Locally delivered antibodies combined with systemic antibiotics confer synergistic protection against antibiotic-resistant burn wound infection.
BACKGROUND
Nosocomially derived gram-negative infections, particularly from antibiotic-resistant pathogens, are a cause of morbidity in patients with severe burn wounds.


METHODS
Locally delivered polyclonal antibodies and systemically infused ceftazidime were combined in a lethal murine burn wound model against a virulent Pseudomonas aeruginosa strain that exhibits intermediate resistance to ceftazidime.


RESULTS
Survival was synergistically enhanced in cohorts of burned mice treated both locally (subeschar) with pooled polyclonal human immunoglobulin G (1-mg dose) and intravenously with infused ceftazidime (0.44 mg dose). Enhancement of survival correlated with reduced bacterial quantitation in local and systemic tissue observed in separate burned cohorts. Burned, infected mice treated prophylactically with either individual treatment at the same dose or a combination of both treatments administered systemically showed no survival enhancement as compared with the untreated control group.


CONCLUSIONS
Treatment of antibiotic-resistant burn wound infections with antibiotics together with locally delivered immunoglobulins may improve antibiotic protective effects against antibiotic-resistant pathogens.
Felts
A G
AG
Anthony G. Gristina Institute for Biomedical Research, Herndon, Virginia, USA. jbslunt@biocache.com
Grainger
D W
DW
Slunt
J B
JB
D000818:Animals; D002056:Burns / Q000150:complications*; D002442:Ceftazidime / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003428:Cross Infection / Q000209:etiology* / Q000401:mortality / Q000628:therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D005260:Female; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D051379:Mice; D008815:Mice, Inbred Strains; D011552:Pseudomonas Infections / Q000209:etiology* / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D014946:Wound Infection / Q000209:etiology* / Q000401:mortality / Q000628:therapy*
D002511:Cephalosporins; D016756:Immunoglobulins, Intravenous; D002442:Ceftazidime