Outcome and Adequacy of Empirical Antibiotherapy in Post-Operative Peritonitis: A Retrospective Study.

Background: Empirical antibiotherapy (EA) should target all bacteria in post-operative peritonitis (PP). Nevertheless, recent studies failed to prove a link between adequacy of EA and prognosis of PP. We sought to confirm this loss of association between adequate EA and prognosis and to analyze the evolution of patients' characteristics and antimicrobial strategies. Methods: This is was retrospective study. Patients with a positive fungal culture were excluded. The cohort was divided into two time periods. Data of survivors and non-survivors were compared within each time period. Differences between the two periods were assessed. A multivariable analysis searched for parameters associated with a higher hospital mortality rate. Results: Two hundred fifty-one patients were included, with 92 patients in the first period (P1) and 152 patients in the second period (P2). Inadequate EA was associated with a worse outcome only in P1. The multivariable analysis in the whole cohort showed that inadequate EA was associated with a higher mortality rate. When the differences noticed between the two periods were entered in the model (presence of resistant gram-positive cocci and EA comprising glycopeptides), inadequate EA was no longer associated with worse outcome. In P1, the most severe patients had more resistant bacteria, hence, had a higher rate of inadequate EA. This artifact disappeared in P2, during which broader antibiotherapies with triple EA were more often prescribed for the most severe patients. Conclusion: This study showed that the link between inadequate EA and outcome of patients with PP was at least partly artifactual in older studies.

Usefulness of Gram stain examination of peritoneal fluid in postoperative peritonitis to guide empirical antibiotherapy.

PURPOSE: In postoperative peritonitis, Gram stain examination (GSE) of peritoneal fluid has been proposed as a guide for the prescription of glycopeptides and antifungal therapy in empirical antibiotherapy. No data support this approach for Gram-positive cocci. We aimed to evaluate the performance of GSE in predicting the results of the culture of peritoneal fluid. METHODS: In this retrospective single-center study, concordance between GSE and culture of peritoneal fluid was assessed for different types of microorganisms. Factors associated with concordance of the two tests were evaluated in the subpopulation of Gram-positive cocci peritonitis. RESULTS: Among the 152 episodes, the GSE was negative in 57 cases. The negative predictive value and the positive predictive value were 41% and 87% for Gram-positive cocci (GPC), 31% and 86% for Gram-negative bacilli, and 78% and 94% for fungi. GSE is not a reliable guide for the choice of empirical antibiotherapy and cannot reliably rule out the presence of GPC at culture. If we aim to achieve a high rate of adequacy, the systematic use of glycopeptide in the empirical antibiotherapy may be considered. CONCLUSION: GSE shows poor performance to predict the results of culture of peritoneal fluid in postoperative peritonitis. Avoiding covering resistant GPC cannot be based on the result of GSE.

Assessment of the National French recommendations regarding the dosing regimen of 8mg/kg of gentamicin in patients hospitalised in intensive care units.

INTRODUCTION: To assess the French National Agency for Medicines and Health Products Safety (ANSM) guidelines concerning the peak plasma concentration (Cmax) of gentamicin when using a loading dose of 8mg/kg administered in patients hospitalised in the intensive care unit (ICU). PATIENTS AND METHODS: A prospective observational cohort study conducted in one ICU. RESULTS: During the study period, 34 patients with a median simplified acute physiology score 2 of 54 [44-70] received a median dose of 8 [7.9-8.1] mg/kg of gentamicin. The median Cmax was 17.5 [15.4-20.7] mg/L and no patient had a Cmax>30mg/L. Twenty-four of 34 patients (71%) had a Cmax>16mg/L. Following multivariate analysis, the only factor associated with Cmax<16mg/L was a positive fluid balance 24hours before gentamicin administration (per 1000mL increment) (OR: 0.37, 95% CI: 0.18-0.77, P=0.008). CONCLUSIONS: These results suggest that a Cmax>30mg/L [which corresponds to approximately 8 times the minimal inhibiting concentrations (MIC) breakpoints for Pseudomonas aeruginosa and Enterobacteriaceae with intermediate sensitivity] of gentamicin as recommended by ANSM guidelines seems impossible to obtain with a loading dose of 8mg/kg in the ICU. A loading dose of 8mg/kg should probably not be used in the empiric antibiotic treatment of infection due to non-fermenting Gram-negative bacilli and Enterobacteriaceae with intermediate sensitivity whose MIC breakpoint is 4mg/L. A Cmax>16mg/L was not reached in almost 30% of patients, particularly in the group with a positive fluid balance who require higher doses than currently recommended.