Silver-enriched microdomain patterns as advanced bactericidal coatings for polymer-based medical devices.

Today, it would be difficult for us to live a full life without polymers, especially in medicine, where its applicability is constantly expanding, giving satisfactory results without any harm effects on health. This study focused on the formation of hexagonal domains doped with AgNPs using a KrF excimer laser (λ=248 nm) on the polyetheretherketone (PEEK) surface that acts as an unfailing source of the antibacterial agent - silver. The hexagonal structure was formed with a grid placed in front of the incident laser beam. Surfaces with immobilized silver nanoparticles (AgNPs) were observed by AFM and SEM. Changes in surface chemistry were studied by XPS. To determine the concentration of released Ag+ ions, ICP-MS analysis was used. The antibacterial tests proved the antibacterial efficacy of Ag-doped PEEK composites against Escherichia coli and Staphylococcus aureus as the most common pathogens. Because AgNPs are also known for their strong toxicity, we also included cytotoxicity tests in this study. The findings presented here contribute to the advancement of materials design in the biomedical field, offering a novel starting point for combating bacterial infections through the innovative integration of AgNPs into inert synthetic polymers.

Current strategies for monitoring and controlling bacterial biofilm formation on medical surfaces.

Biofilms, intricate microbial communities that attach to surfaces, especially medical devices, form an exopolysaccharide matrix, which enables bacteria to resist environmental pressures and conventional antimicrobial agents, leading to the emergence of multi-drug resistance. Biofilm-related infections associated with medical devices are a significant public health threat, compromising device performance. Therefore, developing effective methods for supervising and managing biofilm growth is imperative. This in-depth review presents a systematic overview of strategies for monitoring and controlling bacterial biofilms. We first outline the biofilm creation process and its regulatory mechanisms. The discussion then progresses to advancements in biosensors for biofilm detection and diverse treatment strategies. Lastly, this review examines the obstacles and new perspectives associated with this domain to facilitate the advancement of innovative monitoring and control solutions. These advancements are vital in combating the spread of multi drug-resistant bacteria and mitigating public health risks associated with infections from biofilm formation on medical instruments.

Poly(methylmethacrylate-co-dimethyl acrylamide)-silver nanocomposite prevents biofilm formation in medical devices.

Aim: To investigate whether medical devices coated with a synthesized nanocomposite of poly(methylmethacrylate-co-dimethyl acrylamide) (PMMDMA) and silver nanoparticles (AgNPs) could improve their antibiofilm and antimicrobial activities. We also investigated the nanocomposite's safety. Materials & methods: The nanocomposite was synthesized and characterized using analytical techniques. Medical devices coated with the nanocomposite were evaluated for bacterial adhesion and hemolytic activity in vitro. Results: The nanocomposite formation was demonstrated with the incorporation of AgNPs into the polymer matrix. The nanocomposite proved to be nonhemolytic and significantly inhibited bacterial biofilm formation. Conclusion: The PMMDMA-AgNPs nanocomposite was more effective in preventing biofilm formation than PMMDMA alone and is a promising strategy for coating medical devices and reducing mortality due to hospital-acquired infections.

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Biofilm Inhibition on Medical Devices and Implants Using Carbon Dots: An Updated Review.

Biofilms are an intricate community of microbes that colonize solid surfaces, communicating via a quorum-sensing mechanism. These microbial aggregates secrete exopolysaccharides facilitating adhesion and conferring resistance to drugs and antimicrobial agents. The escalating global concern over biofilm-related infections on medical devices underscores the severe threat to human health. Carbon dots (CDs) have emerged as a promising substrate to combat microbes and disrupt biofilm matrices. Their numerous advantages such as facile surface functionalization and specific antimicrobial properties, position them as innovative anti-biofilm agents. Due to their minuscule size, CDs can penetrate microbial cells, inhibiting growth via cytoplasmic leakage, reactive oxygen species (ROS) generation, and genetic material fragmentation. Research has demonstrated the efficacy of CDs in inhibiting biofilms formed by key pathogenic bacteria such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Consequently, the development of CD-based coatings and hydrogels holds promise for eradicating biofilm formation, thereby enhancing treatment efficacy, reducing clinical expenses, and minimizing the need for implant revision surgeries. This review provides insights into the mechanisms of biofilm formation on implants, surveys major biofilm-forming pathogens and associated infections, and specifically highlights the anti-biofilm properties of CDs emphasizing their potential as coatings on medical implants.

Organic Photo-antimicrobials: Principles, Molecule Design, and Applications.

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.

Plant-derived nanotherapeutic systems to counter the overgrowing threat of resistant microbes and biofilms.

Since antiquity, the survival of human civilization has always been threatened by the microbial infections. An alarming surge in the resistant microbial strains against the conventional drugs is quite evident in the preceding years. Furthermore, failure of currently available regimens of antibiotics has been highlighted by the emerging threat of biofilms in the community and hospital settings. Biofilms are complex dynamic composites rich in extracellular polysaccharides and DNA, supporting plethora of symbiotic microbial life forms, that can grow on both living and non-living surfaces. These enforced structures are impervious to the drugs and lead to spread of recurrent and non-treatable infections. There is a strong realization among the scientists and healthcare providers to work out alternative strategies to combat the issue of drug resistance and biofilms. Plants are a traditional but rich source of effective antimicrobials with wider spectrum due to presence of multiple constituents in perfect synergy. Other than the biocompatibility and the safety profile, these phytochemicals have been repeatedly proven to overcome the non-responsiveness of resistant microbes and films via multiple pathways such as blocking the efflux pumps, better penetration across the cell membranes or biofilms, and anti-adhesive properties. However, the unfavorable physicochemical attributes and stability issues of these phytochemicals have hampered their commercialization. These issues of the phytochemicals can be solved by designing suitably constructed nanoscaled structures. Nanosized systems can not only improve the physicochemical features of the encapsulated payloads but can also enhance their pharmacokinetic and therapeutic profile. This review encompasses why and how various types of phytochemicals and their nanosized preparations counter the microbial resistance and the biofouling. We believe that phytochemical in tandem with nanotechnological innovations can be employed to defeat the microbial resistance and biofilms. This review will help in better understanding of the challenges associated with developing such platforms and their future prospects.

Streptomyces sp.-A Treasure Trove of Weapons to Combat Methicillin-Resistant Staphylococcus aureus Biofilm Associated with Biomedical Devices.

Biofilms formed by methicillin-resistant S. aureus (MRSA) are among the most frequent causes of biomedical device-related infection, which are difficult to treat and are often persistent and recurrent. Thus, new and effective antibiofilm agents are urgently needed. In this article, we review the most relevant literature of the recent years reporting on promising anti-MRSA biofilm agents derived from the genus Streptomyces bacteria, and discuss the potential contribution of these newly reported antibiofilm compounds to the current strategies in preventing biofilm formation and eradicating pre-existing biofilms of the clinically important pathogen MRSA. Many efforts are evidenced to address biofilm-related infections, and some novel strategies have been developed and demonstrated encouraging results in preclinical studies. Nevertheless, more in vivo studies with appropriate biofilm models and well-designed multicenter clinical trials are needed to assess the prospects of these strategies.

The suitability of a glovebox and of a covered still air box design for semi-sterile applications in environmental monitoring.

Laminar flow cabinets (LFCs) ensure a safe working space within which product manipulation can be carried out safely excluding contaminations of the product with the environmental microorganisms. However, for environmental monitoring applications mobile laboratories are required and these prefer the lighter gloveboxes (GB; restricted arm movement) or still air boxes (SAB; free arm movement) over the heavier, more expensive LFCs, which need to be regularly maintained. Nevertheless, the efficiency of simple GBs/SABs (no HEPA filter), in providing semi-sterile working conditions has yet to be clearly defined. Consequently, our aim was to assess the suitability of GBs/SABs for semi-sterile applications by using passive and active bioaerosol sample collection procedures within the interior spaces of these boxes. Prior to sample collection the boxes were pre-treated with different spraying preparations (70% ethanol, 2% detergent or sterile water). For a greater restriction of bioaerosol entry, SABs were constructed with covered arm ports and these were classified as partially covered (SABPC) and completely covered SABs (SABCC). Results showed that ethanol sprayed GB and SABCC exhibited microbial aerosol colony counts of zero after one hour of passive sample collection, and active sample collection revealed counts ranging between 1.9 (for GB) - 2.3 Log10CFU/m3 (for SABCC). However, ethanol sprayed SAB and SABPC were ineffective having colony counts of 6.9 and 6.5 Log10CFU/m3, respectively. Other spraying regimes resulted in even higher colony counts (up to 7.3 Log10CFU/m3). Therefore, the ethanol sprayed GB and SABCC could effectively be used for semi-sterile applications, with the SABCC allowing for an unrestricted arm movement within it.

Varied-shaped gold nanoparticles with nanogram killing efficiency as potential antimicrobial surface coatings for the medical devices.

Medical device-associated infections are a serious medical threat, particularly for patients with impaired mobility and/or advanced age. Despite a variety of antimicrobial coatings for medical devices being explored to date, only a limited number have been introduced for clinical use. Research into new bactericidal agents with the ability to eradicate pathogens, limit biofilm formation, and exhibit satisfactory biocompatibility, is therefore necessary and urgent. In this study, a series of varied-morphology gold nanoparticles in shapes of rods, peanuts, stars and spherical-like, porous ones with potent antibacterial activity were synthesized and thoroughly tested against spectrum of Candida albicans, Pseudomonas aeruginosa, Staphylococcus aureus clinical strains, as well as spectrum of uropathogenic Escherichia coli isolates. The optimization of gold nanoparticles synthesis allowed to develop nanomaterials, which are proved to be significantly more potent against tested microbes compared with the gold nanoformulations reported to date. Notably, their antimicrobial spectrum includes strains with different drug resistance mechanisms. Facile and cost-efficient synthesis of gold nanoparticles, remarkable bactericidal efficiency at nanogram doses, and low toxicity, underline their potential for development as a new coatings, as indicated by the example of urological catheters. The presented research fills a gap in microbial studies of non-spherical gold nanoparticles for the development of antimicrobial coatings targeting multidrug-resistant pathogens responsible for device-associated nosocomial infections.

Genomic diversity and characterization of Listeria monocytogenes from dry-cured ham processing plants.

Genomic diversity of Listeria monocytogenes isolates from the deboning and slicing areas of three dry-cured ham processing plants was analysed. L. monocytogenes was detected in 58 out of 491 samples from the environment and equipment surfaces, all from the deboning area, with differences in prevalence among facilities. The most frequent PCR-serogroup was IIa (74.1%) followed by IIb and IIc, and only one isolate was serogroup IVb. Twenty different pulsotypes and 11 sequence types (STs) grouped into 10 clonal complexes (CCs) were determined. ST121 (CC121) and ST9 (CC9) were the most abundant. Premature stop codons (PMSC6 and PMSC19) associated with attenuated virulence were found in the inlA sequence in 7 out of 12 selected strains. CC121 strains were strong biofilm formers and some harboured the transposon Tn6188, related with increased tolerance to quaternary ammonium compounds. L. monocytogenes clones considered hypovirulent resulted predominant in the deboning areas. The clonal structure and potential virulence of the isolates could help to establish adequate control measures and cleaning protocols for the comprehensive elimination of the pathogen in dry-cured ham processing environment.

Risk factors and biofilm formation analyses of hospital-acquired infection of Candida pelliculosa in a neonatal intensive care unit.

BACKGROUND: Candida pelliculosa is an ecological fungal species that can cause infections in immunocompromised individuals. Numerous studies globally have shown that C. pelliculosa infects neonates. An outbreak recently occurred in our neonatal intensive care unit; therefore, we aimed to evaluate the risk factors in this hospital-acquired fungal infection. METHODS: We performed a case-control study, analysing the potential risk factors for neonatal infections of C. pelliculosa so that infection prevention and control could be implemented in our units. Isolated strains were tested for drug resistance and biofilm formation, important factors for fungal transmission that give rise to hospital-acquired infections. RESULTS: The use of three or more broad-spectrum antimicrobials or long hospital stays were associated with higher likelihoods of infection with C. pelliculosa. The fungus was not identified on the hands of healthcare workers or in the environment. All fungal isolates were susceptible to anti-fungal medications, and after anti-fungal treatment, all infected patients recovered. Strict infection prevention and control procedures efficiently suppressed infection transmission. Intact adhesin-encoding genes, shown by genome analysis, indicated possible routes for fungal transmission. CONCLUSIONS: The use of three or more broad-spectrum antimicrobials or a lengthy hospital stay is theoretically associated with the risk of infection with C. pelliculosa. Strains that we isolated are susceptible to anti-fungal medications, and these were eliminated by treating all patients with an antifungal. Transmission is likely via adhesion to the cell surface and biofilm formation.

Exploiting Generative Design for 3D Printing of Bacterial Biofilm Resistant Composite Devices.

As the understanding of disease grows, so does the opportunity for personalization of therapies targeted to the needs of the individual. To bring about a step change in the personalization of medical devices it is shown that multi-material inkjet-based 3D printing can meet this demand by combining functional materials, voxelated manufacturing, and algorithmic design. In this paper composite structures designed with both controlled deformation and reduced biofilm formation are manufactured using two formulations that are deposited selectively and separately. The bacterial biofilm coverage of the resulting composites is reduced by up to 75% compared to commonly used silicone rubbers, without the need for incorporating bioactives. Meanwhile, the composites can be tuned to meet user defined mechanical performance with ±10% deviation. Device manufacture is coupled to finite element modelling and a genetic algorithm that takes the user-specified mechanical deformation and computes the distribution of materials needed to meet this under given load constraints through a generative design process. Manufactured products are assessed against the mechanical and bacterial cell-instructive specifications and illustrate how multifunctional personalization can be achieved using generative design driven multi-material inkjet based 3D printing.

Development of a high-level light-activated disinfectant for hard surfaces and medical devices.

BACKGROUND: Bacterial spores are an important consideration in healthcare decontamination, with cross-contamination highlighted as a major route of transmission due to their persistent nature. Their containment is extremely difficult due to the toxicity and cost of first-line sporicides. METHODS: Susceptibility of Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli to phenothiazinium photosensitizers and cationic surfactants under white- or red-light irradiation was assessed by determination of minimum inhibitory concentrations, minimum bactericidal concentrations and time-kill assays. B. subtilis spore eradication was assessed via time-kill assays, with and without nutrient and non-nutrient germinant supplementation of photosensitizer, surfactant and photosensitizer-surfactant solutions in the presence and absence of light. RESULTS: Under red-light irradiation, >5-log10 colony-forming units/mL reduction of vegetative bacteria was achieved within 10 min with toluidine blue O (TBO) and methylene blue (MB). Cationic surfactant addition did not significantly enhance spore eradication by photosensitizers (P>0.05). However, addition of a nutrient germinant mixture to TBO achieved a 6-log10 reduction after 20 min of irradiation, while providing 1-2 log10 improvement in spore eradication for MB and pyronin Y. CONCLUSIONS: Light-activated photosensitizer solutions in the presence of surfactants and germination-promoting agents provide a highly effective method to eradicate dormant and vegetative bacteria. These solutions could provide a useful alternative to traditional chemical agents used for high-level decontamination and infection control within health care.

The effect of partial depopulation on Campylobacter introduction in broiler houses.

Poultry is seen as the main reservoir for Campylobacter. Control of this zoonotic pathogen in primary production could potentially reduce the colonization in broiler flocks and consequently reduce the number of human infections. In the present study, 20 broiler flocks from 10 farms, were sampled immediately before and 5 to 7 d after partial depopulation (thinning) for the presence of Campylobacter using cecal droppings and overshoes. At the time of thinning, the catching crew, transportation vehicles, forklift, and transport containers were sampled for the presence of Campylobacter. Samples were cultivated; presumed positive isolates were confirmed by PCR. The isolates were molecularly typed by flaA restriction analysis and pulsed field gel electrophoresis. Results show that all flocks were thinned using Campylobacter-contaminated equipment and materials. One-third of the broiler flocks became colonized after thinning. In 67% of the colonization cases, identical strains were found matching those of container systems, transport trucks, and/or forklifts. This identifies thinning as an important risk factor for Campylobacter introduction into broiler houses. Setup and compliance with biosecurity practices during thinning is essential to prevent Campylobacter colonization of broiler flocks.

Clonal dispersion of Acinetobacter baumannii in an intensive care unit designed to patients COVID-19.

INTRODUCTION: SARS-CoV2 pandemic marks the need to pay attention to bacterial pathogens that can complicate the hospital stay of patients in the intensive care unit (ICU). ESKAPE bacteria which includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae are considered the most important, because of their close relationship with the development of ventilator-associated pneumonia (VAP). The aim of this work was to identify and characterize ESKAPE bacteria and to detect their possible clonal spread in medical devices, patients, and medical personnel of the ICU for COVID-19 patients of the Hospital Juarez de Mexico. METHODOLOGY: Genetic identification of ESKAPE bacteria was performed by analyzing the 16S rRNA gene. Resistance assays were performed according to the CLSI guidelines. Assembly of AdeABCRS operon and inhibition assays of pumps efflux in Acinetobacter baumannii isolates were performed. Associated gene involved in biofilm formation (icaA) was performed in isolates belonging to the Staphylococcus genus. Finally, typing by ERIC-PCR and characterization of mobile genetic element SCCmec were done. RESULTS: Heterogeneous distribution of ESKAPE and non-ESKAPE bacteria was detected in various medical devices, patients, and medical personnel. Acinetobacter baumannii and Staphylococcus aureus were the predominant ESKAPE members. The analysis of intergenic regions revealed an important clonal distribution of A. baumannii (AdeABCRS+). Genotyping of SCCmec mobile genetic elements and the icaA gene showed that there is no clonal distribution of S. aureus. CONCLUSIONS: Clonal spread of A. baumannii (AdeABCRS+) highlights the importance of adopting good practices for equipment disinfection, surfaces and management of COVID-19 patients.

Bacterial strains colonizing the sensor electrodes of a continuous glucose monitoring system in children with diabetes.

INTRODUCTION: The higher frequency of infections in diabetic patients is caused by a hyperglycemic environment, which promotes immune dysfunction. People with diabetes are more prone to skin infections. A continuous glucose monitoring (CGM) system provides information on changes in blood glucose (BG) levels throughout the day. Its use facilitates optimal therapeutic decisions for a diabetic patient. One of the factors limiting the use of CGM is inflammation at the insertion site. AIM OF THE STUDY: The aim of the study was the microbiological identification of the bacterial strains which are found on CGM sensor electrodes. MATERIAL AND METHODS: We performed microbiological tests on patients' CGM Enlite Medtronic electrodes, which were removed after 6 days of usage according to the manufacturer's instructions. 31 sensors were examined from 31 children (14 girls) aged from 0.5 to 14.6 years. The microbiological analysis was routinely performed at the Department of Children's Diabetology Medical University of Silesia in Katowice, Poland. RESULTS: 12 (39%) of the electrodes were colonized. In 11 (92%) cases the electrodes were colonized by one bacteria strain. 7 times methicillin-sensitive coagulase negative staphylococcus (MSCNS) was detected. We also found one case of Klebsiella pneumoniae, Ochrobactrum tritici, Bacillus sonorensis and methicillin-resistant coagulase-negative Staphylococci (MRCNS) colonization. One electrode was colonized by the mixed flora Enterococcus faecalis, methicillin-susceptible coagulase-negative Staphylococci (MSCNS), Pseudomonas stutzeri, methicillin-susceptible Staphylococcus aureus (MSSA). The median HbA1c in the group with colonization of electrodes was 6, 85% (6, 3-7, 6%) versus 6, 3% (5, 8-7, 5%) in the group without colonization. The median BMI in the group with colonization of the electrodes was 17.10 kg/m2 (16.28-18.62 kg/m2) versus 15.98 kg/m2 (15.14-17.96 kg/m2) in the group without colonization. Statistically, significantly more frequently electrodes are colonized in older children (median age in the group with colonization of electrodes 11.43 years (6.52-12.27 years), without colonization 8.42 years. (3.098-9.375 years); (p = 0.033). CONCLUSIONS: It seems that older children are more likely to have their sensor electrode colonized by bacterial strains.

Evaluating Candida albicans biofilm formation in silkworms.

Candida albicans is a pathogenic fungus that causes deep mycosis in immunocompromised patients and forms a biofilm on catheter surfaces. Here we showed that C. albicans infection of silkworms led to biofilm formation on the surface of polyurethane fibers, a catheter substrate material, while inside the silkworm body. Silkworms inserted with polyurethane fibers survived for at least 48 hours. When silkworms inserted with polyurethane fibers were subsequently infected with C. albicans, biofilm formed on the surface of the polyurethane fiber within 24 hours in the silkworm body. These results suggest that silkworms can be used to evaluate C. albicans biofilm formation.

Strategies for antimicrobial peptide coatings on medical devices: a review and regulatory science perspective.

Indwelling and implanted medical devices are subject to contamination by microbial pathogens during surgery, insertion or injection, and ongoing use, often resulting in severe nosocomial infections. Antimicrobial peptides (AMPs) offer a promising alternative to conventional antibiotics to reduce the incidence of such infections, as they exhibit broad-spectrum antimicrobial activity against Gram-negative and Gram-positive bacteria, microbial biofilms, fungi, and viruses. In this review-perspective, we first provide an overview of the progress made in this field over the past decade with an emphasis on the local release of AMPs from implant surfaces and immobilization strategies for incorporating these agents into a wide range of medical device materials. We then provide a regulatory science perspective addressing the characterization and testing of AMP coatings based on the type of immobilization strategy used with a focus on the US market regulatory niche. Our goal is to help narrow the gulf between academic studies and preclinical testing, as well as to support a future literature base in order to develop the regulatory science of antimicrobial coatings.

The role of medical equipment in the spread of nosocomial infections: a cross-sectional study in four tertiary public health facilities in Uganda.

BACKGROUND: With many medical equipment in hospitals coming in direct contact with healthcare workers, patients, technicians, cleaners and sometimes care givers, it is important to pay close attention to their capacity in harboring potentially harmful pathogens. The goal of this study was to assess the role that medical equipment may potentially play in hospital acquired infections in four public health facilities in Uganda. METHODS: A cross-sectional study was conducted from December 2017 to January 2018 in four public health facilities in Uganda. Each piece of equipment from the neonatal department, imaging department or operating theatre were swabbed at three distinct points: a location in contact with the patient, a location in contact with the user, and a remote location unlikely to be contacted by either the patient or the user. The swabs were analyzed for bacterial growth using standard microbiological methods. Seventeen bacterial isolates were randomly selected and tested for susceptibility/resistance to common antibiotics. The data collected analyzed in STATA version 14. RESULTS: A total of 192 locations on 65 equipment were swabbed, with 60.4% of these locations testing positive (116/192). Nearly nine of ten equipment (57/65) tested positive for contamination in at least one location, and two out of three equipment (67.7%) tested positive in two or more locations. Of the 116 contaminated locations 52.6% were positive for Bacillus Species, 14.7% were positive for coagulase negative staphylococcus, 12.9% (15/116) were positive for E. coli, while all other bacterial species had a pooled prevalence of 19.8%. Interestingly, 55% of the remote locations were contaminated compared to 66% of the user contacted locations and 60% of the patient contacted locations. Further, 5/17 samples were resistant to at least three of the classes of antibiotics tested including penicillin, glycylcycline, tetracycline, trimethoprim sulfamethoxazole and urinary anti-infectives. CONCLUSION: These results provides strong support for strengthening overall disinfection/sterilization practices around medical equipment use in public health facilities in Uganda. There's also need for further research to make a direct link to the bacterial isolates identified and cases of infections recorded among patients in similar settings.