Higher Minimum Inhibitory Concentration Values Research Articles

Population pharmacokinetics of meropenem in critically ill children with different renal functions.

We aimed to develop a meropenem population pharmacokinetic (PK) model in critically ill children and simulate dosing regimens in order to optimize patient exposure. Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem PK was investigated using a non-linear mixed-effect modeling approach. Forty patients with an age of 16.8 (1.4-187.2) months, weight of 9.1 (3.8-59) kg, and estimated glomerular filtration rate (eGFR) of 151 (19-440) mL/min/1.73m2 were included. Eleven patients received continuous replacement renal therapy (CRRT). Concentration-time courses were best described by a two-compartment model with first-order elimination. Body weight (BW), eGFR, and CRRT were covariates explaining the between-subject variabilities on central/peripheral volume of distribution (V1/V2), inter-compartment clearance (Q), and clearance (CL): V1i = V1pop × (BW/70)1, Qi= Qpop × (BW/70)0.75, V2i = V2pop × (BW/70)1, CLi = (CLpop × (BW/70)0.75) × (eGFR/100)0.378) for patients without CRRT and CLi = (CLpop × (BW/70)0.75) × 0.9 for patients with CRRT, where CLpop, V1pop, Qpop, and V2pop are 6.82L/h, 40.6L, 1L/h, and 9.2L respectively normalized to a 70-kg subject. Continuous infusion, 60 and 120mg/kg per day, is the most adequate dosing regimen to attain the target of 50% fT > MIC and 100% fT > MIC for patients infected by bacteria with high minimum inhibitory concentration (MIC) value (> 4mg/L) without risk of accumulation except in children with severe renal failure. Continuous infusion allows reaching the fT > MIC targets safely in children with normal or increased renal clearance.

Emergence of mcr-1 conferred colistin resistance among bacterial isolates from urban sewage water in India.

Increased use of colistin, a last resort drug due to failure of carbapenems, has possibly contributed in development and spread of resistance to colistin among Enterobacteriaceae. The colistin belongs to the family of polymyxins, cationic polypeptides, with broad-spectrum activity against Gram-negative bacteria. In this study, we obtained 253 non-duplicate bacterial isolates from sewage water in Delhi and phenotypically screened for colistin resistance. Of the 47 positive isolates, the colistin resistance gene mcr-1 was detected among 5 isolates. Based on 16S ribosomal RNA-based identification, bacterial isolates were found to be Escherichia coli, Aeromonas veronii, and Aeromonas dhakensis. Extended spectrumβ-lactamases (ESBL)-resistant determinants CTX-M and TEM were detected in all five mcr-1 positive isolates. On the basis of literature survey, this is the first report of mcr-1 gene from Aeromonas veronii and Aeromonas dhakensis worldwide. Furthermore, mcr-1 gene has not been reported earlier from sewage water in India. Antibiotic susceptibility test of all five isolates against 9 different classes of drugs revealed multidrug-resistant phenotype with high minimum inhibitory concentration values. In vitro transconjugation studies showed successful transfer of mcr-1 and other ESBL-resistant determinants. The occurrence of colistin resistance phenotype conferred by plasmid-based mcr-1 gene in the environment and an ever-increasing list of bacterial isolates is a cause of concern. A comprehensive survey of different water bodies and epidemiological studies are required to assess the risk of dissemination of resistance determinants.

Carbapenemase-Producing Elizabethkingia Meningoseptica from Healthy Pigs Associated with Colistin Use in Spain.

Carbapenems are considered last-resort antimicrobials, especially for treating infections involving multidrug-resistant Gram-negative bacteria. In recent years, extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Gram-negative bacteria have become widespread in hospitals, community settings, and the environment, reducing the range of effective therapeutic alternatives. The use of colistin to treat infection caused by these multi-drug bacteria may favour the selection and persistence of carbapenem-resistant bacteria. In this study, it is described, for the first time to our knowledge, a carbapenemase-producing isolate of Elizabethkingia meningoseptica from healthy pigs in Spain. The isolate we report was recovered during a study to detect colistin-resistant bacteria from faecal samples of healthy food-production animals using a chromogenic selective medium. Unexpectedly, we found an isolate of Elizabethkingia meningoseptica with high Minimum Inhibitory Concentration (MIC) values for several antibiotics tested. Molecular analysis did not show any mcr family genes related with colistin resistance, but two carbapenemase genes, blaB-12_1 and blaGOB-17_1, were detected. This finding in healthy animals could suggest that colistin may favour the selection and persistence of carbapenem-resistant bacteria.

High prevalence of itraconazole resistance among Candida parapsilosis isolated from Iran.

Background and Purpose:Candida parapsilosis isolates usually have a low minimum inhibitory concentration (MIC) against azoles. Although Candida parapsilosis isolates usually have low MICs against azoles, recent studies candida invasive infections due to azole resistant-C. parapsilosis isolates . Regarding this, the main aim of this study was to determine the susceptibility pattern of Iranian clinical C. parapsilosis against available azole antifungal drugs.Materials and Methods:This study was conducted on 105 previously-identified isolates of C. parapsilosis sensu stricto. For the purpose of the study, the isolates were subjected to antifungal susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), voriconazole (VRZ), and two new azole drugs, namely luliconazole (LUZU) and lanoconazole (LZN). The broth microdilution reference method adopted in this study was according to the Clinical & Laboratory Standards Institute M27-A3 and M27-S4 documents.Results:According to the results, 89% (n=94) of C. parapsilosis isolates showed a MIC of ≥ 1 µg/ml, indicating resistance against ITZ. Multi-azole resistance was observed in 3.8% of the isolates. In addition, LUZU and LZN demonstrated the highest efficacy with the MIC50 values of 0.5 and 1 µg/ml, respectively.Conclusion:The majority of the isolates showed high MIC values against ITZ. This may have been associated with the long-term ITZ prophylaxis/therapy in patients infected with candidiasis. Hence, the adoption of an appropriate antifungal agent is a crucial step for starting the treatment.

Culturable halophilic bacteria inhabiting Algerian saline ecosystems: A source of promising features and potentialities

This paper aims to characterize halophilic bacteria inhabiting Algerian Saline Ecosystems (Sebkha and Chott) located in arid and semi-arid ecoclimate zones (Northeastern Algeria). In addition, screening of enzymatic activities, heavy metal tolerance and antagonistic potential against phytopathogenic fungi were tested. A total of 74 bacterial isolates were screened and phylogenetically characterized using 16S rRNA gene sequencing. The results showed a heterogeneous group of microorganisms falling within two major phyla, 52 strains belonging to Firmicutes (70.2%) and 22 strains (30.8%) of γ-Proteobacteria. In terms of main genera present, the isolates were belonging to Bacillus, Halobacillus, Lentibacillus, Oceanobacillus, Paraliobacillus, Planomicrobium, Salicola, Terribacillus, Thalassobacillus, Salibacterium, Salinicoccus, Virgibacillus, Halomonas, Halovibrio, and Idiomarina. Most of the enzymes producers were related to Bacillus, Halobacillus, and Virgibacillus genera and mainly active at 10% of growing salt concentrations. Furthermore, amylase, esterase, gelatinase, and nuclease activities ranked in the first place within the common hydrolytic enzymes. Overall, the isolates showed high minimal inhibitory concentration values (MIC) for Ni2+ and Cu2+ (0.625 to 5mM) compared to Cd2+ (0.1 to 2mM) and Zn2+ (0.156 to 2mM). Moreover, ten isolated strains belonging to Bacillus, Virgibacillus and Halomonas genera, displayed high activity against the pathogenic fungi (Botrytis cinerea, Fusarium oxyporum, F. verticillioides and Phytophthora capsici). This study on halophilic bacteria of unexplored saline niches provides potential sources of biocatalysts and novel bioactive metabolites as well as promising candidates of biocontrol agents and eco-friendly tools for heavy metal bioremediation.

Epidemiological aspects and characterization of the resistance profile of Fusarium spp. in patients with invasive fusariosis.

Introduction. The remarkable intrinsic resistance of Fusarium species to most antifungal agents results in high mortality rates in the immunocompromised population.Aims. This study aimed to investigate the epidemiology, clinical features and antifungal susceptibility of Fusarium isolates in patients with invasive fusariosis.Methodology. A total of 27 patients admitted to a referral hospital from January 2008 to June 2017 were evaluated. Antifungal susceptibility testing of isolates was performed by broth microdilution according to the Clinical and Laboratory Standards Institute guidelines.Results. Haematological malignancy was the predominant underlying condition, with an incidence of invasive fusariosis of 14.8 cases per 1000 patients with acute lymphoid leukaemia and 13.1 cases per 1000 patients with acute myeloid leukaemia. The Fusarium solani species complex (FSSC) was the most frequent agent group, followed by the Fusarium oxysporum species complex (FOSC). Voriconazole showed the best activity against Fusarium, followed by amphotericin B. Itraconazole showed high minimum inhibitory concentration values, indicating in vitro resistance. Clinical FSSC isolates were significantly (P<0.05) more resistant to amphotericin B and voriconazole than FOSC isolates.Conclusion. The present antifungal susceptibility profiles indicate a high incidence of fusariosis in patients with haematological malignancy. Species- and strain-specific differences in antifungal susceptibility exist within Fusarium in this setting.

Apiotrichum veenhuisii isolated from a pediatric patient with acute myeloid leukemia: The first case in humans

ABSTRACTThis is the first report of the yeast Apiotrichum veenhuisii (formerly Trichosporon veenhuisii) causing disease in humans; its virulence and in vitro behavior against antifungals were also studied. The sample was isolated from biopsy fragments of disseminated lesions on the skin of a pediatric patient with acute myeloid leukemia. The studied virulence factors evidenced that the strain tested negative for secretion of the enzymes proteinase, phospholipase, and hemolysin. The isolate was characterized as low biofilm producer. Except for amphotericin B and voriconazole, the sample presented high minimum inhibitory concentration values against azole and echinocandins.

Characterization of an Outbreak of Infectious Coryza (Avibacterium paragallinarum) in Commercial Chickens in Central California.

In 2017, the Turlock branch of the California Animal Health & Food Safety laboratory system received a significant increase in infectious coryza (IC) necropsy cases, with a total of 54 submissions originating from commercial broilers (n = 40), commercial layers (n = 11), and backyard chickens (n = 3). Layer flocks positive for IC were distributed within the adjacent counties of Merced and Stanislaus, while broiler flocks were concentrated within Merced County. The backyard flocks were located in Alameda and Sacramento counties. The clinical and pathologic presentation was consistent with IC, although septicemic lesions were also noticed. Avibacterium paragallinarum was isolated and identified by PCR from the respiratory tract as well as from extrarespiratory sites. Polymicrobial infections involving other viral (infectious bronchitis virus, infectious bursal disease virus) and bacterial (Mycoplasma spp., Escherichia coli, Ornithobacterium rhinotracheale, Gallibacterium anatis biovar haemolytica) agents were commonly reported. Thirteen selected Av. paragallinarum isolates were successfully characterized as serovar C (Page scheme) and serovar C2 (Kume scheme). They shared a unique enterobacterial repetitive intergenic consensus (ERIC) PCR, differing from the four reference strains, and showed consistent high minimum inhibitory concentration values for tetracycline, suggesting a common origin from a single clone. Based on these results, high biosecurity standards and proper immunization of susceptible, multi-age flocks should always be implemented and adjusted as needed. The importance of backyard flocks should not be underestimated due to their unique epidemiologic role.

Propionibacterium acnes Infection in Disc Material and Different Antibiotic Susceptibility in Patients With Lumbar Disc Herniation.

Low back pain is an important, worldwide clinical problem from which human populations are suffering. It has been suggested that Propionibacterium acnes is associated with low back pain. The objective of this clinical study is to evaluate the P. acnes infection in the disc material and antibiotic susceptibility in patients with disc herniation. A total of 120 patients with disc herniation surgery were enrolled in the study. The samples were excited during discectomy and then cultured in both anaerobic and aerobic incubations. Minimum inhibitory concentration (MIC) was performed for determination of antibiotic susceptibility. Of 120 samples, 60 (50%) samples were positive for microorganisms. Disc herniation was at the level of L4-L5 in 63 cases and L5-S1 in 57 cases. According to the results and presence of P. acnes in more than 35% of the cultured samples, the presence of P. acnes in lumbar disc herniation is a suspected element leading to this condition. After analysis of the antibiotics, the lowest MIC value was identified for amoxicillin, ciprofloxacin, erythromycin, rifampicin, tetracycline, vancomycin; the moderate MIC value was for fusidic acid; and the highest MIC value was for gentamicin and trimethoprim.

Essential oil of four medicinal plants and protective properties in plum fruits against the spoilage bacteria and fungi

There are limited studies available regarding the chemical composition of essential oils and their activities against fruit spoilage bacteria and fungi. In this study, chemical composition of essential oils from medicinal plants namely Acorus calamus, Allium sativum, Mucuna pruriens, and Sesamum indicum L showed invitro antibacterial and antifungal properties against fruits spoilage microbes were evaluated. Gas Chromatograph-Mass Spectrometry analysis confirmed the presence of major metabolites namely Hydroxylamine (98.26%), 1,2,4 - trimethoxy-5-1-propenyl (93.07%), Dodecanoic acid, 1,2,3-propanetriyl ester (92.64) and 2-diisoprophylphosphinnoethane (67.97%) from the studied plants. The minimum inhibitory concentration of the essential oils against bacteria were ranged from 11.3 ± 2.3 to 617 ± 4.9 μg/ml and fungi were ranged from 1.1 ± 0.4 to 292 ± 3.2 μg/ml, respectively. Among the essential oil, Allium sativum showed significant antibacterial activity with least minimum inhibitory concentration and minimum bactericidal concentrations (11.3 ± 2.3 μg/ml and 24 ± 1.6 μg/ml) while Sesamum indicum oil showed the least activity with high minimum inhibitory concentration and minimum bactericidal concentrations values (460 ± 11.9 μg/ml and 940 ± 12.8 μg/ml). Interestingly, Allium sativum documented the highest antifungal activity against Penicillium notatum and also significantly inhibited the growth of other tested fungal species such as, Aspergillus niger, Aspergillus flavus and Rhizopus microsporus. Among all tested essential oils, in combination of studied antibiotics, essential oils from Allium sativum showed excellent synergistic activity against seven out of nine spoilage microbes. Two-way analysis of variance showed significant depletion of pathogenic microorganism due to the effect of essential oils (p < 0.05). In addition, essential oil from Allium sativum significantly reduced the growth of Aspertillus flavus and Aspergillus niger on plum fruit. Results revealed the application of essential oil from Allium sativum counter Aspergillus flavus growth and prevented deterioration of plum fruit.

Methicillin-Resistant Staphylococcus Strains Isolated from Adult Intensive Care Units with E-test MIC Values of Different Antibiotic Research

Objective: Nasocomial infections are major health problems due to their high morbidity and mortality, prolonged hospital duration and higher treatment costs. Methicillin-resistant staphylococcus species became one of the leading bacteria causing nasocomial infections especially in intensive care units, recently. The minimum inhibitory concentration value of an antibiotic gives the concentration of antibiotic needed to inhibit the bacteria in the infection area. Careful monitoring of minimal inhibitory concentration (MIC) values is necessary especially during long-term treatments of meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-resistant coagulase-negative staphylococci (MRCoNS) infections 1,2 . Increasing antibiotic resistance in methicillin-resistant staphylococci, has led to the need for different antibiotics. Methods: A total of 60 meticillin-resistant staphylococci strains isolated in Microbiology Laboratory of Dicle University Hospital, from clinical specimens of patients in adult Intensive Care Units (ICUs) between April 2013 and March 2014 were included in this study. After identification with conventional and automated system, the antibiotic susceptibility rates of vancomycin, teicoplanin, daptomycin, linezolid, quinupristin/dalfopristin, tigecycline, ceftaroline were determined by E-test method. Results: The majority of the samples (26.7%) were sent from Pulmonary Diseases and Tuberculosis intensive care unit and the blood samples were the most common materials (80%) . All staphylococcal strains in our study were determined as susceptible to vancomycin, daptomycin, linezolid, teicoplanin and tigecycline. One (1.6%) MRCoNS isolate was resistant to quinupristin/dalfopristin while 11 (36.6%) of the MRSA isolates were resistant to ceftaroline. In comparison with the MIC values of MRSA and MRCoNS, only tigecycline was significantly different. Thirty MRSA strains were evaluated in terms of vancomycin-intermediate Staphylococcus aureus /heteroresistant vancomycin-intermediate Staphylococcus aureus (VISA/hVISA) with macro E-test method; any VISA/hVISA isolate was not detected. Antibiotic concentrations below the MIC level, not only leads to treatment failure but also causes mutant bacteria to appear. In order to control the resistance to antibiotics in the treatment of infections due to MRSA and MRCoNS agents, the clinician should be notified of the MIC values of the drugs and the treatment should be planned accordingly. VISA/hVISA isolates should be considered in treatment failures of infections due to MRSA which are in vitro susceptible to vancomycin. Further testing is needed to detect these isolates. Despite the fact that ceftaroline is not a drug used in our country, the high resistance rate in our study is remarkable. This situation may be due to the intensive use of other beta-lactam antibiotics. Therefore, antibiotic susceptibility results should be taken into consideration during planning the treatment of infections. The high average MIC values of tigecycline in MRCoNS infections should also be monitored carefully

Evaluation of in vitro antimicrobial susceptibility of Bacillus anthracis strains isolated during anthrax outbreaks in Italy from 1984 to 2017.

Anthrax, caused by Bacillus anthracis, is a non-contagious infectious disease that affects a wide range of animal species (primarily ruminants) including humans. Due to the often-fatal outcome in humans, quick administration of definitely effective antimicrobials is crucial either as prophylaxis or as a clinical case therapy. In this study, 110 B. anthracis strains, temporally, geographically, and genetically different, isolated during anthrax outbreaks in Italy from 1984 to 2017, were screened using a broth microdilution method to determine their susceptibility to 16 clinically relevant antimicrobial agents. The strains were isolated from various matrices (human, animal, and environmental samples) and were representative of thirty distinct genotypes previously identified by 15-loci multiple-locus variable-number of tandem repeats analysis. The antimicrobials tested were gentamicin, ceftriaxone, streptomycin, penicillin G, clindamycin, chloramphenicol, vancomycin, linezolid, cefotaxime, tetracycline, erythromycin, rifampin, amoxicillin, ciprofloxacin, doxycycline, and trimethoprim. All isolates were susceptible to most of the tested antimicrobials, with the exception of trimethoprim for which all of them showed high minimal inhibitory concentration values. An intermediate level of susceptibility was recorded for ceftriaxone and cefotaxime. Although the Centers for Disease Control and Prevention recommend the use of doxycycline, ciprofloxacin, penicillin G, and amoxicillin for treatment of human cases and for post-exposure prophylaxis to anthrax spores, this study shows a high degree of in vitro susceptibility of B. anthracis to many other antimicrobials, suggesting the possibility of an alternative choice for prophylaxis and therapy.

Acinetobacter species in laboratory mice: species survey and antimicrobial resistance.

The extra-hospital epidemiology of Acinetobacter infections is a subject of debate. In recent years, the prevalence of animal multidrug-resistant Acinetobacter infections has increased considerably. The goal of the present study was to specify Acinetobacter species isolated from laboratory mice and to test them for their antimicrobial susceptibility. During routine microbiological monitoring of laboratory mice, 12 Acinetobacter spp. were isolated. By means of 16S rRNA and rpoB gene sequencing, seven of the isolates were identified as Acinetobacter radioresistens, three isolates belonged to Acinetobacter genomospecies 14BJ, one isolate was classified as Acinetobacter pitii and one as Acinetobacter sp. ANC 4051. The distribution of the minimal inhibitory concentration (MIC) values was uniform for 21 of the 23 antimicrobial agents tested, whereas a broad MIC distribution was recorded for tulathromycin and streptomycin. The MIC values recorded were low for the majority of the antibiotics tested. Nevertheless, very high MIC values, which will probably render a therapeutic approach using these substances unsuccessful, were recorded for florfenicol, tiamulin, tilmicosin and cephalothin in most of the isolates. In conclusion, we document colonization of laboratory mice with different Acinetobacter species, displaying similar antibiotic susceptibility profiles, with possible implications in the Acinetobacter epidemiology as well as in the husbandry and experimentation of the colonized animals.

Antibiotic susceptibility testing of Mycoplasma hyopneumoniae field isolates from Central Europe for fifteen antibiotics by microbroth dilution method.

Mycoplasma hyopneumoniae infections are responsible for significant economic losses in the swine industry. Commercially available vaccines are not able to inhibit the colonisation of the respiratory tract by M. hyopneumoniae absolutely, therefore vaccination can be completed with antibiotic treatment to moderate clinical signs and improve performances of the animals. Antibiotic susceptibility testing of M. hyopneumoniae is time-consuming and complicated; therefore, it is not accomplished routinely. The aim of this study was to determine the in vitro susceptibility to 15 different antibiotics of M. hyopneumoniae isolates originating from Hungarian slaughterhouses and to examine single-nucleotide polymorphisms (SNPs) in genes affecting susceptibility to antimicrobials. Minimum inhibitory concentration (MIC) values of the examined antibiotics against 44 M. hyopneumoniae strains were determined by microbroth dilution method. While all of the tested antibiotics were effective against the majority of the studied strains, high MIC values of fluoroquinolones (enrofloxacin 2.5 μg/ml; marbofloxacin 5 μg/ml) were observed against one strain (MycSu17) and extremely high MIC values of macrolides and lincomycin (tilmicosin, tulathromycin and lincomycin >64 μg/ml; gamithromycin 64 μg/ml; tylosin 32 μg/ml and tylvalosin 2 μg/ml) were determined against another, outlier strain (MycSu18). Amino acid changes in the genes gyrA (Gly81Ala; Ala83Val; Glu87Gly, according to Escherichia coli numbering) and parC (Ser80Phe/Tyr; Asp84Asn) correlated with decreased antibiotic susceptibility to fluoroquinolones and a SNP in the nucleotide sequence of the 23S rRNA (A2059G) was found to be associated with increased MIC values of macrolides. The correlation was more remarkable when final MIC values were evaluated. This study presented the antibiotic susceptibility profiles of M. hyopneumoniae strains circulating in the Central European region, demonstrating the high in vitro efficacy of the tested agents. The observed high MIC values correlated with the SNPs in the examined regions and support the relevance of susceptibility testing and directed antibiotic therapy.

Antibiotic susceptibility profiles of Mycoplasma hyorhinis strains isolated from swine in Hungary

Mycoplasma hyorhinis is a common pathogen of swine causing mainly polyserositis and arthritis, but it has also been implicated as a cause of pneumonia. The economic losses due to M. hyorhinis infection could be reduced by antibiotic treatment. The aim of this study was to determine minimal inhibitory concentrations (MIC) of antibiotics potentially used to combat M. hyorhinis in swine production.Thirty-eight Hungarian M. hyorhinis strains isolated between 2014 and 2017 were examined by microbroth dilution tests for fifteen antimicrobial agents. Low MIC values of tetracyclines (MIC50 0.078 μg/ml for doxycycline, ≤0.25 μg/ml for oxytetracycline) and pleuromutilins (MIC50 0.156 μg/ml for tiamulin, ≤0.039 μg/ml for valnemulin) were detected against all strains. Fluoroquinolones (MIC50 0.625 μg/ml), gentamicin (MIC50 1 μg/ml) and florfenicol (MIC50 2 μg/ml) inhibited the growth of Hungarian isolates at moderate MIC values. Most of the strains were inhibited by spectinomycin with low or moderate MIC values (MIC50 4 μg/ml) except one strain (>64 μg/ml). Numerous isolates showed decreased susceptibility to macrolides and lincomycin (MIC90 >64 for tylosin, tilmicosin, tulathromycin, gamithromycin, lincomycin, 8 μg/ml for tylvalosin).This study serves as evidence for the increasing resistance to macrolides and lincomycin in mycoplasmas, and also reports the occurrence of strains with extremely high MIC values to spectinomycin thus emphasizes the importance of the prudent use of antibiotics. Based on our results, tetracyclines and pleuromutilins are the most active compounds in vitro against the Hungarian M. hyorhinis strains.

Detection of beta-lactamase-negative ampicillin resistance in Haemophilus influenzae in Belgium

Haemophilus influenzae, a frequent colonizer of the respiratory tract, is the causative agent of several clinically important infections. In cases that require therapeutic intervention, laboratory susceptibility testing can detect beta-lactam antibiotic resistance and guide the best treatment course. In the absence of a beta-lactamase, beta-lactam resistance may be due to an altered form of the PBP3 protein, encoded by the ftsI gene. While these so-called beta-lactamase-negative ampicillin-resistant (BLNAR) strains are of serious clinical interest, identification in the clinical laboratory is not always straightforward. In the current study, the ftsI genes of a set of phenotypic BLNAR H. influenzae isolates taken from samples collected in the UZ Brussel hospital in Belgium were sequenced and re-tested at the National Reference Laboratory (NRC). Non-silent mutations in the ftsI gene were found in 100% of the isolates. Although 30% of the isolates were classified by the NRC as beta-lactamase-negative ampicillin-sensitive (BLNAS) strains based on the EUCAST guidelines on ampicillin minimal inhibitory concentration (MIC), all isolates showed MIC values ≥1 mg/L. These relatively high MIC values indicate a decreased susceptibility to ampicillin, and suggest that sequencing of the ftsI gene should be used as part of an antibiotic susceptibility testing (AST) algorithm in the clinical laboratory. This would allow clinicians to make better informed decisions regarding patient treatment.

Fungicidal versus Fungistatic activity of five Iranian essences against fluconazole resistant Candida species

Introduction: Antifungal resistant is one of the causes of high mortality rates during invasive candidiasis. Since development of new antifungal agents is limited, researchers have focused on natural products including essential oils (EOs) with antifungal properties. In immunocompromised patients fungicidal activity is of benefit. This study was designed to evaluate chemical composition and fungicidal/fungistatic activities of five Iranian EOs and against fluconazole resistant Candida species.Methods: To determine chemical composition of EOs gas chromatography-mass spectroscopy (GC/MS) was employed. Fluconazole resistant Candida species were chosen and minimum inhibitory concentration (MIC) values of studied EOs were determined by broth microdilution method. Minimum fungicidal concentration (MFC) was determined as the lowest concentration with no fungal growth on solid media. Fungicidal activity was calculated by MFC/MIC ratio.Results: The results showed that C. albicans and C. tropialis isolates were susceptible to itraconazole (ITC) and voriconazole (VRC) while one species of C. glabrata and C. krusei each was resistant to itraconzaole; and itraconazole resistant C. glabrata isolate was resistance to voriconzaole as well. Among tested EOs, the ones from Cinnamomum cayennense, Origanum majorana var. majoranoides and Andropogon citratus had the highest anti-Candida activity. Artemisia aromatica A. Nelson had the highest MIC value against Candida isolates. All EOs in this study had fungicidal activity.Conclusion: In general, the tested natural compounds are suitable to be used as anti-Candida. However more studies are needed on each chemical compound to evaluate its antifungal activity alone or in combination with other agents.

Novel Alkylimidazolium Ionic Liquids as an Antibacterial Alternative to Pathogens of the Skin and Soft Tissue Infections.

Keeping in mind the concept of green chemistry, this research aims to synthesize and characterize new ionic liquids (ILs) derived from N-cinnamyl imidazole with different sizes of alkyl chains (1, 6, 8, and 10 carbon atoms), and evaluate their antibacterial activity against Skin and soft tissue infections (SSTIs) causative bacteria. The antibacterial screening was carried out by agar well diffusion and the Minimum Inhibitory Concentration (MIC) and Half Maximum Inhibitory Concentration (IC50) of the different ILs were determined by microdilution in broth, also Molecular dynamics simulations were performed to study the interaction mechanism between ILs and membranes. The MIC value in Gram-positive bacteria showed that as the hydrocarbon chain increases, the MIC value decreases with a dose-dependent effect. Furthermore, Gram-negative bacteria showed high MIC values, which were also evidenced in the antibacterial screening. The molecular dynamics showed an incorporation of the ILs with the longer chain (10 C), corresponding to a passive diffusion towards the membrane surface, for its part, the ILs with the shorter chain due to its lack of hydrophobicity was not incorporated into the bilayer. Finally, the new ILs synthesized could be an alternative for the treatment of Gram-positive bacteria causative of SSTIs.

Antimycobacterial, Enzyme Inhibition, and Molecular Interaction Studies of Psoromic Acid in Mycobacterium tuberculosis: Efficacy and Safety Investigations.

The current study explores the antimycobacterial efficacy of lichen-derived psoromic acid (PA) against clinical strains of Mycobacterium tuberculosis (M.tb). Additionally, the inhibitory efficacy of PA against two critical enzymes associated with M.tb, namely, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), as drug targets for antituberculosis therapy were determined. PA showed a profound inhibitory effect towards all the M.tb strains tested, with minimum inhibitory concentrations (MICs) ranging between 3.2 and 4.1 µM, and selectivity indices (SIs) ranging between 18.3 and 23.4. On the other hand, the standard drug isoniazid (INH) displayed comparably high MIC values (varying from 5.4 to 5.8 µM) as well as low SI values (13.0–13.9). Interestingly, PA did not exhibit any cytotoxic effects on a human liver hepatocellular carcinoma cell line even at the highest concentration tested (75 µM). PA demonstrated remarkable suppressing propensity against UGM compared to standard uridine-5'-diphosphate (UDP), with 85.8 and 99.3% of inhibition, respectively. In addition, PA also exerted phenomenal inhibitory efficacy (half maximal inhibitory concentration (IC50) value = 8.7 µM, and 77.4% inhibition) against TBNAT compared with standard INH (IC50 value = 6.2 µM and 96.3% inhibition). Furthermore, in silico analysis validated the outcomes of in vitro assays, as the molecular interactions of PA with the active sites of UGM and TBNAT were unveiled using molecular docking and structure–activity relationship studies. Concomitantly, our findings present PA as an effective and safe natural drug plausible for use in controlling tuberculosis infections.

Effect of Extracts of Capparis spinosa, Withania somnifera and Peganum harmala on Aspergillus flavus Growth and Expression of Major Genes in Aflatoxin Biosynthetic Pathway

Background: Aflatoxins, a polyketide group derived from furanocoumarins, are highly toxic carcinogens produced by Aspergillus flavus and other closely related species. Objectives: In this research, the effects of Capparis spinosa, Withania somnifera, and Peganum harmala extracts on A. flavus growth and the expression of some major genes in aflatoxin biosynthetic pathway were investigated. Methods: Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were measured and the expression of aflQ, aflO, aflS, and aflR genes was evaluated by using quantitative real-time polymerase chain reaction (qRT-PCR) technique. Results: Capparis spinosa extract had the lowest MIC value (200 mg/mL) and the extracts of W. somnifera and P. harmala had the highest MIC value (400 mg/mL). The extracts of W. somnifera and P. harmala had no fungicidal activity, and the C. spinosa extract had the lowest MFC value (400 mg/mL) and had the highest fungicidal effect on A. flavus. The expression of aflQ, aflO, aflS, and aflR genes was significantly decreased by the C. spinosa extract. Conclusions: In general, the C. spinosa extract could have fungicidal and inhibitory effects on A. flavus and reduce expression of major genes in the aflatoxin biosynthetic pathway.