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Antibiotics
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Antimicrobials Use: Clinical Safety to Environmental Risk—Learning from...
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Antimicrobials Use: Clinical Safety to Environmental Risk—Learning from One Health Approach

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: 28 February 2025 | Viewed by 22973

Special Issue Editors

Dr. Anabela Almeida

E-Mail Website
Guest Editor
Escola Universitária Vasco da Gama (EUVG), Campus Universitário, Av. José R. Sousa Fernandes, Coimbra, Portugal
Interests: human and veterinary pharmacology; antibiotic resistance; risk assessment; bioanalysis and biomarkers
Dr. Leonor M. Meisel

E-Mail Website
Guest Editor
Research Institute for Medicines – iMED.ULisboa, Lisboa, Portugal
Interests: pharmacology; toxicology; risk assessment; pre-clinical safety; regulatory science
Dr. Ana Fortuna

E-Mail Website
Guest Editor
Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
Interests: personalized medicine; pharmacokinetics; therapeutic drug monitoring; antiepileptic drugs; antidepressant drugs; nose-to-brain delivery; ABC efflux transporters
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antimicrobials, including antibiotic, antiviral and antifungal drugs, are increasingly assuming an important role in global public health. They are especially relevant considering emergent infectious diseases.

Significant challenges in the human and veterinary clinical setting are rising due to antimicrobial resistance (AMR). Increasing risks in this topic demand new approaches: for instance, triggering further pharmacokinetic-pharmacodynamic (PK/PD) procedures. In addition, clinical pharmacokinetics may contribute to the rational application of antimicrobials and reduce morbidity and mortality from hospital infections. Therefore, monitoring programs are essential to supervise consumption and AMR data trends to further understand the issue and anticipate/implement measures.

Data are scarce concerning antimicrobial resistance’s monitoring in surface water and groundwater, environmental fate and ecotoxicological effects, mainly regarding antiviral and antifungal drugs. To perform prioritisation analysis, it is also essential to know the relationship between their consumption in human or animal settings and environment occurrence. Pharmacokinetic characteristics, physicochemical features and environmental fate may help elucidate this complex puzzle, and ecopharmacovigilance programmes are pre-eminent. Furthermore, AMR selection risks should be prospected to identify the human–animal–environment relationship.

Thus, in the view of the One Health engagement, optimising the use of antimicrobial medicines in human and animal health and the environmental charge is a crucial procedure for surveillance and minimisation of the potential risks.

Dr. Anabela Almeida
Dr. Leonor M. Meisel
Dr. Ana Fortuna
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antimicrobials
  • antifungals
  • antiviral
  • environment
  • antimicrobial resistance
  • pharmacokinetics
  • risk-assessment
  • prioritisation
  • One-Health

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Published Papers (7 papers)

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Research

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14 pages, 1088 KiB  
Article
Analysis of Antibiotics in Bivalves by Ultra-High Performance Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry
by André M. P. T. Pereira, Andreia Freitas, Angelina Pena and Liliana J. G. Silva
Antibiotics 2023, 12(5), 913; https://doi.org/10.3390/antibiotics12050913 - 15 May 2023
Viewed by 2029
Abstract
The presence of pharmaceuticals in aquatic ecosystems mostly originates from wastewater treatment plants (WWTPs) and such a situation can be responsible for significant negative impacts on natural ecosystems, such as estuarine and coastal areas. Bioaccumulation of pharmaceuticals, namely antibiotics, in exposed organisms is [...] Read more.
The presence of pharmaceuticals in aquatic ecosystems mostly originates from wastewater treatment plants (WWTPs) and such a situation can be responsible for significant negative impacts on natural ecosystems, such as estuarine and coastal areas. Bioaccumulation of pharmaceuticals, namely antibiotics, in exposed organisms is known to have remarkable effects on different trophic levels of non-target organisms such as algae, invertebrates and vertebrates, including the emergence of bacterial resistance. Bivalves are a highly appreciated seafood product, as they are fed by filtering water, and can bioconcentrate chemicals, being ideal for biomonitoring environmental health hazards in coastal and estuarine ecosystems. To use this sentinel species, an analytical strategy was developed to be used in accessing antibiotics, from human and veterinary medicine, and evaluate their occurrence as emerging pollutants in aquatic environments. The optimized analytical method was fully validated according to the European requirements defined by the Commission Implementing Regulation 2021/808. The validation comprised the following parameters: specificity, selectivity, precision, recovery, ruggedness, linearity, and the decision limit CCα, as well as the limit of detection (LoD) and limit of quantification (LoQ). The method was validated for 43 antibiotics to allow their quantification in both contexts, environmental biomonitoring and food safety. Full article
(This article belongs to the Special Issue Antimicrobials Use: Clinical Safety to Environmental Risk—Learning from One Health Approach)
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20 pages, 980 KiB  
Article
Predicted Environmental Risk Assessment of Antimicrobials with Increased Consumption in Portugal during the COVID-19 Pandemic; The Groundwork for the Forthcoming Water Quality Survey
by Anabela Almeida, Cristina De Mello-Sampayo, Ana Lopes, Rita Carvalho da Silva, Paula Viana and Leonor Meisel
Antibiotics 2023, 12(4), 652; https://doi.org/10.3390/antibiotics12040652 - 25 Mar 2023
Cited by 7 | Viewed by 3023
Abstract
The environmental release of antimicrobial pharmaceuticals is an imminent threat due to ecological impacts and microbial resistance phenomena. The recent COVID-19 outbreak will likely lead to greater loads of antimicrobials in the environment. Thus, identifying the most used antimicrobials likely to pose environmental [...] Read more.
The environmental release of antimicrobial pharmaceuticals is an imminent threat due to ecological impacts and microbial resistance phenomena. The recent COVID-19 outbreak will likely lead to greater loads of antimicrobials in the environment. Thus, identifying the most used antimicrobials likely to pose environmental risks would be valuable. For that, the ambulatory and hospital consumption patterns of antimicrobials in Portugal during the COVID-19 pandemic (2020–2021) were compared with those of 2019. A predicted risk assessment screening approach based on exposure and hazard in the surface water was conducted, combining consumption, excretion rates, and ecotoxicological/microbiological endpoints in five different regions of Portugal. Among the 22 selected substances, only rifaximin and atovaquone demonstrated predicted potential ecotoxicological risks for aquatic organisms. Flucloxacillin, piperacillin, tazobactam, meropenem, ceftriaxone, fosfomycin, and metronidazole showed the most significant potential for antibiotic resistance in all analysed regions. Regarding the current screening approach and the lack of environmental data, it is advisable to consider rifaximin and atovaquone in subsequent water quality surveys. These results might support the forthcoming monitorisation of surface water quality in a post-pandemic survey. Full article
(This article belongs to the Special Issue Antimicrobials Use: Clinical Safety to Environmental Risk—Learning from One Health Approach)
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16 pages, 3354 KiB  
Article
Predictive Factors of Piperacillin Exposure and the Impact on Target Attainment after Continuous Infusion Administration to Critically Ill Patients
by Javier Martínez-Casanova, Erika Esteve-Pitarch, Helena Colom-Codina, Víctor Daniel Gumucio-Sanguino, Sara Cobo-Sacristán, Evelyn Shaw, Kristel Maisterra-Santos, Joan Sabater-Riera, Xosé L. Pérez-Fernandez, Raül Rigo-Bonnin, Fe Tubau-Quintano, Jordi Carratalà and Ariadna Padullés-Zamora
Antibiotics 2023, 12(3), 531; https://doi.org/10.3390/antibiotics12030531 - 7 Mar 2023
Cited by 2 | Viewed by 2065
Abstract
Critically ill patients undergo significant pathophysiological changes that affect antibiotic pharmacokinetics. Piperacillin/tazobactam administered by continuous infusion (CI) improves pharmacokinetic/pharmacodynamic (PK/PD) target attainment. This study aimed to characterize piperacillin PK after CI administration of piperacillin/tazobactam in critically ill adult patients with preserved renal function [...] Read more.
Critically ill patients undergo significant pathophysiological changes that affect antibiotic pharmacokinetics. Piperacillin/tazobactam administered by continuous infusion (CI) improves pharmacokinetic/pharmacodynamic (PK/PD) target attainment. This study aimed to characterize piperacillin PK after CI administration of piperacillin/tazobactam in critically ill adult patients with preserved renal function and to determine the empirical optimal dosing regimen. A total of 218 piperacillin concentrations from 106 patients were simultaneously analyzed through the population PK approach. A two-compartment linear model best described the data. Creatinine clearance (CLCR) estimated by CKD-EPI was the covariate, the most predictive factor of piperacillin clearance (CL) interindividual variability. The mean (relative standard error) parameter estimates for the final model were: CL: 12.0 L/h (6.03%); central and peripheral compartment distribution volumes: 20.7 L (8.94%) and 62.4 L (50.80%), respectively; intercompartmental clearance: 4.8 L/h (26.4%). For the PK/PD target of 100% fT>1×MIC, 12 g of piperacillin provide a probability of target attainment > 90% for MIC < 16 mg/L, regardless of CLCR, but higher doses are needed for MIC = 16 mg/L when CLCR > 100 mL/min. For 100% fT>4×MIC, the highest dose (24 g/24 h) was not sufficient to ensure adequate exposure, except for MICs of 1 and 4 mg/L. Our model can be used as a support tool for initial dose guidance and during therapeutic drug monitoring. Full article
(This article belongs to the Special Issue Antimicrobials Use: Clinical Safety to Environmental Risk—Learning from One Health Approach)
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16 pages, 461 KiB  
Article
Therapeutic Drug Monitoring of Amikacin in Neutropenic Oncology Patients
by Maria Aquino, Maria Tinoco, Joana Bicker, Amílcar Falcão, Marília Rocha and Ana Fortuna
Antibiotics 2023, 12(2), 373; https://doi.org/10.3390/antibiotics12020373 - 11 Feb 2023
Cited by 1 | Viewed by 3156
Abstract
Amikacin is the antibiotic of choice for the treatment of Gram-negative infections, namely, those in neutropenic oncology patients. No populational pharmacokinetic studies are currently available reporting amikacin pharmacokinetics in neutropenic oncology patients despite their specific pathophysiological features and treatments. A large-scale retrospective study [...] Read more.
Amikacin is the antibiotic of choice for the treatment of Gram-negative infections, namely, those in neutropenic oncology patients. No populational pharmacokinetic studies are currently available reporting amikacin pharmacokinetics in neutropenic oncology patients despite their specific pathophysiological features and treatments. A large-scale retrospective study was herein conducted to specifically investigate the effects that tumor diseases have on the pharmacokinetic parameters of amikacin and identify whether chemotherapy, the lag time between administration of chemotherapy and amikacin, age and renal function contribute to amikacin pharmacokinetics in neutropenic cancer patients. A total of 1180 pharmacokinetic analysis from 629 neutropenic patients were enrolled. The daily dose administered to oncology patients was higher than that administered to non-oncology patients (p < 0.0001). No statistical differences were found in amikacin concentrations, probably because drug clearance was increased in cancer patients (p < 0.0001). Chemotherapy influenced amikacin pharmacokinetics and drug clearance decreased as the lag time enhanced. The elderly group revealed no statistical differences between the doses administered to both the oncology groups, suggesting that the impact of ageing is stronger than chemotherapy. Our research suggests that cancer patients require higher initial doses of amikacin, as well as when chemotherapy is received less than 30 days before amikacin treatment has started. Full article
(This article belongs to the Special Issue Antimicrobials Use: Clinical Safety to Environmental Risk—Learning from One Health Approach)
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Review

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38 pages, 584 KiB  
Review
Extended Spectrum β-Lactamase-Producing Enterobacterales of Shrimp and Salmon Available for Purchase by Consumers in Canada—A Risk Profile Using the Codex Framework
by F. Carl Uhland, Xian-Zhi Li, Michael R. Mulvey, Richard Reid-Smith, Lauren M. Sherk, Hilary Ziraldo, Grace Jin, Kaitlin M. Young, Mark Reist and Carolee A. Carson
Antibiotics 2023, 12(9), 1412; https://doi.org/10.3390/antibiotics12091412 - 6 Sep 2023
Cited by 1 | Viewed by 2063
Abstract
The extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-EB) encompass several important human pathogens and are found on the World Health Organization (WHO) priority pathogens list of antibiotic-resistant bacteria. They are a group of organisms which demonstrate resistance to third-generation cephalosporins (3GC) and their presence has [...] Read more.
The extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-EB) encompass several important human pathogens and are found on the World Health Organization (WHO) priority pathogens list of antibiotic-resistant bacteria. They are a group of organisms which demonstrate resistance to third-generation cephalosporins (3GC) and their presence has been documented worldwide, including in aquaculture and the aquatic environment. This risk profile was developed following the Codex Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance with the objectives of describing the current state of knowledge of ESBL-EB in relation to retail shrimp and salmon available to consumers in Canada, the primary aquacultured species consumed in Canada. The risk profile found that Enterobacterales and ESBL-EB have been found in multiple aquatic environments, as well as multiple host species and production levels. Although the information available did not permit the conclusion as to whether there is a human health risk related to ESBLs in Enterobacterales in salmon and shrimp available for consumption by Canadians, ESBL-EB in imported seafood available at the retail level in Canada have been found. Surveillance activities to detect ESBL-EB in seafood are needed; salmon and shrimp could be used in initial surveillance activities, representing domestic and imported products. Full article
(This article belongs to the Special Issue Antimicrobials Use: Clinical Safety to Environmental Risk—Learning from One Health Approach)
26 pages, 1229 KiB  
Review
Antifungals: From Pharmacokinetics to Clinical Practice
by Anália Carmo, Marilia Rocha, Patricia Pereirinha, Rui Tomé and Eulália Costa
Antibiotics 2023, 12(5), 884; https://doi.org/10.3390/antibiotics12050884 - 9 May 2023
Cited by 18 | Viewed by 7418
Abstract
The use of antifungal drugs started in the 1950s with polyenes nystatin, natamycin and amphotericin B-deoxycholate (AmB). Until the present day, AmB has been considered to be a hallmark in the treatment of invasive systemic fungal infections. Nevertheless, the success and the use [...] Read more.
The use of antifungal drugs started in the 1950s with polyenes nystatin, natamycin and amphotericin B-deoxycholate (AmB). Until the present day, AmB has been considered to be a hallmark in the treatment of invasive systemic fungal infections. Nevertheless, the success and the use of AmB were associated with severe adverse effects which stimulated the development of new antifungal drugs such as azoles, pyrimidine antimetabolite, mitotic inhibitors, allylamines and echinochandins. However, all of these drugs presented one or more limitations associated with adverse reactions, administration route and more recently the development of resistance. To worsen this scenario, there has been an increase in fungal infections, especially in invasive systemic fungal infections that are particularly difficult to diagnose and treat. In 2022, the World Health Organization (WHO) published the first fungal priority pathogens list, alerting people to the increased incidence of invasive systemic fungal infections and to the associated risk of mortality/morbidity. The report also emphasized the need to rationally use existing drugs and develop new drugs. In this review, we performed an overview of the history of antifungals and their classification, mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) characteristics and clinical applications. In parallel, we also addressed the contribution of fungi biology and genetics to the development of resistance to antifungal drugs. Considering that drug effectiveness also depends on the mammalian host, we provide an overview on the roles of therapeutic drug monitoring and pharmacogenomics as means to improve the outcome, prevent/reduce antifungal toxicity and prevent the emergence of antifungal resistance. Finally, we present the new antifungals and their main characteristics. Full article
(This article belongs to the Special Issue Antimicrobials Use: Clinical Safety to Environmental Risk—Learning from One Health Approach)
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14 pages, 1265 KiB  
Review
Parasiticides: Weapons for Controlling Microbial Vector-Borne Diseases in Veterinary Medicine; The Potential of Ethnobotanic/Phytoparasiticides: An Asset to One Health
by Rita Carvalho da Silva, Leonor Meisel, Nóemia Farinha, Orlanda Póvoa and Cristina De Mello-Sampayo
Antibiotics 2023, 12(2), 341; https://doi.org/10.3390/antibiotics12020341 - 6 Feb 2023
Cited by 2 | Viewed by 2226
Abstract
Some ectoparasites are vectors of illness-causing bacteria and viruses, and these are treated with antibiotic and antiviral drugs, which eventually contribute to the excessive use of antimicrobials. Therefore, the control of ectoparasites is crucial, and the challenge will be to manage them in [...] Read more.
Some ectoparasites are vectors of illness-causing bacteria and viruses, and these are treated with antibiotic and antiviral drugs, which eventually contribute to the excessive use of antimicrobials. Therefore, the control of ectoparasites is crucial, and the challenge will be to manage them in a sustainable way. Data from a preliminary ethnobotanical survey was reanalyzed to obtain information on the use of various plant species in companion animals and livestock as ectoparasiticides. The survey responses were reviewed for traditional use of plants as ectoparasiticides, and cross-sectional bibliographic research was undertaken. The following plants were selected among the nine mentioned plants: Juglans regia, Daphne gnidium and Ruta graveolens, which have the most potential to be developed as veterinary ectoparasiticides. Moreover, the absence of published data for Plantago lanceolata and Cistus populifolius suggests that their traditional use as ectoparasiticides is noted here for the first time. In summary, these plants could give promising plant-derived veterinary ectoparasiticides that, ultimately, will help reduce and even avoid the excessive use of antimicrobials. Full article
(This article belongs to the Special Issue Antimicrobials Use: Clinical Safety to Environmental Risk—Learning from One Health Approach)
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