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Titolo:
Influence of in-vivo endotoxin liberation on anti-anaerobic antimicrobial efficacy
Autore:
Rotimi, VO; Al-Sweih, NN; Anim, JT; Ahmed, K; Verghese, TL; Khodakhast, FB;
Indirizzi:
Kuwait Univ, Fac Med, Dept Microbiol, Safat 13110, Kuwait Kuwait Univ Safat Kuwait 13110 Med, Dept Microbiol, Safat 13110, Kuwait
Titolo Testata:
JOURNAL OF CHEMOTHERAPY
fascicolo: 5, volume: 13, anno: 2001,
pagine: 510 - 518
SICI:
1120-009X(200110)13:5<510:IOIELO>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTIBIOTIC-INDUCED RELEASE; NEGATIVE BACTERIAL SEPSIS; ESCHERICHIA-COLI; INVITRO; AGENTS; CEFTAZIDIME; IMIPENEM; THERAPY;
Keywords:
gram-negative anaerobic bacteria; endotoxin; systemic infections; septic shock; antimicrobial therapy; Bacteroides fragilis; Fusobacterium nucleatum;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Rotimi, VO Kuwait Univ, Fac Med, Dept Microbiol, POB 24923, Safat 13110, Kuwait Kuwait Univ POB 24923 Safat Kuwait 13110 , Safat 13110, Kuwait
Citazione:
V.O. Rotimi et al., "Influence of in-vivo endotoxin liberation on anti-anaerobic antimicrobial efficacy", J CHEMOTHER, 13(5), 2001, pp. 510-518

Abstract

The ability of cefoxitin, clindamycin, imipenem, meropenem, metronidazole and piperacillin-tazobactam to cause Gram-negative anaerobic bacteria to release endotoxin and the influence of such liberated endotoxin on antibioticefficacy were investigated in in-vivo experiments in animal models. Experimental infections in various animal models (mice, hamster and infant rats) with cultures of wild and reference strains of Bacteroides fragilis group and Fusobacterium spp. were carried out by injecting these animals with different inocula (10(6), 10(7) and 10(8) cfu/ml) of the bacterial suspension. Appropriate doses of the test antibiotics were then injected and the plasmalipopolysaccharide (endotoxin) release measured by the Limulus Amoebocyte Lysate (LAL) Assay. Evidence of worsening of the outcome of the infections post-therapy was assessed, including histopathological changes in the internal organs. Infection with generalized septicemia was established with F. nucleatum in the mice and hamster models while with the B. fragilis group, infections only led to intra-abdominal abscess formation. Plasma endotoxin release was higher in animals infected with F. nucleatum than B. fragilis and was unrelated to the bacterial inoculum. Imipenem, meropenem and cefoxitin, in that order, induced the highest levels of endotoxin activities in theanimal model, particularly following F. nucleatum infection. Histological examination of the internal organs of various animals showed variation in the pattern of histopathological changes; grades 3-4 inflammatory changes inthe liver were observed in the Fusobacterium-infected animals that were treated with the carbapenems and cefoxitin. Therapy with the other antibiotics did not exacerbate anaerobic sepsis. In this study, bacteremia did not lead to massive endotoxin release and antibiotic therapy appeared not to havenegatively influenced the outcome of most of the Gram-negative anaerobic infections, except for infections caused by Fusobacterium spp. However, it is conceivable that if the gastrointestinal tract is the source of the endotoxin in patients with systemic inflammatory response syndrome, then the obligate anaerobes like Bacteroides and Fusobacterium species, which are members of the gut flora, may play a major role in the unfavorable outcome of antibiotic therapy in some of these infections.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/05/20 alle ore 13:29:58