A Threshold Logistic Modelling Approach for Identifying Thresholds between Antibiotic Use and Methicillin-Resistant Staphylococcus aureus Incidence Rates in Hospitals.

The aim of this study was to demonstrate the utility of threshold logistic modelling, an innovative approach in identifying thresholds and risk scores in the context of population antibiotic use associated with methicillin-resistant Staphylococcus aureus (MRSA) incidence rates in hospitals. The study also aimed to assess the impact of exceeding those thresholds that resulted in increased MRSA rates. The study was undertaken in a 700-bed hospital in England between January 2015 and December 2021 (84 monthly observations). By employing the threshold logistic modelling approach, we: (i) determined the cut-off percentile value of MRSA incidence that defines a critical level of MRSA; (ii) identified thresholds for fluoroquinolone and co-amoxiclav use that would accelerate MRSA incidence rates and increase the probability of reaching critical incidence levels; (iii) enabled a better understanding of the effect of antibiotic use on the probability of reaching a critical level of resistant pathogen incidence; (iv) developed a near real-time performance monitoring feedback system; (v) provided risk scores and alert signals for antibiotic use, with the ability to inform hospital policies, and control MRSA incidence; and (vi) provided recommendations and an example for the management of pathogen incidence in hospitals. Threshold logistic models can help hospitals determine quantitative targets for antibiotic usage and can also inform effective antimicrobial stewardship to control resistance in hospitals. Studies should work toward implementing and evaluating the proposed approach prospectively, with the aim of determining the best counter-measures to mitigate the risk of increased resistant pathogen incidence in hospitals.

Identifying Antibiotic Use Targets for the Management of Antibiotic Resistance Using an Extended-Spectrum ß-Lactamase-Producing Escherichia coli Case: A Threshold Logistic Modeling Approach.

The aim of this study was to develop a logistic modeling concept to improve understanding of the relationship between antibiotic use thresholds and the incidence of resistant pathogens. A combined approach of nonlinear modeling and logistic regression, named threshold logistic, was used to identify thresholds and risk scores in hospital-level antibiotic use associated with hospital-level incidence rates of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli). Threshold logistic models identified thresholds for fluoroquinolones (61.1 DDD/1000 occupied bed days (OBD)) and third-generation cephalosporins (9.2 DDD/1000 OBD) to control hospital ESBL-producing E. coli incidence. The 60th percentile of ESBL-producing E. coli was determined as the cutoff for defining high incidence rates. Threshold logistic analysis showed that for every one-unit increase in fluoroquinolones and third-generation cephalosporins above 61.1 and 9.2 DDD/1000 OBD levels, the average odds of the ESBL-producing E. coli incidence rate being ≥60th percentile of historical levels increased by 4.5% and 12%, respectively. Threshold logistic models estimated the risk scores of exceeding the 60th percentile of a historical ESBL-producing E. coli incidence rate. Threshold logistic models can help hospitals in defining critical levels of antibiotic use and resistant pathogen incidence and provide targets for antibiotic consumption and a near real-time performance monitoring feedback system.

Daptomycin in the Clinical Setting: 8-Year Experience with Gram-positive Bacterial Infections from the EU-CORE(SM) Registry.

INTRODUCTION: The aim of this study was to evaluate the clinical outcomes and safety of daptomycin therapy in patients with serious Gram-positive infections. METHODS: Patients were enrolled in the European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)), a non-interventional, multicenter, observational registry. The real-world data were collected across 18 countries (Europe, Latin America, and Asia) for patients who had received at least one dose of daptomycin between January 2006 and April 2012. Two-year follow-up data were collected until 2014 for patients with endocarditis, intracardiac/intravascular device infection, osteomyelitis, or orthopedic device infection. RESULTS: A total of 6075 patients were enrolled. The most common primary infections were complicated skin and soft tissue infection (31.7%) and bacteremia (20.7%). Staphylococcus aureus was the most frequently reported pathogen (42.9%; methicillin-resistant S. aureus [MRSA], 23.2%), followed by Staphylococcus epidermidis and other coagulase-negative staphylococci (CoNS, 28.5%). The most commonly prescribed dose of daptomycin was 6 mg/kg/day (43.6%), and the median duration of therapy was 11 (range 1-300) days. Overall clinical success rate was 80.5%, and was similar whether daptomycin was used as first-line (82.9%) or second-line (79.2%) therapy. Clinical success rates were high in patients with S. aureus (83.9%; MRSA 83.0%) and CoNS (including S. epidermidis, 82.5%) infections. The majority of patients with endocarditis or intracardiac/intravascular device infection (86.7%) or osteomyelitis/orthopedic device infection (85.9%) had a sustained response during the 2-year follow-up period. There were no new or unexpected safety findings. CONCLUSION: Results from real-world clinical experience showed that daptomycin is a valuable therapeutic option in the management of various difficult-to-treat Gram-positive infections. FUNDING: This study was funded by Novartis Pharma AG.

Prevalence of blaTEM , blaSHV and blaCTX-M genes in clinical isolates of Escherichia coli and Klebsiella pneumoniae from Northeast India.

AIM: This study was carried out to determine the presence of blaTEM , blaSHV and blaCTX-M genes in extended-spectrum ß-lactamase (ESBL) producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) at a tertiary care referral hospital in Northeast India. MATERIALS AND METHODS: A total of 270 E. coli and 219 K. pneumoniae isolates were recovered during the period between August 2009 and July 2010. Kirby-Bauer disk diffusion method was performed to determine the antibiotic resistance pattern. Screening and phenotypic confirmatory test for ESBL production were performed using standard disc diffusion methods. Each of the initial ESBL screening test isolate was investigated for the presence of blaTEM , blaSHV and blaCTX-M genes via polymerase chain reaction (PCR) using gene-specific primers. RESULTS: Phenotypic confirmatory test able to detect ESBL production in 73.58% of E. coli and 67.24% of K. pneumoniae. However, PCR amplification showed the presence of one or more ESBL genes in each of the initial ESBL screening positive isolate. Among three ESBL genotypes, the most prevalent genotype was found to be blaCTX-M in E. coli (88.67%) and blaTEM in K. pneumoniae (77.58%) ESBL producing isolates. Majority of ESBL producing isolates possess more than one ESBL genes. CONCLUSION: This study constituted a primer report on high prevalence of blaTEM and blaCTX-M genes in ESBL producing isolates of E. coli and K. pneumoniae and denotes the need of more extensive studies on these antibiotic genes to determine the magnitude of the problem of antibiotic resistance exiting in this locality.

Impact of universal screening on MRSA bacteremias in a single acute NHS organisation (2006-12): interrupted time-series analysis.

BACKGROUND: In November 2004, a national target was set for the English hospital trusts to reduce the Meticillin-Resistant Staphylococcus aureus (MRSA) bacteremia rate by 60% by April 2008 against the number during 2003/04 (baseline year). In our organisation the number of MRSA bacteremias had risen since 2002 and peaked at 75 in 2005/06. A target was set to reduce the number and series of specific and non- specific interventions was introduced including universal MRSA screening. This study analyzes the impact of universal MRSA screening using a quasi-experimental design using routinely gathered data. METHODS: This study used data gathered routinely for clinical governance, quality control, financial management and outbreak monitoring purposes. Interrupted Time Series (ITS) analysis of 15 pre- and 19 post- universal MRSA screening (and decolonisation) quarterly numbers of bacteremias was carried out where Meticillin-Sensitive Staphylococcus aureus (MSSA) numbers served as non-equivalent dependent variable (control). RESULTS: An immediate sharp fall in MRSA bacteremias was observed following the universal MRSA screening (and decolonisation) commenced in Q2, 2007. The number dropped sharply from 23 (Q2, 2007) to 10 (Q3, 2007) for all MRSA bacteremias, and, from 15 (Q2, 2007) to 6 (Q3, 2007) for bacteremias ≥48 hours of hospitalization. The declining trend continued reaching zero in Q2, 2009 and Q4, 2010 for those with ≥48 hours of hospitalization and all bacteremias, respectively. ITS analysis revealed significant impact of universal MRSA screening on all MRSA bacteremias (ß2 -0.554, p 0.000) and those with ≥48 of hospitalization (ß2 -0.577, p 0.001). Impact estimation predicted 17 and 13 bacteremias for all and those with ≥48 hours hospitalization, respectively in the 19th quarter post-intervention, if the intervention did not occur. The number of MRSA isolates from non-blood culture systemic sources as percentage of admissions also dropped significantly from 3.32% in Q2, 2007 to 1.51% in Q3, 2007 (ß2 -0.506, p 0.000) which is still running low at 0.33% at the end of Q1, 2012. On the other hand, there was no statistically significant impact of universal screening on MSSA bacteremias. CONCLUSIONS: We conclude that of all interventions, the universal MRSA screening (and decolonisation) is the most effective intervention associated with significant and sharp drop in MRSA burden.

Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study.

BACKGROUND: Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-beta-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK. METHODS: Enterobacteriaceae isolates were studied from two major centres in India--Chennai (south India), Haryana (north India)--and those referred to the UK's national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene bla(NDM-1) was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan. FINDINGS: We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries. INTERPRETATION: The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed.

Realistic model for the output beam profile of stripe and tapered superluminescent light-emitting diodes.

We present a new model to analyse the spatial characteristics of the output beam of conventional (straight-stripe) and tapered superluminescent light-emitting diodes. The device model includes both spontaneous and stimulated emission processes as well as a nonuniform carrier density distribution to correctly represent current spreading and carrier diffusion effects. Near- and far-field intensity profiles computed with this model are accurately verified over a wide range of injection currents by comparisons with experimental results measured from in-house fabricated devices.

Characterization of angled tapered superluminescent LEDs.

We present a detailed analysis of the output beam of high-power edge-emitting angled tapered superluminescent LEDs (A-TSLEDs). A device model, including spontaneous and stimulated emission processes as well as the typical nonuniform carrier-density distribution due to current spreading and carrier diffusion, has been developed and used to interpret the experimentally obtained characteristics of inhouse-fabricated A-TSLEDs. The good match between measured and theoretical results indicates that the model reproduces the A-TSLED operation very satisfactorily and clearly explains the role of the collecting lens on the pronounced asymmetry of some of the measured optical intensity profiles.