Cystitis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D., Usama Talib, BSc, MD [2]

Overview

A major proportion of the urinary tract infections resolves on its own if left untreated. Complications can occur but not very frequently. Cystitis can though increase morbidity and the goal of therapy is early resolution of infectious symptoms. 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.

The increasing resistance to various drugs is a growing challenge. One aspect of increasing drug resistance is the gram negative bacteria population that produces extended spectrum beta lactamase. Hyperbaric oxygen is used to treat hemorrhagic cystitis associated with exposure to radiation and emphysematous cystitis, as presence of gas in the bladder wall interferes with the tissue oxygenation. Proper oxygenation may help to curtail the associated damage.

Principles of Medical Therapy

• The choice of therapy depends on whether the patient has uncomplicated vs complicated cystitis, known patient allergies, and regional resistance patterns.
• Cystitis among men is always considered complicated cystitis and should be managed accordingly.
• Symptomatic women with no history of urinary tract infection or a lab-confirmed infection are recommended to undergo testing for urinary tract infection by urinalysis or dipstick testing for the detection of pyuria.
• Symptomatic women who have had frequent recurrences in the past and prior confirmation of urinary tract infections may be treated empirically.
• For women with first-time cystitis, a urine culture is not required prior to administration of empiric therapy.
• Discontinuation of the drug causing cystitis is the first approach for cystitis caused by a drug. Similarly in case of a foreign body like a stone or catheter that lead to cystitis, removal is necessary. The associated conditions like BPH, have to be treated to make sure that the patient does not have to face recurrence of urinary tract infection.

Acute Uncomplicated Cystitis

Patients with acute uncomplicated cystitis may be treated using a single antimicrobial therapy using either a single dose or a 3-day regimen. Nitrofurantoin is preferred over Fluoroquinolones in treating uncomplicated cystitis due to the increasing resistance to fluoroquinolones. The following list of antimicrobial agents may be administered:

• Empiric Therapy:

• Preferred regimen (1): Fosfomycin tromethamine 3 g PO single dose
• Preferred regimen (2): Nitrofurantoin monohydrate/macrocrystals 100 mg PO bid for 5 days
• Preferred regimen (3): Trimethoprim-Sulfamethoxazole 160/800 mg PO double-strength tablet bid for 3 days
• Preferred regimen (4): Trimethoprim 100 mg PO bid for 3 days
• Preferred regimen (5): Pivmecillinam 400 mg bid for 5 days
• Alternative regimen (1): Ciprofloxacin 250 mg PO bid for 3 days
• Alternative regimen (2): Levofloxacin 250 mg PO qd for 3 days
• Alternative regimen (3): Ofloxacin 200–400 mg po bid
• Alternative regimen (4): Norfloxacin 400 mg PO bid for 3 days
• Alternative regimen (5): Gatifloxacin 200 mg PO qd for 3 days
• Alternative regimen (6): Amoxicillin-clavulanate 500/125 mg po tid or 875/125 mg po bid
• Alternative regimen (7): 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
• Note (1): Avoid Nitrofurantoin and Fosfomycin if pyelonephritis is suspected
• Note (2): Avoid Trimethoprim-based regimens if resistance regional prevalence exceeds 20% or if patient had a prior UTI within the past 3 months
• Note (3): β-lactam-based regimens are less effective than other available agents and are only indicated when other agents cannot be used.

• Pivmecillinam and Fosfomycin are considered first line agents for uncomplicated cystitis due to their strong action against gram negative organisms like the EColi, which are the most common pathogens causing cystitis and their ability to cause less side effects as compared to Fluroquinolonesand beta lactam drugs.
• The use of ibuprofen marks the alternate therapeutic option for treating uncomplicated symptomatic Cystitis.

Complicated Cystitis

• Patients with complicated cystitis generally require a longer duration of therapy compared with patients with uncomplicated cystitis.
• Patients who meet at least one of the following criteria are considered to have complicated cystitis:

• Male gender
• Pregnant women
• Presence of symptoms for more than 7 days
• Metabolic diseases like diabetes mellitus
• Hospital acquired cystitis
• Children with genitourinary abnormalities
• Patients suspected to be at high risk of developing complications or treatment failure, including:

• Patients with ureteric stents
• Patients with urinary stone
• Patients with neurogenic bladder
• Immunocompromised patients
• Renal failure patients
• Renal transplant patients

• Empiric Therapy:

• Preferred regimen (1): Ofloxacin 200–400 mg po bid.
• Preferred regimen (2): Ciprofloxacin 250 mg bid po or Cipro XR 500 mg q24h
• Preferred regimen (3): Levofloxacin 250–750 mg po q24.

• Special attention to the choice of antimicrobial therapy is required when administering antimicrobial agents to children and pregnant/lactating women. In pregnancy, Nitrofurantoin, Sulfonamide, Trimethoprim, and fluoroquinolones should be avoided.
• A single dose of Fosfomycin is a good option to treat cystitis in a pregnant patients.
• The duration of therapy for the management of cases of complicated cystitis is not well established. The majority of clinical trials evaluated the efficacy of antimicrobial agents over 7-14 days (range: 5-20 days).
• The general consensus is to treat complicated cases of complicated cystitis for 7 days.
• Long-term therapy among high-risk patients is not established and is often tailored on an individual basis.

Catheter Associated UTIs

• 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 out come of treatment with less complications.

• Regimen : TMP-SMX DS 1 tab bid x 3 days

Duration of treatment

• Depends on the response to treatment regardless of the catheter is still placed or not. For quick resolution, a 7 days regimen is recommended. While delayed clinical improvement needs extended regimen (10-14 days).
• For mild catheter associated UTI, levofloxacin for 5 days is recommended. While 3 days regimen of antimicrobials is recommended for women≤65 with lower urinary symptoms only after catheter removal.

Relapses

True relapses may be caused by uropathogenic Escherichia coli that is protected under a biofilm.

Recurrent Cystitis

In case of a case of recurrent cystitis, urine cultures must be performed and long acting agent be used initially like a Fluroquinolone.

• Recurrent Cystitis may be attributed to the developing resistance to the old therapies. This can be related to the extended spectrum beta lactamase producting gram negative bacteria. It can also be attributed to a particular strain of Ecoli Sequence type 131 (ST131).
• Patients with recurrent cystitis may require prolonged prophylactic antimicrobial therapy for 6-12 months.
• The same antimicrobial agents that are indicated for uncomplicated cystitis are also indicated for recurrent cystitis.
• In case of a recurrent infection within 6 months of adequate therapy, a different first line agent should be used to treat the recurrence.
• Patients with recurrent cystitis should be re-evaluated at the time of completion of therapy.
• Hyaluronic acid is considered to be effective in patients with recurrent Cystitis, interstitial cystitis and hemorrhagic cystitis.

Prophylaxis for Recurrent Cystitis

The following aspects about prophylaxis of recurrent cystitis must be kept in mind.

• If recurrence is associated with sexual activity, prophylaxis can be given after each intercourse.
• If recurrence is relate to pregnancy, the patient can be given a prophylaxis for the duration of pregnancy.
• If recurrence is associated with diabetes, BPH or another disease prophylaxis is give after first episode of cystitis to prevent subsequent episodes.
• To view the list of regimens indicated for the primary prevention of cystitis, click here.