In the name of GOD

URINARY TRACT INFECTION Dr.Hedayati

Acute uncomplicated cystitis and pyelonephritis in women Acute uncomplicated cystitis, pyelonephritis, and asymptomatic bacteriuria in men Acute complicated cystitis and pyelonephritis Approach to the adult with asymptomatic bacteriuria Urinary tract infections and asymptomatic bacteriuria in pregnancy

Acute uncomplicated cystitis and pyelonephritis in women

Most episodes of cystitis and pyelonephritis are generally considered to be uncomplicated in otherwise healthy nonpregnant adult women. A complicated urinary tract infection, whether localized to the lower or upper tract, is associated with an underlying condition that increases the risk of failing therapy.

Common Risk factors : recent sexual intercourse recent spermicide use history of urinary tract infection

MICROBIOLOGY Escherichia coli 75 to 95% Enterobacteriaceae: Proteus mirabilis Klebsiella pneumoniae Staphylococcus saprophyticus

Antimicrobial resistance Resistance rates >20 % : ampicillin & trimethoprim use of TMP-SMX in the preceding 3 to 6 months was an independent risk factor for TMP-SMX resistance in women with acute uncomplicated cystitis. Fluoroquinolone resistance rates were <10 %. Resistance rates for first and second generation oral cephalosporins and amoxicillin-clavulanic acid are : <10 %. Nitrofurantoin : good in vitro activity.

CLINICAL MANIFESTATIONS Dysuria may also be a manifestation of vaginitis or urethritis.

DIAGNOSIS A pelvic examination is indicated if factors suggesting vaginitis or urethritis are present. Pregnancy testing is also appropriate. Urinalysis in the absence of urine culture is sufficient for diagnosis of uncomplicated cystitis if symptoms are consistent with UTI. Imaging studies are not routinely required for diagnosis of acute uncomplicated pyelonephritis.

Urinalysis Pyuria : almost all women with acute cystitis or pyelonephritis Its absence : alternative diagnosis or in a patient with pyelonephritis, the presence of an obstructing lesion . Pyuria : ≥10 leukocytes/microL . White blood cell casts in the urine are diagnostic of upper tract infection.

…Urinalysis The presence of hematuria is helpful since it is common in the setting of UTI but not in urethritis or vaginitis. Hematuria is not a predictor for complicated infection and does not warrant extended therapy.

…Urinalysis Dipsticks : leukocyte esterase (reflecting pyuria) nitrite (reflecting the presence of Enterobacteriaceae, which convert urinary nitrate to nitrite) Leukocyte esterase : detect >10 leukocytes per HPF(sensitivity of 75 to 96 percent; specificity of 94 to 98 percent) The nitrite test is fairly sensitive and specific for detecting ≥10(5) CFU negative results should be interpreted with caution False positive nitrite tests can occur with substances that turn the urine red, such as phenazopyridine or ingestion of beets.

Urine culture Urine culture and antimicrobial susceptibility testing of uropathogens should be performed in all women with acute pyelonephritis.

TREATMENT Cystitis Nitrofurantoin :100 mg orally twice daily for 5 days early clinical efficacy rate with 5 to 7 day regimen 90 to 95 % Nitrofurantoin should be avoided : if there is suspicion for early pyelonephritis, is contraindicated when GFR<60 mL/minute.

TREATMENT …Cystitis Cotrimoxazole : 160/800 mg twice daily for 3 days early clinical efficacy rate with 3 to 7 day regimen 86 to 100 % Empiric TMP-SMX should be avoided : if the prevalence of resistance is known to exceed 20 % if the patient has taken TMP-SMX for cystitis in the preceding 3 months ***Trimethoprim (100 mg twice daily for three days) is used in place of TMP-SMX and is considered equivalent

TREATMENT …Cystitis Fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin in 3-day regimens) are reasonable alternative agents. very effective for treatment of acute cystitis.

TREATMENT …Cystitis Amoxicillin-clavulanate : for duration of 7 days Other beta lactams, such as cephalexin, are less well studied but may be acceptable in certain settings. Ampicillin or amoxicillin should NOT be used for empiric treatment.

TREATMENT Pyelonephritis: Outpatient management is acceptable for patients with mild to moderate illness who can be stabilized with rehydration and antibiotics in an outpatient facility and discharged on oral antibiotics under close supervision. Inpatient management is warranted in the setting of severe illness with high fever, pain, and marked debility, inability to maintain oral hydration or take oral medications, pregnancy, or concerns about patient compliance.

TREATMENT …Pyelonephritis/Outpatient: Ciprofloxacin (500 mg orally twice daily for 7 days or levofloxacin (750 mg orally once daily for 5 to 7 days) Fluoroquinolone resistance > 10 %, an initial intravenous dose of a long acting parenteral antimicrobial such as ceftriaxone (1 gram), should be administered.

TREATMENT …Pyelonephritis/Outpatient: Cotrimoxazole (160/800 mg twice-daily). If these agents is used in the absence of susceptibility data, an initial intravenous dose of a long-acting parenteral antimicrobial should be administered Ciprofloxacin or levofloxacin can be used in 5 to 7 day regimens in most patients with mild to moderate disease who have a rapid response to treatment. The duration of treatment with cotrimoxazole is 14 days, but clinical experience suggests that 7 to 10 days is effective in women who have a rapid response to treatment. Oral beta lactam agents are less effective than other agents for treatment of pyelonephritis .If the pathogen is susceptible and an oral beta lactam agent is continued, it should be administered for at least 14 days.

TREATMENT …Pyelonephritis/Inpatient: initially with an intravenous antimicrobial regimen suc: fluoroquinolone aminoglycoside extended-spectrum cephalosporin, extended-spectrum penicillin, carbapenem.

Follow-up Follow-up urine cultures are not needed in patients with acute cystitis or pyelonephritis whose symptoms resolve on antibiotics

Symptomatic therapy Clinical manifestations should respond to antimicrobial therapy within 48 hours. In the interim, for some patients a urinary analgesic such as oral phenazopyridine (200 mg three times daily) may be useful to relieve discomfort due to severe dysuria. A two day course is usually sufficient to allow time for symptomatic response to antimicrobial therapy and minimize inflammation. This agent should not be used chronically since it may mask clinical symptoms requiring clinical evaluation

Acute uncomplicated cystitis, pyelonephritis, and asymptomatic bacteriuria in men

It has been conventional to consider all UTIs (and presumably asymptomatic bacteriuria) in men as complicated, since the majority occur in infants or the elderly in association with urologic abnormalities, such as bladder outlet obstruction (eg, due to prostatic hyperplasia) or instrumentation. Acute uncomplicated UTIs occur in a small number of men between 15 and 50 years of age.

ASYMPTOMATIC BACTERIURIA Positive urine culture in the absence of symptoms. Asymptomatic bacteriuria in young healthy men is rare . Among the elderly, the prevalence of asymptomatic bacteriuria is lower in men than in women.

…ASYMPTOMATIC BACTERIURIA Screening for asymptomatic bacteriuria is warranted prior to transurethral resection of the prostate or other urologic procedures for which mucosal bleeding is anticipated . It is appropriate to perform urinalysis prior to hip arthroplasty if a urinary catheter is expected to be in place postoperatively. An abnormal urinalysis should prompt urine culture, and the presence of urinary tract infection (eg, ≥10(4) CFU/mL) warrants treatment with three days of antibiotic therapy prior to surgery.

ACUTE CYSTITIS AND PYELONEPHRITIS Diagnosis A urine culture should be performed in all men with symptoms suggestive of cystitis. An evaluation for causative factors should be pursued .If an underlying risk factor is not obvious, further evaluation should be considered. Men with recurrent cystitis should undergo evaluation for prostatitis. Urologic evaluation is probably not necessary in young healthy men with no obvious complicating factors who have a single episode of cystitis that responds promptly to antimicrobial treatment. Imaging studies are not routinely required for diagnosis of acute uncomplicated pyelonephritis.

ACUTE CYSTITIS AND PYELONEPHRITIS Diagnosis The presence of hematuria is helpful since it is common in the setting of UTI but not in urethritis. Hematuria is not a predictor for complicated infection and does not warrant extended therapy.

Urine culture A midstream urine culture is recommended to confirm the diagnosis of urinary tract infection in men, using colony count criteria of ≥10(4) CFU/mL . The spectrum of isolates causing uncomplicated cystitis in men is similar to that in women.

Differential diagnosis Chronic prostatitis should be considered in men with cystitis, particularly in those men who have recurrent UTIs. Urethritis must be considered in sexually active men.

Treatment Cystitis Treatment duration of 7 to 14 days given the possibility of associated prostatitis, which may be difficult to discern clinically. Nitrofurantoin and beta-lactams should usually not be used in men with cystitis, since they do not achieve reliable tissue concentrations and would be less effective for occult prostatitis.

Follow up Persistent symptoms after 48 to 72 hours of appropriate antimicrobial therapy or recurrent symptoms within a few weeks of treatment should have evaluation for complicated infection .

Acute complicated cystitis and pyelonephritis

Diabetes Pregnancy History of acute pyelonephritis in the past year Symptoms for seven or more days before seeking care Antimicrobial resistant uropathogen Hospital acquired infection Renal failure Urinary tract obstruction Presence of an indwelling urethral catheter, stent, nephrostomy tube or urinary diversion Recent urinary tract instrumentation Functional or anatomic abnormality of the urinary tract History of urinary tract infection in childhood Renal transplantation Immunosuppression

Acute complicated pyelonephritis is progression of upper urinary tract infection to emphysematous pyelonephritis, renal corticomedullary abscess, perinephric abscess, or papillary necrosis.

MICROBIOLOGY The microbial spectrum of complicated UTI is broader and includes the above organisms as well as Pseudomonas, Serratia, and Providencia species, in addition to enterococci, staphylococci, and fungi . In addition, organisms causing complicated cystitis are more likely to be resistant to commonly used oral antimicrobials recommended for uncomplicated cystitis

Chronic pyelonephritis is an uncommon cause of chronic tubulointerstitial disease due to recurrent infection, such as infection in association with a chronically obstructing kidney stone or vesicoureteral reflux. Affected patients can present with weeks to months of insidious symptoms.

Radiographic imaging Persistent clinical symptoms after 48 to 72 hours of appropriate antibiotic therapy for acute uncomplicated urinary tract infection pyelonephritis who also have symptoms of renal colic or history of renal stones, diabetes, infection with a particularly virulent organism, history of prior urologic surgery, immunosuppression, repeated episodes of pyelonephritis, or urosepsis .

…Radiographic imaging CT : study of choice to detect complicated urinary tract infection CT : more sensitive than IVPor renal ultrasound CT without contrast has become the standard radiographic study for demonstrating calculi, gas-forming infections, hemorrhage, obstruction, and abscesses. Contrast is needed to demonstrate alterations in renal perfusion.

…Radiographic imaging CT findings may include localized hypodense lesions due to ischemia induced by marked neutrophilic infiltration and edema Resolution of radiographic hypodensities may lag behind clinical improvement by up to three months .

…Radiographic imaging Renal ultrasound is appropriate in patients for whom exposure to contrast or radiation is undesirable . MRI is not advantageous over CT except when avoidance of contrast dye or ionizing radiation is warranted .

TREATMENT Cystitis Oral fluoroquinolone such as ciprofloxacin (500 mg orally twice daily) or levofloxacin (750 mg orally once daily) for 5 to 14 days. Short regimens are appropriate in patients with mild to moderate symptoms and rapid clinical response. Fluoroquinolones are comparable or superior to other broad spectrum antibiotics, including parenteral regimens

…TREATMENT …Cystitis Nitrofurantoin, cotrimoxazole and oral beta-lactams are poor choices for empiric oral therapy in complicated cystitis.

…TREATMENT …Cystitis Parenteral therapy :patients who cannot tolerate oral therapy patients with infection due to resistant organisms. levofloxacin ,ceftriaxone ,an aminoglycoside ,an extended-spectrum beta-lactam, or a carbapenem. The presence of gram-positive cocci is suggestive of enterococci and requires treatment with ampicillin or amoxicillin . After clinical improvement is observed, parenteral therapy can be switched to oral therapy. The duration of treatment for acute complicated cystitis is 5 to 14 days.

…TREATMENT Pyelonephritis Initially as inpatients. Broad-spectrum parenteral antibiotics Underlying urinary tract anatomic or functional abnormalities Antibiotics alone may not be successful unless such underlying conditions are corrected. Antibiotics should be administered for at least 10 to 14 days; Treatment may be completed with oral therapy Acceptable agents include levofloxacin, ciprofloxacin, or trimethoprim-sulfamethoxazole

Follow-up not needed in patients with acute cystitis or pyelonephritis whose symptoms resolve on antibiotics. Patients with persistent or recurrent symptoms within a few weeks of treatment for acute complicated urinary tract infection should have a reevaluation

Approach to the adult with asymptomatic bacteriuria

CLINICAL DEFINITIONS The presence of pyuria (≥10 leukocytes/mm3 of uncentrifuged urine) is not sufficient for diagnosis of bacteriuria

Women Two consecutive clean-catch voided urine specimens with isolation of the same organism in quantitative counts of ≥10(4) cfu/mL. A single positive urine specimen with ≥10(5) cfu/m.

Men single clean-catch voided urine specimen with isolation of a single organism in quantitative counts of ≥10(5) cfu/mL . In general, external contamination during voiding among men is an extremely unlikely cause of significant bacteriuria.

Catheterized specimens single catheterized specimen with isolation of a single organism in quantitative counts of ≥10(2) cfu/mL. There have been no comparisons of culture yields from urethral catheterized specimens and suprapubic aspiration specimens

EPIDEMIOLOGY Women :Pregnant and non-pregnant women have a similar prevalence. Diabetic women :correlated with duration and presence of long term complications of diabetes, rather than with metabolic parameters of diabetes control . Men :Diabetic men do not appear to have a higher prevalence of bacteriuria than nondiabetic men

WHOM TO TREAT pregnant women patients undergoing urologic procedures in which mucosal bleeding is anticipated

WHOM NOT TO TREAT Diabetic patients Patients with spinal cord injury Indwelling urethral catheters.

Avoiding treatment of asymptomatic bacteriuria is important for reducing development of antibiotic resistance, and a hospital and ambulatory performance measure for not treating asymptomatic bacteriuria in adults has been proposed

Urinary tract infections and asymptomatic bacteriuria in pregnancy

Diagnosis Isolation of Lactobacillus warrants treatment if it is the only organism isolated in consecutive urine cultures with high colony counts, although the significance in pregnancy is not known.

…Diagnosis Screening for asymptomatic bacteriuria should be performed at 12 to 16 weeks gestation Rescreening is generally not performed in low risk women, but can be considered in women at high risk for infection (eg, presence of urinary tract anomalies, hemoglobin S, or preterm labor)

Treatment Penicillins and cephalosporins are safe in pregnancy. ceftriaxone, may be inappropriate the day before parturition because of the possibility of bilirubin displacement and subsequent kernicterus. Nitrofurantoin and sulfonamides : birth defects .The safest course is to avoid using nitrofurantoin in the first trimester. Nitrofurantoin : hemolytic anemia in the mother and fetus with G-6PD deficiency Sulfonamides should be avoided in the last days before delivery because they can increase the level of unbound bilirubin in the neonate. Trimethoprim is generally avoided in the first trimester because it is a folic acid antagonist . Fluoroquinolones and tetracyclines are contraindicated during pregnancy.

Nitrofurantoin (100 mg orally every 12 hours for five to seven days) Amoxicillin (500 mg orally every 12 hours for three to seven days) Amoxicillin-clavulanate (500 mg orally every 12 hours for three to seven days) Cephalexin (500 mg orally every 12 hours for three to seven days)

Follow-up a week after completion of therapy repeated monthly until the completion of the pregnancy.

Follow-up If the follow-up culture is positive [≥10(5) cfu/mL] with the same species of bacteria (persistent bacteriuria), another course of antimicrobial based on susceptibility data should be administered - either the same antimicrobial in a longer course (eg, seven days, if a three-day regimen was used previously) or a different antimicrobial in a standard regimen.

Follow-up If the follow-up culture is positive with a different species or if the follow-up culture is not positive [<10(5) cfu/mL], but then a subsequent follow-up culture is positive (with the same or different species), both scenarios imply recurrent bacteriuria and treatment should be administered with one of the recommended regimens based on antimicrobial susceptibility testing. True persistent bacteriuria implies initial therapy was inadequate and thus requires modification different therapeutic approach than in women who develop recurrent bacteriuria.

Suppressive therapy persists after two or more courses of therapy. Nitrofurantoin (50 to 100 mg orally at bedtime) for the duration of the pregnancy may be used if the organism is susceptible. Monthly cultures are not necessary if suppressive therapy is administered; however, breakthrough bacteriuria can occur during suppressive therapy, so at least one later culture, such as at the start of the third trimester, should be performed to ensure suppression is working. If a follow-up culture is positive [≥10(5) cfu/mL], another course of antimicrobial based on susceptibility data should be administered. The suppressive regimen should be reassessed and adjusted if needed.

ACUTE CYSTITIS It is reasonable to use a quantitative count ≥10(3) cfu/mL in a symptomatic pregnant woman as an indicator of symptomatic UTI.

Treatment Nitrofurantoin (100 mg orally every 12 hours for five to seven days) Cefpodoxime (100 mg twice daily for three to seven days) Amoxicillin-clavulanate (500 mg orally every 12 hours for three to seven days) TMP-SMX (one double strength twice daily for three days) in the second trimester Amoxicillin (for treatment of enterococcus; 500 mg twice daily every 12 hours seven days).

Follow-up As asymptomatic bacteriuria

Suppressive therapy As asymptomatic bacteriuria

Recurrent infection antimicrobial prophylaxis for the duration of pregnancy. It is reasonable to use postcoital prophylaxis if the UTI is thought to be sexually related, which is common. If the woman has other conditions that potentially increase the risk of urinary complications during episodes of UTI (eg, diabetes or sickle cell trait), prophylaxis should be considered after the first UTI during pregnancy .The choice of antimicrobial should be based on the susceptibility profile of the cystitis strains. Ideally, daily or postcoital prophylaxis with low dose nitrofurantoin (50 to 100 mg PO postcoitally or at bedtime) or cephalexin (250 to 500 mg PO postcoitally or at bedtime) can be used.

Prior recurrent UTI As a result, we recommend postcoital prophylaxis in pregnant women who have recurrent UTIs that appear to be temporally related to sexual intercourse. The preferred regimen is a single postcoital dose of either cephalexin (250 mg) or nitrofurantoin (50 mg).

ACUTE PYELONEPHRITIS Parenteral beta-lactams are the preferred antibiotics. Carbapenems are usually effective in the treatment of serious extended-spectrum beta lactamase (ESBL)-producing strains causing infections pregnant women should have definite improvement within 24 to 48 hours. Once afebrile for 48 hours, patients can be switched to oral therapy and discharged to complete 10 to 14 days of treatment . If symptoms and fever persist beyond the first 24 to 48 hours of treatment, a repeat urine culture and urinary tract imaging studies should be performed to rule out persistent infection and urinary tract pathology.

Preventing recurrence low dose antimicrobial prophylaxis with an agent to which the organism is susceptible is warranted for the remainder of the pregnancy; reasonable options include nitrofurantoin (50 to 100 mg orally at bedtime) or cephalexin (250 to 500 mg orally at bedtime) .

Failure of outpatient therapy Outpatient therapy of pregnant women with pyelonephritis does not recommend initiating therapy of pyelonephritis to pregnant women in the outpatient setting.

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