URINARY TRACT INFECTION
Dr. S. Fishbane
OVERVIEW:
UTI is an extremely common medical problem, with an unpredictable natural history. Many infections resolve spontaneously, but others can progress to destroy the kidney, or via gram negative sepsis, the host. Intelligent management of UTI requires a thorough knowledge of the pathophysiology involved, and medical care which is tailored to the clinical setting.
The term UTI implies causation by gram negative gut flora of the group Enterobacteraciae. Rarely, UTI can result from virus, fungus, TB, staph, or other creatures, but the pathophysiology is entirely different. Also implicit in the diagnosis of UTI is the exclusion of infections which only involve the uretha, such as gonoccal urethritis or the acute urethral syndrome, discussed below.
DIAGNOSIS:
Normal urine is sterile. UTI can therefore be diagnosed if a single viable gram negative bacterium inhabits the urinary tract (kidney, ureters, bladder). In reality, the bacteria causing UTI multiply in log phase growth in normal urine, and most people with urinary tract infection have 104-106 bacteria/ml. The acute number will depend on the urine flow rate, characteristics of the urine, the duration of infection, etc. The problem in diagnosis is that of contamination arising from voided specimens passing through the non-sterile distal urethra. For this reason, clinicians use the criteria of 105 bacteria/ml of “clean catch” urine to diagnose UTI. At this level, < 1% of the represent contaminants. At counts of 1000-10,000/ml, there is a 50/50 chance the result represents contamination. Such a count may represent true infection, but to be sure a second culture showing the same organism might be more convincing. The second criteria for diagnosing UTI is the presence of pyuria (> 5 WBC/HPF) on the urinalysis.
Note how arbitrary the 105 cut off really is. For example, the interpretation of a colony count depends on how the sample was collected. If you cultured 1000 randomly selected women, 970 would be truly sterile, and 30 would have asymptomatic infection. The colony count in this population would depend entirely on the way you collect the urines.
Suprapublic aspirates done under sterile conditions are the “gold standard” for diagnosing UTI, and would reveal the true populations of infected and non-infected women. Clean catch collections or samples collected by “sterile” bladder catheterization would approximate this distribution but due to many contaminated cultures there would be many more false positive cultures. Random voided cultures are essentially useless – a positive culture is much more likely to represent contamination than true infection. In practice, use the clean catch or bladder catheterization technique.
BACTERIA:
Urine is bacteriostatic to most of the commensual organisms inhabiting the perineum and vagina: lactobacillus, corynebacterium, diptheroids, staph albus. In contrast, many gram negative organisms thrive in urine. Most infections are caused by aerobic gram negative rods of the GI tract. The cause of infection in uncomplicated outpatients is typically as follows:
85% f all UTI = E Coli (but only certain serotypes)
10 % = Klebsiella, Proteus, Pseudomonas, Enterobacter
< 5% = Staph aureus, entercoccus, chlamydia, fungus, TB, other
If the UTI is acquired in the hospital, the causal organism is less likely to be E. Coli, and more likely to be another gram negative bacterium or Staph. The gram negative rods not only thrive in urine, they are specially adapted to cause infection by having fimbriae with terminal receptors for specific glycolipids and glycoproteins. E. coli species which cause UTI’s typically have fimbriae with a terminal receptor for the “P” antigen. The P antigen is a blood group marker which is also found on the surface of cells lining the perineum and urinary tract. Approximately 75% of the population expresses the P antigen, and these individuals are particularly susceptible to UTI’s. The P antigen is also found in vaginal and prostatic secretions: these secreted P antigens are protective in that they bind to the bacterial receptor, preventing binding of the organism to the surface epithelium. The individuals most susceptible to UTI are those who express P antigen on their cells and lack P antigen in their secretions.
PATHOPHYSIOLOGY:
Sterility is normally maintained by the free flow of urine through an anatomically normal urinary tract. The low pH, high osm, and high NH3 content of urine are bacteristatic, as are prostatic secretions and the anti-bacterial antibodies present.
DEFENSE MECHANISMS: Free flow of urine. Normal anatomy = physical barriers:
Urethral length, urethral/ureteral valves, antegrade flow
Bacteriostatic properties of urine: acid, urea, osms, and NH3
Bacteriostatis properties of prostatic secretions
P antigen in secretions; no P antigen on cells
PREDISPOSING FACTORS: Female sex (no prostate, pregnancy, short urethra), old age,
Obstruction, P antigen on cells, no P antigen in secretions, any anatomic lesions
Of papilla or lower tract.
The natural defense mechanisms against infection works extremely well – 105 E. coli injected into the bladder are cleared, and 105 injected IV do not cause pyelonephritis. Essentially the only way to produce pyelonephritis experimentally is direct medullary injection of bacteria (100 bacteria will do – WBC function is paralyzed in the medulla due to osms, high H+ and NH4+ content), or in the presence of obstruction.
UTI due to staph aureus, TB, & virus is thought to be via the bloodstream – not ascending infection. Most infections, however, are caused by gram negative rods which are thought to initiate infection by the “ascending” route:
EPIDEMIOLOGY:
Most urinary tract infections are asymptomatic. If you did “perfect” (contaminant-free) cultures, the number of people with true UTI would look like this:
The higher incidence in females reflects the shorter urethra and lack of a prostate. The increased incidence in the teens represents urethral trauma due to sex; the general increase with advancing old age reflects obstruction, cystocele, etc. Below age 50, UTI is almost entirely a disease of females. The only afflicted males have abnormal anatomy.
SYNDROMES OF
INFECTION
Urethral Infections have to be excluded before considering the diagnosis of UTI. There are 2 types:
Gonococcal
Non-gonococcal = NGU = acute urethral syndrome
Urethral infection presents with dysuria, frequency, pyuria and sometimes hematuria. (The same presentation as cystitis.) The only distinguishing finding is urethral discharge. UTI is further excluded when you find no bacteria on UA, gram stain, or less than 104 on culture. NGU is caused by chlamydia, mycoplasmas, rarely by gram negative bacteria, and the cause cannot be identified in 1/3. Treatment of choice is minocycline 100 mg BID x 7 days, although not everyone will respond.
Non-urethral, non-UTI infections also have to be excluded. Many women will present with symptoms of cysitis, but the cause is vaginitis, cervicitis, genital herpes, etc. A physical exam is thus helpful in women with the symptoms of a UTI to exclude these entities.
Assymptomatic Bacteriuria is 50 times more common than cystitis, 5000 times as common as pyelonephritis. In most cases, the infection is confined to the bladder, and clears spontaneously. The entity is of concern for 2 reasons:
1) This is the pool from which symptomatic cystitis and pyelonephritis develop.
2) Assympotmatic infection can induce definite morbidity in infants, pregnant females, and in the presence of anatomic abnormalities. These 3 groups should be identified, treated and followed to ensure sterile urine.
Cystitis, in the symptomatic form, is intolerable to the patient who will immediately seek medical attention.
Sx: dysuria (burning, 20 to WBC’s), frequency (sense of having to urinate frequently), and sometimes abdominal or flank pain, or fever.
Sns: hematuria, urinary odor, sometimes fever or abdominal tenderness
Dx: exclude vaginitis, cervicitis, Herpes, etc.
exclude GC and NGU (no discharge, bacterial rod present).
Exclude pyelonephritis (no/WBC, no/ESR, no flank pain, no WBC casts)
Demonstrate: Pyuria (>5 WBC/HPF), bacteriuria (>105 on culture, or >1/HPF on unspun urine. Culture is optional in simple cases with a positive
UA.
Rx: single dose - amoxicillin 3.0 gm PO
- TMP/SMX 3 gm PO
3 day course of norfloxacin, 400 mg BID; TMP/SMX 500 mg BID
7-10 day course of ampicillin, TMP/SMX, or norfloxacin
F/U: Must show urine to be sterile after Rx
Must evaluate all males for anatomic abnormalities, and all females after the 3rd infection.
Pyelonephritis is the most serious type of UTI, with a substantial morbidity and mortality. The approach and treatment are entirely different from simple cystitis. Although some patients will have the classical presentation, many will behave as if they only have cystitis. An enormous effort has been expended on ways to differentiate upper tract infection (pyelonephritis) from lower tract infection (cystitis). The obvious problem is that all patients with pyelo also have cystitis, and the symptoms of the latter may predominate. The gold standards are kidney biopsy, ureteral catheterization, or the bladder washout technique – all of which are quite impractical, and are used only in research protocols. The clinician must rely on more mundane tests:
Symptoms & signs: The classical presentation of pyelo is with fever, flank pain, ANV, and flank tenderness (CVAT).
UA: WBC casts diagnostic of pyelo, RTE cells suggestive.
CBC: WBC, ESR, and > 95% specific for pyelo
Renal function: Loss of concentrating ability suggests pyelo
Antibody – coated bacteria: Present in pyelo if infection >1 week old.
20% False + rate: Technique, vaginal bugs, prostatitis, bladder CA, stones.
20% False + rate: Technique, infection too brief, pregnancy, Pseudomonas.
Pyelonephritis represents infection of a single (sometimes multiple) papilla and may progress to involve the entire wedge-shaped section of kidney that the infected papilla drains. With cure, a cortical scar may overlie a blunted papilla as the evidence of this prior infection. Untreated, the infection may involve the whole kidney (pyonephrosis), rupture through the capsul (perinephric abscess), or lead to gram negative sepsis. All these serious sequelae are much more likely in the presence of obstruction, which must be identified and relieved.
COMPLICATIONS
OF PYELONEPHRITIS
§ SEPSIS, DEATH
§ LOCAL
§ ABSCESS FORMATION
§ GAS FORMATION
§ PERINEPHRIC ABSCESS
§ OBSTRUCTION
§ LATE SEQUELAE
§ SCARS
§ HYPERTENSION
§ RENAL INSUFFICIENCY
Rx of pyelonephritis:
Hospitalize
Parenteral antibodies = 10-21 day Rx (single dose cures no one, relapse common
after only 7 day Rx)
Get KUB on admission (to R/O stones, emphysematous pyelo, mass lesions).
Get IVP on day 3-4 in the infection is not obviously responding to R/O
obstruction.
Prove sterility during and after therapy.
Get IVP on all males 2 months later, and females after 3rd episode.
Newer aspects of therapy:
Effective results in animal models of UTI from immunization with P antigens.
Short course of antibx for uncomplicated infections.
Prophylactic antibiotics for predictable infections (post-intercourse).
Antioxidants (allopurinol, superoxide dismutase) to prevent inflammatory damage.
SPECIAL TOPICS
Nosocomial UTI = acquired in the hospital. 3% of all admissions “acquire” (=are given) UTI, due to urethral instrumentation usually in the form of the Foley Catheter. For all practical purposes, anyone with a Foley will be infected by the second week, and you cannot eradicate the infection until the Foley is taken out. At this point, most of the infections clear spontaneously, some require treatment. Always use a closed drainage system, never open it, always hang the bag below the patient, and get the catheter out ASAP.
Staghorn calculi are branched stones filling the renal pelvis and calyces, due to bacteria producing NH3 from urea (“urea-splitter”, most often Proteus or Klebsiella, but some strains of most Enterobacteraciae can do it too). The NH3 precipitates “triple phosphate” = MgNH4PO4. Infection cannot be cured until the staghorn is surgically removed.
