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1.  Screening and control of methicillin-resistant Staphylococcus aureus in 186 intensive care units: different situations and individual solutions 
Critical Care  2011;15(6):R285.
Introduction
Controversy exists about the benefit of screening for prevention of methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs) and recent studies have shown conflicting results. The aim of this observational study was to describe and evaluate the association between MRSA incidence densities (IDs) and screening and control measures in ICUs participating in the German Nosocomial Infection Surveillance System.
Methods
The surveillance module for multidrug-resistant bacteria collects data on MRSA cases in ICUs with the aim to provide a national reference and a tool for evaluation of infection control management. The median IDs of MRSA cases per 1000 patient-days (pd) with the interquartile range (IQR) were calculated from the pooled data of 186 ICUs and correlated with parameters derived from a detailed questionnaire regarding ICU structure, microbiological diagnostics and MRSA screening and control measures. The association between questionnaire results and MRSA cases was evaluated by generalized linear regression models.
Results
One hundred eighty-six ICUs submitted data on MRSA cases for 2007 and 2008 and completed the questionnaire. During the period of analysis, 4935 MRSA cases occurred in these ICUs; of these, 3928 (79.6%) were imported and 1007 MRSA cases (20.4%) were ICU-acquired. Median MRSA IDs were 3.23 (IQR 1.24-5.73), 2.24 (IQR 0.63-4.30) and 0.64 (IQR 0.17-1.39) per 1000 pd for all cases, imported and ICU-acquired MRSA cases, respectively. MRSA IDs as well as implemented MRSA screening and control measures varied widely between ICUs. ICUs performing universal admission screening had significantly higher MRSA IDs than ICUs performing targeted or no screening. Separate regression models for ICUs with different screening strategies included the incidence of imported MRSA cases, the type of ICU, and the length of stay in independent association with the number of ICU-acquired MRSA cases.
Conclusions
The analysis shows that MRSA IDs and structural parameters differ considerably between ICUs. In response, ICUs have combined screening and control measures in many ways to achieve various individual solutions. The incidence of imported MRSA cases might be helpful for consideration in the planning of MRSA control programmes.
doi:10.1186/cc10571
PMCID: PMC3388634  PMID: 22118016
2.  Community-Acquired Methicillin-Resistant Staphylococcus aureus: Prevalence and Risk Factors  
Journal of Athletic Training  2006;41(3):337-340.
Reference/Citation: Salgado CD, Farr BM, Calfee DP. Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors. Clin Infect Dis.20033613113912522744.
Clinical Question: What are the prevalence rates and risk factors associated with community-acquired methicillin-resistant Staphylococcus aureus (MRSA)?
Data Sources: Studies were identified by searching MEDLINE (January 1966–February 2002) and abstracts from scientific meetings (1996–2001). Reviews of citations and reference lists were performed to identify additional eligible studies. The search terms included Staphylococcus aureus , infection, colonization, methicillin resistance, community-acquired, community-onset, prevalence, frequency, and risk factors.
Study Selection: The search was limited to English-language investigations identified from the electronic and manual searches. Studies were divided into 2 groups, as follows: group 1, retrospective or prospective studies that reported the prevalence of community-acquired MRSA (CA-MRSA) among hospital patients who were colonized (presence of bacteria without infection) or infected with MRSA; and group 2, studies that reported the prevalence of MRSA colonization in the community. The studies were evaluated independently by 2 authors, and case reports were excluded.
Data Extraction: Data extraction and study quality assessment procedures were not fully explained. The outcome measures for hospital patients were definitions of CA-MRSA used in the study, prevalence of CA-MRSA, sample size, number and type of risk factors assessed, and number of patients with ≥1 health care–associated risk factor. The studies were grouped based on type, retrospective or prospective. The pooled prevalence of CA-MRSA was calculated for each group (retrospective or prospective) and was limited to the prevalence among patients with MRSA. The proportion of patients who reported ≥1 health care–associated risk factor was also calculated. The outcome measures among community members were prevalence of MRSA, sample size, number and type of risk factors assessed, number of members with ≥1 risk factor, and MRSA strain type, when available. The studies were grouped based on the population surveyed (surveillance cultures, contacts with MRSA-colonized individuals, or sport team members or day care contacts). The pooled prevalence of MRSA colonization and the proportion of members with ≥1 reported risk factor were calculated for each of the study populations listed above. The proportion of CA-MRSA strains that represented typical nosocomial (infection that develops in the hospital) strains was also determined. Chi-square analysis was performed to compare proportions and to determine heterogeneity among the studies.
Main Results: Specific search criteria identified 104 studies for review, of which 57 met inclusion and exclusion criteria. Thirty-nine studies focused on CA-MRSA among hospital patients who were colonized or infected with MRSA. Of these, 32 groups (27 retrospective, 5 prospective) reported the prevalence of CA-MRSA using clinical specimens. Seven groups identified risk factors of CA-MRSA among patients previously diagnosed with MRSA. Thirteen different definitions of CA-MRSA were used in 31 of these studies, and 8 groups did not report the definitions used. The isolation of MRSA within 48 hours of hospital admission, with or without recent admission to a hospital or long-term care facility, or previous history of MRSA colonization were the most common definitions in the studies.
The risk factors included recent hospitalization (range, 1–24 months before identification of MRSA infection or colonization), recent outpatient visit (usually within 12 months), recent nursing home admission (usually within 12 months), recent antibiotic exposure (range, 1–12 months), chronic illness (eg, end-stage renal disease, diabetes, or malignancy), injection drug use, and close contact with a person who had risk factor(s) for MRSA acquisition. The presence of health care–associated risk factors was examined in 17 of the retrospective studies, and the median number of factors studied was 2 (range, 1–6). Among 4121 patients in these studies, 86.1% were found to have ≥1 health care–associated risk factor. All authors of prospective studies (5) examined health care–associated risk factors, and the median number of factors studied was 4 (range, 2–4). Among the 636 patients, 86.9% had ≥1 health care–associated risk factor. In the 7 studies with 515 patients previously diagnosed with MRSA, 84.7% had ≥1 health care–associated risk factor. The most common risk factors assessed in the 17 retrospective studies were recent hospitalization and chronic illness requiring health care visits.
The pooled CA-MRSA prevalence was 30.2% (range, 1.9%– 96%) among 5932 patients from the 27 retrospective studies and 37.3% (range, 18.2%–51.2%) among 636 patients from the 5 prospective studies. Eighteen groups reported the prevalence of MRSA colonization in the community. Ten of these reported MRSA prevalence using surveillance cultures, 4 examined colonization status of household contacts with discharged hospital patients with nosocomial MRSA colonization, and 4 reported colonization status of sports team members or day care contacts of persons colonized with MRSA. In the 10 surveillance studies, the pooled MRSA colonization prevalence was 1.3% (95% confidence interval [CI], 1.04%–1.53%; range, 0.2%– 7.4%) among 8350 community members. Nine of these studies were stratified based on culture samples taken before the assessment of risk factors, and among 4825 people, the pooled MRSA colonization prevalence was 2.1%. When examining health care–associated risk factors, the median number of factors studied was 5 (range, 1–10), and 47.5% with MRSA had ≥1 health care–associated risk factor. The risk factors included those previously identified. In the remaining surveillance study, the MRSA colonization prevalence was 0.20% among 3525 people without prior health care contact. Compared with subjects in the 9 stratified studies with a health care contact, subjects in this study were 90% less likely to have MRSA (relative risk, 0.10; 95% CI, 0.05–0.21). Cultures for 3898 subjects in 7 of the 10 surveillance studies were obtained at the time of a hospital admission, an outpatient clinic visit, or an emergency department visit, and the pooled prevalence of MRSA colonization was 1.8%. In 3 studies in which cultures were obtained outside of a health care facility (schools, day care centers, homeless shelters, or military bases), the pooled MRSA colonization prevalence among 4452 subjects was reported to be 0.76%. Therefore, subjects in a health care facility were 2.35 times more likely to carry MRSA than were subjects outside of a health care facility (95% CI, 1.56–3.53). In one study examining 94 subjects in a semiclosed community, the prevalence of MRSA colonization was 7.4%. These subjects were 36 times more likely to carry MRSA than were subjects who were not in a semiclosed community (95% CI, 13.7–94.7).
The studies also identified 70 MRSA isolates (pure form of an organism in a microbial culture) from subjects who reported no health care–associated risk factors. Strain typing was performed with 32 isolates, and 29 (91%) isolates were similar to strains identified in hospitals. The colonization status of 191 household contacts of 93 patients with nosocomial MRSA colonization discharged from the hospital was examined in 4 studies. The results demonstrated that 17.8% of the contact subjects were colonized with a strain of MRSA having the same antibiogram (record of the susceptibility of bacteria to antibiotics) as the index case (initial individual with the strain). The authors reported that subjects who had household contacts with MRSA-colonized patients were 14 times more likely to be colonized than were community subjects without a known MRSA contact (95% CI, 9.8–20.1). In 4 studies examining 517 sports team members or day care contacts of persons known to be colonized with MRSA, 5.4% demonstrated colonization of MRSA with the same strain as the index case.
Conclusions: Based on the available data, the prevalence of MRSA among community members without health care–associated risk factors was relatively low. However, 85% of hospital patients diagnosed with CA-MRSA and 47.5% of healthy community members colonized with MRSA were found to have ≥1 health care–associated risk factor. The risk factors identified were recent hospitalization, outpatient visit, nursing home admission, antibiotic exposure, chronic illness, injection drug use, and close contact with a person with risk factor(s). Most MRSA colonization occurred among community members who had health care–associated risk factors or contact with persons with risk factors. The evidence indicated that control of MRSA in the community may require control of MRSA in the health care setting (hospital, health care office, and nursing home). The absence of a standardized definition for CA-MRSA and questions regarding the actual site of colonization versus acquisition should be considered in the interpretation of these findings.
PMCID: PMC1569547  PMID: 17043704
infectious diseases
3.  Evaluation of rapid screening and pre-emptive contact isolation for detecting and controlling methicillin-resistant Staphylococcus aureus in critical care: an interventional cohort study 
Critical Care  2006;10(1):R25.
Introduction
Rapid diagnostic tests may allow early identification of previously unknown methicillin-resistant Staphylococcus aureus (MRSA) carriers at intensive care unit (ICU) admission. The aim of this study was twofold: first, to assess whether a new molecular MRSA screening test can substantially decrease the time between ICU admission and identification of MRSA carriers; and, second, to examine the combined effect of rapid testing and pre-emptive contact isolation on MRSA infections.
Method
Since November 2003, patients admitted for longer than 24 hours to two adult ICUs were screened systematically on admission using quick, multiplex immunocapture-coupled PCR (qMRSA). Median time intervals from admission to notification of test results were calculated for a five-month intervention phase (November 2003–March 2004) and compared with a historical control period (April 2003–October 2003) by nonparametric tests. ICU-acquired MRSA infection rates were determined for an extended surveillance period (January 2003 through August 2005) and analyzed by Poisson regression methods.
Results
During the intervention phase, 97% (450/462) of patients admitted to the surgical ICU and 80% (470/591) of patients admitted to the medical ICU were screened. On-admission screening identified the prevalence of MRSA to be 6.7% (71/1053). Without admission screening, 55 previously unknown MRSA carriers would have been missed in both ICUs. Median time from ICU admission to notification of test results decreased from 87 to 21 hours in the surgical ICU (P < 0.001) and from 106 to 23 hours in the medical ICU (P < 0.001). In the surgical ICU, 1,227 pre-emptive isolation days for 245 MRSA-negative patients were saved by using the qMRSA test. After adjusting for colonization pressure, the systematic on-admission screening and pre-emptive isolation policy was associated with a reduction in medical ICU acquired MRSA infections (relative risk 0.3, 95% confidence interval 0.1–0.7) but had no effect in the surgical ICU (relative risk 1.0, 95% confidence interval 0.6–1.7).
Conclusion
The qMRSA test decreased median time to notification from four days to one day and helped to identify previously unknown MRSA carriers rapidly. A strategy linking the rapid screening test to pre-emptive isolation and cohorting of MRSA patients substantially reduced MRSA cross-infections in the medical but not in the surgical ICU.
doi:10.1186/cc3982
PMCID: PMC1550853  PMID: 16469125
4.  Decreasing healthcare-associated infections (HAI) is an efficient method to decrease healthcare-associated Methicillin-resistant S.aureus (MRSA) infections Antimicrobial resistance data from the German national nosocomial surveillance system KISS 
Background
By analysing the data of the intensive care unit (ICU) component of the German national nosocomial infection surveillance system (KISS) during the last ten years, we have observed a steady increase in the MRSA rates (proportions) from 2001 to 2005 and only a slight decrease from 2006 to 2010. The objective of this study was to investigate the development of the incidence density of nosocomial MRSA infections because this is the crucial outcome for patients.
Findings
Data from 103 ICUs with ongoing participation during the observation period were included. The pooled incidence density of nosocomial MRSA infections decreased significantly from 0.37 per 1000 patient days in 2001 to 0.15 per 1000 patient days in 2010 (RR = 0.40; CI95 0.29-0.55). This decrease was proportional to the significant decrease of all HCAI during the same time period (RR = 0.61; CI95 0.58-0.65).
Conclusions
The results underline the need to concentrate infection control activities on measures to control HCAI in general rather than focusing too much on specific MRSA prevention measures. MRSA rates (proportions) are not a very useful indicator of the situation.
doi:10.1186/2047-2994-1-3
PMCID: PMC3415117  PMID: 22958746
Surveillance; MRSA; epidemiology; Staphylococcus aureus
5.  Incidence of and Risk Factors for Community-Associated Methicillin-Resistant Staphylococcus aureus Acquired Infection or Colonization in Intensive-Care-Unit Patients▿  
Journal of Clinical Microbiology  2010;48(12):4439-4444.
The incidence of and risk factors for acquiring community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) among patients staying in intensive care units (ICUs) remain unclear. We enrolled patients staying in two ICUs at the Far Eastern Memorial Hospital during the period of 1 September 2008 to 30 September 2009 to clarify this issue. Surveillance cultures for MRSA were taken from nostril, sputum or throat, axillae, and the inguinal area in all enrolled patients upon admission to the ICU, every 3 days thereafter, and on the day of discharge from the ICU. For each MRSA isolate, we performed multilocus sequence typing, identified the type of staphylococcal cassette chromosome mec, detected the presence of the Panton-Valentine leukocidin gene, and conducted drug susceptibility tests. Among the 1,906 patients who were screened, 203 patients were carriers of MRSA before their admission to the ICU; 81 patients acquired MRSA during their stay in the ICU, including 31 who acquired CA-MRSA. The incidence rates of newly acquired MRSA and CA-MRSA during the ICU stay were 7.9 and 3.0 per 1,000 patient-days, respectively. Prior usage of antipseudomonal penicillins and antifungals and the presence of a nasogastric tube were found to be independent risk factors for acquiring CA-MRSA during the ICU stay when data for CA-MRSA carriers and patients without carriage of MRSA were compared (P = 0.0035, 0.0330, and 0.0262, respectively). Prior usage of carbapenems was found to be a protective factor against acquiring CA-MRSA when data for patients with CA-MRSA and those with health care-associated MRSA acquired during ICU stay were compared (P = 0.0240).
doi:10.1128/JCM.00784-10
PMCID: PMC3008468  PMID: 20926713
6.  Quantifying Type-Specific Reproduction Numbers for Nosocomial Pathogens: Evidence for Heightened Transmission of an Asian Sequence Type 239 MRSA Clone 
PLoS Computational Biology  2012;8(4):e1002454.
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.
Author Summary
Different strains of hospital pathogens may differ in their ability to spread between patients and respond differently to control measures. Attempts to quantify such between-strain variation are lacking in high prevalence settings. We analysed data from concurrent outbreaks with different MRSA strains in two adult intensive care units. MRSA is usually carried by patients asymptomatically, and most of our data came from routine screening swabs used to detect such carriage. We divided strains into two groups: common United Kingdom strains and strains from a type often found in Southeast Asia. We developed a new method to estimate how transmission changes over time and compared results with those from an adaptation of a previously described approach. An advantage of the new method is that it makes weaker assumptions about the process generating the data. The methods gave broadly similar results: the introduction of daily antiseptic bodywashes for all patients was the only intervention associated with a substantial fall in transmission, but this intervention was less effective for the Asian strain. This work should be useful for assessing the between-strain variation in the transmission of other hospital pathogens, and for assessing the impact of interventions on patient-to-patient transmission.
doi:10.1371/journal.pcbi.1002454
PMCID: PMC3325179  PMID: 22511854
7.  Reduction of Methicillin-Resistant Staphylococcus aureus Infection among Veterans in Atlanta 
OBJECTIVE
Describe local changes in the incidence of community-onset and hospital-onset methicillin-resistant Staphylococcus aureus (MRSA) infection and evaluate the impact of MRSA active surveillance on hospital-onset infection.
DESIGN
Observational study using prospectively collected data.
SETTING
Atlanta Veterans Affairs Medical Center (AVAMC).
PATIENTS
All patients seen at the AVAMC over an 8-year period with clinically and microbiologically proven MRSA infection.
METHODS
All clinical cultures positive for MRSA were prospectively identified, and corresponding clinical data were reviewed. MRSA infections were classified into standard clinical and epidemiologic categories. The Veterans Health Administration implemented the MRSA directive in October 2007, which required active surveillance cultures in acute care settings.
RESULTS
The incidence of community-onset MRSA infection peaked in 2007 at 5.45 MRSA infections per 1,000 veterans and decreased to 3.14 infections per 1,000 veterans in 2011 (P ≤ .001 for trend). Clinical and epidemiologic categories of MRSA infections did not change throughout the study period. The prevalence of nasal MRSA colonization among veterans admitted to AVAMC decreased from 15.8% in 2007 to 11.2% in 2011 (P < .001 for trend). The rate of intensive care unit (ICU)–related hospital-onset MRSA infection decreased from October 2005 through March 2007, before the MRSA directive. Rates of ICU-related hospital-onset MRSA infection remained stable after the implementation of active surveillance cultures. No change was observed in rates of non-ICU-related hospital-onset MRSA infection.
CONCLUSIONS
Our study of the AVAMC population over an 8-year period shows a consistent trend of reduction in the incidence of MRSA infection in both the community and healthcare settings. The etiology of this reduction is most likely multifactorial.
doi:10.1086/668776
PMCID: PMC3677855  PMID: 23221194
8.  Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation 
PLoS Medicine  2013;10(12):e1001577.
In this paper, Choi and colleagues analyzed levels of mitochondrial DNA in two prospective observational cohort studies and found that increased mtDNA levels are associated with ICU mortality, and improve risk prediction in medical ICU patients. The data suggests that mtDNA could serve as a viable plasma biomarker in MICU patients.
Background
Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients.
Methods and Findings
Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6–15.8, p = 1×10−7) and ME ARDS (OR 8.4, 95% CI 2.9–24.2, p = 9×10−5) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10−4) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers.
Conclusions
Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Intensive care units (ICUs, also known as critical care units) are specialist hospital wards that provide care for people with life-threatening injuries and illnesses. In the US alone, more than 5 million people are admitted to ICUs every year. Different types of ICUs treat different types of problems. Medical ICUs treat patients who, for example, have been poisoned or who have a serious infection such as sepsis (blood poisoning) or severe pneumonia (inflammation of the lungs); trauma ICUs treat patients who have sustained a major injury; cardiac ICUs treat patients who have heart problems; and surgical ICUs treat complications arising from operations. Patients admitted to ICUs require constant medical attention and support from a team of specially trained nurses and physicians to prevent organ injury and to keep their bodies functioning. Monitors, intravenous tubes (to supply essential fluids, nutrients, and drugs), breathing machines, catheters (to drain urine), and other equipment also help to keep ICU patients alive.
Why Was This Study Done?
Although many patients admitted to ICUs recover, others do not. ICU specialists use scoring systems (algorithms) based on clinical signs and physiological measurements to predict their patients' likely outcomes. For example, the APACHE II scoring system uses information on heart and breathing rates, temperature, levels of salts in the blood, and other signs and physiological measurements collected during the first 24 hours in the ICU to predict the patient's risk of death. Existing scoring systems are not perfect, however, and “biomarkers” (molecules in bodily fluids that provide information about a disease state) are needed to improve risk prediction for ICU patients. Here, the researchers investigate whether levels of circulating cell-free mitochondrial DNA (mtDNA) are associated with ICU deaths and whether these levels can be used as a biomarker to improve risk prediction in ICU patients. Mitochondria are cellular structures that produce energy. Levels of mtDNA in the plasma (the liquid part of blood) increase in response to trauma and infection. Moreover, mtDNA activates molecular processes that lead to inflammation and organ injury.
What Did the Researchers Do and Find?
The researchers measured mtDNA levels in the plasma of patients enrolled in two prospective observational cohort studies that monitored the outcomes of ICU patients. In the Brigham and Women's Hospital Registry of Critical Illness study, blood was taken from 200 patients within 24 hours of admission into the hospital's medical ICU. In the Molecular Epidemiology of Acute Respiratory Distress Syndrome study (acute respiratory distress syndrome is a life-threatening inflammatory reaction to lung damage or infection), blood was taken from 243 patients within 48 hours of admission into medical and non-medical ICUs at two other US hospitals. Patients admitted to medical ICUs with a raised mtDNA level (3,200 or more copies of a specific mitochondrial gene per microliter of plasma) had a 7- to 8-fold increased risk of dying within 28 days of admission compared to patients with mtDNA levels of less than 3,200 copies/µl plasma. There was no evidence of an association between raised mtDNA levels and death among patients admitted to non-medical ICUs. The addition of an elevated mtDNA level to a clinical model for risk prediction that included the APACHE II score and biomarkers that are already used to predict ICU outcomes improved the net reclassification index (an indicator of the improvement in risk prediction algorithms offered by new biomarkers) of 28-day mortality among medical ICU patients in both studies.
What Do These Findings Mean?
These findings indicate that raised mtDNA plasma levels are associated with death in medical ICUs and show that, among patients in medical ICUs, measurement of mtDNA plasma levels can improve the prediction of the risk of death from the APACHE II scoring system, even when commonly measured biomarkers are taken into account. These findings do not indicate whether circulating cell-free mtDNA increased because of the underlying severity of illness or whether mtDNA actively contributes to the disease process in medical ICU patients. Moreover, they do not provide any evidence that raised mtDNA levels are associated with an increased risk of death among non-medical (mainly surgical) ICU patients. These findings need to be confirmed in additional patients, but given the relative ease and rapidity of mtDNA measurement, the determination of circulating cell-free mtDNA levels could be a valuable addition to the assessment of patients admitted to medical ICUs.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001577.
The UK National Health Service Choices website provides information about intensive care
The Society of Critical Care Medicine provides information for professionals, families, and patients about all aspects of intensive care
MedlinePlus provides links to other resources about intensive care (in English and Spanish)
The UK charity ICUsteps supports patients and their families through recovery from critical illness; its booklet Intensive Care: A Guide for Patients and Families is available in English and ten other languages; its website includes patient experiences and relative experiences of treatment in ICUs
Wikipedia has a page on ICU scoring systems (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001577
PMCID: PMC3876981  PMID: 24391478
9.  Geographic Distribution of Staphylococcus aureus Causing Invasive Infections in Europe: A Molecular-Epidemiological Analysis 
PLoS Medicine  2010;7(1):e1000215.
Hajo Grundmann and colleagues describe the development of a new interactive mapping tool for analyzing the spatial distribution of invasive Staphylococcus aureus clones.
Background
Staphylococcus aureus is one of the most important human pathogens and methicillin-resistant variants (MRSAs) are a major cause of hospital and community-acquired infection. We aimed to map the geographic distribution of the dominant clones that cause invasive infections in Europe.
Methods and Findings
In each country, staphylococcal reference laboratories secured the participation of a sufficient number of hospital laboratories to achieve national geo-demographic representation. Participating laboratories collected successive methicillin-susceptible (MSSA) and MRSA isolates from patients with invasive S. aureus infection using an agreed protocol. All isolates were sent to the respective national reference laboratories and characterised by quality-controlled sequence typing of the variable region of the staphylococcal spa gene (spa typing), and data were uploaded to a central database. Relevant genetic and phenotypic information was assembled for interactive interrogation by a purpose-built Web-based mapping application. Between September 2006 and February 2007, 357 laboratories serving 450 hospitals in 26 countries collected 2,890 MSSA and MRSA isolates from patients with invasive S. aureus infection. A wide geographical distribution of spa types was found with some prevalent in all European countries. MSSA were more diverse than MRSA. Genetic diversity of MRSA differed considerably between countries with dominant MRSA spa types forming distinctive geographical clusters. We provide evidence that a network approach consisting of decentralised typing and visualisation of aggregated data using an interactive mapping tool can provide important information on the dynamics of MRSA populations such as early signalling of emerging strains, cross border spread, and importation by travel.
Conclusions
In contrast to MSSA, MRSA spa types have a predominantly regional distribution in Europe. This finding is indicative of the selection and spread of a limited number of clones within health care networks, suggesting that control efforts aimed at interrupting the spread within and between health care institutions may not only be feasible but ultimately successful and should therefore be strongly encouraged.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The bacterium Staphylococcus aureus lives on the skin and in the nose of about a third of healthy people. Although S. aureus usually coexists peacefully with its human carriers, it is also an important disease-causing organism or pathogen. If it enters the body through a cut or during a surgical procedure, S. aureus can cause minor infections such as pimples and boils or more serious, life-threatening infections such as blood poisoning and pneumonia. Minor S. aureus infections can be treated without antibiotics—by draining a boil, for example. Invasive infections are usually treated with antibiotics. Unfortunately, many of the S. aureus clones (groups of bacteria that are all genetically related and descended from a single, common ancestor) that are now circulating are resistant to methicillin and several other antibiotics. Invasive methicillin-resistant S. aureus (MRSA) infections are a particular problem in hospitals and other health care facilities (so-called hospital-acquired MRSA infections), but they can also occur in otherwise healthy people who have not been admitted to a hospital (community-acquired MRSA infections).
Why Was This Study Done?
The severity and outcome of an S. aureus infection in an individual depends in part on the ability of the bacterial clone with which the individual is infected to cause disease—the clone's “virulence.” Public-health officials and infectious disease experts would like to know the geographic distribution of the virulent S. aureus clones that cause invasive infections, because this information should help them understand how these pathogens spread and thus how to control them. Different clones of S. aureus can be distinguished by “molecular typing,” the determination of clone-specific sequences of nucleotides in variable regions of the bacterial genome (the bacterium's blueprint; genomes consist of DNA, long chains of nucleotides). In this study, the researchers use molecular typing to map the geographic distribution of MRSA and methicillin-sensitive S. aureus (MSSA) clones causing invasive infections in Europe; a MRSA clone emerges when an MSSA clone acquires antibiotic resistance from another type of bacteria so it is useful to understand the geographic distribution of both MRSA and MSSA.
What Did the Researchers Do and Find?
Between September 2006 and February 2007, 357 laboratories serving 450 hospitals in 26 European countries collected almost 3,000 MRSA and MSSA isolates from patients with invasive S. aureus infections. The isolates were sent to the relevant national staphylococcal reference laboratory (SRL) where they were characterized by quality-controlled sequence typing of the variable region of a staphylococcal gene called spa (spa typing). The spa typing data were entered into a central database and then analyzed by a public, purpose-built Web-based mapping tool (SRL-Maps), which provides interactive access and easy-to-understand illustrations of the geographical distribution of S. aureus clones. Using this mapping tool, the researchers found that there was a wide geographical distribution of spa types across Europe with some types being common in all European countries. MSSA isolates were more diverse than MRSA isolates and the genetic diversity (variability) of MRSA differed considerably between countries. Most importantly, major MRSA spa types occurred in distinct geographical clusters.
What Do These Findings Mean?
These findings provide the first representative snapshot of the genetic population structure of S. aureus across Europe. Because the researchers used spa typing, which analyzes only a small region of one gene, and characterized only 3,000 isolates, analysis of other parts of the S. aureus genome in more isolates is now needed to build a complete portrait of the geographical abundance of the S. aureus clones that cause invasive infections in Europe. However, the finding that MRSA spa types occur mainly in geographical clusters has important implications for the control of MRSA, because it indicates that a limited number of clones are spreading within health care networks, which means that MRSA is mainly spread by patients who are repeatedly admitted to different hospitals. Control efforts aimed at interrupting this spread within and between health care institutions may be feasible and ultimately successful, suggest the researchers, and should be strongly encouraged. In addition, this study shows how, by sharing typing results on a Web-based platform, an international surveillance network can provide clinicians and infection control teams with crucial information about the dynamics of pathogens such as S. aureus, including early warnings about emerging virulent clones.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000215.
This study is further discussed in a PLoS Medicine Perspective by Franklin D. Lowy
The UK Health Protection Agency provides information about Staphylococcus aureus
The UK National Health Service Choices Web site has pages on staphylococcal infections and on MRSA
The US National Institute of Allergy and Infectious Disease has information about MRSA
The US Centers for Disease Control and Infection provides information about MRSA for the public and professionals
MedlinePlus provides links to further resources on staphylococcal infections and on MRSA (in English and Spanish)
SRL-Maps can be freely accessed
doi:10.1371/journal.pmed.1000215
PMCID: PMC2796391  PMID: 20084094
10.  Universal Glove and Gown Use and Acquisition of Antibiotic resistant bacteria in the ICU: A Randomized Trial 
Importance
Antibiotic-resistant bacteria are associated with increased patient morbidity and mortality. It is unknown whether wearing gloves and gowns for all patient contact in the intensive care unit (ICU) decreases acquisition of antibiotic-resistant bacteria.
Objective
To assess whether wearing gloves and gowns for all patient contact in the ICU decreases acquisition of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) compared with usual care.
Design, Setting, and Participants
Cluster-randomized trial in 20 medical and surgical ICUs in 20 US hospitals from January 4, 2012, to October 4, 2012.
Interventions
In the intervention ICUs, all health care workers were required to wear gloves and gowns for all patient contact and when entering any patient room.
Main Outcomes and Measures
The primary outcome was acquisition of MRSA or VRE based on surveillance cultures collected on admission and discharge from the ICU. Secondary outcomes included individual VRE acquisition, MRSA acquisition, frequency of health care worker visits, hand hygiene compliance, health care–associated infections, and adverse events.
Results
From the 26 180 patients included, 92 241 swabs were collected for the primary outcome. Intervention ICUs had a decrease in the primary outcome of MRSA or VRE from 21.35 acquisitions per 1000 patient-days (95% CI, 17.57 to 25.94) in the baseline period to 16.91 acquisitions per 1000 patient-days (95% CI, 14.09 to 20.28) in the study period, whereas control ICUs had a decrease in MRSA or VRE from 19.02 acquisitions per 1000 patient-days (95% CI, 14.20 to 25.49) in the baseline period to 16.29 acquisitions per 1000 patient-days (95% CI, 13.48 to 19.68) in the study period, a difference in changes that was not statistically significant (difference, −1.71 acquisitions per 1000 person-days, 95% CI, −6.15 to 2.73; P = .57). For key secondary outcomes, there was no difference in VRE acquisition with the intervention (difference, 0.89 acquisitions per 1000 person-days; 95% CI, −4.27 to 6.04, P = .70), whereas for MRSA, there were fewer acquisitions with the intervention (difference, −2.98 acquisitions per 1000 person-days; 95% CI, −5.58 to −0.38; P = .046). Universal glove and gown use also decreased health care worker room entry (4.28 vs 5.24 entries per hour, difference, −0.96; 95% CI, −1.71 to −0.21, P = .02), increased room-exit hand hygiene compliance (78.3% vs 62.9%, difference, 15.4%; 95% CI, 8.99% to 21.8%; P = .02) and had no statistically significant effect on rates of adverse events (58.7 events per 1000 patient days vs 74.4 events per 1000 patient days; difference, −15.7; 95% CI, −40.7 to 9.2, P = .24).
Conclusions and Relevance
The use of gloves and gowns for all patient contact compared with usual care among patients in medical and surgical ICUs did not result in a difference in the primary outcome of acquisition of MRSA or VRE. Although there was a lower risk of MRSA acquisition alone and no difference in adverse events, these secondary outcomes require replication before reaching definitive conclusions.
doi:10.1001/jama.2013.277815
PMCID: PMC4026208  PMID: 24097234
11.  Successful Control of Methicillin-Resistant Staphylococcus aureus in Endemic Neonatal Intensive Care Units—A 7-Year Campaign 
PLoS ONE  2011;6(8):e23001.
Background
Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important nosocomial pathogens in the intensive care unit (ICU) worldwide, including Taiwan. Since 1997, our neonatal ICUs (NICUs) had become endemic for MRSA.
Methodology/Principal Findings
To control MRSA spread in our NICUs, we implemented a series of infection control measures stepwise, including reinforcement of hand hygiene since January 2000, augmentation of aseptic care over the insertion site of central venous catheter since July 2001, introduction of alcohol-based handrubs since April 2003, surveillance culture for MRSA and cohort care for the colonized patients between March 2003 and February 2004, and surveillance culture with subsequent decolonization of MRSA between August 2005 and July 2006. After implementation of these measures, MRSA healthcare-associated infection (HAI) density reduced by 92%, from 5.47 episodes per 1000 patient-days in 1999 to 0.45 episodes per 1000 patient-days in 2006; MRSA bloodstream infection reduced from 40 cases in 1999 to only one case in 2006. Compared to those obtained during the period of surveillance culture without decolonization, both rates of MRSA colonization (8.6% vs. 41%, p<0.001) and infection (1.1% vs. 12%, p<0.001) decreased significantly during the period of surveillance and decolonization. Molecular analysis of the clinical isolates during the study period showed that the endemic clone, which dominated between 1998 and 2005, almost disappeared in 2006, while the community clones increased significantly in 2006–2007.
Conclusion/Significance
Through infection control measures, MRSA HAIs can be successfully controlled, even in areas with high levels of endemic MRSA infections such as our NICUs.
doi:10.1371/journal.pone.0023001
PMCID: PMC3155524  PMID: 21857979
12.  Automated Detection of Infectious Disease Outbreaks in Hospitals: A Retrospective Cohort Study 
PLoS Medicine  2010;7(2):e1000238.
Susan Huang and colleagues describe an automated statistical software, WHONET-SaTScan, its application in a hospital, and the potential it has to identify hospital infection clusters that had escaped routine detection.
Background
Detection of outbreaks of hospital-acquired infections is often based on simple rules, such as the occurrence of three new cases of a single pathogen in two weeks on the same ward. These rules typically focus on only a few pathogens, and they do not account for the pathogens' underlying prevalence, the normal random variation in rates, and clusters that may occur beyond a single ward, such as those associated with specialty services. Ideally, outbreak detection programs should evaluate many pathogens, using a wide array of data sources.
Methods and Findings
We applied a space-time permutation scan statistic to microbiology data from patients admitted to a 750-bed academic medical center in 2002–2006, using WHONET-SaTScan laboratory information software from the World Health Organization (WHO) Collaborating Centre for Surveillance of Antimicrobial Resistance. We evaluated patients' first isolates for each potential pathogenic species. In order to evaluate hospital-associated infections, only pathogens first isolated >2 d after admission were included. Clusters were sought daily across the entire hospital, as well as in hospital wards, specialty services, and using similar antimicrobial susceptibility profiles. We assessed clusters that had a likelihood of occurring by chance less than once per year. For methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE), WHONET-SaTScan–generated clusters were compared to those previously identified by the Infection Control program, which were based on a rule-based criterion of three occurrences in two weeks in the same ward. Two hospital epidemiologists independently classified each cluster's importance. From 2002 to 2006, WHONET-SaTScan found 59 clusters involving 2–27 patients (median 4). Clusters were identified by antimicrobial resistance profile (41%), wards (29%), service (13%), and hospital-wide assessments (17%). WHONET-SaTScan rapidly detected the two previously known gram-negative pathogen clusters. Compared to rule-based thresholds, WHONET-SaTScan considered only one of 73 previously designated MRSA clusters and 0 of 87 VRE clusters as episodes statistically unlikely to have occurred by chance. WHONET-SaTScan identified six MRSA and four VRE clusters that were previously unknown. Epidemiologists considered more than 95% of the 59 detected clusters to merit consideration, with 27% warranting active investigation or intervention.
Conclusions
Automated statistical software identified hospital clusters that had escaped routine detection. It also classified many previously identified clusters as events likely to occur because of normal random fluctuations. This automated method has the potential to provide valuable real-time guidance both by identifying otherwise unrecognized outbreaks and by preventing the unnecessary implementation of resource-intensive infection control measures that interfere with regular patient care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Admission to a hospital is often a life-saving necessity—individuals injured in a road accident, for example, may need immediate medical and surgical attention if they are to survive. Unfortunately, many patients acquire infections, some of which are life-threatening, during their stay in a hospital. The World Health Organization has estimated that, globally, 8.7% of hospital patients develop hospital-acquired infections (infections that are identified more than two days after admission to hospital). In the US alone, 2 million people develop a hospital-acquired infection every year, often an infection of a surgical wound, or a urinary tract or lung infection. Infections are common among hospital patients because increasing age or underlying illnesses can reduce immunity to infection and because many medical and surgical procedures bypass the body's natural protective barriers. In addition, poor infection control practices can facilitate the transmission of bacteria—including meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE)—and other infectious agents (pathogens) between patients.
Why Was This Study Done?
Sometimes, the number of cases of hospital-acquired infections increases unexpectedly or a new infection emerges. Such clusters account for relatively few health care–associated infections, but, because they may arise from the transmission of a pathogen within a hospital, they need to be rapidly identified and measures implemented (for example, isolation of affected patients) to stop transmission if an outbreak is confirmed. Currently, the detection of clusters of hospital-acquired infections is based on simple rules, such as the occurrence of three new cases of a single pathogen in two weeks on the same ward. This rule-based approach relies on the human eye to detect infection clusters within microbiology data (information collected on the pathogens isolated from patients), it focuses on a few pathogens, and it does not consider the random variation in infection rates or the possibility that clusters might be associated with shared facilities rather than with individual wards. In this study, the researchers test whether an automated statistical system can detect outbreaks of hospital-acquired infections quickly and accurately.
What Did the Researchers Do and Find?
The researchers combined two software packages used to track diseases in populations to create the WHONET-SaTScan cluster detection tool. They then compared the clusters of hospital-acquired infection identified by the new tool in microbiology data from a 750-bed US academic medical center with those generated by the hospital's infection control program, which was largely based on the simple rule described above. WHONET-SaTScan found 59 clusters of infection that occurred between 2002 and 2006, about three-quarters of which were identified by characteristics other than a ward-based location. Nearly half the cluster alerts were generated on the basis of shared antibiotic susceptibility patterns. Although WHONET-SaTScan identified all the clusters previously identified by the hospital's infection control program, it classified most of these clusters as likely to be the result of normal random variations in infection rates rather than the result of “true” outbreaks. By contrast, the hospital's infection control department only identified three of the 59 statistically significant clusters identified by WHONET-SaTScan. Furthermore, the new tool identified six previously unknown MRSA outbreaks and four previously unknown VRE outbreaks. Finally, two hospital epidemiologists (scientists who study diseases in populations) classified 95% of the clusters detected by WHONET-SaTScan as worthy of consideration by the hospital infection control team and a quarter of the clusters as warranting active investigation or intervention.
What Do These Findings Mean?
These findings suggest that automated statistical software should be able to detect clusters of hospital-acquired infections that would escape detection using routine rule-based systems. Importantly, they also suggest that an automated system would be able to discount a large number of supposed outbreaks identified by rule-based systems. These findings need to be confirmed in other settings and in prospective studies in which the outcomes of clusters detected with WHONET-SaTScan are carefully analyzed. For now, however, these findings suggest that automated statistical tools could provide hospital infection control experts with valuable real-time guidance by identifying outbreaks that would be missed by routine detection methods and by preventing the implementation of intensive and costly infection control measures in situations where they are unnecessary.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000238.
The World Health Organization's Prevention of Hospital-Acquired Infections, A Practical Guide contains detailed information on all aspects of hospital-acquired infections
MedlinePlus provides links to information on infection control in hospitals (in English and Spanish)
The US Centers for Disease Control and Prevention also provides information on infectious diseases in health care settings (in English and Spanish)
The WHONET/Baclink software and the SatScan software, the two components of WHONET-SaTScan are both available on the internet (the WHONET-SaTScan cluster detection tool is freely available as part of the version of WHONET/BacLink released June 2009)
doi:10.1371/journal.pmed.1000238
PMCID: PMC2826381  PMID: 20186274
13.  Trends in Staphylococcus aureus bacteraemia and impacts of infection control practices including universal MRSA admission screening in a hospital in Scotland, 2006–2010: retrospective cohort study and time-series intervention analysis 
BMJ Open  2012;2(3):e000797.
Objectives
To describe secular trends in Staphylococcus aureus bacteraemia (SAB) and to assess the impacts of infection control practices, including universal methicillin-resistant Staphylococcus aureus (MRSA) admission screening on associated clinical burdens.
Design
Retrospective cohort study and multivariate time-series analysis linking microbiology, patient management and health intelligence databases.
Setting
Teaching hospital in North East Scotland.
Participants
All patients admitted to Aberdeen Royal Infirmary between 1 January 2006 and 31 December 2010: n=420 452 admissions and 1 430 052 acute occupied bed days (AOBDs).
Intervention
Universal admission screening programme for MRSA (August 2008) incorporating isolation and decolonisation.
Primary and secondary measures
Hospital-wide prevalence density, hospital-associated incidence density and death within 30 days of MRSA or methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia.
Results
Between 2006 and 2010, prevalence density of all SAB declined by 41%, from 0.73 to 0.50 cases/1000 AOBDs (p=0.002 for trend), and 30-day mortality from 26% to 14% (p=0.013). Significant reductions were observed in MRSA bacteraemia only. Overnight admissions screened for MRSA rose from 43% during selective screening to >90% within 4 months of universal screening. In multivariate time-series analysis (R2 0.45 to 0.68), universal screening was associated with a 19% reduction in prevalence density of MRSA bacteraemia (−0.035, 95% CI −0.049 to −0.021/1000 AOBDs; p<0.001), a 29% fall in hospital-associated incidence density (−0.029, 95% CI −0.035 to −0.023/1000 AOBDs; p<0.001) and a 46% reduction in 30-day mortality (−15.6, 95% CI −24.1% to −7.1%; p<0.001). Positive associations with fluoroquinolone and cephalosporin use suggested that antibiotic stewardship reduced prevalence density of MRSA bacteraemia by 0.027 (95% CI 0.015 to 0.039)/1000 AOBDs. Rates of MSSA bacteraemia were not significantly affected by screening or antibiotic use.
Conclusions
Declining clinical burdens from SAB were attributable to reductions in MRSA infections. Universal admission screening and antibiotic stewardship were associated with decreases in MRSA bacteraemia and associated early mortality. Control of MSSA bacteraemia remains a priority.
Article summary
Article focus
This study describes the changing epidemiology of MRSA and MSSA bacteraemia in a large inpatient population from Scotland over a 5-year period.
Second, it evaluates the impact of universal MRSA admission screening, and other infection control practices, on hospital-wide rates of MRSA bacteraemia.
Key messages
Recent declines in clinical burdens from SAB in North East Scotland were attributable to a reduction in invasive MRSA infections.
Compared with a strategy of targeted screening in high-risk environments, universal admission screening may significantly reduce rates of MRSA bacteraemia and associated early mortality alongside improvements in antibiotic stewardship and infection control.
Strategies to reduce clinical burdens from MSSA bacteraemia are required if progress towards national targets for all SAB is to be sustained.
Strengths and limitations of this study
Without a contemporary control, this study did not prove causality but a temporal association between universal admission screening and rates of MRSA bacteraemia.
ARIMA modelling accounted for the non-independence of data and stochastic elements in time series of infections, and the dynamic effects of changes in other aspects of care.
Findings may be limited to large public hospitals with intensive care units and endemic MRSA but low rates of MRSA infection.
doi:10.1136/bmjopen-2011-000797
PMCID: PMC3378947  PMID: 22685226
14.  Hospital-wide infection control practice and Meticillin-resistant Staphylococcus aureus (MRSA) in the intensive care unit (ICU): an observational study 
JRSM Open  2014;5(10):2054270414547145.
Summary
Objectives
To estimate trends in infection/colonisation with meticillin-resistant Staphylococcus aureus (MRSA) in an intensive care unit (ICU).
Design
Observational study of results of ICU admission and weekly screens for MRSA.
Setting and Participants
All ICU admissions in 2001–2012.
Interventions
ICU admissions were screened for MRSA throughout. In late 2006, screening was extended to the whole hospital and extra measures taken in ICU.
Main outcome measures
Prevalence of MRSA in ICU admissions and number acquiring MRSA therein.
Results
In all, 366 of 6565 admissions to ICU were MRSA positive, including 270 of 4466 coming from within the hospital in which prevalence increased with time prior to transfer to ICU. Prevalence in this group was 9.4% (8.2–10.6) in 2001–2006, decreasing to 3.4% (2.3–4.5) in 2007–2009 and 1.3% (0.6–2.0) in 2010–2012, p < 0.001, due to decreased prevalence in those spending >5 days on wards before ICU admission: 18.9% (15.6–22.2) in 2001–2006, 7.1% (4.0–10.2) in 2007–2009 and 1.6% (0.1–3.1) in 2010–2012, p < 0.001. In addition, 201 patients acquired MRSA within ICU, the relative risk being greater when known positives present: 4.34 (3.98–4.70), p < 0.001. Acquisition rate/1000 bed days decreased from 13.3 (11.2–15.4) in 2001–2006 to 3.6 (2.6–4.6) in 2007–2012, p < 0.0001. Of 41 ICU-acquired MRSA bacteraemias, 38 were in 2001–2006. The risk of bacteraemia in those acquiring MRSA decreased from 25% (18.1–31.9) in 2001–2006 to 6.1% (0–12.8) thereafter, p = 0.022.
Conclusions
Following better hospital-wide infection control, fewer MRSA-positive patients were admitted to ICU with a parallel decrease in acquisition therein. Better practice there reduced the risk of bacteraemia.
doi:10.1177/2054270414547145
PMCID: PMC4221953  PMID: 25383196
MRSA; ICU; Infection Control
15.  Increase in the Prevalence of Carbapenem-Resistant Acinetobacter Isolates and Ampicillin-Resistant Non-Typhoidal Salmonella Species in Korea: A KONSAR Study Conducted in 2011 
Infection & Chemotherapy  2014;46(2):84-93.
Background
Antimicrobial surveillance is important for providing an up-to-date understanding of the epidemiology of antimicrobial resistance and for creating a forum for rational drug development. In this study, we analyzed antimicrobial test data generated in 2011 by hospitals and commercial laboratories participating in the Korean Nationwide Surveillance of Antimicrobial Resistance program (KONSAR).
Materials and Methods
Data on the results of susceptibility tests conducted in 32 hospitals and two commercial laboratories were analyzed. Data on isolates from patients admitted to an intensive care unit (ICU) and those admitted to other wards were compared. Intermediate susceptibility was not analyzed and duplicate isolates were excluded.
Results
Escherichia coli was the most prevalent organism identified in both the hospital and commercial laboratories. Among the hospital isolates, methicillin-resistant Staphylococcus aureus (MRSA), penicillin G-non-susceptible Streptococcus pneumoniae, and ampicillin-resistant Enterococcus faecium remained as prevalent as they were in 2009. The proportion of vancomycin-resistant E. faecium (VR-EFM) slightly decreased from 29% in 2009 to 23% in 2011. Resistance rates of Klebsiella pneumoniae to ceftazidime, cefoxitin, fluoroquinolone, and amikacin were 24%, 14%, 27%, and 8%, respectively. Resistance rates of Pseudomonas aeruginosa to fluoroquinolone, ceftazidime, imipenem, and amikacin were 33%, 20%, 22%, and 16%, respectively, whereas those of Acinetobacter spp. resistance were 71%, 66%, 64, and 51%, respectively. The prevalence of oxyimino-cephalosporin-resistant E. coli and K. pneumoniae, carbapenem-resistant Acinetobacter spp. and P. aeruginosa, MRSA, and VR-EFM among ICU isolates was higher than those among non-ICU isolates. Extended-spectrum β-lactamase-producing E. coli and K. pneumoniae, imipenem-resistant P. aeruginosa, and VR-EFM were more prevalent among isolates from commercial laboratories than those from hospitals. Resistance rates of K. pneumoniae to ceftazidime and amikacin decreased from 32% and 24% in 2005 to 24% and 8% in 2011, respectively. The resistance rate of P. aeruginosa to amikacin decreased from 22% in 2005 to 16% in 2011. The proportion of imipenem-resistant Acinetobacter spp. increased from 16% in 2005 to 64% in 2011.
Conclusions
The prevalence of MRSA, penicillin G-non-susceptible S. pneumoniae, and ampicillin-resistant E. faecium among clinical isolates tested in laboratories remained high. Multidrug resistance was more prevalent among isolates from ICUs. The prevalence of ceftazidime-resistant and amikacin-resistant K. pneumoniae and amikacin-resistant P. aeruginosa decreased after 2005, while the prevalence of imipenem-resistant Acinetobacter spp. increased.
doi:10.3947/ic.2014.46.2.84
PMCID: PMC4091365  PMID: 25024870
Antimicrobial resistance surveillance; KONSAR; Staphylococcus; Acinetobacter; Pseudomonas aeruginosa
16.  Increasing Burden of Methicillin-Resistant Staphylococcus aureus Hospitalizations at US Academic Medical Centers, 2003–2008 
OBJECTIVE
The incidence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in the United States decreased during 2005–2008, but noninvasive community-associated MRSA (CA-MRSA) infections also frequently lead to hospitalization. We estimated the incidence of all MRSA infections among inpatients at US academic medical centers (AMCs) per 1,000 admissions during 2003–2008.
DESIGN
Retrospective cohort study.
SETTING AND PARTICIPANTS
Hospitalized patients at 90% of nonprofit US AMCs during 2003–2008.
METHODS
Administrative data on MRSA infections from a hospital discharge database (University HealthSystem Consortium [UHC]) were adjusted for underreporting of the MRSA V09.0 International Classification of Diseases, Ninth Revision, Clinical Modification code and validated using chart reviews for patients with known MRSA infections in 2004–2005, 2006, and 2007.
RESULTS
The mean sensitivity of administrative data for MRSA infections at the University of Chicago Medical Center in three 12-month periods during 2004–2007 was 59.1%. On the basis of estimates of billing data sensitivity from the literature and the University of Chicago Medical Center, the number of MRSA infections per 1,000 hospital discharges at US AMCs increased from 20.9 (range, 11.1–47.7) in 2003 to 41.7 (range, 21.9–94.0) in 2008. At the University of Chicago Medical Center, among infections cultured more than 3 days prior to hospital discharge, CA-MRSA infections were more likely to be captured in the UHC billing–derived data than were healthcare-associated MRSA infections.
CONCLUSIONS
The number of hospital admissions for any MRSA infection per 1,000 hospital admissions overall increased during 2003–2008. Use of unadjusted administrative hospital discharge data or surveillance for invasive disease far underestimates the number of MRSA infections among hospitalized patients.
doi:10.1086/666640
PMCID: PMC3682488  PMID: 22759545
17.  One-day point prevalence of emerging bacterial pathogens in a nationwide sample of 62 German hospitals in 2012 and comparison with the results of the one-day point prevalence of 2010 
Background: Antibiotic resistance of bacterial pathogens is an emerging problem worldwide. To combat multidrug resistant organisms (MRDOs) networks of care providers have been established in all states in Germany. The HICARE-network, a project to combat MRDOs, founded by the Federal Ministry of Education and Research, has published data from 2010 of a voluntary, German-wide, multicenter point-prevalence survey in 2011 conducted in collaboration with the German Society of Hospital Hygiene. The aim of the present survey was the re-evaluation of the situation in 2012.
Method: The survey was conducted as a voluntary, anonymous, point-prevalence in May 2012 using routine data of microbiological diagnostics of the hospitals. As in the former survey of 2010 it was differentiated between primary, secondary and tertiary care hospitals and only data from intensive care units, surgical and medical wards were collected. Based on the survey form used in 2010, an updated version was used including more pathogens and corrected issues observed in the former survey. Methicillin-resistant Staphylococcus aureus (MRSA) (total as well as separated in hospital-acquired (HA), community-acquired (CA) and lifestock-associated (LA) MRSA), vancomycin resistant Staphylococcus aureus (VRSA/GRSA), vancomycin resistant Enterococcus faecalis resp. Enterococcus faecium (VR-E. faecalis resp. VR-E. faecium), extended-spectrum-beta-lactamase-building (ESBL) E. coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP), multiresistant Acinetobacter spp. (MAB), multiresistant Pseudomonas spp. (MRP), carbapenemase-producing Enterobacteriaceae (CRE) as well as Clostridium difficile (CD) infections and severe infections requiring ICU-treatment were included in the survey along with additional data on screening strategy, the equipment with infection control staff and possible confounders.
Results: Out of 1,550 hospitals asked to participate, 62 returned data (4%). Data from 56 hospitals including primary (26), secondary (20) and tertiary (10) care hospitals were analyzable (3.6%).
The most frequently reported organisms were MRSA 1.53% [CI95: 1.32–1.75], followed by CDAD 1.30% [CI95: 1.11–1.50], ESBL-EC 0.97% [CI95: 0.80–1.14], and ESBL-KP 0.27% [CI95: 0.18–0.36], regardless of the level of care. Prevalence of MRDOs depended on the level of care and on the type of ward, as expected. Overall prevalence was highest on intensive care wards, and prevalences were remarkably high on medical wards compared to surgical wards.
All tertiary care providers employed their own infection control nurse, while only ~70% of the secondary and primary care hospitals did. Surprisingly, in two of the ten participating tertiary care providers neither an internal nor an external infection control doctor was available.
Discussion: With more than 13,000 patients in 56 hospitals distributed all over Germany, the survey included more than three times as many patients as the first survey and therefore not only adds valuable information about the epidemiology of emerging nosocomial pathogens, but also helps to raise awareness of the problem of antibacterial resistance in Germany. The prevalences reported seem to be comparable to the results of the former survey and of other surveys published. Some hospitals reported to have no infection control personnel available at all. This statement is in line with another survey published in this issue.
doi:10.3205/dgkh000212
PMCID: PMC3746607  PMID: 23967398
point prevalence; MRDOs; HICARE-network; MRSA; CDAD; ESBL; VRE; infection control staff; type of screening
18.  Methicillin-Resistant Staphylococcus aureus Colonization and Risk of Subsequent Infection in Critically Ill Children: Importance of Preventing Nosocomial Methicillin-Resistant Staphylococcus aureus Transmission 
Methicillin-resistant Staphylococcus aureus (MRSA) colonization is a risk factor for infection in critically ill children. Almost half of children who acquired MRSA colonization in our ICU developed an MRSA infection during their hospitalization or after discharge, highlighting the importance of preventing nosocomial MRSA transmission.
Background. Methicillin-resistant Staphylococcus aureus (MRSA) colonization is a predictor of subsequent infection in hospitalized adults. The risk of subsequent MRSA infections in hospitalized children colonized with MRSA is unknown.
Methods. Children admitted to an academic medical center’s pediatric intensive care unit between March 2007 and March 2010 were included in the study. Anterior naris swabs were cultured to identify children with MRSA colonization at admission. Laboratory databases were queried and National Healthcare Safety Network definitions applied to identify patients with MRSA infections during their hospitalization or after discharge.
Results. The MRSA admission prevalence among 3140 children was 4.9%. Overall, 56 children (1.8%) developed an MRSA infection, including 13 (8.5%) colonized on admission and 43 (1.4%) not colonized on admission (relative risk [RR], 5.9; 95% confidence interval [CI], 3.4–10.1). Of those, 10 children (0.3%) developed an MRSA infection during their hospitalization, including 3 of 153 children (1.9%) colonized on admission and 7 of 2987 children (0.2%) not colonized on admission (RR, 8.4; 95% CI, 2.7–25.8). African-Americans and those with public health insurance were more likely to get a subsequent infection (P < .01 and P = .03, respectively). We found that 15 children acquired MRSA colonization in the pediatric intensive care unit, and 7 (47%) developed a subsequent MRSA infection.
Conclusions. MRSA colonization is a risk factor for subsequent MRSA infection in children. Although MRSA colonized children may have lower risks of subsequent infection than adults, children who acquire MRSA in the hospital have similarly high rates of infection. Preventing transmission of MRSA in hospitalized children should remain a priority.
doi:10.1093/cid/cir547
PMCID: PMC3189167  PMID: 21878424
19.  Impact of surveillance of hospital-acquired infections on the incidence of ventilator-associated pneumonia in intensive care units: a quasi-experimental study 
Critical Care  2012;16(4):R161.
Introduction
The preventive impact of hospital-acquired infection (HAI) surveillance is difficult to assess. Our objective was to investigate the effect of HAI surveillance disruption on ventilator-associated pneumonia (VAP) incidence.
Methods
A quasi-experimental study with an intervention group and a control group was conducted between 1 January 2004 and 31 December 2010 in two intensive care units (ICUs) of a university hospital that participated in a national HAI surveillance network. Surveillance was interrupted during the year 2007 in unit A (intervention group) and was continuous in unit B (control group). Period 1 (pre-test period) comprised patients hospitalized during 2004 to 2006, and period 2 (post-test period) involved patients hospitalized during 2008 to 2010. Patients hospitalized ≥48 hours and intubated during their stay were included. Multivariate Poisson regression was fitted to ascertain the influence of surveillance disruption.
Results
A total of 2,771 patients, accounting for 19,848 intubation-days at risk, were studied; 307 had VAP. The VAP attack rate increased in unit A from 7.8% during period 1 to 17.1% during period 2 (P <0.001); in unit B, it was 7.2% and 11.2% for the two periods respectively (P = 0.17). Adjusted VAP incidence rose in unit A after surveillance disruption (incidence rate ratio = 2.17, 95% confidence interval 1.05 to 4.47, P = 0.036), independently of VAP trend; no change was observed in unit B. All-cause mortality and length of stay increased (P = 0.028 and P = 0.038, respectively) in unit A between periods 1 and 2. In unit B, no change in mortality was observed (P = 0.22), while length of stay decreased between periods 1 and 2 (P = 0.002).
Conclusions
VAP incidence, length of stay and all-cause mortality rose after HAI surveillance disruption in ICU, which suggests a specific effect of HAI surveillance on VAP prevention and reinforces the role of data feedback and counselling as a mechanism to facilitate performance improvement.
doi:10.1186/cc11484
PMCID: PMC3580751  PMID: 22909033
20.  Successful control of a Methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit: a retrospective, before-after study 
BMC Infectious Diseases  2013;13:440.
Background
Aim of this study was to provide a detailed description of a Methicillin-resistant Staphylococcus aureus (MRSA) outbreak management strategy in the neonatal intensive care unit of a university hospital.
Methods
This was a retrospective, “before-after” study, over two consecutive 18-month periods. The outbreak management strategy was performed by a multidisciplinary team and included: extensive healthcare workers (HCW) involvement, education, continuous hand-hygiene training and active MRSA colonization surveillance. The actions implemented were identified based on an anonymous, voluntary, reporting system, carried out among all the HCW, and regular audit and feedback were provided to the nursing staff.
The main measured outcome was the rate of MRSA infections before and after the implementation of the outbreak management strategy. Piecewise linear Poisson regression was performed and the model adjusted for confounding variables. The secondary outcome was the rate of laboratory-confirmed bloodstream infections before and after the outbreak management strategy. The rates of MRSA colonization, implementation of proposed actions, observed compliance for hand-hygiene and insertion/care of central lines were also recorded during the second period.
Results
1015 newborns were included. The rate of MRSA infections throughout the two periods fell from 3.5 to 0.7 cases per 1000 patient-days (p=0.0005). The piecewise Poisson regression analysis adjusted for confounding variables showed a significant decrease in the MRSA infection rate after the outbreak management strategy (p=0.046). A significant decrease in positive laboratory confirmed blood cultures was observed over the two periods (160 vs 83; p<0.0001). A significant decline in the MRSA colonization rate occurred over the second period (p=0.001); 93% of the proposed actions were implemented. The compliance rate for hand-hygiene and insertion/care of central lines was respectively 95.9% and 62%.
Conclusions
The implementation of multiple, simultaneous, evidence-based management strategies is effective for controlling nosocomial infections. Outbreak management strategies may benefit from tools improving the communication between the institutional and scientific leadership and the ground-level staff. These measures can help to identify individualized solutions addressing specific unit needs.
doi:10.1186/1471-2334-13-440
PMCID: PMC3849690  PMID: 24053628
Quality-improvement; Practices; Newborn; Hospital-acquired infection; Community; Endemic; Voice, Bundle
21.  Methicillin-resistant Staphylococcus aureus nosocomial infection trends in Hospital Universiti Sains Malaysia during 2002-2007 
Annals of Saudi Medicine  2010;30(5):358-363.
BACKGROUND AND OBJECTIVES:
Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen that causes severe morbidity and mortality in many hospitals worldwide. The aim of the present study was to assess the burden of MRSA nosocomial infection, its association with factors of interest, and its antimicrobial susceptibility.
METHODS:
This was a retrospective analysis of a database of all S aureus that were cultured from patients admitted to the different wards of Hospital Universiti Sains Malaysia (HUSM) over a period of 6 years.
RESULTS:
The MRSA infections rate was 10.0 per 1000 hospital admissions. The incidence density rate of MRSA infections during the study period was 1.8 per 1000 patient-days, with annual rates ranging from 0.95 to 3.47 per 1000 patient-days. Duration of hospitalization, previous antibiotic use, and bedside invasive procedures were significantly higher among MRSA than methicillin-sensitive S aureus patients (P>.05). The highest number of MRSA infections were found in orthopedic wards (25.3%), followed by surgical wards (18.2%) and intensive care units (ICUs) (16.4%). All MRSA isolates were resistant to erythromycin (98.0%), co-trimoxazole (94.0%) and gentamicin (92.0%). Clindamycin was the best antibiotic with only 6% resistance. All MRSA isolates were sensitive to vancomycin.
CONCLUSION:
The rate of nosocomial MRSA infection per 1000 admissions was higher than that in other studies. The three factors associated most significantly with acquired MRSA infections included duration of hospitalization, antibiotic use, and bedside invasive procedures. This study confirmed that vancomycin-resistant S aureus has not yet been established in HUSM.
doi:10.4103/0256-4947.67077
PMCID: PMC2941247  PMID: 20697171
22.  The impact of serum vancomycin levels and minimum inhibitory concentrations of methicillin-resistant Staphylococcus aureus on mortality in patients with nosocomial pneumonia 
BACKGROUND:
Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure is not uncommon, even when the minimum inhibitory concentration (MIC) of the MRSA strain is within the susceptible range for vancomycin.
OBJECTIVE:
To describe the relationship between molecular markers such as the mecA and agrII genes, serum vancomycin levels and vancomycin MICs, and the 30-day mortality rate of patients with nosocomial MRSA pneumonia in an intensive care unit (ICU).
METHODS:
The present study was a prospective cohort study including all patients with MRSA hospital-acquired pneumonia or ventilator-associated pneumonia who were admitted to the ICU of a tertiary care hospital between June 2009 and December 2011. The MIC for vancomycin was determined using the E-test and broth microdilution methods. Variables analyzed included age, sex, comorbid conditions, serum vancomycin trough concentration, the Acute Physiology and Chronic Health Evaluation II (APACHE) score and the presence of the agrII gene. The primary outcome was mortality at 30 days.
RESULTS:
Thirty-six (42.4%) patients died within 30 days of the index MRSA culture. A multiple regression analysis that included the variables of MIC (determined using the E-test or broth microdilution methods), APACHE II score, serum vancomycin level and the presence of agrII revealed that only the APACHE II score was related to the 30-day mortality rate (P=0.03). Seven patients (9.0%) with isolates exhibiting an MIC ≥1.5 μg/mL according to the E-test method died, and nine patients (11.6%) survived (P=0.76). Of the patients for whom MICs were determined using the broth microdilution method, 11 (14.1%) patients with MICs of 1.0 μg/mL died, and 16 (20.5%) survived (P=0.92). The median APACHE II score of survivors was 22.5, and the median score of nonsurvivors was 25.0 (P=0.03). The presence of the agrII gene was not related to the 30-day mortality rate.
CONCLUSIONS:
Patients with severe hospital-acquired pneumonia presented with MRSA isolates with low to intermediate vancomycin MICs in the ICU setting. At the Hospital de Clínicas de Porto Alegre (Porto Alegre, Brazil), the 30-day mortality rate was high, and was similar among patients with severe hospital-acquired pneumonia infected with MRSA isolates that exhibited MICs of ≤1.5 μg/mL determined using the E-test method and ≤1.0 μg/mL determined using the broth microdilution method in those who achieved optimal serum vancomycin levels. The APACHE II scores which provides an overall estimate of ICU mortality were independently associated with mortality in the present study, regardless of the MICs determined. Molecular markers, such as the agrII gene, were not associated with higher mortality in the present study.
PMCID: PMC3852462  PMID: 24421835
Methicillin-resistant Staphylococcus aureus; Nosocomial pneumonia; Vancomycin
23.  Intensive care unit-acquired urinary tract infections in a regional critical care system 
Critical Care  2005;9(2):R60-R65.
Introduction
Few studies have evaluated urinary tract infections (UTIs) specifically acquired within intensive care units (ICUs), and the effect of such infections on patient outcome is unclear. The objectives of this study were to describe the occurrence, microbiology, and risk factors for acquiring UTIs in the ICU and to determine whether these infections independently increase mortality.
Methods
A surveillance cohort study was conducted among all adults admitted to multi-system and cardiovascular surgery ICUs in the Calgary Health Region (CHR, population about 1 million) between 1 January 2000 and 31 December 2002.
Results
During the 3 years, 4465 patients were admitted 4915 times to a CHR ICU for 48 hours or more. A total of 356 ICU-acquired UTIs (defined as at least 105 colony-forming units/ml of one or two organisms 48 hours or more after ICU admission) occurred among 290 (6.5%) patients, yielding an overall incidence density of ICU-acquired UTIs of 9.6 per 1000 ICU days. Four bacteremic/fungemic ICU-acquired UTIs occurred (0.1 per 1000 ICU days). Development of an ICU-acquired UTI was more common in women (relative risk [RR] 1.58; 95% confidence interval [CI] 1.43–1.75; P < 0.0001) and in medical (9%) compared with non-cardiac surgical (6%), and cardiac surgical patients (2%). The most common organisms isolated were Escherichia coli (23%), Candida albicans (20%), and Enterococcus species (15%). Antibiotic-resistant organisms were identified among 14% isolates. Although development of an ICU-acquired UTI was associated with significantly higher crude in-hospital mortality (86/290 [30%] vs. 862/4167 [21%]; RR = 1.43; 95% CI 1.19–1.73; P < 0.001); an ICU-acquired UTI was not an independent predictor for death.
Conclusions
Development of an ICU-acquired UTI is common in critically ill patients. Although a marker of increased morbidity associated with critical illness, it is not a significant attributable cause of mortality.
doi:10.1186/cc3023
PMCID: PMC1175915  PMID: 15774051
incidence; intensive care unit; mortality; urinary tract infection
24.  Introduction of Medical Emergency Teams in Australia and New Zealand: a multi-centre study 
Critical Care  2008;12(2):R46.
Introduction
Information about Medical Emergency Teams (METs) in Australia and New Zealand (ANZ) is limited to local studies and a cluster randomised controlled trial (the Medical Emergency Response and Intervention Trial [MERIT]). Thus, we sought to describe the timing of the introduction of METs into ANZ hospitals relative to relevant publications and to assess changes in the incidence and rate of intensive care unit (ICU) admissions due to a ward cardiac arrest (CA) and ICU readmissions.
Methods
We used the Australian and New Zealand Intensive Care Society database to obtain the study data. We related MET introduction to publications about adverse events and MET services. We compared the incidence and rate of readmissions and admitted CAs from wards before and after the introduction of an MET. Finally, we identified hospitals without an MET system which had contributed to the database for at least two years from 2002 to 2005 and measured the incidence of adverse events from the first year of contribution to the second.
Results
The MET status was known for 131 of the 172 (76.2%) hospitals that did not participate in the MERIT study. Among these hospitals, 110 (64.1%) had introduced an MET service by 2005. In the 79 hospitals in which the MET commencement date was known, 75% had introduced an MET by May 2002. Of the 110 hospitals in which an MET service was introduced, 24 (21.8%) contributed continuous data in the year before and after the known commencement date. In these hospitals, the mean incidence of CAs admitted to the ICU from the wards changed from 6.33 per year before to 5.04 per year in the year after the MET service began (difference of 1.29 per year, 95% confidence interval [CI] -0.09 to 2.67; P = 0.0244). The incidence of ICU readmissions and the mortality for both ICU-admitted CAs from wards and ICU readmissions did not change. Data were available to calculate the change in ICU admissions due to ward CAs for 16 of 62 (25.8%) hospitals without an MET system. In these hospitals, admissions to the ICU after a ward CA decreased from 5.0 per year in the first year of data contribution to 4.2 per year in the following year (difference of 0.8 per year, 95% CI -0.81 to 3.49; P = 0.3).
Conclusion
Approximately 60% of hospitals in ANZ with an ICU report having an MET service. Most introduced the MET service early and in association with literature related to adverse events. Although available in only a quarter of hospitals, temporal trends suggest an overall decrease in the incidence of ward CAs admitted to the ICU in MET as well as non-MET hospitals.
doi:10.1186/cc6857
PMCID: PMC2447594  PMID: 18394192
25.  Mortality and Hospital Stay Associated with Resistant Staphylococcus aureus and Escherichia coli Bacteremia: Estimating the Burden of Antibiotic Resistance in Europe 
PLoS Medicine  2011;8(10):e1001104.
The authors calculate excess mortality, excess hospital stay, and related hospital expenditure associated with antibiotic-resistant bacterial bloodstream infections (Staphylococcus aureus and Escherichia coli) in Europe.
Background
The relative importance of human diseases is conventionally assessed by cause-specific mortality, morbidity, and economic impact. Current estimates for infections caused by antibiotic-resistant bacteria are not sufficiently supported by quantitative empirical data. This study determined the excess number of deaths, bed-days, and hospital costs associated with blood stream infections (BSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (G3CREC) in 31 countries that participated in the European Antimicrobial Resistance Surveillance System (EARSS).
Methods and Findings
The number of BSIs caused by MRSA and G3CREC was extrapolated from EARSS prevalence data and national health care statistics. Prospective cohort studies, carried out in hospitals participating in EARSS in 2007, provided the parameters for estimating the excess 30-d mortality and hospital stay associated with BSIs caused by either MRSA or G3CREC. Hospital expenditure was derived from a publicly available cost model. Trends established by EARSS were used to determine the trajectories for MRSA and G3CREC prevalence until 2015. In 2007, 27,711 episodes of MRSA BSIs were associated with 5,503 excess deaths and 255,683 excess hospital days in the participating countries, whereas 15,183 episodes of G3CREC BSIs were associated with 2,712 excess deaths and 120,065 extra hospital days. The total costs attributable to excess hospital stays for MRSA and G3CREC BSIs were 44.0 and 18.1 million Euros (63.1 and 29.7 million international dollars), respectively. Based on prevailing trends, the number of BSIs caused by G3CREC is likely to rapidly increase, outnumbering the number of MRSA BSIs in the near future.
Conclusions
Excess mortality associated with BSIs caused by MRSA and G3CREC is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. A foreseeable shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections will exacerbate this situation and is reason for concern.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Antimicrobial resistance—a consequence of the use and misuse of antimicrobial medicines—occurs when a microorganism becomes resistant (usually by mutation or acquiring a resistance gene) to an antimicrobial drug to which it was previously sensitive. Then standard treatments become ineffective, leading to persistent infections, which may spread to other people. With some notable exceptions such as TB, HIV, malaria, and gonorrhea, most of the disease burden attributable to antimicrobial resistance is caused by hospital-associated infections due to opportunistic bacterial pathogens. These bacteria often cause life-threatening or difficult-to-manage conditions such as deep tissue, wound, or bone infections, or infections of the lower respiratory tract, central nervous system, or blood stream. The two most frequent causes of blood stream infections encountered worldwide are Staphylococcus aureus and Escherichia coli.
Why Was This Study Done?
Although hospital-associated infections have gained much attention over the past decade, the overall effect of this growing phenomenon on human health and medical services has still to be adequately quantified. The researchers proposed to fill this information gap by estimating the impact—morbidity, mortality, and demands on health care services—of antibiotic resistance in Europe for two types of resistant organisms that are typically associated with resistance to multiple classes of antibiotics and can be regarded as surrogate markers for multi-drug resistance—methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli.
What Did the Researchers Do and Find?
Recently, the Burden of Resistance and Disease in European Nations project collected representative data on the clinical impact of antimicrobial resistance throughout Europe. Using and combining this information with 2007 prevalence data from the European Antibiotic Resistance Surveillance System, the researchers calculated the burden of disease associated with methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli blood stream infections. This burden of disease was expressed as excess number of deaths, excess number of days in hospital, and excess costs. Using statistical models, the researchers predicted trend-based resistance trajectories up to 2015 for the 31 participating countries in the European region.
The researchers included 1,293 hospitals from the 31 countries, typically covering 47% of all available acute care hospital beds in most countries, in their analysis. For S. aureus, the estimated number of blood stream infections totaled 108,434, of which 27,711 (25.6%) were methicillin-resistant. E. coli caused 163,476 blood stream infections, of which 15,183 (9.3%) were resistant to third-generation cephalosporins. An estimated 5,503 excess deaths were associated with blood stream infections caused by methicillin-resistant S. aureus (with the UK and France predicted to experience the highest excess mortality), and 2,712 excess deaths with blood stream infections caused by third-generation cephalosporin-resistant E. coli (predicted to be the highest in Turkey and the UK). The researchers also found that blood stream infections caused by both methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli contributed respective excesses of 255,683 and 120,065 extra bed-days, accounting for an estimated extra cost of 62.0 million Euros (92.8 million international dollars). In their trend analysis, the researchers found that 97,000 resistant blood stream infections and 17,000 associated deaths could be expected in 2015, along with increases in the lengths of hospital stays and costs. Importantly, the researchers estimated that in the near future, the burden of disease associated with third-generation cephalosporin-resistant E. coli is likely to surpass that associated with methicillin-resistant S. aureus.
What Do These Findings Mean?
These findings show that even though the blood stream infections studied represent only a fraction of the total burden of disease associated with antibiotic resistance, excess mortality associated with these infections caused by methicillin-resistant S. aureus and third-generation cephalosporin-resistant E. coli is high, and the associated prolonged length of stays in hospital imposes a considerable burden on health care systems in Europe. Importantly, a possible shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections is concerning. Such forecasts suggest that despite anticipated gains in the control of methicillin-resistant S. aureus, the increasing number of infections caused by third-generation cephalosporin-resistant Gram-negative pathogens, such as E. coli, is likely to outweigh this achievement soon. This increasing burden will have a big impact on already stretched health systems.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001104.
The World Health Organization has a fact sheet on general antimicrobial resistance
The US Centers for Disease Control and Prevention webpage on antibiotic/antimicrobial resistance includes information on educational campaigns and resources
The European Centre for Disease Control provides data about the prevalence of resistance in Europe through an interactive database
doi:10.1371/journal.pmed.1001104
PMCID: PMC3191157  PMID: 22022233

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