Efficacy of antimicrobials in preventing resistance in solid organ transplant recipients:A systematic review of clinical trials

BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ transplantation.AIM To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant recipients.METHODS A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and meta-analyses.This review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial resistance.The search strategy involved analyzing multiple databases,including PubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language restrictions.RESULTS After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were studied.The most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also analyzed.The antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and colistin-neomycin.Of concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;P<0.05).The total reported deaths in three clinical trials were 75,and there were 24 graft rejections in two studies.CONCLUSION All clinical trials reported significant proportions of antimicrobial-resistant microorganisms following interventions.More high-quality randomized clinical trials are needed to corroborate these results.

Analysis of the Efficacy of Xuebijing Combined with Antimicrobials in the Treatment of Intensive Care Unit Patients with Severe Pneumonia

Objective:To analyze the therapeutic effect of Xuebijing+antimicrobials in intensive care unit(ICU)patients with severe pneumonia.Methods:60 ICU patients with severe pneumonia from June 2021 to June 2023 were selected and divided by the random number table method,with 30 cases in each group.The observation group received Xuebijing+antimicrobial treatment,while the control group received only antimicrobial treatment.The differences in rehabilitation indexes,test indexes,and inflammation indexes were compared between the two groups.Results:Mechanical ventilation time,fever reduction time,cough relief time,and hospitalization time of the observation group were significantly shorter than those of the control group(P<0.05);C-reactive protein,procalcitonin,and white blood cell count of the observation group were significantly lower than those of the control group(P<0.05);interleukin-6 and tumor necrosis factor-aαof the observation group were significantly lower than those of the control group(P<0.05).Conclusion:The treatment of severe pneumonia patients in ICU with Xuebijing+antibacterial drugs can reduce inflammation,enhance immune function,shorten the pneumonia recovery time,and reduce the adverse reactions of severe pneumonia.

Transitioning antimicrobials from intravenous to oral in pediatric acute uncomplicated osteomyelitis

Osteomyelitis is a bone infection that requires prolonged antibiotic treatment and potential surgical intervention.If left untreated,acute osteomyelitis can lead to chronic osteomyelitis and overwhelming sepsis.Early treatment is necessary to prevent complications,and the standard of care is progressing to a shorter duration of intravenous(Ⅳ) antibiotics and transitioning to oral therapy for the rest of the treatment course.We systematically reviewed the current literature on pediatric patients with acute osteomyelitis to determine when and how to transition to oral antibiotics from a short Ⅳ course.Studies have shown that switching to oral after a short course(i.e.,3-7 d) of Ⅳ therapy has similar cure rates to continuing long-term Ⅳ therapy.Prolonged Ⅳ use is also associated with increased risk of complications.Parameters that help guide clinicians on making the switch include a downward trend in fever,improvement in local tenderness,and a normalization in C-reactive protein concentration.Based on the available literature,we recommend transitioning antibiotics to oral after 3-7 d of Ⅳ therapy for pediatric patients(except neonates) with acute uncomplicated osteomyelitis if there are signs of clinical improvement,and such regimen should be continued for a total antibiotic duration of four to six weeks.

Anti-diabetics and antimicrobials:Harmony of mutual interplay

Diabetes is one of the four major non-communicable diseases,and appointed by the world health organization as the seventh leading cause of death worldwide.The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes.The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes,assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation.On a parallel basis,microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment,all of which can be reversed by antimicrobial treatment.Standing at the crossroads between diabetes,immunity and infection,we aim in this review at projecting the interplay between immunity and diabetes,shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents.Furthermore,we focused on the antidiabetic drugs that can confer antimicrobial or anti-virulence activities.

Insights into the effects of pulsed antimicrobials on the chicken resistome and microbiota from fecal metagenomes

Antimicrobial resistance has become a global problem that poses great threats to human health. Antimicrobials are widely used in broiler chicken production and consequently affect their gut microbiota and resistome. To better understand how continuous antimicrobial use in farm animals alters their microbial ecology, we used a metagenomic approach to investigate the effects of pulsed antimicrobial administration on the bacterial community, antibiotic resistance genes(ARGs) and ARG bacterial hosts in the feces of broiler chickens. Chickens received three 5-day courses of individual or combined antimicrobials, including amoxicillin, chlortetracycline and florfenicol. The florfenicol administration significantly increased the abundance of mcr-1 gene accompanied by floR gene, while amoxicillin significantly increased the abundance of genes encoding the AcrAB-tolC multidrug efflux pump(marA, soxS, sdiA, rob, evgS and phoP).These three antimicrobials all led to an increase in Proteobacteria. The increase in ARG host, Escherichia, was mainly attributed to the β-lactam, chloramphenicol and tetracycline resistance genes harbored by Escherichia under the pulsed antimicrobial treatments. These results indicated that pulsed antimicrobial administration with amoxicillin,chlortetracycline, florfenicol or their combinations significantly increased the abundance of Proteobacteria and enhanced the abundance of particular ARGs. The ARG types were occupied by the multidrug resistance genes and had significant correlations with the total ARGs in the antimicrobial-treated groups. The results of this study provide comprehensive insight into pulsed antimicrobial-mediated alteration of chicken fecal microbiota and resistome.

Interactions of naturally occurring compounds with antimicrobials

Antibiotics are among the most often used medications in human healthcare and agriculture.Overusing these substances can lead to complications such as increasing antibiotic resistance in bacteria or a toxic effect when administering large amounts.To solve these problems,new solutions in antibacterial therapy are needed.The use of natural products in medicine has been known for centuries.Some of them have antibacterial activity,hence the idea to combine their activity with commercial antibiotics to reduce the latter's use.This review presents collected information on natural compounds(terpenes,alkaloids,flavonoids,tannins,sulfoxides,and mycotoxins),of which various drug interactions have been observed.Many of the indicated compounds show synergistic or additive interactions with antibiotics,which suggests their potential for use in antibacterial therapy,reducing the toxicity of the antibiotics used and the risk of further development of bacterial resistance.Unfortunately,there are also compounds which interact antagonistically,potentially hindering the therapy of bacterial infection.Depending on its mechanism of action,each compound can behave differently in combination with different antibiotics and when acting against various bacterial strains.

Antibacterial activities of some plant extracts alone and in combination with different antimicrobials against multidrug-resistant Pseudomonas aeruginosa strains

Objective:To evaluate the possible in vitro interaction between ethanolic extracts of Rhus coriaria[R.coriaria)(seed),Sacropoterium spinosum(S.spinosum)(seed),Rosa damascena(R. damascene)(flower) and certain known antimicrobial drugs including oxytetracycline HCl, penicillin C,cephalexin,sulfadimethoxine as sodium,and enr of loxacin.This synergy study was carried out against 3 clinical strains of multidrug-resistant Pseudomonas aeruginosa (P.aeruginosa).Methods:Evaluation of synergy interaction between plant extracts and antimicrobial agents was carried out using microdilution method.Results:The results of this study showed that there is a decrease in the MIC in case of combination of ethanolic plant extracts and test antimicrobial agents.The most interesting result was that the combination between R. coriaria and these antibiotics,showed a high decrease in minimum inhibitory concentration(MIC), and a strong bactericidal activity against these strains.Conclusions:These results may indicate that combinations between R.coriaria extract and these antibiotics could be useful in fighting emerging drug-resistance P.aeruginosa,which may due to that R.coriaria extract contain natural inhibitors working by different mechanisms or inhibiting efflux pumps.Now we have experiments underway leading to the identification of the active molecules present in R.coriaria.Further,in vivo experiments are needed to confirm pseudomonal protection.

The interaction of nanostructured antimicrobials with biological systems:Cellular uptake,trafficking and potential toxicity

Nanomaterials have been found increasing applications in the food sector.Nanostructured antimicrobials can be incorporated either to food matrix of food packaging or to provide extended safety and quality.However,the interactions and effects of nanomaterials with biological systems are still poorly understood.Nanoparticles can enter the organism by oral,dermal and inhalation routes and distributed to different tissues by the circulatory system.Increasing evidence indicate that targeting to specific tissues,cellular uptake and intracellular fate of nanoparticles are strongly influenced by size,shape and surface properties.The specific characteristics of nanomaterials are also determinant for their toxicity in higher organisms.The dose,exposure time and administration route are important aspects influencing toxicity of nanoparticles as well.Both in vitro and in vivo evaluation studies on different types of nanostructures have providing information to support a better understanding about the interactions of nanoscale materials with biological systems.

Rapid detection of antimicrobial residues in poultry: A consequence of non-prudent use of antimicrobials

A cross sectional survey was conducted in three major poultry markets at Enugu Urban area of Enugu State, South Eastern, Nigeria, to determine the prevalence of antimicrobial residues in commercial broiler birds using Premi? Test Kit. Antimicrobials generally due to their availability over the counter and non-enforcement of legislature on irrational use are often abused in both veterinary and medical practice in most developing countries. The misuse and overuse of these drugs lead to deposition of violative levels of antimicrobial residues in animal tissues meant for human consumption with several health consequences when consumed. Premi? Test like all other microbiological tests is based on the principle of inhibition and was able to detect antibiotic residues in 42 (60%) of the 70 sampled commercial birds from three major poultry markets in the study area. It detected also residues in 90 out of the 280 different organ matrices made up of 70 samples of each organ, of which Kidney was the highest at 48.6%, Gizzard (30.1%), liver (25.8%), and muscle (24.3%) in that order. No association was found between the occurrence of antibiotic residues and the location of the poultry markets sampled at P < 0.05 while a strong association between antibiotic residues and the organ type at

The Occurrence of Bacteria of the Genus Aeromonas spp.in Oreochromis niloticus(Tilapia)and in the Water of Amateur Sport Fish Ponds and Sensitiveness to Antimicrobials

Since amateur fishing in fishponds has been on the increase in Brazil, there is a great concern on the microbiological quality of fish. One hundred and thirty-eight samples were collected during the dry and rainy periods in ten fish farms. Aeromonas spp. counts and tests for sensitiveness to antimicrobials were performed, coupled to the physical and chemical analyses of water. Tests revealed that 70% of samples were contaminated by Aeromonas spp., with water averaging 2.92 Log CFU/100 mL during the rainy period and 3.16 Log CFU/100 mL during the dry one. Fish contaminated by Aeromonas spp. averaged 2.58 Log CFU/100 mL during the rainy period and 3.53 Log CFU/100 mL during the dry one. Aeromonas spp. samples were multi-resistant to 2 or 8 antimicrobials in 62.5% of the samples. Ampicillin was the antimicrobial with the highest resistance percentage rate. Results showed that fish bred in amateur fish farms constituted a health risk for the population.

K-PD Model and Its Application in Research of Veterinary Antimicrobials

With the development of the PK-PD model,its application in veterinary antimicrobials has also received great attention.This paper expounded the theory of PK-PD model,and made a brief analysis of the dosing regimens of various antibiotics according to the parameters of antimicrobial drugs,in order to optimize the clinical drug delivery plan and promote the rational use of clinical antibiotics.

Main Microbial Genres and Its Profile of Resistance and Sensitivity to Antimicrobials Used in the Treatment of Oncological Patients with Febril Neutropenia

Objective: To determine the main microbial genotypes and their antimicrobial resistance and susceptibility profile commonly used in the treatment of oncologic patients with febrile neutropenia, carried out through the review of the clinical histories of the patients’ medical records at the Hospital do Cancer de Muriaé-Fundacao Cristiano Varella. Methods: Quantitative research, determined the susceptibility profile of microorganisms in patients with febrile neutropenia from April 2007 to April 2008 by reviewing clinical histories of patients’ medical records at the referred hospital. Results: Of the total of 8 patients evaluated with Gram-negative microorganisms, 50% of the patients were female and 50% were male. Of the 18 patients evaluated with Gram-positive microorganisms 66% were female and 34% male. Gram-positive bacteria are prevalent and cause around 60% of documented bacteremias, although Gram-negative bacteria are more common in febrile neutropenic patientes. Conclusion: Exaggerated use of antimicrobials in hospitalized patients leads to the suppression of drug-sensitive microorganisms from the intestinal flora and promotes the persistence and growth of resistant bacteria. The antibiotic should be used in a curative manner with other therapeutic measures with the determined bacterial infection.

Characterization of Natural Antimicrobials in Food System

There has been a rising interest in using natural antimicrobial compounds in food industry due to current trend of giving value to natural and renewable resources. These antimicrobials provide new modalities to ensure microbial safety and extend the shelf-life of foodstuffs. Natural antimicrobials can be directly added into the food, but several efforts have been made to find alternative solutions to the aim of avoiding undesirable inactivation. Some different ways such as, dipping, spraying, and coating treatment of food are currently applied to product before packaging considered as valid options. The present paper aims to review the use of natural compounds to control microbiological and physicochemical shelf life of major food categories such as, meat, fish, dairy-based products, fruit and vegetables, and cereal-based products.

Occurrence of Antimicrobials in River Water Samples from Rural Region of the State of Rio de Janeiro, Brazil

The occurrence of antimicrobials in the aquatic environment and drinking water has raised the question of their impact on the environment and public health. Animal production is one of the most expressive activities of Brazilian agribusiness. In order to ensure the productivity and competitiveness of the sector, the use of drugs for therapeutic and prophylactic purposes is a common practice. Due to the continuous release of antimicrobials into the environment, the aim of this study was to compare the frequency of detection of tetracyclines and sulfonamides in surface water collected from rural areas in Lidice District of Rio Claro, in the State of Rio de Janeiro, Brazil. An investigative study was conducted with 24 river water samples analyzed by high-performance liquid chromatography coupled to tandem mass spectrometry and the aim of this study was to determine residues of sulfonamides and tetracyclines based on the USEPA method 1694. The results indicated the presence of sulfamethoxazole and oxytetracycline concentrations at the ng·L-1 level. The applied method showed overall good performance with recoveries above 57%, method detection limits ≤ 7.17 ng·L-1, method quantification limits ≤ 23.90 ng·L-1 and good linearity.

Microbiological Assessment and Antimicrobials’ Use in an Infectious Diseases Department in Mali

The use of antimicrobials without microbiological proof is frequent and contributes to the emergence of resistance. The aim was to identify the organisms isolated during laboratory examinations and the type of antimicrobials consumed by patients hospitalized to Infectious Diseases’ Clinic. This is a cross-sectional and analytical study, carried out from January 1 to December 31, 2017 in the Infectious Diseases Department of Point “G” Teaching Hospital in Mali. All biological specimens from patients during the study period were analyzed. In total, 322 patients benefited from microbiological test, with a mean age of 40.9 ± 12.2 years (range 15 and 74 years) with a sex ratio of 0.93. Only 5.6% of patients were HIV negative. In all participants, a total of 658 microbiological specimen were taken, 224 (34.0%) identified at least one pathogen including bacteria in more than a half of the cases (58.5%). On the report of bacteriological analysis, the most frequently identified organisms were Mycobacterium tuberculosis (42.2%) mainly in sputum;Escherichia coli (24.2%) and Klebsiella pneumoniae (7.8%) commonly in urine and Gardnerella vaginalis (7.0%) exclusively in vaginal secretions. Candida albicans (5/8) and Cryptococcus neoformans (3/8) were the most common fungi while Plasmodium falciparum (96.4%) represented the parasite frequently found in blood. From a therapeutic standpoint, 1143 antimicrobials were prescribed to 322 admitted patients, i.e. 3.55 anti-infectives per patient. Antibiotics (excluding tuberculosis drugs), antiparasitics and antifungals represented respectively 46.2%;18.8% and 15.1% of anti-infectives. Antibiotic therapy was effective in 274 (85.1%) patients and among them, only 76 (27.7%) cases were based on microbiological evidence. Antibiotics are the most widely used antimicrobials in an infectious disease department. Empiric treatments are common but must be minimized by the search for microbiological evidence.

In Silico Approach for the Identification of Potential Targets and Specific Antimicrobials for Streptococcus mutans

Tooth decay affects most of the population in developed countries. The multifactorial etiology of the disease includes multiple bacterial species, S. mutans is the main pathogen associated with the disease. This bacterium adheres to the tooth surface and allows the colonization of other microorganisms resulting in dental biofilm. Several therapeutic agents are available to treat or prevent tooth decay, but none, with the exception of fluoride, has significantly influenced the disease’s global burden. Moreover, the probable development of resistance of microorganisms to existing antibacterial agents and the scarcity of good antimicrobial agents motivates this effort for innovation. The detailed knowledge obtained in recent years on the S. mutans allowed the identification of potential targets in this microorganism, enabling the development of specific drugs to combat tooth decay. Thus, the identification of potential targets in these pathogens is the first step in the discovery process of new therapeutic agents. Currently, the experimental assays used for this purpose are expensive and time consuming. In contrast, bioinformatics methods to predict drug targets are cheap, quick and workaday in the biotechnology. This article will review the potential drug targets in S. mutans, as well as the bioinformatics methods used to identify these targets and effective drugs for specific pharmacological treatment of dental caries.

Structural engineering of antimicrobials for optimal broad-spectrum activity

Antimicrobial materials are a crucial component in eradicating and managing the spread of infectious diseases.They are expected to act on a broad-spectrum of microbes,including emerging pathogens which could cause the next Disease X.Herein,we reassessed a series of antimicrobial imidazolium polymers on our shelves and uncovered extended functionality through dual modes of action.By redesigning their structures,a truly broadspectrum antimicrobial material with optimized activity against bacteria(G+ve,G-ve)and fungi,as well as enveloped and non-enveloped viruses was developed.We demonstrated that the imidazolium polymer exhibits dual modes of function against microbes:targeting the microbial membrane and binding DNA.The latter DNA binding affinity was found to be key against non-enveloped viruses.With this insight,we designed small molecule compounds that exhibited optimum broad-spectrum antimicrobial activity and excellent efficacy against ESKAPE group of pathogens that are responsible for some of the deadliest nosocomial infections worldwide.Our results could also shed light on the design of broad-spectrum antimicrobial compounds against Disease X.

Use of antimicrobials in food animals and impact of transmission of antimicrobial resistance on humans

Antimicrobial resistance leads to failure of clinical antimicrobial therapy,and has raised urgent global public health concern.Humans can acquire antimicrobial resistance fromdrugs through the food chain or the environment(contaminated water,air,soil,or manure).While antimicrobials have been regular supplements in animal feed that maintain health and improve productivity of livestock,their over-use in feeding forage has led to a rise in antibacterial resistance.This review summarizes the current use of antimicrobials in livestock,the harmful effects of antimicrobial resistance,and the comprehensive combat measures.

Phosphorus utilization response of pigs and broiler chickens to diets supplemented with antimicrobials and phytase

Three experiments were conducted to evaluate the phosphorus(P) utilization responses of pigs and broiler chickens to dietary supplementation with antimicrobials and phytase and to determine if P digestibility response to phytase is affected by supplementation with antimicrobials. Experiment 1 used 4 diets(a basal negative control formulated to contain 0.41% total P and 0.71% calcium [Ca] without added antimicrobials, basal negative control with added carbadox, basal negative control with added tylosin, or basal negative control with added virginiamycin) and six 18-kg barrows in individual metabolism crates per diet. There was no effect of antimicrobials on P and Ca digestibility or retention. Carbadox supplementation increased(P < 0.05) digestibility and retention of gross energy(GE) and supplementation with tylosin increased(P < 0.05) N retention relative to the basal negative control diet. Experiment 2 used eight 19-kg barrows in individual metabolism crates per treatment and 9 dietary treatments arranged in a 3×3 factorial of antimicrobials(none, tylosin, or virginiamycin) and phytase(0, 500, or 1,500 FTU/kg).Phytase addition to the diets linearly increased(P< 0.05) apparent total tract digestibility or retention of P, Ca, nitrogen(N) and GE. Supplementation with antimicrobials did not affect apparent total tract digestibility or retention of P, Ca, N or GE. There were linear effects(P < 0.01) of phytase on Ca utilization in diets that were not supplemented with antimicrobials but only tendencies(P < 0,10) in diets supplemented with tylosin or virginiamycin. Phytase linearly improved(P < 0.05) N utilization in diets supplemented with tylosin or virginiamycin but not in diets without added antimicrobials. Experiment 3 was a broiler chicken experiment with the same experimental design as Exp. 2 but feeding 8 birds per cage and 10 replicate cages per diet. Antimicrobial supplementation improved(P < 0.05) feed efficiency and adding tylosin improved(P < 0.05) tibia ash but did not affect nutrient utilization, Dietary phytase improved(P < 0.01) growth performance, tibia ash and apparent ileal digestibility and retention of P regardless of antimicrobial supplementation. Overall, phytase supplementation improved growth performance and nutrient digestibility and retention, regardless of supplementation of diets with antimicrobials. Supplementation of diets with antimicrobials did not affect P digestibility or retention because of a lack of interaction between antimicrobials and phytase, there was no evidence that P digestibility response to phytase is affected by supplementation with antimicrobials.

Use of graphene nanocomposites for air disinfection in dental clinics:A game-changer in infection control

This manuscript features the promising findings of a study conducted by Ju et al,who used graphene nanocomposites for air disinfection in dental clinics.Their study demonstrated that,compared with conventional filters,graphene nanocom-posites substantially improved air quality and reduced microbial contamination.This manuscript highlights the innovative application of graphene materials,emphasizing their potential to enhance dental clinic environments by minimizing secondary pollution.On the basis of the unique antimicrobial properties of gra-phene and the original study’s rigorous methodology,we recommend using gra-phene nanocomposites in clinical settings to control airborne infections.