Surveillance and Stewardship: Where Infection Prevention and Antimicrobial Stewardship Intersect

Colonization with multidrug-resistant organisms (MDROs) is a risk factor for subsequent infection. Surveillance for MDROs, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacterales, and carbapenemase-producing organisms, is commonly conducted in hospitals to prevent spread of MDROs, in part to reduce the potential for additional infections. Although colonization is a risk factor for infection, data on colonization with various MDROs are often not considered when selecting anti-infective therapy. There are conflicting data on the strength of the positive and negative predictive values of the colonization test results to guide therapeutic strategies. Defining therapeutic strategies for patients with complicated or drug-resistant infections or to select antimicrobial prophylaxis before performing prostate biopsies often falls under the purview of the antimicrobial stewardship team. Should colonization data, which are often present in the patient\u27s medical record from routine infection prevention measures, be reviewed before selecting therapy for infections or for prophylaxis? In this perspective, we will explore the intersection of infection control and antimicrobial stewardship activities

Lagunas y obstáculos en la aplicación y el funcionamiento de los programas de administración de antimicrobianos: Resultados de una evaluación de necesidades con métodos mixtos educativos y conductuales en Francia, Estados Unidos, México e India

Antecedentes: La evidencia muestra una adherencia limitada a los principios de administración antimicrobiana (AMS). Objetivos: Identificar las lagunas educativas y las barreras sistémicas que obstaculizan la adhesión a los principios de la AMS. Métodos: Se realizó un estudio de métodos mixtos que combina un análisis temático de entrevistas cualitativas (enero-febrero de 2021) y un análisis inferencial de encuestas cuantitativas (mayo-junio de 2021). Se seleccionaron deliberadamente participantes de Francia, EE.UU., México y la India a partir de paneles en línea de profesionales de la salud para incluir a médicos infectólogos, especialistas en control de infecciones, microbiólogos clínicos, farmacólogos o farmacéuticos que se espera que apliquen los principios de la MGA en su entorno de práctica (por ejemplo, clínica, hospital académico o comunitario). Este estudio se ha guiado por un marco de análisis de carencias. Resultados: La muestra final incluyó 383 participantes (n = 33 entrevistas; n = 350 encuestas). Los resultados de los métodos mixtos indicaron que los conocimientos y habilidades de los participantes no eran óptimos para facilitar la aplicación personal y colectiva de los principios de la MGA. Los datos de la encuesta indicaron un desfase entre el conocimiento ideal y el actual de los protocolos de MGA, especialmente entre los farmacólogos (Δ0,95/4,00, p < 0,001). También se midieron las diferencias entre los niveles de conocimientos ideales y los actuales, que fueron mayores entre los especialistas en control infeccioso (Δ1,15/4,00, P < 0,001), para convencer a los directivos de los hospitales de que asignen recursos a los programas de MGA. Los obstáculos sistémicos ya existentes (por ejemplo, tiempo, financiación o formación insuficientes) se percibieron como agravados durante la pandemia COVID-19 (el 72% de los participantes en la encuesta estuvieron de acuerdo). Las deficiencias más acusadas se registraron en India y Francia. Conclusiones: Las necesidades educativas de los profesionales y los países incluidos en este estudio pueden informar las futuras actividades de desarrollo profesional continuo en AMS. Debería considerarse la posibilidad de obtener financiación adicional para abordar las barreras sistémicas percibidas. Las evaluaciones locales están justificadas para validar los resultados y la idoneidad de las intervenciones.Background: Evidence shows limited adherence to antimicrobial stewardship (AMS) principles. Objectives: To identify educational gaps and systemic barriers obstructing adherence to AMS principles. Methods: A mixed-methods study combining a thematic analysis of qualitative interviews (January-February 2021) and inferential analysis of quantitative surveys (May-June 2021) was conducted. Participants from France, the USA, Mexico and India were purposively sampled from online panels of healthcare professionals to include infectious disease physicians, infection control specialists, clinical microbiologists, pharmacologists or pharmacists expected to apply AMS principles in their practice setting (e.g. clinic, academic-affiliated or community-based hospital). A gap analysis framework guided this study. Results: The final sample included 383 participants (n = 33 interviews; n = 350 surveys). Mixed-methods findings indicated suboptimal knowledge and skills amongst participants to facilitate personal and collective application of AMS principles. Survey data indicated a gap in ideal versus current knowledge of AMS protocols, especially amongst pharmacologists (Δ0.95/4.00, P < 0.001). Gaps in ideal versus current skill levels were also measured and were highest amongst infectious control specialists (Δ1.15/4.00, P < 0.001), for convincing hospital executives to allocate resources to AMS programmes. Already existing systemic barriers (e.g. insufficient dedicated time/funding/training) were perceived as being aggravated during the COVID-19 pandemic (72% of survey participants agreed). Reported gaps were highest in India and France. Conclusions: The educational needs of professionals and countries included in this study can inform future continuous professional development activities in AMS. Additional funding should be considered to address perceived systemic barriers. Local assessments are warranted to validate results and suitability of interventions

A pharmacist-led prospective antibiotic stewardship intervention improves compliance to community-acquired pneumonia guidelines in 39 public and private hospitals across South Africa

Introduction: Pharmacists in low-middle-income countries (LMIC) are few and lack antibiotic stewardship (AS) training. The ability was assessed of non-specialised pharmacists to implement stewardship interventions and improve adherence to the South African community-acquired pneumonia (CAP) guideline in public and private hospitals. Methods: This was a multicentre, prospective cohort study of adult CAP patients hospitalised between July 2017 and July 2018. A CAP bundle was developed of seven process measures (diagnostic and AS) that pharmacists used to audit compliance and provide feedback. CAP bundle compliance rates and change in outcome measures [mortality, length of stay (LOS) and infection-related (IR)-LOS] during pre- and post-implementation periods were compared

Trends in and predictors of carbapenem consumption across North American hospitals: Results from a multicenter survey by the MAD-ID research network

This Special Issue is dedicated to the late Dr. Charles (Charlie) D. Hufford, former Professor of Pharmacognosy and Associate Dean for Research and Graduate Studies at University of Mississippi [...]

Clinical Outcomes in Patients with Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Bloodstream Infection

The prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections varies in the literature, a problem complicated by the lack of routine screening procedures; however, limited data suggest that hVISA has been associated with persistent bloodstream infections (BSI) and vancomycin failure, yet these studies have been confounded by design issues. We conducted this study to compare the characteristics of patients with BSI caused by hVISA with those with vancomycin-susceptible Staphylococcus aureus (VSSA) treated with vancomycin. This retrospective, multicenter matched (1:1) cohort study compared the clinical characteristics and outcomes of hVISA and VSSA. Patients with hVISA methicillin-resistant Staphylococcus aureus (MRSA) BSI from 2004 to 2012 were matched to VSSA-MRSA BSI patients. The primary outcome was failure of vancomycin treatment, defined as a composite of persistent bacteremia (≥7 days), persistent signs and symptoms, change of MRSA antibiotic, recurrent BSI, or MRSA-related mortality. We identified 122 matched cases. The overall vancomycin failure rate was 57% (82% hVISA versus 33% VSSA; P \u3c 0.001). The individual components of failure in hVISA versus VSSA were persistent bacteremia, 59% versus 21% (P \u3c 0.001); change in MRSA therapy, 54% versus 25% (P = 0.001); MRSA-related mortality, 21% versus 10% (P = 0.081); and recurrence of BSI, 26% versus 2% (P \u3c 0.001). Using logistic regression analysis and adjusting for covariates, hVISA (adjusted odds ratio [aOR], 11.1; 95% confidence interval [CI], 4.3 to 28.7) and intensive care unit (ICU) admission (aOR, 4.5; 95% CI, 1.8 to 11.6) were still independently associated with vancomycin failure. Relative to VSSA BSI, patients with hVISA were more likely to experience failure of vancomycin treatment, including persistent bacteremia and recurrence. Our results indicate that hVISA was responsible for considerable morbidity

Multicenter Study of High-Dose Daptomycin for Treatment of Enterococcal Infections

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggests that daptomycin \u3e 6mg/kg/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (\u3e 6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two-hundred and forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by 49 (20%) Enterococcus faecalis and 21 (9%) Enterococcus spp., overall 204 (83%) were VRE. Enterococcal infections included bacteremia (173, 71%), intra-abdominal (35, 14%) and bone/joint (25, 10%). The median dose and duration of HD-daptomycin was 8.2 mg/kg/day (IQR 7.7-9.7) and 10 days (IQR 6-15), respectively. Overall clinical success rate was 89% (193/218) and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR 2-5). Thirty-day all cause mortality rate was 27% and 5 (2%) patients developed daptomycin nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult to treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections

Multicenter Study of High-Dose Daptomycin for Treatment of Enterococcal Infections

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin- resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at>6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.Keywords: Skin structure infections, Staphylococcus aureus, Outcomes registry, Vancomycin resistant enterococcus, Retrospective case series, Quinupristin dalfopristin, Cubicin(R), Complicated skin, Risk factors, Clinical outcomes, Bloodstream infection

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far