Cystitis medical therapy

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Steven C. Campbell, M.D., Ph.D.

Overview

Antimicrobial therapy is indicated in cystitis. The treatment of cystitis depends on the disease course (acute uncomplicated vs. complicated) and the rates of resistance in the community. Due to the risk of the infection spreading to the kidneys (complicated UTI) and the high complication rate in diabetics and the elderly population, prompt treatment is almost always recommended.

Principles of Medical Therapy

• Acute uncomplicated cystitis definition includes Premenopausal, nonpregnant women with no known urological abnormalities or comorbidities,postmenopausal women or well-controlled diabetic female patients.

• The decision to use antimicrobials should be case based, in other words it should depend on the patients specifics like allergy and compliance history, availability and cost of treatment and resistant rates at the local community.

• Being the most common cause of cystitis (75-90%), E.Coli susceptibility should be considered when choosing the appropriate empirical antimicrobial. Other organisms like Proteus mirabilis, Klebsiella pneumoniae and Staphylococcus saprophyticus are less common.

• Nitrofurantoin, Fosfomycin and Mecillinam are prefered as first line treatment because they have less resistance among other antibacterials with similar efficacy.

• TMP-SMX is preferred in areas where the resistance rates are less than 20%.

• Nitrofurantoin, Fosfomycin and Mecillinam should not be used when pyelonephritis is suspected, because they have weak penetration to the renal tissue.
• Use of broad-spectrum antimicrobials like Fluoroquinolones have resulted in multidrug resistant organisms,so they are used as alternative to the first line drugs in case of allergy, unavailability or intolerance.
• Beta-lactams have less efficacy than Fluoroquinolones. While Ampicillin and Amoxicillin should be avoided due to high rate of resistance.
• Post-therapy urine culture is recommended only for pregnant women, multiple early recurrences with the same strain of bacteria and for persistent hematuria.

Acute Uncomplicated Cystitis

• Preferred regimen: Nitrofurantoin monohydrate/macrocrystal 100 mg bid 5 days (avoid if early pyelonephritis suspected) OR Trimethoprim-sulfamethoxazole 160/800 mg (one DS tablet) bid 3 days (avoid if resistance prevalence is known to exceed 20 or if used for UTI in previous 3 months) OR Fosfomycin trometamol 3 gm single dose (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected) OR Pivmecillinam 400 mg bid 5 days (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected)
• Alternative regimen (1): Fluoroquinolones, Ofloxacin, Ciprofloxacin, and Levofloxacin, use for 3 days.
• Alternative regimen (2): β-Lactam agents, including Amoxicillin-clavulanate, Cefdinir, Cefaclor, and Cefpodoxime-proxetil, for 3–7-days

Complicated/Catheter Associated cystitis

Cases of Complicated cystitis include: all men with the infection, pregnant women, children with metabolic or anatomical abnoramlities, and all patients with risk of serious complications and/or failure of treatment(stones, obstruction, immunocompromised patients, neurogenic bladder, renal failure,transplant patients) considered as complicated infections

• Urinary infections in catheterized patients tend to be polymicrobial with more resistant uropathogens.
• Urine culture:should be taken before initiation the antimicrobial therapy. For infected patients with indwelling catheters more than 2 weeks, the catheter should be replaced, and urine culture should be sampled from the new catheter to improve the outcome of treatment with less complications.

Duration of Treatment

• The duration of treatment depends on the response to treatment regardless of whether the catheter is still in place. For quick resolution, a 7 days regimen is recommended, while patients with delayed clinical improvement need an extended treatment regimen of 10-14 days.
• For mild catheter-associated UTIs, Levofloxacin for 5 days is recommended. A 3 day regimen of antimicrobials is recommended for women ≤ 65 with lower urinary symptoms only after catheter removal.

Cystitis in Pregnancy

• Urine culture is obtained after completion of antimicrobials regimen.
• Nitrofurantoin and Sulfonamides (category B) are not preferred before delivery. Nitrofurantoin should be avoided when G6PD deficiency is suspected with the fetus due to the risk of hemolytic anemia. Sulfonamides have been associated with increased unbound bilirubin levels in fetal blood and kernicterus.
• Trimethoprim (category C) is a folic acid antagonist, therefore it is not used in the first trimester to avoid the risk of possible birth defects.

Recurrent Cystitis

Recurrent cystitis suggests antimicrobial resistance.

• When there is recurrence or persistence of urinary symptoms within 1-2 weeks of treatment of uncomplicated cystitis, broad spectrum fluoroquinolones should be initiated after a urine culture.
• Recurrent cystitis that occurs at least one month after successful treatment is treated with a short course (7 days) of first line antimicrobial therapy, .
• Recurrence within 6 month of successful treatment should be treated with another first line agent than the one used first time.
• In postmenopausal women, it's recommended to evaluate correctable factors like cystocele, incontinence and residual urine volume ≥50 ml.

==Empiric Therapy for Acute Cystitis== Adapted from Clin Infect Dis. 2011;52(5):e103-20.

Acute Bacterial Uncomplicated Cystitis Preferred Regimen ▸ Nitrofurantoin 100 mg PO q12h × 5 days OR ▸ TMP 100 mg PO q12h ×3 days OR ▸ Fosfomycin 3 gm PO single dose OR If resistence<20% or if used for UTI >3 months ▸ TMP-SMX ‡ 1 DS tab PO q12h × 3 days OR Not FDA approved but used in some European countries ▸ Pivmecillinam 400 mg PO q12h 3-7 days Alternative Regimen ▸ Fluoroquinolones for 3 days ▸Ofloxacin 200–400 mg PO bid OR ▸Ciprofloxacin 250 mg bid PO or Cipro XR 500 mg q24h OR ▸Levofloxacin 250–750 mg PO q24 OR ▸ β-lactam agents for 3-7 days ▸Amoxicillin-clavulanate 500/125 mg PO q8h or 875/125 mg PO q8h OR ▸Cefdinir 300 mg PO q12h or 600 mg PO q24 OR Cefaclor 250-500 mg PO q8h OR ▸Cefpodoxime proxetil 100-200 mg PO q12h OR Cephalexin250-500 mg PO q6h not studied well but effective.

Complicated/Catheter Associated Cystitis Preferred Regimen Mild Infection ▸ Levofloxacin 750 mg PO q24 × 5 days Delayed Response ▸ Levofloxacin 750 mg PO q24 × 10-14 days After Catheter Removal ▸ Levofloxacin 750 mg PO q24 × 3 days Acute Cystitis in Pregnancy Preferred Regimen ▸Nitrofurantoin 100 mg PO q12h × 3-5 days OR ▸ Fosfomycin 3 g PO single dose OR ▸Amoxicillin-clavulanate 500/125 mg PO q12h × 3-5 days OR ▸ Amoxicillin 500 mg PO q12h × 3-5 days OR ▸Cephalexin 500 mg PO q12h × 3-5 days OR ▸ TMP-SMX DS 1 tab PO q12h × 3-5 days avoid in first trimester(TMP) and third trimester (SMX).