Urinary Tract Infections (UTI) PDF

Clinical Pharmacy and therapeutics 2 Urinary Tract Infections (UTI) Bara’a Shawaqfeh, Ph.D Al Zaytoonah University of Jordan  Introduction UTI is the presence of pathogenic microorganisms in the genitourinary tract with associated signs and symptoms of...

Clinical Pharmacy and therapeutics 2 Urinary Tract Infections (UTI) Bara’a Shawaqfeh, Ph.D Al Zaytoonah University of Jordan  Introduction UTI is the presence of pathogenic microorganisms in the genitourinary tract with associated signs and symptoms of infection. UTIs represent a diverse array of syndromes based on location within the urinary tract, including acute cystitis, pyelonephritis, and prostatitis The organisms present have the potential to invade the tissues of the urinary tract and adjacent structures. Infection may be limited to the growth of bacteria in the urine, which frequently may not produce symptoms.  Introduction Cont’d A UTI can present as several syndromes associated with an inflammatory response to microbial invasion and can range from asymptomatic bacteriuria to pyelonephritis with bacteremia or sepsis. Due to the inherently short urethra and proximity to the perirectal area, bacteria often colonize the female urethra  Introduction Cont’d Pyelonephritis (infection of one or both kidneys) can occur in persons without functional or anatomic abnormalities of the urinary tract and is considered by the FDA to be a subset of complicated UTI. The types of bacterial pathogens generally responsible for complicated UTIs include the Enterobacteriaceae as well as other Gram-negative bacteria and Gram-positive bacteria, including enterococci. Enterobacteriaceae are also the most common bacterial pathogens identified in uncomplicated UTIs. Majority of uncomplicated UTIs are caused by Escherichia coli  Epidemiology UTIs are the most commonly occurring bacterial infections and account for 8 million patient visits annually. Approximately 1 in 3 females will have had a UTI by age 24 years. Infections in men occur much less frequently until the age of 65 years, at which point the incidence rates in men and women are similar  Risk factors Risk factors for men 1. Intercourse with an infected woman 2. Prostate hyperplasia Common risk factors for both men and women include: 1. DM Risk factors for women. 2. Urologic instrumentation 1. Sexual intercourse 3. Renal transplantation 2. Lack of voiding after intercourse 4. Neurogenic bladder 3. Use of a diaphragm contraceptive 5. Urinary tract obstruction 4. Pregnancy  Clinical presentation Sign and symptoms for Lower UTI (Cystitis):  Dysuria, urgency, frequency, nocturia, suprapubic heaviness, Suprapubic tenderness on examination, and Gross hematuria Sign and symptoms for Upper UTI (Pyelonephritis):  Flank pain, fever, nausea, vomiting, Costa vertebral tenderness, and malaise Laboratory Tests  Bacteriuria  Pyuria (WBC count more than 10/mm3 [10 × 106/L])  Nitrite positive urine (with nitrite reducers)  Leukocyte esterase positive urine  Antibody coated Bacteria (upper UTI)  Bacteriuria Bacteriuria, or bacteria in the urine, does not always represent infection. For this reason a number of quantitative diagnostic criteria have been created to identify the amount of bacteria in the urine that most likely represents true infection (hence the term significant bacteriuria). Asymptomatic bacteriuria (ASB) is a common finding, particularly among those 65 years of age and older , when there is significant bacteriuria (>105 bacteria/mL of urine) in two consecutive urine cultures in the absence of symptoms. Symptomatic a bacteriuria or acute urethral syndrome consists of symptom s of frequency and dysuria in the absence of significant bacteriuria. This syndrome is commonly associated with Chlamydia infections.  Principles of treatment The goals of treatment are:  to eradicate the invading organism;  to prevent or treat consequences of infection;  to prevent, if possible , recurrence of infection. Recurrent UTIs in healthy non-pregnant women, two or more UTIs occurring within 6 months or three or more UTIs occurring within 1 year, are a common problem Reinfection  Recurrence of bacteriuria caused by a new organism account for the majority of recurrent UTIs Relapse  Recurrence of bacteriuria caused by the same organism (usually indicate a persistent infectious source)  Principles of treatment Cont’d The management of a patient with a UTI includes: initial evaluation, selection of an antibacterial agent, duration of therapy and follow-up evaluation. The initial selection is based primarily on the severity of the presenting signs and symptoms, the site of infection and whether the infection is determined to be uncomplicated or complicated. Other considerations include antibiotic susceptibility, side-effect potential, cost, current antimicrobial exposure, and the comparative inconvenience of different therapies  Principles of treatment Cont’d The treatment goal in uncomplicated cystitis and pyelonephritis is to eradicate the causative organism. Empirical antibiotic therapy should be chosen with consideration of local resistance patterns to minimize the chance of patients failing therapy. Therapy should be chosen that is likely to cover the pathogen in the face of increasing resistance while causing minimal collateral damage.  Pharmacological therapy Antimicrobial therapy (empirical) is the cornerstone of treatment in UTIs. This therapy should ideally be: well tolerated, narrowing antimicrobial spectrum, lend itself to patient compliance (taken as infrequently as possible), have adequate concentrations at the site of the infection, and have good oral bioavailability.  Pharmacological therapy Cont’d Adjunctive Therapy If the patient has intense dysuria, offering a bladder analgesic, such as phenazopyridine (a local analgesic effect on the urinary tract), for 1-2 days is a considerate gesture on the part of the treating physician.  Avoid use if the patient has a sulfa allergy, and Many authors advise stressing the intake of plenty of fluids to promote a dilute urine flow  Pharmacological therapy Cont’d Indication Antibiotic Oral dose Interval Duration (days) Lower Urinary Tract Infection (Cystitis) Uncomplicated Trimethoprim-sulfamethoxazole 1 DS tablet BID 3 Nitrofurantoin monohydrate 100 mg BID 5 Fosfomycin 3g OID 1 Ciprofloxacin 250 mg BID 3 Levofloxacin 250 mg OID 3 Amoxicillin + clavulanic acid 500 +125 mg TID 5-7 Pivmecillinam 400 mg BID 3 Complicated Trimethoprim-sulfamethoxazole 1 DS tablet BID 7-10 Ciprofloxacin 250-500 mg BID 7-10 Levofloxacin 250 mg OID 10 750 mg OID 5 Amoxicillin + clavulanic acid 500+125 mg TID 7-10  Pharmacological therapy Cont’d Indication Antibiotic Oral dose Interval Duration (days) Lower Urinary Tract Infection (Cystitis) Recurrent Infections Nitrofurantoin monohydrate 50 mg OID 6 months Trimethoprim-sulfamethoxazole 1/2 SS tablet OID 6 months Acute pyelonephritis Trimethoprim-sulfamethoxazole 1 DS tablet BID 14 Ciprofloxacin 500 mg BID 14 1000 mg OID 7 Levofloxacin 250 OID 10 750 OID 5 Amoxicillin + clavulanic acid 500+125 mg TID 14  Evidence Based Empirical Treatment of UTIs and Prostatitis Diagnosis Pathogens Treatment Comments Acute uncomplicated E. Coli 1. Nitrofurantoin * 5 days * Short course therapy more effective cystitis Staphylococcus 2. Trimethoprim-sulfamethoxazole * 3 than single dose Saprophyticus daysa * Reserve fluoroquinolones as 3. Fosfomycin * 1 dosea alternative to development of 4. Fluoroquinolone * 3 daysa resistance 5. β-lactamases * 3-7 daysa * If a β lactam must be used, 6. Pivmecillinam * 3-7 days amoxicillin clavulanate, cefdinir , cefaclor , or cefpodoxime proxetil for 3 to 7 days are the preferred choices. Pregnancy E. Coli 1. Amoxicillin + clavulanic acid * 7 Staphylococcus days Saprophyticus 2. Cephalosporin * 7days 3. Trimethoprim-sulfamethoxazole * 3 days The first line therapy is marked with red Evidence Based Empirical Treatment of UTIs and Prostatitis Cont’d Diagnosis Pathogens Treatment Comments Acute pyelonephritis Uncomplicated E. Coli 1. Quinolone * 7 days Can be managed as outpatient 2. Trimethoprim-sulfamethoxazole * 3 days a Gram positive Amoxicillin + clavulanic acid * 14 days bacteria Complicated E. Coli 1. Quinolone * 14 days Severity of illness will P. Mirabilis 2. Extended spectrum penicillin + determine duration of IV K. Pneumonia aminoglycoside therapy; culture results should P. Aeruginosa direct therapy Enterococcus Oral therapy may complete 14 Faecalis days of therapy Prostatitis E. Coli 1. Trimethoprim-sulfamethoxazole * 4-6 Acute Prostatitis may require K. Pneumonia weeks IV therapy initially Proteus spp. 2. Quinolone * 4-6 weeks Chronic Prostatitis may require P. aeruginosa longer treatment period or surgery Management of UTI in females Management of UTI in females Cont’d  Symptomatic Abacteriuria Symptomatic abacteriuria or acute urethral syndrome represents a clinical syndrome in which females present with dysuria and pyuria, but the urine culture reveals less than 105 bacteria/mL of urine. Acute urethral syndrome accounts for more than half the complaints of dysuria seen in the community today. Infections typically involve small numbers of coliform bacteria, including:  E. coli, Staphylococcus spp., or Chlamydia trachomatis.  Additional causes include Neisseria gonorrhoeae, Gardnerella vaginalis, and Ureaplasma urealyticum. Most patients presenting with pyuria will, in fact, have infection that requires treatment. If antimicrobial therapy is ineffective, a culture should be obtained. If the patient reports recent sexual activity, therapy for C. trachomatis should be considered. Chlamydial treatment should consist of 1 g azithromycin or doxycycline 100 mg twice daily for 7 days. Often, concomitant treatment of all sexual partners is required to cure chlamydial infections.  Asymptomatic Abacteriuria Asymptomatic Abacteriuria is the finding of two consecutive urine cultures with more than 105 organisms/mL of the same organism in the absence of urinary symptoms. Most patients with Asymptomatic Abacteriuria are older females. Also, pregnant females frequently present with Asymptomatic Abacteriuria. Although these individuals typically respond to treatment, relapse and reinfection are common and chronic Asymptomatic Abacteriuria is difficult to eradicate. The management of Asymptomatic Abacteriuria depends on the age of the patient and whether or not the person is pregnant. In children, because of a greater risk of developing renal scarring and longstanding renal damage, treatment should consist of the same conventional courses of therapy as used for symptomatic infection. The greatest risk of renal damage occurs during the first 5 years of life. In non-pregnant females, therapy is controversial; however, treatment has little effect on the natural course of infections. Persons with bacteriuria along with other systemic signs suggesting severe infection should be treated empirically with broad spectrum antimicrobial therapy until other causes are ruled out.  Cystitis in Men Asymptomatic bacteriuria and symptomatic urinary tract infection are much less common in men than in women:  longer urethral length , drier periurethral environment (with less frequent colonization around the urethra), and antibacterial substances in prostatic fluid All is considered complicated, since the majority occur in infants or the elderly in association with urologic abnormalities, such as bladder outlet obstruction (e.g, due to prostatic hyperplasia) or instrumentation.  Acute uncomplicated UTIs occur in a small number of men between 15 and 50 years of age.  Risk factors associated with these infections include insertive anal intercourse and lack of circumcision  Cystitis in Men Cont’d Little evidence exists on treating them.  they should be treated as a probable complicated infection, (2 weeks of therapy, if failure of treatment up to 6 weeks of therapy) Men should receive the same treatment as women with the following special consideration:  exception of nitrofurantoin, which has poor tissue penetration  14 days is the recommended treatment length, because the likelihood of complicating factors is higher than in women.  Cystitis in Men Cont’d Initial therapy should be for 10 to 14 days. Parenteral therapy may be required in certain situations, such as in severely ill patients, in the presence of acute prostatitis or epididymitis and in patients who cannot tolerate oral medications. A comparison of 2 week versus 6 week therapy in males with recurrent infections who were given trimethoprim–sulfamethoxazole had cure rates of 29% and 62%, respectively. Follow up cultures at 4 to 6 weeks after treatment are important in males to ensure bacteriologic cure. Many patients require longer periods of treatment and possible alterations in antibiotics, depending on culture and sensitivity results and clinical response. Clinical and lab findings in patients with acute pyelonephritis  Acute pyelonephritis A presentation of high grade fever (more than 38.3 C) and severe flank pain should be treated as acute pyelonephritis and warrants aggressive management. Severely ill patients with pyelonephritis should be hospitalized and IV antimicrobials administered initially. However, milder cases may be managed with orally administered antibiotics in an outpatient setting. Signs and symptoms of nausea, vomiting, and dehydration may require hospitalization. At the time of presentation, a Gram stain of the urine should be performed along with a urinalysis, culture, and sensitivity tests. The Gram stain should indicate the morphology of the infecting organism(s) and help direct the selection of an appropriate antibiotic. However, the precise identity and susceptibility of the infecting organism(s) will be unknown initially, warranting empirical therapy.  Acute pyelonephritis Cont’d In the mild to moderate symptomatic patient in whom oral therapy is considered, an effective agent should be administered for 7 to 14 days, depending on the agent used.  Fluoroquinolones (ciprofloxacin or levofloxacin) orally for 7 to 10 days are the first line choice in mild to moderate pyelonephritis.  Other options include trimethoprim–sulfamethoxazole for 14 days.  If amoxicillin–clavulanate or an oral cephalosporin is used, it is recommended to give an initial long-acting parenteral antimicrobial such as ceftriaxone first and continue the oral agent for 10 to 14 days.  If a Gram stain reveals gram positive cocci, Enterococcus faecalis should be considered and treatment directed against this potential pathogen (ampicillin).  Acute pyelonephritis Cont’d In the seriously ill patient, parenteral therapy should be administered initially. A number of antibiotic regimens have been used as empirical therapy, including  an IV fluoroquinolone,  an aminoglycoside with or without ampicillin,  and extended spectrum cephalosporins with or without an aminoglycoside  and carbapenems. Other options include:  aztreonam,  the β-lactamase inhibitor combinations (eg, ampicillin–sulbactam, piperacillin–tazobactam, cetazidime/avabactamand cefetolozone/tazobactam),  carbapenems (eg, imipenem, meropenem, doripenem, or ertapenem),  novel boronic acid based β-lactamase inhibitor (eg, meropenem, vaborbactam), and  IV trimethoprim–sulfamethoxazole. Effective therapy should stabilize the patient within 12 to 24 hours. A significant reduction in urine bacterial concentrations should occur in 48 hours. If bacteriologic response has not occurred, an alternative agent should be considered based on susceptibility testing Outpatient treatment option for non-pregnant women with acute pyelonephritis Inpatient treatment option for non-pregnant women with acute pyelonephritis Pregnant women with acute pyelonephritis should be hospitalized and treated initially with a second- or third-generation cephalosporin, and then assessed to determine whether further treatment as an outpatient is appropriate.  UTI in pregnancy Increased risk because  Physiologic changes,  both hormonal and mechanical Factors increase risk  dilation of the ureters and renal pelvises, and reduced bladder tone  increased urinary pH and glycosuria Increased risk for  acute pyelonephritis, because 7% have asymptomatic bacteriuria, screening is necessary.  preterm birth, and retardation  Unexplained perinatal death (stillbirth) Pregnant women should be screened for bacteriuria by urine culture at least once during early pregnancy (12-16 weeks gestation) or at their first prenatal visit. All positive urine cultures, including asymptomatic bacteriuria, should be treated in pregnant women.  UTI in pregnancy Cont’d Treatment can be accomplished with a variety of FDA category B drugs including: amoxicillin, cephalosporin (cephalexin)  Trimethoprim-sulfamethoxazole (3rd trimester hyperbilirubinemia),  Sulfonamides just before birth may cause fetal hyperbilirubinemia, while trimethoprim early in pregnancy is teratogenic  Nitrofurantoin (3rd trimester hemolytic anemia)  Fluoroquinolones or tetracyclines should not be used during pregnancy (FDA Category C). (contraindicated) A seven day course is recommended with follow-up urine cultures (1-2 weeks after completion of therapy) to document sterile urine. (then monthly until birth) Persistent bacteruria requires re-treatment  Catheterized patients An indwelling catheter is commonly used in various health care settings, and is associated with UTIs. direct infection introduction during catheterization (via colonization and subsequently traveling the length of the catheter through bacterial motility or capillary action). Occur at a rate of 5% per day of catheter presence. The approach in the setting of a patient with bacteriuria and an indwelling urinary catheter follows two paths:  In asymptomatic patients with catheterization: hold antibiotics and remove the catheter if possible.  In symptomatic patients: antibiotics used with removal of the catheter if possible. (treatment as complicated infection) In both of the above situations, if discontinuation of the catheter is not possible, the patient should be re-catheterized with a new urinary catheter if the previous catheter is greater than 2 weeks old.  Catheterized patients Cont’d The following regimens are recommended for prophylaxis of recurrent UTIs:  Nitrofurantoin 50 mg orally daily.  One-half trimethoprim-sulfamethoxazole single-strength (SS) tablet (Trimethoprim 40 mg-sulfamethoxazole 200 mg) orally daily. Recurrent UTI is defined as at least two UTIs in six months or at least three UTIs in 12 months, without evidence of structural abnormalities. Prophylaxis should be considered in all renal transplant patients to prevent infection of the graft. Systemic antimicrobial prophylaxis should not be routinely used in patients with foley catheters because of concern about selection of antimicrobial resistance. Prophylactic treatment  Post exposure prophylaxis In some women, reinfection is associated with sexual intercourse. Voiding immediately after intercourse may help prevent reinfection. A single dose of trimethoprim-sulfamethoxazole single strength or nitrofurantoin 50 to 100 mg can be given prophylactically post intercourse.