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Intravenous L-alanyl-L-glutamine: an adjuvant in the management of immunocompromised patients with invasive fungal rhinosinusitis




Invasive fungal rhinosinusitis is a potentially fatal infection in immunocompromised patients. Glutamine, a conditionally essential amino acid, is an energy source for rapidly dividing cells, particularly those of the immune system. This randomized, double-blind, placebo-controlled, two-group parallel study was designed to investigate intravenous l-alanyl-l-glutamine as an immune adjuvant in the management of patients with invasive fungal rhinosinusitis.

Patients and methods

Fourteen patients with invasive fungal rhinosinusitis undergoing endoscopic debridement and with postoperative admission to the ICU were included in this study. Group D (n = 7) received the standard protocol therapy and l-alanyl-l-glutamine 0.5 mg/kg/day infusion postoperatively for 10 days; group C (n = 7) received only the standard protocol therapy with the same volume and rate of saline postoperatively for 10 days as well. The primary outcome measure was patient response, either cure or persistence, whereas secondary outcome included length of ICU stay, ICU survival, hospital survival, and complications.


In group D there was significant improvement in response rate as all five patients who survived in group D had a complete cure (100%), whereas in group C among the three patients who survived only one (33%) patient was completely cured. There was significant decrease in length of ICU stay (P = 0.003) and incidence of complications (P = 0.03) in group D compared with group C. The incidence of intracranial extension, renal impairment, and septic shock as well as ICU and hospital survival, was decreased in group D compared with group C but did not reach statistical significance.


Intravenous l-alanyl-l-glutamine 0.5 mg/kg/day infusion postoperatively for 10 days in patients with invasive fungal rhinosinusitis undergoing endoscopic debridement resulted in a better response accompanied with a decrease in ICU length of stay and complication rate.


  1. Chopra H, Kapil D, Neha C, Sanjeev P, Vikrant M. Invasive fungal rhinosinusitis: our experience. Clin Rhinol 2009; 2: 21–25.

    Article  Google Scholar 

  2. Valera FC, do Lago T, Tamashiro E, Yassuda CC, Silveira F, Anselmo-Lima WT. Prognosis of acute invasive fungal rhinosinusitis related to underlying disease. Int J Infect Dis 2011; 15: e841–e844.

    Article  Google Scholar 

  3. Diamond RD, Haudenschild CC, Erickson NF III. Monocyte-mediated damage to Rhizopus oryzae hyphae in vitro. Infect Immun 1982; 38: 292–297.

    Article  CAS  Google Scholar 

  4. Waldorf AR. Pulmonary defense mechanisms against opportunistic fungal pathogens. Immunol Ser 1989; 47: 243–271.

    CAS  PubMed  Google Scholar 

  5. Waldorf AR, Ruderman N, Diamond RD. Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus. J Clin Invest 1984; 74: 150–160.

    Article  CAS  Google Scholar 

  6. Canadian clinical practice guidelines: updated recommendations. Available at: [Last accessed on 2014 Oct 21].

  7. Santora R, Kozar RA. Molecular mechanisms of pharmaconutrients. J Surg Res 2010; 161: 288–294.

    Article  CAS  Google Scholar 

  8. Mizock BA. Immunonutrition and critical illness: an update. Nutrition 2010; 26: 701–707.

    Article  CAS  Google Scholar 

  9. Windle EM. Glutamine supplementation in critical illness: evidence, recommendations, and implications for clinical practice in burn care. J Burn Care Res 2006; 27: 764–772.

    Article  Google Scholar 

  10. Marik PE, Zaloga GP. Immunonutrition in high-risk surgical patients: a systematic review and analysis of the literature. JPEN J Parenter Enteral Nutr 2010; 34: 378–386.

    Article  Google Scholar 

  11. Bone RC, Balk RA, Cerra FB, et al. ACCP/SCCM Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20: 964–974.

    Google Scholar 

  12. Moghadami M, Ruzbahani H, Badiee P, Faramarzi A, Peymani P, Lankarani K. Invasive fungal sinusitis in immunocompromised patients: a multicenter, university hospital experience in Shiraz. Adv Infect Dis 2013; 3: 263–268.

    Article  Google Scholar 

  13. Li Y, Li Y, Li P, Zhang G. Diagnosis and endoscopic surgery of chronic invasive fungal rhinosinusitis. Am J Rhinol Allergy 2009; 23: 622–625.

    Article  Google Scholar 

  14. Ingley AP, Parikh SL, DelGaudio JM. Orbital and cranial nerve presentations and sequelae are hallmarks of invasive fungal sinusitis caused by Mucor in contrast to Aspergillus. Am J Rhinol 2008; 22: 155–158.

    Article  Google Scholar 

  15. Wilhelm J, Hettwer S, Hammer D, Schürmann M, Amoury M, Ebelt H, Werdan K. Scoring patients with a suspected infection in the emergency department (ED): comparison of the ED-specific MEDS score with APACHE II and SOFA score. Crit Care 2010; 14: P251.

    Article  Google Scholar 

  16. Forte DN, Ranzani OT, Stape N, Taniguchi LU, Toledo-Maciel A, Park M. APACHE II and SOFA scores for intensive care and hospital outcome prediction in oncologic patients. Crit Care 2007; 11: 1.

    Google Scholar 

  17. Gillespie MB, O’Malley BW Jr, Francis HW. An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host. Arch Otolaryngol Head Neck Surg 1998; 124: 520–526.

    Article  CAS  Google Scholar 

  18. Stehle P, Zander J, Mertes N, Albers S, Puchstein C, Lawin P, Fürst P. Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet 1989; 1: 231–233.

    Article  CAS  Google Scholar 

  19. Ziegler TR, Young LS, Benfell K, et al. Clinical and metabolic efficacy of glutamine supplemented parenteral nutrition after bone marrow transplantation: a randomized, double-blind, controlled study. Ann Intern Med 1992; 116: 821–828.

    Article  CAS  Google Scholar 

  20. Mertes N, Schulzki C, Goeters C, Winde G, Benzing S, Kuhn KS, et al. Cost containment through l-alanyl-l-glutamine supplemented total parenteral nutrition after major abdominal surgery: a prospective randomized double-blind controlled study. Clin Nutr 2000; 19: 395–401.

    Article  CAS  Google Scholar 

  21. Karwowska KA, Dworacki G, Trybus M, Zeromski J, Szulc R. Influence of glutamine-enriched parenteral nutrition on nitrogen balance and immunologic status in patients undergoing elective aortic aneurysm repair. Nutrition 2001; 17: 475–478.

    Article  CAS  Google Scholar 

  22. Exner R, Tamandl D, Goetzinger P, et al. Perioperative GLY-GLN infusion diminishes the surgery-induced period of immunosuppression: accelerated restoration of the lipopolysaccharide estimulated tumor necrosis factor-alpha response. Ann Surg 2003; 237: 110–115.

    Article  Google Scholar 

  23. Wischmeyer PE, Lynch J, Liedel J, Wolfson R, Riehm J, Gottlieb L, Kahana M. Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med 2001; 29: 2075–2080.

    Article  CAS  Google Scholar 

  24. Griffiths RD, Allen KD, Andrews FJ, Jones C. Infection, multiple organ failure, and survival in the intensive care unit: influence of glutamine-supplemented parenteral nutrition on acquired infection. Nutrition 2002; 18: 546–552.

    Article  CAS  Google Scholar 

  25. Déchelotte P, Hasselmann M, Cynober L, Allaouchiche B, Coëffier M, Hecketsweiler B, et al. l-alanyl-l-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study. Crit Care Med 2006; 34: 598–604.

    Article  Google Scholar 

  26. Goeters C, Wenn A, Mertes N, Wempe C, Van Aken H, Stehle P, Bone HG. Parenteral l-alanyl-l-glutamine improves 6-month outcome in critically ill patients. Crit Care Med 2002; 30: 2032–2037.

    Article  CAS  Google Scholar 

  27. Novak F, Heyland DK, Avenell A, Drover JW, Su X. Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med 2002; 30: 2022–2029.

    Article  CAS  Google Scholar 

  28. Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B. Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev 2003; 29: 501–513.

    Article  CAS  Google Scholar 

  29. Allen K, Griffiths RD, Jones C. Reduced fungal infection in critically ill patients randomized to a glutamine containing parenteral nutrition. Br J Anaesth 2000; 84: 690–691.

    Article  Google Scholar 

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Correspondence to Mohamed M. Elsharnouby MD.

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Elsharnouby, N.M., Elsharnouby, M.M., Elewa, G. et al. Intravenous L-alanyl-L-glutamine: an adjuvant in the management of immunocompromised patients with invasive fungal rhinosinusitis. Egypt J Otolaryngol 32, 1–6 (2016).

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