Inefficiency of medical therapies used in order to cure patients with bacterial infections requires not only to actively look for new therapeutic strategies but also to carefully select antibiotics ...based on variety of parameters, including microbiological. Minimal inhibitory concentration (MIC) defines in vitro levels of susceptibility or resistance of specific bacterial strains to applied antibiotic. Reliable assessment of MIC has a significant impact on the choice of a therapeutic strategy, which affects efficiency of an infection therapy. In order to obtain credible MIC, many elements must be considered, such as proper method choice, adherence to labeling rules, and competent interpretation of the results. In this paper, two methods have been discussed: dilution and gradient used for MIC estimation. Factors which affect MIC results along with the interpretation guidelines have been described. Furthermore, opportunities to utilize MIC in clinical practice, with pharmacokinetic /pharmacodynamic parameters taken into consideration, have been investigated. Due to problems related to PK determination in individual patients, statistical estimation of the possibility of achievement of the PK/PD index, based on the Monte Carlo, was discussed. In order to provide comprehensive insights, the possible limitations of MIC, which scientists are aware of, have been outlined.
Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant
In this study, we compared the
activities and MIC distributions of ...delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA,
, and
genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240
isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC
values for
isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (
> 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (
= 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by
that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion,
susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within
that endowed
with linezolid, but not delpazolid, resistance was identified.
The purpose of the study was to assess a phenolic compound that was extracted from the brown seaweed Enteromorpha intestinalis (Linn.), Nees (1820) for its antibacterial activities on different ...bacterial pathogens of fish illnesses. Hexane and methanol were utilized to extract bioactive compounds from the seaweed. Phytochemical analysis of the methnaolic extracts have revealed the presence of carbohydrates and glycosides, saponins, alkaloids, amino acids, flavonoids, fixed oil and fat, phenol compounds, tannins, and steroids. The bacterial pathogens of fish, including Providencia vermicola, Aeromonas hydrophila, Vibrio harveyi, and Aeromonas caviae, were targeted for antibacterial assessment. Among them, the methanolic crude extract and fraction-1 of E. intestinalis have shown maximum activity against A. hydrophila (22 ± 0.13 and 33 ± 0.56 µg/mL). Column chromatography was employed to isolate effective seaweed fraction, while FT-IR and HPLC were utilized for characterization. The phytochemical analysis confirmed the presence of various compounds in both extracts. The crude methanolic extract of E. intestinalis have demonstrated the maximum efficacy beside the tested bacterial pathogens. The FT-IR analysis revealed functional groups associated with polymeric structures in the seaweed extracts, including alcohols, phenols, aromatics, alkyl halides, aliphatic amines, alkynes, and alkenes. Overall, the methanolic extract of E. intestinalis exhibited significant antibacterial activity as a result of the phenolic chemicals that are present. The study provides valuable baseline data, emphasizing the need for further research towards developing antibacterial drug formulations.
Abstract Background Resistance to ceftazidime-avibactam was reported, and it is important to investigate the mechanisms of ceftazidime/avibactam resistance in K. pneumoniae with mutations in bla KPC. ...Results We report the mutated bla KPC is not the only mechanism related to CZA resistance, and investigate the role of outer porin defects, efflux pump, and relative gene expression and copy number of bla KPC and ompk35/36. Four ceftazidime/avibactam-sensitive isolates detected wild type bla KPC-2, while 4 ceftazidime/avibactam-resistant isolates detected mutated bla KPC (bla KPC-51, bla KPC-52, and bla KPC-33). Compared with other ceftazidime/avibactam-resistant isolates with the minimal inhibitory concentration of ceftazidime/avibactam ranging 128–256 mg/L, the relative gene expression and copy number of bla KPC was increased in the isolate which carried bla KPC-51 and also showed the highest minimal inhibitory concentration of ceftazidime/avibactam at 2048 mg/L. The truncated Ompk35 contributes rare to ceftazidime/avibactam resistance in our isolates. No significant difference in minimal inhibitory concentration of ceftazidime/avibactam was observed after the addition of PABN. Conclusions Increased gene expression and copy number of mutated bla KPC can cause high-level ceftazidime/avibactam resistance.
Extensively drug-resistant tuberculosis (XDR-TB) is a deadly form of TB that can be incurable due to its extreme drug resistance. In this study, we aimed to explore the
susceptibility to bedaquiline ...(BDQ), delamanid (DMD), linezolid (LZD), clofazimine (CLO), moxifloxacin (MFX), and gatifloxacin (GAT) of 90 XDR-TB strains isolated from patients in China. We also describe the genetic characteristics of XDR-TB isolates with acquired drug resistance. Resistance to MFX, GAT, LZD, CLO, DMD, and BDQ was found in 82 (91.1%), 76 (84.4%), 5 (5.6%), 5 (5.6%), 4 (4.4%), and 3 (3.3%) isolates among the XDR-TB strains, respectively. The most frequent mutations conferring fluoroquinolone resistance occurred in codon 94 of the
gene (57.8%), and the strains with these mutations (69.2%) were associated with high-level MFX resistance compared to strains with mutations in codon 90 (25.0%) (
< 0.01). All 5 CLO-resistant isolates exhibited ≥4-fold upward shifts in the BDQ MIC, which were attributed to mutations of codons 53 (60.0%) and 157 (20.0%) in the Rv0678 gene. Additionally, mutation in codon 318 of the
gene was identified as the sole mutation related to DMD resistance. In conclusion, our data demonstrate that the XDR-TB strains exhibit a strikingly high proportion of resistance to the current anti-TB drugs, whereas BDQ, DMD, LZD, and CLO exhibit excellent
activity against XDR-TB in the National Clinical Center on TB of China. The extensive cross-resistance between OFX and later-generation fluoroquinolones indicates that MFX and GAT may have difficulty in producing the desired effect for XDR-TB patients.
The European Committee on Antimicrobial Susceptibility Testing (EUCAST) is an international susceptibility testing committee, organized by the European Society for Clinical Microbiology and ...Infectious Diseases (ESCMID) and functioning as the breakpoint advisory committee of the European Medicines Agency (EMA). The original remit of EUCAST was to harmonize European clinical breakpoints, but very soon, the activities expanded beyond the borders of Europe and included newly licensed agents in Europe. Among the milestones were the aggregating of large numbers of MIC distributions, creating software to display these distributions, the EUCAST concept of identifying epidemiological cutoff values (ECOFF), and the development of a EUCAST disk diffusion method. The EUCAST Development Laboratory has played a critical role in the development of antimicrobial susceptibility testing (AST) methodology, including development work for novel antimicrobial agents and for rapid AST directly from blood culture bottles. EUCAST has several standing subcommittees, including for AST in fungi (AFST) and mycobacteria (AMST) and for microorganisms of veterinary interest (VetCAST), and
subcommittees on subjects such as anaerobic bacteria, MIC and zone diameter distributions and epidemiological cutoff values, the relationship between phenotypic and genotypic resistance, and expert rules and methods for the detection of resistance mechanisms. All EUCAST decisions are subjected to the EUCAST public consultation process, the only exception being breakpoints of novel antimicrobial agents where confidentiality agreements during the licensing process prevent public participation. EUCAST has recently revised the definitions of clinical susceptibility interpretive categories S, I, and R, acknowledging the intimate relationship between drug exposure and susceptibility reporting.
Diseases management has been the greatest challenge to agriculture leading to huge crop failure, represented in low-profit production. Phytopathogenic fungi are among pathogens causing a variety of ...agricultural diseases. Various nanoparticles (NPs) have previously been employed to combat phytopathogenic fungi. Post-harvest deterioration due to fungal invasion is the most imperative cause of loss of ginger (Zingiber officinale) production. In the present study, four fungal pathogens isolated from soft-rot infected ginger were identified as Pythium spp. (isolate I and II), one Fusarium sp. (isolate III) and one Aspergillus sp. (isolate IV). Moringa oleifera mediated zinc oxide (ZnONPs) and sulfur nanoparticles (SNPs) were characterized by UV–Visible spectrophotometry and showed absorption maxima at 356 nm and 295 nm. Average size of NPs under Nanoparticle Tracking Analyzer was 78 nm and 26 nm respectively, confirmed by FESEM. Stable NPs with zeta potential of −14.1 mV (Standard deviation = 4.51 mV) and −21.1 mV (Standard deviation = 9.56 mV) were synthesized. FTIR detected the presence of various functional groups in NPs. In vitro antifungal activity was assessed by Kirby-Bauer disc diffusion assay and MIC values compared to antibiotic ketoconazole and fungicide mancozeb. Time kill assay represented the minimum time required by selected NPs to inhibit the growth of test pathogenic fungi. ZnONPs and SNPs can be used for further antifungal studies in the field as novel nanofungicides. Extrapolated and uncontrolled use can lead to the inhibition of germination, reduction in photosynthesis rate, and disruption of the plant roots. Thorough small-scale experimentation is necessary before commercialization.
•Moringa oleifera extract used for ZnONPs synthesis.•ZnONPs were evaluated for in vitro antifungal activity.•ZnOnPs were found significantly antifungal against test fungi.•ZnONPs can be used to design nano-based fungicide for agriculture use.
The aim of this study was to evaluate the antimicrobial activities of gaseous essential oils (EO gases) against Listeria monocytogenes on the surfaces of a laboratory medium and radish sprouts. We ...determined the minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) values of EO gases from eight EOs extracted from basil leaves, carrot seed, cinnamon bark, cinnamon leaves, clove flower buds, oregano leaves, thyme flowers (linalool), and thyme leaves (thymol) against L. monocytogenes on a nutrient agar supplemented with 1% glucose and 0.025% bromocresol purple (NGBA). Oregano, thyme thymol, and cinnamon bark EO gases showed the strongest antilisterial activities (MIC and MLC, 78.1μL/L). We also investigated the inhibitory and lethal activities of these gases against L. monocytogenes on the surface of radish sprouts. The number of L. monocytogenes after exposure to EO gases at ≥156μL/L was significantly (P≤0.05) lower than that of untreated L. monocytogenes. For example, the initial number of L. monocytogenes on the surface of radish sprouts (ca. 6.3logCFU/g) decreased by 1.4logCFU/g within 24h at 30°C and 43% relative humidity (RH) without EO gas treatment, whereas the number of L. monocytogenes after exposure to oregano, thyme thymol, and cinnamon bark EO gases at 156μL/L decreased by 2.1, 2.1, and 1.8logCFU/g, respectively, after 24h. Although EO gases exerted greater lethal activities at higher concentrations (312 and 625μL/L), L. monocytogenes on the surface of radish sprouts was not completely inactivated. The number of L. monocytogenes on sprouts treated with oregano, thyme thymol, and cinnamon bark EO gases at 625μL/L decreased by 2.7–3.0logCFU/g after 24h at 30°C and 43% RH. Results indicate that EO gases that showed antilisterial activities on a laboratory medium also exhibited reduced lethal activity on the surface of radish sprouts. These findings will be useful when developing strategies to inactivate L. monocytogenes and possibly other foodborne pathogens on sprouts and perhaps other foods using EO gases.
•MICs and MLCs of eight EO gases against L. monocytogenes on a medium were determined.•Lethality of EO gases against L. monocytogenes on radish sprouts was determined.•Oregano, thyme thymol, and cinnamon bark EO gases showed lowest MIC and MLC.•EO gases showed the reduced lethality against L. monocytogenes on radish sprouts.
The objective of this research was to develop antimicrobial nanoemulsions using quillaja saponin as a natural surfactant, carvacrol as an antimicrobial agent, and medium chain triglyceride (MCT) oil ...as a ripening inhibitor. Oil-in-water antimicrobial nanoemulsions were fabricated by homogenizing 10 wt% oil phase (carvacrol and MCT) with 90 wt% aqueous phase (quillaja saponin in 5 mM sodium citrate buffer, pH 3.5). The physical stability and antimicrobial activity of these systems was compared to nanoemulsions formed using a synthetic non-ionic surfactant (Tween 80). Stable nanoemulsions with small mean droplet diameters (d < 150 nm) could be formed by optimizing oil phase composition and surfactant level. The antimicrobial activity of carvacrol nanoemulsions formulated with Q-Naturale® was higher than that formulated with Tween 80. Dialysis and chromatography were used to monitor the transfer of carvacrol from one hydrophobic phase to another, to mimic transport from oil droplets to bacterial cell membranes. The antimicrobial activity depended on the concentration and type of surfactant used and the ability of surfactant micelles to transfer carvacrol through the aqueous phase.
Display omitted
•Carvacrol nanoemulsion with small droplet size (d<150 nm) was made.•The concentration and type of surfactant had effect on antimicrobial activity.•The antimicrobial activity correlated with rate of transfer of carvacrol.
Invasive fungal infections (IFIs) are associated with high mortality rates and timely appropriate antifungal therapy is essential for good outcomes. Emerging antifungal resistance among
and
spp., the ...major causes of IFI, is concerning and has led to the increasing incorporation of in vitro antifungal susceptibility testing (AST) to guide clinical decisions. However, the interpretation of AST results and their contribution to management of IFIs remains a matter of debate. Specifically, the utility of AST is limited by the delay in obtaining results and the lack of pharmacodynamic correlation between minimal inhibitory concentration (MIC) values and clinical outcome, particularly for molds. Clinical breakpoints for
spp. have been substantially revised over time and appear to be reliable for the detection of azole and echinocandin resistance and for outcome prediction, especially for non-neutropenic patients with candidemia. However, data are lacking for neutropenic patients with invasive candidiasis and some non-
spp. (notably emerging
). For
spp., AST is not routinely performed, but may be indicated according to the epidemiological context in the setting of emerging azole resistance among
. For non-
molds (e.g.,
,
or
spp.), AST is not routinely recommended as interpretive criteria are lacking and many confounders, mainly host factors, seem to play a predominant role in responses to antifungal therapy. This review provides an overview of the pre-clinical and clinical pharmacodynamic data, which constitute the rationale for the use and interpretation of AST testing of yeasts and molds in clinical practice.
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