Johansen - The Role of Fosfomycin As Prophylaxis - 20.07.2023
Johansen - The Role of Fosfomycin As Prophylaxis - 20.07.2023
Johansen - The Role of Fosfomycin As Prophylaxis - 20.07.2023
Sources of evidence
• Published series
• Without AP
• With AP
• Registry data Ca. 10% (7-21)
• Comparative studies
• RCTs
• Systematic reviews
Current status on infectious complications after urological procedures
Urodyn studies 6-45%
TURP and TURBT 2.9%
Open prostatectomy SSI 16%
Sources of evidence HOLEP 7.7%
• Published series TUMT 3.3-30%
Urethral sling 2.1-14%
• Without AP Artificial sphincters 1-8%
• With AP Bladder Botulinum toxin inj. 5.8%
Penile prosthesis implant 0.6-22.8%
• Registry data Perc. Nephrolithotomy 3-14%
ESWL 0-12%
• Comparative studies Simple nephrectomy SSI 5%
• RCTs Radical nephrectomy 0-5.2%
RALP 5.6%
• Systematic reviews HIFU 10.8%
Radical cystectomy 15.5-19.5%
Tandogdu Z. Health care associated urinary tract infections in urology departments. Dr. Philos
thesis. Faculty of medicine. University of Oslo, 2020. ISBN 978-82-8377-595-2
Current status on infectious complications after urological procedures
RCTs on prostate biopsy (Modified after Bootsma et al. 2008. Courtesy of Kurt Naber)
• Without AP
2000 75/79/77 • Ciprofloxacin 500 mg p.o. bid + • Bacteraem 3% 7%
tinidazole 600 mg p.o. bid 3 days ia 0-1% 3%
• Placebo
1999
RCT N=110
23/42/45
•
•
•
Ofloxacin 400 mg p.o. SD
TMP/SMX 160/800 mg p.o. SD
No AB
• Bacteriuria 5-7% 26%*
1979
RCT N=89 •
•
TMP/SMX
Placebo
•
•
•
Bacteriuria
Fever
Bacteraem
0% 21%*
18%
• RCTs
• No AB • Bacteraem
1990 16/22 ia 14% 38%
Crawford et al. RCT, patient N=48 • Carbenicillin 3 days • Bacteriuria 9% 36%
• Systematic reviews
blinded • Placebo • Fever
1982 25/23 • Bacteraem 17% 48%
ia 22% 16%
Brown et al. RCT N=19 • Gentamicin 80 mg i.v. • Bacteriuria 44% 20%
• No AB • Fever
1981 9/10 • Bacteraem 50% 22%
ia 40% 33%
Pathogens causing NAUTI
E coli
Pseudomonas
Klebsiella
Enterocooci
Proteus
Staphylococci
Enterobacter
Candida
Others
0 5 10 15 20 25 30 35
% of total
Antibiotic
resistance
All pathogens
Geographic variation of FLQ outpatient prescriptions
vs FLQ resistant HAIs
Courtesy of Jim C. Hu, M.D., MPH
• The procedure
• Contamination categories
• The patient
• Patient related risk factors
• The surgeon
• Technical aspects
• The need for Antimicrobial stewardship
Contamination
Surgical wound classification
• I. Clean
• Uninfected operative wound, …no ”bodily tracts” are entered
• II. Clean-contaminated
• Operative wound involving opening of bodily tracts under controlled conditions…
• III. Contaminated
• Open fresh accidental wounds…gross spillage from gastrointestinal tract…
• IV. Dirty-Infected
• Old traumatic wounds with devitalized tissue…clinical infection or perforated
viscera
Transrectal bx.
Patient related risk factors for nosocomial infections
• High age
• Nutritional status
• Low level of albumin
• Anaemia
• Obesity
• Deficiency of immune response
• Inborn
• Acquired
• Co-morbidity
• Diabetes mellitus
• Connective tissue disorder
• Smoking
• Bacterial colonisation and resistance
Infect Control Hosp Epidemiol 1999.20:250-78
ASA physical status classification and risk of complications
W J Urol 2012;30:39-50
Principles for Perioperative Antibiotic Prophylaxis
Uncomplicated Complicated
Classification of UTI
Clinical diagnosis Grade of severity
Cystitis 1
Mild and moderate
pyelonephritis 2
Severe
pyelonephritis 3
Uncomplicated Urosepsis (simple)* 4
Complicated
Severe urosepsis* 5
Uroseptic shock* 6
Classification of UTI
Clinical diagnosis Grade of severity Phenotype
Cystitis 1 O
Mild and moderate
pyelonephritis 2 R
Severe
pyelonephritis 3 E
Uncomplicated
Urosepsis (simple)* 4 Complicated
N
Severe urosepsis* 5 U
Uroseptic shock* 6 C
Host risk factors in urinary tract infections categorized according to
the ORENUC system
Category of risk factor Examples of risk factors Phenotype
Prematurity, newborn
Pregnancy
Extra-urogenital risk factors with risk of more
severe outcome
Male gender
Badly controlled diabetes mellitus
E
Relevant immunosuppression (not well defined)
Permanent urinary Catheter and non resolvable Long-term external urinary catheter
urological risk factors with risk of more severe
outcome
Non resolvable urinary obstruction
Badly controlled neurogenic bladder disturbances
C
*only under certain circumstances in combination with other risk factors, e.g. pregnancy, urological intervention.
Outline
1. About prostate biopsies
2. Nosocomial infections
3. Principles related to infection prevention
4. Principles of antibiotic prophylaxis
5. Antibiotic prophylactic regimens
6. The role of Fosfomycin trometamol
7. The Norway case
8. Conclusions
Five key PAP measures from ECDC
Perioperative antibiotic Tasks
prophylaxis (PAP) modality
Modality #1 Multidisciplinary antimicrobial Hospitals should establish a multidisciplinary
management (AM) teams AM team who should develop and implement a
protocol of appropriate PAP
Modality #2 Appropriate timing of PAP PAP should be the responsibility of the
anaesthesiologist
Modality #3 Timing of PAP PAP should be administered within 60 minutes
before incision (except vancomycin and
fluoroquinolones), ideally at the time of
anaesthetic induction
Modality #4 Dosing and duration of PAP Although a single dose is preferred, subsequent
doses should be given depending on
the duration of the procedure and the half-life
of the antibiotic, and if significant blood loss
occurs during surgery
Modality #5 Termination of PAP Continuing antibiotic prophylaxis after the end
of surgery is not recommended
ECDC Systematic review and evidence-based guidance on perioperative antibiotic prophylaxis. Stockholm: ECDC; 2013
ABP policy and surgical contamination
Surgical contamination Description ABP principle
Prostate biopsy Fluoroquinolone or Amino/BLI or C2G Fluoroquinolone or TMP SMX or Algorithm fig 4 p52 (TP / TR)
metronidazole
Radical Prostatectomy Fluoroquinolone or Amino/BLI or C2G TMP SMX or C2G or C3G or « too weak to allow the panel to make recommendations
either for or against antibiotic prophylaxis »
Amino/BLI
Ureteroscopy Fluoroquinolone or Amino/BLI or C2G 0 if uncomplicated stone Trimethoprim or C2G or C3G or Amino/BLI
Partial nephrectomy Fluoroquinolone or Amino/BLI or C2G TMP SMX or C2G or C3G or « too weak to allow the panel to make recommendations
either for or against antibiotic prophylaxis »
Amino/BLI
TURP Fluoroquinolone or Amino/BLI or C2G TMP SMX or C2G or C3G or Trimethoprim or C2G or C3G or Amino/BLI
Amino/BLI
TURB Fluoroquinolone or Amino/BLI or C2G Trimethoprim or C2G or C3G or Trimethoprim or C2G or C3G or Amino/BLI
Amino/BLI (if high risk) (if high risk)
EAU recommendations over years
EAU 2005 EAU 2014
Main remarks Poor literature Altemeier Class Poor literature
« No antibiotic prophylaxis is
Cystoscopy Fluoroquinolone or Amino/BLI or C2G 0 0
recommended for clean
Prostate biopsy Fluoroquinolone or Amino/BLI or C2G Fluoroquinolone or TMP SMX or operations,
Algorithm figwhereas
4 p52 (TPa/ TR)
single
metronidazole or 1-day dose is
recommended in clean-
Radical Fluoroquinolone or Amino/BLI or C2G TMP SMX or C2G or C3G or « too weak to allow the panel to make recommendations
contaminated. The approach
Prostatectomy either for or against antibiotic prophylaxis »
Amino/BLI
in contaminated operations
varies with the type
Ureteroscopy Fluoroquinolone or Amino/BLI or C2G 0 if uncomplicated stone Trimethoprim or C2G or C3G or Amino/BLI
of procedure, the level of
Partial Fluoroquinolone or Amino/BLI or C2G TMP SMX or C2G or C3G or « too weak surgical site
to allow the panelcontamination
to make recommendations
nephrectomy either for or against antibiotic prophylaxis »
Amino/BLI and level of difficulty.
Opening of the urinary tract
TURP Fluoroquinolone or Amino/BLI or C2G TMP SMX or C2G or C3G or Trimethoprim or C2G or C3G or Amino/BLI
is considered as clean-
Amino/BLI
contaminated surgery. »
TURB Fluoroquinolone or Amino/BLI or C2G TMP or C2G or C3G or Amino/BLI (if Trimethoprim or C2G or C3G or Amino/BLI
high risk) (if high risk)
EAU recommendations over years
EAU 2005 EAU 2014 EAU 2022
Prostate biopsy Fluoroquinolone or Amino/BLI or C2G Fluoroquinolone or TMP SMX or Algorithm fig. (TP / TR)
metronidazole
Radical Fluoroquinolone or Amino/BLI or C2G TMP SMX or C2G or C3G or « too weak to allow the panel to make recommendations
Prostatectomy either for or against antibiotic prophylaxis »
Amino/BLI
Ureteroscopy Fluoroquinolone or Amino/BLI or C2G 0 if uncomplicated stone Trimethoprim or C2G or C3G or Amino/BLI
Partial nephrectomy Fluoroquinolone or Amino/BLI or C2G TMP SMX or C2G or C3G or « too weak to allow the panel to make recommendations
either for or against antibiotic prophylaxis »
Amino/BLI
TURP Fluoroquinolone or Amino/BLI or C2G TMP SMX or C2G or C3G or Trimethoprim or C2G or C3G or Amino/BLI
Amino/BLI
TURB Fluoroquinolone or Amino/BLI or C2G Trimethoprim or C2G or C3G or Trimethoprim or C2G or C3G or Amino/BLI
Amino/BLI (if high risk) (if high risk)
EAU recommendations over years
EAU 2005 EAU 2014 EAU 2022 French Guidelines 2023
Main remark Poor literature Altemeier Class Poor literature
Cystoscopy Fluoroquinolone or 0 0 0
Amino/BLI or C2G
Prostate biopsy Fluoroquinolone or Fluoroquinolone or TMP SMX Algorithm fig (TP / TR) T Perineal: 0
Amino/BLI or C2G or metronidazole T rectal: Fosfomycin or FQ or targeted
Radical Fluoroquinolone or TMP SMX or C2G or C3G or « too weak to allow the panel to make recommendations 0
Prostatectomy Amino/BLI or C2G either for or against antibiotic prophylaxis »
Amino/BLI
Ureteroscopy Fluoroquinolone or 0 if uncomplicated stone Trimethoprim or C2G or C3G or Amino/BLI C1G or C2G
Amino/BLI or C2G
Partial Fluoroquinolone or TMP SMX or C2G or C3G or « too weak to allow the panel to make recommendations 0
nephrectomy Amino/BLI or C2G either for or against antibiotic prophylaxis »
Amino/BLI
TURP Fluoroquinolone or TMP SMX or C2G or C3G or Trimethoprim or C2G or C3G or Amino/BLI C1G or C2G
Amino/BLI or C2G Amino/BLI
TURB Fluoroquinolone or Trimethoprim or C2G or C3G or Trimethoprim or C2G or C3G or Amino/BLI 0
Amino/BLI or C2G Amino/BLI (if high risk) (if high risk)
Courtesy of F. Bruyere
Recommendations on antibiotic prophylaxis in transrectal bx -
EAU guidelines 2023
Antibiotic prophylaxis in
transrectal bx
Patients with UTI should be treated according to Recommended Standard-Dosage Alternatives in Type 1
susceptibility results antibiotic (< 80kgBW) Beta-Lactam Allergy
Infections ca 10%
Deaths 0.1%
(2500 deaths in Europe/year)
➢ New regulations
➢ Antimicrobial
stewardship
concerns
Discussion 2023
Infections ca 10%
Deaths 0.1%
(2500 deaths in Europe/year)
➢ New regulations
➢ Antimicrobial
stewardship
concerns
Infections ca 10%
Deaths 0.1%
(2500 deaths in Europe/year)
➢ New regulations
Infections and deaths ➢ Antimicrobial
stewardship
can be brought down concerns
to zero!
The role of Fosfomycin trometamol in transperineal prostate bx
Consensus points
After having reached consensus on all points we
concluded as follows:
Outline
1. About prostate biopsies
2. Nosocomial infections
3. Principles related to infection prevention
4. Principles of antibiotic prophylaxis
5. Antibiotic prophylactic regimens
6. The role of Fosfomycin trometamol
7. The Norway case
8. Conclusions
I Roar Gulbrandsen, 68 years
n
t • TR prostate biopsy after MRI findings
r • Day 1.
o • Lower abdominal pain
d • Malaise
u
• Day 2.
c
• Couldn`t find words
t • Balance problems
i • Loss of lateral vision
o • Apoplexia?
n
• Day 6.
• Mors
What are the resistance rates?
A
• Ciprofloxacin
U
2012-2018: 13%-40% 12
Percent of patients hospitalized
A 10
with suspected sepsis
• Co-trimoxazole
2 2012-2018: 28-62% 8
0 6
2
4
3 What are the complication rates?
2
2011-2017: 1.5-9% 0
2011 2012 2013 2014 2015 2016 2017
Information and recommendations to
Norwegian men
A
7
U 7
6
A 6
5
5
4 4
2 3 3
2
0 1
2
1
2 0
0
3 2017 2018
2019 2020 2017 2018
2021 2022 2019 2020
2021 2022
N=2784 N=35143
Outline
1. About prostate biopsies
2. Nosocomial infections
3. Principles related to infection prevention
4. Principles of antibiotic prophylaxis
5. Antibiotic prophylactic regimens
6. The role of Fosfomycin trometamol
7. The Norway case
8. Summary and conclusions
Experience with the GPIU study
Study principles
>120 countries
Other benefits for investigators
• Authorship
• Acknowledgement
• Access to data and slide decks
ESIU
Chair: Zafer Tandogdu
Research group
Chair: Bela Koves
Deep-Uro
Res. ass: Eva Falkensammer
Deep-Uro study principles
I have a dream
Why
We need PDA
• Dedicated investigators from
• strong urology centres who can commit themselves
• to perform complete Deep-Uro study cycles for a
given procedure and
• help provide high-level evidence to support
• publication in high impact journals and
Patient specific
• inform urological guidelines PAP (or no PAP)
• Dedicated industrial partners
Thanks for your attention!