American Journal of Emergency Medicine 33 (2015) 988.e3–988.e4
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Linezolid is a novel and effective treatment for septic pulmonary embolism☆,☆☆ Abstract Septic pulmonary embolism (SPE) is an uncommon and severe infectious disease that requires early diagnosis and proper antibiotic therapy. We present the case of a healthy 14-year-old girl with a history of atopic dermatitis, who developed SPE caused by Staphylococcus aureus bacteremia. We initially administered intravenous doripenem and vancomycin. Four days after her admission, blood and urine cultures yielded penicillinase nonproducing, methicillin-sensitive S aureus, with a minimum inhibitory concentration less than 0.06 μg/mL. However, the administration of penicillin G aggravated her condition; therefore, treatment was switched to linezolid on day 8. Her condition subsequently resolved, and she was discharged 40 days after admission without any complications. To our knowledge, this is the first report regarding the efficacy of linezolid for SPE that is related to community-acquired methicillin-sensitive S aureus bacteremia. The favorable lung tissue transfer of linezolid may have contributed to its efficacy against the SPE. Septic pulmonary embolism (SPE) is a rare disease, in which a sepsis-related bacterial mass causes embolism of the pulmonary artery [1]; this disease is especially rare in children [2]. Thoracic computed tomography reveals characteristic findings, including nodules, patchy infiltrates, cavity, and pleural effusion. Although imaging has facilitated early SPE diagnosis and therapeutic intervention [3], it has a high mortality rate [4]. In addition, due to the increasing use of intravascular devices and catheters, an increasing number of SPE reports have been published [5,6]. Thus, an appropriate antimicrobial therapy is needed to ensure successful treatment outcomes. In this report, we describe the first successful use of linezolid to treat SPE that was caused by penicillinase nonproducing, methicillin-sensitive Staphylococcus aureus (MSSA), after failed penicillin G treatment, in a 14-year-old girl. A 14-year-old girl was brought to the emergency department after 3 days of high fever, poor oral intake, and left shoulder discomfort. She had no history of trauma or drug use. Physical examination revealed a body temperature of 38.5°C, blood pressure of 72/40 mm Hg, respiratory rate of 26/min, heart rate of 128/min, oxygen saturation as measured by pulse oximetry of 81% (room air), Glasgow Coma Scale score of E3V5M6, and poor general health. However, no cardiac or respiratory abnormalities were observed. Laboratory data revealed a coagulation disorder (prothrombin time, 19.3 seconds; activated partial thromboplastin time, 48.8 seconds), severe inflammatory response (C-reactive
☆ Source(s) of support in the form of equipment, drugs, or grants (including grant nos.): None. ☆☆ The name of organization and date of assembly if the article has been presented: Hitachi General Hospital, Ibaraki, Japan. 0735-6757/© 2014 Elsevier Inc. All rights reserved.
protein, 16.4 mg/dL; procalcitonin, N 100 ng/mL), and liver and renal dysfunction (blood urea nitrogen, 38.1 mg/dL; creatinine, 4.0 mg/dL). Blood gas analysis also revealed severe respiratory failure and lactic acidosis (pH 7.34; PCO2, 25.5 mm Hg; PaO2, 6.9 mm Hg; HCO3−, 13.8 mmol/L; lactate, 5.4 mmol/L). Furthermore, thoracic computed tomography revealed scattered minor nodules in the lung, although there was no focal infection or abscess that involved the left shoulder. Therefore, we started intravenous doripenem (0.5 g every 8 hours) and vancomycin (700 mg every 8 hours). On the following day, her respiratory state had deteriorated, and noninvasive positive pressure ventilation was started. Chest computed tomography revealed that the size of the multiple lung nodes had increased (Figure), which suggested an SPE. Based on this finding, the antibiotic regimen was changed to doripenem and linezolid (600 mg every 12 hours) on day 3. Her general condition subsequently improved rapidly, and the ventilation was withdrawn on day 4. Blood and urine cultures revealed MSSA, with a minimum inhibitory concentration of less than 0.06 μg/mL (penicillinase nonproducing); therefore, the doripenem and linezolid regimen was deescalated to intravenous penicillin G (6 000 000 U every 6 hours) and clindamycin (600 mg every 6 hours) on day 5. However, her high fever recurred, and magnetic resonance imaging revealed deterioration of her scapulohumeral periarthritis. On day 8, the doripenem and linezolid was restarted, and her subsequent course was favorable. The girl was discharged on day 40 without any complications. To our knowledge, this is the first report regarding linezolid treatment of SPE. Among previous reports of SPE, MSSA was the most common pathogen, and the antibiotic treatment was modified based on the culture results [7,8]. In our case, blood culture yielded penicillinase nonproducing MSSA, and yet the patient's condition deteriorated after deescalation to penicillin G. This may be caused by the lung tissue transfer of linezolid being more favorable than that of other drugs. When 600 mg of linezolid was orally administered to healthy adults (every 12 hours), the concentration in the alveolar epithelial lining fluid was 420% [9], whereas the plasma concentration remained 100%. In contrast, the lung transfer of penicillin G (ineffective in the present case) after an intramuscular injection of penicillin G (20 000 U/kg) in rabbits was approximately 24%, whereas the blood concentration was 100% [9]. Thus, linezolid is thought to be particularly effective for nosocomial MSSA or methicillin-resistant S aureus pneumonia [10]. Furthermore, linezolid has a different mechanism of action compared with β-lactam antibiotics, as it blocks the initial step of protein synthesis (the formation of the 70S complex during translation initiation), thereby inhibiting protein synthesis. In addition, linezolid exhibits anticytokine and antiinflammatory activity. In an in vitro study, Garcia et al [11] reported that the production of inflammatory cytokines,
988.e4
M. Yasuda et al. / American Journal of Emergency Medicine 33 (2015) 988.e3–988.e4
Kazuma Ohshima, MD Miyuki Yamamoto, MD Kurato Tokunaga, MD Department of Emergency and Critical Care Medicine, Hitachi General Hospital, 2-1-1 Jonan Hitachi, Ibaraki 317-0077, Japan Tatsuma Fukuda, MD Kensuke Nakamura MD, PhD Department of Emergency and Critical Care Medicine, Hitachi General Hospital, 2-1-1 Jonan Hitachi, Ibaraki 317-0077, Japan Department of Emergency and Critical Care Medicine University Hospital The University of Tokyo Hospital, 7-3-1 Hongo Bunkyo Tokyo 113-8655, Japan http://dx.doi.org/10.1016/j.ajem.2014.12.035 Figure. Chest computed tomography demonstrates multiple nodules in both lungs.
such as interleukin 1β, interleukin 6, and tumor necrosis factor α, in lipopolysaccharide-stimulated monocytes from health adults was markedly inhibited 6 hours after linezolid treatment. Lambers et al [12] also reported that linezolid exhibits anticytokine activity by suppressing gene transcription. Although the clinical significance of linezolid's antiinflammatory effects should be examined, they may have helped resolve the patient's condition in the present case. Therefore, linezolid should be considered as an empirical therapy for SPE or as a treatment option in patients who do not respond to other drugs. We reported the first case of SPE that responded to linezolid treatment. Given the favorable lung tissue transfer of linezolid, it should be considered for the treatment of SPE. Maki Yasuda, MD Department of Emergency and Critical Care Medicine, Hitachi General Hospital, 2-1-1 Jonan Hitachi, Ibaraki 317-0077, Japan Corresponding author. Department of emergency and Critical Care Medicine, Hitachi General Hospital 2-1-1 Jonan Hitachi, Ibaraki 317-0077, Japan Tel.: +81 294 23 1111; fax: +81 294 23 8317 E-mail address: [email protected] Ryota Inokuchi, MD Department of Emergency and Critical Care Medicine, Hitachi General Hospital, 2-1-1 Jonan Hitachi, Ibaraki 317-0077, Japan Department of Emergency and Critical Care Medicine, University Hospital The University of Tokyo Hospital, 7-3-1 Hongo Bunkyo Tokyo 113-8655, Japan Department of Emergency Medicine, JR General Hospital 2-1-3 Yoyogi, Shibuya-ku, Tokyo 151-8528, Japan
References [1] Cook Rachel J, Ashton Rendell W, Aughenbaugh Gregory L, Ryu Jay H. Septic pulmonary embolism: presenting features and clinical course of 14 patients. Chest 2005; 128:162–6. [2] Thabet Farah C, Alhejaili Abdurahman S, Alodayani Abdurahman N, Chehab May S. Septic pulmonary embolism secondary to Staphylococcus aureus septic thrombophlebitis in a pediatric patient. Saudi Med J 2013;34(10):1080–2. [3] Sano Tsuyoshi, Homma Sakae. Septic pulmonary emboli. Kokyu 2013;2(1): 58–61. [4] Ye Rui, Zhao Li, Wang Cuihong, Wu Xiaojie, Yan Hengyi. Clinical characteristics of septic pulmonary embolism in adults: a systematic review. Respir Med 2014;108: 1–8. [5] Surov A, Wienke A, Carter JM, Stoevesandt D, Behrmann C, Spielmann RP, et al. Intravascular embolization of venous catheter–causes, clinical signs, and management: a systematic review. JPEN J Parenter Enteral Nutr 2009; 33(6):677–85. [6] Dunn Ryan, Bares Sara, David Michael Z. Central venous catheter-related bacteremia caused by Kocuria kristinae: case report and review of the literature. Ann Clin Microbiol Antimicrob 2011;10:31–5. [7] Goswami Umesh, Brenes Jorge A, Punjabi Gopal V, LeClaire Michele M, Williams David N. Associations and outcomes of septic pulmonary embolism. Open Respir Med J 2014;8:28–33. [8] Conte JE, Golden Jeffrey A, Kipps Juliana, Zurlinden Elisabeth. Intrapulmonary pharmacokinetics of linezolid. Antimicrob Agents Chemother 2002;46(5): 1475–80. [9] George PA, Cha Raymond, Rybak Michael J. In vitro activities of quinupristindalfopristin and cefepime, alone and in combination with various antimicrobials, against multidrug-resistant Staphylococci and Enterococci in an in vitro pharmacodynamic model. Antimicrob Agents Chemother 2002;46(8):2606–12. [10] Tatsuro S, Hiroyuki N. Relation between blood-and tissue-levels of penicillin. J Antibiot B 1951;4(9):537–9. [11] Garcia-Roca P, Mancilla-Ramirez J, Santos-Segura A, Fernandez-Aviles M, CalderonJaimes E. Linezolid diminishes inflammatory cytokine production from human peripheral blood mononuclear cells. Arch Med Res 2006;37:31–5. [12] Lambers C, Burian B, Binder P, Ankersmit H-H, Wagner C, Muller M, et al. Early immunomodulatory effects of linezolid in a human whole blood endotoxin model. Int J Clin Pharmacol Ther 2010;48(7):419–24.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Linezolid is a novel and effective treatment for septic pulmonary embolism☆,☆☆ Abstract Septic pulmonary embolism (SPE) is an uncommon and severe infectious disease that requires early diagnosis and proper antibiotic therapy. We present the case of a healthy 14-year-old girl with a history of atopic dermatitis, who developed SPE caused by Staphylococcus aureus bacteremia. We initially administered intravenous doripenem and vancomycin. Four days after her admission, blood and urine cultures yielded penicillinase nonproducing, methicillin-sensitive S aureus, with a minimum inhibitory concentration less than 0.06 μg/mL. However, the administration of penicillin G aggravated her condition; therefore, treatment was switched to linezolid on day 8. Her condition subsequently resolved, and she was discharged 40 days after admission without any complications. To our knowledge, this is the first report regarding the efficacy of linezolid for SPE that is related to community-acquired methicillin-sensitive S aureus bacteremia. The favorable lung tissue transfer of linezolid may have contributed to its efficacy against the SPE. Septic pulmonary embolism (SPE) is a rare disease, in which a sepsis-related bacterial mass causes embolism of the pulmonary artery [1]; this disease is especially rare in children [2]. Thoracic computed tomography reveals characteristic findings, including nodules, patchy infiltrates, cavity, and pleural effusion. Although imaging has facilitated early SPE diagnosis and therapeutic intervention [3], it has a high mortality rate [4]. In addition, due to the increasing use of intravascular devices and catheters, an increasing number of SPE reports have been published [5,6]. Thus, an appropriate antimicrobial therapy is needed to ensure successful treatment outcomes. In this report, we describe the first successful use of linezolid to treat SPE that was caused by penicillinase nonproducing, methicillin-sensitive Staphylococcus aureus (MSSA), after failed penicillin G treatment, in a 14-year-old girl. A 14-year-old girl was brought to the emergency department after 3 days of high fever, poor oral intake, and left shoulder discomfort. She had no history of trauma or drug use. Physical examination revealed a body temperature of 38.5°C, blood pressure of 72/40 mm Hg, respiratory rate of 26/min, heart rate of 128/min, oxygen saturation as measured by pulse oximetry of 81% (room air), Glasgow Coma Scale score of E3V5M6, and poor general health. However, no cardiac or respiratory abnormalities were observed. Laboratory data revealed a coagulation disorder (prothrombin time, 19.3 seconds; activated partial thromboplastin time, 48.8 seconds), severe inflammatory response (C-reactive
☆ Source(s) of support in the form of equipment, drugs, or grants (including grant nos.): None. ☆☆ The name of organization and date of assembly if the article has been presented: Hitachi General Hospital, Ibaraki, Japan. 0735-6757/© 2014 Elsevier Inc. All rights reserved.
protein, 16.4 mg/dL; procalcitonin, N 100 ng/mL), and liver and renal dysfunction (blood urea nitrogen, 38.1 mg/dL; creatinine, 4.0 mg/dL). Blood gas analysis also revealed severe respiratory failure and lactic acidosis (pH 7.34; PCO2, 25.5 mm Hg; PaO2, 6.9 mm Hg; HCO3−, 13.8 mmol/L; lactate, 5.4 mmol/L). Furthermore, thoracic computed tomography revealed scattered minor nodules in the lung, although there was no focal infection or abscess that involved the left shoulder. Therefore, we started intravenous doripenem (0.5 g every 8 hours) and vancomycin (700 mg every 8 hours). On the following day, her respiratory state had deteriorated, and noninvasive positive pressure ventilation was started. Chest computed tomography revealed that the size of the multiple lung nodes had increased (Figure), which suggested an SPE. Based on this finding, the antibiotic regimen was changed to doripenem and linezolid (600 mg every 12 hours) on day 3. Her general condition subsequently improved rapidly, and the ventilation was withdrawn on day 4. Blood and urine cultures revealed MSSA, with a minimum inhibitory concentration of less than 0.06 μg/mL (penicillinase nonproducing); therefore, the doripenem and linezolid regimen was deescalated to intravenous penicillin G (6 000 000 U every 6 hours) and clindamycin (600 mg every 6 hours) on day 5. However, her high fever recurred, and magnetic resonance imaging revealed deterioration of her scapulohumeral periarthritis. On day 8, the doripenem and linezolid was restarted, and her subsequent course was favorable. The girl was discharged on day 40 without any complications. To our knowledge, this is the first report regarding linezolid treatment of SPE. Among previous reports of SPE, MSSA was the most common pathogen, and the antibiotic treatment was modified based on the culture results [7,8]. In our case, blood culture yielded penicillinase nonproducing MSSA, and yet the patient's condition deteriorated after deescalation to penicillin G. This may be caused by the lung tissue transfer of linezolid being more favorable than that of other drugs. When 600 mg of linezolid was orally administered to healthy adults (every 12 hours), the concentration in the alveolar epithelial lining fluid was 420% [9], whereas the plasma concentration remained 100%. In contrast, the lung transfer of penicillin G (ineffective in the present case) after an intramuscular injection of penicillin G (20 000 U/kg) in rabbits was approximately 24%, whereas the blood concentration was 100% [9]. Thus, linezolid is thought to be particularly effective for nosocomial MSSA or methicillin-resistant S aureus pneumonia [10]. Furthermore, linezolid has a different mechanism of action compared with β-lactam antibiotics, as it blocks the initial step of protein synthesis (the formation of the 70S complex during translation initiation), thereby inhibiting protein synthesis. In addition, linezolid exhibits anticytokine and antiinflammatory activity. In an in vitro study, Garcia et al [11] reported that the production of inflammatory cytokines,
988.e4
M. Yasuda et al. / American Journal of Emergency Medicine 33 (2015) 988.e3–988.e4
Kazuma Ohshima, MD Miyuki Yamamoto, MD Kurato Tokunaga, MD Department of Emergency and Critical Care Medicine, Hitachi General Hospital, 2-1-1 Jonan Hitachi, Ibaraki 317-0077, Japan Tatsuma Fukuda, MD Kensuke Nakamura MD, PhD Department of Emergency and Critical Care Medicine, Hitachi General Hospital, 2-1-1 Jonan Hitachi, Ibaraki 317-0077, Japan Department of Emergency and Critical Care Medicine University Hospital The University of Tokyo Hospital, 7-3-1 Hongo Bunkyo Tokyo 113-8655, Japan http://dx.doi.org/10.1016/j.ajem.2014.12.035 Figure. Chest computed tomography demonstrates multiple nodules in both lungs.
such as interleukin 1β, interleukin 6, and tumor necrosis factor α, in lipopolysaccharide-stimulated monocytes from health adults was markedly inhibited 6 hours after linezolid treatment. Lambers et al [12] also reported that linezolid exhibits anticytokine activity by suppressing gene transcription. Although the clinical significance of linezolid's antiinflammatory effects should be examined, they may have helped resolve the patient's condition in the present case. Therefore, linezolid should be considered as an empirical therapy for SPE or as a treatment option in patients who do not respond to other drugs. We reported the first case of SPE that responded to linezolid treatment. Given the favorable lung tissue transfer of linezolid, it should be considered for the treatment of SPE. Maki Yasuda, MD Department of Emergency and Critical Care Medicine, Hitachi General Hospital, 2-1-1 Jonan Hitachi, Ibaraki 317-0077, Japan Corresponding author. Department of emergency and Critical Care Medicine, Hitachi General Hospital 2-1-1 Jonan Hitachi, Ibaraki 317-0077, Japan Tel.: +81 294 23 1111; fax: +81 294 23 8317 E-mail address: [email protected] Ryota Inokuchi, MD Department of Emergency and Critical Care Medicine, Hitachi General Hospital, 2-1-1 Jonan Hitachi, Ibaraki 317-0077, Japan Department of Emergency and Critical Care Medicine, University Hospital The University of Tokyo Hospital, 7-3-1 Hongo Bunkyo Tokyo 113-8655, Japan Department of Emergency Medicine, JR General Hospital 2-1-3 Yoyogi, Shibuya-ku, Tokyo 151-8528, Japan
References [1] Cook Rachel J, Ashton Rendell W, Aughenbaugh Gregory L, Ryu Jay H. Septic pulmonary embolism: presenting features and clinical course of 14 patients. Chest 2005; 128:162–6. [2] Thabet Farah C, Alhejaili Abdurahman S, Alodayani Abdurahman N, Chehab May S. Septic pulmonary embolism secondary to Staphylococcus aureus septic thrombophlebitis in a pediatric patient. Saudi Med J 2013;34(10):1080–2. [3] Sano Tsuyoshi, Homma Sakae. Septic pulmonary emboli. Kokyu 2013;2(1): 58–61. [4] Ye Rui, Zhao Li, Wang Cuihong, Wu Xiaojie, Yan Hengyi. Clinical characteristics of septic pulmonary embolism in adults: a systematic review. Respir Med 2014;108: 1–8. [5] Surov A, Wienke A, Carter JM, Stoevesandt D, Behrmann C, Spielmann RP, et al. Intravascular embolization of venous catheter–causes, clinical signs, and management: a systematic review. JPEN J Parenter Enteral Nutr 2009; 33(6):677–85. [6] Dunn Ryan, Bares Sara, David Michael Z. Central venous catheter-related bacteremia caused by Kocuria kristinae: case report and review of the literature. Ann Clin Microbiol Antimicrob 2011;10:31–5. [7] Goswami Umesh, Brenes Jorge A, Punjabi Gopal V, LeClaire Michele M, Williams David N. Associations and outcomes of septic pulmonary embolism. Open Respir Med J 2014;8:28–33. [8] Conte JE, Golden Jeffrey A, Kipps Juliana, Zurlinden Elisabeth. Intrapulmonary pharmacokinetics of linezolid. Antimicrob Agents Chemother 2002;46(5): 1475–80. [9] George PA, Cha Raymond, Rybak Michael J. In vitro activities of quinupristindalfopristin and cefepime, alone and in combination with various antimicrobials, against multidrug-resistant Staphylococci and Enterococci in an in vitro pharmacodynamic model. Antimicrob Agents Chemother 2002;46(8):2606–12. [10] Tatsuro S, Hiroyuki N. Relation between blood-and tissue-levels of penicillin. J Antibiot B 1951;4(9):537–9. [11] Garcia-Roca P, Mancilla-Ramirez J, Santos-Segura A, Fernandez-Aviles M, CalderonJaimes E. Linezolid diminishes inflammatory cytokine production from human peripheral blood mononuclear cells. Arch Med Res 2006;37:31–5. [12] Lambers C, Burian B, Binder P, Ankersmit H-H, Wagner C, Muller M, et al. Early immunomodulatory effects of linezolid in a human whole blood endotoxin model. Int J Clin Pharmacol Ther 2010;48(7):419–24.
