Analyse comparative des échecs thérapeutiques entre Céfazoline et Oxacilline chez les patients de réanimation traités pour une pneumopathie à Staphylococcus aureus sensible à la méticilline

Abstract : Introduction: in the intensive care setting, Methicillin-susceptible Staphylococcus aureus (MSSA) is one of the most common pathogen involved in respiratory tract infections. Since the recent shortage of oxacillin, cefazolin is now the preferential antimicrobial agent prescribed for MSSA infections, but the non-inferiority of cefazolin remains to be documented in critically ill patients. Several concerns about an inoculum effect could be responsible for cefazolin underexposure, especially in patients with augmented renal clearance (ARC). The objective of this study was to compare the efficacy of cefazolin and oxacillin as appropriate antibiotic therapy in critically ill patients with MSSA-pneumonia and to identify factors associated with therapeutic failure. Methods: over a 5-year period, in the intensive care units in Bordeaux, patients who presented a pneumonia due to MSSA treated by oxacillin or cefazolin with less than 5 days of empirical antimicrobial therapy were included retrospectively. The main outcome was the rate of therapeutic failure defined by an impaired clinical response with a need for escalating antibiotics or a new pulmonary infection (with MSSA growing at a significant concentration) needing the resumption of antibiotic therapy within 15 days after end-of-treatment. Factors associated with therapeutic failure were analyzed with an univariate and multivariate analysis with a logistic regression. Results: 127 patients were included. The overall therapeutic failure rate was 23%. The therapeutic failure rate was not statistically different between oxacillin-treated patients and cefazolin-treated patients (22 vs. 24%, p = 0.78). Patients experiencing therapeutic failure were more likely to have a longer median duration of mechanical ventilation, ICU or hospital length of stay, without statistical difference in the mortality rate. Factors associated with therapeutic failure were ARC > 130 ml/min/1,73m2. Daily dose, high inoculum (107 CFU/ml) were not associated with therapeutic failure. Discussion: after adjusting for multiple confounders, our study suggests that cefazolin is no worse than oxacillin for the treatment of MSSA-pneumonia in critically ill patients. The inoculum effect was not documented. ARC remains a major factor associated with the important rate of therapeutic failure.
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Master Thesis
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Juliette Rey. Analyse comparative des échecs thérapeutiques entre Céfazoline et Oxacilline chez les patients de réanimation traités pour une pneumopathie à Staphylococcus aureus sensible à la méticilline. Médecine humaine et pathologie. 2018. ⟨dumas-02087660⟩

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