Aminoglycosides against carbapenem-resistant Enterobacteriaceae in the critically ill: the pitfalls of aminoglycoside susceptibility

Expert Review of Anti-Infective Therapy

Volumn 15, Issue 6, 2017, Pages 519-526

  Zavascki, Alexandre P ^a,b   Klee, Brandon O ^c   Bulitta, Jürgen B ^c  

^a HOSPITAL DE CLÍNICAS DE PORTO ALEGRE   (Brazil)

^b FEDERAL UNIVERSITY OF RIO GRANDE DO SUL   (Brazil)

^c UNIVERSITY OF FLORIDA   (United States)

Author keywords

Amikacin; combination therapy; gentamicin; Klebsiella pneumoniae carbapenemase; pharmacokinetics pharmacodynamics; resistance; tobramycin

Indexed keywords

AMIKACIN; AMINOGLYCOSIDE ANTIBIOTIC AGENT; CARBAPENEM DERIVATIVE; CEFEPIME; COLISTIN; DORIPENEM; DOXYCYCLINE; GENTAMICIN; IMIPENEM; LEVOFLOXACIN; MEROPENEM; POLYMYXIN; RIFAMPICIN; TIGECYCLINE; TOBRAMYCIN; ANTIINFECTIVE AGENT;

ACUTE KIDNEY FAILURE; ANTIBIOTIC RESISTANCE; AREA UNDER THE CURVE; ARTICLE; CARBAPENEM RESISTANT ENTEROBACTERIACEAE; COMBINATION DRUG THERAPY; CRITICAL ILLNESS; CRITICALLY ILL PATIENT; DRUG EFFICACY; DRUG SAFETY; DRUG TREATMENT FAILURE; DRUG URINE LEVEL; ENTEROBACTERIACEAE INFECTION; GRAM NEGATIVE SEPSIS; HUMAN; INNER EAR DISEASE; KLEBSIELLA PNEUMONIAE INFECTION; MAXIMUM PLASMA CONCENTRATION; MINIMUM INHIBITORY CONCENTRATION; MONOTHERAPY; NEPHROTOXICITY; NONHUMAN; OTOTOXICITY; PHARMACODYNAMICS; PNEUMONIA; SURVIVAL RATE; URINARY TRACT INFECTION; VESTIBULAR DISORDER; BIOAVAILABILITY; CARBAPENEM-RESISTANT ENTEROBACTERIACEAE; CELL MEMBRANE PERMEABILITY; DOSE CALCULATION; DRUG ADMINISTRATION; DRUG EFFECTS; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; MICROBIAL SENSITIVITY TEST; MICROBIOLOGY; MULTIDRUG RESISTANCE; PATHOLOGY; PROCEDURES; PROTEIN SYNTHESIS;

AMIKACIN; ANTI-BACTERIAL AGENTS; BIOLOGICAL AVAILABILITY; CARBAPENEM-RESISTANT ENTEROBACTERIACEAE; CELL MEMBRANE PERMEABILITY; CRITICAL ILLNESS; DRUG ADMINISTRATION SCHEDULE; DRUG DOSAGE CALCULATIONS; DRUG RESISTANCE, MULTIPLE, BACTERIAL; DRUG THERAPY, COMBINATION; ENTEROBACTERIACEAE INFECTIONS; GENTAMICINS; HUMANS; MICROBIAL SENSITIVITY TESTS; PROTEIN BIOSYNTHESIS;

EID: 85017508509     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1080/14787210.2017.1316193     Document Type: Article

References (57)

1. Munoz-Price LS, Poirel L, Bonomo RA, et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis. 2013;13:785–796.
2. Zavascki AP, Bulitta JB, Landersdorfer CB., Combination therapy for carbapenem-resistant gram-negative bacteria. Expert Rev Anti Infect Ther. 2013;11:1333–1353. Epub 2013/11/07.
3. Almaghrabi R, Clancy CJ, Doi Y, et al. Carbapenem-resistant Klebsiella pneumoniae strains exhibit diversity in aminoglycoside-modifying enzymes, which exert differing effects on plazomicin and other agents. Antimicrob Agents Chemother. 2014;58:4443–4451. Epub 2014/05/29.
4. Bremmer DN, Clancy CJ, Press EG, et al. Shields RK. KPC-producing Klebsiella pneumoniae strains that harbor AAC(6ʹ)-Ib exhibit intermediate resistance to amikacin. Antimicrob Agents Chemother. 2014;58:7597–7600. Epub 2014/10/08.
5. Monaco M, Giani T, Raffone M, et al. Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae:a rapidly evolving problem in Italy, November 2013 to April 2014. Euro Surveill. 2014 Oct 23;19(42):pii:20939.
6. Kontopidou F, Giamarellou H, Katerelos P, et al. Group for the Study of KPCpKpiiicu. Infections caused by carbapenem-resistant Klebsiella pneumoniae among patients in intensive care units in Greece:a multi-centre study on clinical outcome and therapeutic options. Clin Microbiol Infect. 2014;20:O117–23.
7. Bartolleti F, Seco BM, Capuzzo Dos Santos C, et al. Polymyxin B resistance in carbapenem-resistant Klebsiella pneumoniae, Sao Paulo, Brazil. Emerg Infect Dis. 2016;22:1849–1851. Epub 2016/09/21.
8. Vidal L, Gafter-Gvili A, Borok S, et al. Efficacy and safety of aminoglycoside monotherapy:systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2007;60:247–257. Epub 2007/06/15.
9. Milatovic D, Braveny I., Development of resistance during antibiotic therapy. Eur J Clin Microbiol. 1987;6:234–244. Epub 1987/06/01.• This review assessed the risk for emergence of resistance during antibiotic monotherapy in patients. While all antibiotics tested led to some emergence of resistance, the risk for therapeutic failure was higher for aminoglycoside than for non-aminoglycoside monotherapies.
10. Zhanel GG, Lawson CD, Zelenitsky S, et al. Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin. Expert Rev Anti Infect Ther. 2012;10:459–473. Epub 2012/04/20.
11. Bratu S, Tolaney P, Karumudi U, et al. Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY:molecular epidemiology and in vitro activity of polymyxin B and other agents. J Antimicrob Chemother. 2005;56:128–132. Epub 2005/05/27.
12. Endimiani A, Hujer AM, Perez F, et al. Characterization of blaKPC-containing Klebsiella pneumoniae isolates detected in different institutions in the Eastern USA. J Antimicrob Chemother. 2009;63:427–437. Epub 2009/01/22.
13. Endimiani A, Hujer KM, Hujer AM, et al. ACHN-490, a neoglycoside with potent in vitro activity against multidrug-resistant Klebsiella pneumoniae isolates. Antimicrob Agents Chemother. 2009;53:4504–4507. Epub 2009/09/23.
14. Haidar G, Alkroud A, Cheng S, et al. Association between the presence of aminoglycoside-modifying enzymes and in vitro activity of gentamicin, tobramycin, amikacin, and plazomicin against Klebsiella pneumoniae carbapenemase- and extended-spectrum-beta-lactamase-producing Enterobacter species. Antimicrob Agents Chemother. 2016;60:5208–5214. Epub 2016/06/15.
15. Lopez-Camacho E, Gomez-Gil R, Tobes R, et al. Genomic analysis of the emergence and evolution of multidrug resistance during a Klebsiella pneumoniae outbreak including carbapenem and colistin resistance. J Antimicrob Chemother. 2014;69:632–636. Epub 2013/10/25.
16. Rodriguez-Avial I, Pena I, Picazo JJ, et al. In vitro activity of the next-generation aminoglycoside plazomicin alone and in combination with colistin, meropenem, fosfomycin or tigecycline against carbapenemase-producing Enterobacteriaceae strains. Int J Antimicrob Agents. 2015;46:616–621. Epub 2015/09/24.
17. Drusano GL, Ambrose PG, Bhavnani SM, et al. Back to the future:using aminoglycosides again and how to dose them optimally. Clin Infect Dis. 2007;45:753–760.•• Excellent review on the pharmacokinetics and pharmacodynamics of aminoglycosides.
18. CLSI. Performance standards for antimicrobial susceptibility testing. PA, USA:Document M100-S26 Wayne; 2016.
19. Bulitta JB, Ly NS, Landersdorfer CB, et al. Two mechanisms of killing of Pseudomonas aeruginosa by tobramycin assessed at multiple inocula via mechanism-based modeling. Antimicrob Agents Chemother. 2015;59:2315–2327.
20. Yadav R, Landersdorfer CB, Nation RL, et al. Novel approach to optimize synergistic carbapenem-aminoglycoside combinations against carbapenem-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2015;59:2286–2298.
21. Turnidge J. Pharmacodynamics and dosing of aminoglycosides. Infect Dis Clin North Am. 2003;17:503–28, v. Epub 2004/01/09.
22. Lacy MK, Nicolau DP, Nightingale CH, et al. The pharmacodynamics of aminoglycosides. Clin Infect Dis. 1998;27:23–27. Epub 1998/07/24.
23. Rees VE, Bulitta JB, Oliver A, et al. Resistance suppression by high-intensity, short-duration aminoglycoside exposure against hypermutable and non-hypermutable Pseudomonas aeruginosa. J Antimicrob Chemother. 2016;71:3157–3167.
24. Beauchamp D, Labrecque G. Aminoglycoside nephrotoxicity:do time and frequency of administration matter? Curr Opin Crit Care. 2001;7:401–408. Epub 2002/01/24.
25. Yadav R, Bulitta JB, Nation RL, et al. Optimization of synergistic combination regimens against carbapenem- and aminoglycoside-resistant clinical Pseudomonas aeruginosa isolates via mechanism-based pharmacokinetic/pharmacodynamic modeling. Antimicrob Agents Chemother. 2016 Dec 27;61(1):pii:e01011-16.•• This study demonstrated synergy for aminoglycoside plus carbapenem combinations against P. aeruginosa isolates that were highly resistant to both antibiotics. Synergy could be exploited at clinically relevant antibiotic concentrations as shown via mechanism-based Monte Carlo simulations in the presence of the large between-patient variability in pharmacokinetics in critically ill patients.
26. Brasseur A, Hites M, Roisin S, et al. A high-dose aminoglycoside regimen combined with renal replacement therapy for the treatment of MDR pathogens:a proof-of-concept study. J Antimicrob Chemother. 2016 May;71(5):1386–1394.
27. Roger C, Nucci B, Louart B, et al. Impact of 30 mg/kg amikacin and 8 mg/kg gentamicin on serum concentrations in critically ill patients with severe sepsis. J Antimicrob Chemother. 2016;71:208–212.•• Pharmacokinetic study in critically ill patients receiving high doses of either amikacin (30 mg/kg) or gentamicin (8 mg/kg) demonstrating that the target was achieved only in 59% of patients.
28. White BP, Lomaestro B, Pai MP. Optimizing the initial amikacin dosage in adults. Antimicrob Agents Chemother. 2015;59:7094–7096.•• Pharmacokinetic study in critically ill patients in that a high fixed-dosing approach rather than a weight-based regimen is proposed.
29. Roger C, Nucci B, Molinari N, et al. Standard dosing of amikacin and gentamicin in critically ill patients results in variable and subtherapeutic concentrations. Int J Antimicrob Agents. 2015;46:21–27.
30. Blackburn LM, Tverdek FP, Hernandez M, et al. First-dose pharmacokinetics of aminoglycosides in critically ill haematological malignancy patients. Int J Antimicrob Agents. 2015;45:46–53.
31. De Montmollin E, Bouadma L, Gault N, et al. Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen. Intensive Care Med. 2014;40:998–1005.
32. Galvez R, Luengo C, Cornejo R, et al. Higher than recommended amikacin loading doses achieve pharmacokinetic targets without associated toxicity. Int J Antimicrob Agents. 2011;38:146–151.
33. Taccone FS, Laterre PF, Spapen H, et al. Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock. Crit Care. 2010;14:R53.
34. Burdet C, Pajot O, Couffignal C, et al. Population pharmacokinetics of single-dose amikacin in critically ill patients with suspected ventilator-associated pneumonia. Eur J Clin Pharmacol. 2015;71:75–83.
35. Rea RS, Capitano B, Bies R, et al. Suboptimal aminoglycoside dosing in critically ill patients. Ther Drug Monit. 2008;30:674–681.
36. European Committee on Antimicrobial Susceptibility Testing. EUCAST clinical MIC breakpoints. www.eucast.org, accessed 07 February 2017. Available from:www.eucast.org.
37. Gonzalez-Padilla M, Torre-Cisneros J, Rivera-Espinar F, et al. Gentamicin therapy for sepsis due to carbapenem-resistant and colistin-resistant Klebsiella pneumoniae. J Antimicrob Chemother. 2015;70:905–913.
38. Shields RK, Clancy CJ, Press EG, et al. Aminoglycosides for treatment of bacteremia due to carbapenem-resistant Klebsiella pneumoniae. Antimicrob Agents Chemother. 2016;60:3187–3192. Epub 2016/03/02.
39. Brown SA, Riviere JE. Comparative pharmacokinetics of aminoglycoside antibiotics. J Vet Pharmacol Ther. 1991;14:1–35. Epub 1991/03/01.
40. Alexander BT, Marschall J, Tibbetts RJ, et al. Treatment and clinical outcomes of urinary tract infections caused by KPC-producing Enterobacteriaceae in a retrospective cohort. Clin Ther. 2012;34:1314–1323. Epub 2012/06/14.
41. Rodrigues Dos Santos BG, Amaral ES, Fernandes PF, et al. Urinary tract infections and surgical site infections due to carbapenem-resistant Enterobacteriaceae in renal transplant. Transplant Proc. 2016;48:2050–2055. Epub 2016/08/30.
42. Satlin MJ, Kubin CJ, Blumenthal JS, et al. Comparative effectiveness of aminoglycosides, polymyxin B, and tigecycline for clearance of carbapenem-resistant Klebsiella pneumoniae from urine. Antimicrob Agents Chemother. 2011;55:5893–5899. Epub 2011/10/05.
43. Van Duin D, Cober E, Richter SS, et al. Impact of therapy and strain type on outcomes in urinary tract infections caused by carbapenem-resistant Klebsiella pneumoniae. J Antimicrob Chemother. 2015;70:1203–1211. Epub 2014/12/11.
44. Paquette F, Bernier-Jean A, Brunette V, et al. Acute kidney injury and renal recovery with the use of aminoglycosides:a large retrospective study. Nephron. 2015;131:153–160.
45. Avent ML, Rogers BA, Cheng AC, et al. Current use of aminoglycosides:indications, pharmacokinetics and monitoring for toxicity. Intern Med J. 2011;41:441–449. Epub 2011/02/12.
46. Maglio D, Nightingale CH, Nicolau DP. Extended interval aminoglycoside dosing:from concept to clinic. Int J Antimicrob Agents. 2002;19:341–348. Epub 2002/04/30.
47. Tod M, Padoin C, Petitjean O. Clinical pharmacokinetics and pharmacodynamics of isepamicin. Clin Pharmacokinet. 2000;38:205–223. Epub 2000/04/05.
48. Ong LZ, Tambyah PA, Lum LH, et al. Aminoglycoside-associated acute kidney injury in elderly patients with and without shock. J Antimicrob Chemother. 2016 Nov;71(11):3250-3257.
49. Guthrie OW. Aminoglycoside induced ototoxicity. Toxicology. 2008;249:91–96.
50. Drusano GL, Bonomo RA, Bahniuk N, et al. Resistance emergence mechanism and mechanism of resistance suppression by tobramycin for cefepime for Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2012;56:231–242. Epub 2011/10/19.• This study showed that inhibition of protein synthesis by an aminoglycoside resulted in decreased β-lactamase expression in Pseudomonas aeruginosa. This mechanism of synergy contributed to the suppression of emergence of bacterial resistance for aminoglycoside plus cefepime combination regimens.
51. Hirsch EB, Guo B, Chang KT, et al. Assessment of antimicrobial combinations for Klebsiella pneumoniae carbapenemase-producing K. Pneumoniae J Infect Dis. 2013;207:786–793.•• This study showed synergy of the amikacin plus doripenem combination against two CRE isolates that were resistant to both amikacin and doripenem. Synergy was shown in vitro and in a high-inoculum pneumonia infection model in neutropenic mice.
52. Le J, McKee B, Srisupha-Olarn W, et al. In vitro activity of carbapenems alone and in combination with amikacin against KPC-producing Klebsiella pneumoniae. J Clin Med Res. 2011;3:106–110.
53. Tang HJ, Lai CC, Chen CC, et al. Colistin-sparing regimens against Klebsiella pneumoniae carbapenemase-producing K. pneumoniae isolates:combination of tigecycline or doxycycline and gentamicin or amikacin. J Microbiol Immunol Infect. 2016 Mar 31; pii:S1684-1182(16)30024-X.
54. Paul M, Carmeli Y, Durante-Mangoni E, et al. Combination therapy for carbapenem-resistant gram-negative bacteria. J Antimicrob Chemother. 2014;69:2305–2309. Epub 2014/05/30.
55. Zusman O, Altunin S, Koppel F, et al. Polymyxin monotherapy or in combination against carbapenem-resistant bacteria:systematic review and meta-analysis. J Antimicrob Chemother. 2017 Jan;72(1):29-39.
56. Falagas ME, Mavroudis AD. Vardakas KZ. The antibiotic pipeline for multi-drug resistant gram negative bacteria:what can we expect? Expert Rev Anti Infect Ther. 2016;14:747–763. Epub 2016/07/13.
57. USCAST. Aminoglycoside in vitro susceptibility test interpretive criteria evaluations. http://www.uscast.org/news/aminoglycoside-in-vitro-susceptibility-test-interpretation-criteria-evaluations-now-available-for-public-comment2016.