Review
Veterinary Sciences
Longfei Zhang, Hongbing Xie, Yongqiang Wang, Hongjuan Wang, Jianhe Hu, Gaiping Zhang
Summary: Pharmacokinetic/pharmacodynamic (PK/PD) integration models are used to investigate the antimicrobial activity characteristics of drugs targeting pathogenic bacteria through comprehensive analysis of the interactions between PK and PD parameters. PK/PD models have been widely applied in the development of new drugs, optimization of the dosage regimen, and prevention and treatment of drug-resistant bacteria.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Review
Infectious Diseases
Gauri G. Rao, Cornelia B. Landersdorfer
Summary: The use of pharmacokinetic/pharmacodynamic approaches is crucial in optimizing dosage regimens of anti-infectives to maximize efficacy, minimize toxicity and resistance, and ensure a high likelihood of therapeutic success. This involves well-designed preclinical studies, mathematical-model-based analysis, in-silico simulations, and the integration with population pharmacokinetic modelling to consider interindividual variability and predict treatment outcomes in patients. The importance of this approach is highlighted through the example of Polymyxin B, showcasing the necessity of pharmacokinetic/pharmacodynamic modelling in conjunction with experimentation for successful translation to clinical practice.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Microbiology
Jun Mao, Ting Li, Na Zhang, Shuaishuai Wang, Yaowen Li, Yu Peng, Huiping Liu, Guang Yang, Yisong Yan, Lifang Jiang, Yanyan Liu, Jiabin Li, Xiaohui Huang
Summary: The study investigated the synergistic effects of linezolid combined with fosfomycin against Enterococcus, demonstrating a significant reduction in administered dose post-combination treatment, which could lead to decreased adverse effects and development of drug resistance. The potential mechanism of the two-drug combination against Enterococcus was revealed from a quantitative perspective, providing important insights for dose optimization in simulated humans. The findings hope to foster a better relationship between clinicians and patients in addressing antibiotic resistance challenges in the 21st century.
MICROBIOLOGY SPECTRUM
(2021)
Article
Microbiology
Xia Xiao, Weixuan Lan, Yaqin Zhao, Ruichao Li, Yuan Liu, Juan Liu, Zhiqiang Wang
Summary: PK/PD modeling and Monte Carlo simulations were used to predict the efficacy of florfenicol against Pasteurella multocida strains in ducks. The optimal PK/PD parameter was determined, and a rational dosage regimen was suggested for different strains of P. multocida. Additionally, the PK/PD cutoff values for florfenicol against P. multocida were provided for the current marketed dose and the predicted daily dose in mainland China.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Maria Sanz Codina, Milo Gatti, Carla Troisi, Giacomo Fornaro, Zeno Pasquini, Filippo Trapani, Andrea Zanoni, Fabio Caramelli, Pierluigi Viale, Federico Pea
Summary: The study aimed to explore the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous-infusion meropenem and microbiological outcome in critical COVID-19 patients. The study found that patients with optimal meropenem concentrations and pharmacodynamic parameters had a lower rate of microbiological failure.
Article
Infectious Diseases
Alicia Rodriguez-Gascon, Amaia Aguirre-Quinonero, Maria Angeles Solinis Aspiazu, Andres Canut-Blasco
Summary: PK/PD analysis showed that tedizolid has a high probability of treatment success for most staphylococci, enterococci, and streptococci causing ABSSSI, even for those linezolid-resistant strains mediated by the cfr gene.
Review
Infectious Diseases
Kelly L. Maguigan, Mohammad H. Al-Shaer, Charles A. Peloquin
Summary: Beta-lactam antibiotics are the cornerstone for treating Gram-negative infections in critically ill patients, however, dosing adjustments may be necessary due to the unique physiology and increasing resistance rates in the ICU setting. Continuous infusions are often required to achieve desired pharmacokinetic/pharmacodynamic targets, especially when dealing with less-susceptible pathogens such as Pseudomonas aeruginosa.
Article
Pharmacology & Pharmacy
Carmen Flores-Perez, Luis Alfonso Moreno-Rocha, Juan Luis Chavez-Pacheco, Norma Angelica Noguez-Mendez, Janett Flores-Perez, Delfina Ortiz-Marmolejo, Lina Andrea Sarmiento-Arguello
Summary: This study proposes a pharmacokinetic-pharmacodynamic (PK-PD) population model for the use of midazolam in pediatric patients undergoing minor surgery. The results demonstrate that adequate sedation without adverse effects can be achieved at half the usual dose. Further research is needed to optimize dosing schedules and prevent potential adverse effects.
Review
Pharmacology & Pharmacy
Ekram Ahmed Chowdhury, Guy Meno-Tetang, Hsueh Yuan Chang, Shengjia Wu, Hsien Wei Huang, Tanguy Jamier, Jayanth Chandran, Dhaval K. Shah
Summary: Protein therapeutics are successful but expensive and not suitable for long-term treatment. AAV-mediated gene therapy offers an alternative, but there is limited understanding of its key properties.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Veterinary Sciences
Li-li Guo, Rui-yuan Gao, Li-hua Wang, Shu-jun Lin, Bing-hu Fang, Yong-da Zhao
Summary: The study developed a pharmacokinetic/pharmacodynamic model to determine the optimal dosage of tulathromycin in treating respiratory infections, and found a strong correlation between the AUC(168h)/MIC ratio and the antibacterial effectiveness of tulathromycin.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Review
Pharmacology & Pharmacy
Maria Gabriella Matera, Luigino Calzetta, Josuel Ora, Paola Rogliani, Mario Cazzola
Summary: Inhaled drugs play a crucial role in treating lung pathologies, but difficulties persist in assessing lung concentrations and interpreting their therapeutic action. Understanding the PK/PD relationship is essential for predicting therapeutic effects, but challenges remain due to the complex structure of the lungs and physical interactions with drugs. New methods are improving our understanding of inhaled drugs, but regulatory readiness is still a concern, requiring continued reliance on plasma concentrations as a proxy for lung deposition.
EXPERT OPINION ON DRUG DELIVERY
(2021)
Article
Infectious Diseases
Milo Gatti, Renato Pascale, Pier Giorgio Cojutti, Matteo Rinaldi, Simone Ambretti, Matteo Conti, Sara Tedeschi, Maddalena Giannella, Pierluigi Viale, Federico Pea
Summary: This study retrospectively assessed the pharmacokinetic/pharmacodynamic behavior of continuous infusion ceftazidime-avibactam and its microbiological outcome in critically ill renal patients. The results showed that continuous infusion achieved optimal PK/PD targets of ceftazidime-avibactam in most patients and helped minimize the risk of microbiological failure. The study also evaluated the relationship between PK/PD targets and microbiological outcome.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Infectious Diseases
Pasquale Maria Berrino, Milo Gatti, Matteo Rinaldi, Eugenio Brunocilla, Pierluigi Viale, Federico Pea
Summary: This study explores the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) piperacillin-tazobactam or meropenem monotherapy and microbiological outcome in urological patients with Gram-negative infections. The results demonstrate that optimizing beta-lactam treatment through real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program can achieve microbiological eradication in most cases.
Review
Pharmacology & Pharmacy
Hui-Yin Yow, Kayatri Govindaraju, Audrey Huili Lim, Nusaibah Abdul Rahim
Summary: In the era of Bad Bugs, No Drugs, optimizing antibiotic therapy against multi-drug resistant (MDR) pathogens is crucial. Mathematical modelling has played an important role in personalized antibiotic treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Kun Mi, Kaixiang Zhou, Lei Sun, Yixuan Hou, Wenjin Ma, Xiangyue Xu, Meixia Huo, Zhenli Liu, Lingli Huang
Summary: Antimicrobial resistance is a significant public health issue. The semi-mechanistic PK/PD model is a mathematical tool that captures the relationship between dose, exposure, and response in terms of the mechanism, allowing for the optimization of dosage regimens and the suppression of resistance development.
Review
Infectious Diseases
Allison M. Hitchcock, Wesley D. Kufel, Keri A. Mastro Dwyer, Eric F. Sidman
Summary: Lenacapavir is a novel HIV-1 treatment option for patients with multidrug-resistant (MDR) HIV-1 infection. It has a favorable pharmacokinetic profile and has shown good tolerability and efficacy in clinical trials.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)
Article
Infectious Diseases
Roberta Gagliardini, Alessandro Tavelli, Stefano Rusconi, Sergio Lo Caputo, Vincenzo Spagnuolo, Maria Mercedes Santoro, Andrea Costantini, Alessandra Vergori, Franco Maggiolo, Andrea Giacomelli, Giulia Burastero, Giordano Madeddu, Eugenia Quiros Roldan, Antonella d'Arminio Monforte, Andrea Antinori, Alessandro Cozzi-Lepri
Summary: This study evaluated multiple treatment failures to modern antiretroviral therapy in HIV-infected individuals and found that approximately 4% of them were difficult to treat. The difficult to treat group, compared to the non-difficult to treat group, was characterized by older age, higher prevalence of AIDS, lower CD4+ cell count, and higher risk of treatment failure.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2024)