Campbell WR, Li P, Whitman TJ, Blyth DM, Schnaubelt ER, Mende K, Tribble DR
Surg Infect (Larchmt). 2017 Apr;18(3):357-367
BACKGROUND: The contribution of multi-drug-resistant gram-negative bacilli infections (MDRGN-I) in patients with trauma is not well described. We present characteristics of MDRGN-Is among military personnel with deployment-related trauma (2009-2014).
PATIENTS AND METHODS: Data from the Trauma Infectious Disease Outcomes Study were assessed for infectious outcomes and microbial recovery. Infections were classified using standardized definitions. Gram-negative bacilli were defined as multi-drug-resistant if they showed resistance to ≥3 antibiotic classes or were producers of extended-spectrum β-lactamase or carbapenemases.
RESULTS: Among 2,699 patients admitted to participating U.S. hospitals, 913 (33.8%) experienced ≥1 infection event, of which 245 (26.8%) had a MDRGN-I. There were 543 MDRGN-I events (24.6% of unique 2,210 infections) with Escherichia coli (48.3%), Acinetobacter spp. (38.6%), and Klebsiella pneumoniae (8.4%) as the most common MDRGN isolates. Incidence of MDRGN-I was 9.1% (95% confidence interval [CI]: 8.0-10.2). Median time to MDRGN-I event was seven days with 75% occurring within 13 days post-trauma. Patients with MDRGN-Is had a greater proportion of blast injuries (84.1% vs. 62.5%; p < 0.0001), traumatic amputations (57.5% vs.16.3%; p < 0.0001), and higher injury severity (82.0% had injury severity score ≥25 vs. 33.7%; p < 0.0001) compared with patients with either no infections or non-MDRGN-Is. Furthermore, MDRGN-I patients were more frequently admitted to the intensive care unit (90.5% vs. 48.5%; p < 0.0001), colonized with a MDRGN before infection (58.0% vs. 14.7%; p < 0.0001), and required mechanical ventilation (78.0% vs. 28.8% p < 0.0001). Antibiotic exposure before the MDRGN-I event was significantly higher across antibiotic classes except first generation cephalosporins and tetracyclines, which were very commonly used with all patients. Regarding outcomes, patients with MDRGN-Is had a longer length of hospitalization than the comparator group (53 vs. 18 days; p < 0.0001).
CONCLUSIONS: We found a high rate of MDRGN-I in our population characterized by longer hospitalization and greater injury severity. These findings inform treatment and infection control decisions in the trauma patient population.
Goutelle S, Valour F, Gagnieu MC(6), Laurent F(3)(5), Chidiac C(3)(4)(5), Ferry T(3)(4)(5); Lyon Bone and Joint Infection Study Group.
J Antimicrob Chemother. 2018 Apr 1;73(4):987-994.
Background: Ertapenem is a therapeutic option in patients with Gram-negative bone and joint infection (BJI). The subcutaneous (sc) route of administration is convenient in the outpatient setting and has shown favourable pharmacokinetics (PK), but available data on ertapenem are limited.
Objectives: To perform population PK analysis and pharmacokinetic/pharmacodynamics (PK/PD) simulation of ertapenem administered by the intravenous (iv) or sc route to patients with BJI.
Patients and methods: This was a retrospective analysis of PK data collected in patients with BJI who received iv or sc ertapenem. Measured ertapenem concentrations were analysed with a non-parametric population approach. Then, simulations were performed based on the final model to investigate the influence of ertapenem route of administration, dosage and renal function on the probability of achieving a pharmacodynamic (PD) target, defined as the percentage of time for which free plasma concentrations of ertapenem remained above the MIC(fT>MIC) of 40%.
Results: Forty-six PK profiles (13 with iv and 33 with sc ertapenem) with a total of 133 concentrations from 31 subjects were available for the analysis. A two-compartment model with linear sc absorption and linear elimination best fitted the data. Creatinine clearance was found to significantly influence ertapenem plasma clearance. Simulations showed that twice daily dosing, sc administration and renal impairment were associated with an increase in fT>MIC and target attainment.
Conclusions: Our results indicate that 1 g of ertapenem administered twice daily, by the iv or sc route, may optimize ertapenem exposure and achievement of PK/PD targets in patients with BJI.
Kamarova M, Kendall R
Emerg Med J. 2017 Dec;34(12):A869
BACKGROUND: There is a lack of clarity regarding the use of prophylactic antibiotics for patients presenting with penetrating injuries. A structured literature review and review of penetrating injury records in an MTC was undertaken with a view to help guide clinical practice.
METHOD: Searches were conducted on Medline (1946-2017), Embase (1974-2017), and Cochrane (up to 2017) using key words pertaining to penetrating trauma, prophylactic antibiotics and infection. Cases of penetrating injury presenting to one MTC during 2015-2016 were extracted from the TARN database. Patient information (age, sex), injury details (ISS score, anatomical site, nature), antibiotic use in ED, and infectious outcomes were analysed.
RESULTS: A 2012 systematic review by Bosman et al. included 11 RCTs, totaling 1234 patients with blunt and penetrating chest injuries requiring tube thoracostomy. Those that were given prophylactic antibiotics were less likely to develop empyema (OR:0.32), pneumonia (OR:0.51) and wound infections (OR:0.41) compared to placebo. A 2013 Cochrane meta-analysis on penetrating abdominal trauma found no RCTs comparing infection outcomes for prophylactic antibiotics vs placebo. No further trials have since been done. EAST guidelines (2012) recommend a single dose of prophylactic antibiotics for penetrating abdominal trauma. No relevant trials were found for penetrating soft tissue injuries.70 penetrating injuries for 2015-2016 were recorded on TARN, 40 of which were transfers from other hospitals. Half of the total injuries were stabbings, with the rest being shootings, falls and crush injuries. 62.5% of patients were given prophylactic antibiotics in ED. 83% of the remaining patients received antibiotics for another indication.
CONCLUSIONS: Strong evidence exists for the use of prophylactic antibiotics for chest wounds requiring tube thoracostomy. The Cochrane review concluded that there is no evidence base for prophylactic antibiotic use for penetrating abdominal trauma, with EAST recommendations based on weaker evidence. Drawing conclusions about infectious outcomes from TARN data is difficult due to low total numbers, differences in record-keeping for secondary transfers and a high proportion of patients with another requirement for antibiotics.For penetrating thoracic injury requiring chest drain there is evidence of benefit for prophylactic antibiotics, in other patients with penetrating injury due to the current lack of evidence, clinical judgement based on the circumstances of penetrating injury is recommended.