Introducing an antibiotic stewardship program in a pediatric center in China

Background

This study aimed to investigate the effect of antibiotic stewardship programs (ASP) on reducing antimicrobial resistance rate, antibiotics consumption and multi-drug resistance bacterial infections in the pediatric patients.

Methods

This study was carried out in the Pediatric Center of a tertiary hospital of Shandong Province, China. The study duration was separated into two periods according to introduction of ASP (began from April 2011). Before intervention: from April 2009 to March 2011; after intervention: from April 2012 to March 2014. The consumption of antibiotics, defined daily dose (DDD), isolation of multidrug-resistant organisms (MDRO) and resistance rate of antibiotics were analyzed and compared between the two study periods.

Results

Total antibiotics consumption (DDDs) reduced from 56,725 in 2011 to 31,380 in 2014; antibiotic use density (AUD) reduced from 93.8 to 43.5; mean (± SD) antibiotic costs per patient (per quarter) decreased from 637 (± 29) RMB to 462 (± 49) RMB; and the mean total drug consumption (g)/DDD (DDDs) for inpatients decreased from 90.4 (± 3.3) to 56.4 (± 9.5). Multidrug-resistant microorganisms isolation reduced significantly from 463 (20.0) to 216 (6.9%). Resistance rate of general spectrum antibiotics reduced remarkably after intervention. The proportion of patients colonized or infected with Carbapenems-resistant Acinetobacter baumannii was correlated with DDDs of carbapenem.

Conclusions

Implementation of ASP leads to reduced medical expense, decrease of improper and abuse of antibiotics, and reduced antibiotics resistance rate and MDRO isolation. Continuous efforts to improve antibiotic use are required.

     

Appropriate antibiotic use and why it is important: the challenges of bacterial resistance

After the introduction of antibiotics in the mid-20th century, clinicians soon witnessed clinical failures secondary to bacterial resistance. Despite scientists' efforts to synthesize more potent antibiotics during the last five decades, bacterial resistance continues to evolve, in large part because of the overuse and misuse of antibiotics. The treatment of several pathogens, including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant enterococci, is problematic. New solutions are needed to preserve the activity of our current antibiotic armamentarium, to lower the overall risk of bacterial resistance and to successfully treat patients with resistant bacterial infections. Options include: development of new antibiotics to treat resistant organisms; vaccination to prevent infections; and improved use of antibiotics. Because bacteria will eventually develop means to avoid being killed by antibiotics, judicious use of antibiotics by all clinicians is imperative. Appropriate antibiotic use involves selection of a "targeted spectrum" antibiotic, as well as an appropriate dose and duration.     

新生儿病房不同抗生素应用策略对新生儿治疗结局的影响

目的 探讨将新生儿抗生素使用策略由风险评估策略改变为风险评估加感染筛查及监测策略对住院新生儿抗生素使用率以及对治疗结局的影响。方法 采用队列研究,选取2010年1月至2011年5月住院新生儿4 406例为对照组,按照风险评估策略使用抗生素;2011年7月至2012年10月住院新生儿4 476例为研究组,按照风险评估加感染筛查及监测策略使用抗生素。分别对比两组患儿抗生素使用率、平均住院日、再入院率和病死率。结果 抗生素应用策略改变后,住院新生儿抗生素使用率明显降低（P<0.01）;患儿的平均住院日、再入院率和病死率差异无统计学意义（均P >0.05）。结论 将住院新生儿抗生素应用策略由风险评估策略改为风险评估加感染筛查及监测策略,能够明显减少抗生素使用率,而且不会对患儿产生不良影响。     

儿童肺炎链球菌耐药性变迁

肺炎链球菌是儿童呼吸道细菌感染的首位病原。由于抗生素的长期广泛使用,肺炎链球菌对β-内酰胺类、大环内酯类和喹诺酮类等多种抗生素的耐药性增强,耐药肺炎链球菌导致的感染增多,流行范围更广,给临床抗生素的选择带来困难。现回顾近30年来,我国儿童人群肺炎链球菌分离株对常用抗生素耐药性的变迁。肺炎链球菌耐药性快速进展更加强调了防控肺炎链球菌感染和减少抗生素不合理使用的重要性。     

2005-2006年抗生素应用与细菌耐药监测状况分析

目的 了解本地区儿科抗生素的使用情况和细菌耐药性的流行趋势.方法 从医院HIS服务器中提取重庆医科大学附属儿童医院2005年1月-2006年12月所有来院就诊患儿消耗药品的详情,采用限定日剂量(DDD)法分析抗生素的使用趋势;根据儿童感染性疾病的诊断,治疗标准,制定统一的病例报告表(case report form,CRF),以病案室提取的住院病历为依据填写呼吸、感染和PICU病房的CRF表,以此反应患儿的基本情况和抗生素的使用状况;同期临床分离病原细菌采用Kirlby-Bauer法进行药敏检测,按美国临床实验标准委员会2005版标准分析结果,对金黄色葡萄球菌等8种临床常见致病菌耐药性监测的2年资料进行统计分析.结果 2年中抗生素消耗金额分别占同期药品的51.88%、48.17%,抗生素累积DDDs分别占同期药品的11.53%、11.95%,2年中平均有63.29%门诊内科患儿使用抗生素,住院病区人均用抗生素品种最高为3.14个;2年分离8种病原菌5 767株,其中革兰阴性菌占60.20%,主要分离菌为大肠埃希菌(25.30%)、肺炎克雷伯杆菌(23.25%)、铜绿假单胞菌(7.82%)、流感嗜血杆菌(3.83%),肠杆菌科病原菌的产ESBL酶的分离率在50%以上,亚胺培南、头孢吡肟和环丙沙星对肠杆菌科细菌的抗菌活性最强;革兰阳性菌占39.80%%,主要为肺炎链球菌(21.00%),青霉素不敏感率2年分别为63.18%和70.45%;金黄色葡萄球菌检测率为16.79%,青霉素不敏感率2年分别为93.54%和95.89%.结论 2年中抗生素的消耗保持较高水平,ESBL仍然是目前革兰阴性菌中的主要问题,未发现万古霉素耐药肠球菌,对临床分离株的耐药情况应进行流行病学调查及采取相应的控制措施.     

Parental acceptability of the watchful waiting approach in pediatric acute otitis media

AIM: To determine parental knowledge about acute otitis media (AOM) and its antibiotic therapy, antibiotic resistance and the willingness to comply with the watchful waiting (WW) approach in primary care settings in southern Israel. METHODS: The study was conducted in 3 primary care clinics and the pediatric emergency room of Soroka University Medical Center. Questionnaires (20 questions on education background, previous AOM experience, knowledge on antimicrobial resistance and attitude vs the WW approach) were filled by 600 parents (150 at each centers) of children < 6 years of age. RESULTS: Mothers represented 69% of parents; 2% had an education of < 10 school years, 46% had high-school education and 17% had an academic degree. 69% parents reported previous experience with AOM and 56% thought that antibiotics represent the only treatment for AOM. Knowledge on bacterial resistance to antibiotics was reported by 57% of the parents; 86% parents were willing to accept/probably accept the WW approach for their children. Logistic regression analysis revealed a significant association between parental education and knowledge about bacterial resistance to antibiotics and that previous experience with AOM was significantly associated with reluctance to accept the WW approach. More parents with knowledge on bacterial resistance were willing to accept the WW approach compared with parents without such knowledge. No correlation was found between the education level and willingness to accept the WW approach. CONCLUSION: A significant correlation was found between previous parental education and experience with AOM and the knowledge about antibiotic use, bacterial resistance and acceptance of the WW approach.     

Recommended antibiotic therapy in episodes of urinary tract infection

The present article reviews the scientific evidence available on antibiotic treatment of urinary tract infection in childhood. The information from clinical trials is of little use in decision making, because many of these studies evaluate antibiotics with a high level of resistance in Spain. Although some studies allow certain antibiotics to be identified as sufficiently effective, they do not permit clear hierarchies in the choice of therapy to be established. Nevertheless, data are available from clinical trials and systematic reviews on the efficacy of different routes of administration or regimens and on treatment duration, although this information is of doubtful clinical application in some patient groups. If cystitis in older boys is excluded, the distinction between upper and lower urinary tract infection is of little use. Consequently, differentiating between high- and low-risk infections according to the patient's age and the presence of fever and/or general repercussions is preferable. Finally, the choice of antibiotic will largely depend on the antimicrobial resistances of urinary pathogens in Spain.     

Parents, physicians, and antibiotic use

BACKGROUND: Emergence of resistant bacterial pathogens has increased concerns about antibiotic prescribing patterns. Parent expectations and pressure may influence these patterns. OBJECTIVE: To understand how parents influence the prescribing patterns of physicians and what strategies physicians believe are important if we are going to reduce inappropriate use of oral antimicrobial agents. DESIGNS AND METHODS: One thousand pediatricians who are members of the American Academy of Pediatrics were asked to complete a semi-structured questionnaire. The physicians were chosen randomly by the American Academy of Pediatrics. RESULTS: Nine hundred fifteen pediatricians were eligible and 610 surveys were analyzable, for a response rate of 67%. The majority of respondents were male (56%), worked in a group practice (51%), saw an average of 114 patients per week and were in practice for 14 years. Forty percent of the pediatricians indicated that 10 or more times in the past month a parent had requested an antibiotic when the physician did not feel it was indicated. Forty-eight percent reported that parents always, most of the time, or often pressure them to prescribe antibiotics when their children are ill but antibiotics are not indicated. In follow-up questions, approximately one-third of physicians reported they occasionally or more frequently comply with these requests. Seventy-eight percent felt that educating parents would be the single most important program for reducing inappropriate oral antibiotic use and 54% indicated that parental pressure, in contrast to concerns about legal liability (12%) or need to be efficient in practice (19%), contributed most to inappropriate use of oral antibiotics. CONCLUSIONS: Pediatricians acknowledge prescribing antimicrobial agents when they are not indicated. Pediatricians believe educating parents is necessary to promote the judicious use of antimicrobial agents.     

Impact of an antibiotic restriction policy on hospital expenditures and bacterial susceptibilities: a lesson from a pediatric institution in a developing country

BACKGROUND: In an era of growing concern about bacterial resistance and hospital costs, limiting the use of broad spectrum antibiotics is important. OBJECTIVES: To evaluate the effects of an antibiotic restriction policy on expenditures, antimicrobial resistance rates and clinical outcomes of hospitalized children. DESIGN: Starting in January, 1997, a prior consultation with an infectious disease specialist for using restricted antibiotics was required in all hospital areas. A retrospective assessment of study objectives obtained 2 years before (1995, 1996) and 2 years after (1997, 1998) initiation of the restriction policy was performed. SETTING: The present study was conducted in a 500-bed university hospital serving children nationwide of a developing country, Panama. RESULTS: Total expenditures for antimicrobial agents decreased by 50%, from $699,543 (US dollars) during 1995 and 1996 to $347,261 during 1997 and 1998. Susceptibility rates of many nosocomial isolates (especially staphylococci and Gram-negative enteric bacilli) usually improved for restricted antibiotics with >35% reduction in utilization (notably for gentamicin, third generation cephalosporins, piperacillin and vancomycin). Major improvements in bacterial susceptibilities were observed in the nursery, a place harboring microorganisms exhibiting the higher initial resistance rates of the hospital. No differences in days of hospital stay and mortality rates of all patients and of children with nosocomial infections were detected during the study period. CONCLUSIONS: Requirement for prior approval of selected antimicrobial drugs in a pediatric institution decreases hospital expenditures and improves susceptibilities to antibiotics without compromising patient outcomes or length of hospital stays.     

湖南省极低/超低出生体重儿抗生素使用多中心调查报告

目的 对湖南省新生儿病房极低出生体重（VLBW）和超低出生体重（ELBW）患儿住院期间抗生素使用情况进行调查，为规范湖南省新生儿病房住院早产儿抗生素的合理应用提供临床数据。方法 对湖南省24家三级医疗机构新生儿病房上报的2017年1~12月住院VLBW/ELBW患儿抗生素使用情况进行调查。结果 24家医疗机构2017年全年住院VLBW/ELBW患儿共1 442例，抗生素中位使用时间为17 d（范围：0~86 d），抗生素使用时间占住院时间的53.0%。各医疗机构抗生素使用时间占住院时间的百分比差异较大，最高达91.4%，最低为14.6%，2/3（16家）的单位超过50.0%。血及脑脊液细菌培养阳性共113例，细菌培养阳性率为7.84%，各机构细菌培养阳性率不同（0%~14.9%）。败血症常见致病菌中肺炎克雷伯杆菌检出29例（25.7%），大肠杆菌12例（10.6%），金黄色葡萄球菌3例（2.7%）。使用最多的抗生素为第三代头孢菌素类抗生素，占全部抗生素使用的41.00%；其次为青霉素类抗生素（32.10%），再次为碳青霉烯类抗生素（13.15%）。抗生素使用时间占比与出生体重Z值、出生体重与出院体重Z值的差值呈负相关（分别r_s=-0.095、-0.151，均P < 0.01），与病死/放弃率呈正相关（r_s=0.196，P < 0.01）。结论 湖南省新生儿病房住院VLBW/ELBW患儿抗生素使用时间较长，不同医疗机构抗生素使用情况差别大。第三代头孢菌素及碳青霉烯类抗生素使用比例较高。     

Evidence-based adjustment of antibiotic in pediatric complicated appendicitis in the era of antibiotic resistance

Introduction  

Antibiotic resistance is a global issue especially in developed areas. With the emergence of antibiotic resistant-bacteria, the traditional choice of broad spectrum antibiotics may not be effective in complicated appendicitis. We herein report the bacteriology and antibiotic susceptibility of intra-operative peritoneal culture in children with acute appendicitis in Hong Kong. This may guide us to adjust the choice of antibiotics with evidence.     

Proper antibiotic therapy. From penicillin to pharmacogenomic

Antibiotics have always been considered one of the wonder discoveries of the 20th century. The use of penicillin by Flaming, opened up the golden era of antibiotics and now is hard to imagine the practice of medicine without antibiotics. Life-threatening infections, such as meningitis, endocarditis, bacteremic pneumonia sepsis, would again prove fatal. Also aggressive chemotherapy and transplant procedures would prove impossible. Another real wonder has been the rise of antibiotic resistance soon after the clinical use of penicillin in hospitals and communities. Several study demonstrated an excessive amount of antibiotic prescribing for communities patients and inpatients and in some hospital up to 50% of antibiotic usage is inappropriate: the benefits of antibiotic treatment come with the risk of antibiotic resistance development. In hospitals, infections caused by antibiotic-resistant bacteria are associated with higher mortality, morbidity and prolonged hospital stay compared with infections caused by antibiotic-susceptible bacteria. A variety of strategies has been proposed to reduce the cost and improve the quality of medication use. Education, guidelines and evidence based recommendations are considered to be essential elements of any program designed to influence prescribing behavior and can provide a foundation of knowledge that will enhance and increase the acceptance of stewardship strategies. Evidence-based recommendations, an approach to clinical practice helping to make decisions based on clinical expertise and on intimate knowledge of the individual patient's situations, beliefs, and priorities, enhance antimicrobial stewardship, that include appropriate selection, dosing, route, and duration of antimicrobial therapy can maximize clinical cure or prevention of infection while limiting the unintended consequences, such as the emergence of resistance, adverse drug events, and cost. These evidence-based guidelines are not a substitute for clinical judgment, and clinical discretion is always required in their application. Genome studies have identified hundreds of genetic polymorphism important determinants of the efficacy of therapy and several trial demonstrated the successful use of pharmacogenomic testing to reduce the incidence of hypersensitivity reactions in patients. Knowing the phenotype of a patient prior to therapy, optimal dose and type drugs can be prescribed to achieve better management of patients.     

Measuring antibiotic prescribing in hospitalised children in resource‐poor countries: A systematic review

Antibiotic resistance represents a significant threat to global health. Widespread exposure to antibiotics drives the development of antibiotic resistance. Little is known about the exposure to antibiotics of hospitalised children, particularly in resource‐poor countries where the burden of infectious disease is highest. The review sought to identify original research quantifying antibiotic use in hospitalised children in resource countries. The methods used were: A systematic search of the MEDLINE, CINAHL, EMBASE, LILACS and African Index Medicus databases. Eighteen papers were identified and the methodology varied considerably. Only seven used a recognised defined daily dose (DDD) methodology. The studies reveal a high exposure of hospitalised children to antibiotics. With the exception of data from China, the studies were limited by their design. Limited evidence of the variation in drug, dose and total exposure to antibiotic use in hospitalised children in resource‐poor countries exists. An international network of surveillance of both antimicrobial prescribing and resistance using a simple standardised methodology in this context remains an important goal. A simplified paediatric version of the adult DDD methodology is required to allow international comparison between populations.