Urinary Tract Infections Dr. Lamya Alnaim, PharmD

Urinary Tract Infections

Dr. Lamya Alnaim, PharmD

Introduction• UTIs represent a wide variety

of syndromes including urethritis, cystitis, prostatitis, and pyelonephritis.

• One of the most commonly occurring infections.

Introduction• Young women are particularly

susceptible, 40% of all women will suffer at least one UTI at some point.

• Infection in men occurs less frequently until the age of 50, when incidence in men and women is similar.

Definition• It is the presence of

microorganisms in the urinary tract that cannot be accounted for by contamination.

• The organisms have the potential to invade the tissues of the UT and adjacent structures.

Definition• A UTI can manifest as several

syndromes associated with an inflammatory response to microbial invasion that range from asymptomatic bacteriuria to pyelonephritis.

ClassificationAccording to anatomic site of

involvement:

• Lower tract infection: cystitis, urethritis, prostatitis

• Upper tract infection: pyelonephritis, involving the kidneys

ClassificationAccording to Degree

1-Uncomplicated

• Occur in individuals who lack structural or functional abnormalities in the UT that interfere with the normal flow of urine.

• Mostly in healthy females of childbearing age

ClassificationAccording to Degree2-Complicatedpredisposing lesion of the UT

such as congenital abnormality or distortion of the UT, a stone a catheter, prostatic hypertrophy, obstruction, or neurological deficit

• All can interfere with the normal flow of urine and urinary tract defenses.

Recurrent UTIs• Multiple symptomatic infections

with asymptomatic periods• Reinfection: caused by a

different organism than originally isolated and account for the majority of recurrent UTIs.

• Relapse: repeated infections with the same initial organism and usually indicate a persistent infectious source.

Other DefinitionsAsymptomatic bacteriuria

• Common among the elderly

• Bacteiruria > 105 bacteria/ml of urine without symptoms

Symptomatic abacteriuria:

• Symptoms of frequency and dysuria in the absence of significant bacteriuria

Other DefinitionsSignificant bacteriuria

• More than 105 bacteria /ml (CFU) of urine in clean catch specimen

• 1/3 of symptomatic women have CFU counts below this level

• A bacterial count of 100 CFU/ml has a high positive predictive value of cystitis in symptomatic women

Other Definitions

Count less than 105 may represent true infection in certain situations

• Concurrent antibacterial drug administration

• Rapid urine flow

• Low urine PH

• Upper tract obstruction

EtiologyThe microorganism that cause

UTIs usually originate from the bowel flora of the host

Uncomplicated UTI: • E.coli accounts for 85%• S.saprophyticus 5-15%• K.pneumoniae, protues sp,

Pseudomonas, and Enterococcus 5-10%

• S.epidermidis if isolated should be considered a contamination

EtiologyComplicated UTIs• More varied and generally

more resistant• E.coli 50%• K.pneumoniae, protues sp,

Pseudomonas, Enterococcus, Enterobactor sp

EtiologyComplicated UTIs

• Enterococcus fecalis 2nd most frequently isolated organism in hospitalized patients

• S.aureus infection is more commonly a result of bacteremia producing metastatic abscesses in the kidney

• Candida sp is common cause of UTI in critically ill and chronically catheterized patients

Etiology• The majority of UTIs are

caused by a single organism

• In patients with stones , indwelling catheter, or chronic renal abscesses multiple organisms may be isolated

• Although this may be due to contamination and a repeat evaluation should be done.

Predisposing factorsAbnormalities in the UT that

interfere with natural defenses

1-Obstruction can inhibit urine flow, disrupting the natural flushing and voiding effect in removing bacteria from the bladder and resulting in incomplete emptying


interfere with natural defenses.

2-Condition that result in residual urine volumes e.g. prostatic hypertrophy, urethral stricture, calculi, tumors, and drug such as anticholinergic agents, neurological malfunctions associated with stroke, diabetes, and spinal cord injuries.


interfere with natural defenses.

3-Other risk factors include: urinary catheter, mechanical instrumentation, pregnancy, and the use of spermicidies and diaphragms

Clinical presentationsLower tract infection: • Include dysuria, urgency,

frequency, nocturia, suprapubic heaviness, and hematuria in women.

• No systemic symptomsUpper tract infection:• Flank pain, costovertebral

tenderness, abdominal pain, fever, nausea, vomiting and malaise.

Clinical presentationsElderly patients:• Frequently do experience

specific urinary symptoms• Altered mental status, change

sin eating habits, or GI symptoms

Patients with catheters• Will have no lower tract

symptoms• Just flank pain and fever

Laboratory findings

• Symptoms alone are unreliable for diagnosis

• Examination of the urine is the cornerstone of diagnosis

Collection of urine:

• Mid stream clean catch method is preferred method

Laboratory findings

Collection of urine:

• Catheterization for patient who are uncooperative or unable to void, but introduction of bacteria in the bladder occurs at 1-2%

• Suprapubic aspiration bypasses the contaminating organism in the urethra, safe and painless.

Diagnosis:• Based on isolation of

significant numbers of bacteria from a urine specimen

Microscopic examination

• is performed by preparing a gram stain that indicates the morphology of the organism and help direct the selection of an appropriate AB.

Diagnosis:Microscopic examination

• The presence of one organism per oil-immersion field in an un centrifuged sample correlates with 100,000 bacteria/ml

Diagnosis:Pyuria: WBC > 10 WBC/mm3

• it only signifies the presence of inflammation

Sterile pyuria is associated with urinary tuberculosis, chlamydial, and fungal infections

Diagnosis:

Hematuria, non-specific, may indicate other disorders such as calculi or tumor

Protenuria is found in the presence of infection

Diagnosis

Biochemical tests1-dipstick test for nitrite:

bacteria in the urine reduce nitrate→ nitrite

• false –negatives are common and caused by

• gm+ve or pseudomonas that do not reduce

• low urinary PH• frequent voiding and dilute

urine

Diagnosis

Biochemical tests

2- leukocyte esterase dipstick test

• rapid screening test for detecting the presence of pyuria

• LE is found in neutrophills

• Specific for detecting more than 10 WBC/mm3

DiagnosisQuantitative urine culture• Based on properly collected

urine• Urine is normally sterile• Determines the number of

bacteria present in a urine sample

• 1/3 of symptomatic women have bacteria < 105

DiagnosisQuantitative urine culture

• one organism per oil immersion field correlates with 100,000 CFU/ml by culture

Susceptibility

• determine bacterial susceptibility to different antimicrobials

Common Urinalysis Dipstick Findings in Urinary Tract Infection

Finding Significance Comment

Color Typically pale yellow to colorless

Change in urine color is not synonymous with urinary tract infection (UTI) or disease.

Clarity Typically clear Pyuria causes urinary turbidity

Odor Mild characteristic odor

Rancid or ammonia odor in urea-splitting organism

Specific gravity (SG)

Dilute urine = SG </= 1.008

Concentrated urine = SG > 1.020

Dilute or concentrated urine may influence the results of urine chemstrip testing.

Leukocyte esterase (LE)

Test for enzyme present in white blood cell (WBC)

Positive results indicated presence of neutrophils > 4 WBCs/hpf, an indicator of UTI, reported sensitivity of 75% to 90%. Results not valid in neutropenic patient. Decreased sensitivity with increased urinary glucose concentration, high urinary SG, and presence of antimicrobial in urine.

Nitrites Surrogate marker for bacteriuria. Presence indicates bacterial reduction of dietary nitrates to nitrites by select Gram-negative uropathogens including Escherichia coli, Proteus spp. Normally absent in sterile urine and infection caused by enterococci, staphylococci.

Best done on well-concentrated urine such as first AM void. For nitrites to be present, urine should be held in bladder for >/= 1 hour for nitrate-to-nitrite conversion to take place; dietary nitrate intake must be adequate. False negative possible with low colony-count infections.

Protein Dipstick testing most sensitive for albumin

Common in febrile response or represents presence of protein-containing substance such as white blood cells, bacteria, mucous. In UTI, usually trace to 30 mg/dL (1+), seldom >/= 100 mg/dL.

pH Average pH = 5-6 Acid pH = 4.5-5.5 Alkaline pH = 6.5-8

If alkaline urine is found in presence of UTI symptoms and positive leukocyte esterase, likely urea splitting such as Proteus, allowing urea to be split into CO2 and ammonia, causing a rise in the urine's normally acid pH.

Red blood cells (RBCs)

Low number of RBCs noted. Gross hematuria may occur in uncomplicated UTI but may be present in infection complicated by nephrolithiasis

Microscopic hematuria common with urinary tract infection but not in urethritis or vaginitis.

TreatmentDesired outcome• Prevent or treat systemic

consequences of infection• Eradicate the invading

organism• Prevent reoccurrence of

infection

TreatmentNon-specific therapies

1-fluid hydration:

• rapid dilution of bacteria and removal of infection through increased voiding

2-cranberry juice

• increase the antibacterial activity of urine

TreatmentNon-specific therapies

3-urinary analgesics

• phenazopyridine

• has little clinical role in infection because symptoms respond rapidly to anitmicrobial therapy

Acute uncomplicated cystitisMost common form of UTI?• Occur in women of childbearing

age• Can be explained by

– sexual activity– anatomy (short urethra)– delay in micturation– use of diaphragm and

spermicidal

Causes• Mostly cause E.coli• Other causes : S.saprophyticus.

K.pneumonia, Proteus mirabilis

Table 1. Clinical Findings in Women With Dysuria and Pyuria[3,9]

Clinical Findings in Addition to Dysuria and Pyuria

Possible Etiology

Comment

Suprapubic tenderness, pelvic discomfort especially pre- and immediately postvoid, urinary urgency and frequency, small volume voiding, hematuria (micro or macroscopic).

Cystitis, lower urinary tract infection

Gram-negative bacilli (Escherichia coli, Proteus, Klebsiella, others), select Gram-positive organism (Staphylococcus saprophyticus).

Flank pain, fever, CVA tenderness, nausea and vomiting, bacteremia; suprapubic tenderness, urinary urgency and frequency present or absent.

Pyelonephritis Pathogenic organisms revealed by urine culture include Gram-negative bacilli (E coli, Proteus, Klebsiella, others). Kidney stones and obstructive uropathy may be contributors.

Urethral, vaginal discharge in the absence of suprapubic pain or tenderness, urinary frequency, urgency, fever; numerous white blood cells found on microscopic wet mount examination of vaginal discharge

Urethritis Most common as sexually transmitted infection such as Chlamydia trachomatis, Niesseria gonorrhoeae, Trichomonas vaginalis

Irritative voiding symptoms, purulent or mucopurulent vaginal or cervical discharge, report of postcoital bleeding, edema and/or erythema of cervix or cervical os, brisk bleeding induced by endocervical swabbing, numerous white blood cells found on microscopic wet mount examination of vaginal discharge

Mucopurulent cervicitis

N gonorrhoeae, C trachomatis, others.

Irritative voiding symptoms, purulent or mucopurulent vaginal or cervical discharge, fever, abdominal pain, edema and/or erythema of cervix or cervical os, brisk bleeding induced by endocervical swabbing, cervical motion tenderness, possible evidence of tubal-ovarian mass, numerous white blood cells found on microscopic wet mount

Pelvic inflammatory disease

N gonorrhoeae, C trachomatis, E coli, micro-organisms that normally comprise vaginal flora (anaerobes, Helicobacter influenzae, enteric Gram-negative rods, Streptococcus agalactiae), Mycoplasma and Ureaplasma species, others.

Acute uncomplicated cystitisManagement:

• Urinanalysis including microscopic examination, cell count, and LE test

• C&S add little to the choice of therapy empiric therapy

• Regarding the use of laboratory tests to diagnose urinary tract infections, which of the following statements is correct?

• A. In a patient with suspected cystitis, urine dipstick results should be confirmed with a urinalysisB. The urine should always be cultured in outpatients with acute cystitisC. Urine dipstick results usually provide the laboratory information needed to manage young otherwise healthy patients with acute cystitisD. The use of urine dipsticks should be avoided; urinalysis is the test of choice.

Acute uncomplicated cystitisManagement: 1- Single dose therapy • 65-100% cure rate with SMX-

TMP, amoxicillinadvantages of single does:• less expensive • better compliance • low side effects• low potential for development

of resistance

Acute uncomplicated cystitis 1- Single Dose Therapy

• Not all agents are effective as single dose

• 2 DS TMP/SMX is most effective

• Flouroquniolones: 800 mg norfloxacin, 125 mg ciprofloxacin, 200 ofloxacin

• B-lactam are less effective due to increasing resistance and because they are eliminated rapidly and do not achieve high urine concentrations

Acute uncomplicated cystitis2-Three day course• single dose Tx was blamed for high

rate of recurrence within six weeks

• this may be due to failure to eradicate gm-ve bacteria from the rectum

• TMP/SMX or fluoroquinilones is superior to single dose

• Amoxicillian, nitrofurantion, and sulfonamides are not appropriate due to increasing resistance of E.coli


Short course therapy is not appropriate for

• Patient with previous infection with a resistant bacteria

• Male patients

• Complicated UTI


• If symptoms do not respond or they reoccur, a urine culture should be obtained and conventional therapy started

Fluoroqunilones should not be used unless

• patient cannot tolerate TMP/SMX

• They’re a high frequency of resistance due to recent antibiotic use

Acute uncomplicated cystitisManagement: 3-Seven-day course• in pregnant women• diabetic women• women who have had

symptoms for more than one week and are at higher risk for pyelonephritis

Oral treatment regimens for acute uncomplicated cystitis

Agent Normal dosage Side effects, cautions

Ciprofloxacin 250 mg bid for 3 d Drowsiness; increases theophylline levels; avoid in pregnancy; avoid divalent and trivalent cations;

Fosfomycin 3-g single dose Increased incidence of diarrhea and nausea and increased relapse rate

Gatifloxacin 200 mg/d for 3 d Avoid in pregnancy; avoid divalent and trivalent cations

Levofloxacin 250 mg/d for 3 d Avoid in pregnancy; avoid divalent and trivalent cations

Nitrofurantoin 100 mg bid for 7 d

Nitrofurantoin 100 mg qid for 7 d

Idiosyncratic pulmonary fibrosis; avoid in patients with estimated monohydrate/ creatinine clearance < 60 mL/min

Norfloxacin 400 mg bid for 3 d Avoid in pregnancy; avoid divalent and trivalent cations

Ofloxacin 200 mg bid for 3 d Avoid in pregnancy; avoid divalent and trivalent cations

Trimethoprim 100 mg bid for 3 d Nausea

Trimethoprim-sulfamethoxazole

1 double-strength tablet bid for 3 d

Nausea; rash;

Symptomatic abacteriuria

Acute urethral syndrome

• In females, present with dysuria and pyuria

• Urine culture reveals < 105 bacteria /ml

• Accounts for half the complaints of dysuria in women

• Most likely infected with a small number of bacteria

Symptomatic abacteriuria

Causes:

• E.coli, S. saprophyticus, or chalmydia

• Other causes:

• Most patients will require short course therapy as above

Symptomatic abacteriuriaChlamydial treatment

1g of azithromycin or doxycycline 100 mg bid for 7 days

• Concomitant treatment of sexual partner is required to cure this infection and prevent recurrence

Asymptomatic bacteriuria

• Patients with no urinary symptoms

• Have two consecutive urine cultures with > 105

• The majority are elderly and female


• Aggressive treatment does not affect infection, complications or mortality

• Also present in pregnant women

• Relapse and reinfection are common and chronicity occurs which is difficult to eradicate


Management

Groups who benefit from treatment:

• pregnant women

• patient with renal transplant

• Patient who will undergo urinary procedure


Management

• Depend on age and whether they are pregnant

• In children: conventional treatment because of greater risk for renal damage

• In non-pregnant female: controversial


Management

• In elderly: two groups

– Persistent bacteriuria:

– Intermittent bacteriuria

• Mostly seen as a benign disease and does not warrant treatment

• Two cultures should be obtained to confirm the presence of bacteria


Management

• Ambulatory treatment is effective in removing bacteria for 6 months

• Only 50% remained free of bacteria for 1 year

• Hospitalized patients: therapy in non-efficacious

Case 1• A 24-year-old woman comes to the clinic

to discuss recent laboratory results. She went to a local walk-in clinic asking to be screened for a urinary tract infection. She comes to the clinic to review them withyou. She is asymptomatic and has no past medical history. She is married and has a 3-year-old boy. Her physical exam is unremarkable. A urinalysis showed 1+ leukocyte esterase; a urine culture revealed >100000 CFU of Escherichia coli.

Case 1Which of the following management

strategies is the most appropriate for this patient?

• A. Explain that even though the urine culture was positive she does not need treatmentB. Start oral ciprofloxacin for three daysC. Repeat a urine dipstick, and if the presence of pyuria is confirmed start treatmentD. Start oral ampicillin for seven days

Case 1• The IDSA guidelines recommend

screening for and treatment of asymptomatic bacteriuria in only three circumstances: pregnancy, before invasive urologic procedures that are associated with mucosal bleeding, and in women who are found to have catheter-acquired bacteriuria that persists 48 hours after the catheter is removed

Complicated UTI

• Accurate urine culture and susceptibility is necessary to target the pathogen

• Treatment duration at least 10-14 days

Conditions associated with complicated urinary tract infections

Structural abnormalities

Infected renal cyst Kidney abscess Kidney stones Nephrostomy tube Obstruction Ureteral stent Vesicoureteral reflux

Specific patient populations

Patients receiving immunosuppressive therapy Renal transplant recipients Diabetic persons Pregnant women Men

Acute pyelonephritis• Perform uniranalysis, gram

stain, C&S

Severely ill patients

• Should be hospitalized and treated with IV Abs

• Use broad spectrum directed at bacteremia or sepsis

Acute pyelonephritisEmpiric therapy:• 3rd generation cephalosporin

with antipseudomanl activity as ceftazidime, cefoperazone

• Ampicillian + gentamicin• TMP/SMX OR Quionoles• B-lactamase inhibitor

combination: ampicillian/Sulbactam, ticarcillin/clavunate,

• Aztreonam or imipenem

Acute pyelonephritisIf the patient has been

hospitalized for > 6 months:• Consider P.aeruginosa and

enterococci, and multiple organisms

Empiric therapy:• Ticarcillin/clavunate,• Piperacillin/tazobactam• Aztreonam or imipenemIn combination with AG

Acute pyelonephritisManagement

Fluoroquinolones

• major advantages is their oral formulation.

• Use as empiric therapy in this setting may be limited because of resistance rates.

Acute pyelonephritisManagement

• ceftazidime, cefepime, piperacillin, piperacillin/tazobactam, and aztreonam.

• They have reliable activity against many nosocomially acquired gram-negative rods, including P aeruginosa.

Acute pyelonephritisManagementCarbapenems, imipenem-cilastatin

and meropenem.have extremely broad-spectrum

coverage and should be reserved for only the most severe forms of nosocomial infections, such as multiresistant pathogens, sepsis syndrome, overwhelming intra-abdominal infections, or septic shock

Acute pyelonephritis• Effective therapy should

stabilize patient within 12-24 hrs

• Bacterial load should reduce in 48 hrs

If the patient fails to respond in 3-4 days further investigation is necessary to

• Exclude bacterial resistance• Exclude obstruction• Or other disease process

Acute pyelonephritis• Oral therapy can be started

when the patient is febrile for 24 hrs

• Oral therapy should be continued for 2 wks

• Follow-up urine cultures should be obtained 2 wks after end of therapy

Acute pyelonephritisMild cases:

• can be treated orally as outpatients for at least 2 w ks

• Gram –ve bacilli: TMP/SMX or fluoroquiolones

• Gram +ve: cocci: consider enterococcus fecalis, DOC Ampicillin

Treatment of acute pyelonephritis

Agent Normal dosage

Ceftriaxone 1 g/d, IV

or

Cefotaxime ± Aminoglycoside 1 g q8h, IV

400 mg q12h, IV Ciprofloxacin

500 mg bid, PO

1.5 mg/kg q8h or 5 mg/kg q24h, IV Gentamicin ± Ampicillin 1 g q6h, IV

Levofloxacin 500 mg/d, PO or IV

If gram-positive organisms seen on Gram stain:

1.5 g q6h, IV Ampicillin/sulbactam ± Aminoglycoside

Trimethoprim-sulfamethoxazole*

10 mg/kg/d in 2 - 4 divided doses, IV or 1 or 2 double-strength tablets bid, PO

Case 222 year-old woman without any significant

past medical history presents to the emergency room with 2 days of worsening fever, urinary frequency, back pain, nausea and vomiting. She is not able to keep food or liquids down. On physical examination she is febrile and tachycardic. The abdominal exam is normal except for the presence of moderate costovertebral angle tenderness. A blood pregnancy test is negative. A urinalysis is obtained and reveals >50 PMN per high power field and 10-25 red blood cells. Blood cultures are sent to the lab.

Case 2Which of the following management

strategies is the most appropriate for this patient?

A.Order an ultrasound to confirm your clinical impression, and start intravenous antibiotics if needed

B. Admit the patient for administration of intravenous antibiotics, and obtain imaging studies only if the patient does not improve after a few days

C. Start intravenous antibiotics, and order abdominal CT scan to rule out complicated pyelonephritis

D. Discharge the patient home on an oral fluoroquinolone

Infection in males• Infection in males are

considered complicated

• Occur in presence of functional or structural abnormalities that disrupt the normal defense mechanism of urinary tract.

Clinical Findings in Men with Dysuria and Pyuria

Clinical Findings in Addition to Dysuria and Pyuria

Possible Etiology

Comment

Back pain, fever, CVA tenderness, nausea and vomiting, bacteremia

Pyelonephritis Consider urinary tract obstructive process such as BPH, stones. Pathogenic organisms revealed by urine culture include Gram-negative bacilli (Escherichia coli, Proteus, Klebsiella, others)

Back pain, fever, arthralgia, myalgia, rectal pain obstructive voiding symptoms, tender, boggy prostate

Acute prostatitis

Urine culture reveals pathogenic organisms (E coli, Proteus, Klebsiella, others)

Scrotal swelling and redness, fever, epididymal tenderness

Acute epididymitis

Pyuria rate = approximately 25%. May be caused by sexually transmitted organism (Chlamydia trachomatis, Neisseria gonorrhoeae) or uropathogen such as E coli in man with recent urinary tract instrumentation

Urethral discharge in the absence of suprapubic pain, urinary frequency, urgency, fever

Urethritis Most common as sexually-transmitted infection (C trachomatis, N gonorrhoeae)

Infection in malesThe most common causes are

• Instrumentation

• Catheterization

• Renal and urinary stones

• In the elderly the most common cause is bladder outlet obstruction due prostatic hypertrophy.

Infection in malesTreatment

• Urine culture is needed because causative organism is not easily predictable

• A urine culture with>100 CFU/ml is best sign of infection

• If Gm –ve is TMP/SMX or FQ

• Duration therapy should be 10-14 days

Infection in malesTreatment

Parental therapy may be required in

• Severely ill patients

• The presence of acute prostatitis (may need 6-12 weeks)

• Patient who cannot tolerate oral MEDs

Repeat a follow up culture 4-6 weeks after treatment

Case 3• A 53 year-old man with history of benign

prostatic hypertrophy comes to the emergency room complaining of burning with urination and increased urinary frequency. He is afebrile, denies back pain, nausea or vomiting. His past medical history is also significant for hypertension and diabetes. He takes hydrochlorothiazide, enalapril, aspirin, metformin and terazosin. On physical examination his prostate is enlarged, but is not tender. Urine dipstick shows 3+ leukocyte esterase.

Case 3• A 53 year-old man with history of benign

prostatic hypertrophy comes to the emergency room complaining of burning with urination and increased urinary frequency. He is afebrile, denies back pain, nausea or vomiting. His past medical history is also significant for hypertension and diabetes. He takes hydrochlorothiazide, enalapril, aspirin, metformin and terazosin. On physical examination his prostate is enlarged, but is not tender. Urine dipstick shows 3+ leukocyte esterase.

Case 3Which of the following interventions is the

most appropriate for this patient?• A. Start ciprofloxacin, and order urine culture

B. Start Levofloxacin, and order urine culture only of the patient fails to improve after five days of symptoms.C. Start nitrofurantoin empiricallyD. Admit the patient for intravenous piperacillin/tazobactam

Recurrent infectionReinfections:• 80% 0f recurrent infection• Infection by an organism

different from the initial infection

• Mostly occurs in females where reinfection rate is 20%

Factors contributing to infection: 1-sexual intercourse2-diaphram and spermicidal use3- postmenopausal women

Recurrent infectionDivided into two groups:1-Those with less than 2 or 3

episodes per year• Each episode should be

treated as a separate infection• Short course therapy is

appropriate• Can be self administered

Recurrent infectionDivided into two groups:2-Those with more than 3

episodes per year• Long-term prophylaxis may be

needed• Patient should be treated

conventionally before prophylaxis is started

Recurrent infectionRegimen:• TMP/SMX ½ SS tables OD• TMP 100 mg OD• Fluroqunilone• Nitrofurantion 50-100 mg OD• Continued for 6 months• Urine cultures followed

monthly• If symptomatic episodes

develop they should be treated with a full course

Recurrent infectionInfection related to sexual activity:

• Voiding after intercourse

• Single-dose prophylactic with TMP/SMX taken after intercourse

In postmenopausal women

• Recurrent episodes related to decreased estrogen and changes in bacterial flora

• TX: topical estrogen cream

Relapses

• Persistence of the infection with the same organism after therapy

• Usually indicate structural abnormality, renal involvement, or chronic bacterial prostatitis

RelapsesIn women:• If relapse after short course

treat with 2 week course• In-patient who relapse after 2

wk course continue for another 2-4 wks

• If relapse after 6 wks of therapy, urologic evaluation and any obstruction corrected

• May need therapy for 6 months

Relapses

In males

• Relapse usually indicate bacterial prostaitis

• TMP/SMX and fluroquniolones appear to be highly effective for relapses

Case 4• A 26-year-old woman comes to the clinic

complaining of recurrent cystitis. Over the previous year she has had 5 episodes of cystitis that were treated with antibiotics. The symptoms improved rapidly after each course of therapy. The episodes have happened once every two to three months for the last year. Her past medical history is otherwise unremarkable. She uses oral contraceptives for contraception. She has had two urine cultures done during the previous year that showed pansusceptible Escherichia coli. The patient asks for ways to prevent these infections from coming back.

Case 4Based on the history and test results, which of

the following interventions is indicated on this patient?

A.Ask the patient to report the onset of infection as soon as possible, and start treatment if a urine dipstick is positive

B. Offer antibiotic prophylaxisC. Change her contraception to spermicides and

diaphragmsD. Obtain abdominal ultrasound to look for a

secondary cause of recurrent UTIsE. Perform an immunologic evaluation to rule out an underlying immune deficiency

PregnancyPredisposing factors:• Dilation of the renal pelvis and

ureters• Decrease urethral peristalsis• Reduced bladder tone• All lead to urine stasis and

reduced defenses against reflex of bacteria to the kidney

• Hormonal changes predispose to infection

Pregnancy

• Asymptomatic bacteriuria Occur in 4-7%

• 20-40% will develop acute pyelonephritis

• Routine screening for bacteriuria should be performed at the initial prenatal visit and at 28 wks

Pregnancy

• Significant bacteriuria should be treated regardless of symptoms

• Organism is the same for uncomplicated UTI

• Therapy should be for 7 days

PregnancyRegimen• Sulfonamide (not in 3rd

trimester)• amxoicillin• augmentin• cephalexin• nitrofurantion• Not TCN, fluoroquinoloes• Follow up urine culture 1-2 wk

after completing therapy, then monthly until gestation

FDA Pregnancy Risk and Hale's Lactation Risk Categories for Commonly Prescribed Antimicrobials in Urinary Tract Infection

Cat B, L1, L2 Cat C, L3 Cat D, L3

Nitrofurantoin Amoxicillin with clavulanate Amoxicillin Cephalosporins

Fluoroquinolones TMP-SMX

Doxycycline

Lactation Risk Category[23]

L1 -- Safest, controlled study = Fails to demonstrate risk

L2 -- Safer, limited number of woman studied without risk

L3 -- Moderately safe, no controlled study or controlled study shows minimal, nonlife-threatening risk

L4 -- Hazardous, positive evidence of risk, may be used if maternal life-threatening situation

L5 -- Contraindicated, significant, and documented risk

FDA Pregnancy Risk Categories[23]

Category A Category B Category C Category D Category X

Well-controlled human study = no fetal risk in first trimester. No evidence of risk in second, third trimesters. Risk to fetus appears remote.

Animal studies do not demonstrate fetal risk but no controlled study in humans. OR Animal studies show adverse effect but not demonstrated in human study.

No controlled study in humans available. Animals reveal adverse fetal effects.

Positive evidence of human fetal risk. Use in pregnant woman occasionally acceptable despite risk.

Animal or human studies demonstrate fetal abnormality. Evidence of fetal risk based on human study. No indication in pregnancy.

Catheterized patients• Most common cause of hospital

aquired UTI

• diagnosis is difficult, – patients often have some degree of

pyuria

– Virtually all patients with catheters for 1 to 2 wks exhibit bacteriuria, making differentiation of infection from colonization difficult.

– often lack symptoms

• Occur in 5% of patients

Catheterized patientsEtiology

• often polymicrobial.

• Causative agents include P aeruginosa and nosocomial gm –ve rods, with more resistant susceptibility profiles; enterococci; and Candida species.

• Diagnosed with > 100 CFU/ml of urine from catheter

• Urinalysis and urine cultures should always be obtained.

Catheterized patientsManagement1-Asymptomatic, • Remove the catheterDo not treat unless• immunosuppresed patient• Patient at risk of endocarditis• Patient who will undergo

urinary tract instrumentation

Catheterized patients

Management

2-Symptomatic

• Remove the catheter and treat as complicated UTI

Vancomycin-Resistant Enterococci • VRE are often isolated from urine

cultures of patients who have been hospitalized for a prolonged period.

• Most commonly, a urinary catheter is present.

• If the organism is E.faecalis, then penicillin/ampicillin susceptibility is frequently maintained, and ampicillin is the treatment of choice.

VRE • However, most VRE are E.

faecium that are also resistant to ampicillin (VARE) and to multiple other antimicrobials.

• Many VARE are susceptible to nitrofurantoin, and it can be used as long as the patient has a CrCL >60 mL/min

VRE • Chloramphenicol or novobiocin,

with or without other drugs, have been used.

• Two newer antibiotics, quinupristin/dalfopristin and linezolid, have been marketed for gram-positive infections and have activity against VARE.

VRE- Quinupristin/dalfopristin• The 1st injectable streptogramin

antibiotic.

• It inhibit protein synthesis and has bactericidal effect with the exception of VARE.

• spectrum is mostly gm+ve and includes Staphylococcus species (both methicillin-susceptible and methicillin-resistant Staphylococcus aureus), E faecium, and VARE.

• It is not active against other enterococci including E faecalis.

VRE- Quinupristin/dalfopristin• toxicities

– chemical phlebitis (especially when infused via a peripheral line)

– myalgias and arthralgias (particularly in patients with hepatic insufficiency).

– It is a potent, noncompetitive inhibitor of cytochrome P-450 3A4. significantly increase plasma levels of cyclosporine and long-acting benzodiazepines

VRE- Linezolid • The first oxazolidinone antibiotic.

• available as parenteral and oral formulations.

• It inhibits protein synthesis.

• It displays a bacteriostatic effect, except with Streptococcus pneumoniae.

• Its spectrum is broad against gm+ve and includes M-susceptible and MR S aureus, coagulase-negative staphylococci, and many enterococci (including E faecalis, E faecium,).

VRE- Linezolid

Toxicity

– Thrombocytopenia that most commonly occurs after prolonged therapy (more than 17 days).

• Given that linezolid has broader spectrum against the enterococci and is available as an oral formulation, it may be preferred over quinupristin/dalfopristin in the treatment of VARE UTIs.

Fungal Infection

• Many patients with a long-term catheter will have colonization of their bladder with Candida species or, rarely, other fungi.

Fungal Infection

• Usually funguria in the absence of pyuria should not be treated, and the catheter should be removed.

• Funguria should be treated in– renal transplant recipients

– those undergoing an elective urologic procedure.

Fungal InfectionDiagnosis• pyuria (> 20 WBC/hpf) • > 105 fungal organisms / ml of

urine. • Patients may or may not have

systemic findings, such as fever and leukocytosis.

Fungal InfectionTreatment• The catheter should be removed,

since this will result in cure in some patients.

• If C.albicans infection, then oral fluconazole, 100 mg/d, should be prescribed for a 2- to 5-days

• IV fluconazole should be reserved for patients without the ability to take oral medications or in those with ileus or bowel obstruction.

Fungal InfectionTreatment

• Non-albicans Candida species, including C.parapsilosis, C.glabrata, and C.krusei, are becoming more common.

• The Tx should be either low-dose IV amphotericin B (0.1 mg/kg/d) or continuous amphotericin B bladder irrigation.

• Both regimens are effective when given for 2 to 5 days.

Documents

Urinary Tract Infections Dr. Lamya Alnaim, PharmD