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Strains Resistant (strain + resistant)
Selected AbstractsPrevalence and risk factors associated with antiretroviral resistance in HIV-1-infected childrenJOURNAL OF MEDICAL VIROLOGY, Issue 9 2007Constance Delaugerre Abstract In the USA and West Europe, nearly 80% of HIV-1-infected adults, experiencing virologic failure, harbored virus strain resistant to at least one antiretroviral drug. Limited data are available on antiretroviral drug resistance in pediatric HIV infection. The aims of this study were to analyze prevalence of HIV-1 drug resistance and to identify risk factors associated with resistance in this population. Prevalence of genotypic resistance was estimated retrospectively in treated children who experienced virologic failure (with HIV-1-RNA,>,500 copies/ml) followed in Necker hospital between 2001 and 2003. Among 119 children with resistance testing, prevalence of resistance to any drug was 82.4%. Resistance ranged from 76.5% to nucleoside reverse transcriptase inhibitor (NRTI), to 48.7% to non-nucleoside reverse transcriptase inhibitor (NNRTI) and 42.9% to protease inhibitor (PI). Resistance to at least one drug of two classes and three classes (triple resistance) was 31.9 and 26.9%, respectively. Resistance was not associated with geographic origin, HIV-1 subtype, and CDC status. In multivariate analysis, resistance to any drug remained associated independently with current low viral load and high lifetime number of past PI. Triple resistance was independently associated with the high lifetime number of past PI and with gender, particularly among children aged 11 years old or more with a prevalence seven times higher in boys than in girls. In conclusion, antiretroviral resistance is common among treated HIV-1-infected children and prevalence was similar with those observed in adult population in the same year period. However, adolescent boys seem to be at greater risk. J. Med. Virol. 79:1261,1269, 2007. © Wiley-Liss, Inc. [source] Detection of extended-spectrum ,-lactamase-producing Klebsiella pneumoniae in effluents and sludge of a hospital sewage treatment plantLETTERS IN APPLIED MICROBIOLOGY, Issue 1 2008T. Prado Abstract Aims:, To detect ESBL (extended-spectrum ,-lactamase)-producing Klebsiella pneumoniae present in the effluents and sludge of a hospital sewage treatment plant, evaluating the treatment plant's potential to remove these micro-organisms. Methods and Results:, Twenty samples (crude sewage, UASB reactor effluent, filtered effluent and sludge) were collected in the period from May to December 2006, in order to analyse antimicrobial susceptibility and to check ESBL production, the disc-diffusion and the combined disc methods were used. Total and faecal coliform concentrations were also determined. ESBL-producing K. pneumoniae were detected in all samples analysed, representing 46·5% of the total strains isolated. Among the non-ESBL-producing strains, 26% were multiresistant and one strain resistant to eight of the nine antimicrobials tested was detected in the treated effluent. Conclusions:, The hospital wastewater treatment plant did not show a satisfactory efficacy in removing pathogenic micro-organisms, allowing for the dissemination of multiresistant bacteria into the environment. Significance and Impact of the Study:, The inefficacy of hospital wastewater treatment plants can result in routes of dissemination of multiresistant bacteria and their genes of resistance into the environment, thus contaminating water resources, and having serious negative impact on public health. [source] Mitochondrial impacts of insecticidal formate esters in insecticide-resistant and insecticide-susceptible Drosophila melanogasterPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 6 2009Cheol Song Abstract BACKGROUND: Previous research on insecticidal formate esters in flies and mosquitoes has documented toxicity profiles, metabolism characteristics and neurological impacts. The research presented here investigated mitochondrial impacts of insecticidal formate esters and their hydrolyzed metabolite formic acid in the model dipteran insect Drosophila melanogaster Meig. These studies compared two Drosophila strains: an insecticide-susceptible strain (Canton-S) and a strain resistant by cytochrome P450 overexpression (Hikone-R). RESULTS: In initial studies investigating inhibition of mitochondrial cytochrome c oxidase, two proven insecticidal materials (hydramethylnon and sodium cyanide) caused significant inhibition. However, for insecticidal formate esters and formic acid, no significant inhibition was identified in either fly strain. Mitochondrial impacts of formate esters were then investigated further by tracking toxicant-induced cytochrome c release from mitochondria into the cytoplasm, a biomarker of apoptosis and neurological dysfunction. Formic acid and three positive control treatments (rotenone, antimycin A and sodium cyanide) induced cytochrome c release, verifying that formic acid is capable of causing mitochondrial disruption. However, when comparing formate ester hydrolysis and cytochrome c release between Drosophila strains, formic acid liberation was only weakly correlated with cytochrome c release in the susceptible Canton-S strain (r2 = 0.70). The resistant Hikone-R strain showed no correlation (r2 < 0.0001) between formate ester hydrolysis and cytochrome c release. CONCLUSION: The findings of this study provide confirmation of mitochondrial impacts by insecticidal formate esters and suggest links between mitochondrial disruption, respiratory inhibition, apoptosis and formate-ester-induced neurotoxicity. Copyright © 2009 Society of Chemical Industry [source] Biorational insecticides: Mechanism and cross-resistance ,ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 4 2005Isaac Ishaaya Abstract Potency and cross-resistance of various biorational insecticides, exemplified by the whitefly Bemisia tabaci, have been studied. Bemisia tabaci were exposed to the juvenile hormone mimic pyriproxyfen for the past 12 years resulting in an over 2,000-fold resistance, but there was no appreciable cross-resistance with the benzoylphenyl urea novaluron. Similarly, no cross-resistance was found between pyriproxyfen and the two neonicotinoids, acetamiprid and imidacloprid. On the other hand, a slight cross-resistance of 5,13-fold was observed with another neonicotinoid thiamethoxam. Among the neonicotinoids, a resistant strain of B. tabaci to thiamethoxam (,100-fold) showed no appreciable cross-resistance to either acetamiprid or imidacloprid, while another strain 500-fold resistant to thiamethoxam resulted in a mild of 4,6-fold resistance to acetamiprid and imidacloprid. In other assays, B. tabaci strain resistant to thiamethoxam (,100-fold) had no cross-resistance to pyriproxyfen. Our findings indicate that no appreciable cross-resistance was observed between the benzoylphenyl urea novaluron, the juvenile hormone mimic pyriproxyfen, and the neonicotinoids acetamiprid and imidacloprid. Hence, these compounds could be used as components in insecticide resistance management programs. Arch. Insect Biochem. Physiol. 58:192,199, 2005. © 2005 Wiley-Liss, Inc. [source] Emergence of ciprofloxacin resistance in Escherichia coli isolates from outpatient urine samplesCLINICAL MICROBIOLOGY AND INFECTION, Issue 3 2007C. Gagliotti Abstract This study investigated the association between prescription of fluoroquinolones and emergence of ciprofloxacin resistance among Escherichia coli isolates in the urine of outpatients from whom a ciprofloxacin-sensitive E. coli strain had been isolated previously. Patients were identified and followed using the healthcare databases of Emilia-Romagna Region, Italy. The outcome of interest was the first isolation from urine of an E. coli strain resistant to ciprofloxacin. Prescription of fluoroquinolones during the previous 6 months was associated independently with the emergence of ciprofloxacin resistance; the strength of the association varied according to individual fluoroquinolone agents. [source] Coselection for microbial resistance to metals and antibiotics in freshwater microcosmsENVIRONMENTAL MICROBIOLOGY, Issue 9 2006Ramunas Stepanauskas Summary Bacterial resistances to diverse metals and antibiotics are often genetically linked, suggesting that exposure to toxic metals may select for strains resistant to antibiotics and vice versa. To test the hypothesis that resistances to metals and antibiotics are coselected for in environmental microbial assemblages, we investigated the frequency of diverse resistances in freshwater microcosms amended with Cd, Ni, ampicillin or tetracycline. We found that all four toxicants significantly increased the frequency of bacterioplankton resistance to multiple, chemically unrelated metals and antibiotics. An ampicillin-resistant strain of the opportunistic human pathogen Ralstonia mannitolilytica was enriched in microcosms amended with Cd. Frequencies of antibiotic resistance were elevated in microcosms with metal concentrations representative of industry and mining-impacted environments (0.01,1 mM). Metal but not antibiotic amendments decreased microbial diversity, and a weeklong exposure to high concentrations of ampicillin (0.01,10 mg l,1) and tetracycline (0.03,30 mg l,1) decreased microbial abundance only slightly, implying a large reservoir of antibiotic resistance in the studied environment. Our results provide first experimental evidence that the exposure of freshwater environments to individual metals and antibiotics selects for multiresistant microorganisms, including opportunistic human pathogens. [source] Current status of malaria chemotherapy and the role of pharmacology in antimalarial drug research and developmentFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2009Kesara Na-Bangchang Abstract Antimalarial drugs have played a mainstream role in controlling the spread of malaria through the treatment of patients infected with the plasmodial parasites and controlling its transmissibility. The inadequate armory of drugs in widespread use for the treatment of malaria, development of strains resistant to currently used antimalarials, and the lack of affordable new drugs are the limiting factors in the fight against malaria. In addition, other problems with some existing agents include unfavorable pharmacokinetic properties and adverse effects/toxicity. These factors underscore the continuing need of research for new classes of antimalarial agents, and a re-examination of the existing antimalarial drugs that may be effective against resistant strains. In recent years, major advances have been made in the pharmacology of several antimalarial drugs both in pharmacokinetics and pharmacodynamics aspects. These include the design, development, and optimization of appropriate dosage regimens of antimalarials, basic knowledge in metabolic pathways of key antimalarials, as well as the elucidation of mechanisms of action and resistance of antimalarials. Pharmacologists have been working in close collaboration with scientists in other disciplines of science/biomedical sciences for more understanding on the biology of the parasite, host, in order to exploit rational design of drugs. Multiple general approaches to the identification of new antimalarials are being pursued at this time. All should be implemented in parallel with focus on the rational development of new agents directed against newly identified parasite targets. With major advances in our understanding of malaria parasite biology coupled with the completion of the malaria genome, has presented exciting opportunities for target-based antimalarial drug discovery. [source] Susceptibility of hepatitis B virus to lamivudine restored by resistance to adefovirJOURNAL OF MEDICAL VIROLOGY, Issue 3 2009H.L. Zaaijer Abstract Serial monotherapy and add-on regimes for treatment of chronic hepatitis B virus (HBV) infection may induce the accumulation of viral resistance mutations in patients, reducing the options for ongoing viral suppression. The induction of antiviral resistance by serial application of polymerase inhibitors does not necessarily imply that the subsequent combined use of the drugs will fail. Some HIV strains resistant to one polymerase inhibitor show increased susceptibility to another polymerase inhibitor. After failure of sequential lamivudine and adefovir monotherapy, two patients with hepatitis B changed to treatment with lamivudine plus adefovir and had renewed suppression of HBV. To study the mutational history of resistant HBV subpopulations in the two patients, a part of the HBV polymerase gene was amplified, cloned, sequenced, and analyzed for the presence of mutations, in sequential plasma samples. In both patients serial monotherapy caused the replacement in all HBV clones of wild-type virus by classical lamivudine resistant mutants (L180M and M204V/I), which were replaced subsequently by adefovir resistant mutants (A181V and N236T). When finally lamivudine was added to adefovir, the A181V adefovir mutation persisted in all clones and lamivudine-related mutations did not reappear. During 18 months of combination therapy, HBV-DNA levels decreased 10,000, respectively, 1,000-fold, despite the earlier resistance to lamivudine and adefovir. Although clinically insufficient, this effect indicates that HBV polymerase resistance mutations may be antagonistic, which is relevant if chronic HBV infection is to be treated by a combination of polymerase inhibitors. J. Med. Virol. 81:413,416, 2009. © 2009 Wiley-Liss, Inc. [source] HIV-1 integrase inhibitors: 2005,2006 updateMEDICINAL RESEARCH REVIEWS, Issue 1 2008Raveendra Dayam Abstract HIV-1 integrase (IN) catalyzes the integration of proviral DNA into the host genome, an essential step for viral replication. Inhibition of IN catalytic activity provides an attractive strategy for antiretroviral drug design. Currently two IN inhibitors, MK-0518 and GS-9137, are in advanced stages of human clinical trials. The IN inhibitors in clinical evaluation demonstrate excellent antiretroviral efficacy alone or in combination regimens as compared to previously used clinical antiretroviral agents in naive and treatment-experienced HIV-1 infected patients. However, the emergence of viral strains resistant to clinically studied IN inhibitors and the dynamic nature of the HIV-1 genome demand a continued effort toward the discovery of novel inhibitors to keep a therapeutic advantage over the virus. Continued efforts in the field have resulted in the discovery of compounds from diverse chemical classes. In this review, we provide a comprehensive report of all IN inhibitors discovered in the years 2005 and 2006. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 1, 118,154, 2008 [source] Recent advances in antimalarial drug developmentMEDICINAL RESEARCH REVIEWS, Issue 1 2007Suryanaryana Vangapandu Abstract Malaria caused by protozoa of the genus Plasmodium, because of its prevalence, virulence, and drug resistance, is the most serious and widespread parasitic disease encountered by mankind. The inadequate armory of drugs in widespread use for the treatment of malaria, development of strains resistant to commonly used drugs such as chloroquine, and the lack of affordable new drugs are the limiting factors in the fight against malaria. These factors underscore the continuing need of research for new classes of antimalarial agents, and a re-examination of the existing antimalarial drugs that may be effective against resistant strains. This review provides an in-depth look at the most significant progress made during the past 10 years in antimalarial drug development. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 1, 65,107, 2007 [source] A new, broad-spectrum azole antifungal: posaconazole , mechanisms of action and resistance, spectrum of activityMYCOSES, Issue 2006H. Hof Summary Posaconazole, a new triazole antifungal, exerts principally the same mechanism of action as the other azole derivatives, i.e. it inhibits the ergosterol production by binding and inhibiting the lanosterol-14,-demethylase which is present in almost all fungi except Pneumocystis and Pythium. Posaconazole has an exquisitely high affinity to this target. Since posaconazole has a chemical structure different from fluconazole and voriconazole, it can interact with an additional domain of the target so that it may inhibit even mutated strains resistant to fluconazole and voriconazole. In addition posaconazole is a bad substrate for efflux pumps in fungi, so it can stay active when other azoles are already inactive. Furthermore, the spectrum of posaconazole is rather large including also some zygomycetes resistant to other azoles. In conclusion, posaconazole is actually the most potent azole derivative used in medicine. A combination of posaconazole with other groups of antifungals may have a favourable effect. There are several methods to test the in vitro activities of posaconazole including the E-test, though interpretive breakpoints are still lacking. [source] Bacteriologic Comparison of Tonsil Core in Recurrent Tonsillitis and Tonsillar Hypertrophy,THE LARYNGOSCOPE, Issue 12 2007Jin Hyeok Jeong MD Abstract Objectives: Although many bacteriology studies on tonsillar diseases have been completed, all have been confined to children and were characterized by a paucity of cases. The purpose of this study was to analyze the underlying bacterial pathogens in tonsillar disease. Methods: A retrospective study was performed on 824 patients who underwent elective tonsillectomy with or without adenoidectomy. We analyzed the differences between the bacterial pathogens in recurrent tonsillitis and tonsillar hypertrophy with regard to age, season, and antibiotic sensitivity. Results: Among 824 cases, 966 bacterial strains from the tonsil core were isolated. In recurrent tonsillitis, Staphylococcus aureus was the most common pathogen (30.3%), followed by Haemophilus influenzae (15.5%) and group A ,-hemolytic Streptococcus (Streptococcus pyogenes, 14.4%). In patients over 14 years of age, quite differently from other age groups, Klebsiella pneumoniae was isolated at a significantly higher percentage. In tonsillar hypertrophy, H. influenzae was isolated most commonly (31.4%) regardless of age, followed by S. pyogenes (24.2%), S. aureus (22.9%), and Streptococcus pneumoniae (12.6%). Furthermore, mixed infection was common because of its high resistance to penicillin. In both groups, S. pneumoniae was more common in younger patients, whereas K. pneumoniae was relatively common in adults. We found no differences in the detection rate by season; however, H. influenzae was frequently isolated in the tonsillar hypertrophy group regardless of seasonal variations. We also found no difference in the antibiotic sensitivity between the two groups; however, strains resistant to penicillin were relatively prevalent and showed a high sensitivity to third-generation cephalosporin. Conclusions: We observed some differences in the types of bacteria in the tonsillar core between the recurrent tonsillitis and tonsillar hypertrophy groups. Our study indicates that essential bacteria have been changing and, thus, we need to change our choice of antibiotics. [source] Kinetic bactericidal activity of telithromycin, azithromycin and clarithromycin against respiratory pathogens,APMIS, Issue 10 2005L. DRAGO The present study assessed the comparative in vitro killing kinetics of telithromycin, azithromycin and clarithromycin. Minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) were determined against Streptococcus pneumoniae, ,-haemolytic streptococci, Haemophilus influenzae and Moraxella catarrhalis strains characterized by different susceptibilities to ,-lactams and macrolides. For each bacterial species, representative strains were chosen for time-kill studies. Telithromycin showed high activity against all the tested strains with MIC ranging from ,0.004 to 0.5 mg/L for streptococci, from 0.008 to 8 mg/L for H. influenzae, and from 0.008 to 0.5 mg/L for M. catarrhalis. In time-kill studies, telithromycin showed an overall superior bactericidal activity in respect to macrolides, particularly against resistant strains. In conclusion, telithromycin proved to possess bactericidal activity against a wide range of respiratory pathogens, including strains resistant to common macrolides. [source] Bis-Tetrahydrofuran: a Privileged Ligand for Darunavir and a New Generation of HIV Protease Inhibitors That Combat Drug ResistanceCHEMMEDCHEM, Issue 9 2006Two inhibitors that incorporate bis-THF as an effective high-affinity P2 ligand for the HIV-1 protease substrate binding site maintain impressive potency against mutant strains resistant to currently approved protease inhibitors. Crystallographic structures of protein,ligand complexes help to explain the superior antiviral property of these inhibitors and their potency against a wide spectrum of HIV-1 strains. [source] | ||||||||||||||||