Viable adhered Staphylococcus aureus highly reduced on novel antimicrobial sutures using chlorhexidine and octenidine to avoid surgical site infection (SSI)

Background Surgical sutures can promote migration of bacteria and thus start infections. Antiseptic coating of sutures may inhibit proliferation of adhered bacteria and avoid such complications. Objectives This study investigated the inhibition of viable adhering bacteria on novel antimicrobially coated surgical sutures using chlorhexidine or octenidine, a critical factor for proliferation at the onset of local infections. The medical need, a rapid eradication of bacteria in wounds, can be fulfilled by a high antimicrobial efficacy during the first days after wound closure. Methods As a pretesting on antibacterial efficacy against relevant bacterial pathogens a zone of inhibition assay was conducted with middle ranged concentrated suture coatings (22 mu g/cm). For further investigation of adhering bacteria in detail the most clinically relevant Staphylococcus aureus (ATCC (R) 49230 (TM)) was used. Absorbable braided sutures were coated with chlorhexidine-laurate, chlorhexidine-palmitate, octenidine-laurate, and octenidine-palmitate. Each coating type resulted in 11, 22, or 33 mu g/cm drug content on sutures. Scanning electron microscopy (SEM) was performed once to inspect the coating quality and twice to investigate if bacteria have colonized on sutures. Adhesion experiments were assessed by exposing coated sutures to S. aureus suspensions for 3 h at 37 degrees C. Subsequently, sutures were sonicated and the number of viable bacteria released from the suture surface was determined. Furthermore, the number of viable planktonic bacteria was measured in suspensions containing antimicrobial sutures. Commercially available sutures without drugs (Vicryl (R), PGA Resorba (R), and Gunze PGA), as well as triclosan-containing Vicryl (R) Plus were used as control groups. Results Zone of inhibition assay documented a multispecies efficacy of novel coated sutures against tested bacterial strains, comparable to most relevant S. aureus over 48 hours. SEM pictures demonstrated uniform layers on coated sutures with higher roughness for palmitate coatings and sustaining integrity of coated sutures. Adherent S. aureus were found via SEM on all types of investigated sutures. The novel antimicrobial sutures showed significantly less viable adhered S. aureus bacteria (up to 6.1 log) compared to Vicryl (R) Plus (0.5 log). Within 11 mu g/cm drug-containing sutures, octenidine-palmitate (OL11) showed the highest number of viable adhered S. aureus (0.5 log), similar to Vicryl (R) Plus. Chlorhexidine-laurate (CL11) showed the lowest number of S. aureus on sutures (1.7 log), a 1.2 log greater reduction. In addition, planktonic S. aureus in suspensions were highly inhibited by CL11 (0.9 log) represents a 0.6 log greater reduction compared to Vicryl (R) Plus (0.3 log). Conclusions Novel antimicrobial sutures can potentially limit surgical site infections caused by multiple pathogenic bacterial species. Therefore, a potential inhibition of multispecies biofilm formation is assumed. In detail tested with S. aureus, the chlorhexidine-laurate coating (CL11) best meets the medical requirements for a fast bacterial eradication. This suture coating shows the lowest survival rate of adhering as well as planktonic bacteria, a high drug release during the first-clinically most relevant-48 hours, as well as biocompatibility. Thus, CL11 coatings should be recommended for prophylactic antimicrobial sutures as an optimal surgical supplement to reduce wound infections. However, animal and clinical investigations are important to prove safety and efficacy for future applications

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

Ferric carboxymaltose in patients with heart failure and iron deficiency

BACKGROUND: Iron deficiency may impair aerobic performance. This study aimed to determine whether treatment with intravenous iron (ferric carboxymaltose) would improve symptoms in patients who had heart failure, reduced left ventricular ejection fraction, and iron deficiency, either with or without anemia. METHODS: We enrolled 459 patients with chronic heart failure of New York Heart Association (NYHA) functional class II or III, a left ventricular ejection fraction of 40% or less (for patients with NYHA class II) or 45% or less (for NYHA class III), iron deficiency (ferritin level <100 microg per liter or between 100 and 299 microg per liter, if the transferrin saturation was <20%), and a hemoglobin level of 95 to 135 g per liter. Patients were randomly assigned, in a 2:1 ratio, to receive 200 mg of intravenous iron (ferric carboxymaltose) or saline (placebo). The primary end points were the self-reported Patient Global Assessment and NYHA functional class, both at week 24. Secondary end points included the distance walked in 6 minutes and the health-related quality of life. RESULTS: Among the patients receiving ferric carboxymaltose, 50% reported being much or moderately improved, as compared with 28% of patients receiving placebo, according to the Patient Global Assessment (odds ratio for improvement, 2.51; 95% confidence interval [CI], 1.75 to 3.61). Among the patients assigned to ferric carboxymaltose, 47% had an NYHA functional class I or II at week 24, as compared with 30% of patients assigned to placebo (odds ratio for improvement by one class, 2.40; 95% CI, 1.55 to 3.71). Results were similar in patients with anemia and those without anemia. Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality-of-life assessments. The rates of death, adverse events, and serious adverse events were similar in the two study groups. CONCLUSIONS: Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, improves symptoms, functional capacity, and quality of life; the side-effect profile is acceptable. (ClinicalTrials.gov number, NCT00520780)

The impact of intravenous ferric carboxymaltose on renal function: an analysis of the FAIR-HF study.

AIMS: Anaemia and iron deficiency are constituents of the cardio-renal syndrome in chronic heart failure (CHF). We investigated the effects of i.v. iron in iron-deficient CHF patients on renal function, and the efficacy and safety of this therapy in patients with renal dysfunction. METHODS AND RESULTS: The FAIR-HF trial randomized 459 CHF patients with iron deficiency (ferritin 0.20 for interactions). No interaction between the favourable effects of FCM and baseline renal function was seen for the primary endpoints [improvement in Patient Global Assessment (P = 0.43) and NYHA class (P = 0.37) at 24 weeks]. Safety and adverse event profiles were similar in patients with baseline eGFR <60 and ≥60 mL/min/1.73 m(2) . CONCLUSIONS: Treatment of iron deficiency in CHF patients with i.v. FCM was associated with an improvement in renal function. FCM therapy was effective and safe in CHF patients with renal dysfunction.The FAIR-HF study and this analysis were supported by Vifor Pharma, Zurich, Switzerland

The impact of intravenous ferric carboxymaltose on renal function: an analysis of the FAIR-HF study

Aims Anaemia and iron deficiency are constituents of the cardio-renal syndrome in chronic heart failure (CHF). We investigated the effects of i.v. iron in iron-deficient CHF patients on renal function, and the efficacy and safety of this therapy in patients with renal dysfunction. Methods and results The FAIR-HF trial randomized 459 CHF patients with iron deficiency (ferritin &lt;100 mu g/L, or between 100 and 299 mu g/L if transferrin saturation was &lt;20%): 304 to i.v. ferric carboxymaltose (FCM) and 155 to placebo, and followed-up for 24 weeks. Renal function was assessed at baseline and at weeks 4, 12, and 24, using the estimated glomerular filtration rate (eGFR, mL/min/1.73m(2)), calculated from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. At baseline, renal function was similar between groups (62.420.6 vs. 62.9 +/- 23.4 mL/min/1.73m(2), FCM vs. placebo). Compared with placebo, treatment with FCM was associated with an increase in eGFR [treatment effect: week 4, 2.11 +/- 1.21 (P = 0.082); week 12, 2.41 +/- 1.33 (P = 0.070); and week 24, 2.98 +/- 1.44 mL/min/1.73m(2) (P = 0.039)]. This effect was seen in all pre-specified subgroups (P &gt; 0.20 for interactions). No interaction between the favourable effects of FCM and baseline renal function was seen for the primary endpoints [improvement in Patient Global Assessment (P = 0.43) and NYHA class (P = 0.37) at 24 weeks]. Safety and adverse event profiles were similar in patients with baseline eGFR &lt;60 and 60 mL/min/1.73m(2). Conclusions Treatment of iron deficiency in CHF patients with i.v. FCM was associated with an improvement in renal function. FCM therapy was effective and safe in CHF patients with renal dysfunction

Numbers of viable bacteria in suspension incubated for 3 hours with novel antimicrobial sutures.

<p>An initial <i>S</i>. <i>aureus</i> concentration of 1.3 x 10⁸ cfu/ml was used for bacterial suspensions. Chlorhexidine- or octenidine-coated sutures showed a strong inhibition of pathogens in the surrounding suspensions. The triclosan-coated suture Vicryl^® Plus (VP) and the uncoated Gunze suture (G) were used as controls. Fatty acid-coated sutures (PA80, LA80) and commercial sutures without any drug content (V: Vicryl^®, R: PGA Resorba^®) were tested within the non-antimicrobial suture group. Significance levels are p<0.05 (*), p<0.01 (**) and p<0.001 (***); n.s.: not significant, n.a.: not applicable.</p

Rationale and design of Ferinject((R)) 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 &lt; 40% (NYHA II) or &lt; 45% (NYHA III), ID [ferritin &lt; 100 ng/mL or ferritin 100-300 ng/mL when transferrin saturation (TSAT) &lt; 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

Rating levels used for comparative antimicrobial suture evaluation.

<p>Rating levels used for comparative antimicrobial suture evaluation.</p

Zone of inhibition assay for five bacterial species over 48 hours.

<p>Zones of inhibition in millimeter for each coating type at 22 μg/cm drug content (CL22, CP22, OL22, OP22) on sutures. Test strains used were <i>S</i>. <i>aureus</i>, <i>MRSA</i>, <i>S</i>. <i>epidermidis</i>, <i>E</i>. <i>faecalis</i> and <i>E</i>. <i>coli</i> after A) 24 hours and B) 48 hours test period.</p

Numbers of adhered <i>S</i>. <i>aureus</i> colonies on sutures’ surfaces per cm sample after 3 hours of incubation in on average 1.3 x 10⁸ cfu/ml bacterial suspension.

<p>Viably adhered numbers of bacteria and their reductions compared to uncoated Gunze (G) suture. <b>Left</b> (up to dashed line): Sutures coated with antimicrobial substances, such as chlorhexidine-laurate (CL), chlorhexidine-palmitate (CP), octenidine-laurate (OL), and octenidine-palmitate (OP) each with the drug concentration 11, 22, and 33 μg/cm. Novel coated sutures were also compared to commercially available triclosan-containing Vicryl^® Plus (VP) suture. <b>Right</b>: Groups of sutures without active antimicrobial agents, uncoated Gunze (G), coated with fatty acids (PA80, LA80) and commercially available common resorbable sutures (V: Vicryl^®, R: PGA Resorba^®). Significance levels are p<0.05 (*), p<0.01 (**) and p<0.001 (***); n.s.: not significant, n.a.: not applicable.</p