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URINARY TRACT

INFECTION
Dan Gil Manauis
Mariz Kayl Reyes
Objectives

 Recognize the usual symptoms of an uncomplicated urinary tract


infection in females
 Select the specific drug therapy for the treatment of an uncomplicated
UTI after consideration of patient symptoms, objective findings, and
expected clinical response
 Describe the monitoring parameters to ensure efficacy and prevent
toxicity during treatment
 Counsel patients about how to take the regimen, noting relationship with
meals, proper storage, and potential side effects
Urinary Tract Infection

A common type of infection caused by


bacteria that travel up the urethra to the
bladder
It can happen along the urinary tract: the
kidney (pyelonephritis), the bladder
(cystitis), urethra (urethritis)
Types Of UTI
Complicated or Uncomplicated
it depends on the factor that trigger the
infection

Primary or Recurrent
depends on whether the infection is occurring
for the first time or is a repeated event
Uncomplicated UTI

Due to bacterial infection, most often E. coli.


Affect women much more often than men
 Cystitis
 bladder infection; most common UTI
Pyelonephritis
 kidney infection; sometimes spreads to the upper
tract
Complicated UTI
 Occurs in both men and women of any age
also caused by bacteria but they tend to be more severe,
more difficult to treat, and recurrent.
Recurrences can occur in patients with complicated UTI if
the underlying structural or anatomical abnormalities are
not corrected.
Often a result of:

1. Some anatomical or structural abnormality that impairs the


ability of the urinary tract to clear out urine and therefore
bacteria

2. Catheter use in the hospital setting or chronic indwelling


catheter in the outpatient setting

3. Bladder and kidney dysfunction, or kidney transplant


(especially in the first three months of transplant)
Recurrent UTI

Most women who have had an uncomplicated


UTI have occasional recurrences
25-50% of these women can expect another
infection within a year
Recurrences is often categorised as either
reinfection or relapse.
Reinfection

most cases of recurring UTI


occurs several weeks after antibiotic
treatment has cleared up the initial
episode
can be caused by the same bacterial strain
or a different one
Relapse

less common form of recurrent UTI


diagnosed when a UTI recurs within 2
weeks of treatment of the first episode
and is due to treatment failure
usually occurs in pyelonephritis
ASYMPTOMATIC UTI

when a person has no symptoms of


infection but significant number of
bacteria have colonised the urinary tract
harmless in most people and rarely
persist
SYMPTOMS
persistent urge to urinate
burning sensation when urinating
passing frequent, small amounts of urine
blood in the urine (hematuria), or cloudy strong
smelling urine
SYMPTOMS
flank pain, high fever, shaking chills, nausea
and vomiting (associated with
pyelonephritis)
pressure in the pelvis and lower abdomen
and strong smelling urine (associated with
cystitis)
pus in the urine and genital discharge
Risk Factors In Women

 Structure of The Female Urinary Tract


 due to the shortness of the female urethra
 Sexual Behavior
 Frequent or recent sexual activity is the most important risk
factor for UTI
 UTI’s are NOT sexually transmitted infections
 physical act of intercourse produces conditions that incase
susceptibility to the UTI bacteria
Pregnancy

in pregnant women, the presence of the


asymptomatic bacteriuria is associated
with UTI, which can cause early labor and
other serious pregnancy complications
the uterus enlarges and compresses the
ureters and the bladders
Menopause

due to the decrease in


estrogen which thins the walls
of the urinary tract and
reduces its ability to resist
bacteria
Allergies
allergies to soap, vaginal creams, bubble
baths or other chemicals that are used for
the cleansing of the genital area may
cause small injuries that can allow the
penetration of bacteria
Antibiotic Use

Antibiotics often eliminate


Lactobacilli which can cause an
overgrowth in E. coli
Risk Factors in Men
Men become more susceptible to UTI after the age
of 50, when they begin to develop prostate
problems
Benign Prostatic hyperplasia (enlargement of the
prostate gland) can produce obstruction in the
urinary tract which increases the risk for infection
Risk Factor in Children

Catheterization
The longer the urinary catheter is in
place, the higher the risk for growth of
bacteria and an infection
Diagnosis

Urinalysis
Leukocyte Esterase Test
Gram Stain of Urine
Culture and Sensitivity
Diagnosis
Kidney and bladder Magnetic resonance
ultrasound imaging (MRI)
Voiding Radionuclide scan
cystourethrogram Urodynamics
Computerized Cystoscopy
tomography (CT) scan
Laboratory Result

Colony count of at least 100,000


colony forming units (CFU)
Presence of WBC
Pathophysiology
Pathophysiology
Treatment Goal of UTI in Women
Treatment Goal of UTI in Women
Treatment Goal of UTI in Men
Empirical Treatment of UTI
Commonly Used Antimicrobial Agents in
the Treatment of UTI
Agent Advantage Disadvantage
Sulfonamides Inexpensive Have been replaced by more agents
due to resistance
TMP-SMX highly effective against most aerobic used only to treat or prevent
enteric bacteria except Pseudomonas infections that are proven or
aeruginosa strongly suspected to be caused by
bacteria
Penicillins broad-spectrum activity Escherichia coli resistance
has limited amoxicillin use in acute
cystitis.
Cephaloshorins They may be useful in cases of Not active against enterococci;
resistance to amoxicillin and more expensive
trimethoprim-sulfamethoxazole.
Tetracyclines Useful for chlamydial infections Resistance develops rapidly
Commonly Used Antimicrobial Agents in the
Treatment of UTI
Agent Advantage Disadvantage
Fluoroquinolones effective for pyelonephritis and Moxifloxacin should not be
prostatitis used owing to inadequate urinary
concentrations. Expensive.
Nitrofurantoin lack of resistance even after long Adverse effects may limit use (GI
courses of therapy intolerance, neurophaties, pulmonary
reactions)
Azithromycin Excellent efficacy, Low potential for Food reduces absorption rate of
drug interactions, Low rate of side azithromycin capsules
effects, Sustained antimicrobial
activity

Fosfomycin has good distribution into tissues, low Clinical cure rates may be slightly inferior
incidence of adverse events
Treatment Recommendations
Treatment Recommendations
A Case Study on Urinary
Tract Infection
Chief Complaint
“Over the past 24 hours, I’ve been
alternating between urinating frequently
to needing to urinate and not being able
to.”
History of Past Illness
J.M. is a 21 year old woman who
presents in to the University Clinic with
a 24 hour history of dysuria, frequency
and urgency. She also complains of
constipation. She denies sexually active.
Past Medical History
UTI 6 months ago
Bulimia; states that she has been
trying to eat better and is not
vomiting anymore.
Family History

Non-contributory
Social History
Non-smoker
Lives with her mother
Medication History

Allergies: Bactrim (rash)


No current medication
Review of System

Denies flank pain or


Fever
Physical Examination
General Skin
Cooperative Mild facial
woman in no Acne
distress
Physical Examination (Normal value retrieved from:
https://www.nlm.nih.gov/medlineplus/ency/article/002341.htm )

Vital Sign Normal Value Obtained Value Interpretation

Blood Pressure 90/60 mm/Hg to 110/60 mm/Hg Normal


120/80 mm/Hg
Pulse Rate 60 to 100 beats per 68 beats per minute Normal
minute
Respiratory Rate 12 to 18 breaths per 18 breaths per minute Normal
minute
Temperature 97.8°F to 99.1°F 96.2 F Below Normal
(36.5°C to
37.3°C)/average
98.6°F (37°C)
Physical Examination
 HEENT
 PERRLA (Pupils, Equal, Round, Reactive Chest
to Light and Accommodation)
 EOMI (Extraocular Movements Intact)  CTA (Computed Tomography
Angiography)
 Fundi benign
 TMs (Tympanic Movements) intact  Cardiovascular
 RRR (Regular Rate and Rhythm)
 Back
 No CVA (Costovertebral Angle)
tenderness
Physical Examination
 Abdomen  Extremities
 Soft  Pulses 2+ throughout; full
 (+) bowel sounds ROM
 No organomegaly or  Neuro
tenderness  A&O x 3; CN II-XII intact;
 Pelvic reflexes 2+
 No vaginal discharge or  Sensory and motor levels
lesions intact
 LMP 2 weeks ago
Labs
Not obtained
Urinalysis (Normal value retrieved from:
http://emedicine.medscape.com/article/2074001-overview )

Component Normal Value Obtained Value Interpretation

WBC ≤2-5 WBCs/hpf 10-15 cells/hpf Above Normal

RBC ≤2 RBCs/hpf 1-5 cells/hpf Above Normal

Bacteria None 2-5/hpf Above Normal

Nitrite Negative (-) Negative (-) Normal


S.O.A.P.
SUBJECTIVE • Dysuria
• Frequency
• Urgency
• Constipation

OBJECTIVE • Temperature 96.2’F (below normal)


• WBC 10-15 cells/hpf (above normal)
• RBC 1-5 cells/hpf (above normal)
• Bacteria 2-5 cells/hpf (above normal)
ASSESSMENT Uncomplicated Urinary Tract Infection
PLAN Non pharmacological treatment
• Increase intake of water (2L)
• Improve hygiene
• Allow frequent urination
• Completely empty the bladder when
urinating
Pharmacological Treatment
• Nitrofurantoin 100mg po bid for 7 days or
• Fosfomycin 3g po one time admin or
• Ciprofloxacin 250-500mg BID for 3 days
• Phenazopyridine 100-200mg TID for 2 days
Initial Drug Therapy

FIRST LINE TREATMENT:


Nitrofurantoin 100mg po bid for 7
days or
Fosfomycin 3g po one time
administration (Alternative)
Alternative Drug Therapy

ALTERNATIVE TREATMENT:
Ciprofloxacin 250-500mg 1tab BID
for 3 days.
Pain Management in UTI
PHENAZOPYRIDINE
100-200mg by mouth after meals TID for
2 days.
Initial Drug Therapy
DRUG DOSAGE STRENGTH ROUTE FREQUENCY MOA

Nitrofurantoin or 100mg Oral bid for 7 days Inactivates or alters


bacterial ribosomal
proteins and other
macromolecules that
may interfere with
metabolism and cell
wall synthesis.

Fosfomycin or 3g Oral One time Blocks bacterial cell wall


administration synthesis by inactivating
enolpyruvyl transferase
and also reduces
bacterial adherence to
uroepithelial cells.
Initial Drug Therapy
DRUG DOSAGE STRENGTH ROUTE FREQUENCY MOA

Ciprofloxacin 250-500mg 1tab Oral Twice a day for 3 days Inhibits relaxtion of
DNA; Inhibits DNA
Gyrase in susceptible
organisms; promotes
breakage of double-
stranded DNA.

Phenazopyridine 100-200mg Oral Thrice a day for 2 days Acts directly on urinary
tract mucosa when
excreted, to produce
local analgesic effect.
Initial Drug Therapy
DRUG INDICATION RELEVANT TO CASE MONITORING REQUIRED DESIRED THERAPEUTIC
OUTCOME

Nitrofurantoin or Eradicate microorganism Urinalysis WBC: ≤2-5 WBCs/hpf


• WBC RBC: ≤2 RBCs/hpf
• RBC Bacteria: None
• Bacteria

Fosfomycin or Eradicate microorganism Urinalysis WBC: ≤2-5 WBCs/hpf


• WBC RBC: ≤2 RBCs/hpf
• RBC Bacteria: None
• Bacteria

Ciprofloxacin Eradicate microorganism Urinalysis WBC: ≤2-5 WBCs/hpf


• WBC RBC: ≤2 RBCs/hpf
• RBC Bacteria: None
• Bacteria

Phenazopyridine Painful urination Monitor improvement of dysuria Relief of Painful Urination


NITROFURANTOIN

 MECHANISM OF ACTION
 Inactivates or alters bacterial ribosomal proteins and
other macromolecules that may interfere with
metabolism and cell wall synthesis.
NITROFURANTOIN

Common Side Effects: Serious Side Effects  muscle weakness


 dark yellow or brown urine  difficulty breathing  swelling of the lips or tongue
 nausea  excessive tiredness  skin rash
 vomiting  fever or chills
 loss of appetite  chest pain
 persistent cough
 numbness, tingling, or
pinprick sensation in the
fingers and toes
Nitrofurantoin Interactions
Drug Interaction
 Antacids containing magnesium trisilicate, when administered concomitantly with nitrofurantoin,
reduce both the rate and extent of absorption. The mechanism for this interaction probably is
adsorption of nitrofurantoin onto the surface of magnesium trisilicate.
 Uricosuric drugs, such as probenecid and sulfinpyrazone, can inhibit renal tubular secretion of
nitrofurantoin. The resulting increase in nitrofurantoin serum levels may increase toxicity, and the
decreased urinary levels could lessen its efficacy as a urinary tract antibacterial.
Drug/Laboratory Test Interactions
 As a result of the presence of nitrofurantoin, a falsepositive reaction for glucose in the urine may
occur. This has been observed with Benedict's and Fehling's solutions but not with the glucose
enzymatic test.
NITROFURANTOIN

 Proper Storage and Disposal


Keep this medication in the container it came in, tightly
closed, and out of reach of children. Store it at room
temperature and away from excess heat and moisture
(not in the bathroom). Throw away any medication that
is outdated or no longer needed.
FOSFOMYCIN

MECHANISM OF ACTION
Blocks bacterial cell wall synthesis by
inactivating enolpyruvyl transferase and also
reduces bacterial adherence to uroepithelial
cells.
FOSFOMYCIN

Side Effects: Serious Side Effects:


 nausea  fever
 diarrhea  rash
 headache  joint pain
 vaginal itching  swelling of the mouth or
tongue
 runny nose
 yellowing of the skin or eyes
 back pain
FOSFOMYCIN

 Proper Storage and Disposal


Keep this medication in the container it came in, tightly
closed, and out of reach of children. Store it at room
temperature and away from excess heat and moisture
(not in the bathroom). Throw away any medication that
is outdated or no longer needed.
Fosfomycin Interactions
Serious - Use Alternative Significant - Monitor Closely Minor
 bcg vaccine live  bazedoxifene/conjugated  balsalazide
estrogens
 typhoid vaccine live  biotin
 conjugated estrogens
 metoclopramide
 digoxin
 pantothenic acid
 estradiol
 pyridoxine
 estrogens conjugated synthetic
 pyridoxine (antidote)
 estropipate
 thiamine
 mestranol
 sodium picosulfate/magnesium
oxide/anhydrous citric acid
CIPROFLOXACIN

MECHANISM OF ACTION
Inhibits relaxtion of DNA; Inhibits DNA
Gyrase in susceptible organisms; promotes
breakage of double-stranded DNA.
CIPROFLOXACIN

 Adverse Effects
 Nausea
 Abdominal pain
 Diarrhea
 Increase aminotransferase levels.
 Vomiting
 HA
 Increase serum creatinine
 Rash
 restlesness
CIPROFLOXACIN Interactions

 Aluminum Hydroxide  Iron Sucrose


 BCG Vaccine Live  Ondansetron
 Cisapride  Rasagiline
 Clomipramine  Saquinavir
 Clozapine  Theophylline
 Didanosine  Typhoid Vaccine Live
 Dronedaron  Warfarin
 Imipramine
PHENAZOPYRIDINE

MECHANISM OF ACTION
Acts directly on urinary tract mucosa when
excreted, to produce local analgesic effect.
PHENAZOPYRIDINE

 Adverse Effects  Hemolytic anemia


 HA  Skin pigmentation
 Vertigo  Staining of contact
 Rash lenses
 Pruritus  Hepatotoxicity
 Mild GI disturbances
 Methemoglobinemia
PHENAZOPYRIDINE Interaction

Prilocaine
Monitoring
Urinalysis is used as the method of monitoring
the effectiveness of the treatment with the
parameters of:
≤2-5 WBCs/hpf
≤2 RBCs/hpf
No Bacteria
Negative (-) Nitrite
Desired Therapeutic Outcome

Gradual decrease in per hpf of RBC, WBC, and


bacteria until ≤2-5 WBCs/hpf , ≤2 RBCs/hpf ,
No Bacteria, and Negative (-) Nitrite is achieved
at the end of the treatment.
Drug Therapy Timeline

Nitrofurantoin: taken twice a day with meals


and a full glass of water, preferably taken at the
same time everyday for 7 days.
Fosfomycin: pour the entire contents of a single-
dose packet into a glass and add 3 to 4 ounces
(90 to 120 milliliters) of cold water. Stir to
dissolve. Do not use hot water. The dose should
be taken by mouth as soon as it is prepared.
Drug Therapy Timeline

Nitrofurantoin:

6 AM 6 PM

5AM 7AM 8AM 9AM 10AM 11AM 12PM 1PM 2PM 3PM 4PM 5PM 7PM 8PM
Drug Therapy Timeline

Ciprofloxacin:

6 AM 6 PM

5AM 7AM 8AM 9AM 10AM 11AM 12PM 1PM 2PM 3PM 4PM 5PM 7PM 8PM
Drug Therapy Timeline

PHENAZOPYRIDINE:

6 AM 2 PM
10 PM

5AM 7AM 8AM 9AM 10AM 11AM 12PM 1PM 2PM 3PM 4PM 5PM 6PM 7PM 8PM 9PM
Pharmacist Care Plan
Health Care Need Pharmaco- Recommen dation/ Monitoring
therapeutic Goal Measures

Treat uncomplicated UTI Eradicate microorganism  Nitrofurantoin Relief of Symptoms


causing infection 100mg po bid for 7 days or Urinalysis (changes in
 Fosfomycin 3g po or RBC, CBC and Bacterial
 Ciprofloxacin 250- count per hpf)
500mg bid

Treat Dysuria Relieve pain in urination  PHENAZOPYRIDINE 100- Pain scale


200mg by mouth after
meals TID for 2 days.
Pharmacist’s Notes
Recommendation: Treatment with Nitrofurantoin
100mg po bid for 7 days
Discussion: Since there is allergic reaction with
Bactrim, which is supposed to be the first line
agent for recurrent UTI, nitrofurantoin is
recommended.
Pharmacist’s Notes
 Basis for Recommendation: Trimethoprim-sulfamethoxazole or trimethoprim should be used
as first-line therapy because of its low cost and efficacy for uncomplicated urinary tract
infections in women unless the prevalence of resistance to these agents among uropathogens
in the community is greater than 10% to 20%. The fluoroquinolones are more expensive,
broader in spectrum, and therefore, should be reserved for communities with rates of
resistance to trimethoprim of greater than 10% to 20% or in patients who either cannot
tolerate trimethoprim-sulfamethoxazole or have recurrent urinary tract infections. Other
options include a 7-day course of nitrofurantoin or a single dose of fosfomycin. The use of first-
generation cephalosporins or aminopenicillins is generally not recommended because of high
levels of resistance and recurrence. Although resistance to the third-generation cephalosporins
is lower than to the first generation, these agents are considered third-line agents because of
their cost and efficacy.
 Site: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071654/
Pharmacist’s Notes
Recommendation: Treatment with Fosfomycin 3g
po OD
Discussion: It has been found that the effect of a
single dose fosfomycin is comparable to the
effect of a 7-day treatment of nitrofurantoin.
Pharmacist’s Notes
 Basis for Recommendation: There were no clinical differences in patient characteristics
between the 2 groups at study entry. Overall, 94% of pretreatment isolates were
susceptible to fosfomycin and 83% were susceptible to nitrofurantoin. Bacteriologic cure
rates at the first follow-up visit (5 to 11 days after initiation of treatment) were 78% and
86% for fosfomycin and nitrofurantoin, respectively (P = 0.02). At visit 3 (1 week
posttreatment), they were 87% and 81% for fosfomycin and nitrofurantoin, respectively (P
= 0.17). Both treatment groups had an 80% overall clinical success rate (cure and
improvement). Twenty patients (5.3%) who received fosfomycin and 21 patients (5.6%)
who received nitrofurantoin reported an adverse effect related to study medication. The
most common side effects related to fosfomycin treatment were diarrhea (2.4%), vaginitis
(1.8%), and nausea (0.8%). Both bacteriologic and clinical cure rates observed with a single
3-g dose of fosfomycin were comparable to those achieved with a 7-day course of
nitrofurantoin in female patients with acute uncomplicated UTI.
 Site: http://www.ncbi.nlm.nih.gov/pubmed/10890258
References:

 Clinical Pharmacy and Therapeutics 5th Edition (Roger Walker; Kate


Whittlesea)
 Expanded Medicine Blue Book 5th Edition
 Interpreting Laboratory Data: A Point-of-Care Guide
 Pathology and Therapeutics for Pharmacist: A basis for clinical
pharmacy practice 3rd Edition (Rusell J. Greene; Norman D. Harris)
 Pharmacotherapy: A Pathophysiologic Approach 6th Edition
References:
 Fosfomycin
https://www.nlm.nih.gov/medlineplus/druginfo/meds/a697008.html
 Fosfomycin Interactions
http://reference.medscape.com/drug/monurol-fosfomycin-342560#3
 Nitrofurantoin
https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682291.html
 Nitrofurantoin Interactions
http://www.rxlist.com/macrobid-drug/side-effects-interactions.htm
References:

 Comparison of single-dose fosfomycin and a 7-day course of nitrofurantoin


in female patients with uncomplicated urinary tract infection.
http://www.ncbi.nlm.nih.gov/pubmed/10890258
 Management of uncomplicated urinary tract infections
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071654/
 Urinary Tract Infections – Treatment Recommendations
http://www.stueckpharmacy.com/downloads/uti.pdf