A novel series of acyclic nucleosides 2-5 and 13a-c were synthesized by utilizing 4-phenyl-6(naphthalen-2-yl)-2-oxo-1,2-dihydropridine-3-carbonitrile (1) as a key starting material. Chlorination of 1 yielded the chloro analogue 6 that was allowed to react with urea, thiourea, thiosemicarbazide and alicyclic secondary amines to produce the corresponding derivatives 7a-c and 11a-c. Further condensation of 6 with various amino acids provided the compounds 8-10, whereas hydrazinolysis of 6 yielded the hydrazinyl analogue 12 which was condensed with different isothiocyanates and acid anhydrides to afford derivatives 18-20, respectively. Upon treatment of 12 with sodium nitrite, the azide derivative 14 was obtained which was subjected to reaction with various active methylene compounds to obtain the corresponding triazolo derivatives 15-17. The structure assignment of the new compounds is based on chemicaland spectroscopic evidence. Antimicrobial evaluation of the newly synthesized derivatives was performed using ciprofloxacin and fluconazole as reference antibacterial and antifungal drugs. The most effective compounds against the tested bacterial and fungal isolates were the benzothiohydrazide compound 18b followed by the hydrazone and the phthalic anhydride derivatives 13c and 20, respectively.
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Among 77 sporadic single-patient strains, SCCmec types I-IV and four subtypes were identified. Type IV/IVA was most common (42.9%).The distribution of SCCmec types changed over the years. Type IV/IVA strains increased from 33.3% in 2000 to 57.9% in 2004. Type IV strains were resistant to ciprofloxacin in 81.8%, and in 9.1% to tobramycin while type IVA strains were 100% resistant to both antimicrobials. In contrast, non-type IV/IVA strains were resistant to ciprofloxacin in 86.4%, and in 75.0% to tobramycin. Only one strain was PVL positive and harbored SCCmec type III variant. By PFGE analysis, the 33 SCCmec type IV/IVA strains comprised 12 distinct genotypes. 36.4% of 11 CA-MRSA and 43.9% of 66 HA-MRSA harbored SCCmec type IV/IVA.
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Significant decreasing trends in rates of resistance to isoniazid, ethambutol, and at least 1 of the 3 first-line agents were observed among 2625 M. tuberculosis isolates from 2000 through 2006. Among these 2625 isolates, 150 (5.7%) were multidrug resistant, and 10 M. tuberculosis isolates (0.4%) fulfilled the definition of XDR M. tuberculosis. Nine (90%) of 10 patients with XDR TB had a previous history of TB and received anti-TB treatment before acquisition of XDR TB.
In water environment Camp. jejuni is exposed to a wide spectrum of temperatures, which affects its survival and potential to cause waterborne infections. Antimicrobial resistance in Camp. jejuni is increasing, and minor data exist on the effect of antimicrobial resistance on the survival of Camp. jejuni. Water is an important source of campylobacteriosis; thus, we need to have modelling data to predict the survival characteristics of these organisms in water.
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The behavior of the ciprofloxacin (CPFX) complex with copper, Cu(II)L(2), at a mercury electrode has been investigated in borax-boric acid buffer. The adsorption phenomena were observed by linear sweep voltammetry. The mechanism of the electrode reaction was found to be reduction of Cu(II)L(2) adsorbed on the surface of the electrode by an irreversible charge transfer to metal amalgam, Cu(0)(Hg). In the presence of DNA, the formation of the electrochemically non-active complexes Cu(II)L(2)-DNA results in the decrease of the equilibrium concentration of Cu(II)L(2) and its peak current. Under the optimum conditions, the decrease of the peak current is proportional to DNA concentration. The linear ranges are 6.67x10(-8) to 1.20x10(-5)gml(-1) for calf thymus DNA (ctDNA), 3.30x10(-8) to 2.33x10(-6)gml(-1) for fish sperm DNA (fsDNA) and 1.0x10(-8) to 1.2x10(-6)gml(-1) for yeast RNA. The detection limits are 5.00x10(-9), 3.00x10(-9) and 2.50x10(-9)gml(-1), respectively. This method exhibits good recovery and high sensitivity.
Antimicrobial drug use and overuse have been a topic of interest for many years, lately focusing on the growing resistance worldwide. This study was conducted in a small Indian hospital, where more than 80% of all admitted patients received antimicrobial drugs. Penicillin, gentamycin, co-trimoxazole, ciprofloxacin and metronidazole were most commonly used and all antimicrobial drugs were given empirically with no confirmation of the infective agent. Reports of increasing resistance to antimicrobial drugs in India, and elsewhere, necessitates a focus on how antimicrobials drugs are used in relation to investigations of resistance patterns among the local strains of pathogens. This study may be considered a base-line study, though of relevance for other hospitals, in particular in low-income areas, where development of resistance to standard antimicrobial drugs may have severe implications for both patients and health managers.
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In light of the concept of the mutant selection window, i.e., the range between the MIC and the mutant prevention concentration (MPC), MPC-related pharmacokinetic indices should be more predictive of bacterial resistance than the respective MIC-related indices. However, experimental evidence of this hypothesis remains limited and contradictory. To examine the predictive power of the ratios of the area under the curve (AUC24) to the MPC and the MIC, the selection of ciprofloxacin-resistant mutants of four Escherichia coli strains with different MPC/MIC ratios was studied. Each organism was exposed to twice-daily ciprofloxacin for 3 days at AUC24/MIC ratios that provide peak antibiotic concentrations close to the MIC, between the MIC and the MPC, and above the MPC. Resistant E. coli was intensively enriched at AUC24/MPCs from 1 to 10 h (AUC24/MIC from 60 to 360 h) but not at the lower or higher AUC24/MPC and AUC24/MIC ratios. AUC24/MPC and AUC24/MIC relationships of the areas under the time courses of ciprofloxacin-resistant E. coli (AUBCM) were bell-shaped. A Gaussian-like function fits the AUBCM-AUC24/MPC and AUBCM-AUC24/MIC data combined for all organisms (r(2) = 0.69 and 0.86, respectively). The predicted anti-mutant AUC24/MPC ratio was 58 ± 35 h, and the respective AUC24/MIC ratio was 1,080 ± 416 h. Although AUC24/MPC was less predictive of strain-independent E. coli resistance than AUC24/MIC, the established anti-mutant AUC24/MPC ratio was closer to values reported for Staphylococcus aureus (60 to 69 h) than the respective AUC24/MIC ratio (1,080 versus 200 to 240 h). This implies that AUC24/MPC might be a better interspecies predictor of bacterial resistance than AUC24/MIC.
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From October 2011 to September 2012, we collected the specimen from 316 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. All of 357 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, were examined. The isolated bacteria were: Staphylococcus aureus 51, Streptococcus pneumoniae 73, Haemophilus influenzae 88, Pseudomonas aeruginosa (non-mucoid) 34, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 21, and Moraxella catarrhalis 33. Of 51 S. aureus strains, those with 2 μg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 μg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 31 (60.8%) and 20 (39.2%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 μg/mL or less. Against MRSA, vancomycin showed the potent activity and inhibited the growth of all the strains at 1 μg/mL. Linezolid also showed the great activity and inhibited the growth of all the strains at 2 μg/mL. Carbapenems and penems showed the most potent activities against S. pneumoniae and panipenem inhibited the growth of all the strains at 0.125 μg/mL. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.5 and 1 μg/mL, respectively. In contrast, there were high-resistant strains (MIC: > 128 μg/mL) for erythromycin (53.4%) and clindamycin (3 5.6%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 μg/mL or less. Ciprofloxacin showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 μg/mL or less. Against the non-mucoid type of P. aeruginosa, tobramycin had the most potent activity and its MIC90 was 2 μg/mL. Against K. pneumoniae, imipenem had the most potent activity and inhibited the growth of all the strains at 0.125 μg/mL. All the antibacterial agents except ampicillin generally showed a potent activity against M catarrhalis and the MIC90 of them were 2 μg/mL or less. The majority number (52.9%) of the patients with respiratory infection was aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 59.2% and 19.3% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (17.8%), S. pneumoniae (21.6%), and H. influenzae (16.9%). H. influenzae (36.8%) and S. pneumoniae (22.1%) also were frequently isolated from the patients with chronic bronchitis. The bacteria frequently isolated from the patients were S. pneumoniae (23.2%) and H. influenzae (27.3%) before administration of the antibacterial agents. The bacteria frequently isolated from the patients previously treated with cephems were H. influenzae and P. aeruginosa, and the isolation frequencies were 38.5% and 23.1%, respectively. The bacteria frequently isolated from the patients previously treated with macrolides were H. influenzae, the isolation frequencies were 30.0%.
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To report a brucellar orchiepididymitis case and to review the diagnosis and treatment of this pathology.