Tablet Diffusion Research Articles

Synthesis and Antimicrobial and Anticancer Activity of β-Carboline Analogues

The β-carboline alkaloids possess a wide diversity of important biochemical effects and pharmacological properties. A series of β-carboline derivatives were synthesized from L-tryptophan through the Pictet-Spengler reaction and oxidation of K2Cr2O7 via sequential one-pot synthesis method. In vitro anti-bacterial, insecticidal, and cytotoxic activities of all synthesized compounds were investigated by the tablet diffusion, leaf disc, and MTT methods, respectively. Some of the compounds(1a, 1b, 1c and 1j) exhibited obvious anti-bacterial effects and some (1-3) had significant cytotoxic activities against tumor cells 3LL, MCF-7, BGC-823 and QGY-7701, with IC50 values of 7.79, 5.75, 3.53 and 4.02 μg/mL, respectively. No insecticidal activity against third stage instar larvae of Mythimnaseparata Walker were observed under the tested concentration.

Molecular identification and antifungal susceptibility of 186 Candida isolates from vulvovaginal candidiasis in southern China.

There is limited information regarding the molecular epidemiology and antifungal susceptibilities of Candida isolates using the Neo-Sensitabs method in patients with vulvovaginal candidiasis (VVC). From August 2012 to March 2013, 301 non-pregnant patients aged 18-50 years with suspected VVC were prospectively screened at a teaching hospital in southern China. The vaginal isolates were identified by DNA sequencing of internal transcribed spacer and the D1/D2 domain. Antifungal susceptibility testing of seven antifungal agents was performed using the Neo-Sensitabs tablet diffusion method. Candida species were isolated from 186 cases (61.79 %). The most common pathogen was Candida albicans (91.4 %), followed by Candida glabrata (4.3 %), Candida tropicalis (3.2 %) and Candida parapsilosis (1.1 %). The susceptibility rates to C. albicans were higher for caspofungin, voriconazole and fluconazole than those for itraconazole, miconazole, ketoconazole and terbinafine (P<0.01). The resistance rates to C. albicans were 4.7, 6.5, 7.1, 7.6, 12.3, 27.7 and 74.7 % for caspofungin, miconazole, itraconazole, voriconazole, fluconazole, ketoconazole and terbinafine, respectively. No drugs tested apart from fluconazole exhibited differences in resistance between C. albicans and non-albicans Candida isolates. The results demonstrate that, using DNA sequencing, C. albicans is the most common isolate from Chinese patients with VVC. Caspofungin, voriconazole and fluconazole may be preferable to other azoles and terbinafine in the treatment of VVC.

Tablet diffusion, adoption and implementation in academic libraries: A qualitative content analysis of librarians' discourse on blogging platforms

This study examines the evidence on blogs and tweets about the diffusion of tablets in academic libraries to find out why do early adopters or academic librarians adopt tablets and implement them into library services? Results reveal two factors why academic librarians and libraries adopt and integrate tablets.Cette étude examine les traces sur les blogues et les microbillets concernant la diffusion des tablettes dans les bibliothèques universitaires. L’objectif est de déterminer pourquoi les acheteurs précoces ou les bibliothécaires universitaires adoptent les tablettes et les intègrent dans leurs services en bibliothèque. Les résultats révèlent deux facteurs expliquant pourquoi les bibliothécaires universitaires et les bibliothèques adoptent et intègrent les tablettes.

Susceptibility of 100 filamentous fungi: comparison of two diffusion methods, Neo-Sensitabs and E-test, for amphotericin B, caspofungin, itraconazole, voriconazole and posaconazole

We compared the E-test method to that of the Neo-Sensitabs tablet diffusion assay for evaluating the in vitro susceptibility of 100 clinical isolates of filamentous fungi (Aspergillus spp., Fusarium spp., Scedosporium spp., zygomycetes and other molds) to amphotericin B, itraconazole, voriconazole, caspofungin, and posaconazole. We determined the categorical agreement level between E-test minimum inhibitory concentrations (MIC) and tablet end-points, as opposed to the following disagreement parameters: very major error - resistant parameter (R) in E-test and susceptible (S) in tablet; major error - S by E-test and R by tablet; minor error - shifts between S and susceptible dose-dependent (S-DD) or S-DD and R. We also performed linear regression analyses and computed Pearson's correlation coefficients (R values) between the log transforms of MICs and the inhibition zone diameters of the five studied antifungal agents. For itraconazole we obtained 97% categorical agreement and R = -0.727. Categorical agreement for caspofungin and voriconazole was 96% and R =-0.821 and R = -0.789, respectively. For posaconazole the categorical agreement was 94% and R =-0.743. Amphotericin B exhibited a lower degree of agreement (76%, R = -0.672), especially in studies of Aspergillus spp. Our results suggest a potential value of the Neo-Sensitabs assay for in vitro susceptibility testing of molds to itraconazole, voriconazole, caspofungin and posaconazole, while amphotericin B exhibited an overall lower degree of agreement.

Synthesis and Bioactivity of β-Carboline Derivatives

The β-carboline alkaloids possess a wide diversity of important biochemical effects and pharmacological properties. A series of β-carboline derivatives were synthesized from L-tryptophan through the Pictet-Spengler reaction and oxidation of K2Cr2O7 by a sequential one-pot synthesis method. In Vitro antibacterial, insecticidal, and cytotoxic activities of all synthesized compounds were investigated by the tablet diffusion, leaf disc, and MTT methods, respectively. Some of the compounds (1-1, 1-2, 1-3 and 1-12) exhibited obvious antibacterial effects and some (1-3) had significant cytotoxic activities against tumor cells 3LL, MCF-7, BGC-823 and QGY-7701, with IC50 values of 7.79, 5.75, 3.53 and 4.02 μg/mL, respectively. No insecticidal activity against third stage instar larvae of Mythimna separata Walker were observed under the tested concentration.

Correlation between In Vitro Activity of Posaconazole and In Vivo Efficacy against Rhizopus oryzae Infection in Mice

We have evaluated the in vitro activity of posaconazole (PSC) against 50 clinical strains of Rhizopus oryzae using a broth microdilution method, the Neo-Sensitabs tablet diffusion method, and minimal fungicidal concentration (MFC) determination. In general, PSC showed low MICs against this fungus, and the MICs correlated with the inhibition zone diameters. Most of the MFCs, however, were from 1 to 4 dilutions higher than their corresponding MICs. We then investigated the efficacies of several different doses of PSC in a murine model. All treatments began 24 h after challenge and lasted for 7 days. The drug was administered twice a day to mice infected with three strains that showed intermediate PSC susceptibility (MIC = 2 microg/ml) and three PSC-susceptible strains (MIC = 0.25 microg/ml). A dose of 10 mg/kg of body weight was ineffective, while doses of 20 and 30 mg/kg prolonged the survival of the mice. The 50 strains tested were segregated into two groups on the basis of the in vitro data. For the group with the most strains (85%), the strains had low PSC MICs, mice infected with the strains showed higher rates of survival (30 to 40%), and PSC was able to reduce the fungal load in the kidney and less regularly in the brain. For the second group (15% of the strains), the strains had intermediate PSC MICs, mice infected with the strains had lower survival rates (10 to 20%), and PSC treatment resulted in variable and no reductions in the fungal loads in the kidneys and brains, respectively.

A novel polymeric biomaterial based on carboxymethylstarch and its application in controlled drug release

AbstractThis study reports investigation of the sustained release behavior of a model drug (acetylsalicylic acid) from carboxymethylstarch (CMS) based matrix. CMS was prepared by incorporation of carboxymethyl groups in the starch moiety; by reacting starch with sodium salt of monochloro acetic acid in presence of sodium hydroxide. The in vitro drug release study was performed by United States Pharmacopeia rotating paddle method, at various pH. The rate of drug release from the above matrix was found to increase with increase in pH. Further, the release behavior of the drug from the CMS based matrix was found to be non‐Fickian, n value being between 0.80 and 0.85, suggesting that the release was controlled by a combination of tablet erosion and diffusion of the drug from the swollen matrix. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Comparison of Tablet and Disk Diffusion Methods for Fluconazole and Voriconazole In Vitro Activity Testing Against Clinical Yeast Isolates

We have compared a commercially available tablet diffusion method for the In Vitro antifungal susceptibility testing of fluconazole (FCZ) and voriconazole (VCZ) with the disk diffusion method M44 (CLSI) with 282 clinical yeast isolates. The superior stability of antifungal agents in tablets can explain the differences for each category of susceptibility by both methods.Neo-Sensitabs™ tablets antifungal susceptibility testing showed an excellent correlation (0.98 for FCZ and 0.98 for VCZ at 24h and 0.96 for FCZ and 0.94 for VCZ at 48h), a reduced percentage of disagreements (4.6% and 8.2% for FCZ at 24h and 48h respectively; 1.1% and 2.1% for VCZ at 24h and 48h respectively) and the absence of statistically significant difference in comparison with the reference protocol for performing antifungal susceptibility testing with the agar diffusion method.

Species Distribution and Susceptibility to Azoles of Vaginal Yeasts Isolated Prostitutes

Objective. We investigated the use of miconazole among female prostitutes in Costa Rica as well as the distribution of vaginal yeasts and the susceptibility pattern to azoles of strains obtained from this population. Our intention was to relate a frequent use of miconazole to occurrence of vaginal yeasts resistant to azoles. Methods. Vaginal samples were taken from 277 patients that have previously used azoles. Vaginal swabs were obtained for direct microscopy and culture. Yeast isolates were identified by germ tube test and assimilation pattern. Susceptibility testing was determined using a tablet diffusion method. Results. The number of clinical Candida isolates (one from each patient) was 57 (20.6%). C. albicans was the predominant species (70%), followed by C. parapsilosis (12%), C. tropicalis (5.3%), C. glabrata and C. famata (3.5% each), C. krusei, C. inconspicua and C. guilliermondii (1.7% each). The majority of vaginal Candida isolates were susceptible to ketoconazole (91%), fluconazole (96.5%), and itraconazole (98%). A lower susceptibility of some isolates to miconazole (63%) was observed as compared to the other azoles tested. Moreover, the strains, nonsusceptible to miconazole, were more often obtained from patients that have used this antifungal at least four times within the last year before taking the samples as compared to those with three or less treatments (). Conclusion. An indiscriminate use of miconazole, such as that observed among female prostitutes in Costa Rica, results in a reduced susceptibility of vaginal yeasts to miconazole but not to other azoles.

Nasopharyngeal pathogens in children with acute otitis media in a low-antibiotic use country

Objective: Acute otitis media (AOM) is one of the most common diseases of childhood. Knowledge, of which bacteria are the most common pathogens in AOM and their susceptibilities towards antibiotics, is essential for the reasonable empiric treatment. With rapidly increasing frequencies of antibiotic resistance surveillance of the common etiologic pathogens has become pertinent. The purpose of this paper is to present the bacteriological findings and antibiotic susceptibilities, in cultures from nasopharyngeal swabs, in Danish children with AOM. Methods: Children aged up to 10 years who had AOM diagnosed in general practice in Denmark were swabbed in nasopharynx, cultures were incubated and susceptibility testing was performed as tablet diffusion and minimal inhibitory concentrations (MICs) were determined by E-test. Results: We included 331 patients, in 257 bacteria were found, which could be classified as commonly ear pathogenic. The most frequent bacteria found was Streptococcus pneumoniae followed by Haemophilus influenzae and Moraxella catarrhalis. Ninety-six percent of the tested S. pneumoniae were susceptible towards penicillin and 99% towards erythromycin. Eighty-nine percent of the H. influenzae were susceptible to ampicillin and all tested M. catarrhalis were susceptible towards erythromycin. In more than 30% of H. influenzae MIC of phenoxymethylpenicillin were above the level that could be achieved in middle ear fluid. Conclusion: Antimicrobial resistance is still infrequent in pathogens that might cause AOM in children in Denmark; this is probably due to minimal use of antibiotics as well as the use of phenoxymethylpenicillin as primary drug for treatment of AOM. Phenoxymethylpenicillin and azithromycin are not efficient for treating the majority of infections due to H. influenzae.

Cryptococcus neoformans var. neoformans resistant to fluconazole in an HIV-negative patient with chronic lymphocytic leukemia

Cases of fluconazole-resistant Cryptococcus neoformans have been reported in AIDS patients previously treated with fluconazole. We report a case of fluconazole-resistant cryptococcal meningitis in an HIV-negative patient not previously exposed to fluconazole. The patient experienced a clinical relapse after discontinuation of therapy with amphotericin B and subsequent initiation of fluconazole therapy. In vitro resistance was initially verified by Etest and tablet diffusion and later confirmed by NCCLS broth microdilution.

Prevalence of and Detection of Resistance to Ampicillin and other ß-lactam antibiotics in Haemophilus influenzae in Denmark

The susceptibility of Haemophilus influenzae to penicillin V and G, ampicillin and cefuroxime was investigated by MIC, disc and tablet diffusion methods, using chocolate agar as test medium, to determine the prevalence of ampicillin-resistant isolates and the optimal method for their detection. Eighty-six isolates were clinical isolates collected prospectively from July to September 1998 and 22 isolates were clinical isolates with decreased susceptibility to ampicillin previously referred to the reference laboratory. Eighty-seven isolates were ampicillin-susceptible and 16 were ampicillin-resistant. Thirteen produced beta-lactamases. Among the consecutive isolates 12.8% were resistant. With each of the Rosco Neo-sensitabs containing penicillin G, 2.5 microg ampicillin and 33 microg ampicillin, 3 very major errors occurred (resistant isolates misinterpreted as susceptible) and 5-13 major errors (susceptible isolates misinterpreted as resistant). The AB biodisk containing ampicillin (10 microg) was superior to the penicillin V and G discs, i.e. only 1 very major error occurred and major and minor errors were infrequent. The cefuroxime disc identified 4/8 beta-lactamase-negative ampicillin-resistant isolates. Thus, for susceptibility testing with chocolate agar as test medium, the use of an inoculum of 10(5) colony-forming units, 10 microg ampicillin discs and interpretative zone diameters of > or = 28 mm indicating susceptibility and < or = 25 mm indicating resistance was found to produce reliable identification of ampicillin-resistant isolates of H. influenzae.

Sensitivity testing of veterinary pathogens with a semi‐automatic image analysis system compared with tablet diffusion and agar dilution tests*

Summary Recently a commercial computer‐controlled image image analysis system (IAS) was introduced to measure automatically the diameters of inhibition zones in the agar diffusion test. However, there is little information on the precision of this method. In the present study clinical isolates of Salmonella spp. (N = 104), Escherichia coli (N = 100), Pasteurella spp. (N = 99), Actinobacillus pleuropneumoniae (N = 85), porcine streptococci (N = 100), and Staphylococcus aureus (N = 95) were tested in the agar diffusion test, using nineteen different antibiotics in tablets. All inhibition zone diameters were first measured by a laboratory technician and then by the IAS. Although the zone diameters of all bacteria‐antibiotic combinations measured by the IAS and those measured by the laboratory technician showed a significant positive correlation, the size of the inhibition zone diameters measured by the technician and the IAS differed significantly in 59% of the combinations. However, these differences were very small and may have no clinical relevance. The IAS was also used to calculate minimum inhibitory concentrations (MIC values) from the zone diameters. In 82% of the bacteria‐antibiotic combinations MIC values calculated by the IAS showed a significant positive correlation with MIC values obtained with the reference agar dilution test. However, in 92% of the bacteria‐antibiotic combinations, the calculated MIC values differed significantly from the reference values. In some cases these differences were so large that they could be of clinical relevance. The IAS was unable to measure the diameter of inhibition zones of porcine streptococci properly, due to poor contrast. We concluded that when tablets are used as antibiotic carriers the IAS accurately measures the diameter of inhibition zones for bacteria species that give good contrast between the agar and bacterial growth. MIC values determined with the IAS were only indicative of those determined with the reference agar dilution test.

Susceptibility testing of Actinobacillus pleuropneumoniae in Denmark. Evaluation of three different media of MIC-determinations and tablet diffusion tests

This study was conducted to compare the applicability of three different media in sensitivity testing of Actinobacillus pleuropneumoniae by means of MIC and tablet diffusion tests. The media used were: modified PPLO agar, chocolatized Mueller-Hinton-II and Columbia agar supplemented with NAD. Seven antimicrobial agents were tested: ceftiofur, enrofloxacin, penicillin, spectinomycin, tiamulin, trimethoprim + sulfadiazine and tylosin, against 40 randomly selected A. pleuropneumoniae isolates. In general, good agreement was found between results obtained with all combinations of media, most antimicrobials tested and the two – test systems. Some variations between media were observed for spectinomycin, tiamulin and tylosin. For ceftiofur and trimethoprim + sulfadiazine some isolates with low MIC-values were classified as resistant using tablet diffusion, indicating that the break points of resistance for these antimicrobials using the tablet diffusion tests need adjustment. Using current break points for resistance with MIC-determinations, all isolates tested susceptible to ceftiofur, enrofloxacin, penicillin, tiamulin and trimethoprim + sulfadiazine. A larger number of isolates tested resistant to spectinomycin and tylosin on all three media using both MIC determinations and tablet diffusion.

Detection of extended‐spectrum β‐lactamases

The susceptibility testing methods used in Denmark were evaluated with respect to their ability to detect cephalosporin resistance with cefuroxime as indicator, especially resistance caused by extended-spectrum beta-lactamases (ESBLs). Two methods for determination of minimal inhibitory concentration (MIC), three agar diffusion methods, a disc approximation test and the ESBL-Etest were used against a panel of strains producing well-known beta-lactamases. The tablet diffusion test (Rosco Neo Sensitabs) as the most used in Denmark had the lowest detection rate of cefuroxime resistance among ESBL-producing strains. The prediffusion method, which is only used at one laboratory, was the most reliable method for such detection. The MIC methods were in good agreement, but the detection rate for resistance due to ESBLs was low and depended on the antibiotics used. The disc approximation test and the ESBL-Etest both resulted in an acceptable ESBL detection rate. The latter tests discriminated between isolates producing the frequent chromosome-mediated and the in Denmark probably very rare ESBL-mediated cephalosporin resistance. For the evaluation of susceptibility tests such strains require special attention.

Antimicrobial resistance in Salmonella enterica subsp. enterica serovar typhimurium from humans and production animals.

We have studied the frequency of antimicrobial resistance and epidemiological relatedness among 473 isolates of Salmonella enterica subsp. enterica serovar typhimurium (S. typhimurium) from human and veterinary sources. The human strains were clinical isolates from patients with diarrhoea sent to the State Serum Institute during August 1993 (228 isolates). The animal strains were isolated from clinical or subclinical infections in cattle (48 isolates), pigs (99 isolates) or poultry (98 isolates), all from 1993. All strains were tested against 22 different antimicrobial agents used in both human and veterinary medicine with the tablet diffusion method. Strains were also phage-typed and the plasmid content determined in all resistant strains. Ribotyping was performed on selected strains. Of 228 human isolates tested, 19.3% of the strains were resistant to one or more antimicrobial agent compared with 10.4% of strains from cattle, 11.1% of strains from pigs and 9.2% of strains from poultry. Multiple resistance, i.e. resistance against at least four antimicrobial agents, was found in 9.2% of the human strains, but in only two of the cattle isolates. The majority of the multi-resistant strains in humans were from infections contracted outside Denmark, most often in southern Europe or south-east Asia. Resistance in human strains was most common against tetracycline (13%), ampicillin (12%), sulphonamide (12%), streptomycin (10%) and chloramphenicol (8%). The resistance pattern differed somewhat in animal isolates: Poultry strains were usually resistant only to ampicillin, while pig and cattle isolates were most often resistant to sulphonamide, tetracycline and streptomycin. Typing of the strains showed that some animal strains and human strains were indistinguishable. In conclusion, while antimicrobial resistance was present in S. typhimurium isolated from humans and animals in Denmark, multiple resistance was most often acquired outside Denmark.

In vitrosusceptibility of 124Xanthomonas maltophilia(Stenotrophomonas maltophilia) isolates

The in vitro susceptibility of 124 Xanthomonas maltophilia isolates was tested by four methods: Agar dilution (reference method), E-test, a disk diffusion and a tablet diffusion method. Trimethoprim-sulfamethoxazole had the highest activity against X. maltophilia, followed by a combination of aztreonam-clavulanic acid at different ratios, the ratio 1:1 being the most active with a susceptibility rate of 85% as compared to 2% for aztreonam alone. Addition of the beta-lactamase inhibitor tazobactam to piperacillin enhanced the rate of susceptible isolates from 31% to 53%, Relatively few isolates were susceptible to ciprofloxacin (27%) and gentamicin (9%). Generally, the disk diffusion method had a considerably higher frequency of "very major" discrepancies when compared with the agar dilution method than with the other methods. The susceptibility of X. maltophilia to trimethoprim-sulfamethoxazole and ciprofloxacin could reliably be determined by all the diffusion methods tested, but otherwise the agar dilution method is to be preferred. A standardized and reliable diffusion method for susceptibility testing of X. maltophilia remains to be found. Trimethoprim-sulfamethoxazole must be considered the drug of choice in the treatment of severe X. maltophilia infections. The combination aztreonam-clavulanic acid is promising, but must be proved in a clinical setting.

In vitro antimicrobial susceptibility testing of rapidly growing mycobacteria using the tablet diffusion method: resistance pattern of Norwegian Mycobacterium fortuitum and Mycobacterium chelonae isolates

Thirty-one Norwegian clinical isolates of rapidly growing mycobacteria classified as Runyon's group IV, including 20 Mycobacterium fortuitum and 11 Mycobacterium chelonae strains, were found resistant to a majority of tuberculostatic agents. Minimal inhibitory concentration (MIC) was determined for twelve other antimicrobial agents: amikacin, tobramycin, streptomycin, cefoxitin, imipenem, norfloxacin, ciprofloxacin, doxycycline, erythromycin, fusidic acid, co-trimoxazole and capreomycin. The agar plate dilution method was employed and compared with the agar tablet diffusion method. Regression lines were established correlating MIC values and inhibition zones. The agar tablet diffusion method was found to be a simple and useful method for testing antimicrobial susceptibilities of M. fortuitum and M. chelonae, and a good correlation between MIC values and zone sizes with twelve antimicrobial agents was revealed. Correlation coefficients for most of these antimicrobial agents were around -0.90. M. chelonae was generally more resistant than M. fortuitum. Four antimicrobial agents, capreomycin, norfloxacin, ciprofloxacin and amikacin, showed differences between M. fortuitum and M. chelonae large enough to allow the zone diameter to be used diagnostically.

Susceptibility testing of anaerobic bacteria

The relationship between susceptibility testing by an agar dilution test and a tablet diffusion test was studied for 60 anaerobic bacteria (20 B. fragilis, 20 anaerobic cocci, 20 Clostridium species). For cefoxitin, no prediffusion and prediffusion times of one h, three h, 12 h, 24 h and 48 h were examined. For metronidazole, erythromycin, clindamycin, penicillin and imipenem, only 24 h prediffusion and no prediffusion were studied. Measurements were made after incubation for 24 h and 48 h. Prediffusion improved the correlation for all antibiotics tested, and 24 h prediffusion gave the best results. The slope of the regression line increased and the influence of the individual growth parameters on zone size was reduced. Prediction of susceptibility based on three zone breakpoints to estimate MIC was also better with 24 h prediffusion. However, the variation about the regression line for many of the antibiotics was still extremely high. Measurements after 24 h and 48 h incubation times showed almost identical regression equations, except for erythromycin, where the regression lines differed.

Antimicrobial susceptibility and β‐lactamase characterization of Branhamella catarrhalis isolates from 1983/1984 and 1988

Branhamella catarrhalis isolates from lower respiratory tract specimens collected in 1983/84 (n = 50) and 1988 (n = 30) were examined for beta-lactamase production. The percent of beta-lactamase-producing strains increased from 25% to 63% from 1983/84 to 1988. beta-lactamases from 30 strains could be typed, and of these 28 were of the BRO-1 type and two the BRO-2 type. The two beta-lactamase inhibitors, clavulanic acid and brobactam were very active against beta-lactamase extracts whether of the BRO-1 or the BRO-2 type. Susceptibility to a number of antimicrobial agents or combinations of agents was determined by a plate dilution method (MICs) and by a tablet diffusion method. The penicillin tablet (Rosco Neo-Sensitabs) was found to be useful in discriminating between beta-lactamase-producing and non-beta-lactamase- producing strains of B. catarrhalis.