In vitro study on the transmission of multidrug-resistant bacteria from textiles to pig skin

BACKGROUND The survival of microorganisms on textiles and specifically on healthcare profes-sionals’(HCP)attire has been demonstrated in several studies.The ability of microorganisms to adhere and remain on textiles for up to hours or days raises questions as to their possible role in transmission from textile to skin via HCP to patients.AIM To evaluate the presence,survival and transmission of different multidrug-resistant bacteria(MDRB)from HCP attire onto skin.METHODS Three MDRB[methicillin-resistant Staphylococcus aureus(MRSA);vancomycin-resistant Enterococcus faecium(VRE);carbapenem-resistant Klebsiella pneumoniae,(CRKP)]were inoculated on textiles from scrubs(60%cotton-40%polyester)and white coat(100%cotton)at concentrations of 108 colony-forming units(CFU),105 CFU,and 103 CFU per mL.The inoculation of swatches was divided in time intervals of 1 min,5 min,15 min,30 min,1 h,2 h,3 h,4 h,5 h,and 6 h.At the end of each period,textiles were imprinted onto pig skins and each skin square was inverted onto three different selective chromogenic media.Growth from the pig skin squares was recorded for the 3 MDRB at the three above concentrations,for the whole length of the 6-h experiment.RESULTS MRSA was recovered from pig skins at all concentrations for the whole duration of the 6-h study.VRE was recovered from the concentration of 108 CFU/mL for 6 h and from 105 CFU/mL for up to 3 h,while showing no growth at 103 CFU/mL.CRKP was recovered from 108 CFU/mL for 6 h,up to 30 min from 105 CFU/mL and for 1 min from the concentration of 103 CFU/mL.CONCLUSION Evidence from the current study shows that MRSA can persist on textiles and transmit to skin for 6 h even at low concentrations.The fact that all MDRB can be sustained and transferred to skin even at lower concentrations,supports that textiles are implicated as vectors of bacterial spread.

Analysis and control of multidrug-resistant bacteria in hospital

Objective:To investigate the status of multidrug-resistant bacteria and the prevention and control measures of nosocomial in-fection in our hospital.Methods:The annual monitoring of multidrug-resistant bacteria infection was measured to summarize the bacteria species,statistical distribution and antibiotic resistance.Identification of multidrug-resistant bacteria infection in patients infected or hospital acquired infections was taken to analyze the reasons of multidrug-resistant bacteria strain and put forward the relevant measures.Results:The top five of multidrug-resistant strains infections were:Gram-positive bacteria including methicillin-resistant Staphylococcus aureus,Staphylococcus aureus;Gram-negative bacteria including Escherichia coli,Acinetobacter bauman-nii,Klebsiella pneumoniae.Conclusions:The occurrence of multidrug-resistant hospital infections could be prevented by rational use of antibiotics,hand hygiene and disinfection management,and reinforced monitoring of multidrug-resistant bacteria.

Antibacterial activities of ethanol extracts of Philippine medicinal plants against multidrug-resistant bacteria

Objective: To investigate the antibacterial activities of crude ethanol extracts of 12 Philippine medicinal plants.Methods: Crude ethanol extracts from 12 Philippine medicinal plants were evaluated for their antibacterial activity against methicillin-resistant Staphylococcus aureus, vancomycinresistant Enterococcus, extended spectrum β-lactamase-producing, carbapenem-resistant Enterobacteriaceae and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii. Results: The leaf extracts of Psidium guajava, Phyllanthus niruri, Ehretia microphylla and Piper betle(P. betle) showed antibacterial activity against the Gram-positive methicillinresistant Staphylococcus aureus and vancomycin-resistant Enterococcus. P. betle showed the highest antibacterial activity for these bacteria in the disk diffusion(16-33 mm inhibition diameter), minimum inhibitory concentration(19-156 μg/m L) and minimum bactericidal concentration(312 μg/m L) assays. P. betle leaf extracts only showed remarkable antibacterial activity for all the Gram-negative multidrug-resistant bacteria(extended spectrum β-lactamaseproducing, carbapenem-resistant Enterobacteriaceae and metallo-β-lactamase-producing) in the disk diffusion(17-21 mm inhibition diameter), minimum inhibitory concentration(312-625 μg/m L) and minimum bactericidal concentration(312-625 μg/m L) assays. Conclusions: P. betle had the greatest potential value against both Gram-negative and Grampositive multidrug-resistant bacteria. Favorable antagonistic activities were also exhibited by the ethanol extracts of Psidium guajava, Phyllanthus niruri and Ehretia microphylla.

Antibacterial Activity of Essential Oil from <i>Citrus aurantifolia</i>(Christm.) Swingle Peels against Multidrug-Resistant Bacterial Isolates

The study investigated the antibacterial activity of essential oil from the peel of Citrus aurantifolia against eleven multidrug-resistant (MDR) bacterial isolates of clinical origin. The Kirby-Bauer disc diffusion method was used to determine the antibiotic resistance profile of the isolates. Essential oil (EO) from the peels of lime purchased at a market in Ile-Ife was extracted by the hydro-distillation method, while the sensitivity of the isolates to EO was done via agar well diffusion method. The minimum inhibitory and minimum bactericidal concentrations (MIC and MBC) of the EO against the tested isolates were determined following standard methods. All the tested isolates exhibited multidrug resistance (MDR) characteristics. The multiple antibiotics resistant indexes (MARI%) for Gram-positive bacterial isolates ranged between 70% and 100% while that of Gram-negative was 100%. The yield of EO was 1% and the EO demonstrated activities at 25%, 50% and 100% v/v against the MDR bacterial isolates. The activity of EO was mostly not significantly different at the same concentration for all the isolates, and at different concentrations for each of the isolates. The MIC range for Gram-negative and Gram-positive isolates was between 0.195% to 3.125% v/v and 0.39% to 3.125% respectively while the range was between 1.563% to 3.125% and 0.781% to 6.250% v/v for MBC respectively. The study showed that EO from the peel of lime fruits demonstrated excellent in vitro antibacterial activity against MDR bacterial isolates. This potential can be further explored as an alternative for the treatment and management of infections caused by MDR bacterial isolates.

Analysis of Influencing Factors and Predictive Models of Multidrug-resistant Bacterial Infection in Severe Patients

Objective:To investigate the influencing factors of multi-drug resistant bacterial infections in patients with severe disease and establish a predictive model.Methods:207 infected patients in our hospital from 2018 to May 2020 were selected for the study,of which 73 carried drug-resistant bacteria.Results:The risk factor network of people infected with multidrug resistant bacteria is higher than that of people infected with non-multidrug resistant bacteria,and the interaction between risk factors of the former is stronger.Conclusion:Antibiotics must be used appropriately after surgery.When the elderly was abnormal in indicators such as fever and procalcitonin in the ward,they should be considered as high-risk groups of MDRO infection.They need special care and preventive measures.

A Rigid Nanoplatform for Precise and Responsive Treatment of Intracellular Multidrug-Resistant Bacteria

Antibiotic treatment failure against life-threatening bacterial pathogens is typically caused by the rapid emergence and dissemination of antibiotic resistance.The current lack of antibiotic discovery and development urgently calls for new strategies to combat multidrug-resistant(MDR)bacteria,especially those that survive in host cells.Functional nanoparticles are promising intracellular drug delivery systems whose advantages include their high biocompatibility and tunable surface modifications.Inspired by the fact that the rigidity of nanoparticles potentiates their cellular uptake,rigidity-functionalized nanoparticles(RFNs)coated with bacteria-responsive phospholipids were fabricated to boost endocytosis,resulting in the increased accumulation of intracellular antibiotics.Precise delivery and high antibacterial efficacy were demonstrated by the clearing of 99%of MDR bacteria in 4 h using methicillin-resistant Staphylococcus aureus(MRSA)and pathogenic Bacillus cereus as models.In addition,the subcellular distribution of the RFNs was modulated by altering the phospholipid composition on the surface,thereby adjusting the electrostatic effects and reprograming the intracellular behavior of the RFNs by causing them to accurately target lysosomes.Finally,the RFNs showed high efficacy against MRSA-associated infections in animal models of wound healing and bacteremia.These findings provide a controllable rigidity-regulated delivery platform with responsive properties for precisely reprograming the accumulation of cytosolic antibiotics,shedding light on precision antimicrobial therapeutics against intracellular bacterial pathogens in the future.

De novo design of highly efficient type-Ⅰphotosensitizer based onπ-conjugated oligomer for photodynamic eradication of multidrug-resistant bacterial infections

Traditional photosensitizers show limited singlet oxygen generation in hypoxic infection lesions,which greatly suppress their performance in antibacterial therapy.Meanwhile,there still is lack of feasible design strategy for developing hypoxia-overcoming photosensitizers agents.Herein,radical generation ofπ-conjugated small molecules is efficiently manipulated by an individual selenium(Se)substituent.With this strategy,the first proof-of-concept study of a Se-anchored oligo(thienyl ethynylene)(OT-Se)with high-performance superoxide radical(O_(2)^(·-))and hydroxyl radical(·OH)generation capability is present,and achieves efficient antibacterial activities towards the clinically extracted multidrug-resistant bacteria methicillin-resistant S.aureus(MRSA)and carbapenem-resistant E.coli(CREC)at sub-micromolar concentration under a low white light irradiation(30 mW/cm^(2)).The water-dispersible OT-Se shows a good bacteria-anchoring capability,biocompatibility,and complete elimination of multidrug-resistant bacteria wound infection in vivo.This work offers a strategy to boost type-I photodynamic therapy(PDT)performance for efficient antibacterial treatments,advancing the development of antibacterial agents.

Aggregated carbon dots-loaded macrophages treat sepsis by eliminating multidrug-resistant bacteria and attenuating inflammation

Sepsis,caused by uncontrollable infection and inflammatory response,leads to more than 30 million infected patients and results in high morbidity worldwide every year.Currently,no efficient approaches have been developed for sepsis therapy due to antimicrobial resistance and inflammatory storm.Here,we report macrophages loaded with aggregated carbon dots(ACDs)in the lysosome,termed MCDs,to treat sepsis in immunosuppressive mice.The ACDs are constructed by negative CDs and amine-abundant polyethyleneimine(PEI),enabling them to bear the strong antibacterial ability and enhanced photoluminescent efficacy.The ACDs are specifically located in the macrophage lysosomes,efficiently enhancing the multidrug-resistant bacteria-killing ability of MCDs.More importantly,the MCDs possess superior anti-inflammatory effects such as reducing the number of pro-inflammatory(M1)and stimulating anti-inflammatory(M2)macrophages.These effects upregulate the inflammatory cytokines(TNF-α,IL-1β,IL-4,and IL-10),ultimately resulting in increased sepsis survival.Our work provides an intelligent approach to overcoming multidrug-resistant bacteria-induced infection from sepsis patients and paves a new avenue on employing nanoparticle-loaded cells for combating inflammation-related infection.

Multidrug-Resistant of Escherichia coli and Salmonella spp. Strains in Chicken Feces Intended for Consumption in Open Spaces of Ouagadougou, Burkina Faso

Resistant bacteria can be transmitted to humans through feces or contaminated meat from local chickens. Bacterial strains were isolated from the intestinal contents of 400 local chicken samples from various sales sites. These strains were then characterized using bacteriological and biochemical methods to identify resistant strains. In a study conducted in Ouagadougou, we systematically collected chicken fecal samples from 20 locations across the city, followed by isolation and identification of Salmonella spp. using specific enrichment and culture methods, as well as Escherichia coli. Bacterial strains were characterized using antibiotic resistance profiles were determined through agar diffusion tests, revealing sensitivity or resistance to a range of antibiotics based on established scientific criteria. The results showed that out of the 400 samples collected, 81.25% and 63.5% were contaminated by Escherichia coli and Salmonella spp., respectively. Among these, 86.15% of identified Escherichia coli and 50.78% of Salmonella spp. displayed resistance to at least one tested antibiotic. Among 280 Escherichia coli isolates identified resistant to at least one antibiotic, 31.07% were resistant to cefotaxime (CTX), 20.35% to ceftazidime (CAZ), 21.07% to ceftriaxone (CTR), 75% to amoxicillin clavulanic acid (AMC), 23.57% aztreoname (ATM) and 27.14% were resistant to imipenem (IMP). In the case of the 129 Salmonella spp. isolates resistant to at least one tested antibiotic, 34.88% were resistant to CTX;41.08% to CAZ;35.65% to CTR, 92% to AMC, 39.53% to ATM and finally 47.28% were resistant to IMP. Our study revealed high prevalence of resistance in bacterial strains isolated from local chickens sold outdoors in Ouagadougou. These findings raise significant public health concerns, due to the possible transmission of these resistant strains to humans through the consumption of contaminated meat, thus complicating the treatment of bacterial infections.

Clinical Efficacy and Safety Analysis of Tigecycline in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease Combined with Multidrug-Resistant Acinetobacter baumannii Infection

Objective:To study the clinical efficacy and safety of tigecycline in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD)combined with multidrug-resistant Acinetobacter baumannii infection.Methods:113 patients with acute exacerbation of COPD combined with multidrug-resistant Acinetobacter baumannii infection were recruited between January 2021 and January 2023,and given tigecycline treatment.The total effective rate,lung function indexes,related biochemical index levels,and the incidence rate of adverse reactions were observed after the treatment.Results:After the treatment,100 patients were cured,1 case with apparent effect,2 cases were effective,10 cases were ineffective,and the total effective rate was 91.15%.The post-treatment CRP(21.22±3.35 mg/L),PCT(3.18±1.11 ng/L),CRE(76.36±9.24μmol/L),and ALT(37.76±6.99 U/L)were significantly improved as compared to the pre-treatment(P<0.05).After treatment,10 cases of vomiting(8.85%),13 cases of nausea(11.50%),4 cases of diarrhea(3.53%),1 case of abdominal pain(0.88%),and 2 cases of allergy(1.77%)were observed in 113 patients.Conclusion:Tigecycline therapy for patients with acute exacerbation of COPD combined with multidrug-resistant Acinetobacter baumannii infection not only has significant therapeutic efficacy but also has a high degree of safety.

Efficient elimination of multidrug-resistant bacteria using copper sulfide nanozymes anchored to graphene oxide nanosheets

Antibacterial nanomaterials have attracted growing interest for bacterial infection therapy.However,most nanomaterials eliminate bacteria either physically or chemically,which hampers their efficacy when dealing with multidrug-resistant bacteria.To overcome this,we integrated copper sulfide(CuS)nanoparticles with active graphene oxide nanosheets(GO NSs)to synthesize a superior nanocomposite(CuS/GO NC)that acts both physically and chemically on the bacteria.CuS/GO NC was produced using a facile hydrothermal method,whereby the CuS nanoparticles grew and were uniformly dispersed on the GO NSs in situ.We found that the CuS/GO NC possesses a unique needle-like morphology that physically damages the bacterial cell membrane.CuS/GO NC also exhibits high oxidase-and peroxidase-like activity,ensuring efficient generation of the reactive oxygen species•OH from H2O2,which kills bacteria chemically.These features endow the CuS/GO NC with excellent antibacterial capabilities to kill multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus(MRSA)with only a single dose.Additionally,it was found that the CuS/GO NC accelerated the healing of infected wounds in vivo owing to its good biocompatibility as well as facilitation of cell migration and collagen secretion.This study provides a new strategy to combine the physical and chemical antibacterial modes of nanomaterials to develop more effective therapies to combat multidrug-resistant bacterial infections.

Phytochemical-encapsulated nanoplatform for ＂ondemand＂ synergistic treatment of multidrug-resistant bacteria

Though phytochemicals are a promising alternative to traditional antibiotics for combating resistant bacteria, the low water solubility and lack of selectivity seriously hinder their widespread applications. Herein, we constructed a hyaluronidase-activated ＂on-demand＂ delivery nanocarrier to encapsulate plant essential oils （PEOs） for the synergistic treatment of mulfidrug-resistant bacteria. The bioavailability and selectivity of PEOs was enhanced and the antibacterial effect was significantly improved by combining with the photothermal effect of the nanocarrier. This antibacterial system was successfully applied for healing methicillin-resistant Staphylococcus aureus-infected wound with negligible cytotoxicity and biotoxicity in mice. Given the increasing risk of antibiotic resistance, we believe that this phytochemical-encapsulated nanoplatform would provide a long-term solution and be a new powerful tool for skin-associated bacterial infections.

Discovery of ferrocene-carborane derivatives as novel chemical antimicrobial agents against multidrug-resistant bacteria

Antimicrobial resistance has now become a very serious global public health problem. New drug discovery and development are urgently needed to combat the growing threat of multidrug-resistant (MDR) bacteria. The aim of this study was to explore the potential application of three ferrocene-carborane derivatives as new promising agents to confront the problem of increasing antibiotic resistance. The results of agar diffusion bioassay, minimal inhibitory concentrations (MIC) testing and time-kill assay illustrate their broad-spectrum antimicrobial activities to both American Type Culture Collection (ATCC) control strains and MDR clinical isolates. It is evident that the relevant antimicrobial properties are all in a dose-dependent manner and gradually transform into a bactericidal effect from a bacteriostatic effect with the increasing of the drug concentration. Furthermore, these ferrocene-carborane derivatives have no/little toxic effect on normal cells like HELF cells and lead to little hemolysis at their MICs. This raises the possibility to develop novel antimicrobial drugs using these new ferrocene carborane derivants.

Wrapping collagen-based nanoparticle with macrophage membrane for treating multidrug-resistant bacterial infection

Nowadays,multidrug-resistant(MDR)bacterial infectious diseases has become a thorny issue in the healthcare field.Owning to its intrinsic merits,photodynamic therapy(PDT)shows tremendous strengths in fighting against MDR bacterial infections.However,most photodynamic nanoplatforms exhibit unsatisfactory targeting efficiency towards bacteria and infection site,which may compromise the bactericidal effect of PDT.Herein,we firstly reported a bacteria-targeted collagen-based nanoparticle,named Ce6/Col/MM,for treating methicillin-resistant Staphylococ-cus aureus(MRSA)-infected wound.Ce6/Col/MM was fabricated by wrapping chlorin e6(Ce6)-loaded collagen-based nanoparticles with macrophage membrane(MM),showing excellent photodynamic activity and good biocompat-ibility.In vitro studies demonstrated that Ce6/Col/MM could target to bacteria and then exhibit prominent antibacterial capacity against planktonic MRSA under light irradiation.Furthermore,the treatment of MRSA-infected wound in mice with Ce6/Col/MM plus light illumination resulted in potent bacterial inactivation and accelerated wound healing,accompanied by favorable histological compatibility.Collectively,Ce6/Col/MM with superior targeting ability towards bacteria,effective photodynamic antibacterial potency and minimal safety concerns,might be a powerful bactericidal nanoagent for treating infections caused by MDR bacteria。

Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in China

Objective This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline(BR)and the conventional treatment regimen(CR,not containing Bedaquiline)for the treatment of adults with multidrug-resistant tuberculosis(MDR-TB)in China.Methods A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years.The model parameter data were synthesized from the literature,the national TB surveillance information system,and consultation with experts.The incremental cost-effectiveness ratio(ICER)of BR vs.CR was determined.Results BR(vs.CR)had a higher sputum culture conversion rate and cure rate and prevented many premature deaths(decreased by 12.8%),thereby obtaining more quality-adjusted life years(QALYs)(increased by 2.31 years).The per capita cost in BR was as high as 138,000 yuan,roughly double that of CR.The ICER for BR was 33,700 yuan/QALY,which was lower than China's 1×per capita Gross Domestic Product(GDP)in 2020(72,400 yuan).Conclusion BR is shown to be cost effective.When the unit price of Bedaquiline reaches or falls below57.21 yuan per unit,BR is expected to be the dominant strategy in China over CR.

Biocompatible metal-free organic phosphorescent nanoparticles for efficiently multidrug-resistant bacteria eradication

Organic phosphorescence materials with longlived triplet excitons that can highly generate active singlet oxygen(1O2) through the energy transfer with the molecular oxygen under photoexcitation, serve as highly efficient antibacterial agent. Herein, we report bright red-emissive organic phosphorescent nanoparticles(PNPs) based on a metal-free organic phosphor encapsulated with biocompatible block copolymers. The obtained PNPs with an ultra-small particle size of around 5 nm and a long emission lifetime of up to 167 μs showed effective 1O2 generation ability under visible light(410 nm) excitation in aqueous media, which can efficiently eradicate multi-drug resistant bacteria both in vitro and in vivo. This is the first demonstration of metal-free organic PNPs for photodynamic antimicrobial therapy, expanding the application scope of metal-free organic room temperature phosphorescent materials.

Sensorineural Hearing Loss in Multidrug-Resistant Tuberculosis Patients in Kinshasa (Democratic Republic of Congo): Prospective Cohort Study of Therapeutic Regimen with Aminoglycoside versus Bedaquiline

Context: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem in developing countries such as the Democratic Republic of Congo (DRC), which continues to face the emergence of MDR-TB cases. Because of the ototoxic effects of AGs, the World Health Organization (WHO) has recommended the introduction of the bedaquiline regimen. However, very few data are available regarding the susceptibility of bedaquiline to induce hearing loss, hence the present study set out to compare the AG-based regimen and the bedaquiline-based regimen in the occurrence of hearing loss in MDR-TB patients. Methods: This is a prospective multicenter cohort study that included 335 MDR-TB patients, performed in Kinshasa (DRC) during the period from January 2020 to January 2021. Sociodemographic, clinical, biological and audiometric data were analyzed using Stata 17. Repeated-measures analysis of variance was used to compare changes in the degree of hearing loss over time between the two groups of patients on AG and bedaquiline regimens. The double-difference method was estimated using regression with fixed-effects. A p value < 0.05 was considered the threshold for statistical significance. Results: The degree of hearing loss was similar between the two groups at the first month [AGs (28 dB) vs BDQ (30 dB);p = 0.298]. At six months, the mean degree of hearing loss was significantly greater in the aminoglycoside regimen group [AGs (60.5 dB) vs BDQ (44 dB);p < 0.001]. The double difference was significant, with a greater increase in hearing loss in the AGs group (diff-in-diff 18.3;p < 0.001). After adjustment for age and serum albumin, the group receiving the AG-based regimen had a 2-point greater worsening than those with bedaquiline at the sixth month (diff-in-diff 19.8;p Conclusion: Hearing loss is frequent with both treatment regimens, but more marked with the Aminoglycoside-based regimen. Thus, bedaquiline should also benefit for audiometric monitoring in future MDR-TB patients.

Modern approaches for detection of volatile organic compounds in metabolic studies focusing on pathogenic bacteria:Current state of the art

Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific microorganisms,enabling the early diagnosis of infections and the timely implementation of tar-geted therapy.However,complex matrices only contain trace levels of VOCs,and their constituent com-ponents can hinder determination of these compounds.Therefore,modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are needed.In this paper,we discuss bacterial VOC analysis under in vitro conditions,in animal models and disease diagnosis in humans,including techniques for offline and online analysis in clinical settings.We also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis,in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species in-teractions,the kinetics of VOC metabolism,and species-and drug-resistance specificity.

Flexible electrostatic hydrogels from marine organism for nitric oxide-enhanced photodynamic therapy against multidrug-resistant bacterial infection

The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drugresistant bacteria.Thus,the development of novel antibacterial materials is attracting increasing attention.Here,a series of flexible electrostatic hydrogels with excellent antibacterial ability were constructed using a mixture of nitric oxide(NO)-releasing nitrated chitosan(CSNO)and mesotetra(4-carboxyphenyl)porphine(TCPP)with salmon sperm DNA(ssDNA)solution.When cultured with gram-negative bacteria under solar simulator irradiation,TCPP-CSNO_(m)ssDNA_(n) hydrogels released reactive oxygen species(ROS)and NO to produce peroxynitrite ions(ONOO^(−)).ONOO−is efficient at killing bacteria,thereby improving the antimicrobial ability of photodynamic therapy against gram-negative bacteria.The hydrogels exhibited powerful antibacterial activity in vivo when used to treat skin infections caused by drugresistant bacteria,making them a promising candidate for clinical applications.A string of antibacterial hydrogels that release ROS and NO synergistically can bring new possibilities for effectively killing drug-resistant bacteria and be of great value in anti-infection wound dressings and other applications.

Determinants of the Sensorineural Hearing Loss in Patients with Multidrug-Resistant Tuberculosis in Kinshasa (Democratic Republic of the Congo): A Prospective Cohort Study

Background: The onset of the hearing loss is a major challenge during the treatment of multidrug-resistant tuberculosis (MDR-TB). Aminoglycoside-based regimens, to a lesser extent based on bedaquiline, induce ototoxic sensorineural hearing loss. Research on risk factors is essential to enable high-risk individuals to benefit from preventive measures in settings with limited resources. Objective: This study aimed to assess the determinants of the hearing loss in patients with MDR-TB. Methods: This prospective multicenter cohort study included 337 patients with MDR-TB. It was performed in Kinshasa (Democratic Republic of the Congo) between January 2020 and January 2021. Sociodemographic, clinical, biological, therapeutic, and audiometric data were exported and analyzed using Stata 17 and MedCalc. The fixed-effect linear regression panel model was used to assess the degree of the hearing loss over time according to the following covariates: therapeutic regimen (aminoglycosides, bedaquiline, or alternate), stage of chronic kidney disease (CKD), age at inclusion, body mass index, serum albumin level, HIV status, alcohol intake, hypertension, and hemoglobin level. The Hausman test was used to select between fixed- and random-effect estimators. The threshold for statistical significance was set at p Result: A total of 236 patients (70%) received an aminoglycoside-based regimen, 61 (18%) received a bedaquiline-based regimen, and 40 (12%) received aminoglycosides relayed by bedaquiline. The frequency of the hearing loss increased from 62% to 96.3% within six months for all therapeutic regimens. The Hearing loss worsened, with moderate (72.4%) and profound (16%) deafness being predominant. An Exposure to the treatment for more than one month (β coeff: 27.695, Se: 0.793, p β coeff: 6.102, Se: 1.779, p β coeff: 5.610, Se: 1.682, p = 0.001), and an eGFR β coeff: 6.730, Se: 2.70, p = 0.013) were the independent risk factors associated with the hearing loss in patients with MDR-TB. Conclusions: The Hearing loss was more prevalent and worsened during the treatment of the patients with MDR-TB. An Exposure for more than one month, AG-based regimens, advanced age, hypoalbuminemia, and CKD have emerged as the main determinants of the worsening of the hearing loss.