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The growing number of macrolide-resistant strains of Streptococcus pyogenes is an increasing problem worldwide. In this study, we evaluated 62 clinical isolates of S. pyogenes obtained from the upper respiratory tract. Susceptibilities to penicillins, cephalosporins, fluoroquinolones, macrolides, and carbepenems were determined by minimal inhibitory concentrations (MICs). Expressions of macrolide-resistance genes (mefA, ermB, and ermTR) were also examined, by polymerase chain reaction (PCR). All strains were susceptible to beta-lactams. On the other hand, of the 62 S. pyogenes isolates, 6.5%, 6.5%, 6.5%, and 3.2% of the strains were resistant to azithromycin (AZM), roxithromycin (RXM), clarithromycin (CAM), and telithromycin (TEL), respectively. Four (6.5%) strains had a type of macrolide-resistance gene; there were two strains with ermB and two strains with ermTR, and these four strains were resistant to AZM, CAM (one strain was intermediately resistant), and RXM. Strains having ermB were resistant to TEL (MIC, > or = 8 microg/ml), while strains having ermTR were susceptible to TEL. Physicians and researchers need to take into consideration the macrolide resistance of some strains of S. pyogenes.
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Different 3-amino-4-aminoximidofurazan derivatives (PI1-4) were synthesized via protic acid catalysis and subsequently characterized by (1) H NMR and (13) C NMR spectra, recorded at 400 and 100 MHz respectively. We have tested the antimicrobial and antibiofilm activities of these synthetic derivatives (PI1-4) against both Staphylococcus aureus and Pseudomonas aeruginosa. The compounds so tested were also compared with standard antibiotics namely Tobramycin (Ps. aeruginosa) and Azithromycin (Staph. aureus) which were used as a positive control in all experimental sets. All these compounds (PI1-4) exhibited moderate to significant antimicrobial activities against both micro-organisms wherein compound PI3 showed maximum activity. Biofilm inhibition of both micro-organisms was then evaluated by crystal violet and safranin staining, estimation of biofilm total protein and microscopy methods using sub-MIC dose of these compounds. Results showed that all compounds executed anti biofilm activity against both Staph. aureus and Ps. aeruginosa wherein compound PI3 exhibited maximum activity. In relation with microbial biofilm inhibition, we have observed reduction in bacterial motility, proteolytic activity and secreted exo-polysaccharide (EPS) from both Staph. aureus and Ps. aeruginosa when they were grown in presence of these compounds. While addressing the issue of toxicity on host, we have observed that these molecules exhibited minimum level of R.B.C degradation.
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Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major concern worldwide and gonococcal AMR surveillance globally is imperative for public health purposes. In Eastern Europe, gonococcal AMR surveillance is exceedingly rare. However, in 2004 the Russian gonococcal antimicrobial susceptibility programme (RU-GASP) was initiated. The aims of this study were to describe the prevalence and trends of gonococcal AMR from 2009 to 2012, and molecular epidemiological genotypes in 2011 and 2012 in Russia.
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Inter-rater agreement for the grade of TF was significantly higher in the field (kappa coefficient, κ, 0.73, 95% confidence interval, CI 0.67-0.80) than by photographic review (κ = 0.55, 95% CI 0.49-0.63; difference in κ between field grading and photo grading 0.18, 95% CI 0.09-0.26). When field and photographic grades were each assessed as the consensus grade from the three graders, agreement between in-field and photographic graders was high for TF (κ = 0.75, 95% CI 0.68-0.84).
Fifty-six azithromycin-resistant (MICs, 2.0 to 4.0 micro g/ml) Neisseria gonorrhoeae strains with cross-resistance to erythromycin (MICs, 2.0 to 64.0 micro g/ml), isolated in Canada between 1997 and 1999, were characterized, and their mechanisms of azithromycin resistance were determined. Most (58.9%) of them belonged to auxotype-serotype class NR/IB-03, with a 2.6-mDa plasmid. Based on resistance to crystal violet (MICs >or= 1 micro g/ml), 96.4% of these macrolide-resistant strains appeared to have increased efflux. Nine of the eleven strains selected for further characterization were found to have a promoter region mtrR mutation, a single-base-pair (A) deletion in the 13-bp inverted repeat, which is believed to cause overexpression of the mtrCDE-encoded efflux pump. The two remaining macrolide-resistant strains (erythromycin MIC, 64.0 micro g/ml; azithromycin MIC, 4.0 micro g/ml), which did not have the mutation in the mtrR promoter region, were found to have a C2611T mutation (Escherichia coli numbering) in the peptidyltransferase loop in domain V of the 23S rRNA alleles. Although mutations in domain V of 23S rRNA alleles had been reported in other bacteria, including E. coli, Streptococcus pneumoniae, and Helicobacter pylori, this is the first observation of these mutations associated with macrolide resistance in N. gonorrhoeae.
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Minimal inhibitory concentrations (MICs) of azithromycin and lansoprazole alone and in combination were determined for 106 clinical H. pylori isolates by means of an agar dilution technique. Killing kinetics of seven isolates were also studied in fluid medium.
In 2000-2001, 840 clinical isolates of Haemophilus influenzae were collected from laboratories in France, Germany, Italy and Spain (210 isolates/country). Beta-Lactamase production among the isolates varied considerably by country, ranging from 8.1% in Germany to 34.8% in France. H. influenzae from patients or=18 years (16.5%). All isolates were susceptible to amoxicillin-clavulanate, ciprofloxacin and levofloxacin; 99.6% and 98.9% of isolates were susceptible to azithromycin and cefuroxime, respectively. Among the macrolides tested, azithromycin (MIC90, 2 mg/L) was eight-fold more potent than clarithromycin (MIC90, 16 mg/L) and roxithromycin (MIC90, 16 mg/L). Despite variations in beta-lactamase production between different countries, > 99% of all isolates were susceptible to amoxicillin-clavulanate, ciprofloxacin, levofloxacin, and azithromycin.
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Several drug development strategies, including optimization of new antimalarial drug combinations, have been used to counter malaria drug resistance. We evaluated the malaria Sybr green I-based fluorescence (MSF) assay for its use in in vitro drug combination sensitivity assays. Drug combinations of previously published synergistic (atovaquone and proguanil), indifferent (chloroquine and azithromycin), and antagonistic (chloroquine and atovaquone) antimalarial drug interactions were tested against Plasmodium falciparum strains D6 and W2 using the MSF assay. Fifty percent inhibitory concentrations (IC(50)s) were calculated for individual drugs and in fixed ratio combinations relative to their individual IC(50)s. Subsequent isobologram analysis and fractional inhibitory concentration determinations demonstrated the expected drug interaction pattern for each combination tested. Furthermore, we explored the ability of the MSF assay to examine mixed parasite population dynamics, which are commonly seen in malaria patient isolates. Specifically, the capacity of the MSF assay to discern between single and mixed parasite populations was determined. To simulate mixed infections in vitro, fixed ratios of D6 and W2 strains were cocultured with antimalarial drugs and IC(50)s were determined using the MSF assay. Dichotomous concentration curves indicated that the sensitive and resistant parasites composing the genetically heterogeneous population were detectable. Biphasic analysis was performed to obtain subpopulation IC(50)s for comparison to those obtained for the individual malaria strains alone. In conclusion, the MSF assay allows for reliable antimalarial drug combination screening and provides an important method to discern between homogenous and heterogeneous parasite populations.