Urinary tract infections (Dr.Waqqas).pptx

Basics of urinary tract infections like its types, etiology, pathogenesis, clinical features, diagnosis with a microbiological point of view.

1. CASE : A 32 year old female was admitted with dysuria (burning micturition) and increased frequency of micturition for the past 2 days. Culture of the urine specimens revealed lactose fermenting colonies on MacConkey agar. What is your clinical diagnosis and probable etiological agents ? 1

2. PRESENTED BY: WAQQAS AHMED ABHISHEK ALLAD UMESH K MAHAVER 2

3. 3 Unmasking the silent invader : a journey through urinary tract infections

4. CONTENTS URINARY TRACT INFECTION ; CLASSIFICATION NORMAL COMMENSALS DEFENCE MECHANISMS PREDISPOSING FACTORS ETIOLOGY PATHOGENESIS CLINICAL MANIFESTATIONS LAB DIAGNOSIS TREATMENT ETIOLOGICAL AGENTS OF UTI ; BACTERIAL INFECTION VIRAL INFECTION PARASITIC INFECTION FUNGAL INFECTION 4

5. 5 CLASSIFICATION

6. A brief comparison Upper UTI: Kidney , ureter Local n systemic manifestations (fever vomiting abdominal pain) Both ascending(common) and descending routes Less common Lower UTI: Bladder, urethra. Local manifestations : dysuria, urgency, frequency Ascending route More common 6

7. Normal commensals Anaerobes CONS Diptheroids Lactobacillus Potential pathogens : --- enterobacteriaceae , candida sp. 7

8. host Defense mechanisms: Urinary factors : Acidic High osmolality Inhibit bacterial adherence Mechanical flushing Mucosal immunity : 1. cytokines LPS 2. Mucosal IgA Prevent attachment of pathogen 3. Tamm-Horsfall protein (uromodulin) (gp)  anti-adherence factor. 4. Zinc (prostate)  bactericidal 5. Long urethra 8

9. Predisposing factors PREVALENCE  ~10% humans develop UTI at some part GENDER  predominant in females, (short urethra and close proximity of urethral meatus to anus) AGE  during 1 st year , 2% prevalence for both m & f.  male incidence decrease until old age (prostate enlargement )  female incidence keeps increasing , adult – 10 -20%  reinfection – ~ 50% of females of 20-40 years age PREGNANCY due to anatomical and hormonal changes, mostly asymptomatic but sometimes can affect both mother and fetus 9

10. Continued … ABNORMALITY OF UT BACTERIAL VIRULENCE  pili  bacterial adhesion VESICO-URETERAL REFLUX  failure of valve mechanism GENETIC FACTORS  genetically determined receptors present on uroepithelial cells may help in bacterial attachment. Structural ( urethral stricture, stones, prostate, tumor, renal transplant) Functional (neurogenic bladder, due to spinal cord injury or multiple sclerosis) Obstruction and urinary stasis 10

11. etiology GNB Enterobacteriaceae E.coli ( most common, 70%) Klebsiella Enterobacter , proteus , serratia Non-fermenters: pseudomonas acinetobacter. GPB : M.Tb GPC : enterococcus staphylococcus ( aureus , saprophyticus ,epidermidis , agalactiae ) Fungus : candida albicans Parasite : schistosoma haematobium trichomonas vaginalis dioctophyme renale Virus : BK virus adenovirus type 11 and 21 11

12. pathogenesis Bacteria invade UT by 2 routes : ascending and descending routes Ascending route Sexual intercourse enteric endogenous bacteria enter Catheterization the urinary tract. COLONIZATION (adhesion to urethral epithelium) ASCENSION (pathogen ascend to bladder to cause cystitis, facilitated by bac toxins which inhibit peristalsis) 12

13. FURTHER ASCENSION ( vesicoureteric reflux , reach to kidney leading to pyelonephritis ) ACUTE TUBULAR INJURY ( inflammatory cascade continues, tubular obstruction and damage occurs which may lead to interstitial nephritis ) DESCENDING ROUTE (5% of total UTI) BACTEREMIA  HEMATOGENOUS SPREAD TO KIDNEY  INVASION OF RENAL PARENCHYMA Certain organism associated with pyelonephritis indicates descending route (staph. Aureus, salmonella, M.Tb, leptospira) 13

14. CLINICAL MANIFESTATIONS 14

15. ASYMPTOMATIC BACTERIURIA CYSTITIS ACUTE URETHRAL SYNDROME PYELONEPHRITIS Seen in young sexually active females Classic symptoms of lower UTI Bacterial count is often low Pyuria is present AGENTS : mostly due to usual agents of UTI , a few cases may be caused by gonococcus , chlamydia, herpes simplex virus . Inflammation of kidney parenchyma, calyces and renal pelvis . Serious complication of UTI 15

16. LAB DIAGNOSIS SIGNIFICANT BACTERIURIA SPECIMEN COLLECTION TRANSPORT DIRECT EXAMINATION CULTURE ANTIBODY COATED BACTERIA TEST “ Even your waste is not wasted!” 16

17. KASS CONCEPT OF SIGNIFICANT BACTERIURIA (CFU/ml) count of ≥ 10^5  significant 10^4 - 10^5   doubtful significance, correlate clinically <10^4  non-significant, due to commensals Low count can be significant in : Pt on antibiotic or diuretic G+ organism (S.aureus) Pyelonephritis and acute urethral syndrome Suprapubic aspiration Catheterized symptomatic pt , even ≥10^3 is significant Specimen collection 1.Clean voided midstream Urine 2. Suprapubic aspiration 3.Catheter tube 17

18. Transport : sample to be processed immediately , if delay is expected for 1-2 hrs , store in refrigerator or add boric acid for max 24hrs Direct examination : wet mount  pyuria >8 pus cells/mm ³ leukocyte esterase test  rapid , cheap. nitrate reduction ( Griess ) test : +ve for nitrate reducing E.coli Gram staining  not reliable indicator 18

19. CULTURE CULTURE MEDIA : CLED or MCA+BA QUANTITATIVE CULTURE: (counting number of colonies) each colony on plate = one bacterium in urine done by  semi-quantitative (standardized loop technique) quantitative (pour plate method) COLONY APPEARANCE : depends on organism grown . IDENTIFICATION : automated MALDI-TOF or VITEK , or conventional biochemical tests. AST : disk diffusion test (MHA) or automated MIC based methods (VITEK) 19

20. Culture Culture smear and motility testing Biochemical reactions Escherichia coli MAC or CLED : Flat LF BA : gray moist colonies GNB MOTILE Klebsiella pneumoniae MAC or CLED: mucoid LF BA: gray mucoid colonies GNB NON MOTILE Proteus sp MAC or CLED: NLF BA: swarming type of growth GNB (pleomorphic) MOTILE Enterococcus MAC: magenta pink colonies BA: translucent non hemolytic GPC in pair , spectacle shaped NON MOTILE BILE ESCULIN +VE Staph aureus BA: golden yellow hemolytic colonies GPC in clusters NON MOTILE Staph saprophyticus BA: white non hemolytic GPC in clusters NON MOTILE 20

21. ANTIBODY COATED BACTERIA TEST Differentiates upper and lower UTI Upper UTI Due to hematogenous spread , bacteria coated with specific antibodies are found in urine such antibody coated bacteria are detected by immunofluorescence method using fluorescent antihuman globulin. Lower UTI Bacteria found in urine are never coated with specific antibodies . 21

22. TREATMENT Based on AST , Quinolones ( norfloxacin ) Nitrofurantoin Cephalosporins Aminoglycosides Higher antibiotics such as carbapenam (meropenem) Piperacillin - tazobactam Fosfomycin Are used for healthcare associated UTI caused by MDR GNB 22

23. BACTERIAL INFECTIONS OF URINARY TRACT 23

24. BACTERIA CAUSING UTI 24

25. E coli Klebsiella Staphylococcus aureus 25

26. ENTEROBACTERIACEAE CAUSING UTI Gram negative rod shaped bacteria, facultative anaerobes Enterobacteriaceae are important human pathogens and are responsible for diseases such as UTI , gastroenteritis and septicemia . Most important is E. coli . 26

27. UROPATHOGENIC E.COLI UPEC is most common pathogen of UTI 70-75% of all UTI cases. Serotypes : O1, O2, O4, O6, O7 and O75 . Virulence factors of UPEC are: 1) CYTOTOXINS –CNF1 and SAT 2)HEMOLYSINS 3)FIMBRIAE 4) CAPSULAR K ANTIGEN 27

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29. KLEBSIELLA PNEUMONIAE UTI It is usually found as commensal in human intestines It causes infections similar to E. Coli such as UTI, meningitis (neonates), septicemia, and pyogenic infections such as abscesses and wound infections. 29

30. Enterobacter UTI Enterobacter have become increasingly important nosocomial pathogens. They are opportunistic pathogens, implicated in infected wounds, UTI and pneumoniae 30

31. Citrobacter infections These are mostly environmental contaminants isolated from water, soil, food, and feces of man Important species are C.Freundii and C.Koseri They occasionally cause UTI, gall bladder and middle ear infections. Identification is made by MALDI-TOF and VITEK . Or by biochemical tests Treatment: guideline for treatment is same as E. coli 31

32. Proteeae infections Proteae has three genera: Proteus, Morganella and Providencia. There are two antigens – H antigen and O antigen 1)H antigen – flagellar antigen 2)O antigen – somatic antigen Pathogenesis Proteus mirabilis and vulgaris are most common Saprophytes Commensals Infections associated – urinary, wound and soft tissue infections and septicemia, nosocomial outbreaks Struvite stones in bladder – produces urease enzyme to break down urea and forms ammonia that damages renal epithelium and makes urine alkaline. Alkaline urine predisposes to the deposition of phosphate, which leads to formation of renal calculi. 32

33. Laboratory diagnosis of Proteus Pleomorphism : gram negative coccobacilli Odor : putrid fishy or seminal odor in cultures Swarming : ability to swarm on solid media like blood agar, may extend on the whole plate (continuous swarming) or present as concentric circles of growth surrounding the point of inoculum(discontinuous swarming) 33

34. Identification : Automated systems  MALDI-TOF or VITEK Conventional biochemical tests : Catalase +ve Oxidase –ve Indole +ve for P. vulgaris and – ve for P. mirabilis Citrate +ve/-ve Urease +ve TSI -- alkaline/acid (K/A) gas variably present, H2S +ve 34

35. Morganella Species : M. morganii Found in human and animal feces Rarely associated with UTI, pneumonia and wound infection Mostly nosocomial 35

36. Providencia Species : P. rettgeri , P. stuartii , P. alcalifaciens , P. rustigianii , P. heimbachae Nosocomial infections of urinary tract, wounds and burns 36

37. Treatment of Proteeae infections Aminoglycosides 4 th generation Cephalosporins – Cefepime Carbapenems 37

38. Enterococcal infections Most common gram positive cocci causing UTI Virulence factors : Pheromones – help in adjacent cells to facilitate plasmid exchange Extracellular surface protein ESP – helps in adhesion to bladder mucosa Common group D lipoteichoic acid antigen – induces cytokine release like TNF – α 38

39. Clinical manifestations : Urinary tract infections – Health care associated UTU, cystitis is the most common infection caused by enterococci Chronic prostatitis – enterococci can cause chronic prostatitis when urinary tract is manipulated surgically or endoscopically. Bacteraemia and left sided endocarditis involving mitral and aortic valves Intraabdominal, pelvic and soft tissue infections Neonatal infections such as sepsis and meningitis 39

40. Laboratory diagnosis Specimen – urine, blood, exudate, peritoneal fluid Microscopy – gram positive oval cocci arranged in pairs at an angle to each other(spectacle shaped) Culture – a) Blood agar : non hemolytic transculent colonies( rarely α or β hemolysis) b) MacConkey agar : minute magenta pink colonies 4. Bile esculin hydrolysis test – positive 5. E. faecium and E. faecalis differentiated by arabinose fermentation test 6. Accurate identification by MALDITOF / VITEK 40

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42. Treatment For less serious infections – ampicillin, nitrofurantoin or Fosfomycin orally For invasive infections – combination therapy with a cellwall active agent (penicillin or ampicillin) and an aminoglycoside(gentamicin) If resistant to vancomycin, then linezolid streptogramins and daptomycin 42

43. Renal Tuberculosis Genitourinary TB accounts for 10-15% of all extrapulmonary TB Symptoms – dysuria, nocturia, hematuria, flank and abdominal pain, urinary frequency Urinalysis – gives abnormal results – pyuria and hematuria Sterile pyuria – presence of pus cells, negative for routine bacterial urine culture Urine culture for TB – MGIT – Mycobacterium Growth Indicator Tube and LJ medium Radiology – Abdomen CT/MRI shows deformities, obstructions, calcifications, ureteral strictures Treatment – antitubercular therapy 43

44. Post streptococcal glomerulonephritis PSGN Serotypes – following streptococcal pyoderma caused by M serotypes – 47, 49, 55, 57, 60 or rarely following pharyngitis caused by M serotypes 1-4, 12, 25 Pathology – lodging of antigen antibody complexes on glomerular basement membrane followed by complement activation. Streptococcal pyogenic exotoxin B maybe main the nephritogenic antigen involved 44

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46. Clinical presentation Urine retention renal insufficiency, edema, HTN, hematuria, pyuria, proteinuria, oliguria. Diagnosis Elevated streptococcal anti DNase B antibodies compared to rise of ASO and antihyaluronidase Anti-DNase B antibodies titre more than 300-350 units/mL is diagnostic of PSGN and pyoderma. Prognosis Occurs in children 2-14 yrs Good prognosis 46

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48. Perinephric and renal Abscess Develops secondary to UTI rather than direct hematogenous spread Abscess formation – infections ascends from bladder, to kidney then renal parenchyma to produce abscess. Abscess in parenchyma may rupture into perinephric space and cause perinephric abscess Major risk factor – pre-existing renal stones Etiologies – E. coli, Kklebsiella and proteus species Treatment – drainage of pus and antibiotic therapy 48

49. Parasitic infections of urinary system Schistosoma haematobium Trichomonas vaginalis urethritis Dioctophyme renale infection #STD 49

50. Parasitic infections of urinary system Schistosoma haematobium Trichomonas vaginalis urethritis Dioctophyme renale infection #STD 50

51. Urinary schistosomiasis ( bilharziasis ) Schistosomiasis is extremely rare in India Endemic in 53 countries in the middle east, the African continent (across Nile river valley) and the Indian ocean islands (Madagascar, Zanzibar and Pemba) 51

52. Pathogenesis and clinical features Acute  dermatitis at penetration site followed by allergic pruritic papular lesions Chronic  urogenital disease  obstructive uropathies  bladder carcinoma metaplastic changes in urinary mucosa may lead to carcinoma of bladder m/c scc  involvement of other sites - spinal cord -liver, lungs, intestine. 52

53. Urogenital disease Light infection may be asymptomatic , symptoms develop after 3-6 months Main pathogenic mechanism is deposition of egg  Soluble antigens released from eggs provoke delayed type of hypersensitivity rxn  formation of egg granuloma  later undergoes fibrotic changes Heavy infection , deposition of eggs in scrotal lymphatics  elephantiasis in scrotum & penis S. haematobium may be an imp risk factor for potential activation & transmission of HIV Terminal spine  damage bladder mucosa dysuria & hematuria antigens DTH EGG GRANULOMA FIBROTIC CHANGES Obstruction to lower ureter Hydroureter & hydronephrosis 53

54. Lab diagnosis Urine microscopy Terminal hematuria portion of urine is collected b/w 12 to 3pm , concentrated by centrifugation or by membrane filtration , Detection of non - operculated terminal spined egg Histopathology Demonstrate eggs  Bladder mucosal biopsy or wet cervical biopsy specimens ( in females ) Antibody detection Antibodies against HAMA – S.haematobium adult worm microsomal antigen HAMA-FAST-ELISA HAMA-EITB Elevated IgE and IgG4 Antigen detection (ELISA or dipstick assay) Indicates recent infection Used for monitoring treatment response Useful when urine microscopy fails to detect eggs CCA and CAA (circulating cathodic & anodic antigens) 54

55. PRAZIQUANTEL is DOC , given 20 mg /kg /dose , two doses in single day METRIFONATE can be given alternatively , it is administered in multiple oral doses over weeks ; hence not preferred in control programs. 55

56. Dioctophyme renale infection (giant kidney worm) Commonly known as giant kidney worm is a nematode of lower animals , human infection is extremely rare . LIFE CYCLE : ingestion of fish infected with larva  larva penetrates intestine and reach kidney  transform into adult worm  large adult worm can block kidney and ureter  lay eggs , passed in urine. CLINICAL FTS : hematuria and renal colic, extensive destruction of kidney parenchyma may occur LAB DIAGNOSIS : eggs in urine , eggs are oval shaped, contain an embryo surrounded by characteristic thick sculptured or pitted egg shell NO STANDARD TREATMENT IS AVAILABLE PREVENTION : proper cooking of fish before consuming. 56

57. Adenovirus cystitis BK virus infection Viral infection of urinary tract 57

58. Polyomavirus family, ds DNA . Bk virus causes nephropathy in kidney transplant recipients, Can also cause hemorrhagic cystitis in HSC transplant recipient. BK VIRUS DIAGNOSIS RENAL BIOPSY shows inflammatory infiltrate, fibrosis and tubular injury. +ve immunohistochemistry PCR identification of BK viremia (BK virus DNA in blood) +features of nephropathy Asymptomatic BK viruria less specific , may not be clinically significant. There is no specific treatment available, BUT Cidofovir used for refractory cases 58

59. ADENOVIRUS CYSTITIS ADENOVIRUS serotypes 11 and 21 can cause acute hemorrhagic cystitis in children, especially in boys. Standard treatment of this disorder consists of hydration, diuresis and analgesics. Failure of this measures leads to multiple blood transfusions, severe patient morbidity And possible death When conservative therapy is unsuccessful, there is no proved standard of care. 59

60. Fungal infections of urinary tract Candiduria 104 – 105 CFU\ml of yeasts detected from urine Causes : Contamination during collection, bladder colonization or upper UTI due to hematogenous or ascending infection from bladder No treatment recommended for asymptomatic patient. 60

61. Treatment in following situations  symptomatic cystitis or pyelonephritis  neutropenic or immunosuppressive  critically-ill patients ( higher risk of invasive candidiasis)  low birth weight infants  pt undergoing urologic manipulation  if upper pole \ bladder wall invasion\obstruction is associated. DOC  fluconazole 14 days Fluconazole resistance   oral flucytosine or parenteral amphotericin B 61

62. references Apurba S Sastry , Essentials of MEDICAL MICROBIOLOGY. 3 rd edition Baveja textbook of microbiology , 5 th edition Ananthanarayan and paniker textbook of microbiology. Sciencephotolibrary.com Asiaresearchnews.com shutterstock.com Sciencedirect.com 62

63. Any doubts ? Any suggestions ? 63

64. THANK YOU The end