Urinary tract infection

It is slide on urinary tract infection with recent updated definition and management

1. Urinary Tract Infection Dr. Navin Adhikari IM Resident, NAMS

2. CONTENT Epidemiology Terminology Etiopathogenesis Microorganism Risk Factors Innate Host Response Clinical Features Acute Simple Cystitis Pyelonephritis Protatitis Diagnosis Treatment Complications

3. UTI UTI is inflammation of urinary tract due to infectious agent , comprises of variety of clinical entities, from subclinical infection asymptomatic bacteriuria to disease like cystitis, prostatitis , and pyelonephritis . T he most common manifestation of UTI is acute cystitis and A cute cystitis is far more prevalent among women than a mong men.

4. Epidemiology Between 1 year and ~50 years of age, UTI and recurrent UTI are predominantly diseases of females. As many as 50–80% of women in the general population acquire at least one UTI during their lifetime - uncomplicated cystitis in most cases. About 20–30% of women who have had one episode of UTI will have recurrent episodes . Approximately 3% of non-pregnant adult women and 5% of pregnant women have asymptomatic bacteriuria .

5. TERMINOLOGY Lower tract UTI – involvement of urinary bladder, urethra and/or prostate. a. Cystitis b. Urethritis c. Protatitis Upper tract UTI – involvement of ureter , collecting ducts and/or renal parenchyma a. Ureteritis b.Pyelitis c. Pyelonephritis

6. Traditionally uncomplicated urinary tract infection refers to acute cystitis or pyelonephritis in nonpregnant outpatient women without anatomic abnormalities or instrumentation of the urinary tract. Complicated UTI has been defined as cystitis or pyelonephritis in a patient with underlying urologic abnormalities.Individuals who do not fit into either category have often been treated as having a complicated UTI by default.

7. Defination According to Uptodate Acute complicated urinary tract infection (UTI ) to refer to an acute UTI with any of the following features , which suggest that the i nfection extends beyond the bladder . Fever >99.9°F/37.7°C. Other signs or symptoms of systemic illness (including chills or rigors, significant fatigue or malaise beyond baseline). Flank pain . Costovertebral angle tenderness . Pelvic or perineal pain in men , which can suggest accompanying prostatitis . By this definition, pyelonephritis is a complicated UTI , regardless of patient characteristics. In the absence of any of above symptoms, patients with UTI to have acute simple cystitis(uncomplicated UTI) .

8. ETIOPATHOGENESIS

9. MICROORGANISMS

10. VIRULENCE Ability to adhere to epithelial cells determines the degree of virulence of the organism. For E. coli, virulent factors include a. flagellae (for motility), b. aerobactin (for iron acquisition in the iron-poor environment of the urinary tract), c. haemolysin (for pore forming) and d. adhesins on the bacterial fimbriae and on the cell surface. There are two types of E. coli: those with type 1 fimbriae (with adhesin known as FimH ) associated with cystitis ; and those with type P fimbriae (with adhesin known as PapG ) commonly responsible for pyelonephritis .

11. RISK FACTORS Previous UTI Lack of circumcision (children and young adults) Urologic instrumentation or surgery Urethral catheterization Urinary tract obstruction, including calculi Neurogenic bladder Renal transplantation Sexual intercourse New sex partner Insertive rectal intercourse Lack of urination after intercourse

12. Spermicidal contraceptive jellies Diaphragm use Pregnancy Lower socioeconomic group Diabetes sickle cell trait in pregnancy Functional or mental impairment Estrogen deficiency (loss of vaginal lactobacilli) Prostatic enlargement Condom catheter drainage Bladder prolapse

13. ROUTE OF INVASION 1. Ascending Route In the majority of UTIs, bacteria establish infection by ascending from the urethra to the bladder. Continuing ascent up the ureter to the kidney is the pathway for most renal parenchymal infections. Most common route of invasion. 2. Hematogenous Route Accounts for less than 2 % of documented UTIs and usually results from bacteremia caused by relatively virulent organisms, such as Salmonella and S. aureus . 3. Lymphatic route

14. INNATE HOST DEFENCES Neutrophils – adhesins activate receptors, e.g. Toll receptor 4, on the mucosal surface, phagocytosis Urine osmolality and pH – urinary osmolality >800 mOsm /kg and low or high pH reduce bacterial survival Complement – complement activation with IgA production by uroepithelium Commensal organisms – such as lactobacilli, corynebacteria , streptococci and bacteroides Urine flow – urine flow and normal micturition wash out bacteria. Urine stasis promotes UTI Uroepithelium – mannosylated proteins , have antibacterial properties, interfere with bacterial binding to uroepithelium , Disruption of this uroepithelium by trauma (e.g. sexual intercourse or catheterization) predisposes to UTI. Cranberry juice contain a large-molecular-weight factor ( proanthrocyanidins ) that prevents binding of E. coli to the uroepithelium

15. EPIDEMIOLOGICAL TRIAD The interplay of host, pathogen, and environmental factors determines whether tissue invasion and symptomatic infection will ensue. For example, bacteria often enter the bladder after sexual intercourse, but normal voiding and innate host defense mechanisms in the bladder eliminate these organisms. Any foreign body in the urinary tract, such as a urinary catheter or stone, provides an inert surface for bacterial colonization. Abnormal micturition and/or significant residual urine volume promotes infection.

16. CLINICAL FEATURES

17. ACUTE SIMPLE CYSTITIS The typical symptoms of cystitis are dysuria , urinary frequency, and urgency. Nocturia , hesitancy, suprapubic discomfort, and gross hematuria are often noted as well. The probability of cystitis is greater than 50 percent in w omen with any of these symptoms and greater than 90 percent inwomen without vaginal discharge or irritation. The differential diagnosis includes urethritis due to sexually transmitted disease , urethritis associated with r eactive arthritis , urethritis and cystitis but no bacteria are cultured from the urine (the ‘ urethral syndrome ’).

18. DIAGNOSTIC APPROACH

19. PYELONEPHRITIS Mild pyelonephritis can present as low-grade fever with or without lower-back or costovertebral -angle pain. S evere pyelonephritis can manifest as high fever, rigors, nausea, vomiting, and flank and/or loin pain . Symptoms are generally acute in onset, and symptoms of cystitis may not be present. The fever of pyelonephritis typically exhibits a high spiking “picket-fence” pattern and resolves over 72 h of therapy. The differential diagnosis of acute pyelonephritis includes pyelonephrosis , acute appendicitis, diverticulitis, cholecystitis , salpingitis , ruptured ovarian cyst or ectopic pregnancy.

20. PROSTATITIS Acute bacterial prostatitis presents as dysuria , frequency, and pain in the prostatic pelvic or perineal area . Fever and chills are usually present, and symptoms of bladder outlet obstruction are common.  The presence of typical symptoms of prostatitis should prompt digital rectal exam , and the finding of an edematous and tender prostate on physical exam in this setting usually establishes the diagnosis of acute bacterial prostatitis . Chronic bacterial prostatitis presents more insidiously as recurrent episodes of cystitis , sometimes with associated pelvic and perineal pain. Prostadynia (prostatic pain in the absence of active infection) may be a very persistent sequel to bacterial prostatitis .

21. DIAGNOSIS

22. URINALYSIS URINE SAMPLE- Collection of a midstream urine, with or without cleaning of the urethral meatus , at the time of clinical evaluation likely produces a reasonable specimen for analysis. MICROSCROPY Pyuria - Number of leukocytes >10/ microL is significant. Sterile Pyuria - P yuria in the absence of apparent bacterial infection . Causes of sterile pyuria include: use of antimicrobial, urine sample with vaginal leukocytes from vaginal secretions, Chronic interstitial nephritis, Nephrolithiasis , Uroepithelial tumor, Infection with atypical organisms, such as Chlamydia , Ureaplasma urealyticum , or tuberculosis, Intra-abdominal inflammatory process adjacent to the bladder.

23. White blood cell casts in the urine are indicative of kidney inflammation, which may reflect pyelonephritis or other renal conditions. DIPSTICK Detects the presence of leukocyte esterase and nitrite in the urine. Leukocyte esterase corresponds to pyuria and nitrite reflects the presence of Enterobacteriaceae , which convert urinary nitrate to nitrite. Leukocyte esterase may be used to detect >10 leukocytes per high power field (sensitivity of 75 to 96 percent; specificity of 94 to 98 percent) . A positive nitrite test is a reliable index of significant bacteriuria , although a negative test does not exclude bacteriuria .

24. URINE CULTURE The detection of bacteria in a urine culture is the diagnostic gold standard for UTI. should not be performed in nonpregnant patients without any symptoms consistent with a UTI, as bacteriuria does not indicate a UTI in an asymptomatic patient

25. TREATMENT

26. INDICATIONS FOR HOSPITALIZATION FOR COMPLICATED UTI Septic or critically ill patient persistently high fever ( eg , >38.4°C/>101°F) or pain marked debility, inability to maintain oral hydration or take oral medications. suspected urinary tract obstruction concerns regarding patient adherence. Other patient with uncomplicated UTI and acute complicated UTI of mild to moderate severity who can be stabilized can be managed in outpatient basis or emergency department and discharged on oral antimicrobials with close follow-up. Empiric antimicrobial therapy should be initiated promptly . taking into account risk factors for drug resistance.

27. Antimicrobial For Uncomplicated UTI

28. Antimicrobial in Other Conditions PREGNANCY Nitrofurantoin , ampicillin , and the cephalosporins are considered relatively safe in early pregnancy. Sulfonamides should clearly be avoided both in the first trimester (because of possible teratogenic effects) and near term (because of a possible role in the development of kernicterus ). Fluoroquinolones are avoided because of possible adverse effects on fetal cartilage development. P regnant women with ASB are treated for 4–7 days . With overt pyelonephritis , parenteral β- lactam therapy with or without aminoglycosides is the standard of care.

29. PROSTATITIS A 7- to 14-day course of a fluoroquinolone or TMP SMX is recommended if the uropathogen is susceptible. Therapy can be tailored to urine culture results and should be continued for 2–4 weeks . For documented chronic bacterial prostatitis , a 4- to 6-week course of antibiotics is often necessary. Recurrences, which are not uncommon in chronic prostatitis , often warrant a 12-week course of treatment.

30. RESPONSE TO THERAPY If therapy is appropriate , clinical response should occur within 24 hours with treatment of cystitis . With pyelonephritis , response should occur by 48 to 96 hours. Lack of response by 72 hours should be an indication for imaging studies. F our patterns of response of bacteriuria to antimicrobial therapy—cure, persistence, relapse, and reinfection Bacteriologic Cure is defined as negative urine cultures on chemotherapy and during the follow-up period, usually 1 to 2 weeks. Bacteriologic Persistence- It is persistence of significant bacteriuria after 48 hours of treatment. Causes are the urinary levels of the drug are inordinately low (i.e., from not taking the agent, insufficient dosage, poor intestinal absorption, or poor renal excretion, as in renal insufficiency or resistent strain.

31. RELAPSE AND REINFECTION If UTI is recurrent it is necessary to distinguish between relapse and reinfection . Relapse is diagnosed by recurrence of bacteriuria with the same organism within 7 days of completion of antibacterial treatment and implies failure to eradicate infection usually in conditions such as stones, scarred kidneys, polycystic disease or bacterial prostatitis . Reinfection is when bacteriuria is absent after treatment for at least 14 days, usually longer, followed by recurrence of infection with the same or different organisms . This is the result of reinvasion of a susceptible tract with new organisms. Approximately 80% of recurrent infections are due to reinfection

32. NONANTIMICROBIAL THERAPY A high (2 L daily) fluid intake is encouraged during treatment. Increased fluid intake has some disadvantages of increased vesicoureteral reflux and possibly cause acute urinary retention in the partially obstructed bladder. The larger urine output results in dilution of antibacterial substances normally present in the urine and may make symptoms of dysuria worse. To acidify the urine , it is often necessary to modify the diet by restriction of agents that tend to alkalinize the urine (e.g., milk, fruit juices [except cranberry juice], sodium bicarbonate) Use of Canberry juice - disable the ability of E. coli to adhere to the epithelial cells of the urethra. Analgesics can be used if flank pain or dysuria is severe.

33. Prophylactic Measures For Recurrent UTI 2 L daily fluid intake . V oiding at 2- to 3-hour intervals with double micturition if reflux is present . Voiding before bedtime and after intercourse avoidance of spermicidal jellies and bubble baths and other chemicals in bathwater. avoidance of constipation, which may impair bladder emptying . Nitrofurontoin 50-100mg at bedtime daily.

34. ASB The presence of bacteriuria (≥10 5 colony-forming units/ mL of a uropathogen ) with or without pyuria in the absence of any symptom that could be attributable to a UTI is called asymptomatic bacteriuria and generally does not warrant treatment in nonpregnant patients who are not undergoing urologic surgery. Asymptomatic bacteriuria during pregnancy has been associated with adverse pregnancy outcomes, increased risk of preterm birth, low birth weight, and perinatal mortality . It is also assossiated with risk of progression to pyelonephritis because of pressure on the bladder and ureters from the enlarging uterus. ASB is treated in pregnancy, urological surgery and renal transpant patient.

35. Approach in ASB

36. CATHETER-ASSOCIATED UTI It is bacteriuria with symptoms of UTI in a catheterized patient . A ccepted threshold for bacteriuria to meet the definition of CAUTI is ≥103 CFU/ mL of urine. The etiology of CAUTI is diverse , and urine culture results are essential to guide treatment. Treatment is usually avoided in asymptomatic patients, as this may promote antibiotic resistance. E vidence supports the practice of catheter change during treatment for CAUTI . The goal is to remove biofilm -associated organisms that could serve as a nidus for reinfection . Antimicrobial catheters impregnated with silver or nitrofurazone have not been shown to provide significant clinical benefit.

37. COMPLICATIONS Acute Complicated UTI Sepsis Multiple organ system dysfunction Shock Acute renal failure. Acute Pyelonephritis R enal corticomedullary abscess P erinephric abscess E mphysematous pyelonephritis P apillary necrosis Xanthogranulomatous pyelonephritis

38. EMPHYSEMATOUS PYELONEPHRITIS Emphysematous pyelonephritis is a gas-producing , necrotizing infection involving the renal parenchyma and, in some cases, perirenal tissue. Diabetes mellitus and urinary tract obstruction are the major risk factors. These infections are usually due to Escherichia coli or Klebsiella pneumoniae , other causative organisms include Proteus , Enterococcus , Pseudomonas , Clostridium , and, rarely, Candida spp. Diagnosis by plain films of the abdomen and/or computed tomography (CT). Such radiographs reveal air in the renal parenchyma, bladder, or surrounding tissue in 50 to 85 percent of cases

39. Clinical features are fevers, chills, flank or abdominal pain, nausea, and vomiting. Treatment includes nephrectomy or open drainage along with systemic antibiotics.

40. XANTHOGRANULOMATOUS PYELONEPHRITIS This is an uncommon chronic interstitial infection of the kidney most often caused by Proteus Clinically presents with fever, weight loss, loin pain and a palpable enlarged kidney. It is usually unilateral and associated with staghorn calculi. CT scanning shows up intrarenal abscesses as lucent areas within the kidney. Nephrectomy is the treatment of choice; antibacterial treatment rarely, if ever, eradicates the infection.

41. REFLUX NEPHROPATHY This was called chronic pyelonephritis or atrophic pyelonephritis , and it results from vesicoureteric reflux, infection acquired in infancy or early childhood. There is papillary damage, tubulointerstitial nephritis and cortical scarring in areas adjacent to ‘ clubbed calyces’. Diagnosis based on CT of kidney Meticulous early detection and control of infection , with or without ureteral reimplantation to create a competent valve, can prevent further scarring and allow normal growth of the kidneys

42. URETHRAL SYNDROME It is a bacteriuric frequency or dysuria . Common causes are postcoital bladder trauma, vaginitis , atrophic vaginitis or urethritis in the elderly, and interstitial cystitis ( Hunner’s ulcer). Interstitial cystitis is an uncommon condition affecting women over the age of 40 years. It presents with frequency, dysuria and often severe suprapubic pain. Cystoscopy shows typical inflammatory changes with ulceration of the bladder base.Treatment include oral prednisolone therapy, bladder instillation of sodium cromoglicate or dimethyl sulphoxide and bladder stretching under anaesthesia. Predominant frequency and passage of small volumes of urine (‘ irritable bladder ’) is possibly consequent on previous UTI or conditioned by psychosexual factors .

43. References Uptodate 2021 Harrison's Principles of Internal Medicine, 20 th Edition. Davidson Principles and Practice of medicine 23 rd Edition. Kumar & Clark's Clinical Medicine, 7th Edition Mandell , Douglas, and Bennett's Principles and Practice of Infectious Disease, Eight Edition

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