Efficacy and Safety of N-Acetylcysteine Versus Alpha-Lipoic Acid in Colistin-Induced Nephrotoxicity
Summary
Healthcare- associated infections that caused by multi-drug-resistant Gram-negative bacteria (MDR G-ve) represent the most important problem that face the critically ill patients in the ICU. The available broad-spectrum antibiotics as penicillin, fluoroquinolones, aminoglycosides, and β-lactams fail to overcome these aggressive organisms. Accordingly, this led to the reconsideration of old drugs such as polymyxin B and polymyxin E (also known as colistin) that were previously considered to be too toxic for clinical use in the treatment of MDR G-ve bacteria. Colistin can be used as monotherapy or in combination with other antibiotics as high dose tigecycline, carbapenem or high-dose ampicillin/sulbactam. Colistin associated acute kidney injury (CA-AKI) is the frequently observed side effect in ICU patients treated with colistin that may lead to cessation of treatment. Accordingly, it is important to monitor renal functions prior to and during colistin treatment to detect the early signs of renal injury and minimize long term renal dysfunction. Inflammation with release of reactive oxygen species (ROS) can lead to renal tubular cells apoptosis. Several animal studies proved the beneficial effect of the concomitant use of antioxidants as N-acetylcysteine, alpha lipoic acid in preventing or attenuating colistin induced nephrotoxicity by their potent antioxidant effects Therefore, a clinical trial will be carried out to evaluate the efficacy and safety of N-acetylcysteine versus Alpha-lipoic acid in the prevention of colistin-induced nephrotoxicity in critically ill patients.
Timeline
- Start
- 2024-11-01
- Primary completion
- 2026-01-01
- Completion
- 2026-02-01
Publications
- Background Aslan AT, Akova M. The Role of Colistin in the Era of New beta-Lactam/beta-Lactamase Inhibitor Combinations. Antibiotics (Basel). 2022 Feb 20;11(2):277. doi: 10.3390/antibiotics11020277.
- Background Alshaya AI, Bin Saleh K, Aldhaeefi M, Baderldin HA, Alamody FO, Alhamdan QA, Almusallam MA, Alshaya O, Al Sulaiman K, Alshareef S, Alowais SA, Al Harbi SA, Alghamdi G. Colistin Loading Dose in Septic Patients with Gram Negative Infections. Infect Drug Resist. 2022 Apr 24;15:2159-2166. doi: 10.2147/IDR.S361244. eCollection 2022.
- Background Assimakopoulos SF, Karamouzos V, Lefkaditi A, Sklavou C, Kolonitsiou F, Christofidou M, Fligou F, Gogos C, Marangos M. Triple combination therapy with high-dose ampicillin/sulbactam, high-dose tigecycline and colistin in the treatment of ventilator-associated pneumonia caused by pan-drug resistant Acinetobacter baumannii: a case series study. Infez Med. 2019 Mar 1;27(1):11-16.
- Background Al-Abdulkarim DA, Alzuwayed OA, Al Ammari M, Al Halwan S, Al Maklafi N, Thomas A. Colistin-induced Nephrotoxicity in a Tertiary Teaching Hospital. Saudi J Kidney Dis Transpl. 2020 Sep-Oct;31(5):1057-1061. doi: 10.4103/1319-2442.301171.
- Background Badri S, Soltani R, Sayadi M, Khorvash F, Meidani M, Taheri S. Effect of N-acetylcysteine against Vancomycin-Induced Nephrotoxicity: A Randomized Controlled Clinical Trial. Arch Iran Med. 2020 Jun 1;23(6):397-402. doi: 10.34172/aim.2020.33.
- Background Bialvaei AZ, Samadi Kafil H. Colistin, mechanisms and prevalence of resistance. Curr Med Res Opin. 2015 Apr;31(4):707-21. doi: 10.1185/03007995.2015.1018989. Epub 2015 Mar 19.
- Background Briguori C, Colombo A, Violante A, Balestrieri P, Manganelli F, Paolo Elia P, Golia B, Lepore S, Riviezzo G, Scarpato P, Focaccio A, Librera M, Bonizzoni E, Ricciardelli B. Standard vs double dose of N-acetylcysteine to prevent contrast agent associated nephrotoxicity. Eur Heart J. 2004 Feb;25(3):206-11. doi: 10.1016/j.ehj.2003.11.016.
- Background Brown DL, Masselink AJ, Lalla CD. Functional range of creatinine clearance for renal drug dosing: a practical solution to the controversy of which weight to use in the Cockcroft-Gault equation. Ann Pharmacother. 2013 Jul-Aug;47(7-8):1039-44. doi: 10.1345/aph.1S176. Epub 2013 Jun 11.
- Background Cakir T, Polat C, Basturk A, Gul M, Aslaner A, Durgut H, Sehirli AO, Aykac A, Bahar L, Sabuncuoglu MZ. The effect of alpha lipoic acid on rat kidneys in methotrexate induced oxidative injury. Eur Rev Med Pharmacol Sci. 2015;19(11):2132-9.
- Background Cakirlar FK, Ciftci IH, Gonullu N. OXA-type Carbapenemases and Susceptibility of Colistin and Tigecycline Among Carbapenem-Resistant Acinetobacter Baumannii Isolates from Patients with Bacteremia in Turkey. Clin Lab. 2015;61(7):741-7. doi: 10.7754/clin.lab.2014.141116.
- Background Ceylan B, Ozansoy M, Kilic U, Yozgat Y, Ercan C, Yildiz P, Aslan T. N-acetylcysteine suppresses colistimethate sodium-induced nephrotoxicity via activation of SOD2, eNOS, and MMP3 protein expressions. Ren Fail. 2018 Nov;40(1):423-434. doi: 10.1080/0886022X.2018.1489286.
- Background Chien HT, Lin YC, Sheu CC, Hsieh KP, Chang JS. Is colistin-associated acute kidney injury clinically important in adults? A systematic review and meta-analysis. Int J Antimicrob Agents. 2020 Mar;55(3):105889. doi: 10.1016/j.ijantimicag.2020.105889. Epub 2020 Jan 8.
- Background Dai C, Tang S, Velkov T, Xiao X. Colistin-Induced Apoptosis of Neuroblastoma-2a Cells Involves the Generation of Reactive Oxygen Species, Mitochondrial Dysfunction, and Autophagy. Mol Neurobiol. 2016 Sep;53(7):4685-700. doi: 10.1007/s12035-015-9396-7. Epub 2015 Aug 28.
- Background Dalfino L, Puntillo F, Mosca A, Monno R, Spada ML, Coppolecchia S, Miragliotta G, Bruno F, Brienza N. High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? A preliminary study. Clin Infect Dis. 2012 Jun;54(12):1720-6. doi: 10.1093/cid/cis286. Epub 2012 Mar 15.
- Background Eljaaly K, Bidell MR, Gandhi RG, Alshehri S, Enani MA, Al-Jedai A, Lee TC. Colistin Nephrotoxicity: Meta-Analysis of Randomized Controlled Trials. Open Forum Infect Dis. 2021 Jan 21;8(2):ofab026. doi: 10.1093/ofid/ofab026. eCollection 2021 Feb.
- Background El-Sayed Ahmed MAE, Zhong LL, Shen C, Yang Y, Doi Y, Tian GB. Colistin and its role in the Era of antibiotic resistance: an extended review (2000-2019). Emerg Microbes Infect. 2020 Dec;9(1):868-885. doi: 10.1080/22221751.2020.1754133.
- Background Epperson LC, Weiss ST, Cao DJ. A Case Report of a Severe, Unusually Delayed Anaphylactoid Reaction to Intravenous N-Acetylcysteine During Treatment of Acute Acetaminophen Toxicity in an Adolescent. J Med Toxicol. 2021 Jan;17(1):75-79. doi: 10.1007/s13181-020-00804-5. Epub 2020 Aug 21.
- Background Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.
- Background Gai Z, Samodelov SL, Kullak-Ublick GA, Visentin M. Molecular Mechanisms of Colistin-Induced Nephrotoxicity. Molecules. 2019 Feb 12;24(3):653. doi: 10.3390/molecules24030653.
- Background Garnacho-Montero J, Amaya-Villar R, Ferrandiz-Millon C, Diaz-Martin A, Lopez-Sanchez JM, Gutierrez-Pizarraya A. Optimum treatment strategies for carbapenem-resistant Acinetobacter baumannii bacteremia. Expert Rev Anti Infect Ther. 2015 Jun;13(6):769-77. doi: 10.1586/14787210.2015.1032254. Epub 2015 Apr 12.
- Background Giamarellou H, Poulakou G. Multidrug-resistant Gram-negative infections: what are the treatment options? Drugs. 2009 Oct 1;69(14):1879-901. doi: 10.2165/11315690-000000000-00000.
- Background Gunay E, Kaya S, Baysal B, Yuksel E, Arac E. Evaluation of prognosis and nephrotoxicity in patients treated with colistin in intensive care unit. Ren Fail. 2020 Nov;42(1):704-709. doi: 10.1080/0886022X.2020.1795878.
- Background Gupta S, Portales-Castillo I, Daher A, Kitchlu A. Conventional Chemotherapy Nephrotoxicity. Adv Chronic Kidney Dis. 2021 Sep;28(5):402-414.e1. doi: 10.1053/j.ackd.2021.08.001.
- Background Gyuraszova M, Gurecka R, Babickova J, Tothova L. Oxidative Stress in the Pathophysiology of Kidney Disease: Implications for Noninvasive Monitoring and Identification of Biomarkers. Oxid Med Cell Longev. 2020 Jan 23;2020:5478708. doi: 10.1155/2020/5478708. eCollection 2020.
- Background Heil EL, Bork JT, Abbo LM, Barlam TF, Cosgrove SE, Davis A, Ha DR, Jenkins TC, Kaye KS, Lewis JS 2nd, Ortwine JK, Pogue JM, Spivak ES, Stevens MP, Vaezi L, Tamma PD. Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process. Open Forum Infect Dis. 2021 Oct 11;8(10):ofab434. doi: 10.1093/ofid/ofab434. eCollection 2021 Oct.
- Background Hu Q, Chen J, Sun S, Deng S. Mortality-Related Risk Factors and Novel Antimicrobial Regimens for Carbapenem-Resistant Enterobacteriaceae Infections: A Systematic Review. Infect Drug Resist. 2022 Nov 28;15:6907-6926. doi: 10.2147/IDR.S390635. eCollection 2022.
- Background Ibrahim ME. Prevalence of Acinetobacter baumannii in Saudi Arabia: risk factors, antimicrobial resistance patterns and mechanisms of carbapenem resistance. Ann Clin Microbiol Antimicrob. 2019 Jan 3;18(1):1. doi: 10.1186/s12941-018-0301-x.
- Background Inchai J, Liwsrisakun C, Theerakittikul T, Chaiwarith R, Khositsakulchai W, Pothirat C. Risk factors of multidrug-resistant, extensively drug-resistant and pandrug-resistant Acinetobacter baumannii ventilator-associated pneumonia in a Medical Intensive Care Unit of University Hospital in Thailand. J Infect Chemother. 2015 Aug;21(8):570-4. doi: 10.1016/j.jiac.2015.04.010. Epub 2015 May 7.
- Background Jafari F, Elyasi S. Prevention of colistin induced nephrotoxicity: a review of preclinical and clinical data. Expert Rev Clin Pharmacol. 2021 Sep;14(9):1113-1131. doi: 10.1080/17512433.2021.1933436. Epub 2021 Jun 9.
- Background Jin J, Zhu J, Zhu Z, Kim WY, O'Rourke J, Lin Z, Chen M. Clinical efficacy and nephrotoxicity of intravenous colistin sulfate in the treatment of carbapenem-resistant gram-negative bacterial infections: a retrospective cohort study. Ann Transl Med. 2022 Oct;10(20):1137. doi: 10.21037/atm-22-4959.
- Background Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratala J, El Solh AA, Ewig S, Fey PD, File TM Jr, Restrepo MI, Roberts JA, Waterer GW, Cruse P, Knight SL, Brozek JL. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63(5):e61-e111. doi: 10.1093/cid/ciw353. Epub 2016 Jul 14.
- Background Kengkla K, Kongpakwattana K, Saokaew S, Apisarnthanarak A, Chaiyakunapruk N. Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis. J Antimicrob Chemother. 2018 Jan 1;73(1):22-32. doi: 10.1093/jac/dkx368.
- Background Kilic I, Ayar Y, Ceylan I, Kaya PK, Caliskan G. Nephrotoxicity caused by colistin use in ICU: a single centre experience. BMC Nephrol. 2023 Oct 13;24(1):302. doi: 10.1186/s12882-023-03334-8.
- Background Larki RA, Jamali B, Meidani M, Mousavi S. Serum Cystatin C for Evaluation of Acute Kidney Injury in Adults Treated with Colistin. J Res Pharm Pract. 2018 Oct-Dec;7(4):178-181. doi: 10.4103/jrpp.JRPP_18_53.
- Background Lee YM, Bae SY, Won NH, Pyo HJ, Kwon YJ. Alpha-lipoic acid attenuates cisplatin-induced tubulointerstitial injuries through inhibition of mitochondrial bax translocation in rats. Nephron Exp Nephrol. 2009;113(4):e104-12. doi: 10.1159/000235754. Epub 2009 Aug 27.
- Background Levey AS, Perrone RD, Madias NE. Serum creatinine and renal function. Annu Rev Med. 1988;39:465-90. doi: 10.1146/annurev.me.39.020188.002341.
- Background Liang CA, Lin YC, Lu PL, Chen HC, Chang HL, Sheu CC. Antibiotic strategies and clinical outcomes in critically ill patients with pneumonia caused by carbapenem-resistant Acinetobacter baumannii. Clin Microbiol Infect. 2018 Aug;24(8):908.e1-908.e7. doi: 10.1016/j.cmi.2017.10.033. Epub 2017 Nov 3.
- Background Liu J, Shu Y, Zhu F, Feng B, Zhang Z, Liu L, Wang G. Comparative efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for multiple drug-resistant and extensively drug-resistant Acinetobacter baumannii infections: A systematic review and network meta-analysis. J Glob Antimicrob Resist. 2021 Mar;24:136-147. doi: 10.1016/j.jgar.2020.08.021. Epub 2020 Sep 2.
- Background Mazuski JE, Tessier JM, May AK, Sawyer RG, Nadler EP, Rosengart MR, Chang PK, O'Neill PJ, Mollen KP, Huston JM, Diaz JJ Jr, Prince JM. The Surgical Infection Society Revised Guidelines on the Management of Intra-Abdominal Infection. Surg Infect (Larchmt). 2017 Jan;18(1):1-76. doi: 10.1089/sur.2016.261.
- Background Mirjalili M, Mirzaei E, Vazin A. Pharmacological agents for the prevention of colistin-induced nephrotoxicity. Eur J Med Res. 2022 May 7;27(1):64. doi: 10.1186/s40001-022-00689-w.
- Background Modi K, Padala SA, Gupta M. Contrast-Induced Nephropathy. 2025 Jan 4. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK448066/
- Background Morgan A, Galal MK, Ogaly HA, Ibrahim MA, Abd-Elsalam RM, Noshy P. Tiron ameliorates oxidative stress and inflammation in titanium dioxide nanoparticles induced nephrotoxicity of male rats. Biomed Pharmacother. 2017 Sep;93:779-787. doi: 10.1016/j.biopha.2017.07.006. Epub 2017 Jul 12.
- Background Mosayebi S, Soltani R, Shafiee F, Assarzadeh S, Hakamifard A. Evaluation of the Effectiveness of N-Acetylcysteine in the Prevention of Colistin-Induced Nephrotoxicity: A Randomized Controlled Clinical Trial. J Res Pharm Pract. 2022 May 25;10(4):159-165. doi: 10.4103/jrpp.jrpp_90_21. eCollection 2021 Oct-Dec.
- Background Nang SC, Azad MAK, Velkov T, Zhou QT, Li J. Rescuing the Last-Line Polymyxins: Achievements and Challenges. Pharmacol Rev. 2021 Apr;73(2):679-728. doi: 10.1124/pharmrev.120.000020.
- Background Nation RL, Garonzik SM, Li J, Thamlikitkul V, Giamarellos-Bourboulis EJ, Paterson DL, Turnidge JD, Forrest A, Silveira FP. Updated US and European Dose Recommendations for Intravenous Colistin: How Do They Perform? Clin Infect Dis. 2016 Mar 1;62(5):552-558. doi: 10.1093/cid/civ964. Epub 2015 Nov 25.
- Background Nation RL, Garonzik SM, Thamlikitkul V, Giamarellos-Bourboulis EJ, Forrest A, Paterson DL, Li J, Silveira FP. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis. 2017 Mar 1;64(5):565-571. doi: 10.1093/cid/ciw839. Epub 2016 Dec 23.
- Background Nguyen H, Pellegrini MV, Gupta V. Alpha-Lipoic Acid. 2024 Jan 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK564301/
- Background Oktan MA, Heybeli C, Ural C, Kocak A, Bilici G, Cavdar Z, Ozbal S, Arslan S, Yilmaz O, Cavdar C. Alpha-lipoic acid alleviates colistin nephrotoxicity in rats. Hum Exp Toxicol. 2021 May;40(5):761-771. doi: 10.1177/0960327120966043. Epub 2020 Oct 28.
- Background Ordooei Javan A, Shokouhi S, Sahraei Z. A review on colistin nephrotoxicity. Eur J Clin Pharmacol. 2015 Jul;71(7):801-10. doi: 10.1007/s00228-015-1865-4. Epub 2015 May 27.
- Background Ozkan G, Ulusoy S, Orem A, Alkanat M, Mungan S, Yulug E, Yucesan FB. How does colistin-induced nephropathy develop and can it be treated? Antimicrob Agents Chemother. 2013 Aug;57(8):3463-9. doi: 10.1128/AAC.00343-13. Epub 2013 Apr 29.
- Background Ozyilmaz E, Ebinc FA, Derici U, Gulbahar O, Goktas G, Elmas C, Oguzulgen IK, Sindel S. Could nephrotoxicity due to colistin be ameliorated with the use of N-acetylcysteine? Intensive Care Med. 2011 Jan;37(1):141-6. doi: 10.1007/s00134-010-2038-7. Epub 2010 Sep 16.
- Background Plachouras D, Karvanen M, Friberg LE, Papadomichelakis E, Antoniadou A, Tsangaris I, Karaiskos I, Poulakou G, Kontopidou F, Armaganidis A, Cars O, Giamarellou H. Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria. Antimicrob Agents Chemother. 2009 Aug;53(8):3430-6. doi: 10.1128/AAC.01361-08. Epub 2009 May 11.
- Background Prasannan BK, Mukthar FC, Unni VN, Mohan S, Vinodkumar K. Colistin Nephrotoxicity-Age and Baseline kidney Functions Hold the Key. Indian J Nephrol. 2021 Sep-Oct;31(5):449-453. doi: 10.4103/ijn.IJN_130_20. Epub 2021 Sep 21.
- Background Rabi R, Enaya A, Sweileh MW, Aiesh BM, Namrouti A, Hamdan ZI, Abugaber D, Nazzal Z. Comprehensive Assessment of Colistin Induced Nephrotoxicity: Incidence, Risk Factors and Time Course. Infect Drug Resist. 2023 May 15;16:3007-3017. doi: 10.2147/IDR.S409964. eCollection 2023.
- Background Rigatto MH, Falci DR, Zavascki AP. Clinical Use of Polymyxin B. Adv Exp Med Biol. 2019;1145:197-218. doi: 10.1007/978-3-030-16373-0_14.
- Background Sant B, Rao PV, Nagar DP, Pant SC, Bhasker AS. Evaluation of abrin induced nephrotoxicity by using novel renal injury markers. Toxicon. 2017 Jun 1;131:20-28. doi: 10.1016/j.toxicon.2017.03.007. Epub 2017 Mar 10.
- Background Somani SM, Husain K, Whitworth C, Trammell GL, Malafa M, Rybak LP. Dose-dependent protection by lipoic acid against cisplatin-induced nephrotoxicity in rats: antioxidant defense system. Pharmacol Toxicol. 2000 May;86(5):234-41. doi: 10.1034/j.1600-0773.2000.d01-41.x.
- Background Tsuji BT, Pogue JM, Zavascki AP, Paul M, Daikos GL, Forrest A, Giacobbe DR, Viscoli C, Giamarellou H, Karaiskos I, Kaye D, Mouton JW, Tam VH, Thamlikitkul V, Wunderink RG, Li J, Nation RL, Kaye KS. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019 Jan;39(1):10-39. doi: 10.1002/phar.2209.
- Background Tumbarello M, Losito AR, Giamarellou H. Optimizing therapy in carbapenem-resistant Enterobacteriaceae infections. Curr Opin Infect Dis. 2018 Dec;31(6):566-577. doi: 10.1097/QCO.0000000000000493.
- Background Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, Whitley RJ. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004 Nov 1;39(9):1267-84. doi: 10.1086/425368. Epub 2004 Oct 6. No abstract available.
- Background Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Scheld WM, van de Beek D, Bleck TP, Garton HJL, Zunt JR. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis. 2017 Mar 15;64(6):e34-e65. doi: 10.1093/cid/ciw861.
- Background Tylicki L, Rutkowski B, Horl WH. Antioxidants: a possible role in kidney protection. Kidney Blood Press Res. 2003;26(5-6):303-14. doi: 10.1159/000073936.
- Background Wang SH, Yang KY, Sheu CC, Chen WC, Chan MC, Feng JY, Chen CM, Wu BR, Zheng ZR, Chou YC, Peng CK; T.-CARE (Taiwan Critical Care, Infection) Group. The necessity of a loading dose when prescribing intravenous colistin in critically ill patients with CRGNB-associated pneumonia: a multi-center observational study. Crit Care. 2022 Apr 4;26(1):91. doi: 10.1186/s13054-022-03947-9.
- Background Winter MA, Guhr KN, Berg GM. Impact of various body weights and serum creatinine concentrations on the bias and accuracy of the Cockcroft-Gault equation. Pharmacotherapy. 2012 Jul;32(7):604-12. doi: 10.1002/j.1875-9114.2012.01098.x. Epub 2012 May 10.
- Background Yahav D, Franceschini E, Koppel F, Turjeman A, Babich T, Bitterman R, Neuberger A, Ghanem-Zoubi N, Santoro A, Eliakim-Raz N, Pertzov B, Steinmetz T, Stern A, Dickstein Y, Maroun E, Zayyad H, Bishara J, Alon D, Edel Y, Goldberg E, Venturelli C, Mussini C, Leibovici L, Paul M; Bacteremia Duration Study Group. Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial. Clin Infect Dis. 2019 Sep 13;69(7):1091-1098. doi: 10.1093/cid/ciy1054.
- Background Yahav D, Giske CG, Gramatniece A, Abodakpi H, Tam VH, Leibovici L. New beta-Lactam-beta-Lactamase Inhibitor Combinations. Clin Microbiol Rev. 2020 Nov 11;34(1):e00115-20. doi: 10.1128/CMR.00115-20. Print 2020 Dec 16.
- Background Yousef JM, Chen G, Hill PA, Nation RL, Li J. Ascorbic acid protects against the nephrotoxicity and apoptosis caused by colistin and affects its pharmacokinetics. J Antimicrob Chemother. 2012 Feb;67(2):452-9. doi: 10.1093/jac/dkr483. Epub 2011 Nov 28.
- Background Yu SN, Kim T, Park SY, Lee YM, Park KH, Lee EJ, Jeon MH, Choo EJ, Kim TH, Lee MS, Park SY. Predictors of Acute Kidney Injury and 28-Day Mortality in Carbapenem-Resistant Acinetobacter baumannii Complex Bacteremia. Microb Drug Resist. 2021 Aug;27(8):1029-1036. doi: 10.1089/mdr.2020.0312. Epub 2021 Mar 3.
- Background Zhang J, McCullough PA. Lipoic Acid in the Prevention of Acute Kidney Injury. Nephron. 2016;134(3):133-140. doi: 10.1159/000448666. Epub 2016 Sep 8.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | N-acetylcysteine | Small molecule | 1200 mg | Other |
| Subject | alpha-lipoic acid | Small molecule | 600 mg | Other |
| Background | Colistin | Other / unclassified | 150 mg | Intravenous |
| Background | Colistin | Other / unclassified | 180 mg | Intravenous |