Antimicrobial resistance is a multifaceted crisis, imposing a serious threat to global health. The traditional antibiotic pipeline has been exhausted, prompting research into alternate antimicrobial ...strategies. Inspired by nature, antimicrobial peptides are rapidly gaining attention for their clinical potential as they present distinct advantages over traditional antibiotics. Antimicrobial peptides are found in all forms of life and demonstrate a pivotal role in the innate immune system. Many antimicrobial peptides are evolutionarily conserved, with limited propensity for resistance. Additionally, chemical modifications to the peptide backbone can be used to improve biological activity and stability and reduce toxicity. This review details the therapeutic potential of peptide-based antimicrobials, as well as the challenges needed to overcome in order for clinical translation. We explore the proposed mechanisms of activity, design of synthetic biomimics, and how this novel class of antimicrobial compound may address the need for effective antibiotics. Finally, we discuss commercially available peptide-based antimicrobials and antimicrobial peptides in clinical trials.
Infection transmission in healthcare is multifaceted and by in large involves the complex interplay between a pathogen, a host and their environment. To prevent transmission, infection prevention ...strategies must also consider these complexities and incorporate targeted interventions aimed at all possible transmission pathways. One strategy to prevent and control infection is environmental cleaning. There are many aspects to an environmental cleaning strategy. We believe the key to successfully reducing the risk of healthcare-associated infections through the environment, is to design and implement a multimodal intervention. This paper aims to provide an overview of important considerations for designing a meaningful and sustainable environmental program for healthcare facilities.
Antibiotic resistance is a growing global health problem when the discovery and development of novel antibiotics are diminishing. Various strategies have been proposed to address the problem of ...growing antibacterial resistance. One such strategy is the development of hybrid antibiotics. These therapeutic systems have been designed for two or more pharmacophores of known antimicrobial agents. This review highlights the latest development of antibiotic hybrids comprising two antibiotics (cleavable and non-cleavable) and combinations of biocidal and novel compounds to treat bacterial infections. The approach of dual-acting hybrid compounds has a promising future in overcoming drug resistance in bacterial pathogens.
Bacteria readily acquire resistance to traditional antibiotics, resulting in pan-resistant strains with no available treatment. Antimicrobial resistance is a global challenge and without the ...development of effective antimicrobials, the foundation of modern medicine is at risk. Combination therapies such as antibiotic–antibiotic and antibiotic–adjuvant combinations are strategies used to combat antibiotic resistance. Current research focuses on antimicrobial peptidomimetics as adjuvant compounds, due to their promising activity against antibiotic-resistant bacteria. Here, for the first time we demonstrate that antibiotic–peptidomimetic combinations mitigate the development of antibiotic resistance in Staphylococcus aureus and Pseudomonas aeruginosa. When ciprofloxacin and gentamicin were passaged individually at sub-inhibitory concentrations for 10 days, the minimum inhibitory concentrations (MICs) increased up to 32-fold and 128-fold for S. aureus and P. aeruginosa, respectively. In contrast, when antibiotics were passaged in combination with peptidomimetics (Melimine, Mel4, RK758), the MICs of both antibiotics and peptidomimetics remained constant, indicating these combinations were able to mitigate the development of antibiotic-resistance. Furthermore, antibiotic–peptidomimetic combinations demonstrated synergistic activity against both Gram-positive and Gram-negative bacteria, reducing the concentration needed for bactericidal activity. This has significant potential clinical applications—including preventing the spread of antibiotic-resistant strains in hospitals and communities, reviving ineffective antibiotics, and lowering the toxicity of antimicrobial chemotherapy.
The prevention and treatment of biofilm-mediated infections remains an unmet clinical need for medical devices. With the increasing prevalence of antibiotic-resistant infections, it is important that ...novel approaches are developed to prevent biofilms forming on implantable medical devices. This study presents a versatile and simple polydopamine surface coating technique for medical devices, using a new class of antibiotics-antimicrobial peptidomimetics. Their unique mechanism of action primes them for activity against antibiotic-resistant bacteria and makes them suitable for covalent attachment to medical devices. This study assesses the anti-biofilm activity of peptidomimetics, characterises the surface chemistry of peptidomimetic coatings, quantifies the antibacterial activity of coated surfaces and assesses the biocompatibility of these coated materials. X-ray photoelectron spectroscopy and water contact angle measurements were used to confirm the chemical modification of coated surfaces. The antibacterial activity of surfaces was quantified for
,
and
, with all peptidomimetic coatings showing the complete eradication of
on surfaces and variable activity for Gram-negative bacteria. Scanning electron microscopy confirmed the membrane disruption mechanism of peptidomimetic coatings against
. Furthermore, peptidomimetic surfaces did not lyse red blood cells, which suggests these surfaces may be biocompatible with biological fluids such as blood. Overall, this study provides a simple and effective antibacterial coating strategy that can be applied to biomaterials to reduce biofilm-mediated infections.
Healthcare-associated infections (HAIs) are a common, costly, yet largely preventable complication impacting patients in healthcare settings globally. Improving routine cleaning and disinfection of ...the hospital environment has been shown to reduce the risk of HAI. Contaminated shared medical equipment presents a primary transmission route for infectious pathogens, yet is rarely studied. The CLEEN study will assess how enhanced cleaning and disinfection of shared medical equipment affects the rate of HAIs in a tertiary hospital setting. The initiative is an evidence-based approach combining staff training, auditing and feedback to environmental services staff to enhance cleaning and disinfection practices.
The CLEEN study will use a stepped wedge randomised controlled design in 10 wards of one large Australian hospital over 36 weeks. The intervention will consist of 3 additional hours per weekday for the dedicated cleaning and disinfection of shared medical equipment on each ward. The primary outcome is to demonstrate the effectiveness of improving the quality and frequency of cleaning shared medical equipment in reducing HAIs, as measured by a HAI point prevalence study (PPS). The secondary outcomes include the thoroughness of equipment cleaning assessed using fluorescent marker technology and the cost-effectiveness of the intervention.
Evidence from the CLEEN study will contribute to future policy and practice guidelines about the cleaning and disinfection of shared medical equipment. It will be used by healthcare leaders and clinicians to inform decision-making and implementation of best-practice infection prevention strategies to reduce HAIs in healthcare facilities.
Australia New Zealand Clinical Trial Registry ACTRN12622001143718.
The novel coronavirus disease 2019 (COVID-19) pandemic has brought to light the role of environmental hygiene in controlling disease transmission. Healthcare facilities are hot spots for infectious ...pathogens where physical distancing and personal protective equipment (PPE) are not always sufficient to prevent disease transmission. Healthcare facilities need to consider adjunct strategies to prevent transmission of infectious pathogens. In combination with current infection control procedures, many healthcare facilities are incorporating ultraviolet (UV) disinfection into their routines. This review considers how pathogens are transmitted in healthcare facilities, the mechanism of UV microbial inactivation and the documented activity of UV against clinical pathogens. Emphasis is placed on the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as well as multidrug resistant organisms (MDROs) that are commonly transmitted in healthcare facilities. The potential benefits and limitations of UV technologies are discussed to help inform healthcare workers, including clinical studies where UV technology is used in healthcare facilities.
There is a paucity of high-quality evidence based on clinical endpoints for routine cleaning of shared medical equipment. We assessed the effect of enhanced cleaning and disinfection of shared ...medical equipment on health-care-associated infections (HAIs) in hospitalised patients.
We conducted a stepped-wedge, cluster randomised, controlled trial in ten wards of a single hospital located on the central coast of New South Wales, Australia. Hospitals were eligible for inclusion if they were classified as public acute group A according to the Australian Institute of Health and Welfare, were located in New South Wales, had an intensive care unit, had a minimum of ten wards, and provided care for patients aged 18 years or older. Each cluster consisted of two randomly allocated wards (by use of simple randomisation), with a new cluster beginning the intervention every 6 weeks. Wards were informed of their allocation 2 weeks before commencement of intervention exposure, and the researcher collecting primary outcome data and audit data was masked to treatment sequence allocation. In the control phase, there was no change to environmental cleaning practices. In the intervention phase, a multimodal cleaning bundle included an additional 3 h per weekday for the dedicated cleaning and disinfection of shared medical equipment by 21 dedicated cleaning staff, with ongoing education, audit, and feedback. The primary outcome was the number of confirmed cases of HAI, as assessed by a fortnightly point prevalence survey and measured in all patients admitted to the wards during the study period. The completed trial is registered with Australia New Zealand Clinical Trials Registry (ACTRN12622001143718).
The hospital was recruited on July 31, 2022, and the study was conducted between March 20 and Nov 24, 2023. We assessed 220 hospitals for eligibility, of which five were invited to participate, and the first hospital to formally respond was enrolled. 5002 patients were included in the study (2524 50·5% women and 2478 49·5% men). In unadjusted results, 433 confirmed HAI cases occurred in 2497 patients (17·3%, 95% CI 15·9 to 18·8) in the control phase and 301 confirmed HAI cases occurred in 2508 patients (12·0%, 10·7 to 13·3) in the intervention phase. In adjusted results, there was a relative reduction of –34·5% (–50·3 to –17·5) in HAIs following the intervention (odds ratio 0·62, 95% CI 0·45 to 0·80; p=0·0006), corresponding to an absolute reduction equal to –5·2% (–8·2 to –2·3). No adverse effects were reported.
Improving the cleaning and disinfection of shared medical equipment significantly reduced HAIs, underscoring the crucial role of cleaning in improving patient outcomes. Findings emphasise the need for dedicated approaches for cleaning shared equipment.
National Health and Medical Research Council.
Healthcare acquired infections (HAIs) are associated with increased mortality, morbidity and prolonged hospital stays. Microbiological contamination of the hospital environment directly contributes ...to HAIs. Optimising environmental cleaning reduces transmission of HAIs. The hyperbaric chamber poses a specific challenge for infection control as certain disinfectants and alcohol-based hand sanitisers are prohibited due to fire risk. Patients often possess multiple risk factors for HAIs. This study compared the bacteria remaining on a surface (bioburden) after a standard clean and after adjunctive disinfection with an ultraviolet-C (UV-C) robot.
Internal hyperbaric chamber surfaces were first manually cleaned with Clinell® universal wipes and the floor was mopped with Whiteley neutral detergent. Allocated surfaces were swabbed using sterile cotton swabs and processed using a standard microbial culture and a bacteria-specific rapid metabolic assay. Bacterial contamination was also measured by direct contact plating on flat surfaces. The plexiglass ports were covered to protect from potential UV-C mediated damage and used as a negative control. A UV-C disinfection robot was then used to disinfect the chamber for 30 min, whereafter surfaces were swabbed again.
There was a significantly greater mean reduction in bioburden following adjunctive UV-C disinfection than with standard cleaning alone. The surfaces not routinely manually cleaned (e.g., bench, phone) showed greatest reduction in bacterial load following UV-C cleaning.
There was a significant reduction in the bacterial load in the chamber following an adjunctive UV-C clean compared with that of a standard clean. Adjunctive cleaning of the hyperbaric chamber environment with a non-touch UV-C device shows promise as a method to reduce HAIs.
Evidence from a previous systematic review indicates that patients admitted to a room where the previous occupant had a multidrug-resistant bacterial infection resulted in an increased risk of ...subsequent colonisation and infection with the same organism for the next room occupant. In this paper, we have sought to expand and update this review.
A systematic review and meta-analysis was undertaken. A search using Medline/PubMed, Cochrane and CINHAL databases was conducted. Risk of bias was assessed by the ROB-2 tool for randomised control studies and ROBIN-I for non-randomised studies.
From 5175 identified, 12 papers from 11 studies were included in the review for analysis. From 28,299 patients who were admitted into a room where the prior room occupant had any of the organisms of interest, 651 (2.3%) were shown to acquire the same species of organism. In contrast, 981,865 patients were admitted to a room where the prior occupant did not have an organism of interest, 3818 (0.39%) acquired an organism(s). The pooled acquisition odds ratio (OR) for all the organisms across all studies was 2.45 (95% CI: 1.53–3.93. There was heterogeneity between the studies (I2 89%, P < 0.001).
The pooled OR for all the pathogens in this latest review has increased since the original review. Findings from our review provide some evidence to help inform a risk management approach when determining patient room allocation. The risk of pathogen acquisition appears to remain high, supporting the need for continued investment in this area.
•Admission to a room previously occupied by a patient infected +/- colonised with a pathogen is a risk factor for acquisition•Continued investment and research in cleaning services in healthcare facilities is needed.•Findings may help inform a risk management approach for determining patient room allocation.
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