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15 pages, 753 KiB

Open AccessEditor’s ChoiceReview

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 - 3 Dec 2022

Cited by 27 | Viewed by 17167

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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8 pages, 495 KiB

Open AccessArticle

Early Empirical Antibiotic Therapy Modification in Sepsis Using Beta-Lacta Test Directly on Blood Cultures

by Assaf Mizrahi, Françoise Jaureguy, Héloise Petit, Gauthier Péan de Ponfilly, Etienne Carbonnelle, Alban Le Monnier, Jean-Ralph Zahar and Benoît Pilmis

Int. J. Transl. Med. 2022, 2(3), 448-455; https://doi.org/10.3390/ijtm2030034 - 26 Aug 2022

Cited by 3 | Viewed by 2370

Abstract

Background: Sepsis caused by multi-drug-resistant Gram-negative bacilli lead physicians to prescribe broad-spectrum antibiotic therapy, such as carbapenems. Rapid susceptibility testing can help with the rational use of antibiotics. The aim of this study was to measure the clinical impact associated with rapid reporting of Beta-Lacta test (BLT) directly on blood cultures positive with Gram-negative bacilli. Methods: In an observational, multicentric, prospective study, we included patients with sepsis caused by Enterobacterales observed on Gram staining of the positive blood cultures. BLT and antimicrobial susceptibility testing (AST) were performed directly on the blood cultures. Clinical impact was measured on the proportion of patients for whom the probabilistic antibiotic therapy was modified according to BLT, including patients receiving carbapenem. Results: 170 patients were included, of whom 44 (25.9%) were receiving inadequate empirical antibiotic therapy. Among them, 27 (15.9%) benefited from an early modification, according to the BLT results. Among 126 (74.1%) patients receiving appropriate probabilistic antibiotic therapy, we modified the antibiotic therapy for 28 (16.5%) of them, including 4/14 (28.5%) de-escalation from carbapenem to a third-generation cephalosporin. Conclusions: Implementation of BLT performed directly on blood cultures allowed us to rapidly modify the empirical antibiotic therapy for about one-third of patients with sepsis caused by Enterobacterales. Full article

(This article belongs to the Special Issue Translational Aspects of Infectious Diseases: From Bench to Bedside 2.0)

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12 pages, 2061 KiB

Open AccessArticle

Use of Whole-Genome Sequencing to Explore Mycobacterium tuberculosis Complex Circulating in a Hotspot Department in France

by Typhaine Billard-Pomares, Julie Marin, Pauline Quagliaro, Frédéric Méchaï, Violaine Walewski, Samira Dziri and Etienne Carbonnelle

Microorganisms 2022, 10(8), 1586; https://doi.org/10.3390/microorganisms10081586 - 6 Aug 2022

Cited by 3 | Viewed by 2522

Abstract

The Seine-Saint-Denis is the French metropolitan department with the highest incidence of tuberculosis (TB). Our aim was to explore epidemiological and phylogenetic characteristics of TB strains in this hotspot department. We performed WGS on 227 strains of Mycobacterium tuberculosis complex isolated from patients at the Avicenne Hospital from 2016 to 2021 and randomly selected to represent the clinical diversity of French TB localization. Clinical and demographic data were recorded for each TB patient. The mean age of patients was 36 years old. They came from Africa (44%), Asia (27%), Europe (26%) and America (3%). Strains isolated from extrapulmonary samples were associated with Asian patients, whereas strains isolated from pulmonary samples were associated with European patients. We observed a high level of lineage diversity in line with the known worldwide diversity. Interestingly, lineage 3 was associated with lymph node TB. Additionally, the sensitivity of WGS for predicting resistance was 100% for rifampicin, isoniazid and ethambutol and 66.7% for pyrazinamide. The global concordance with drug-susceptibility testing using the phenotypic approach was 97%. In microbiology laboratories, WGS turns out to be an essential tool for better understanding local TB epidemiology, with direct access to circulating lineage identification and to drug susceptibilities to first- and second-line anti-TB drugs. Full article

(This article belongs to the Special Issue Diversity of Mycobacterium tuberculosis)

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11 pages, 1886 KiB

Open AccessArticle

Clinical Failure and Emergence of Resistance during Third Generation Cephalosporin Therapy for Enterobacter spp. Infection: Is the Risk Overestimated? A Prospective Multicentric Study

by Benoît Pilmis, Thibaud Delerue, Anna Belkacem, Pauline Caraux-Paz, Solen Kernéis, Sophie Alviset, Etienne Canoui, Assaf Mizrahi, Alexandre Bleibtreu, Matthieu Lafaurie, Etienne Carbonnelle and Jean-Ralph Zahar

Hygiene 2021, 1(2), 69-79; https://doi.org/10.3390/hygiene1020007 - 20 Aug 2021

Cited by 1 | Viewed by 3333

Abstract

Background: Clinical and microbiological guidelines recommend treating infections caused by Enterobacter spp. with cefepime or carbapenems. The main objective of this study was to assess the risk of clinical failure with third generation cephalosporin (3GC) therapy compared to other β-lactams for infections caused by Enterobacter spp. Our secondary objective was to evaluate the risk of emergence of resistance during therapy. Methods: We conducted a prospective observational study in seven French hospitals over an 18-month period including all patients with a pulmonary and/or bloodstream infection due to Enterobacter spp. susceptible to 3GC. Results: Seventy-four patients were included in our study. Among them, 26 (35%) received a 3GC as a first-line treatment, and clinical improvements were observed for 13/21 (62%) of them. Four (5%) cases of emergence of 3GC resistance were observed during therapy including one in the 3GC group. 3GC therapy can be safely used as first-line therapy especially for non-severe patients suffering from pulmonary or bloodstream infections due to Enterobacter spp. Conclusions: Emergence of 3GC resistance remains a rare event, and there is a lack of evidence of the benefit of last-line antibiotics therapies. Full article

(This article belongs to the Section Infectious Disease Epidemiology, Prevention and Control)

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