URINARY CATHETERS

Instrumentation or catheterization of the urinary tract is an important predisposing

factor for health care–associated UTI. Catheter-associated UTI, the most common

type of hospital-acquired infection, occurs in up to 30% of catheterized patients.

23

Catheterization and other forms of urologic instrumentation are present as risk factors

for infection in 65% to 95% of all hospital-acquired UTI.

22 These UTIs also are a

major cause of nosocomial gram-negative bacteremia.

21

,

23 Other urologic procedures,

such as cystoscopy, transurethral surgery, prostate biopsy, and upper urinary tract

endoscopy, are much less likely to result in infection unless there is preexisting

bacteriuria or other contaminated sites (e.g., prostate, renal stones). Any obstruction

to the free flow of urine (e.g., urethral stenosis, stones, tumor) or mechanical

difficulty in evacuating the bladder (e.g., prostatic hypertrophy, urethral stricture)

also predisposes patients to UTI. Furthermore, infections associated with urethral or

renal pelvic obstruction can lead to rapid destruction of the kidney and sepsis.

1

Catheter infection can occur by bacterial entry from several routes. The urethral

meatus and the distal third of the urethra normally are colonized by bacteria;

therefore, initial catheter insertion can introduce bacteria into the bladder. Bacteria

contaminating catheter junctions and the urine collection bag can migrate through the

catheter lumen to the bladder, initiating infection.

23 The extraluminal space in the

urethra also has been considered a potential route of contamination. The risk of

infection is directly related to catheter insertion technique, care of the catheter,

duration of catheterization, and the susceptibility of the patient. A diagnostic or

single, short-term catheterization is associated with a much lower risk of infection

than indwelling, long-term catheterization.

23 Despite careful technique, the risk of

contaminating a sterile bladder with urethral bacteria is always present. The

incidence of infection after a single catheterization is 1% in healthy young women

and 20% in debilitated patients. Each reinsertion of the catheter introduces a risk of

infection.

23

Infections have been reduced dramatically by the closed sterile drainage system,

the most common type of catheter currently in use. With this system, the drainage tube

leads from the catheter directly to a closed plastic collection bag. The overall

incidence of infection from the closed system with careful insertion and maintenance

is about 20%; the risk increases to 50% after 14 days of catheterization.

23 Condom

catheters are associated with a lower incidence of bacteriuria than indwelling

urethral catheters. These catheters avoid problems associated with insertion of a tube

directly into the urinary tract; nevertheless, urine within the catheters may have high

concentrations of organisms so that colonization of the urethra and subsequent cystitis

may develop.

23

Application of antibacterial substances to the collection bag or the catheter–

urethral interface does not decrease the incidence of bacteriuria.

23

,

35

,

36 The use of

antimicrobial-coated catheters (e.g., silver, rifampin plus minocycline) has been

shown in some studies to decrease rates of bacteriuria and UTI.

23

,

35

,

36 The overall

effects of these catheters on infection rates, patient outcomes, and antibiotic

resistance are not known, however. The routine use of antibiotic-coated catheters is

not currently recommended.

23

,

35

Clinical Presentation

Symptoms commonly associated with lower UTI (e.g., cystitis) include burning on

urination (dysuria), frequent urination, suprapubic pain, blood in the urine

(hematuria), and back pain. Patients with upper tract infection (e.g., acute

pyelonephritis) may also present with loin pain, costovertebral angle (CVA)

tenderness, fever, chills, nausea, and vomiting.

1–5,37

Clinical signs and symptoms correlate poorly with either the presence or the extent

of the infection. Symptoms common to lower UTI often are the only positive findings

in upper UTI (i.e., subclinical pyelonephritis).

1

,

4 The probability of true infection in

women who present with one or more symptoms of UTI is only about 50%.

38 The

presence of dysuria, back pain, pyuria, hematuria, bacteriuria, and a history of

previous UTI may enhance the probability of true infection; the absence of dysuria or

back pain, and history of vaginal discharge or irritation significantly decrease the

likelihood of infection.

38

,

39 The combination of dysuria plus urgency or frequency in

the absence of vaginal discharge or irritation increases the probability of true

infection to greater than 90%.

38

,

39 Fever, chills, flank pain, nausea and vomiting, or

CVA tenderness are highly suggestive of acute pyelonephritis rather than cystitis.

4

,

5

,

37

Many elderly patients with UTI are asymptomatic without pyuria. Additionally,

because many patients have frequency and dysuria, it is difficult to distinguish

between noninfectious and infectious causes based on symptoms.

1 Nonspecific

symptoms, such as failure to thrive and fever, may be the only manifestations of UTI

in neonates and children younger than 2 years of age.

1

Diagnosis

Diagnosis of UTI based on clinical findings alone is accurate in only approximately

70% of patients.

40 Urinalysis (UA) is a series of laboratory tests commonly

performed in patients suspected of having a UTI; in combination with appropriate

clinical findings, the UA effectively improves the overall diagnostic accuracy for

UTI.

41 A technician first performs a macroscopic analysis by describing the color of

the urine; measuring its specific gravity; and estimating the pH and glucose, protein,

ketone, blood, and bilirubin contents using a rapid “dipstick” method. Then the urine

sediment, obtained by centrifugation, is examined under a microscope for the

presence and quantity of leukocytes, erythrocytes, epithelial cells, crystals, casts, and

bacteria.

Rapid diagnostic dipstick tests are widely available and easily performed. The

nitrite test detects nitrite formation from the reduction of nitrates by bacteria.

Although a positive nitrite reading is useful, false-negative results do occur.

40

Dipstick testing can also be used to perform the leukocyte esterase test, which detects

the esterase activity of activated leukocytes in the urine. A positive test correlates

well with significant pyuria

42

; however, both false-negative and false-positive

findings can occur with the leukocyte esterase panel as well.

40 Nitrite and leukocyte

esterase tests are useful in ruling out the presence of infection if results of both tests

are negative, whereas positive results of both tests in combination are highly

suggestive of the presence of infection.

40

Microscopic examination of urine sediment in patients with documented UTI

reveals many bacteria (usually >20 per high-power field [HPF]). Gram staining of

uncentrifuged (“unspun”) urine shows at least one organism per immersion oil field

and usually correlates with a positive urine culture. Pyuria

p. 1485

p. 1486

(i.e., ≥8 white blood cells [WBC] per milliliter [mL] of unspun urine or 2–5

WBC/HPF of centrifuged urine) is frequently seen in patients with UTI. WBC casts

in the urine strongly suggest acute pyelonephritis.

1

,

41

The gold-standard criterion for the diagnosis of UTI is the urine culture with a

positive UA.

1–3,37 Proper interpretation of these cultures depends, however, on

appropriate urine collection techniques. Urinating into a sterile collection cup using

the midstream clean-catch technique is the most practical method of urine collection.

This method of urine specimen collection is especially useful for male patients, but it

is less useful in female patients because contamination is extremely difficult to

avoid.

1 The external urethral area must first be thoroughly cleaned and rinsed, then

the urine specimen collected after initiation of the urine stream (hence “midstream”).

Urinary catheterization for a urine culture sample yields fairly reliable results if

performed carefully. However, infections can result from the procedure itself

because organisms might be introduced into the bladder at the time of catheterization.

Suprapubic bladder aspiration generally is not painful and is quite reliable. It is not

practical for routine office or clinic practice, but it may be useful when voided urine

samples repeatedly yield questionable results or when patients have voiding

problems. Because contamination is negligible, any number of bacteria found by this

method reflects infection.

1–3

Urine must be plated on culture media within 20 minutes of collection to avoid

erroneously high colony counts from bacterial growth in urine at room temperature.

Otherwise, urine should be promptly refrigerated until it can be cultured. Colony

counts are also affected by the concentration of bladder urine; bacterial counts are

higher in first-voided morning urines compared with those obtained from the same

patient later in the day.

1

,

37

Greater than 10

5 colonies of bacteria/mL cultured from a midstream urine

specimen confirms a UTI. A single, carefully collected urine specimen provides 80%

reliability, and two consecutive cultures of the same organism are virtually

diagnostic.

1–3

It is important to understand that the classic definition of UTI as greater

than or equal to 10

5 bacteria/mL is fairly inaccurate in diagnosing patients with UTI.

Approximately 30% to 50% of actual cases of acute cystitis have less than 10

5

bacteria/mL.

5

,

13

In a symptomatic patient, using a definition of greater than or equal to

10

2 bacteria/mL is more accurate and avoids failure to diagnose infection in many

patients.

5

Diagnosis of UTI in men also requires different interpretation of laboratory data.

Contamination of urinary specimens is much less likely to occur in men compared

with women, and numbers of bacterial colonies in specimens are therefore much

lower. Greater than 10

3 bacteria/mL is thus highly suggestive of UTI in men.

11

,

12

In

addition, although a positive nitrite test in a symptomatic man is highly indicative of

the presence of an acute UTI, a negative nitrite test does not necessarily exclude

infection and should be confirmed with a urine culture.

43

Diagnosis of UTI in children is particularly problematic because of the difficulties

and high contamination rates associated with commonly used methods of urine

specimen collection. Suprapubic aspiration is the most accurate method in children,

followed by urinary bladder catheterization.

3

,

37 Although clean-catch and bag

methods (i.e., collecting urine into a bag placed around the urogenital area) are most

susceptible to contamination and inaccurate results, they are also the most preferred

methods for parents and health care personnel because they are simple and

noninvasive. The choice of diagnostic tests for children will therefore vary and be

based on the experience, skill, and preferences of those involved with the child.

37

Simplified culture methods such as the filter-paper method (e.g., Testuria-R), dipslide method (e.g., Uricult), and pad-culture method (Microstix) are as reliable as

traditional laboratory methods for bacterial identification and quantification. The

filter-paper method is relatively inexpensive but does not differentiate between

gram-positive and gram-negative organisms. The dip-slide and pad-culture methods

are accurate, differentiate between gram-positive and gram-negative organisms, and

are similar in cost. The dip-slide method has the added advantages of ease of storage

and a nitrite indicator pad.

Overview of Drug Therapy

The cornerstone of effective treatment of UTI is the appropriate selection and use of

antibiotics. Antibiotic treatment of UTI has been well studied and, compared to many

other infectious diseases, the choice of specific antibiotic and duration of therapy for

acute, uncomplicated infections are reasonably clear. Recently published consensus

guidelines from the Infectious Diseases Society of America (IDSA) and the European

Society for Microbiology and Infectious Diseases (ESMID) recommend a 5-day

course of nitrofurantoin, trimethoprim–sulfamethoxazole (TMP–SMX) for 3 days, or

a single dose of fosfomycin trometamol as first-line antibiotics for treatment of acute

uncomplicated cystitis in women.

20 Whereas nitrofurantoin and TMP–SMX are

familiar agents, fosfomycin is a previously little used antibiotic which has been

available for many years. However, it has recently made a resurgence in clinical use

because of low rates of resistance among common uropathogens. Fosfomycin also

has usefulness against multidrug-resistant pathogens which are becoming more

common in certain practice settings; these include methicillin-resistant S. aureus,

vancomycin-resistant enterococci, and extended spectrum β-lactamase (ESBL)-

producing gram-negative bacteria.

20

,

44 Fluoroquinolones and β-lactam antibiotics,

such as amoxicillin–clavulanate or various cephalosporins, are recommended by the

IDSA/ESMID guidelines as alternative agents for treating acute uncomplicated

cystitis.

20 These same guidelines recommend fluoroquinolones, cephalosporins,

aminoglycosides, TMP–SMX, extended-spectrum penicillins (i.e., piperacillin–

tazobactam), or a carbapenem for the treatment of acute pyelonephritis in women.

20

The choice of a specific agent for pyelonephritis depends primarily on whether or not

the patient is hospitalized or treated as an outpatient, local susceptibility patterns,

and whether therapy is empiric or based on known susceptibilities. The duration of

therapy for acute pyelonephritis ranges from 5 to 14 days and is dependent on which

specific antibiotic is being used.

20 Parameters for monitoring response to treatment of

either uncomplicated cystitis or pyelonephritis are primarily resolution of clinical

signs and symptoms, and repeat urinary cultures are not usually required. Patients

with complicated UTI or recurrent infections may require additional monitoring and

long-term follow-up, and antibiotic selection must be guided by culture and

susceptibility (C&S) testing. Patient monitoring related to the safety and tolerability

of antibiotic therapy is required regardless of type of infection, as is effective patient

counseling.

LOWER URINARY TRACT INFECTION

Initial Patient Evaluation and Determining Goals of

Therapy

CASE 71-1

QUESTION 1: V.Q., a 20-year-old woman with no previous history of UTI, complains of burning on urination,

frequent urination of a

p. 1486

p. 1487

small amount, and bladder pain. She has no fever or CVA tenderness. A clean-catch midstream urine sample

shows gram-negative rods on Gram stain. A urine sample for culture and susceptibility testing is ordered, and

the results of a UA are as follows:

Appearance, straw-colored (normal, straw)

Specific gravity, 1.015 (normal, 1.002–1.028)

pH, 8.0 (normal, 5.5–7.0)

Protein, glucose, ketones, bilirubin, and blood, all negative (normal, all negative)

WBC, 10 to 15 cells/LPF (normal, 0–2 cells/LPF)

Red blood cells (RBC), 0 to 1 cells/LPF (normal, 0–2 cells/LPF)

Bacteria, many (normal, 0 to rare)

Epithelial cells, 3 to 5 cells/LPF (normal, 0 to few cells/LPF)

Based on these findings, V.Q. is presumed to have a lower UTI. What should be the goals of therapy of

V.Q.’s infection at this time? What factors should be considered before selecting an antibiotic for V.Q.?

The goals of therapy for treatment of acute cystitis are to effectively eradicate the

infection and prevent associated complications, while minimizing adverse effects and

costs associated with drug therapy. To accomplish these goals, selection of a specific

antimicrobial agent should be made after considering several factors: (a) most likely

pathogens, (b) resistance rates within the specific geographic area, (c) desired

duration of therapy, (d) clinical efficacy and toxicity profiles of various agents, (e)

cost and availability of specific agents, and (f) patient characteristics such as

allergies, compliance history, and underlying comorbidities.

20 Because resistance

rates among various pathogens vary considerably among geographic areas, clinicians

must be familiar with resistance rates prevalent within their specific practice

area.

20

,

45

,

46

Drug treatment of a lower UTI often is started before C&S results are known

because the most probable infecting organisms and their susceptibility to antibiotics

can be predicted reasonably well (Table 71-1). Approximately 75% to 95% of

community-acquired infections are caused by Enterobacteriaceae (especially E.

coli). Although these organisms may be sensitive to ampicillin, amoxicillin, and the

sulfonamides (such as TMP–SMX), resistance to these agents is common.

45–49

Ampicillin resistance occurs in 25% to 70% of community-acquired isolates

45–49

;

resistance nationwide is currently about 30% to 40%.

1

,

5

,

20

,

45–49 TMP–SMX has been

a traditional agent of choice for many years; however, TMP–SMX resistance has

significantly increased in recent years and may be as high as 20% to 40% among

community-acquired E. coli isolates in some geographic areas.

20

,

45–49 Although

traditionally associated with hospital-acquired infections, resistance among E. coli

and Klebsiella caused by production of ESBL enzymes which confer resistance to

penicillins and cephalosporins has also been steadily increasing among communityacquired pathogens.

50

,

51 Another relatively common organism is S. saprophyticus.

Most strains are susceptible to sulfonamides, TMP–SMX, penicillins, and

cephalosporins. Commonly used medications and doses are shown in Table 71-2.

ROLE OF URINE CULTURES

CASE 71-1, QUESTION 2: Is it necessary to order a pretreatment urine C&S test for V.Q.?

Many investigators question the value of pretreatment urine cultures for acute

uncomplicated UTI.

1

,

2

,

5

,

20 Women with lower UTI usually have pyuria on UA and

respond rapidly to appropriate antimicrobial treatment. Pyuria may be a better

predictor of treatable infection than the colony count obtained on urine culture.

Furthermore, the urine culture accounts for a large portion of the cost of treating a

patient with a UTI.

52 Consequently, in patients such as V.Q. with uncomplicated,

acute, lower UTI, it is more cost-effective to order a UA and, if pyuria is present on

UA, to forego a urine culture. Instead, the patient should be empirically treated with a

conventional course of antibiotic therapy. If V.Q. remains symptomatic 48 hours

later, a C&S test can then be ordered. Considerations are quite different in patients

with complicated infections. In complicated UTI, predisposing factors that lead to

infection and frequent history of previous antibiotic use make both causative

pathogens and associated antibiotic susceptibilities much less predictable. Use of

C&S testing is therefore commonly recommended for treatment of complicated UTI

in order to choose appropriate antibiotics.

1–3,5,20

Table 71-1

Overview of Treatment of Urinary Tract Infections

Organisms Commonly Found Antibacterial of Choice

Uncomplicated UTI

Escherichia coli TMP–SMX

a

Proteus mirabilis TMP–SMX

a

Klebsiella pneumoniae TMP–SMX

a

Enterococcus faecalis Ampicillin, amoxicillin

Staphylococcus saprophyticus First-generation cephalosporin or TMP–SMX

Complicated UTI

b,c

E. coli First-, second-, or third-generation cephalosporin;

TMP–SMX

c

P. mirabilis First-, second-, or third-generation cephalosporin

K. pneumoniae First-generation cephalosporin; fluoroquinolone

Enterococcus faecalis Ampicillin or vancomycin ± aminoglycoside

Pseudomonas aeruginosa Antipseudomonal penicillin ± aminoglycoside;

ceftazidime; cefepime; fluoroquinolone; carbapenem

Enterobacter Fluoroquinolone; TMP-SMX; carbapenem

Indole-positive Proteus Third-generation cephalosporin; fluoroquinolone

Serratia Third-generation cephalosporin; fluoroquinolone

Acinetobacter Carbapenem; TMP-SMX

Staphylococcus aureus Penicillinase-resistant penicillin; vancomycin

aCaution in communities with increased resistance (>10%–20%).

bDrug selection based on culture and susceptibility testing when possible.

cOral therapy when appropriate. Nitrofurantoin, fosfomycin, fluoroquinolone, or cephalosporins should be used in

areas with increased TMP–SMX resistance.

TMP–SMX, trimethoprim–sulfamethoxazole; UTI, urinary tract infection.

INITIAL ANTIBIOTIC SELECTION

CASE 71-1, QUESTION 3: What antibiotics may be appropriate for treatment of V.Q.’s infection?

p. 1487

p. 1488

Table 71-2

Commonly Used Oral Antimicrobial Agents for Acute Urinary Tract

Infections

1–3,5,29,47,48,91

Drug

Usual Dose

Pregnancy

a Breast Milk

a Comments

b Adult Pediatric

Amoxicillin 250 mg every 8

hours or 3 g

single dose

20–40 mg/kg/day

in 3 doses

Crosses placenta

(cord) = 30%

(maternal)

c

Small amount

present

High resistance

rates, not for

empiric use.

Amoxicillin +

potassium

clavulanate

500 + 125 mg

every 12 hours

20 mg/kg/day

(amoxicillin

content) in 3

doses

Unknown Unknown

Ampicillin 250–500 mg

every 6 hours

50–100

mg/kg/day in 4

doses

Crosses placenta Variable

amount; milk =

1–30% of

serum

c

High resistance

rates, not for

empiric use.

Should be taken

on an empty

stomach. Cephalexin 250–500 mg

every 6 hours

15–30 mg/kg/day

in 4 doses

Crosses placenta Enters breast

milk

Cephalosporins

are alternate

choices for

patients allergic

to penicillins,

although crosshypersensitivity

can occur. May

be associated

with higher

failure rates

compared to

other drug

classes.

Cefaclor 250–500 mg

every 8 hours

20–40 mg/kg/day

in 2–3 doses

Crosses placenta Small amount

present

Cefpodoxime

proxetil

100 mg every 12

hours

10 mg/kg/day in

2 doses

Crosses placenta Variable

amounts; milk =

0–16% of

serum

Cefdinir 300 mg every 12

hours or 600 mg

every 24 hours

14 mg/kg/day in

1 or 2 doses

Crosses placenta Not detectable

after single 600

mg dose

Norfloxacin

d 400 mg every 12

hours

Avoid Arthropathy in

immature animals

Unknown Avoid antacids,

divalent and

trivalent cations,

and sucralfate.

Monitor INR in

patients on

warfarin. May

cause

dizziness.

e

Ciprofloxacin

d 250–500 mg

every 12 hours

Avoid Arthropathy in

immature animals

Unknown Alternate

choice for

patients allergic

to β-lactams.

e

Useful for

pseudomonal

infection.

Levofloxacin 250 mg every 24

hours

Avoid Arthropathy in

immature animals

Milk = 100% of

serum

c

Nitrofurantoin 100 mg every 12

hours (e.g.,

Macrobid)

50–100 mg every

6 hours (e.g.,

Macrodantin)

5–7 mg/kg/day in

2–4 doses

Hemolytic anemia

in newborn

Variable

amounts; not

detectable up to

30%; may

cause hemolysis

in G6PDdeficient baby

Alternate

choice. To be

taken with food

or milk. May

cause brown or

rust-yellow

discoloration of

urine.

Sulfamethoxazole

(SMX)

1 g every 12

hours

60 mg/kg/day in

2 doses

Crosses placenta;

displacement of

Enters breast

milk;

Alters bowel

flora to favor

bilirubin may lead

to

hyperbilirubinemia

and kernicterus,

avoid after 32

weeks of

gestation;

teratogenic in

some animal

studies

displacement of

bilirubin may

lead to neonatal

jaundice; may

cause hemolysis

in G6PDdeficient baby

resistant

organisms. To

be taken on an

empty stomach

with a full glass

of water.

Photosensitivity

may occur.

p. 1488

p. 1489

Trimethoprim

(TMP)

100 mg every 12

hours

Crosses placenta

(cord) = 60%;

(maternal) folate

antagonism,

avoid during first

trimester;

teratogenic in

rats

(milk) >1

(serum)

c

Alternate

choice.

TMP–SMX 160 + 800 mg

every 12 hours

10 mg/kg/day

(TMP component

in 2 doses)

Crosses placenta

(cord) = 60%;

(maternal) folate

antagonism,

avoid during first

trimester;

teratogenic in

rats

(milk) >1

(serum)

c

To be taken on

an empty

stomach with a

full glass of

water.

Photosensitivity

may occur.

Monitor HIVinfected patients

closely for

development of

adverse

hematologic

reactions.

First-line agent

for prostatitis.

Fosfomycin 3 g single dose No data Crosses placenta Unknown Recommended

option for

uncomplicated

cystitis.

aAlso see Chapter 49, Obstetric Drug Therapy.

b

Includes unique patient consultation information in italics.

cDenotes drug concentration.

dMay increase theophylline concentrations when given concurrently. Carefully monitor theophylline serum

concentrations during quinolone use.

eSame comments apply to all fluoroquinolones.

G6PD, glucose-6-phosphate dehydrogenase; HIV, human immunodeficiency virus; TMP–SMX, trimethoprim–

sulfamethoxazole.

Updated IDSA/ESMID guidelines for the treatment of acute uncomplicated cystitis

and pyelonephritis were published in 2011, and serve as the basis for selection of

antibiotics in V.Q. (Table 71-3).

20 The recommended first-line agents for treatment of

this patient’s uncomplicated cystitis include TMP–SMX, nitrofurantoin, and

fosfomycin trometamol; a fourth recommended antibiotic, pivmecillinam, is not

commercially available in the United States.

TMP–SMX is effective for therapy of uncomplicated cystitis.

1–3,20,53 Gram-positive

and gram-negative organisms, with the notable exceptions of Enterococcus, P.

aeruginosa, and anaerobes, are generally susceptible to TMP–SMX.

20

,

54 Although

TMP–SMX may appear active against enterococci in vitro, clinical efficacy against

this pathogen does not always correlate well and is variable. Individually,

trimethoprim and sulfamethoxazole are bacteriostatic, but in combination they are

bactericidal against most urinary pathogens.

54 Furthermore, this combination is

almost uniformly successful in the treatment of uncomplicated UTI, even against

organisms that originally were resistant to either agent alone. Although rates of

trimethoprim resistance have increased over the past several years,

20

,

45–49,55

resistance rates remain relatively low in some geographic areas and trimethoprim

alone may be effective in managing UTI in many patients.

The ratio of trimethoprim to sulfamethoxazole in the available tablet products is

1:5 (e.g., 80 mg trimethoprim and 400 mg sulfamethoxazole). This combination has

been chosen to achieve peak serum concentrations of the two drugs that approximate

a 1:20 ratio. This ratio is optimal for synergistic activity against most

microorganisms, although the drugs remain synergistic and bactericidal in ratios

ranging from 1:5 to 1:40 in vitro.

54