Efficacy of the novel topical antimicrobial agent PXL150 in a mouse model of surgical site infections.
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ABSTRACT:
SUBMITTER: Hakansson J
PROVIDER: S-EPMC3993255 | biostudies-literature | 2014 May
REPOSITORIES: biostudies-literature
Publications
Efficacy of the novel topical antimicrobial agent PXL150 in a mouse model of surgical site infections.
Håkansson Joakim J Björn Camilla C Lindgren Kerstin K Sjöström Emma E Sjöstrand Veronika V Mahlapuu Margit M
Antimicrobial agents and chemotherapy 20140303 5
Antimicrobial peptides have recently emerged as a promising new group to be evaluated in the therapeutic intervention of infectious diseases. This study evaluated the anti-infectious effect of the short, synthetic, broad-spectrum antimicrobial peptide PXL150 in a mouse model of staphylococcal surgical site infections. We found that administration of PXL150, formulated in an aqueous solution or in a hydroxypropyl cellulose gel, significantly reduced the bacterial counts in the wound compared with ...[more]
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Project description:Surgical-site infections (SSIs) occur in 2-5% of patients undergoing surgery in the US alone, impacting 300 000-500 000 lives each year, and presenting up to 11 times greater risk of death compared to patients without SSIs. The most common cause of SSI is Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) is the most common pathogen in community hospitals. Current clinical devices used for approximating incisions and traumatic lacerations include sutures, adhesives, tapes, or staples with or without antimicrobial incorporation. However, current closure technologies may not provide adequate protection against infection, are susceptible to wound dehiscence, and can result in delayed biomechanical recoveries. Laser-activated tissue repair is a sutureless technique in which chromophore-loaded sealants convert laser light energy to heat in order to induce rapid tissue sealing. Here, we describe the generation and evaluation of laser-activated sealant (LASE) biomaterials, in which, indocyanine green (ICG), an FDA-approved dye, was embedded in a silk fibroin matrix and cast into films as wound sealants. Silk-ICG films were subjected to different near-infrared (NIR) laser powers to identify temperatures optimal for laser sealing of soft tissues. A mathematical model was developed in order to determine the photothermal conversion efficiency of LASEs following laser irradiation. NIR laser activation of silk-ICG LASEs increased the recovery of skin biomechanical strength compared to sutured skin in full-thickness incisional wounds in immunocompetent mice, and live animal imaging indicated persistence of silk-ICG LASEs over several days. LASEs loaded with the antibiotic vancomycin demonstrated higher efficacies for combating MRSA infections in a mouse model of surgical site infection compared to antibacterial sutures. Our results demonstrate that LASEs can be loaded with antimicrobial drugs and may serve as new multifunctional biomaterials for rapid tissue sealing, repair and surgical site protection following surgery.
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Project description:PurposeUse of mesh is essential in hernia repair. A common complication after hernia repair is surgical site infection (SSI), which poses a risk in spreading to the mesh, possibly causing mesh infection. Topical antimicrobial pretreatment of mesh may potentially reduce SSI risk in hernia repair and has shown promising results in in vitro and in vivo studies. Clinical evidence, however, is more important. This systematic review aims to provide an overview of available clinical evidence for antimicrobial pretreated mesh in hernia repair surgery to reduce SSI.MethodsWe report in accordance with PRISMA guidelines. CENTRAL, EMBASE, CINAHL and PubMed were searched up to October 2023 for studies that investigated the use of antimicrobial pretreated mesh on SSI incidence in adults undergoing hernia repair. The primary outcome was SSI incidence. We also collected data on pathogen involvement, hernia recurrence, and mesh infection. A meta-analysis on SSI risk and GRADE-assessment was performed of eligible studies.ResultsWe identified 11 eligible studies (n = 2660 patients); 5 randomized trials and 6 cohort studies. Investigated interventions included pre-coated mesh, antibiotic carriers, mesh soaked or irrigated with antibiotic or antiseptic solution. Meta-analysis showed no significant reduction in SSI for antibiotic pretreated polypropylene mesh (RR 0.76 [95% CI 0.27; 2.09]; I2 50%).ConclusionData on topical mesh pretreatment to reduce SSI risk after hernia repair is limited. Very low certainty evidence from randomized trials in hernia repair surgery shows no significant benefit for antibiotic mesh pretreatment for SSI reduction, but data are imprecise due to optimal information size not being met.
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Project description:ImportanceWorld Health Organization guidelines recommend administering surgical antimicrobial prophylaxis (SAP), including cefuroxime, within 120 minutes prior to incision. However, data from clinical settings supporting this long interval is limited.ObjectiveTo assess whether earlier vs later timing of administration of cefuroxime SAP is associated with the occurrence of surgical site infections (SSI).Design, setting, and participantsThis cohort study included adult patients who underwent 1 of 11 major surgical procedures with cefuroxime SAP, documented by the Swissnoso SSI surveillance system between January 2009 and December 2020 at 158 Swiss hospitals. Data were analyzed from January 2021 to April 2023.ExposuresTiming of cefuroxime SAP administration before incision was divided into 3 groups: 61 to 120 minutes before incision, 31 to 60 minutes before incision, and 0 to 30 minutes before incision. In addition, a subgroup analysis was performed with time windows of 30 to 55 minutes and 10 to 25 minutes as a surrogate marker for administration in the preoperating room vs in the operating room, respectively. The timing of SAP administration was defined as the start of the infusion obtained from the anesthesia protocol.Main outcomes and measuresOccurrence of SSI according to Centers for Disease Control and Prevention definitions. Mixed-effects logistic regression models adjusted for institutional, patient, and perioperative variables were applied.ResultsOf 538 967 surveilled patients, 222 439 (104 047 men [46.8%]; median [IQR] age, 65.7 [53.9-74.2] years), fulfilled inclusion criteria. SSI was identified in 5355 patients (2.4%). Cefuroxime SAP was administered 61 to 120 minutes prior to incision in 27 207 patients (12.2%), 31 to 60 minutes prior to incision in 118 004 patients (53.1%), and 0 to 30 minutes prior to incision in 77 228 patients (34.7%). SAP administration at 0 to 30 minutes was significantly associated with a lower SSI rate (adjusted odds ratio [aOR], 0.85; 95% CI, 0.78-0.93; P < .001), as was SAP administration 31 to 60 minutes prior to incision (aOR, 0.91; 95% CI, 0.84-0.98; P = .01) compared with administration 61 to 120 minutes prior to incision. Administration 10 to 25 minutes prior to incision in 45 448 patients (20.4%) was significantly associated with a lower SSI rate (aOR, 0.89; 95% CI, 0.82-0.97; P = .009) vs administration within 30 to 55 minutes prior to incision in 117 348 patients (52.8%).Conclusions and relevanceIn this cohort study, administration of cefuroxime SAP closer to the incision time was associated with significantly lower odds of SSI, suggesting that cefuroxime SAP should be administrated within 60 minutes prior to incision, and ideally within 10 to 25 minutes.
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Project description:The emergence of resistant pathogens is a burden on mankind and threatens the existence of our species. Natural and plant-derived antimicrobial agents need to be developed in the race against antibiotic resistance. Nanotechnology is a promising approach with a variety of products. Biosynthesized silver nanoparticles (AgNP) have good antimicrobial activity. We prepared AgNPs with trans-cinnamic acid (TCA) and povidone-iodine (PI) with increased antimicrobial activity. We synthesized also AgNPs with natural cinnamon bark extract (Cinn) in combination with PI and coated biodegradable Polyglycolic Acid (PGA) sutures with the new materials separately. These compounds (TCA-AgNP, TCA-AgNP-PI, Cinn-AgNP, and Cinn-AgNP-PI) and their dip-coated PGA sutures were tested against 10 reference strains of microorganisms and five antibiotics by zone inhibition with disc- and agar-well-diffusion methods. The new compounds TCA-AgNP-PI and Cinn-AgNP-PI are broad spectrum microbicidal agents and therefore potential coating materials for sutures to prevent Surgical Site Infections (SSI). TCA-AgNP-PI inhibits the studied pathogens stronger than Cinn-AgNP-PI in-vitro and on coated sutures. Dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), Fourier Transform infrared spectroscopy (FT-IR), Raman, x-ray diffraction (XRD), microstructural analysis by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) confirmed the composition of TCA-AgNP-PI and Cinn-AgNP-PI. Smart solutions involving hybrid materials based on synergistic antimicrobial action have promising future perspectives to combat resistant microorganisms.
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Project description:BackgroundSurgical site infections (SSI) are an important cause of peri-surgical morbidity with risks that vary extensively between patients and surgeries. Quantifying SSI risk would help identify candidates most likely to benefit from interventions to decrease the risk of SSI.MethodsWe randomly divided all surgeries recorded in the National Surgical Quality Improvement Program from 2010 into a derivation and validation population. We used multivariate logistic regression to determine the independent association of patient and surgical covariates with the risk of any SSI (including superficial, deep, and organ space SSI) within 30 days of surgery. To capture factors particular to specific surgeries, we developed a surgical risk score specific to all surgeries having a common first 3 numbers of their CPT code.ResultsDerivation (n = 181 894) and validation (n = 181 146) patients were similar for all demographics, past medical history, and surgical factors. Overall SSI risk was 3.9%. The SSI Risk Score (SSIRS) found that risk increased with patient factors (smoking, increased body mass index), certain comorbidities (peripheral vascular disease, metastatic cancer, chronic steroid use, recent sepsis), and operative characteristics (surgical urgency; increased ASA class; longer operation duration; infected wounds; general anaesthesia; performance of more than one procedure; and CPT score). In the validation population, the SSIRS had good discrimination (c-statistic 0.800, 95% CI 0.795-0.805) and calibration.ConclusionSSIRS can be calculated using patient and surgery information to estimate individual risk of SSI for a broad range of surgery types.
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