Patients with community-onset (CO) methicillin-resistant
(MRSA) infections contribute to MRSA contamination of the home environment and may be reexposed to MRSA strains from this reservoir. This ...study evaluates One Health risk factors, which focus on the relationship between humans, animals, and the environment, for the increased prevalence of multiple antimicrobial-resistant MRSA isolates in the home environment. During a trial of patients with CO-MRSA infection, MRSA was isolated from the household environment at the baseline and 3 months later, following randomization of patients and household members to mupirocin-based decolonization therapy or an education control group. Up to two environmental MRSA isolates collected at each visit were tested. MRSA isolates were identified in 68% (65/95) of homes at the baseline (
= 104 isolates) and 51% (33/65) of homes 3 months later (
= 56 isolates). The rates of multidrug resistance (MDR) were 61% among isolates collected at the baseline and 55% among isolates collected at the visit 3 months later. At the baseline, 100% (14/14) of MRSA isolates from rural homes were MDR. While antimicrobial use by humans or pets was associated with an increased risk for the isolation of MDR MRSA from the environment, clindamycin use was not associated with an increased risk for the isolation of MDR MRSA. Incident low-level mupirocin-resistant MRSA strains were isolated at 3 months from 2 (5%) of 39 homes that were randomized to mupirocin treatment but none of the control homes. Among patients recently treated for a CO-MRSA infection, MRSA and MDR MRSA were common contaminants in the home environment. This study contributes to evidence that occupant use of antimicrobial drugs, except for clindamycin, is associated with MDR MRSA in the home environmental reservoir. (This study has been registered at ClinicalTrials.gov under registration no. NCT00966446.)
MRSA is a common bacterial agent implicated in skin and soft tissue infections (SSTIs) in both community and health care settings. Patients with CO-MRSA infections contribute to environmental MRSA contamination in these settings and may be reexposed to MRSA strains from these reservoirs. People interact with natural and built environments; therefore, understanding the relationships between humans and animals as well as the characteristics of environmental reservoirs is important to advance strategies to combat antimicrobial resistance. Household interactions may influence the frequency and duration of exposure, which in turn may impact the duration of MRSA colonization or the probability for recurrent colonization and infection. Therefore, MRSA contamination of the home environment may contribute to human and animal recolonization and decolonization treatment failure. The aim of this study was to evaluate One Health risk factors that may be amenable to intervention and may influence the recovery of MDR and mupirocin resistance in CO-MRSA isolates.
We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent ...methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38–17·40), prior MRSA infection (OR 3·59; 95% CI 1·05–12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7–159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08–0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.
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Background. We conducted a case-control study to identify risk factors for efflux overexpression, an important mechanism of fluoroquinolone resistance, among patients with fluoroquinolone-resistant ...Escherichia coli (FQREC) gastrointestinal tract colonization. Methods. Three annual fecal surveillance surveys were performed hospital-wide, and all patients colonized with FQREC (levofloxacin minimum inhibitory concentration, >8 µg/mL) were included in the study. Cases and controls were defined on the basis of overexpression of the AcrAB efflux pump, as measured by the organic solvent tolerance (OST) assay. A multivariable logistic regression model was developed to identify risk factors for OST positivity among patients with FQREC colonization. Results. Eighty-nine patients were colonized with FQREC: 44 (49.4%) and 45 (50.6%) patients had isolates that were OST-positive and OST-negative, respectively. On multivariable analyses, location on the surgical service was significantly associated with recovery of an OST-positive isolate (odds ratio, 7.36; 95% confidence interval, 1.82-29.7; P = .005). Furthermore, patients who had received a first-generation cephalosporin in the 30 days prior to sampling were less likely to have an OST-positive isolate (odds ratio, 0.20; 95% confidence interval, .04-.94; P = .04). Conclusions. Among phenotypically identical FQREC isolates, different factors may drive the emergence of different resistance mechanisms. Further studies are needed to elucidate the relationship between antimicrobial use and specific resistance mechanisms.
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Summary The prevalence of urinary tract infections caused by fluoroquinolone-resistant Gram-negative bacilli (FQ-resistant GNB-UTIs) has been increasing. Previous studies that explored risk factors ...for FQ resistance have focused only on UTIs caused by Escherichia coli and/or failed to distinguish colonisation from infection. We conducted a case–control study at two medical centres within the University of Pennsylvania Health System to identify risk factors for FQ resistance among healthcare-acquired GNB-UTIs. Subjects with positive urine cultures for GNB and who met Centers for Disease Control and Prevention criteria for healthcare-acquired UTI were eligible. Cases were subjects with FQ-resistant GNB-UTI and controls were subjects with FQ-susceptible GNB-UTI matched to cases by month of isolation and species of infecting organism. In total, 251 cases and 263 controls were included from 1 January 2003 to 31 March 2005. Independent risk factors (adjusted odds ratio; 95% confidence interval) for FQ resistance included male sex (2.03; 1.21–3.39; P = 0.007), African-American race (1.80; 1.10–2.94; P = 0.020), chronic respiratory disease (2.58; 1.18–5.62; P = 0.017), residence in a long term care facility (4.41; 1.79–10.88; P = 0.001), hospitalisation within the past two weeks (2.19; 1.31–3.64; P = 0.003), hospitalisation under a medical service (2.72; 1.63–4.54; P < 0.001), recent FQ exposure (15.73; 6.15–40.26; P < 0.001), recent cotrimoxazole exposure (2.49; 1.07–5.79; P = 0.033), and recent metronidazole exposure (2.89; 1.48–5.65; P = 0.002).
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We identified eight consecutive patients who presented with a skin or soft tissue infection due to MRSA. Of seven household members of these cases, three were colonized with MRSA. The mean duration ...of MRSA colonization in index cases was 33 days (range 14–104), while mean duration of colonization in household cases was 54 days (range 12–95). There was a borderline significant association between having a concurrent colonized household member and a longer duration of colonization (mean 44 days vs. 26 days, P=0·08).
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Past studies exploring risk factors for fluoroquinolone (FQ) resistance in urinary tract infections (UTIs) focused only on UTIs caused by Gram-negative pathogens. The epidemiology of FQ resistance in ...enterococcal UTIs has not been studied. We conducted a case-control study at two medical centres within the University of Pennsylvania Health System in order to identify risk factors for FQ resistance in enterococcal UTIs. Subjects with positive urine cultures for enterococci and meeting CDC criteria for healthcare-acquired UTI were eligible. Cases were subjects with FQ-resistant enterococcal UTI. Controls were subjects with FQ-susceptible enterococcal UTI and were frequency matched to cases by month of isolation. A total of 136 cases and 139 controls were included from 1 January 2003 to 31 March 2005. Independent risk factors adjusted OR (95% CI) for FQ resistance included cardiovascular diseases 2·24 (1·05–4·79), P=0·037, hospitalization within the past 2 weeks 2·08 (1·05–4·11), P=0·035, hospitalization on a medicine service 2·15 (1·08–4·30), P<0·030, recent exposure to β-lactamase inhibitors (BLIs) 14·98 (2·92–76·99), P<0·001, extended spectrum cephalosporins 9·82 (3·37–28·60), P<0·001, FQs 5·36 (2·20–13·05), P<0·001 and clindamycin 13·90 (1·21–10·49), P=0·035. Use of BLIs, extended spectrum cephalosporins, FQs and clindamycin was associated with FQ resistance in enterococcal uropathogens. Efforts to curb FQ resistance should focus on optimizing use of these agents.
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Abstract
Aims
The 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation combining creatinine and cystatin C provides a better estimation of glomerular filtration rate (GFR) ...compared to the creatinine-only equation.
Methods and results
CKD-EPI creatinine-cystatin C equation (creatinine-cystatin) was compared to creatinine-only (creatinine) equation in a subpopulation of Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF). Patients were categorized according to difference in eGFR using the two equations: Group 1 (<−10 mL/min/1.73 m2, i.e. creatinine-cystatin more than 10 mL/min lower than creatinine), Group 2 (>−10 and <10 mL/min/1.73 m2), and Group 3 (>10 mL/min/1.73 m2, i.e. creatinine-cystatin more than 10 mL/min higher than creatinine). Cystatin C and creatinine were available in 1966 patients at randomization. Median (interquartile range) eGFR difference was −0.7 (−6.4–4.8) mL/min/1.73 m2. Compared to creatinine, creatinine-cystatin led to a substantial reclassification of chronic kidney disease stages. Overall, 212 (11%) and 355 (18%) patients were reallocated to a better and worse eGFR category, respectively. Compared to patients in Group 2, those in Group 1 (lower eGFR with creatinine-cystatin) had higher mortality and those in Group 3 (higher eGFR with creatinine-cystatin) had lower mortality. Increasing difference in eGFR (due to lower eGFR with creatinine-cystatin compared to creatinine) was associated with increasing elevation of biomarkers (including N-terminal pro-B-type natriuretic peptide and troponin) and worsening Kansas City Cardiomyopathy Questionnaire clinical summary score. The reason why the equations diverged with increasing severity of heart failure was that creatinine did not rise as steeply as cystatin C.
Conclusion
The CKD-EPI creatinine-only equation may overestimate GFR in sicker patients.
Clinical Trial Registration
URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01035255.
Structured Graphical Abstract
Structured Graphical Abstract
eGFR diff, estimated glomerular filtration rate difference; HF, heart failure; NYHA, New York Heart Association; KCCQ-CSS, Kansas City Cardiomyopathy Questionnaire clinical summary score; NT-proBNP, N-terminal pro-B-type natriuretic peptide; Y-axis (left) and green lines show the gap in estimated glomerular filtration rate (eGFR) between the 2021 CKD-EPI 2021 creatinine and cystatin C (crcys-21) and creatinine only (cr-21) equation (a negative value indicates a lower value with crcyst-21). The Y-axis (right) shows plasma cystatin C (red) and creatinine (blue) concentrations. The X-axis shows plasma NT-proBNP concentration. The panel at the top right shows how other patient characteristics varied across the range of NT-proBNP and crcyst-21-cr-21 difference. As the severity of heart failure increased, creatinine rose less steeply than cystatin C and GFR estimated by crcyst-21 was progressively lower than GFR estimated by cr-21.
Abstract
Background
Transthyretin cardiac amyloidosis (TTR-CA) is a rare disease characterized by the deposition of abnormal proteins in the heart, which can lead to heart failure (HF) and death. ...Echocardiography provides valuable diagnostic and prognostic information in CA, but indices of left ventricular performance alone cannot thoroughly characterise patients with restrictive cardiomyopathy. Evaluating the hemodynamic profile by studying the forward flow and left ventricular filling pressure (LVFP) already proved its value in stratifying disease severity in patients with heart failure (HF).
Purpose
This study evaluated the prognostic relevance of a non-invasive hemodynamic categorization of TTR-CA patients based on the estimation of stroke volume index (SVi) and systolic pulmonary artery pressure (PAPs).
Methods
Baseline clinical, transthoracic echocardiogram and laboratory data were collected prospectively in patients with diagnosed TTR-CA. Patients were classified into four groups based on forward flow (SVi < or ≥30 ml/m2) and systolic pulmonary artery pressure (PAPs ≥ or <40 mmHg). The four profiles obtained were Profile-A, normal-flow, normal-pressure; Profile-B, low-flow, normal-pressure; Profile-C, normal-flow, high-pressure; Profile-D, low-flow, high-pressure. We assessed the incidence of the composite endpoint of cardiovascular death and HF hospitalization accordingly to the hemodynamic profile. We performed univariate and multivariate Cox regression using profile A as a reference for HR estimation (profile A corresponding to HR=1).
Results
Fifty-nine patients were enrolled in the analysis (Table). Over a mean follow-up of 35.9 months (IQR 11.7 - 51.2 months) 23 patients met the composite endpoint (10%, 23%, 43%, 60% for Profile A, B, C and D respectively). Compared to Profile A, Profile D showed the greatest risk of CV mortality and HF hospitalization (HR 10.17), followed by Profile C (HR 6.77) and B (HR 3.45), with P-value=0.015. The C-statistic for the model was 0.72. Kaplan-Meier curves confirmed that patients with PAPs >40 mmHg and SVi< 30 ml/m2 presented the highest risk of the composite endpoint (Log-rank P = 0.010) (Figure). Hemodynamic profiling remained an independent predictor of outcome even after adjusting for the NAC stage (Profile B, HR 2.26; Profile C, HR 6.96; Profile D, HR 17.13; P-value=0.0012).
Conclusions
The proposed echocardiographically-derived hemodynamic classification based on forward-flow and LVFP estimation is useful for TTR-CA patients risk stratification. Patients with low SVi and high PAPs have the greatest risk of CV death and HF hospitalization, even after adjustment for NAC stage. These findings highlight the importance of early detection and monitoring of hemodynamic changes in TTR-CA patients for tailored management and to improve outcomes.Table.Figure.
Abstract
Background
Glucagon-like Peptide-1 receptor agonists (GLP-1RAs) have been shown to lower cardiovascular risk, and they are likely to reduce the incidence of all-cause and cardiovascular ...mortality in patients with type 2 diabetes. In this study-level analysis we investigated how metabolic and blood pressure changes are related to the reduction of cardiovascular events with GLP-1RAs.
Methods
We included seven randomized, placebo-controlled trials (ELIXA, LEADER, SUSTAIN-6, REWIND, EXSCEL, PIONEER 6, Harmony Outcomes) reporting incidence of one or more of the following outcomes: MACE, stroke, myocardial infarction, cardiovascular death, all-cause death, for a total of 56004 patients. A Pearson correlation analysis between logHR for the occurrence of outcome and placebo-corrected changes in Hb1Ac, systolic blood pressure and weight was performed.
Findings
Reduction of HbA1c level was significantly related to the reduction of MACE, Pearson R 0.86 (p=0.006) and stroke, Pearson R 0.79 (p=0.018). The reduction of weight instead, showed a robust correlation, not only with reduction of MACE, Pearson R 0.75 (p=0.032) and stroke, Pearson R 0.71 (p=0.047), but also with reduction of both cardiovascular death, Pearson R 0.95 (p=0.003; Picture 1) and all-cause death, Pearson R 0.91 (p=0.013). Reduction of SBP was significantly related to the reduction of both cardiovascular death, Pearson R 0.84 (p=0.036) and all-cause death, Pearson R 0.88 (p=0.020), but not of MACE.
Discussion
Mechanism of GLP-1RAs in preventing MACE is not fully understood. Other drugs that improve glycemic control did not showed convincing effect on cardiovascular outcome. Our finding prompts some considerations: both weight loss and control of HbA1c levels could play a role in MACE reduction. On the other hand, GLP1-RAs could act through other mechanisms and the metabolic effect could be a marker of the drug potency and dosage. Based on mechanistic studies, a theorized mechanism of cardiovascular benefit seen with GLP-1 RA is thought to be an anti-atherothrombotic and lipid plaque stabilization effect. This seems particularly convincing seeing the strong relationship of weight change and major events reduction. Notably, reduction in cardiovascular mortality and all-cause mortality was not related to the anti-hyperglycemic effect. Contrarily the body weight and SBP reduction were strongly related to both cardiovascular and all-cause mortality. These features could support the presumption of a hypothetic GLP1-RAs mechanism in modulation of lipidic profile and in RAAS inhibition, which have been already proved as beneficial for primary and secondary cardiovascular prevention.
Conclusion
Cardiovascular protection from GLP1-RAs is not primarily related to HbA1c reduction itself. Our data suggest that GLP-1RAs with the greater metabolic impact, such as liraglutide and semaglutide, should be used to treat diabetic patients to prevent MACE and CV death.
Funding Acknowledgement
Type of funding sources: None.
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