Using a longitudinal model to estimate the effect of methicillin-resistant staphylococcus aureus infection on length of stay in an intensive care unit

Healthcare-associated methicillin-resistant Staphylococcus aureus(MRSA) infection may cause increased hospital stay or, sometimes, death. Quantifying this effect is complicated because it is a time-dependent exposure: infection may prolong hospital stay, while longer stays increase the risk of infection. We overcome these problems by using a multinomial longitudinal model for estimating the daily probability of death and discharge. We then extend the basic model to estimate how the effect of MRSA infection varies over time, and to quantify the number of excess ICU days due to infection. We find that infection decreases the relative risk of discharge (relative risk ratio = 0.68, 95% credible interval: 0.54, 0.82), but is only indirectly associated with increased mortality. An infection on the first day of admission resulted in a mean extra stay of 0.3 days (95% CI: 0.1, 0.5) for a patient with an APACHE II score of 10, and 1.2 days (95% CI: 0.5, 2.0) for a patient with an APACHE II score of 30. The decrease in the relative risk of discharge remained fairly constant with day of MRSA infection, but was slightly stronger closer to the start of infection. These results confirm the importance of MRSA infection in increasing ICU stay, but suggest that previous work may have systematically overestimated the effect size.

An investigation of contact transmission of methicillin-resistant staphylococcus aureus

Hand hygiene is critical in the healthcare setting and it is believed that methicillin-resistant Staphylococcus aureus (MRSA), for example, is transmitted from patient to patient largely via the hands of health professionals. A study has been carried out at a large teaching hospital to estimate how often the gloves of a healthcare worker are contaminated with MRSA after contact with a colonized patient. The effectiveness of handwashing procedures to decontaminate the health professionals' hands was also investigated, together with how well different healthcare professional groups complied with handwashing procedures. The study showed that about 17% (9–25%) of contacts between a healthcare worker and a MRSA-colonized patient results in transmission of MRSA from a patient to the gloves of a healthcare worker. Different health professional groups have different rates of compliance with infection control procedures. Non-contact staff (cleaners, food services) had the shortest handwashing times. In this study, glove use compliance rates were 75% or above in all healthcare worker groups except doctors whose compliance was only 27%.

Nasal carriage of Staphylococcus aureus, including community-associated methicillin-resistant strains, in Queensland adults

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are emerging in southeast Queensland, Australia, but the incidence of carriage of CA-MRSA strains is unknown. The aim of this study was to assess the nasal carriage rate of S. aureus, including CA-MRSA strains, in the general adult population of southeast Queensland. 396 patients presenting to general practices in two Brisbane suburbs and 303 volunteers randomly selected from the electoral rolls in the same suburbs completed a medical questionnaire and had nasal swabs performed for S. aureus. All isolates of S. aureus underwent antibiotic susceptibility testing and single-nucleotide polymorphism (SNP) and binary typing, including determination of Panton–Valentine leukocidin (PVL). The nasal carriage rate of methicillin-susceptible S. aureus (MSSA) was 202/699 (28%), a rate similar to that found in other community-based nasal carriage studies. According to multivariate analysis, nasal carriage of S. aureus was associated with male sex, young adult age group and Caucasian ethnicity. Only two study isolates (one MSSA and one CA-MRSA) carried PVL. The nasal carriage rate of MRSA was low, at 5/699 (0.7%), and only two study participants (0.3%) had CA-MRSA strains. CA-MRSA is an emerging cause of infection in southeast Queensland, but as yet the incidence of carriage of CA-MRSA in the general community is low.

Single nucleotide polymorphism (SNP) - genotyping of Community Acquired Methicillin-Resistant Staphylococcus aureus, including the subtyping of PVL toxin producers using Real-Time PCR

Staphylococcus aureus is a common pathogen that causes a variety of infections including soft tissue infections, impetigo, septicemia toxic shock and scalded skin syndrome. Traditionally, Methicillin-Resistant Staphylococcus aureus (MRSA) was considered a Hospital-Acquired (HA) infection. It is now recognised that the frequency of infections with MRSA is increasing in the community, and that these infections are not originating from hospital environments. A 2007 report by the Centers for Disease Control and Prevention (CDC) stated that Staphylococcus aureus is the most important cause of serious and fatal infections in the USA. Community-Acquired MRSA (CA-MRSA) are genetically diverse and distinct, meaning they are able to be identified and tracked by way of genotyping. Genotyping of MRSA using Single nucleotide polymorphisms (SNPs) is a rapid and robust method for monitoring MRSA, specifically ST93 (Queensland Clone) dissemination in the community. It has been shown that a large proportion of CA-MRSA infections in Queensland and New South Wales are caused by ST93. The rationale for this project was that SNP analysis of MLST genes is a rapid and cost-effective method for genotyping and monitoring MRSA dissemination in the community. In this study, 16 different sequence types (ST) were identified with 41% of isolates identified as ST93 making it the predominate clone. Males and Females were infected equally with an average patient age of 45yrs. Phenotypically, all of the ST93 had an identical antimicrobial resistance pattern. They were resistant to the β-lactams – Penicillin, Flu(di)cloxacillin and Cephalothin but sensitive to all other antibiotics tested. Virulence factors play an important role in allowing S. aureus to cause disease by way of colonising, replication and damage to the host. One virulence factor of particular interest is the toxin Panton-Valentine leukocidin (PVL), which is composed of two separate proteins encoded by two adjacent genes. PVL positive CA-MRSA are shown to cause recurrent, chronic or severe skin and soft tissue infections. As a result, it is important that PVL positive CA-MRSA is genotyped and tracked. Especially now that CA-MRSA infections are more prevalent than HA-MRSA infections and are now deemed endemic in Australia. 98% of all isolates in this study tested positive for the PVL toxin gene. This study showed that PVL is present in many different community based ST, not just ST93, which were all PVL positive. With this toxin becoming entrenched in CA-MRSA, genotyping would provide more accurate data and a way of tracking the dissemination. PVL gene can be sub-typed using an allele-specific Real-Time PCR (RT-PCR) followed by High resolution meltanalysis. This allows the identification of PVL subtypes within the CA-MRSA population and allow the tracking of these clones in the community.

Multivariate Markov Process Models for the transmission of methicillin-resistant Staphylococcus Aureus in a hospital ward

Methicillin-resistant Staphylococcus Aureus (MRSA) is a pathogen that continues to be of major concern in hospitals. We develop models and computational schemes based on observed weekly incidence data to estimate MRSA transmission parameters. We extend the deterministic model of McBryde, Pettitt, and McElwain (2007, Journal of Theoretical Biology 245, 470–481) involving an underlying population of MRSA colonized patients and health-care workers that describes, among other processes, transmission between uncolonized patients and colonized health-care workers and vice versa. We develop new bivariate and trivariate Markov models to include incidence so that estimated transmission rates can be based directly on new colonizations rather than indirectly on prevalence. Imperfect sensitivity of pathogen detection is modeled using a hidden Markov process. The advantages of our approach include (i) a discrete valued assumption for the number of colonized health-care workers, (ii) two transmission parameters can be incorporated into the likelihood, (iii) the likelihood depends on the number of new cases to improve precision of inference, (iv) individual patient records are not required, and (v) the possibility of imperfect detection of colonization is incorporated. We compare our approach with that used by McBryde et al. (2007) based on an approximation that eliminates the health-care workers from the model, uses Markov chain Monte Carlo and individual patient data. We apply these models to MRSA colonization data collected in a small intensive care unit at the Princess Alexandra Hospital, Brisbane, Australia.

Implementation Guide for Surveillance of Staphylococcus aureus Bacteraemia -- [Consultation Edition]

The Implementation Guide for the Hospital Surveillance of SAB has been produced by the Healthcare Associated Infection (HAI) Technical Working Group of the Australian Commission on Safety and Quality in Health Care (ACSQHC), and endorsed by the HAI Advisory Group. The Technical Working Group is made up of representatives invited from surveillance units and the ACSQHC, who have had input into the preparation of this Guide. The Guide has been developed to ensure consistency in reporting of SAB across public and private hospitals to enable accurate national reporting and benchmarking. It is intended to be used by Australian hospitals and organisations to support the implementation of healthcare associated Staphylococcus aureus bacteraemia(SAB) surveillance using the endorsed case definition1 in the box below and further detail in the Data Set Specification.

Tangled Webs : Using Bayesian Networks in the Fight Against Infection

Bayesian networks (BNs) provide a statistical modelling framework which is ideally suited for modelling the many factors and components of complex problems such as healthcare-acquired infections. The methicillin-resistant Staphylococcus aureus (MRSA) organism is particularly troublesome since it is resistant to standard treatments for Staph infections. Overcrowding and understa�ng are believed to increase infection transmission rates and also to inhibit the effectiveness of disease control measures. Clearly the mechanisms behind MRSA transmission and containment are very complicated and control strategies may only be e�ective when used in combination. BNs are growing in popularity in general and in medical sciences in particular. A recent Current Content search of the number of published BN journal articles showed a fi�ve fold increase in general and a six fold increase in medical and veterinary science from 2000 to 2009. This chapter introduces the reader to Bayesian network (BN) modelling and an iterative modelling approach to build and test the BN created to investigate the possible role of high bed occupancy on transmission of MRSA while simultaneously taking into account other risk factors.

Spatial analysis of community-onset Staphylococcus aureus bacteremia in Queensland, Australia

OBJECTIVES To investigate and describe the relationship between indigenous Australian populations, residential aged care services, and community-onset Staphylococcus aureus bacteremia (SAB) among patients admitted to public hospitals in Queensland, Australia. DESIGN Ecological study. METHODS We used administrative healthcare data linked to microbiology results from patients with SAB admitted to Queensland public hospitals from 2005 through 2010 to identify community-onset infections. Data about indigenous Australian population and residential aged care services at the local government area level were obtained from the Queensland Office of Economic and Statistical Research. Associations between community-onset SAB and indigenous Australian population and residential aged care services were calculated using Poisson regression models in a Bayesian framework. Choropleth maps were used to describe the spatial patterns of SAB risk. RESULTS We observed a 21% increase in relative risk (RR) of bacteremia with methicillin-susceptible S. aureus (MSSA; RR, 1.21 [95% credible interval, 1.15-1.26]) and a 24% increase in RR with nonmultiresistant methicillin-resistant S. aureus (nmMRSA; RR, 1.24 [95% credible interval, 1.13-1.34]) with a 10% increase in the indigenous Australian population proportion. There was no significant association between RR of SAB and the number of residential aged care services. Areas with the highest RR for nmMRSA and MSSA bacteremia were identified in the northern and western regions of Queensland. CONCLUSIONS The RR of community-onset SAB varied spatially across Queensland. There was increased RR of community-onset SAB with nmMRSA and MSSA in areas of Queensland with increased indigenous population proportions. Additional research should be undertaken to understand other factors that increase the risk of infection due to this organism.

Changes in healthcare-associated Staphylococcus aureus bloodstream infections after the introduction of a national hand hygiene initiative

Background. Interventions that prevent healthcare-associated infection should lead to fewer deaths and shorter hospital stays. Cleaning hands (with soap or alcohol) is an effective way to prevent the transmission of organisms, but rates of compliance with hand hygiene are sometimes disappointingly low. The National Hand Hygiene Initiative in Australia aimed to improve hand hygiene compliance among healthcare workers, with the goal of reducing rates of healthcare-associated infection. Methods. We examined whether the introduction of the National Hand Hygiene Initiative was associated with a change in infection rates. Monthly infection rates for healthcare-associated Staphylococcus aureus bloodstream infections were examined in 38 Australian hospitals across 6 states. We used Poisson regression and examined 12 possible patterns of change, with the best fitting pattern chosen using the Akaike information criterion. Monthly bed-days were included to control for increased hospital use over time. Results. The National Hand Hygiene Initiative was associated with a reduction in infection rates in 4 of the 6 states studied. Two states showed an immediate reduction in rates of 17% and 28%, 2 states showed a linear decrease in rates of 8% and 11% per year, and 2 showed no change in infection rates. Conclusions. The intervention was associated with reduced infection rates in most states. The failure in 2 states may have been because those states already had effective initiatives before the national initiative’s introduction or because infection rates were already low and could not be further reduced.

Molecular characterization of endocarditis-associated Staphylococcus aureus

Infective endocarditis (IE) is a life-threatening infection of the heart endothelium and valves. Staphylococcus aureus is a predominant cause of severe IE and is frequently associated with infections in health care settings and device-related infections. Multilocus sequence typing (MLST), spa typing, and virulence gene microarrays are frequently used to classify S. aureus clinical isolates. This study examined the utility of these typing tools to investigate S. aureus epidemiology associated with IE. Ninety-seven S. aureus isolates were collected from patients diagnosed with (i) IE, (ii) bloodstream infection related to medical devices, (iii) bloodstream infection not related to medical devices, and (iv) skin or soft-tissue infections. The MLST clonal complex (CC) for each isolate was determined and compared to the CCs of members of the S. aureus population by eBURST analysis. The spa type of all isolates was also determined. A null model was used to determine correlations of IE with CC and spa type. DNA microarray analysis was performed, and a permutational analysis of multivariate variance (PERMANOVA) and principal coordinates analysis were conducted to identify genotypic differences between IE and non-IE strains. CC12, CC20, and spa type t160 were significantly associated with IE S. aureus. A subset of virulence-associated genes and alleles, including genes encoding staphylococcal superantigen-like proteins, fibrinogen-binding protein, and a leukocidin subunit, also significantly correlated with IE isolates. MLST, spa typing, and microarray analysis are promising tools for monitoring S. aureus epidemiology associated with IE. Further research to determine a role for the S. aureus IE-associated virulence genes identified in this study is warranted.

UafB is a serine-rich repeat adhesin of Staphylococcus saprophyticus that mediates binding to fibronectin, fibrinogen and human uroepithelial cells

Staphylococcus saprophyticus is an important cause of urinary tract infection (UTI), particularly among young women, and is second only to uropathogenic Escherichia coli as the most frequent cause of UTI. The molecular mechanisms of urinary tract colonization by S. saprophyticus remain poorly understood. We have identified a novel 6.84 kb plasmid-located adhesin-encoding gene in S. saprophyticus strain MS1146 which we have termed uro-adherence factor B (uafB). UafB is a glycosylated serine-rich repeat protein that is expressed on the surface of S. saprophyticus MS1146. UafB also functions as a major cell surface hydrophobicity factor. To characterize the role of UafB we generated an isogenic uafB mutant in S. saprophyticus MS1146 by interruption with a group II intron. The uafB mutant had a significantly reduced ability to bind to fibronectin and fibrinogen. Furthermore, we show that a recombinant protein containing the putative binding domain of UafB binds specifically to fibronectin and fibrinogen. UafB was not involved in adhesion in a mouse model of UTI; however, we observed a striking UafB-mediated adhesion phenotype to human uroepithelial cells. We have also identified genes homologous to uafB in other staphylococci which, like uafB, appear to be located on transposable elements. Thus, our data indicate that UafB is a novel adhesin of S. saprophyticus that contributes to cell surface hydrophobicity, mediates adhesion to fibronectin and fibrinogen, and exhibits tropism for human uroepithelial cells.

Prevalence of methicillin resistance and virulence determinants of Staphylococcus aureus in diabetic foot ulcers

Background Diabetic foot ulceration (DFU) is a multifactorial process and is responsible for considerable morbidity and contributes to the increasing cost of health care worldwide. The diagnosis and identification of these ulcers remains a complex problem. Bacterial infection is promoted in the diabetic foot wound by decreased vascular supply and impaired host immune response. As conventional clinical microbiological methods are time-consuming and only identifies about 1% of the wound microbiota, detection of bacteria present in DFUs using molecular methods is highly advantageous and efficient. The aim of this study was to assess the virulence and methicillin resistance profiles of Staphylococcus aureus detected in DFUs using DNA-based methods. Methods A total of 223 swab samples were collected from 30 patients from March to October 2012. Bacterial DNA was extracted from the swab samples using standard procedures and was used to perform polymerase chain reaction (PCR) using specific oligonucleotide primers. The products were visualized using agarose gel electrophoresis. Results S. aureus was detected in 44.8% of samples. 25% of the S. aureus was methicillin-resistant S. aureus harboring the mecA gene. The alpha-toxin gene was present in 85% of the S. aureus positive samples. 61% of the S. aureus present in DFU samples harbored the exfoliatin factor A gene. Both the fibronectin factor A and fibronectin factor B gene were detected in 71% and 74% of the S. aureus positive samples. Conclusions DNA-based detection and characterization of bacteria in DFUs are rapid and efficient and can assist in accurate, targeted antibiotic therapy of DFU infections. The majority of S. aureus detected in this study were highly virulent and also resistant to methicillin. Further studies are required to understand the role of S. aureus in DFU trajectory.

How costs change with infection prevention efforts

Purpose of review: To describe articles since January 2013 that include information on how costs change with infection prevention efforts. Recent findings: Three articles described only the costs imposed by nosocomial infection and so provided limited information about whether or not infection prevention efforts should be changed. One article was found that described the costs of supplying alcohol-based hand run in low-income countries. Eight articles showed the extra costs and cost savings from changing infection prevention programmes and discussed the health benefits. All concluded that the changes are economically worthwhile. There was a systematic review of the costs of methicillin-resistant Staphylococcus aureus control programmes and a methods article for how to make cost estimates for infection prevention programmes. Summary: The balance has shifted away from studies that report the high cost of nosocomial infections toward articles that address the value for money of infection prevention. This is good as simply showing a disease is high cost does not inform decisions to reduce it. More research, done well, on the costs of implementation, cost savings and change to health benefits in this area needs to be done as many gaps exist in our knowledge.