CORRESPONDENCE A Solemn Declaration from the World Alliance against Antibiotic Resistance To the Editor: Antibiotic resistance is increasing exponentially in many countries (1). Three years ago, we created a World Alliance against Antibiotic Resistance to raise the awareness of health care professionals, politicians, policy makers, consumers, and the general public. The alliance is a group of 720 people from many different horizons, coming from 55 different countries. It is supported by 145 medical societies or other professional groups. In June 2014, a solemn declaration against antibiotic resistance was launched. This document proposes 10 different actions to tackle antibiotic resistance. Can we win this war? Probably yes, but huge and sustainable efforts will be necessary. There are countries, such as the Scandinavian ones or the Netherlands, in which resistance is still very low (2). Those countries use very low volumes of antibiotics and have an excellent hygienic program. Therefore, it is feasible. The evolution of methicillin-resistant Staphylococcus aureus prevalence in Europe is another matter of hope. As a result of an intensive usage of isolation and of hand-rub alcoholic solutions, prevalence of this infection has been decreased in many European countries (2), as well as in the United States. Enterobacteriaceae harboring extended spectrum beta-lactamases and carbapenemases are still limited in many countries. To be successful, we need a very strong and urgent political involvement worldwide (3, 4) and international coordination by the World Health Organization. n

Author disclosures are available with the text of this letter at www.atsjournals.org. Jean Carlet, M.D. Hopital ˆ St Joseph Paris, France

References 1. Carlet J, Collignon P, Goldmann D, Goossens H, Gyssens IC, Harbarth S, Jarlier V, Levy SB, N’Doye B, Pittet D, et al. Society’s failure to protect a precious resource: antibiotics. Lancet 2011;378: 369–371. 2. European Centre for Disease Prevention and Control. Antimicrobial resistance interactive database (EARS-Net). Stockholm, Sweden: European Centre for Disease Prevention and Control [accessed 2014 Sept 10]. Available from: http://www.ecdc.europa.eu/en/ healthtopics/antimicrobial_resistance/database/Pages/database. aspx 3. Carlet J, Pulcini C, Piddock LJ. Antibiotic resistance: a geo-political issue. Clin Microbiol Infect 2014;20:949–953. 4. Laxminarayan R, Duse A, Wattal C, Zaidi AK, Wertheim HF, Sumpradit N, Vlieghe E, Hara GL, Gould IM, Goossens H, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis 2013; 13:1057–1098.

Copyright © 2015 by the American Thoracic Society

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Development of a Hypercoagulable Status in Patients Undergoing Off-Pump Lung Transplantation despite Prolonged Conventional Coagulation Tests To the Editor: Lung transplantation is associated with high postoperative rates of venous thromboembolism (VTE). In-hospital rates of VTE after transplantation have been estimated at 6–12%, despite thromboprophylaxis (1, 2), and even at 36% in post mortem studies (3). This is elevated in comparison with the general surgical patient population, in which VTE rates are estimated at around 4% (4). Therefore, postoperative initiation of thromboprophylaxis with low-molecular-weight heparin is highly recommended in this group of patients to prevent morbidity and mortality (5). It is not exactly known which factors cause the high risk for VTE in the early postoperative period after lung transplantation. We have previously reported on the progressive changes in hemostatic function of patients undergoing a liver transplantation (6, 7). In these studies, we have found that the coagulation/ anticoagulation equilibrium shifted toward “hypercoagulability” during the procedure. Here, we report our findings on changes in the balance regulating coagulation and anticoagulant dynamics during lung transplantation. Because a cardiopulmonary bypass system is known to induce profound changes in the hemostatic system (8), we studied 10 patients transplanted without a cardiopulmonary bypass system (off pump) (Table 1). To further distinguish the specific effect of the lung transplant procedure on hemostasis from the perioperative effects that accompany any surgical procedure in the thorax of a similar approach and extent, we also included 11 patients undergoing off-pump coronary artery bypass graft (CABG) surgery to serve as controls for the various tests performed in this study. We first assessed plasma samples taken from patients undergoing off-pump lung transplantation or CABG by the prothrombin time (PT) and activated partial thromboplastin time (APTT) (Figures 1A and 1B; APTT not shown). In both patient groups, the PT and APTT were normal at the start of surgery but were significantly elevated at the end of the procedures, although the increase after CABG was less pronounced. At 5 days after surgery, PT and APTT values had returned to baseline. We next performed thrombin generation testing in plasma in the presence and absence of a soluble form of thrombomodulin, the physiological activator of the endogenous anticoagulant protein C pathway, and calculated the thrombomodulin sensitivity ratio (TM-SR), as described (7). A TM-SR greater than 1 reflects an increased resistance to the anticoagulant action of thrombomodulin. The endogenous thrombin generating potential in samples without addition of thrombomodulin was identical between healthy control patients and patients during lung transplantation, and when thrombomodulin was added to the test mixture, the endogenous thrombin-generating potential decreased in both groups (data not shown). However, the anticoagulant action of Author Contributions: Conception and design: I.T.A.P., M.E.E., R.J.P., and T.L.; drafting manuscript: K.R., G.C.G.H., and T.L.; patient inclusion: K.R.; laboratory analyses: J.A. and J.C.M.M.; and analysis and interpretation: K.R., G.C.G.H., J.C.M.M., W.v.d.B., R.J.P., M.E.E., and T.L. All authors revised and approved the manuscript.

American Journal of Respiratory and Critical Care Medicine Volume 191 Number 2 | January 15 2015

A solemn declaration from the World Alliance against Antibiotic Resistance.

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