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

被引:72
作者
Katz, D. E. [1 ]
Lindfield, K. C. [1 ]
Steenbergen, J. N. [1 ]
Benziger, D. P. [1 ]
Blackerby, K. J. [1 ]
Knapp, A. G. [1 ]
Martone, W. J. [1 ]
机构
[1] Cubist Pharmaceut Inc, Med Commun, Lexington, MA 02421 USA
关键词
D O I
10.1111/j.1742-1241.2008.01854.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Methicillin-susceptible and -resistant (MRSA) Staphylococcus aureus are significant causes of complicated skin and skin structure infections (cSSSI). The bactericidal antibiotic daptomycin is approved for gram-positive cSSSI at 4 mg/kg/day for 7-14 days, but the optimal dose level and duration of therapy have not been firmly established. This pilot study evaluated the efficacy and safety of daptomycin at 10 mg/kg every 24 h for 4 days [high-dose short duration (HDSD) regimen] vs. standard of care therapy with vancomycin or semi-synthetic penicillin for the treatment of cSSSI. Methods: This was a semi-single blind, randomised, multicentre, comparative trial. The primary efficacy end-point was the clinical response 7-14 days posttherapy. Results: One hundred patients were randomised; 48 in each arm were treated. The treatment groups were well balanced with respect to demographics, comorbidities and the type of infection (75% because of MRSA). Overall, clinical success rates were 75.0% (36/48) for daptomycin and 87.5% (42/48) for comparator (95% confidence interval for the difference: -27.9, 2.9). The median duration of comparator therapy was 8 days. Two comparator patients and no daptomycin patients experienced treatment-related serious adverse events requiring hospitalisation. Conclusion: We found that the HDSD regimen had a safety profile similar to that seen in previous studies. Although the differences were not statistically significant, clinical success rates for comparator were higher than for daptomycin. In post hoc analyses HDSD daptomycin performed better in some subgroups (e.g. outpatients) than in others (e.g. certain MRSA infections). These observations require confirmation in larger trials.
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页码:1455 / 1464
页数:10
相关论文
共 43 条
[11]   Survey of infections due to Staphylococcus species:: Frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999 [J].
Diekema, DJ ;
Pfaller, MA ;
Schmitz, FJ ;
Smayevsky, J ;
Bell, J ;
Jones, RN ;
Beach, M .
CLINICAL INFECTIOUS DISEASES, 2001, 32 :S114-S132
[12]   Mutant selection window hypothesis updated [J].
Drlica, Karl ;
Zhao, Xilin .
CLINICAL INFECTIOUS DISEASES, 2007, 44 (05) :681-688
[13]   The crisis of resistance: Identifying drug exposures to suppress amplification of resistant mutant subpopulations [J].
Drusano, GL ;
Louie, A ;
Deziel, M ;
Gumbo, T .
CLINICAL INFECTIOUS DISEASES, 2006, 42 (04) :525-532
[14]   Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection [J].
Engemann, JJ ;
Carmeli, Y ;
Cosgrove, SE ;
Fowler, VG ;
Bronstein, MZ ;
Trivette, SL ;
Briggs, JP ;
Sexton, DJ ;
Kaye, KS .
CLINICAL INFECTIOUS DISEASES, 2003, 36 (05) :592-598
[15]  
FIGUEROA DA, 2007, 47 INT C ANT AG CHEM
[16]   Testing the mutant selection window hypothesis with Staphylococcus aureus exposed to daptomycin and vancomycin in an in vitro dynamic model [J].
Firsov, Alexander A. ;
Smirnova, Maria V. ;
Lubenko, Irene Yu. ;
Vostrov, Sergey N. ;
Portnoy, Yury A. ;
Zinner, Stephen H. .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2006, 58 (06) :1185-1192
[17]   Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus [J].
Fowler, Vance G., Jr. ;
Boucher, Helen W. ;
Corey, G. Ralph ;
Abrutyn, Elias ;
Karchmer, Adolf W. ;
Rupp, Mark E. ;
Levine, Donald P. ;
Chambers, Henry F. ;
Tally, Francis P. ;
Vigliani, Gloria A. ;
Cabell, Christopher H. ;
Link, Arthur Stanley ;
DeMeyer, Ignace ;
Filler, Scott G. ;
Zervos, Marcus ;
Cook, Paul ;
Parsonnet, Jeffrey ;
Bernstein, Jack M. ;
Price, Connie Savor ;
Forrest, Graeme N. ;
Faetkenheuer, Gerd ;
Gareca, Marcelo ;
Rehm, Susan J. ;
Brodt, Hans Reinhardt ;
Tice, Alan ;
Cosgrove, Sara E. .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (07) :653-665
[18]   Once-daily dosing of aminoglycosides: review and recommendations for clinical practice [J].
Freeman, CD ;
Nicolau, DP ;
Belliveau, PP ;
Nightingale, CH .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1997, 39 (06) :677-686
[19]   In vitro bactericidal activity of daptomycin against staphylococci [J].
Fuchs, PC ;
Barry, AL ;
Brown, SD .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2002, 49 (03) :467-470
[20]   Short-course antimicrobial therapy of respiratory tract infections [J].
Guay, DRP .
DRUGS, 2003, 63 (20) :2169-2184