1/30/17 UTI Pathophyiology - Lebowitz Flashcards
bacteriuria
pyuria
UTI
bacteriuria: presence of bacteria in urine (normally sterile)
pyuria: presence of WBCs in urine → gen indication of infl response of urothelium
UTI: infl response of urothelium to bacterial invasion, usually assoc with bacteriuria and pyuria
clinical dx of cystitis
clinical findings will predice UTI to 90% prob
culture not recommended or required in uncomplicated cases
only recommended if:
- complicated URI
- atypicaly sx
- persistent sx post-tx
- recurrent sx within a month
symptoms/associations:
- dysuria, frequency, urgency
- suprapubic pain
- hematuria
- fever: inconsistent finding
- sexual history
- hx of prior inf
- antibiotic use
- sx suggesting upper tract inf
- acute urethral syndrome
mechanisms of:
- dysuria
- freq/urgency
- hematuria
- suprapubic tenderness
- fever/sweats/chills
- CVA tenderness/flank pain
ddx of UTI
- UTI
- urethritis (chlamydia, gonorrhea, herpes)
- vaginitis (fungal, trichomonas, bacterial)
- prostatitis
- nephrolithiasis
- interstitial cystitis
- trauma
- urinary TB
- urinary tract neoplasm
- intraabd abscess
- sepsis (non-GU source)
- overactive bladder
basic principles of dx/testing
urine?
contamination?
definitive dx
bladder urine should be sterile
BUT voided specimens will have some amount of contamination (surface)
use approp collection/handling methods
definitive diagnosis by means of:
- urinalysis
- urine culture
- quantitative urine culture
pathogenesis of UTI
-
contamination
- orgs introduced during collection of processing urine
-
colonization
- organisms present in urin, but no illness/no sx
- variable significance
- doesn’t necessarily req tx
-
infection (UTI)
- combo of pathogens within urinary system and infl response
- symptomatic, requires tx
types of UTI, pathogenesis
uncomplicated
complicated
recurrent
reinfection
persistent
uncomplicated: inf in healthy pt with anatomically and functionally normal urinary tract
complicated: inf assoc with factors incr colonization and decr efficacy of tx
- anatomical/functional abnormality of urinary tract (enlarged prostate, stone disease, diverticulum, neurogenic bladder)
- immunocompromised host
- MDR bacteria
recurrent: occurs after documented inf resolved
reinfection: new event w reintro of bacteria into urinary tract
persistent: caused by same bacteria from focus of inf
progression of UTI
(bottom to top)
- colonization
- uropithelium penetration
- role of FIMBRIA
- biofilms
- ascension
- pyelonephritis: infection of renal parenchyma
- acute kidney injury
- tubular obstruction/damage → interstitial edema
- interstitial nephritis → AKI
success of UTI bacterial inf depends on…
- size of inoculum
- host defense mechs
- virulence factors of bacteria
* bacterial adherence (mediated by surface mols and pili → promote attachment, allow persistence)
host defenses of urinary tract
1. urine
- acidic pH
- high osmolality
- inhibitors of bact adherence
- comp inhibitors of attachment to uroepithelial cells
- mechanical flushing
2. mucosal immunity
- urothelial cytokines/chemokines
- mucopolysacch lining → more difficult to penetrate
- mucosal IgA
- sex-specific
- women: protective vaginal flora
- men: prostatic secretions w bactericidal Zn; longer urethra
host factors defending against UTI:
periurethral and urethral region
urinary factors
bladder
kidney
periurethral/urethral region colonized by
- Lactobacilli
- coagulase (-) staph
- Cornyebacterium
- Streptococci
*changes in E2, low vaginal pH, cervical IgA affect colonization
urinary factors
bladder
- epithelium expressed TLRs → recog bacteria, initiate infl response, induce exfoliation of cells/allow excretion of bacterial colonization
kidney
- local immunoglobulin/ab synth in response to inf → IgG, secretory IgA
alterations in defense mechs that predispose to UTIs
- reduced urine flow
-
factors promoting colonization
- sexual activity, spermicides (incr binding), estrogen depletion, antibiotic explosure (kill flora)
-
factors that facilitate ascent
- catheterization
- urinary/fecal incontinence
- residual urine w bladder wall ischemia
- VUR (vesicoureteral reflux)
- underlying disease (diabetes, papillary necrosis, HIV)
- pregnancy
features of uropathogenic bacteria
pili
pili: surface appendanges used by bateria to adhere to host tissues
- key for biofilms
- incr ability of bacteria to adhere to tissue → evade phagocytosis by PMNs
- types of pili:
-
type I pili
- adhere to mannose receptors in urinary epithelial monosacch lining
- bind to PMNs
- major cause of cystitis
-
type P pili
- mannose-resistant
- adhere to renal glycolipid receptors (DgalDgal residues) on renal epithelia
- cause cystitis and pyelonephritis
-
hemolysins
- cytotoxic: form transmembrane pores in host cell membranes
-
K antigens
- promote bacterial virulence by decr ability of abs and/or complement to bind bacterial surface
- K1 composed of polymer of n0acetyl neuraminic acid (antiphagocytic, works as an antigenic disguise)
-
type I pili
asymptomatic bacteriuria
treat? or no?
no need for treatment in most cases
however, always treat:
- pregnant women
- prior to urologic surgery
- hip replacement candidates (will have to undergo long catherization)
IF TREATING: tx based on results of urine culture and sensitivity
acute uncomplicated UTIs
sporadic, comm-acquired cases
present w typical sx: dysuria, freq, suprapubic pain
NO URINARY SX WITHIN LAST MONTH
micro:
- urine cultures typically unnecessary
- E. coli (75-95%), Enterocbacteriaceae (Proterus, mirabilis, Klebsiella pneumonia), Staph saphrophyticus
UTI treatment
antibiotics chosen for:
- urinary excretion
- low tox risk
- high oral bioavailability
- low cost
*IV tx preferred for complicated UTIs
meds:
-
trimethoprim-sulfamethoxazole
- blocks folic acid synth → purine synth interrupted
-
nitrofurantoin
- directly damages microbial DNA (bacteria metabolize toxic intermediates of nitrofurantoin more rapidly than human cells)
-
fosfomycin
- inhibits bacterial cell wall biosynth by inactivating bacterial MurA (emzyme catalying peptidoglycan biosynth)
-
fluoroquinolones
- inhibition of DNA gyrase, topo IV (req for DNA repl, transc)
- try to avoid except in severe inf! bc of resistance emerging
acute uncomplicated pyelonephritis
infection of kidney/upper urinary tract
- general UTI sx (dysuria, freq, urg, suprapubic pain)
- also…
- fever
- flank pain
- CVA tenderness
believed to be “severe” if sx accompanied by n/v
same workup, same causative organisms
antibiotic choice: depends on outpatient/inpatient
- outpatient: long acting parenteral antibiotics (ex. ceftriaxone), fluoroquinolones; trimethoprim-sulfamethoxazole, beta lactam (only if pathogen known)
- inpatient: IV fluoroquinolones, aminoglycoside, ext spectrum cephalosporin, ext spectrum penicillin, carbapenem
complicated UTIs
associated with structural or functional anormality or presence of underlying disease that..
- incr risk of serious outcome
- incr risk of failing initial therapy
bacterial spectrum considered much larger than uncomplicated UTIs
complicated UTIs - treatment
E. coli still accounts for 75-95%, but in this set of UTIs, fluoroquinolone resistance more common and ESBL-producing E. coli (ext spectrum beta lactamase) more common
E. coli, Klebsiella, Staph sapro, as well as…
- Pseudomonas
- Serratia
- Providencia
- Enterococci
- Staphylococci
- fungi
use empiric antibiotics for longer periods of time:
- oral fluoroquinolones
- IV: ceftriaxone, ertapenem, aminoglycosides, vancomycin or ampicillin, antifungals
catheter associated UTI
******
why so imp?
treatment
most common healthcare-assoc infection
leading cause of secondary hospital bacteremia
15-25% of pts are catheterized for 2-4d
- 3-8% per day you have catheter get UTI
- eventually all will develop bacteriuria as bacteria track up the catheter forming a biofilm or ascend through the lumen on the catheter
treatment: broad spectrum antibiotics for 10-14 days OR amphotericin if fungal, guided by urine culture results
- often resistant to fluoroquinolones
- need to remove catheter (can replace if necessary)
complicated UTI
pregnancy
in pregnant women…
- asymp bacteriuria: 2-7%
- 30-40% of these → UTIs
- associated with…
- low birth weight
- preterm birth
- incr perinatal mortality
- acute cystitis: 1-2%
- pyelonephritis: 0.5-2%
often occrs in first trimester
linked to physiological changes in pregnancy:
- sm muscle relaxation/ureteral dilatation
- displ of ureter by enlarging uterus → stasis of urine
- incr pressure on bladder from gravid uterus
ALL POSITIVE CULTURES → TREATMENT
- redo culture in 1wk, 2wk, 1mo → might need
complicated UTI
pregnancy
treatment
fluoroquinolones and trimethoprim-sulfamethoxazole are CONTRAINDICATED bc of teratogenicity!
- TMP: folic acid antagonist → abnormal embryonic devpt in animals
- sulfonamides: can displace bilirubin from pl binding sites and can increase kernicterus
- fluoroquinolones: teratogenic in animal models
- aminoglycosides: risk of fetal ototoxicity
cephalosporins, penicillins, aztrenam, carbapenems (except imipenem-cilastin), nitrofurantoin all ok
UTI in children
risks of pyelonephritis
when to hospitalize
if proceeds to pyelonephritis…
- renal scarring
- HTN
- impaired renal fx
hospitalize if:
- under 2 months
- clinical urosepsis
- any immunocompromised child
- vomiting/inability to take oral meds
- failure to respond to tx
- lack of adequate followup
*
vesicoureteral reflux
assoc with UTI in children
primary VUR: incompetent or inadequate closure of UVjx during bladder contraction
- growth results in spontaneous resolution of low-grade VUR
secondary VUR: abnormally high bladder pressures result in incompetence of UVJ closure
- assoc w anatomic abnormalities (posterior urethral valves)
- functional bladder obstruction
genetics involved
VUR dx
demonstration of reflux from bladder to urinary tract on imaging with voiding cystourethrogram (VCUG)
prostatitis
affects young to middle-aged men
symptoms:
- bladder irritation
- outlet obstruction
- blood in semen
- painful ejaculation
pathophys: bacteria enter prostate via urine reflux from urethra/bladder through prostatic ducts
E. coli, Proteus spp, Klembiella/Enterobacter/Serratia, P. aerunginosa, S. aureus, Streptococci, Enterococci
sterile pyuria
infectious and non-infectious causes
INFECTIOUS
- genitourinary TB (27% of cases) - most common site after lungs, lymph nodes
NON-INFECTIOUS
anything that inflames the urinary tract
UTI of transplated kidneys
all considered complicated bc patients are immunosuppressed
all cystitis is essentially pyelonephritis
- short ureter
- ALWAYS reflux through anastomosis of donor ureter to bladder
- most kidney transplat centers place ureteric stents, which are removed in first months post transplant
almost always decr in kidney fx with episodes of cystitis
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