Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 1 Urinary tract infections in men:...

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

[email protected]


Professor????


No!


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


Cross-talk

Not only important for bacteria

Also for people working with:E. coliUTIAntibiotic resistanceetc


Menu

Primitive creatures

UTI - classification

Febrile UTI in men - clinic

Virulence factors


Clinicians-primitive creatures!

Internal medicine vs Surgeons

Is this of any good for my patients?


Giving a diagnosis

X no. of symptoms/signs=diagnosis

The most usual is the most abundant!

Ex. Fever + bacteriuria


Bacterial virulence factors:are they important to know for the

treating physician?


No!


Just UTI - define!!

Women Men Children

Asymptomatic Symptomatic

Febrile UTI Lower UTI

Sporadic Recurrent

Complicating factors


Virulence Host factors

Infection No infection


• 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


• Lower UTI = ”Cystitis”

• Febrile UTI = ”Upper” UTI = ”Pyelo.”

• Prostatitis – Acute, Kron bact., Kron abact.,

Prostatodynia

• Urethritis

Male UTI


Febrile UTI in men

-the Gothenburg prospective study


• Temperature 38.0°C

• Clinical signs/symptoms of UTI

• Positive urine culture

104 cfu/mL MSU

Inclusion criteria


• 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


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)


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


?Is the prostate frequently

involved in men withfebrile urinary tract

infection?


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


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


• At entry • After 3 months

49 mL 35 mL

(14 - 104 mL) (15 - 91 mL)

Prostate volume in 55 men with febrile UTI (range)


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.


?Is the prostate frequently

involved in men withfebrile urinary tract

infection?


Yes!


Acutepyelonephritis

FebrileUTI

Acuteprostatitis

One infection – different manifestations

Febrile UTI in men


?Is it always necessary to examine the upper and

lower urinary tract after a febrile UTI?


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.


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.


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.


?Is it always necessary to examine the upper and

lower urinary tract after a febrile UTI?


No!


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


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


• Ab concentration in the prostate

• High pH, calcifications, reflux

• Quinolones, (trimethoprim), ((doxycycline)) to obtain ab in prostatic secretion

Treatment


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.


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


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


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


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


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%


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.


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.


Acutepyelonephritis

FebrileUTI

Acuteprostatitis

One infection – different manifestations

Febrile UTI in men


Conclusions - general

Studies of very well characterized patients and bugs with specified infections (prospective)

Multidisciplinary in-/output of importance (cross–talk)


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.


Thank you!

Peter Ulleryd, Sahlgrenska University Hospital, Göteborg, Sweden 1 Urinary tract infections in men:...

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