem (1 g/d) for 4 weeks and meropenem (2 g, 3×/d). The patient's fever completely resolved after 21 days of this regimen. On the 30th day, a CTA showed nothing unusual except a distal right anastomotic pseudoaneurysm (maximum diameter, 18 mm). We successfully treated the pseudoaneurysm by means of percutaneous endovascular relining, with use of an 11 × 90-mm Zenith® iliac leg (Cook Medical Inc.; Bloomington, Ind). The patient recovered uneventfully, had normal hematologic test results, and was discharged from the hospital 7 days postprocedurally.

Follow-up clinical examinations and laboratory tests were scheduled at 6 weeks; 3, 6, and 12 months; and annually thereafter. Monitoring with CTA was performed at 6, 12, and 24 months. At the patient's 3-year follow-up evaluation, he was in good clinical condition, with no laboratory or radiologic signs of persistent or recurrent infection (Fig. 3).

Fig. 3

At the 3-year follow-up evaluation, computed tomographic angiograms show A) no evidence of recurrent infection (axial view), and B) good graft patency and correct positioning of the right iliac stent-graft (volume-rendered 3-dimensional reconstruction).

Fig. 3

At the 3-year follow-up evaluation, computed tomographic angiograms show A) no evidence of recurrent infection (axial view), and B) good graft patency and correct positioning of the right iliac stent-graft (volume-rendered 3-dimensional reconstruction).

Discussion

The incidence of endograft infection after EVAR has been reported in major series as 0.2% to 0.9%,7,8,12–15  although the actual rate is difficult to estimate.19  Those percentages might rise, given the projected increases in numbers of EVAR procedures.

The absence of a standardized follow-up protocol and the heterogeneous, nonspecific symptoms in the early phase of endograft infection can cause extensive delays in final diagnosis. Accordingly, at the time of treatment, patients often present in poor clinical condition and with a poor prognosis.19 

When open conversion is planned in these patients, high surgical risk is posed by their typically older age and poor clinical condition, by suprarenal or supraceliac aortic clamping, and by the technical challenges of endograft removal, especially in nonelective circumstances.12  The high mortality rates reported in all series thus far are of great concern. In one report, 16% of patients who underwent extra-anatomic reconstruction died, compared with 5.8% who had in situ reconstruction.7  For these reasons, less invasive treatments have been recommended for patients who have severe underlying diseases.7–13  Results in those cases seem somewhat inferior to those in complete excision. Hart and colleagues20  found a 13% rate of recurrent infection in patients who underwent complete graft excision and a 27% rate in those who underwent partial graft salvage. The postoperative mortality rates were 27% and 40% in the 2 treatment groups, respectively. These discouraging results are compounded by the lack of a specific and effective antibiotic therapy. In fact, microbiologic tests are negative in approximately 30% of cases, and a multibacterial cause has been reported in approximately 20% of endograft infections.21  Therefore, even after successful surgical endograft removal, concerns exist about proper antibiotic protocols. In accordance with accumulated knowledge about treating aortic-graft infections,22–27  we chose to perform complete endograft excision and in situ aortic reconstruction in our patient.

Microbiologic tests of our patient's explanted endograft revealed a very rare microorganism. Sepsis from CPKP is associated with a high mortality rate (13%–58%).16,17  Results are even worse when colistin resistance is detected,28  because colistin is the core component of several therapeutic combinations.29  Patients who had sepsis caused by colistin-resistant CPKP had a significantly higher mortality rate than did patients who had colistin-susceptible CPKP infections (40.6% vs 20.3%; P=0.04).28 

Some authors have reported successful results from a double-carbapenem regimen (ertapenem and either meropenem or doripenem).30–33  Ertapenem activity is greatly affected by carbapenemases, so it might act as a suicide substrate. After the carbapenemase receptors have been bound by ertapenem, the second carbapenem (meropenem or doripenem) can then exert its antimicrobial activity.31,34 

Because of the sparse data on endograft infections caused by colistin-resistant CPKP, we treated our patient with ertapenem and meropenem. The double-carbapenem regimen induced a clinical response (initial defervescence), and a microbiologic response (no growth in blood cultures) 48 hours after antibiotic therapy was started. Complete regression of symptoms occurred in 21 days. The distal anastomotic pseudoaneurysm was detected during the scheduled 30-day CTA and was treated by deploying another endograft. Placing another graft in a recently infected anatomic field could have been hazardous, but we proceeded because the patient was judged to be clinically well and free from infection. The combined surgical removal of the endograft and the new pharmacologic treatment protocol provided a satisfactory result in our patient.

References

1.
Greenhalgh
RM
,
Brown
LC
,
Kwong
GP
,
Powell
JT
,
Thompson
SG
;
EVAR trial participants
.
Comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled trial
.
Lancet
2004
;
364
(
9437
):
843
8
.
2.
Prinssen
M
,
Verhoeven
EL
,
Buth
J
,
Cuypers
PW
,
van Sambeek
MR
,
Balm
R
,
et al
.
A randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms
.
N Engl J Med
2004
;
351
(
16
):
1607
18
.
3.
Lederle
FA
,
Freischlag
JA
,
Kyriakides
TC
,
Padberg
FT
Jr,
Matsumura
JS
,
Kohler
TR
,
et al
.
Outcomes following endovascular vs open repair of abdominal aortic aneurysm: a randomized trial
.
JAMA
2009
;
302
(
14
):
1535
42
.
4.
Chaikof
EL
,
Brewster
DC
,
Dalman
RL
,
Makaroun
MS
,
Illig
KA
,
Sicard
GA
,
et al
.
The care of patients with an abdominal aortic aneurysm: the Society for Vascular Surgery practice guidelines
.
J Vasc Surg
2009
;
50
(
4 Suppl
):
S2
49
.
5.
Sampram
ES
,
Karafa
MT
,
Mascha
EJ
,
Clair
DG
,
Greenberg
RK
,
Lyden
SP
,
et al
.
Nature, frequency, and predictors of secondary procedures after endovascular repair of abdominal aortic aneurysm
.
J Vasc Surg
2003
;
37
(
5
):
930
7
.
6.
Hobo
R
,
Buth
J
;
EUROSTAR collaborators
.
Secondary interventions following endovascular abdominal aortic aneurysm repair using current endografts. A EUROSTAR report
.
J Vasc Surg
2006
;
43
(
5
):
896
902
.
7.
Ducasse
E
,
Calisti
A
,
Speziale
F
,
Rizzo
L
,
Misuraca
M
,
Fiorani
P.
Aortoiliac stent graft infection: current problems and management
.
Ann Vasc Surg
2004
;
18
(
5
):
521
6
.
8.
Sharif
MA
,
Lee
B
,
Lau
LL
,
Ellis
PK
,
Collins
AJ
,
Blair
PH
,
Soong
CV.
Prosthetic stent graft infection after endovascular abdominal aortic aneurysm repair
.
J Vasc Surg
2007
;
46
(
3
):
442
8
.
9.
Hobbs
SD
,
Kumar
S
,
Gilling-Smith
GL.
Epidemiology and diagnosis of endograft infection
.
J Cardiovasc Surg (Torino)
2010
;
51
(
1
):
5
14
.
10.
Fiorani
P
,
Speziale
F
,
Calisti
A
,
Misuraca
M
,
Zaccagnini
D
,
Rizzo
L
,
Giannoni
MF.
Endovascular graft infection: preliminary results of an international enquiry
.
J Endovasc Ther
2003
;
10
(
5
):
919
27
.
11.
Brinster
CJ
,
Fairman
RM
,
Woo
EY
,
Wang
GJ
,
Carpenter
JP
,
Jackson
BM.
Late open conversion and explantation of abdominal aortic stent grafts
.
J Vasc Surg
2011
;
54
(
1
):
42
6
.
12.
Kelso
RL
,
Lyden
SP
,
Butler
B
,
Greenberg
RK
,
Eagleton
MJ
,
Clair
DG.
Late conversion of aortic stent grafts
.
J Vasc Surg
2009
;
49
(
3
):
589
95
.
13.
Laser
A
,
Baker
N
,
Rectenwald
J
,
Eliason
JL
,
Criado-Pallares
E
,
Upchurch
GR
Jr.
Graft infection after endovascular abdominal aortic aneurysm repair
.
J Vasc Surg
2011
;
54
(
1
):
58
63
.
14.
Heyer
KS
,
Modi
P
,
Morasch
MD
,
Matsumura
JS
,
Kibbe
MR
,
Pearce
WH
,
et al
.
Secondary infections of thoracic and abdominal aortic endografts
.
J Vasc Interv Radiol
2009
;
20
(
2
):
173
9
.
15.
Phade
SV
,
Keldahl
ML
,
Morasch
MD
,
Rodriguez
HE
,
Pearce
WH
,
Kibbe
MR
,
Eskandari
MK.
Late abdominal aortic endograft explants: indications and outcomes
.
Surgery
2011
;
150
(
4
):
788
95
.
16.
Munoz-Price
LS
,
Poirel
L
,
Bonomo
RA
,
Schwaber
MJ
,
Daikos
GL
,
Cormican
M
,
et al
.
Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases
.
Lancet Infect Dis
2013
;
13
(
9
):
785
96
.
17.
Tumbarello
M
,
Viale
P
,
Viscoli
C
,
Trecarichi
EM
,
Tumietto
F
,
Marchese
A
,
et al
.
Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy
.
Clin Infect Dis
2012
;
55
(
7
):
943
50
.
18.
Lemaire
SA
,
Jones
MM
,
Conklin
LD
,
Carter
SA
,
Criddell
MD
,
Wang
XL
,
et al
.
Randomized comparison of cold blood and cold crystalloid renal perfusion for renal protection during thoracoabdominal aortic aneurysm repair
.
J Vasc Surg
2009
;
49
(
1
):
11
9
.
19.
Capoccia
L
,
Mestres
G
,
Riambau
V.
Current technology for the treatment of infection following abdominal aortic aneurysm (AAA) fixation by endovascular repair (EVAR)
.
J Cardiovasc Surg (Torino)
2014
;
55
(
3
):
381
9
.
20.
Hart
JP
,
Eginton
MT
,
Brown
KR
,
Seabrook
GR
,
Lewis
BD
,
Edmiston
CE
Jr,
et al
.
Operative strategies in aortic graft infections: is complete graft excision always necessary?
Ann Vasc Surg
2005
;
19
(
2
):
154
60
.
21.
Cernohorsky
P
,
Reijnen
MM
,
Tielliu
IF
,
van Sterkenburg
SM
,
van den Dungen
JJ
,
Zeebregts
CJ.
The relevance of aortic endograft prosthetic infection
.
J Vasc Surg
2011
;
54
(
2
):
327
33
.
22.
Menna
D
,
Capoccia
L
,
Sirignano
P
,
Esposito
A
,
Rossi
M
,
Speziale
F.
Infective etiology affects outcomes of late open conversion after failed endovascular aneurysm repair
.
J Endovasc Ther
2015
;
22
(
1
):
110
5
.
23.
Liberatore
M
,
Misuraca
M
,
Calandri
E
,
Rizzo
L
,
Speziale
F
,
Iurilli
AP
,
Anagnostou
C.
White blood cell scintigraphy in the diagnosis of infection of endovascular prostheses within the first month after implantation
.
Med Sci Monit
2006
;
12
(
3
):
MT5
9
.
24.
Speziale
F
,
Rizzo
L
,
Fadda
GF
,
Fiorani
P
,
Alfani
D
,
Rossi
M.
Surgical approach for the treatment of secondary aortoenteric fistulae
.
Eur J Vasc Endovasc Surg
1998
;
16
(
6
):
530
4
.
25.
Fiorani
P
,
Speziale
F
,
Rizzo
L
,
Taurino
M
,
Giannoni
MF
,
Lauri
D.
Long-term follow-up after in situ graft replacement in patients with aortofemoral graft infections
.
Eur J Vasc Endovasc Surg
1997
;
14
Suppl A
:
111
4
.
26.
Speziale
F
,
Rizzo
L
,
Sbarigia
E
,
Giannoni
MF
,
Massucci
M
,
Maraglino
C
,
et al
.
Bacterial and clinical criteria relating to the outcome of patients undergoing in situ replacement of infected abdominal aortic grafts
.
Eur J Vasc Endovasc Surg
1997
;
13
(
2
):
127
33
.
27.
Santini
C
,
Baiocchi
P
,
Venditti
M
,
Brandimarte
C
,
Tarasi
A
,
Rizzo
L
,
et al
.
Aorto-femoral graft infections: a clinical and microbiological analysis
.
J Infect
1993
;
27
(
1
):
17
26
.
28.
Capone
A
,
Giannella
M
,
Fortini
D
,
Giordano
A
,
Meledandri
M
,
Ballardini
M
,
et al
.
High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality
.
Clin Microbiol Infect
2013
;
19
(
1
):
E23
30
.
29.
Kontopoulou
K
,
Protonotariou
E
,
Vasilakos
K
,
Kriti
M
,
Koteli
A
,
Antoniadou
E
,
Sofianou
D.
Hospital outbreak caused by Klebsiella pneumoniae producing KPC-2 beta-lactamase resistant to colistin
.
J Hosp Infect
2010
;
76
(
1
):
70
3
.
30.
Bulik
CC
,
Nicolau
DP.
Double-carbapenem therapy for carbapenemase-producing Klebsiella pneumoniae
.
Antimicrob Agents Chemother
2011
;
55
(
6
):
3002
4
.
31.
Giamarellou
H
,
Galani
L
,
Baziaka
F
,
Karaiskos
I.
Effectiveness of a double-carbapenem regimen for infections in humans due to carbapenemase-producing pandrug-resistant Klebsiella pneumoniae
.
Antimicrob Agents Chemother
2013
;
57
(
5
):
2388
90
.
32.
Daikos
GL
,
Markogiannakis
A.
Carbapenemase-producing Klebsiella pneumoniae: (when) might we still consider treating with carbapenems?
Clin Microbiol Infect
2011
;
17
(
8
):
1135
41
.
33.
Qureshi
ZA
,
Paterson
DL
,
Potoski
BA
,
Kilayko
MC
,
Sandovsky
G
,
Sordillo
E
,
et al
.
Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens
.
Antimicrob Agents Chemother
2012
;
56
(
4
):
2108
13
.
34.
Thomson
KS.
Double-carbapenem therapy not proven to be more active than carbapenem monotherapy against KPC-positive Klebsiella pneumoniae
.
Antimicrob Agents Chemother
2012
;
56
(
7
):
4037
8
.

Author notes

From: Vascular and Endovascular Surgery Division, Department of Surgery, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy