Microbiology of the Urinary Tract PDF

Microbiology of the Urinary Tract Dr Dave Hamilton MRCP FRCPath BSc Microbiology York Trust Learning Outcomes 1. Outline the syndromes of urethritis, cystitis and pyelonephritis 2. Describe the epidemiology of urinary tract infections (UTI) 3. Describe the nature of the common organisms causing UTI...

Microbiology of the Urinary Tract Dr Dave Hamilton MRCP FRCPath BSc Microbiology York Trust Learning Outcomes 1. Outline the syndromes of urethritis, cystitis and pyelonephritis 2. Describe the epidemiology of urinary tract infections (UTI) 3. Describe the nature of the common organisms causing UTI 4. Describe the diagnostic criteria for UTI 5. Outline the role of antibiotics in the prevention and management of uncomplicated UTI 6. Be enthralled by our immune system Urinary tract infection classification Route of acquisition – Ascending versus haematogenous Site of infection – Involvement of urethra – urethritis (lower) – Involvement of bladder – cystitis (lower) – Involvement of kidney – pyelonephritis (“upper UTI”) Community-acquired versus nosocomial Urinary tract infection - epidemiology How frequent are they? Who gets them? When do they get them? What causes them? Why do get they them? UTI – how frequent are they? Most common bacterial infection seen in primary care (5% of all consultations) About 5% of women each year present to their GP with UTI symptoms. Up to 50% of women, during their lifetime, will suffer from a symptomatic UTI (1 in 5 of these will experience one or more recurrences) Commonest cause of nosocomial infection T Hooton Uncomplicated Urinary Tract Infection,Engl J Med 2012; 366:1028-1031. Who gets UTI and when do they get them? Which bacteria cause UTI? Commonest cause of UTI is Escherichia coli UTI-causing (uropathogenic) E. coli (UPEC) are distinct from other disease causing types e.g. E. coli O157 which are associated with intestinal disease UPEC belong to a restricted number of serotypes They are members of the bacterial flora of the large bowel Resident population of UPEC important in individuals who experience relapsing/recurring UTI M Wilson and L Gaido Laboratory Diagnosis of Urinary Tract Infections in Adult Patients Clin Infect Dis. 2004; 38:1150–8 Other causes of UTI Viruses – Adenoviruses Associated with haemorrhagic cystitis – BK and JC viruses Associated with infection and graft failure in patients following kidney transplants Mycobacterium tuberculosis Parasitic infection – Schistosoma haematobium A Kumar, J Turney, A Brown and M McMahon1 Unusual bacterial infections of the urinary tract in diabetic patients—rare but frequently. lethal. Nephrol. Dial. Transplant. (2001) 16 (5): 1062-1065 Two principal routes of acquisition Ascending – From urethra to bladder (causing cystitis) – From the bladder to the kidney (causing pyelonephritis) Haematogenous – From blood to kidney (causing pyelonephritis or renal abscess) Host defences against UTI Urine flow and micturition Urine chemistry (osmolality; pH; organic acids) Secreted factors – sIgA (secretory IgA) – Lactoferrin: an iron chelator Mucosal defences – Mucopolysaccharides - glucoseaminoglycan – Few receptors Bacterial virulence factors Uropathogenic E. coli – Type 1 fimbriae – Bind to mannose residues on host cells – Associated with cystitiscausing strains Are you experienced? Understanding bladder innate immunity in the context of recurrent urinary tract infection. O'Brien et al. Curr Opin Infect Dis. 2015 Feb;28(1):97-105 Bacterial virulence factors Uropathogenic E. coli – Type P fimbriae adhere to urinary tract cells – K Antigen – Prevents immune cells phagocytosing the E.coli Both help cause infection, especially of the upper tract - pyelonephritis Risk Factor Explanation Female sex Shorter urethra Urethra opens into introitus Closer to perineum/anus Anatomic abnormality e.g. Congenital abnormalities of urinary tract Diverticula Prostatic hypertrophy Reflux of urine from bladder to kidney Stagnant urine Residual urine after incompleted emptying of bladder Functional abnormality Neurological disorders Spina bifida Multiple sclerosis Incomplete emptying of bladder Requirement for catheterisation Catheterisation Bypasses host defences Acts as foreign body Biofilm formation Pregnancy Dilated ureters Imcomplete bladder emptying Gestatinal glycosuria? Foreign body (e.g. stones) Mucosal damage Bacteria less accessible to host defences Urinary tract surgery/instrumentation Mucosal damage Direct introduction of bacteria into tract Patients may have pre-op infection/bacteriuria Patients frequently catheterized Insertion of foreign bodies e.g. stents Stalenhoef van Dissel, van Nieuwkoop. Febrile urinary tract infection in the emergency room. Curr Opin Infect Dis. 2015 Feb;28(1):106-11 UTI in pregnancy Bacteriuria and lower UTI – Some studies show Associated with lower birth weight Premature delivery Increased perinatal morbidity Increased risk of development of pyelonephritis (in up to 30% of infections) Also associated with prematurity, low birth weight Foetal loss The patient with UTI Cystitis – – – – – Frequency Dysuria Urgency Suprapubic discomfort Fever usually absent or low grade – In infants Failure to thrive Poor feeding – In elderly Signs may be absent Sudden onset of confusion Pyelonephritis – May have symptoms of cystitis – Loin pain – Fever – Rigors – Renal angle tenderness Diagnosis of UTI - Urinalysis Detects High negative predictive value (good at ruling out UTI) – Protein Positive predictive value is lower (some false positive’s) – Blood Nitrite may be falsely negative – Leucocyte esterase – Nitrites – Some bacteria just are – Low numbers of bacteria Leukocyte esterase may be falsely negative – Patient taking antibiotics E.g. cefalexin – High glucose in urine Laboratory diagnosis of UTI – urine microscopy White cells – Presence suggests UTI Epithelial cells – Presence suggests contamination Red cells – In females may be associated with menstruation – Can occur in infection.. – …but may also be seen with stones/tumours Diagnosis of UTI In this real urine result there is a low number of red cells, a high number of white cells (WBC) suggesting infection and a low number of epithelial cells suggesting contamination is unlikely. Diagnosis of UTI In this case E coli has been cultured. Sensitivities to the most useful antibiotics for UTI have been provided. Nosocomial UTI Commonest nosocomial infection May follow urological surgery or instrumentation… But most are associated with urinary catheterisation Urinary catheters Bypass defence mechanisms of lower urinary tract Act as a foreign body Bacterial form biofilm on catheters 5% -10% increase in prevalence of bacteriuria each day the catheter remains in situ Nicolle LE Catheter associated urinary tract infections. Antimicrob Resist Infect Control. 2014 Jul 25;3:23 Catheter-associated UTI prevention What works – Not catheterising the patient – Limit duration of catheterisation – Aseptic insertion – Closed drainage systems – In some patients Ag++-bonded catheters What doesn’t work – Application of soap/antiseptics to urethral meatus – Disinfectants in drainage bag – Antiseptic/antibiotic irrigation of bladder Urinary catheters All catheters eventually get colonised Catheter-associated bacteriuria does NOT require antimicrobials Only treat if the patient has signs/symptoms of infection “Urethral syndrome” As many as 50% of women with clinical features of cystitis have negative urine cultures Explanation – Low counts of bacteria – Fastidious bacterial which do not grow on routine culture media eg ureoplasma – Non-infective inflammation – Sexually transmitted pathogens such as Chlamydia trachomatis Phillip H1, Okewole I, Chilaka V. Enigma of urethral pain syndrome: why are there so many ascribed etiologies and therapeutic approaches? Int J Urol. 2014 Jun;21(6):544-8. 2014 Jan 21. Management of uncomplicated lower UTI Maintain good hydration May resolve spontaneously – 50% in otherwise fit women If antimicrobials indicated – Short courses (3d) are as effective as longer… …and reduce selective pressure for resistance …and may result in fewer side effects Choice of antimicrobials – Depends on local resistance patterns – Agents which achieve high concentrations in urine Antimicrobial Features Trimethoprim Cheap Active against most agents of uropathogens associated with uncomplicated UTI Nitrofurantoin Very high urine concentrations achieved Not active against Proteus species Does not achieve effective concentrations in kidney and should NOT be used if upper tract infection suspected Ampicillin/amoxicillin Should NOT be used empirically high rates of resistance (65-70% in E. coli) Quinolones – e.g. ciprofloxacin NOT indicated for empiric therapy Management of recurrent UTI Women with >3 episodes annually may benefit from antimicrobial prophylaxis – Optimal duration not identified – But 6 month’s Rx often used – “Rotation” of antibiotics – Despite limited evidence Other interventions – Voiding post-intercourse – HRT in post-menopausal women Alternative approach – Self-medication proanthocyanidins Management of recurrent UTI Women with >3 episodes annually may benefit from antimicrobial prophylaxis – Optimal duration not identified – But 6 month’s Rx often used – “Rotation” of antibiotics may help prevent emergence of resistance Other interventions – Voiding post-intercourse – HRT in post-menopausal women Alternative approach – Self-medication proanthocyanidins Management of recurrent UTI Women with >3 episodes annually may benefit from antimicrobial prophylaxis – – – Optimal duration not identified But 6 month’s Rx often used “Rotation” of antibiotics may help prevent emergence of resistance Other interventions – – Voiding postintercourse HRT in postmenopausal women Alternative approach – Self-medication In 2008, the Cochrane review supported cranberry potential use only in recurrent UTI prophylaxis for young women. Even for this indication, further clinical trials (double-blinded, randomized, placebo-controlled) displayed no differences between cranberry consumption and controls. The efficacies in other groups of subjects, such as the elderly or paediatric populations with neurogenic bladder, are even more questionable. Hisano M. Cranberries and lower urinary tract infection prevention. Clinics. 2012 Jun; 67(6): 661–667 Children Send urine sample if temp >38c for >24 hours Clean catch Pad Suprapubic aspirate Children 3 years leukocyte esterase and nitrite Children risk factors poor urine flow history suggesting previous UTI or confirmed previous UTI recurrent fever of uncertain origin antenatally-diagnosed renal abnormality family history of vesicoureteric reflux (VUR) or renal disease constipation dysfunctional voiding enlarged bladder abdominal mass evidence of spinal lesion poor growth high blood pressure. Children Treatment Lower tract: – Amoxicillin, trimethoprin or cephalexin Upper Tract Mild – Co-amoxiclav Upper Tract severe – Cefotaxime or gentamicin < 3 months ‘Fever in the Under 5’s NICE guideline CG160’ Children In children infection may indicate underlying abnormalities of the urinary tract. Imaging may be appropriate. Urinary tract infection in under 16s: diagnosis and management. NICE 2007,CG54. Children Summary UTI are common Upper/lower and simple/complicated Microbial host interactions Diagnosis Treatment Children and catheters [email protected] Very happy to discuss any issues around inection through your learning journey.