Efficacy and safety of ciprofloxacin (Bay 0 9867) in the treatment of patients with complicated urinary tract infections

In an open study 28 patients were treated for complicated UTI with ciprofloxacin 250 mg every 12 h for 10 days. The most frequently isolated species were Escherichia coli and Klebsiella pneumoniae. All pathogens were sensitive to ciprofloxacin in vitro. Twenty-three of the 28 patients (82%) were free of infection 5-9 days after therapy. A persistent infection was noted in two patients (7%) and a reinfection in three patients (11%). Four to six weeks after the end of therapy, 18 patients (64%) were still totally free of infection. Clinical resolution of symptoms and signs occurred in 27 patients (96%). Adverse reactions were spontaneously reported by four of the 28 patients (14%) and by 11 (39%) after detailed inquiry. Most side effects were of gastrointestinal or neurological nature. This small open study supports the view, that ciprofloxacin may be useful in the treatment of complicated UTI.     

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.     

Treatment of complicated urinary tract infection in adults: combined analysis of two randomized, double-blind, multicentre trials comparing ertapenem and ceftriaxone followed by appropriate oral therapy

The efficacy and safety of parenteral ertapenem, a Group 1 carbapenem, 1 g once a day, for the treatment of complicated urinary tract infections (UTIs; i.e. acute pyelonephritis, UTI in men, or UTI associated with obstruction, foreign body or a urological abnormality interfering with normal voiding) in adults, were compared with those of parenteral ceftriaxone, 1 g once a day, in two similarly designed prospective, double-blind, randomized studies. In both studies, patients could be switched to an oral agent after > or = 3 days of parenteral study therapy. At entry, 850 patients were stratified according to whether they had acute pyelonephritis or other complicated UTI without acute pyelonephritis. Two hundred and fifty-six patients in the ertapenem group and 224 in the ceftriaxone group were microbiologically evaluable. Ninety-six per cent of these patients were switched to oral therapy, usually ciprofloxacin; the median (range) duration of parenteral and total therapy, respectively, was 4 (2-14) days and 13 (14-18) days for ertapenem and 4 (2-14) days and 13 (3-17) days for ceftriaxone. The most common pathogens were Escherichia coli and Klebsiella pneumoniae, which accounted for 64.7% and 9.8% of isolates, respectively. At the primary efficacy endpoint 5-9 days after treatment, 229 (89.5%) patients who received ertapenem and 204 (91.1%) patients who received ceftriaxone had a favourable microbiological response (95% confidence interval, -7.4 to 4.0), indicating that outcomes in the two treatment groups were equivalent. Success rates in both treatment groups were similar when compared by stratum and severity of infection. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. In this combined analysis, ertapenem was highly effective therapy for the treatment of complicated UTIs in adults with moderate-to-severe disease.     

Influence of three-day antimicrobial therapy and lactobacillus vaginal suppositories on recurrence of urinary tract infections.

Forty-one adult women with acute lower urinary tract infections (UTI) were randomly treated for three days with norfloxacin or trimethoprim/sulfamethoxazole (TMP/SMX). Infection was eradicated in 100% of norfloxacin-treated patients and in 95% of TMP/SMX-treated patients. UTI recurred in 29% of patients treated with norfloxacin and in 41% of those treated with TMP/SMX. Post-therapy vaginal administration of lactobacillus suppositories resulted in a recurrence rate of UTI of only 21%, while in patients given sterilized skim-milk suppositories the recurrence rate was 47%. This study indicates that lactobacillus vaginal suppositories are safe and may be effective in reducing the recurrence of UTI following antimicrobial therapy.     

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.     

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.     

乌司他丁在风心病合并恶病质患者瓣膜置换术后的临床应用

[目的]探讨风心痛合并恶病质综合征(SOCC)患者,瓣膜置换术后应用乌司他丁(UTI)的效果.[方法]56例风心病合并SOCC患者分成两组:UTI治疗组(UTI,n=26)在常规治疗的基础上,每天静脉注射UTI 6U(每次2U,3次/日).对照组(n=30)仅采用常规治疗.术后即刻和d3,分别测定肝功能,肾功能、凝血功能、炎症介质以及临床指标的变化.[结果]术后即刻,两组患者各项指标无统计学差异.术后da,治疗组的各项生化指标较对照组明显降低,其中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)具有非常显著性差异(P<0.01),血尿素氮(BUN)、肌酐(Cr)、PT、APTT具有显著性差异(P<0.05);炎症介质TNF-α、IL-6较对照组明显降低(P<0.05);两组患者在SBP、尿量、心率无明显差异.[结论]鸟司他丁能押制风心病合并SOCC患者瓣膜置换术后的部分炎症介质的释放,并保护肝肾等重要脏嚣功能,对术后早期的应激反应有良好的临床疗效.     

Antibiotic prescribing patterns for adult urinary tract infections within emergency department and urgent care settings

Urinary tract infections (UTI) are a common reason for emergency department (ED) and urgent care (UC) visits. Fluoroquinolones (FQ) are frequently prescribed for treatment of UTI in the outpatient setting; however, data evaluating prescribing patterns after FDA safety warnings is limited, especially in UC. The study goal was to investigate and compare antimicrobial prescribing for UTIs in a single-site ED and an off-site UC in an urban, academic health system. This retrospective study included patients presenting with a UTI to the ED or UC between January and June 2018. Those 18 years or older with uncomplicated, complicated UTI, or pyelonephritis were included. Exclusion criteria were catheter-related UTI, urinary tract abnormalities, immunocompromised, or hospitalization. Primary outcome was FQ prescribing rate for all UTI in the ED and UC. Secondary outcomes were rates of non-FQ prescribing, re-presentation, bug-drug mismatch, and treatment durations. 184 patients were included. FQ prescribing rate was similar in ED and UC (21.2% vs. 16.3%, p = 0.4). Non-FQs prescribed in ED and UC were nitrofurantoin (20.2% vs 53.6%), beta-lactams (46.1% vs 22.6%), and trimethoprim/sulfamethoxazole (12.5% vs. 5%). A longer than recommended duration was identified in 46.3% UC patients compared to 21.2% ED patients. Thirty-day re-presentation with persistent UTI symptoms occurred more frequently in the ED compared to UC (13.5% vs. 7.5%). Predictors of FQ prescribing on logistic regression were male, recurrent UTI, and malignancy. FQ prescribing rate for UTI treatment was low with no difference between ED and UC. Opportunity exists to improve treatment duration and antimicrobial choice.     

Multiclinic comparative study of norfloxacin and trimethoprim-sulfamethoxazole for treatment of urinary tract infections

Three hundred seventy patients with upper or lower urinary tract infections were entered into a multicenter, open comparative study. A total of 190 patients were treated with norfloxacin, and 180 patients were treated with trimethoprim-sulfamethoxazole. The percentage of strains susceptible to norfloxacin (99%) was significantly greater (P less than 0.001) than the percentage of strains susceptible to trimethoprim-sulfamethoxazole (90%). The percentages of patients with bacteriological outcomes of eradication were greater in the norfloxacin group (97%) than in the trimethoprim-sulfamethoxazole group (90%). The difference was significant (P less than 0.05). Seven patients (three treated with norfloxacin, four treated with trimethoprim-sulfamethoxazole) experienced early reinfection. Of 370 patients entered into the study, 20 patients experienced clinical adverse effects that were probably or definitely related to the study drug; 6 patients were in the group that received norfloxacin, and 14 were in the group that received trimethoprim-sulfamethoxazole. Study antimicrobial agents were discontinued because of clinical adverse effects in eight patients (norfloxacin, one patient; trimethoprim-sulfamethoxazole, seven patients). Three patients receiving norfloxacin and four patients receiving trimethoprim-sulfamethoxazole had laboratory adverse effects which were classified as probably or definitely drug related. None of the clinical or laboratory adverse effects was serious.     

Selective antimicrobial modulation of the intestinal tract by norfloxacin in human volunteers and in gnotobiotic mice associated with a human fecal flora

Intestinal endogenous members of the family Enterobacteriaceae were eliminated in 12 human volunteers treated with 400 or 800 mg of oral norfloxacin per day for 5 days. No clones resistant to quinolone derivatives were isolated. Counts of aerotolerant streptococci were affected to various degrees, depending on their susceptibility to norfloxacin. During treatment, counts of anaerobes remained above 9.8 log10 CFU/g of feces. A total of 932 anaerobic isolates from the predominant flora (over 10(9) CFU/g) in fecal samples obtained before or during norfloxacin treatment were classified by a simple morphological and physiological scheme. The composition of this flora was fairly stable from one sample to another before treatment and was not substantially modified by norfloxacin. Intestinal resistance to colonization by exogenous microorganisms was studied in gnotobiotic mice associated with a human fecal flora. The composition of the fecal flora of the human donor and the fecal concentrations of norfloxacin in the volunteers were reproduced in the intestine of the mice. Resistance to colonization by exogenous microorganisms was reduced by norfloxacin for only 2 of 14 (14%) of the strains tested. These results suggest that norfloxacin is a good candidate for selective antimicrobial modulation of the intestinal tract in humans.     

Pharmacokinetics, in-vitro activity, therapeutic efficacy and clinical safety of aztreonam vs. cefotaxime in the treatment of complicated urinary tract infections

The minimal inhibitory concentrations (MICs) of aztreonam and cefotaxime were determined against 400 isolates from urological in-patients with complicated and/or hospital acquired urinary tract infections (UTI). Against the Gram-negative rods the activities of both antibiotics were comparable except for higher activity of aztreonam against Pseudomonas aeruginosa. The pharmacokinetic study in nine elderly patients showed a prolonged plasma half life of aztreonam (2.7 h) as compared to younger volunteers (1.6-1.9 h). In a prospective randomized study 39 urological patients with complicated and/or hospital acquired UTI were treated with 1 g aztreonam or cefotaxime iv twice daily for 4 to 15 days. Cure was obtained in 5 out of 18 patients in the aztreonam and 7 out of 20 patients in the cefotaxime group. There were 3 superinfections, 7 relapses and 3 reinfections in the aztreonam group and 1 failure, 1 superinfection, 6 relapses and 5 reinfections in the cefotaxime group. There was no significant difference in therapeutic efficacy between the two antibiotics. Both antibiotics were tolerated well and seem to be equally effective in the treatment of complicated UTI caused by sensitive organisms.     

Urinary tract infection in primary health care in northern Sweden. III. Bacteriology in relation to clinical and epidemiological factors

The spectrum of bacteria causing urinary tract infection (UTI) and their patterns of drug resistance were found to be more associated with the process of selecting the patients and their sex and age than with the symptoms of the patient (lower, upper or asymptomatic UTI). UTI caused by Staphylococcus saprophyticus was seen mainly in female patients in primary health care (PHC), showed a peak in August and was rarely complicated by therapeutic failures or recurrences. The average risk of resistance of the infecting strain to the seven drugs tested increased from eight per cent for the uncomplicated and 17% for the average PHC patient to 36% among PHC patients with indwelling catheter or urinary incontinence, whereas recurrences of UTI were associated with a surprisingly small increase of drug resistance. In all UTI patient groups studied, the lowest incidences of bacterial resistance were recorded for trimethoprim and co-trimoxazole (0-17%). Thus, rational selection of UTI therapy in PHC requires knowledge of the influence of clinical factors on the expected bacteriology including the local pattern of drug resistance.     

Bacterial urinary tract infections--what is only an annoyance,when is risk involved?

Bacterial UTI are common infections in outpatients as well as in the hospital. The discrimination in uncomplicated and complicated UTI has been proven clinically relevant. Diagnosis of UTI is based on patients history, physical examination and laboratory testing of urine and blood. Bacterial virulence factors on the one hand and the integrity of the defense mechanisms of the host on the other hand determine the course of the infection. If the defense is deteriorated by genetic or acquired complicating factors, complications and long term sequelae are at risk. Symptoms of uncomplicated UTI are usually unambiguously detectable, whereas in complicated UTI initial symptoms can be more discrete, because of sometimes lower pathogenetic properties of uropathogens. In uncomplicated UTI the most important pathogen is Escherichia coli. In complicated UTI the bacterial spectrum is wider, including Gram-positive bacteria and multiresistant pathogens. Therapy in uncomplicated UTI is essentially antibacterial, whereas in complicated UTI additional treatment of complicating factors is mandatory.     

Assessment and Optimization of the Empiric Treatment of Urinary Tract Infections in an Academic Emergency Department Observation Unit

BackgroundPoor adherence to evidence-based guidelines and overuse of broad-spectrum antibiotics has been noted in the emergency department (ED). There is limited evidence on guideline-congruent empiric therapy for urinary tract infections (UTIs) and uropathogen susceptibilities in the ED observation unit (EDOU).ObjectiveThe primary objective was to evaluate the prescribing patterns for the empiric treatment of UTI in the EDOU. Secondary objectives were to analyze uropathogen susceptibilities in the EDOU and implement an algorithm for the empiric treatment of UTI.MethodsThis study retrospectively reviewed adult patients who received empiric UTI treatment in the EDOU from January 1, 2018 to April 1, 2018. Eligible patients were categorized as having either uncomplicated or complicated cystitis, or pyelonephritis based on their clinical diagnosis. Antimicrobial therapy was evaluated in accordance with national practice guidelines, institutional guidelines, and local antimicrobial susceptibility patterns.ResultsPatients with uncomplicated or complicated cystitis (n = 115) were provided guideline-congruent empiric treatment in 87% of cases. Patients with pyelonephritis (n = 35) were provided guideline-congruent empiric treatment in 57% of cases. Susceptibility patterns of uropathogens isolated from this patient sample differed slightly from the institutional antibiogram, notably depicting a lower Escherichia coli susceptibility rate. Fluoroquinolones were prescribed for a longer than recommended duration in 18 patients (60%).ConclusionsThe majority of patients in this study were provided guideline-congruent empiric therapy. Nevertheless, there are opportunities to optimize empiric UTI treatment and improve antibiotic stewardship in the EDOU.     

Comparative trial of norfloxacin and trimethoprim-sulfamethoxazole in the treatment of women with localized, acute, symptomatic urinary tract infections and antimicrobial effect on periurethral and fecal microflora

Forty-three women with acute, symptomatic urinary tract infections were randomized to receive either norfloxacin (400 mg) twice daily or trimethoprim-sulfamethoxazole (160-800 mg) twice daily for 10 days. Of the 43 patients, 7 (16%) had low-count bacteriuria and pyuria and were included in the evaluation. Escherichia coli was isolated in 72% of the infections, whereas coagulase-negative staphylococci were isolated in 14%. All isolates were susceptible to the assigned study drug. The MICs for 90% of the strains susceptible to norfloxacin and trimethoprim-sulfamethoxazole were less than or equal to 2 and less than or equal to 0.8-16 micrograms/ml, respectively. The cure rates for norfloxacin and trimethoprim-sulfamethoxazole were 95 and 90%, respectively. There were 17 patients with presumptive upper tract infections; only 1 of these relapsed after therapy. The effects on the periurethral flora were similar in both groups, but the infecting organism was eradicated from the fecal flora in 93% of the patients treated with norfloxacin and in 57% of the patients treated with trimethoprim-sulfamethoxazole. More early reinfections occurred in the trimethoprim-sulfamethoxazole group, with resistant organisms appearing in urine and in the periurethral and fecal flora in all cases. Three patients in each group experienced adverse clinical effects, but these were more severe in the trimethoprim-sulfamethoxazole group. No adverse hematological or biochemical changes were noted. From these results, we concluded that norfloxacin is at least as effective as trimethoprim-sulfamethoxazole in the therapy of acute, symptomatic urinary tract infections in women.     

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.     

Impact of urinary tract infection on nursing and healthcare-associated pneumonia

Nursing and healthcare-associated pneumonia (NHCAP), a concept of pneumonia proposed by the Japanese Respiratory Society, mostly occurs among elderly people in long-term care facilities. Similarly, the risk of urinary tract infection (UTI) also increases with age, with UTIs common among those in long-term care. Therefore, NHCAP is sometimes complicated by the presence of a UTI. However, pneumonia complicated by a UTI has not been clinically well characterized. We retrospectively analyzed 376 patients with NHCAP admitted to our hospital over a three-year period. Sixty-seven patients (17.8%) showed complications by a UTI. Patients with a UTI had lower renal function (higher blood urea nitrogen [P = 0.001], higher creatinine [P = 0.001]), lower systolic blood pressure (P = 0.04), higher A-DROP scores (P = 0.005) and higher positive blood culture rates (P = 0.03) than those without a UTI. Furthermore, based on urine, sputum and blood culture results, nearly half of the microorganisms (4/7) in blood cultures were identical with those of urine, suggesting that a concurrent UTI increases positive blood culture rates. Multivariate analysis showed that UTI was not an independent factor associated with 30-day mortality (P = 0.17), although patients with a UTI showed higher 30-day mortality (P = 0.04) than those without a UTI in univariate analysis. In summary, patients with NHCAP and a UTI were more prone to complications than those without a UTI, although UTI itself did not affect the prognosis of patients with NHCAP. A concurrent UTI had a negative impact on the severity of NHCAP.