What is Urinary Tract Infection?

Acute infection of urinary tract by bacteria is UTI (urinary tract infection). Presence of pathogenic microorganisms (mainly bacteria) in urine, urethra, urinary bladder, kidney, or prostate is urinary tract infection. Urinary tract infection may be lower urinary tract infection or upper urinary tract infection. Lower urinary tract infection includes urethritis (infection/inflammation of urethra) and cystitis (infection/inflammation of urinary bladder) and upper urinary tract infection includes acute pyelonephritis, prostatitis (infection/inflammation of prostate gland) and intrarenal and perinephric abscesses.

Generally UTI is considered to exist if “properly collected” mid stream urine sample shows presence of more than 100,000 milliliter of urine. But many cases of urinary tract infection there may be lesser number of bacteria, e.g. presence of 100-10000 bacteria per milliliter with symptoms may also constitute urinary tract infection. If urine sample is collected from a patient with already present catheter or urine sample collected by suprapubic aspiration with a needle with proper aseptic precautions, the bacterial colony count of 100-10,000 generally indicate urinary tract infection. On the other hand bacterial colony count of more than 100,000 may not indicate urinary tract infection if midstream urine sample is taken, especially if there are several species of bacterial colony, which may be due to contamination of urine sample during collection.

Urinary tract infection may recur after treatment with antibiotics, which may be due to new infection or may be due to incomplete treatment and persistence of same infecting strain of bacteria, which can be found out by finding the species, antibiotic sensitivity, same serotype, and molecular type. Relapse of urinary tract infection with same strain of bacteria may also be due to persistent vaginal or intestinal colonization with the same organism which leads to rapid re-infection.

What common organisms cause urinary tract infection?

There are many microorganisms which can cause urinary tract infection. The organisms are Escherichia coli, Klebsiella species, Enterobacter species, Proteus species, Chlamydia trachomatis, Neisseria gonorrhoeae, Staphylococcus saprophyticus, Staphylococcus epidermidis, Staphylococcus aureus, enterococci, etc. Ureaplasma urealyticum, Mycoplasma genitalium, Mycoplasma hominis may also cause UTI occasionally.

The commonest organism to cause UTI is Escherichia coli which are a gram-negative bacillus, which causes approximately 80% of cystitis and pyelonephritis in patients without catheter, any anatomical abnormalities in urinary system, or urinary stone. Other gram-negative bacilli which cause uncomplicated urinary tract infection are Proteus and Klebsiella species and rarely Enterobacter species.

What are the sources of UTI?

The bacteria gain entry to cause UTI mainly through urethra to bladder and from urinary bladder the bacteria ascend to infect kidneys and renal parenchymal. Distal urethra and vaginal introitus in women genarlly harbor (colonize) diphtheroids, streptococcal species, lactobacilli, and staphylococcal species, but they generally do not cause UTI.

Women are more prone to UTI and gram negative bacteria that commonly cause UTI reside in the bowel and colonize the vaginal introitus, the periurethral skin, and the distal urethra to cause UTI. Why colonization occurs is not clear, but alteration of the normal vaginal flora by use of antibiotics, genital infections, use of contraceptives, especially spermicidal vaginal jelly etc. might play a role. Normally lactobacilli which are dominant flora of vagina produce H₂O₂ and loss of this flora may facilitate colonization of E. coli. Small number of bacteria frequently gains entry to the bladder, but infection only occurs if the strain is pathogenic and the inoculum size is big enough and also if local and systemic host defense is favorable for infection to establish. Recent studies also suggests that E. coli may invade bladder epithelium and form intracellular colonies known as “biofilms” which may become persistent and act as source of recurrent UTI.

Normally the bacteria that gains entry to the bladder are cleared by flushing, dilution, antibacterial property of urine (due to high urea concentration and high osmolarity), and the bladder mucosa. The secretion of male prostate gland also has antibacterial properties. The epithelial cells of bladder also secrete cytokines and chemokines, mainly interleukin (IL) 6 and IL-8, which causes invasion of polymorphonuclear leukocytes which also helps to clear the bacteria in urine.

What risk factors of UTI?

Several factors can affect the severity of UTI, e.g. gender, sexual activity, genetics, obstruction to urine outflow, pregnancy, bladder dysfunction, virulence of the infecting microorganisms, vesicoureteral reflux etc.

Gender:

The female urethra is prone to colonization by microorganisms and consequently females suffer from UTI more commonly than males. The colonization of female urethra by microorganisms is favored by its short length of approximately 4 cm (as well as it is straighter than male urethra), it is near to anus and the opening is beneath the labia.

Sexual activity:

Sexual intercourse can cause entry of microorganisms into urinary bladder in females and cause cystitis. Voiding of urine after intercourse can reduce incidence of cystitis, probably by removing microorganisms which are introduced during intercourse. Use of spermicidal jelly, diaphragm, cervical cap, spermicide-coated condoms during intercourse can also increase the risk of UTI, by altering the normal flora of vagina.

Genetics:

At present there are some evidences, which suggest genetical factors can play a role in increase incidences of UTI in certain populations. Patients with recurrent UTI generally have history of UTI in the mother. The epithelial receptors, to which microorganisms (e.g. E. coli) get attached to cause UTI, are genetically mediated, at least to some extent. Persons with the lack of these receptors are at lower risk of developing UTI.

Obstruction:

Any obstruction to free urine outflow can predispose UTI. The obstruction may be due to tumor, stone, prostate gland hypertrophy, stricture etc. which cause hydronephrosis and cause increased incidence of UTI. The infection of urinary tract due to obstruction can damage renal cells (nephrons) rapidly, therefore need urgent identification and repairing of the obstructive lesion. If the obstruction is minor and not causing UTI, it should be evaluated carefully to decide if surgical repairing is required, because the benefit may be very less in compare to the risk of introducing infection.

Pregnancy:

UTI, especially upper UTI is very common during pregnancy and approximately 2-8% pregnant women suffer from UTI. The increased incidence of upper UTI in pregnancy is due to decreased peristalsis of ureters, decreased tone of ureteric muscles and temporary incompetence of vesicoureteral valves during pregnancy. Catheterization of bladder during delivery or after delivery can increase the incidence of UTI.

UTI (especially upper UTI) during pregnancy can result in low birth weight babies, neonatal deaths, premature delivery etc.

Bladder dysfunction:

Diabetes spinal cord injury, tabes dorsalis, multiple sclerosis etc. can interfere with enervation of bladder and predispose UTI. The increase in UTI may also be due to stasis of urine for long time, use of catheters for drainage, bone demineralization (due to prolonged immobility which causes hypercalciuria and calculus formation and increased infection) etc.

Virulence of the infecting microorganisms:

Virulence of the microorganism is an important factor in the causation of UTI and any other infection. All the strains of E. coli can not initiate infection. Highly virulent E. coli generally contains fimbriae, which are hairlike proteinaceous surface appendages that is used for attaching to the epithelial receptors to initiate infection.

Vesicoureteral reflux:

Vesicoureteral reflux is reflux of urine from the urinary bladder up into the ureters (sometimes up to renal pelvis of kidney). Vesicoureteral reflux commonly occurs during urination or if the bladder pressure is elevated for some reason. Vesicoureteral reflux is common among children, especially if there is some anatomic abnormality of the urinary tract. Vesicoureteral reflux is diagnosed by taking voiding cystourethrogram, which shows retrograde movement of radiopaque or radioactive material.

What are the symptoms of UTI?

The clinical presentation of UTI generally does not depend on the location (in bladder, urethra or ureter) of the infection in the urinary tract and type (cystitis, pyelonephritis, urethritis etc.) and it is difficult to determine the location of infection clinically.

Symptoms of cystitis:

Increased frequency, urgency of urination is common symptoms of cystitis. Suprapubic pain and tenderness as well as pain during urination is also seen. Urine can become cloudy (due to presence of large number of white blood cells and bacteria, which can be detected) or contain blood (in approximately 30% of cases) and foul smelling. Fever of more than 101°F (38.3°C), nausea and vomiting generally indicate concomitant renal infection (so does costovertebral angle tenderness), although absence of these does not rule out concomitant renal infection.

Symptoms of acute pyelonephritis:

Generally symptoms of acute pyelonephritis are fever with chills, nausea, vomiting, abdominal pain, and diarrhea, which starts rapidly over few hours or within a day. Fever, high pulse rate, generalized body ache and marked tenderness on deep pressure in one or both costovertebral angles are also seen in acute pyelonephritis. The range of severity of illness may be great, with mild symptoms in some cases and severe signs and symptoms of gram-negative sepsis in some patients.

Symptoms of urethritis:

Dysuria (painful micturition), frequency, and pyuria (pus in urine) etc. are common symptoms of urethritis. Hematuria (blood in urine), suprapubic pain, and sudden onset of illness, with duration of illness of less than 3 days, suggest urethritis (E. coli UTI). Sexually transmitted infections with chlamydial or gonococcal infection may have the symptoms of a gradual onset of illness, no suprapubic pain, and more than 7 days of symptoms.

What investigations are done for diagnosis of UTI?

The two important investigations used for diagnosis of UTI are urine culture (and colony count) and urine microscopy. Urine culture is done to determine the type of bacteria and number of bacteria per milliliter of urine. In symptomatic as well as asymptomatic patients, demonstration of 100, 000 or more per ml (any single species of bacteria) on two consecutive urine samples indicate UTI and need to initiate antibiotic therapy. If urine is collected from renal pelvis or ureters, it may contain less than 100, 000 per ml and still indicate infection. If urine is collected by suprapubic aspiration, the presence of any number of bacteria indicates UTI. Similarly, presence of even 100 bacteria per ml in urine may indicate infection if urine is collected by catheterization. For collecting urine sample the periurethral area (the area surrounding urethral opening) should not be cleaned with antiseptic, as it may reduce bacterial count and give false negative result. Voiding of urine before collecting urine sample and excess drinking of water may also reduce bacterial count. Antibiotic treatment for any reason, high urea concentration, high osmolarity, low pH etc. may prevent bacterial multiplication and give low bacterial count despite presence of UTI.

Microscopic examination of uncentrifuged urine may be of great diagnostic value in UTI, especially for symptomatic patients. Because bacteria can only be detected by microscopy, if the bacterial count is 100, 000 or more per ml and lower bacterial counts can not be detected. That is why demonstration of bacteria in urine (usually by Gram-stained uncentrifuged urine) provides firm evidence of bacterial infection. But non detection of bacteria in urine by microscopy does not rule out UTI.

How UTI is treated?

For treatment of UTI, certain guidelines and principles should be followed. The following are the principles and guidelines that need to be followed while treating UTI:

1. Relief of symptoms of UTI is not always the indication of complete bacteriological cure.
2. If there is any predisposing factor found (stone or obstruction), it should be corrected.
3. Quantitative urine culture should be done before starting empirical antibiotic therapy and antibiotic sensitivity should always be used to guide the treatment of UTI, except uncomplicated cystitis in women.
4. Despite increase in the incidence of resistant strains the initial UTI is generally due to antibiotic-sensitive strains.
5. Every treatment of UTI should be classified as cure or failure. A cure is complete relief from symptoms plus urine culture that is not indicative of UTI. A failure of treatment is indicated by persistence of symptoms (may be less severe than before) and/or persistence bacteriuria (with culture) immediately after completion of complete antibiotic course.
6. Generally lower UTI need short course of antibiotic therapy and upper UTI need longer course of antibiotic therapy. Early recurrence (before 2 weeks) with same strain generally indicates presence of an unresolved upper tract focus of infection (especially after short course antibiotic therapy for lower UTI like cystitis) or persistent vaginal colonization. Recurrence after 2 weeks of completion of antibiotic therapy generally indicates reinfection (with new strains or due to persistence of the same strain in the vaginal and/or rectal flora).
7. Antibiotic resistance should be suspected if there are repeated infections, recent hospitalization (for any reason including complicated UTI) or instrumentation (use of catheter for long duration).

The antibiotic of choice and treatment regimen for UTI depends on the infecting strains of the bacteria, type of infection, complications (if any), mitigating factors/circumstances (if any, like diabetes, pregnancy, calculi etc.) etc.

Acute cystitis:

Most common organisms involved in acute uncomplicated cystitis are E. coli and S. saprophyticus which cause more than 90–95% of cystitis. A 3-day regimen of trimethopime/sulphamethoxazole (TMP-SMX) combination 80/400 mg or a fluoroquinolone like norfloxacin (400 mg 12 hourly), ciprofloxacin (400 mg 12 hourly), levofloxacin (250 mg per day), ofloxacin (200 mg 12 hourly) etc. are preferred for uncomplicated acute cystitis. If the resistance to TMP-SMX is more than 20% in a locality, than a fluoroquinolone or nitrofurantoin should be used.

If there is any complicating factor like diabetes, age more than 65 years or use of diaphragm is there the treatment of cystitis is 7-day regimen of either TMP-SMX or a 7-day regimen of a fluoroquinolone.

Commonly males with UTI have some anatomical abnormality or have involvement of prostate gland and need 7- to 14-day course of a fluoroquinolone, instead of commonly employed 3-day course for women.

Acute pyelonephritis:

Acute uncomplicated pyelonephritis in women is in most cases due to E. coli and a7-14 day course of a fluoroquinolone is commonly used with satisfactory results. Drugs like ampicillin or TMP-SMX should not be used as empirical therapy, as more than 25% of E. coli at present are resistant to these drugs. If possible for first few days antibiotics should be given intravenously. If patient do not respond to treatment within 72 hours, the patient should be investigated for suppurative foci, calculi, or urologic disease.

Complicated UTIs:

Complicated UTIs generally occur due to use of catheters (especially for longer duration), instrumentation, and any anatomical abnormality in the urinary tract, stones, any obstruction, immunosuppression, renal disease, or diabetes. The common organisms involved in complicated UTI are E. coli, Klebsiella, Proteus, Pseudomonas, enterococci, and staphylococci. These organisms are resistant to antibiotics.

In UTIs of mild symptoms empirical antibiotic therapy should be started with a fluoroquinolone like ciprofloxacin or levofloxacin and changed (if required) to appropriate antibiotics once culture and antibiotic sensitivity results are known. But in severe cases of UTIs (acute severe pyelonephritis or suspected urosepsis) patient should be hospitalized and parenteral broad spectrum antibiotics therapy started.

UTI in diabetes patients can have serious outcome if not properly and quickly managed in hospital. UTI with diabetes may be complicated by presence of renal suppurative foci, papillary necrosis, emphysematous infection, and infection by uncommon organisms. Treatment should be started either with imipenem (extended-spectrum penicillin) alone, or with a newer generation cephalosporin (ceftriaxone or ceftazidime) plus an aminoglycoside (e.g. gentamicin). Once culture and antibiotic sensitivity results are available, appropriate antibiotic should be started, if needed. Treatment is generally for 10-21 days and follow-up cultures should be done 2-4 weeks after complition of antibiotic therapy.

What is the prognosis of UTI?

Uncomplicated UTI generally results in complete resolution of symptoms as well as complete bacteriological cure in most of the cases. Very rarely, if ever, renal impairment occurs from UTI. Repeated upper tract infections are generally due to relapse rather than reinfection and repeated cystitis is generally due to reinfections rather than relapses. In case of repeated upper tract infections, underlying anatomic (urologic) abnormality may be present and sought. If there is no urologic abnormality or renal stone, antibiotic treatment for 6 weeks after culture and sensitivity can eradicate an unresolved focus of infection.

How UTI can be prevented?

Women who suffer from recurrent symptomatic UTI of 3 or more episodes per year may need appropriate antibiotic prophylaxis of long duration. The commonly used antibiotics for prophylaxis of UTI are cotrimoxazole (trimethopime/sulphamethoxazole combination 80/400 mg), trimethopime (alone) 100 mg, and nitrofurantoin 50 mg. the antibiotics can be used either daily dose or thrice weekly doses. Fluoroquinolones can also be used for this purpose. The appropriate antibiotic prophylaxis should be started after complete bacteriological cure of UTI with full antibiotic course. Postmenopausal women without use of oral estrogen replacement can prevent UTI by using topical intravaginal estrogen cream.

Additional measures that can help in preventing UTI are avoidance of spermicidal jelly and voiding of urine soon after intercourse. Drinking plenty of water can also be helpful, as it can dilute the bacterial load and flush the bacteria out of the bladder.

If recurrent UTI is related to sexual intercourse, prophylactic use of the above antibiotics regimen can be useful.

In men the above antibiotic prophylactic regimen can be used in case of chronic prostatitis and for those undergoing prostatectomy (during operation and post operative period).

What should be done in asymptomatic bacteriuria?

Asymptomatic bacteriuria if seen among catheterized patients, the best approach for these patients is removal of catheter and short course antibiotic therapy, with appropriate antibiotic, preferably after culture and antibiotic sensitivity test. If catheter can not be removed, than asymptomatic bacteriuria should be ignored till catheter can be removed or there is development of symptoms or risk of developing bacteremia is high, as treatment without removal of catheter is generally unsuccessful and frequently results in development of antibiotic resistant strains. If symptoms of UTI develop in presence of catheter and catheter can not be removed it should be managed by systemic antibiotics or urinary bladder antiseptics.

Asymptomatic bacteriuria in noncatheterized patients is commonly seen in elderly patients and antibiotic treatment is not recommended (nor necessary) unless it becomes symptomatic, as it may cause development of antibiotic resistant strains of organisms. In case of asymptomatic bacteriuria with high risk such as renal transplants, obstruction, neutropenia etc. treatment with one week appropriate (after culture and antibiotic sensitivity test) oral antibiotics can be given. If bacteriuria still persists, patient can be monitored without further treatment. In some cases with high risk of complication 4-6 weeks therapy may be necessary.

How to treat UTI in pregnancy?

If acute cystitis occurs during pregnancy, it is treated by one week treatment with amoxicillin, nitrofurantoin, TMP-SMX or a cephalosporin (e.g. cefpodoxime proxetil). Urine test should be done in all pregnant women to detect asymptomatic bacteriuria, if detected should receive one week treatment as above. Urine culture should be done after treatment to ensure cure and repeated culture done till delivery. If there is recurrent cystitis during pregnancy continuous low-dose prophylaxis with nitrofurantoin is given. If acute pyelonephritis develops during pregnancy, patient should be hospitalized and treated with parenteral cephalosporin or imipenem.