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.

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.

Eravacycline for the treatment of complicated intra-abdominal infections.

Introduction: Complicated intra-abdominal infections (cIAIs) are among the most frequent infections, contributing to significant morbidity and healthcare costs. Several medical needs remain unmet, related to the pharmacokinetic capacities of the available drugs and their limited spectrum of activity for targeting multidrug-resistant Gram-negative and Gram-positive bacteria. Eravacycline, a new synthetic fluorocycline, could have useful properties in cIAIs.Areas covered: The antimicrobial activity of eravacycline against the microorganisms most frequently cultured in cIAIs has been confirmed in worldwide panels of clinical isolates, including enterococci, ESBL-producing Enterobacteriaceae, Acinetobacter baumannii and anaerobes. Pharmacokinetic data demonstrate interesting characteristics with good tissue concentrations including biliary tract and digestive tissues. At a conventional dosage of 1 mg/kg q12h, no adjustment is required on the basis of race or gender, or in elderly (≥ 65 years old) patients, patients with renal impairment or patients undergoing hemodialysis. Phase 2 and 3 trials assessing the clinical efficacy and safety of eravacycline demonstrated non-inferiority versus carbapenems and a good safety profile.Expert opinion: Eravacycline may be particularly suitable for the treatment of cIAIs. Results from clinical trials and real-world data are now expected in specific subgroups of patients to confirm the safety profile and efficacy observed in registration trials.

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.

Efficacy and toxicity of intravenous iron in a mouse model of critical care anemia*.

OBJECTIVE: Anemia is common in critically ill patients, due to inflammation and blood loss. Anemia can be associated with iron deficiency and low serum hepcidin levels. However, iron administration in this setting remains controversial because of its potential toxicity, including oxidative stress induction and sepsis facilitation. The objective of this work was to determine the efficacy and toxicity of iron administration using a mouse model mimicking critical care anemia as well as a model of acute septicemia. DESIGN: Prospective, randomized, open label controlled animal study. SETTING: University-based research laboratory. SUBJECTS: C57BL/6 and OF1 mice. INTERVENTIONS: Intraperitoneal injection of zymosan inducing generalized inflammation in C57BL/6 mice, followed in our full model by repeated phlebotomies. A dose equivalent to 15 mg/kg of ferric carboxymaltose was injected intravenously on day 5. To assess the toxicity of iron in a septicemia model, OF1 mice were simultaneously injected with iron and different Escherichia coli strains. MEASUREMENTS AND MAIN RESULTS: To investigate the effect of iron on oxidative stress, we measured reactive oxygen species production in the blood using luminol-amplified chemiluminescence and superoxide dismutase 2 messenger RNA levels in the liver. These markers of oxidative stress were increased after iron administration in control mice but not in zymosan-treated mice. Liver catalase messenger RNA levels decreased in iron-treated control mice. Iron administration was not associated with increased mortality in the septicemia model or in the generalized inflammation model. Iron increased hemoglobin levels in mice fed with a low iron diet and subjected to phlebotomies and zymosan 2 wks after treatment administration. CONCLUSIONS: Adverse effects of intravenous iron supplementation by ferric carboxymaltose seem to be minimal in our animal models. Furthermore, iron appears to be effective in correcting anemia, despite inflammation. Studies of efficacy and safety of iron in critically ill patients are warranted.

Anesthesia and perioperative management of patients who undergo transfemoral transcatheter aortic valve implantation: an observational study of general versus local/regional anesthesia in 125 consecutive patients.

OBJECTIVE: To describe differences in intra- and postoperative care between general (GA) and local/regional anesthesia (LRA) in consecutive high-risk patients with aortic stenosis who underwent transfemoral transcatheter aortic valve implantation (TAVI). DESIGN: A retrospective review of data collected in an institutional registry. SETTING: An academic hospital. PARTICIPANTS: One hundred twenty-five consecutive patients with severe aortic stenosis who underwent transfemoral TAVI. INTERVENTIONS: GA versus LRA followed by postoperative care. Complications were defined by pre-established criteria. MATERIAL AND METHODS: Consecutive patients referred for transfemoral TAVI between October 2006 and October 2010 initially underwent GA (n = 91) followed by LRA after March 2010 (n= 34). Results are presented as mean ± standard deviation or median (25-75 percentiles) as appropriate. GA and LRA TAVI patients had similar preoperative characteristics. LRA was associated with a significantly shorter procedure duration (LRA: 80 [67-102]; GA: 120 [90-140 minutes]; p < 0.001), hospital stay (LRA: 8.5 [7-14.5]; GA: 15.5 [10-24] days; p < 0.001), intraoperative requirements of catecholamines (LRA 23%; GA: 90% of patients; p < 0.001), and volume expansion (LRA: 11 [8-16]; GA: 22 [15-36] mL/kg; p < 0.001). There were significant differences in delta creatinine (day 1, preoperative creatinine values; LRA: 0 [-12 to 9]; GA: -15 (-25 to 2.9) µmol, p < 0.004). The frequency of any postoperative complications was 38% (LRA) and 77% (GA) (p = 0.11). Thirty-day mortality was 7% (GA) and 9% (LRA) (p = 0.9). CONCLUSIONS: This observational study suggests that LRA was associated with less intraoperative hemodynamic instability and significant shortening of the procedure and hospital stay. Changes in the anesthetic technique adapted to changes in TAVI interventional techniques and did not increase the rate of postoperative complications.

Rapid adaptation of antibiotic therapy for community-acquired peritonitis using direct cultures on antibiotic agar plates: pilot study.

BACKGROUND: Treatment of peritonitis requires prompt surgery and antibiotic therapy. It usually takes two or three days to obtain definitive results of peritoneal cultures and to adapt empirical antibiotic therapy. We assessed the potential time gain associated with direct culture of peritoneal samples on antibiotic agar (AA). METHODS: Peritoneal samples from 31 consecutive patients undergoing surgery for suspected community-acquired peritonitis were cultured according to the standard method and on AA containing one of the following five regimens: amoxicillin/clavulanic acid + gentamicin, ticarcillin/clavulanic acid + gentamicin, cefotaxime +metronidazole, piperacillin/tazobactam, or ertapenem. We compared the treatment modifications made by physicians aware only of the results of the standard method with the modifications the AA method would have indicated. RESULTS: Fewer isolates were identified by direct culture on AA than by the standard method (17 vs. 45; p = 0.0001), but definitive results were obtained much more rapidly (median 1 [range 1-3] days vs. 3 [range 2-7] days; p < 0.0001). Antibiotic regimens were changed for 14 patients on the basis of the results of the standard method (broader antibiotic spectrum and narrower spectrum in seven patients each). With the AA method, these changes could have been indicated after a median of 1 (range 1-2) days instead of 4 (range 1-11) days (p = 0.0006). The AA method missed only one resistant bacterial strain and isolated nine strains not detected by the standard method, including an extended-spectrum beta-lactamase-producing Escherichia coli. A complicated outcome was more frequent in patients having isolates found with the AA but not the standard method (86% vs. 21%; p = 0.003). CONCLUSION: Use of the AA method for culture of peritoneal samples from patients with community-acquired peritonitis speeds appropriate adaptation of antibiotic therapy and warrants further investigation.