MIC Index Research Articles

Comparative Efficacy of Continuous Ceftazidime Infusion vs. Intermittent Bolus against In Vitro Ceftazidime-Susceptible and -Resistant Pseudomonas aeruginosa Biofilm.

Background: As the anti-biofilm pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics are not well-defined, we have evaluated the PK/PD indices for different regimens of ceftazidime (CAZ; with/without colistin) against Pseudomonas aeruginosa biofilm. Methods: We have used the Center for Disease Control and Prevention Biofilm Reactor with two susceptible (PAO1 and HUB-PAS) and one resistant (HUB-XDR) strains of P. aeruginosa. The regimens were CAZ monotherapies (mimicking a human dose of 2 g/8 h, CAZ-IB; 6 g/daily as continuous infusion at 50 mg/L, CAZ-CI50; and 9 g/daily at 70 mg/L, CAZ-CI70) and CAZ-colistin combinations. Efficacy was correlated with the CAZ PK/PD parameters. Results: CAZ-CI70 was the most effective monotherapy against CAZ-susceptible strains (Δlog CFU/mL 54-0 h = -4.15 ± 0.59 and -3.05 ± 0.5 for HUB-PAS and PAO1, respectively; p ≤ 0.007 vs. other monotherapies), and adding colistin improved the efficacy over CAZ monotherapy. CAZ monotherapies were ineffective against the HUB-XDR strain, and CAZ-CI50 plus colistin achieved higher efficacy than CAZ-IB with colistin. The PK/PD index that correlated best with anti-biofilm efficacy was fAUC0-24h/MIC (r2 = 0.78). Conclusions: CAZ exhibited dose-dependent anti-biofilm killing against P. aeruginosa, which was better explained by the fAUC0-24h/MIC index. CAZ-CI provided benefits compared to CAZ-IB, particularly when using higher doses and together with colistin. CAZ monotherapies were ineffective against the CAZ-resistant strain, independently of the optimized strategy and only CAZ-CI plus colistin appeared useful for clinical practice.

In Vitro and In Vivo Evaluation of Synergistic Effects of Everolimus in Combination with Antifungal Agents on Exophiala dermatitidis.

To investigate the combined function of the novel oral mTOR inhibitor, everolimus, with antifungal agents and their potential mechanisms against Exophiala dermatitidis, the CLSI microliquid-based dilution method M38-A2, chequerboard technique, and disk diffusion testing were performed. The efficacy of everolimus was evaluated in combination with itraconazole, voriconazole, posaconazole, and amphotericin B against 16 clinically isolated strains of E. dermatitidis. The synergistic effect was determined by measuring the MIC and fractional inhibitory concentration index. Dihydrorhodamine 123 was used for the quantification of ROS levels. The differences in the expression of antifungal susceptibility-associated genes were analyzed following different types of treatment. Galleria mellonella was used as the in vivo model. While everolimus alone showed minimal antifungal effects, combinations with itraconazole, voriconazole, posaconazole, or amphotericin B resulted in synergy in 13/16 (81.25%), 2/16 (12.5%), 14/16 (87.75%), and 5/16 (31.25%) of isolates, respectively. The disk diffusion assay revealed that the combination of everolimus and antifungal drugs showed no significant increase in the inhibition zones compared with the single agent, but no antagonistic effects were observed. Combination of everolimus and antifungal agents resulted in increased ROS activity (everolimus + posaconazole versus posaconazole [P < 0.05], everolimus + amphotericin B versus amphotericin B [P < 0.002]). Simultaneously, compared to mono-treatment, the combination of everolimus + itraconazole suppressed the expression of MDR2 (P < 0.05) and the combination of everolimus + amphotericin B suppressed the expression of MDR3 (P < 0.05) and CDR1B (P < 0.02). In vivo, combinations of everolimus and antifungal agents improved survival rates, particularly the combination of everolimus + amphotericin B (P < 0.05). In summary, the in vivo and in vitro experiments performed in our study suggest that the combination of everolimus with azoles or amphotericin B can have synergistic effects against E. dermatitidis, potentially due to the induction of ROS activity and inhibition of efflux pumps, providing a promising new approach for the treatment of E. dermatitidis infections. IMPORTANCE Cancer patients with E. dermatitidis infection have high mortality if untreated. Clinically, the conventional treatment of E. dermatitidis is poor due to the long-term use of antifungal drugs. In this study, we have for the first time investigated the interaction and action mechanism of everolimus combined with itraconazole, voriconazole, posaconazole, and amphotericin B on E. dermatitidis in vitro and in vivo, which provided new ideas and direction for further exploring the mechanism of drug combination and clinical treatment of E. dermatitidis.

Antibacterial efficacy of Citrus hystrix (makrut lime) essential oil against clinical multidrug-resistant methicillin-resistant and methicillin-susceptible Staphylococcus aureus isolates

The increasing incidence of methicillin-resistant S. aureus is a major public health concern. Recently, the performance of Citrus hystrix essential oil (CHEO) has been shown to contain broad-spectrum antibacterial activity. Therefore, this study aims to determine the antibacterial activity of CHEO alone and in combination with gentamicin against panels of clinical isolates of methicillin-susceptible S. aureus (MSSA, n = 45) and methicillin-resistant S. aureus (MRSA, n = 40). Antibiotic susceptibility testing revealed multidrug-resistant (MDR) patterns among 3 MSSA isolates and 39 MRSA isolates, indicating that the clinical MRSA isolates were associated with MDR (p < 0.05). For the drug resistant isolates, resistance was observed toward most antibiotics, except for chloramphenicol, trimethoprim-sulfamethoxazole, linezolid, and vancomycin. Antibacterial screening by disk diffusion demonstrated that CHEO alone had certain antibacterial activity toward all MSSA isolates (IZD: 16.0 ± 4.7 mm) and MRSA isolates (IZD: 16.5 ± 4.2 mm) (p > 0.05). The MIC values of CHEO are 18.3 ± 6.1 mg/mL in MSSA isolates and 17.9 ± 6.9 mg/mL in MRSA isolates (p > 0.05). The antibacterial activity of CHEO demonstrated the bactericidal effect with MIC index 1.0–1.4. Time-killing kinetics revealed that CHEO at 1 × MIC completely killed MSSA and MRSA within 12 h. Moreover, the checkerboard titration demonstrated the synergistic and additive interactions of CHEO with gentamicin with FIC index 0.012–0.625. CHEO against human epidermal keratinocyte; HaCaT cell line demonstrated the IC50 value at 2.15 mg/mL. The use of CHEO as an alternative antibacterial agent would reduce the emergence of resistant bacteria, especially MDR MRSA.

Therapeutic Drug Monitoring of Antibiotics Is Needed in the Treatment of Sepsis

The article presents the results of a prospective on e-c enter observational clinical study. The level of therapeutic drug monitoring antibiotics was studied in patients with sepsis. The objective: to assess the impact of pharmacokinetics and pharmacodynamics parameters of the main classes of antibacterial drugs using specific indices to improve the effectiveness of ongoing antimicrobial therapy in patients with sepsis asscoaited with the infectious process with pa n-r esistant nosocomial microflora. Subjects and Methods. A total of 8 patients with sepsis meetiing the criteria of Sepsi s-3 were included. Carbapenems, oxazolidinones, and aminoglycosides were used in the treatment. Concentrations of drugs in blood plasma were studied by hig h-p erformance liquid chromatography with mass spectrometry. Analysis of the effectiveness of treatment was performed on the third day of therapy. Results. The T &gt; MIC index reached 40% of the time interval between the two administrations for MIC for Pseudomonas aeruginosa in only two cases for group II carbapenems. In both cases, high peak concentrations of the drug (19.5 and 35.4 m g/L , respectively) were observed, a low static volume of antibiotic distribution (0.06 l/k g and 0,09 l/k g) and reduced total clearance of the drug (7.18 and 4.11 m l/h r) were noted. The peak concentration of amikacin was low (3.35 m g/l ), while the time to achieve it and the level of static volume distribution (356.5 liters) increased. The peak concentration of linezolid was reduced in all observations and amounted to 4.04 and 3.35 m g/l . The time of its achievement was increased (3.27 and 6.6 hours), the ratio of AU C / M IC was low and made 76.8 and 59.2. The resolution of organ dysfunction and reduction of manifestations of infectious intoxication were noted only in three patients on the third day of observation. Conclusion. Static pharmacokineti c/p harmacodynamic criteria may serve as a guideline for antimicrobial therapy. Limitations in changing the tactics of antimicrobial therapy based on the use instruction nevertheless allow optimizing treatment by controlling the volume of distribution of the drug, presence of renal or hepatic insufficiency that, however, does not guarantee treatment success. The volume of therapeutic drug monitoring of antibiotics sufficient for compilation of static pharmakinetic models, does not meet the requirements of modern intensive care.

Studies on the Antibacterial Susceptibility of Uropathogens to Senna alata Extracts in Calabar, Cross River State, Nigeria

Background: Senna alata is an underutilized shrub found in many countries and is known for its traditional use in the treatment of dermatophytes and other related diseases. Therefore, this study aimed at evaluating the phytochemical and antibacterial effects of S. alata leaves extracts against bacterial isolates obtained from urinary tract infection patients in Calabar.&#x0D; Methodology: Matured fresh leaves of Senna alata were collected within Calabar, Cross River state, Nigeria, in May 2022 and identified by a botanist in the Department of Botany, University of Calabar. The leaves of S. alata were extracted with water, methanol and ethyl acetate using maceration and soxhlet methods. Phytochemical analysis was conducted to detect the presence of bioactive compounds using standard methods. The crude extracts of S. alata were investigated for antibacterial properties using agar well diffusion method and mechanisms of antibiosis determined using MBC/MIC ratio.&#x0D; Results: In both methods of extraction, methanol yielded more extracts compared to other solvents. Soxhlet methanol extract (SaMeSh) had the highest (12.21%) percentage yield while maceration ethyl acetate extract (SaEaMa) had the least (4.77%) percentage yield. The phytochemicals assayed revealed the presence of saponins, tannins, flavonoids, anthraquinones, terpenoids and steroids. However, terpenoids was not detected in methanol and ethyl acetate extracts. Senna alata extracts demonstrated broad spectrum of activity against the tested isolates at various concentrations with organic solvents exhibiting the highest antibacterial activity. However, the observed activity varied with respect to concentration of extract and types of organisms. The MIC values ranged from 31.25 to 250 mg/mL and MBC values from 62.5 to 500 mg/mL. The MIC index of the crude extracts against the test uropathogens was ≤8.&#x0D; Conclusion: This study indicates that S. alata could be a source of novel antimicrobial agent. Further research is required to isolate, characterize and identify bioactive constituents responsible for the observed activity.

Evaluation of the antibacterial and antifungal potentials of peptide-rich extracts from selected Nigerian plants

Introduction: Host defence peptides (HDPs) has gained wide recognition as a potential source of antimicrobial agents because of their abundance in nature, low incidence of reported resistance, and their immunomodulatory properties. This study investigated the presence and antimicrobial activities of bioactive peptides in seven selected plants from the Rubiaceae, Apocynaceae, and Euphorbiaceae families. Methods: The reversed-phase solid-phase extraction was used to obtain the peptide-rich fractions from the crude extracts of the plants, and the circular peptides were chemically detected by a modified G-250 spray on a developed TLC plate. The peptide fraction and crude extracts were screened for their antimicrobial activities using the broth microdilution method. The rate of kill study was conducted for the peptide fractions Euphorbia hirta and Nauclea diderichii Results: The study revealed Nauclea diderichii peptide-rich fraction as the most potent on the tested strains of gram-positive and gram-negative bacteria and fungi (MIC = 7.8, 15.63-62.5, and 7.8 μg/mL respectively). Euphorbia hirta and Nauclea diderichii peptide fractions exhibited bactericidal activity (MIC index ≤4, and >3Log 10 reduction of initial inoculum) and have a broad spectrum of activity, which further validates their ethnomedicinal use in the management of diverse infectious diseases, including enteric and respiratory tract infections. The peptide fractions of all the plants are more potent than the crude extracts. Conclusion: This study established the antimicrobial potentials of the peptide-rich fractions from these plant species, and the basis for further investigation to isolate and characterize the bioactive peptides responsible for their antimicrobial activities.

Potent Anti-Cutibacterium acnes Activity of the Essential Oils Derived from Allium sativum, Gerdenia jasminoides, and Hedychium coronarium Cultivated in Thailand

Plant oils derived from medicinal herbs have furnished bioactive synergistics, as well as antibacterial and antifungal properties. The study was to evaluate the antibacterial activity of essential oils (EOs) against Cutibacterium acnes and to analyze the chemical compositions of the effective oils. The experiment was conducted using a completely randomized design with duplications. Three EOs obtained from Allium sativum (garlic), Gardenia jasminoides (gardenia), and Hedychium coronarium (hydechium) cultivated in Thailand were tested for antibacterial activity using an agar well diffusion assay and the macro-dilution method. The chemical compositions of the selected oil were determined by gas chromatography and mass spectrometry (GC-MS). To compare the data, Duncan’s multiple range test (DMRT) was performed, and significance was determined at the p &lt; 0.05 level. The results showed that garlic oil had the highest potent inhibitory zone on C. acnes, according to the findings. As a bactericidal, garlic oil had MIC and MBC values of 0.39 and 0.78 mg/mL, and even a MIC index (MBC/MIC) of 4. Diallyl thiosulfinate (allicin) (20.53%), 1,3-dithiane (12.53%), cyclic octaatomic sulfur (5.02%), 1,4-dihydro-2,3-benzoxathiin-3-oxide (4.73%), and carvone (3.40%) were the major components of garlic oil. The results suggest that garlic oil might be used to develop topical anti-acne treatments.

EEG Delta/Theta Ratio and Microstate Analysis Originating Novel Biomarkers for Malnutrition-Inflammation Complex Syndrome in ESRD Patients.

The Malnutrition-Inflammation Score (MIS) was initially proposed to evaluate malnutrition-inflammation complex syndrome (MICS) in end-stage renal disease (ESRD) patients. Although MICS should be routinely evaluated to reduce the hospitalization and mortality rate of ESRD patients, the inconvenience of the MIS might limit its use. Cerebral complications in ESRD, possibly induced by MICS, were previously assessed by using spectral electroencephalography (EEG) via the delta/theta ratio and microstate analysis. Correspondingly, EEG could be used to directly assess MICS in ESRD patients, but the relationships among MICS and these EEG features remain inconclusive. Thus, we aimed to investigate the delta/theta ratio and microstates in ESRD patients with high and low risks of MICS. We also attempted to identify the correlation among the MIS, delta/theta ratio, and microstate parameters, which might clarify their relationships. To achieve these objectives, a total of forty-six ESRD subjects were willingly recruited. We collected their blood samples, MIS, and EEGs after receiving written informed consent. Sixteen women and seven men were allocated to low risk group (MIS ≤ 5, age 57.57 ± 14.88 years). Additionally, high risk group contains 15 women and 8 men (MIS > 5, age 59.13 ± 11.77 years). Here, we discovered that delta/theta ratio (p < 0.041) and most microstate parameters (p < 0.001) were significantly different between subject groups. We also found that the delta/theta ratio was not correlated with MIS but was strongly with the average microstate duration (ρ = 0.708, p < 0.001); hence, we suggested that the average microstate duration might serve as an alternative encephalopathy biomarker. Coincidentally, we noticed positive correlations for most parameters of microstates A and B (0.54 ≤ ρ ≤ 0.68, p < 0.001) and stronger negative correlations for all microstate C parameters (−0.75 ≤ ρ ≤ −0.61, p < 0.001). These findings unveiled a novel EEG biomarker, the MIC index, that could efficiently distinguish ESRD patients at high and low risk of MICS when utilized as a feature in a binary logistic regression model (accuracy of train-test split validation = 1.00). We expected that the average microstate duration and MIC index might potentially contribute to monitor ESRD patients in the future.

Synergistic effect of thymoquinone and nystatin in the treatment of oral candidiasis; an in vitro study.

The effectiveness of antifungal agents may be insufficient against resistant strains in some cases of oral candidiasis. The aim of this study was to evaluate the antifungal effect of thymoquinone against Candida albicans, Candida tropicalis, Candida glabrata and Candida krusei strains and the synergistic antifungal activity of these strains in combination with nystatin. To evaluate in vitro antifungal activity and interactions between thymoquinone and nystatin, substances were tested against Candida albicans ATCC 10,231, C. tropicalis ATCC 750, C.krusei ATCC 6258 and C. glabrata ATCC 2001 standard strains both individually and combinationally via microdilution method. MIC and ΣFIC index value were analysed. The Kruskal Wallis test and Bonferroni test were used for statistical evaluations. Statistical significance was set at p < 0.05. A statistically significant difference was observed between the mean ranks of all Candida species and doses of thymoquinone, nystatin, and the combination thymoquinone-nystatin (p < 0.05). MIC values for thymoquinone were determined as 15 μg/mL for C. albicans, C. tropicalis and C. krusei while it was 30 μg/mL for C. glabrata. Moreover, MIC for nystatin was found as 1.875 μg/mL for C. albicans, C. tropicalis and C. krusei, whereas it was 7.5 μg/mL in C. glabrata. Interaction assays and ΣFIC index value revealed that, TQ and nystatin have a synergistic effect against to all strains. Thymoquinone was found to have antifungal activity on Candida species and synergistic effect when combined with nystatin.

PK/PD integration and pharmacodynamic cutoff of cefquinome against cow mastitis due to Escherichia coli.

Cefquinome is the fourth generation of cephalosporin approved solely in animal usage. In order to slow down the resistance development of E.coli to cefquinome, and to protect and maintain the effectiveness of cefquinome, an ex vivo PK/PD modeling of cefquinome against E.coli in cows after intramammary infusion administration was conducted. The epidemiologic cutoff (ECOFF) and pharmacodynamic cutoff (COPD) of cefquinome against E.coli in lactation cows after intramammary infusion administration were recommended. The MICs of cefquinome against 1073clinical E.coli isolates ranged from 0.015 to >64μg/ml, and the ECOFF was defined as 0.125μg/ml. The pharmacokinetic results showed that cefquinome maintained high concentration in milk for a long period with the T1/2β of 10.60h after intramammary infusion in dairy cows. The drug concentration in skimmed milk was still as high as 0.15mg/ml after 48h. Cefquinome displayed bacterial killing effect at 2× MIC with the initial inoculum of 106 cfu/ml in vitro; however, the same effect was attained with a concentration as high as 32× MIC with the initial inoculum of 108 cfu/ml both in artificial medium and in skimmed milk. The initial inoculum is an important factor on time-killing curve accounting for weakened killing pattern of cefquinome. The AUC0-24h /MIC index correlated well with ex vivo efficacy. The AUC0-24h /MIC values for bactericidal effect were 50, 016, and 67,644, respectively, for initial inoculum of 106 and 108 cfu/ml, indicating the bacterial loading or the severity of infection would infect the PK/PD modeling results. The ex vivo PK/PD-based population dose prediction indicated a target attainment rate (TAR) at the existing daily dose (75mg/udder) of 84.77% against E.coli. Thus, it was recommended as rational dosage. The COPD of cefquinome against E.coli was determined as 8μg/ml at the dose of 75mg/udder. The derived ECOFF, COPD, together with ex vivo PK/PD-based population dose prediction served as important steps in the establishment of optimum dose regimen and provided a useful interpretative criterion to categorize the antimicrobial susceptibility testing results of cefquinome.

Анализ кривой обучения хирургов в зависимости от сложности нефрометрической оценки при выполнении лапароскопической резекции почки у пациентов с локализованными образованиями паренхимы почки

Aim to analyze the learning curve of surgeons while performing laparoscopic partial nephrectomy in patients with localized renal parenchymal lesions by calculating the MIC (negative surgical margin, ischemia, and complications) index depending on tumor complexity according to the R.E.N.A.L. and PADUA nephrometric scores. Materials and methods the retrospective study included the results of laparoscopic partial nephrectomies in 320 patients with localized renal parenchymal lesions. The procedures were carried out by four surgeons from the Institute of Urology and Human Reproductive Health of FGAOU VO I.M. Sechenov First Moscow State Medical University, Moscow, Russia (EC-1; ESH-4; EB-7; ME-13) from January 2014 to June 2019. At baseline, all operators had experience of performing at least 30 laparoscopic interventions. In addition to the standard preoperative examination, a 3D virtual planning was carried out using the Amira 3D modeling program. In all cases, the nephrometric assessment of complexity was performed according to the R.E.N.A.L. and PADUA scores. The learning curve was assessed based on the results of operations based on the MIC index. All surgical interventions were divided into eras. In the era, 40 consecutive procedures for each operator were evaluated. Acquired skills were assessed over two eras. Results The average age of patients, of which 191 (59.7%) were men, was 54.4+/-11.37 years. The average body mass index was 28.55+/-3.85 kg/m2, the absolute volume of kidney lesions was 26.72+/-43.72 cm3, the average Charlson comorbidity index was 1.46+/-1.29, the average R.E.N.A.L. and PADUA scores were 6.38+/-1.75 and 7.92+/-1.51, respectively, the average duration of procedure was 150.36+/-50.18 min, the average blood loss was 227.94+/-280.22 ml, the average time thermal ischemia was 13.28+/-7.82 min. Postoperative complications were seen in 36 (11.2%) cases, of which grade III and more according to Clavien-Dindo developed in 8 patients (2.5%). A positive surgical margin was found in 4 (1.2%) patients. The overall MIC index was achieved in 243 (75.9%) cases; in era 1 it was seen in 71.9% cases in comparison with 80% in era 2. With the 1st degree of complexity (152 (47.5%) patients), MIC was achieved in 80.9% of cases, compared to 76.6% and 56.8% in patients with 2nd degree of complexity (n=124, 38.8%) and 3rd degree of complexity (n=44, 13.8%), respectively. Rate of MIC achievement in eras 1 and 2 for different surgeons were as following: 65% and 72.5%, 75 and 80%, 87.5 and 85% and 60 and 82.5%, for operator 1, 4, 7 and 13, respectively. Age, tumor complexity, R.E.N.A.L. score and PADUA score were the most significant parameters for determining MIC, identified on the basis of the criterion of equality of group means of discrete analysis. Conclusion In all surgeons, the MIC index increased with the accumulation of experience in performing laparoscopic partial nephrectomy, but was lower with an increased degree of complexity of procedures. The minimum number of laparoscopic partial nephrectomies required to achieve an MIC more or equal 70% should be at least 40.

Antimycobacterial, antimicrobial, antioxidant activities and in silico PASS investigations of root fractions and extract of Cordia dichotoma Forst

Indian cherry (Cordia dichotoma Forst.) is a medicinally important plant widely consumed as an indigenous remedy for several ailments in the India. Although it is widely used plant by the population, there are no studies on root proving these medicinal claims. The present study was designed to investigate antimicrobial, antimycobacterial and antioxidant activities of Cordia dichotoma Forst. roots and in silico biological activities prediction using PASS. Methanolic extract was prepared and further fractions were obtained by liquid–liquid partitioning. Agar well diffusion assay and disc diffusion method were selected for antimicrobial activity. Antimycobacterial activity was estimated against Mycobacterium tuberculosis. For antioxidant activity, DPPH and hydrogen peroxide (H2O2) radical scavenging assay were employed. All the tested samples exhibited diverse pattern of sensitivity for tested strains. The value of MIC, MMC and MIC index showed that P. vulgaris and K. pneumonia were the most sensitive for ME and CF, whereas A. fumigates and V. myditis were sensitive to CF and AF. Microorganism susceptible index was 100 for P. vulgaris and K. pneumonia bacteria, and A. fumigates and V. myditis fungi. CF exhibited best activity against M. tuberculosis with lowest MIC of 30 mg/ml and highest activity index of 0.85. Dose dependent antioxidant activity was observed in both the assay. This data provides evidence that Cordia dichotoma Forst. roots have potent antibacterial, antimycobacterial, antioxidant, and moderate antifungal activity and a potential cure for infectious diseases like tuberculosis.

Synthesis of oligoguanidine - Based on polycondensation and compare their Antimicrobial Activities with Chloramine B

Oligoguanidine with chain extension were synthesized by condensation and cross-linking polymerizations in an attempt to increase molecular weight and charge density of the anti microbial oligoguanidine. The reactions are procedure at 170 oC for 5h with ratio molar of HMDA: GHC = 1: 1.1, refined by vacuum filter at 60 oC. The Oligoguanidine OHMG.HCl synthesized has molecular weight equal 521 g/mol, chain structure and good water solubility. The comparison results of the antimicrobial activities of oligoguanidine with chloramine B indicated that MIC index of OHMG.HCl is 5ppm during MIC index of chloramine B is 50 ppm; MBC of OHMG.HCl is 12 minutes and MBC of chloramine B is 11 minutes; The SEM, TEM imagines exhibited clear biocide, low residue microorganism of OHMG.HCl. The LC-MS spectrum indicates the presence of haloacetic acid following the bactericidal action of chloramphen B, while OHGM.HCl is not available. This result confirms the environmental friendliness of oligoguanidine.

Identification of the In Vivo Pharmacokinetics and Pharmacodynamic Driver of Iclaprim.

The neutropenic murine thigh infection model was used to define the pharmacokinetic/pharmacodynamic index linked to efficacy of iclaprim against Staphylococcus aureus ATCC 29213 and Staphylococcus pneumoniae ATCC 10813. The 24-h area under the curve (AUC)/MIC index was most closely linked to efficacy for S. aureus (R2, 0.65), while both the 24-h AUC/MIC and the percentage of time that drug concentrations remain above the MIC (%T>MIC) were strongly associated with effect (R2, 0.86 for both parameters) for S. pneumoniae.

Antibacterial Activity of Azadirachta indica Leaf Extracts Against Some Pathogenic Standards and Clinical Bacterial Isolates

Background: Azadirachta indica A. Juss (Neem) has been used against a few diseases in traditional medicine. This study was conducted to evaluate the antibacterial activity of Neem leaves extract against some antibiotic sensitive and resistant strains of important human pathogenic bacteria. Methods: The antimicrobial activities of ethanol, methanol, and ethyl acetate extracts of Azadirachta indica A. juss leaves were evaluated against some pathogenic bacterial strains including S. aureus ATCC 6538, E. faecalis ATCC 1394, P. aeroginosa ATCC 9027, E.coli, ATCC 25922, and their clinical isolates using agar well diffusion and MTT microdilution methods. MBC was determined by subculturing from microdilution assays. Results: The results revealed that methanol extract has the strongest growth inhibitory effect on both standard and clinical isolated strains of P. aeroginosa. Ethyl acetate and ethanol extracts, showing a growth inhibitory effect on both standard and hospital isolated strains of S. aureus. In the case of E. faecalis, ethanol and methanol extracts showed the highest growth inhibitory effect against standard and clinical strains, respectively. According to the MIC index results, the methanol extract has a bactericidal activity against both standard and nosocomial strains of S. aureus and P. aeroginosa and bacteriostatic activity against nosocomial strain of E. faecalis. Ethanol extract showed bactericidal activity against both standard and nosocomial strains of E. faecalis and P. aeroginosa and bacteriostatic activity against nosocomial strain of S. aureus. Ethyl acetate extract had shown bactericidal activity against standard strains of S. aureus and P. aeroginosa and bacteriostatic against nosocomial strain of S. aureus and standard strain of E. faecalis. Conclusions: Results revealed that Neem may be a prospective therapeutic agent to combat antibiotic resistant bacteria.

Anti-Dermatophytic Potential of Formulated Extract of Cola nitida (Vent.) Schott&amp; Endl. (Stem Bark)

The antifungal activities of stem bark ethanolic extract of Cola nitida [Vent.) Schott & Endl. against fungi associated with dermatophytes was determined in vitro by agar cup diffusion, agar dilution technique, and time kill assay. The result showed that the extract at concentrations ranging between 6 mg/mL to 0.5 mg/mL produced zone of inhibition between 10 ± 0.1 and 25 ± 0.2 mm against the test fungi. The MIC and MFC of the extract ranged from 22.5 to 3120 µg/mL and 45 to 3120 µg/mL respectively. The MICs for Trichophyton rubrum and T. tonsurans were less than 100 µg/mL and the mechanism of antibiosis indicated that the formulated ethanolic extract was highly fungicidal. Since lower MIC and MFC indicates higher efficacy, the MIC/MFC in this study are within the range of ≤ 100 and ≥ 1000 µg/mL. The highest MIC in this study is 3120 µg/mL and active extract are those having MIC values ≤ 8000 µg/mL. The MIC index values, being less than or equal to 2, indicated the fungicidal attribute of the formulated ethanolic extract and suggested that fungicidal effects be expected on all the tested dermatophytes. In the time kill assay, the percentage log reduction of the viable cell count ranged between 0.35 Log10 cfu/mL at 2 hr to 0.96 Log10 cfu/mL at 4 hr for T. tonsurans while it ranged between 0.29 Log10 cfu/mL at 2 hr to 0.85 Log10 cfu/ml. The results showed that the extract exhibited a broad spectrum antifungal activity and justifies the use of Cola nitida in folkloric medicine for the treatment of various skin diseases in Nigeria.

Breaking the resistance of Escherichia coli: Antimicrobial activity of Berberis lycium Royle.

The antimicrobial activity of root bark of Berberis lycium and its principal component berberine was tested against a panel of microbial strains using agar well diffusion test and further analyzed using micro-broth dilution method. Preliminary analysis, on the basis of zone of Inhibition (ZOI) showed that the methanolic extract of B.lycium was highly effective against Escherichia coli (ZOI 41±1mm). Among the bacterial strains E.coli was found to be most susceptible and among fungi Candida albicans was the most susceptible for berberine as well as the crude methanolic extract of the plant. Methanolic extract of the plant was more effective for E.coli (MIC 1.7±1.18; MBC 2.4±1.18) than berberine (MIC 3.5±0.57) (p<0.05), whereas berberine was more effective than crude extracts for C.albicans. In addition, E.coli showed the development of resistant colonies after 72h when tested with berberine but the development of such colonies was not observed with the methanolic extract of the plant. This could be due to the presence of resistance breaking molecules in the crude methanolic extract of B.lycium. Also the MIC index of crude methanolic extract was 1.39 for E.coli, which showed the mode of action to be bactericidal. HPLC analysis revealed the presence of berberine at highest concentration in methanolic extract of the plant, followed by aqueous extract. Potentiation of this berberine by resistance breaking molecules in the crude extract could be a possible explanation for its strong effectiveness.

Biological activities of leaves of ethnomedicinal plant, Borassus flabellifer Linn. (Palmyra palm): An antibacterial, antifungal and antioxidant evaluation

Plants contain a variety of phytochemicals that have the ability to exert effect on human body. Among them Borassus flabellifer Linn. is a medicinally important plant. In traditional medicine different parts of plants are being used for their medicinal properties. The methanol extract was obtained from powdered leaves and further fractions were prepared. Antimicrobial potential was investigated using eight pathogenic strains of bacteria and fungi by agar well diffusion method. Broth dilution method was employed to MIC and MMC of active samples and MIC index value was determined. ME was subjected to preliminary phytochemical analysis; and 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) radical scavenging activity. Phytochemical screening revealed the presence of several phytochemicals. The ME showed dose dependent radical scavenging activity as evidenced by IC50 values for DPPH (40.19μg/ml) and H2O2 (30.92μg/ml) radicals. The inhibition zones and MIC values for bacterial strains were in the range of 10–16mm and 50–70μg/ml, respectively. All the samples showed an inhibitory effect on fungal strains with inhibition zone (10–17mm) and MFC (50–70μg/ml). Samples exhibited diverse patterns of antibacterial and antifungal effects. Among the tested samples, methanol extract and acetone fraction (AF) had potent antibacterial and antifungal activities. These results lead to the conclusion that the plant has a broad spectrum antimicrobial and antioxidant activity and could be a potential option for treating various infectious diseases. The strong antioxidant property of methanol extract might be employed in the development of natural antioxidants for agro-food and pharmaceutical industries.

Studies on Optimization of Growth Parameters for Enhanced Production of Antibiotic Alkaloids by Isolated Marine actinomycetes

The aim of the present study is to optimize the growth conditions for improved production of alkaloids by promising marine actinomycetes isolated from marine sediments collected on Kakinada coast. The bioactive compounds were extracted from the isolated actinomycetes using organic solvents and screened for alkaloids using qualitative tests. The presence of alkaloids in the crude methanolic extract was confirmed by UV spectroscopic analysis and quantified by BCG method. The effect of pH, temperature, carbon and nitrogen sources on the growth and fermentative production of alkaloids was optimized. The strain was improved for enhanced production of alkaloids by physical and chemical mutagenesis. The antimicrobial activity of the crude alkaloid extract was determined by the well diffusion method. The isolated strain exhibited the highest growth and alkaloid production at pH 6 and temperature 30oC in 7 days. The alkaloid production was significantly increased 4.5-folds with UV treatment for 30 min and further 5.5-folds with ethidium bromide treatment (30µg/mL) for 1h. The resultant double mutant strain exhibited significantly high antimicrobial activity against S.aureus compared to other bacterial strains with MIC index less than 4. The isolated double mutant strain of actinomycetes can be a potential source of antibiotic alkaloids.

Polyprenols of Ginkgo biloba Enhance Antibacterial Activity of Five Classes of Antibiotics.

Polyprenol (GBP) from Ginkgo biloba Leaves (GBL) is an important lipid with many bioactive effects. The effect of GBP on antibacterial properties of five antibiotics belonging to different classes was through analysis of inhibition halos, MIC, and FIC index. And we studied the time-killing curves and Ca2+ mobilization assay in Staphylococcus aureus cells treated with GBP microemulsion and gentamicin sulfate under MIC/2 conditions. These results showed that the GBP microemulsion (average diameter 90.2 nm) combining with gentamicin sulfate had the highest enhancing antibacterial effect against Staphylococcus aureus, and the MIC value was 33.0 μg/mL. The increase of the antibacterial effect of tested antibiotics was positively correlated with the decrease of the average diameter of GBP microemulsion. Moreover, GBP microemulsion enhanced antibacterial effect and prolonged antibacterial time of GBP combining with gentamicin sulfate against Staphylococcus aureus. GBP microemulsion could enhance the ability of gentamicin inducing an increase in intracellular calcium concentrations to Staphylococcus aureus. GBP microemulsion could help some classes of antibiotics to inhibit or kill bacteria. This study supports the fact that GBP microemulsion obviously can not only reduce the dosage of some classes of antibiotics, but also reduce the frequency of the antibiotic use in vitro.