Nonbacterial Cystitis Treatment & Management

  • Author: Lynda A Frassetto, MD; Chief Editor: Edward David Kim, MD, FACS   more...
 
Updated: Apr 21, 2010
 

Medical Therapy

Treatment of nonbacterial cystitis depends on the etiology, when it can be determined.

Infectious Etiologies

If the host is immunocompromised, treatment regimens may need to be adjusted. Some medications, such as acyclovir, also require dose adjustment for patients with a decreased glomerular filtration rate.

Herpes simplex

In recent years, several antiviral agents chemically related to acyclovir have been shown to be effective against HSV-1 and HSV-2. Treatment for immunocompetent adults includes acyclovir 400 mg 5 times/day for 7 days or valacyclovir 500 mg bid for 5-10 days.

Viral-associated hemorrhagic cystitis

Ganciclovir and vidarabine have been used in some cases of CMV or adenoviral-associated hemorrhagic cystitis 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 polyoma virus 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 is usually recommended because of the concern of renal parenchymal damage from the virus. Mycophenolate mofetil has been associated with more adenoviral infections than azathioprine.

Chlamydia

Chlamydia can be treated with doxycycline 100 mg bid for 7 days, azithromycin 1 g orally as a single dose, erythromycin 500 mg qid for 7 days, or one of the fluoroquinolones, such as ofloxacin 300 mg bid for 7 days. Erythromycin, azithromycin, and amoxicillin can also be used in pregnant women.

Mycobacteria

Mycobacterial treatment begins with 3 or 4 agents, generally starting with isoniazid (INH) and rifampin (RIF) and another 1 or 2 agents, depending on the probable sensitivities of the organism and the underlying state of the immune system. Standard treatment regimens include INH 300 mg/d, RIF 600 mg qd, ethambutol (EMB) 15 mg/kg, and pyrazinamide 2 g/d. Other drugs that can be used include streptomycin 0.75-1 g/d, ethionamide (ETH) 1 g/d, or one of the fluoroquinolones. 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.

Schistosomiasis

The current recommended treatment for schistosomiasis is two oral doses of praziquantel 40 mg/kg for 1 day, resulting in cure rates of 83%-100%. All patients with schistosomiasis should be treated, regardless of disease severity.[31]

Funguria

Treatment is recommended only when the funguria is symptomatic or in cases of fungal colonization when host factors increase the risk of fungemia.[19] Fungal cystitis in immunocompetent patients with indwelling catheters may simply 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. Susceptibility testing 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 optimizing diabetes management.[19]

Recently, several new antifungal agents called echinocandins that are active against azole and polyene-resistant pathogens have been developed. One trial that compared one of these newer agents, 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, a newly approved echinocandin, can often be used against fungi that are resistant to azole antifungal agents.

Noninfectious Etiologies

Noninfectious etiologies include radiation cystitis, chemical cystitis, autoimmune cystitis, and interstitial cystitis.

Radiation cystitis

While minor bleeding episodes due to radiation treatment stops 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. The long-term results of hyperbaric oxygen in 11 patients was reported by Del Pizzo—3 had complete resolution of symptoms, 3 had persistent symptoms, and 5 had initial improvement but then relapsed.[32] In a more recent review by Chong et al of 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.[33]

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).[34]

Urinary diversion surgery is presently the surgical treatment of choice in patients whose symptoms fail to resolve.

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 drug metabolites, detoxifying them in a manner similar to the physiologic cysteine-cystine system. Recently, Ballen and colleagues have 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.[35]

Autoimmune cystitis

Treatment of autoimmune diseases generally relies on a combination of symptomatic relief, anti-inflammatory, 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 that 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.[12]

Painful bladder syndrome/interstitial cystitis

Please see Interstitial Cystitis for treatment options.

Medications

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.

Antimicrobial agents

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Rifampin (Rifadin, Rifadin IV, Rimactane) inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which in turn blocks RNA transcription. The dosage in adults is 600 mg PO qd for 6 mo. Rifampin induces microsomal enzymes, which may decrease effects of other drugs. Blood pressure may increase with coadministration of enalapril. Coadministration with isoniazid or pyrazinamide may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur).

Obtain CBC counts and baseline clinical chemistries prior to and throughout rifampin therapy. In liver disease, weigh benefits against risk of further liver damage. Interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur. Rifampin is a pregnancy category C drug.

Isoniazid (Laniazid, Nydrazid) is an isonicotinic acid hydrazide (INH), which is part of a triple-drug regimen. The adult dosage is 300 mg PO qd for 6 mo. Previous isoniazid-associated hepatic injury or other severe adverse reactions are contraindications. Daily alcohol ingestion may predispose to isoniazid-related hepatitis. Aluminum salts may decrease isoniazid serum levels (administer 1-2 h before taking aluminum salts). Isoniazid may increase anticoagulants effects with coadministration and may inhibit metabolic clearance of benzodiazepines. Carbamazepine toxicity or isoniazid hepatotoxicity may result from concurrent use (monitor carbamazepine concentrations and liver function). Coadministration with cycloserine may increase CNS side effects (eg, dizziness). Acute behavioral and coordination changes may occur with coadministration of disulfiram. Coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy.

Isoniazid may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin. Monitor patients with active chronic liver disease or severe renal dysfunction; periodic ophthalmologic examinations during isoniazid therapy are recommended even when visual symptoms do not occur. Isoniazid is a pregnancy category C drug.

Pyrazinamide’s mechanism of action is unknown. It is well absorbed from GI tract and hydrolyzed to active metabolite in liver. Note that 70% is excreted in urine within 24 h. Treat patients with drug-resistant disease with individualized regimens. The adult dose is 2 g PO qd for 2 months. Contraindications include severe hepatic damage and acute gout. Coadministration with rifampin may result in higher rate of hepatotoxicity than with either agent alone (discontinue if alterations in LFTs occur). Use only in combination with other effective antituberculous agents. Pyrazinamide inhibits renal excretion of urates and may result in hyperuricemia (usually asymptomatic). Perform baseline serum uric acid determinations and discontinue drug upon signs of hyperuricemia with acute gouty arthritis. Perform baseline LFTs (closely monitor in liver disease) and discontinue drug if signs of hepatocellular damage appear. Caution in history of diabetes mellitus. Pyrazinamide is a pregnancy category C drug.

Ethambutol (Myambutol) diffuses into actively growing mycobacterial cells, such as tubercle bacilli. It impairs cell metabolism by inhibiting synthesis of one or more metabolites, which in turn causes cell death. No cross-resistance has been demonstrated. Mycobacterial resistance is frequent with previous therapy. Use in these patients in combination with previously unadministered second-line drugs. The adult dose is 15 mg/kg PO qd for 2 mo. Optic neuritis is a contraindication, unless clinically indicated. Aluminum salts may delay and reduce absorption (give several hours before or after ethambutol dose). Reduce dose in impaired renal function. Ethambutol may have reversible visual adverse effects if promptly discontinued. Ethambutol is a pregnancy category C drug.

Antifungal agents

Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Amphotericin B, conventional (Amphocin, Fungizone) is produced from a strain of Streptomyces nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules.

A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B may reside in ability to cause auto-oxidation of cell membranes. The adult dose is 0.5 mg/kg IV qd for 7-14 d; 50 mcg/mL bladder irrigation continuously for 5 days.

Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension. Corticosteroids, digitalis, and thiazides may potentiate hypokalemia. The risk of renal toxicity is increased with cyclosporine. Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC counts, and hemoglobin concentrations. Resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for more than 7 d. Hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion). Fever and chills are not uncommon after first few administrations of drug. Rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock. Amphotericin B is a pregnancy category B drug.

Fluconazole (Diflucan) is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. It has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Fluconazole is available in tablet form for oral administration, as a powder for oral suspension, and as a sterile solution for IV use. It has fewer adverse effects and better tissue distribution than older systemic imidazoles. The adult dosage is 200 mg PO/IV qd for 7-14 d. Probenecid, zidovudine, or cimetidine coadministration prolongs half-life and increases CNS toxicity of valacyclovir. Adjust dose for renal insufficiency; closely monitor if rashes develop, and discontinue drug if lesions progress.

Fluconazole may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) when taken with underlying medical conditions (eg, AIDS, malignancy) or while taking multiple concomitant medications. It is not recommended for breastfeeding mothers. Convenience and efficacy of single-dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with oral fluconazole versus intravaginal agents. Fluconazole is a pregnancy category C drug.

Antiviral agents

Nucleoside analogs are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit HSV polymerase with 30-50 times the potency of human alpha-DNA polymerase.

Acyclovir (Zovirax) is a prodrug activated by phosphorylation by virus-specific thymidine kinase that inhibits viral replication. Guanylate kinase converts the monophosphate form into diphosphate and triphosphate analogues that inhibit viral DNA replication. It has affinity for viral thymidine kinase and, once phosphorylated, causes DNA chain termination when acted on by DNA polymerase. It inhibits activity of both HSV-1 and HSV-2. Patients experience less pain and faster resolution of cutaneous lesions when used within 48 h from rash onset. It may prevent recurrent outbreaks. Early initiation of therapy is imperative. The adult dosage is 400 mg PO 5 times/day for 7 days. Concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity of acyclovir. Caution in renal failure or when using nephrotoxic drugs. Acyclovir is a pregnancy category B drug.

Valacyclovir (Valtrex) is a prodrug rapidly converted to the active drug acyclovir. It is more expensive than acyclovir but has a more convenient dosing regimen. The adult dosage is 500 mg PO bid for 5-10 days. ACE inhibitors, cyclosporin, and potassium-sparing diuretics cause increased risk of hyperkalemia. Caution in renal failure (decrease dose) and coadministration of nephrotoxic drugs; it is associated with onset of hemolytic uremic syndrome. Valacyclovir is a pregnancy category B drug.

Valganciclovir (Valcyte) is an L-valyl ester prodrug of ganciclovir used for cytomegalovirus (CMV) disease prophylaxis in various solid organ transplants. Ganciclovir is a synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human CMV in vitro and in vivo. Viral activity is halted due to inhibition of viral DNA synthesis. It has the advantage of qd or bid PO administration. It achieves serum levels comparable to those obtained with IV ganciclovir. The adult dosage is 450 mg PO bid for 21 d. Contraindications include severe renal dysfunction or hemodialysis; pregnancy; breastfeeding; or an absolute neutrophil count < 500 cells/µL, a platelet count of < 25,000/µL, or hemoglobin level of < 8 g/dL.

Interactions with valganciclovir are similar to those reported with ganciclovir. Coadministration with cytotoxic drugs such as dapsone, vinblastine, doxorubicin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogs may result in additive toxicity of rapidly dividing cell populations including bone marrow, spermatogonia, germinal layers of skin and GI mucosa (coadminister only if benefits outweigh risks).

Coadministration with imipenem-cilastatin may cause generalized seizures (use only if benefits outweigh risks). Serum creatinine levels may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B. In presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h prior to or simultaneously with ganciclovir. Bioavailability of ganciclovir may decrease in presence of zidovudine, while bioavailability of zidovudine is increased in the presence of ganciclovir.

Strict adherence to dosage guidelines of valganciclovir is essential to avoid overdose. Valganciclovir tablets may not be substituted for ganciclovir capsules on one-to-one basis; adjust dose according to CrCl in impaired renal function. Valganciclovir may cause granulocytopenia, anemia and thrombocytopenia. It is not indicated for CMV disease prevention in liver transplantation (higher CMV disease incidence in liver transplantation compared to prophylaxis with ganciclovir). Valganciclovir is a pregnancy category C drug.

Anthelmintic

Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Praziquantel (Biltricide) increases cell membrane permeability in susceptible worms, resulting in loss of intracellular calcium, massive contractions, and paralysis of musculature. In addition, it produces vacuolization and disintegration of schistosome tegument. This is followed by attachment of phagocytes to parasite and death. Tablets should be swallowed whole with some liquid during meals. Keeping tablets in mouth may reveal bitter taste, which can produce nausea or vomiting. The adult dosage is 40 mg/kg PO bid for 1 day. Ocular cysticercosis is a contraindication. Hydantoins may reduce serum praziquantel concentrations, possibly leading to treatment failures.

Destruction of parasite within eyes can cause irreparable lesions (ocular cysticercosis should not be treated with praziquantel). Caution while driving or performing other tasks requiring alertness on the day of and following treatment. Minimal increases in liver enzymes have been reported. When schistosomiasis or fluke infection is associated with cerebral cysticercosis, hospitalize the patient for duration of treatment. Praziquantel is a pregnancy category B drug.

Antidote

These agents counteract the toxic effects of drugs.

Mesna (Mesnex): In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity. It inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity. The adult dosage is 240 mg IV at 0, 4, 8 h after ifosfamide dose. It may increase warfarin effects. Mesna does not prevent hemorrhagic cystitis in all patients (monitoring for hematuria in the morning prior to ifosfamide or cyclophosphamide dose required). It does not prevent or alleviate other toxicities associated with ifosfamide or cyclophosphamide. Common adverse effects include hypotension, headache, GI toxicity, and limb pain. Mesna is a pregnancy category B drug.

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Doxycycline (Bio-Tab, Doryx, Doxy, Periostat, Vibramycin, Vibra-Tabs) is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. It is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations. It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. The adult dosage is 100 mg PO bid. Severe hepatic dysfunction is a contraindication.

The bioavailability of doxycycline decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate. Tetracyclines can increase hypoprothrombinemic effects of anticoagulants and can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy. Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment. Reduce dose in renal impairment. Consider drug serum level determinations in prolonged therapy. Tetracycline use during tooth development (last one-half of pregnancy through age 8 y) can permanently discolor teeth. Fanconi-like syndrome may occur with outdated tetracyclines. Doxycycline is a pregnancy category D drug.

Azithromycin (Zithromax) acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. It concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues. It is used to treat mild-to-moderate microbial infections. The adult dosage is 1 g PO once.

Contraindications to azithromycin use include hepatic impairment. Do not administer with pimozide. Azithromycin may increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids. Nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine. Site reactions can occur with IV route; bacterial or fungal overgrowth may result from prolonged antibiotic use. It may increase hepatic enzymes and cholestatic jaundice. Caution in patients with impaired hepatic function or prolonged QT intervals. Azithromycin is a pregnancy category B drug.

Ofloxacin (Floxin) penetrates the prostate well and is effective against N gonorrhea and C trachomatis. It is a pyridine carboxylic acid derivative with broad spectrum bactericidal effect. The adult dosage is 300 mg PO bid for 7 d. Antacids, iron salts, and zinc salts may reduce serum levels. Administer antacids 2-4 h before or after taking fluoroquinolones. Cimetidine may interfere with metabolism of fluoroquinolones. Ciprofloxacin reduces therapeutic effects of phenytoin. Probenecid may increase ciprofloxacin serum concentrations. Ofloxacin may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels) and may increase effects of anticoagulants (monitor PT). In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic). Adjust dose in renal function impairment. Superinfections may occur with prolonged or repeated antibiotic therapy. Ofloxacin is a pregnancy category C drug.

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Surgical Therapy

Surgical treatment is rarely needed for nonbacterial cystitis. Most infectious etiologies are treated with systemic and, in some cases, local pharmacotherapy. 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.

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

Schistosomiasis should be treated first with medical management, with surgery reserved for cases that do not respond to medical therapy or for patients with intractable gross hematuria. Obstructive uropathy due to ureteral strictures is the most common sequela. Ureteral stricture is managed 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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Follow-up

For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center, Women's Health Center, and Procedures Center. Also, see eMedicine's patient education articles Bladder Control Problems, Blood in the Urine, Cystoscopy, and Pain During Intercourse.

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Complications

Drug toxicity

Many of the medications mentioned above have adverse effects. Some have been mentioned in the Treatment section. In this section, some other common adverse effects are listed.

  • Hepatic toxicity can be caused by many of the antituberculosis medications, including INH, RIF, pyrazinamide (PZA), and ETH. INH is metabolized primarily by acetylation; approximately 50% of whites and African Americans are slow acetylators, which can lead to higher blood levels and increased toxicity. Hepatocellular dysfunction severe enough to require changing regimens may occur in 3-5% of patients. Alcohol use increases the risk of INH-related hepatitis. The risk of developing fatal hepatitis increases with increasing age, from approximately 0 of 1000 patients younger than 20 years to 23 of 100 patients aged 50-64 years.
  • RIF induces cytochrome P450 metabolizing enzymes. Patients taking other medications (eg, anticonvulsants, antiarrhythmics, azole antifungal agents, calcium channel blockers, some antibiotics, anticoagulants) metabolized by these enzymes may have significant lowering of drug levels because of increased metabolic rates.
  • Cyclophosphamide use is associated with an increased risk for secondary leukemias and bladder cancer and may cause infertility in patients of reproductive age.
  • Intravenous dosing of amphotericin B usually requires pretreatment of the patient with Tylenol and Benadryl to minimize the fevers, chills, or allergic symptoms. Amphotericin B treatment often causes diarrhea (30%), electrolyte abnormalities (15-30%), elevations in liver enzymes (10-20%), and renal disease (20-40%). Intravesical instillation of amphotericin B is much better tolerated than intravenous infusion.

Radiation toxicity

Radiation of living tissues increases the risk of damage to the matrix and the cellular components and to DNA. The effect is dose and tissue dependent. Doses greater than 65 Gy have been associated with late bladder problems. Inability to adequately shield the surrounding tissues can lead to bladder and bowel complications after prostate or cervical radiation, including bleeding, scarring, and pain in 5-20% of patients. In one retrospective review of radiation treatment for prostate cancer, impotence was a common problem.[36]

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Outcome and Prognosis

Infectious etiologies

Infectious causes of nonbacterial cystitis, such as HSV-1 or HSV-2, can now be treated; however, the treatment does not eliminate the dormant virus integrated into the host genome, so the disease can recur.

Both chlamydial and mycobacterial infections can be cured. For chlamydial disease, cure is not protective and the disease can be reacquired. In addition, while mycobacterial infections can generally be cured with regimens containing 3 or 4 drugs, in the review by Mnif et al of 60 cases of urogenital tuberculosis, only 2 were cured by medical therapy alone.[37] Fifty-four patients required surgical intervention, including nephrectomy (43), ureterovesical reimplantation (7), augmentation enterocystoplasty (11), or other ureteral diversions (5). Two patients whose medical and nutritional status was poor to begin with died despite aggressive therapy.

Fungal infections are usually curable, depending on the underlying health status of the patient. Because patients with severe immunosuppression (eg, those with untreatable malignancies, AIDS, poorly-controlled diabetes, transplant patients) are the ones most likely to develop these infections, some patients may require continued treatment to ensure that the infection does not recur.

Noninfectious etiologies

Radiation cystitis, when it does occur, is usually mild and does not require specific therapy.[36] The incidence of bleeding, scarring, and/or obstruction increases over time, and symptoms may occur for the first time many years after the radiation treatment. Some patients with heavy bleeding, strictures, or obstruction may require urinary diversion surgery for symptom relief.[38]

Chemical cystitis due to chemotherapy agents is generally mild, with no long-term consequences, and stops when the medications are stopped.

No known cures exist for autoimmune disease–associated cystitis, but symptoms can often be controlled with anti-inflammatory agents or corticosteroids.

Eosinophilic cystitis often recurs despite resection of the lesion and anti-inflammatory treatments, so long-term follow-up is required.[12]

Interstitial cystitis

Interstitial cystitis is probably the most difficult disease to treat. The symptoms of many patients can be ameliorated, although not completely eradicated, with medical treatment and a combined modality therapy program.

Relief of symptoms in the highly selected subset of patients who undergo surgery has been reported to be 60-90% for supra-trigonal cystectomy and more variable for total cystectomy. Some patients have continued pain despite total cystourethrectomy, emphasizing the poorly understood nature of the disease.

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Future and Controversies

Many controversies exist in nonbacterial cystitis, including possible etiologic agents, methods of diagnosis, and treatment, especially for noninfectious causes.

The National Institutes of Health (NIH) has sponsored research on the topic of nonbacterial cystitis, and several organizations are devoted to helping patients with nonbacterial cystitis (particularly interstitial cystitis) and promoting research.

Advances in understanding the pathophysiology of complex pain syndromes have demonstrated growth of bridging neurons in the dorsal horns of the spinal cord between the type C pain fibers and the type A pain fibers, indicating perception of pain started by stimulus that is usually nonpainful. Another example of neural cross-talk in rats is an experiment that demonstrated increased muscle spasm in the bladder with colonic irritation and in the colon with bladder irritation, perhaps helping to explain the concomitant occurrences of irritable bowel syndrome, pelvic pain syndrome, and interstitial cystitis.

Other anti-inflammatory agents are also under investigation, such as IPD-1151T, an immunoregulatory agent that suppresses T cell–mediated cytokines responsible for IgE production and eosinophilia, as well as IL-4 and IL-5.

Some kinds 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 (P < 0.001) in females treated with TF for this disorder.[39]

More information about interstitial cystitis and support information for patients can be obtained from the following associations:

  • Interstitial Cystitis Association
  • 51 Monroe St. Suite 1402
  • Rockville, MD 20580
  • Telephone toll-free: 1-800-help ICA
  • Email: ICAmail@ichelp.com
  • WWW.ichelp.org
  • American Foundation for Urologic Disease, Inc.
  • 300 West Pratt St. Suite 401
  • Baltimore, MD 21201
  • Telephone toll-free: 1-800-242-2383

The following is a Web site about interstitial cystitis: HealthlinkUSA

Patient materials and links (a urologic opinion of interstitial cystitis) can be found at the following:

  • Cystitis Support Group - United Kingdom
  • Interstitial Cystitis Network
  • The Interstitial Cystitis Network is a large archive of information on the Web for interstitial cystitis, including patient materials, a research library, and physician referrals.
  • The NIH maintains a patient information site for Interstitial Cystitis.
  • Urology Channel is another good source of general health information about urological subjects with a nice review of interstitial cystitis.
  • Also see Interstitial Cystitis.
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Contributor Information and Disclosures
Author

Lynda A Frassetto, MD  Clinical Professor, Department of Internal Medicine, University of California at San Francisco School of Medicine

Lynda A Frassetto, MD is a member of the following medical societies: American College of Physicians and American Society of Nephrology

Disclosure: Nothing to disclose.

Coauthor(s)

Benjamin N Breyer, MD  Clinical Instructor, Department of Urology, University of California, San Francisco Medical Center

Benjamin N Breyer, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, American Urological Association, and Endourological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Erik T Goluboff, MD  Professor, Department of Urology, College of Physicians and Surgeons, Columbia University; Director of Urology, Allen Pavilion, New York Presbyterian Hospital

Erik T Goluboff, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Urological Association, Medical Society of the State of New York, New York Academy of Medicine, Phi Beta Kappa, and Society for Basic Urologic Research

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

J Stuart Wolf Jr, MD, FACS  The David A Bloom Professor of Urology, Director, Division of Endourology and Stone Disease, Department of Urology, University of Michigan Medical School

J Stuart Wolf Jr, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, Catholic Medical Association, Endourological Society, Society for Urology and Engineering, Society of Laparoendoscopic Surgeons, Society of University Urologists, and Society of Urologic Oncology

Disclosure: Baxter Healthcare Consulting fee Consulting

Chief Editor

Edward David Kim, MD, FACS  Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, and Tennessee Medical Association

Disclosure: Lilly Consulting fee Advisor; Astellas Consulting fee Speaking and teaching; Watson Consulting fee Speaking and teaching; Allergan Consulting fee Speaking and teaching

References

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Gross anatomy of the female pelvis.
Gross anatomy of the bladder.
Female perineal anatomy. The urogenital diaphragm and levator ani muscles have been removed, revealing the internal pudendal nerves and vessels, the rectum, and the posterior vaginal wall.
Schistosomiasis of the ureter.
Gross pathology, bladder with candidal infection and hemorrhage.
Infiltration of yeast in the bladder wall.
 
 
 
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