Comparable efficacies of the antimicrobial peptide human lactoferrin 1-11 and gentamicin in a chronic methicillin-resistant Staphylococcus aureus osteomyelitis model

被引:66
作者
Faber, C
Stallmann, HP
Lyaruu, DM
Joosten, U
von Eiff, C
Amerongen, AV
Wuisman, PIJM
机构
[1] Vrije Univ Amsterdam, Med Ctr, Dept Orthopaed Surg, NL-1007 MB Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Ctr Dent, Dept Oral Cell Biol, Amsterdam, Netherlands
[3] Marien Hosp, Dept Trauma & Hand Surg, Osnabruck, Germany
[4] Univ Munster, Inst Med Microbiol, D-4400 Munster, Germany
[5] ACTA, Dept Oral Biochem, Amsterdam, Netherlands
关键词
D O I
10.1128/AAC.49.6.2438-2444.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The therapeutic efficacy of an antimicrobial peptide, human lactoferrin 1-11 (hLF1-11), was investigated in a model of chronic methicillin-resistant Staphylococcus aureus (MRSA) (gentamicin susceptible) osteomyelitis in rabbits. We incorporated 50 mg hLF1-11/g or 50 mg gentamicin/g cement powder into a calcium phosphate bone cement (Ca-P) and injected it into the debrided tibial cavity, creating a local drug delivery system. The efficacy of hLF1-11 and gentamicin was compared to that of a sham-treated control (plain bone cement) (n = 6) and no treatment (infected only) (n = 5). The results were evaluated by microbiology, radiology, and histology. MRSA was recovered from all tibias in both control groups (n = 11). On the other hand, hLF1-11 and gentamicin significantly reduced the bacterial load. Furthermore, no growth of bacteria was detected in five out of eight and six out of eight specimens of the hLF1-11- and gentamicin-treated groups, respectively. These results were confirmed by a significant reduction of the histological disease severity score by hLF1-11 and gentamicin compared to both control groups. The hLF1-11-treated group also had a significantly lower radiological score compared to the gentamicin-treated group. This study demonstrates the efficacy of hLF1-11 incorporated into Ca-P bone cement as a possible therapeutic strategy for the treatment of osteomyelitis, showing efficacy comparable to that of gentamicin. Therefore, the results of this study warrant further preclinical investigations into the possibilities of using hLF1-11 for the treatment of osteomyelitis.
引用
收藏
页码:2438 / 2444
页数:7
相关论文
共 31 条
[1]   Ciprofloxacin implants for bone infection.: In vitro-in vivo characterization [J].
Castro, C ;
Sánchez, E ;
Delgado, A ;
Soriana, I ;
Núñez, P ;
Baro, M ;
Perera, A ;
Évora, C .
JOURNAL OF CONTROLLED RELEASE, 2003, 93 (03) :341-354
[2]  
CRAIG WA, 1995, J CHEMOTHERAPY, V7, P47
[3]   Potential therapeutic role of cationic peptides in three experimental models of septic shock [J].
Giacometti, A ;
Cirioni, O ;
Ghiselli, R ;
Mocchegiani, F ;
Del Prete, MS ;
Viticchi, C ;
Kamysz, W ;
Lempicka, E ;
Saba, V ;
Scalise, G .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2002, 46 (07) :2132-2136
[4]   Peptide antibiotics [J].
Hancock, REW .
LANCET, 1997, 349 (9049) :418-422
[5]   DIFFUSION OF ANTIBIOTICS FROM ACRYLIC BONE-CEMENT INVITRO [J].
HILL, J ;
KLENERMAN, L ;
TRUSTEY, S ;
BLOWERS, R .
JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME, 1977, 59 (02) :197-199
[6]   GENOMIC DNA FINGERPRINTING BY PULSED-FIELD GEL-ELECTROPHORESIS AS AN EPIDEMIOLOGIC MARKER FOR STUDY OF NOSOCOMIAL INFECTIONS CAUSED BY METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS [J].
ICHIYAMA, S ;
OHTA, M ;
SHIMOKATA, K ;
KATO, N ;
TAKEUCHI, J .
JOURNAL OF CLINICAL MICROBIOLOGY, 1991, 29 (12) :2690-2695
[7]  
Jenny G, 1988, Reconstr Surg Traumatol, V20, P36
[8]   Methicillin-resistant Staphylococcus aureus nosocomial acquisition and carrier state in a wound care center [J].
Kac, G ;
Buu-Hoï, A ;
Hérisson, E ;
Biancardini, P ;
Debure, C .
ARCHIVES OF DERMATOLOGY, 2000, 136 (06) :735-739
[9]   Carrier systems for the local delivery of antibiotics in bone infections [J].
Kanellakopoulou, K ;
Giamarellos-Bourboulis, EJ .
DRUGS, 2000, 59 (06) :1223-1232
[10]   Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis:: a randomised trial [J].
Levin, M ;
Quint, PA ;
Goldstein, B ;
Barton, P ;
Bradley, JS ;
Shemie, SD ;
Yeh, T ;
Kim, SS ;
Cafaro, DP ;
Scannon, PJ ;
Giroir, BP .
LANCET, 2000, 356 (9234) :961-967