烧伤病房MRSA医院感染暴发的PFGE分型研究

利用表型分型和基因分型的方法解析医院感染常见致病菌——耐甲氧西林金黄色葡萄球菌(MRSA)造成医院感染暴发的可能传播途径。本实验对某医院烧伤科、ICU、肿瘤科病房内从患者和环境分离的19株MRSA,进行了16种抗生素的耐药性实验和全基因组稀有位点限制性内切酶酶切脉冲凝胶电泳(PFGE)分析,并聚类分析归纳了菌株之间的相关性。结果发现在19株MRSA中有11株属于同一个菌种A型,在这些菌株中,有8株属于相同的克隆亚型A1型,分别来自烧伤科和ICU患者以及烧伤科医生、护士的手。4株属于B型,均分离自同一烧伤病房。这暗示该医院可能存在MRSA(A型)院内感染的暴发,并且存在B型流行的潜在危险。MRSA很有可能通过医护工作人员的手及鼻腔等媒介在患者间传播。因此,加强医护人员的感染控制观念,利用灵敏、可靠且分辨率强的分型技术加强MRSA感染监控至关重要。     

ICU病区耐甲氧西林金黄色葡萄球菌感染的流行病学调查

目的通过对ICU病区耐甲氧西林金黄色葡萄球菌（MRSA）感染进行流行病学调查,并经过耐药菌谱的分析,探讨临床分离菌株的同源性,为预防和控制医院感染提供参考.方法对2005年3月7日～3月29日ICU病区感染MRSA的10例患者及医院环境进行了流行病学调查分析.结果ICU病区MRSA的感染率为47.6%.且环境中空气、陪护人员手、医务人员等亦培养出MRSA,通过耐药谱分析显示细菌具有高度同源性.结论该次MRSA感染为局部暴发流行.医院必须加强室内外环境和空气监控,防止交叉感染,严格无菌侵入性操作和抗生素的使用原则,从而有效减少MRSA院内感染的发生.     

Modelling the costs and effects of selective and universal hospital admission screening for methicillin-resistant Staphylococcus aureus

Background

Screening at hospital admission for carriage of methicillin-resistant Staphylococcus aureus (MRSA) has been proposed as a strategy to reduce nosocomial infections. The objective of this study was to determine the long-term costs and health benefits of selective and universal screening for MRSA at hospital admission, using both PCR-based and chromogenic media-based tests in various settings.

Methodology/Principal Findings

A simulation model of MRSA transmission was used to determine costs and effects over 15 years from a US healthcare perspective. We compared admission screening together with isolation of identified carriers against a baseline policy without screening or isolation. Strategies included selective screening of high risk patients or universal admission screening, with PCR-based or chromogenic media-based tests, in medium (5%) or high nosocomial prevalence (15%) settings. The costs of screening and isolation per averted MRSA infection were lowest using selective chromogenic-based screening in high and medium prevalence settings, at $4,100 and $10,300, respectively. Replacing the chromogenic-based test with a PCR-based test costs $13,000 and $36,200 per additional infection averted, and subsequent extension to universal screening with PCR would cost $131,000 and $232,700 per additional infection averted, in high and medium prevalence settings respectively. Assuming $17,645 benefit per infection averted, the most cost-saving strategies in high and medium prevalence settings were selective screening with PCR and selective screening with chromogenic, respectively.

Conclusions/Significance

Admission screening costs $4,100–$21,200 per infection averted, depending on strategy and setting. Including financial benefits from averted infections, screening could well be cost saving.     

Quantifying type-specific reproduction numbers for nosocomial pathogens: evidence for heightened transmission of an Asian sequence type 239 MRSA clone

An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes.     

A stochastic mathematical model of methicillin resistant Staphylococcus aureus transmission in an intensive care unit: predicting the impact of interventions

OBJECTIVES: To estimate the transmission rate of MRSA in an intensive care unit (ICU) in an 800 bed Australian teaching hospital and predict the impact of infection control interventions. METHODS: A mathematical model was developed which consisted of four compartments: colonised and uncolonised patients and contaminated and uncontaminated health-care workers (HCWs). Patient movements, MRSA acquisition and daily prevalence data were collected from an ICU over 939 days. Hand hygiene compliance and the probability of MRSA transmission from patient to HCW per discordant contact were measured during the study. Attack rate and reproduction ratio were estimated using Bayesian methods. The impact of a number of interventions on attack rate was estimated using both stochastic and deterministic versions of the model. RESULTS: The mean number of secondary cases arising from the ICU admission of colonised patients, also called the ward reproduction ratio, R(w), was estimated to be 0.50 (95% CI 0.39-0.62). The attack rate was one MRSA transmission per 160 (95% CI 130-210) uncolonised-patient days. Results were not sensitive to uncertainty in measured model parameters (hand hygiene rate and transmission probability per contact). Hand hygiene was predicted to be the most effective intervention. Decolonisation was predicted to be relatively ineffective. Increasing HCW numbers was predicted to increase MRSA transmission, in the absence of patient cohorting. The predictions of the stochastic model differed from those of the deterministic model, with lower levels of colonisation predicted by the stochastic model. CONCLUSIONS: The number of secondary cases of MRSA colonisation within the ICU in this study was below unity. Transmission of MRSA was sustained through admission of colonised patients. Stochastic model simulations give more realistic predictions in hospital ward settings than deterministic models. Increasing staff does not necessarily lead to reduced transmission of nosocomial pathogens.     

护理管理在医院感染控制中的作用

目的分析护理环节存在的安全隐患,总结护理管理的对策,控制医院感染的发生。方法分析总结院内感染的预防、监测,加强护理环节质控,及时反馈、总结管理的对策、方法、体会,防止医院感染事件发生。结果因认识不足,手卫生、医疗器具消毒灭菌不彻底、医院感染链的存在、侵入性操作、住院时间及环境因素等引起院内感染。结论针对院内感染的主要危险因素,科室制订了完善的制度,做好护理管理"五到位",有效地控制了院内感染的发生。     

呼吸重症监护病房2008年至2011年医院感染病原菌分布及危险因素分析

目的：对我院呼吸重症监护病房（RICU）临床分离的非重复性感染病原菌的耐药性进行调查,分析RICU院内感染的危险因素。方法：收集RICU 2008年-2011年临床分离的非重复性感染病原菌及相关临床资料分析医院感染的危险因素。结果：（1）2008-2011年RICU院内感染发生率为34.15%,每年分离的前3位病原菌均为鲍曼不动杆菌、金黄色葡萄球菌及铜绿假单胞菌;（2）大肠杆菌连续4年ESBLs检出率为100%,四年间肺炎克雷伯菌ESBLs检出率最高达95.5%,葡萄球菌中MRSA检出率较高（〉89.6%）;（3）RICU院内感染以下呼吸道感染最为常见,其次为泌尿道感染,血液感染位于第3位;（4）多因素非条件logistic回归分析发现机械通气、住院时间〉15天及联合应用抗菌药物是RICU医院感染的危险因素。结论：（1）连续4年RICU感染病原菌以革兰阴性杆菌为主;（2）ESBLs和MRSA检出率较高,给临床抗感染治疗带来巨大的挑战;（3）机械通气、住院时间〉15天及联合应用抗菌药物是RICU医院感染的危险因素。     

Transmission dynamics of methicillin-resistant Staphylococcus aureus in a medical intensive care unit in India

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is a global pathogen and an important but seldom investigated cause of morbidity and mortality in lower and middle-income countries where it can place a major burden on limited resources. Quantifying nosocomial transmission in resource-poor settings is difficult because molecular typing methods are prohibitively expensive. Mechanistic statistical models can overcome this problem with minimal cost. We analyse the transmission dynamics of MRSA in a hospital in south India using one such approach and provide conservative estimates of the organism''s economic burden.

Methods and Findings

Fifty months of MRSA infection data were collected retrospectively from a Medical Intensive Care Unit (MICU) in a tertiary hospital in Vellore, south India. Data were analysed using a previously described structured hidden Markov model.Seventy-two patients developed MRSA infections and, of these, 49 (68%) died in the MICU. We estimated that 4.2% (95%CI 1.0, 19.0) of patients were MRSA-positive when admitted, that there were 0.39 MRSA infections per colonized patient month (0.06, 0.73), and that the ward-level reproduction number for MRSA was 0.42 (0.08, 2.04). Anti-MRSA antibiotic treatment costs alone averaged $124/patient, over three times the monthly income of more than 40% of the Indian population.

Conclusions

Our analysis of routine data provides the first estimate of the nosocomial transmission potential of MRSA in India. The high levels of transmission estimated underline the need for cost-effective interventions to reduce MRSA transmission in hospital settings in low and middle income countries.     

Curiosities of the methicillin-resistant Staphylococcus aureus survey - possibility of pseudo-outbreak and transmission to household contacts

Methicillin-resistant Staphylococcus aureus (MRSA) is currently one of the most prevalent antibiotic-resistant pathogens in hospitals, but it is also emerging as a community-acquired pathogen. We analysed the clinical and microbiological data of the patients in a county teaching hospital regarding MRSA. During the examination period (1996-2010), four outbreaks and one pseudo-outbreak occurred. It also became evident that health care workers and their families are possibly at risk of becoming carriers of MRSA. The importance of the molecular epidemiological investigation (pulsed-field gel-electrophoresis (PFGE)) typing and hygienic measures in order to detect and control MRSA outbreaks must be emphasised. Following infection control guidelines seems to be cost-effective method of controlling the nosocomial transmission of MRSA.     

Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolates from clinical specimens of patients with nosocomial infection: are there unnoticed silent outbreaks?

Bacteriological and epidemiological studies were carried out on 90 isolates of methicillin-resistant Staphylococcus aureus (MRSA) at Turgut Ozal Medical Center of In?nü University, (Malatya/Turkey). MRSA isolates were obtained from patients with nosocomial infections. Staphylococcus aureus clinical isolates were collected between May 2004-May 2005. Isolates were tested for resistance to methicillin. Antimicrobial susceptibility testing and slime production evaluation was performed. Genotype studies were carried out by arbitrarily primed polymerase chain reaction (AP-PCR) and consequent cluster analysis. All of the isolates were mecA-positive in a PCR-based assay; all exhibited resistance to oxacillin, by agar dilution (MICs > or = 4 mg/L) and disc diffusion methods, and multiple antibiotics. Most MRSA isolates were collected in intensive care units. Of 90 samples, 53 were found to be unrelated to the others while the remaining 37 strains were either identical or closely related. Dendrogram analysis identified nine major clusters. These data support the opinion that MRSA are significant nosocomial pathogens in intensive care units and that resistant clones may be transmitted between patients. Molecular epidemiological tools are helpful for understanding transmission patterns and sources of infection, and are useful for measuring outcomes of intervention strategies implemented to reduce nosocomial MRSA.     

Hospital-acquired infection: present and future impact and need for positive action

Surveillance of infections at the Ottawa General Hospital between September 1, 1971 and August 31, 1972 showed that the overall infection rate was 13.5% of which 5.6% was community-acquired while 7.9% was of nosocomial origin. These figures are comparable to those for equivalent hospitals in the United States and lower than those reported from the Boston City Hospital, but they nevertheless indicate that over half the infected patients in the hospital were infected after admission. Urinary tract infections accounted for 44.8% of all nosocomial infections and clearly dominated the picture. The postoperative wound infection rate was 3.9% and accounted for only 18% of nosocomial infections. It is probable that these findings are representative of general hospitals throughout Canada and indicate conditions which will not long be tolerated. The knowledge and techniques exist for the prevention of all hospital cross-infection and much autogenous infection. Specific measures are suggested for working towards this goal. These are (1) the replacement of archaic hospitals and hospital facilities, (2) the establishment in every hospital of an efficient surveillance program, (3) the institution of good catheterization and catheter care techniques, and (4) the establishment by hospitals of a quality control program whereby a specific explanation is required for every infection occurring within the hospital.     

Patient Referral Patterns and the Spread of Hospital-Acquired Infections through National Health Care Networks

Rates of hospital-acquired infections, such as methicillin-resistant Staphylococcus aureus (MRSA), are increasingly used as quality indicators for hospital hygiene. Alternatively, these rates may vary between hospitals, because hospitals differ in admission and referral of potentially colonized patients. We assessed if different referral patterns between hospitals in health care networks can influence rates of hospital-acquired infections like MRSA. We used the Dutch medical registration of 2004 to measure the connectedness between hospitals. This allowed us to reconstruct the network of hospitals in the Netherlands. We used mathematical models to assess the effect of different patient referral patterns on the potential spread of hospital-acquired infections between hospitals, and between categories of hospitals (University medical centers, top clinical hospitals and general hospitals). University hospitals have a higher number of shared patients than teaching or general hospitals, and are therefore more likely to be among the first to receive colonized patients. Moreover, as the network is directional towards university hospitals, they have a higher prevalence, even when infection control measures are equally effective in all hospitals. Patient referral patterns have a profound effect on the spread of health care-associated infections like hospital-acquired MRSA. The MRSA prevalence therefore differs between hospitals with the position of each hospital within the health care network. Any comparison of MRSA rates between hospitals, as a benchmark for hospital hygiene, should therefore take the position of a hospital within the network into account.     

Close encounters in a pediatric ward: measuring face-to-face proximity and mixing patterns with wearable sensors

Background

Nosocomial infections place a substantial burden on health care systems and represent one of the major issues in current public health, requiring notable efforts for its prevention. Understanding the dynamics of infection transmission in a hospital setting is essential for tailoring interventions and predicting the spread among individuals. Mathematical models need to be informed with accurate data on contacts among individuals.

Methods and Findings

We used wearable active Radio-Frequency Identification Devices (RFID) to detect face-to-face contacts among individuals with a spatial resolution of about 1.5 meters, and a time resolution of 20 seconds. The study was conducted in a general pediatrics hospital ward, during a one-week period, and included 119 participants, with 51 health care workers, 37 patients, and 31 caregivers. Nearly 16,000 contacts were recorded during the study period, with a median of approximately 20 contacts per participants per day. Overall, 25% of the contacts involved a ward assistant, 23% a nurse, 22% a patient, 22% a caregiver, and 8% a physician. The majority of contacts were of brief duration, but long and frequent contacts especially between patients and caregivers were also found. In the setting under study, caregivers do not represent a significant potential for infection spread to a large number of individuals, as their interactions mainly involve the corresponding patient. Nurses would deserve priority in prevention strategies due to their central role in the potential propagation paths of infections.

Conclusions

Our study shows the feasibility of accurate and reproducible measures of the pattern of contacts in a hospital setting. The obtained results are particularly useful for the study of the spread of respiratory infections, for monitoring critical patterns, and for setting up tailored prevention strategies. Proximity-sensing technology should be considered as a valuable tool for measuring such patterns and evaluating nosocomial prevention strategies in specific settings.     

Quantifying Cost-Effectiveness of Controlling Nosocomial Spread of Antibiotic-Resistant Bacteria: The Case of MRSA

Background

The costs and benefits of controlling nosocomial spread of antibiotic-resistant bacteria are unknown.

Methods

We developed a mathematical algorithm to determine cost-effectiveness of infection control programs and explored the dynamical interactions between different epidemiological variables and cost-effectiveness. The algorithm includes occurrence of nosocomial infections, attributable mortality, costs and efficacy of infection control and how antibiotic-resistant bacteria affect total number of infections: do infections with antibiotic-resistant bacteria replace infections caused by susceptible bacteria (replacement scenario) or occur in addition to them (addition scenario). Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was used for illustration using observational data on S. aureus bacteremia (SAB) in our hospital (n = 189 between 2001–2004, all being methicillin-susceptible S. aureus [MSSA]).

Results

In the replacement scenario, the costs per life year gained range from € 45,912 to € 6590 for attributable mortality rates ranging from 10% to 50%. Using € 20,000 per life year gained as a threshold, completely preventing MRSA would be cost-effective in the replacement scenario if attributable mortality of MRSA is ≥21%. In the addition scenario, infection control would be cost saving along the entire range of estimates for attributable mortality.

Conclusions

Cost-effectiveness of controlling antibiotic-resistant bacteria is highly sensitive to the interaction between infections caused by resistant and susceptible bacteria (addition or replacement) and attributable mortality. In our setting, controlling MRSA would be cost saving for the addition scenario but would not be cost-effective in the replacement scenario if attributable mortality would be <21%.     

Prevention and treatment of nosocomial infections, with special reference to antibiotic policy

Hospital infections are of a major and growing health concern worldwide. They are the cause of appreciable economic loss, but what raises the particular alarm, both ethically and as a public health problem, is their continuous trend towards increasing lethality. The incidence of nosocomial infections can be prevented by creating a system of barriers that would interrupt their spread and transmission. Apart from strict adherence to general hygiene rules and the rational employment of examination methods it is essential in this respect that a prime attention is paid to the sensible use of antimicrobials, i.e. the persuance of a sound antibiotic policy. Its integral components are the systematic laboratory control, continuous epidemiological surveillance of bacterial drug resistance patterns, study of variations in the biological properties of multiple resistant bacterial strains, and the development of, and adherence to, effective and indicated treatment schedules. The particular problems related to bacterial enzyme activities and the genetic information (plasmids) coding for resistance to antimicrobials, as well as the virulence and pathogenicity of agents responsible for the onset of hospital infection are also discussed in this context. It is pointed out that for an effective hospital infection control it is essential to avoid the onesided pressure of badly applied antibiotic therapy.     

Prevention of hospital infection

The prevention of nosocomial infections is an important aspect of patient care, particularly in high-risk areas such as intensive care units (ICUs). Local hospital leadership needs to develop easily defined infection-control policies that are evidence-based. These infection-control policies also require the presence of a dedicated group of infection-control practitioners to provide education, collect surveillance data, and oversee the implementation of the local infection-control plan.     

Methicillin-resistant Staphylococcus aureus infection and hospitalization in high-risk patients in the year following detection

Background

Many studies have evaluated methicillin-resistant Staphylococcus aureus (MRSA) infections during single hospitalizations and subsequent readmissions to the same institution. None have assessed the comprehensive burden of MRSA infection in the period after hospital discharge while accounting for healthcare utilization across institutions.

Methodology/Principal Findings

We conducted a retrospective cohort study of adult patients insured by Harvard Pilgrim Health Care who were newly-detected to harbor MRSA between January 1991 and December 2003 at a tertiary care medical center. We evaluated all MRSA-attributable infections associated with hospitalization in the year following new detection, regardless of hospital location. Data were collected on comorbidities, healthcare utilization, mortality and MRSA outcomes. Of 591 newly-detected MRSA carriers, 23% were colonized and 77% were infected upon detection. In the year following detection, 196 (33%) patients developed 317 discrete and unrelated MRSA infections. The most common infections were pneumonia (34%), soft tissue (27%), and primary bloodstream (18%) infections. Infections occurred a median of 56 days post-detection. Of all infections, 26% involved bacteremia, and 17% caused MRSA-attributable death. During the admission where MRSA was newly-detected, 14% (82/576) developed subsequent infection. Of those surviving to discharge, 24% (114/482) developed post-discharge infections in the year following detection. Half (99/185, 54%) of post-discharge infections caused readmission, and most (104/185, 55%) occurred over 90 days post-discharge.

Conclusions/Significance

In high-risk tertiary care patients, newly-detected MRSA carriage confers large risks of infection and substantial attributable mortality in the year following acquisition. Most infections occur post-discharge, and 18% of infections associated with readmission occurred in hospitals other than the one where MRSA was newly-detected. Despite gains in reducing MRSA infections during hospitalization, the risk of MRSA infection among critically and chronically ill carriers persists after discharge and warrants targeted prevention strategies.     

Potent In Vitro Bactericidal Activity of Polymyxin B against Methicillin-Resistant Staphylococcus aureus (MRSA)

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) carried by inpatients or healthy hospital personnel by topical use of antibiotics is an important step for preventing outbreak of MRSA nosocomial infection. In the screening of the antibiotic best suited for this purpose, we have found that polymyxin B, a commonly used antibiotic for gram-negative infection, had an unexpected strong cytokilling activity towards MRSA clinical strains, which was more potent than that of vancomycin or gentamicin. The data suggested that polymyxin B could be an antibiotic of choice in the treatment of topical carriage of or infection caused by MRSA.     

Modeling methicillin-resistant Staphylococcus aureus in hospitals: Transmission dynamics, antibiotic usage and its history

ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) infection has been prevalent in many hospitals worldwide. To investigate the transmission dynamics of MRSA and how certain factors influence the prevalence of MRSA infection when antibiotics are given to patients to treat or prevent bacteria infections either from MRSA itself or other pathogens, mathematical modeling was used. Our results suggest that: (i) MRSA always persists in the hospital when there is admission of colonized and infectious patients; (ii) the longer duration of treatment in infectious patients, the less probability of a successful treatment, the longer duration of contamination in health care workers (HCWs), and the higher number of required contacts of patients may lead to the higher prevalence of MRSA infection; (iii) in an attempt to control the prevalence of MRSA infection, the possible ways are to treat patients with antibiotic exposure as quickly and efficiently as possible, and to screen, isolate, and decolonize colonized and infectious patients at admission; (iv) in addition, other strategies such as using antimicrobial susceptibility tests to help treating patients with MRSA infection with the right antibiotics, constantly developing novel drugs, and strict hand-washing of HCWs, for example, may also help to reduce the prevalence of MRSA infection.     

Identification and discrimination of Staphylococcus aureus strains using matrix-assisted laser desorption/ionization-time of flight mass spectrometry

Staphylococcus aureus is an important human pathogen frequently resistant to a wide range of antibiotics. Methicillin-resistant S. aureus (MRSA) strains are common nosocomial pathogens that pose a world-wide problem. Rapid and accurate discrimination between methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus is essential for appropriate therapeutic management and timely intervention for infection control. We report here the application of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) for monitoring the bacterial fingerprints expressed by two well characterized S. aureus strains ATCC 29213 (MSSA) and ATCC 43330 (MRSA). Consistent strain-specific data were obtained from subcultures analyzed over a period of three months as well as after changing the growth media from Mueller-Hinton to blood agar indicating the reliability of the method. The bacterial fingerprints of these two strains were compared to independent clinical isolates of S. aureus. A uniform signature profile for MRSA could not be identified. However, the bacterial fingerprints obtained proved to be specific for any given strain. This study demonstrates that MALDI-TOF MS is a powerful method for rapid identification of clonal strains of S. aureus, which might be useful for tracking nosocomial outbreaks of MRSA and for epidemiologic studies of infections diseases in general.