1. Definitions
1. Urinary tract infection (UTI) is defined as the presence of microorganisms in the urine that cannot be accounted for by contamination. The organisms have the potential to invade the tissues of the UT and adjacent structures Infections of the urinary tract represent a wide variety of syndromes, including urethritis, cystitis, prostatitis, and pyelonephritis. 3. A UTI can range from asymptomatic bacteriuria to pyelonephritis with bacteremia or sepsis. 4. Pyuria: WBCs in urine Bacteriuria: bacteria cultured from the urine

2. UTI classification 1) By anatomic site of involvement :
A) Lower tract infections :
cystitis (bladder), urethritis (urethra), prostatitis (prostrate gland) and epididymitis.
B) Upper tract infections :
Peylonephritis (involves the parenchyma of the kidneys)
2) Uncomplicated/Complicated ?
A) Uncomplicated UTIs are not associated with structural or neurologic abnormalities that may interfere with the normal flow of urine or the voiding mechanism. E.g, normal healthy females (15-45 years)
B ) Complicated UTIs are the result of a predisposing lesion of the urinary tract, such as : a congenital abnormality or distortion of the urinary tract, stone, indwelling catheter, prostatic hypertrophy , obstruction, or neurologic deficit that interferes with the normal flow of urine and urinary tract defenses.

3. Complicated UTIs may be subdivided into
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 (cUTI).
Complicated UTIs are defined by the FDA as a clinical syndrome characterized by pyuria and a documented microbial pathogen on culture of urine or blood, accompanied by local and systemic signs and symptoms including fever (i.e., oral or tympanic temperature greater than 38 degrees Celsius), chills, malaise, flank pain, back pain, and/or costovertebral angle pain or tenderness that occur in the presence of a functional or anatomical abnormality of the urinary tract or in the presence of catheterization.
Complicated UTIs may be subdivided into
Structural abnormalities
Metabolic/hormonal abnormalities
Impaired host responses
Unusual pathogens
Male, Pregnant women, infants and any patient pass cathetarization with UTIare examples of complicated cases

4. Etiology Complicated/ Nosocomial UTI: Uncomplicated UTI:
E.coli
Klebseilla pneumoniae
Proteus spp
Pseudomonas aeruginosa
Enterococcus spp
Enterobacter spp
Staphylococcus saprophyticus
Uncomplicated UTI:
E.coli (most common)
Most are caused by single organisms except in pateints with stones , indwelling urinary catheters or chronic renal abscesses

5. Clinical Presentation of Urinary Tract Infections (UTIs) in Adults
Signs and symptoms
Lower UTI: dysuria(pain on urination), urgency, frequency, nocturia, suprapubic heaviness ,gross hematuria
Upper UTI: flank pain, fever, nausea, vomiting, malaise , presence of costovertebral tenderness
Laboratory tests (Urinalysis)
Bacteriuria
Pyuria (WBC >10/mm3)[>10 x 106/L]
Nitrite-positive urine (with nitrite reducers)
Leukocyte esterase-positive urine
Antibody-coated bacteria (upper UTI)

6. Bacteriuria -It does not always represent infection
Bacteriuria -It does not always represent infection. “Significant bacteriuria” is the amount of bacteria in the urine that most likely represents true infection.
Asymptomatic bacteriuria : ( 65 years of age and older, females , pregnants)when there is significant bacteriuria in two consecutive urine cultures in the absence of symptoms. Relapse and reinfection are v.common. Chronic cases are difficult to eradicate. Management depends on the age of the patient and whether or not the patient is pregnant.
In children(greater risk of developing renal scarring and longstanding renal damage- greatest risk occurs during the first 5 years of life), treatment should consist of the same conventional courses of therapy as that used for symptomatic infection
In nonpregnant females, therapy is controversial; however, treatment has little effect on the natural course of infections.

7. Treatment The goals of treatment : eradicate the invading organism
prevent or treat consequences of infection
prevent recurrence of infection
An optimal approach to therapy includes consideration of antimicrobial resistance and collateral damage (ecological adverse effects of antimicrobial therapy).

8. Uncomplicated Cystitis (Women)
Predominantly caused by E.coli (85%).Therefore, management approach includes urinalysis and empiric therapy without a urine culture.
Fluoroquinolones should be reserved for patients with suspected or possible pyelonephritis due to the collateral damage risk. Instead, a 3-day course of trimethoprim–sulfamethoxazole, a 5-day course of nitrofurantoin, or a one-time dose of fosfomycin should be considered as first-line therapy.
Follow-up urine cultures are not necessary in patients who respond.
Adjunctive Therapy: If the patient has intense dysuria, offering a bladder analgesic, such as phenazopyridine (Pyridium), for 1-2days

10. Cystitis in Men ( complicated cystitis)
Considered complicated, since the majority occur in infants, male, pregnant, 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).
2 weeks of therapy, if treatment fails then up to 6 weeks of therapy.
A urine culture should be obtained before treatment, because the cause of infection in men is not as predictable as in women.
Men should receive the same treatment as women but:
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 .
14 days is the recommended treatment length because the likelihood of complicating factors is higher than in women.
Appropriate antimicrobials for empiric treatment of acute uncomplicated cystitis in men include trimethoprim-sulfamethoxazole and fluoroquinolones.

11. Overview of Outpatient Antimicrobial Therapy for Lower Tract Infections in Adults
Prophylactic Therapy
nitrofurantoin cannot be used to treat anything other than simple cystitis.
Nitrofurantoin and the quinolone antibiotics are mutually antagonistic in vitro. It is not known whether this is of clinical significance, but the combination should be avoided
Nitrofurantoin can cause nausea and vomiting, fever, rash, hypersensitivity pneumonitis.[citation needed] It can also cause pulmonary fibrosis.[11] All these side effects are much more common in the elderly.
Patients should be informed that nitrofurantoin colours urine a dark orange-brown; this is completely harmless.

13. Pyelonephritis: Inpatients/Outpatients ?
Treated as outpatients:
Women with mild to moderate cases of pyelonephritis (low-grade fever and a normal to slightly elevated peripheral white blood cell count, without nausea or vomiting)
stabilized with rehydration and antibiotics in an outpatient facility
discharged on oral antibiotics under close supervision
Hospitalization:
The case is severe (vomiting, decreased food intake and dehydration)
Comorbidities , hemodynamic instability, male sex, metabolic derangement, pregnancy, severe flank/abdominal pain, toxic appearance, unable to take liquids by mouth , body temperature >39.4 ⁰C

14. Uncomplicated pyelonephritis Outpatient

15. Complicated pyelonephritis (Inpatient)

16. ESBL –producing E.coli is resistant to beta lactams, third generation cephalosporins

17. UTI in Pregnancy
Increased risk why ? due to physiologic (hormonal and mechanical) changes + dilation of the ureters and renal pelvises + reduced bladder tone + increased urinary pH + glycosuria preterm birth and retardation + unexplained perinatal death pregnant women should be screened for bacteriuria by urine culture at least once during early pregnancy (12-16 wks) or at their prenatal visit

18. UTI in Pregnancy
Tetracyclines should be avoided because of teratogenic effects (Category C)
Trimethoprim/Sulfamethoxazole : Sulfonamides should not be administered during the third trimester because of the possible development of fatal hyperbilirubinemia. Trimethoprim is teratogenic.
Fluoroquinolones should be avoided (they inhibit cartilage and bone development in the newborn)
Avoid nitrofurantoin (3rd trimester hemolytic anemia)

19. Prophylactic Treatment of Recurrent UTI
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.
The following regimens are recommended for prophylaxis of recurrent UTIs:
Nitrofurantoin 50 mg orally daily.
One-half trimethoprim-sulfamethoxazole (TMP-SMX) single-strength (SS) tablet (Trimethoprim 40 mg-sulfamethoxazole 200 mg) orally daily.