detailed lecture about urinary tract infection and treatemnt .

1. ‫الرحمي‬ ‫الرمحن‬ ‫هللا‬ ‫سم‬‫ب‬
Dr. Mohammad Hussin Kassem
Nephrology specialist
Update in
Urinary tract infection

3. Anatomy and Physiological review

4. Physiological review

5. Bladder innervation


6. inflammatory response of the urothelium to bacterial invasion
that is usually associated with bacteriuria and pyuria.
Bacteriuria : is the presence of bacteria in the urine, which is
normally free of bacteria (might be contamination )
Pyuria : the presence of white blood cells (WBCs) in the urine,
 Note : Pyuria without bacteriuria warrants evaluation for
tuberculosis, stones, or cancer.

7. Most common :
1- Uropathogens ( typically Escherichia coli) present in the rectal
flora enter the bladder through the urethra after an interim phase of
periurethral and distal urethral colonization.
2- Colonizing uropathogens may also come from a sex partner’s
vagina, rectum, or penis.
Rarely : Hematogenous :
seeding of the urinary tract by potential uropathogens such as
Staphylococcus aureus is the source of some UTIs, but this is more
likely to occur in the setting of persistent bloodstream infection or
urinary tract obstruction.

8. • The intact urine drainage and bladder contraction .
• Poly saccharide layer .
• Bactericidal agents .
• Tamm Hounsfield .
• High osmolality .
• Phagocytosis .
• Ammonia .
• In men : the prostate secretion and the the greater
distance between the usual source of uropathogens
(anus and urethral meatus),

9. • UTIs are considered to be the most common bacterial infection. 1
• Acute uncomplicated cystitis may recur in 27% to 44% of healthy women, even
though They have a normal urinary tract . 2
• half of all women will experience a UTI during their lifetime.
• (Catheter-associated bacteriuria is the most common source of gram-negative
bacteremia in hospitalized patients.3
• Asymptomatic bacteriuria is one of the most common infectious
• 2% to 7% encountered during pregnancy , (Hooton et al, 2000)
• 1-(Patton et al, 1991; Hooton and Stamm, 1997;
• Foxman 2002).
2-Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am. 1997;11:551-581
• 3- Stamm WE, Hooton TM. Management of urinary tract infections in adults. N Engl J Med. 1993;329:1328-1334

10. • 80% of nosocomial UTIs are
secondary to an indwelling
urethral catheter .
• The indications for an
indwelling catheter are
urinary retention, severe
pressure ulcers where
healing is compromised by
incontinence, or for
hemodynamically unstable
patients whose urinary
output must be closely
monitored . Sedor and Mulholland, 1999; Foxman2002 ,

11. • community-acquired UTIs is nearly $1.6 billion in the
United States alone (Foxman, 2002);
• the annual cost of nosocomial UTIs has been estimated to
range from between $515 million and $548 million (Jarvis,
1996).
• Each CAUTI is estimatedto cost between $589 and $758
(Tambyah et al, 2002; Anderson et al, 2007).
• In patients requiring intensive care, the cost is roughly
$2,000 per nosocomial UTI (Chen et al, 2009)

12. 1- asymptomatic bacteriuria
2- young women with acute uncomplicated cystitis,
3- young women with recurrent cystitis,
4- young women with acute uncomplicated pyelonephritis,
5- adults with acute cystitis with following condition :
Male sex – Elderly – Pregnancy - Diabetes mellitus - Recent urinary tract
instrumentation - Childhood urinary tract infection
Symptoms for more than 7 days at presentation
6- complicated UTI : *
Obstruction or other structural factor ( stones – structure – diverticula- istula- condiut
–cyst – malignancy )
Functional abnormality ( neurologic bladder – reflux ) .
Foreign bodies .
Other conditions : renal failure – MDR- RTX- pyelonephritis in men- hospital acquired
..
• . Nicolle LE. A practical guide to the management of complicated urinary tract infection. Drugs. 1997;53:583-592

13. • defined as two separate consecutive clean-voided
urine specimens, both with 10*5 or more colony-
forming units per milliliter (cfu/ml) of the same
uropathogen in the absence of symptoms
referable to the urinary tract
• screening for or treatment of asymptomatic
bacteriuria is not appropriate and should be
discouraged (Nicolle et al, 2005).

14. • 5% of young adult women,
• rarely in men younger than 50.
• older than 70 : prevalence of 16% of ambulatory women
• 19% of ambulatory men
• who are institutionalized: up to 50% of elderly women
• 40% of elderly men.
• Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America
• guidelines for the diagnosis and treatment of asymptomatic bacteriuria in
• adults. Clin Infect Dis. 2005;40:643.
• 8. Hooton TM, Scholes D, Stapleton AE, et al. A prospective study of asymptomatic
• bacteriuria in young sexually active women. N Engl J Med. 2000;343:
• 992-997.

15. When to treat ?

16. Factors Modulating Risk for Acute
Uncomplicated Urinary Tract Infections
in Women
Behavioral:
• sexual intercourse .
Use of spermicidal products .
Recent antimicrobial use .
Suboptimal voiding habits .
Uropathogen Determinants
• Escherichia coli virulence
determinants: P, S, Dr, and
type 1 fimbriae; hemolysin;
aerobactin; serum resistance

17. Genetic:
• innate and adaptive immune response,
• Enhanced epithelial cell adherence,
• antibacterial factors in urine and
bladder mucosa,
• no secretor of ABO blood group
antigens,
• P1 blood group phenotype,
• HLA A3 : more epithelial cell
receptivity for ( upec )
• uropathogenic E. coli
Reduced CXCR1 expression ( IL 8 receptor)
• previous history of recurrent cystitis
Biological :
• estrogen deficiency in
postmenopausal women,
• glycosuria (including from SGLT-1
inhibitors)
• Other :
• Pregnancy
• Diabetes .
• Urine intervention .
• Structural abnormalities .

18. Acute Uncomplicated Cystitis in
Young Women
• Sx : acute onset of dysuria,
• frequency, urgency, or suprapubic pain.
• Uncomplicated describes an infection in a healthy
patient with a structurally and functionally normal urinary tract
• Acute dysuria DD :
1- acute cystitis;
2- acute urethritis from Chlamydia trachomatis, Neisseria gonorrhea, or herpes
simplex virus infections;
3- vaginitis caused by Candida spp. or Trichomonas vaginalis.6 These three
entities can
• Pyuria is present in almost all women with acute cystitis as well as in most
women with urethritis caused by N.gonorrhoeae or C. trachomatis, and its
absence strongly suggests an alternative diagnosis.
• Hematuria (microscopic or gross) is common in women with UTI but not in
women with urethritis or vaginitis.

19. • The urine c/s is not indicated .
• The Infectious Diseases Society of America (IDSA)
consensus definition of cystitis is :
• 10*3 cfu/ml or more.
• Rubin RH, Shapiro ED, Andriole VT, et al. Evaluation of new anti-infective
• drugs for the treatment of urinary tract infection. Clin Infect Dis. 1992;15:
• S216-S227

20. Women who present with complaints
of dysuria and frequency
Treat with short – course therapy
Follow – up 4-7 days later
Asymptomatic
No further
intervention
Symptomatic
Urinalysis, urine culture
Bacteriuria
with or
without
pyuria
pyuria no
Bacteriuria
Both
negative
Treat with
extended
course
Treat for
Chlamydia
trachomatis
Observe,
treat with
urinary
analgesia

21. If still sx
and has documented persistent infection, a longer
course of therapy based on sensitivities, usually
with a fluoroquinolone, should
be used.

23. Abx and Ecological effect ‘ collateral damage ‘
• The use of some broad-spectrum ABX Lead to Infection with multi-drug resistance .
• IDSA guidelines give equal weight to the risk of ecological adverse effects and drug
effectiveness in the recommendations.
• cephalosporin and fluoroquinolones affect the normal fecal flora
 Use of fluoroquinolones has been linked to infection with MRSA and with increasing
fluoroquinolone resistance in gram-negative bacilli, such as psdomonas aeruginosa
 broad-spectrum cephalosporins, in particular, have been Associated withc collateral damage,
and subsuquant infection with vancomycin-resistant enterococci ( VRE) , extended spectrum
b-lactamase–producing Klebsiella pneumoniae (ESBL ) , blactam-resistantAcinetobacter species
and Clostridium difficile
• Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines
• for the treatment of acute uncomplicated cystitis and pyelonephritis inwomen: A 2010 update by the Infectious Diseases Society of America and the
• European Society for Microbiology and Infectious Diseases. Clin Infect Dis.
• 2011;52:e103-e120.
• Paterson DL. "Collateral damage" from cephalosporin or quinolone
• antibiotic therapy. Clin Infect Dis 2004; 38(Suppl. 4):S341–5.

24. The preserved invitro susceptibility of
E.Coli to nitrofurantoin,fosfomycin,and mecillinam
over many years of use suggests these antimicrobials
cause only minor Collateral damage .
Kahlmeter G. An international survey of the antimicrobial susceptibility of
pathogens from uncomplicated urinary tract infections: the ECO.SENS
Project. J Antimicrob Chemother 2003; 51:69–76.
Naber KG, Schito G, Botto H, Palou J, Mazzei T. Surveillance study in
Europe and Brazil on clinical aspects and Antimicrobial Resistance
Epidemiology in Females with Cystitis (ARESC): implications for
empiric therapy. Eur Urol 2008; 54:1164–75

27. Fosfomycin (trometamol)
• phosphonicacidderivative
• appears to have a role as a therapeutic agent effective against
ESBL E. coli UTIs .
• A 3-g single-dose
• 83% -91% bacterial cure rate against vancomycin-resistant
enterococci (VRE), methicillin-resistant S. aureus (MRSA), and
extended spectrumb-lactamase (ESBL)–producing gram-
negative rods available .
Susceptibility data are also not uniformly
• available, because testing is not routinely performed in many
clinical laboratories.
• Rodríguez-Baño J, Alcalá JC, Cisneros JM, et al. Community infections
• caused by extended-spectrum beta-lactamase-producing Escherichia coli.
• Arch Intern Med. 2008;168:1897-1902
• IDSA 2010 guidelines . For the treatemnt of uncomplicated cystitis .

28. Nitrofurantoin.
The prevalence of E. coli resistance to nitrofurantoin is generally less than5%,
• inactive against Proteus spp. and some Enterobacter and Klebsiella spp.
• resistance to nitrofurantoin remains low and it is well tolerated and
efficacious in a 5-day regimen rather than 7 days .
• an effective agent for treatment of acute cystitis.
• minimal propensity for collateral damage,
• It is an attractive agent for cystitis.
• Avoid use in the pregnant at term for the possibility of hemolytic anemia .

29. Recurrent Acute Uncomplicated Cystitis
in Women
Recurrent UTI more than 2 / 6 months , or more than 3 in 12 months .
• Persistence of infecting strain in the fecal flora .
• Or later reservoir of uropathogens in the bladder epitheium .
• TX :
• Behavioral modification : such as avoiding spermicides, increasing fluid
intake, and ensuring post coital micturition,
• Cranberry juice : small study showed benefit bur RCT showed no benefit .
• Prophylaxis antibiotics :
• continuous prophylaxis, post coital prophylaxis, and intermittent self-
treatment .
• Postmenopausal : topical estrogen to restore the vaginal flora .
• Radiology study is not indicated usually .
Barbosa-Cesnik C, Brown MB, Buxton M, et al. Cranberry juice fails to prevent recurrent urinary tract
infection: Results from a randomized placebocontrolled trial. Clin Infect Dis. 2011;52:23-30.

31. 4- adults with acute cystitis
-special category – (DM-pregnant - male )
1- may respond poorly to short-course therapy.
Clinicians
2- warrant special attention because of the
serious complications that can occur if
treatment is inadequate.
3- A urine culture specimen should be obtained
routinely in patient before treatment .
4- special consideration for treatemnt .*

32. 5-Acute Uncomplicated Pyelonephritis
in Women
• Acute pyelonephritis is a
clinical syndrome of :
• chills, fever,
• flank pain *
• bacteriuria and pyuria,
• Sx : from mild illness to
sepsis , shock or renal
failure .
• Selected patient may be
treated in op setting after
stabilizing in UCC.

33. Uncomplicated pyelonephritis .
Urine work up :
• Urine c/s : more than 10*4 of
cfu/ml in up to 95 % Of pts .
Radiobiology work up :
• Indicated if :
• Sever sepsis , shock , to rule
out the complication or
obstruction .
• No improvement within 72
hours .
• Recurrence within less than
2 weeks .
• Ct : showed area of lowe
density due to edema.

34. Practical point ….
• In case of presence the symptoms or the
infection .
• Us pelvis with bladder evaluation pre and post
voiding is indicated specially in diabetic and
elderly to rule out any significant residual
urine in the bladder and then the drainage is
indicated .

35. Treatemnt :
Intravenous Oral
NO role for NITRUFORANTOIN or
FOSFOMYCINE IN pyelonephrotis . .
The duration of tx 7-14 days .

36. Complicated Infections
• Obstruction or other structural factor (
stones – structure – diverticula- fistula-
conduit –cyst – malignancy )
• Functional abnormality ( neurologic bladder
– reflux ) .
• Foreign bodies .
• Other conditions : renal failure – MDR- RTX-
pyelonephritis in men- hospital acquired

37. Complicated Infections
• Classic signs and symptoms / or non specific
• + Bacteriuria /pyuria ( not presence in case of obstruction)
• Urine culture should always be performed in patients with suspected complicated
UTI
• More than 10*3 of cfu/ml for dx .
• If possible Correction of any underlying anatomic, functional, or metabolic defect
must be attempted .
• For mild case 5 days of oral florquinolon is a good choice pending the further
investigations .
• In case of community prevelance of E. coli florquinolon resistance in known to be
higher than 10% , may give one dose of parental agent prior to give oral
florquinolon .
• For sever case the hospitalization is indicated for Parentral treatemnt
• Course of 10-14 days of total treatment

38. Risk factor for MDR.
Age> 60 .
Liver pathology .
Diabetes mellitus .

39. Indication for hospitalization
• Septic / critically ill ( tachycardia , hypotensive )
• Persistent high fever .
• Marked debility .
• Inability to maintain oral fluid .
• In patient management is warranted .
• Any concern about patient adherence .

40. Modified
based on
urine c/s

42. NOT CRITICAL
Risk for MRD .
CRTICALLY ILL .
SEPSIS

43. Fungal uti
• The funguria is common .
• The vast majority of fungal is candida .
• Risk factor: urinary tract drainage devices - DM – prior
abx – malignancy .
Usually it is Asymptomatic .
If it is symptomatic the evaluation should be done
(c/s – radiology evaluation ).
Persistent candiduria should be investigated in diabetic ,
those who have other urologic abnormalities ,

44. Indication o Treatment :
• Neuropenic pateint ( ANC < 1500 cells/microL) .
• In case of any intervention on urinary tract .
• Low birthweight infant .(< 1500 g) .
 Fluconazole or Aphotricine B in case of resistant .
 COMINATION of amphoticine B and flucytosine in case of pyelonephitis .
 Liposomal amphotrisine B should NOT be used in fungal uti because it is
NOT penetrate the kidney .
 Bladder irrigation with amphotrisine B is not recommended .
 In salvage case and WHEN we could not use amphotricine b may we use
micafungin .
 Little experince for voriconazole , posaconazole ,isavuconazole , non of
which achieve adequate concentration in the urine .
• 2018 up to date .

45. Uti in pregnant :
Urinary stasis due to hormonal and mechanical .
asymptomatic bacteriuria occurs in 2 to 7 % without tx 30-40 % will
develop symptomatic uti .
Screening for ALL pregnant at 12-16 wks. gestation ,
Diagnostic if More than 10*5 cfu/ml .
The tx well decrease the risk by 70-80 %
Indication for treatment and then should repeat the c/s after one week
then monthly until delivery .
• Untreated bacteriuria has been associated with increase risk of
preterm birth , low birth weight , and perinatal mortality .
• Pyelonephritis is indication for hospitalization and prophylaxis
treatment .

47. Aminoglycoside have been assoiciated with fetal ototoxicity and this regime should be used
only if intolerance precludes the use of less toxic agents .
Some animal studey shown adverse fetal effect Imipemen –cispaltine

48. Mixed growth :
 Long standing Foley
catheter
 Bladder dysfunction
 Shunt or diversion .
 Contamination
Lees bacterial growth
 Staph saprophyte
 Candada sp .
 During antibiotics use .
 Urinary obstrection .
 Not communicated Renal
abscess .

49. How to select the antibiotics
• Susceptible : ( look at the mic )
• Excretion in the Urinary in High concentration
( not to use the azithromycin and tygacyclin ,
liposomal amphotericin )
• Safe ( tray to avoid the nephrotoxic if there is a
risk for AKI) .
• Available in oral form .
• cheap .
• Minimal ecologic changes .

50. Pyuria with negative c/s
• Vaginitis .
• TB .
• stone .
• Foreign body .
• Anaerobic bacteria .
• Bilharzia .
• Bladder Tumor .
• Interstitial nephritis .
• Chlamydia and other atypical infection .

52. Extended-Spectrum β-Lactamase-
:Producing Gram-Negative Bacilli
More Likely:
Klebsiella sp
E. coli
Proteus mirabilis
Less Common:
Enterobacter sp
P. aeruginosa
Citrobacter freundii
Morganella
morganii
Serratia marcescens

53. Limited treatment options:
Carbapenems
Polymyxins
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