The treatment of urinary tract infections and use of ciprofloxacin extended release

Urinary tract infections (UTIs) are one of the most common reasons people seek medical attention. There are > 50% of women who will have at least one UTI during their lifetime and most of these will require a physician visit and antibiotic treatment. The high prevalence continues to the in-patient setting where genitourinary infections are the most common nosocomial infection. The efficient diagnosis and effective treatment of UTIs is a major healthcare concern. Factors such as economic efficiency and emerging resistance are increasingly becoming more important considerations in providing patient care. In out-patient uncomplicated UTIs, Escherichia coli has been implicated in < or = 75-90% of cases. Although the prevalence in the in-patient setting decreases, E. coli is still the most common bacteria identified and present in 21-54% of urinary isolates. Trimethoprim-sulfamethoxazole has been the preferred first-line agent for uncomplicated out-patient UTIs where local resistance is < 10 - 20%. In recent years, resistance has superseded this threshold in most regions of the US and Europe. In these areas with increased resistance, fluoroquinolones have become a common first-line agent. Ciprofloxacin has been one of the most widely used fluoroquinolones and has a well-known safety profile, as well as excellent activity against most of the common uropathogens. Ciprofloxacin extended release (ER) is a recently released once-daily formulation that has been increasingly used with good clinical success. The pharmacokinetic and pharmacodynamic parameters of ciprofloxacin ER are shown to be at least equal to twice-daily ciprofloxacin and may even confer superiority as ciprofloxacin ER achieves a higher maximum serum concentration. This is supported by clinical studies, which have shown at least as effective clinical cure and bacteriological eradication rates. These studies have also demonstrated similar tolerability and side-effect profiles. Ciprofloxacin ER combines traditional ciprofloxacin's proven track record of efficacy and safety with favourable pharmacokinetics and convenient once-daily dosing. Increased patient compliance is associated with decreased treatment failures and can help slow the development of antimicrobial resistance. Economic considerations are also increasingly important and providing convenient and effective treatment leading to high clinical success decreases overall costs.     

Ciprofloxacin extended release: in the treatment of urinary tract infections and uncomplicated pyelonephritis

Ciprofloxacin extended release (XR) is a new oral formulation of a fluoroquinolone that allows once-daily administration while maintaining therapeutic serum levels of the drug. The maximum plasma concentrations (Cmax) of once-daily ciprofloxacin XR 500 mg was higher than that of twice-daily ciprofloxacin immediate release 250 mg and the Cmax of once-daily ciproflocaxin XR 1000 mg was higher than that of twice-daily ciprofloxacin 500 mg. No accumulation of ciprofloxacin XR at steady state was observed in healthy men and all other pharmacokinetic parameters were similar to those of the immediate-release formulation. In patients with uncomplicated urinary tract infection (UTI), bacteriological eradication rates were similar in recipients of ciprofloxacin XR and immediate-release ciprofloxacin at the test-of-cure (TOC) visit, as were rates of persistence or new infection. Clinical cure rates were also similar in the two treatment groups. Bacteriological eradication occurred in 89% of ciprofloxacin XR and 85% of immediate-release ciprofloxacin recipients with complicated UTIs or acute uncomplicated pyelonephritis at the TOC visit. Clinical cure rates were also similar in the two treatment groups. black triangle Ciprofloxacin XR was generally well tolerated in patients with uncomplicated or complicated UTIs or acute uncomplicated pyelonephritis and showed similar tolerability to that of the immediate-release formulation.     

The treatment of urinary tract infections and use of ciprofloxacin extended release

Urinary tract infections (UTIs) are one of the most common reasons people seek medical attention. There are > 50% of women who will have at least one UTI during their lifetime and most of these will require a physician visit and antibiotic treatment. The high prevalence continues to the in-patient setting where genitourinary infections are the most common nosocomial infection. The efficient diagnosis and effective treatment of UTIs is a major healthcare concern. Factors such as economic efficiency and emerging resistance are increasingly becoming more important considerations in providing patient care. In out-patient uncomplicated UTIs, Escherichia coli has been implicated in ≤ 75 – 90% of cases. Although the prevalence in the in-patient setting decreases, E. coli is still the most common bacteria identified and present in 21 – 54% of urinary isolates. Trimethoprim–sulfamethoxazole has been the preferred first-line agent for uncomplicated out-patient UTIs where local resistance is < 10 – 20%. In recent years, resistance has superseded this threshold in most regions of the US and Europe. In these areas with increased resistance, fluoroquinolones have become a common first-line agent. Ciprofloxacin has been one of the most widely used fluoroquinolones and has a well-known safety profile, as well as excellent activity against most of the common uropathogens. Ciprofloxacin extended release (ER) is a recently released once-daily formulation that has been increasingly used with good clinical success. The pharmacokinetic and pharmacodynamic parameters of ciprofloxacin ER are shown to be at least equal to twice-daily ciprofloxacin and may even confer superiority as ciprofloxacin ER achieves a higher maximum serum concentration. This is supported by clinical studies, which have shown at least as effective clinical cure and bacteriological eradication rates. These studies have also demonstrated similar tolerability and side-effect profiles. Ciprofloxacin ER combines traditional ciprofloxacin's proven track record of efficacy and safety with favourable pharmacokinetics and convenient once-daily dosing. Increased patient compliance is associated with decreased treatment failures and can help slow the development of antimicrobial resistance. Economic considerations are also increasingly important and providing convenient and effective treatment leading to high clinical success decreases overall costs.     

Fosfomycin trometamol in a single dose versus seven days nitrofurantoin in the treatment of acute uncomplicated urinary tract infections in women

In general practice acute uncomplicated urinary tract infections in women are treated with different courses of antibiotics. In this study the efficacy and tolerability of a single dose of 3 g fosfomycin trometamol and the conventional treatment with nitrofurantoin 50 mg four times daily for seven days were compared. In a randomized, double-blind, double-dummy trial in 31 general practices in the Netherlands 231 patients with symptoms of acute dysuria, stranguria and/or urinary frequency received treatment. Evaluation was based on resolution of symptoms, dipslide results and side-effects at 4, 9 and 42 days after starting the treatment. The clinical cure rates and bacteriological cure rates were not significantly different between the treatment groups. Side-effects were reported at day 4 by 43% of the women receiving single-dose treatment, compared with 25% of the women in the seven-day treatment group, a significant difference. At day 9 the groups did not significantly differ in the number of patients with side-effects. Almost all side-effects were mild and gastro-intestinal complaints were reported most. Taking into account the convenience of taking a single dose we conclude that fosfomycin trometamol is a reasonable alternative to 7 days nitrofurantoin 50 mg four times a day in the treatment of women with symptoms of acute uncomplicated urinary tract infections in general practice.     

Pharmacotherapy of lower urinary tract infections and pyelonephritis in children

This review focuses on the treatment of urinary tract infections (UTI) in children. Acute pyelonephritis (an infection involving the renal parenchyma), acute cystitis (infection limited to the lower urinary tract) and asymptomatic bacteriuria (absence of clinical symptoms) have to be clearly distinguished. Whereas antibiotics are needed in pyelonephritis and cystitis, they should be used only exceptionally in cases of asymptomatic bacteriuria, as they may be potentially harmful and select more virulent bacteria. In case of pyelonephritis, there should be no delay in beginning the treatment in order to decrease the risk of long term complication in particular renal scars. Predisposing conditions for UTI should be evaluated carefully. New concepts concerning analysis of virulence profile or specific host immune response might bring more comprehension to UTI, but yet these concepts do not influence clinical practice. Any recommendation about (initial) antibiotic treatment should be regularly updated and adapted to local resistance profiles and to economical factors in different health systems.     

Quinolones in the treatment of uncomplicated urinary tract infections

In comparative clinical studies the quinolones have been shown to be effective in a short-course (3-5 days) or a single dose therapy in uncomplicated urinary tract infections. Comparative clinical trials of single dose therapy with the fluoroquinolones and trimethoprim or co-trimoxazole (trimethoprim/ sulfamethoxazole) for acute bacterial cystitis have shown equivalent efficacy. Studies on the use of quinolones for the treatment of uncomplicated acute pyelonephritis have also been reviewed. The results from several comparative trials which compared the fluoroquinolones with netilmicin, co-trimoxazole, cefadroxil, or ceftazidime have been comparable. Some of the fluoroquinolones can be administered in parenteral and oral forms enabling the patient to be discharged from hospital earlier, a more cost-effective option. The fluoroquinolones, in particular norfloxacin, have also been shown to be effective as prophylactic agents for patients with recurrent symptomatic urinary tract infections. The optimal dosage and length of prophylactic treatment have not yet been clearly defined.     

Finafloxacin for the treatment of urinary tract infections

Introduction: In the past decade, the indiscriminate use of fluoroquinolones in the prophylaxis and treatment of urinary tract infections (UTIs) has led to an increase of antibiotic resistance patterns. Finafloxacin is a new generation fluoroquinolone with interesting preclinical characteristics and pH-related efficacy.

Areas covered: This review summarizes finafloxacin’s safety profile and prospectively evaluates its specific use in the treatment of UTIs. This article was based on a Medline English literature search.

Expert opinion: In vitro and in vivo studies have shown that finafloxacin expresses its full antibacterial activity in acidic environments and is able to exert significant bactericidal effects in difficult-to-treat infections. Finafloxacin has a broad antibacterial spectrum and efficient pharmacokinetic absorption. Moreover, it undergoes extensive tissue distribution, resulting in good antibacterial activity for daily dosages from 400 to 800 mg. This novel compound has also been successfully tested on biofilm-related Escherichia coli. Finafloxacin has demonstrated a good safety and tolerability profile in humans when administered orally or intravenously and is thus an interesting compound for the treatment of UTIs. However, further prospective randomized clinical trials will be necessary to confirm these preliminary results before definitive conclusions can be made.     

碳青霉烯类耐药大肠杆菌尿路感染的危险因素探讨

目的 探讨碳青霉烯类耐药大肠埃希菌（CREco）的耐药性及患者发生CREco尿路感染的危险因素。方法 收集2015年1月—2017年12月在天津医科大学第二医院住院期间发生尿路感染,且尿培养结果为大肠埃希菌的患者资料共120例。采用病例对照研究方法分2组,病例组为感染CREco的患者24例,在出现CREco尿路感染的科室内按照性别及年龄（±5岁范围内）匹配的原则选取同时期发生碳青霉烯类敏感大肠埃希菌（CSEco）尿路感染患者作为对照,病例组与对照组按照1∶4比例匹配。比较2组的致病菌对18种抗菌药物的耐药性。探讨住院患者发生CREco尿路感染的危险因素。结果 本院住院患者感染的CREco对氨苄西林等12种抗菌药物均表现出很强的耐药性,耐药率均高于70%;对除氨苄西林、庆大霉素、复方新诺明及替加环素外,其他14种抗菌药物的耐药率明显高于CSEco组（均P＜0.05）。多因素分析结果显示,留置导尿管（OR=5.719,95%CI：2.084~15.697,P＜0.01）和检出前住院时间长（OR=9.325,95%CI：1.962~44.330,P＜0.01）是住院患者发生CREco尿路感染的独立危险因素。结论 住院患者尿路感染的CREco耐药形势严峻,患者留置导尿管时应严格遵守标准化操作及临床指征,尽量缩短其住院时间, 减少医院环境下的暴露,降低CREco所致尿路感染的风险。     

Anti-infective treatment of bacterial urinary tract infections

Bacterial urinary tract infections (UTI) are frequently found in the outpatient as well as in the nosocomial setting. The bacterial UTI can be stratified into uncomplicated and complicated UTI. Antibiotic resistance is continuously increasing in uncomplicated as well as complicated UTI. In uncomplicated UTI efforts are made to use antibiotic substances exclusively for this indication. In complicated UTI as broad spectrum antibiotics are increasingly used, the higher the antimicrobial resistance rates are reported. There are two predominant aims in the antimicrobial treatment of both uncomplicated and complicated UTI: 1.) rapid and effective response to therapy, prevention of complications and prevention of recurrence in the individual patient treated, and 2.) prevention of emergence of resistance to anti-infective agents in the microbial environment. The use of antibiotics has to keep up with the continuous change in antimicrobial resistance and the tailored needs in the individual patient. Antibiotic substances therefore need to become evaluated for each indication and continuously followed for clinical usage. The knowledge of structure-activity relationships of antimicrobial substances and bacterial resistance mechanisms to antibiotics help to use antibiotics better in daily routine and design new derivatives and substances. The aim of this review is to describe the chemistry and structure-activity relationships of current antibiotics and promising substances in development for the treatment of UTI.     

New 4-quinolones in the treatment of urinary tract infections

The new fluorinated quinolones norfloxacin, ciprofloxacin and pefloxacin were evaluated in urinary infections. Bacteriological cure rates in both uncomplicated and complicated urinary tract infections ranged from 85% to 99%. Clinical cure rates were often lower due to the underlying conditions in the urinary tract. Patients with neurological bladder disease were cured in a relatively high percentage of theirPseudomonas infection after three months treatment with norfloxacin. Pharmacokinetics of ciprofloxacin in prostatic tissue and fluid will probably offer an advance in the treatment of chronic urinary infections due to an infectious prostatic focus. Definitely drug related side effects (of gastro-intestinal, neurological or allergic nature) were mild in most cases. The new 4-quinolones should be followed with interest concerning their activity in urological infections in general as well as specifically. The minor influence on the natural human flora and the possibility to decrease plasmid-mediated resistance are of major importance.     

舒氨新在治疗泌尿系统感染中的应用

自1995年8至10月份,单独使用舒氨新治疗泌尿系统感染患者40例,取得较好疗效。剂量:每日3～6克溶于5％的葡萄糖溶液中分两次静脉滴入,每次60～90分钟,连续用药7～14天。结果:痊愈22例(55％),显效15例(37.5％),进步1例(2.5％),无效2例(5％),总有效率为92.5％。     

喹诺酮类药物在下呼吸道感染中的临床应用

下呼吸道感染为最常见的感染性疾病,也是多器官功能衰竭重要合并症和致死原因。呼吸喹诺酮对重要的呼吸道感染病原菌如肺炎链球菌、流感嗜血杆菌、卡他莫拉菌和非典型呼吸道致病菌具有良好的抗菌活性,其药效学和药代动力学特点在治疗下呼吸道感染中具有独特的优势,各国临床治疗指南均将呼吸喹诺酮列为下呼吸道感染(LRTIs)经验治疗的选择药物之一。本文综述了近年来呼吸喹诺酮类药物以及新研发的治疗下呼吸道感染的喹诺酮类药物在临床治疗和系统评价的最新进展。     

加替沙星与左氧氟沙星治疗泌尿道感染的疗效比较

目的 :比较加替沙星与左氧氟沙星治疗敏感性细菌引起的泌尿道感染的疗效及安全性。方法 :以左氧氟沙星为对照 ,在 4 8名受试者中进行了随机双盲、双模拟、平行对照试验。A组 2 4例 ,每日给予加替沙星 4 0 0mg口服 ,B组 2 4例 ,每日给予左氧氟沙星 4 0 0mg口服 ,疗程 7～ 14d。结果 :A组病人用药后临床痊愈率为 10 0 % ,有效率为 10 0 % ,B组的痊愈率为 92 % ,有效率为 92 %。 2组间疗效比较 ,差异无显著意义 (P >0 .0 5 ) ;A组和B组的细菌清除率均为 10 0 % ,P >0 .0 5 ;2组不良反应发生率分别为 8%和 12 % ,P >0 .0 5。结论 :加替沙星治疗泌尿道感染疗效及安全性与左氧氟沙星相仿。     

Current anti-infective treatment of bacterial urinary tract infections

Antibiotic resistance nowadays plays an important role in the treatment of uncomplicated and complicated urinary tract infections (UTIs). In uncomplicated UTI efforts are made to use antibiotic substances exclusively for this indication. In complicated UTI substances with activity against bacteria harbouring common resistance mechanisms are investigated. Additionally pharmacokinetic/ pharmacodynamic parameters are used to improve dosing strategies.     

Netilmicin in the treatment of severe or complicated urinary tract infections

Netilmicin is a new aminoglycoside antibiotic with pharmacological similarities to gentamicin, tobramycin and sisomicin. Fourteen of 15 patients with a severe or complicated urinary tract infection were cured by treatment with a seven day course of netilmicin. In one patient the infecting organism was not eradicated. No significant side effects were noted and no ototoxicity was detected. Four patients had a significant, but reversible, deterioration in renal function as defined by an increase in the plasma creatinine of 0.03 mmol/l or greater. Work in experimental animals has shown netilmicin to be significantly less ototoxic and nephrotoxic than other clinically available aminoglycosides. If this finding is confirmed in large-scale comparative trials in man, netilmicin should prove a most useful and effective new antibiotic for the treatment of severe gram-negative sepsis.     

司氟沙星治疗泌尿道感染的临床疗效

目的 :评价司氟沙星对泌尿道感染的疗效。方法 :对 5 6例细菌性泌尿道感染患者予司氟沙星 10 0～ 2 0 0mg·d-1,po ,疗程 7～ 14d。结果 :治愈率为 87 5 %,有效率为 94 6 %,只有 2例 (3 6 %)出现了轻微的不良反应。结论 :司氟沙星适用于泌尿道感染。     

Characterization of extended spectrum beta-lactamase-producing Klebsiella pneumoniae from Beijing, China

Fourteen clinical isolates of Klebsiella pneumoniae with extended-spectrum beta-lactamases (ESBLs) were detected by the double disk synergy test and the Etest ESBL strip. Co-resistances included high MICs for aminoglycosides, fluoroquinolones, tetracyclines, and trimethoprim/sulphamethoxazole. Co-resistance was not observed in five of the 14 strains. These isolates were all genetically distinct as determined by the automated ribotyping method. Isoelectric focusing documented the presence of multiple beta-lactamases (one to four per isolate) with pIs ranging from 5.4 to 8.4. The majority of isolates contained beta-lactamases with pI values of 7.6 and 8.4 consistent with SHV-type ESBLs and an Amp C enzyme, respectively. Emerging ESBL strains in K. pneumoniae compromise the use of agents such as cefotaxime, ceftriaxone, ceftazidime in China; leading to the expansion of quality infection control practices and formulary management programmes to minimize clonal expansion.