Trimethoprim-associated electrolyte and acid-base abnormalities.

INTRODUCTION: The antimicrobial trimethoprim is structurally related to potassium-sparing diuretics and may consequently lead to derangements in electrolyte and acid-base balance. Since no report so far analyzed the literature documenting individual cases with electrolyte and acid-base derangements induced by trimethoprim, a systematic review was carried out. EVIDENCE ACQUISITION: We retained 53 reports documenting 68 cases (42 males and 26 females 23 to 96 years of age) of electrolyte or acid-base derangements occurring on trimethoprim for about 5 days. EVIDENCE SYNTHESIS: One hundred five electrolyte imbalances were detected in the 68 patients: hyperkalemia (>5.0 mmol/L) in 62 (91%), hyponatremia (<135 mmol/L) in 29 (43%) and metabolic acidosis (pH<7.38 and bicarbonate <19 mmol/L) in 14 (21%) cases. Following possible predisposing factors for electrolyte and acid-base abnormalities were found in 54 (79%) patients: high-dose trimethoprim, comedication with drugs that have been associated with electrolyte and acid-base derangements, preexisting kidney disease, age ≥80 years and diabetes mellitus. CONCLUSIONS: High-dose trimethoprim, comedicated with drugs that have been associated with electrolyte and acid-base derangements, poor kidney function, age ≥80 years and diabetes mellitus predispose to trimethoprim-associated electrolyte and acid-base abnormalities. Clinicians must recognize patients at risk, possibly avoid drug combinations that may worsen the problem and monitor the laboratory values.

Single-dose versus 3-day cotrimoxazole prophylaxis in transurethral resection or greenlight laser vaporisation of the prostate: study protocol for a multicentre randomised placebo controlled non-inferiority trial (CITrUS trial).

BACKGROUND: Transurethral resection of the prostate (TURP) and Greenlight laser vaporisation (GL) of the prostate are frequently performed urological procedures. For TURP, a single-dose antimicrobial prophylaxis (AP) is recommended to reduce postoperative urinary tract infections. So far, no international recommendations for AP have been established for GL. In a survey-based study in Switzerland, Germany and Austria, urologists reported routinely extending AP primarily for 3 days after both interventions. We therefore aim to determine whether single-dose AP with cotrimoxazole is non-inferior to 3-day AP with cotrimoxazole in patients undergoing TURP or GL of the prostate. METHODS/DESIGN: We will conduct an investigator-initiated, multicentre, randomised controlled trial. We plan to assess the non-inferiority of single-dose AP compared to 3-day AP. The primary outcome is the occurrence of clinically diagnosed symptomatic urinary tract infections which are treated with antimicrobial agents within 30 days after randomisation. The vast majority of collected outcomes will be assessed from routinely collected data. The sample size was estimated to be able to show the non-inferiority of single-dose AP compared to 3-day AP with at least 80% power (1 - ß = 0.8) at a significance level of α = 5%, applying a 1:1 randomisation scheme. The non-inferiority margin was determined in order to preserve 70% of the effect of usual care on the primary outcome. For an assumed event rate of 9% in both treatment arms, this resulted in a non-inferiority margin of 4.4% (i.e. 13.4% to 9%). To prove non-inferiority, a total of 1574 patients should be recruited, in order to have 1416 evaluable patients. The study is supported by the Swiss National Science Foundation. DISCUSSION: For AP in TURP and GL, there is a large gap between usual clinical practice and evidence-based guidelines. If single-dose AP proves non-inferior to prolonged AP, our study findings may help to reduce the duration of AP in daily routine-potentially reducing the risk of emerging resistance and complications related to AP. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03633643 . Registered 16 August 2018.

L-Methionine associated with Hibiscus sabdariffa and Boswellia serrata extracts are not inferior to antibiotic treatment for symptoms relief in patients affected by recurrent uncomplicated urinary tract infections: Focus on antibiotic-sparing approach.

OBJECTIVE: To evaluate the efficacy of a phytotherapic combination of L-Methionine associated with Hibiscus sabdariffa and Boswellia serrata for treatment of acute episodes of uncomplicated urinary tract infections (UTI) in women affected by recurrent UTIs. MATERIALS AND METHODS: In this randomized phase III clinical trial, adult females with uncomplicated UTI were enrolled into one of the following treatment groups: Group A: phytotherapic combination 1 tablet in the morning and 1 tablet in the evening for 7 days; Group B: Short term antibiotic treatment according to international guidelines recommendations. At baseline, all patients were evaluated by a urologist and quality of life (QoL) questionnaires and mid-stream urine culture. Same clinical and laboratory investigations were repeated at each follow-up visit. RESULTS: Forty-six patients were enrolled in Group A and 47 in Group B. At the first follow-up (30 days), both groups showed a statistically significant improvement in quality of life scores as compared with baseline assessment [Group A: (QoL 94.3 VS 98.5 p < 0.001); Group B: (QoL 94.5 VS 98.7 p < 0.001)]. An improvement from baseline was also seen at the second followup evaluation after 3 months [Group A: (QoL 94.3 VS 99.1 p < 0.001); Group B: (QoL 94.5 VS 98.1 p < 0.001)]. At the second follow-up visit, a statistically significant difference in QoL was reported between the two groups (99.1 VS 98.1; p < 0.003) and a transition from UTI to asymptomatic bacteriuria (ABU) was observed 12 of 46 (26%) patients in Group A, while no patients in Group B demonstrated ABU (p = 0.007). CONCLUSIONS: Here, we demonstrated that this phytotherapic combination is able, in comparison to antibiotic treatment, to improve patients quality of life, reducing symptoms in acute setting and preventing the recurrences. Interestingly, a significantly higher proportion of patients in the phytotherapy group had ABU after three months. Our findings are of great interest in an antibiotic stewardship perspective.

Impact of Allergy and Resistance on Antibiotic Selection for Recurrent Urinary Tract Infections in Older Women.

OBJECTIVES: To review the impact of antibiotic allergy and resistance in older women with recurrent urinary tract infections (RUTIs) as determinants for a suitable oral antibiotic treatment choice. METHODS: A prospectively maintained database of women 65 years old and older with documented RUTIs (≥3 UTI/y) and trigonitis on cystoscopy was reviewed. Demographic data, known drug allergies, renal function, antibiotic susceptibility of most recent urine culture, allergy, or resistance to trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones, and nitrofurantoin were obtained. RESULTS: From 2006 to 2014, 86 women with RUTIs met study criteria. Mean age was 77.9 ± 7.8, with 94% being Caucasian. An estimated glomerular filtration rate >30 mL/min was noted in 94%. The percentage of women allergic, resistant, or both allergic and resistant to TMP-SMX was 33%, 29%, and 15%, to fluoroquinolones was 14%, 34%, and 8.1%, or nitrofurantoin was 16%, 14%, and 5%, respectively. Twenty-eight percent (24 of 86) of women who were allergic and/or resistant to TMP-SMX and fluoroquinolones were sensitive to nitrofurantoin. Twenty percent (17 of 86) were allergic and/or resistant to all 3 antibiotics. Women who were allergic or resistant to TMP-SMX had a significantly higher number of other antibiotic resistances compared with women sensitive to TMP-SMX (4.9 ± 3.6 vs 2.1 ± 2.3; P < .0001). Similarly, women with fluoroquinolone allergy or resistance had significantly more antibiotic resistances than those who were fluoroquinolone sensitive (5.8 ± 3.5 vs 2.3 ± 2.5; P < .0001). CONCLUSION: Because of allergy and/or antibiotic resistance, several first-line antibiotics are not available for many older women with RUTIs. In nearly a third of women, nitrofurantoin was the only viable alternative.

A Seven-Day Course of TMP-SMX May Be as Effective as a Seven-Day Course of Ciprofloxacin for the Treatment of Pyelonephritis.

BACKGROUND: The Infectious Diseases Society of America guidelines recommend either 14 days of trimethoprim-sulfamethoxazole (TMP-SMX) or 7 days of ciprofloxacin for the treatment of pyelonephritis. Antibiotic courses of 7 days of TMP-SMX vs 7 days of ciprofloxacin for pyelonephritis have not been previously compared. We evaluated the odds of a subsequent, symptomatic urinary tract infection (UTI) for women with Escherichia coli pyelonephritis receiving a 7-day course of TMP-SMX vs a 7-day course of ciprofloxacin. METHODS: Women ages 16 years and older with E. coli pyelonephritis presenting to 5 health care facilities in the greater Maryland area between 2010 and 2016 receiving either TMP-SMX or ciprofloxacin were included. Patients were excluded if they met any of the following criteria: (a) pregnancy, (b) dialysis dependency, (c) E. coli not susceptible to the treatment prescribed, (d) polymicrobial urine culture, or (e) >48 hours of antibiotic therapy other than TMP-SMX or ciprofloxacin. RESULTS: Of 272 women meeting eligibility criteria, 81 (30%) and 191 (70%) received 7 days of TMP-SMX and 7 days of ciprofloxacin, respectively. In an adjusted model, the likelihood of a recurrent UTI within 30 days for the TMP-SMX and ciprofloxacin groups was similar (adjusted odds ratio 2.30; 95% confidence interval, 0.72-7.42). CONCLUSIONS: Our findings suggest that 7 days of TMP-SMX therapy may result in similar clinical outcomes compared with 7 days of ciprofloxacin for the treatment of pyelonephritis. Considering the frequency of pyelonephritis and risks of antibiotic resistance and associated toxicities, decreasing the duration of antibiotic therapy for pyelonephritis may impact a large number of women.

Efficacy of an orally administered combination of hyaluronic acid, chondroitin sulfate, curcumin and quercetin for the prevention of recurrent urinary tract infections in postmenopausal women.

OBJECTIVE: To assess whether the orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin and quercetin could be effective in preventing recurrent cystitis in postmenopausal women and whether its efficacy was conditioned by the concurrent use of local estrogen therapy. STUDY DESIGN: This was a prospective evaluation of 145 postmenopausal women consecutively recruited from the database of three different investigators. All women should have mild-to-moderate urogenital atrophy and a history of recurrent urinary tract infections (≥2 episodes within 6 months or ≥3 episodes within 12 months documented by positive urine cultures) during the last year. Patients were assigned to three different therapeutic regimens: the first group was treated only with vaginal estrogens, the second group only with HA, CS, curcumin and quercetin per os, and the third group was treated with HA, CS, curcumin and quercetin associated with local estrogens. We evaluated the number of patients with <2 infective episodes in the 6-month follow-up and <3 episodes in the 12-month follow-up (main aim definition) and the reduction of related symptoms through a Visual Analog Scale (VAS) and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. Student's t-test and chi-squared test were used for data analysis as appropriate. RESULTS: At 6-month follow up, the main aim rate was 8%, 11.1% and 25% in the three groups, respectively (p<0.05 compared to baseline only in group 3). Although the reduction in the number of recurrent episodes became significant in all groups at 1 year follow-up, the main aim rate was almost double in women receiving both local estrogens and oral therapy (group 3) compared to those receiving single treatments. The improvement of related symptoms was significant in all groups at 12-month follow-up. CONCLUSIONS: In postmenopausal women, the combination of HA, CS, curcumin and quercetin per os was effective in preventing recurrent urinary tract infections, especially if administered with vaginal estrogen therapy.

Evaluation of the Risk of Nitrofurantoin Lung Injury and Its Efficacy in Diminished Kidney Function in Older Adults in a Large Integrated Healthcare System: A Matched Cohort Study.

OBJECTIVES: To determine the risk to older adults of lung injury associated with treatment of cystitis using nitrofurantoin and the risk of treatment failure in the presence of diminished creatinine clearance (CrCl). DESIGN: Retrospective, matched cohort. SETTING: Integrated healthcare system. PARTICIPANTS: Individuals aged 65 and older with a diagnosis of cystitis between 2007 and 2012 who were given nitrofurantoin (N = 13,421) were matched 1:3 on age, sex, race and ethnicity, and prescription date with individuals who were given other antibiotics for cystitis. MEASUREMENTS: Conditional logistic regression determined the association between nitrofurantoin and lung injury in the matched cohort. In participants exposed to nitrofurantoin, chronic treatment was compared with acute treatment using multivariable logistic regression. Treatment failure was compared in three CrCl groups. RESULTS: Nitrofurantoin exposure was not statistically significantly associated with lung injury (adjusted risk ratio (aRR) = 0.90, 95% confidence interval (CI) = 0.80-1.00), but chronic nitrofurantoin therapy was associated with greater risk of lung injury than acute exposure (aRR = 1.53, 95% CI = 1.04, 2.24). Treatment failure rates did not differ according to CrCl. CONCLUSION: This large, retrospective, matched-cohort study conducted in older adults supports the 2012 American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults recommendations against the use nitrofurantoin for long-term suppressive treatment of cystitis but not the recommendation against its use in poor renal function because of the risk of treatment failure.

[Prevention and alternative methods for prophylaxis of recurrent urinary tract infections in women]. / Vorbeugung und alternative Methoden der Prophylaxe rezidivierender Harnweginfektionen der Frau.

General recommendations to prevent recurrent urinary tract infections (rUTI) result in about one-third of patients remaining free of recurrences. Oral and parenteral immunotherapy were effective in several controlled studies for prevention of rUTI. These therapies can be combined with acute antibiotic therapy. Vaginal prophylaxis with oestriol has proven its positive effect without serious gynaecological side effects. Also there is increasing evidence that cranberries prevent rUTI. The exact mode (juice, tablets or preserved berries), dosage and duration of this therapy remain to be defined. There are also promising therapy modalities such as changing bacterial gut flora, general immune response (acupuncture, inpatient rehabilitation) and urine acidity.

[Recurrent urinary tract infection in women. Long-term antibiotic prophylaxis]. / Rezidivierende Harnwegsinfektionen der Frau. Antibiotische Langzeitprophylaxe.

Urinary tract infections (UTI) are among the most frequent bacterial infections in women. Mostly young women and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI), defined as >or=3 UTI/year. Modifiable predisposing factors are rare. The differential diagnosis between relapse and reinfection is decisive for therapy. Antibiotic prophylaxis has emerged as one of the most important therapeutic principles in rUTI. Depending on the drug utilized, the various modes of action are described as reducing the number of uropathogens in the gut and vaginal flora and/or in repeatedly eliminating bacteria from the urine. According to the European Association of Urology guidelines, nitrofurantoin, trimethoprim, and cotrimoxazole are available as first-line drugs. Cephalexin and the quinolones should be restricted to specific indications. Depending on the case, long-term antibiotic prophylaxis for 6 months, postcoital single dose prophylaxis, or patient-initiated self-start therapy can all be used successfully. Given the correct indications, the recurrence rate of rUTI can be reduced by 95%.

Efficacy and safety of a novel once-daily extended-release ciprofloxacin tablet formulation for treatment of uncomplicated urinary tract infection in women.

The efficacy and safety of a novel once-daily extended-release ciprofloxacin (ciprofloxacin ER) 500-mg dose were compared with those of an immediate-release ciprofloxacin (ciprofloxacin IR) 250-mg twice-daily dose, each administered orally for 3 days in the treatment of acute uncomplicated urinary tract infection (uUTI) in women. Adult female outpatients (mean age, 39 years) with clinical signs and symptoms of acute uUTI and a positive pretreatment urine culture (> or =10(5) CFU/ml) were enrolled in a multicenter, randomized, double-blind, noninferiority trial. Patients were assessed at a test-of-cure visit (4 to 11 days posttreatment) and a late-posttreatment visit (4 to 6 weeks posttreatment) for microbiological and clinical outcomes and safety. The primary efficacy endpoint and microbiological eradication rate at the test-of-cure visit in the ciprofloxacin ER group (254/272; 93.4%) were noninferior to those in the ciprofloxacin IR group (225/251; 89.6%) (95% confidence interval [CI] of difference, -0.99%, 8.59%). Clinical-cure rates at the test-of-cure visit were 85.7% (233/272) for ciprofloxacin ER and 86.1% (216/251) for ciprofloxacin IR (95% CI of difference, -6.37%, 5.57%). At the late-posttreatment visit, microbiological and clinical outcomes were similar for the two treatments and consistent with test-of-cure results. Both treatments were well tolerated, but the frequencies of nausea and diarrhea were lower in the ciprofloxacin ER group than in the ciprofloxacin IR group (nausea, ER, 0.6%; IR, 2.2%; P = 0.033; diarrhea, ER, 0.2%; IR, 1.4%; P = 0.037). Once-daily ciprofloxacin ER was safe, effective, and noninferior to twice-daily ciprofloxacin IR in the treatment of acute uUTI. Additionally, ciprofloxacin ER was associated with significantly reduced frequencies of nausea and diarrhea.

Women's quality of life is decreased by acute cystitis and antibiotic adverse effects associated with treatment.

BACKGROUND: Although acute cystitis is a common infection in women, the impact of this infection and its treatment on women's quality of life (QOL) has not been previously described. OBJECTIVES: To evaluate QOL in women treated for acute cystitis, and describe the relationship between QOL, clinical outcome and adverse events of each of the interventions used in the study. DESIGN: Randomized, open-label, multicenter, treatment study. SETTING: Two family medicine outpatient clinics in Iowa. PATIENTS: One-hundred-fifty-seven women with clinical signs and symptoms of acute uncomplicated cystitis. INTERVENTION: Fifty-two patients received trimethoprim/sulfamethoxazole 1 double-strength tablet twice daily for 3 days, 54 patients received ciprofloxacin 250 mg twice daily for 3 days and 51 patients received nitrofurantoin 100 mg twice daily for 7 days. MEASUREMENTS: QOL was assessed at the time of enrollment and at 3, 7, 14 and 28 days after the initial visit. QOL was measured using a modified Quality of Well-Being scale, a validated, multi-attribute health scale. Clinical outcome was assessed by telephone interview on days 3, 7, 14 and 28 using a standardized questionnaire to assess resolution of symptoms, compliance with the prescribed regimen, and occurrence of adverse events. RESULTS: Patients experiencing a clinical cure had significantly better QOL at days 3 (p = 0.03), 7 (p < 0.001), and 14 (p = 0.02) compared to patients who failed treatment. While there was no difference in QOL by treatment assignment, patients experiencing an adverse event had lower QOL throughout the study period. Patients treated with ciprofloxacin appeared to experience adverse events at a higher rate (62%) compared to those treated with TMP/SMX (45%) and nitrofurantoin (49%), however the difference was not statistically significant (p = 0.2). CONCLUSION: Patients experiencing cystitis have an increase in their QOL with treatment. Those experiencing clinical cure have greater improvement in QOL compared to patients fail therapy. While QOL is improved by treatment, those reporting adverse events have lower overall QOL compared to those who do not experience adverse events. This study is important in that it suggests that both cystitis and antibiotic treatment can affect QOL in a measurable way.

Urinary tract infection: traditional pharmacologic therapies.

Urinary tract infections (UTIs) are common bacterial infections, particularly in women. Antimicrobial therapy is seldom indicated for asymptomatic infection, but antimicrobial therapy is usually indicated for amelioration of symptoms. Management of acute uncomplicated UTI (cystitis) is generally straightforward, with a predictable distribution of uropathogens isolated. First-line treatment of acute uncomplicated UTI has traditionally involved a 3-day regimen of trimethoprim-sulfamethoxazole (TMP-SMX) or TMP alone for patients with sulfa allergies. Increasing resistance among community-acquired Escherichia coli to TMP-SMX worldwide has led to a reassessment of the most appropriate empiric therapy for these infections. Alternative first-line agents include the fluoroquinolones, nitrofurantoin, and fosfomycin. Factors to be considered in the selection of appropriate antimicrobial therapy include pharmacokinetics, spectrum of activity of the antimicrobial agent, resistance prevalence for the community, potential for adverse effects, and duration of therapy. Ideal antimicrobial agents for UTI management have primary excretion routes through the urinary tract to achieve high urinary drug levels. In addition, there are special considerations in the management of UTI among selected populations, including postmenopausal and pregnant women, and for women with frequent recurrent UTIs.

Life threatening hyperkalemia and acidosis secondary to trimethoprim-sulfamethoxazole treatment.

We present a 77-year-old male with moderate chronic renal insufficiency from diabetic nephropathy who developed severe metabolic acidosis and life threatening hyperkalemia on treatment with regular dose of trimethoprim-sulfamethoxazole (TMP-SMZ) for urinary tract infection. The metabolic acidosis and hyperkalemia resolved upon appropriate medical intervention and discontinuation of TMP-SMZ. While hyperkalemia has commonly been reported with high dose of TMP-SMZ, severe metabolic acidosis is quite uncommon with regular dose TMP-SMZ. We emphasize that patients with renal tubular acidosis (RTA), renal insufficiency, aldosterone deficiency, old age with reduced renal mass and function, and angiotensin converting enzyme (ACE)-inhibitor therapy are at high risk of developing these severe and potentially life threatening complications.

Management of urinary tract infections in the elderly.

Urinary tract infection (UTI) is the most common infection and the first cause of bacteremia in the elderly. With increasing age the female to male ratio decreases and UTI becomes almost half as frequent in men compared to women. Significant bacteriuria exists in about 40% of institutionalized women. But asymptomatic bacteriuria is neither the cause of morbidity nor associated with a higher mortality rate and thus should not be treated. Symptomatic infection in women without complicating factors is most often caused by E. coli and may be treated with 3 or 7 day regimens of trimethoprim-sulfamethoxazole or fluoroquinolones (FQ). In the presence of symptoms of upper tract infection or complicating factors, urine culture is mandatory and will detect multiple and/or resistant microorganisms in most cases. Empirical treatment has to be adapted according to the sensitivity once established and should be administered for at least 10 days. Most of the patients above 65 and virtually all patients above 80 present either with general debility or diabetes or other factors such as bladder outflow obstruction or abnormal bladder function and have to be considered as presenting with complicated UTI. Indwelling catheters should be removed if possible, otherwise be changed.

[Drug therapy in the old age. Drug effects in the elderly]. / Arzneimitteltherapie im Alter. Misten Sie die Pillendöschen aus!

The frequency of multimorbidity in elderly patients may mislead the physician into practicing polypragmasy (polypharmacy), resulting in unpredictable drug interactions. Such interactions are a quite common cause of hospitalization in geriatric patients. Pharmacokinetics are often altered in the aged, and individualized medication should take into consideration not only the patient's age, liver and kidney function, but also the individual variability of hepatic metabolism and drug absorption from the gastrointestinal tract dictated by genetic polymorphism. Drug treatment in the elderly should always be carefully assessed as to its risks and benefits, and, where indicated, certain medications should be replaced by or omitted.

Efficacy and safety of ciprofloxacin oral suspension versus trimethoprim-sulfamethoxazole oral suspension for treatment of older women with acute urinary tract infection.

OBJECTIVES: To compare the efficacy and safety of ciprofloxacin (CIP) oral suspension to trimethoprim/sulfamethoxazole (TMP/SMX) oral suspension among older women with acute urinary tract infections (UTIs). DESIGN: Prospective, randomized, open-label, multicenter study of older women (age 65 and older). SETTING: Community and nursing home. PARTICIPANTS: A total of 261 older women were evaluable for safety. Of these, 172 (86 community, 86 nursing home) were evaluable for clinical and bacteriological efficacy. INTERVENTION: Patients were randomized to a 10-day regimen of either CIP (250 mg/5 mL twice daily) or TMP/SMX (160/800 mg/20 mL twice daily). MEASUREMENTS: Clinical response 4 to 10 days posttherapy. RESULTS: For the efficacy-valid population, posttherapy clinical resolution was statistically superior following CIP (97%) versus TMP/SMX (85%) (95% CI=2.0-21.3; P= .009). Eradication of pretreatment bacterial isolates posttherapy was also higher following CIP (95%) versus TMP/SMX (84%) (95% CI=2.7-21.3; P= .019). For the intent-to-treat population, posttherapy clinical resolution was significantly higher in the CIP group (96%) than in the TMP/SMX group (87%) (95% CI=0.2-16.7; P= .025). Safety was assessed in the intent-to-treat population and the incidence of drug-related adverse events were significantly lower following CIP (17%) than following TMP/SMX (27%) (P= .047). Premature discontinuation due to these events was also less prevalent with CIP than with TMP/SMX (2% vs 11%, respectively) (P= .004). CONCLUSION: CIP suspension showed higher clinical success and bacteriological eradication rates than did TMP/SMX for both community-based and nursing home-residing older women with acute UTIs. Furthermore, CIP suspension was associated with significantly lower rates of adverse events and premature discontinuations compared with TMP/SMX suspension.

A trial comparing low-dose, short-course ciprofloxacin and standard 7 day therapy with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary tract infection.

The study was undertaken to compare the safety and efficacy of twice-daily ciprofloxacin for 3 days with standard 7 day therapy with either co-trimoxazole or nitrofurantoin in the treatment of women with acute, uncomplicated urinary tract infections (UTI). This multicentre, prospective, randomized, double-blind trial compared oral ciprofloxacin (100 mg bd) for 3 days with co-trimoxazole (160/800 mg bd) or nitrofurantoin (100 mg bd) for 7 days. Bacteriological and clinical evaluations were performed at study entry, during therapy and 4-10 days and 4-6 weeks after the completion of therapy. The primary efficacy parameter was eradication of the causative organism 4-10 days following treatment. Of 713 women enrolled and evaluable for safety, 521 were evaluable for efficacy (168 ciprofloxacin, 174 co-trimoxazole, 179 nitrofurantoin). Escherichia coli (83%) was the most frequently isolated pathogen in all treatment groups. Bacteriological eradication was reported in 88% of ciprofloxacin patients, 93% of co-trimoxazole patients and 86% of nitrofurantoin patients. At the 4-6 week follow-up, ciprofloxacin had statistically significantly higher eradication rates (91%) than co-trimoxazole (79%; 95% confidence limit (CL) = -20.6%, -3.9%) and nitrofurantoin (82%; 95% CL = -17.1%, -0.9%). Clinical resolution 4-10 days after therapy and at the 4-6 week follow-up was similar among the three treatment groups. The overall incidence of treatment-emergent adverse events was not significantly different (P = 0.093) among the three drug regimens, although co-trimoxazole was associated with a greater number of adverse events than ciprofloxacin (P < or = 0.05). Ciprofloxacin also caused fewer episodes of nausea than either of the other agents (P < or = 0.01).

A randomized trial of short-course ciprofloxacin, ofloxacin, or trimethoprim/sulfamethoxazole for the treatment of acute urinary tract infection in women. Ciprofloxacin Urinary Tract Infection Group.

PURPOSE: Bladder infections are very common in otherwise healthy women, and short-course antimicrobial treatment appears effective for many episodes of cystitis. This study reports the results of short-course ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole therapy. PATIENTS AND METHODS: We performed a randomized, double-blind study of the efficacy and safety of a 3-day course of oral ciprofloxacin 100 mg twice daily, ofloxacin 200 mg twice daily, or trimethoprim/sulfamethoxazole 160/800 mg twice daily in women with acute, uncomplicated, symptomatic lower urinary tract infection. RESULTS: A total of 866 patients were enrolled, of whom 688 (79%) were evaluated for the efficacy of treatment (229 treated with ciprofloxacin, 228 treated with trimethoprim/sulfamethoxazole, and 231 treated with ofloxacin). The most frequent reason for exclusion was the failure to identify a pretreatment pathogen. The most commonly isolated pathogen was Escherichia coli (81%). Eradication of the pretreatment pathogen at the end of therapy occurred in 94% of ciprofloxacin, 93% of trimethoprim/sulfamethoxazole, and 97% of ofloxacin-treated patients. At follow-up evaluation at 4 to 6 weeks, recurrence rates (relapse or reinfection) were 11% in the ciprofloxacin, 16% in the trimethoprim/sulfamethoxazole, and 13% in the ofloxacin treatment group. Clinical success at the end of therapy was 93% in the ciprofloxacin, 95% in the trimethoprim/sulfamethoxazole, and 96% in the ofloxacin treatment groups. The frequency of all adverse events was 31% for ciprofloxacin, 41% for trimethoprim/sulfamethoxazole, and 39% for ofloxacin-treated patients (P = 0.03). Premature discontinuation of study drug due to an adverse event was more common in trimethoprim/sulfamethoxazole-treated patients (n = 9) compared with those given ciprofloxacin (n = 2) or ofloxacin (n = 1; P = 0.02). CONCLUSION: Ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole had similar efficacy when given for 3 days to treat acute, symptomatic, uncomplicated lower urinary tract infection in women.