A 23-year-old woman was married a year ago. Since then, she has experienced five attacks of acute cystitis, all characterized by dysuria, increased frequency, and urgency. Each case was diagnosed on the basis of the clinical picture and a laboratory finding of bacteriuria. The urine bacterial counts in these cases ranged from 104 to 106 organisms/ml. Lab tests indicated that the first, second, and fifth infections were caused by Escherichia coli, while the third infection was caused by an enterococcus and the fourth infection was caused by Proteus mirabilis. Each infection responded to short-term treatment with trimethoprim sulfamethoxazole. The recurrences occurred at intervals of 3 weeks to 3 months following completion of antibiotic therapy. For the past two days, the woman has once again been experiencing dysuria, increased frequency, and urgency, so she goes to see her physician. Her vital signs are T = 37.2°C, P = 100, R = 18, and BP = 110/75 mm Hg. Physical examination reveals a mild tenderness to palpation in the suprapubic area, but no other abnormalities. A bimanual pelvic examination reveals a normal-sized uterus and adnexae with no apparent adnexal tenderness. No vaginal discharge is noted. The cervix appears normal.

Question 3.1: What is the differential diagnosis for this set of symptoms? What is your preliminary diagnosis?

The differential includes acute cystitis, a more extensive UTI, vaginitis, and urethritis. Urethritis would most likely be caused by a sexually transmitted pathogen. There are no other symptoms that would point to an STD and the patient's history does not suggest this alternative. Vaginitis is a reasonable possibility, but the physical examination did not reveal any obvious symptoms of this type of infection. There are no indications of an upper UTI (e.g., fever and/or flank pain), so it would appear that the patient simply has yet another case of acute cystitis. In women who present with 1 or more symptoms of UTI, the probability of infection is approximately 50%. Specific combinations of symptoms (eg, dysuria and frequency without vaginal discharge or irritation) raise the probability of UTI to more than 90%, effectively ruling in the diagnosis based on history alone.

Question 3.2: What tests should you order to confirm your preliminary diagnosis?

The most appropriate tests would include urinalysis with microscopic evaluation of clean-catch urine for bacteria and pyuria, a urine culture, and a CBC with differential.

Test Results

Laboratory tests indicate a Hgb of 13.6 g/dL, Hct 40.7%, MCV 84, and WBC count 10,910/microliter. White blood cells and bacteria are evident in the urine sediment. A urine culture indicates approximately 106 bacterial cells/ml. A Gram stain of the urine reveals Gram-positive cocci. The Gram-positive bacterium is isolated and is found to be catalase positive and coagulase negative.

Question 3.3: Do the test results support your preliminary diagnosis? What is the most likely identity of the causative agent in this case?

The results support a diagnosis of acute cystitis. Enterococci, group B streptococci, and some staphylococci are known to cause UTIs. The positive catalase test eliminates enterococci and Group B streptococci. The negative coagulase test eliminates Staphylococcus aureus. At present, the coagulase-negative Staphylococcus species that is mostly likely to cause cystitis in a young woman is Staphylococcus saprophyticus.

Question 3.4: What things must be considered when taking a sample for analysis in a case like this? What instructions should be given to the lab?

The methods for obtaining urine for culture are:

Random collection taken at any time of day with no precautions regarding contamination.

The sample may be dilute, isotonic, or hypertonic and may contain white cells, bacteria, and squamous epithelium as contaminants. In women, the specimen may contain vaginal contaminants such as trichomonads, yeast, and during menses, red cells.

Early morning collection of the sample before ingestion of any fluid.

This is usually hypertonic and reflects the ability of the kidney to concentrate urine during dehydration which occurs overnight. If all fluid ingestion has been avoided since 6 p.m. the previous day, the specific gravity usually exceeds 1.022 in healthy individuals.

Clean-catch, midstream urine specimen collected after cleansing the external urethral meatus.

A cotton sponge soaked with benzalkonium hydrochloride is useful and non-irritating for this purpose. A midstream urine is one in which the first half of the bladder urine is discarded and the collection vessel is introduced into the urinary stream to catch the last half. The first half of the stream serves to flush contaminating cells and microbes from the outer urethra prior to collection. This sounds easy, but it isn't (try it yourself before criticizing the patient). It can be messy, which reduces compliance.

Catherization of the bladder through the urethra.

This method for urine collection is carried out only in special circumstances, i.e., in a comatose or confused patient. This procedure risks introducing infection and traumatizing the urethra and bladder, thus producing iatrogenic infection or hematuria.

Suprapubic transabdominal needle aspiration of the bladder.

When done under ideal conditions, this provides the purest sampling of bladder urine. This is a good method for infants and small children.

The laboratory request form should be filled out properly. In general, a colony count and speciation of organisms present will be done for routine bacterial organisms. A sensitivity may be done if you indicate, but the lab will probably not do this if it appears that contamination is present (e.g., multiple organisms present) and the clinical indications are not present (e.g., hospitalized patient, indwelling catheter, etc). In general the laboratory will report the presence of yeasts (such as Candida sp.). If you desire more complex testing, such as for Mycoplasma, Ureaplasma, or Chlamydia, then you must indicate and collect the samples appropriately.

Question 3.5: What are the possible causes of recurrent lower UTIs? Which of these is most likely in this case?

Recurrence of UTI may be either a relapse (i.e., the reappearance of the original infection) or, far more commonly, reinfection, which is the occurrence of a new infection. Relapse is caused by the same organism that caused the original infection and usually occurs within 2 weeks following completion of antibiotic therapy. The short time frame suggests that the causative organism has persisted in the urinary tract or nearby, possibly because of an anatomic problem such as a stone or obstruction. A subclinical kidney infection (pyelonephritis or renal abscess) is another possibility. This patient's history does not support a diagnosis of relapse because the identity of the infectious agent changes from one incident to the next and the recurrences did not occur soon enough after completing antibiotic therapy. Reinfections can be caused by a different organism or by the same organism that caused the original infection. They can occur at any time after the original infection and do not imply an anatomical abnormality. It is not at all unusual for young women to experience a series recurrent UTIs that are unrelated to anatomical abnormalities or other conditions. In fact, 10% of all women experience this problem at some point in their lives.

Question 3.6: How should this case be treated?

The major goal here is to interrupt the cycle of colonization of the introitus and infection of the bladder. Success is achieved with drugs such as trimethoprim-sulfamethoxazole or some quinolones, which reach high concentrations not only in urine but also in vaginal secretions. Treatment generally requires long term prophylaxis (low dose), which may be administered either continuously or postintercourse (preferred).