Etiology

The most common etiologic organism is Escherichia coli, responsible for approximately 80% of cases.[3][6]​​​​ Other less common etiologic organisms include Staphylococcus saprophyticus, Klebsiella pneumoniae, Proteus mirabilis, and other bacteria, including Pseudomonas, Enterococcus, Enterobacter, and group B streptococci.​[4]​​

High antibiotic usage for urinary tract infections (UTIs) such as acute cystitis has led to growing rates of antibiotic resistance. Of particular concern is the rise in infections caused by extended-spectrum beta-lactamase (ESBL)-producing organisms. Genes encoding the ESBL enzyme, which inactivates antibiotics such as penicillins and cephalosporins, are most prevalent in E coli, K pneumoniae, Klebsiella oxytoca, and P mirabilis. These organisms often have additional genes or mutations that confer resistance to a broad range of antibiotics. Infection with ESBL-producing organisms may therefore have important treatment implications.[11]​​ See Management approach.

UTIs such as acute cystitis can be classified as uncomplicated or complicated.[1][8]​​​​ The etiology of complicated UTI may be due to anatomic or functional abnormalities.[1]

  • Anatomic abnormality is mostly due to the presence of posterior urethral valves, strictures, or stones.

  • Functional abnormality most commonly results from lower urinary tract dysfunction of neurogenic (e.g., spina bifida) or non-neurogenic origin (e.g., voiding dysfunction), as well as dilating vesicoureteral reflux.

Pathophysiology

Escherichia coli or other bacteria that are normally found in the gastrointestinal tract or vagina can be introduced into the urethra resulting in infection. This may happen during sexual intercourse, as is common in young sexually active women, or through gradual colonization of the adjacent tissues. Bacteria may also be introduced into the normally sterile urinary tract through instrumentation, as in cystoscopy or use of a urinary catheter. Compromised natural defenses, that is, bladder outlet or immunological abnormalities, allow bacteria easier access or survival, respectively, whereas an intravesical pathology, such as a bladder stone, harbors bacteria.

Certain strains of E coli express bacterial virulence factors that promote their uropathogenicity. In one study, the presence of virulence factors alpha-hemolysin, P fimbriae, and mannose-resistant hemagglutination type IVa was associated with the progression of cystitis to acute pyelonephritis.[12] Tamm-Horsfall protein, which is the most abundant protein present in normal urine, binds to the P fimbriae of the E coli, and helps to protect the uroepithelium from colonization with uropathogenic E coli.[13]

Classification

Complicated

More extensive evaluation and longer course of treatment may be required in the presence of the following:[1]

  • Anatomic or functional abnormalities within the urinary tract

  • Male sex

  • Pregnancy

  • Immunosuppression (e.g., renal transplant)

  • Diabetes

  • Incomplete voiding

  • Indwelling urinary catheter

  • Recent instrumentation

  • Healthcare-associated infection

  • Infection with extended spectrum beta-lactamase-producing organisms or other multidrug resistant organisms.

Uncomplicated

Patient lacks any of the complicating factors listed above.[1]

Acute uncomplicated cystitis should be differentiated from asymptomatic bacteriuria (ABU). ABU is defined as the presence of bacterial growth ≥10⁵ colony-forming units/mL in 2 consecutive midstream samples in women and 1 sample in men, in the absence of urinary tract symptoms.[1] ABU is considered not to be infection, but rather a commensal colonization. 

Recurrent

A recurrent urinary tract infection may be complicated or uncomplicated, and is defined as at least 3 cases per year, or 2 cases within 6 months.[1]

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