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A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions...
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A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions in the Fields of Hospital-Acquired Infections and Optimization of Anti-infective Treatments

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 31387

Special Issue Editor

Prof. Dr. Vincent Jullien

E-Mail Website
Guest Editor
Pharmacology – Hospital Practitioner, Sorbonne Paris Nord University Pharmacology Unit, Paris Seine Saint-Denis University Hospital, Bobigny, France
Interests: pharmacokinetics and pharmacodynamics of anti-infective drugs; population pharmacokinetics in children; therapeutic drug monitoring

Special Issue Information

Dear Colleagues,

Professor Jean-François Timsit has significantly contributed to the field of infectious diseases in critically ill patients. His research covers a wide range of topics, including sepsis and antimicrobial therapy, catheter-related infections, ventilator-associated pneumonia, quality of care improvement, prognostic models, and competing risks. Prof. Timsit has demonstrated that subcutaneous tunnelling can reduce, by two-thirds, the incidence of internal-jugular-catheter-related infections and that skin antisepsis with chlorhexidine–alcohol reduced the incidence of catheter-related infections by six-fold and that of catheter-related bloodstream infections by five-fold compared with 5% povidone–iodine alcohol. In addition, Prof. Timsit discovered, concerning the EMPIRICUS trial, that more intensive treatment does not necessarily lead to a better outcome in ICU patients. Indeed, the day-28 fungal-infection-free survival in non-neutropenic and candida-colonized ICU patients with ICU-acquired sepsis was not improved by empirical treatment with micafungin. Furthermore, Prof. Timsit also investigated the pharmacokinetics/pharmacodynamics of many antimicrobial drugs and has contributed to international recommendations for therapeutic drug monitoring in ICU patients.

Prof. Timsit graduated from the University of Paris-Cité with a thesis in epidemiology and healthcare evaluation and has supervised 28 master’s and 10 PhD theses in the past 15 years. He is currently a professor of intensive care medicine at Paris-Cité University and the Head of the Medical and Infectious Diseases ICU at Bichat Hospital. He is a leader in critical care teaching in the Parisian area and the group leader of the Infectious Diseases in Critical Care section in the research unit Inserm U1137 (IAME) at Paris-Cité University.

Prof. Timsit heads the chair of the Critical Care section of the ECCMID (ESGCIP) and serves as an editor and deputy editor for several international journals. He has authored more than 600 indexed papers (Web of Science H index of 73) published in international peer-reviewed journals. He is also the president of the OUTCOME REA research network.

Antibiotics is pleased to announce a Special Issue in recognition of Professor Jean-François Timsit’s outstanding contributions to the knowledge of hospital-acquired infections and antimicrobial treatment. This Special Issue is dedicated to all aspects of sepsis and antimicrobials in ICU patients with an emphasis on the following topics (though others will be considered):

  • Nosocomial infections;
  • Ventilator-acquired pneumonia and hospital-acquired pneumonia;
  • Catheter infections;
  • Antimicrobial agents against multidrug-resistant pathogens;
  • Antibiotic stewardship in ICU patients;
  • Resistance emergence in ICU patients;
  • Prognostic models in ICU patients;
  • Pharmacokinetics and pharmacodynamics of antimicrobials in ICU patients.

Regular articles, communications, and reviews are all welcome.

Prof. Dr. Vincent Jullien
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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.

Published Papers (7 papers)

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Research

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18 pages, 4285 KiB  
Article
Behavioral Components and Context of Antimicrobial Prescription in a Tertiary Hospital in Portugal
by Ana Paula Muniz Almeida-Costa, José-Artur Paiva, António Jorge Santos Almeida, Elisabete Barbosa and Sofia Correia
Antibiotics 2023, 12(6), 1032; https://doi.org/10.3390/antibiotics12061032 - 08 Jun 2023
Cited by 1 | Viewed by 966
Abstract
Consumption of antimicrobials is an important driver of antimicrobial resistance. There is limited knowledge of the key determinants of antimicrobial prescribing behavior in hospitals. An understanding of these determinants is required for the successful design, adoption, and implementation of quality improvement interventions in [...] Read more.
Consumption of antimicrobials is an important driver of antimicrobial resistance. There is limited knowledge of the key determinants of antimicrobial prescribing behavior in hospitals. An understanding of these determinants is required for the successful design, adoption, and implementation of quality improvement interventions in Antimicrobial Stewardship Programs (ASP). This study aimed to describe the main factors that influence the doctor’s decision on antimicrobials prescribing and to identify the behaviors that drive physicians’ decision making. A structured web-based questionnaire focused on behavioral components of antimicrobial prescription was applied to the medical staff of three different departments—Internal Medicine, General Surgery, and Intensive Care Medicine—of a university hospital. All doctors agreed that inadequate use of antimicrobials increases AMR. A total of 77% of the surgeons and 100% of the internists and intensivists perceived antimicrobial prescription as a priority in the department. Full autonomy in antimicrobial prescription was preferred by internists (64%) but not by surgeons (18%) and intensivists (24%). Most physicians were keen to have ASP advice, but most did not want advice from colleagues of the same service. Almost all surgeons ask for advice when prescribing, but only 68% of the internists do it. Less than half of all physicians and only 25% of the surgeons felt free to prescribe contrary to guidelines. Most physicians, particularly in Intensive Care Medicine (94%), adopt the “wait and see” strategy when no microbiologic confirmation is available, but 27% of the surgeons start empirical therapy. In conclusion, the context of antimicrobial prescription, autonomy, and confidence in antimicrobial prescription demonstrated heterogeneity between the three departments and this should be considered when planning ASP. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions in the Fields of Hospital-Acquired Infections and Optimization of Anti-infective Treatments)
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15 pages, 821 KiB  
Article
Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment
by Olivier Pajot, Karim Lakhal, Jérome Lambert, Antoine Gros, Cédric Bruel, Thierry Boulain, Denis Garot, Vincent Das, Jean François Timsit, Charles Cerf, Bertrand Souweine, Cendrine Chaffaut, Hervé Mentec, Jean Ralph Zahar, Jean Paul Mira and Vincent Jullien
Antibiotics 2022, 11(11), 1664; https://doi.org/10.3390/antibiotics11111664 - 19 Nov 2022
Viewed by 2375
Abstract
Background: Strong evidence suggests a correlation between pharmacodynamics (PD) index and antibiotic efficacy while dose adjustment should be considered in critically ill patients due to modified pharmacokinetic (PK) parameters and/or higher minimum inhibitory concentrations (MICs). This study aimed to assess pharmacodynamic (PD) target [...] Read more.
Background: Strong evidence suggests a correlation between pharmacodynamics (PD) index and antibiotic efficacy while dose adjustment should be considered in critically ill patients due to modified pharmacokinetic (PK) parameters and/or higher minimum inhibitory concentrations (MICs). This study aimed to assess pharmacodynamic (PD) target attainment considering both antibiotics serum concentrations and measured MICs in these patients. Method: A multicentric prospective open-label trial conducted in 11 French ICUs involved patients with Gram-negative bacilli (GNB) ventilator-associated pneumonia (VAP) confirmed by quantitative cultures. Results: We included 117 patients. Causative GNBs were P. aeruginosa (40%), Enterobacter spp. (23%), E. coli (20%), and Klebsiella spp. (16%). Hence, 117 (100%) patients received β-lactams, 65 (58%) aminoglycosides, and two (1.5%) fluoroquinolones. For β-lactams, 83% of the patients achieved a Cmin/MIC > 1 and 70% had a Cmin/MIC > 4. In the case of high creatinine clearance (CrCL > 100 mL/min/1.73 m2), 70.4% of the patients achieved a Cmin/MIC ratio > 1 versus 91% otherwise (p = 0.041), and 52% achieved a Cmin/MIC ratio > 4 versus 81% (p = 0.018). For aminoglycosides, 94% of the patients had a Cmax/MIC ratio > 8. Neither β-lactams nor aminoglycosides PK/PD parameters were associated clinical outcomes, but our data suggest a correlation between β-lactams Cmin/MIC and microbiological success. Conclusion: In our ICU patients treated for GNB VAP, using recommended antibiotic dosage led in most cases to PK/PD targets attainment for aminoglycosides and β-lactams. High creatinine clearance should encourage clinicians to focus on PK/PD issues. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions in the Fields of Hospital-Acquired Infections and Optimization of Anti-infective Treatments)
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9 pages, 1105 KiB  
Article
Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study
by Léo Mimram, Sophie Magréault, Younes Kerroumi, Dominique Salmon, Benjamin Kably, Simon Marmor, Anne-Sophie Jannot, Vincent Jullien and Valérie Zeller
Antibiotics 2022, 11(11), 1462; https://doi.org/10.3390/antibiotics11111462 - 23 Oct 2022
Cited by 2 | Viewed by 1916
Abstract
A population PK model of clindamycin orally administered to patients with prosthetic joint infections (PJIs) was developed using NONMEM 7.5. Monte-Carlo simulations were run to determine the probability of obtaining bone clindamycin concentrations equal to at least the MIC or four times the [...] Read more.
A population PK model of clindamycin orally administered to patients with prosthetic joint infections (PJIs) was developed using NONMEM 7.5. Monte-Carlo simulations were run to determine the probability of obtaining bone clindamycin concentrations equal to at least the MIC or four times the MIC for several MIC values and dosing regimens. One hundred and forty plasma concentrations prospectively obtained from 20 patients with PJIs were used. A one-compartment model with first-order absorption and elimination appropriately described the data. Mean PK-parameter estimates (F being the bioavailability) were: apparent clearance, CL/F = 23 L/h, apparent distribution volume, V/F = 103 l and absorption rate constant, Ka = 3.53/h, with respective interindividual variabilities (coefficients of variation) of 14.4%, 8.2% and 59.6%. Neither goodness-of-fit curves nor visual predictive checks indicated bias. The currently recommended 600 mg q8h regimen provided a high probability of obtaining concentrations equal to at least the MIC, except for MIC ≥ the clinical breakpoint for Staphylococcus spp. (0.25 mg/L). For such MIC values, higher daily doses and q6h regimens could be considered. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions in the Fields of Hospital-Acquired Infections and Optimization of Anti-infective Treatments)
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Review

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0 pages, 688 KiB  
Review
Optimized Treatment of Nosocomial Peritonitis
by Jan J. De Waele, Federico Coccolini, Leonel Lagunes, Emilio Maseda, Stefano Rausei, Ines Rubio-Perez, Maria Theodorakopoulou and Kostoula Arvaniti
Antibiotics 2023, 12(12), 1711; https://doi.org/10.3390/antibiotics12121711 - 08 Dec 2023
Cited by 1 | Viewed by 1636
Abstract
This comprehensive review aims to provide a practical guide for intensivists, focusing on enhancing patient care associated with nosocomial peritonitis (NP). It explores the epidemiology, diagnosis, and management of NP, a significant contributor to the mortality of surgical patients worldwide. NP is, per [...] Read more.
This comprehensive review aims to provide a practical guide for intensivists, focusing on enhancing patient care associated with nosocomial peritonitis (NP). It explores the epidemiology, diagnosis, and management of NP, a significant contributor to the mortality of surgical patients worldwide. NP is, per definition, a hospital-acquired condition and a consequence of gastrointestinal surgery or a complication of other diseases. NP, one of the most prevalent causes of sepsis in surgical Intensive Care Units (ICUs), is often associated with multi-drug resistant (MDR) bacteria and high mortality rates. Early clinical suspicion and the utilization of various diagnostic tools like biomarkers and imaging are of great importance. Microbiology is often complex, with antimicrobial resistance escalating in many parts of the world. Fungal peritonitis and its risk factors, diagnostic hurdles, and effective management approaches are particularly relevant in patients with NP. Contemporary antimicrobial strategies for treating NP are discussed, including drug resistance challenges and empirical antibiotic regimens. The importance of source control in intra-abdominal infection management, including surgical and non-surgical interventions, is also emphasized. A deeper exploration into the role of open abdomen treatment as a potential option for selected patients is proposed, indicating an area for further investigation. This review underscores the need for more research to advance the best treatment strategies for NP. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions in the Fields of Hospital-Acquired Infections and Optimization of Anti-infective Treatments)
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15 pages, 753 KiB  
Review
When and How to Use MIC in Clinical Practice?
by Sophie Magréault, Françoise Jauréguy, Etienne Carbonnelle and Jean-Ralph Zahar
Antibiotics 2022, 11(12), 1748; https://doi.org/10.3390/antibiotics11121748 - 03 Dec 2022
Cited by 5 | Viewed by 10037
Abstract
Bacterial resistance to antibiotics continues to be a global public health problem. The choice of the most effective antibiotic and the use of an adapted dose in the initial phase of the infection are essential to limit the emergence of resistance. This will [...] Read more.
Bacterial resistance to antibiotics continues to be a global public health problem. The choice of the most effective antibiotic and the use of an adapted dose in the initial phase of the infection are essential to limit the emergence of resistance. This will depend on (i) the isolated bacteria and its resistance profile, (ii) the pharmacodynamic (PD) profile of the antibiotic used and its level of toxicity, (iii) the site of infection, and (iv) the pharmacokinetic (PK) profile of the patient. In order to take account of both parameters to optimize the administered treatment, a minimal inhibitory concentration (MIC) determination associated with therapeutic drug monitoring (TDM) and their combined interpretation are required. The objective of this narrative review is thus to suggest microbiological, pharmacological, and/or clinical situations for which this approach could be useful. Regarding the microbiological aspect, such as the detection of antibiotic resistance and its level, the preservation of broad-spectrum β-lactams is particularly discussed. PK-PD profiles are relevant for difficult-to-reach infections and specific populations such as intensive care patients, cystic fibrosis patients, obese, or elderly patients. Finally, MIC and TDM are tools available to clinicians, who should not hesitate to use them to manage their patients. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions in the Fields of Hospital-Acquired Infections and Optimization of Anti-infective Treatments)
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19 pages, 972 KiB  
Review
Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis
by Johnny Zakhour, Sima L. Sharara, Joya-Rita Hindy, Sara F. Haddad and Souha S. Kanj
Antibiotics 2022, 11(10), 1432; https://doi.org/10.3390/antibiotics11101432 - 18 Oct 2022
Cited by 9 | Viewed by 11963
Abstract
Pseudomonas aeruginosa is a pathogen often encountered in a healthcare setting. It has consistently ranked among the most frequent pathogens seen in nosocomial infections, particularly bloodstream and respiratory tract infections. Aside from having intrinsic resistance to many antibiotics, it rapidly acquires resistance to [...] Read more.
Pseudomonas aeruginosa is a pathogen often encountered in a healthcare setting. It has consistently ranked among the most frequent pathogens seen in nosocomial infections, particularly bloodstream and respiratory tract infections. Aside from having intrinsic resistance to many antibiotics, it rapidly acquires resistance to novel agents. Given the high mortality of pseudomonal infections generally, and pseudomonal sepsis particularly, and with the rise of resistant strains, treatment can be very challenging for the clinician. In this paper, we will review the latest evidence for the optimal treatment of P. aeruginosa sepsis caused by susceptible as well as multidrug-resistant strains including the difficult to treat pathogens. We will also discuss the mode of drug infusion, indications for combination therapy, along with the proper dosing and duration of treatment for various conditions with a brief discussion of the use of non-antimicrobial agents. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions in the Fields of Hospital-Acquired Infections and Optimization of Anti-infective Treatments)
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Other

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6 pages, 213 KiB  
Perspective
Antimicrobial Stewardship: Leveraging the “Butterfly Effect” of Hand Hygiene
by Adrian John Brink and Guy Antony Richards
Antibiotics 2022, 11(10), 1348; https://doi.org/10.3390/antibiotics11101348 - 03 Oct 2022
Cited by 1 | Viewed by 1362
Abstract
It is vital that there are coordinated, collaborative efforts to address the threat of antimicrobial resistance (AMR) and to prevent and control the spread of hospital-onset infections, particularly those due to multidrug-resistant (MDR) pathogens. The butterfly effect is a concept in which metaphorically [...] Read more.
It is vital that there are coordinated, collaborative efforts to address the threat of antimicrobial resistance (AMR) and to prevent and control the spread of hospital-onset infections, particularly those due to multidrug-resistant (MDR) pathogens. The butterfly effect is a concept in which metaphorically speaking, small, seemingly trivial events ultimately cascade into something of far greater consequence, more specifically by having a non-linear impact on very complex systems. In this regard, antimicrobial stewardship programs (ASP), when implemented alongside infection prevention control (IPC) interventions in hospitals, particularly hand hygiene (HH), are significantly more effective in reducing the development and spread of AMR bacteria than implementation of ASP alone. In this perspective, we briefly review the evidence for the combined effect, and call for closer collaboration between institutional IPC and ASP leadership, and for well-functioning IPC programs to ensure the effectiveness of ASP. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions in the Fields of Hospital-Acquired Infections and Optimization of Anti-infective Treatments)
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