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Electrolyte and Acid-Base Disorders Triggered by Aminoglycoside Or Colistin Therapy: a Systematic Review

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antibiotics Review Electrolyte and Acid-Base Disorders Triggered by Aminoglycoside or Colistin Therapy: A Systematic Review Martin Scoglio 1,* , Gabriel Bronz 1, Pietro O. Rinoldi 1,2, Pietro B. Faré 3,Céline Betti 1,2, Mario G. Bianchetti 1, Giacomo D. Simonetti 1,2, Viola Gennaro 1, Samuele Renzi 4, Sebastiano A. G. Lava 5 and Gregorio P. Milani 2,6,7 1 Faculty of Biomedicine, Università della Svizzera Italiana, 6900 Lugano, Switzerland; [email protected] (G.B.); [email protected] (P.O.R.); [email protected] (C.B.); [email protected] (M.G.B.); [email protected] (G.D.S.); [email protected] (V.G.) 2 Department of Pediatrics, Pediatric Institute of Southern Switzerland, Ospedale San Giovanni, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland; [email protected] 3 Department of Internal Medicine, Ospedale La Carità, Ente Ospedaliero Cantonale, 6600 Locarno, Switzerland; [email protected] 4 Division of Hematology and Oncology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; [email protected] 5 Pediatric Cardiology Unit, Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, and University of Lausanne, 1011 Lausanne, Switzerland; [email protected] 6 Pediatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy 7 Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy * Correspondence: [email protected] Citation: Scoglio, M.; Bronz, G.; Abstract: Aminoglycoside or colistin therapy may alter the renal tubular function without decreasing Rinoldi, P.O.; Faré, P.B.; Betti, C.; the glomerular filtration rate. This association has never been extensively investigated. We conducted Bianchetti, M.G.; Simonetti, G.D.; a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews Gennaro, V.; Renzi, S.; Lava, S.A.G.; and Meta-Analyses recommendations. Databases searched included United States National Library et al. Electrolyte and Acid-Base of Medicine, Excerpta Medica, and Web of Science. For the final analysis, we evaluated 46 reports, Disorders Triggered by published after 1960, describing 82 cases. A total of 286 electrolyte and acid-base disorders were Aminoglycoside or Colistin Therapy: reported. Hypomagnesemia, hypokalemia, and hypocalcemia were reported in more than three A Systematic Review. Antibiotics 2021, 10, 140. https://doi.org/10.3390/ quarter of cases. Further disorders were, in decreasing order of frequency, metabolic alkalosis, antibiotics10020140 hyponatremia, hypophosphatemia, hypouricemia, hypernatremia, and metabolic acidosis. Six electrolyte and acid-base disorders were reported in seven cases, five in 12 cases, four in 16 cases, Academic Editors: three in 31 cases, two in 11 cases, and one in five cases. Laboratory features consistent with a loop Patricia Agudelo-Romero and of Henle/distal tubular dysfunction were noted in 56 (68%), with a proximal tubular dysfunction Jose Caparros-Martin in three (3.7%), and with a mixed dysfunction in five (6.1%) cases. The laboratory abnormality was Received: 30 December 2020 unclassified in the remaining 18 (22%) cases. Treatment with aminoglycosides or colistin may trigger Accepted: 27 January 2021 a proximal tubular or, more frequently, a loop of Henle/distal tubular dysfunction. Published: 1 February 2021 Keywords: dyselectrolytemia; aminoglycosides; colistin; hypomagnesemia; hypokalemia; hypocalcemia Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. 1. Introduction Parenteral aminoglycoside antimicrobials are often prescribed for the treatment of infections caused by mycobacteria, Neisseria gonorrhoeae, and protozoa [1,2]. However, the most common application of these antimicrobials is for infections caused by aerobic Copyright: © 2021 by the authors. Gram-negative bacteria [1]. Since many patients affected by cystic fibrosis have chronic Licensee MDPI, Basel, Switzerland. pulmonary infection with Pseudomonas aeruginosa, many cystic fibrosis patients receive This article is an open access article frequent and prolonged courses of these antimicrobials [2]. distributed under the terms and ≥ conditions of the Creative Commons A mild renal impairment that is almost always reversible occurs in 10% of subjects re- Attribution (CC BY) license (https:// ceiving an aminoglycoside for a prolonged period [1]. On the other hand, the glycopeptide creativecommons.org/licenses/by/ antibiotic colistin, which is used parenterally for infections caused by multi-drug resistant 4.0/). Gram-negative bacteria, possesses a nephrotoxicity similar to that of aminoglycosides [3]. Antibiotics 2021, 10, 140. https://doi.org/10.3390/antibiotics10020140 https://www.mdpi.com/journal/antibiotics Antibiotics 2021, 10, x FOR PEER REVIEW 2 of 9 A mild renal impairment that is almost always reversible occurs in ≥10% of subjects receiving an aminoglycoside for a prolonged period [1]. On the other hand, the glycopep- tide antibiotic colistin, which is used parenterally for infections caused by multi-drug re- Antibiotics 2021, 10, 140 2 of 9 sistant Gram-negative bacteria, possesses a nephrotoxicity similar to that of aminoglyco- sides [3]. It has been known for about 70 years that aminoglycoside therapy may sporadically alter theIt renal has been tubular known function for about without 70 years decreasing that aminoglycoside the glomerular therapy filtration may rate sporadically [4]. Since thisalter association the renal has tubular never function been extensively without decreasing investigated, the glomerular we performed filtration a systematic rate [4]. Sincere- viewthis of association the published has never literature. been extensivelyThe purpose investigated, of this review we is performed to document a systematic the pattern review of electrolyteof the published and acid-base literature. disorder The and purpose the time of of this resolution review isfollowing to document aminoglycoside the pattern or of colistinelectrolyte therapy. and acid-base disorder and the time of resolution following aminoglycoside or colistin therapy. 2. Results 2. Results 2.1. Search Results—Completeness of Reporting 2.1. Search Results—Completeness of Reporting The literature search process is summarized in Figure 1. For the final analysis, we The literature search process is summarized in Figure1. For the final analysis, we evaluated 46 reports [5–50] published between 1961 and 2020 in English (N = 45) and evaluated 46 reports [5–50] published between 1961 and 2020 in English (N = 45) and Spanish (N = 1). They had been reported from the following countries: United States of Spanish (N = 1). They had been reported from the following countries: United States of AmericaAmerica (N (N = 12), = 12), India India (N (N = 8), = 8), United United Kingdo Kingdomm (N (N = 7), = 7), Turkey Turkey (N (N = 4), = 4), Ireland Ireland (N (N = 3), = 3), Greece,Greece, Israel, Israel, Taiwan Taiwan (N (N = =2), 2), Australia, Australia, Be Belgium,lgium, Canada, Canada, Croatia, Croatia, Paraguay, Paraguay, and and Spain Spain (N(N = 1). = 1). A total A total of of82 82cases cases were were identified identified am amongong the the articles articles reviewed, reviewed, including including 15 15 cystic cystic fibrosisfibrosis patients patients (nine (nine females females and and six six males males 15 15 toto 30 30 years years of ofage). age). Reporting Reporting completeness completeness waswas high high in in31 31 (38%), (38%), moderate moderate in in 37 37 (45%), (45%), and and low low in in the the remaining remaining 14 14 (17%) (17%) cases. cases. Records identified Records identified Records identified throughsearchin the through search in the through search in National Library Excerpta Medica the Web of Science Database Database Database (N = 651 ) (N = 3234 ) (N = 219 ) Records screened after duplicates removed (N = 3871) Records excluded (N = 3746) - No original articles (N = 2423) - Not including humans (N = 902) - Abstracts (N = 223) - Not pertaining (N = 198) Full-text assessed in detail for eligibility (N = 125) Records excluded (N = 81) - No orginal cases (N = 41) - Not pertaining (N = 20) - Animal studies (N = 7) - With kidney injury (N = 13) Secondary references (N = 1) Personal files (N = 1) Full-text articles included (N = 46) Figure 1. Flowchart of the literature search process. Figure2.2. Findings1. Flowchart of the literature search process. The baseline characteristics of the patients are listed in Table1. Fifty-eight (71%) patients were ≥20 years of age, 19 (23%) were 3 to 19 years of age, three (3.7%) were 4 weeks to 2 years of age, and two (2.4%) < 4 weeks of age. Approximately half of the cases were non-tuberculous or tuberculous respiratory infections. The other common infections included abdominal, urinary, and drug-induced neutropenia; Aminoglycosides Antibiotics 2021, 10, x FOR PEER REVIEW 3 of 9 Antibiotics 2021, 10, x FOR PEER REVIEW 3 of 9 Antibiotics 2021, 10, x FOR PEER REVIEW 3 of 9 2.2. Findings 2.2. Findings The baseline characteristics of the patients are listed in Table 1. Fifty-eight (71%) pa- The baseline characteristics of the patients are listed in Table 1. Fifty-eight (71%) pa- tients2.2. Findings were ≥ 20 years of age, 19 (23%) were 3 to 19 years of age, three (3.7%) were 4 weeks tients were ≥ 20 years of age, 19 (23%) were 3 to 19 years of age, three (3.7%) were 4 weeks to 2 years of age, and two (2.4%)
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