Les carbapénèmes

Wolff, Marianne de; Joly-Guillou, M.-L.; Pajot, Olivier

doi:10.1016/s1624-0693(09)75318-6

Cited by 13 publications

(5 citation statements)

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“…A total of 297 samples were available for PK modelling, with a median of six samples per individual (Figure ). Imipenem concentrations at peak (0.5 h) and trough were 34.1 [12.3–67.5] and 1.9 mg l −1 [0.5–10.1], respectively.…”

Section: Resultssupporting

confidence: 83%

“…Due to its broad spectrum, imipenem is often prescribed for initial empirical treatment of ventilator‐associated pneumonia (VAP) in critically ill patients with risk factors for multidrug‐resistant Gram‐negative bacilli . It is a hydrophilic molecule characterized by a half‐life ( t 1/2 ) of 1 h, low plasma protein binding (<20%) and a predominantly renal excretion close to 70% . In healthy subjects, the clearance is 12.1 l h −1 and the volume of distribution ( V d ) of the central compartment is 9.6 l after 1000 mg every 8 h (q8h) with 0.5 h infusion .…”

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator‐associated pneumonia and evaluation of dosage regimens

Couffignal

Pajot

Laouénan

et al. 2014

Brit J Clinical Pharma

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Aims Significant alterations in the pharmacokinetics (PK) of antimicrobials have been reported in critically ill patients. We describe PK parameters of imipenem in intensive care unit (ICU) patients with suspected ventilator‐associated pneumonia and evaluate several dosage regimens. Methods This French multicentre, prospective, open‐label study was conducted in ICU patients with a presumptive diagnosis of ventilator‐associated pneumonia caused by Gram‐negative bacilli, who empirically received imipenem intravenously every 8 h. Plasma imipenem concentrations were measured during the fourth imipenem infusion using six samples (trough, 0.5, 1, 2, 5 and 8 h). Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm in Monolix 4.2. A Monte Carlo simulation was performed to evaluate the following six dosage regimens: 500, 750 or 1000 mg with administration every 6 or 8 h. The pharmacodynamic target was defined as the probability of achieving a fractional time above the minimal inhibitory concentration (MIC) of >40%. Results Fifty‐one patients were included in the PK analysis. Imipenem concentration data were best described by a two‐compartment model with three covariates (creatinine clearance, total bodyweight and serum albumin). Estimated clearance (between‐subject variability) was 13.2 l h−1 (38%) and estimated central volume 20.4 l (31%). At an MIC of 4 μg ml−1, the probability of achieving 40% fractional time > MIC was 91.8% for 0.5 h infusions of 750 mg every 6 h, 86.0% for 1000 mg every 8 h and 96.9% for 1000 mg every 6 h. Conclusions This population PK model accurately estimated imipenem concentrations in ICU patients. The simulation showed that for these patients, the best dosage regimen of imipenem is 750 mg every 6 h and not 1000 mg every 8 h.

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Section: Resultssupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator‐associated pneumonia and evaluation of dosage regimens

Couffignal

Pajot

Laouénan

et al. 2014

Brit J Clinical Pharma

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“…Furthermore, the mechanism for carbapenem resistance in our study was never involved carbapenemase production. The main mechanism of resistance to imipenem in P. aeruginosa is well known and remains due to a modification of the outer membrane protein OprD [4,15]. Resistance to carbapenems may result from combined mechanisms of resistance associating β-lactamases and decreased outer membrane permeability, or from carbapenemases as KPC-type enzymes, metallo-β-lactamases, or oxacillinase as OXA-48 [1].…”

Section: Discussionmentioning

confidence: 99%

“…Carbapenems exert their bactericidal activity by binding to penicillin-binding proteins, PLPs, in particular PLP1a, 1b, and 2, resulting in lower endotoxin release during lysis of gram-negative bacilli. Thus, they are often the antibiotics of choice in the ICU for nosocomial infections [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Risk factors for acquisition of carbapenem-resistance during treatment with carbapenem in the intensive care unit: a prospective study

Labaste

Grossac

Vardon-Bounes

et al. 2019

Eur J Clin Microbiol Infect Dis

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The emergence of carbapenemases in gram-negative aerobes is worrying. The aim of this prospective study was to estimate the incidence of acquisition of carbapenem-resistance during treatment in ICU and to identify the risk factors. This was a prospective, observational, cohort study. This study was conducted at intensive care unit, academic medical center, Toulouse Rangueil University Hospital. Patients were included if they received antibiotic treatment with carbapenem for more than 48 h. Biological samples were taken in accordance with current practice in the unit. The main endpoint was the occurrence of bacterial resistance to carbapenems occurring between the onset of treatment and the patient's exit from the ICU. Uni-and multi-variate analyses were carried out. Of the 364 patients admitted to the unit between May and November 2014, 78 were included in our study and 16 (20.51%) developed resistance. The two main risk factors were a length of stay in ICU of more than 29 days (HR = 3.61, p = 0.01) and the presence of Pseudomonas aeruginosa in the samples taken before the start of treatment (HR = 5.31, p = 0.002). No resistance due to carbapenemase production was observed in this study. The prescription of carbapenems in the ICU setting must adhere to the expert guidelines. In light of our results, special attention must be paid to patients whose stay in intensive care is prolonged, and those in whom Pseudomonas aeruginosa is isolated from bacteriological samples taken before the beginning of antibiotic therapy.

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“…The resistance of Enterobacteriaceae to carbapenems remained marginal with sensitivity rates of 98-100% [28], making carbapenems the best treatment for ESBL-producing Enterobacteriaceae [9]. Unfortunately, the misuse of these molecules has led to the emergence of resistance to these antibiotics, especially in Klebsiella pneumoniae [29].…”

Section: Discussionmentioning

confidence: 99%

Epidemiology and Sensitivity to Antibiotics of Enterobacteriaceae Producing Extended-Spectrum Beta-Lactamases (ESBL) in the Region of Nouakchott (Mauritania)

Salem¹

2022

JGMCP

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Introduction: Extended-spectrum beta-lactamases (ESBL) are a large heterogeneous family of bacterial enzymes discovered in 1980. They are induced either by plasmids or by mutation of the natural genome in the bacterium. Both mechanisms give affected bacteria the ability to hydrolyze a very wide variety of beta-lactams. (ESBL)-producing bacteria represent a major concern due to their epidemic spread and their multiresistance to antibiotics The purpose of this study was to: determine their frequency of ESBL, know their distribution according to sex, hospital department, assess their levels of resistance to antibiotics and educate clinicians on the rational prescription of antibiotics. Materials and Methods: This is a retrospective study which was carried out within the central laboratory of the National Hospital Center of Nouakchott (CHN) over two years. The antibiogram was carried out by the method of diffusion in agar medium or on the Vitek-2 automaton (Biomérieux®) The production of ESBLs has been demonstrated by looking for a synergy between clavulanic acid and third-generation cephalosporins according to the usual techniques. Results: Out of 650 species of Enterobacteriaceae, 18.46% produced ESBL, including 58% in hospitalized patients and 42% in outpatients. The ESBL resistance rate was high to quinolones, aminoglycosides (except amikacin) and cotrimoxazole, fosfomycin and carbapenems retain good activity. Discussion: ESBLs are increasingly incriminated in both community-acquired and nosocomial infections and represent a real public health problem. In fact, 42% of ESBL isolated during our study came from outpatient consultations. This dissemination of ESBL in the community is alarming and could be explained, in part, by the anarchic use of antibiotics, it has also been mentioned by several studies. Fosfomycin retains excellent efficacy against ESBL in our study with 90% sensitivity. The resistance of Enterobacteriaceae to carbapenems remained marginal with sensitivity rates of 98 to 100% , making them the best treatment against ESBL-producing Enterobacteriaceae. However, the misuse of these molecules has led to the emergence of resistance to these antibiotics, especially in certain enterobacteriaceae. Conclusion: Considering the results of our study and the data from the literature, it clearly appears that ESBLs are taking an increasingly important place among multiresistant bacteria. The increase in resistance should be compared with the increase in antibiotic consumption. These trends are problematic because they promote not only the emergence and spread of ESBL enterobacteriaceae, but also those of carbapenemase-producing enterobacteriaceae (CPE). Faced with this worrying situation and given the increased risk of therapeutic impasse caused by these multi-resistant strains; very early detection of ESBL germ infections, isolation of patients carrying a transmissible infection and rational use of antibiotics should be carried out.

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Les carbapénèmes

Cited by 13 publications

References 0 publications

Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator‐associated pneumonia and evaluation of dosage regimens

Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator‐associated pneumonia and evaluation of dosage regimens

Risk factors for acquisition of carbapenem-resistance during treatment with carbapenem in the intensive care unit: a prospective study

Epidemiology and Sensitivity to Antibiotics of Enterobacteriaceae Producing Extended-Spectrum Beta-Lactamases (ESBL) in the Region of Nouakchott (Mauritania)

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