Fibrin glue as a local drug-delivery system for bacteriophage PA5.

Fibrin glue has been used clinically for decades in a wide variety of surgical specialties and is now being investigated as a medium for local, prolonged drug delivery. Effective local delivery of antibacterial substances is important perioperatively in patients with implanted medical devices or postoperatively for deep wounds. However, prolonged local application of antibiotics is often not possible or simply inadequate. Biofilm formation and antibiotic resistance are also major obstacles to antibacterial therapy. In this paper we test the biocompatibility of bacteriophages incorporated within fibrin glue, track the release of bacteriophages from fibrin scaffolds, and measure the antibacterial activity of released bacteriophages. Fibrin glue polymerized in the presence of the PA5 bacteriophage released high titers of bacteriophages during 11 days of incubation in liquid medium. Released PA5 bacteriophages were effective in killing Pseudomonas aeruginosa PA01. Overall, our results show that fibrin glue can be used for sustained delivery of bacteriophages and this strategy holds promise for many antibacterial applications.

Risk factors for critical limb ischemia in patients undergoing femoral cannulation for venoarterial extracorporeal membrane oxygenation: Is distal limb perfusion a mandatory approach?

BACKGROUND: Venoarterial extracorporeal membrane oxygenation support is a well-established tool in the care of severe refractory cardiac and respiratory failure. The application of this support may serve as a bridge to transplant, recovery or to implantation of a ventricular assist device. Venoarterial extracorporeal membrane oxygenation support can be administered through an open surgical access via the common femoral or axillary artery or a percutaneous approach using Seldinger technique. Both techniques may obstruct the blood flow to the lower limb and may cause a significant ischemia with possible limb loss. Malperfusion of the distal limb can be avoided using an ipsilateral distal limb perfusion, which may be established by adding a single-lumen catheter during venoarterial extracorporeal membrane oxygenation treatment to overcome the obstruction. The aim of this study is to distinguish the presence or absence of a distal limb perfusion regarding the incidence of distal limb ischemia. Furthermore, expected risk factors of open and percutaneous femoral venoarterial extracorporeal membrane oxygenation installation were evaluated for the development of distal limb ischemia. METHODS: Between January 2012 and September 2015, 489 patients received venoarterial extracorporeal membrane oxygenation support at our institution. In total, 307 patients (204 male, 103 female) with femoral cannulation were included in the analysis. The cohort was distinguished by the presence (group A; n = 237) or absence (group B; n = 70) of a distal limb perfusion during peripheral venoarterial extracorporeal membrane oxygenation treatment. Furthermore, a risk factor analysis for the development of distal limb ischemia was performed. RESULTS: The main indications for venoarterial extracorporeal membrane oxygenation therapy were a low cardiac output syndrome (LCOS) (53%) and failed weaning of extracorporeal circulation (23%). A total of 23 patients (7.49%) under venoarterial extracorporeal membrane oxygenation support developed severe distal limb malperfusion (3.38% in group A vs 21.42% in group B). Preemptive installation of distal limb perfusion extended the intervention-free intervals to 7.8 ± 19.3 days in group A and 6.3 ± 12.5 in group B. A missing distal limb perfusion (p = 0.001) was identified as a main risk factor for critical limb ischemia. Other comorbidities such as arterial occlusion disease (p = 0.738) were not statistically significantly associated. Surgical intervention due to vascular complications after extracorporeal membrane oxygenation explantation was needed in 14 cases (4.22% in group A and 5.71% in group B). CONCLUSION: We were able to identify the absence of distal limb perfusion as an independent risk factor for the development of critical distal limb ischemia during femoral venoarterial extracorporeal membrane oxygenation treatment. The application of a distal limb perfusion should be considered as a mandatory approach in the context of femoral venoarterial extracorporeal membrane oxygenation treatment regardless of the implantation technique.

MitraClip procedure prior to left ventricular assist device implantation.

BACKGROUND: Functional mitral valve regurgitation is a frequent consequence of left ventricular dysfunction in patients with severe heart failure and is associated with a poor prognosis. It is hypothesized that in this patient group the mitral valve repair, respectively replacement, improves hemodynamics and clinical symptoms. As operative interventions with the help of heart-lung-machine are high risk procedures in these cases, the transcatheter mitral repair with MitraClip® (Abbott Vascular, IL, USA) has recently become frequently used. Most of these cases experience a progress in left ventricular dysfunction, which finally leads to in an implantation of a left ventricular assist device. In this report, we describe a series of six cases in which patients with end stage heart failure and consecutive functional mitral valve regurgitation were supported with a left ventricular assist device after MitraClip implantation. We aimed to investigate, whether the MitraClip implantation leads to an improvement of the hemodynamic prior left ventricular assist device (LVAD)-implantation. METHODS: We retrospectively analyzed the data of 6 patients (5 males, 1 female) with severe heart failure, who underwent LVAD implantation after the MitraClip procedure. The mean age at MitraClip procedure was 64.6 years, mean age at time of LVAD implantation was 65.5 years. The parameters examined were cardiac index (CI), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and the pulmonary capillary wedge pressure (PCWP). RESULTS: All patients had functional mitral regurgitation (MR). Severity of MR was reduced successfully in all treated patients. All patients were discharged with MR I-II and NYHA functional class III or IV after MitraClip procedure. The mean CI was 2.93 before MitraClip procedure and 2.36 before LVAD-Implantation. Mean LVEDD was 71 mm before MitraClip, mean LVEDD was 70.6 mm before LVAD, and 63.2mm after LVAD implantation respectively. The mean PCWP was 21.5 mmHg before MitraClip and 19.8 mmHg before LVAD implantation respectively. The mean left ventricular ejection fraction (LVEF) was 19.2% before MitraClip, the mean LVEF was 17.6% before LVAD and 15% after LVAD implantation. Two of the LVAD implanted patients died due to post-operative complications. There were no complications after MitraClip procedure. CONCLUSIONS: Our presented patient cohort presented little hemodynamic improvement after the MitraClip procedure. There was no clinical benefit for the patients after MitraClip procedure, progressing left ventricular dysfunction could not be prevented and resulted in subsequent LVAD implantation.

Local Anesthetics delivered through Pleural Drainages improve Pain and Lung Function after Cardiac Surgery.

OBJECTIVE: Pleural tubes after coronary artery bypass graft (CABG) surgery usually cause pain resulting interalia in an impact of postoperative breathing. Therefore, the influence of intrapleural lidocaine application through special double-lumen chest tubes with respect to pain relief and lung function was investigated and compared with placebo. METHODS: In this study, 40 patients who underwent CABG got intrapleural injection either with 2% lidocaine (n = 20) or placebo (0.9% saline solution) (n = 20) on the first 2 days after surgery. Pain was measured by pain intensity numeric rating scale (NRS) (0 = no pain; 10 = the most intense pain) and lung function by portable spirometer. RESULTS: On the first postoperative day (POD1), mean pain reduction was NRS 1.9 for the lidocaine group with an improvement of the forced expiratory volume in 1 second (FEV1) of 0.51 L. Similar results were shown on the second postoperative day (POD2) with a decreased pain level of mean NRS 1.65 and an FEV1 improvement of 0.26 L. In comparison, results of the placebo group showed no significant pain reduction, neither on the POD1 (NRS 0.35; p = 0.429) nor on the POD2 (NRS 0.55; p = 0.159). Also, there was no significant influence of FEV1 after placebo on the POD1 (FEV1 = 0.048 L; p = 0.70) or on the POD2 (FEV1 = 0.0135 L; p = 0.925). CONCLUSION: Intrapleural application of lidocaine is a safe and feasible method to reduce drainage-related pain and improving lung function after CABG.

Antibiotic therapy following polymerase chain reaction diagnosis of infective endocarditis: a single centre experience.

OBJECTIVES: Conventional culture methods often fail in the aetiological diagnosis of infective endocarditis (IE), complicating adequate IE treatment. Therefore, in addition to culture diagnostic methods, our clinical department uses a broad-range 16S and 18S rDNA polymerase chain reaction (PCR) and sequencing test to detect and identify IE agents. METHODS: Between 2009 and 2013, we performed 246 valve replacements due to endocarditis. In 46 patients with culture-negative IE or incongruent preoperative microbiological diagnostics, heart valve (HV) samples were PCR-analysed and PCR products subsequently sequenced for phylogenetic analysis. RESULTS: The molecular diagnosis led us to change the antibiotic regimen in 7 of 46 patients. CONCLUSIONS: The PCR results demonstrate that the molecular test is a useful diagnostic tool for the rapid diagnosis of IE. Furthermore, the molecular diagnosis had a significant, direct impact on the therapy of IE. This suggests that using PCR can improve antibiotic treatment, particularly in cases of culture-negative IE. Consequently, molecular analysis of micro-organisms in HV samples should be performed routinely where preoperative diagnosis remains unclear.

Prevention of pacemaker infections with perioperative antimicrobial treatment: an in vitro study.

AIMS: The antimicrobial treatment of pacemaker casings with antiseptics (povidone-iodine or octenidine dihydrochloride) or antibiotics (vancomycin, daptomycin, cefuroxime, Tazobac, or nebacetin) was analysed in vitro for its biocompatibility and efficacy in preventing the bacterial adhesion of Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli to cardiac-implantable electrophysiological devices (CIEDs). METHODS AND RESULTS: Titan platelets (0.4 cm²) cut from pacemaker casings were impregnated with seven different antimicrobial solutions: two antiseptics and five antibiotics. Subsequently, they were challenged with bacterial contamination by four test strains over a 24 h incubation period. Bacterial adherence was quantified using the colony-forming-unit method after cell recovery with sonication and examined with confocal laser scanning electron microscopy. Simultaneously, the biocompatibility of the antimicrobial impregnation was assessed using pre-treated titan platelets in a culture of human fibroblasts, skeletal myoblasts, and microvascular endothelial cells. After a 48 h incubation, cell vitality was measured using the 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H/tetrazolium monosodium (WST-8) assay. The immersion of pacemaker casings in antiseptic or antibiotic solutions applies an antimicrobial coating that can significantly reduce bacterial adhesion. The studied impregnations differed in their antimicrobial efficacy and toxicity. CONCLUSION: Compared with the two antiseptics and the other tested antibiotics, nebacetin showed the best ratio of efficacy to toxicity. Nebacetin showed good in vitro antibacterial activity against both Gram-positive and Gram-negative pathogens without impairing human cell vitality. It is a safe and effective candidate for CIED impregnation.

Antibiotic pretreatment of heart valve prostheses to prevent early prosthetic valve endocarditis.

BACKGROUND AND AIM OF THE STUDY: Prosthetic valve endocarditis (PVE), a rare but major complication after heart valve replacement surgery, has potentially catastrophic consequences despite maximal treatment. Thus, preventive measures are essential. The study aim was to investigate the effect of pretreating heart valve prostheses with the antibiotics baneomycin and daptomycin, with and without surgical sealant fibrin glue as a drug-releasing substance. The biocompatibility of baneocin and daptomycin was also investigated. METHODS: Samples of polyethylene terephthalate (PTE), as used for the sewing cuffs of prosthetic heart valves, were tested; untreated samples served as controls. All samples were contaminated with Staphylococcus epidermidis, and colony-forming units (CFUs) then counted. Cytotoxicity tests were performed using the MTT-assay to evaluate the effects of baneomycin and daptomycin on cell proliferation and wound healing. RESULTS: Untreated and fibrin glue-coated samples were directly infected with a bacterial count of 2.82 +/- 0.63 x 10(5) CFU/ml and 2.80 +/- 1.07 x 10(5) CFU/ml, on average. Baneocin-impregnated samples were sterile for 1.9 +/- 0.38 days, with a subsequent bacterial count of 2.26 +/- 0.6 x 10(5) CFU/ml, while daptomycin-impregnated samples were sterile for 2.9 +/- 0.38 days, with a subsequent bacterial count of 1.81 +/- 0.53 x 10(5) CFU/ml. Samples coated with a fibrin glue-baneocin mixture were sterile for 3.14 +/- 0.38 days, after which the bacterial count was 0.74 +/- 0.47 x 10(5) CFU/ml. After coating with a fibrin glue-daptomycin mixture, samples were sterile for 7.0 +/- 0.58 days, and the bacterial count was 0.70 +/- 0.56 x 10(5) CFU/ml. CONCLUSION: In this in-vitro study, the pretreatment of prosthetic heart valves with antibiotics reduced the risk of bacterial adhesion and consequent infection. The combination of antibiotics with fibrin glue prolonged this preventive effect, with baneocin demonstrating a better biocompatibility than daptomycin. On the basis of its antibacterial efficacy, daptomycin appears to be a more suitable antibiotic to prevent early PVE with Gram-positive bacteria. The soaking of prosthetic heart valves in antibiotic solutions prior to implantation, in combination with fibrin glue in cases of suspected endocarditis, can prevent the development of early PVE. This preventive strategy should be investigated for use as a standard procedure in clinical practice.

Prevention of early vascular graft infection using regional antibiotic release.

BACKGROUND: Infections after prosthetic replacement of the aorta remain a serious and life-threatening complication. The only appropriate treatment is the surgical removal of the infected prosthesis. Accordingly, there is a need for new procedures to prevent the infection of vascular prostheses. This in vitro experiment investigated the effect of the pretreatment of vascular prostheses with antibiotics (daptomycin or baneocin) and the effect of antibiotics combined with fibrin sealant as possible prophylaxis of perioperative graft infection. METHODS: Untreated prostheses served as controls. Pretreated prostheses of double woven velour vascular grafts were contaminated with Staphylococcus epidermidis, and colony-forming units were counted each day (CFU/mL). RESULTS: The period of sterility differed significantly as a function of the pretreatment. Uncoated prostheses were immediately non-sterile and exhibited 2.63 ± 0.61 × 10(5) CFU/mL. Baneocin pretreatment resulted in sterility for 1.7 ± 0.6 (95% confidence interval (CI) 1.0-2.4) d before we detected 2.14 ± 0.57 × 10(5) CFU/mL on the prostheses. Pretreatment with daptomycin yielded 2.9 ± 0.4 (CI 2.6-3.2) and fibrin sealant/baneocin compound yielded 3.1 ± 0.3 (CI 2.9-3.3) d of sterility, after which 1.81 ± 0.86 × 10(5) CFU/mL and 1.04 ± 0.77 × 10(5) CFU/mL were recorded. Finally, pretreatment with fibrin sealant/daptomycin led to sterility for 7.1 ± 0.3 (CI 6.9-7.3) d, after which 0.77 ± 0.60 × 10(5) CFU/mL were observed on the prostheses. CONCLUSIONS: The risk of vascular graft infection is reduced by pretreating the prostheses with antibiotics. The antibiotic/fibrin compound exhibited an effect of delayed antibiotic release. Vascular prostheses should therefore be pretreated with antibiotic solution to reduce bacterial adhesion. This procedure might be an effective prophylaxis for perioperative vascular graft infection and provides suitable protection for the prosthetic material.