OUTPATIENT ANTIMICROBIAL THERAPY FOR ENDOVASCULAR

AORTIC REPAIR INFECTION; A FIVE YEAR RETROSPECTIVE

EVALUATION

Dr. Niamh Allen (1), Dr. Mohamed Eltayeb (1), Dr. Grace O’Regan (1), Dr. Aoife Seery(1), Dr. Cora Mc Nally (1), Prof. Samuel McConkey (1)(2), Dr. Eoghan de Barra (1)(2)

1. Beaumont Hospital, Dublin, Ireland

2. Royal College of Surgeons (RCSI) , Dublin, Ireland

OVERVIEW

• 1% of endovascular aortic repair (EVAR) devices become infected- high mortality rate [1].

• OPAT database• 5-year period from 2014-2018; infected EVAR

• Median age 76 (65-85)

• Median Charleston co-morbidity index 6.5

• 11 abdominal aorta, 1 fem-pop

• At our centre 400 EVARs placed in that time period

OVERVIEW OF PRESENTATION

1. Brief description of 3 cases2. Case definitions - MAGIC criteria3. Clinical features4. Causative Organisms5. Management

a. General principlesb. Our cohort (medical/surgical)c. Commonly used antimicrobials on OPAT

6. Outcomes7. Take home points

CASE 1

• 70 yr old male

• BG: A fib, IHD, PVD

• Infra-renal EVAR 13/6/17 -elective

• Bilateral ax/fem grafts 21/7/17

• Day 3 post-op • fever, raised wcc, fast AF• Wound clinically infected• BC+ pseudomonas• Imaging: fluid and gas collection

R+ L groin• Femoral aspirate culture

positive pseudomonas

→ AGI; diagnosed, early (<4 months)

1. Lyons, O. T. A., Baguneid, M., Barwick, T. D., Bell, R. E., Foster, N., Homer-Vanniasinkam, S., … Price, N. M. (2016). Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC). European Journal of Vascular and Endovascular Surgery, 52(6), 758–763.

DIAGNOSTIC CRITERIA: MANAGEMENT OF AORTIC GRAFT INFECTION

COLLABORATION (MAGIC)

CASE 1 - MANAGEMENT AND PROGRESS

• 12 weeks piptaz (OPAT) → PO ciprofloxacin

• June 2018; collection axillary site → drainage + piptaz (OPAT)

• Mild erythematous rash on tazocin – continue and observe

• Oct 2018 - recurrence of collections

• Daptomycin added

• Elective admission for surgery

• Planned EVAR explant and later plan for removal of infected ax/fem grafts

CASE 1 – PROGRESS CONT.

• Stormy post-op course – prolonged ICU admission

• Further 4/12 IV antibiotics

• Eventually d/c to rehab April 2019 on PO cipro

• No further plans for ax/fem explant

• Life long suppression

CASE 1 HIGHLIGHTS

• Consensus approach of 6-12 weeks iv antibiotics followed by oral suppressive therapy

• Prolonged and recurrent use of IV antibiotics – induction and break-throughs on oral

• OPAT as a bridge to surgical explantation

• Antibiotic S/Es

• Piptaz – drug rash

• Daptomycin – eosinophilic pneumonitis

• Multiple re-admissions (n=6)

CASE 2

• 80 year old gentleman

• BG: A.fib, IHD w/ PCI, retinal vein occlusion

• Infrarenal EVAR 2012

• Elective procedure due to AAA of 5.7cm

• No post-op complications

CASE 2- 3 ½ YEARS LATER

• Pyrexic, tender abdomen, raised inflammatory markers

• BC positive for salmonella enteriditis

→ Dx of aortitis with presumed graft infection

→ Ceftriaxone IV x 3/52 on OPAT suspected case → Pyrexia, raised inflammatory markers, expansion of fluid on imaging

CASE 2 - MANAGEMENT AND PROGRESS

• May 2016 – 6 months later

• Biopsy of necrotic para- aortic node

• Psoas haematoma and lumbar artery injury

• Further 6 weeks IV antibiotics (OPAT)

• October 2016 – interval imaging

• progressive aortitis

• psoas abscess

• aorto-duodenal fistula

→ Seeded Salmonella infection.

→Antibiotics cover broadened; 6/12 on OPAT

CASE 2- MANAGEMENT AND PROGRESS

• February 2017; worsening back pain and air in sac

• Not for further vascular intervention

• Suppressive rx with Cefixime

• Palliative treatment

• 2018 – 2 further courses of OPAT

• BSI strep anginosus

• expansion of aneurysm and new para-aortic collection

• Each time back to suppressive therapy

CASE 2 HIGHLIGHTS

• Delayed presentation with infection

• 40 months post deployment

• Polymicrobial

• Fistula

• High risk of surgical intervention

• Haematoma and arterial bleed post biopsy

• Progression despite appropriate antimicrobial therapy

• OPAT as a palliative measure

• 76 yr old male

• BG: HTN, PVD, glaucoma, psoriasis, smoker

• Emergency EVAR April 2016– 11cm AAA

• Complicated by EVAR limb occlusion: Fem-fem bypass 5/52 post EVAR

• 11 months post EVAR (March 17)

• Leucocytosis, abdo/back pain, pyrexia, anorexia

• No positive micro

• Imaging: peri-graft gas, ?vertebral osteomyelitis

• AGI – diagnosed, late (>4 months)

• Taz/Vanc as inpatient → Ertapenem x 8/52 (OPAT) → PO suppression

CASE 3

CASE 3- MANAGEMENT AND PROGRESS

• Re-admitted May 18 – vertebral extension + organisms identified

• Enterococcus gallinum + enterococcus faecalis from BC (PICC)

• Not for surgical intervention

• Linezolid + antifungal cover added

• Vertebral biopsy 16s – bacteroides caccae

• July 2018

• Discharged on ertapenem, fluconazole PO and metronidazole PO

CASE 3 - MANAGEMENT AND PROGRESS

• August 2018

• retroperitoneal spread

• not a surgical candidate

• meropenem, caspofungin, linezolid PO + discharged on OPAT

• Sept 2018

• iatrogenic anaemia, Hb 6.6g/dL• Linezolid and caspofungin discontinued

• Currently

• Maintinaed on co-amoxiclav + fluconazole PO• March 2019 further 2/52 IV therapy

• Lifelong suppression

CASE 3 HIGHLIGHTS

• Polymicrobial infection - no micro initially

• Vertebral biopsy and positive BC

• Consideration of fungal infection

• Fistula

• Role of IV versus PO antibiotics

• Long term PO antibiotics

• Prolonged and recurrent use of IV antibiotics for clinical flares

• Multiple re-admissions

• Antibiotic S/Es

• Option of surgical intervention re-visited on each admission

CASE DEFINITIONS

7

6

6

3

2

3

4

0 2 4 6 8 10

FEVER

ANOREXIA

ABDO/ GROIN PAIN

BACK PAIN

BLEEDING

LEUCOCYTOSIS

BLOOD CULTURES POSITIVE

CLINICAL FEATURES

• Pain (n=9), fever (n=7), anorexia (n=6)

• Leucocytosis in 3/12

• Blood cultures positive 4/12

CAUSATIVE ORGANISMS

• Causative organisms identified in 8/12 (66.6%)

CAUSATIVE ORGANISMS CONT.

0

1

2

3

4

5

coag neg staph pseudomonas candida bacteroides salmonella strep C/G MSSA VRE anaerobes

Causative Organisms Identified

Gram +Gram -Fungal

ORGANISMS IN PUBLISHED DATA

MANAGEMENT PRINCIPLES

• Sample for micro – risk vs benefits

• Treat as polymicrobial

• Suspect fistula

• Induction therapy: 6 weeks iv antibiotics (potentially longer)

• Long-term oral suppression• Expect break-through

• Consideration for explantation

MANAGEMENT ; SURGICAL

• Surgical explantation with debridement + long term ABx is standard of care but

• Co-morbidity profile

• Nature of the devices- not made to be removed

• 2/11 had surgical explantation

1

2

4

1

3

1

0 1 2 3 4 >5

Number of Antimicrobial Switches

MANAGEMENT; MEDICAL

• Median days on OPAT 46, total 864

3

4

4

10

OPAT Antimicrobials

piptaz

cephalosporin

carbapenem

vancomycin

daptomycin

teicoplanin

caspofungin

>1 antimicrobial

OUTCOMES

• 10/12 (83.3%) re-admitted to hospital at least once, median 4, range 0-6

• Median bed days 67, range 9-199, total 922

10

2

Re-admitted post diagnosis

Yes

No

OUTCOMES

• 4/12 (33.3%) died - at 5, 10, 27 and 72 months• Multiple co-morbidities and older (Charlson 7-12,

median age 84)

• At median 29 months in published data – all dead who had no explantation (1).

• In our data 8/12 alive at median of 24 months follow up.

• Palliative care referral offered to ¾ who died

• 8/12 alive• 6 on long-term PO antibiotics (1 intermittently on

OPAT)

• 2 off antibiotics

TAKE HOME POINTS

• Prolonged antibiotic therapy, often complex• Polymicrobial infections requiring >1 anti-microbial• Long hospital stays and multiple re-admissions• High mortality rates• The role and optimal timing of surgical explanation unclear; technically difficult

and patient co-morbidities• Roles of OPAT• Temporizing measure• Bridge to graft explantation• Break-throughs on oral suppression• Palliative intervention in some cases

THANK YOU!

REFERENCES

1. Lyons, O. T. A., Patel, A. S., Saha, P., Clough, R. E., Price, N., & Taylor, P. R. (2013). A 14-year experience with aortic endograft infection: Management and results. European Journal of Vascular and Endovascular Surgery, 46(3), 306–313.

2. Lyons, O. T. A., Baguneid, M., Barwick, T. D., Bell, R. E., Foster, N., Homer-Vanniasinkam, S., … Price, N. M. (2016). Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC). European Journal of Vascular and Endovascular Surgery, 52(6), 758–763.

FURTHER EVALUATION NEEDED…

• Role and duration of OPAT where no oral option available• Complications• Line related• antimicrobial S/Es etc

ADDITIONAL PRESENTERS NOTES

• Antibiotici therapy – current status of those alive: 5 patients are currently on long term antibiotic and are all PO, and 2 off antibiotics the remaining 4 are dead.

• Explantation: 1/11 had surgical removal of the Femro-popliteal bybpass graft with primary outcome death after 72 months of follow up. 2/11 patients had undergone sinus excision and one died within 5 months after diagnosis of infection.

• Comparison of mortality: our series at median follow up of 24 months 4/11 dead (1 had explantation, 2 had temporising measures, 8 had no surgical management). Compared to literature A 14-year experience with aortic endograft infection: Management and results. In which the mortality rate is 100% without surgical explanation. (1) – at median f/u of 29 months

• Describing the results in 3 domains:

• 1- the case definitions using the MAGIC criteria ( 8 diagnosed), of those 8 patients there are 2 currently not antibiotics and no available data on one patient.

• 2- management: surgical definitive i.e Explantaion was not performed to any patient but other measures like sac aspiration were done for 3/11 2 of them are diagnosed based on MAGIC. All patients were under surveillance CT/US. Broad spectrum antibiotic were used in 10/11 with as initial management with one patient was put on fluconazole

• 3- primary out come death is 4/11, all were diagnosed cases, index indication was rupture in 2/4.

• To add further:

• MAGIC to be used as its easily applied to define the case.

• antibiotic choice in negative culture patients will be broad spectrum (what to choose first clinically in circumstances like aortoenteric fistula or thoracenteric fistula) and on the other hand should be guided with the sensitivity result.

• Surgical explantation with debridement + long term ABx is standard of care but given the com-morbidity profile the nature of the devices which isn’t made to be removed the best chance will be temporizing surgical measures in addition to long term suppressive therapy with antibiotic and consideration of palliative care referral earlier.