Rahul Batra

Efficacy and Limitation of a Chlorhexidine-Based Decolonization Strategy in Preventing Transmission of Methicillin-Resistant Staphylococcus aureus in an Intensive Care Unit

BACKGROUND Surface-active antiseptics, such as chlorhexidine, are increasingly being used as part of intervention programs to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission, despite limited evidence and potential for resistance. We report on the effect of an antiseptic protocol on acquisition of both endemic MRSA and an outbreak strain of MRSA sequence type 239 (designated TW). METHODS Interrupted time-series data on MRSA acquisitions in two 15-bed intensive care units were analyzed using segmented regression models to estimate the effects of sequential introduction of an educational campaign, cohorting, and a chlorhexidine-based antiseptic protocol on transmission of TW and non-TW MRSA strains. Representative TW and non-TW MRSA strains were assessed for carriage of qacA/B genes and antiseptic susceptibility. RESULTS The antiseptic protocol was associated with a highly significant, immediate 70% reduction in acquisition of non-TW MRSA strains (estimated model-averaged incidence rate ratio, 0.3; 95% confidence interval, 0.19-0.47) and an increase in acquisition of TW MRSA strains (estimated model-averaged incidence rate ratio, 3.85; 95% confidence interval, 0.80-18.59). There was only weak evidence of an effect of other interventions on MRSA transmission. All TW MRSA strains (21 of 21 isolates) and <5% (1 of 21 isolates) of non-TW MRSA strains tested carried the chlorhexidine resistance loci qacA/B. In vitro chlorhexidine minimum bactericidal concentrations of TW strains were 3-fold higher than those of non-TW MRSA strains, and in vivo, only patients with non-TW MRSA demonstrated a reduction in the number of colonization sites in response to chlorhexidine treatment. CONCLUSION A chlorhexidine-based surface antiseptic protocol can interrupt transmission of MRSA in the intensive care unit, but strains carrying qacA/B genes may be unaffected or potentially spread more rapidly.

Genome Sequence of a Recently Emerged, Highly Transmissible, Multi-Antibiotic- and Antiseptic-Resistant Variant of Methicillin-Resistant Staphylococcus aureus, Sequence Type 239 (TW)

The 3.1-Mb genome of an outbreak methicillin-resistant Staphylococcus aureus (MRSA) strain (TW20) contains evidence of recently acquired DNA, including two large regions (635 kb and 127 kb). The strain is resistant to a wide range of antibiotics, antiseptics, and heavy metals due to resistance genes encoded on mobile genetic elements and also mutations in housekeeping genes.

An Outbreak in an Intensive Care Unit of a Strain of Methicillin-Resistant Staphylococcus aureus Sequence Type 239 Associated with an Increased Rate of Vascular Access Device—Related Bacteremia

BACKGROUND Patients in intensive care units are at high risk of developing methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We report an epidemiological and bacterial genomic analysis of a 2-year outbreak in an intensive care unit of a variant of MRSA sequence type 239 (hereafter designated TW). METHODS A cohort study was conducted to compare risk factors for MRSA bacteremia in patients who acquired TW versus patients who acquired non-TW strains of MRSA. Genetic analysis of TW was performed using multilocus sequence typing and microarray analysis. RESULTS Patients who acquired TW were more likely than patients who acquired non-TW strains of MRSA to have MRSA isolated from blood samples (47% vs. 13%; P<.001) and to have MRSA-positive vascular access device-sample cultures (59% vs. 26%; P<.001), but less likely to have MRSA isolated from screening swab samples (30% vs. 71%; P<.001). This increased rate of TW bacteremia was confined to the first week after acquisition of TW infection. Using Cox regression analysis, the adjusted hazard ratio for bacteremia with TW was 4.5 times that of non-TW strains of MRSA (95% confidence interval, 2.25-9.00; P<.001). Microarray analysis revealed that TW had accumulated all detectable mobile genetic elements that were variably expressed by other epidemic strains of MRSA sequence type 239 in the United Kingdom. CONCLUSIONS To our knowledge, this is the first report to provide direct evidence that strains of MRSA can differ in their ability to cause bacteremia. Further genetic and in vitro analysis of the TW strain may provide insight into the mechanism of vascular access device-related bacteremia in the intensive care unit environment.

Screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus in intensive care units: cost effectiveness evaluation

Objective To assess the cost effectiveness of screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus (MRSA) in intensive care units. Design Economic evaluation based on a dynamic transmission model. Setting England and Wales. Population Theoretical population of patients on an intensive care unit. Main outcome measures Infections, deaths, costs, quality adjusted life years (QALYs), incremental cost effectiveness ratios for alternative strategies, and net monetary benefits. Results All decolonisation strategies improved health outcomes and reduced costs. Although universal decolonisation (regardless of MRSA status) was the most cost effective in the short term, strategies using screening to target MRSA carriers may be preferred owing to the reduced risk of selecting for resistance. Among such targeted strategies, universal admission and weekly screening with polymerase chain reaction coupled with decolonisation using nasal mupirocin was the most cost effective. This finding was robust to the size of intensive care units, prevalence of MRSA on admission, proportion of patients classified as high risk, and precise value of willingness to pay for health benefits. All strategies using isolation but not decolonisation improved health outcomes but costs were increased. When the prevalence of MRSA on admission to the intensive care unit was 5% and the willingness to pay per QALY gained was between £20 000 (€23 000;

Using a Longitudinal Model to Estimate the Effect of Methicillin-resistant Staphylococcus aureus Infection on Length of Stay in an Intensive Care Unit

32 000) and £30 000, the best such strategy was to isolate only those patients at high risk of carrying MRSA (either pre-emptively or after identification by admission and weekly screening for MRSA using chromogenic agar). Universal admission and weekly screening using polymerase chain reaction based detection of MRSA coupled with isolation was unlikely to be cost effective unless prevalence was high (10% of patients colonised with MRSA on admission). Conclusions MRSA control strategies that use decolonisation are likely to be cost saving in an intensive care unit setting provided resistance is lacking, and combining universal screening using polymerase chain reaction with decolonisation is likely to represent good value for money if untargeted decolonisation is considered unacceptable. In intensive care units where decolonisation is not implemented, evidence is insufficient to support universal screening for MRSA outside high prevalence settings.

An Association Between Bacterial Genotype Combined With a High-Vancomycin Minimum Inhibitory Concentration and Risk of Endocarditis in Methicillin-Resistant Staphylococcus aureus Bloodstream Infection

Health-care-associated methicillin-resistant Staphylococcus aureus (MRSA) infection may cause increased hospital stay, or sometimes death. Quantifying this effect is complicated because the exposure is time dependent: infection may prolong hospital stay, while longer stays increase infection risk. In this paper, the authors overcome these problems by using a multinomial longitudinal model to estimate the daily probability of death and discharge. They then extend the basic model to estimate how the effect of MRSA infection varies over time and to quantify number of excess days in the intensive care unit due to infection. They found that infection decreased the relative risk of discharge (relative risk ratio = 0.68, 95% credible interval: 0.54, 0.82). Infection on the first day of admission resulted in a mean extra stay of 0.3 days (95% credible interval: 0.1, 0.5) for a patient with an Acute Physiology and Chronic Health Evaluation II score of 10 and 1.2 days (95% credible interval: 0.5, 2.0) for a patient with a 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. Results confirm the importance of MRSA infection in increasing stay in an intensive care unit but suggest that previous work may have systematically overestimated the effect size.

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

INTRODUCTION Antimicrobial resistance and bacterial virulence factors may increase the risk of hematogenous complications during methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). This study reports on the impact of increasing vancomycin minimum inhibitory concentrations (V-MICs) and MRSA clone type on risk of hematogenous complications from MRSA BSI during implementation of an effective MRSA control program. METHODS In sum, spa typing, staphylococcal cassette chromosome mec allotyping, and vancomycin and teicoplanin MICs were performed on 821 consecutive MRSA bloodstream isolates from 1999 to 2009. Prospectively collected data, including focus of infection, were available for 695 clinically significant cases. Logistic and multinomial logistic regression was used to determine the association between clone type, vancomycin MIC (V-MIC), and focus of infection. RESULTS MRSA BSIs decreased by ∼90% during the 11 years. Typing placed isolates into 3 clonal complex (CC) groups that had different population median V-MICs (CC30, 0.5 μg/mL [n = 349]; CC22, 0.75 μg/mL [n = 272]; non-CC22/30, 1.5 μg/mL [n = 199]). There was a progressive increase in the proportion of isolates with a V-MIC above baseline median in each clonal group and a disproportionate fall in the clone group with lowest median V-MIC (CC30). In contrast, there were no increases in teicoplanin MICs. High V-MIC CC22 isolates (1.5-2 μg/mL) were strongly associated with endocarditis (odds ratio, 12; 95% confidence interval, 3.72-38.9) and with a septic metastasis after catheter-related BSI (odds ratio, 106; 95% confidence interval, 12.6-883) compared with other clone type/V-MIC combinations. CONCLUSIONS An interaction between clone type and V-MIC can influence the risk of endocarditis associated with MRSA BSI, implying involvement of both therapeutic and host-pathogen factors.

Comparison of Different Strategies for Providing Fecal Microbiota Transplantation to Treat Patients with Recurrent Clostridium difficile Infection in Two English Hospitals: A Review

An important determinant of a pathogens 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.

Frequent undetected MRSA ward-based transmission linked to patient sharing between hospitals

Fecal microbiota transplant (FMT) has emerged as a highly efficacious treatment for difficult cases of refractory and/or recurrent Clostridium difficile infection (CDI). There have been many well-conducted randomized controlled trials and thousands of patients reported in case series that describe success rates of approximately 90% following one or more FMT. Although the exact mechanisms of FMT have yet to be fully elucidated, replacement or restoration of a ‘normal’ microbiota (or at least a microbiota resembling those who have never had CDI) appears to have a positive effect on the gut dysbiosis that is thought to exist in these patients. Furthermore, despite being aesthetically unappealing, this ‘ultimate probiotic’ is a particularly attractive solution to a difficult problem that avoids repeated courses of antibiotics. The lack of clarity about the exact mechanism of action and the ‘active ingredient’ of FMT (e.g., individual or communities of bacteria, bacteriophage, or bioactive molecules such as bile acids) has hindered the ability to produce a standardized and well-characterized FMT product. There is no standard method to produce material for FMT, and there are a multitude of factors that can vary between institutions that offer this therapy. Only a few studies have directly compared clinical efficacy in groups of patients who have been treated with FMT prepared differently (e.g., fresh vs. frozen) or administered by different route (e.g., by nasojejunal tube, colonoscopy or by oral administration of encapsulated product). More of these studies should be undertaken to clarify the superiority or otherwise of these variables. This review describes the methods and protocols that two English NHS hospitals independently adopted over the same time period to provide FMT for patients with recurrent CDI. There are several fundamental differences in the methods used, including selection and testing of donors, procedures for preparation and storage of material, and route of administration. These methods are described in detail in this review highlighting differing practice. Despite these significant methodological variations, clinical outcomes in terms of cure rate appear to be remarkably similar for both FMT providers. Although both hospitals have treated only modest numbers of patients, these findings suggest that many of the described differences may not be critical factors in influencing the success of the procedure. As FMT is increasingly being proposed for a number of conditions other than CDI, harmonization of methods and techniques may be more critical to the success of FMT, and thus it will be important to standardize these as far as practically possible.

Intensive care unit (ICU)-acquired bacteraemia and ICU mortality and discharge: addressing time-varying confounding using appropriate methodology

We report significant undetected ward-based transmission of methicillin-resistant Staphylococcus aureus in the English national health system, which is predominantly attributable to patient sharing between hospitals. We propose a context-appropriate measure that could limit the spread of antibiotic-resistant bacteria in England.