Urinary tract infections in men: the classical urovirulent E. coli?
description
Transcript of Urinary tract infections in men: the classical urovirulent E. coli?
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 1
Urinary tract infections in men:
the classical urovirulent E. coli?
Peter Ulleryd Regional Medical Officer
Communicable Disease ControlVästra Götaland, Sweden
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 2
Professor????
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 3
No!
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 4
Torsten SandbergInfectious Diseases, Sahlgrenska University Hospital
Jonas Hugosson, Gunnar Aus, Svante Bergdahl and Björn Zackrisson
Urology, Sahlgrenska University Hospital, Göteborg
Knut Lincoln Clinical Bacteriology, Sahlgrenska University Hospital
Flemming ScheutzThe international E. coli and Klebsiella centre (WHO), Copenhagen
James R. Johnson
VA Medical Center, Minneapolis
Co-workers
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 5
Cross-talk
Not only important for bacteria
Also for people working with:E. coliUTIAntibiotic resistanceetc
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 6
Menu
Primitive creatures
UTI - classification
Febrile UTI in men - clinic
Virulence factors
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 7
Clinicians-primitive creatures!
Internal medicine vs Surgeons
Is this of any good for my patients?
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 8
Giving a diagnosis
X no. of symptoms/signs=diagnosis
The most usual is the most abundant!
Ex. Fever + bacteriuria
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 9
Bacterial virulence factors:are they important to know for the
treating physician?
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 10
No!
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 11
Just UTI - define!!
Women Men Children
Asymptomatic Symptomatic
Febrile UTI Lower UTI
Sporadic Recurrent
Complicating factors
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 12
Virulence Host factors
Infection No infection
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 13
• Most UTI in men are complicated
• Less E. coli than in women
• Often Pseudomonas, Serratia, enterococci………
Traditionally
- anatomic abnormalities in the newborn- prostatic obstruction in the elderly
UTI in men
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 14
• Lower UTI = ”Cystitis”
• Febrile UTI = ”Upper” UTI = ”Pyelo.”
• Prostatitis – Acute, Kron bact., Kron abact.,
Prostatodynia
• Urethritis
Male UTI
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 15
Febrile UTI in men
-the Gothenburg prospective study
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 16
• Temperature 38.0°C
• Clinical signs/symptoms of UTI
• Positive urine culture
104 cfu/mL MSU
Inclusion criteria
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 17
• Transrectal ultrasound (TRUS)
• Residual urine
• Uroflowmetry
• Urography
• Cystoscopy
• Prostate-specific antigen (PSA)
At entry and after3 months
During follow-up
At entry and follow-up
Investigations
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 18
Median age 63 years (18 – 86) Previous history of UTI 38 (44%) Flank pain and/or costovertebral angle 31 (36%)tenderness
Median temperature 39.5°C (38.0 – 41.4) Median C-reactive protein 130 mg/L (9 – 420)
Characteristics of men with febrile UTI (n=86)
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 19
Urinary isolates Blood isolates Escherichia coli1 67 (78 %) 10Klebsiella pneumoniae 7Enterobacter aerogenes 1 1Enterobacter agglomerans 1 1Proteus mirabilis 1 1Enterococci 4Staphylococcus epidermidis 3 1Group B streptococci 2
1 In one case together with Serratia marcescens
Bacteriological findings in 86 patients with febrile UTI
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 20
?Is the prostate frequently
involved in men withfebrile urinary tract
infection?
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 21
14.0
1.52.0
2.93.6
0
5
10
15
0 n=70
1 n=69
3 n=55
6 n=50
12 n=41
months
PS
A (
µg
/L)
Fig 2. Median serum PSA after an episode of febrile UTI
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 22
Monthsa No. of Serum PSA (µg/L) No (%) of patients with patients Median Range serum PSA >4 µg/L
0 70 14 0.54-140 58(83)
1 69 3.6 0.43-21 30(43)
3 55 2.9 0.38-19 23(42)
6 50 2.0 0.37-20 16(32)
12 41 1.5 0.36-16 10(24)
a Time after an episode of febrile UTI.
Serum PSA after an episode of febrile UTI
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 23
• At entry • After 3 months
49 mL 35 mL
(14 - 104 mL) (15 - 91 mL)
Prostate volume in 55 men with febrile UTI (range)
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 24
Changes in serum PSA and prostate volume between the acute stage of infection and 3 months later in 49 men with febrile UTI
Reduction in prostate volume
>10% 10%
Reduction in serum PSA
>25% 40 4
25% 2 3
BJU Int 1999;84:470-4.
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 25
?Is the prostate frequently
involved in men withfebrile urinary tract
infection?
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 26
Yes!
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 27
Acutepyelonephritis
FebrileUTI
Acuteprostatitis
One infection – different manifestations
Febrile UTI in men
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 28
?Is it always necessary to examine the upper and
lower urinary tract after a febrile UTI?
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 29
Peter Ulleryd, Infektion, Sahlgrenska Universitetssjukhuset/Östra
Radiological abnormalities of the upper urinary tract in 83 men with febrile UTI
Previously Totalb
unknowna
Renal cortical scarring with orwith no calyceal deformity 4 12
Renal cyst 4 5
Unilateral duplication of collecting system 2 2
Renal calyceal stones 1 1
Bilateral ureteric dilatationc 0 1
Single kidney 0 1
a11 findings in 9 patients. b22 findings in 19 patients.cAssociated with an orthotopic ileal bladder.
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 30
Lower urinary tract abnormalities in 83 men with febrile UTI
Abnormality No. (%) of findingsa
Infravesical obstruction fromBPH requiring TURP 10 Urethral stricture 5 Bladder diverticulum 5 Bladder stones 3 Bladder cancer 1 Phimosis 1 Post-void residual urine >50 mLb 13(22)
Peak urine flow rate <10 mL/sb 8(15)
a46 abnormal findings in 35 patients.bBased on the best performance during the acute stage or at follow-
up.
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 31
Characteristics of 15 men with febrile UTI who had surgically correctable lesions that were previously unrecognised (n = 85).
No. of History Acute Hematuriaa Recurrent patients of voiding urinary symptomatic difficulties retention UTIb Infravesical obstruction from BPH requiring TURP 5 5 2 1 Urethral stricture 5 1 1 1 Bladder stones 3 3 2 1 Renal calyceal stones 1 1 Bladder cancer 1 1 1
a As measured by dipstick analysis at follow-up after 1 month. b Within 1 month after the end of antibiotic treatment.
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 32
?Is it always necessary to examine the upper and
lower urinary tract after a febrile UTI?
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 33
No!
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 34
Conclusion • Routine imaging of the upper urinary tract
seem dispensable. • To reveal abnormalities of clinical importance,
evaluation should primarily be focused on the lower urinary tract.
BJU Int 2001;88:15-20
Urological evaluation of male febrile UTI
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 35
At 1 (+3 and 6) months: • Clinical control including urinary and
obstructive symptoms• Dipstick for hematuria• Urine culture• Repetition of eventual abnormal laboratory
tests • Post-void residual• Peak flow rate• DRE
Proposed urological evaluation of male febrile UTI
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 36
• Ab concentration in the prostate
• High pH, calcifications, reflux
• Quinolones, (trimethoprim), ((doxycycline)) to obtain ab in prostatic secretion
Treatment
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 37
Cumulative cure rate (% )
Ciprofloxacin 500 mg bid
2 weeks 4 weeks (n=38) (n=34)
2 weeks post-treatment: n=38 n=34
Bacteriological cure 34(89) 33(97)
Clinical cure 35(92) 33(97)
After 12 months: n=32 n=33
Bacteriological cure 19(59) 25(76)
Clinical cure 23(72) 27(82)
Scand J I nfect Dis 2003;35(1):34-9.
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 38
CID 1994;18:579-84
Virulence characteristics of E. coli in febrile UTI
Men Women
n=74 Uncomplicated Complicated FU Hemolysin 74% 51% 41%
P-fimbriae 51% 80% 65%
Aerobactin 46% 73%
Suggesting differences in host-parasite relationships in the male and female urinary tract.
TS
JJ
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 39
Earlier studies of haemolysin in male UTI
Barnes RC,Daifuku R, Roddy RE, Stamm WE. Lancet, 1986.
10/11 isolates
Spach DH, Stapleton AE, Stamm WE. JAMA 1992.
10/14 isolates
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 40
Later studies of haemolysin in male UTI
Andreu et al 22/30 73%
Terai et al 72/107 69% Ruiz et al 30/37 81%
CNF1 was also very commonly foundconcomitantly with the haemolysin gene
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 41
Prevalence of virulence factorsJR Johnson et al 2005
FUTI urine (n=70)
Uninfected, rectal (n=70)
FUTI isolates exibited a significantly higher prevalence of virulence-associated phylogenetic groups, serotypes, and extraintestinal virulence genes.
Including haemolysin and CNF-1
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 42
Comparison concurrent U+R isolatesJR Johnson et al 2005, n=65
3 last rectal isolates+morph distinct
Only the urine isolate in 25 %Urine clone + additional clone in 22%Only nonurine clones in 54%
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 43
Figure 1. Distribution of virulence factor scores among concurrent urine (n = 65) and rectal (n = 67) Escherichia coli isolates from 65 men with febrile urinary tract infection. Only rectal isolates that differed clonally from the host's urine isolate are included in the rectal group. Fractional scores were rounded down to the next lowest integer value.
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 44
Cytotoxic necrotizing factor type 1 (CNF1)
Contribute to prostatic inflammation by E. coli in a rat model.
Rippere-Lampere KE, Inf Imm, 2001.
However, another murine model, but female, demonstrated no evidence of CNF1- associated inflammation of the urinary tract.
Johnson DE, FEMS Imm, 2000.
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 45
Acutepyelonephritis
FebrileUTI
Acuteprostatitis
One infection – different manifestations
Febrile UTI in men
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 46
Conclusions - general
Studies of very well characterized patients and bugs with specified infections (prospective)
Multidisciplinary in-/output of importance (cross–talk)
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 47
Conclusions Male FUTI
E. coli of course.
Pathogenesis - Deep, Dip, Dep.
Do not take PSA.
If investigation - aim low.
Treatment for the prostate also.
Common sense allowed.
Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 48
Thank you!