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Single-dose treatment of acute cystitis with fosfomycin tromethamine.

OBJECTIVE: To review the clinical pharmacology of fosfomycin tromethamine, a new antimicrobial agent for the treatment of uncomplicated lower urinary tract infections (UTIs). DATA SOURCE: Publications in English on fosfomycin, fosfomycin tromethamine, and fosfomycin trometamol (MEDLINE, 1970-1997), as well as unpublished studies submitted to the Food and Drug Administration (FDA), were reviewed. STUDY SELECTION: Comparative, randomized, controlled studies were used to analyze the efficacy and safety of fosfomycin tromethamine. DATA SYNTHESIS: Fosfomycin tromethamine is an oral antimicrobial indicated for the treatment of uncomplicated lower UTIs. This agent is active in the urine against common uropathogens that are associated with cystitis in women, including organisms resistant to other antibiotics. A single dose of fosfomycin tromethamine is well absorbed and produces therapeutic concentrations in the urine for 2-4 days. Comparative clinical trials suggest that a single dose of fosfomycin tromethamine 3.0 g is as clinically effective as 7- to 10-day treatment regimens of standard agents used to treat UTIs, such as nitrofurantoin, norfloxacin, and trimethoprim/sulfamethoxazole. Fosfomycin tromethamine is well tolerated and appears safe to use during pregnancy. CONCLUSIONS: Fosfomycin tromethamine is the only antimicrobial to be approved by the FDA for single-dose therapy in women with acute cystitis. It is as effective and safe as multidose comparators and appears safe to use during pregnancy. The acquisition cost of this new drug will need to be weighed against the improved compliance and convenience associated with its use in the treatment of uncomplicated UTIs.

Acute Disease↗

Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis.

The role of anandamide in the development of inflammatory hyperalgesia and visceral hyperreflexia was studied in the rat urinary bladder. Animals were given intraperitoneal cyclophosphamide injection, which evokes painful hemorrhagic cystitis accompanied by increased bladder reflex activity. The vanilloid receptor 1 [transient receptor potential vanilloid 1 (TRPV1)] antagonist capsazepine, applied onto the serosal surface of bladders, significantly reduced the hyperreflexia. Mass spectrometric analysis revealed that cyclophosphamide injection significantly and persistently increased the anandamide content of bladder tissues. The increase in the anandamide content paralleled the development of reflex hyperactivity. Anandamide (1-100 microm), applied onto the serosal surface of naive bladders, increased the reflex activity in a concentration-dependent manner. Repeated anandamide applications did not produce desensitization of the response. The anandamide-evoked effect was blocked by capsazepine or by instillation of resiniferatoxin, the ultrapotent TRPV1 agonist, into the bladders 24 hr before the anandamide challenge. The cannabinoid 1 receptor antagonist SR141716A [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide] significantly increased the potency of anandamide in enhancing bladder reflex activity in naive but not in cyclophosphamide-injected animals. Application of the fatty acid amide hydrolyze inhibitor palmitoylisopropylamine onto the serosal surface of bladders also increased the reflex activity both in naive and cyclophosphamide-injected rats. This latter effect in naive animals was blocked by capsazepine and by resiniferatoxin pretreatment. Finally, intravesical instillation of anandamide (50 microm) increased c-fos expression in the spinal cord, which was reduced by capsazepine or by resiniferatoxin pretreatment. These results suggest that anandamide, through activating TRPV1, contributes to the development of hyperreflexia and hyperalgesia during cystitis.

Acrolein↗

Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis - comparison of the effects of dexamethasone and Mesna.

Chemotherapy with oxazaphosphorines, such as cyclophosphamide (CYP), is often limited by unacceptable urotoxicity. Without uroprotection, hemorrhagic cystitis (HC) becomes dose-limiting. To compare the uroprotective efficacy of classical 2-mercaptoethanesulfonic acid (Mesna) treatment with dexamethasone in CYP-induced HC, male Wistar rats (150-200 g; N = 6 in each group) were treated with saline or Mesna (40 mg/kg, ip) immediately and 4 and 8 h after ip administration of CYP (200 mg/kg). One, 2 or 3 doses of Mesna were replaced with dexamethasone (1 mg/kg, ip). The animals were sacrificed 24 h later. Cystitis was evaluated by determining the changes in bladder wet weight (BWW) and by macroscopic and microscopic analysis. CYP treatment induced a marked increased in BWW (162%, P<0.05), which was significantly inhibited by treatment with 3 doses of Mesna (P<0.05; 80%). The replacement of 1 or 2 doses of Mesna with dexamethasone reduced the increase in BWW by 83.3 and 95%, respectively. Macroscopic analysis of the bladder of rats with CYP-induced HC showed severe edema and hemorrhage, confirmed by microscopic analysis, that also showed mucosal erosion, inflammatory cell infiltration and ulcerations. The replacement of 1 or 2 doses of Mesna with dexamethasone inhibited the CYP-induced increase in BWW and almost abolished the macroscopic and microscopic alterations, with no significant difference between the effects of Mesna and dexamethasone, indicating that both drugs were efficient in blocking HC. However, although the replacement of all Mesna doses with dexamethasone reduced the edema, it did not prevent HC, suggesting that Mesna is necessary for the initial uroprotection.

Animals↗

Steroid pulse therapy in lupus cystitis.

A middle-aged woman with lupus cystitis showed no other symptoms of lupus vasculitis. Cystoscopic findings revealed mucosal hemorrhage and hyperemia. Histological studies of the bladder showed mucosal edema, inflammatory cellular infiltration and the deposition of immune complexes along the vessels. She was treated with a combination of intravenous methylprednisolone pulse therapy and oral prednisolone. Cystoscopy and histological findings showed appreciable improvement. Elevated urinary levels of chemokines such as interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF) decreased during convalescence. These results suggest that the early diagnosis and treatment with steroid pulse therapy achieves improvement of an unusual vasculitis symptom, lupus cystitis.

Anti-Inflammatory Agents↗

Severe interstitial cystitis associated with Sjögren's syndrome.

A 53-year-old woman presented with oliguria, urinary frequency, abdominal pain and severe edema of the lower extremities. Her serum creatinine was 8.1 mg/dl. Computed tomographic and ultrasonographic studies showed a severely dilated urinary bladder, and bilateral hydroureteronephrosis. Examination of a urinary bladder biopsy specimen showed subepithelial edema and infiltration by lymphocytes and plasmacytes. However, the patient complainted of dry mouth and dry eyes. Ophthalmologically, the Schirmer test was positive. A biopsy of the minor salivary glands in the lip showed chronic sialoadenitis. A diagnosis of Sjögren's syndrome complicated by interstitial cystitis was made. Since she had been anuric, secondary to urinary obstruction, intermittent self-catheterization was started. Combination of corticosteroid and cyclosporin therapy was initiated. Spontaneous urination began, and gradually the patient's symptoms remitted. After 8 months of therapy, bladder capacity increased from 140 ml to 350 ml, and she voided approximately 1,200 ml by herself and 600 ml by catheterization daily. This case suggests that when severe interstitial cystitis is associated with Sjögren's syndrome, a therapeutic trial of corticosteroids and cyclosporin may be beneficial.

Cyclosporine↗

[A case report of childhood systemic lupus erythematosus complicated with lupus cystitis].

The patient was a 13-year-old girl. In August 2000, she presented with a fever, together with diarrhea, vomiting, arthralgia, nasal bleeding and malaise, and was examined by another physician. Because her platelet count was low, and there were positive reactions for anti-nuclear antibodies, anti-DNA antibodies and platelet-associated IgG, idiopathic thrombopenic purpura, and systemic lupus erythematosus (SLE) was suspected. From January 2001, when she caught measles, she reported abdominal pain, and urinalysis indicated urinary protein and occult blood, and the left kidney was found hydronephrotic. At the same time left ureter stenosis and dilatation were demonstrated. Symptoms were disappeared by hydration and treatment with NSAIDs, but 2 months later fever and erythematous patches seen on both cheeks led to the proper diagnosis of SLE, and she was admitted to our hospital. Intravenous pyelography revealed hydronephrosis on left kidney, constriction and dilatation of the left ureter, and intracystic endoscopy showed erythema at the orifice of the left ureter. The pathological examination indicated the presence of vasculitis, and finally lupus cystitis was diagnosed. Intravenous cyclophosphamide (IVCY)-pulse therapy was introduced to a total of 8 times over the period of a year, and maintenance therapy with predonisolone and azathioprin was also used. After completion of the IVCY-pulse therapy, the hydronephrosis and constriction of the ureter were disappeared. No side effects of IVCY-pulses were observed, and the patient is now in remission. We reported a case of childhood SLE complicated with lupus cystitis and successfully treated by IVCY-pulse therapy and maintenance predonisolone and azathioprin.

Adolescent↗

Encrusted cystitis secondary to Corynebacterium matruchotii infection in a horse.

A 17-year-old gelding was evaluated because of dysuria, inappetence, and weight loss. Cystoscopy revealed severe mucosal ecchymoses with luminal hemorrhage and accumulations of crystalloid sludge. Analysis of a urine sample revealed isosthenuria, an alkaline pH, pyuria, hematuria, bacteriuria, and numerous calcium carbonate crystals. Histologic examination of bladder mucosa biopsy specimens revealed severe neutrophilic infiltration with mineralization. A diagnosis of encrusted cystitis exacerbated by sabulous urolithiasis was made. A Corynebacterium sp susceptible to penicillin, sulfonamide, and enrofloxacin was cultured from the urine and the bladder mucosa biopsy specimens. The horse was treated with penicillin G potassium, IV, for 5 days, followed by trimethoprim-sulfamethoxazole for 4 weeks. Bladder lavage was performed daily for the first 3 days with a balanced electrolyte solution and dimethyl sulfoxide in an attempt to aid expulsion of necrotic debris and crystalline sludge from the bladder. Molecular phylogenetic analysis based on the 16S rDNA gene sequence was used to identify the isolate and determine its phylogenetic position. Results indicated that the isolate was closely related to Corynebacterium matruchotii. To our knowledge, encrusted cystitis secondary to C matruchotii has not been previously identified in a horse.

Animals↗

Traditional acupuncture and electrical stimulation of the posterior tibial nerve. A trial in chronic interstitial cystitis.

A prospective study on the symptomatic effect of traditional Chinese acupuncture treatment and transcutaneous nerve stimulation (TENS) of the tibial nerve in patients with interstitial cystitis is presented. There was no difference in voiding frequency, mean voided volume, maximal voided volume or visual analogue scale symptom scores before or after treatment with either TENS or acupuncture. Only one patient became improved both subjectively and objectively after acupuncture for a short period of time. Even though the present material involves a small group of patients, it seems that the two methods, as applied in this study, have a very limited effect in patients with interstitial cystitis.

Acupuncture Therapy↗

Interstitial cystitis and bladder mastocytosis in a woman with chronic urticaria.

A patient with chronic urticaria and angioedema developed endoscopically confirmed interstitial cystitis. Bladder biopsy revealed bladder mastocytosis with > 60 mast cells/mm2 (normal < 10) in the detrusor and submucosa. Most of the mast cells were activated and degranulated. The occurrence of IC in a patient with urticaria and angioedema, diseases both associated with mast cell pathophysiology, supports the role of mast cells in interstitial cystitis.

Adult↗

Emphysematous cystitis.

Emphysematous cystitis is characterized by gas collection within the bladder wall and lumen. We report two cases of emphysematous cystitis of the urinary bladder in a 67-year-old and a 63-year-old women. They presented with bladder irritation symptoms such as dysuria, hematuria and frequency. Urinalysis showed pyuria. Cystoscopic examination revealed that bladder mucosa was studded with vesicles varying in size and arranged in clumps. CT scans of the pelvis showed mottled gas bubbles within the bladder. They were treated with antibiotics. Four days after the treatment, the symptoms subsided and plain abdominal film showed no evidence of gas shadows in the pelvic cavity.

Aged↗

Hemorrhagic cystitis due to intravesical instillation of gentian violet completely recovered with conservative therapy.

Chemical cystitis due to intravesical instillation of gentian violet or crystal violet is rare and all of the reported cases have been in adults using undiluted solution, which resulted in long-term sequelae. This is a case report on a 16-month-old boy with hemorrhagic cystitis after the instillation of diluted gentian violet into the bladder to rule out bladder injury during inguinal herniorrhaphy. Although he was completely recovered with conservative therapy, gentian violet, even when diluted, should not be used on the urinary tract.

Administration, Intravesical↗

Interstitial cystitis: a primary care perspective.

Interstitial cystitis is more common than previously thought and is often diagnosed only when pain, frequency, and urgency become continuous and severe. Its diagnosis is straightforward, and effective therapies are available. Physicians should keep the diagnosis of interstitial cystitis in mind for all patients presenting with pelvic pain or urinary symptoms.

Amitriptyline↗

Comparison of uroprotective efficacy of mesna and amifostine in Cyclophosphamide- induced hemorrhagic cystitis in rats.

BACKGROUND: Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP). AIM: In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna. SETTING AND DESIGN: This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University. MATERIALS AND METHODS: Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four groups. Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. Bladders of animals were assessed macroscopically and histologically 24 h later. Gross assessment for presence of edema and hemorrhage and histological evaluation of damage to the bladder were scored according to Gray's criteria. STATISTICAL ANALYSIS USED: For macroscopic and microscopic data, we used statistical evaluation by Kruskal-Wallis nonparametric analysis of variance followed by the Mann-Whitney U-test. RESULTS: All the animals in group II had evidence of HC. Significant histological damage and macroscopic changes were present in this group compared to control group (P<0.001). The median scores for bladder damage in group III and IV were significantly lower compared to group II (P<0.001). When the median scores for bladder damage of group I, III, and IV were compared, there was no significant difference among these groups. CONCLUSION: This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis.

Amifostine↗

[Two case reports of eosinophilic cystitis--clinical review of 43 cases in Japan].

Two cases of eosinophilic cystitis are reported. Case 1 was a 7-year-old boy with pollakisuria and case 2 was a 20-year-old man with right lower abdominal pain. They were suspected of bladder sarcoma after the examinations by cystoscopy, IVP, ultrasonography, CT and NMR-CT. Transurethral, percutaneous and open biopsies were performed and histological examination revealed massive infiltration of eosinophils mainly in the vesical muscle layer without malignant cells. We could establish the diagnosis only by biopsy. In case 1, IgE RAST was positive for tick and case 2 seemed to be allergic to rare beef. We presumed that they caused eosinophilic cystitis.

Adult↗

[Clinical study on female patients with bladder irritability--comparison between cystitis and urethral syndrome].

We analysed the clinical background of female who had no underlying disease but consulted out urology outpatient clinic with a chief complaint of symptoms of bladder irritation. Overally, 50.1% (102/200 cases) of the cases had urethral syndrome, without pyria or bacteriuria. Plotting of the age distribution of the urethral syndrome cases showed a bell-shaped curve, with the peak at the 40-49 year-old age bracket. The age distribution for the cystitis cases showed two peaks: at 20-29 years of age and 60-69 years of age. These results indicate that the cases of urethral syndrome involve multiple factors with increasing age. Examination of the external genitalia revealed the urethral smear specimens to be positive for leukocytes in 48.9% (88/180 cases) of the total urethral syndrome cases and in 72.7% (16/22 cases) of the urethral syndrome cases positive for urethral bacteria. Accordingly, it was surmised that there is considered to be a precursor of cystitis-as a cause of urethral syndrome cases. In addition, the rates of detection of chlamydia trachomatis from the vagina and urethra of the urethral syndrome cases in the reproductive age range of (2/34 cases) for the urethra. However, these rates were about the same as those determined for healthy volunteers. Nevertheless, it was surmised that urethritis or vaginitis caused by C. trachomatis was one of the causes of the symptoms of bladder irritation in some of the cases. Accordingly, it was concluded that infection due to C. trachomatis cannot be ignored as a possible cause of urethral syndrome.

Adult↗

Recurrent cystitis and bladder mass in two adults with chronic granulomatous disease.

Two men, aged 23 and 20 years, with recurrent episodes of severe cystitis and X-linked chronic granulomatous disease were studied. Ultrasonography showed large discrete bladder masses that mimicked bladder carcinoma in both patients. Urine and bladder biopsy cultures were negative and histopathologic findings were consistent with chronic inflammation. One patient improved with symptomatic therapy on two occasions; the other patient required prolonged intravenous antibiotic therapy before fever and dysuria resolved. The possible mechanisms by which such inflammatory bladder masses might arise are discussed and eight previously reported cases of chronic granulomatous disease with cystitis are reviewed. From this clinical experience, we recommend prolonged antibiotic therapy. In patients who fail to respond to antibiotic therapy, steroids may be cautiously administered.

Adult↗

Lupus cystitis: primary bladder manifestations of systemic lupus erythematosus.

Clinical and radiographic findings of cystitis are reported in six patients with systemic lupus erythematosus. All patients had clinical manifestations of cystitis; radiography showed the bladder capacities were reduced and the bladder walls were thickened and irregular. Ureterohydronephrosis was found in some patients. Abnormal clinical and roentgenographic findings were reversed with high-dose corticosteroid therapy. These patients had concomitant widespread multisystem manifestations, especially of the central nervous system and gastrointestinal tract. No explanation for the bladder findings could be found other than lupus erythematosus. Urinary bladder involvement may be a primary manifestation of systemic lupus erythematosus, sometimes overshadowed by other major organ system disease. Corticosteroids appear to reverse most of the acute manifestations but the long-term prognosis is not known and may not be favorable.

Adrenal Cortex Hormones↗

Varied sonographic manifestations of cystitis.

In a retrospective study of 90 cases that had both abdominal ultrasound examinations of the bladder and cystoscopy, four cases of proven cystitis were identified. The sonographic appearance of cystitis is varied, depending on the severity of the process, and several manifestations of involvement detectable by ultrasonography are outlined.

Candidiasis↗