scholarly journals Pseudomonas aeruginosa Susceptibility in Spain: Antimicrobial Activity and Resistance Suppression Evaluation by PK/PD Analysis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1899
Author(s):  
Ana Valero ◽  
Alicia Rodríguez-Gascón ◽  
Arantxa Isla ◽  
Helena Barrasa ◽  
Ester del Barrio-Tofiño ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Nationwide Survey ◽  
Resistance Mechanisms ◽  
World Health ◽  
Sample Type ◽  
Healthcare Associated Infection ◽  
Drug Concentrations ◽  
Medical Wards ◽  
Health Organization

Pseudomonas aeruginosa remains one of the major causes of healthcare-associated infection in Europe; in 2019, 12.5% of invasive isolates of P. aeruginosa in Spain presented combined resistance to ≥3 antimicrobial groups. The Spanish nationwide survey on P. aeruginosa antimicrobial resistance mechanisms and molecular epidemiology was published in 2019. Based on the information from this survey, the objective of this work was to analyze the overall antimicrobial activity of the antipseudomonal antibiotics considering pharmacokinetic/pharmacodynamic (PK/PD) analysis. The role of PK/PD to prevent or minimize resistance emergence was also evaluated. A 10,000-subject Monte Carlo simulation was executed to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) considering the minimum inhibitory concentration (MIC) distribution of bacteria isolated in ICU or medical wards, and distinguishing between sample types (respiratory and non-respiratory). Ceftazidime/avibactam followed by ceftolozane/tazobactam and colistin, categorized as the Reserve by the Access, Watch, Reserve (AWaRe) classification of the World Health Organization, were the most active antimicrobials, with differences depending on the admission service, sample type, and dose regimen. Discrepancies between EUCAST-susceptibility breakpoints for P. aeruginosa and those estimated by PK/PD analysis were detected. Only standard doses of ceftazidime/avibactam and ceftolozane/tazobactam provided drug concentrations associated with resistance suppression.

scholarly journals Improving the Role and Contribution of Pharmacokinetic Analyses in Antimalarial Drug Clinical Trials

2014 ◽  
Vol 58 (10) ◽  
pp. 5643-5649 ◽  
Author(s):  
Katherine Kay ◽  
Eva Maria Hodel ◽  
Ian M. Hastings
Keyword(s):  
Antimalarial Drug ◽  
Theoretical Data ◽  
Drug Efficacy ◽  
Cost Effective ◽  
Field Studies ◽  
World Health ◽  
Efficacy Trials ◽  
Drug Concentrations ◽  
Health Organization ◽  
Study Designs

ABSTRACTIt is now World Health Organization (WHO) policy that drug concentrations on day 7 be measured as part of routine assessment in antimalarial drug efficacy trials. The rationale is that this single pharmacological measure serves as a simple and practical predictor of treatment outcome for antimalarial drugs with long half-lives. Herein we review theoretical data and field studies and conclude that the day 7 drug concentration (d7c) actually appears to be a poor predictor of therapeutic outcome. This poor predictive capability combined with the fact that many routine antimalarial trials will have few or no failures means that there appears to be little justification for this WHO recommendation. Pharmacological studies have a huge potential to improve antimalarial dosing, and we propose study designs that use more-focused, sophisticated, and cost-effective ways of generating these data than the mass collection of single d7c concentrations.

scholarly journals Emerging mosquito resistance to piperonyl butoxide-synergized pyrethroid insecticide and its mechanism

2021 ◽  
Author(s):  
Guofa Zhou ◽  
Yiji Li ◽  
Brook Jeang ◽  
Xiaoming Wang ◽  
Daibin Zhong ◽  
...  
Keyword(s):  
Culex Quinquefasciatus ◽  
Resistance Mechanisms ◽  
Piperonyl Butoxide ◽  
World Health ◽  
Metabolic Enzyme ◽  
Enzyme Expression ◽  
Glutathione S Transferase ◽  
Expression Levels ◽  
P450 Enzyme ◽  
Health Organization

Piperonyl butoxide (PBO)-synergized pyrethroid products are widely available for the control of pyrethroid-resistant mosquitoes. To date, no study has formally examined mosquito resistance to PBO-synergized insecticides. We used Culex quinquefasciatus as a model mosquito examined the insecticide resistance mechanisms of mosquitoes to PBO-synergized pyrethroid using modified World Health Organization tube bioassays and biochemical analysis of metabolic enzyme expressions prior- and post-PBO exposure. We measured mosquito mortalities and metabolic enzyme expressions in mosquitoes with/without pre-exposure to different PBO concentrations and exposure durations. We found that field Culex quinquefasciatus mosquitoes were resistant to all insecticides tested, including PBO-synergized pyrethroids (mortality ranged from 3.7±4.7% to 66.7±7.7%), except malathion. Field mosquitoes had elevated levels of carboxylesterase (COE, 3.8-fold) and monooxygenase (P450, 2.1-fold) but not glutathione S-transferase (GST) compared to susceptible mosquitoes. When the field mosquitoes were pre-exposed to 4% PBO, the 50% lethal concentration of deltamethrin was reduced from 0.22% to 0.10%, compare to 0.02% for susceptible mosquitoes. Knockdown resistance gene mutation (L1014F) rate was 62% in field mosquitoes. PBO pre-exposure suppressed P450 enzyme expression levels by 25~34%, GST by 11%, and had no impact on COE enzyme expression. Even with the optimal PBO concentration and exposure duration, field mosquitoes had significantly higher P450 enzyme expression levels after PBO exposure compared to laboratory controls. These results demonstrate that PBO alone may not be enough to control highly pyrethroid resistant mosquitoes due to the multiple resistance mechanisms. Mosquito resistance to PBO-synergized insecticide should be closely monitored.

Insecticide Resistance in Anopheles stephensi in Somali Region, Eastern Ethiopia

2020 ◽  
Author(s):  
Solomon Yared ◽  
Araya Gebressielasie ◽  
Lambodhar Damodaran ◽  
Victoria Bonnell ◽  
Karen Lopez ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Anopheles Stephensi ◽  
Mortality Rates ◽  
Resistance Mechanisms ◽  
World Health ◽  
Malaria Vectors ◽  
Eastern Ethiopia ◽  
Pyrethroid Insecticides ◽  
Pirimiphos Methyl ◽  
Health Organization

Abstract Background: The movement of malaria vectors into new areas is a growing concern in the efforts to control malaria. The recent report of Anopheles stephensi in eastern Ethiopia has raised the necessity to understand the insecticide resistance status of the vector in the region to better inform vector-based interventions. The aim of this study was to evaluate insecticide resistance in An. stephensi in eastern Ethiopia using two approaches: 1) World Health Organization (WHO) bioassay tests in An. stephensi and 2) genetic analysis of insecticide resistance genes in An. stephensi in eastern Ethiopia. Methods: Mosquito larvae and pupae were collected from Kebridehar. Insecticide susceptibility of An. stephensi was tested with malathion 5%, bendiocarb 0.1%, propoxur 0.1%, deltamethrin 0.05%, permethrin 0.75%, Pirimiphos-methyl 0.25% and DDT 4%, according to WHO standard protocols. Results: All An. stephensi samples were resistant to carbamates, with mortality rates 23% and 21% for bendiocarb and propoxur, respectively. Adult An. stephensi was also resistant to pyrethroid insecticides with mortality rates 67% for deltamethrin and 53% for permethrin. Resistance to DDT and malathion was detected in An. stephensi with mortality rates of 32% as well as An. stephensi was resistance to pirimiphos-methyl with mortality rates 14%. Analysis of the voltage gate sodium channel gene (vgsc) revealed the absence of kdr L1014 mutations. Conclusion: Overall, these findings support that An. stephensi is resistant to several classes of insecticides, most notably pyrethroids. However, the absence of the kdr L1014 gene may suggest non-target site resistance mechanisms. Continuous insecticide resistance monitoring should be carried out in the region to confirm the documented resistance and exploring mechanisms conferring resistance in An. stephensi in Ethiopia.

Spanish nationwide survey on Pseudomonas aeruginosa antimicrobial resistance mechanisms and epidemiology

2019 ◽  
Vol 74 (7) ◽  
pp. 1825-1835 ◽  
Author(s):  
Ester del Barrio-Tofiño ◽  
Laura Zamorano ◽  
Sara Cortes-Lara ◽  
Carla López-Causapé ◽  
Irina Sánchez-Diener ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Nationwide Survey ◽  
Resistance Mechanisms

scholarly journals Evaluating insecticide resistance across African districts to aid malaria control decisions

2020 ◽  
Vol 117 (36) ◽  
pp. 22042-22050 ◽  
Author(s):  
Catherine L. Moyes ◽  
Duncan K. Athinya ◽  
Tara Seethaler ◽  
Katherine E. Battle ◽  
Marianne Sinka ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Pyrethroid Resistance ◽  
Resistance Mechanisms ◽  
World Health ◽  
Malaria Vector Control ◽  
Ensemble Model ◽  
Metabolic Resistance ◽  
The World ◽  
Susceptibility Tests ◽  
Health Organization

Malaria vector control may be compromised by resistance to insecticides in vector populations. Actions to mitigate against resistance rely on surveillance using standard susceptibility tests, but there are large gaps in the monitoring data across Africa. Using a published geostatistical ensemble model, we have generated maps that bridge these gaps and consider the likelihood that resistance exceeds recommended thresholds. Our results show that this model provides more accurate next-year predictions than two simpler approaches. We have used the model to generate district-level maps for the probability that pyrethroid resistance inAnopheles gambiaes.l. exceeds the World Health Organization thresholds for susceptibility and confirmed resistance. In addition, we have mapped the three criteria for the deployment of piperonyl butoxide-treated nets that mitigate against the effects of metabolic resistance to pyrethroids. This includes a critical review of the evidence for presence of cytochrome P450-mediated metabolic resistance mechanisms across Africa. The maps for pyrethroid resistance are available on the IR Mapper website, where they can be viewed alongside the latest survey data.

scholarly journals Comparison of the Activity of a Human Simulated, High-Dose, Prolonged Infusion of Meropenem against Klebsiella pneumoniae Producing the KPC Carbapenemase versus That against Pseudomonas aeruginosa in an In Vitro Pharmacodynamic Model

2009 ◽  
Vol 54 (2) ◽  
pp. 804-810 ◽  
Author(s):  
Catharine C. Bulik ◽  
Henry Christensen ◽  
Peng Li ◽  
Christina A. Sutherland ◽  
David P. Nicolau ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
High Performance ◽  
Resistance Mechanisms ◽  
Free Drug ◽  
Pharmacodynamic Model ◽  
High Dose ◽  
Prolonged Infusion ◽  
Drug Concentrations

ABSTRACT We have previously demonstrated that a high-dose, prolonged-infusion meropenem regimen (2 g every 8 h [q8h]; 3-hour infusion) can achieve 40% free drug concentration above the MIC against Pseudomonas aeruginosa with MICs of ≤16 μg/ml. The objective of this experiment was to compare the efficacy of this high-dose, prolonged-infusion regimen against carbapenemase-producing Klebsiella pneumoniae isolates with the efficacy against P. aeruginosa isolates having similar meropenem MICs. An in vitro pharmacodynamic model was used to simulate human serum concentrations. Eleven genotypically confirmed K. pneumoniae carbapenemase (KPC)-producing isolates and six clinical P. aeruginosa isolates were tested for 24 h, and time-kill curves were constructed. High-performance liquid chromatography (HPLC) was used to verify meropenem concentrations in each experiment. Meropenem achieved a rapid ≥3 log CFU reduction against all KPC isolates within 6 h, followed by regrowth in all but two isolates. The targeted %fT>MIC (percent time that free drug concentrations remain above the MIC) exposure was achieved against both of these KPC isolates (100% fT>MIC versus MIC = 2 μg/ml, 75% fT>MIC versus MIC = 8 μg/ml). Against KPC isolates with MICs of 8 and 16 μg/ml that did regrow, actual meropenem exposures were significantly lower than targeted due to rapid in vitro hydrolysis, whereby targeted %fT>MIC was reduced with each subsequent dosing. In contrast, a ≥3 log CFU reduction was maintained over 24 h for all Pseudomonas isolates with meropenem MICs of 8 and 16 μg/ml. Although KPC and P. aeruginosa isolates may share similar meropenem MICs, the differing resistance mechanisms produce discordant responses to a high-dose, prolonged infusion of meropenem. Thus, predicting the efficacy of an antimicrobial regimen based on MIC may not be a valid assumption for KPC-producing organisms.

scholarly journals Detection of a novel mutation G511T in the 530 loop in 16S rRNA in multi drugs resistant Mycobacterium tuberculosis isolated from Sudanese patients

2018 ◽  
Author(s):  
Yousif Mohammed Alfatih ◽  
Abeer Babiker Idris ◽  
Hadeel Gassim Hassan ◽  
Eman O M Nour ◽  
Nihad M A Elhaj ◽  
...  
Keyword(s):  
16S Rrna ◽  
Molecular Mechanisms ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
World Health ◽  
Bacterial Disease ◽  
Global Public Health ◽  
Mdr Tb ◽  
Health Organization

Background: Tuberculosis (TB) is a bacterial disease considered as a global public health emergency by the World Health Organization (WHO) since 1993. In Sudan, MDR-TB represents a growing threat and one of the most important challenges that faced national tuberculosis program to establish a comprehensive multidrug-resistant tuberculosis management system. Objective: To characterize the diversity and frequency of mutations in Sudanese MDR-TB strains isolated from Wad Madani, Al-Gadarif and Khartoum using 16S rRNA and phylogeny approach. Material and Methods: A total of 60 MDR-TB isolates from Wad-Madani, Al-Gadarif and Khartoum were tested with molecular LPA (Genotype MTBDR plus) and GeneXpert MTB/RIF assay and Spoligotyping to confirm their resistance to RIF and INH. Sequencing and phylogenetic analysis was carried out using in silico tools. Result: This study revealed the circulation of different Sudanese MDR-TB strains isolated from Wad Madani and Al-Gadarif belonging to two distinct common ancestors. Two isolates from Wad Madani (isolate3 and isolate11) found in one main group which characterized by a novel mutation G511T in the 530 loop. Conclusion: The recurrence of C217A mutation in Wad Madani (isolate11) indicates the spread of this mutation in Sudanese MDR-TB strains and the diversity of this inheritance leading to generate new G511T novel mutation. So, understanding the molecular characterization of resistance mechanisms in MD-TB can facilitate the early detection of resistance, the choice of appropriate treatment and ultimately the management of MD-TB transmission. Bioinformatics approaches provide helpful tools for analyzing molecular mechanisms of resistance in pathogens.

scholarly journals Pharmacokinetics of antiretroviral drugs in infancy

2009 ◽  
Vol 10 (4) ◽  
pp. 54
Author(s):  
Helen McIlleron ◽  
Hermien Gous
Keyword(s):  
Hiv Infection ◽  
Antiretroviral Treatment ◽  
Hiv Transmission ◽  
Antiretroviral Drugs ◽  
The Body ◽  
World Health ◽  
Highly Active ◽  
Drug Concentrations ◽  
One Year ◽  
Health Organization

Infancy (from birth until 1 year of age) is a time of rapid changes within the body of a child. These changes affect pharmacokinetics in many ways. The CHER study1 showed that early antiretroviral treatment reduces mortality and disease progression amongst infants acquiring HIV infection before 12 weeks of age. As a result the World Health Organization has recently revised treatment initiation recommendations in children less than one year of age: all infants under 12 months of age with confirmed HIV infection should be started on antiretroviral therapy, irrespective of clinical or immunological stage2. Dosing in infants is challenging because drug concentrations are highly variable, there is frequently scant pharmacokinetic information in young children, and few suitable drug formulations are available. Furthermore, adherence to treatment is reliant on the caregiver, rather than the patient. Peri- and postnatal HIV transmission are reduced by maternal highly active antiretroviral treatment (HAART). However, the benefits and risks to breast fed infants of exposure to maternal antiretroviral drugs during lactation are poorly understood. In this article we review the pharmacokinetics of antiretroviral drugs relevant to South African infants, and highlight some of the challenges to delivering antiretroviral treatment in safe and effective doses.

scholarly journals Antibiotic resistance trends and mechanisms in the foodborne pathogen,Campylobacter

2017 ◽  
Vol 18 (2) ◽  
pp. 87-98 ◽  
Author(s):  
Yizhi Tang ◽  
Liangxing Fang ◽  
Changyun Xu ◽  
Qijing Zhang
Keyword(s):  
Antibiotic Resistance ◽  
Efflux Pump ◽  
Foodborne Pathogen ◽  
Resistance Mechanisms ◽  
World Health ◽  
Antibiotic Resistant ◽  
Innovative Strategies ◽  
Control And Prevention ◽  
Antibiotic Selection Pressure ◽  
Health Organization

AbstractCampylobacteris a major foodborne pathogen and is commonly present in food producing animals. This pathogenic organism is highly adaptable and has become increasingly resistant to various antibiotics. Recently, both the Centers for Disease Control and Prevention and the World Health Organization have designated antibiotic-resistantCampylobacteras a serious threat to public health. For the past decade, multiple mechanisms conferring resistance to clinically important antibiotics have been described inCampylobacter, and new resistance mechanisms constantly emerge in the pathogen. Some of the recent examples include theerm(B)gene conferring macrolide resistance, thecfr(C)genes mediating resistance to florfenicol and other antimicrobials, and a functionally enhanced variant of the multidrug resistance efflux pump, CmeABC. The continued emergence of new resistance mechanisms illustrates the extraordinary adaptability ofCampylobacterto antibiotic selection pressure and demonstrate the need for innovative strategies to control antibiotic-resistantCampylobacter. In this review, we will briefly summarize the trends of antibiotic resistance inCampylobacterand discuss the mechanisms of resistance to antibiotics used for animal production and important for clinical therapy in humans. A special emphasis will be given to the newly discovered antibiotic resistance.

scholarly journals Antimicrobial Activity of Hypericum perforatum Essential Oil

2016 ◽  
Vol 12 (3-4) ◽  
Author(s):  
Vesna Kalaba ◽  
Jovana Glušac ◽  
Milka Stijepić ◽  
Dragana Kalaba ◽  
Dragica Đurđević Milosević
Keyword(s):  
Antimicrobial Activity ◽  
Essential Oil ◽  
Hypericum Perforatum ◽  
Public Awareness ◽  
Multidrug Resistant ◽  
World Health ◽  
Antimicrobial Drugs ◽  
Antimicrobial Substances ◽  
Health Organization ◽  
And Control

European Centre for Disease Prevention and Control (ECDC) and World Health Organization (WHO) initiate public awareness campaign about antimicrobial substances and their rational uses due to the increasing prevalence of multidrug resistant strains of bacteria. The objective of this study was to evaluate antimicrobial activity of Hypericum perforatum essential oil and reference antimicrobial drugs against the growth of certain bacteria Staphylococcus aureus, Salmonella typhimurium i Pseudomonas aeruginosa.

Sign in / Sign up

Export Citation Format

Share Document