Article, Emergency Medicine

Linezolid is a novel and effective treatment for septic pulmonary embolism

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American Journal of Emergency Medicine

journal homepage: www. elsevier. com/ locate/ajem

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 ug/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 trans- fer 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, respirato- ry 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 thrombo- plastin 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.

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; HCO, 13.8 mmol/L; lactate, 5.4 mmol/L). Furthermore, thoracic computed tomog- raphy revealed scattered minor nodules in the lung, although there was no focal infection or abscess that involved the left shoulder. There- fore, 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 in- creased (Figure), which suggested an SPE. Based on this finding, the an- tibiotic 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 ug/mL (penicillinase nonproducing); therefore, the doripenem and linezolid regimen was deescalated to intravenous peni- cillin G (6000000 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.

3

To our knowledge, this is the first report regarding linezolid treat- ment of SPE. Among previous reports of SPE, MSSA was the most com- mon 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 trans- fer 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 (20000 U/kg) in rabbits was ap- proximately 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 com-

pared with ?-lactam antibiotics, as it blocks the initial step of Protein Synthesis (the formation of the 70S complex during translation initia- tion), 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,

0735-6757/(C) 2014

Image of Figure

Figure. Chest computed tomography demonstrates multiple nodules in both lungs.

such as interleukin 1?, interleukin 6, and tumor necrosis factor ?, 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. There- fore, 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

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

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