Nonbacterial and Noninfectious Cystitis Treatment & Management

Updated: Mar 09, 2018
  • Author: Lynda A Frassetto, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Treatment

Approach Considerations

Treatment of nonbacterial cystitis addresses the specific cause. Noninfectious etiologies that require separate consideration are radiation cystitis, chemical cystitis, autoimmune cystitis, and interstitial cystitis. For treatment options in painful bladder syndrome/interstitial cystitis, see Interstitial Cystitis. Surgical treatment is rarely needed for nonbacterial cystitis.

With infectious cystitis, the cause may be viral, chlamydial, mycobacterial, schistosomal, or fungal. Most infectious cases are treated with systemic and, in some cases, local pharmacotherapy. If the patient is taking immunosuppressive medication, the treatment regimen may need to be adjusted.

Some types of infectious, recurrent, nonbacterial cystitis are being treated with transfer factor (TF) specific for the kind of infection (Candida, herpes). De Vinci and associates demonstrated a marked decrease in the number of recurrences in females treated with oral TF for this disorder. [28]

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Treatment of Infectious Nonbacterial Cystitis

Viral cystitis

Treatment for immunocompetent adults with cystitis from herpes simplex virus–1 (HSV-1) or HSV-2 includes acyclovir 400 mg 5 times daily for 7 days or valacyclovir 500 mg twice daily for 5-10 days. Acyclovir requires dose adjustment for patients with a decreased glomerular filtration rate.

Ganciclovir and vidarabine have been used in some cases of hemorrhagic cystitis from cytomegalovirus (CMV) or adenovirus in patients who have undergone bone marrow transplantation. [29, 30] Valganciclovir is an oral prodrug with greater intestinal absorption than ganciclovir.

Cystitis due to BK polyomavirus reportedly resolved without treatment in 9 pediatric patients. However, in adults who have undergone renal transplantation, cidofovir and a decrease in the dose of immunosuppressants are usually recommended, because of the concern of renal parenchymal damage from the virus. [31]  Treatment with leflunomide and fluoroquinolone antibiotics have also been reported. [4] Mycophenolate mofetil has been associated with more adenoviral infections than azathioprine.

In a phase II study of 45 infections in 38 patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), Tzannou et al demonstrated the therapeutic efficacy of adoptively transferred, virus-specific T cells (VSTs) that recognized Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6). A single infusion produced complete or partial response in 92% of patients, including response in 100% of the 16 patients with BKV infections, 94% of the 17 patients with CMV infections, 71% of the 7 patients with AdV infections, 2 of the 2 patients with EBV infections, and 2 of 3 patients with HHV-6 infections. Complete resolution of gross hematuria by week 6 was observed in 13 of 14 patients treated for BKV-associated hemorrhagic cystitis. [32]

Chlamydial cystitis

Treatment regimens for cystitis caused by Chlamydia include the following:

  • Doxycycline, 100 mg twice daily for 7 days

  • Azithromycin, 1g orally as a single dose

  • Erythromycin, 500 mg 4 times daily for 7 days

  • A fluoroquinolone (eg, ofloxacin, 300 mg twice daily for 7 days)

Erythromycin, azithromycin, and amoxicillin can also be used in pregnant women.

Mycobacterial cystitis

Mycobacterial treatment begins with 3 or 4 agents, generally including isoniazid (INH) and rifampin (RIF), depending on the probable sensitivities of the organism and the underlying state of the immune system. A standard regimen is as follows:

  • INH 300 mg/day

  • RIF 600 mg once daily

  • Ethambutol (EMB) 15 mg/kg/day

  • Pyrazinamide 2 g/day

Other drugs that can be used include streptomycin 0.75-1g/day, ethionamide (ETH) 1g/day, or a fluoroquinolone. Treatment regimens are modified when the actual drug sensitivities are determined. Drug toxicities sufficient to require a change in regimen occur in up to 5% of patients.

Surgery is rarely needed to treat tuberculosis of the genitourinary system.  However, when surgery is necessary, complex reconstruction is often required.

Fungal cystitis

Treatment is recommended only when the funguria is symptomatic or in cases of fungal colonization when host factors increase the risk of fungemia. [25] Fungal cystitis in immunocompetent patients with indwelling catheters may respond to removal of the catheter without further treatment of the infection. If removal of the catheter is not an option, treatment with oral azole antifungal agents or bladder irrigations containing amphotericin B, 50 mcg/mL for 5 days, can be instituted.

In immunosuppressed patients, another option may be intravenous amphotericin B, depending on the degree of dissemination of the infection. Azole antifungal agents are often not effective against Candida species. [14] Testing for susceptibility to antifungal agents may be necessary if patients have previously received therapy for fungal infections. Measures to reduce risk factors include removing urinary catheters; limiting antibiotic treatment; and, in patients with diabetes, optimizing management of glycemia. [25]

Echinocandins (eg, caspofungin, micafungin), a newer class of agents that are active against azole- and polyene-resistant fungi, are a possible alternative. One trial that compared caspofungin with amphotericin B for invasive candidiasis demonstrated similar efficacy and markedly fewer side effects for caspofungin. Some infectious disease specialists consider caspofungin to be first-line therapy against invasive non-albicans candidal species. Micafungin can often be used against fungi that are resistant to azole antifungal agents.

If bladder outlet obstruction is suspected in the setting of severe funguria, a Foley catheter or suprapubic tube can be placed. After resolution of the infection, benign prostatic hyperplasia should be managed surgically.

Schistosomal cystitis

All patients with schistosomiasis should be treated, regardless of disease severity. [33] The current recommended treatment for schistosomiasis is 2 oral doses of praziquantel 40 mg/kg for 1 day. This regimen results in cure rates of 83-100%.

Surgery should be reserved for cases that do not respond to medical therapy or for patients with intractable gross hematuria. Schistosomiasis can cause large granulomas in the bladder, which may warrant surgical extirpation.

Obstructive uropathy due to ureteral strictures is the most common sequela. Management of ureteral stricture is based on the stricture length and location. Deep, nonhealing bladder ulcers may require partial cystectomy, while biopsy-proven bladder cancer often requires radical cystectomy.

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Treatment of Noninfectious Nonbacterial Cystitis

Radiation cystitis

While minor bleeding episodes due to radiation treatment stop without treatment, severe bleeding may require hospitalization for therapy. Clot evacuation and continuous bladder irrigation are the standard treatment for heavy bleeding. A small number of patients with severe bleeding require further treatment. Methods that have been tried include hyperbaric oxygen therapy and chemical therapy. Urinary diversion surgery is the surgical treatment of choice in patients whose symptoms fail to resolve. [34, 35, 36]

In a study by Del Pizzo et al of long-term results of hyperbaric oxygen in 11 patients, 3 had complete resolution of symptoms, 3 had persistent symptoms, and 5 had initial improvement but then relapsed. [37] In a review by Chong et al of hyperbaric oxygen therapy in 60 patients with radiation cystitis, 80% had complete or partial resolution of the hematuria, and 96% (27 of 28) of patients treated within 6 months of the onset of hematuria had complete resolution of symptoms. [38]

Srisupundit and colleagues reported good short-term results (follow-up, 1-9 mo) in 13 of 20 patients treated with an intravenous infusion of a chemically stabilized chlorite matrix tetrachlorodecaoxygen (TCDO). [39]

Chemical cystitis

Chemical cystitis from chemotherapy agents, such as cyclophosphamide, may resolve with hydration or with discontinuation of the drug. Another alternative is mesna, a semisynthetic sulfhydryl compound that reacts chemically with the drug metabolites that cause urotoxicity, detoxifying them in a manner similar to the physiologic cysteine-cystine system.

Ballen and colleagues suggested that extremely aggressive hydration with intravenous fluids and diuretics to maintain a urine output greater than 150 mL/h may be as effective a therapy as mesna, as well as being much less expensive. [40]

Autoimmune cystitis 

Treatment of autoimmune diseases generally relies on a combination of symptomatic relief, anti-inflammatory drugs, and immunosuppressive agents. In the last several years, monoclonal antibodies to tumor necrosis factor (TNF)–alpha and several of the interleukins have markedly improved symptoms in some of the rheumatic diseases. The greater variety of immunologic targets amenable to treatment modification has allowed rheumatologists to tailor combinations of drugs to yield improved efficacy with fewer symptoms.

At present, no therapy for eosinophilic cystitis is curative. Treatments that have been tried include anti-inflammatory therapies with nonsteroidal anti-inflammatory drugs and steroids and transurethral resection of the bladder lesion. [3] Other anti-inflammatory agents are under investigation, such as IPD-1151T, an immunoregulatory agent that suppresses T cell–mediated cytokines responsible for immunoglobulin-E (IgE) production and eosinophilia, as well as interleukin-4 (IL-4) and IL-5.

Ketamine-induced cystitis (KC)

There is no standard for diagnosing and treating ketamine-induced cystitis. Treatment currently involves symptom management. Different therapeutic strategies for different clinical stages of KC have been proposed. [41]  In the early stage, but not the later stage of disease, ketamine cessation together with other medications may resolve lower urinary tract symptoms. [42]

Wu et al classified 81 patients into three stages (I–III) according to the severity of the disease, the dose, and the duration of ketamine abuse. Patients in stage I were treated with behavioral modification and pharmacotherapy, patients in stage II with hydrodistention and patients in stage III with surgical intervention due to rapid progression after conservative therapy. All patients in three stages demonstrated improvements in void volume, micturition interval, nocturnal void frequency and Pelvic Pain and Urgency/Frequency (PUF) score (all P < 0.05) after treatment. [41]

In a study of thirty-six patients with KC refractory to conservative pharmacotherapy treated with botulinum toxin A injection along with bladder hydrodistention, all achieved relef of symptoms. The nocturia time was markedly reduced, while bladder capacity, the interval between micturition, the void volume, and the maximum flow rate were increased at 1 month. Additionally, the O’Leary–Sant interstitial cystitis symptom index (ICSI) and problem index (ICPI) scores were significantly improved. [41]

A number of small studies have shown positive results from surgical intervention with augmentation enterocystoplasty for KC following failure of conservative treatment.  [18, 41, 43]

 

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