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.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

Capoccia, Laura

Mansour, WASSIM AHMAD

Menna, Danilo

Montelione, Nunzio

Sirignano, Pasqualino

Speziale, Francesco

Texas Heart Institute Journal

English

PubMed

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.</jats:p

Nunzio Montelione

Danilo Menna

Pasqualino Sirignano

Laura Capoccia

Wassim Mansour

Francesco Speziale

Crossref

Open Conversion after Aortic Endograft Infection Caused by Colistin-Resistant, Carbapenemase-Producing Klebsiella pneumoniae

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.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

MONTELIONE, NUNZIO

MENNA, DANILO

SIRIGNANO, PASQUALINO

CAPOCCIA, LAURA

MANSOUR, WASSIM  AHMAD

SPEZIALE, Francesco

Archivio della ricerca- Università di Roma La Sapienza

Texas Heart Institute Journal • Oct. 2016, Vol. 43, No. 5 http://dx.doi.org/10.14503/THIJ-15-5265      453© 2016 by the Texas Heart ® Institute, HoustonOpen Conversion after Aortic Endograft InfectionCaused by Colistin-Resistant, Carbapenemase-Producing Klebsiella pneumoniaeA 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 pneu-moniae, 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. (Tex Heart Inst J 2016;43(5):453-7)E ndovascular 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 f irst 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 ReportIn 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 inflamma-tory 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 cul-ture contained >100,000 colony-forming units of Pseudomonas aeruginosa and Serratia marcescens. Examination of the central venous catheter tip used during the EVAR pro-cedure 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 thick-ening 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 (tem-perature, 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. CaseReportsNunzio Montelione, MDDanilo Menna, MDPasqualino Sirignano, MDLaura Capoccia, MDWassim Mansour, MDFrancesco Speziale, MDKey words: Anti-bacterial agents/therapeutic use; aortic aneurysm, abdominal/surgery; bacterial infections/drug therapy/etiology/micro-biology; blood vessel pros-thesis implantation/adverse effects; drug therapy, combination; endovascular procedures/adverse effects; Klebsiella pneumoniae/drug effects/growth & develop-ment; postoperative compli-cations; prosthesis-related infections/diagnosis/drug therapy/microbiology/sur-gery; treatment outcomeFrom: Vascular and Endo-vascular Surgery Division, Department of Surgery, Poli-clinico Umberto I, Sapienza University of Rome, 00161 Rome, ItalyAddress for reprints: Nunzio Montelione, MD, Vascular and Endovascular Surgery Division, Policlinico Umberto I, Sapienza Univer-sity of Rome, Viale del Poli-clinico 155, 00161 Rome, ItalyE-mail:  nunzio_montelione@ hotmail.itOct. 2016, Vol. 43, No. 5454      Open Conversion after K. pneumoniae Endograft InfectionAn emergency CTA showed a perigraft gas collection, consistent with endograft infection (Fig. 1). Even in the absence of melena, an esophagogastro-duodenoscopy was performed, to exclude a secondary aortoenteric f istula. 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 methylpred-nisolone).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). 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 accor-dance 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 pseudo-aneurysm by means of percutaneous endovascular relin-ing, 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 postprocedur-ally. Follow-up clinical examinations and laboratory tests were scheduled at 6 weeks; 3, 6, and 12 months; and annually thereafter. Monitoring with CTA was per-formed at 6, 12, and 24 months. At the patient’s 3-year follow-up evaluation, he was in good clinical condition, Fig. 1  Preoperative computed tomographic angiogram shows periprosthetic fluid and gas collections associated with inflam-mation of the aortic wall.Fig. 2  Intraoperative photographs show A) evidence of graft infection and B) the completed reconstruction.ABTexas Heart Institute Journal  Open Conversion after K. pneumoniae Endograft Infection      455with no laboratory or radiologic signs of persistent or recurrent infection (Fig. 3).DiscussionThe incidence of endograft infection after EVAR has been reported in major series as 0.2% to 0.9%,7,8,12-15 al-though the actual rate is diff icult 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 suprace-liac aortic clamping, and by the technical challenges of endograft removal, especially in nonelective circum-stances.12 The high mortality rates reported in all se-ries 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 reconstruc-tion.7 For these reasons, less invasive treatments have been recommended for patients who have severe un-derlying diseases.7-13 Results in those cases seem some-what 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 discour-aging 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 approximate-ly 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 in-fections,22-27 we chose to perform complete endograft excision and in situ aortic reconstruction in our patient. Microbiologic tests of our patient’s explanted endo-graft 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 signifi-cantly 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 antimi-crobial activity.31,34 Because of the sparse data on endograft infections caused by colistin-resistant CPKP, we treated our pa-tient 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 ABFig. 3  At the 3-year follow-up evaluation, computed tomo-graphic 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).Oct. 2016, Vol. 43, No. 5456      Open Conversion after K. pneumoniae Endograft Infectionstarted. 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 f ield 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, Thomp-son 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 Sam-beek MR, Balm R, et al. A randomized trial comparing conventional and endovascular repair of abdominal aortic an-eurysms. 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 endo-vascular vs open repair of abdominal aortic aneurysm: a ran-domized 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 abdomi-nal 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 sec-ondary procedures after endovascular repair of abdominal aortic aneurysm. J Vasc Surg 2003;37(5):930-7.  6. Hobo R, Buth J; EUROSTAR collaborators. Secondary in-terventions following endovascular abdominal aortic aneu-rysm 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, Fio-rani 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: pre-liminary 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 ab-dominal 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 ab-dominal 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 ab-dominal 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 en-dograft explants: indications and outcomes. Surgery 2011;150 (4):788-95.16. Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Dai-kos 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 thera-py. 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 dur-ing 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 aneu-rysm (AAA) fixation by endovascular repair (EVAR). J Car-diovasc 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, Spe-ziale F. Infective etiology affects outcomes of late open conver-sion 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 En-dovasc 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, Ko-teli 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.Texas Heart Institute Journal  Open Conversion after K. pneumoniae Endograft Infection      45730. Bulik CC, Nicolau DP. Double-carbapenem therapy for car-bapenemase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 2011;55(6):3002-4.31. Giamarellou H, Galani L, Baziaka F, Karaiskos I. Effective-ness of a double-carbapenem regimen for infections in hu-mans 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, Sandov-sky 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 Che-mother 2012;56(7):4037-8.

Open conversion after aortic endograft infection. Caused by colistin-resistant, carbapenemase-producing Klebsiella pneumoniae

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Open conversion after aortic endograft infection. Caused by colistin-resistant, carbapenemase-producing Klebsiella pneumoniae

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