CASE

PRESENTATION

1
 OVERVIEW
• CASE
• Background
• Definitions and criteria
• Disease characteristics – causative organisms,
pathogenesis, clinical features & complications
• Clinical assessment
• Role of the medical microbiologist
• LABORATORY DIAGNOSIS
• Treatment
• Prevention 2
 CASE
• A 64 year old male with chief complaints of:

 Abdominal distention since 4 days

 Decreased frequency and urine output since 2 days
 Altered sensorium since I day

3
HISTORY OF PRESENTING ILLNESS:
• Patient was apparently well, developed
abdominal distention, gradual onset since 4
days associated with decreased frequency and
urine output past 2 days

• H/O altered sensorium since 2 days, not

responding to oral commands

4
HISTORY OF PRESENTING ILLNESS:

• H/o decreased food intake

• H/o difficulty passing stools

• No h/o fever/cough/ breathless/ chest pain

5
 PAST HISTORY
• K/C/O chronic liver disease with portal hypertension
since 2 years with recurrent episodes of pedal
edema and abdominal distention
• Four hospital admissions past two years for the
same
• Hepatic encephalopathy two months ago, treated
and recovered
6
Twelve days prior to the current admission
underwent PCNL ( Percutaneous nephrolithiostomy)
with a DJ stent in situ in the left kidney, had multiple
small calculi in upper and mid lower calyces, no
hydronephrosis, no perinephric collection

USG abdomen done post PCNL showed chronic

parenchymal disease with portal hypertension,
moderate ascites, b/l grade 1 renal echopattern 7
• Admitted post PCNL with complaints of decreased
urine output and abdominal distention,
discharged with the diagnosis and treatment for
hepatic encephelopathy

• No h/o diabetus mellitus/ hypertension/bronchial

asthma/ ischemic heart disease

8
 COURSE IN THE HOSPITAL
• The patient came to the casualty with the
present complaints

• He was admitted in the ICU after thorough

clinical examination and laboratory
investigations:

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 CLINICAL EXAMINATION
• General physical examination:

• Elderly male, drowsy, disoriented, not

responding to oral commands
• Pallor present
• Icterus, cyanosis, lymphedanopathy absent
• Bilateral pitting pedal edema present
• Flapping tremors present

10
• Vital signs:
• Body temperature: afebrile
• Pulse: 80/ minute, regular rhythm
• Blood pressure: 130/ 70 mm of Hg, right arm supine
position
• Systemic examination:
• Cardiovascular system : Normal heart sounds, no
abnormal findings
• Respiratory system: clear, no added sounds 11
• Per abdomen:

• Soft, non tender

• Free fluid present

• Shifting dullness present

• Penile swelling with active purulent discharge

from the urethral meatus present

12
 Investigations
• On admission:
PARAMETER REPORT NORMAL RANGE

Serum creatinine 1.0 0.4-1.4

Serum urea 42 10-50

Serum sodium 118 136-149

Serum potassium 5.4 3.5-5.3

Serum chloride 86.3 95-111

Serum bicarbonate 21.9 23-27

13
PARAMETER REPORT NORMAL RANGE
Heamoglobin 9.1 12-16
Total count 6600 4000-10000
Direct N 92( LEFT SHIFT) 50-70
count L 6 20-40
E 1 0-6
M 1 0-10
ESR 08 0-10
Platelet count 74000 1,50,000-4,00,000
PT 39.9 12.4-16.3

PT CONTROL 14.9
INR 3.00
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• Urine analysis report
PARAMETER REPORT NORMAL RANGE
Colour Yellow
Specific gravity 42
Urine reaction 118 136-149
Glucose 5.4 3.5-5.3
Ketone 86.3 95-111
Protein 21.9 23-27
Urobilnogen normal

Bile salts +
Bile pigments +

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• Urine analysis report
PARAMETER REPORT NORMAL RANGE

Pus cells 2-3 Up tp 5/HPF

RBC 4-5 0-2/HPF

Epithelial cells 1-2

Casts nil

Crystals nil

Comment Plenty of yeast like budding cells

16
Urethral meatal swab culture:
Gram stain: PMNLS+, epithelial cells++, Gram positive cocci+++,
Gram positive bacilli+++, Gram negative bacilli+++
Organism Growth Susceptible Intermediate Resistant
isolated
Klebsiella spp Heavy Amikacin Cefaperazone Ampicillin
growth Chloramphenicol Cefotaxime
Ceftazidime(6mm)
Ciprofloxacin
Ertapenem
Ofloxacin
Piperacillin
Piperacillin-
tazobactam
ESBL PRODUCER- Ceftazidime clavulinic acid(22mm)
Enterococcus Heavy Ampicillin, Chloramphenicol Amikacin, high
spp growth Cotrimoxazole Piperacillin- level gentamycin
Tetracycline tazobactam & streptomycin,
Vancomycin Erythromycin,
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Penicillin
• Ascitic tap was done and 550 ml of fluid was drained

• Urologist reference:
 Catheterization
 USG Abdomen
 Urine culture

Organisms at the tip of the urethra- ? colonizers with

active potential to cause UTI
Chloramphenicol was advised for treatment based on
the antibiotic susceptibility pattern of both isolates18
 USG abdomen findings

• Cirrhosis of liver with portal hypertension

• Gross ascites and splenomegaly

• Overdistended bladder with internal

septations and loculations- signs of retention

• B/l mimimal pleural effusion

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 Urine Culture
First sample – Mixed growth
Repeat sample-
Wet mount: Numerous pus cells,
no RBCs seen/HPF

Gram stain: Numerous pus cells,

numerous Gram negative bacilli
and 1-2 Gram positive cocci in
pairs/OIF

-Klebsiella spp >105 CFU/ml

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 Susceptible
Amikacin,ampicillin sulbactam,
Amoxyclav, cefaperazone
sulbactam, cotrimoxazole,
gentamycin, netillin, nitrofurantion
Resistant
Ampicillin, cefotaxime, cefuroxime,
ciprofloxacin, ertapenem,
ceftazidime (6mm), nalidixic acid,
norfloxacin, piperacillin, piperacillin
tazobactam
ESBL PRODUCER- Ceftazidime
clavulinic acid(24mm)
21
 Treatment
• Admission to the ICU
• Serum electrolytes and renal function parameters
monitored on a daily basis
• Fluid intake and urine output monitored
• Condom catheterization was done
• RT feed and bowel wash
• Inj Cefotaxime 1g given 8 hourly
• Inj Ranitidine 50mg iv 8 hourly
• Tab Aldactone 50mg 1-1-0
• Tab Rifagut 50 mg 1-1-1
• Inj Vitamin K 10mg 22
• Patient was shifted to the ward following
improvement
• Urine culture though showed growth, signs and
symptoms of UTI did not worsen, antibiotics were
therefore not initiated
• However his liver function test parameters and
consciousness state worsened
• He developed spontaneous bacterial peritonitis
therefore was shifted back to the ICU: 23
 DIAGNOSIS
Acute urethritis (post PCNL) and

spontaneous bacterial peritonitis with

chronic parenchymal liver disease with

portal hypertension in

hepatic encephelopathy Grade IV 24

 BACKGROUND
• Urinary tract infection is one of the most common

bacterial infections that lead patients to seek

medical care

• A vast majority have an uncomplicated presentation

• Complicated UTI arises when there are risk factors

for a severe clinical course or a secondary harm 25

• Diagnosis is not always straightforward, if
based only on clinical symptoms it is most
often wrong

• Immediate treatment is usually started based

on history and symptoms without
confirmation

• Many false positive cases remain accepted

26
• Guideline recommendations for antibiotic
treatment of UTI are often not implemented in
practice

• Complicated UTI has special recommendations

as greater diagnostic accuracy and different
therapeutic strategies are necessary
27
 DEFINITIONS:
• Complicated UTI: An infection associated with a
condition, such as structural or functional
abnormalities of the genitourinary tract or the
presence of an underlying disease, which
increases the risks of acquiring an infection or
of failing therapy
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• Two criteria are mandatory-

A positive urine culture and

One or more of the following factors:

1. The presence of an indwelling catheter, stent or
splint (urethral, ureteral, renal) or the use of
intermittent bladder catheterization
2. A post-void residual urine of > 100 mL
3. An obstructive uropathy of any aetiology, e.g.
bladder outlet obstruction (including neurogenic
urinary bladder), stones and tumour
29
4. Vesicoureteric reflux or other functional
abnormalities

5. Urinary tract modifications, such as an ileal loop or

pouch

6. Chemical or radiation injuries of the uroepithelium

7. Peri- and post-operative UTI

8. Renal insufficiency and transplantation, diabetes

mellitus and immunodeficiency
30
• Quantitative criteria:

108 cfu/L( 105 cfu/mL)

Suprapubic aspirate or catheterization- >102 cfu/mL

• Complicated UTI can arise in a heterogeneous group

of patients – children, men and pregnant women

• Neither patient age nor gender per se are a part of

the definition of a complicated UTI

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Recurrent UTIs:

• Relapse: infection with an organism similar to

the pre therapy isolate usually following
persistence of the organism in the
genitourinary tract

• Re infection: recurrent infection with a new

organism

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CHARACTERISTICS OF COMPLICATED UTI:

• Causative organisms

• Genitourinary abnormalities

• Patient population

• Clinical presentation

• Complications of infection

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 Causative organisms:
• Most common: Escherichia coli

• Symptomatic complicated UTI- less prevalence of

genotypic and phenotypic virulence characteristics

 Less likely to originate from a uropathogenic clone

 Host abnormality is the principle determinant not

the organism factor

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• Other Gram negative organisms: Klebsiella
pneumoniae, Proteus mirabilis, Providencia stuartii and
Morganella morganii, Pseudomanas aeruginosa

• Gram positive organisms: Enterococci spp, other Group

B streptococcus and CONS

• Candida spp
*Elderly, chronic urological devices: POLYMICROBIAL
*Repeated antibiotics & nosocomial infection:
antimicrobial resistance
37
 Genitourinary abnormalities:
• Interference with normal voiding leads to
impaired flushing of bacteria
Mechanism of infection:
• Obstruction with incomplete urinary drainage
• Persistence of bacteria in bio films on stones or
indwelling devices
• Increased introduction of organisms into the
genitourinary tract through instrumentation
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39
 MECHANISM ASSOCIATED CONDITIONS

OBSTRUCTION Ureteric or urethral strictures,

tumors of the urinary tract,
urolithiasis, prostatic
hypertrophy, diverticulae,
pelvicalyceal obstruction,
renal cysts, congenital
abnormalities

INSTRUMENTATION Indwelling catheter,

intermittent catheterization,
uretric stent, nephrostomy
tube, urological procedures40
 MECHANISM ASSOCIATED
CONDITIONS
IMPAIRED VOIDING Neurogenic bladder,
cystocele, vesicoureteral
reflux, ileal conduit

METABOLLIC ABNORMALITIES Nephrocalcinosis,

medullary sponge kidney,
renal failure

IMMUNOCOMPROMISED Renal transplant

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URINARY STONES VESICO URETRIC REFLUX
42
BENIGN PROSTATIC HYPERTROPHY

CATHETERIZATION 43
 Patient population
• Male UTIs
• Postmenopausal women with recurrent UTIs
• Children and pregnant women
• Structural and functional abnormalities
• Immunosuppressed patients
• Urological or renal disease, kidney stones
• Post catheterizated patients, inpatients discharged
within previous two weeks
44
 Clinical features
Asymptomatic presentation- most common
clinical presentation
• When symptomatic:
-Dysuria - Costovertebral angle tenderness
-Urgency - Suprapubic pain
-Frequency - Fever
-Flank pain
45
• Severe obstructive acute pyelonephritis & urosepsis

• Catheter-associated post-operative UTI, disappears

on removal of catheter

• Lower urinary tract symptoms caused by other

urological disorders, such as benign prostatic
hyperplasia (BPH), TURP etc

• Concomitant medical conditions- diabetes mellitus

and renal failure
46
 Complications
• Paraurethral, renal or perirenal abcess

• Metastatic spread: bone, joint, endocarditis

• Occur more common in patients with

co morbidities

• Renal failure, septic shock leading to death

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 MANAGEMENT
• CLINICAL ASSESSMENT:
• Symptomatic patients- clinical features are
straightforward
• Neurological illnesses, chronic catheterization
assessment is difficult
increased bladder, leg spasms- autonomic
dysreflexia, fatigue, fever etc
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ROLE OF THE MEDICAL MICROBIOLOGIST
• Physicians rely on a small number of laboratory

investigations before instituting treatment

• UTI accounts for a significant part of workload in

clinical microbiology laboratories

• Urine analysis mainly excludes bacteriuria

49
• Recurrent UTIs, treatment failures, complications,
inpatients – urine culture is advised

• Urine culture- absolute diagnostic reliability and

maximizes specific treatment- GOLD STANDARD in
diagnosis

• Laboratory diagnosis to identify the causative agent

of infection and implementing the right antibiotic
treatment requires considerable effort
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 LABORATORY DIAGNOSIS
• A urine specimen for culture should ideally be obtained
before the initiation of antimicrobial therapy

• Details on the requisition slip:

 Method of collection

 Date and time of collection

 Patient demographic information

 Clinically relevant details- stones, catheters, anatomic

defects, antibiotics etc 51
 Correct
Correct Correct Correct
transport and
collection processing interpretation
handling

52
 Specimen collection
• Clean catch midstream urine sample

• Supra pubic aspiration

• Indwelling catheter

• Straight catheterization
53
 Specimen transport
• Urine specimens should be

plated within 2 hours after

collection unless they have

been refrigerated or kept in

a preservative

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 Macroscopic examination
1. turbid due to the presence of pus cells and
microorganisms
2. milky colour - chyluria
3. red in colour - haematuria
4. brown/greenish brown- bilirubin
5. brown and cloudy - haemoglobin
6. yellow-orange - urobilin
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56
 Specimen processing
• Detection of pyuria and bacteruria by urine
microscopy:

WET MOUNT

GRAM STAIN

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WET MOUNT

58
 WET MOUNT
Advantages:
• Direct observation of leukocytes
• Rapid and practical technique
Disadvantages:
• Leukocytes deteriorate quickly if the sample is not
fresh or adequately preserved
• Inaccurate because of inadequate standardization

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GRAM STAIN

60
 GRAM STAIN
Advantages:
• Immediate information of the infective
organism, guides antimicrobial therapy
Disadvantages:
• Sensitive only if concentration of bacteria >105
cfu/mL
• May not detect bacteria in the range of 102-
103cfu/mL
61
 Other nonculturable methods:
• Detection of bacteriuria by nitrite and catalase test

• Detection of pyuria by urinary leukocyte excretion

rate, counting leukocytes using haemocytometer

• Detection of pyuria by leukocyte esterase test

• Simultaneous detection of pyuria and bacteruria

using nitrite and leukocyte esterase detection kits

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 Significance of urine analysis in UTIs
• Pyuria is present in asymptomatic bacteriuria
• Non infectious causes of urinary tract
inflammation in patients at risk for developing
complicated UTIs also cause pyuria
• Pyuria is consistent with but not diagnostic of
UTI
• High negative predictive value
• Casts are non specific
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 Urine culture
Differential/selective medium

 Mac Conkey’s medium - presumptive diagnosis of

bacteriuria

 CLED medium differentiates NLFs from LFs and

prevents the swarming Proteus

 Eosin methylene blue agar to differentiate and

isolates GNBs from mixed population of bacteria

 Blood agar for Gram positive cocci 64

 Urine culture methods
A. Semi quantitative methods:
i) Calibrated loop method
ii) Dip slide method
iii) Filter paper method

B. Quantitative methods:
i) Pour plate method
ii) Surface viable count - Spreading method
- Miles Misra method
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• Semi quantitative method using the calibrated
loop

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• Incubated overnight at 35-370C in ambient air
for 24 hours

• Total number of colonies X 100 (if 0.01 ml

/loop) = CFU/ml

67
• Advantages:
 Quantifies the magnitude of the infection regarding
the number of organisms in CFU/mL
 Yields a continuous dilution of specimen and dilution
of inoculum results in the growth of individual
colonies of bacteria
 Provides isolated colonies for subsequent
identification and ASTs
 Practical and fast
68
 Interpretation
• The relevance of microbial growth needs adequate
interpretation
• No growth, gross contamination – usually
unambiguous and easy to report
• Mixed culture in varying quantities are difficult to
interpret
• Algorithms and interpretative guidelines are made
to establish the clinical relevance
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 Result Specific specimen type/ Workup
associated clinical
condition, if known
>104 CFU/Ml of a single CCMS urine/ Complete
potential pathogen or pyelonephritis, acute
for each of two cystitis, asymptomatic
potential pathogens bacteriuria or
catheterized urine
>103 CFU/ml of a single CCMS urine/ Complete
potential pathogen symptomatic males or
catheterized urines or
acute urethral syndrome
> Three organism types CCMS urine None. Because of
with no predominant possible
organism contamination, ask
for another
specimen 70
 Result Specific specimen type/ Workup
associated clinical
condition, if known

Either two ore three CCMS urine Complete workup

organism types with for the
predominant growth of predominating
one organism type and organism(s),
< 104 CFU/ml of the description of the
other organism(s) other organism(s)
>103 CFU/ml of any Suprapubic aspirates, any Complete
number of organism other surgically obtained
types( set up with a urine( ileal conduit,
0.001 ml and a 0.01 ml cystoscopy samples)
calibrated loop)

Bailey and Scott’s diagnostic Microbiology – 12th edition , Pg 853

71
Antimicrobial susceptibility testing

• Individual laboratory guidelines based on the

health care setting

• First line and second line drugs for the isolates

• Developed, performed and reported according

to the CLSI guidelines

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73
 Follow up culture
• Advised for patients who:
Do not respond to therapy
Recurrent UTI
Anatomic or functional abnormalities
Unexplained urine analysis findings

Not recommended for patient treated for

asymptomatic bacteriuria, acute uncomplicated
cystitis or pyelonephritis or if there is evidence of
response to treatment
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 Role of urine culture in diagnosis
• GOLD STANDARD
• Ideally before the initiation of antimicrobial
treatment
108 cfu/L( 105 cfu/Ml)

Suprapubic aspirate or catheterization - >102

cfu/mL

75
FILTER PAPER METHOD DIP STICK METHOD

Automated methods: Bac T Screen 2000 system,

UTI screen system, Vitek system
76
 Characterization of underlying
abnormalities
• Based on patient age, sex, history and clinical
findings
• Diagnostic imaging – pelvic USG, intravenous
pyelography, CT, MRI
• Urological assessment- cystoscopy, retrograde
pyelography

77
 Treatment
• Empirical treatment is difficult- a wide variety
of microorganisms cause UTI and increased
likelihood of resistance

• Reserved only when the clinical presentation

is of sufficient severity

• If clinically feasible, should be delayed until

results of urine culture are available
78
• Oral therapy is appropriate in most episodes
• Parentral therapy- impaired gastrointestinal
absorption, hemodynamic instability, infecting
organism resistant to oral agents
• Duration- 7 days for lower UTI, 10- 14 days for
upper UTI for effective outcome
• Anticipated outcome in 48-72 hours
• Failure to respond- suspect drug resistance and
other differential diagnoses. 79
 Prevention
• Characterizing and correcting the underlying
abnormality causing UTI
• Prophylactic antimicrobial treatment is currently
not recommended
• Suppressive therapy only in selected patients with
persistent risk factors or abnormalities
• Urological devices to be used only when there are
clear clinical indications
• Aseptic techniques, closed drainage, limit potential
infection and trauma to the urinary tract
80
 CONCLUSION
• Clinical history and findings are insufficient to make

a diagnosis of complicated UTI

• Laboratory diagnosis is necessary to identify the

pathogen and its antimicrobial susceptibility pattern

• Urine analysis is not a surrogate for urine culture

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• Culture reports require correlating clinical

information which is available only to clinicians

• Knowing the strengths and limitations of the

laboratory in the diagnosis of complicated UTI

will help in implementing better treatment

guidelines and patient care.

82
 REFERENCES
1. Diagnostic Microbiology 12th edition by Bailey & Scott
2. Campbell-Walsh Urology 9th ed. Philadelphia, PA: Saunders
Elsevier, 2007
3. Smith’s General Urology 16th edition 2004. Tanagho and
MacAnnich. Chapter 13. “Bacterial infections of the Urinary tract”
Nguyen, Hiep. pp203-227
4. Harrison’s Principle of Internal Medicine 17th edition by Fauci et
al
5. Mims’ Medical Microbiology. 4th Edition
6. Gould CV, Umscheid CA, Agarwal RK, Kuntz G, Pegues. DA, and
Healthcare Infection Control Practices Advisory Committee
Guideline for prevention of catheter-associated urinary tract
infections 2009. Infect Control Hosp Epidemiol 2010;31:319-26
83
7. Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice
JC, et al. Diagnosis, prevention, and treatment of catheter-
associated urinary tract infection in adults: 2009 International
Clinical Practice Guidelines from the Infectious Diseases Society
of America. Clin Infect Dis 2010;50:625–63.
8. Schmiemann G, Kniehl E, Gebhardt K, Matejczyk MM, Hummers-
Pradier E. The diagnosis of urinary tract infection: a systematic
review. Dtsch Arztebl Int. 2010;107(21):361–367
9. Pallett A, Hand K. Complicated urinary tract infections: practical
solutions for the treatment of multi resistant Gram-negative
bacteria. J Antimicrob Chemother 2010;65(Suppl 3):iii25-33
10. Nicolle L, AMMI Canada Guidelines Committee: Complicated
urinary tract infection in adults.Can J Infect Dis Med Microbiol
2005, 16:349-360
11. Shoskes, D.(2011): Urinary Tract Infections Retrieved From: The
American Urological Association Educational Review Manual in
84
rd
Urology: 3 Edition Chapter: 23 Page: 737-766
Thank You 85