Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients

Chung-Chih Lai, Wang-Huei Sheng, Jann-Tay Wang, Aristine Cheng, Yu-Chung Chuang, Yee-Chun Chen, Shan-Chwen Chang, Chung-Chih Lai, Wang-Huei Sheng, Jann-Tay Wang, Aristine Cheng, Yu-Chung Chuang, Yee-Chun Chen, Shan-Chwen Chang

Abstract

Background: Increasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics. However, clinical data on using daptomycin at doses above 6 mg/kg in Asian population are limited.

Methods: A retrospective observational cohort study of all hospitalized adult patients treated with daptomycin (> 6 mg/kg) for at least 72 hours was performed in Taiwan.

Results: A total of 67 patients (40 males) with a median age of 57 years received a median dose of 7.61 mg/kg (range, 6.03-11.53 mg/kg) of daptomycin for a median duration of 14 days (range, 3-53 days). Forty-one patients (61.2%) were in intensive care units (ICU). Sites of infections included complicated skin and soft tissue infections (n = 16), catheter-related bacteremia (n = 16), endocarditis (n = 11), primary bacteremia (n = 10), osteomyelitis and septic arthritis (n = 9), and miscellaneous (n = 5). The median Pitt bacteremia score among the 54 (80.6%) patients with bacteremia was 4. The most common pathogen was methicillin-resistant Staphylococcus aureus (n = 38). Fifty-nine patients (88.1%) were treated with daptomycin after glycopepetide use. Overall, 52 (77.6%) patients achieved clinical success. The all-cause mortality rate at 28 day was 35.8%. In multivariate analysis, the significant predictors of in-hospital mortality in 54 bacteremic patients were malignancies (P = 0.01) and ICU stay (P = 0.02). Adverse effects of daptomycin were generally well-tolerated, leading to discontinuation in 3 patients. Daptomycin-related creatine phosphokinase (CPK) elevations were observed in 4 patients, and all received doses > 8 mg/kg.

Conclusions: Treatment with high dose daptomycin as salvage therapy was generally effective and safe in Taiwan. CPK level elevations were more frequent in patients with dose > 8 mg/kg.

References

    1. Arbeit RD, Maki D, Tally FP, Campanaro E, Eisenstein BI. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis. 2004;38(12):1673–1681. doi: 10.1086/420818.
    1. Fowler VG Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA. et al.Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355(7):653–665. doi: 10.1056/NEJMoa053783.
    1. Tally FP, DeBruin MF. Development of daptomycin for gram-positive infections. J Antimicrob Chemother. 2000;46(4):523–526. doi: 10.1093/jac/46.4.523.
    1. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C, Sakr Y. et al.International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323–2329. doi: 10.1001/jama.2009.1754.
    1. Huang YT, Hsiao CH, Liao CH, Lee CW, Hsueh PR. Bacteremia and infective endocarditis caused by a non-daptomycin-susceptible, vancomycin-intermediate, and methicillin-resistant Staphylococcus aureus strain in Taiwan. J Clin Microbiol. 2008;46(3):1132–1136. doi: 10.1128/JCM.01844-07.
    1. Julian K, Kosowska-Shick K, Whitener C, Roos M, Labischinski H, Rubio A, Parent L, Ednie L, Koeth L, Bogdanovich T. et al.Characterization of a daptomycin-nonsusceptible vancomycin-intermediate Staphylococcus aureus strain in a patient with endocarditis. Antimicrob Agents Chemother. 2007;51(9):3445–3448. doi: 10.1128/AAC.00559-07.
    1. Sharma M, Riederer K, Chase P, Khatib R. High rate of decreasing daptomycin susceptibility during the treatment of persistent Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis. 2008;27(6):433–437. doi: 10.1007/s10096-007-0455-5.
    1. Chambers HF, Basuino L, Diep BA, Steenbergen J, Zhang S, Tattevin P, Alder J. Relationship between susceptibility to daptomycin in vitro and activity in vivo in a rabbit model of aortic valve endocarditis. Antimicrob Agents Chemother. 2009;53(4):1463–1467. doi: 10.1128/AAC.01307-08.
    1. Rose WE, Leonard SN, Rybak MJ. Evaluation of daptomycin pharmacodynamics and resistance at various dosage regimens against Staphylococcus aureus isolates with reduced susceptibilities to daptomycin in an in vitro pharmacodynamic model with simulated endocardial vegetations. Antimicrob Agents Chemother. 2008;52(9):3061–3067. doi: 10.1128/AAC.00102-08.
    1. Rose WE, Rybak MJ, Kaatz GW. Evaluation of daptomycin treatment of Staphylococcus aureus bacterial endocarditis: an in vitro and in vivo simulation using historical and current dosing strategies. J Antimicrob Chemother. 2007;60(2):334–340. doi: 10.1093/jac/dkm170.
    1. Benvenuto M, Benziger DP, Yankelev S, Vigliani G. Pharmacokinetics and tolerability of daptomycin at doses up to 12 milligrams per kilogram of body weight once daily in healthy volunteers. Antimicrob Agents Chemother. 2006;50(10):3245–3249. doi: 10.1128/AAC.00247-06.
    1. Wu G, Abraham T, Rapp J, Vastey F, Saad N, Balmir E. Daptomycin: evaluation of a high-dose treatment strategy. Int J Antimicrob Agents. 2011;38(3):192–196. doi: 10.1016/j.ijantimicag.2011.03.006.
    1. Bassetti M, Nicco E, Ginocchio F, Ansaldi F, de Florentiis D, Viscoli C. High-dose daptomycin in documented Staphylococcus aureus infections. Int J Antimicrob Agents. 2010;36(5):459–461. doi: 10.1016/j.ijantimicag.2010.07.011.
    1. Figueroa DA, Mangini E, Amodio-Groton M, Vardianos B, Melchert A, Fana C, Wehbeh W, Urban CM, Segal-Maurer S. Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program. Clin Infect Dis. 2009;49(2):177–180. doi: 10.1086/600039.
    1. Katz DE, Lindfield KC, Steenbergen JN, Benziger DP, Blackerby KJ, Knapp AG, Martone WJ. A pilot study of high-dose short duration daptomycin for the treatment of patients with complicated skin and skin structure infections caused by gram-positive bacteria. Int J Clin Pract. 2008;62(9):1455–1464. doi: 10.1111/j.1742-1241.2008.01854.x.
    1. Kullar R, Davis SL, Levine DP, Zhao JJ, Crank CW, Segreti J, Sakoulas G, Cosgrove SE, Rybak MJ. High-dose daptomycin for treatment of complicated gram-positive infections: a large, multicenter, retrospective study. Pharmacotherapy. 2011;31(6):527–536. doi: 10.1592/phco.31.6.527.
    1. Moise PA, Hershberger E, Amodio-Groton MI, Lamp KC. Safety and clinical outcomes when utilizing high-dose (> or =8 mg/kg) daptomycin therapy. Ann Pharmacother. 2009;43(7):1211–1219. doi: 10.1345/aph.1M085.
    1. Lai CC, Sheng WH, Wang JT, Liao CH, Ho MW, Chen CJ, Chen DL, Chou MU, Lee CM, Lin YC. et al.Safety and efficacy of daptomycin for the treatment of hospitalized adult patients in Taiwan with severe staphylococcal infections. J Microbiol Immunol Infect. 2012;45(1):52–57. doi: 10.1016/j.jmii.2011.09.018.
    1. Liang SH, Sheng WH, Huang YT, Wu FL, Chang SC. Pharmacokinetics and safety of multiple intravenous doses of daptomycin in a Taiwanese adult population. Chemotherapy. 2009;55(2):91–96. doi: 10.1159/000192392.
    1. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. doi: 10.1016/0021-9681(87)90171-8.
    1. Feldman C, Alanee S, Yu VL, Richards GA, Ortqvist A, Rello J, Chiou CC, Chedid MB, Wagener MM, Klugman KP. Severity of illness scoring systems in patients with bacteraemic pneumococcal pneumonia: implications for the intensive care unit care. Clin Microbiol Infect. 2009;15(9):850–857. doi: 10.1111/j.1469-0691.2009.02901.x.
    1. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; 18th informational supplement. M100-S18. Clinical and Laboratory Standards Institute W, PA; 2008.
    1. Wang JT, Liao CH, Fang CT, Chie WC, Lai MS, Lauderdale TL, Lee WS, Huang JH, Chang SC. Prevalence of and risk factors for colonization by methicillin-resistant Staphylococcus aureus among adults in community settings in Taiwan. J Clin Microbiol. 2009;47(9):2957–2963. doi: 10.1128/JCM.00853-09.
    1. Boucher HW, Sakoulas G. Antimicrobial resistance: perspectives on daptomycin resistance, with emphasis on resistance in Staphylococcus aureus. Clin Infect Dis. 2007;45(5):601–608. doi: 10.1086/520655.
    1. Chuang YC, Chang SC, Wang WK. High and increasing Oxa-51 DNA load predict mortality in Acinetobacter baumannii bacteremia: implication for pathogenesis and evaluation of therapy. PLoS One. 2010;5(11):e14133. doi: 10.1371/journal.pone.0014133.
    1. Bhavnani SM, Rubino CM, Ambrose PG, Drusano GL. Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: data from a randomized trial of patients with bacteremia and endocarditis. Clin Infect Dis. 2010;50(12):1568–1574. doi: 10.1086/652767.
    1. Miller BA, Gray A, Leblanc TW, Sexton DJ, Martin AR, Slama TG. Acute eosinophilic pneumonia secondary to daptomycin: a report of three cases. Clin Infect Dis. 2010;50(11):e63–e68. doi: 10.1086/652656.
    1. Falagas ME, Giannopoulou KP, Ntziora F, Vardakas KZ. Daptomycin for endocarditis and/or bacteraemia: a systematic review of the experimental and clinical evidence. J Antimicrob Chemother. 2007;60(1):7–19. doi: 10.1093/jac/dkm137.
    1. Lichterfeld M, Ferraro MJ, Davis BT. High-dose daptomycin for the treatment of endocarditis caused by Staphylococcus aureus with intermediate susceptibility to glycopeptides. Int J Antimicrob Agents. 2010;35(1):96.
    1. Rybak MJ. The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin Infect Dis. 2006;42(Suppl 1):S35–S39.
    1. Moore CL, Osaki-Kiyan P, Haque NZ, Perri MB, Donabedian S, Zervos MJ. Daptomycin versus vancomycin for bloodstream infections due to methicillin-resistant Staphylococcus aureus with a high vancomycin minimum inhibitory concentration: a case–control study. Clin Infect Dis. 2012;54(1):51–58. doi: 10.1093/cid/cir764.
    1. Pai MP, Norenberg JP, Anderson T, Goade DW, Rodvold KA, Telepak RA, Mercier RC. Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin. Antimicrob Agents Chemother. 2007;51(8):2741–2747. doi: 10.1128/AAC.00059-07.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever