Associations between antibiotic use and changes in susceptibility patterns of Pseudomonas aeruginosa in a private, university-affiliated teaching hospital: an 8-year-experience: 1995-2002

Increasing resistance in Pseudomonas aeruginosa to multiple antibiotics has been observed and is posing therapeutic dilemmas. Antibiotic utilization is one factor that has been associated with the emergence of antimicrobial resistance. We examined the overall and specific antimicrobial use in relation to changes in susceptibility patterns in P. aeruginosa. Regression analysis was performed to explore the relationships between annual antibiotic use and the incidence of resistant P. aeruginosa. There were statistically significant relationships between increasing anti-pseudomonal cephalosporin and levofloxacin use and the increasing incidence of ciprofloxacin resistant P. aeruginosa. However, there was not an association between other fluoroquinolone or overall fluoroquinolone use and this change. In addition, there was no association between increasing anti-pseudomonal cephalosporin use and cefepime resistant P. aeruginosa. No statistical relationship was seen with overall antibiotic use and the development of resistance in P. aeruginosa, suggesting that the development of resistance is associated with the use of individual agents, rather than overall antibiotic consumption.     

Acne vulgaris: a review of antibiotic therapy

Antibiotic therapy has been integral to the management of inflammatory acne vulgaris for many years. Systemic antibiotics work via antibacterial, anti-inflammatory and immunomodulatory modes of action, and have been found to be useful in managing moderate-to-severe acne. Commonly prescribed antibiotics include tetracyclines, erythromycin and trimethoprim, with or without sulfamethoxazole. In selecting the appropriate antibiotic for patients needing to receive topical or systemic antibiotic therapy, the clinician should take into account the severity of the acne, cost-effectiveness, the safety profile of the drug and the potential for development of resistance. The widespread and long-term use of antibiotics over the years has unfortunately led to the emergence of resistant bacteria. The global increase in the antibiotic resistance of Propionibacterium acnes may be a significant contributing factor in treatment failures. It is therefore essential that clinicians prescribing antibiotics for the treatment of acne adopt strategies to minimise further development of bacterial resistance. This includes addressing compliance issues, using combination therapies, avoiding prolonged antibiotic treatment, and avoiding concomitant topical and oral antibiotics with chemically dissimilar antibiotics.     

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.     

活性氧在细菌耐抗生素机制中的作用

细菌对抗生素的耐药性以惊人的速度蔓延,阐明抗生素导致细菌死亡内在机制,对提高抗生素药效以及寻找新型抗生素显得尤为迫切。近期研究表明,抗生素引起的细菌内活性氧物质(reactive oxygen species,ROS)产生,是导致细菌细胞死亡的关键原因。该文对ROS、SOS和细菌耐药性方面的最新研究进行了综述和探讨,为开发新型抗菌药物,遏制细菌感染和耐药性提供新的思路。     

5种铜绿假单胞菌高危克隆的流行及耐药情况

摘要：细菌引起的感染分为社区感染和医院内感染,社区感染的细菌通常对抗生素敏感,较容易控制,而院内感染较难 治疗。铜绿假单胞菌(Pseudomonas aeruginosa)是机会性感染的非发酵革兰阴性细菌,一种引起医院内感染的常见细菌,并容易 感染术后患者及烧伤患者,影响患者的治疗与恢复。抗生素治疗是人们抵御细菌感染性疾病的有效手段,但是随着抗生素的大 量使用,抗生素耐药性细菌不断产生,泛耐药(extensively drug resistant, XDR)甚至是全耐药(pandrug-resistant bacteria, PDR)铜绿 假单胞菌已在世界多地医院被检出。而这种广泛的耐药性往往集中在几种特定的铜绿假单胞菌基因型中,如ST111、ST175、 ST235、ST308和ST664等;由于无药可用,使得它们所引发的感染异常危险,因此被称为高危克隆。本文就目前国际流行的 5种铜绿假单胞菌高危克隆进行系统性综述,包括其流行情况、耐药谱、耐药机制及治疗手段,为高危克隆的甄别和防治提 供借鉴。     

Optimizing antimicrobial prescribing

Antibiotics are universally prescribed drugs. Because they exert selective pressure and because of the innate bacterial ability for adaptation, even the appropriate clinical use of these potentially life-preserving agents inevitably fosters the development and spread of resistance by a variety of microorganisms. Inappropriate use has accelerated and increased the magnitude of a problem that is now considered a public health crisis. For Gram-positive pathogens some compounds offer limited hope, but for Gram-negative organisms no new drugs with radically increased spectra are available for clinical trials. Patients with serious infections due to multiresistant organisms are experiencing adverse, sometimes fatal, clinical outcomes. Use of multiple drugs increases side effects and exposes additional susceptible bacteria to selective pressure. There is evidence that the appropriate use of currently available antibiotics can be associated with a reduction of the spread of resistance. Antibiotic stewardship programmes and the antibiotic 'care bundle' approach can be effective measures to lengthen the useful life of antibiotics and can be implemented in most clinical situations.     

Novel antibiotics for the treatment of Staphylococcus aureus

Staphylococcus aureus is a leading cause of nosocomial and community-acquired infection associated with significant morbidity and mortality. Antibiotic treatment of infections owing to S. aureus have become increasingly challenging as the pathogen has acquired a broad spectrum of antibiotic resistance mechanisms. In particular, emergence and spread of methicillin-resistant S. aureus (MRSA) progressed to a global health threat. The glycopeptides antibiotics vancomycin and teicoplanin have remained as the drugs of last resort for more than 20 years. Fortunately, in addition to the glycopeptides, several novel antibiotics including linezolid, daptomycin, tigecycline, quinupristin/dalfopristin and ceftobiprole acting against MRSA have been recently introduced into clinical practice broadening therapeutic options. Although the arsenal of antistaphylococcal drugs has filled up in recent years, the rate of MRSA infection continues to be high in most countries. This demands an ongoing search for new antibacterials and lead compounds as well as development of alternative therapies and faster diagnostics to ensure effective anti-staphylococcal therapy in the future.     

中药抗幽门螺杆菌感染的研究进展

幽门螺杆菌(Helicobacter pylori,Hp)是一种常见的染病菌株,随着抗菌药物的广泛使用和滥用,耐药性逐年上升,目前西医临床治疗方案存在复发率高、不良反应多或严重以及易产生耐药性的风险。相对于抗菌类药物的局限性,现代研究显示中药有良好的抗Hp作用,且不易产生耐药性。本文对中药抗HP相关研究进展进行论述,为中药抗Hp的进一步研究和产品开发提供思路。     

Antimicrobial peptides: Their physicochemical properties and therapeutic application

Antibiotic resistance has become a global public health problem, thus there is a need to develop a new class of antibiotics. Natural antimicrobial peptides have got an increasing attention as potential therapeutic agents. Antimicrobial peptides are small cationic peptides with broad antimicrobial activity. They can serve as critical defense molecules protecting the host from the invasion of bacteria. Even though they possess a different mode of action compared to traditional antibiotics, antimicrobial peptides couldn’t go into the drug markets because of problems in application such as toxicity, susceptibility to proteolysis, manufacturing cost, size, and molecular size. Nevertheless, antimicrobial peptides can be new hope in developing novel, effective and safe therapeutics without antibiotic resistance. Thus, it is necessary to discover new antimicrobial sources in nature and study their structures and physicochemical properties more in depth.     

Antibiotic usage in animals: impact on bacterial resistance and public health.

Antibiotic use whether for therapy or prevention of bacterial diseases, or as performance enhancers will result in antibiotic resistant micro-organisms, not only among pathogens but also among bacteria of the endogenous microflora of animals. The extent to which antibiotic use in animals will contribute to the antibiotic resistance in humans is still under much debate. In addition to the veterinary use of antibiotics, the use of these agents as antimicrobial growth promoters (AGP) greatly influences the prevalence of resistance in animal bacteria and a poses risk factor for the emergence of antibiotic resistance in human pathogens. Antibiotic resistant bacteria such as Escherichia coli, Salmonella spp., Campylobacter spp. and enterococci from animals can colonise or infect the human population via contact (occupational exposure) or via the food chain. Moreover, resistance genes can be transferred from bacteria of animals to human pathogens in the intestinal flora of humans. In humans, the control of resistance is based on hygienic measures: prevention of cross contamination and a decrease in the usage of antibiotics. In food animals housed closely together, hygienic measures, such as prevention of oral-faecal contact, are not feasible. Therefore, diminishing the need for antibiotics is the only possible way of controlling resistance in large groups of animals. This can be achieved by improvement of animal husbandry systems, feed composition and eradication of or vaccination against infectious diseases. Moreover, abolishing the use of antibiotics as feed additives for growth promotion in animals bred as a food source for humans would decrease the use of antibiotics in animals on a worldwide scale by nearly 50%. This would not only diminish the public health risk of dissemination of resistant bacteria or resistant genes from animals to humans, but would also be of major importance in maintaining the efficacy of antibiotics in veterinary medicine.     

Mutation and evolution of antibiotic resistance: antibiotics as promoters of antibiotic resistance?

Antibiotic resistance appearance and spread have been classically considered the result of a process of natural selection, directed by the use of antibiotics. Bacteria, that have to face the antibiotic challenge, evolve to acquire resistance and, under this strong selective pressure, only the fittest survive, leading to the spread of resistance mechanisms and resistant clones. Horizontal transference of resistance mechanisms seems to be the main way of antibiotic resistance acquisition. Nevertheless, recent findings on hypermutability and antibiotic-induced hypermutation in bacteria have modified the landscape. Here, we present a review of the last data on molecular mechanisms of hypermutability in bacteria and their relationship with the acquisition of antibiotic resistance. Finally, we discuss the possibility that antibiotics may act not only as selectors for antibiotic resistant bacteria but also as resistance promoters.     

小儿大肠埃希菌和肺炎克雷伯菌超广谱β-内酰胺酶的检测及防治对策

目的　探讨小儿大肠埃希菌和肺炎克雷伯菌超广谱β-内酰胺酶(ESLBs)的耐药情况及防治措施。方法　对51例小儿患者细菌培养为大肠埃希菌和肺炎克雷伯菌的药物敏感率,结合临床综合分析。结果　有27例患儿为ESLBs阳性,药物敏感率高低依次为亚胺硫霉素、丁胺卡那霉素、哌拉西林/他唑巴坦(piperacillin/tazobactoam)、环丙氟哌酸、头孢西丁,这五种抗生素药物敏感率依次为96.3%、74.1%、70.4%、63.0%和55.%。其他抗生素敏感率均在25.9%以下。应用头孢曲松钠(菌必治)者细菌产ESLBs明显多于不用菌必治者(P<0.01)。结论　对ESLBs阳性细菌的感染首选亚胺硫霉素。不滥用抗生素,严格做好消毒隔离预防措施。     

Lethal drug probe in China: the case of Xinfu clindamycin

In China, antibiotics are prescribed frequently, not only for bacterial infections but also for viruses, including the common cold, as well as other illnesses.12 Chinese people tend to believe that antibiotics are a cure for many diseases from skin infections to life-threatening lung ailments; and antibiotics are their first choice when they think about buying medication.3 Antibiotic abuse is particularly severe in small- and medium-sized towns and rural areas where doctors are not as well educated as in the large cities. Statistics from the World Health Organization reveal that the use of antibiotics in Chinese hospitals can be as high as 80 percent of overall cases, compared with the international average of 30 percent.3 Besides being one source of the specific public health disaster described in the remainder of this article, overprescribing generally leads to building up of resistance to antibiotics, making it more difficult to treat bacterial infections in the future.     

Molecular targets for design of novel inhibitors to circumvent aminoglycoside resistance

Aminoglycosides are a class of clinically important antibiotics used in the treatment of infections caused by Gram-positive and Gram-negative organisms. They are bactericidal, targeting the bacterial ribosome, where they bind to the A-site and disrupt protein synthesis. Antibiotic resistance is a growing problem for all classes of anti-infective agents. One of the first groups of antibiotics to encounter the challenge of resistance was the aminoglycoside -aminocyclitol family. Initially, the resistance that emerged in organisms such as Mycobacterium tuberculosis was restricted to modification of the antibiotic targets, which we now know to be the bacterial ribosomal rRNA and proteins. As new aminoglycosides came to the clinic, however, the prevalence of chemical modification mechanisms of resistance became dominant. Enzymatic modification of aminoglycosides through kinases (O-phosphotransferases, APHs), O-adenyltransferases (ANTs) and N-acetyltransferases (AACs) has emerged in virtually all clinically relevant bacteria of both Gram-positive and Gram-negative origin. Although their clinical use has been extensive, their toxicity and the prevalence of resistance in clinical strains have prompted the pharmaceutical industry to look for alternatives. Whereas the search for novel targets for antibiotics from the genomic information is ongoing, no antibacterial agent based on these efforts has so far entered clinical trials. Meanwhile, structural knowledge of the ribosome, the target for aminoglycosides, has invigorated the field of antibiotic development. It is expected that knowledge of the binding interactions of aminoglycosides and the ribosome would lead to concepts in drug design that would take us away from the parental structures of aminoglycosides in the direction of different structural classes that bind to the same ribosomal target sites as aminoglycosides. The challenge to ensure the continued use of these highly potent antibacterial agents will require the effective management of resistance at several levels. One potential mechanism of circumventing resistance is the development of inhibitors of modification enzymes, a methodology that is now well established in the beta-lactam field. This approach requires knowledge of resistance at the molecular and atomic levels for the rational design of inhibitory molecules. The understanding of the molecular basis for aminoglycoside resistance modification has been greatly enhanced by the recent availability of representative 3D-structures from the three classes of modifying enzymes: kinases, acetyltransferases and adenyltransferases. The challenge is now to firmly establish the mechanisms of enzyme action and to use this information to prepare effective and potent inhibitors that will reverse antibiotic resistance. In this review, we discuss the molecular mechanisms of resistance of aminoglycosides specifically on aminoglycoside-modifying enzymes and newly developed strategies to circumvent resistance including antisense technology, which is an example of new strategy to deal with antibiotic resistance.     

Antibiotic resistance in the aquatic environment: Analytical techniques and interactive impact of emerging contaminants

Antibiotic pollution is becoming an increasingly severe threat globally. Antibiotics have emerged as a new class of environmental pollutants due to their expanding usage and indiscriminate application in animal husbandry as growth boosters. Contamination of aquatic ecosystems by antibiotics can have a variety of negative impacts on the microbial flora of these water bodies, as well as lead to the development and spread of antibiotic-resistant genes. Various strategies for removing antibiotics from aqueous systems and environments have been developed. Many of these approaches, however, are constrained by their high operating costs and the generation of secondary pollutants. This review aims to summarize research on the distribution and effects of antibiotics in aquatic environments, their interaction with other emerging contaminants, and their remediation strategy. The ecological risks associated with antibiotics in aquatic ecosystems and the need for more effective monitoring and detection system are also highlighted.     

Targeting the subtypes of breast cancer: rethinking investigational drugs

Importance of the field: Antibiotic resistance in bacterial pathogens has increased worldwide leading to treatment failures. Concerns have been raised about the use of biocides as a contributing factor to the risk of antimicrobial resistance (AMR) development. In vitro studies demonstrating increase in resistance have often been cited as evidence for increased risks. It is therefore important to understand the mechanisms of resistance employed by bacteria toward biocides used in consumer products and their potential to impart cross-resistance to therapeutic antibiotics.

Areas covered: In this review, the mechanisms of resistance and cross-resistance reported in the literature toward biocides commonly used in consumer products are summarized. The physiological and molecular techniques used in describing and examining these mechanisms are reviewed and application of these techniques for systematic assessment of biocides for their potential to develop resistance and/or cross-resistance is discussed.

Expert opinion: The guidelines in the usage of biocides in household or industrial purpose should be monitored and regulated to avoid the emergence of any MDR strains. The genetic and molecular methods to monitor the resistance development to biocides should be developed and included in preclinical and clinical studies.     

儿科病房肺炎克雷伯菌呼吸道分离株耐药性分析

目的 了解本院儿科病房肺炎克雷伯菌呼吸道分离株耐药性,为临床合理使用抗生素提供依据.方法 应用TDR-300B自动微生物分析系统进行细菌鉴定及药敏试验,采用WHONET5.6对2015年1月至2016年12月本院儿科病房呼吸道标本分离的肺炎克雷伯菌对临床常用的12种抗菌药物的耐药性进行统计分析.结果 儿科病房肺炎克雷伯菌呼吸道分离株对阿米卡星、美罗培南、左氧氟沙星和哌拉西林/他唑巴坦的耐药率低(0％～12.2％);对其余8种抗生素耐药率较高(24.5％ ～ 100.0％);2016年分离株对左氧氟沙星耐药率显著高于2015年,而2016年分离株对头孢西丁的耐药率则显著低于2015年.结论 儿科病房肺炎克雷伯菌呼吸道分离株耐药严重,临床工作者应合理应用抗菌药物,延缓耐药菌的产生,并加强细菌耐药监测和医院感染控制措施以防止耐药菌的播散.     

Do Biocides Select for Antibiotic Resistance?*

Some similarities exist between bacterial resistance to antibiotics and to biocides, and gram-negative bacteria that have developed resistance to cationic biocides may also be insusceptible to some antibiotics. Outer membrane changes are believed to be responsible for this non-specific increase in resistance. Efflux, another important resistance mechanism, is associated with the qacA/B gene system in staphylococci that confers low-level resistance to cationic agents including chlorhexidine salts and quaternary ammonium compounds. It has been proposed that the introduction into clinical practice of chlorhexidine and quaternary ammonium compounds has resulted in the selection of staphylococci containing qacA genes on multiresistance plasmids. A linkage between low-level resistance to triclosan and to antibiotics has recently been claimed to occur in Escherichia coli, with the bisphenol selecting for chromosomally-mediated antibiotic resistance. A key issue in many studies has been the use of biocides at concentrations significantly below those used clinically. It remains to be determined how an increase to low-level resistance to cationic biocides can be held responsible for the selection of antibiotic-resistant bacteria.     

Animal growth promoters: to ban or not to ban? A risk assessment approach

The use of antibiotics for animal growth promotion has been controversial because of the potential transfer of antibiotic resistance from animals to humans. Such transfer could have severe public health implications in that treatment failures could result. We have followed a risk assessment approach to evaluate policy options for the streptogramin-class of antibiotics: virginiamycin, an animal growth promoter, and quinupristin/dalfopristin, a antibiotic used in humans. Under the assumption that resistance transfer is possible, models project a wide range of outcomes depending mainly on the basic reproductive number (R(0)) that determines the potential for person-to-person transmission. Counter-intuitively, the benefits of a ban on virginiamycin were highest for intermediate values of R(0), and lower for extremely high or low values of R(0).     

北京市房山区良乡医院外科Ⅰ类切口手术预防性应用抗菌药物分析

目的：了解我院Ⅰ类切口手术围术期预防性应用抗菌药物在卫生部抗菌药物专项整治活动前后的变化,为临床合理用药提供参考。方法：选取自2011年1月-2013年9月我院Ⅰ类切口手术病历合计3725份,对围术期预防性应用抗菌药物情况按合理用药指标进行统计。结果：经过3年的整治,我院Ⅰ类切口手术围术期预防性应用抗菌药物各项合理用药指标基本达到卫生部整治方案的要求,Ⅰ类切口手术围术期预防性应用抗菌药物合理情况持续提高。结论：卫生部抗菌药物专项整治活动对Ⅰ类切口手术围术期预防性应用抗菌药物促进作用明显。