Isolation of fluoroquinolone-resistant rectal Escherichia coli after treatment of acute uncomplicated cystitis

OBJECTIVES: Given increasing rates of co-trimoxazole resistance among uropathogens causing acute uncomplicated cystitis, fluoroquinolones, nitrofurantoin and fosfomycin are often considered as alternative empirical therapy. The choice between these drugs should depend in part on whether they are associated with the isolation of drug-resistant microbial flora. We conducted a randomized treatment trial to assess the effects of ciprofloxacin, nitrofurantoin and fosfomycin on the rectal microbial flora of women with acute uncomplicated cystitis, including isolation of fluoroquinolone-resistant strains. METHODS: Pre-menopausal women presenting with acute uncomplicated cystitis were randomized to treatment with 3 days of ciprofloxacin, 7 days of nitrofurantoin, or a single dose of fosfomycin. Women were followed for 1 month for evaluation of clinical and microbiological responses as well as for isolation of resistant rectal E. coli. RESULTS: Sixty-two women (25 ciprofloxacin, 17 nitrofurantoin, 20 fosfomycin) were enrolled and eligible for analysis. All three regimens were well tolerated and resulted in >90% clinical and bacteriological cure. The prevalence of rectal E. coli was markedly decreased by ciprofloxacin and fosfomycin, but not by nitrofurantoin. One woman treated with ciprofloxacin had emergence of two ciprofloxacin-resistant rectal E. coli strains within 10 days of completing therapy. No emergence of resistance was observed in the other two treatment groups. CONCLUSIONS: This study demonstrates that fluoroquinolone-resistant E. coli remain infrequent in the rectal flora of women with uncomplicated cystitis in Seattle. However, a 3 day course of a fluoroquinolone for treatment of uncomplicated cystitis was followed by isolation of fluoroquinolone-resistant rectal E. coli in one patient.     

Comparison of once-daily extended-release ciprofloxacin and conventional twice-daily ciprofloxacin for the treatment of uncomplicated urinary tract infection in women

BACKGROUND: Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the first choice for empiric therapy of acute uncomplicated urinary tract infection (UTI) in women. In areas where resistance to TMP/SMX is known to be high, ciprofloxacin and other fluoroquinolones are recommended as first-line choices for the empiric therapy of UTI. OBJECTIVE: This study compared the efficacy and safety profile of once-daily extended-release ciprofloxacin 500 mg (referred to hereafter as ciprofloxacin QD) with those of conventional ciprofloxacin 250 mg BID, each administered orally for 3 days, in the treatment of uncomplicated UTI in women. METHODS: In this multicenter, prospective, randomized, double-blind, double-dummy, Phase III trial, adult women with clinical signs and symptoms of acute uncomplicated UTI, pyuria, and a positive pretherapy urine culture (>/=10(5) colony-forming units/mL) received ciprofloxacin QD or ciprofloxacin BID. Bacteriologic and clinical outcomes were assessed at the test-of-cure visit (4-11 days after completion of therapy) and the late follow-up visit (25-50 days after completion of therapy). RESULTS: The intent-to-treat population consisted of 891 patients (444 ciprofloxacin QD, 447 ciprofloxacin BID); 422 patients were evaluable for efficacy (199 ciprofloxacin QD, 223 ciprofloxacin BID). At the test-of-cure visit, bacteriologic eradication was achieved in 94.5% (188/199) of the ciprofloxacin QD group and 93.7% (209/223) of the ciprofloxacin BID group (95% CI, -3.5 to 5.1). Clinical cure was achieved in 95.5% (189/198) of the ciprofloxacin QD group and 92.7% (204/220) of the ciprofloxacin BID group (95% CI, -1.6 to 7.1). Bacteriologic and clinical outcomes at the late follow-up visit were consistent with the test-of-cure findings. The rate of eradication of Escherichia coli, the most prevalent organism, was >97% in each treatment group. Rates of drug-related adverse events were similar with the once- and twice-daily ciprofloxacin regimens (10% and 9%, respectively). CONCLUSION: Extended-release ciprofloxacin 500 mg given once daily for 3 days was as effective and well tolerated as conventional ciprofloxacin 250 mg given twice daily for 3 days in the treatment of acute uncomplicated UTI in women.     

Fosfomycin tromethamine in uncomplicated urinary tract infections: a clinical study

The aim of our study was to verify if the empiric therapy with a single dose of 3 g fosfomycin tromethamine in patients with uncomplicated urinary tract infections (UTIs) was able to clinically resolveand to microbiologically eradicate the infection. A total of 387 out of the 400 patients (274 cases with acute and 113 cases with recurrent uncomplicated UTIs) were enrolled in the clinical study. Clinical and microbiological assessments were performed before and at 8-10 days after the administration. At follow-up high clinical recovery (88.9%) and bacteriological (94.9%) eradication rates were achieved. Gastrointestinal side effects were found in only 4.3% of patients. In conclusion, a single-dose administration regimen of fosfomycin tromethamine should be encouraged as a first choice of drug therapy for uncomplicated UTIs.     

Comparative pharmacokinetics of tromethamine fosfomycin and calcium fosfomycin in young and elderly adults.

The pharmacokinetics of two oral forms of fosfomycin, tromethamine (trometamol) salt and calcium salt, were studied in five young (age, 29 +/- 3 [standard deviation] years) and eight elderly (age, 72 +/- 6 years) adults. The subjects received a single 40-mg/kg (body weight) (approximately equal to 3-g) calcium fosfomycin dose and a 25-mg/kg (approximately equal to 2-g) tromethamine fosfomycin dose in fosfomycin acid form. Blood and urine samples were collected for 24 h. Antibiotic concentrations in serum and urine were measured by microbiological assay. In all subjects, the peak levels of the calcium salt in serum were two- to fourfold lower than those of the tromethamine salt (6 to 7 and 18 to 22 micrograms/ml, respectively), indicating poor intestinal absorption of the calcium form. The elimination half-life of the two oral forms was about 5 h in young adults, and the half-life was only moderately longer in elderly subjects, with large individual variations: 8.28 +/- 5.51 h for tromethamine fosfomycin and 11.80 +/- 6.86 h for calcium fosfomycin. In elderly subjects, absorption of the tromethamine salt form was not modified, but the time to peak level was delayed for the calcium salt (2.58 +/- 0.54 h versus 1.41 +/- 0.67 h in young adults). Pharmacokinetic elimination of the two forms of fosfomycin was only moderately affected in elderly subjects; we observed lower urinary elimination, about 58 versus 28% of the dose in 24-h urines for the tromethamine salt and decreased renal clearance of both forms. However, the dosages of tromethamine and calcium fosfomycin need not be adjusted for elderly subjects who have endogenous creatinine clearances above 50 ml/min per 1.73 m2.     

A multicentre study of flumequine in the treatment of urinary tract infections

The efficacy and safety of flumequine were evaluated in the treatment of 121 cases uncomplicated (65.5%) and complicated (34.5%) urinary tract infections (UTI) when given as a dose of 400 mg bd. Duration of treatment ranged from 7-15 days, with a mean of 10. Thirty days post-therapy, cure persisted in 92.3% of the patients with uncomplicated UTI and in 53.7% of those with complicated UTI. Relapse or re-infection occurred in 34.1% of the patients with complicated UTI, and in 12.2%, the infecting organism did not respond to treatment. Flumequine was generally well tolerated. In 27.3% of patients gastrointestinal, and neurological disorders and skin rashes developed which in most cases were mild. Only two patients were withdrawn from the treatment. It is concluded that flumequine, administered at 800 mg daily, is highly effective in treating uncomplicated and complicated UTI.     

Comparison of sparfloxacin and ciprofloxacin in the treatment of community-acquired acute uncomplicated urinary tract infection in women. Sparfloxacin Multicenter Uncomplicated Urinary Tract Infection Study Group.

Urinary tract infection (UTI) is a common illness, with > or =30% of all women experiencing a UTI during their lifetime. Less than a decade ago, the standard therapy for acute uncomplicated UTIs involved treatment with > or =7 days of an antibacterial agent, but recent studies using a variety of newly introduced antibiotics, including the fluoroquinolones, have demonstrated that a 1- to 5-day treatment regimen can be equally effective. This randomized, double-masked, multicenter study was conducted to compare the efficacy and tolerability of a single dose of sparfloxacin with those of a 3-day regimen of sparfloxacin and a 7-day regimen of ciprofloxacin in the treatment of women with community-acquired acute uncomplicated urinary tract infection. A total of 1175 women were enrolled; 395 received sparfloxacin as a single 400-mg dose on day 1, 394 received sparfloxacin as a 400-mg loading dose on day 1 followed by 200 mg once daily for 2 additional days, and 386 received ciprofloxacin 250 mg twice daily for 7 days. Patients were comparable with respect to demographic characteristics and underlying conditions. A total of 954 patients were clinically assessable; 490 of these were also bacteriologically assessable. All patients treated were included in the tolerability analysis. Escherichia coli (75.4%), Klebsiella pneumoniae (4.9%), Enterococcus faecalis (4.6%), and Staphylococcus saprophyticus (4.1%) were the most commonly isolated organisms. In the all-treated population, clinical success was achieved 5 to 9 days after therapy in 91.8%, 92.2%, and 91.6% of patients in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; bacteriologic success was observed in 91.7%, 92.6%, and 96.6% of those in the 3 groups. Sustained clinical success rates 4 to 6 weeks after therapy were 76.6%, 80.2%, and 79.5% in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; sustained bacteriologic success rates were 80.7%, 90.1%, and 92.6%. The most common adverse events were nausea, headache, vaginal thrush, dizziness, and diarrhea; >92% of adverse events were mild or moderate in severity. The 2 drugs had comparable frequencies of adverse events, except for photosensitivity, which occurred in 3.3% of the 3-day sparfloxacin group, 1.3% of the single-dose sparfloxacin group, and 0.3% of the ciprofloxacin group (P = 0.005). The 3-day sparfloxacin regimen was effective and well tolerated. The initial response to single-dose sparfloxacin treatment was comparable to the response to the other 2 regimens, but the single-dose regimen proved less effective over time, with higher rates of clinical recurrence and bacteriologic relapse. Sparfloxacin provides an alternative to ciprofloxacin for patients with acute uncomplicated urinary tract infection who are not at risk for photosensitivity reactions or adverse events associated with a prolonged corrected QT interval.     

Single-dose fosfomycin trometamol versus 5-day cephalexin regimen for treatment of uncomplicated lower urinary tract infections in women.

A randomized study was conducted to assess the clinical and microbiological efficacies of a single 3-g dose of fosfomycin trometamol for the treatment of uncomplicated lower urinary tract infections in women compared with a 5-day regimen of cephalexin at 0.5 g four times daily. One hundred twelve women, all of whom had documented infections with bacteria sensitive to both antibiotics, were included. Fifty-eight women received fosfomycin trometamol, and 54 women received cephalexin. The two groups did not differ in age, severity, or duration of current urinary tract infection, menstrual status, sexual activity, or use of contraceptives. Ninety percent of pathogens in the fosfomycin trometamol group and 81% in the cephalexin group were Escherichia coli (the difference is not significant [NS]). A clinical evaluation at the 5-day follow-up showed that 91% of the women in each group were free of symptoms, while five women in each group were considered therapy failures and were treated by another antibiotic course. A microbiological evaluation at the 5-day follow-up showed a 91% eradication rate in the fosfomycin trometamol group and an 83% eradication rate in the cephalexin group (NS). At the 1-month follow-up, a clinical evaluation demonstrated prolonged resolution in 86 and 78%, respectively, of the participating women (NS). A microbiological evaluation at 1 month demonstrated prolonged eradication in 47 (81%) women treated with fosfomycin trometamol and in 37 (68%) women treated with cephalexin (NS). Three and six women, respectively, had relapsed. No adverse reactions were reported by the fosfomycin trometamol-treated women, while three women treated with cephalexin reported mild adverse reactions but completed the study period. Fosfomycin trometamol in a single 3-g dose is as effective as a 5-day regimen of cephalexin for the treatment of uncomplicated lower urinary tract infection in women.     

Novel, single-dose microsphere formulation of azithromycin versus 7-day levofloxacin therapy for treatment of mild to moderate community-acquired Pneumonia in adults

This randomized, double-blind, noninferiority study was designed to demonstrate that a single 2.0-g oral dose of a novel microsphere formulation of azithromycin was at least as effective as 7 days of levofloxacin, 500 mg/day, in the treatment of adult patients with mild to moderate community-acquired pneumonia (Fine classes I, II, and III). In total, 427 subjects were randomly assigned to receive either a single 2.0-g dose of azithromycin microspheres (n = 213) or a 7-day regimen of levofloxacin (n = 214). At baseline, 219 of 423 (51.8%) treated subjects had at least one pathogen identified by culture, PCR, or serology. The primary end point was the clinical response (cure or failure) in the "clinical per protocol" population at test of cure (days 13 to 24). Clinical cure rates were 89.7% (156 of 174) for azithromycin microspheres and 93.7% (177 of 189) for levofloxacin (treatment difference, -4.0%; 95% confidence interval, -9.7%, 1.7%). Bacteriologic success at test of cure in the "bacteriologic per protocol" population was 90.7% (97 of 107) for azithromycin microspheres and 92.3% (120 of 130) for levofloxacin (treatment difference, -1.7%; 95% confidence interval, -8.8%, 5.5%). Both treatment regimens were well tolerated; the incidence of treatment-related adverse events was 19.9% and 12.3% for azithromycin and levofloxacin, respectively. A single 2.0-g dose of azithromycin microspheres was at least as effective as a 7-day course of levofloxacin in the treatment of mild to moderate community-acquired pneumonia in adult outpatients.     

Antibiotic prescribing for adult bacteriuria and pyuria in community hospital emergency departments

ObjectiveTo describe emergency department (ED) antibiotic prescribing for urinary tract infections (UTIs) and asymptomatic bacteriuria (ASB) and to identify improvement opportunities.MethodsPatients treated for UTI in 16 community hospital EDs were reviewed to identify prescribing that was unnecessary (any treatment for ASB, duration >7 days for cystitis or >14 days for pyelonephritis) or suboptimal [ineffective antibiotics (nitrofurantoin/fosfomycin) or duration <7 days for pyelonephritis]. Duration criteria were based on recommendations for complicated UTI since criteria for uncomplicated UTI were not reviewed. 14-day repeat ED visits were evaluated.ResultsOf 250,788 ED visits, UTI was diagnosed in 13,466 patients (5%), and 1427 of these (11%) were manually reviewed. 286/1427 [20%, 95% CI: 18–22%] met criteria for ASB and received 2068 unnecessary antibiotic days [mean (±SD) 7 (2) days]. Mean treatment duration was 7 (2) days for cystitis and 9 (2) days for pyelonephritis. Of 446 patients with cystitis, 128 (29%) were prescribed >7 days (total 396 unnecessary). Of 422 pyelonephritis patients, 0 (0%) were prescribed >14 days, 20 (5%) were prescribed <7 days, and 9 (2%) were given ineffective antibiotics. Overall, prescribing was unnecessary or suboptimal in 443/1427 [31%, 95% CI: 29–33%] resulting in 2464/11,192 (22%) unnecessary antibiotic days and 8 (0.5%) preventable ED visits.ConclusionsAmong reviewed patients, poor UTI prescribing in 16 EDs resulted in unnecessary antibiotic days and preventable readmissions. Key areas for improvement include non-treatment of ASB and shorter durations for cystitis.     

Longer than recommended empiric antibiotic treatment of urinary tract infection in women: an avoidable waste of money

CONTEXT: Current Israeli guidelines for the empiric treatment of uncomplicated urinary tract infection (UTI) in women recommend nitrofurantoin for 5 days. Some physicians nevertheless opt for ofloxacin, which should be prescribed for 3 days according to universally accepted guidelines. OBJECTIVE: To evaluate the economic consequences of longer than recommended durations of antibiotic therapy in the empiric treatment of uncomplicated UTI in women. DESIGN, SETTING AND PATIENTS: Data were derived from the electronic records of one of the four health maintenance organizations in Israel. The sample included all women aged 18-75 years who were diagnosed with acute cystitis or UTI from January 2001 to June 2002 and were empirically treated with antibiotics. Of the 7738 patients identified, 1138 received nitrofurantoin and 1054 ofloxacin. The excess expenditure accrued due to longer than recommended therapy with these drugs was evaluated. RESULTS: The rate of adherence was 22.23% for nitrofurantoin (95% CI=19.81%, 24.65%), and 4.08% for ofloxacin (95% CI=2.88%, 5.28%). The average excess expenditure per case was 5.78 USD (US Dollar) with ofloxacin and 3.43 USD with nitrofurantoin, resulting in an annual loss to the health maintenance organizations of approximately 19,000 USD. When extrapolated to the national population of 6.5 million, the loss due to inappropriate treatment of adult women is 190,000 USD. CONCLUSIONS: The lack of adherence to national and international guidelines with regard to the recommended duration of antibiotic treatment of UTI in women resulted in a significant and avoidable waste of health system resources. This study suggests that drug utilization analyses that concentrate solely on the choice of drug may be overlooking important information.     

Phase III, randomized, double-blind study of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis

BACKGROUND: Clarithromycin has an established efficacy and safety profile in the treatment of respiratory tract infections. OBJECTIVE: The purpose of this study was to compare the clinical and bacteriologic efficacy and tolerability of clarithromycin extended-release and immediate-release formulations in patients with acute exacerbation of chronic bronchitis (AECB). METHODS: In a phase III, randomized, double-blind, parallel-group, multicenter study. patients aged > or =12 years with signs and symptoms of AECB and a productive cough with purulent sputum received treatment with extended-release (two 500-mg tablets once daily) or immediate-release (one 500-mg tablet twice daily) clarithromycin for 7 days. Assessments were performed before treatment, within 48 hours after treatment, and at the test-of-cure visit (study days 19-21). Patients who took > or =1 dose of study drug were included in the safety analysis. RESULTS: Of 620 patients randomized and treated, 182 were clinically and bacteriologically assessable (100 in the extended-release group and 82 in the immediate-release group). Treatment groups were well matched with respect to demographic characteristics and medical and social history. At the test-of-cure visit, 83% (83/100) of patients in the extended-release and 82% (67/82) of patients in the immediate-release group achieved clinical cure; 86% (85/99) and 85% (70/82), respectively, demonstrated bacteriologic cure. Overall pathogen eradication rates were 86% (100/116) in the extended-release group and 88% (86/98) in the immediate-release group. The most frequently reported adverse events were diarrhea (6% in extended-release group vs 4% in immediate-release group; no significant difference), taste alterations (4% in each group), and nausea (3% in each group); no clinically meaningful changes in laboratory values or vital signs, as assessed by the investigator, were observed. CONCLUSION: This study suggests that clarithromycin extended-release and immediate-release formulations have equivalent clinical and bacteriologic efficacy and tolerability in patients with AECB.     

Chapter 2-5-3c. Anaerobic infections (individual fields): skin and soft tissue infections––foot infection

Fosfomycin calcium is a fosfomycin antimicrobial agent with a characteristic structure. After oral administration, the drug is absorbed and excreted via the kidneys in the unchanged form, without being metabolized in the body. It is, therefore, indicated for the treatment of urinary tract diseases, including cystitis and pyelonephritis. In the present study, the clinical usefulness of fosfomycin calcium (FOSMICIN^® TABLETS 500) administered orally at the dosage of 1 g (two tablets) three times daily for 2 days was examined in female patients, who were at least 20 years of age, with acute uncomplicated cystitis of bacterial origin. Of the 48 patients enrolled between February 2008 and August 2008, 39 were evaluable for efficacy and safety. Overall evaluation of the cure revealed that microbiological eradication rate (microbiological outcome) and clinical efficacy rate (clinical outcome) at 5–9 days after drug administration (visit 2) were 94.9%. Determination of the microbiological and clinical outcomes for the evaluation of recurrence at 4–6 weeks after drug administration (visit 3) were 75.8 and 85.7%, respectively. Of the 48 patients, 40 (83.3%) returned to the clinic at visit 3. The causative bacterial species for cystitis was Escherichia coli in 31 (79.5%) of the 39 patients evaluable for efficacy and safety. Adverse drug reactions observed during the administration and follow-up periods included mild diarrhea and loose stools in 1 patient each, neither requiring any specific treatment. Evaluation of cure at visit 2 in patients in whom the causative bacterial species for the infection was E. coli revealed a microbiological outcome of 93.5%, and clinical outcome was 96.8%. Furthermore, evaluation for recurrence at visit 3 revealed a microbiological outcome of 74.1% and clinical outcome of 82.1%. When the patients were divided by age into an under 60 years of age group and an over 60 years of age group, the microbiological and clinical outcomes determined for evaluation of cure at visit 2 were 96.4 and 92.9%, respectively, and the corresponding rates determined for the evaluation of recurrence at visit 3 were 87.0 and 96.0%, respectively, in the under 60 years of age group. In the over 60 years of age group, the corresponding microbiological outcome and clinical outcome rates evaluated for cure were 90.9 and 100%, respectively, and those evaluated for recurrence were 50.0 and 60.0%, respectively. These results indicate the usefulness of fosfomycin calcium administered at 1 g three times daily for 2 days for acute uncomplicated cystitis.     

Pivmecillinam versus sulfamethizole for short-term treatment of uncomplicated acute cystitis in general practice: a randomized controlled trial

Objective

To investigate whether short-term treatment with pivmecillinam was more effective than sulfamethizole in patients with acute uncomplicated urinary tract infection (UTI).

Design

Randomized controlled trial.

Setting

General practice, Denmark.

Subjects

Patients (n = 167) with uncomplicated UTI confirmed by positive urine phase-contrast microscopy.

Main outcome measures

Drug efficacy based on clinical and bacteriological cure.

Results

Urinary symptoms disappeared first in patients treated with pivmecillinam, but after five days there was no significant difference in clinical cure rate between the two antibiotics. At the follow-up visit 7–10 days after initiation of treatment, 95.4% of patients treated with pivmecillinam and 92.6% of patients treated with sulfamethizole had no persistent cystitis symptoms (difference 2.8%, CI −4.5%; 10.0%). Bacteriological cure was observed in 68.8% of patients randomized to pivmecillinam and in 77.9% randomized to sulfamethizole (difference −9.2%, CI −24.7%; 6.3%). Some 26.8% of patients randomized to pivmecillinam experienced a new UTI within 6 months after treatment compared with 18.4% of patients randomized to sulfamethizole (difference 8.4%, CI −4.5%;21.4%). No patients developed septicaemia with urinary pathogens within one year after initial treatment.

Conclusion

Patients treated with a three-day regime of pivmecillinam experienced faster relief of symptoms compared with patients treated with a three-day regime of sulfamethizole. Five days after initiation of treatment there was no significant difference in clinical and bacteriological cure between the two antibiotic regimes.     

Efficacy of a 14-day course of oral ciprofloxacin therapy for acute uncomplicated pyelonephritis

This study aimed to evaluate the efficacy and safety of oral antibacterial treatment with fluoroquinilone for acute uncomplicated pyelonephritis Thirteen female patients with acute uncomplicated pyelonephritis were treated with oral fluoroquinilone (ciprofloxacin; CPFX). They received 200 mg of the drug three times a day while febrile (3–5 days). Once they become afebrile, the same dose of the drug, given twice a day, was given for another 9–11 days. The mean duration of the course of CPFX was 14 days. Symptoms were evaluated, and laboratory examinations, including urine culture and measurement of the minimal inhibitory concentration (MIC) of CPFX were conducted before treatment, and 3, 7, 14, 21, and/or 28 days after the initiation of the treatment. Of the 13 patients, only 5 needed to be hospitalized, and the period of hospitalization was only a few days. On the 14th day after the commencement of treatment, bacteriologic and clinical cure rates were 100%. Escherichia coli was the most common uropathogen, being isolated from the urine of 8 patients. No clinical relapse of the disease was found during a follow-up period of up to 4 weeks. The patients tolerated the drug well without developing any serious adverse effects. Oral antimicrobial chemotherapy with fluoroquinolone, given on an outpatient or short-term hospitalization basis, achieved satisfactory bacteriological and clinical outcomes in the treatment of acute uncomplicated pyelonephritis. This treatment regimen is indicated for patients with this disease who are not in a serious condition with complications such as shock. Received: January 29, 2001 / Accepted: April 7, 2001     

The expanding role of fluoroquinolones

There has been a growing rate of resistance among common urinary tract pathogens, such as Escherichia coli, to traditional antimicrobial therapies including the "gold standard" trimethoprim-sulfamethoxazole (TMP-SMX). Consequently, fluoroquinolone antimicrobial agents have taken on an expanding management role for UTIs. In fact, the recent Infectious Diseases Society of America clinical management guidelines for UTI recommend fluoroquinolones as first-line therapy for uncomplicated UTI in areas where resistance is likely to be of concern. Fluoroquinolones have demonstrated high bacteriologic and clinical cure rates, as well as low rates of resistance, among most common uropathogens. There are currently 7 fluoroquinolones with indications for UTI in the United States. However, only 3 are commonly used: levofloxacin, ciprofloxacin, and, to a lesser extent, gatifloxacin. Many of the fluoroquinolone agents have once-daily dosing regimens, enhancing patient adherence. In addition, levofloxacin and gatifloxacin have same-dose bioequivalency between their intravenous and oral formulations, allowing for "switch" or step-down therapy from parenteral to oral formulations of the same agent at the same dose.Fluoroquinolones are indicated for the management of acute uncomplicated UTIs, as well as complicated and severe UTI and pyelonephritis, in adults. They are the first-line treatment of acute uncomplicated cystitis in patients who cannot tolerate sulfonamides or TMP, who live in geographic areas with known resistance >10% to 20% to TMP-SMX, or who have risk factors for such resistance. Fluoroquinolone properties include a broad spectrum of coverage, low rates of resistance, and good safety profiles.     

Risk factors for ciprofloxacin resistance among Escherichia coli strains isolated from community-acquired urinary tract infections in Turkey

OBJECTIVES: To determine the risk factors for community-acquired ciprofloxacin-resistant Escherichia coli urinary tract infection (UTI). METHODS: The study was performed with isolates from community-acquired UTIs collected from 15 centres representing six different geographic regions of Turkey. All microbiological procedures were carried out in a central laboratory. Multivariate analysis was performed for detection of risk factors for resistance. Use of quinolones more than once within the last year, living in a rural area, having a urinary catheter, age >50 and complicated infections were included in the model as variables and logistic regression was performed. RESULTS: A total of 611 gram-negative isolates were studied: 321 were isolated from uncomplicated UTI and 290 were isolated from complicated UTI. E. coli was the causative agent in 90% of the uncomplicated UTIs and in 78% of the complicated UTIs (P < 0.001). Seventeen percent of E. coli strains isolated from uncomplicated cases and 38% of E. coli strains isolated from complicated UTI were found to be resistant to ciprofloxacin. In multivariate analysis, age over 50 [odds ratio (OR): 1.6; confidence interval (CI): 1.08-2.47; P = 0.020], ciprofloxacin use more than once in the last year (OR: 2.8; CI: 1.38-5.47; P = 0.004) and the presence of complicated UTI (OR: 2.4; CI: 1.54-3.61; P < 0.001) were found to be associated with ciprofloxacin resistance. Detection of strains of E. coli producing extended-spectrum beta-lactamase (ESBL) enzymes was two times more common in the patients who received ciprofloxacin than those who did not (15% versus 7.4%). CONCLUSIONS: The increasing prevalence of infections caused by antibiotic-resistant bacteria makes the empirical treatment of UTIs more difficult. One of the important factors contributing to these high resistance rates might be high antibiotic use. Urine culture and antimicrobial susceptibility testing are essential in Turkey for patients with UTI who have risk factors for resistance, such as previous ciprofloxacin use. Fluoroquinolone-sparing agents such as nitrofurantoin and fosfomycin should be evaluated as alternative therapies by further clinical efficacy and safety studies.     

Economic assessment of three antimicrobial therapies for uncomplicated urinary tract infection in women.

This retrospective cohort study used North Carolina Medicaid paid-claims data to assess clinical and economic outcomes of treatments for urinary tract infection (UTI). The study population comprised female Medicaid recipients, between 15 and 64 years of age, with a paid claim filed for a primary diagnosis of UTI or acute UTI from January 1 to June 30, 1994, who were treated with ciprofloxacin, nitrofurantoin, or trimethoprim/sulfamethoxazole (TMP/SMZ). Patients had follow-up for 6 months after the primary diagnosis. Patients who did not receive further treatment for UTI with 1 of the 3 drugs within 30 days after initial treatment were assumed to be cured. Costs were measured as the sum of reimbursements for UTI-related medical services and drug treatments. Outcomes for 409 patients were assessed. Cure rates of initial treatment with ciprofloxacin, nitrofurantoin, and TMP/SMZ were 81%, 88%, and 93%, respectively. Cost-effectiveness ratios of initial treatment with the 3 drugs were $150.80, $81.20, and $69.00, respectively. When efficacy rates generated from published randomized clinical studies were applied, cost-effectiveness ratios for the 3 drugs were $130.96, $86.17, and $72.00, respectively. A decision model of treatment pattern and associated costs is presented. Several patient variables indicate that the ciprofloxacin group included more severe cases of UTI than did the other groups. Study limitations, confounders, and future research suggestions are discussed. Our results show that treatment for >7 days results in a better cure rate regardless of the drug used than does treatment for < or =7 days and that TMP/SMZ is the most cost-effective of the 3 drugs for UTI or acute UTI.     

Clinical Appraisal of Fosfomycin in the Era of Antimicrobial Resistance

Fosfomycin is recommended as one of the first-line agents for treatment of urinary tract infections (UTIs) in the latest guidelines endorsed by the Infectious Diseases Society of America (IDSA) and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). We evaluated the use of fosfomycin among inpatients at a tertiary care hospital between 2009 and 2013. UTI cases were defined using physician diagnosis and the National Healthcare Safety Network (NHSN) surveillance definitions. The number of patients treated with fosfomycin increased from none in 2009 to 391 in 2013. Among 537 patients who received fosfomycin for any indication during this period, UTI was the most common indication (74%), followed by asymptomatic bacteriuria (10%). All except 19 patients received a single dose of fosfomycin. Escherichia coli was the most common organism involved (52%). For 119 patients with UTIs, after exclusion of those with negative urine culture results, negative urinalysis results, receipt of additional agents, or indeterminate clinical outcomes, the clinical success rate at 48 h was 74.8%. Of 89 patients who met the criteria for NHSN-defined UTIs, 89.9% had successful outcomes. Recurrent infections occurred in 4.3% of cases, and mild adverse events were observed in 2.0%. All 100 randomly selected extended-spectrum β-lactamase (ESBL)-producing E. coli clinical isolates from this period were susceptible to fosfomycin. In conclusion, the use of fosfomycin has increased substantially since implementation of the updated guidelines at this hospital. Fosfomycin was used mainly for the treatment of physician-diagnosed UTIs, and the clinical outcomes were generally favorable. Fosfomycin maintained activity against E. coli despite the increased use of the agent.     

Preliminary report on DU-6859a for urinary tract infection

The efficacy safety, and clinical value of DU-6859a, a novel new quinolone antimicrobial, were evaluated in a multicenter study. The subjects were selected from among patients aged 20 to 79 years with mild to moderate uncomplicated or complicated urinary tract infection (UTI). DU-6859a was administered orally after meals at a dose of 50–100 mg once or twice daily for 3–7 days. The clinical efficacy rate for all target infections was determined to be 88.5%, (100/113) by the attending physicians. The efficacy rate was 100% (21/21) for acute uncomplicated cystitis, 84.9% (62/73) for complicated cystitis, and 88.9% (16/18) for complicated pyelonephritis. The overall clinical efficacy rate and the eradication rate for urinary pathogens were determined according to the Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents for UTI proposed by the Japanese UTI Committee. The rates were, respectively, 100% (9/9) and 100% (11/11) for acute uncomplicated UTI and 88.0% (66/75) and 91.2% (93/102) for complicated UTI. Clinical adverse reactions were experienced in seven (5/7%) out of 123 evaluable patients, but all symptoms were mild. Laboratory adverse reactions, such as slight elevations of GOT and/or GPT, were noted in 13 (12.1%) out of 107 evaluable patients. DU-6859a showed excellent clinical efficacy against acute uncomplicated and complicated UTI which reflected its high antibacterial activity in vitro and did not cause any clinically significant adverse reactions. These results show that DU-6859a is worthy of further clinical studies for the treatment of UTI.     

Efficacy of cefaclor AF in the treatment of skin and skin-structure infections.

Cefaclor advanced formulation (cefaclor AF) was compared with cefaclor for the treatment of skin and skin-structure infections in a double-blind study at 28 centers in North America. Of the 563 patients originally randomized, 278 patients received cefaclor AF (375 mg twice daily) and 285 patients received cefaclor (250 mg three times daily). A total of 154 patients treated with cefaclor AF and 157 patients treated with cefaclor qualified for the efficacy analysis after completing 7 days of therapy. At the post-therapy visit, favorable clinical response rates for evaluable patients were 97.4% in the cefaclor AF group and 94.9% in the cefaclor group; favorable bacteriologic response rates were 85.7% and 84.1%, respectively. At the late post-therapy evaluation, 7 to 14 days after completion of therapy, favorable clinical response rates were 90.1% in the cefaclor AF group versus 89.9% in the cefaclor group, and favorable bacteriologic response rates were 88.7% and 86.9%, respectively. No significant difference was seen between the groups in clinical or bacteriologic efficacy at either evaluation or in the frequency of nature of side effects reported during the study.