PRINCIPLES OF PERI-OPERATIVE ANTIMICROBIAL PROPHYLAXIS … ESU... · EAU guidelines 2016 ....

PRINCIPLES OF PERI-OPERATIVE

ANTIMICROBIAL PROPHYLAXIS IN

UROLOGY AND

SOME EXAMPLES OF DAILY CARE

Magnus Grabe, M.D., Ph.D.

University of Lund, Sweden

ESU AMU AMP/MG

Photos: M Grabe

Urological Infections

Prostate cancer

Stone disease

Kidney

transplant

ation

MAGI Pelvic pain?

Paediatric

BPH

TCC +

other ca Female

urology

Neurogenic

dysfuntion

Therapy

Antimicrobial prophylaxis in surgery

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Evidence for antimicrobial prophylaxis in

urology (examples)

• Strong evidence:

• TUR-P

• Trans-rectal core biopsy of the prostate

• Moderate evidence:

• Advances endourological procedures (PNL, RIRS, URS)

• Low, controversial or no evidence:

• Cystoscopy

• ESWL

• TUR-BT

• No demonstrated evidence:

• Most other procedures - operations

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Reasons for a model for antimicrobial

prophylaxis

10 per cent healthcare associated infections in

urology (GPIU studies)

Antibiotic resistance dramatic development

Few new antimicrobial agents in the “pipe-line”

Limited evidence for peri-operative antimicrobial

prophylaxis for most procedures

Urologist are big users – and misusers of

antimicrobial agents

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NEED FOR A MODEL!

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Principle of perioperative antimicrobial prophylaxis

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Decrease the load of liberated bacteria in the surgical site

Antimicrobial drug

Bacteria, e.g. E. coli, Klebsiella sp,

Proteus sp

Effective surgery

Low pressure

Optimal drainage

Antimicrobial regimen

• Choice of antibiotic

• Dosage (normal)

• Administration

• Oral = parenteral

• TMP-SMZ (< 20% Resist)

• Aminoglycoside

• Directed when known or

expected species

• Be parsimonious with

• Cephalosporins

• Avoid

• Fluoroquinolones

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Because of the selection of resistance



• Dosage (normal)

• Administration

• Oral = parenteral

• Timing

• 1 h prior (oral)

• 30-0 min (i.v.)


• Aminoglycoside

• Directed when known or

expected species


• Cephalosporins

• Avoid


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• Dosage (normal)

• Administration • Oral = parenteral

• Timing • 1 h prior (oral)

• 30-0 min (i.v.)

• Duration • Single dose

• Prolonged?


• Aminoglycoside

• Directed when known or expected species


• Cephalosporins

• Avoid


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”Collateral damage”

Antibiotic ”drivers”

Cephalosporins

Re-infection with resistant strains

F-quinolones

MRSA

ESBL E. coli Gram neg bacteria

inkl pseudomonas Clostridium difficile

VRE

ESBL E. coli, Klebsiella BL Acinetobacter Clostridum difficile

Paterson, CID, 2004 ESU AMU AMP/MG

CLASSIFICATION OF UROLOGICAL

PROCEDURES IN RELATION TO

LEVEL OF CONTAMINATION

Based on CDC Guidelines on prevention of SSI Mangram et al. Infect Control Hosp Epidemiol 1999;20:250-78

Adapted for urological procedures by EAU

Section on infections in Urology (ESIU)

Urological Infections 2011-2015

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Grabe et al. World J Urol 2011

Clean

Clean-

contaminated

(UT)

Contaminated

Infected

Level of contamination

at surgery

Individual

Risk factors

Antimicrobial agents

Allergic reactions

Unnecessary use

Unnecessary dosage

Resistance development

Collateral damage

Etc…

The EAU guidelines model

Opinion of infectious

diseases people and

microbiologists

Expected

pathogens

C-C (GIT)

Clean

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Patient’s

caracteristics

Patient’s

risk factors

Surgical field contamination: Urology

Surgical

contamination

Description Principle of

antimicrobial

prophylaxis

Clean (I) Urinary, genital or alimentary tracts not entered

Uninfected operative wound and no evidence of

inflammation. No break in technique.

Blunt trauma.

Clean-contaminated

(UT) (IIA)

Urinary or genital tracts entered with no or little

(controlled ) spillage. No break in technique

Clean-contaminated

(bowel) (IIB)

Gastrointestinal tract entered, no or little

(controlled) spillage. No break in technique

Contaminated

(III)

UT or GI tracts entered, spillage of GI content;

inflammatory tissue; major break in technique;

Open, fresh accidental wounds

Bacterial growth in urine

Dirty (IV) Pre-existing infection; viscera perforation

Old traumatic wound

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Grabe et al, WJU 2011

Mangram et al, 1999

Clean but entering the lower UT

Surgical field contamination: Urology

Surgical

contamination


antimicrobial

prophylaxis

Clean (I) Urinary, genital or alimentary tracts not entered

Uninfected operative wound and no evidence of

inflammation. No break in technique.

Blunt trauma.

No

Clean-contaminated

(UT) (IIA)

Urinary or genital tracts entered with no or little

(controlled ) spillage. No break in technique Yes

Single dose If prolonged =

treatment Clean-contaminated

(bowel) (IIB)

Gastrointestinal tract entered, no or little

(controlled) spillage. No break in technique

Contaminated

(III)

UT or GI tracts entered, spillage of GI content;

inflammatory tissue; major break in technique;

Open, fresh accidental wounds

Bacterial growth in urine

Pre-operative

control

Dirty (IV) Pre-existing infection; viscera perforation

Old traumatic wound Treatment

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Grabe et al, WJU 2011

Mangram et al, 1999

Clean but entering the lower UT

Clean: Cystoscopy

Surgical

contamination


antimicrobial

prophylaxis

Clean (I)

Cystoscopy

Urodynamic studies (no RF)

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Very low frequency of clinical UTI

Smooth, atraumatic, short procedure,

no mucosal breach

Clean: Cystoscopy

Surgical

contamination


antimicrobial

prophylaxis

Clean (I)

NO Cystoscopy

Urodynamic studies (no or low RF)

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Herr, J Urol, 2015:

2 435 Neg urine culture: 1,4% UTI treatment

673 ABU: 3,7% UTI treatment

Clean-contaminated procedures

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TUR-BT Nephron – sparing

tumor resection

Bladder cancer/TUR-BT: Surgical site contamination

level and antibiotic prophylaxis

Procedure Class GR AMP - ABP Remarks

Cystoscopy +

fulguration

I

Clean

B

TUR-BT

(no BU)

II

Clean-

Contaminated

C

TUR-BT (large,

necrosis, and

or BU)

III

Contaminated

C

TUR-BT

Infected

IV

Infected

A

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EAU guidelines and Swedish National Guidelines on Urothelial Cancer Management

Bladder cancer/TUR-BT: Surgical site contamination

level and antibiotic prophylaxis

Procedure Class GR AMP - ABP Remarks

Cystoscopy +

fulguration

I

Clean

B No general Risk factors as for

cystoscopy

TUR-BT

(no BU)

II

Clean-

Contaminated

C General

Single dose

Risk factors as for

cystoscopy

TUR-BT (large,

necrosis, and

or BU)

III

Contaminated

C General

Control +

perioperative

Necrotic tissues

BU must be

controlled

TUR-BT

Infected

IV

Infected

A Treatment

Well documented

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EAU guidelines and Swedish National Guidelines on Urothelial Cancer Management

ESWL

Surgical

contamination

Extracorporeal shock-wave lithotripsy ABP policy

Clean (I) Standard kidney and ureter stone (no

obstruction, no BU, no history UTI, no

stent)

Clean-contaminated

(UT) (IIA) Standard kidney and ureter stone

(moderate obstruction but no

drainage/stent, no BU, or history UTI)

Clean-contaminated

(bowel) (IIB)

Contaminated

(III) Complex kidney and/or ureter stone

(obstruction with nephrostomy

drainage/stent, or BU, or history UTI)

Dirty (IV) Infected environment

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ESWL

Surgical

contamination

Extracorporeal shock-wave lithotripsy ABP policy

Clean (I) Standard kidney and ureter stone (no

obstruction, no BU, no history UTI, no

stent)

No

Clean-contaminated

(UT) (IIA) Standard kidney and ureter stone

(moderate obstruction but no

drainage/stent, no BU, or history UTI)

Single dose

Clean-contaminated

(bowel) (IIB)

Contaminated

(III) Complex kidney and/or ureter stone

(obstruction with nephrostomy

drainage/stent, or BU, or history UTI)

Preoperative

control BU +

perioperative

Dirty (IV) Infected environment Therapy

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Principle of perioperative antimicrobial prophylaxis

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Decrease the load of liberated bacteria in the surgical site

Antimicrobial drug

Bacteria, e.g. E. coli, Klebsiella sp,

Proteus sp

Effective surgery

Low pressure

Optimal drainage

URS - PCNL – RIRS

Surgical

contamination

Ureteroscopic and Percutaneous

stone management

ABP policy

Clean (I) Uncomplicated distal stone (no

obstruction, no BU, no stent, no RF)

Clean-contaminated

(UT) (IIA) Uncomplicated kidney or ureteric stone

(no or mild obstruction, nu BU, not

impacted, no stent; history of UTI)

Clean-contaminated

(bowel) (IIB)

Contaminated

(III) Complex kidney or ureteric stone

(moderate or sever obstruction,

“impacted” with nephrostomy

drainage/stent, presence of BU)


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URS - PCNL – RIRS

Surgical

contamination

Ureteroscopic and Percutaneous

stone management

ABP policy

Clean (I) Uncomplicated distal stone (no

obstruction, no BU, no stent, no RF)

No

Clean-contaminated

(UT) (IIA) Uncomplicated kidney or ureteric stone

(no or mild obstruction, nu BU, not

impacted, no stent; history of UTI)

Single dose

Clean-contaminated

(bowel) (IIB)

Contaminated

(III) Complex kidney or ureteric stone

(moderate or sever obstruction,

“impacted” with nephrostomy

drainage/stent, presence of BU)

Preoperative

control BU +

perioperative


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Clean-contaminated procedures

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TUR-BT Nephron – sparing

tumor resection

Open or laparoscopic/robotic assisted procedures

Surgical

contamination

Examples of procedures ABP policy

Clean (I) Simple nephrectomy

Planned scrotal surgery, vasectomy,

varicocoele

Clean-contaminated

(UT) (IIA) Pelvic-ureteric junction repair

Nephron-sparing tumour resection

Total prostatectomy, bladder

resection/repair

Clean-contaminated

(bowel) (IIB) Urine diversion (small intestine), ileal

conduit, orthotopic bladder replacement

Contaminated

(III) Urine diversion (large intestine)

Spillage (any major), concomitent GI

inflammatory disease. Trauma surgery


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Open or laparoscopic/robotic assisted procedures

Surgical

contamination

Examples of procedures ABP policy

Clean (I) Simple nephrectomy

Planned scrotal surgery, vasectomy,

varicocoele

No

Clean-contaminated

(UT) (IIA) Pelvic-ureteric junction repair

Nephron-sparing tumour resection

Total prostatectomy, bladder

resection/repair

Single dose

Clean-contaminated

(bowel) (IIB) Urine diversion (small intestine), ileal

conduit, orthotopic bladder replacement

Single dose

“6 h”/1 day

Contaminated

(III) Urine diversion (large intestine)

Spillage (any major), concomitant GI

inflammatory disease. Trauma surgery

Preoperative

control BU +

perioperative


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RISK FACTORS General

Individual

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Who will be the next victim?

Who is at risk?

PAUSA 2011 09 08

Photo: M Grabe

Risk factors

• General health status (ASA score)

• General risk factors

• Specific risk factors (ORENUC groups)

• Endogenous

• Exogenous

• Type of surgery and surgical field contamination burden

• Level of invasiveness, duration, technique

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General risk factors

• High age

• Nutritional status

• Low level of albumin

• Anaemia

• Deficiency of immune response

• Co-morbidity

• Diabetes mellitus – high glucose level (uncontrolled)

• Connective tissue disorder

• Living style

• Smoking

• Obesity

• Alcohol consumtion

• Bacterial colonisation

• Lack of control of risk factors

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Infect Control Hosp Epidemiol

1999.20:250-78

“Big five” in Urology • History of UTI or Male Accessory gland infection

• Urogenital infection (e.g. acute prostatitis)

• In association of urological procedure

• Presence of Asymptomatic bacteriuria (ABU)

• Catheterisation

• Complicated urological condition

• Complicated stone situation

• Obstructive tumour

• Long pre-operative hospitalisation

• Antibiotic use/tretment

• Within 6 months

• Recent use of quinolones

• Travel in highly prevalent countries

• Colonisation with Multi Resistant strains

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DETECTION OF BACTERIURIA

Prior to urological procedures

What is the best?

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EAU guidelines 2016

Detection of bacteriuria prior to urological procedures

• Aim: • Reduce risk of infectious complications

• Controlling any bacteriuria

• Urine culture: the standard?

• Method: Systematic search review • 3 033 title

• 210 full text review

• 18 studies investigating accuracy of alternative methods

• Alternative methods: • Reagents strips (dipstick) urinanalyse

• Automated microscopy

• Dipslide culture

• Flow cystometry

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Detection of bacteriuria prior to urological procedures

Method Studies Results

Dipstick 16 Best diagnostic accuracy: at least one of nitrite

and leucocyte esterase detected

Low sensitivity (0,8) – limited use

Automated

microscopy

2 High sensitivity (0,98)

Low specificity (0,59)

Optimum diagnostic threshold not determined

Dipslide culture 2 Low accuracy – new studies needed

Flow cystometry 0 Poor quality

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Urine culture prior to urological surgery

• Detect asymptomatic bacteriuria

• Classify as contaminated procedure

• Detect any resistant strain

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Preoperative bacteriuria has to

be controlled

(1-3-5 days treatment)

Validation

• The EAU Urological Infection guidelines version

2015 are peer-reviewed by independent,

internationally recognised reviewers

• Studies that support the strategy (worldwide)

• Directed (examples)

• Japan (Higuchi et al, 2011)

• Italy (Cai et al, 2014, 2015)

• Germany (Magistro et al, 2014)

• Meta-analysis

• More centres adopt progressively the strategy

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Adherence to EAU Guidelines

Parameter “Before” adherence “After” adherence

Period Dec 2008 to Dec 2010 Jan 2011 to Oct 2013

Number procedures 2 619 3 529

Post-operative infectious

complications

117 (4,5%) 180 (5.1%)

(p = 0.27)

Costs of drugs € 76 980 € 36 700

Indirect costs € 45 870 € 29 560

E. Coli resistance for

Piperacillin/tazobactam

Gentamycin

Ciprofloxacin

Reduced (p=0.03)

Reduced (p=0.02)

Reduced (p=0.03)

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Cai et al. EAU Abstract 136, 2015 – based on GPIU studies

Adherence reduce costs and resistance

Message to take home

• Peri-operative Antimicrobial Prophylaxis aims are

reducing infectious complications at surgery

• Antimicrobial prophylaxis is in principle only one single

dose prior to surgery

• Evidence exists only for a few interventions

• There is a need for a model

• Based on level of contamination

• Level of surgical difficulty and time

• All procedures with the same name are not identicale

• Patient assessment is a key factor for prevention

• Antimicrobial prophylaxis according to the EAU model is

gaining support – a tool for reflection and structure

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EAU Guidelines 2015 (peer-reviewed Nov 2014)

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European Section of Infection in Urology (ESIU)

Use the EAU guidelines

2015 and 2016

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