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Featured Application: Staphylococcus epidermidis CECT 4183 presents a good capacity for its application in the bioremediation of Cu(II) in contaminated water, and at the same time, its cellular extract has a good capacity to synthesize CuO-NPs with potential applications in nanomedicine. Copper contamination of natural waters is a global problem that affects ecosystems and public health, yet this metal is an essential micronutrient and has important applications. The efficacy of Staphylococcus epidermidis CECT 4183 as a Cu(II) biosorbent in synthetic solutions and its potential ability to synthesize CuO nanoparticles (CuO-NPs) from its cellular extract was investigated. In addition, the biocidal potential of the nanoparticles was evaluated against five microorganisms. Using response surface methodology, the optimal operating conditions were determined to be biomass dose, 0.2 g/L, and pH 5.5. Equilibrium tests were performed, and biosorption isotherms were obtained for four models with a maximum biosorption capacity of 48.14 mg/g for the Langmuir model. Different spectroscopic and microscopic techniques were used to determine the mechanisms involved in the biosorption process, which was dominated by surface physicochemical interactions with strong involvement of methyl, methylene, carbonyl, amino, and phosphate groups. The techniques also allowed for characterizing the obtained nanoparticles, which had a quasi-spherical morphology and an average size of 14 nm. Finally, biocidal tests showed that the CuO-NPs had a good inhibitory capacity for the microorganisms tested, with minimum inhibitory concentrations (MIC) between 62.5 and 500 µg/mL for bacteria and between 1000 and 2000 µg/mL for yeasts. S. epidermidis CECT 4183 showed good potential for Cu(II) bioremediation and for the synthesis of CuO-NPs with biocidal capacity. S. epidermidis CECT 4183 showed good potential for use in Cu(II) biosorption, and its cell extract presented a high capacity for the green synthesis of CuO-NPs, which at the same time turned out to be good biocidal agents. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study was to develop gradient diffusion strips with substances capable of potentiating the action of antibiotics for the treatment of infections caused by multidrug-resistant strains of K. pneumoniae. Materials and Methods. The substances azidothymidine and baicalin were used to evaluate the joint action of combinations of antibiotics with substances that potentiate their action. Determination of susceptibility to combinations of antibiotics (gentamicin, cefotaxime, ciprofloxacin and chloramphenicol) with the listed substances was carried out by a modified gradient-diffusion method (cross-test). We used gradient diffusion strips, which was made in the Saint-Petersburg Pasteur Institute. We investigated clinical multidrug-resistant K. pneumoniae strains (n = 20). The result of the joint action of a combination of two compounds was assessed by calculating the fractional inhibitory concentrations ΣFIC. Results. The values of MIC decreased eightfold when azidothymidine was combined with gentamicin and two times when combined with ciprofloxacin. MIC values were not reduced by the combination of azidothymidine with cefotaxime or chloramphenicol. It has been established that azidothymidine has antibacterial activity against strains of K. pneumoniae: MIC50 – 1 μg/ml and MIC90 – 2 μg/ml. The MIC50 and MIC90 values for baicalin were > 256 μg/ml. A synergistic antibacterial effect was detected when azidothymidine was combined with gentamicin (ΣFIC 0.33–0.50). An additive effect (ΣFIC 0.65–0.84) was detected when azidothymidine was combined with ciprofloxacin. Baikalin reduced the MIC value of cefotaxime by half, and the MIC50 values for gentamicin also decreased by half. Baicalin did not affect the susceptibility of multidrug-resistant K. pneumoniae strains to ciprofloxacin and chloramphenicol. Synergism was detected in the combination of baicalin and cefotaxime (ΣFIC 0.52 – 0.75 – additive effect). Conclusions. The development of gradient diffusion strips with azidothymidine and baicalin makes it possible to simplify methods for assessing the joint action of combinations of these substances with antibiotics and to avoid time-consuming preparatory steps. Our study demonstrated that azidothymidine exhibits synergistic activity in combination with gentamicin and ciprofloxacin and baicalin – in combination with cefotaxime. Further studies are needed to evaluate the potential use of these combinations in practical healthcare.

Addition of antibiotics to semen extenders was taken for granted for many years, from the time that commercial artificial insemination in livestock first began many decades ago. However, there is now a growing realisation that this non-therapeutic utilisation of antibacterial agents is contrary to current recommendations for prudent use that medical and veterinary professionals are advised to follow. Furthermore, antibiotics are not benign, having negative effects on sperm samples, the inseminated female, personnel and potentially the environment. The purpose of this review is three-fold: to highlight the fact that antibiotics are used in semen extenders, with the result that considerable amounts are used globally in animal breeding, to review recent studies on the negative aspects of using antibiotics for this purpose, and to look at possible alternatives. Recent changes in the legislation regarding semen extenders occurred in some, but not all, countries, leaving question marks for semen producers as to whether antibiotics should be added to semen extenders or not. Antimicrobial resistance is a global problem of monumental proportions, requiring radical action to stem its progress. One of the questionable uses of antibiotics is in semen doses used for artificial insemination, which may be contrary to current recommendations to restrict antibiotics for therapeutic purposes. This review describes some of the problems arising from antibiotic use in semen extenders and suggests some alternatives. Photographs by Jane M. Morrell. This article belongs to the Collection Dedication to Jim Cummins. [ABSTRACT FROM AUTHOR]

Objective: Catheter-associated urinary tract infections make one of the leading nosocomial diseases worldwide. Most of the bacteria causing catheter-associated urinary tract infections form protective biofilms inside which the pathogens would be more resistant to antimicrobial agents, making the treatment more complicated resulting in severe sufferings of the patients with prolonged morbidity, increased hospital expenses and comparatively higher mortality. Treatment of infections caused by two of such pathogens - Enterococcus faecalis and Escherichia coli are challenging and the pharmaceutical world is trying to find alternative antimicrobial agents. Thus, the current investigation is a trial to repurpose paroxetine - an anti-depression drug to evaluate its antibacterial potentials against these pathogens. Material and methods The repurposing of paroxetine to evaluate its efficiency against Enterococcus faecalis and Escherichia coli was performed by agar diffusion method. Using microdilution protocols, the minimal inhibitory concentration was also calculated. To qualitatively analyse the anti-biofilm activity of the drug, paroxetine was coated on catheters and the activity was evaluated against the bacterial growth. Results: Paroxetine exhibited promising antibacterial activity and the minimum inhibitory concentrations were found to be 75 µg/ml and 37.5 µg/ml against Enterococcus faecalis and Escherichia coli respectively. The drug could also reduce the formation of biofilms by 72% in the case of Enterococcus faecalis and by 86% in case of Escherichia coli. Paroxetine also shown to possess potential anti-adhesive properties. Conclusion: The results suggest that the anti-depression drug paroxetine has antibacterial, anti-biofilm and anti-adhesive properties against two of the most prevalent bacteria involved in catheter-associated urinary tract infections. [ABSTRACT FROM AUTHOR]

Copper contamination of natural waters is a global problem that affects ecosystems and public health, yet this metal is an essential micronutrient and has important applications. The efficacy of Staphylococcus epidermidis CECT 4183 as a Cu(II) biosorbent in synthetic solutions and its potential ability to synthesize CuO nanoparticles (CuO-NPs) from its cellular extract was investigated. In addition, the biocidal potential of the nanoparticles was evaluated against five microorganisms. Using response surface methodology, the optimal operating conditions were determined to be biomass dose, 0.2 g/L, and pH 5.5. Equilibrium tests were performed, and biosorption isotherms were obtained for four models with a maximum biosorption capacity of 48.14 mg/g for the Langmuir model. Different spectroscopic and microscopic techniques were used to determine the mechanisms involved in the biosorption process, which was dominated by surface physicochemical interactions with strong involvement of methyl, methylene, carbonyl, amino, and phosphate groups. The techniques also allowed for characterizing the obtained nanoparticles, which had a quasi-spherical morphology and an average size of 14 nm. Finally, biocidal tests showed that the CuO-NPs had a good inhibitory capacity for the microorganisms tested, with minimum inhibitory concentrations (MIC) between 62.5 and 500 µg/mL for bacteria and between 1000 and 2000 µg/mL for yeasts. S. epidermidis CECT 4183 showed good potential for Cu(II) bioremediation and for the synthesis of CuO-NPs with biocidal capacity. S. epidermidis CECT 4183 showed good potential for use in Cu(II) biosorption, and its cell extract presented a high capacity for the green synthesis of CuO-NPs, which at the same time turned out to be good biocidal agents.

The EU‐FORA programme 'Quantitative tools in microbial and chemical risk assessment' was dedicated to training on predictive microbiology fundamentals, implementation of different modelling strategies, design of experiments and software tools such as MATLAB, GInaFiT and DMFit. The fellow performed MATLAB training on maximum specific growth rate (μmax) determination according to the Ratkowsky model. GInaFiT training on different models for bacterial inactivation and DMFit training on growth parameters of Vibrio parahaemolyticus were also carried out. Optical density measurements of V. parahaemolyticus bacterial cultures were performed. The obtained kinetics of optical density measurements were used to estimate μmax. Hereafter, Minimum inhibitory concentrations and non‐inhibitory concentrations of aminoglycoside antibiotics were estimated based on the quantification of the fractional areas of the optical density vs time. It can be concluded that the results of the quantitative characterisation of V. parahaemolyticus are reliable and can be used for exposure assessments. Also, the turbidimetric assay can be applied for successful estimation of minimum inhibitory concentrations and non‐inhibitory concentrations. [ABSTRACT FROM AUTHOR]

The antimicrobial effect of colloidal nanosilver (AgNPs) at concentrations of 20 and 30 ppm against reference Esherichia coli, Salmonella enterica, Staphylococcus aureus, Clostridium perfringens, Candida albicans strains and two clinical isolates (Pseudominas aeruginosa and Streptococcus pyogenes) was tested. The classical agar diffusion method, determination of the minimum inhibitory concentrations (MIC) and the time of antimicrobial action of AgNPs were used. In the studies performed by the agar diffusion method, a very good inhibitory effect of AgNPs 30 ppm and to a much lesser extent of AgNPs 20 ppm, was reported against all studied microorganisms. The studied Gram-negative bacteria showed higher sensitivity to both preparations compared to the Gram-positive microorganisms (P>0.05). The lowest sensitivity was reported for S. aureus and C. albicans, and the highest  for P. aeruginosa and S. pyogenes. The lowest MICs of AgNPs 20 ppm were reported for P. aeruginosa and C. perfringens. For them, the MIC50 was 1 μg/mL, and for the rest  2 μg/mL. Again, C. perfringens showed the highest sensitivity to AgNPs 30 ppm with MIC50 0.5 μg/mL, and the lowest one was that of S. aureus with MIC50 2 μg/mL. For the Gram-positive bacteria MIC values were higher than for Gram-negative ones. AgNPs 20 ppm and AgNPs 30 ppm inactivated all bacterial strains tested at final concentrations of 103 cells/mL and 104 cells/mL within 5 min; only C. albicans persisted longer. The tested microorganisms remained viable for significantly longer time in the presence of AgNPs 20 ppm and AgNPs 30 ppm when in suspensions with a density of 106 cells/mL. These results are promising for the successful use of AgNPs for disinfection, as well as for topical therapy of infections involving these bacterial species.

Abstract The EU‐FORA programme ‘Quantitative tools in microbial and chemical risk assessment’ was dedicated to training on predictive microbiology fundamentals, implementation of different modelling strategies, design of experiments and software tools such as MATLAB, GInaFiT and DMFit. The fellow performed MATLAB training on maximum specific growth rate (μmax) determination according to the Ratkowsky model. GInaFiT training on different models for bacterial inactivation and DMFit training on growth parameters of Vibrio parahaemolyticus were also carried out. Optical density measurements of V. parahaemolyticus bacterial cultures were performed. The obtained kinetics of optical density measurements were used to estimate μmax. Hereafter, Minimum inhibitory concentrations and non‐inhibitory concentrations of aminoglycoside antibiotics were estimated based on the quantification of the fractional areas of the optical density vs time. It can be concluded that the results of the quantitative characterisation of V. parahaemolyticus are reliable and can be used for exposure assessments. Also, the turbidimetric assay can be applied for successful estimation of minimum inhibitory concentrations and non‐inhibitory concentrations.

Data on antifungal susceptibility of Cryptococcus neoformans are limited in Japan. A total of 89 C. neoformans strains isolated from 83 non-human immunodeficiency virus-infected patients with cryptococcosis between 1997 and 2021 in Nagasaki, Japan, were investigated. Using the reference method M27-Ed4 by the Clinical and Laboratory Standards Institute, the minimum inhibitory concentration for 90% of isolates of fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine were 4, 0.125, 0.06, 0.5, and 4 µg/ml, respectively, which were below the reported epidemiological cutoff values, without any detectable non-wild-type strains. Our findings imply no increasing trend of antifungal-resistant C. neoformans in Nagasaki, Japan. [ABSTRACT FROM AUTHOR]

The emergence of carbapenem-resistant Enterobacterales (CRE) has been recognized as a significant concern globally. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor that has demonstrated activity against isolates producing class A, C, and D β-lactamases. Here-in, we evaluated the in vitro activity of CZA and comparator antimicrobial agents against 858 CRE isolates, arising from the Southeast Asian region, collected from a large tertiary hospital in Singapore. These CRE isolates mainly comprised Klebsiella pneumoniae (50.5%), Escherichia coli (29.4%), and Enterobacter cloacae complex (17.1%). Susceptibility rates to levofloxacin, imipenem, meropenem, doripenem, aztreonam, piperacillin/tazobactam, cefepime, tigecycline, and polymyxin B were low. CZA was the most active β-lactam agent against 68.9% of the studied isolates, while amikacin was the most active agent among all comparator antibiotics (80% susceptibility). More than half of the studied isolates (51.4%) identified were Klebsiella pneumoniae carbapenemase (KPC)-2 producers, 25.9% were New Delhi metallo-β-lactamase (NDM) producers, and Oxacillinase (OXA)-48-like producers made up 10.7%. CZA was the most active β-lactam agent against KPC-2, OXA-48-like, and Imipenemase (IMI) producers (99.3% susceptible; MIC50/90: ≤1/2 mg/L). CZA had excellent activity against the non-carbapenemase-producing CRE (91.4% susceptible; MIC50/90: ≤1/8 mg/L). Expectedly, CZA had no activity against the metallo-β-lactamases (MBL)-producing CRE (NDM- and Imipenemase MBL (IMP) producers; 27.2% isolates), and the carbapenemase co-producing CRE (NDM + KPC, NDM + OXA-48-like, NDM + IMP; 3.0% isolates). CZA is a promising addition to our limited armamentarium against CRE infections, given the reasonably high susceptibility rates against these CRE isolates. Careful stewardship and rational dosing regimens are required to preserve CZA's utility against CRE infections. [ABSTRACT FROM AUTHOR]

The harmful effects following the ingestion of mycotoxin-contaminated food include the induction of cancers, mutagenicity, immune suppression, and toxicities that target organs of the digestive, cardiovascular, and central nervous systems. Synthetic fungicides are generally associated with a high toxic residue in food and the development of excessive fungal resistance. This study aimed to determine the antifungal activities against mycotoxigenic fungi of selected South African plant leaves and potentially develop plant-derived bio-fungicides, and, furthermore, to explore the in vitro antioxidant activity and the phytochemical spectra of the compounds of the selected medicinal plant extracts. The extracts were tested for antifungal activity against phytopathogenic strains using a microdilution broth assay. Bauhinia galpinii extracts exhibited the lowest minimum inhibitory concentration (MIC) against C. cladospoides and P. haloterans at 24 h incubation periods. C. caffrum had good antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) with 50% inhibitory concentration (IC50) values of 0.013 mg/mL while B. galpini had IC50 values of 0.053 against free radicals of 2,2′-azinobis (3-ethylbenzthiazoline-6-suphonic acid (ABTS). The antimycotoxigenic and antioxidant activity exerted by both B. galpinii and C. caffrum may well be attributed to high TPC. In the GC-ToF-MS analysis, all the selected medicinal plants exhibited the presence of Hexadecanoic acid at varying % areas, while both B. galpinii and C. caffum exhibited the presence of lupeol at % area 2.99 and 3.96, respectively. The compounds identified, particularly the ones with higher % area, may well explain the biological activity observed. Although the selected medicinal plants exhibited a notable biological activity, there is a need to explore the safety profiles of these plants, both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Abstract Antimicrobial resistance (AMR) is a global health issue and surveillance of AMR can be useful for understanding AMR trends and planning intervention strategies. Salmonella, widely distributed in food-producing animals, has been considered the first priority for inclusion in the AMR surveillance program by the World Health Organization (WHO). Recent advances in rapid and affordable whole-genome sequencing (WGS) techniques lead to the emergence of WGS as a one-stop test to predict the antimicrobial susceptibility. Since the variation of sequencing and minimum inhibitory concentration (MIC) measurement methods could result in different results, this study aimed to develop WGS-based random forest models for predicting MIC values of 24 drugs using data generated from the same laboratories in Taiwan. The WGS data have been transformed as a feature vector of 10-mers for machine learning. Based on rigorous validation and independent tests, a good performance was obtained with an average mean absolute error (MAE) less than 1 for both validation and independent test. Feature selection was then applied to identify top-ranked 10-mers that can further improve the prediction performance. For surveillance purposes, the genome sequence-based machine learning methods could be utilized to monitor the difference between predicted and experimental MIC, where a large difference might be worthy of investigation on the emerging genomic determinants.

ABSTRACT As meropenem-clavulanic acid is recommended for the treatment of drug-resistant tuberculosis, the repurposing of new carbapenem combinations may provide new treatment options, including oral alternatives. Therefore, we studied the in vitro activities of meropenem-vaborbactam, meropenem-clavulanic acid, and tebipenem-clavulanic acid. One hundred nine Mycobacterium tuberculosis complex (MTBC) clinical isolates were tested, of which 69 were pan-susceptible and the remaining pyrazinamide- or multidrug-resistant. Broth microdilution MICs were determined using the EUCAST reference method. Meropenem and tebipenem were tested individually and in combination with vaborbactam 8 mg/L and clavulanic-acid 2 and 4 mg/L, respectively. Whole-genome sequencing was performed to explore resistance mechanisms. Clavulanic acid lowered the modal tebipenem MIC approximately 16-fold (from 16 to 1 mg/L). The modal meropenem MIC was reduced twofold by vaborbactam compared with an approximately eightfold decrease by clavulanic acid. The only previously described high-confidence carbapenem resistance mutation, crfA T62A, was shared by a subgroup of lineage 4.3.4.1 isolates and did not correlate with elevated MICs. The presence of a β-lactamase inhibitor reduced the MTBC MICs of tebipenem and meropenem. The resulting MIC distribution was lowest for the orally available drugs tebipenem-clavulanic acid. Whether this in vitro activity translates to similar or greater clinical efficacy of tebipenem-clavulanic acid compared with the currently WHO-endorsed meropenem-clavulanic acid requires clinical studies. IMPORTANCE Repurposing of already approved antibiotics, such as β-lactams in combination with β-lactamase inhibitors, may provide new treatment alternatives for drug-resistant tuberculosis. Meropenem-clavulanic acid was more active in vitro compared to meropenem-vaborbactam. Notably, tebipenem-clavulanic acid showed even better activity, raising the potential of an all-oral treatment option. Clinical data are needed to investigate whether the better in vitro activity of tebipenem-clavulanic acid correlates with greater clinical efficacy compared with the currently WHO-endorsed meropenem-clavulanic acid.

ABSTRACT Antimicrobial peptides (AMPs) are a promising alternative to antibiotics to combat drug resistance in pathogenic bacteria. However, the development of AMPs with high potency and specificity remains a challenge, and new tools to evaluate antimicrobial activity are needed to accelerate the discovery process. Therefore, we proposed MBC-Attention, a combination of a multi-branch convolution neural network architecture and attention mechanisms to predict the experimental minimum inhibitory concentration of peptides against Escherichia coli. The optimal MBC-Attention model achieved an average Pearson correlation coefficient (PCC) of 0.775 and a root mean squared error (RMSE) of 0.533 (log μM) in three independent tests of randomly drawn sequences from the data set. This results in a 5–12% improvement in PCC and a 6–13% improvement in RMSE compared to 17 traditional machine learning models and 2 optimally tuned models using random forest and support vector machine. Ablation studies confirmed that the two proposed attention mechanisms, global attention and local attention, contributed largely to performance improvement. IMPORTANCE Antimicrobial peptides (AMPs) are potential candidates for replacing conventional antibiotics to combat drug resistance in pathogenic bacteria. Therefore, it is necessary to evaluate the antimicrobial activity of AMPs quantitatively. However, wet-lab experiments are labor-intensive and time-consuming. To accelerate the evaluation process, we develop a deep learning method called MBC-Attention to regress the experimental minimum inhibitory concentration of AMPs against Escherichia coli. The proposed model outperforms traditional machine learning methods. Data, scripts to reproduce experiments, and the final production models are available on GitHub.

Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with β-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce. Therefore, we performed a systematic review collating the minimum inhibitory concentrations (MICs) of carbapenems, with or without a β-lactamase inhibitors for MTB, MABC, and MAC. The databases PubMed and Web of Science were searched for the relevant articles in English up until September 21, 2022. Screening of studies was performed by two independent reviewers. MIC data by recommended methods with at least five individual MICs were included. Data were reported as MIC range, MIC50, modal MIC, and/or histograms when individual MICs were available. The study protocol was registered at PROSPERO (CRD42021258537). After screening, a total of 75 studies with MIC data for carbapenems with or without β-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the β-lactamase inhibitor clavulanic acid resulted in the most significant reduction of MICs. For MABC, the addition of avibactam to tebipenem resulted in a 64-fold reduction of modal MIC. Data were insufficient for the analysis of MAC. Carbapenems, and in particular the novel oral compound tebipenem, in combination with clavulanic acid for MTB and avibactam for MABC may be an untapped potential for difficult-to-treat mycobacterial infections. [ABSTRACT FROM AUTHOR]

The antimicrobial effect of colloidal nanosilver (AgNPs) at concentrations of 20 and 30 ppm against reference Esherichia coli, Salmonella enterica, Staphylococcus aureus, Clostridium perfringens, Candida albicans strains and two clinical isolates (Pseudominas aeruginosa and Streptococcus pyogenes) was tested. The classical agar diffusion method, determination of the minimum inhibitory concentrations (MIC) and the time of antimicrobial action of AgNPs were used. In the studies performed by the agar diffusion method, a very good inhibitory effect of AgNPs 30 ppm and to a much lesser extent of AgNPs 20 ppm, was reported against all studied microorganisms. The studied Gram-negative bacteria showed higher sensitivity to both preparations compared to the Gram-positive microorganisms (P>0.05). The lowest sensitivity was reported for S. aureus and C. albicans, and the highest - for P. aeruginosa and S. pyogenes. The lowest MICs of AgNPs 20 ppm were reported for P. aeruginosa and C. perfringens. For them, the MIC50 was 1 µg/mL, and for the rest - 2 µg/mL. Again, C. perfringens showed the highest sensitivity to AgNPs 30 ppm with MIC50 0.5 µg/mL, and the lowest one was that of S. aureus with MIC50 2 µg/mL. For the Gram-positive bacteria MIC values were higher than for Gram-negative ones. AgNPs 20 ppm and AgNPs 30 ppm inactivated all bacterial strains tested at final concentrations of 10³ cells/mL and 104 cells/mL within 5 min; only C. albicans persisted longer. The tested microorganisms remained viable for significantly longer time in the presence of AgNPs 20 ppm and AgNPs 30 ppm when in suspensions with a density of 106 cells/mL. These results are promising for the successful use of AgNPs for disinfection, as well as for topical therapy of infections involving these bacterial species. [ABSTRACT FROM AUTHOR]

Antimicrobial drug resistance in Neisseria gonorrhoeae has been documented all over the world. However, the situation in Sub-Saharan Africa has received little attention. It is critical to establish diagnostics and extend surveillance in order to prevent the emergence of illnesses that are resistant to several treatments. Monitoring antimicrobial susceptibility is critically required in order to gather data that may be utilised to produce treatment recommendations that will result in effective therapy, a decrease in gonorrhoeae-related difficulties and transmission, and effective therapy. Government authorities may set research and preventive objectives, as well as treatment recommendations, using data from the Gonococcal Antimicrobial Surveillance Program (GISP). Local and state health authorities may use GISP data to make choices about the allocation of STI prevention services and resources, to guide preventative planning, and to disseminate information about the most successful treatment practices. Using molecular and culture approaches, we investigated the occurrence of antibiotic resistance in isolates from KwaZulu Natal, South Africa. The great majority of gonococcal isolates (48% showed absolute resistance to ciprofloxacin), with penicillin and tetracycline resistance rates of 14% each. Only one of the gonococcal isolates tested positive for azithromycin resistance, with a minimum inhibitory concentration (MIC) of 1.5 µg/mL. Ceftriaxone was effective against all gonococcal isolates tested. [ABSTRACT FROM AUTHOR]

Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with β-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce. Therefore, we performed a systematic review collating the minimum inhibitory concentrations (MICs) of carbapenems, with or without a β-lactamase inhibitors for MTB, MABC, and MAC. The databases PubMed and Web of Science were searched for the relevant articles in English up until September 21, 2022. Screening of studies was performed by two independent reviewers. MIC data by recommended methods with at least five individual MICs were included. Data were reported as MIC range, MIC50, modal MIC, and/or histograms when individual MICs were available. The study protocol was registered at PROSPERO (CRD42021258537). After screening, a total of 75 studies with MIC data for carbapenems with or without β-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the β-lactamase inhibitor clavulanic acid resulted in the most significant reduction of MICs. For MABC, the addition of avibactam to tebipenem resulted in a 64-fold reduction of modal MIC. Data were insufficient for the analysis of MAC. Carbapenems, and in particular the novel oral compound tebipenem, in combination with clavulanic acid for MTB and avibactam for MABC may be an untapped potential for difficult-to-treat mycobacterial infections.

Background: Streptococcus mutans is considered as a major microorganism causing tooth decay, affecting individuals globally. Different types of chewing sticks possess anti cariogenic properties, traditionally been consumed in maintaining dental hygiene. Usage of these sticks can be economical in developing and rural regions where dental caries is a major health concern. Objective: The current study aims to evaluate antibacterial action of different type of chewing sticks extract on Streptococcus mutans. Methods: Aqueous extracts of Azadiracta indica (Neem), Melia azedarach (Bakain), Mangifera indica (Mango), Salvadora persica (Peelu), Terminalia chebula (Harhar), Dalbeigia sissoo (Tali) and Juglans regia (Akhrot) plants which have justified folk use were prepared in Punjab University College of Pharmacy, Punjab University. Next, in vitro antimicrobial activity was studied by broth dilution method in Post Graduate Medical Institute, Lahore. Moreover, minimum inhibitory concentration (MIC) as well as the minimum bactericidal concentration (MBC) were quantitatively evaluated on basis of turbidity index. Results: There is a significant effect of aqueous extracts of plants on the bacterial inhibition. MIC and MBC values were in the range of 6.125 to 100 mg/mL against S. mutans. The notable effect occurred with aqueous extracts of Azadiracta indica showing MIC and MBC values as 6.25mg/mL and 12.5 mg/mL, respectively. Alternatively, Salvadora persica demonstrated 8.33mg/mL and 16.66 mg/mL values of these parameters Conclusions: Each plant studied exhibited moderate to high antibacterial activity against tested bacterial strain. However, Azadirachta indica and Salvadora persica aqueous extracts showed promising effect against Streptococcus mutans [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a global health issue and surveillance of AMR can be useful for understanding AMR trends and planning intervention strategies. Salmonella, widely distributed in food-producing animals, has been considered the first priority for inclusion in the AMR surveillance program by the World Health Organization (WHO). Recent advances in rapid and affordable whole-genome sequencing (WGS) techniques lead to the emergence of WGS as a one-stop test to predict the antimicrobial susceptibility. Since the variation of sequencing and minimum inhibitory concentration (MIC) measurement methods could result in different results, this study aimed to develop WGS-based random forest models for predicting MIC values of 24 drugs using data generated from the same laboratories in Taiwan. The WGS data have been transformed as a feature vector of 10-mers for machine learning. Based on rigorous validation and independent tests, a good performance was obtained with an average mean absolute error (MAE) less than 1 for both validation and independent test. Feature selection was then applied to identify top-ranked 10-mers that can further improve the prediction performance. For surveillance purposes, the genome sequence-based machine learning methods could be utilized to monitor the difference between predicted and experimental MIC, where a large difference might be worthy of investigation on the emerging genomic determinants. [ABSTRACT FROM AUTHOR]

Delay in the results of standard phenotypic susceptibility tests is the main obstacle to adequate antibiotic treatment. For this reason, the European Committee for Antimicrobial Susceptibility Testing has proposed the Rapid Antimicrobial Susceptibility Testing for the disk diffusion method directly from blood culture. However, to date, there are no studies evaluating early readings of polymyxin B broth microdilution (BMD), the only standardized methodology for assessing susceptibility to polymyxins. This study aimed to evaluate modifications in the BMD technique for polymyxin B using fewer antibiotic dilutions and reading after an incubation time of 8–9 hr (early reading) in comparison to 16–20 hr of incubation (standard reading) for isolates of Enterobacterales, Acinetobacter baumannii complex, and Pseudomonas aeruginosa. A total of 192 isolates of gram-negative bacteria were evaluated and the minimum inhibitory concentrations were read after early and standard incubations. The early reading presented 93.2% of essential agreement and 97.9% of categorical agreement with the standard reading of BMD. Only three isolates (2.2%) presented major errors and only one (1.7%) presented a very major error. These results indicate a high agreement between the early and the standard reading times of BMD of polymyxin B. [ABSTRACT FROM AUTHOR]

Background Rifampin-resistant and/or multidrug-resistant tuberculosis (RR/MDR-TB) treatment requires multiple drugs, and outcomes remain suboptimal. Some drugs are associated with improved outcome. It is unknown whether particular pharmacokinetic-pharmacodynamic relationships predict outcome. Methods Adults with pulmonary RR/MDR-TB in Tanzania, Bangladesh, and the Russian Federation receiving local regimens were enrolled from June 2016 to July 2018. Serum was collected after 2, 4, and 8 weeks for each drug's area under the concentration-time curve over 24 hours (AUC0–24). Quantitative susceptibility of the M. tuberculosis isolate was measured by minimum inhibitory concentrations (MICs). Individual drug AUC0–24/MIC targets were assessed by adjusted odds ratios (ORs) for favorable treatment outcome, and hazard ratios (HRs) for time to sputum culture conversion. K-means clustering algorithm separated the cohort of the most common multidrug regimen into 4 clusters by AUC0–24/MIC exposures. Results Among 290 patients, 62 (21%) experienced treatment failure, including 30 deaths. Moxifloxacin AUC0–24/MIC target of 58 was associated with favorable treatment outcome (OR, 3.75; 95% confidence interval, 1.21–11.56; P =.022); levofloxacin AUC0–24/MIC of 118.3, clofazimine AUC0–24/MIC of 50.5, and pyrazinamide AUC0–24 of 379 mg × h/L were associated with faster culture conversion (HR >1.0, P <.05). Other individual drug exposures were not predictive. Clustering by AUC0–24/MIC revealed that those with the lowest multidrug exposures had the slowest culture conversion. Conclusions Amidst multidrug regimens for RR/MDR-TB, serum pharmacokinetics and M. tuberculosis MICs were variable, yet defined parameters to certain drugs—fluoroquinolones, pyrazinamide, clofazimine—were predictive and should be optimized to improve clinical outcome. Clinical Trials Registration NCT03559582. [ABSTRACT FROM AUTHOR]

Background and Aim: Brucellosis is a contagious livestock disease with a significant economic impact. This study aimed to compare the efficacy of antibiotics used alone or in combination with silver nanoparticles (AgNPs) against Brucella melitensis Rev 1 in vitro. Materials and Methods: AgNps conjugated with ciprofloxacin was synthesized and thoroughly characterized by ultraviolet visible spectrophotometry (UV-vis). The antimicrobial effect of ciprofloxacin alone and ciprofloxacin conjugated with AgNPs against B. melitensis Rev 1 was determined by minimum inhibitory concentration (MIC) and the erythrocyte hemolytic assay determined the capability of conjugation to cause hemolysis in human erythrocyte. Results: The UV-vis spectra of both silver-drug nanoconjugates showed a characteristic surface plasmon resonance band at 420 nm. The MIC assays showed that AgNPs conjugation to antibiotics enhanced the antibacterial potential of the selected antibiotics against B. melitensis Rev 1 relative to non-conjugated antibiotics. The results show that low concentrations of AgNPs can kill B. melitensis Rev 1. The MICs of ciprofloxacin and ciprofloxacin–AgNPs were 0.75 and 0.05 μM, respectively. Conclusion: The conjugation of ciprofloxacin with AgNPs enhanced the antibacterial effects against B. melitensis Rev 1. In addition, this conjugation appears to inhibit the capability of this bacterium to adapt to the presence of antibiotics, thereby inhibiting bacterial resistance. Further studies are required to examine its potential as an in vivo treatment.

Background: Biofilms are a major challenge in treating infections. Clinically, biofilms are often associated with chronic infections, so rapid and accurate methods of investigating the antibiotic susceptibility of biofilm bacteria are very important for faster diagnosis and treatment. In this study, a new modified microplate method was proposed to evaluate the antibiotic susceptibility of alive bacteria in the biofilm. Materials and Methods: The study was conducted on clinical isolates of Pseudomonas aeruginosa and standard strain over a period of one year. The susceptibility test was conducted according to a modified version of the Calgary biofilm device method. In the last step, to study the living bacteria in the biofilm, oxidative-fermentative (OF) medium was used to measure the acid production following the use of glucose by the bacteria. The biofilm-growing bacteria was determined by observing the color changing and also measuring optical density (OD) at 427 nm of OF medium. Results: The method in this study could evaluate the effect of antibiotics on biofilm bacteria based on glucose metabolism. The results indicated that this method can quickly and easily identify alive bacteria in biofilm at a low cost and without the need for any special devices. Conclusion: Although biofilms are involved in most incurable clinical cases, there is currently no guideline to assist physicians in treating biofilm-related infections. Therefore, it is necessary to establish a specific sensitivity test for biofilm or to approve a new method for routine use in diagnostic laboratories.

Biofilm formation has been identified as one of the major pathways by which pathogens evade the effect of antimicrobial agents, leading to drug resistance in general. The imidazole ring provides a promising scaffold for the design of viable antimicrobial agents. In this work, halogenated benzyl derivatives of imidazole were synthesized and evaluated for antimicrobial and anti-biofilm activity. Molecular docking was used to analyse interactions between the compounds and the transcriptional regulator protein, LasR - a major protein that has downstream effect on biofilm formation in Pseudomonas aeruginosa. Results from the study revealed the marked potency of the halogenated compounds as antimicrobial agents. Antimicrobial susceptibility tests showed that the bromo- derivatives were very active against Gram-positive bacteria. The chloro- derivatives, on the other hand portrayed, a broad spectrum of antimicrobial activity. Notably, N-2-chlorobenzyl imidazole appeared to be the most potent antimicrobial agent with an MIC of 0.250 mg/mL against P. aeruginosa. Despite the relatively low antimicrobial effects displayed by the fluoro- derivatives, N-3-fluorobenzyl imidazole was identified to be a very good anti-biofilm agent with 5.3 µg/mL of the compound needed to inhibit biofilm formation by 50% (BIC50). Furthermore, all the compounds inhibited biofilms produced by Pseudomonas aeruginosa at sub-MIC concentrations. Predictions from molecular docking studies suggest that the compounds may not target the LasR protein in eliciting their anti-biofilm property.

Background: The rare occurrence of human cryptococcosis caused by Cryptococcus gattii sensu lato leads to difficulties in establishing the antifungal susceptibility profile between species of this potentially lethal pathogen, which may be crucial for treating cryptococcosis. Objective: To establish an antifungal susceptibility profile of C. gattii s.l. in Taiwan. Methods: A total of 104 environmental C. gattii s.l. strains (including multilocal sequence typing ST7, ST106, ST274, ST328, ST546, ST548 and ST630) and 21 previously collected clinical strains (including ST7, ST44, ST06, ST274, ST328 and ST329) were included in this study. We determined the minimum inhibitory concentrations (MICs) of six antifungal agents (itraconazole, fluconazole, voriconazole, posaconazole, flucytosine and amphotericin B) against environmental C. gattii s.l. strains and compared the antifungal susceptibility profiles of environmental strains with those of clinical strains. Results: The antifungal susceptibility data demonstrated that the MICs of antifungal agents against environmental strains were comparable to those against clinical strains. Compared with strains of Cryptococcus deuterogattii, those of C. gattii sensu stricto were more susceptible to azoles and flucytosine. The differences in antifungal susceptibility between the strains of each sequence type (ST) were significant. Correlation analysis of MICs revealed cross‐resistance between azoles in environmental strains of C. gattii s.l. Geographic differences in the antifungal susceptibility of C. gattii s.l. isolated from different cities in Taiwan were observed in this study. Conclusion: Clinical and environmental strains were indistinguishable in antifungal susceptibility. The antifungal susceptibility of C. gattii s.l. is associated with STs. Therefore, establishing an ST‐oriented domestic antifungal susceptibility database may help treat C. gattii s.l.‐induced cryptococcosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Taurolidine is active against a wide variety of micro organisms, including bacteria and fungi. Mucormycosis is one of the life-threatening opportunistic fungal infections, especially in immunocompromised patients. Currently, the emergence of Mucormycosis during the COVID-19 pandemic raises public health concerns regarding untoward morbidity and mortality among SARS-CoV-2 patients. It is well-known that delayed and inappropriate antifungal therapy leads to increased morbidity and mortality. This study aimed to investigate the in-vitro antifungal activity of taurolidine to evaluate its effects against clinical isolates of Mucorales.Materials and Methods: This study included previously collected clinical Mucorales isolates. The minimum in vitro inhibitory concentration (MIC) of amphotericin B, caspofungin, voriconazole, posaconazole, and itraconazole was determined using the broth microdilution method.Results: All clinical isolates showed full sensitivity to amphotericin B. Posaconazole MIC range from 8 μg/mL to 0.032 μg/mL. The MIC range of voriconazole and caspofungin were determined to be 2-8 µg/mL and 0.5-16 µg/mL, respectively. Growth of the isolates was entirely inhibited in 1000 µg/mL concentration of taurolidine. In microscopic observations, morphological effects on hyphal growth were observed at 500 µg/mL concentration.Conclusion: In conclusion, this is an updated experience of using taurolidine against Mucorales. However, our in-vitro findings need to be confirmed in well-designed clinical trials aimed at treating invasive Mucormycosis infections.

The emergence of carbapenem-resistant Enterobacterales (CRE) has been recognized as a significant concern globally. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor that has demonstrated activity against isolates producing class A, C, and D β-lactamases. Here-in, we evaluated the in vitro activity of CZA and comparator antimicrobial agents against 858 CRE isolates, arising from the Southeast Asian region, collected from a large tertiary hospital in Singapore. These CRE isolates mainly comprised Klebsiella pneumoniae (50.5%), Escherichia coli (29.4%), and Enterobacter cloacae complex (17.1%). Susceptibility rates to levofloxacin, imipenem, meropenem, doripenem, aztreonam, piperacillin/tazobactam, cefepime, tigecycline, and polymyxin B were low. CZA was the most active β-lactam agent against 68.9% of the studied isolates, while amikacin was the most active agent among all comparator antibiotics (80% susceptibility). More than half of the studied isolates (51.4%) identified were Klebsiella pneumoniae carbapenemase (KPC)-2 producers, 25.9% were New Delhi metallo-β-lactamase (NDM) producers, and Oxacillinase (OXA)-48-like producers made up 10.7%. CZA was the most active β-lactam agent against KPC-2, OXA-48-like, and Imipenemase (IMI) producers (99.3% susceptible; MIC50/90: ≤1/2 mg/L). CZA had excellent activity against the non-carbapenemase-producing CRE (91.4% susceptible; MIC50/90: ≤1/8 mg/L). Expectedly, CZA had no activity against the metallo-β-lactamases (MBL)-producing CRE (NDM- and Imipenemase MBL (IMP) producers; 27.2% isolates), and the carbapenemase co-producing CRE (NDM + KPC, NDM + OXA-48-like, NDM + IMP; 3.0% isolates). CZA is a promising addition to our limited armamentarium against CRE infections, given the reasonably high susceptibility rates against these CRE isolates. Careful stewardship and rational dosing regimens are required to preserve CZA’s utility against CRE infections.

Abstract Background In the past decade, Mycoplasma synoviae (M. synoviae) infection has become widely prevalent in China, has caused serious economic losses and has become one of the most important diseases in the chicken industry. Medication is a general approach for the control of M. synoviae infection, but antibiotics are sometimes ineffective in clinical practice. To investigate the sensitivity of M. synoviae to antimicrobials commonly used in the treatment of M. synoviae infection, the antibiotic susceptibility of 32 M. synoviae strains isolated from China from 2016 to 2019 were determined using the minimum inhibitory concentration (MIC) method. Results All isolates had low MIC values for the combination of lincomycin and spectinomycin, pleuromutilin, and macrolides. However, the M. synoviae isolates displayed variance in MICs for doxycycline hydrochloride with a range of 0.25 to 8 μg/mL, and oxytetracycline hydrochloride with a range of 0.5 to 8 μg/mL. Three and one M. synoviae isolates showed intermediate MIC values to doxycycline hydrochloride and oxytetracycline hydrochloride, respectively. High MIC values for enrofloxacin were detected in all isolates with MICs ranging from 4 to 32 μg/mL. Furthermore, comparison of the parC QRDR identified a mutation at nucleotide position 254 (C254T) resulting in a Thr 85 Ile amino acid change in all M. synoviae isolates and the reference strain ATCC 25204 being resistant to enrofloxacin. Moreover, mutations at Glu 804 Gly and Thr 686 Ala of gyrA QRDR were identified in all M. synoviae isolates and ATCC 25204. The mutation in the QRDR of the parE gene resulted in amino acid changes at positions 197 (Pro to Ser) in 27/32 M. synoviae isolates. Conclusion Three nonsynonymous mutations in gyrA and parE were first identified to be related to enrofloxacin resistance. Our results showed that M. synoviae resistance to enrofloxacin is widespread.

The microbiological profile, associated risk factors and demographic characteristics of patients with IE has changed in the recent times. In the present study, the antibiotic susceptibility profile of 66 isolates (40 from IDU and 26 from non IDU) recovered over a period of three years from the patients with definitive diagnosis of IE along with their absolute minimum inhibitory concentrations (MIC-μg/ml) was determined as per CLSI, 2017 guidelines. Staphylococcus aureus was found to be the predominant pathogen associated with IE out of which 90.2% isolates were MRSA, although none of the isolates were found resistant to vancomycin, teicoplanin, daptomycin and linezolid. Pseudomonas aeruginosa isolates were 100% susceptible to carbapenams, however variable resistance was observed against other antimicrobials. All Enterococci were found to be 100% susceptible to linezolid and daptomycin, whereas vancomycin resistant enterococci phenotype was observed in 25% of the Enterococcal isolates. A noticeable difference in the antimicrobial susceptibility profile and their MICs were observed in the present study, as compared to published literature across the globe and within the country. However, no statistically significant difference (λ 2 test, p > 0.01)in the AST pattern of isolates from IDU vs. Non IDU was observed. After reviewing the local antibiogram it seems that we need to have our own regional guidelines, which may partially replace the currently prevailing AHA/ESC guidelines.

OBJECTIVE: Salmonella isolates have been discovered in many regions of the world. We investigated the prevalence and resistance of Salmonella isolates in raw milk of healthy dairy cows on farms in different regions of Henan Province, China. MATERIALS AND METHODS: From July 2020 to November 2021, 422 raw milk samples were collected. The minimum inhibitory concentrations (MICs) of 16 antimicrobial agents against 89 Salmonella strains detected from the raw milk samples were determined using the broth microdilution method, and the resistance genes for fluoroquinolones were identified using polymerase chain reaction. RESULTS: Eighty-nine (21.09%) Salmonella isolates were recovered from 422 raw milk samples. The Salmonella strains exhibited high resistance to amoxicillin (100.00%), tylosin (95.50%), and lincomycin (95.50%). Additionally, tigecycline showed good activity against Salmonella, with an MIC50 of 0.25 µg/mL. All Salmonella isolates showed multidrug resistance (MDR), and >50% of the strains showed resistance to more than six antimicrobials. The strains from Jiaozuo exhibited 100% resistance to amoxicillin, terramycin, tylosin, and lincomycin. Two efflux pump genes, oqxA and oqxB, had the highest carrying rates of 66.29% and 64.04%, respectively. Additionally, the carrying rates of oqxA and oqxB were high in Shangqiu, Zhengzhou, and Jiaozuo. The carrying rates of aac(6')-Ib-cr in Shangqiu and Zhengzhou were 33.33% and 38.46%, respectively. CONCLUSIONS: This study revealed a high prevalence of Salmonella isolates obtained from raw milk of healthy dairy cows in different regions of Henan Province, China. The Salmonella strains exhibited various degrees of MDR. Salmonella can be transmitted to humans via consumption of contaminated raw milk; thus, the presence of resistance genes poses a potential threat to public health, highlighting the need for vigilant monitoring of Salmonella isolates. [ABSTRACT FROM AUTHOR]

Background and Aim: Hospital-acquired infections are considered a major health concern worldwide because of the increasing morbidity and mortality rate. Hence, selecting the most efficient disinfectants in a clinic is crucial. This study evaluated the antibacterial efficacy of seven mostly used disinfectants against clinically isolated Escherichia coli. Materials and Methods: For this purpose, minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of Aniosyme DD1 0.5%, Steranios 2%, Aniospray 29 and Surfanios 0.5% at Hazrat Valiasr hospital and PROSEPT® Floor 0.75%, PROSEPT® Instru 0.05% and PROSEPT® Med used at Ayatollah Mousavi hospital were determined both in the presence and absence of bovine serum albumin (BSA) using microbroth dilution assay. Results: The results indicate that PROSEPT® Med had the lowest MIC and MBC values, followed by Aniospray 29 and PROSEPT® Instro, and the presence of BSA reduced antibacterial activities of disinfectants. Conclusion: The disinfectants applied at Ayatollah Mousavi hospital generally had higher antibacterial activities. Due to the importance of nosocomial pathogens at healthcare centers, selecting the most potent, fast-acting, and efficient disinfectants to prevent hospital-acquired infections is essential. [ABSTRACT FROM AUTHOR]

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The Clinical and Laboratory Standards Institute has published epidemiological cut-off values for susceptibility data generated at 22°°C and read after 44-48 h for florfenicol, oxolinic acid and oxytetracycline against Aeromonas salmonicida. The cut-off values for the minimum inhibitory concentration (MIC) and disc diffusion were derived from data obtained by 1 laboratory and 2 laboratories respectively. The present work reports the generation of susceptibility data from additional laboratories and the calculation of provisional cut-off values from aggregations of these data with previously published data. With respect to MIC data, the provisional cut-off values, derived from aggregations of the data from 4 laboratories, were ≤4 µg ml-1 for florfenicol, ≤0.0625 µg ml-1 for oxolinic acid and ≤1 µg ml-1 for oxytetracycline. For disc diffusion data, the provisional cut-off values derived from aggregations of the data from 5 laboratories were ≥30 mm for florfenicol, ≥32 mm for oxolinic acid and ≥25 mm for oxytetracycline. In addition, a cut-off value of ≥29 mm for ampicillin was derived from the aggregation of data from 4 laboratories.

The harmful effects following the ingestion of mycotoxin-contaminated food include the induction of cancers, mutagenicity, immune suppression, and toxicities that target organs of the digestive, cardiovascular, and central nervous systems. Synthetic fungicides are generally associated with a high toxic residue in food and the development of excessive fungal resistance. This study aimed to determine the antifungal activities against mycotoxigenic fungi of selected South African plant leaves and potentially develop plant-derived bio-fungicides, and, furthermore, to explore the in vitro antioxidant activity and the phytochemical spectra of the compounds of the selected medicinal plant extracts. The extracts were tested for antifungal activity against phytopathogenic strains using a microdilution broth assay. Bauhinia galpinii extracts exhibited the lowest minimum inhibitory concentration (MIC) against C. cladospoides and P. haloterans at 24 h incubation periods. C. caffrum had good antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) with 50% inhibitory concentration (IC50) values of 0.013 mg/mL while B. galpini had IC50 values of 0.053 against free radicals of 2,2′-azinobis (3-ethylbenzthiazoline-6-suphonic acid (ABTS). The antimycotoxigenic and antioxidant activity exerted by both B. galpinii and C. caffrum may well be attributed to high TPC. In the GC-ToF-MS analysis, all the selected medicinal plants exhibited the presence of Hexadecanoic acid at varying % areas, while both B. galpinii and C. caffum exhibited the presence of lupeol at % area 2.99 and 3.96, respectively. The compounds identified, particularly the ones with higher % area, may well explain the biological activity observed. Although the selected medicinal plants exhibited a notable biological activity, there is a need to explore the safety profiles of these plants, both in vitro and in vivo.

Background and Aim: Brucellosis is a contagious livestock disease with a significant economic impact. This study aimed to compare the efficacy of antibiotics used alone or in combination with silver nanoparticles (AgNPs) against Brucella melitensis Rev 1 in vitro. Materials and Methods: AgNps conjugated with ciprofloxacin was synthesized and thoroughly characterized by ultraviolet visible spectrophotometry (UV-vis). The antimicrobial effect of ciprofloxacin alone and ciprofloxacin conjugated with AgNPs against B. melitensis Rev 1 was determined by minimum inhibitory concentration (MIC) and the erythrocyte hemolytic assay determined the capability of conjugation to cause hemolysis in human erythrocyte. Results: The UV-vis spectra of both silver-drug nanoconjugates showed a characteristic surface plasmon resonance band at 420 nm. The MIC assays showed that AgNPs conjugation to antibiotics enhanced the antibacterial potential of the selected antibiotics against B. melitensis Rev 1 relative to non-conjugated antibiotics. The results show that low concentrations of AgNPs can kill B. melitensis Rev 1. The MICs of ciprofloxacin and ciprofloxacin-AgNPs were 0.75 and 0.05 μM, respectively. Conclusion: The conjugation of ciprofloxacin with AgNPs enhanced the antibacterial effects against B. melitensis Rev 1. In addition, this conjugation appears to inhibit the capability of this bacterium to adapt to the presence of antibiotics, thereby inhibiting bacterial resistance. Further studies are required to examine its potential as an in vivo treatment. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is an infectious disease caused predominantly by Mycobacterium tuberculosis (Mtb). It was responsible for approximately 1.4 million deaths worldwide in 2019. The lack of new drugs to treat drug‐resistant strains is a principal factor for the slow rise in TB infections. Our aim is to aid the development of new TB treatments by describing improvements (last decade, 2011–2021) to nitro(NO2)‐based compounds that have shown activity or pharmacological properties (e.g., anti‐proliferative, anti‐kinetoplastid) against Mtb. For all compounds, we have included final correlations of minimum inhibitory concentrations against Mtb (H37Rv). [ABSTRACT FROM AUTHOR]

Natural antimicrobials (NAM) are promising candidates for the successful control of poultry-borne bacteria, carrying potent antimicrobial activity (AMA) against a wide range of multidrug-resistant pathogens. Individual activities of carvacrol, eugenol, trans-cinnamaldehyde, oregano, and thymol, along with the combined activity of paired compounds, were examined using broth microdilution and checkerboard techniques. The characteristic interactions between the compounds were calculated using an improved method, based on combination index (CI) values. The bacteria examined herein were selected due to their known genetic resistance to at least one antibiotic. Our results indicated that thymol was most effective, exhibiting the lowest minimum inhibitory concentration (MIC) value against Salmonella pullorum , Escherichia coli , and Klebsiella pneumoniae , establishing the order of antimicrobial efficacy as: thymol > oregano > carvacrol > trans-cinnamaldehyde > eugenol. In the interaction study, the paired combination of carvacrol and thymol showed synergistic effects and was highly effective in reducing the antibiotic resistance of all the evaluated pathogens. Notably, all CI values were <1.0 in evaluations of S. pullorum , indicating the absence of antagonism between eugenol and thymol (or oregano). In K. pneumoniae , majority of CI values, which had a few concentration points, were smaller than 1.0, indicating a synergistic effect between eugenol and carvacrol (oregano or thymol), and trans-cinnamaldehyde and carvacrol. In E. coli , apart from some concentration points, some CI values were smaller than 1.0, demonstrating a synergistic effect between eugenol and carvacrol, and thymol and carvacrol (eugenol or oregano). It is therefore of great significance to investigate and illuminate the minimal effect concentration of these five components when they are used in combination as feed additives. Moreover, the improved evaluation method of this study provides a precise and extensive means to assess the synergistic effects of NAM. [ABSTRACT FROM AUTHOR]

Purpose: In 2019, minimum inhibitory concentration (MIC) breakpoints of ciprofloxacin and levofloxacin for Enterobacterales were lowered. This study sought to determine whether there is a correlation between MIC and outcomes in those receiving fluoroquinolones (FQs) for urinary tract infections (UTIs) caused by Enterobacterales pathogens. Methods: This was a retrospective study of adult patients treated with ciprofloxacin or levofloxacin for a UTI caused by an Enterobacterales pathogen. Patients were placed into low MIC (ciprofloxacin: ≤ 0.25 mcg/mL; levofloxacin ≤ 0.5 mcg/mL), intermediate MIC (ciprofloxacin: 0.5–2 mcg/mL; levofloxacin: 1–4 mcg/mL), or high MIC groups (ciprofloxacin: > 2 mcg/mL; levofloxacin: > 4 mcg/mL). The primary outcome was UTI recurrence, defined as hospital admission, emergency department or clinic visit due to UTI, or antibiotic prescription within 28 days of FQ initiation. Results: A total of 1022 patients were included: 887, 75, and 60 with a low, intermediate, and high MIC, respectively. UTI recurrence within 28 days occurred most frequently in the high MIC group (20.5% vs. 25.3% vs. 60%; P < 0.01). Risk factors for UTI recurrence identified by multivariable analysis were those with a high MIC (high vs. low MIC: OR 5.20, 95% CI 2.99–9.05, P < 0.01; high vs. intermediate MIC: OR 4.72, 95%CI 2.22–10.03, P < 0.01), a complicated UTI (OR 1.85, 95% CI 1.35–2.54; P < 0.01), a history of recurrent UTIs (OR 1.84, 95% CI 1.29–2.62; P < 0.01), or a respiratory disorder (OR 1.58, 95% CI 1.04–2.42; P = 0.03). Conclusion: This study supports separate, less stringent FQ MIC breakpoint interpretive criteria for UTIs caused by Enterobacterales pathogens. [ABSTRACT FROM AUTHOR]

Natural antimicrobials (NAM) are promising candidates for the successful control of poultry-borne bacteria, carrying potent antimicrobial activity (AMA) against a wide range of multidrug-resistant pathogens. Individual activities of carvacrol, eugenol, trans-cinnamaldehyde, oregano, and thymol, along with the combined activity of paired compounds, were examined using broth microdilution and checkerboard techniques. The characteristic interactions between the compounds were calculated using an improved method, based on combination index (CI) values. The bacteria examined herein were selected due to their known genetic resistance to at least one antibiotic. Our results indicated that thymol was most effective, exhibiting the lowest minimum inhibitory concentration (MIC) value against Salmonella pullorum, Escherichia coli, and Klebsiella pneumoniae, establishing the order of antimicrobial efficacy as: thymol > oregano > carvacrol > trans-cinnamaldehyde > eugenol. In the interaction study, the paired combination of carvacrol and thymol showed synergistic effects and was highly effective in reducing the antibiotic resistance of all the evaluated pathogens. Notably, all CI values were

Abstract Background Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM), and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011–2018. Methods We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011–2018, a collection of 76 isolates were selected for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of CAZ, CAZ-AVI, ATM and ATM-AVI were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more active in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from “Resistant” or “Intermediate” with CAZ or ATM alone to “Susceptible” with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 4-fold lower than the MIC of CAZ or ATM alone. Results For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03–64, 1–1024, 0.016–64, and 0.06–64 μg/mL, respectively. In combined therapy, AVI was active at restoring the activity of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs. 56.58%, P

Antimicrobial drug resistance in Neisseria gonorrhoeae has been documented all over the world. However, the situation in Sub-Saharan Africa has received little attention. It is critical to establish diagnostics and extend surveillance in order to prevent the emergence of illnesses that are resistant to several treatments. Monitoring antimicrobial susceptibility is critically required in order to gather data that may be utilised to produce treatment recommendations that will result in effective therapy, a decrease in gonorrhoeae-related difficulties and transmission, and effective therapy. Government authorities may set research and preventive objectives, as well as treatment recommendations, using data from the Gonococcal Antimicrobial Surveillance Program (GISP). Local and state health authorities may use GISP data to make choices about the allocation of STI prevention services and resources, to guide preventative planning, and to disseminate information about the most successful treatment practices. Using molecular and culture approaches, we investigated the occurrence of antibiotic resistance in isolates from KwaZulu Natal, South Africa. The great majority of gonococcal isolates (48% showed absolute resistance to ciprofloxacin), with penicillin and tetracycline resistance rates of 14% each. Only one of the gonococcal isolates tested positive for azithromycin resistance, with a minimum inhibitory concentration (MIC) of 1.5 µg/mL. Ceftriaxone was effective against all gonococcal isolates tested.

Background: In the past decade, Mycoplasma synoviae (M. synoviae) infection has become widely prevalent in China, has caused serious economic losses and has become one of the most important diseases in the chicken industry. Medication is a general approach for the control of M. synoviae infection, but antibiotics are sometimes ineffective in clinical practice. To investigate the sensitivity of M. synoviae to antimicrobials commonly used in the treatment of M. synoviae infection, the antibiotic susceptibility of 32 M. synoviae strains isolated from China from 2016 to 2019 were determined using the minimum inhibitory concentration (MIC) method. Results: All isolates had low MIC values for the combination of lincomycin and spectinomycin, pleuromutilin, and macrolides. However, the M. synoviae isolates displayed variance in MICs for doxycycline hydrochloride with a range of 0.25 to 8 μg/mL, and oxytetracycline hydrochloride with a range of 0.5 to 8 μg/mL. Three and one M. synoviae isolates showed intermediate MIC values to doxycycline hydrochloride and oxytetracycline hydrochloride, respectively. High MIC values for enrofloxacin were detected in all isolates with MICs ranging from 4 to 32 μg/mL. Furthermore, comparison of the parC QRDR identified a mutation at nucleotide position 254 (C254T) resulting in a Thr 85 Ile amino acid change in all M. synoviae isolates and the reference strain ATCC 25204 being resistant to enrofloxacin. Moreover, mutations at Glu 804 Gly and Thr 686 Ala of gyrA QRDR were identified in all M. synoviae isolates and ATCC 25204. The mutation in the QRDR of the parE gene resulted in amino acid changes at positions 197 (Pro to Ser) in 27/32 M. synoviae isolates. Conclusion: Three nonsynonymous mutations in gyrA and parE were first identified to be related to enrofloxacin resistance. Our results showed that M. synoviae resistance to enrofloxacin is widespread. [ABSTRACT FROM AUTHOR]

Vibrio cholerae is an etiological cause of cholera and has been implicated in several epidemics. Exploration of the antimicrobial signatures of culinary spices has become an important industrial tool to suppress the growth of foodborne bacterial pathogens including Vibrio spp. The antibiofilm and antimotility activities of some selected natural antimicrobial agents were then evaluated. All the extracts showed vibriostatic activities with minimum inhibitory concentration (MIC) ranging from 0.1% to 0.4%. Cinnamon and black pepper demonstrated significant biofilm inhibition activity from 94.77% to 99.77% when administered at 100% MIC. Black pepper extract also demonstrated the highest biofilm inhibition activity against the established biofilms of V. cholerae O1 and O139. Cinnamon, calabash nutmeg, and black pepper significantly inhibited swimming and swarming motility by 85.51% to 94.87%. Sub-MICs (50% and 75%) of some extracts were also effective as an antibiofilm and antimotility agent against the tested strains. The findings of our study suggest the potential application of natural antimicrobial agents such as spices in food to inhibit biofilm formation and motility, which consequently mitigate the virulence and persistence of the pathogen in the food supply chain. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the relationships between treatment outcomes of patients with urogenital Chlamydia trachomatis infections and minimum inhibitory concentrations (MICs) and drug resistance genes. Methods: The clinical data of 92 patients diagnosed with Chlamydia trachomatis (C. trachomatis) infections were collected. Of these patients, 28 received regular treatment with azithromycin and 64 received minocycline. All patients underwent three monthly follow-ups after the completion of treatment. The microdilution method was used for the in vitro susceptibility tests. The acquisition of 23S rRNA mutations and presence of the tet(M) gene were detected by gene amplification and sequencing. Results: The MICs of azithromycin, clarithromycin, erythromycin, tetracycline, doxycycline, and minocycline were comparable for isolates from the treatment failure and treatment success groups. Higher detection rates of 23S rRNA gene mutations and tet(M) were found in the treatment failure group (57.14% and 71.43%, respectively) than in the treatment success group (14.29% and 30.23%, respectively) (p < 0.05). The A2057G, C2452A, and T2611C gene mutations of 23S rRNA were detected in eight clinical isolates from the azithromycin treatment failure group, while the T2611C gene mutation was detected in one clinical strain from the treatment success group. Conclusions: The detection of resistance genes could better explain the high treatment failure rate than the MIC results in patients with urogenital C. trachomatis infections, highlighting the need for genetic antimicrobial resistance testing in infected patients.

Introduction: Micafungin is a recommended echinocandin antifungal agent for candidemia treatment and prophylaxis. However, overuse of echinocandin antifungals may cause resistance. There is currently no information available regarding the low susceptibility associated with using micafungin. This study investigated the effect of micafungin use on changes in the detected Candida species and low susceptibility. Methods: We conducted a retrospective survey and included records of Candida spp. detected in blood cultures from January 2010 to December 2018 in our hospital. Survey items included clinical outcomes at 30 days after positive cultures, patient characteristics, and drug prescription status. Patient background information included gender, previous hospitalization, stay in the intensive care unit, comorbidities, and history of surgery (within 90 days before candidemia onset) and drug exposure. Species detected and their minimum inhibitory concentrations (MICs) and amount of antifungal prescriptions by department were investigated. Risk factors for detecting C. parapsilosis and for low susceptibility to micafungin were evaluated using multivariate analysis. Results: A total of 153 Candida clinical blood isolates were collected and C. albicans was the most prevalent species, followed by C. parapsilosis and C. glabrata. In the analysis by department, antifungal use and non-albicans Candida species were most frequently detected in the hematology department. Multivariate analysis showed that prior micafungin use increased the risk of C. parapsilosis (odds ratio (OR) 4.22; 95% confidence interval (CI) 1.39-12.79; p = 0.011). MIC90 of micafungin on C. glabrata and C. parapsilosis was 1.0 μg/mL. Prior micafungin use was clarified as a risk factor resulting in MIC > 0.06 μg/mL for micafungin in non-parapsilosis Candida species (OR 13.2; 95% CI 3.23-54.2; p < 0.01). Conclusion: Prior micafungin use increased the risk of C. parapsilosis and the MIC > 0.06 μg/mL of micafungin in non-parapsilosis Candida species. Since there are only a few antifungal options, further antifungal stewardship considering azole antifungal agents use is required. [ABSTRACT FROM AUTHOR]

Ceftolozane-tazobactam is a cephalosporin/β-lactamase inhibitor combination developed for use against some β-lactam- and multidrug-resistant Gram-negative organisms. This study aimed to evaluate the in vitro activity of ceftolozane–tazobactam against clinical bacterial isolates at the University Hospital of Marrakech. This is a descriptive and analytical prospective study. A total of 143 Enterobacterales and 48 Pseudomonas aeruginosa isolates were collected from January 2018 to December 2018 from patients with respiratory, urinary and intra-abdominal infections. The identification was made by Phoenix automated system (BioMérieux). MIC50/90 were tested by broth microdilution for ceftolozane-tazobactam, and other drugs using dried panels. Antimicrobial susceptibility results were interpreted according to CLSI guidelines. Ceftolozane-tazobactam inhibited 98% of Escherichia coli (MIC50/90; 0.25/0.5 μg/mL). The susceptibility rate of Klebsiella pneumoniae to ceftolozane-tazobactam was 68.8% (MIC50/90, 0.5/>32 μg/mL); other Enterobacterales have shown susceptibility rates of 80.4% (MIC50/90; 0.5/8 μg/mL). In carbapenemase-producing K. pneumoniae, the blaOXA-48 mutation was found in two isolates. Susceptibility of P. aeruginosa to ceftolozane-tazobactam was 91.7% (MIC50/90, 0.5/>32 μg/mL). In non-carbapenemase-producing P. aeruginosa, AmpC mutations were found in all isolates. Ceftolozane-tazobactam was satisfactorily active against a wide range of tested isolates and offers clinicians a potential therapeutic option even against resistant strains in patients with intra-abdominal infections, urinary tract infections and nosocomial pneumonia.

Abstract Swine dysentery (SD) is an important endemic disease of pigs throughout the world. The most common aetiological agent is the anaerobic intestinal spirochaete Brachyspira hyodysenteriae. The related spirochaete Brachyspira pilosicoli causes a milder form of colitis. We report the first isolation of B. hyodysenteriae and B. pilosicoli from a pig farm in Hong Kong. Faecal samples containing mucus or fresh blood were collected from the ground where finisher pigs had just been loaded into a truck for transport to the abattoir. The samples were subjected to selective anaerobic culture and PCR for B. hyodysenteriae and B. pilosicoli, and two isolates of both species were obtained. The B. hyodysenteriae isolates showed clinical resistance to tylosin and lincomycin, whilst the B. pilosicoli isolates were resistant to tylosin and showed intermediate susceptibility to lincomycin. The B. hyodysenteriae isolates were subjected to multilocus sequence typing and a single previously undescribed sequence type (ST250) was identified. Disease was not recorded in other pigs on the farm, but it may have been masked by the use of antimicrobials. Further work is required to examine the distribution of these two pathogens in this and other farms in Hong Kong and in adjoining mainland China.

Background and Aim: Because of complexity in root canals, irrigating solutions are needed in addition to mechanical instrumentation for thorough cleansing of the root canal system. This in-vitro study was designed to determine the inhibitory effect of arginine, protamine, and aqueous extracts of green tea and aloe vera against Enterococcus faecalis (E. faecalis), which causes endodontic failure. Materials and Methods: In this experimental study, aqueous extracts of green tea and aloe vera and protamine at a concentration of 400 mg/ml and arginine at a concentra-tion of 160 mg/ml were used. E. faecalis was cultured on Mueller-Hinton broth, and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the test materials against these microorganisms were determined using serial dilutions and according to the microdilution test. The positive control was 2.5% sodium hypochlorite (NaOCl). Results: Aqueous extract of aloe vera has high antibacterial activity against E. faecalis (MIC=12.5 mg/ml and MBC=100 mg/ml), and protamine had the least effect (MIC=400 mg/ml and MBC>400 mg/ml) compared to other test materials. NaOCl, with MIC and MBC of 0.25 mg/ml against E. faecalis, showed higher antibacterial activity compared to other test materials. Conclusion: Among the tested materials, except for NaOCl as a positive control, aqueous extract of aloe vera showed better antibacterial properties against E. faecalis.

Introduction: Fungi broadly exist in the environment. Growing interest for natural and safe additives as well as concerns about synthetic fungicide have led to development of various fungicides. This study aimed to examine the effect of walnut thin shell ethanolic extract on the growth of Penicillium species. Methods: Antifungal effects were assessed at four different concentrations ranging from 5 to 350 mg/ml. The extract dilutions were exposed to the desired fungi using the broth dilution method, and minimum inhibitory concentrations (MIC) of fungi were determined and compared with the effects of nystatin and fluconazole. Results: The MIC for Penicillium italicum was 15 mg/ml for both walnut thin shell and fluconazole whereas it was 30 mg/ml for nystatin. Moreover, the minimum fungicidal concentration (MFC) for walnut thin shell, fluconazole and nystatin were 250, 30 and 60 mg/ml, respectively. The MIC for Penicillium expansum was 30 mg/ml for both walnut thin shell and fluconazole while it was 40 mg/ml for nystatin. The results also revealed that the MFC for these inhibitors was 300, 40 and 70 mg/ml, respectively. Furthermore, the MIC for Penicillium digitatum forboth the shell walnut extract and nystatin was 40 mg/ml while it was 20 mg/ml for fluconazole. The MFC for walnut thin shell, fluconazole and nystatin were 325, 100 and 70 mg/ml, respectively. Conclusion: Thin walnut shell extract has significant antifungal effects on Penicillium species and could be used as a natural antifungal. More research is required to assess the use of the extract for treatment of fungal infections.