Pharmacokinetic/pharmacodynamic analysis as a tool for surveillance of the activity of antimicrobials against Pseudomonas aeruginosa strains isolated in critically ill patients

Valero, Ana; Isla, Arantxazu; Rodríguez-Gascón, Alicia; Calvo, Begoña; Canut, Andrés; Solinís, Maria Ángelés

doi:10.1016/j.eimc.2018.10.013

Cited by 12 publications

(10 citation statements)

References 28 publications

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“…The use of PK/PD analyses can ameliorate this risk and improve the likelihood of selecting an effective dose regimen, thereby increasing the likelihood of success. These tools have also been applied to identify changes in the antimicrobial activity of antibiotics, providing complementary information to the simple assessment of MIC values [33][34][35], and to establish PK/PD breakpoints [14] as well.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Analysis of Tedizolid Phosphate Compared to Linezolid for the Treatment of Infections Caused by Gram-Positive Bacteria

et al. 2021

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Tedizolid and linezolid have antibacterial activity against the most important acute bacterial skin and skin-structure infection (ABSSSIs) pathogens. The objective of this work was to apply PK/PD analysis to evaluate the probability of attaining the pharmacodynamic target of these antimicrobials based on the susceptibility patterns of different clinical isolates causing ABSSSI. Pharmacokinetic and microbiological data were obtained from the literature. PK/PD breakpoints, the probability of target attainment (PTA) and the cumulative fraction of response (CFR) were calculated by Monte Carlo simulation. PTA and CFR are indicative of treatment success. PK/PD breakpoints of tedizolid and linezolid were 0.5 and 1 mg/L, respectively. Probability of treatment success of tedizolid was very high (>90%) for most staphylococci strains, including MRSA and coagulase-negative staphylococci (CoNS). Only for methicillin- and linezolid-resistant S. aureus (MLRSA) and linezolid resistant (LR) CoNS strains was the CFR of tedizolid very low. Except for LR, daptomycin-non-susceptible (DNS), and vancomycin-resistant (VRE) E. faecium isolates, tedizolid also provided a high probability of treatment success for enterococci. The probability of treatment success of both antimicrobials for streptococci was always higher than 90%. In conclusion, for empiric treatment, PK/PD analysis has shown that tedizolid would be adequate for most staphylococci, enterococci, and streptococci, even those LR whose linezolid resistance is mediated by the cfr gene.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Analysis of Tedizolid Phosphate Compared to Linezolid for the Treatment of Infections Caused by Gram-Positive Bacteria

et al. 2021

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“…These mechanisms include upregulation of efflux pumps, insertion of porins, production of beta-lactamases, and target site alteration (8). Resistance is an increasing problem, and it has been independently associated with higher in-hospital mortality, prolonged hospital length of stay, and higher costs (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Increasing resistance also poses a clinical challenge in terms of both empiric and definitive antibiotic selection.…”

Section: Methodsmentioning

confidence: 99%

Pseudomonas aeruginosainfection in intensive care: Epidemiology, outcomes, and antimicrobial susceptibilities

Kula

Hudson

Sligl

2020

Official Journal of the Association of Medical Microbiology and

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BACKGROUND:Pseudomonas aeruginosa (PA) infection in the intensive care unit (ICU) contributes to substantial mortality. In this study, we describe the epidemiology, antimicrobial susceptibilities, and outcomes of ICU patients with pseudomonal infection. METHODS: ICU patients with PA were identified and classified as colonized or infected. Infected patients were reviewed for source, patient characteristics, antimicrobial susceptibilities, appropriateness of empiric antimicrobial therapy, and 30-day mortality. Independent predictors of mortality were identified using multivariable logistic regression. RESULTS: One hundred forty (71%) patients with PA were infected. Mean patient age was 55 (SD 18) years; 62% were male. Admission categories included medical (71%), surgical (20%), and trauma or neurological (9%). Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 19 (SD 10). One hundred twenty-six (90%) patients were mechanically ventilated, 102 (73%) required vasopressors, and 27 (19%) received renal replacement; 32 (23%) died within 30 days. Infection was nosocomial in 101 (72%) cases. Sources were respiratory (66%), skin-soft tissue (11%), urinary (10%), blood (5%), surgical (5%), gastrointestinal (2%), or unknown (1%). Twenty (14%) isolates were multi-drug resistant; 6 (4%) were extensively drug resistant. Empiric antimicrobial therapy was effective in 97 (69%) cases. Liver disease (adjusted OR [aOR] 6.2, 95% CI 1.5 to 25.7; p = 0.01), malignancy (aOR 5.0, 95% CI 1.5 to 17.3; p = 0.01), and higher APACHE II score (aOR 1.1, 95% CI 1.0 to 1.1; p = 0.02) were independently associated with 30-day mortality. CONCLUSIONS: PA infection in ICU is most commonly respiratory and associated with substantial mortality. Existing malignancy, liver disease, and higher APACHE II score were independently associated with mortality.

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“…The development and establishment of programs of integrated epidemiologic surveillance on antimicrobial activity is essential to determine risk factors, to identify temporal trends in resistance patterns, and to guide the clinician towards appropriate empiric treatments [70]. Antimicrobial stewardship programs are needed to choose the treatment properly in terms of optimal choice of drug, dosage, and duration of treatment, which leads to a reduction of treatment-related costs, an improvement in clinical outcomes and safety, and a reduction or a stabilization of antimicrobial resistance [71][72][73][74]. Standard surveillance indices, based on MIC values, can be useful but they are not enough to detect changes on the whole activity of antimicrobial agents, since some less evident variations in MIC distribution could lead to a loss of treatment efficacy [71,75].…”

Section: Pk/pd Analysis As a Tool For Surveillance Of Antibacterial Activitymentioning

confidence: 99%

“…Antimicrobial stewardship programs are needed to choose the treatment properly in terms of optimal choice of drug, dosage, and duration of treatment, which leads to a reduction of treatment-related costs, an improvement in clinical outcomes and safety, and a reduction or a stabilization of antimicrobial resistance [71][72][73][74]. Standard surveillance indices, based on MIC values, can be useful but they are not enough to detect changes on the whole activity of antimicrobial agents, since some less evident variations in MIC distribution could lead to a loss of treatment efficacy [71,75]. The PK/PD analysis has proved to be a useful tool to establish empirical antimicrobial therapy recommendations, since it allows evaluating the overall activity of antimicrobial treatments by predicting the probability of success for a treatment, incorporating the variability of the pharmacokinetic parameters and the bacterial population MIC distribution (local MIC distributions).…”

Section: Pk/pd Analysis As a Tool For Surveillance Of Antibacterial Activitymentioning

confidence: 99%

“…Additionally, many publications include the PK/PD analysis as a key point for the treatment optimization and surveillance of antibacterial activity. As an example, different studies about P. aeruginosa isolates conclude that susceptibility rates and the probability of treatment success estimated by the PK/PD analysis are complementary tools for surveillance purposes and both should be considered together when making decisions to guide antimicrobial therapy [71,72,75]. A recently published review about treatment optimization for sexually transmitted infections also highlights the urgent needs of systematic PK/PD evaluation to ensure resistance suppression and bacterial eradication at all sites of infection [97].…”

Section: Pk/pd Analysis As a Tool For Surveillance Of Antibacterial Activitymentioning

confidence: 99%

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The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials

2021

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Pharmacokinetic/pharmacodynamic (PK/PD) analysis has proved to be very useful to establish rational dosage regimens of antimicrobial agents in human and veterinary medicine. Actually, PK/PD studies are included in the European Medicines Agency (EMA) guidelines for the evaluation of medicinal products. The PK/PD approach implies the use of in vitro, ex vivo, and in vivo models, as well as mathematical models to describe the relationship between the kinetics and the dynamic to determine the optimal dosing regimens of antimicrobials, but also to establish susceptibility breakpoints, and prevention of resistance. The final goal is to optimize therapy in order to maximize efficacy and minimize side effects and emergence of resistance. In this review, we revise the PK/PD principles and the models to investigate the relationship between the PK and the PD of antibiotics. Additionally, we highlight the outstanding role of the PK/PD analysis at different levels, from the development and evaluation of new antibiotics to the optimization of the dosage regimens of currently available drugs, both for human and animal use.

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Pharmacokinetic/pharmacodynamic analysis as a tool for surveillance of the activity of antimicrobials against Pseudomonas aeruginosa strains isolated in critically ill patients

Cited by 12 publications

References 28 publications

Pharmacokinetic/Pharmacodynamic Analysis of Tedizolid Phosphate Compared to Linezolid for the Treatment of Infections Caused by Gram-Positive Bacteria

Pharmacokinetic/Pharmacodynamic Analysis of Tedizolid Phosphate Compared to Linezolid for the Treatment of Infections Caused by Gram-Positive Bacteria

Pseudomonas aeruginosainfection in intensive care: Epidemiology, outcomes, and antimicrobial susceptibilities

The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials

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