Higher third-generation cephalosporin prescription proportion is associated with lower probability of reducing carbapenem use: a nationwide retrospective study

The ongoing extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) pandemic has led to an increasing carbapenem use, requiring release of guidelines for carbapenem usage in France in late 2010. We sought to determine factors associated with changes in carbapenem use in intensive care units (ICUs), medical and surgical wards between 2009 and 2013

Efficacy and quality of antibacterial generic products approved for human use: a systematic review.

International audienceBACKGROUND: Concerns have recently emerged about the efficacy and the quality of antibacterial generic products approved for use in humans. METHODS: We searched Medline and Embase for original research articles on antibacterial generic products published in English or French before July 2013. RESULTS: We selected 37 original research articles: 15 on β-lactams, 10 on glycopeptides, and 12 on other antibacterial agents. The majority of articles (73.0%) were published during 2008-2012. Study designs included analytical chemistry (n = 9), in vitro susceptibility studies (n = 14), animal experiments (n = 6, including 5 using the neutropenic mouse thigh infection model), and clinical studies in humans (n = 15). Of the 37 studies, 14 (37.8%) suggested that some generic products may be inferior to the innovator in terms of purity (n = 2), in vitro activity (n = 3), in vivo efficacy in experimental models (n = 4), clinical efficacy (n = 2), taste (n = 2), or compliance and acceptability in children (n = 1). The majority of in vitro studies (78.6%) found no significant difference between generic products and the innovator. Most (5/6) in vivo studies suggesting a difference between generic products and the innovator were performed in an animal model that is not validated for the evaluation of the efficacy of antibacterial agents. The level of evidence was constantly low in clinical studies. CONCLUSIONS: Published data on antibacterial generic products are limited and heterogeneous, thus precluding any attempt to generalize the study results. This systematic review suggests that additional evidence would be needed before considering a revision of the marketing authorization process for antibacterial generic products

Carbapenem use in French hospitals: A nationwide survey at the patient level.

International audienceThe objective of this study was to evaluate the characteristics of carbapenem use in French healthcare settings in order to guide future actions. Healthcare facilities voluntarily participated in a nationwide cross-sectional survey in 2011. Medical data and reasons for carbapenem treatment (CPR) and discontinuation were recorded for all patients treated with carbapenems. A total of 2338 patients were recorded by 207 facilities. The median duration of CPR was 8 days, and 31.4% of patients received CPR for >10 days. An antibiotic consultant was involved in the initial choice of CPR in 36.8% of cases. CPR was chosen on an empirical (EP) basis for 1229 patients (52.6%), mainly because of severe sepsis (48.6%) or a perceived risk of bacterial resistance (33.7%). Among EP patients, de-escalation was more frequent in the case of intervention of an antibiotic consultant (35.1%) than without intervention (22.9%) (P<0.01). Among the 1109 patients receiving CPR initially based on bacteriological results, 607 (54.7%) had ESBL-producing Enterobacteriaceae and 397 (35.8%) had Gram-negative bacilli susceptible to at least one β-lactam other than carbapenems or to fluoroquinolones. Among the latter, de-escalation was performed in 59 cases (14.9%). The intervention of an antibiotic consultant did not favour de-escalation in this group. In conclusion, carbapenems are frequently used for treating suspected or confirmed multidrug-resistant bacteria, and overall CPR duration is long. De-escalation is frequently not implemented despite isolates being susceptible to other drugs. More frequent antibiotic consultant intervention may help to decrease carbapenem use in the case of EP treatment

Development and validation of a questionnaire for quantitative assessment of perceived discomforts in critically ill patients.

International audiencePURPOSE: To develop and validate the IPREA (Inconforts des Patients de REAnimation) questionnaire for the assessment of discomfort perceived by patients related to their intensive care unit (ICU) stay. METHODS: This was a two step-study comprising a phase of item generation conducted in one ICU and a phase of psychometric evaluation during a multicenter prospective cohort study in 14 ICUs. Patients were unselected consecutive adult surviving ICU patients. On the day of ICU discharge, a nurse asked patients to rate the severity of 16 discomfort sources, from 0 to 100. Ten percent of patients were randomly chosen to be questioned again to assess the reproducibility. RESULTS: Of 1,380 eligible patients, 1,113 survived and 868 patients could be questioned. The highest scores were for sleep deprivation (35 ± 33), being restrained by tubing, wires, and cables (33 ± 30), pain (32 ± 30), and thirst (32 ± 34). No multidimensional structure was identified. The mean overall score of discomfort was 22 ± 14. Internal consistency was satisfactory using Cronbach's alpha coefficient (0.78). The test-retest reliability study found average measure intraclass correlations ranging from 0.70 to 0.92. The mean duration of the questionnaire administration was 10 ± 7 min. CONCLUSION: The psychometric properties and acceptability of the IPREA questionnaire make it a potential instrument for measuring discomfort perceived by unselected ICU patients

Defining standard and high dosages for β-lactam agents administered by intermittent, prolonged or continuous infusion: a PK/PD simulation study

International audienceBackground: The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable β-lactams, standard and high dosages have been proposed for short-infusion regimens only.Objectives: To evaluate dosages for β-lactams administered by prolonged infusion (PI) and continuous infusion (CI).Methods: Monte Carlo simulations were performed for seven injectable β-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable.Results: Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam.Conclusions: These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary

One test microbial diagnostic microarray for identification of Mycoplasma mycoides subsp. mycoides and other Mycoplasma species

The present study describes the use of microarray technology for rapid identification and differentiation of Mycoplasma mycoides subsp. mycoides from other mycoplasmas that may be pathogenic to ruminants, including those of the Mycoplasma mycoides cluster, genetically and antigenically strictly correlated with Mycoplasma mycoides subsp. mycoides. A microarray containing genetic sequences of 55 different bacterial species from Acholeplasma, Mycoplasma, Spiroplasma and Ureaplasma genera was constructed. Sequences to genes of interest were collected in FASTA format from NCBI. The collected sequences were processed with OligoPicker software. Oligonucleotides were then checked for their selectivity with BLAST searches in GenBank. The microarray was tested with ATCC/NCTC strains of Mycoplasma spp. of veterinary importance in ruminants including Mycoplasma belonging to the mycoides cluster as well as Mycoplasma mycoides subsp. mycoides and Mycoplasma mycoides subsp. capri field strains. The results showed that but one ATCC/NCTC reference strains hybridized with their species-specific sequences showed a profile/signature different and distinct from each other. The heat-map of the hybridization results for the nine genes interrogated for Mycoplasma mycoides subsp. mycoides demonstrated that the reference strain Mycoplasma mycoides subsp mycoides PG1 was positive for all of the gene sequences spotted on the microarray. CBPP field, vaccine and reference strains were all typed to be M. mycoides subsp. mycoides, and seven of the nine strains gave positive hybridization results for all of the nine genes. Two Italian strains were negative for some of the genes. Comparison with non-Mycoplasma mycoides subsp. mycoides reference strains showed some positive signals or considerable homology to Mycoplasma mycoides subsp. mycoides genes. As expected, some correlations were observed between the strictly genetically and antigenically correlated Mycoplasma mycoides subsp. mycoides and Mycoplasma mycoides subsp. capri strains. Specifically, we observed that some Italian Mycoplasma mycoides subsp. mycoides strains were positive for two out of the three Mycoplasma mycoides subsp. capri genes, differently from what has been observed for other European or African Mycoplasma mycoides subsp. mycoides strains. This study highlighted the use of microarray technology as a simple and effective method for a single-step identification and differentiation of Mycoplasma mycoides subsp. mycoides from other mycoplasmas that may be pathogenic to ruminants, including those of the Mycoplasma mycoides cluster, genetically and antigenically strictly correlated with Mycoplasma mycoides subsp. mycoides. The opportunity to discriminate several mycoplasmas in a single analysis enhances diagnostic rapidity and may represent a useful tool to screen occasionally mycoplasmas affecting animal farming in territories where diagnostic laboratory support is limited. The heat-map of the hybridization results of the comparative genomic hybridizations DNA-designed chip clearly indicates that the microarray performs well for the identification of the tested Mycoplasma mycoides subsp. mycoides reference and field strains, discriminating them from other mycoplasmas.Peer reviewed: YesNRC publication: Ye

Are infection specialists recommending short antibiotic treatment durations? An ESCMID international cross-sectional survey

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