Pharmacotherapy of Urinary Tract Infections
PST 06106
Basic Pharmacotherapy
Session 18:
Pharmacotherapy of Urinary Tract Infections
Learning Objectives
By the end of this session students are expected to be able to
:
Define
urinary tract infections
Explain pathophysiology of urinary tract infections
Explain the clinical presentation of urinary tract infections
Outline diagnosis of urinary tract infections
Describe pharmacological treatment of urinary tract infections
Describe the monitoring of urinary tract infections
therapy
Activity: Buzzing
What
is Urinary Tract Infections?
Definition of Urinary Tract Infections
Urinary Tract Infections (UTI
)
UTI is defined as the presence of microorganisms in the urinary tract that cannot be accounted for by contamination.
The organisms present have the potential to invade the tissues of the urinary tract and adjacent structures.
Infection may be limited to the growth of bacteria in the urine, which frequently may not produce symptoms.
A UTI can present as several syndromes associated with an inflammatory response to microbial invasion and can range from asymptomatic bacteriuria to pyelonephritis with bacteremia or sepsis.
Definition of Urinary Tract Infections
Cont.….
UTIs are classified by lower and upper urinary tract infections.
Upper tract infection include pyelonephritis (an infection involving the kidneys) represents
Lower
tract infections correspond to cystitis (bladder),
Also, UTIs are designated as uncomplicated or complicated.
Uncomplicated infections occur in individuals who lack structural or functional abnormalities of the urinary tract that interfere with the normal flow of urine or voiding mechanism.
Definition of Urinary Tract Infections
Cont.….
These infections occur in females of child-bearing age (15 to 45 years) who are otherwise
normal healthy individuals.
Complicated UTIs are the result of a predisposing lesion of the urinary tract, such as a congenital abnormality or distortion of the urinary tract, a stone, indwelling catheter, prostatic hypertrophy, obstruction, or neurologic deficit that interferes with the normal
Classification of UTI
Pathophysiology of Urinary Tract Infections
The bacteria causing UTIs usually originate from bowel flora of the host.
Although virtually every organism is associated with UTIs, certain organisms predominate as a result of specific virulence factors.
The most common cause of UTIs is
Escherichia coli
, which accounts for 80% to 90% of community-acquired
infections.
Additional causative organisms in uncomplicated infections
include
Staphylococcus
saprophyticus
,
Klebsiella
pneumoniae, Proteus
spp.,
Pseudomonas aeruginosa
, and
Enterococcus
spp.
Pathophysiology
cont
…
Pathogenic organisms have differing degrees of pathogenicity (virulence), which play a role in the development and severity of infection.
Bacteria that adhere to the epithelium of the urinary tract are associated with colonization and infection
The mechanism of adhesion of gram-negative bacteria, particularly E. coli, is related to bacterial fimbriae that are rigid, hair-like appendages of the cell wall
These
fimbriae adhere to specific glycolipid components on epithelial cells
The most common type of fimbriae is type 1, which binds to mannose residues present in glycoproteins
Pathophysiology
Cont.
…
Glycosaminoglycan and Tamm-
Horsfall
protein are rich in mannose residues that readily trap those organisms that contain type 1 fimbriae, which are then washed out of the bladder.
Other fimbriae are mannose resistant and are associated more frequently with pyelonephritis, such as P fimbriae, which bind avidly to specific glycolipid receptors on
uroepithelial
cells
These bacteria are resistant to washout or removal by glycosaminoglycan and are able to multiply and invade tissue, and causing infection
Clinical Presentation of UTIs
Signs and symptoms
Lower UTI: dysuria, urgency, frequency,
nocturia
, suprapubic heaviness
Gross hematuria
Upper UTI: flank pain, fever, nausea, vomiting,
malaise
Physical examination
Upper UTI: costovertebral
tenderness
Clinical
Presentation of
UTIs
Cont
…
Laboratory tests
Bacteriuria
Pyuria (white blood cell count >10/mm 3 )
Nitrite-positive urine (with nitrite reducers)
Leukocyte esterase-positive urine
Antibody-coated bacteria (upper UTI
)
Diagnosis of UTIs
Symptoms alone are unreliable for the diagnosis of bacterial UTIs.
The key to the diagnosis of UTI is the ability to demonstrate significant numbers of microorganisms in an appropriate urine specimen to distinguish contamination from infection.
Diagnosis of
UTIs Cont.…
Urine testing
The gold standard for a urine test is to perform a bacteriological urine culture, with identification of the pathogen, with quantification and sensitivity testing.
To test whether the patient has a UTI at all, orientating indirect methods are often used in practice to detect the bacteria or inflammation (dip sticks).
The bacterial count may be assessed by urine microscopy and immersion culture media.
Midstream urine is normally collected
Diagnosis of
UTIs Cont.…
Dip sticks
Urine dip sticks are one of the most frequently used instruments for diagnostic testing if there is clinical evidence that a patient is suffering from UTI.
Multistix
are most often used, which may be able to detect nitrite (a metabolic product of typical pathogens of the urinary tract), leukocyte esterase, protein and blood (as a marker of inflammation
).
Diagnosis of UTIs Cont.…
Dip
sticks……
If
nitrite is detected, this increases the probability of a urinary tract infection, with a likelihood ratio [LR] of 2.6 to 10.6.
However, the sensitivity is relatively low.
In contrast, the detection of leukocyte esterase increases the probability to a lesser degree (LR 1.0 to 2.6). The detection of blood is admittedly highly sensitive, but the specificity is low.
Activity
: Small Group Discussion
What
is the treatment of
UTI
?
Pharmacological Treatment of UTIs
The management of a patient with a UTI includes;
Initial evaluation,
Selection of an antibacterial agent and duration of therapy, and
Follow-up
evaluation.
The initial selection of an antimicrobial agent for the treatment of UTI is based primarily on;
The severity of the presenting signs and symptoms,
The site of infection, and
Whether the infection is determined to be uncomplicated or complicated.
Other considerations include antibiotic susceptibility, side-effect potential, cost, and the comparative inconvenience of different
therapies
.
Empirical
Treatment of UTIs
Treatment
of UTI according to Pathogen
Monitoring of UTI Therapy
In asymptomatic post-treatment patients routine urinalysis and/or urine culture is not recommended
In patients with persistent symptoms, microbiological screening is recommended.
In women whose symptoms do not resolve by end of treatment, and in those whose symptoms resolve but recur within two weeks, urine culture and antimicrobial susceptibility testing should be performed
For therapy in this situation, one should assume that the infecting organism is not susceptible to the agent originally used.
Retreatment with a seven day regimen using another agent should be considered
Antibiotic treatments may be repeated with a more prolonged course, higher dosage and/or different compounds for patients with recurrent
infections
Key Points
UTI
is defined as the presence of microorganisms in the urinary tract that cannot be accounted for by contamination.
UTIs are classified by lower and upper urinary tract infections.
The most common cause of UTIs is
Escherichia coli
, which accounts for 80% to 90% of community-acquired
infections
Signs and Symptoms of UTI include
dysuria, urgency, frequency,
nocturia
, suprapubic heaviness
Variety of antibiotics can be used for the treatment of UTI
Evaluation
What
is UTIs?
What is the pathophysiology of
UTIs?
What are the signs and symptoms of uncomplicated UTI?
How is the treatment of Uncomplicated UTI?
References
Wells
BG,
DiPiro
J,
Schwinghammer
T (2013),
Pharmacotherapy Handbook
(6
th
Ed). New York, NY: McGraw-Hill.
DiPiro
JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):
Pharmacotherapy: A Pathophysiologic Approach
(7
th
ed
): New York, NY: McGraw-Hill.
Katz M D.,
Matthias KR.,
Chisholm-Burns M A.,
Pharmacotherapy(2011)
Principles & Practice Study Guide: A Case-Based Care Plan Approach
:
New York, NY: McGraw-Hill.
Schwinghammer
TL, Koehler JM (2009)
Pharmacotherapy Casebook: A Patient-Focused Approach
(7
th
ed
): New York, NY: McGraw-Hill.
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