Performance and Impact on Antibiotic Prescriptions of a Multiplex PCR in a Real-Life Cohort of Critically Ill Patients with Suspected Ventilated Pneumonia: A Retrospective Monocentric Observational Study.

Pulmonary multiplex polymerase chain reaction (m-PCR) allows rapid pathogen detection. We aimed to assess its impact on initial antibiotic prescriptions in ventilated patients with suspected pneumonia. Between November 2020 and March 2022,ventilated patients with suspected pneumonia hospitalized in our ICU who benefited from respiratory sampling simultaneously tested using conventional microbiological methods and m-PCR were included. The proportion of appropriate changes in the initial antibiotic therapy following m-PCR results was assessed. We analyzed 104 clinical samples. Of the 47 negative m-PCR results, 16 (34%) led to an appropriate antibiotic strategy: 8 cessationsand 8 lack of initiation. Of the 57 positive m-PCR results, 51 (89%) resulted in an appropriate antibiotic strategy: 33 initiations, 2 optimizations, and 9 de-escalations. In the multivariate analysis, a positive m-PCR was associated with an appropriate antibiotic change (OR: 96.60; IC95% [9.72; 960.20], p < 0.001). A higher SAPS II score was negatively associated with an appropriate antibiotic change (OR: 0.96; IC95% [0.931; 0.997], p = 0.034). In our cohort, a positive m-PCR allowed for early initiation or adjustment of antibiotic therapy in almost 90% of cases. A negative m-PCR spared antibiotic use in onethird of cases. The impact of m-PCR results was reduced in the most severe patients.

A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France.

OBJECTIVE: To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. METHODS: This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. RESULTS: At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. CONCLUSIONS: Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.

Rapid containment of coincident outbreaks with 2 carbapenem-resistant Klebsiella pneumoniae strains in an intensive care unit.

In our intensive care unit, coincident outbreaks were caused by concomitant cross-transmission of 2 carbapenem-resistant Klebsiella pneumoniae strains harboring distinct mechanisms of resistance. One strain produced extended-spectrum ß-lactamase in combination with reduced permeability. The other produced oxacillinase-48 carbapenemase. Rapid phenotypic detection of carbapenemase production allowed timely implementation of appropriate infection control measures.

Crystal structure of the pyrazinamidase of Mycobacterium tuberculosis: insights into natural and acquired resistance to pyrazinamide.

Pyrazinamidase (PncA) activates the first-line antituberculous drug pyrazinamide into pyrazinoic acid. The crystal structure of the Mycobacterium tuberculosis PncA protein has been determined, showing significant differences in the substrate binding cavity when compared to the pyrazinamidases from Pyrococcus horikoshii and Acinetobacter baumanii. In M. tuberculosis, this region was found to hold a Fe(2+) ion coordinated by one aspartate and three histidines, one of them corresponding to His57 which is replaced by Asp in Mycobacterium bovis, a species naturally resistant to pyrazinamide. The binding cavity also contains a Cys138-Asp8-Lys96 motif evocating a cysteine-based catalytic mechanism. Mutants have been constructed and investigated by kinetic and thermal shift assays, highlighting the importance of protein folding and thermal stability in the pyrazinamidase activity.

Growth of Yersinia pseudotuberculosis in human plasma: impacts on virulence and metabolic gene expression.

BACKGROUND: In man, infection by the Gram-negative enteropathogen Yersinia pseudotuberculosis is usually limited to the terminal ileum. However, in immunocompromised patients, the microorganism may disseminate from the digestive tract and thus cause a systemic infection with septicemia. RESULTS: To gain insight into the metabolic pathways and virulence factors expressed by the bacterium at the blood stage of pseudotuberculosis, we compared the overall gene transcription patterns (the transcriptome) of bacterial cells cultured in either human plasma or Luria-Bertani medium. The most marked plasma-triggered metabolic consequence in Y. pseudotuberculosis was the switch to high glucose consumption, which is reminiscent of the acetogenic pathway (known as "glucose overflow") in Escherichia coli. However, upregulation of the glyoxylate shunt enzymes suggests that (in contrast to E. coli) acetate may be further metabolized in Y. pseudotuberculosis. Our data also indicate that the bloodstream environment can regulate major virulence genes (positively or negatively); the yadA adhesin gene and most of the transcriptional units of the pYV-encoded type III secretion apparatus were found to be upregulated, whereas transcription of the pH6 antigen locus was strongly repressed. CONCLUSION: Our results suggest that plasma growth of Y. pseudotuberculosis is responsible for major transcriptional regulatory events and prompts key metabolic reorientations within the bacterium, which may in turn have an impact on virulence.