Activity Of Antimicrobial Drugs Research Articles

Antimicrobial Action Mechanisms of Natural Compounds Isolated from Endophytic Microorganisms.

Infectious diseases are a significant challenge to global healthcare, especially in the face of increasing antibiotic resistance. This urgent issue requires the continuous exploration and development of new antimicrobial drugs. In this regard, the secondary metabolites derived from endophytic microorganisms stand out as promising sources for finding antimicrobials. Endophytic microorganisms, residing within the internal tissues of plants, have demonstrated the capacity to produce diverse bioactive compounds with substantial pharmacological potential. Therefore, numerous new antimicrobial compounds have been isolated from endophytes, particularly from endophytic fungi and actinomycetes. However, only a limited number of these compounds have been subjected to comprehensive studies regarding their mechanisms of action against bacterial cells. Furthermore, the investigation of their effects on antibiotic-resistant bacteria and the identification of biosynthetic gene clusters responsible for synthesizing these secondary metabolites have been conducted for only a subset of these promising compounds. Through a comprehensive analysis of current research findings, this review describes the mechanisms of action of antimicrobial drugs and secondary metabolites isolated from endophytes, antibacterial activities of the natural compounds derived from endophytes against antibiotic-resistant bacteria, and biosynthetic gene clusters of endophytic fungi responsible for the synthesis of bioactive secondary metabolites.

Green Tea (Camellia sinensis) Extract is Effective against Biofilms of Staphylococcus aureus and Pseudomonas aeruginosa, and Interferes on the Activity of Antimicrobial Drugs

Background: Given the lack of options for treating infectious diseases, it is urgent to explore new antimicrobials. Plant food historically represents relevant sources of antimicrobial molecules. Objective: Here, we show that green tea can eradicate biofilms and planktonic cells of clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa. Methods: We conducted in vitro antimicrobial activity tests (MIC, MBC, MBEC). Cytotoxicity tests were conducted using BGM cells. We used UPLC and GC-MS to detect flavonoids and other relevant phytomolecules. The antioxidant potential was assessed using the β-carotene bleaching test. The extract was combined to clinically relevant antimicrobial drugs in vitro to investigate possible synergism or antagonism. Results: To the best of our knowledge, MIC values are among the lowest ever described for the alcoholic extract (8 μg/mL). The extract presented elevated antioxidant potential and was not toxic to BGM cells. When the extract was combined to clinically relevant antimicrobial drugs, statistically significant antagonism was frequent for the drugs used against S. aureus isolates, whilst significant synergism was observed for some drugs used against P. aeruginosa isolates. Conclusion: Our data open doors for exploring isolated molecules from green tea extract against bacterial biofilms, and for developing formulations for clinical treatments.

The Problem of Antibiotic Resistance Control: A Possible Alternative to Antimicrobials in Veterinary Medicine

Aim of Study: The study included prospects for using autogenous immunobiological drugs as an alternative to antimicrobials. Materials and Methods: For the analysis databases of WHO–World Health Organization, WOHA–World Organization for Animal Health, FAO–Food and Agricultural Organization, CDC–Center for Control and of disease prevention in the USA, ECDC– European Center for Disease Control and Prevention, EFSA–European Food Safety Authority, as well as informational Internet resources of scientific journals, normative legal acts of Ukraine. The Results: According to the results of the conducted analysis, the global spread of microorganisms resistant to the action of antimicrobial drugs was established, which jeopardizes the possibility of effective treatment of infectious diseases. In Ukraine, as in other developed countries of the world, strict regulation of the circulation of antimicrobials has been adopted at the legislative level, which inevitably leads to the limitation of their use. International experience shows that restrictions on the use of antimicrobial agents should be compensated by measures aimed at increasing the level of biosafety. The use of autogenous immunobiological drugs for the specific prevention of infectious diseases of bacterial etiology can be a reasonable alternative to antibiotics in veterinary medicine. Conclusions: The introduction of new rules for the circulation of veterinary antimicrobial drugs will significantly affect the level of use of antimicrobial drugs. A reasonable alternative to antimicrobial agents is the use of autogenous immunobiological agents.

Standing on the shoulders of microbes: How cancer biologists are expanding their view of hard-to-kill persister cells.

Similar to persister bacterial cells that survive antibiotic treatments, some cancer cells can evade drug treatments. This Commentary discusses the different classes of persister cells and their implications for developing more efficient cancer treatments.

О РАЗВИТИИ АНТИБИОТИКОРЕЗИСТЕНТНОСТИ В АСПЕКТЕ ПОЛИКЛИНИЧЕСКОЙ СЛУЖБЫ

Background. Antibiotic resistance is a worldwide problem that is the main cause of the increase in the number of purulent-inflammatory diseases and postsurgical complications. Aim. The aim of the present study was to monitor antibiotic resistance of microorganisms isolated in the course of microbiological study in otorhinolaryngological and surgical patients of the outpatient department of a single preventive health institution. Material and methods. A statistical analysis of the results of microbiological studies, excretions of patients undergoing outpatient treatment in surgical and otorhinolaryngological departments of outpatient clinic No1 of the state budget institution «City Clinical Hospital No 7» of Tver is presented. We processed 280 findings of microbiological studies of ear, nose, pharynx and wound surface cultures for 2019. Results and discussion. It was found that the spectrum of dominant microorganism species in 2019 detected during swabbing of surgical and otorhinolaryngological patients treated in the outpatient clinic included gram-negative Escherichia coli and Klebsiella pneumonia and gram-positive Staphylococcus aureus and Streptococcus pyogenes microorganisms. Among the microorganisms presented, strains with multiple resistance to the action of antimicrobial drugs were identified. According to the total number of resistant microorganisms it was found that among antibacterial drugs, antibiotics of Aminopenicillin class, including those protected by protease inhibitors, as well as fluoroquinolones of the 2nd generation have the lowest clinical efficacy in the given medical institution. Conclusion. The findings of the present study indicate a rapid rate of spread of resistance genes among nosocomial strains of microorganisms, which necessitates continuous monitoring of antibiotic sensitivity by various specific laboratory methods. The results of laboratory studies should be used when prescribing antibiotic therapy for a particular patient, and the results of this study should be considered when selecting an empirical antibiotic, since they reflect the resistance of the most common pathogens. Key words: antibiotic resistance, antibiotics, cephalosporins, fluoroquinolones.

Drug Resistance in Nontuberculous Mycobacteria: Mechanisms and Models.

Simple SummaryRecently, there has been a considerable rise in infections caused by nontuberculous mycobacteria (NTM). These mycobacteria, which comprise a large and diverse range of species, have developed resistance to most conventional antibiotics, rendering their treatments unsatisfactory. This review summarizes the mechanisms and strategies adopted by NTMs to evade the action of antimicrobial drugs and techniques that can be used to develop better therapies against them. We also suggest some ways to accelerate the drug development pipeline by utilizing a combination of computational, laboratory and animal testing methods.The genus Mycobacteria comprises a multitude of species known to cause serious disease in humans, including Mycobacterium tuberculosis and M. leprae, the responsible agents for tuberculosis and leprosy, respectively. In addition, there is a worldwide spike in the number of infections caused by a mixed group of species such as the M. avium, M. abscessus and M. ulcerans complexes, collectively called nontuberculous mycobacteria (NTMs). The situation is forecasted to worsen because, like tuberculosis, NTMs either naturally possess or are developing high resistance against conventional antibiotics. It is, therefore, important to implement and develop models that allow us to effectively examine the fundamental questions of NTM virulence, as well as to apply them for the discovery of new and improved therapies. This literature review will focus on the known molecular mechanisms behind drug resistance in NTM and the current models that may be used to test new effective antimicrobial therapies.

Role of microorganisms isolated from cows with mastitis in Moscow region in biofilm formation.

Background and Aim:Mastitis is one of the most important diseases of cows and the most expensive pathology for the dairy industry. Therefore, this study was conducted to explore the role of microorganisms isolated from cows with mastitis in the formation of biofilms under the conditions of farm biogeocenosis in the Moscow region.Materials and Methods:Periodic visits to 12 farms in the Moscow region were conducted to explore the microbial profile of the udder of cows with mastitis. During the visits, 103 milk samples from sick animals were collected and examined. Through microbiological analyses, 486 cultures of microorganisms were identified, which are assigned to 11 genera. Mastitis in cows is caused not only by a single pathogen but also by microbial associations, which included two to seven microbial isolates.Results:It was observed that 309 isolates (63.6%) from the total number of isolated microorganisms could form a biofilm. The ability to form biofilms was most frequently observed in Staphylococcus aureus (18.8%), Escherichia coli (11.9%), and Staphylococcus uberis (11.7%) cultures from the total number of biofilm-forming microbial cultures. Low biofilm-forming ability among the isolated microorganisms was found in lactobacilli, wherein only 20 (22.5%) Lactobacillus strains had the ability to form biofilms. The isolated microorganisms exhibited different sensitivities to antimicrobial agents, which cause difficulty in selecting an antimicrobial agent that would act on all aspects of the parasitocenosis.Conclusion:A high proportion of microorganisms isolated from cows with mastitis have the ability to form biofilms. The isolated microorganisms exhibited different and highly heterogeneous sensitivity to the action of antimicrobial drugs. This causes difficulty in using these tools for the effective control of mastitis in cows, which is frequently caused by pathogenic associations of microbial biofilms. Therefore, it is important to explore novel and more effective methods to combat this disease.

Antibiofilm potential of Psidium guajava and Passiflora edulis pulp extracts against Staphylococcus aureus, cytotoxicity, and interference on the activity of antimicrobial drugs

BackgroundPathogenic strains of Staphylococcus aureus can cause several diseases including septicemia and endocarditis, in spite of being a commensal species of the human microbiota. The current drug resistance of S. aureus raises the need for new antimicrobials, and natural products represent a feasible source for prospection of such compounds, due to features including the diversity of structures and mechanisms of action. Here, we provide evidence of the antimicrobial activity of methanolic of Psidium guajava and Passiflora edulis pulps against planktonic cells and biofilms of clinical isolates of S. aureus.ResultsThe extracts were effective against the strains in concentrations up to 7.81 and 250 μg/mL for planktonic cells and biofilms, respectively. Antagonistic interactions of the extracts to antimicrobial drugs were observed. The pulps caused no cytotoxic effects on BGM cells. GC-MS analysis found relevant molecules, and UPLC analysis suggested the presence of flavonoids. To the best of our knowledge, this is the first antibiofilm evidence of such extracts.ConclusionThe extracts seem to be safe and effective enough for more studies aiming at exploring isolated antimicrobial molecules using in vivo models for the treatment of staphylococcal diseases.

Антимикробная активность нитрофурала в различных лекарственных формах

Проведена сравнительная оценка антимикробной активности препаратов нитрофурала методом диффузии в агар. Определены зоны задержки роста микроорганизмов под действием гелей и растворов, содержащих твердую дисперсию нитрофурала с концентрацией действующего вещества 0,02 и 0,04 %, а также фурацилиновой мази 0,2 %. В качестве тест-штаммов использовали: Staphylococcus aureus, Staphylococcus epidermidis и Escherichia coli. На основании полученных экспериментальных данных сделан вывод о более высокой антимикробной активности препаратов, содержащих твердую дисперсию нитрофурала, по сравнению с препаратами, представленными на фармацевтическом рынке.

Post-antibiotic effect of marbofloxacin, enrofloxacin and amoxicillin against selected respiratory pathogens of pigs

The post-antibiotic effect is defined as the period of bacterial growth suppression that persists after a limited exposure of organisms to antimicrobials and knowledge of its duration is important in establishing and optimising current dosing schedules for the treatment of bacterial infections. The post-antibiotic effect of marbofloxacin, enrofloxacin and amoxicillin were evaluated in vitro for Actinobacillus pleuropneumoniae, Haemophilus parasuis and Pasteurella multocida strains which originated from clinical samples of diseased pigs and were confirmed as susceptible to all tested antimicrobials based on determination of minimal inhibitory concentrations. The post-antibiotic effect for individual antimicrobials was monitored at five and ten times minimum inhibitory concentrations for one and two hours. The duration of the post-antibiotic effect for tested antimicrobials was found to exhibit the following order for all tested pathogens: marbofloxacin > enrofloxacin > amoxicillin. The longest duration of post-antibiotic effect of all tested antimicrobials was found in A. pleuropneumoniae and the shortest post-antibiotic effect duration was detected in P. multocida. No statistical differences in post-antibiotic effect duration were found within marbofloxacin and enrofloxacin in A. pleuropneumoniae and H. parasuis strains. In P. multocida strains there was a statistically significant difference (P = 0.0189). On the other hand, the differences between amoxicillin and marbofloxacin or enrofloxacin were statistically significant in all cases (P-values ranged between 0.0058 and 0.008). The prolonged post-antibiotic effect of fluoroquinolones and amoxicillin on important Gram-negative swine pathogens was confirmed. The results can be used to clarify the effect and mechanism of action of antimicrobial drugs in veterinary medicine.

Микробиологическая оценка воздействия высокой температуры на антибактериальную активность противомикробных препаратов.

Микробиологическая оценка воздействия высокой температуры на антибактериальную активность противомикробных препаратов.

Antimicrobial resistance profile of microbial pathogens isolated from hospitals of Colatina-ES in the period of 2008-2010

A resistência bacteriana é um mecanismo usado pelas bactérias para interferir na ação dos antibióticos e vem crescendo consideravelmente, se tornando um grande problema de saúde pública. O presente estudo avaliou o perfil de resistência de cepas de Staphylococcus aureus, Pseudomonas aeruginosa e Escherichia coli e a suscetibilidade das mesmas à alguns antimicrobianos. Para isso realizou-se uma pesquisa quantitativa utilizando os resultados de antibiogramas constantes nos livros de registro microbiologia do laboratório LAC - Santa Maria, situado em Colatina - ES. As amostras foram coletadas rotineiramente de pacientes internados em dois hospitais (Santa Maria e São José) e examinados pelo laboratório. No livro de registro obteve-se um total de 446 isolados microbianos identificados, dos quais 277 cepas foram identificadas como: S. aureus (36,5%), P. aeruginosa (32,5%) e E. coli (31%), os 169 restantes englobam os outros micro-organismos. Quanto ao perfil de resistência e sensibilidade, as cepas de P. aeruginosa foram mais sensíveis ao antibiótico sulbactam, E. Coli à ampicilina e ácido nalidíxico, e Staphylococcus à amicacina e ceftriaxone. Relaciona-se o maior isolamento de Stapylococcus, P. aeruginosa e E. coli provavelmente por serem micro-organismos encontrados colonizando ambientes hospitalares e a comunidade com grande potencial de disseminação. Quanto ao perfil de resistência se torna útil na seleção de drogas especificas para determinados micro-organismo. Palavras-chave: Resistência. Antibióticos. Micro-organismos.

Activity of antimicrobial drugs against bacterial pathogens under mild hypothermic conditions

BackroundInfections are a common problem in cardiac arrest survivors. Antimicrobial drugs are often administered in routine care during treatment of patients with mild therapeutic hypothermia (MTH). Because there is to date no evidence for the pharmacodynamics of antimicrobial drugs under MTH conditions, we investigated the in vitro activity of common antimicrobials against clinically relevant bacterial pathogens. Material and methodsActivities of antimicrobial drugs against clinically relevant bacterial pathogens were assessed in vitro by disk diffusion and broth microdilution assays at normothermic (37°C) and hypothermic (32°C) conditions. ResultsSeventy-three bacterial isolates were tested in disk diffusion and 15 in broth microdilution assays. Mean differences in zone diameters and minimal inhibitory concentration ratios were 0.6 mm (95% confidence interval, 0.3-0.9 mm) and 0.98 (95% confidence interval, 0.95-1.02), respectively, meeting predefined criteria for equivalence of in vitro antimicrobial activity. ConclusionsThe presented data provide reassuring evidence that the intrinsic activity of antimicrobials seems to be unaltered in MTH. However, further studies evaluating the pharmacokinetics including target site concentrations of the respective drugs and in vivo pharmacodynamics are necessary to complement our understanding of the appropriate use of antimicrobials in MTH.

Abstract 135: In Vitro Activity of Antimicrobial Drugs Against Clinically Relevant Bacterial Pathogens Under Mild Hypothermic Conditions

Aim: Infections are a common problem in cardiac arrest survivors. Antimicrobial drugs are often administered in routine care during treatment of patients with mild therapeutic hypothermia. Since there is to date no evidence for the pharmacodynamics of antimicrobial drugs under mild therapeutic hypothermia conditions, we investigated the in vitro activity of common antimicrobials against clinically relevant bacterial pathogens. Methods: Activities of antimicrobial drugs against clinically relevant bacterial pathogens were assessed in vitro by disc diffusion and broth microdilution assays at normothermic (37°C) and hypothermic (32°C) conditions. Results: 73 bacterial isolates were tested in disc diffusion and 15 in broth microdilution assays. Mean differences in zone diameters and minimal inhibitory concentration ratios were 0.6 mm (95% confidence interval: 0.3-0.9 mm) and 0.98; (95% confidence interval: 0.95 - 1.02), respectively, meeting predefined criteria for equivalence of in vitro antimicrobial activity. Conclusion: The presented data provide reassuring evidence that the intrinsic activity of antimicrobials seems to be unaltered in mild therapeutic hypothermia. However, further studies evaluating the pharmacokinetics including target site concentrations of the respective drugs and in vivo pharmacodynamics are necessary to complement our understanding of the appropriate use of antimicrobials in mild therapeutic hypothermia

Profits before people? The risks of selling antibiotics

Half of all antibiotics are prescribed unnecessarily. Every antibiotic prescribed increases the risk of resistance, so it is vital that nurses only prescribe antibiotics when they are certain they will make a real difference to patient health (Dryden et al, 2009). In fact, last month, the situation reached the point where the chief medical officer Dame Professor Sally Davies, herself described the risk of antibiotic resistance as a bigger threat than global warming and warned the UK could be facing an ‘apocalyptic scenario’ (Woods, 2013). Speaking to MPs at a science and technology committee meeting, Dame Sally said: ‘The apocalyptic scenario is that, if I need a new hip in 20 years, I’ll die from a routine infection because we have run out of antibiotics.’ Dame Sally warned MPs that 80% of gonorrhoea cases were resistant to antibiotics and the number of cases among young and middle-aged people was on the rise. She also warned that tuberculosis was poised to become a major threat to health. There are about 440 000 new cases of drug-resistant tuberculosis every year (Woods, 2013). Increasing longevity, expectations and medical advances have led to a rise in the use of antibiotics, but often antibiotics are not prescribed wisely and the consequence of this is rising antimicrobial resistance (AMR), which describes the ability of a microorganism to resist the action of antimicrobial drugs.. Drugs that once saved lives are becoming ineffective (World Health Organization, 2012). In Europe, for example, 25 000 people died in 2007 because they could no longer be treated with antibiotics. (European Centre for Disease Prevention and Control (ECDC) and European Medicines Agency (EMEA), 2009). As resistance to antibiotics grows, prescribers have been forced to prescribe second, third and even fourth line antibiotics. Consequently, multi-drug resistant bacteria are becoming more common. Antibiotics revolutionised healthcare and saved millions of lives. Widespread antimicrobial resistance could plunge us into a post-antibiotic era where infections once easily treated could kill. Most antibiotics are prescribed in primary care and the number of doses per 1000 people of population varies worldwide. Prescribers give antibiotics to patients when none are needed. They prescribe ineffective antibiotics (WHO, 2012: 33). and broad-spectrum antibiotics when narrow spectrum drugs would be safer. Prescribers may feel pressurised by patients to prescribe and they may lack the confidence to say no. They might also lack the time to make a proper diagnosis. Moreover, importantly, they may not understand that a one-size approach in prescribing does not fit all. It has been argued that non-medical prescribers may follow the poor example set by senior colleagues (WHO, 2012: 33). The UK prescribes fewer doses than some countries and has succeeded in reducing antibiotic use, but there is much to be done (ESAC, 2009). Unfortunately, proposals to sell a range of medicines including trimethoprim and ciprofloxacin may undo all the gains we’ve made and unleash the rip tide of antibiotic resistance. The National Pharmacy Association (NPA) aims to roll out a scheme to 12 500 pharmacies in a bid to give patients the right to buy 16 medicines without a prescription, including trimethoprim, ciprofloxacin and doxycycline Patients will be able to obtain medicines after completing an online medical questionnaire and having a face-to-face consultation with the pharmacist or using a walk-in service.

Biosensor Applications in the Field of Antibiotic Research—A Review of Recent Developments

Antibacterials are among of the most important medications used in health care. However, their efficacy is increasingly impeded by a tremendous and globally spread bacterial resistance phenomenon. This bacterial resistance is accelerated by inadequate application of antibacterial drugs in humans, the widespread veterinary use of antibacterials, and antibacterial occurrence in the environment and food. Further, there is a lack of development of innovative novel drugs. Therefore, the search for novel antibacterials has to be intensified and the spread of antibacterials in the environment has to be restricted. Due to the fundamental progress in biosensor development and promising applications in the antibiotic field, this review gives for the first time an overview on the use and prospects of biosensor applications in that area. A number of reports have applied biosensors of different design and techniques to search for antibacterials in environmental and foodstuff matrices. These studies are discussed with respect to the analytical values and compared to conventional techniques. Furthermore, biosensor applications to elucidate the mode of action of antimicrobial drugs in vitro have been described. These studies were critically introduced referring to the informational value of those simulations. In summary, biosensors will be illustrated as an innovative and promising, although not yet comprehensively applied, technique in the antibacterial field.

Comparison of in vivo and in vitro inactivation of endospores of Rhinosporidium seeberi following dapsone treatment

Rhinosporidiosis in humans and animals, caused by Rhinosporidium seeberi, can now be termed an emerging infective disease worldwide. The pharmacokinetics of dapsone when used as an antimicrobial agent in patients with rhinosporidiosis was compared with its pharmacodynamics in the inactivation of purified rhinosporidial endospores in vitro. A marked discrepancy was noted between the in vitro inactivation, which commenced on day 1 and was a maximum at day 4, whereas earlier reports on the response of endospores in patients under dapsone therapy indicated that the degeneration and disappearance of the endospores was not observed for 18–36 weeks after therapy began. Reasons for this discrepancy that operate in vivo are postulated: (a) impermeability of the barriers of down-growths of squamous epithelium in which the endospore-containing rhinosporidial sporangia are embedded; (b) presence of a mucoid matrix in which the endospores exist within the sporangia. These explanations contribute to resolving the controversial problem of general correlations between in vitro and in vivo results from studies on the action of antimicrobial drugs.

Comparison of in vivo and in vitro inactivation of endospores of <i>Rhinosporidium seeberi</i> following dapsone treatment

Rhinosporidiosis in humans and animals, caused by Rhinosporidium seeberi, can now be termed an emerging infective disease worldwide. The pharmacokinetics of dapsone when used as an antimicrobial agent in patients with rhinosporidiosis was compared with its pharmacodynamics in the inactivation of purified rhinosporidial endospores in vitro. A marked discrepancy was noted between the in vitro inactivation, which commenced on day 1 and was a maximum at day 4, whereas earlier reports on the response of endospores in patients under dapsone therapy indicated that the degeneration and disappearance of the endospores was not observed for 18–36 weeks after therapy began. Reasons for this discrepancy that operate in vivo are postulated: (a) impermeability of the barriers of down-growths of squamous epithelium in which the endospore-containing rhinosporidial sporangia are embedded; (b) presence of a mucoid matrix in which the endospores exist within the sporangia. These explanations contribute to resolving the controversial problem of general correlations between in vitro and in vivo results from studies on the action of antimicrobial drugs.

Recovery of antibacterial sensitivity of ESBLs-producing fowl <I>E. coli</I> by sulbactam and EDTA

To determine effect of sulbactam and EDTA on antibacterial activity of antimicrobial drugs in vitro,MIC of 10 antimicrobial agents alone and their respective combinations with sulbactam,EDTA and sulbactam+ EDTA against ESBLs-producing E.coli,were determined by using broth microdilution method.The results showed that sulbactam and EDTA can enhance antibacterial activity of parts of antimicrobial agents,the resistant rate of ESBIs-producing isolates to third generation cephalosporin ceftiofur,cefotaxime was higher than 80% and the resistant rates to fluoroquinolones,doxycycline,florfenicol,amikacin and fosfomycin were up to 100%.All the ESBIs-producing isolates were sensitive to cefepime.The resistant rate to third generation cephalosporin cefotaxime,florfenicol,amikacin and fosfomycin combinations with sulbactam,were lower than that to antibacterial drugs alone,is 0,88.9%,88.9%,0 respectively.The resistant rate to gatifloxacin,doxycycline,florfenicol,amikacin and fosfomycin combinations with EDTA,were lower than that to antibacterial drugs alone,is 30%,11.1%,22.2%,11.1%,0 respectively.The resistant rates of most strains to sulbactom+EDTA amikacin,fosfomycin,florfenicol and ceftiofur combinations were much lower than those combinations either only sulbactam or EDTA and were all 0.

Calorimetric Characterization of the Inhibitory Action of Antimicrobial Drugs and a Proposal of Bacteriostatic/Bactericidal Index

Calorimetric Characterization of the Inhibitory Action of Antimicrobial Drugs and a Proposal of Bacteriostatic/Bactericidal Index