Biomedical Engineering Reference
In-Depth Information
3.1
Conventional Treatment
Antibiotic treatment for nontyphoidal salmonellosis is not recommended because it
may prolong the illness (Grassl and Finlay 2008 ; McCormick 2004 ; Owens and
Warren 2010 ).
Antimicrobial therapy is indicated for patients with typhoid fever and should
be considered on a case-by-case basis to include patients with severe symptoms
(Wiström et al. 1992 ). Antibiotics are currently indicated for infants up to
2 months of age, elderly, immunocompromised, those with a history of sickle
cell disease or prosthetic grafts, or patients who have extraintestinal findings.
Treatment of those at-risk patients should last 2-5 days or until the patient is
afebrile (McCormick 2004 ).
Traditional first-line antibiotic medications include ampicillin, chlorampheni-
col, and trimethoprim-sulfamethoxazole. Salmonella antibiotic resistance is a
global concern that includes multi-drug resistant strains (Weinberger and Keller
2005 ). Resistance to these first-line antibiotics defines multi-drug resistance in
S. enterica (Crump and Mintz 2010 ). Salmonella infections are commonly treated
with fluoroquinolones such as CIP Despite the increase in CIP resistance in typhoid
and paratyphoid, it is still considered the drug of choice by many physicians.
However, in the case of treatment failures, a third-generation cephalosporin such as
ceftriaxone and macrolide are good alternatives (Owens and Warren 2010 ; Threlfall
et al. 2008 ).
3.2
Preclinical Delivery Systems
3.2.1
Biodistribution and Therapeutic Efficacy
of Parenteral Liposomes
Early work was focused in the encapsulation of aminoglycosides in multilamellar
vesicles. In one of them, GEN was loaded in ~1 mm oligolamellar liposomes (par-
tially hydrogenated eggPC: eggPG: chol: alpha-tocopherol) and i.v. administered to
mice orally infected with S. dublin . Of ten mice, eight survived after a single i.v.
injection of 2 mg of liposomal GEN /kg compared with 0 of 10 treated with the
same amount of free GEN. All mice survived after treatment with a single i.v. or
i.p. injection of 20 mg of liposomal GEN/ kg, whereas that dose of free drug was
completely ineffective and caused neuromuscular paralysis when injected rapidly
i.v. In mice treated with liposomal GEN, there was a steady decrease in the number
of salmonellae in spleens for 2 weeks after treatment. High concentrations of GEN
were present in the spleen for at least 10 days after treatment. Although GEN was
not detected in the mesenteric lymph nodes of mice treated with liposomal GEN,
bacterial counts in the nodes also decreased over time. Small numbers of bacteria
remained viable in the mesenteric lymph nodes and Peyer's patches but not in the
spleens of mice treated with 20-80 mg/kg. Mice treated with doses of liposomal
Search WWH ::




Custom Search