Avoiding laboratory pitfalls in infectious diseases

In today's medical care environment, clinicians are challenged to order clinically relevant, cost effective laboratory tests and antibiotic therapy. Together, physicians and laboratories must have guidelines and strategies that can provide quality patient care, while minimising costs and preventing further emergence of antimicrobial drug resistance. Five clinical vignettes that demonstrate these principles are presented.     

The need to look at antibiotic resistance from a health systems perspective

Current use, misuse, and overuse of antibiotics raise dangers and ethical dilemmas that cannot be solved in isolation, exclusively within a health system building block or even within the health sector only. There is a need to tackle antibiotic resistance emergence and containment on levels ranging from individuals, households, and the communities, to health care facilities, the entire health sector, and finally to national and global levels. We analyse emergence of antibiotic resistance based on interdependencies between health systems resources. We further go beyond the health system building blocks, to look at determinants of antibiotic resistance referring to wider global dynamics. Multi-level governance is the key for successful action in containment strategies. This will involve, in a comprehensive way, patients, health facilities where they receive care, health systems to which these facilities pertain, and the wider national context as well as the global community that influences the functioning of these health systems. In order to be effective and sustainable in both high and low-resource settings, implementation of containment interventions at all these levels needs to be managed based on existing theories and models of change. Although ministries of health and the global community must provide vision and support, it is important to keep in mind that containment interventions for antibiotic resistance will target individuals, consumers as well as providers.     

Whole genome sequence of colistin-resistant Escherichia coli from western India

BackgroundWith virtually dried out new antibiotic discovery pipeline, emergence and spread of antimicrobial resistance is a cause for global concern. Colistin, a cyclic polypeptide antibiotic, often regarded as last resort for multi drug resistance gram-negative bacteria, is also rendered ineffective by horizontal transfer of resistance genes. Surveillance of colistin resistance in GNB is essential to ascertain molecular epidemiology.MethodsWhole genome sequencing (WGS) of an unusual colistin resistant urinary isolate of Escherichia coli was performed using Illumina MiSeq platform using 2x250bp V2 chemistry by following the manufactures protocol (Illumina Inc. USA). Multiple web-based bio-informatic tools were utilized to ascertain antibiotic resistant genes.ResultsAn approximate 5.4 Mb of genome of the urinary isolate AFMC_UC19 was sequenced successfully. Mobile colistin resistance gene (mcr) on the plasmid responsible for horizontal spread was absent in the isolate.ConclusionColistin resistance has been reported previously in Klebsiella pneumoniae and it is a rare occurrence in Escherichia coli in Indian setting. Although the isolate lack mcr mediated colistin resistance, emergence and spread of colistin resistant in gram-negative bacteria pose a threat.     

Common bacteria whose susceptibility to antimicrobials is no longer predictable

The widespread use of antibiotics has been responsible for the development of numerous problems including the emergence of multidrug resistant bacteria, increased number of nosocomial- and community-acquired infections, less than optimal patient outcome, and increased health care costs. Of equal concern is the emergence of resistance in clinical isolates to antibiotics that were once considered "standard" with predictable in vitro susceptibility patterns. Such resistance has been especially notable in organisms that are commonly encountered in a variety of infections including, Streptococcus pneumoniae, Staphylococcus aureus. Enterococci, Klebsiella pneumoniae, and Escherichia coli. It is important for the clinical microbiology laboratory to provide the practicing clinician with accurate and timely antimicrobial susceptibility information which requires the application of standardized and approved in vitro testing methods. The laboratory also serves as a sentinel by maintaining an active monitoring and surveillance program in which current in vitro susceptibility patterns can be compared with local, regional, and national data bases.     

Is antibiotic resistance a problem? A practical guide for hospital clinicians

Antibiotic resistance is an important concern for patients, physicians, healthcare managers, and policymakers. Inappropriate antimicrobial prescribing fuels the evolution of resistance, while poor basic hygiene facilitates the spread of resistant microbes between patients and healthcare staff. The development of infection with a resistant pathogen may lead to poorer health and economic outcomes. The problem for the frontline clinician, however, is how to balance the responsibility of prudent prescribing with the risk of sub-optimally treating a patient who may be infected with a resistant pathogen. This article discusses how hospital physicians can use severity and risk factor assessment, and knowledge of local microbial epidemiology, to guide empiric antibiotic prescribing. Most patients hospitalised with a community acquired bacterial infection in the UK can still be managed with a traditional first line antibiotic(s). In contrast, regimens that account for resistance are often required in patients with hospital acquired infections, particularly if the patient is critically ill.     

Emergence and spread of antibiotic resistance: setting a parameter space

The emergence and spread of antibiotic resistance among human pathogens is a relevant problem for human health and one of the few evolution processes amenable to experimental studies. In the present review, we discuss some basic aspects of antibiotic resistance, including mechanisms of resistance, origin of resistance genes, and bottlenecks that modulate the acquisition and spread of antibiotic resistance among human pathogens. In addition, we analyse several parameters that modulate the evolution landscape of antibiotic resistance. Learning why some resistance mechanisms emerge but do not evolve after a first burst, whereas others can spread over the entire world very rapidly, mimicking a chain reaction, is important for predicting the evolution, and relevance for human health, of a given mechanism of resistance. Because of this, we propose that the emergence and spread of antibiotic resistance can only be understood in a multi-parameter space. Measuring the effect on antibiotic resistance of parameters such as contact rates, transfer rates, integration rates, replication rates, diversification rates, and selection rates, for different genes and organisms, growing under different conditions in distinct ecosystems, will allow for a better prediction of antibiotic resistance and possibilities of focused interventions.     

2018年NICE咽喉痛（急性）抗菌药物处方指南解读（一）——抗菌药物处方选用和自我保健方案

咽喉痛是耳鼻咽喉科常见疾病,抗菌药物治疗是临床医生的主要手段。抗菌药物选用的单一性和疗程的不规范导致了越来越多的不合理用药的发生。咽喉痛（急性）抗菌药物处方是英国国家卫生与临床优化研究所（NICE）2018年1月最新发布的指南,此指南详细制定了治疗急性咽喉痛的抗菌药物处方策略,其目的是限制抗菌药物的应用,减少抗菌药物耐药性发生。因其引用的2014的研究报告中60%的患者均是咽喉痛,故此指南对咽喉痛的症状和治疗所给出的抗菌药物选用标准清晰明确,非常适合耳鼻咽喉科和全科医生使用。本文就此指南中急性咽喉痛抗菌药物的选用和自我保健方案,结合相关文献进行复习。     

Antibiotic consumption and antibiotic stewardship in Swedish hospitals

Background. The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals.

Results. The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e.g. bloodstream infections and hospital-acquired pneumonia—data on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens.

Conclusions. Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels.     

Mechanisms of bacterial resistance to antimicrobial agents

The 20th century has been considered the antimicrobial era--whereas the 21st century may well represent the post-antimicrobial era. The reason for this dramatic change, should it come to pass, is the development of bacterial resistance to antimicrobial agents. This emerging resistance is now challenging the clinical utility of many antimicrobial agents such that the chemotherapy of hospitalized patients with serious infections has been compromised. If the problem with resistance is to be successfully dealt with by clinicians, the mechanisms of such resistance must be known and understood. This paper thus reviews the most important mechanisms of resistance as well as some of the most important pathogens having these mechanisms. An understanding of these important microbial resistance mechanisms will help the clinician identify circumstances in which resistance may be a problem as well as evaluating the potential usefulness of an alternate antimicrobial agent against resistant microbes.     

整合子与鲍曼不动杆菌多重耐药机制研究进展

鲍曼不动杆菌是一种不发酵葡萄糖的革兰阴性球杆菌,是重要的条件致病菌,常引起医院内感染。随着临床上广谱抗菌药物的大量应用,出现了多重耐药菌株,该菌引起的院内感染并有逐年上升趋势,给临床抗感染化疗提出了严峻的挑战。整合子-基因盒系统能捕获外来耐药基因,在整合子中形成多种耐药基因的组合和排列,是细菌耐药性播散的机制之一,对细菌基因组的进化具有重要意义。现就整合子-基因盒的结构、表达以及与鲍曼不动抗菌多重耐药的关系进行简要综述。     

Antibiotic resistance in bacteria - an emerging public health problem

The discovery and eventual introduction of anti-microbial agents to clinical medicine was one of the greatest medical triumphs of the twentieth century that revolutionized the treatment of bacterial diseases. However, the gradual emergence of populations of antibiotic-resistant bacteria resulting from use, misuse and outright abuse of antibiotics has today become a major public health problem of global proportions. This review paper examines the origins and molecular epidemiology of resistance genes, global picture of antibacterial resistance, factors that favour its spread, strategies for its control, problems of control and the consequences of failure to contain antibiotic resistance in bacteria.     

Use of antimicrobial agents for upper respiratory tract infections in Taiwanese children

Upper respiratory tract infections (URTIs) are mostly caused by viruses. Antibiotic misuse for viral URTIs in children is a serious problem that not only results in selection of resistant strains of bacteria but also wastes millions of dollars each year in Taiwan. Antibiotic resistance among common respiratory bacterial pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis has become a major issue for public health. The common cold, acute pharyngotonsillitis, acute otitis media, acute sinusitis, acute bronchitis, influenza and acute epiglottitis are the most frequently encountered acute URTIs in out-patient clinics. This article recommends the judicious use of antimicrobial agents for these seven common pediatric URTIs, based on local epidemiological data and the recommendations of the Infectious Disease Society of Taiwan and the American Academy of Pediatrics. With education and behavior modification, practitioners will help to reduce antibiotic overuse, and the goal of reducing antimicrobial resistance may be accomplished.     

The crisis of antibiotic-resistance in bacteria

Significant increases in the prevalence of resistance to antibiotics have been observed in common pathogen of humans worldwide. The consequences of the appearance and spread of antimicrobial resistance have included increasing morbidity, mortality, and cost of health care. The increasing use of antimicrobial agents promotes the appearance and spread of bacterial resistance. Strict clinical guidelines on antibiotic prescribing and firm guidance on the optimum length of treatment is required. These strategies can be utilized as a part of a multidisciplinary approach to limit the appearance and dissemination of antimicrobial resistance, in addition to, surveillance of antibiotic resistance rates both locally and nationally.     

WHONET Software for the Surveillance of Antimicrobial Susceptibility

Continuous surveillance of local antimicrobial susceptibility patterns is a must for combating emerging antimicrobial resistance. WHONET is an effective computerized microbiology laboratory data management and analysis program that can provide guidance for empiric therapy of infections, alert clinicians of trends of antimicrobial resistance, guide drug-policy decisions and preventive measures. The program facilitates sharing of data amongst different hospitals by putting each laboratory data into a common code and file format, which can be merged for national or global collaboration of antimicrobial resistance surveillance. The system can be implemented in hospital laboratories of Armed Forces at no additional cost. Cumulative analysis of surveillance data obtained from various hospitals of Armed Forces at higher centers may help in formulating health policies and control measures at various levels.Key Words: Antimicrobial susceptibility, Surveillance, WHONET     

Resistance to antibiotics: are we in the post-antibiotic era?

Serious infections caused by bacteria that have become resistant to commonly used antibiotics have become a major global healthcare problem in the 21st century. They not only are more severe and require longer and more complex treatments, but they are also significantly more expensive to diagnose and to treat. Antibiotic resistance, initially a problem of the hospital setting associated with an increased number of hospital-acquired infections usually in critically ill and immunosuppressed patients, has now extended into the community causing severe infections difficult to diagnose and treat. The molecular mechanisms by which bacteria have become resistant to antibiotics are diverse and complex. Bacteria have developed resistance to all different classes of antibiotics discovered to date. The most frequent type of resistance is acquired and transmitted horizontally via the conjugation of a plasmid. In recent times new mechanisms of resistance have resulted in the simultaneous development of resistance to several antibiotic classes creating very dangerous multidrug-resistant (MDR) bacterial strains, some also known as "superbugs". The indiscriminate and inappropriate use of antibiotics in outpatient clinics, hospitalized patients and in the food industry is the single largest factor leading to antibiotic resistance. In recent years, the number of new antibiotics licensed for human use in different parts of the world has been lower than in the recent past. In addition, there has been less innovation in the field of antimicrobial discovery research and development. The pharmaceutical industry, large academic institutions or the government are not investing the necessary resources to produce the next generation of newer safe and effective antimicrobial drugs. In many cases, large pharmaceutical companies have terminated their anti-infective research programs altogether due to economic reasons. The potential negative consequences of all these events are relevant because they put society at risk for the spread of potentially serious MDR bacterial infections.     

我国主要传疟媒介抗药性研究进展

杀虫剂在农业及传染性疾病防控工作中广泛而大量的应用,在降低虫媒传染病的同时也导致了媒介对杀虫剂耐药现象的发生。中国于2010年启动全国消除疟疾行动计划,提出到2020年全国实现消除疟疾目标,传疟按蚊抗药性的出现,成为我国消除疟疾工作中面临的重要问题。本文对我国主要传疟媒介抗药性的检测方法、按蚊抗性水平、蚊媒对杀虫剂的抗性机制的研究进展进行综述,以期为我国消除疟疾媒介防控策略的制订提供参考依据。     

Physicians’ knowledge,perceptions, and attitudes toward antimicrobial prescribing in Riyadh,Saudi Arabia

Objectives:

To assess knowledge, perceptions, and attitudes toward antimicrobial prescribing among physicians practicing in Riyadh, Saudi Arabia.

Methods:

A questionnaire was developed and distributed to physicians working in hospitals in Riyadh, Saudi Arabia between June and August 2013. The results were analyzed using Stata 12 software.

Results:

Two hundred and twelve (84.8%) full responses were returned. Most respondents perceived antimicrobial resistance as a significant problem in their daily practice (119, 56.1%) and at a national level (148, 69.8%). Inappropriate empirical therapy (101, 47.6%) and excessive use of antimicrobials in healthcare settings (66, 31.1%) were believed to be the main contributors to increasing bacterial resistance. Respondents favor treating infection rather than colonization (98, 46.2%), and physician education (74, 34.9%) as the most effective interventions to reduce antimicrobial resistance. Many respondents (95, 44.8%) do not feel confident in their knowledge of antimicrobial prescribing. Two-thirds of the respondents (135, 63.7%) have local antimicrobial guidelines, of which 90 (66.7%) felt were useful. Most respondents (160, 75.5%) considered their local infectious diseases service to be very helpful.

Conclusion:

There are considerable unmet training and education need for physicians in the area of antimicrobial prescribing. Local antimicrobial guidelines need revision to ensure they are more relevant and helpful for medical practitioners.The importance of judicious clinical use of antimicrobial agents and increasing rates of antimicrobial resistance have been the subject of numerous studies in the last decade.1-6 These studies involved either health care workers such as physicians, medical students, or pharmacists, or the general public. Several factors may contribute to inappropriate antimicrobial usage, including doctors’ knowledge and experiences, uncertain diagnosis, patients’ expectations, pharmaceutical marketing influences, and unregulated antibiotic dispensing.1 Despite continuous efforts to improve antimicrobial prescribing and address issues such as self-prescribing, unnecessary use for viral infections, dosing errors, and excessive treatment durations, rates of antimicrobial resistant infections continue to rise globally.7-10 Investigators from different parts of the world have identified knowledge gaps regarding antimicrobial prescribing and growing concern over the increasing antimicrobial resistance among healthcare workers.6,11,12 The development and implementation of wide ranging educational programs for both physicians and the general population are among the commonly recommended strategies to help address those concerns.13 In Saudi Arabia, accurate, denominated antimicrobial prescribing data is not available. It is however, important to note that antimicrobials are the third most commonly prescribed group of medications in the country.14 Furthermore, antibiotics are prescribed to 44-88% of patients who present to primary healthcare centers with upper respiratory tract infections (URTI).15 In dental practice, Al-Harthi et al16 found that healthcare workers believed that antimicrobials are excessively used and that their participants did not find hospital guidelines as helpful as other resources. Family and caretakers beliefs, especially among parents of young children, along with peer pressure are also significant contributing drivers of antimicrobial misuse.17 Better understanding the physicians’ knowledge, perception, and attitude toward antimicrobial prescribing is essential for formulating effective antimicrobial stewardship programs. The objective of this study was to assess knowledge, perceptions, and attitudes in relation to antibiotic prescribing among physicians practicing in hospitals in Riyadh, Saudi Arabia.     

Gestational and Perinatal Factors in Brain Damage

Until relatively recently, studies in this field emphasized the physical events surrounding the transfer of the infant from the uterus to the bassinette. Current investigators are devoting much more attention to intrauterine and early neonatal environment. This is not to say that mechanical factors should be forgotten or that they are unimportant, but that there seem to be factors as yet unknown which in modern practice may make a significantly greater contribution to the problem of brain damage than does direct obstetric trauma.

Genetic, developmental and infective factors have been reviewed. The interrelated factors of prematurity, anoxia, trauma and brain hemorrhage have been discussed. The contribution which traumatic obstetrics has made to the problem of brain damage can be minimized by general application of standards of obstetric care and practice which are now well established. The modern practice of obstetrics must extend its active interest far beyond the goal of a living mother and child-the future health of both must be its concern. Obstetrics must be considered as an opportunity to practise a philosophy of preventive medical care in the broadest sense.

     

铜绿假单孢菌和葡萄球菌耐药性分析

目的探讨铜绿假单孢菌和葡萄球菌感染及耐药性特点,为临床医生合理使用抗生素提供试验依据.方法常规分离培养,再严格按照MICROSCAN细菌鉴定及药敏试验的要求进行.结果铜绿假单孢菌最敏感的药物为亚胺硫霉素,耐药性为15.0%,葡萄球菌对万古霉素均敏感.结论临床医生应根据细菌的药敏结果对症治疗,直接选用广谱抗生素药物进行治疗不可取.