UTIs & Treatment
IBC
* intracellular bacterial communities - stay, change morphology, become filamentous, resist phagocytosis - theory = recurrent UTIs happen b/c of IBCs
Fosfomycin - MOA & what it treats
- 40% bioavailable - interferes w/ cell-wall synthesis (like beta-lactams) - also inhibits phosphoenolpyruvate synthetase - TREATS gram-positive & gram-negative bacteria - active against some MDR gram-neg rods, ESPECIALLY ESBLS - Pseudomonas & acinetobacter are often resistant
45 y/o man w/ type I diabetes & neurogenic bladder performs self-catheterization using good technique - shows up c/o dysuria & bladder spasms but no fever or flank pain - urine sample detects leukocyte esterase (WBCs) & nitrites (bacteria) on dipstick - most likely has ? Best empiric choice of antibiotics is?
- Acute cystitis - Treat w/ Nitrofurantoin
27 y/o woman admitted to hospital w/ 1 day of fever/chills & right-sided flank pain - PMH is normal & ROS is notable for 3 days of dysuria/frequency - febrile & WBC is HIGH - looks uncomfortable & has right-sided costovertebral angle (CVA) tenderness to percussion - blood cultures show TONS of white cells in urine, 25 RBCs & 3+ bacteria Her diagnosis is? Gram stain shows a few GNRs - what is the most appropriate empiric choice of antibiotics for her infection?
- Acute pyelonephritis - IV ceftriaxone - why? - going to treat most of the E. colis
Types of UTIs -
- Ascending vs Descending - simple vs complicated
Clinical presentation
- Cystitis - inflammation of bladder - Dysuria - painful urination, frequency, nocturia - Pos urine cultures - Pyelonephritis - inflammation of kidney, flank pain, fever, nausea - Asymptomatic bacteriuria --> Bacteria may be in bladder or kidney - Two consecutive cultures of >105 CFU/ml of the same organism. --> Prostatitis: swelling of the prostate, can be caused by bacterial infection. • Perineal or suprapubic pain, hesitancy, fever • Bacterial cultures can be negative or vague
Descending UTIs
- Hematogenous infection - comes from BLOOD into the kidney - very RARE - going to be a LOT sicker than someone w/ a normal UTI
18 y/o present at health center c/o nausea, loss of appetite, & left flank pain for 5 days - was on holiday w/ boyfriend in Caribbean that summer & just moved into new dorm 6 days ago What is the most likely site of her primary problem?
- Kidney!
Pyuria without bacteruria -- could be __________________?
- NGU (STD), TB, Calculi, malignancy -- all can produce pus cells w/o bacteria
Upper UTI
- Pyelonephritis - fever, flank pain
Which infectious agent is the 2nd most common cause of ascending UTIs?
- Staph saprophyticus, 2nd to E. coli
(contd) c/o fever/chills (aka very high fever) off & on for 5 days - started at same time noted increased urinary frequency & dysuria - took leftover amoxicillin that she got for cystitis 4 months ago - treated it successfully then - WORRIED b/c noted blood in urine What tests would you order to diagnose the patient's problem? Which best represents the infectious agents likely to colonize the U tract of the woman? What led you to the conclusion that she had pyelonephritis & not cystitis?
- Urine culture - Staph saprophyticus, E. coli, Proteus, Pseudomonas * staph aureus is not a normal pathogen of the U tract - her fever, flank pain, & physical
Susceptibility testing is required for ...?
- all recurrent or complicated cases
Most strains of E. coli are sensitive to amoxicillin. What resulted in the amoxicillin resistance of her E. coli?
- amoxicillin taken for her previous infection selected a resistant variant of E. coli from her normal flora --> will not cause resistance, b/c antibiotic
Infectious Urolithiasis
- associated w/ Proteus spp & other UREASE producing organisms --> bring pH of urine up (alkalinizes) & give bacteria opportunity to grow - Urease --> causes precipitation of struvite stones - stones can serve as growth niche for bacteria
Always treat pregnant women w/ asymptomatic bacteruria - why?
- associated w/ increased incidence of maternal mortality & premature births - pyelonephritis later in pregnancy & UTI - TREAT AGGRESSIVELY - in non pregnant women, don't treat unless symptomatic - do treat in diabetics, someone undergoing urologic surgery, structural abnormality
32 y/o woman presents to gyno for routine exam - 18 weeks pregnant & doing well - c/o nausea/vomiting until 14th wk but since has had no complaints - has no other significant med hx - results of P/E are normal - results of lab studies are normal except urinalysis which shows 3+ bacteria. What is your conclusion?
- asymptomatic bacteruria, treatment needed
Type 1 pili mediated invasion
- bacteria induces cytoskeletal rearrangement - recruitment & activation of inflammatory cells (PMNs) - cell dies - bacteria is exfoliated - invasion of underlying epithelium, where it can remain for long periods of time by forming IBCs
Complicated infections
- caused by anatomic abnormalities - spread to other parts of the body, or are resistant to antibiotics - more difficult to cure
Who do you image?
- children - adults w/ recurrent UTIs - those who have blood in urine - complicated UTI
Lab Diagnosis
- clean catch midstream urine (MSU) - only specimen you have to quantify - chance of contamination w/ organisms on skin - catheterized or needle aspirate in newborns & infants = preferred
How does bacteria act?
- comes from colon, attaches & resists urine flush, can be internalized in bladder or kidney, then release cytokines causing inflammation - different strains produce different inflammatory results
To culture or not to culture? When do we culture?
- complicated UTI - MUST - pregnant women - obstruction of urine - immunocompromised - catheterized - repeated infections - neurogenic bladder - pyelonephritis - aka upper UTI
Women w/ sx of UTI - need to know if ---
- complicating conditions - pregnancy, etc. - back pain? - vaginal discharge? - if unclear do dipstick - if still unclear do culture
Bacteruria w/o Pyuria could be ______________ ?
- contamination or colonization
How do you prevent UTIs?
- don't put in Foley catheters !!!! - take them out the moment you can - do NOT give antibiotics (f*cks w/ the microbiome & can cause resistance) - good hydration - correct anatomic problems - remove stones - CRANBERRY juice -
Urethra
- females = very short - more exposed to perianal & perineal bacteria
Treatment (not drugs)
- fix predisposing factors to infection - remove catheter - control diabetes or other illness - correct obstruction
Urolithiasis
- formation of stones - due to formation of infectious or non-infectious causes
Phase variation
- gene expression of Type 1 & P pili is subject to this - can turn pili on or off depending on the environment - formation of the "on" complex depends on inversion (type 1) or differential methylation (P-pili)
E. coli virulence factors
- has Adhesins = P-pili & Type-1 pili - -
P/E & urine sample = temp of 39, left costovertebral angle tenderness, urine is cloudy & foul smelling --> Gram stain shows neutrophils (PMNs, pus cells) & long gram negative rods --> isolate on maconkey agar = shows no contamination w/ a significant count --> shows up pink = lactose fermenter
- has infected urine (pus) - probably has E. coli - pink = neutral red, pH change --> may be infected w/ Pseudomonas proteus ** lab says it is amoxicillin resistant, chloramphenicol resistant, gentamicin resistant E. coli - conclude she has Pyelonephritis due to E. coli
35 y/o man - c/o dysuria - no discharge, only burning/pain on urination - P/E = afebrile, normal vitals - Urinalysis = leukocyte esterase dipstick test positive = 20-30 WBCs, 0-5 RBCs & 3+ bacteria. What does he have?
- has simple, lower UTI - treat w/ long course antibiotics b/c is male
What led to the conclusion that she had pyelonephritis & not cystitis?
- her fever, flank pain, & physical
Why should you not use Nitrofurantoin for Kidney infection?
- it doesn't get into the kidney tissue very well
P-pili
- just the RECEPTORS are different from Type-1 pili - binds to digalactosides on human urinary tract cells - encoding gene = PAP --> pyelonephritis associated pili (a lot of cases w/ pyelonephritis, are associated w/ PAP, but not all) - P-pilus binds host cell & induces synthesis of other virulence factors - PAP genes are clustered on bacterial chromosome in Pathogenicity Islands
Antibiogram
- lists most commonly diagnosed bacteria in the hospital - tells you which organisms are most common, which ones are resistant to which antibiotics, how to treat them in general
Urinalysis
- look for WBCs - Normal = 2-5 WBCs (unless they are dehydrated, then it is more) - Infection = >10 - Leukocyte esterase test = detects WBCs, sometimes used to screen samples for culture - Automated urinalysis = more accurate, but anything > 5 indicates infection - Identifying via microscope = microscopic bacteruria = not a very reliable indicator (identify colony number) - Nitrite test = limited utility - GRAM stain of uncentrifuged urine = good! Urine culture = BEST METHOD - only specimen that requires quantification - don't leave sitting around in order to avoid contamination - quantitative calibrated loop method - CUTOFF = 10^2 CFU/mL
Ascending UTIs
- most common - go up from the colon/rectum - can cause cystitis & if they go up further, pyelonephritis ** infection of lower urinary tract --> bladder, urethra, both - infection of upper urinary tract --> pyelonephritis, infrarenal abscesses - infection of associated glands & tissues --> epididymitis, prostatitis
Toxicity of Nitrofurantoin
- nausea/vomiting - allergic rash - 1% & reversible pulmonary hypersensitivity (due to long-term use) - Beers criteria = avoid for long-term suppression in ages >65 OR w/ significant kidney dysfunction (won't get into them or you may become more toxic) - don't give to anyone w/ G6PD deficiency
Fosfomycin side-effects
- not bad = diarrhea, nausea, ab pain IV form = used in Europe, may be nephroprotective
What is the single most common reason for the increase in UTIs in older men?
- obstruction of the urethra
Simple (uncomplicated) infections
- occurs in healthy U tracts - doesn't spread to other parts of body - resolves readily WITHOUT treatment
Urine flush
- one of the best defenses against infection & will dislodge a lot of the bacteria that tries to hold on
Calculi formation
- partially d/t diet & dehydration - bacteria increase pH - attach - produce extracellular polysaccharide - crystals start attaching & precipate, getting bigger & bigger - they will dis-attach & reattach & then form a stone ** ONLY 10% are due to infection
Predisposing factors
- poor hygiene - intro of bacteria = during sex or catheter - obstruction preventing complete emptying of bladder = enlarged prostate, anatomic abnormalities, stones/adhesions - Neurogenic bladder blocking emptying - immunosuppression - temporary alteration in anatomy/physio (pregnancy, b/c of anatomical change) - others : low estrogen, spermicides, douching
Nitrofurantoin - MOA
- poorly understood, but interferes w/ replication of DNA? - bacteriacidal - works against various Gram-positive cocci including staph, enterococcus, & strep - also gram-negative enteric bacteria like E. coli NOT pseudomonas
Type-1 pili
- present in a lot of the E. coli found in our intestines - virulence factor that is also found in people w/o UTIs - but allows bacteria to bind to urethra, & bind to epithelium of bladder/kidney/ureters - attach to mannose-containing glycoproteins - proteinaceous appendages - just like hair - but tip is STICKY - usually peritrichous = expressed evenly on the surface
35 y/o woman w/ 2 days of burning on urination & today noticed blood in urine - married, monogamous - no h/o STDs - had UTI last year - WHAT else do you need to know to diagnose UTI?
- probably has acute cystitis - ask if sx are similar to previous time - ask if she has vaginal discharge - treat w/ Nitrofurantoin
Situations when lower counts may be significant
- pts being treated by antimicrobials - men - when organisms other than E. coli & proteus are present
Her urine grows a lot of E. coli AND extended spectrum beta-lactamase producer --> doesn't make sense, but then you find out her bf is veteran who returned w/ soft-tissue trauma w/ 2o infection --> he probably gave it to her. What is the best antibiotic now?
- still pretty sick, so must give IV - in this case IV meropenem b/c you can't trust the cephalosporines - give a CARBAPENEM
Bladder
- the longer the urine stays static in the bladder, the more likely infections will take hold
UTIs are rare in men, except when =
- they have urologic abnormalities - have unprotected anal intercourse - have AIDS w/ CD4+ count less than 200
What imaging do you do?
- ultrasound - IVP - Cystoscopy - CT scan
Occurrence of UTIs in women
- uncommon in infancy - incidence increases in adolescent & adult women - bacteriuria in elderly women is 40%
Occurrence of UTIs in men
- uncommon in infancy - rare in young men/boys w/o abnormalities - incidence increases after age 50
Host defenses
- urethra = longer in males - CONSTANT FLORA = bacteria is washed out, MOST IMPORTANT - phagocytic epithelial cells = macrophage, neutrophil, monocyte - complete emptying of bladder - local Ab production in kidney - ureterovesical valve prevents retrograde flow
Lower UTI
- urethritis, cystitis - frequency, urgency, malaise
Treatment (drugs)
- urinary analgesics - phenazopyridine - antibiotics = Nitrofurantoins (not Fluoroquinolones anymore b/c you want to reserve them for really bad cases)
Oral Nitrofurantoin
- used to treat lower infections b/c doesn't get into kidney parenchyma very well
Dysuria causes
- vaginitis - urethritis - cystitis - non-infectious
Choosing antibiotics
- want it to excrete through urinary tract - must kill E. coli - must cause high conc in urine/vaginal excretions - Short or long course depending on situation - men get LONG course antibiotics
Nitrofurantoin
- well-absorbed orally, high bioavailability, rapidly cleared by kidneys - used to treat & prevent UTIs - long-term prophylaxis has side-effects
Asymptomatic bacteruria
- when you have bacteria & WBCs in the urine but no SX - NOT an indication for antibiotics
Fosfomycin
- wide tissue distribution w/ good penetration of U tract - bacteriacidal - long 1/2 life: 4-8 hours - 95% renal elimination - used for UNCOMPLICATED UTIs
28 y/o male had sex w/ prostitute in Seattle 1 week ago - noted burning sensation on urination & yellow discharge - microscopic exam of discharge reveals 4+ leukocyte esterase & gram stain showing gram-negative intracellular diplococci w/ neutrophils (PMNs) - what is it? What is the best course of action?
-- Neisseria gonorrhea -- Administer ceftriaxone & azithromycin - draw blood for VDRL & HIV Ab - arrange for wife to be examined & treated ** b/c you have to treat chlamydia w/ gonorrhea & need to test for other STDs
pH of urine
5-6
Complication of Pyelonephritis
Acute papillary necrosis - due to predisposition from diabetic status
Pathogens of CAUTI
Bacterial = E. coli Non-bacterial = candida (create proper environment for bacteria to attach, not really causing infection) --> so you STILL want to treat for bacteria not w/ antifungals
What body sample do you NEVER refrigerate?
CSF
How do you treat Extended Spectrum Baso Lactam bacteria?
Carbapenems (meropenem, ertapenem)
CAUTI
Catheter-associated UTI - b/c catheters are the perfect niche for biofilm colonization
What is the most common source from which UTIs caused by E. coli, are acquired in otherwise young healthy women?
Colonic bacterial reservoir
UTI
E. coli - candida is implicated BUT NOT as a pathogen
Most common cause of Hospital-acquired UTI
E. coli - BUT other gram-negatives are a close 2nd
Most common cause of Community-acquired UTI
E. coli - can cause to Malakoplakia (rare presentation of yellow plaques in bladder due to lack of functioning macrophages)
Pathogenesis involves 3 things
Host innate immunity - Urinary tract function - Bacterial virulence traits ** together they cause UTIs, and can lead to renal damage (pyelonephritis)
What do you use to treat pyelonephritis then?
IV Ceftriaxone - penetrates tissue & kills the bacteria
Clinical features - special groups
Newborns = poor feeding, jaundice Infants = poor feeding, not thriving, vomiting Children = irritability, eating poorly, loss of bowel control Elderly people = change in mental status, don't feel well
Etiology of UTIs=
almost always E. coli - have intestinal normal flora - intestinal pathogens - extraintestinal pathogens
Diagnosis of asymptomatic bacteruria =
growth of 10^5 colonies of a single bacterial species per mL of urine in 2 consecutive urine cultures
Alkanization =
has nothing to do with the attachment of the pili
UTIs are the 2nd/3rd most common ______________ ____________ in US adults
nosocomial infection
