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Introduction: Healthcare-associated infections are a global public health issue with farreaching individual and economic repercussions. The microorganism’s multi-resistance frequently increases the risk that can be lowered by using biomolecules of medicinal plant essential oils (EOs). This study investigated the phytochemical components and antimicrobial potential of the EOs of Moroccan Origanum compactum and Ruta montana gathered from Taza Region. Methods: The EOs’ chemical analysis was performed by GC/MS and their antimicrobial effects were assessed by the microplate dilution method against eight nosocomial resistantbacterial strains. Results: The main constituents of O. compactum EO were Thymol (29.56%), carvacrol (26.44%), γ-terpinene (18.86%) and p-cymene (12.01%), while those of R. montana EO were 2-undecanone (85.76%), 2-nonanone (3.95%), 2-decanone (3.67%) and 2-dodecanone (1.94%). The O. compactum EO had important antimicrobial effects on all bacteria experienced. The lower minimum inhibitory concentration (MIC) values were obtained for the tested Staphylococcus species (0.062%, 0.125% (v/v)) while the highest one (2% (v/v)) was obtained for Klebsiella pneumonia and Pantoea spp. The R. montana EO showed MIC values of 4% (v/v) for Pantoea spp. and 8% (v/v) for the other tested strains except K. pneumonia for which no effect was shown. Conclusion: Therefore, these EOs, especially the O. compactum one, have an interesting antibacterial potential against nosocomial infections and might be used to develop new antimicrobial agents.

Context: At present, commonly encountered infections like urinary tract infections (UTIs) are becoming more and more difficult to treat. UTIs caused by extended-spectrum β-lactamase (ESBL) organisms tend to lead to uncertain outcomes and prolong hospitalization as these organisms are multidrug resistant. Such a situation has forced clinicians to reconsider the use of old antibiotics like fosfomycin. Aims: To determine fosfomycin susceptibility among ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates causing UTI in a tertiary care center in Western India. Settings and Design: This is a cross-sectional study done in the Department of Microbiology between July 2021 and July 2022. Methods and Material: Urine samples from all outpatients and inpatients with suspected UTI which were received in the microbiology laboratory were inoculated in appropriate culture media. Pure growth of bacteria with a significant colony count was identified and antibiotic susceptibility testing was done as per standard guidelines. Statistical Analysis Used: The collected data were entered in a Microsoft Excel sheet and analyzed. Results: A total of 437 urine samples were collected from which 39 isolates of ESBL E. coli and 10 isolates of ESBL Klebsiella pneumoniae were obtained. All the E. coli isolates were sensitive to fosfomycin, while two of the Klebsiella pneumoniae isolates were resistant to fosfomycin. Conclusions: Older antibiotics like fosfomycin and nitrofurantoin attain high concentrations in the urinary tract, have a minimal impact on gastrointestinal flora, and do not develop resistance as compared to many other antibiotics. Therefore, fosfomycin should be preferred for the treatment of uncomplicated UTIs caused by resistant strains.

Aim: The development of carbon quantum dots (C-QDs) as nanotrackers to understand drug–pathogen interactions, virulence and multidrug resistance. Methods: Microwave synthesis of C-QDs was performed using citric acid and polyethylene glycol. Further, in vitro toxicity was evaluated and imaging applications were demonstrated in Candida albicans isolates. Results: Well-dispersed, ultra small C-QDs exhibited no cyto/microbial/reactive oxygen species-mediated toxicity and internalized effectively in Candida yeast and hyphal cells. C-QDs were employed for confocal imaging of drug-sensitive and -resistant cells, and a study of the yeast-to-hyphal transition using atomic force microscopy in Candida was conducted for the first time. Conclusion: These biocompatible C-QDs have promising potential as next-generation nanotrackers for in vitro and in vivo targeted cellular and live imaging, after functionalization with biomolecules and drugs. Scientists have used radiolabeled drugs and radioactive tracking agents for the imaging and study of drug resistance in microbial pathogens. But, these radiolabeled drugs or radiotrackers pose health hazards and environmental risks. However, such limitations can be overcome by designing nontoxic, environment-friendly, nanotechnology-based fluorescent imaging agents. This study demonstrates the development and application of cost-effective, nontoxic carbon-based quantum dots for imaging of drug-sensitive and -resistant microbial strains and transition to different morphological forms (yeast-to-hyphae transition) in fungal pathogens. The results demonstrated the suitability of carbon quantum dots as next-generation nano-based bioimaging/tracking agents for cellular imaging. The availability of such nontoxic fluorescent tracking agents is likely to offer promising solutions in therapeutics and diagnostics by providing insight into various mechanisms and functional links related to drug resistance, virulence and pathogenicity. [ABSTRACT FROM AUTHOR]

Context: At present, commonly encountered infections like urinary tract infections (UTIs) are becoming more and more difficult to treat. UTIs caused by extended‑spectrum β‑lactamase (ESBL) organisms tend to lead to uncertain outcomes and prolong hospitalization as these organisms are multidrug resistant. Such a situation has forced clinicians to reconsider the use of old antibiotics like fosfomycin. Aims: To determine fosfomycin susceptibility among ESBL‑producing Escherichia coli and Klebsiella pneumoniae isolates causing UTI in a tertiary care center in Western India. Settings and Design: This is a cross‑sectional study done in the Department of Microbiology between July 2021 and July 2022. Methods and Material: Urine samples from all outpatients and inpatients with suspected UTI which were received in the microbiology laboratory were inoculated in appropriate culture media. Pure growth of bacteria with a significant colony count was identified and antibiotic susceptibility testing was done as per standard guidelines. Statistical Analysis Used: The collected data were entered in a Microsoft Excel sheet and analyzed. Results: A total of 437 urine samples were collected from which 39 isolates of ESBL E. coli and 10 isolates of ESBL Klebsiella pneumoniae were obtained. All the E. coli isolates were sensitive to fosfomycin, while two of the Klebsiella pneumoniae isolates were resistant to fosfomycin. Conclusions: Older antibiotics like fosfomycin and nitrofurantoin attain high concentrations in the urinary tract, have a minimal impact on gastrointestinal flora, and do not develop resistance as compared to many other antibiotics. Therefore, fosfomycin should be preferred for the treatment of uncomplicated UTIs caused by resistant strains. [ABSTRACT FROM AUTHOR]

Ocular pathologies present significant challenges to achieving effective therapeutic results due to various anatomical and physiological barriers. Natural products such as flavonoids, alone or in association with allopathic drugs, present many therapeutic actions including anticancer, anti-inflammatory, and antibacterial action. However, their clinical employment is challenging for scientists due to their low water solubility. In this study, we designed a liquid formulation based on rutin/sulfobutylether-β-cyclodextrin (RTN/SBE-β-CD) inclusion complex for treating ocular infections. The correct stoichiometry and the accurate binding constant were determined by employing SupraFit software (2.5.120) in the UV-vis titration experiment. A deep physical–chemical characterization of the RTN/SBE-β-CD inclusion complex was also performed; it confirmed the predominant formation of a stable complex (Kc, 9660 M−1) in a 1:1 molar ratio, with high water solubility that was 20 times (2.5 mg/mL) higher than the free molecule (0.125 mg/mL), permitting the dissolution of the solid complex within 30 min. NMR studies revealed the involvement of the bicyclic flavonoid moiety in the complexation, which was also confirmed by molecular modeling studies. In vitro, the antibacterial and antibiofilm activity of the formulation was assayed against Staphylococcus aureus and Pseudomonas aeruginosa strains. The results demonstrated a significant activity of the formulation than that of the free molecules. [ABSTRACT FROM AUTHOR]

Objective(s): Virulent strains of Pseudomonas aeruginosa exhibit multidrug resistance by intrinsic and extrinsic mechanisms which are regulated by quorum sensing signalling systems. This includes the production of auto-inducers and their transcriptional activators to activate various virulence factors resulting in host infections. The present study is thus aimed to detect the virulence factor production, quorum sensing activity, and susceptibility pattern of P. aeruginosa to antibiotics from clinical specimens.Materials and Methods: A total of 122 isolates of P. aeruginosa were phenotypically characterized by standard protocols and were categorized into MDR and non-MDR based on the antibiotic susceptibility profiles. Pyocyanin, alkaline protease and elastase production were assessed by qualitative and quantitative methods. Crystal violet assay was carried out for the quantification of biofilms. The genetic determinants of virulence were detected by PCR.Results: Out of the 122 isolates, 80.3% of isolates were MDR and the production of virulence factors was in positive correlation with the presence of genetic determinants and 19.6% were non-MDR, but still showed the production of virulence factors, as confirmed by both phenotypic and genotypic methods. Few carbapenem-resistant strains were detected which did not show the production of virulence factors by both methods.Conclusion: The study concludes, though the strains were non-MDR, they were still capable of producing the virulence factors which may be responsible for the dissemination and chronicity of the infection caused by P. aeruginosa.

Iron coating was introduced as one of the novel techniques to improve physicochemical and biological properties of silver nanoparticles (AgNPs). In the current experiment, impact of iron coating on the antimicrobial potency of AgNPs was investigated against methicillin-resistance Staphylococcus aureus (MRSA). To obtain more accurate data about the antimicrobial potency of examined nanostructures, the experiment was done on the 10 isolates of MRSA which were isolated from skin lesions. AgNPs and iron-coated AgNPs (Fe@AgNPs) were fabricated based on a green one-pot reaction procedure. Minimal inhibitory concentration (MIC) of Fe@AgNPs was not significantly different with MIC of AgNPs against eight out of 10 examined MRSA isolates. Also, by iron coating a reduction in the minimal inhibitory concentration (MIC) of AgNPs was observed against two MRSA isolates. The average MIC of AgNPs against 10 MRSA isolates was calculated to be 2.16 ± 0.382 mg/mL and this value was reduced to 1.70 ± 0.638 mg/mL for Fe@AgNPs. However, this difference was not considered significant statistically (P-value > 0.05). From productivity point of view, it was found that iron coating would improve the productivity of the synthesis reaction more than fivefold. Productivity of AgNPs was calculated to be 1.02 ± 0.07 g/L, meanwhile this value was 5.25 ± 0.05 g/L for Fe@AgNPs. Iron coating may provide another economic benefit to reduce final price of AgNPs. It is obvious that the price of a particular nanostructure made of silver and iron is significantly lower than that of pure silver. These findings can be considered for the fabrication of economic and potent antimicrobial nanoparticles. [ABSTRACT FROM AUTHOR]

Two issues embedded in air pollution research are considered to be the long-observed effect of outdoor exposure to sunlight having a germicidal effect—the Open Air Factor (OAF)—and the wavelength dependence and implications of the use of UV-C light indoors to achieve germicidal action. Suggestions are made about the mechanism of the OAF and about the possible emergence of resistant strains indoors. [ABSTRACT FROM AUTHOR]

Eimeria tenella, an intestinal parasite, has brought huge economic losses to the poultry industry. The prevalence and severity of the development of drug resistance has increased the challenge of coccidiosis control. We previously identified the enolase 2 of E. tenella (EtENO2) was differentially expressed in drug-sensitive (DS) and drug-resistant strains using RNA-seq. In this study, the expression of EtENO2 in diclazuril-resistant (DZR), maduramicin-resistant (MRR), and salinomycin-resistant (SMR) strains was analyzed by quantitative real-time PCR (qRT-PCR) and western blots. EtENO2 was highly expressed in several drug-resistant strains compared with the DS strain. The qRT-PCR showed that the transcription level of EtENO2 in the field-isolated resistant strains was upregulated compared with the DS strain. The enzyme activity results indicated that the catalytic activity of EtENO2 in the drug-resistant strains was higher than in the DS strain. In addition, qRT-PCR and western blots showed that the expression level of EtENO2 was higher in second generation merozoites (SM) and unsporulated oocysts (UO) than that in sporozoites (SZ) and sporulated oocysts (SO). Immunofluorescence localization revealed that EtENO2 was distributed throughout SZ and SM and on the surface of the parasites. After the SZ invasion DF-1 cells, it was also observed on the parasitophorous vacuole membrane. Our secretion experiments found that EtENO2 could be secreted outside the SZ. This study indicated that EtENO2 might be related to the interaction between E. tenella and host cells and be involved in the development of E. tenella resistance to some anticoccidial drugs.

Antibiotic resistance (ABR) is a global issue that draws the attention of all healthcare experts in the veterinary and medical fields. Of various factors, indiscriminate and unregulated antibiotic usage in the animals reared for food production, especially in cows and buffa¬loes suffering from mastitis, contribute significantly to the rising incidence of resistant bac¬teria. A literature survey reveals the spread of resistant strains of mastitis-causing bacteria, like Staphylococcus aureus and Escherichia coli, to humans. In addition, antibiotic residues detected in milk samples against all major groups of antibiotics are likely to enter the human body through the food chain and aggravate the condition. The cumulative effects of ABR have emerged as a silent killer. The benefits of systematic surveillance on ABR in India are yet to be available. Here is an attempt to understand the ABR burden in India associated with bovine milk and its mitigation strategies. [J Adv Vet Anim Res 2023; 10(1.000): 21-29]

Ocular pathologies present significant challenges to achieving effective therapeutic results due to various anatomical and physiological barriers. Natural products such as flavonoids, alone or in association with allopathic drugs, present many therapeutic actions including anticancer, anti-inflammatory, and antibacterial action. However, their clinical employment is challenging for scientists due to their low water solubility. In this study, we designed a liquid formulation based on rutin/sulfobutylether-β-cyclodextrin (RTN/SBE-β-CD) inclusion complex for treating ocular infections. The correct stoichiometry and the accurate binding constant were determined by employing SupraFit software (2.5.120) in the UV-vis titration experiment. A deep physical–chemical characterization of the RTN/SBE-β-CD inclusion complex was also performed; it confirmed the predominant formation of a stable complex (Kc, 9660 M−1) in a 1:1 molar ratio, with high water solubility that was 20 times (2.5 mg/mL) higher than the free molecule (0.125 mg/mL), permitting the dissolution of the solid complex within 30 min. NMR studies revealed the involvement of the bicyclic flavonoid moiety in the complexation, which was also confirmed by molecular modeling studies. In vitro, the antibacterial and antibiofilm activity of the formulation was assayed against Staphylococcus aureus and Pseudomonas aeruginosa strains. The results demonstrated a significant activity of the formulation than that of the free molecules.

Antibiotic resistance (ABR) is a global issue that draws the attention of all healthcare experts in the veterinary and medical fields. Of various factors, indiscriminate and unregulated antibiotic usage in the animals reared for food production, especially in cows and buffaloes suffering from mastitis, contribute significantly to the rising incidence of resistant bacteria. A literature survey reveals the spread of resistant strains of mastitis-causing bacteria, like Staphylococcus aureus and Escherichia coli, to humans. In addition, antibiotic residues detected in milk samples against all major groups of antibiotics are likely to enter the human body through the food chain and aggravate the condition. The cumulative effects of ABR have emerged as a silent killer. The benefits of systematic surveillance on ABR in India are yet to be available. Here is an attempt to understand the ABR burden in India associated with bovine milk and its mitigation strategies. [ABSTRACT FROM AUTHOR]

This study reports the antimicrobial activities of the biopolymers poly[3-(3,4-dihydoxyphenyl)glyceric acid] (PDHPGA) and poly[2-methoxycarbonyl-3-(3,4-dihydroxyphenyl)oxirane] (PMDHPO), extracted from the six plants of Boraginaceae family: Symphytum asperum (SA), S. caucasicum (SC), S. gr and iflorum (SG), Anchusa italica (AI), Cynoglosum officinale (CO), and Borago officinalis (BO) collected in various parts of Georgia. The study revealed that the antibacterial activities were moderate, and biopolymers from only three plants showed activities against all tested bacteria. Biopolymers from CO stems as well as SC and AI did not show any activity except low activity against a resistant P. aeruginosa strain, which was the most resistant among all three resistant strains. On the other hand, the antifungal activity was better compared to the antibacterial activity. Biopolymers from BO stems exhibited the best activities with MIC/MFC at 0.37–1.00 mg/mL and 0.75–1.5 mg/L, respectively, followed by those from SG stems. Biopolymers from SC and AI roots showed antifungal activities against all six fungi, in contrast to the antibacterial activity, while biopolymers from CO stems and SA roots had activities against four fungi and one fungus, respectively. The sugar-based catechol-containing biopolymers from BO stems demonstrated the best activities among all tested biopolymers against T. viride, P. funiculosum, P. cyclpoium var verucosum, and C. albicans (MIC 0.37 mg/mL). In addition, biopolymers from SG stems were half as active against A. fumigatus and T. viride as ketoconazole. Biopolymers from all plant materials except for CO stems showed higher potency than ketoconazole against T. viride. For the first time, it was shown that all plant materials exhibited better activity against C. albicans, one of the most dreadful fungal species. [ABSTRACT FROM AUTHOR]

The resistance of bacteria to the disinfectants used is one of the pressing health problems requiring to be addressed in order to prevent formation and spread of resistant strains. Bacterial resistance leads to a sharply decreased effectiveness of anti-epidemic measures and contributes to maintaining a high morbidity level. In the context of the growing HAI incidence rate and related polyetiology, the large adaptive potential of opportunistic microorganisms, and the growing resistance to antimicrobial drugs, it is necessary to search for new or modify the corresponding substances of plant or synthetic origin exerting antimicrobial action used as antimicrobial agents. One of the representatives of this class of compounds are polyguanidines, characterized by high antimicrobial activity and low toxicity. Due to the high reactivity of the guanidine group, as well as ease of synthesis and relative availability of raw materials, N-phenyl- and N-octyl-substituted derivatives of polyhexamethylene guanidine hydrochloride were able to be obtained by melt polycondensation, their molecular weight characteristics were measured as well as the structure investigated by IR spectroscopy. An earlier study on the acute toxicity for polyhexamethylene guanidine hydrochloride derivatives after a single oral drug intake in laboratory animals (white mice) allowed to establish the following LD50 values: polyhexamethylene guanidine hydrochloride — 850.0±112.02 mg/ kg; N-phenyl-substituted polyhexamethylene guanidine hydrochloride — 1399.9±120.51 mg/kg; N-octyl-substituted polyhexamethylene guanidine hydrochloride — 1150.0±137.40 mg/kg. Such values, according to the tabulation of hazard classes, allow the synthesized derivatives to be classified into the fourth hazard class and open up an opportunity for using disinfectants as active components. The evaluation of the antibacterial sample properties was carried out by using serial dilutions in agar on hospital bacterial and fungal strains isolated from the biomaterial of patients at the Republican Clinical Hospital named after V.I. Semashko, according to the clinical guidelines “Laboratory diagnosis of community-acquired pneumonia” 2014, “Bacteriological analysis of urine” 2014, “Determination of the susceptibility of microorganisms to antimicrobial drugs” 2015. It was found that N-substituted derivatives exhibit a greater antimicrobial effect compared with unsubstituted polymer. The most sensitive to all the drugs presented was the yeast-like fungi Candida albicans (No. 2495) (complete suppression), as well as methicillin-resistant S. aureus (no. 2544), and the substituted samples almost completely suppress its growth. The most resistant strains are P. aeruginosa (No. 2281), A. baumannii (No. 2806) and K. pneumoniae (No. 3023), the percentage of reduction of these bacteria under the action of substituted samples does not exceed 41%, which is accounted for by their multi-resistance.

Florfenicol was widely used as antibiotic in the livestock and poultry breeding industry, resulting in a serious problem of drug resistance. In order to solve the resistance of florfenicol, this study designed and synthesized a new series of florfenicol-polyarginine conjugates and tested for antimicrobial activities. Drug-sensitive bacteria, gram-negative bacteria Escherichia coli (E. coli) and gram-positive Staphylococcus aureus (S. aureus), were sensitive to several of the compounds tested. These conjugates also showed excellent activity against drug-resistant strains such as methicillin-resistant S. aureus (MRSA) and florfenicol resistant Escherichia coli strains (2017XJ30, 2019XJ20), one of which as E6 had a minimum inhibitory concentration of 12.5 μmol/L. These conjugates did not allow bacteria to develop resistance and also decreased bacterial growth by membrane depolarization and disruption. Additionally, florfenicol succinate (C1) showed certain activity after coupling with arginine. This suggested that conjugating arginine to florfenicol succinate effectively modulated the properties of prodrugs. These new conjugates may provide useful insights for expanding the pool of antibiotics.

The widespread use of drugs has exacerbated the resistance of Eimeria tenalla to anti-coccidial drugs. Using RNA-seq, we previously found the ATPase ASNA1 homolog of E. tenella (EtASNA1) was differentially expressed in resistant strains and drug sensitive (DS) strain. In our study, we used western blotting and quantitative real-time PCR (qRT-PCR) to analyze the translational and transcriptional levels of EtASNA1 in a diclazuril-resistant (DZR) strain, maduramicin-resistant (MRR) strain, salinomycin-resistant (SMR) strain, and DS strain and found EtASNA1 was highly expressed in three drug-resistant strains. The qRT-PCR and western blotting results also showed that the expression levels of EtASNA1 increased with increasing drug concentration, and the transcription levels of the DZR strains isolated from the field were higher than those of the DS strain. In addition, we used in vivo and in vitro tests to analyze the changes of EtASNA1 expression after DZR, MRR, and DS strain infections in chickens, and in vitro inoculation of DF-1 cells in the presence of drugs. The addition of drugs caused expression to be upregulated. The results of qRT-PCR and western blotting also showed that the expression levels of EtASNA1 in second-generation merozoites (SM) and unsporulated oocysts (UO) were significantly higher than those in the other two developmental stages. The immunofluorescence localization of EtASNA1 indicated that the protein was distributed throughout the sporozoites (SZ) and SM, except for the refractile bodies of SZ. In vitro inhibition experiments showed that anti-EtASNA1 antibody incubation significantly inhibited SZ invasion of DF-1 cells. The above results showed that EtASNA1 may be related to host cell invasion of E. tenella and may be involved in the development of E. tenella resistance to some drugs.

Objective To analyze copy number variations (CNVs) of pfpm2 gene in 122 imported cases of Palciparum falciparum (P.f) infection in Changsha from 2016 to 2019 for predicting the risk of imported drug-resistant P.f strains in Changsha. Methods We collected dried blood spot samples of anticoagulated peripheral venous blood from 122 patients with a single infection of P.f, who were treated in designated medical facilities for malaria in Changsha in the years of 2016-2019. For each specimen, the CNVs of pfpm2 gene were detected in parallel with the standard strain 3D7 using real-time PCR. The CNVs values of the samples were compared across the years and also among different source countries of the cases. Results We analyzed a total of 122 P.f strains isolated from imported cases from 25 countries. The mean value of CNVs of pfpm2 gene in the 122 strains was significantly higher than that of the standard strain 3D7 (1.222±0.422 vs 1.007±0.023, P < 0.001). There were 23 Strains Whose CNVs Values of pfpm2 gene were higher than 1.5, which were imported from 12 countries including Nigeria (6/15), Congo (5/18), Cote d'Ivoire (2/5) and Sierra Leone (2/8). The percentage of strains with pfpm2 CNVs >1.5 was 13.2% (5/38) in 2016, 16.0% (4/25) in 2017, 22.9% (8/35) in 2018 and 25.0% (6/24) in 2019 respectively. The mean value of pfpm2 gene CNVs was 1.061±0.323 in 2016, 1.184±0.247 in 2017, 1.292±0.571 in 2018 and 1.414±0.360 in 2019, showing significant differences across the years except the years of 2017 and 2018 or 2018 and 2019 (P < 0.05, P < 0.001). The mean values of pfpm2 gene CNVs of the strains from Nigeria, Cote d'Ivoire, Tanzania and Burundi were significantly higher than the overall mean of the 122 strains (P < 0.05). Conclusion The CNVs of pfpm2 gene of P.f imported from African countries to Changsha are increased year by year, suggesting an increase in the risk of drug-resistant P.f strains in Changsha. Some clinical P.f strains from West Africa may have developed drug resistance, and thus may show poor response to current antimalarial drugs.

To prepare and characterize silver nanoparticles from Guava leaves (Psidium guajava), extracts (chloroform and ethanol). The fabricated silver nanoparticles were tested on resistant fungal strains, Aspergillus niger and Candida glabrata. Psidium guajava leaf extracts were obtained by cold maceration method, by using Chloroform and Ethanol. To one mL of extract 2mM silver nitrate solution was added. The mixture was kept overnight in a dark chamber at room temperature. The solution was centrifuged at 10,000 rpm for 15 minutes and filtered by wattman filter paper after centrifugation. Psidium guajava leaf extract based silver nanoparticles were prepared and evaluated for anti-fungal activity by microtitre well plate method on resistant strains Aspergillus niger and Candida glabrata. The silver nanoparticles showed significant activity at 120 µL, Nystatin was used as standard.

This study reports the antimicrobial activities of the biopolymers poly[3-(3,4-dihydoxyphenyl)glyceric acid] (PDHPGA) and poly[2-methoxycarbonyl-3-(3,4-dihydroxyphenyl)oxirane] (PMDHPO), extracted from the six plants of Boraginaceae family: Symphytum asperum (SA), S. caucasicum (SC), S. gr and iflorum (SG), Anchusa italica (AI), Cynoglosum officinale (CO), and Borago officinalis (BO) collected in various parts of Georgia. The study revealed that the antibacterial activities were moderate, and biopolymers from only three plants showed activities against all tested bacteria. Biopolymers from CO stems as well as SC and AI did not show any activity except low activity against a resistant P. aeruginosa strain, which was the most resistant among all three resistant strains. On the other hand, the antifungal activity was better compared to the antibacterial activity. Biopolymers from BO stems exhibited the best activities with MIC/MFC at 0.37–1.00 mg/mL and 0.75–1.5 mg/L, respectively, followed by those from SG stems. Biopolymers from SC and AI roots showed antifungal activities against all six fungi, in contrast to the antibacterial activity, while biopolymers from CO stems and SA roots had activities against four fungi and one fungus, respectively. The sugar-based catechol-containing biopolymers from BO stems demonstrated the best activities among all tested biopolymers against T. viride, P. funiculosum, P. cyclpoium var verucosum, and C. albicans (MIC 0.37 mg/mL). In addition, biopolymers from SG stems were half as active against A. fumigatus and T. viride as ketoconazole. Biopolymers from all plant materials except for CO stems showed higher potency than ketoconazole against T. viride. For the first time, it was shown that all plant materials exhibited better activity against C. albicans, one of the most dreadful fungal species.

Objectives: The association between Helicobacter pylori and chronic spontaneous urticaria (CSU) is controversial. Therefore, we aimed to directly diagnose H pylori by polymerase chain reaction (PCR) in gastric tissue from patients with CSU and to investigate the association between H pylori eradication therapy and CSU remission.Methods: Twenty-seven of 72 patients with CSU who were positive for H pylori stool antigen and PCR in gastric biopsy specimens were randomized to receive either anti-H pylori treatment or placebo.Results: Patients with H pylori were found to have significantly lower hemoglobin concentrations with microcytic hypochromic anemia and a significantly higher occurrence of dyspepsia symptoms. All H pylori-treated patients (except two) showed significant improvement of the urticaria itching and red wheals after 2 weeks of therapy compared with the placebo group (P < .001). The response rate to treatment was 85.7% (12 patients; 95% confidence interval, 64.3%-100.0%). The two patients who failed to eradicate H pylori had an H pylori strain resistant to amoxicillin.Conclusions: An association was observed between CSU and presence of H pylori infection in the gastric tissue. Whether this is a causal relationship or not remains to be discovered, but treatment of H pylori can significantly improve the symptoms of CSU. [ABSTRACT FROM AUTHOR]

To prepare and characterize silver nanoparticles from Guava leaves (Psidium guajava), extracts (chloroform and ethanol). The fabricated silver nanoparticles were tested on resistant fungal strains, Aspergillus niger and Candida glabrata. Psidium guajava leaf extracts were obtained by cold maceration method, by using Chloroform and Ethanol. To one mL of extract 2mM silver nitrate solution was added. The mixture was kept overnight in a dark chamber at room temperature. The solution was centrifuged at 10,000 rpm for 15 minutes and filtered by wattman filter paper after centrifugation. Psidium guajava leaf extract based silver nanoparticles were prepared and evaluated for anti-fungal activity by microtitre well plate method on resistant strains Aspergillus niger and Candida glabrata. The silver nanoparticles showed significant activity at 120 μL, Nystatin was used as standard. [ABSTRACT FROM AUTHOR]

Avian coccidiosis is a widespread and economically significant poultry disease caused by several Eimeria species, including Eimeria tenella. Previously, E. tenella serine/threonine protein phosphatase (EtSTP) was found to be differentially expressed in drug‐sensitive (DS) and drug‐resistant strains using RNA‐seq. In the present study, we found that transcription and translation levels of EtSTP were higher in diclazuril‐resistant (DZR) strains and maduramicin‐resistant (MRR) strains than in DS strains using quantitative real‐time PCR (qPCR) and Western blotting. Enzyme activity results indicated that the catalytic activity of EtSTP was higher in the two drug‐resistant strains than in DS strains. Western blot and qPCR analysis also showed that expression levels of EtSTP were higher in unsporulated oocysts (UO) and second‐generation merozoites (SM). Indirect immunofluorescence localization showed that EtSTP was located in most areas of the parasite with the exception of refractile bodies, and fluorescence intensity was enhanced during development. In vitro inhibition experiments showed that the ability of sporozoites (SZ) to invade cells was significantly decreased after treatment with anti‐rEtSTP antibody. These results indicated that EtSTP acted mainly during the developmental and reproductive stages of the parasite and may be related to the resistance of coccidia to external drug pressure. [ABSTRACT FROM AUTHOR]

Background: Extended spectrum beta-lactamases are produced by Gram-negative bacteria and most strains producing them belong to the family Enterobacteriaceae. The greatest challenge with ESBL-producing Enterobacteriaceae is their propensity to acquire multidrug resistance traits. This study aimed at determining the prevalence of ESBL-producing Enterobacteriaceae among selected tertiary hospitals in south-eastern Nigeria. Methods: A total of 400 Enterobacteriaceae isolates were obtained from patients attending five selected tertiary hospitals and were identified to species level by Gram staining and conventional biochemical tests. Screening for ESBL production was determined by the Kirby-Bauer disk diffusion method using 30µg disk of ceftriaxone, cefuroxime, cefpodoxime, ceftazidime, and aztreonam while confirmatory test was done using combination disk test based on the 2016 CLSI guidelines. Results: The prevalence of ESBL production among Enterobacteriaceae isolates from selected hospitals in southeast Nigeria is 61.5% (246 of 400). Among the isolates obtained, the highest prevalence was observed in Klebsiella oxytoca (100%) while the least prevalence was seen in Morganella morganii (50.0%). Escherichia coli and Klebsiella pneumoniae had rates of 61.8% and 62.3% respectively. Among the States of the south-east Nigeria, selected hospital in Ebonyi had a prevalence of 83.5%, Abia 63.6%, Anambra 61.5%, Enugu 51.7% and Imo 36.5%. The prevalence of ESBL-producing Enterobacteriaceae differ significantly between the States (p=0.000). Conclusion: ESBL-producing Enterobacteriaceae strains have been isolated from different participants, from the selected tertiary hospitals in south-eastern Nigeria. Therefore, we report a high prevalence of ESBL-producing Enterobacteriaceae in south-eastern Nigeria. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Three novel 3-O-tetraacetoglupiranosil derivatives from Aloe vera are described. • Aloe anthraquinones and several derivatives were tested against influenza virus. • 3- O -tetraacetoglupiranosil derivatives were the most active against influenza virus. • Agricultural residues from Aloe vera could be a potential source of pharmaceutical use. Abstract Aloe vera is a crop of wide economic value of worldwide distribution, and a rich source of quinone components. Recently, antiviral aloe anthraquinones had been reported against human influenza virus. In the present work two anthraquinones, aloesaponarin-I (1) and aloesaponarin-II (2) were isolated from A. vera roots, and six derivatives were obtained by methylation (3), acetylation (4) and O -glycosyl (5-6) reactions starting from (1). Additionally, a new Tetra- O -acetyl-β- d -glucopyranosyl derivative from 2 was also prepared. All compounds were evaluated against two strains of influenza virus AH1N1 by cytopathic effect reduction assay (CPE). The antiviral activity was determined by the ability of compounds to inhibit virus replication on Madin Darby Canine Kidney cells (MDCK). New derivatives 3-(2´,3´,4´,6´-Tetra-O-acetyl-β- d -glucopyranosyl-aloesaponarin-I (5) and 3 -(2´,3´,4´,6´-Tetra-O-acetyl-β- d -glucopyranosyl- aloesaponarin-II (7) showed a cytopathic reduction effect against influenza strain A/Yucatán/2370/09 with IC 50 of 30.77 and 13.70 μM, and against the virus A/Mexico/InDRE797/10 with IC 50 of 62.28 and 19.47 μM, respectively. To assess the effect of derivatives 5 and 7 during one cycle of replication (0–10 h), a time-of-addition experiment was performed. As a result it was found that both compounds were most effective when added 6–10 h post-infection and significantly inhibited viral titre (> 70%) at the concentrations of 50 and 100 μM. Based on the structural analysis of the compounds, it was suggested that the Tetra-O-acetyl-β- d -glucopyranosyl substituent at the C3 position of the anthraquinone might have an effect against the influenza AH1N1 virus. [ABSTRACT FROM AUTHOR]

Abstract In current research, five series of mono- and di-substituted piperazine derivatives have been synthesized. For di-substituted derivatives, ciprofloxacin was selected and hybrids were synthesized via substitution at piperazinyl- N 4 . In vitro antibacterial studies of all synthesized compound were carried out against American Type Culture Collection (ATCC) strains; E. coli (ATCC 25922), P. aeruginosa (ATCC 15442), K. pneumoniae (ATCC 1705), B. subtilis (ATCC 6633) and S. aureus (ATCC 6538). The potent series of compounds were further evaluated for their potential against clinically isolated resistant strains of E. coli , P. aeruginosa , S. aureus , and S. hemolytic. The reaction of piperazinyl-NH of ciprofloxacin with selected drugs resulted in pronounced growth inhibition of standard as well as resistant bacterial strains. Hybrid compounds 14b , 16a , 16d and CGS-20 showed excellent bacterial growth inhibition against standard and resistant strains. In vitro results were further correlated by using in silico tools. Molecular docking studies were carried out using MOE (Molecular Operating Environment) software. DNA gyrase used as a target and all compounds were docked against this specific target. Graphical abstract Image 1 Highlights • Mono- and di-substituted piperazine derivatives were synthesized. • In di-substituted derivatives, ciprofloxacin-drug hybrids were synthesized. • Compounds were evaluated against normal and resistant bacterial strains. • Excellent in vitro bacterial strain inhibition by some compounds. • Molecular docking studies on DNA gyrase as target. [ABSTRACT FROM AUTHOR]

Background: The contamination of ophthalmic solutions in ophthalmic practices remains an important cause of a myriad of secondary eye infections and a source of aggravation of ocular disorders such as corneal ulcers and keratitis. The aim of this study was to investigate the possible microbial contamination of fluorescein sodium dye solutions used in eye clinics in Ghana.Methods: Fluorescein sodium solutions were collected from various eye clinics in Ghana. Twenty-one samples of multiple-use fluorescein ophthalmic solutions were collected from various regions in Ghana. Eighteen unopened bottles yet to be used were also collected to serve as controls from the same facilities. The solutions were inoculated in different culture plates (blood agar, MacConkey agar, Sabouraud dextrose agar and plate count agar). The resulting microbial growth was identified using standard microbial identification techniques. Susceptibility tests were performed to ascertain the clinical importance of the organisms identified.Results: Positive cultures were recorded for all 21 multiple-use bottles (in-use) collected, but there were no positive cultures for the unopened bottles (yet to be used). Six different genera of bacteria were identified from fluorescein solutions, including resistant strains of Staphylococci spp., Bacillus spp., Klebsiella spp., Pseudomonas spp., Haemophilus spp. and Bordetella spp. Pseudomonas spp. were the most common bacterial contaminants. For fungi contaminations, Aspergillus spp., Penicillium spp. and Cladosporium spp. were isolated. The most common fungal contaminants were Aspergillus spp.Conclusions: Multiple-use bottles of fluorescein solution used in eye clinics in Ghana were contaminated with clinically important strains of bacteria and fungi. [ABSTRACT FROM AUTHOR]

This paper presents a deterministic SIS model for the transmission dynamics of malaria, a life-threatening disease transmitted by mosquitos. Four species of the parasite genus Plasmodium are known to cause human malaria. Some species of the parasite have evolved into strains that are resistant to treatment. Although proportions of Plasmodium species vary considerably between geographic regions, multiple species and strains do coexist within some communities. The mathematical model derived here includes all available species and strains for a given community. The model has a disease-free equilibrium, which is a global attractor when the reproduction number of each species or strain is less than one. The model possesses quasi-endemic equilibria; local asymptotic stability is established for two species, and numerical simulations suggest that the species or strain with the highest reproduction number exhibits competitive exclusion.

Ceftaroline is a new fifth generation cephalosporin, active mostly against Gram-positive cocci, e.g. Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus). It is used in treating acute bacterial skin and skin structure infections, community acquired respiratory tract infections and methicillin-resistant S. aureus bacteremia. The main resistance mechanisms of bacteria to β-lactam antibiotics, including ceftaroline, are mutations in PBP2a, PBP3 and PBP4. Clinically significant resistance has been noted among both archived and newly-isolated strains in a laboratory test using serial passages. Ceftaroline-resistant strains have also been found in patients suffering from cystic fibrosis, ventilator-associated pneumonia and infectious endocarditis. Irresponsible antibiotic treatment using ceftaroline or other antibiotics (due to a possibility of a cross-resistance) can lead to the spread of ceftaroline resistance and, consequently, its loss of value. DOI: http://dx.doi.org/10.5281/zenodo.1304435

Infections caused by Salmonella spp. (salmonellosis) are very frequent, being the second major cause of foodborne diseases worldwide. Given the growing emergence of antibiotic-resistant strains, alternatives are sought for treatment using essential oils as products that stand out for their potential as antimicrobials. The objective of this work was to determine the antibacterial activity of essential oils from plants grown in Cuba on Salmonella enterica strains. The essential oils were obtained by hydrodistillation or expression. The evaluation of the antibacterial action of 15 oils was carried out by agar diffusion. The promising ones were selected and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by the serial dilution technique. The essential oils of Ocimum gratissimum L., Lippia graveolens (Kunth) and Thymus vulgaris L. inhibited the growth of Salmonella enterica strains, including antibiotic-resistant strains. MIC and MBC values of the oils ranged between 0.5 mg/mL and 1 mg/mL. These essential oils are promising candidates for the development of antibacterial products for the control of salmonellosis. [ABSTRACT FROM AUTHOR]

Ceftaroline is a new fifth generation cephalosporin, active mostly against Gram-positive cocci, e.g. Staphylococcus aureus (including methicillinresistant Staphylococcus aureus). It is used in treating acute bacterial skin and skin structure infections, community acquired respiratory tract infections and methicillin-resistant S. aureus bacteremia. The main resistance mechanisms of bacteria to ß-lactam antibiotics, including ceftaroline, are mutations in PBP2a, PBP3 and PBP4. Clinically significant resistance has been noted among both archived and newly-isolated strains in a laboratory test using serial passages. Ceftaroline-resistant strains have also been found in patients suffering from cystic fibrosis, ventilatorassociated pneumonia and infectious endocarditis. Irresponsible antibiotic treatment using ceftaroline or other antibiotics (due to a possibility of a crossresistance) can lead to the spread of ceftaroline resistance and, consequently, its loss of value. [ABSTRACT FROM AUTHOR]

This work describes the synthesis, characterization and biological evaluation of three platinum complexes of the type [Pt(DMSO)(L)Cl]Cl, in which L represents a fluoroquinolone, namely, ciprofloxacin (cpl), ofloxacin (ofl), or sparfloxacin (spf). The new complexes were characterized by elemental analysis, high-resolution mass spectrometry (HRESIMS) and 1 H, 13 C and 195 Pt NMR (nuclear magnetic resonance). The spectral data suggest that the fluoroquinolones act as bidentate ligands coordinated to Pt(II) through the nitrogen atoms of the piperazine ring. Microbiological assays against wild type Mycobacterium tuberculosis (ATCC 27294) showed that all complexes have been very potent, exhibiting antitubercular potency at concentrations <2 μM, although none of the complexes presented higher potency than established anti-TB drugs. As to the resistant strains, the complex with sparfloxacin, [Pt(DMSO)(spf)Cl]Cl exhibited the best potential against most Mycobacterium tuberculosis clinical isolates. The cytotoxicity of these compounds was also evaluated in three breast cell lines: MCF-10 (a healthy cell), MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). In both tumor cell lines, [Pt(DMSO)(spf)Cl]Cl was more active and more selective than cisplatin. Flow cytometry analysis revealed that [Pt(DMSO)(spf)Cl]Cl induced late apoptotic cell death in MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

Treatment of animal African trypanosomiasis (AAT) requires urgent need for safe, potent and affordable drugs and this has necessitated this study. We investigated the trypanocidal activities and mode of action of selected 3-aminosteroids against Trypanosoma brucei brucei. The in vitro activity of selected compounds of this series against T. congolense (Savannah-type, IL3000), T. b. brucei (bloodstream trypomastigote, Lister strain 427 wild-type (427WT)) and various multi-drug resistant cell lines was assessed using a resazurin-based cell viability assay. Studies on mode of antitrypanosomal activity of some selected 3-aminosteroids against Tbb 427WT were also carried out. The tested compounds mostly showed moderate-to-low in vitro activities and low selectivity to mammalian cells. Interestingly, a certain aminosteroid, holarrhetine (10, IC50 = 0.045 ± 0.03 µM), was 2 times more potent against T. congolense than the standard veterinary drug, diminazene aceturate, and 10 times more potent than the control trypanocide, pentamidine, and displayed an excellent in vitro selectivity index of 2130 over L6 myoblasts. All multi-drug resistant strains of T. b. brucei tested were not significantly cross-resistant with the purified compounds. The growth pattern of Tbb 427WT on long and limited exposure time revealed gradual but irrecoverable growth arrest at ≥ IC50 concentrations of 3-aminosteroids. Trypanocidal action was not associated with membrane permeabilization of trypanosome cells but instead with mitochondrial membrane depolarization, reduced adenosine triphosphate (ATP) levels and G2/M cell cycle arrest which appear to be the result of mitochondrial accumulation of the aminosteroids. These findings provided insights for further development of this new and promising class of trypanocide against African trypanosomes.

Background: The diagnosis of Chronic Suppurative otitis media (CSOM) implies a permanent abnormality of the pars tensa or flaccida, most likely a result of earlier acute otitis media or negative middle ear pressure. Changes in the microbiological flora following the advent of sophisticated synthetic antibiotics increase the relevance of antibiotic sensitivity to plan a general outline of treatment for a patient with a chronically discharging ear. Aim: To evaluate the bacteriological causes of CSOM. To know their antibiotic sensitivity pattern to commonly used antibiotics. Study Design: Prospective Observational Study. Materials and Methods: Sixty patients of Suppurative otitis media both unilateral and bilateral who present with active purulent discharge for to Ear, Nose and Throat (ENT) Department will be prospectively studied. Patients were of all age group, both sexes and had symptoms of active ear discharge for more than 6 weeks. Patients suffering from SOM who are on systemic antibiotics and on topical medications to the ear were not included in the study. Results: Of the 60 patients 64% were males with maximum incidence in 26-50 y age group.55% of patients were from lower Socio Economic Status.Of the organisms isolated Staph. Aureus(35%) was most predominant followed by Pseudomonas(31%).All gram positive organisms were susceptible to Co-trimoxazole, Vancomycin , Gentamycin and all Gram negative to Meropenam, Aztreonam, Piperacillin. Conclusion: The patients should also be advised to take the drugs for the complete prescribed duration. This will not only help in minimizing the complications, but also help in preventing the emergence of resistant strains. [ABSTRACT FROM AUTHOR]

Mastitis is an important economic disease causing production losses in dairy industry. Antibiotics are becoming ineffective in controlling mastitis due to the emergence of resistant strains requiring the development of novel therapeutic agents. In this study, the authors present the phytochemical synthesis of silver nanoparticles (AgNPs) with acetyl‐11‐α‐keto‐β‐boswellic acid and evaluation of their activity in Staphylococcus aureus induced murine mastitis. Boswellic acid mediated AgNP (BANS) were oval, polydispersed (99.8 nm) with an minimum inhibitory concentration of 0.033 µg ml−1 against S. aureus, inhibitory concentration (IC50) of 30.04 µg ml−1 on mouse splenocytes and safe at an in vivo acute oral dose of 3.5 mg kg−1 in mice. Mastitis was induced in lactating mice by inoculating S. aureus (log10 5.60 cfu) and treated 6 h post‐inoculation with BANS (0.12 mg kg−1, intramammary and intraperitoneal), and cefepime (1 mg kg−1, intraperitoneal). S. aureus inoculated mice showed increased bacterial load, neutrophil infiltration in mammary glands and elevated C‐reactive protein (CRP) in serum. Oxidative stress was also observed with elevated malondialdehyde level, superoxide dismutase (SOD) and catalase (CAT) activities. BANS treatment significantly (P < 0.05) reduced bacterial load, CRP, SOD, CAT activities and neutrophil infiltration in affected mammary glands. BANS could be a potential therapeutic agent for managing bovine mastitis. [ABSTRACT FROM AUTHOR]

A collection of 1,2,3-triazoles unsaturated fatty acid mimics were efficiently synthesized by click chemistry. The 1,4-disubstituted analogs prepared covered different alkyl chain lengths and triazole positions. The compounds were subsequently tested against Mycobacterium tuberculosis , being most of them active with some of the analogs displaying activity at micromolar concentration. The most potent member of the series has the triazole moiety on the C-2 position with a carbon chain of eight or ten carbon atoms. The 1,5-isomers of the most active analog were significantly less active than the original isomer. The activity of the selected hit was assayed on several clinical MTB multi-drug resistant strains providing the same MIC. [ABSTRACT FROM AUTHOR]

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The major use of antibiotics is for the treatment and prevention of diseases. Antibiotics are used in the livestock industry to enhance growth rate, increase feed efficiency and reduce disease development. But unscrupulous use of antibiotic plays a major role in the emerging public health crisis of antibiotic resistance. The issue becomes more relevant on a future perspective because the global use of antimicrobials for food animal production is predicted to increase by 67% in 2030. This issue required timely intervention in India because India is a hotspot with higher consumption (30 kg/km2) for industrial poultry production, which is expected to grow 312% by 2030. But on same time complete ban on the use of antibiotic growth promoters (AGP) can create an economic loss of 44.1 billion USD in global meat production. Antibiotic residues in food have twofold concern; one is potential threat of direct toxicity in humans and the second is possible development of resistant strains and failure of antibiotic therapy in clinical cases. This review critically analyzes global trends in the use of AGP, its incidence, methods of detection and associated health concerns and suggests possible ways to reduce the residues in foods of animal origin.

This paper presents a deterministic SIS model for the transmission dynamics of malaria, a life-threatening disease transmitted by mosquitos. Four species of the parasite genus Plasmodium are known to cause human malaria. Some species of the parasite have evolved into strains that are resistant to treatment. Although proportions of Plasmodium species vary considerably between geographic regions, multiple species and strains do coexist within some communities. The mathematical model derived here includes all available species and strains for a given community. The model has a disease-free equilibrium, which is a global attractor when the reproduction number of each species or strain is less than one. The model possesses quasi-endemic equilibria; local asymptotic stability is established for two species, and numerical simulations suggest that the species or strain with the highest reproduction number exhibits competitive exclusion. [ABSTRACT FROM PUBLISHER]

Silver nanoparticles (AgNPs) were biosynthesized via a green route using ten different plants extracts (GNP1‐ Caryota urens, GNP2‐Pongamia glabra, GNP3‐ Hamelia patens, GNP4‐Thevetia peruviana, GNP5‐Calendula officinalis, GNP6‐Tectona grandis, GNP7‐Ficus petiolaris, GNP8‐ Ficus busking, GNP9‐ Juniper communis, GNP10‐Bauhinia purpurea). AgNPs were tested against drug resistant microbes and their biofilms. These nanoparticles (NPs) were characterised using UV‐vis spectroscopy, transmission electron microscope, Fourier transform infrared spectroscopy, X‐ray diffraction and Image J software. Most of the AgNPs were distributed over a range of 1 of 60 nm size. The results indicated that AgNPs were antibacterial in nature without differentiating between resistant or susceptible strains. Moreover, the effect was more prominent on Gram negative bacteria then Gram positive bacteria and fungus. AgNPs inhibited various classes of microbes with different concentration. It was also evident from the results that the origin or nature of extract did not affect the activity of the NPs. Protein and carbohydrate leakage assays confirmed that the cells lysis is one of the main mechanisms for the killing of microbes by green AgNPs. This study suggests that the action of AgNPs on microbial cells resulted into cell lysis and DNA damage. Excellent microbial biofilm inhibition was also seen by these green AgNPs. AgNPs have proved their candidature as a potential antibacterial and antibiofilm agent against MDR microbes. [ABSTRACT FROM AUTHOR]

We present a mathematical model that describes treatment of a fungal infection in an immune compromised patient in which both susceptible and resistant strains are present with a mutation allowing the susceptible strain to become resistant as well as a back mutation allowing resistant fungus to again become susceptible. The resulting nonlinear differential equations model the biological outcome, in terms of strain growth and cell number, when an individual is treated with a fungicidal or fungistatic drug. The model demonstrates that under any levels of the drug both strains will be in stable co-existence and high levels of treatment will never completely eradicate the susceptible strain. A modified model is then described in which the drug is changed to one in which both strains are susceptible, and subsequently, at the appropriate level of treatment, complete eradication of both fungal strains ensues. We discuss the model and implications for treatment options within the context of an immune compromised patient. [ABSTRACT FROM AUTHOR]

A series of hybrid molecules referred to as 'reversed chloroquines' (RCQs) were designed, synthesized, and tested against chloroquine resistant strains of Plasmodium falciparum. The designed compounds contain bulky aromatic groups and chloroquine like nucleus linked with each other via two or three carbon alkyl linkers . Five compounds were designed based on the structure - activity relationship. These five compounds have been successfully synthesized, of which three compounds show significant antimalarial activity in vitro. A modification of the reversal agent (RA) like moiety was designed using substituted biphenyl groups. The aminoalkyl substitution of the heterocycle and tertiary aliphatic aminoalkyl nitrogen atom with two- or three-carbon bridges to the heteroaromatic nitrogen is required for potential 'resistance reversal activity'. The synthesized compounds were screened for their in vitro antimalarial activity as characterized by the 50% inhibitory concentration (IC), cytotoxic concentration (CC), and selectivity index (SI). These compounds did not show any cytotoxic effect. One of these compounds ( 5), which contains two-carbon linker chain, unsaturation at position 2, and chlorine substituted biphenyls in RA-like moiety, was found to possess appreciable and promising in vitro antimalarial activity against the chloroquine sensitive 3D7 strain of P. falciparum. [ABSTRACT FROM AUTHOR]

Despite the resistance developed by the Mycobacterium tuberculosis (MTb) strains, isoniazid (INH) has been recognized as one of the best drug for treatment of Tuberculosis (Tb). The coordination of INH to ruthenium metal centers was investigated as a strategy to enhance the activity of this drug against the sensitive and resistant strains of MTb. The complexes trans -[Ru(NH 3 ) 4 (L)(INH)] 2+ (L = SO 2 or NH 3 ) were isolated and their chemical and antituberculosis properties studied. The minimal inhibitory concentration (MIC) data show that [Ru(NH 3 ) 5 (INH)] 2+ was active in both resistant and sensitive strains, whereas free INH (non-coordinated) showed to be active only against the sensitive strain. The coordination of INH to the metal center in both [Ru(NH 3 ) 5 (INH)] 2+ and trans -[Ru(NH 3 ) 4 (SO 2 )(INH)] 2+ complexes led to a shift in the INH oxidation potential to less positive values compared to free INH. Despite, the ease of oxidation of INH did not lead to an increase in the in vitro INH activity against MTb, it might have provided sensitivity toward resistant strains. Furthermore, ruthenium complexes with chemical structures analogous to those described above were synthesized using the oxidation products of INH as ligands (namely, isonicotinic acid and isonicotinamide). These last compounds were not active against any strains of MTb. Moreover, according to DFT calculations the formation of the acyl radical, a proposed intermediate in the INH oxidation, is favored in the [Ru(NH 3 ) 5 (INH)] 2+ complex by 50.7 kcal mol −1 with respect to the free INH. This result suggests that the stabilization of the acyl radical promoted by the metal center would be a more important feature than the oxidation potential of the INH for the antituberculosis activity against resistant strains. [ABSTRACT FROM AUTHOR]