Resistant plasmid profile analysis of multidrug resistant Escherichia coli isolated from urinary tract infections in Abeokuta, Nigeria

Background: Multi-drug resistant Escherichia coli has become a major threat and cause of many urinary tract infections (UTIs) in Abeokuta, Nigeria.Objectives: This study was carried out to determine the resistant plasmids of multidrug resistant Escherichia coli isolated from (Urinary tract infections)UTIs in Abeokuta.Methods: A total of 120 Escherichia coli isolates were obtained from urine samples collected from patients attending inpatient and outpatient clinics presenting UTI; with their biodata. Antibiotics susceptibility was performed and multi-drug resistant isolates were selected for plasmid profiling. Plasmids were extracted by the alkaline lysis method, electrophoresed on 0.8% agarose gel and profiled using a gel-photo documentation system gel.Results: Escherichia coli isolates obtained shows high resistance to cloxacillin (92.5%), amoxicillin (90.8%), ampicillin (90.8%), erythromycin (75.8%), cotrimoxazole (70.0%), streptomycin (70.0%) and tetracycline (68.3%) while 85.8% and 84.2% were susceptible to gentamycin and ceftazidime respectively. Sixteen Escherichia coli strains were observed to be resistant to more than two classes of antibiotics. The resistant plasmid DNA was detectable in 6(37.5%) of the 16 multidrug resistant Escherichia coli having single sized plasmids of the same weight 854bp and were all resistant to erythromycin, cefuroxime, cloxacillin, amoxicillin, ampicillin and cotrimoxazole.Conclusion: This study has highlighted the emergence of multidrug resistant R-plasmids among Escherichia coli causing urinary tract infections in Abeokuta, Nigeria. There is a high level of resistance to many antimicrobials that are frequently used in Abeokuta, Nigeria.Keywords: Escherichia coli, UTI, R-plasmid, multidrug resis

Effect of ferric carboxymaltose on calculated plasma volume status and clinical congestion: a FAIR‐HF substudy

Iron deficiency worsens symptoms, quality of life, and exercise capacity in chronic heart failure (CHF) and might do so by promoting fluid retention. We assessed whether iron repletion improved congestion in CHF and appraised the prognostic utility of calculated plasma volume status (PVS), a novel index of congestion, in the FAIR‐HF data set. Methods and results In FAIR‐HF, 459 iron deficient CHF patients were randomized to intravenous ferric carboxymaltose (FCM) or saline and assessed at 4, 12, and 24 weeks. Using weight and haematocrit, we calculated PVS in 436 patients. At baseline, PVS and weight were −5.5 ± 7.7% and 76.9 ± 14.3 kg, with peripheral oedema evident in 35% of subjects. Higher PVS values correlated to other congestion surrogates such as lower serum albumin. At 4 weeks, FCM was associated with greater reductions in weight (0.02) and PVS (P −4% at baseline predicted worse outcomes even after adjustment for treatment assignment (hazard ratio 1.88, 95% confidence interval 1.01-3.51, 0.046). Conclusions Intravenous iron therapy with FCM is associated with early reductions in PVS and weight, implying that decongestion might be one mechanism via which iron repletion aids CHF patients. Calculated PVS is of prognostic utility in this cohort

The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET

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Future perspectives on treatment with erythropoiesis-stimulating agents in high-risk patients

Patients with chronic kidney disease (CKD) have a high burden of mortality and cardiovascular morbidity. Additional strategies to modulate cardiovascular risk in this population are needed. Anaemia has been associated with adverse outcomes in CKD populations, and the ability to modify this parameter with the use of erythropoiesis-stimulating agents has been a topic of much debate. Data on the effects of anaemia correction on cardiovascular outcomes and survival in CKD have been both discordant and controversial. It is hoped that the ongoing Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT) will help to redress the current clinical gaps and the uncertainty over the optimal management of anaemia in patients with CKD and type 2 diabetes mellitus. Anaemia is also increasingly being recognized as an important comorbid condition in patients with symptomatic heart failure. The ongoing Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HFTM) trial is designed to determine whether the treatment of anaemia improves outcomes in such patients

Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload

Background The mitochondrial unfolded protein response (UPRmt) is activated when misfolded proteins accumulate within mitochondria and leads to increased expression of mitochondrial chaperones and proteases to maintain protein quality and mitochondrial function. Cardiac mitochondria are essential for contractile function and regulation of cell viability, while mitochondrial dysfunction characterizes heart failure. The role of the UPRmt in the heart is unclear. Objectives The purpose of this study was to: 1) identify conditions that activate the UPRmt in the heart; and 2) study the relationship among the UPRmt, mitochondrial function, and cardiac contractile function. Methods Cultured cardiac myocytes were subjected to different stresses in vitro. Mice were subjected to chronic pressure overload. Tissues and blood biomarkers were studied in patients with aortic stenosis. Results Diverse neurohumoral or mitochondrial stresses transiently induced the UPRmt in cultured cardiomyocytes. The UPRmt was also induced in the hearts of mice subjected to chronic hemodynamic overload. Boosting the UPRmt with nicotinamide riboside (which augments NAD+ pools) in cardiomyocytes in vitro or hearts in vivo significantly mitigated the reductions in mitochondrial oxygen consumption induced by these stresses. In mice subjected to pressure overload, nicotinamide riboside reduced cardiomyocyte death and contractile dysfunction. Myocardial tissue from patients with aortic stenosis also showed evidence of UPRmt activation, which correlated with reduced tissue cardiomyocyte death and fibrosis and lower plasma levels of biomarkers of cardiac damage (high-sensitivity troponin T) and dysfunction (N-terminal pro–B-type natriuretic peptide). Conclusions These results identify the induction of the UPRmt in the mammalian (including human) heart exposed to pathological stresses. Enhancement of the UPRmt ameliorates mitochondrial and contractile dysfunction, suggesting that it may serve an important protective role in the stressed heart

Health economic assessment of ferric carboxymaltose in patients with iron deficiency and chronic heart failure based on the FAIR-HF trial: an analysis for the UK

AIMS: The purpose of this study was to evaluate the cost-effectiveness of iron repletion using intravenous (i.v.) ferric carboxymaltose (FCM) in chronic heart failure (CHF) patients with iron deficiency with or without anaemia. Cost-effectiveness was studied from the perspective of the National Health Service in the UK. METHODS AND RESULTS: A model-based cost-effectiveness analysis was used to compare iron repletion with FCM with no iron treatment. Using data from the FAIR-HF trial and publicly available sources and publications, per patient costs and clinical effectiveness of FCM were estimated compared with placebo. Cost assessment was based on study drug and administration costs, cost of CHF treatment, and hospital length of stay. The incremental cost-effectiveness ratio (ICER) of FCM use was expressed as cost per quality-adjusted life year (QALY) gained, and sensitivity analyses were performed on the base case. The time horizon of the analysis was 24 weeks. Mean QALYs were higher in the FCM arm (difference 0.037 QALYs; bootstrap-based 95% confidence interval 0.017-0.060). The ICER of FCM compared with placebo was €4414 per QALY gained for the FAIR-HF dosing regimen. Sensitivity analyses confirmed the base case result to be robust. CONCLUSION: From the UK payers' perspective, managing iron deficiency in CHF patients using i.v. FCM was cost-effective in this analysis. The base case ICER was clearly below the threshold of €22 200-€33 300/QALY gained (£20 000-£30 000) typically used by the UK National Institute for Health and Clinical Excellence and proved to be robust in sensitivity analysis. Improved symptoms and better quality of life contributed to this result

A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency. Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models. Results: Among 75 randomized patients, mean (SD) age for iron therapy (n = 37) versus placebo (n = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m2], TSAT (23 [12] vs. 21 [6])%; SF (57 [64] vs. 62 [33]) μg/l; Hb (122.4 [9.2] vs. 127 [13.2] g/l); 6MWT (384 [95] vs. 469 [142] meters) at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks (P < 0.02), and Hb at 12 weeks (P = 0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy. Conclusion: This trial did not demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in nondialysis patients with CKD who are iron-deficient

Iron deficiency in worsening heart failure is associated with reduced estimated protein intake, fluid retention, inflammation and antiplatelet use

AIMS: Iron deficiency (ID) is common in heart failure (HF) patients and negatively impacts symptoms and prognosis. The aetiology of ID in HF is largely unknown. We studied determinants and the biomarker profile of ID in a large international HF cohort. METHODS AND RESULTS: We studied 2357 worsening HF patients from the BIOSTAT-CHF cohort. ID was defined as transferrin saturation <20%. Univariable and multivariable logistic regression models were constructed to identify determinants for ID. We measured 92 cardiovascular markers (Olink Cardiovascular III) to establish a biomarker profile of ID. The primary endpoint was the composite of all-cause mortality and first HF rehospitalization. Mean age (±standard deviation) of all patients was 69 ± 12.0 years, 26.1% were female and median N-terminal pro B-type natriuretic peptide levels (+interquartile range) were 4305 (2360-8329) ng/L. Iron deficiency was present in 1453 patients (61.6%), with highest prevalence in females (71.1% vs. 58.3%; P < 0.001). Independent determinants of ID were female sex, lower estimated protein intake, higher heart rate, presence of peripheral oedema and orthopnoea, chronic kidney disease, lower haemoglobin, higher C-reactive protein levels, lower serum albumin levels, and P2Y12 inhibitor use (all P < 0.05). None of these determinants were sex-specific. The biomarker profile of ID largely consisted of pro-inflammatory markers, including paraoxonase 3 (PON3) and tartrate-resistant acid phosphatase type 5. In multivariable Cox proportional hazard regression analyses, ID was associated to worse outcome, independently of predictors of ID (hazard ratio 1.25, 95% confidence interval 1.06-1.46; P = 0.007). CONCLUSION: Our data suggest that the aetiology of ID in worsening HF is complex, multifactorial and seems to consist of a combination of reduced iron uptake (malnutrition, fluid overload), impaired iron storage (inflammation, chronic kidney disease), and iron loss (antiplatelets)

Rationale and design of Ferinject® Assessment in patients with IRon deficiency and chronic Heart Failure (FAIR-HF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia

Iron deficiency (ID) and anaemia are common in patients with chronic heart failure (CHF). The presence of anaemia is associated with increased morbidity and mortality in CHF, and ID is a major reason for the development of anaemia. Preliminary studies using intravenous (i.v.) iron supplementation alone in patients with CHF and ID have shown improvements in symptom status. FAIR-HF (Clinical Trials.gov NCT00520780) was designed to determine the effect of i.v. iron repletion therapy using ferric carboxymaltose on self-reported patient global assessment (PGA) and New York Heart Association (NYHA) in patients with CHF and ID. This is a multi-centre, randomized, double-blind, placebo-controlled study recruiting ambulatory patients with symptomatic CHF with LVEF < 40% (NYHA II) or < 45% (NYHA III), ID [ferritin < 100 ng/mL or ferritin 100-300 ng/mL when transferrin saturation (TSAT) < 20%], and haemoglobin 9.5-13.5 g/dL. Patients were randomized in a 2:1 ratio to receive ferric carboxymaltose (Ferinject((R))) 200 mg iron i.v. or saline i.v. weekly until iron repletion (correction phase), then monthly until Week 24 (maintenance phase). Primary endpoints are (i) self-reported PGA at Week 24 and (ii) NYHA class at Week 24, adjusted for baseline NYHA class. This study will provide evidence on the efficacy and safety of iron repletion with ferric carboxymaltose in CHF patients with ID with and without anaemia

A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD.

INTRODUCTION: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency. METHODS: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models. RESULTS: Among 75 randomized patients, mean (SD) age for iron therapy (n = 37) versus placebo (n = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m2], TSAT (23 [12] vs. 21 [6])%; SF (57 [64] vs. 62 [33]) μg/l; Hb (122.4 [9.2] vs. 127 [13.2] g/l); 6MWT (384 [95] vs. 469 [142] meters) at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks (P < 0.02), and Hb at 12 weeks (P = 0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy. CONCLUSION: This trial did not demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in nondialysis patients with CKD who are iron-deficient