Electronic ISSN 2287-0237

VOLUME

CURRENT MANAGEMENT OF URINARY TRACT INFECTIONS

FEBRUARY 2012 - VOL.3 | CONTINUING MEDICAL EDUCATION

Urinary Tract Infections (UTIs) are among the most common infections in both the out and inpatient settings. Increasing  antimicrobial resistance of urinary pathogens has highlighted the need for reevaluation of the treatment options.1-3 Since management of UTIs widely varies, these guidelines may help  physicians choose cost-effective options. 4-10

Diagnosing a UTIs often requires examination of a urine sample in addition to clinical signs or symptoms (Table 1). However, many guidelines indicate that a urine culture is not needed in most cases of uncomplicated lower UTI or cystitis.11, 12 Escherichia coli remains the most common etiologic agent of community-acquired,  uncomplicated UTIs, particularly in women under 50 years of age,  with Staphylococcus saprophyticus the second commonest. For this reason, in treating uncomplicated cystitis, the first-line empiric  antibiotic recommendations are those which are narrow-spectrum and used predominantly only for this indication.

Factors of functional and anatomical alterations play the important  role in the pathogenesis of UTIs. In women, the shortness of  urethra, with its close proximity to the anus, makes it easy for  bacteria to ascend the genito-urinary tract. Therefore, fecal-perineal- urethral contamination is the most common cause of UTIs.

Altered vaginal flora (AVF) also plays a similar role in the pathogenesis of UTI in women. Lactobacilli is the dominant bacteria  found in the vagina, possessing antimicrobial properties that  regulate the local vaginal host defenses, by maintaining an acidic pH and producing hydrogen peroxide. The use of lactobacillus- containing probiotics has been studied as a potential prophylactic  for recurrent UTIs. However, the efficacy of this result of UTI  prophylaxis remains as yet inconclusive. Alteration in vaginal flora can also be observed in UTIs occurring in postmenopausal women, because estrogen stimulates the proliferation of lactobacilli and  reduces local pH.13-14

Bacteriuria is the most common finding in pregnant women.  Many studies have shown that upper UTI or acute pyelonephritis is more common in the second or third trimester of pregnant women with asymptomatic bacteriuria. For this reason asymptomatic bacteriuria in pregnant women has to be treated.15, 16

Table 1: Definition of terms20

The risk of developing symptomatic UTI is increased in diabetes.17 Asymptomatic bacteriuria is also increased in patients with diabetes over a longer duration. However studies showed only a weak correlation between increased risk of symptomatic UTIs and poor control of diabetes and microalbuminuria or macrovascular  complications, also, antibiotic treatment did not decrease incidence of symptomatic UTI.18, 19 

An appropriate antibiotic varies according to the following information or criteria:

  1. Patient’s individual risk
  2. Patient’s previous antibiotic treatment
  3. Pathogen spectrum and susceptibility
  4. Pathogen resistance prevalence
  5. Drug effects including adverse reactions 

1. Trimethoprim-Sulfamethoxazole for 3 days is an  appropriate choice of therapy in USA, if local resistance rate of uropathogens causing cystitis do not exceed 20% (A-I)

2. Fluoroquinolones : Oflocaxin, Ciprofloxacin and Levofloxacin are highly effective in 3 days regimens (A-I)

In many countries, where the uropathogen resistance to Trimetoprim-Sulfamethoxazole and Fluoroquinoloneis high, those agents may no longer be recommended for empiric treatment of UTI.

3. Fosfomycin trometamal, 3 gm sachet, in a single dose is an alternative for those with drug-resistant UTIs, but it appears to be less efficacious when compared with the standard 3-5 days regimen of other antibiotics according  to data published. 23, 24

4. ß-lactam antibiotics, including Cephalosporin  (2nd or 3rd generation), and betalactam-betalactamase inhibitors, such as amoxicillin-clavulanate/ampicillin- sulbactam, in 3-7 days regimens are appropriate choices when other agents cannot be used. (B-III)  

From a clinical point of view, acute pyelonephritis  should be considered as tissue infection of the whole  urinary tract; whereas an exact anatomical distinction on clinical grounds can often not be made. Blood and urine cultures should always be performed, and initial empirical intravenous antibiotic should be started as fast as  possible, due to the somewhat higher incidence of bacteria  in adult pyelonephritis. (A-III)

Most patients with acute pyelonephritis require  hospitalization and initially intravenously administered  empiric antibiotics, such as cephalosporin, fluoroquinolone, aminoglycoside or carbapenem; the choice between  these agents should be based on local resistance data. Later, the antibiotic regimen should be tailored on the basis of susceptibility results.

Table 2: Strength of recommendations and Quality of Evidence

NOTE. Data is from periodic health examination. Canadian Task Force on the Periodic Health Examination. Health Canada, 1979.
Adapted and Reproduced with the permission of the Minister of Public Works and Government Services Canada, 2009

The appropriacy of the initial or empirical antibiotic for acute pyelonephritis also depends on the severity of illness at presentation as well as local resistance and  comorbidity of patients, and host factors.

For some areas of the world, including Thailand, the prevalence of Fluoroquinolone resistance exceeds 10%; therefore the generally recommended initial antibiotic is a parenteral 3rd generation long-acting cephalosporin, normally ceftriaxone.

A 3-day course of highly effective antibiotics or  tissue-directed antibiotic such as Trimethoprim-Sulfame thoxazole and Fluoroquinolone, is recommended for  women and a 7-day course for men.25 If ß-lactam is used, the duration recommended is 5 days for women,  of all ages. 

Most published guidelines recommend a 14 days regimen (A-I),4, 26-30 however a 7-10 days regimen is also recommended if a highly active agent, such as Fluoroquinolone, is used.

Recently, the Infectious Diseases Society of America in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) have systematically updated ISDA clinical practice guidelines for treating acute uncomplicated cystitis and pyelonephritis in women. (Table 2) 4, 32

Definition of asymptomatic bacteriuria 33, 34

  1. Asymptomatic women, defined as 2 consecutive voided urine culture with isolation of the same bacteria, counts ≥ 105 CFU/ml (B-II)
  2. A single, clean-catch voided urine of ≥ 105 CFU/ml (B-II)
  3. A single catheterized urine of ≥ 105 CFU/ml in women or men (A-II)

Asymptomatic bacteriuria is common in many groups of patients with indwelling catheters, where there is a very high prevalence of asymptomatic bacteriuria; such as in patients with spinal cord injury, where the prevalence ranges between 23-89.35

Studies have shown that it is worth treating asymptomatic bacteriuria only in pregnant women and patients in whom a urinary tract intervention is intended that may be expected to damage the mucosa. 

Urinary tract infections are responsible for a large proportion of antibiotic administrations; bacterial resistance is increasing. For this reason, in treating UTIs, treatment recommendation should take into account to the efficacy of the antibiotics and also, especially factors relating to their sustainability. Asymptomatic bacteriuria should only be treated in a few exceptional cases, such as during pregnancy or before genitourinary tract interventions.

Q1. Which of the following duration of antibiotics for treatment of uncomplicated cystitis is not correct?

a. 3 days of Fluoroquinolone is adequate
b. 5 days of oral Cephalosporin is adequate
c. Single dose of Fosfomycin trometamol is effective
d. Single dose of Parenteral Ceftrioxane is effective
e. 5 days of Amoxycillin-Clavulanate is effective

Q2. What is the most appropriate and cost-effective parenteral antibiotic for acute pyelonephritis?

a. Cefuroxime
b. Ceftazidime
c. Ceftotaxime
d. Ceftriaxone
e. Ampicillin-Sulbactam

Q3. In which of the following patients does asymptomatic bacteriuria need to be treated with antibiotic?

a. Diabetes Mellitus
b. The elderly
c. Pregnant women
d. Hypertension
e. Spinal cord injury

Q4. Regarding duration of antibiotic in acute pyelonephritis, which of the following is not correct?

a. Based on current evidence, 14 days is recommended
for most antibiotics
b. If Fluoroquinolone is used, 7-10 days is probably
adequate
c. If 3rd generation Cephalosporin is used, 7-10 days
is adequate
d. If Amoxycillin-Clavulanic is used, 14 days is
recommended
e. In bacteremic patient, duration should be more
than 14 days.

Q5. Duration of antibiotic therapy for UTI could be shorter if using tissue-directed antibiotic(s) such as…?

a. Ciprofloxacin
b. Cefdinir
c. Cefditoren
d. Levofloxacin
e. Amoxicillin-clavulanate

Answer 1: d. Duration of treatment of uncomplicated cystitis with any ß-lactam recommended by most authors is 3-5 days.

Answer 2: d. Ceftriaxone is the most cost-effective parenteral antibiotic, due to good PK-PD against uropathogens.

Answer 3: c. From many published studies, antibiotic treatment is only beneficial in pregnant women with asymptomatic bacteriuria.

Answer 4: e. From many published studies, duration of antibiotic in bacteremic adult pyelonephritis did not differ from non bacteremic patients.

Answer 5: a and d. Fluoroquinolones are tissue-directed antibiotics with high tissue and urine concentration, so called good PK/PD, bactericidal: for this reason duration could be shorter than ß-lactam.