URINARY TRACT INFECTION/ CYSTITIS/ PYELONEPHRITIS/ URETHRITIS

     Urinary tract infections (UTI) are a common complaint encountered in primary care.  The typical patient is an adult female; however, infections in older male patients and young females are not uncommon.  Enteric gram negative bacilli are the usual pathogens associated with UTIs.  The majority of cases are related to infection with Escherichia coli.  Other common pathogens include Proteus, Klebsiella, Enterobacter, Serratia, and Pseudomonas species, along with Staphylococcus saprophyticus.  However, virtually any organism to include bacteria, mycobacteria and fungal elements may cause infection of the urinary tract.  Urinalysis will often reveal a “positive” reduction of nitrates to nitrites and/or leukocytes plus possibly hematuria or proteinuria.  Nitrate reduction will not take place when gram positive pathogens or Pseudomonas aeruginosa are the underlying infectious agents.  Urine microscopy will show at least 10 WBC/HPF of spun sediment which are predominantly neutrophils.  If eosinophils are the predominat cell type, suspect interstitial nephritis.  If WBC casts are noted, pyelonephritis is present.  Urine cultures which contain 10⁵ or more bacteria per milliliter are diagnostic.  In symptomatic female patients, cultures with as few as 10² bacteria per milliliter may be diagnostic.  Lesser bacteria counts need to be interpreted in conjunction with the patient’s symptoms.

     Pyelonephritis may involve the renal tubules, interstitium or pelvis.  There are acute and chronic forms of this disorder.  Acute symptoms are secondary to bacterial infection with the above pathogens in the majority of cases and often respond well to antibiotic therapy.  Acute infections often present with flank pain, dysuria, fever, and chills.  Gastrointestinal upset to include nausea, vomiting and anorexia may also be present.  Leukocytosis with a left shift is often detected on CBC.  Blood cultures should be obtained as bacteremia is noted in some patients and may help guide therapy.  Chronic symptoms may be secondary to infection along with vesicoureteral reflux or obstruction.  Chronic pyelonephritis may progress to kidney failure from scarring of the renal interstitium.  Initial therapy for acute pyelonephritis is based on the suspected organism, and E. coli is the most common infectious agent. Therapy should be for at least 14 days.  If patients are not suffering from severe nausea and vomiting and are immunocompetent they may be treated on an outpatient basis with oral antibiotics.  If patients can not tolerate orals, are suffering from hypotension or orthostatic changes in vital signs, or if they appear “toxic”, initial therapy may need to be administered intravenously in a hospital setting until symptoms subside and then the patient may continue the full course of therapy with oral antibiotics on an outpatient basis.  If symptoms are severe or do not respond to appropriate antibiotics within 72 hours, or if the patient is immunocompromised, a renal ultrasound may be needed to eliminate the possibility of a renal or perinephric abscess.

     Cystitis is the more common type of infection in which patients present with dysuria, urinary frequency, urgency, suprapubic discomfort, hematuria and/or foul smelling urine.  Many cases are spontaneous but an increased incidence of infection is seen with structural abnormalities of the urinary tract (staghorn calculi, prostatic hypertrophy, polycystic kidney disease), invasive urethral instrumentation (most commonly Foley catheterization), or any process which impairs the flow of urine (bladder outlet obstruction, neurogenic bladder).  Patient populations which exhibit a higher incidence of infection include pregnant women and female patients with diabetes mellitus or sickle cell anemia.

     Special considerations in the pregnant patient include the need to treat asymptomatic bacteruria.  Treatment is necessary in this patient population as asymptomatic bacteruria predisposes to an increased incidence of preterm labor and/or pyelonephritis.  Nitrofurantoin is the drug of choice in the pregnant patient.

     Adult females are most commonly affected.  In uncomplicated cases, culture is often unnecessary, and empiric therapy with either trimethoprim/sulfamethoxazole, nitrofurantoin, or a fluoroquinolone for three days is adequate.  If dysuria is severe, pyridium 200 mg PO TID x 2 days may alleviate the discomfort.  Patients should be warned that their urine and other bodily secretions may turn orange and that contact lenses should not be worn during therapy as staining may occur.  If infection persists or recurs then culture may be necessary to guide therapy, and a prolonged course of antibiotics (1-2 weeks) may be required.  Recurrent infections may be secondary to reinfection (different etiologic agents) or relapse (the same organism persists).  If infections continue, evaluation of the urinary tract for structural abnormalities or an infectious foci (abscess or calculi) may be required.  If infection is persistent, if the patient is immunocompromised,  or if urinalysis reveals sterile pyuria, consider tuberculosis or fungal infections.  Urine for fungal culture and mycobacterial culture will evaluate for these possible pathogens.  Also, a urine culture for Mycoplasma hominis and Ureaplasma urealyticum should be ordered as these not uncommon organisms require special media. A positive PPD will show if the patient has TB infection (but not necessarily active disease), although patients with TB may suffer from bacterial cystitis.  Appropriate therapy includes the same agents used for pulmonary tuberculosis continued for a full year.  Fungal UTIs are often sensitive to ketoconazole or itraconazole.

     Elderly women differ from younger female patients in that the incidence of asymptomatic bacteruria (positive urine culture in a patient with no symptoms of infection) is much higher and the course of therapy for even uncomplicated infections is longer.  Asymptomatic bacturia should not be treated as recurrence is common.  Although if a patient recently developed a change in mentation and had bacturia without other symptoms, a trial of an appropriate antibiotic would not be unreasonable.  The reason being that UTIs can cause acute altered mental status in the elderly, and the patients may not complain of symptoms in their altered state.  If the altered mentation does not improve with appropriate antibiotic therapy, then a different etiology should be suspected.  While E. coli is a common pathogen in older female patients, their incidence of infection with other enteric pathogens (Proteus, Klebsiella, Enterobacter, Serratia, or Pseudomonas species) and polymicrobial infections is higher than younger adult female patients.  Fluroquinolones are the first line agents for this patient population, and therapy should be continued for 7 to 10 days.  The regular ingestion of cranberry juice and the use of oral or vaginal estrogen replacement therapy (along with progesterone in patients who have not had their uterus removed) may help decrease the incidence of infection in patients who suffer recurrent UTIs.  Estrogen therapy lowers the vaginal pH and allows recolonization with lactobacilli.  Lactobacilli, which are nonuropathic, serve to maintain a low vaginal pH which is prohibitive to the growth of common urinary pathogens.

     UTIs are uncommon in younger male patients; however, male patients who are past middle age or are institutionalized have an incidence of infection equal to their female counterparts.  The increase in UTIs with advancing age is believed to be related to hypertrophy of the prostate gland.  E. coli, plus Proteus and Providencia species account for most infections in men.  A 10 day course of treatment with trimethoprim-sulfamethoxazole or a fluoroquinolone is recommended for empiric therapy.  Antibiotic selection may be changed if dictated by persistent symptoms and culture sensitivities.  When symptoms recur a repeat culture will help determine if there is relapse (same organism from prior infection) or reinfection (new organism).  In patients with relapse consider anatomic or functional abnormalities such as prostatic calculi, prostatic abscess, infected renal cysts, renal abscess, or more commonly chronic bacterial prostatitis.  At this point, it is prudent to start prolonged antibiotic therapy with the appropriate agent as dictated by sensitivity testing for 6 to 12 weeks.  If symptoms then recur, evaluation of the urinary tract (CT Urogram, voiding studies) or referral to a urologist is prudent.

     Urethritis may be caused by many different pathogens.  Common etiologies include Chlamydia trachomatis, Neisseria gonorrhoeae, and herpes simplex virus.  Cultures for C. trachomatis and N. gonorrhoeae are advised.  If herpes is suspected, an empiric trial of therapy may prove useful.  If symptoms persist despite an antiviral (acyclovir, valcyclovir, or famcyclovir) then another etiology should be considered.  Severe niacin deficiency may result in pellagra (dermatitis, diarrhea, mental status changes, and mucus membrane inflammation which may manifest as urethritis). Urethritis with associated arthritis should raise suspicion of N. gonorrhoeae infection or possible Reiter's syndrome.