Transcript Final Case Study - Cal State LA

Case Study #1: E. coli
Tania Guevara
Anthony
Edmund
March 11, 2009
California State University of Los Angeles
Case Summary
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Age
-19 yr old female
Medical History
-History of urinary tract infection (UTI)-4 mts prior to
admission
-Treated with oral ampicillin-Resistance to ampicillin can
occur because the oral medication is rapidly excreted and
the duration of significant drug concentration in the urine
is short. An additional reason is that ß-lactams are
relatively ineffective in clearing gram negative rods from
the vaginal and colonic mucosa, thus possibly
predisposing to recurrences when used to treat UTI
Case Summary
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Symptoms
Five Days Prior to Admission
-Nausea w/out vomiting
One Day Prior to Admission
-Left flank pain
-Fevers (38.8oC)
-Chills
-Increased urinary frequency
-Foul smelling urine
Physical examination
- Left costovertebral angle tenderness
Urinalysis
-Notable for >50 WBC/ high power field, 3-10RBC/ high
power field, and 3+ bacteria
-Urinary culture was positive for >100,000 CFU of an
org/ml
Case Summary
>50 WBC
-Pyuria refers to the presence of abnormal numbers of
leukocytes that may appear with infection in either the
upper or lower urinary tract. White cells from the vagina,
especially in the presence of vaginal and cervical infections,
may contaminate the urine. If two or more leukocytes per
each high power field appear in non-contaminated urine,
the specimen is probably abnormal.
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3-10 RBC
-Theoretically, no red cells should be found, but some find
their way into the urine even in very healthy individuals.
However, if one or more red cells can be found in every
high power field, and if contamination can be ruled out, the
specimen is probably abnormal.
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Case Summary
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3+ bacteria
-Bacteria are common in urine specimens because of the
abundant normal microbial flora of the vagina and because
of their ability to rapidly multiply in urine standing at room
temperature.
-Diagnosis of bacteriuria in a case of suspected urinary tract
infection requires culture. A colony count may also be done
to see if significant numbers of bacteria are present.
Generally, more than 100,000/ml of one organism reflects
significant bacteriuria.
Key Information Pointing to
Diagnosis
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UTI are a bacterial infection of the urinary bladder (cystitis)
or of the kidneys (pyelonephritis)
Nearly all UTI’s are caused by bacteria and enter the
urethral opening and move upward to the urinary bladder
and sometimes the kidneys
Possible pathogens for a UTI:
-E.coli
-enterobacteriae
Klebsiella
-P. mirabilis
-P. aeroginosa
-Enterococci (group D)
-Staphylococcus
Key Information Pointing to
Diagnosis
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Cystitis (lower UTI)- sudden onset, frequency, urgency,
burning, or painful voiding of small vol. of urine. Nocturia
with suprapubic and lower back pain is common. Urine is
turbid, gross hematuria, and pneumaturia can result. Low
grade fever.
Pyelonephritis (Upper UTI)-Chills, fevers, flank pain,
nausea, and vomiting. Costovertebral angle percussion
tenderness is generally present in the infected side.
Most common common organism causing this type of
infection if E. coli (uropathogenic E. coli-UPEC)
Key Information Pointing to
Diagnosis
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UTI’s are more frequent in women because they have a shorter
urethra, which makes it easier for bacteria to move up the urinary
tract and provide less barrier to the bacterial invasion
The Diagnosis for Case #
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The diagnosis provides clear evidence to support that the
patient is suffering from a pyelonephritis UTI caused by
Uropathogenic E. coli organism.
Classification,Gram Stain Results, and
Microscopic Appearance of Pathogen X
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Classification-more than 15 genera
-Escherichia
Morphology and General Characteristics
-Gram negative, non-sporing, rod shape bacteria
-NF of intestinal tract, some are enteric pathogens and
others are urinary or respiratory pathogens
-Anaerobes
-Oxidase (-)
-Ferment glucose and may/not produce gas
-Reduce nitrate to nitrite
-If motile-by peritrichous flagella
Classification,Gram Stain Results, and
Microscopic Appearance of Pathogen X
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Most grow well on a variety of lab media
-Lactose fermenters:
On CBA they all produce large and dull gray colonies. Beta
hemolytic
Differentiation is based on biochemical reactions and
differences in antigenic structures (O, H, and K1)
Diseases and Pathogenesis of
Disease Caused by Pathogen X
Virulence Factors
-Toxins
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Enterotoxins (LT/ST)
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Shiga-type toxin
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Enteroaggregative ST-like toxin
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Endotoxin
-Type III Secretion System
-Adhesion (pili or fimbriae and non-fimbrial)
VF that protect the bacteria from host
-Capsule
-Iron capturing ability
-Outer membrane proteins
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Virulence factors of recognized importance in the pathogenesis of urinary
tract infection (UTI) include: adhesins (P fimbriae, certain other mannoseresistant adhesins, and type 1 fimbriae), the aerobactin system,
hemolysin, K capsule, and resistance to serum killing
Diseases and Pathogenesis of
Disease Caused by Pathogen X
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In women who suffer from recurrent UTI’s- suggest that
this may be due to the formation of pod-like E. coli biofilms
inside the bladder epithelial cells
-Bacteria living on the edges of the biofilms may break off
leading to a round of infection.
Diagnosis/Isolation/Identification
• UTI Diagnosis
 A culture of the bacteria may be done to determine the
type of bacteria
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A clean-catch urine specimen. This test involves
cleansing the area around the urethral opening and
collecting a mid-stream urine sample, preventing
bacteria in the genital area from contaminating the
sample.
 Urinalysis is performed to determine the level of white
blood cells that destroy harmful bacteria (leukocytes) in
the urine. A large number of these cells may indicate
bacterial infection.
 Dipstick:
- check for appearance and color of urine
-pH or concentration
Diagnosis/Isolation/Identification
 Microscopic test
-Blood cells (e.g., red blood cells, white blood cells;
indicate hematuria or infection)
-Casts (e.g., hyaline, granular; may indicate kidney
disease)
-Cells from the lining of the urinary tract (epithelial cells)
-Crystals (may indicate metabolic disease)
-Fat (may indicate nephrotic syndrome or diabetic
neuropathy)
-Renal tubular cells (may indicate acute tubular
necrosis)
Therapy, Prevention and Prognosis
of Patient Infected with UTI
Therapy
-are often treated with antibacterial drugs.
-The type of drug used and the duration of treatment depend
on the type of bacteria
-Most UTI’s are treated with trimethoprim-sulfamethoxazole
(e.g. Bactrim, Cotrim, Septra), amoxicillin (e.g. Amoxil,
Trimox), or fluoroquinolones (e.g. Levaquin, Cipro).
-The infection may improve within a couple of days, but 1 to
2 weeks of medication may be prescribed to prevent a
kidney infection.
Note: UTIs that are caused by bacteria such as Chlamydia
trachomatis and mycoplasma hominis require a longer
course of treatment with tetracycline (e.g. Achromycin),
trimethoprim-sulfamethoxazole, or doxycycline
(e.g.Periostat).
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Prevention and Prognosis of
Patient Infected with UTI
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Drink plenty of water every day.
Urinate when you feel the need; don't resist the urge to urinate.
Wipe from front to back to prevent bacteria around the anus from
entering the vagina or urethra.
Take showers instead of tub baths.
Cleanse the genital area before sexual intercourse.
Avoid using feminine hygiene sprays and scented douches, which
may irritate the urethra.
Some doctors suggest drinking cranberry juice.
Prognosis:
12-13 cases annually per 10,000 population in women. UTIs. The
elderly are at increased risk for such infections because the
bladder doesn't empty fully due to certain prostate and bladder
conditions.
Primary Research Article Contributing to the
Understanding of the Disease caused by E.
coli
Mysorekar, Indira U, et al., 2007, Mechanisms of Uropathogenic Escherichia
coli Persistence and Eradication From The Urinary Tract, Proceedings of the
National Academy of Sciences of the United States of America, 103:
14170-14175.
-Study aim to demonstrate in a murine model of UTI, that UPEC
established quiescent intracellular reservoirs (QIR’s) in Lamp 1+
endosomes within urinary bladder epithelium, thus resulting in reoccuring
UTI’s.
-However, treatment of infected bladder harboring QIR’s with the cationic
protein, protamine sulfate, would lead to epithelial exfoliation and
eradication of bacteria in 100% of the animals.
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Set-Up:
Mice- 6-8 wks female C57BL/6 mice, all maintained under pathogen free
conditions
Bacterial strains- UTI89, a UPEC strain recovered from human patient w
cystitis, transformed, and grown as a static culture
Inoculation of mice-Mice were anesthetized and inoculated w/ 50 ul of 107
CFU bacteria (bladders removed and processed for microscopy, histology,
and CFU titration)
Primary Research Article cont’d
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CFU titration-Bacterial titers were determine by plating serial
dilutions of bladder homogenates
BrdU labeling-some mice received an intraperitoneal injection of
an aq. solution of BrdU.
Histologic and IFA analysis-bladders were dissected and cut
longitudinally.
SEM
Whole mount Analysis-Mice were killed, bladders were
bisected and sprayed with PBS to observe outline of mature
facet cells and visualize nuclei.
Urine analysis- At indicated times, mice were induced to
urinate by applying gentle pressure to the skin just below
the occiput,
Statistical Analysis
Primary Research Article cont’d
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Findings:
QIR’s within bladder may be a source of recurrent UTI’s.
Inducing epithelial exfoliation may be a therapeutic avenue for
treating this infection.
Relatedness to Topic:
-Since pyelonephritis often succeeds initial cystitis, this
particular study can help prevent pyelonephritis from occurring
by resolving cystitis.
Take Home Message
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UPEC involves the organism E. coli which is a gram negative rod
that causes UTI.
Typical symptoms include chills, fevers, flank pain, nausea, and
vomiting. Costovertebral angle percussion tenderness is generally
present in the infected side.
Pathogen is Uropathogenic E. coli
UTI diagnosis can be performed from a clean catch urine
specimen, urinalysis, and microscopic test.
Therapy is based on antibiotics that include include
fluoroquinolones, amoxillin, trimethoprim, etc.
Symptoms of a bladder infection usually disappear within 24 - 48
hours after treatment begins. If you have a kidney infection, it
may take 1 week or longer for your symptoms to go away.
Prevention to infection includes drinking plenty of water and
cranberry juice, taking showers instead of baths, and good
genital hygiene.
Nearly all UTI’s are caused by bacteria and enter the urethral
opening and move upward to the urinary bladder and sometimes
the kidneys
Pyelonephritis is very common, with 12-13 cases annually per
10,000 population in women. UTIs. The elderly are at increased
risk for such infections because the bladder doesn't empty fully
due to certain prostate and bladder conditions.
References
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Mysorekar, Indira U, et al., 2007, Mechanisms of Uropathogenic
Escherichia coli Persistence and Eradication From The Urinary
Tract, Proceedings of the National Academy of Sciences of the
United States of America, 103: 14170-14175.
Rosen, David et al, 2007, Detection of Intracellular Bacterial
Communities in human Urinary Tract Infection, Journal Pmed,
(4)12; e 329.
Dr Mcqueen. "Enterobacteriaceae." Enterobacteriaceae. Bio 244,
Los Angeles. 22 Jan. 2009.
Mahon, Connie et al. Textbook of Diagnostic Microbiology. 3rd Ed.
St. Louis: Missouri, 2007.
About.com. 10 March 2009.
<http://www.womenshealth.about.com/cs/bladderhealth/a/UTI.ht
m>
FamilyDoctor.org. 10 March 2009.
http://www.familydoctor.org/online/famdocen/home/women/genhealth/190.printerview.html
Kidney and Urological Home. 10 March 2009.
<http://www.kidney.niddk.nih.gov/kudiseases/pubs/uti_ez/#2>
Urology Channel. 10 March 2009.
<http://www.familydoctor.org/online/famdocen/home/women/gen
-health/190.printerview.html>