Background: The impact of operating room air quality on the risk of surgical site infection (SSI) is a topic of debate. This systematic review explores correlation between intra-operative air contamination during clean surgery and (i) wound contamination, and (ii) the incidence of SSI. Methods: Medline, EMBASE and the Cochrane Library were searched for original articles that investigated correlation between intra-operative airborne bacteria and either intra-operative wound contamination or the incidence of SSI in clean surgery. Three reviewers screened retrieved articles independently for eligibility, using Rayyan, and assessed quality and risk of bias using the Integrated Quality Criteria for the Review of Multiple Study Designs methodology. A narrative synthesis of the heterogenous data was performed following the Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. Results: Thirteen publications encompassing 11 studies (total 18,694 patients) were included. Eight studies focused on wound contamination, two of which showed significant correlation with intra-operative air contamination. Five studies examined the incidence of SSI, three of which showed significant correlation with air contamination and one of which showed significant correlation with the ventilation system. Conclusion: Most studies on correlation between air quality and wound contamination exhibited significant variations and were likely underpowered. However, one study with over 3000 wound samples found significant correlation between wound contamination and air quality. Despite the limited and diverse studies on air contamination and the incidence of SSI, there appears to be correlation. However, more well-powered studies are needed to understand the impact of contamination levels <100 colony-forming units/m3 on wound contamination and the incidence of SSI

Background: Surgical site infection (SSI) following orthopedic surgery is a complication associated with morbidity and economic burden. Transmission of airborne bacteria that settle into surgical wounds constitutes a risk factor for SSIs. However, monitoring microbial contamination inside operating rooms with conventional methods is resource and time-consuming. Aim: This study aimed to assess correlation between a biofluorescent particle counter (BFPC) and conventional air sampling, to enable real-time monitoring of airborne contamination. Additionally, the study aimed to analyze correlation between particles near the surgical site and particles 1 meter away, to evaluate the feasibility of distance-based measurements. Methods: Correlation analysis was conducted to compare colony-forming units (CFU) collected using a Sartorius MD8 air sampler with biofluorescent viable particles detected by BioTrak 9510-BD, both positioned near the surgical site. Additionally, correlation between particle counts measured by AeroTrak 6510, positioned 1 meter away, and total particle counts measured by the BioTrak near the surgical site was evaluated. Sampling took place in two operating rooms: one with turbulent mixed airflow (TMA) and one with unidirectional airflow (UDAF). Results: Negligible to low correlation between biofluorescent particles and CFU was observed, both in UDAF (n = 100) and TMA (n = 22). However, strong correlation was found between BFPC and particle counter measurements of total numbers of particles (Rp = 0.634-0.769, P <.001). Conclusion: While BFPCs offer real-time monitoring of airborne contamination, their predictive ability for CFU levels remains uncertain. Yet, the strong correlation between particles in the surgical site and particles measured 1 meter away suggests feasibility to conduct future studies with larger cohorts. 

Background: Bacterial airborne contamination in the operating room during surgery indicates an increased risk for surgical site infection. The conventional surveillance method for bacteria in the air is by air sampling, plating, and counting of colony-forming units (CFU). Particle counting measures particles in the air, typically in sizes of 1-20 µm, and has been suggested as an alternative to CFU measurements. The primary aim was to investigate the correlation between the number of airborne CFU and particles during surgery. The secondary aim was to explore whether different ventilation settings influence the correlation between CFU and particles. Methods: The databases Cochrane, Embase, and Medline were searched for relevant publications. Due to the heterogeneity of the data, meta-analysis was not possible and a narrative analysis was performed instead. Results: The review included 11 studies. Two of the studies (n = 2) reported strong correlation between particles and CFU (Rp = 0.76 and Rc = 0.74). The remaining studies observed moderate correlation (n = 3), low correlation (n = 3), or no correlation (n = 3). Based on the primary results from this study, ventilation attribution to distinguish the correlation between particles and CFU had no or little contribution. Conclusions: Due to the lack of convincing evidence of correlation and lack of high-quality studies performing measurements in a standardized way, the studies could not provide the necessary evidence that show that particle counting could be used as a substitution for conventional air bacterial assessment. Further studies are warranted to strengthen the conclusion. © 2023 The Authors

Cellulose nanofibrils (CNFs) were obtained by applying a chemical pretreatment consisting of autoclaving the pulp fibers in sodium hydroxide, combined with 2,2,6,6-tetramethylpiperidinyl-1-oxyl-mediated oxidation. Three levels of sodium hypochlorite were applied (2.5, 3.8, and 6.0 mmol/g) to obtain CNF qualities (CNF_2.5, CNF_3.8, and CNF_6.0) with varying content of carboxyl groups, that is, 1036, 1285, and 1593 μmol/g cellulose. The cytotoxicity and skin irritation potential (indirect tests) of the CNFs were determined according to standardized in vitro testing for medical devices. We here demonstrate that autoclaving (121 °C, 20 min), which was used to sterilize the gels, caused a modification of the CNF characteristics. This was confirmed by a reduction in the viscosity of the gels, a morphological change of the nanofibrils, by an increase of the ultraviolet-visible absorbance maxima at 250 nm, reduction of the absolute zeta potential, and by an increase in aldehyde content and reducing sugars after autoclaving. Fourier-transform infrared spectroscopy and wide-angle X-ray scattering complemented an extensive characterization of the CNF gels, before and after autoclaving. The antibacterial properties of autoclaved carboxylated CNFs were demonstrated in vitro (bacterial survival and swimming assays) on Pseudomonas aeruginosa and Staphylococcus aureus. Importantly, a mouse in vivo surgical-site infection model on S. aureus revealed that CNF_3.8 showed pronounced antibacterial effect and performed as good as the antiseptic Prontosan wound gel.

The rapid development of microbial resistance to conventional antibiotics has accelerated efforts to find anti-infectives with a novel mode-of-action, which are less prone to bacterial resistance. Intense nonclinical and clinical research is today ongoing to evaluate antimicrobial peptides (AMPs) as potential next-generation antibiotics. Currently, multiple AMPs are assessed in late-stage clinical trials, not only as novel anti-infective drugs, but also as innovative product candidates for immunomodulation, promotion of wound healing, and prevention of post-operative scars. The efforts to translate AMP-based research findings into pharmaceutical product candidates are expected to accelerate in coming years due to technological advancements in multiple areas, including an improved understanding of the mechanism-of-action of AMPs, smart formulation strategies, and advanced chemical synthesis protocols. At the same time, it is recognized that cytotoxicity, low metabolic stability due to sensitivity to proteolytic degradation, and limited oral bioavailability are some of the key weaknesses of AMPs. Furthermore, the pricing and reimbursement environment for new antimicrobial products remains as a major barrier to the commercialization of AMPs.

A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged β-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G' = 0.5-8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.

Antimicrobial peptides, also known as host defense peptides, have recently emerged as a promising new category of therapeutic agents for the treatment of infectious diseases. This study evaluated the preclinical in vitro, ex vivo, and in vivo antimicrobial activity, as well as the potential to cause skin irritation, of human kininogen-derived antimicrobial peptide DPK-060 in different formulations designed for topical delivery. We found that DPK-060 formulated in acetate buffer or poloxamer gel caused a marked reduction of bacterial counts of Staphylococcus aureus in vitro (minimum microbicidal concentration <5 μg/ml). We also found that DPK-060 in poloxamer gel significantly suppressed microbial survival in an ex vivo wound infection model using pig skin and in an in vivo mouse model of surgical site infection (≥99 or ≥94% reduction in bacterial counts was achieved with 1% DPK-060 at 4 h post-treatment, respectively). Encapsulation of DPK-060 in different types of lipid nanocapsules or cubosomes did not improve the bactericidal potential of the peptide under the applied test conditions. No reduction in cell viability was observed in response to administration of DPK-060 in any of the formulations tested. In conclusion, the present study confirms that DPK-060 has the potential to be an effective and safe drug candidate for the topical treatment of microbial infections; however, adsorption of the peptide to nanocarriers failed to show any additional benefits.

Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing ≥99% of microorganisms in vitro, was in the range of 3-50 μg/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-α) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400 μg/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections.

Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs.

The rapid emergence of antibiotic-resistant microbes worldwide and the urgent need of new antimicrobial agents have stimulated interest in antimicrobial peptides (AMPs) as new therapeutics for treatment of infectious diseases. AMPs are present in all living species and constitute an important part of the innate immune system in multicellular organisms, including humans. AMPs display a remarkably broad spectrum of antimicrobial activity covering both Gram-positive and Gram-negative bacteria, including many antibiotic-resistant strains, as well as fungi, viruses, and protozoa. Further, in contrast to many conventional antibiotics, AMPs rapidly kill bacteria instead of just inhibiting bacterial growth. In addition, AMPs act as modulators of the innate immune system and, importantly, bacteria seem less efficient in developing resistance towards AMPs than towards conventional antibiotics. Together these properties make AMPs highly attractive as a new class of antimicrobials, with clinical potential also extending to diseases where inflammation is part of the pathology. The aim of this thesis was to study novel AMPs with respect to their mechanism of action (MOA), antimicrobial spectrum, propensity to select for resistance, and in vivo efficacy and safety. To achieve this, we used a number of in vitro and in vivo assays, together generating a comprehensive preclinical evaluation of the peptides. The hypothesis was that the AMPs in this thesis have potential to be developed as therapeutic agents for several infectious and inflammatory conditions, including treatment of skin and soft tissue infections and prevention of postsurgical adhesion formation. The results showed that all AMPs tested (i.e. PXL03, PXL150, HLR1r, and five variants of CEN1 HC-Br) had broad antimicrobial spectra in vitro with varying sensitivity to salt and serum. Furthermore, PXL150 caused a rapid permeabilization of bacterial membrane in vitro, indicating that this is at least one part of the MOA of this peptide. Under selection pressure in vitro, bacteria did not develop resistance to the peptides tested, i.e. PXL150 and CEN1 HC. Interestingly, all peptides showed anti-inflammatory activity by inhibiting the secretion of proinflammatory mediators from stimulated human cell lines. In addition, PXL01, PXL150, and HLR1r demonstrated fibrinolytic ability in vitro by suppressing the release of plasminogen activator inhibitor-1 (PAI-1). In ex vivo and in vivo skin/wound infection models, the peptides reduced the number of viable bacteria and yeast cells. Further, PXL01 decreased postsurgical adhesion formation in vivo. Notably, nonclinical safety studies showed that PXL150 was safe and well tolerated. In conclusion, several of the peptides evaluated in this thesis demonstrated a promising preclinical efficacy and safety profile motivating further development as drug candidates for local treatment of infectious and inflammatory conditions.