Resistance of bacteria in urinary tract infections

Bacterial infection of the urinary tract is a common health problem in young women but also the most common nosocomial infection (>33%) contributing to the mortality of patients, and increasing the duration and cost of hospitalization. Escherichia coli is the most predominant organism and its prevalence varies in different studies. The high consumption of inappropriately prescribed antibiotics, combined with multiple pathology and frequent use of invasive devices, is a major factor contributing to high levels of resistance. There is a serious decrease in susceptibility of E. coli strains to amoxycillin, due to the presence of R-TEM enzymes, to cotrimoxazole and trimethoprim. Nitrofurantoin and fosfomycin-trometamol remain highly active against urinary Enterobacteriaceae, with over 90% of E. coli being susceptible. Knowledge of the most likely causative organisms and the prevalence of resistance pathogens to antimicrobial agents is essential to select antibiotics and to establish guidelines for the empirical treatment of urinary tract infections.     

Clinical experience with indanyl carbenicillin in urinary tract infections

Summary

A trial was carried out in 30 patients to assess the effectiveness of indanyl carbenicillin in acute or chronic urinary tract infections, many of which were complicated by a pathological urological or medical condition. In all patients, infection was due to a single species of pathogen: E. coli (19), Proteus (6), and Pseudomonas (5). Oral doses of 1 g indanyl carbenicillin were given 6-hourlyfor an average of 10 days.

Results showed a clinical and bacteriological cure in 13 {43.8 %)patients. In 6 patients, although there was initial clinical improvement, the pathogen developed resistance during therapy. In 7 patients, there was super-infection with another organism. Four patients were withdrawn early in treatment because of side-effects, mainly gastrointestinal in origin. Indanyl carbenicillin proved very effective in eradicating all strains of Proteus and Pseudomonas and 12 (70.6%) of the 17 strains of E. coli in patients completing the full course of treatment.     

The impact of resistance on the management of urinary tract infections

Urinary tract infections requiring treatment are extremely common. It is estimated that between 20 and 50% of adult women will have had at least one symptomatic urinary tract infection. When considering the optimal therapy of any infection, patient factors, organism factors, drug factors (e.g. pharmacokinetics), side-effects and cost as well as antimicrobial resistance all need to be considered. This paper deals with the impact of increasing antibiotic resistance on the management of urinary tract infections.     

真菌性尿路感染的发病机制与诊断标准

本文根据多年的临床观察经验,并参考相关文献资料,系统论述了真菌性尿路感染的流行病学、发病机制、病理、临床表现、检查及诊断标准,对进一步研究该疾病的发病机制,更好地治疗该疾病提供了理论依据。     

Spectrum and antibiotic resistance of uropathogens from hospitalized patients with urinary tract infections: 1994-2000

During the period 1994–2000 all uropathogens cultured from urine of hospitalized urological patients were identified and susceptibility was tested against 11 antibacterials. Duplicated isolates were eliminated. There was no general trend of increased of resistance apart from E. coli to ciprofloxacin (10.4% in 2000). Vancomycin-resistant staphylococci or enterococci was not significant. The lowest overall rates of resistance were found with piperacillin/tazobactam followed by ciprofloxacin and trimethoprim/sulphamethoxazole. Ciprofloxacin was the best oral antibiotic for the empirical treatment of urinary tract infection (UTI) due to Gram-negative rods and ampicillin/sulbactam for the treatment of UTI with Gram-positive cocci.     

In vitro antibacterial activity of various cephems against clinical isolates from complicated urinary tract infections

In vitro antibacterial activity of several cephems (CEZ as the first generation (group A); CTM and CMZ as the second generation (group B); CMX, CPZ, LMOX, CTX and CZX as the third generation (group C)) against 8 species, each of 54 strains, of Gram-negative clinical isolates from complicated urinary tract infection was compared by determination of the MICs. The following results were obtained: The most sensitive drugs against each species in MIC80; CTX (MIC80 0.20 microgram/ml) against E. coli, CMX (1.56 microgram/ml) against K. pneumoniae, LMOX (0.39 microgram/ml) against P. mirabilis, LMOX (0.78 microgram/ml) against Indole (+) Proteus, CMX and CPZ (50 micrograms/ml) against E. cloacae, CMX and LMOX (50 micrograms/ml) against C. freundii, CMX (3.13 micrograms/ml) against S. marcescens and CPZ (25 micrograms/ml) against P. aeruginosa The most sensitive drugs against each species in MICS100; CMX (MIC100 3.13 micrograms/ml) against E. coli, CMX (6.25 micrograms/ml) against K. pneumoniae, CTX (0.78 microgram/ml) against P. mirabilis, LMOX (1.56 microgram/ml) against Indole (+) Proteus, CPZ (100 micrograms/ml) against E. cloacae, CMX (100 micrograms/ml) against C. freundii, CMX (12.5 microgram/ml) against S. marcescens and CPZ (50 micrograms/ml) against P. aeruginosa. In each species, the group C were most sensitive followed by those of the group B. Many isolates were highly resistant to the group A (especially in C. freundii, S. marcescens and P. aeruginosa).     

Focus on ceftazidime-avibactam for optimizing outcomes in complicated intra-abdominal and urinary tract infections

Introduction: Complicated intra-abdominal infections and urinary tract infections are frequently associated with Gram-negative bacteria and treatment can be hampered by the involvement of resistant organisms. A common resistance mechanism is β-lactamase production which confers resistance to β-lactam antibiotics.

Areas covered: This article summarizes β-lactamases found among Gram-negative bacteria as well as providing an overview of complicated intra-abdominal infections and urinary tract infections and the impact inappropriate antibiotic therapy and antibiotic resistance has in their treatment. The author reviews the activity of ceftazidime-avibactam, including animal model data and microbiological data from Phase II clinical trials. This article also highlights Phase III clinical trials of ceftazidime-avibactam that are ongoing or completed and briefly discusses other β-lactamase inhibitor combinations currently in development.

Expert opinion: The increasing problem and complexity of β-lactamase resistance has been met by resurgence in the development of β-lactamase inhibitor combinations. These show promise in the treatment of resistant infections. One β-lactamase inhibitor in advanced development with a broad spectrum of activity is avibactam, covering class A, class C and some class D enzymes. Importantly, the activity of avibactam also includes carbapenemases such as the KPC and OXA-48. The combination of avibactam with the cephalosporin ceftazidime is attractive, given the spectrum of antimicrobial activity and the low toxicity of the cephalosporin class.     

加替沙星联合阿奇霉素治疗泌尿系统感染的临床研究

目的 分析加替沙星联合阿奇霉素治疗泌尿系统感染的临床疗效,总结治疗泌尿系统感染的有效方法及安全性.方法 选择94例泌尿系统感染患者,随机分为两组,观察组47例采用加替沙星联合阿奇霉素治疗,对照组47例仅使用加替沙星治疗,两组疗程均为7～10d,对两组的有效率、细菌清除率及不良反应进行比较.结果 观察组总有效率为100.00％,对照组总有效率为82.98％,两组总有效率比较差异有统计学意义(P＜0.05).观察组细菌清除率为100.00％,对照组细菌清除率为82.98％,两组细菌清除效果比较差异有统计学意义(P＜0.05).观察组不良反应发生率为6.37％,对照组不良反应发生率为4.26％,两组不良反应发生情况比较差异无统计学意义(P＞0.05).结论 加替沙星联合阿奇霉素治疗泌尿系统感染效果显著,且不良反应少,使用安全,可作为泌尿系统感染的首选药物.     

Antimicrobial activity of imipenem against 1386 clinical isolates

1386 isolates from clinical specimens were tested against imipenem by disc agar diffusion. The bacteria used in this study consisted of Escherichia coli, Enterobacter aerogenes, E. agglomerans, E. cloacae, Klebsiella pneumoniae, K. oxytoca, K. ozanae, Proteus mirabilis, P. vulgaris, Providencia stuartii, P. rettgeri, Acinetobacter calcoaceticus, Citrobacter diversus, C. freundii, Morganella morganii, Serratia liquefaciens, S. marcescens, Hafnia alvei, Aeromonas hydrophila, Pseudomonas aeruginosa, P. cepacia, P. maltophila, P. fluorescens, Staphylococcus aureus, S. epidermidis, S. saprophyticus, pneumococcus, Lancefield group A, B and D streptococci, viridans streptococci, diphtheroids and Bacillus species. In vitro activity of imipenem was compared with the following antibiotics: ampicillin, amikacin, carbenicillin, cefoperazone, cefoxitin, cephalothin, chloramphenicol, clindamycin, colistin, erythromycin, gentamicin, methicillin, penicillin, tetracycline, tobramycin, trimethoprim-sulfamethoxazole and vancomycin. Of the 819 strains of Enterobacteriaceae tested, 99.5% were susceptible to imipenem. Ninety-seven percent strains of P. aeruginosa were also susceptible to imipenem. All the 161 isolates of S. aureus and 116 of the 117 isolates of enterococci exhibited in vitro susceptibility to this antibiotic. All gram positive bacteria tested were inhibited by imipenem except 28% isolates of S. epidermidis and 5% isolates of S. agalactiae.     

Meropenem-vaborbactam for the treatment of complicated urinary tract infections including acute pyelonephritis

Introduction: Meropenem-vaborbactam is a new beta-lactam/beta-lactamase inhibitor combination that combines a carbapenem antibiotic with a first-in-class, boronic acid pharmacophore, serine beta-lactamase inhibitor which has potent inhibitory activity against class A carbapenemases, especially Klebsiella pneumoniae carbapenemases (KPC), in addition to other class A and class C beta-lactamases. The US Food and Drug Administration has recently approved meropenem-vaborbactam for the treatment of adult patients with complicated urinary tract infections including acute pyelonephritis.

Areas covered: A PubMed search was performed to gather the most current and relevant articles regarding meropenem-vaborbactam. In this review the authors discuss the chemistry, mechanism of action, pharmacokinetics, pharmacodynamics, antimicrobial spectrum, and efficacy and safety of meropenem-vaborbactam for the treatment of complicated urinary tract infections including acute pyelonephritis

Expert opinion: Although meropenem-vaborbactam is approved for treatment for complicated urinary tract infections including acute pyelonephritis, it is unlikely, at this point, to be utilized widely beyond cases that are caused by KPC-producing Enterobacteriaceae. It may also be a potential treatment option for complicated urinary tract infections caused by KPC-producing Enterobacteriaceae that are resistant to ceftazidime-avibactam. Long-term safety data with this novel beta-lactamase inhibitor is still needed although early data suggests that it will be safe and well tolerated.     

Emerging resistance problems and future perspectives in pharmacotherapy for complicated urinary tract infections

Introduction: Urinary tract infections (UTIs) are among the most common infectious diseases and contribute to high financial burden worldwide. Administration of appropriate antibiotic therapy is the key to achieving good therapeutic outcomes. The authors review the current status of global or regional epidemiology, especially on the antimicrobial resistance and several potential agents against complicated UTIs by multidrug-resistant (MDR) pathogens.

Areas covered: The authors summarized the susceptibility status on several major surveillance programs on uropathogens, focusing on Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci. Besides, the current perspectives of several potential antimicrobials against MDR uropathogens available for UTIs were also reviewed.

Expert opinion: High resistance to broad-spectrum antibiotics, especially to extended-spectrum β-lactams, carbapenems, and fluoroquinolones among uropathogens emerges as a critical problem in many countries. Appropriate antimicrobial stewardship and continuous surveillance are necessary to monitor the trends of susceptibility for main pathogens. For these MDR uropathogens, polymyxin, fosfomycin, tigecycline, nitrofurantoin, linezolid, and daptomycin might be potential treatments for patients with uncomplicated and complicated UTIs in some countries, although they might not be approved by their regulation. However, more clinical evidence and more extensive meta-analyses are needed to evaluate and confirm the effectiveness of their usage in countries with a high prevalence of multidrug resistance.     

Antimicrobial activity of sultamicillin against clinical isolates from upper respiratory tract infections II

In an attempt to examine the effect of sulbactam (SBT) on beta-lactamase activity, three hundred clinical isolates from the infected upper respiratory tract were tested for MICs and disk sensitivities of ampicillin (ABPC) and sultamicillin (SBTPC). beta-lactamase production was tested using the acidometry disk method (beta-Check, Taito Pfizer Co.). For strains such as Klebsiella spp. which form mucoid type colonies, we used the SS culture medium which, by reducing the influence of huge amounts of capsular material, allows a better reaction to the acidometry disk. Penicillinase, produced by Branhamella catarrhalis, Haemophilus influenzae, Neisseria spp., etc. was detected clearly by direct application of portions of colonies onto acidometry disks. For cephalosporinase, however, a direct application of such fractions resulted in weak reactions. We, therefore, used fractions which had undergone the enzyme induction, and obtained better reactions. Sensitivities of tested bacteria to ABPC and SBTPC were inversely related to MIC values. beta-Lactamase-producing strains showed weaker sensitivity to ABPC than non-producing strains. To SBTPC, however, beta-lactamase-producing strains and non-producing strains showed very similar sensitivity. We thus confirmed that the inhibitory action of SBT to beta-lactamase can well be demonstrated using the disk sensitivity method.     

Cefdinir activity against contemporary North American isolates from community-acquired urinary tract infections

Cefdinir is an oral cephalosporin approved by the US Food and Drug Administration in 1997 for the treatment of community-acquired (CA) respiratory tract and uncomplicated skin and soft tissue infections. The objective of the present study was to evaluate the in vitro activity of cefdinir against recent clinical isolates collected from CA-urinary tract infections (UTIs), a possible expanded indication. A total of 456 isolates from CA-UTI were collected from medical centres in North America (NA; United States and Canada) in 2003 and susceptibility tested by NCCLS reference broth microdilution methods. Cefdinir and cefpodoxime were the most active compounds tested against Escherichia coli (98.7% susceptibility), followed by nitrofurantoin (97.0%) and ciprofloxacin (95.0%). Cefdinir was 8- to 16-fold more potent than cefuroxime axetil and cefprozil against E. coli, Klebsiella spp. and Staphylococcus saprophyticus. The activity of cefdinir was most similar to that of cefpodoxime against E. coli and Klebsiella spp., but cefpodoxime showed inferior activity against S. saprophyticus. The cefdinir spectrum was significant superior (+3.8 to 16.5%) to that of trimethoprim/sulphamethoxazole against all pathogens evaluated. The cefdinir spectrum and potency were comparable or superior to other orally administered beta-lactams tested against recent (2003) clinical isolates from CA-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.     

FDA关于抗菌药物治疗复杂性泌尿道感染与肾盂肾炎临床试验的考虑

本文介绍了美国食品药品监督管理局(FDA)关于抗菌药物治疗复杂性泌尿道感染与肾盂肾炎临床试验的考虑。在开发药物以治疗这2种疾病时,应进行具有足够统计学意义和良好对照的试验,来确定其安全性和有效性,即其有效性较批准药物相似或更优效。这些研究中的主要有效性参数,应该是微生物学的检查结果,研究中应建立这些患者的临床治愈与细菌清除之间的总体相关性。     

Detection of the icaADBC gene cluster and biofilm formation in Staphylococcus epidermidis isolates from catheter-related urinary tract infections

Biofilm production in Staphylococcus epidermidis is an important virulence factor that is mediated by the expression of the icaADBC operon. In this study 41 S. epidermidis isolates obtained from catheter-related urinary tract infections were analyzed for the presence of the icaADBC operon and biofilm formation. Eighteen of 41 isolates (44%) were shown to carry ica-specific DNA, but only 11 isolates (27%) produced biofilms spontaneously under normal growth conditions. Upon induction by external stress or antibiotics, biofilm formation could be stimulated in five of seven ica-positive, biofilm-negative isolates, indicating that the icaADBC expression was down-regulated in these strains. Genetic analyses of the ica gene clusters of the remaining two ica-positive, biofilm-negative strains revealed a spontaneous icaC::IS256 insertion in one strain. Insertion of the element caused a target site duplication of seven base pairs and a biofilm-negative phenotype. After repeated passages the insertion mutant was able to revert to a biofilm-forming phenotype which was due to the precise excision of IS256 from the icaC gene. The data show that icaC::IS256 integrations occur during S. epidermidis polymer-related infections and the results highlight the biological relevance of the IS256-mediated phase variation of biofilm production in S. epidermidis during an infection.     

巴洛沙星对泌尿道病原菌的体外抗菌活性

目的:评价巴洛沙星对泌尿道病原菌的体外抗菌活性。方法:收集泌尿道感染病人尿液中所分离到的249株病原菌,其中革兰阳性菌90株(金黄色葡萄球菌30株、表皮葡萄球菌27株、粪肠球菌18株、B溶血性链球菌15株)、革兰阴性菌159株(大肠埃希菌84株、肺炎克雷伯菌20株、肠杆菌属25株、奇异变形杆菌15株、铜绿假单胞菌15株),采用琼脂二倍稀释法,测定巴洛沙星与左氧氟沙星对该249株泌尿道病原菌的最低抑菌浓度(MIC)。结果:巴洛沙星对革兰阳性菌的MIC_(90)(2～8 mg·L~(-1))是左氧氟沙星MIC_(90)(2～16 mg·L~(-1))的1/4～1/2或相等,对革兰阴性菌的MIC_(90)(4～32 mg·L~(-1))是左氧氟沙星MIC_(90)(2～16 mg·L~(-1))的2～4倍或相等。结论:巴洛沙星对革兰阳性菌和革兰阴性菌均具有抗菌活性,其中对革兰阳性菌的作用稍强于或等于左氧氟沙星,对革兰阴性菌的作用等于或稍弱于左氧氟沙星。     

加替沙星治疗急性泌尿系统感染疗效研究

目的评价加替沙星注射液治疗急性泌尿系统感染的临床疗效与安全性。方法采用随机单盲对照试验,以左氧氟沙星注射液为对照,两组药物的用量用法均为200mg、ivgtt、q12h、疗程7～14d。治疗前后均行尿液细菌学检查。结果加替沙星组和左氧氟沙星组的临床疗效和细菌清除率分别为84.62%、83.08%;91.8%、90.0%(P>0.05)。且两组药物的临床副反应率分别为9.2%与7.7%。结论加替沙星是治疗急性泌尿系统感染的安全、有效的抗生素。     

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％。