Explore the vast range of titles available.

Chronic non-healing wounds have become a major worldwide healthcare burden. The impact of biofilms on chronic wound infection is well established. Despite increasing understanding of the underlying mechanism of biofilm formation in chronic wounds, current strategies for biofilm diagnosis in chronic wounds are still far from ideal. In this review, we briefly summarize the mechanism of biofilm formation and focus on current diagnostic approaches of chronic wound biofilms based on morphology, microbiology, and molecular assays. Innovative biotechnological approaches, such as wound blotting and transcriptomic analysis, may further shed light on this unmet clinical need. The continuous development of these sophisticated diagnostic approaches can markedly contribute to the future implementation of point-of-care biofilm detection in chronic wound care. The impact of biofilms on delayed wound healing has drawn increasing attention. Their importance led to the establishment of biofilm-based wound care where chronic wounds are treated using multipronged strategies to remove biofilms over wound beds to facilitate the recovery of epithelial integrity. Current clinical and preclinical diagnostic techniques fail to accurately identify pathogens and the precise location of biofilms over wound surfaces, rendering timely medical or surgical intervention to eradicate biofilms elusive. Wound blotting is a novel biotechnology that predicts wound outcomes and localizes biofilms on wound surfaces by determining the distribution pattern of tumor necrosis factor-alpha (TNF-α) and biofilm mucopolysaccharides. The rapid and objective analysis offered by this technique may assist clinicians in treating chronic wound biofilms.

Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host–defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas aeruginosa skin wound infection and found significantly delayed wound closure in infected skin wounds. This delay was associated with impaired bacterial clearance in the absence of MCs. Engraftment of MCs restored both bacterial clearance and wound closure. Bacterial killing was dependent on IL-6 released from MCs, and engraftment with IL-6–deficient MCs failed to control wound infection. Treatment with recombinant IL-6 enhanced bacterial killing and resulted in the control of wound infection and normal wound healing in vivo. Taken together, our results demonstrate a defense mechanism for boosting host innate immune responses, namely effects of MC-derived IL-6 on antimicrobial functions of keratinocytes.

Background Staphylococcus aureus is the most common organism responsible for orthopaedic surgical site infections (SSIs). Patients who are carriers for methicillin-sensitive S. aureus or methicillin-resistant S. aureus (MRSA) have a higher likelihood of having invasive S. aureus infections. Although some have advocated screening for S. aureus and decolonizing it is unclear whether these efforts reduce SSIs. Questions/purposes The purposes of this study were to determine (1) whether S. aureus screening and decolonization reduce SSIs in orthopaedic patients and (2) if implementing this protocol is cost-effective. Methods Studies for this systematic review were identified by searching PubMed, which includes MEDLINE (1946–present), EMBASE.com (1974–present), and the Cochrane Library’s (John Wiley & Sons) Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTAD), and the NHS Economic Evaluation Database (NHSEED). Comprehensive literature searches were developed using EMTREE, MeSH, and keywords for each of the search concepts of decolonization, MRSA, and orthopedics/orthopedic surgery. Studies published before 1968 were excluded. We analyzed 19 studies examining the ability of the decolonization protocol to reduce SSIs and 10 studies detailing the cost-effectiveness of S. aureus screening and decolonization. Results All 19 studies showed a reduction in SSIs or wound complications by instituting a S. aureus screening and decolonization protocol in elective orthopaedic (total joints, spine, and sports) and trauma patients. The S. aureus screening and decolonization protocol also saved costs in orthopaedic patients when comparing the costs of screening and decolonization with the reduction of SSIs. Conclusions Preoperative screening and decolonization of S. aureus in orthopaedic patients is a cost-effective means to reduce SSIs. Level of Evidence Level IV, systematic review of Level I–IV studies. See the Guidelines for Authors for a complete description of levels of evidence.

Bacteriophage (phage) therapy is a promising therapeutic modality for multidrug-resistant bacterial infections, but its application is mainly limited to personalized therapy due to the narrow host range of individual phages. While phage cocktails targeting all possible bacterial receptors could theoretically confer broad coverage, the extensive diversity of bacteria and the complexity of phage-phage interactions render this approach challenging. Here, using screening protocols for identifying “complementarity groups” of phages using non-redundant receptors, we generate effective, broad-range phage cocktails that prevent the emergence of bacterial resistance. We also discover characteristic interactions between phage complementarity groups and particular antibiotic classes, facilitating the prediction of phage-antibiotic as well as phage-phage interactions. Using this strategy, we create three phage-antibiotic cocktails, each demonstrating efficacy against ≥96% of 153 Pseudomonas aeruginosa clinical isolates, including biofilm cultures, and demonstrate comparable efficacy in an in vivo wound infection model. We similarly develop effective Staphylococcus aureus phage-antibiotic cocktails and demonstrate their utility of combined cocktails against polymicrobial (mixed P. aeruginosa/S. aureus ) cultures, highlighting the broad applicability of this approach. These studies establish a blueprint for the development of effective, broad-spectrum phage-antibiotic cocktails, paving the way for off-the-shelf phage-based therapeutics to combat multidrug-resistant bacterial infections. The application of phage therapy for multidrug-resistant infections is mainly limited to personalized therapy due to the narrow host range of individual phages. Here, Kim et al. identify groups of phages that use non-redundant receptors, and present a blueprint for the development of effective, broad-spectrum phage-antibiotic combinations.

The application of photothermal therapy to treat bacterial infections remains a challenge, as the high temperatures required for bacterial elimination can damage healthy tissues. Here, we develop an exogenous antibacterial agent consisting of zinc-doped Prussian blue (ZnPB) that kills methicillin-resistant Staphylococcus aureus in vitro and in a rat model of cutaneous wound infection. Local heat triggered by the photothermal effect accelerates the release and penetration of ions into the bacteria, resulting in alteration of intracellular metabolic pathways and bacterial killing without systemic toxicity. ZnPB treatment leads to the upregulation of genes involved in tissue remodeling, promotes collagen deposition and enhances wound repair. The efficient photothermal conversion of ZnPB allows the use of relatively few doses and low laser flux, making the platform a potential alternative to current antibiotic therapies against bacterial wound infections. Here, the authors apply transition metal doping in combination with phototermal therapy to treat Staphylococcus aureus -infected wounds, and show that release of ions by local heat enhances bacteria clearance and promotes tissue repair in a rat model of MRSA-infected wounds

The declining efficacy of existing antibiotics potentially jeopardises outcomes in patients undergoing medical procedures. We investigated the potential consequences of increases in antibiotic resistance on the ten most common surgical procedures and immunosuppressing cancer chemotherapies that rely on antibiotic prophylaxis in the USA. We searched the published scientific literature and identified meta-analyses and reviews of randomised controlled trials or quasi-randomised controlled trials (allocation done on the basis of a pseudo-random sequence—eg, odd/even hospital number or date of birth, alternation) to estimate the efficacy of antibiotic prophylaxis in preventing infections and infection-related deaths after surgical procedures and immunosuppressing cancer chemotherapy. We varied the identified effect sizes under different scenarios of reduction in the efficacy of antibiotic prophylaxis (10%, 30%, 70%, and 100% reductions) and estimated the additional number of infections and infection-related deaths per year in the USA for each scenario. We estimated the percentage of pathogens causing infections after these procedures that are resistant to standard prophylactic antibiotics in the USA. We estimate that between 38·7% and 50·9% of pathogens causing surgical site infections and 26·8% of pathogens causing infections after chemotherapy are resistant to standard prophylactic antibiotics in the USA. A 30% reduction in the efficacy of antibiotic prophylaxis for these procedures would result in 120 000 additional surgical site infections and infections after chemotherapy per year in the USA (ranging from 40 000 for a 10% reduction in efficacy to 280 000 for a 70% reduction in efficacy), and 6300 infection-related deaths (range: 2100 for a 10% reduction in efficacy, to 15 000 for a 70% reduction). We estimated that every year, 13 120 infections (42%) after prostate biopsy are attributable to resistance to fluoroquinolones in the USA. Increasing antibiotic resistance potentially threatens the safety and efficacy of surgical procedures and immunosuppressing chemotherapy. More data are needed to establish how antibiotic prophylaxis recommendations should be modified in the context of increasing rates of resistance. DRIVE-AB Consortium.

Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p<0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p<0·001). Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication. DFID-MRC-Wellcome Trust Joint Global Health Trial Development Grant, National Institute of Health Research Global Health Research Unit Grant.

ABSTRACT Biofilms complicate wound care by causing recurrent infections that are often resistant to debridement and are highly antibiotic‐tolerant. We investigated whether the addition of a biofilm dispersal agent could improve the efficacy of debridement. The previous studies have indicated that a glycoside hydrolase cocktail of alpha‐amylase and cellulase can act as a potent biofilm dispersal agent. With in vitro and ex vivo Pseudomonas aeruginosa biofilm models, we compared glycoside hydrolases against other, clinically relevant, enzymatic debridement agents (papain, bromelain, and collagenase). Glycoside hydrolase biofilm dispersal was dose‐dependent. However, at doses of 1% or above, glycoside hydrolases outperformed, or were comparable, to other enzymatic debridement agents. With our in vivo surgical wound infection model, we evaluated biofilm dispersal using infection dissemination as a proxy. We found that sharp debridement followed by multiple glycoside hydrolase treatments enhanced biofilm dispersal. Furthermore, a single dose of glycoside hydrolase in combination with debridement decreased infection load in acute wounds. Similarly, when we treated established 5‐day‐old infections, we saw a decrease in infection load and no infection dissemination. Overall, our data suggest that debridement enhances the efficacy of a topical antibiotic ointment, allowing for greater infection clearance.

Background Mycoplasma hominis is a part of the microflora of the urogenital tract; however, extra-urogenital infections due to M. hominis are rare. Herein, we present a case study of a patient who successfully recovered from a sternal wound infection caused by M. hominis. Case presentation We report a case of sternal wound infection caused by M. hominis following tricuspid valvuloplasty. The patient developed a severe infection despite postoperative antimicrobial therapy. Wound sample cultures grew pinpoint-sized colonies on blood agar plates, which were identified as M. hominis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Based on the results of the antibiotic susceptibility test, effective infection management was achieved using a combination of moxifloxacin and doxycycline. Conclusions The potential role of M. hominis as a causative agent of postoperative infections after thoracotomy may be underestimated. M. hominis should be highly suspected when patients have an indwelling catheter or when perioperative wound samples show numerous leukocytes with no visible bacteria, and are unresponsive to standard empirical treatment for postoperative infections.

Since its discovery approximately 200 years ago, chitosan, as a cationic natural polymer, has been widely used as a topical dressing in wound management owing to its hemostatic, stimulation of healing, antimicrobial, nontoxic, biocompatible and biodegradable properties. This article covers the antimicrobial and wound-healing effects of chitosan, as well as its derivatives and complexes, and its use as a vehicle to deliver biopharmaceuticals, antimicrobials and growth factors into tissue. Studies covering applications of chitosan in wounds and burns can be classified into in vitro, animal and clinical studies. Chitosan preparations are classified into native chitosan, chitosan formulations, complexes and derivatives with other substances. Chitosan can be used to prevent or treat wound and burn infections not only because of its intrinsic antimicrobial properties, but also by virtue of its ability to deliver extrinsic antimicrobial agents to wounds and burns. It can also be used as a slow-release drug-delivery vehicle for growth factors to improve wound healing. The large number of publications in this area suggests that chitosan will continue to be an important agent in the management of wounds and burns.