Effect of Lidocaine and Epinephrine on Staphylococcus aureus in a Guinea Pig Model of Surgical Wound Infection

ABSTRACT Staphylococcus aureusinfection is not associated with the development of protective immunity, and disease relapses occur frequently. We hypothesize that protein A, a factor that binds immunoglobulin Fcγ and cross-links VH3 clan B cell receptors (IgM), is the staphylococcal determinant for host immune suppression. To test this, vertebrate IgM was examined for protein A cross-linking. High VH3 binding activity occurred with human and guinea immunoglobulin, whereas mouse and rabbit immunoglobulins displayed little and no binding, respectively. Establishing a guinea pig model of S. aureus bloodstream infection, we show that protein A functions as a virulence determinant and suppresses host B cell responses. Immunization with SpAKKAA, which cannot bind immunoglobulin, elicits neutralizing antibodies that enable guinea pigs to develop protective immunity.IMPORTANCE Staphylococcus aureusis the leading cause of soft tissue and bloodstream infections; however, a vaccine with clinical efficacy is not available. Using mice to model staphylococcal infection, earlier work identified protective antigens; however, corresponding human clinical trials did not reach their endpoints. We show that B cell receptor (IgM) cross-linking by protein A is an important immune evasion strategy of S. aureus that can be monitored in a guinea pig model of bloodstream infection. Further, immunization with nontoxigenic protein A enables infected guinea pigs to elicit antibody responses that are protective against S. aureus. Thus, the guinea pig model may support preclinical development of staphylococcal vaccines.

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An outbreak of Staphylococcus aureus surgical wound infection associated with excess overtime employment of operating room personnel

American Journal of Infection Control ◽

10.1016/0196-6553(83)90101-3 ◽

1983 ◽

Vol 11 (2) ◽

pp. 63-67 ◽

Cited By ~ 10

Author(s):

Barbara Russell ◽

N.Joel Ehrenkranz ◽

Phineas J. Hyams ◽

Carin A. Gribbie

Keyword(s):

Staphylococcus Aureus ◽

Wound Infection ◽

Operating Room ◽

Surgical Wound Infection ◽

Surgical Wound ◽

Operating Room Personnel

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Synergism between Poly-(1-6)-β-d-Glucopyranosyl-(1-3)-βd-Glucopyranose Glucan and Cefazolin in Prophylaxis of Staphylococcal Wound Infection in a Guinea Pig Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.9.2449 ◽

1998 ◽

Vol 42 (9) ◽

pp. 2449-2451 ◽

Cited By ~ 22

Author(s):

Allen B. Kaiser ◽

Douglas S. Kernodle

Keyword(s):

Guinea Pig ◽

Antibiotic Prophylaxis ◽

Wound Infection ◽

Guinea Pigs ◽

Pig Model ◽

Activating Agent ◽

Guinea Pig Model

ABSTRACT To determine whether the infection-preventing capability of the neutrophil-activating agent poly-(1-6)-β-d-glucopyranosyl-(1-3)-β-d-glucopyranose glucan (PGG-glucan) can be enhanced with antibiotic prophylaxis, we administered PGG-glucan and cefazolin, alone and in combination, to guinea pigs inoculated with isolates of staphylococci. Guinea pigs receiving both PGG-glucan and cefazolin had 50% infective doses that were 8- to 20-fold higher than those obtained with cefazolin alone and 100- to 200-fold higher than those obtained with PGG-glucan alone. PGG-glucan and cefazolin are synergistic in their ability to prevent staphylococcal wound infection.

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Vaccination with Detoxified Leukocidin AB Reduces Bacterial Load in a Staphylococcus aureus Minipig Deep Surgical Wound Infection Model

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab219 ◽

2021 ◽

Author(s):

J Fernandez ◽

H Sanders ◽

J Henn ◽

J M Wilson ◽

D Malone ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Wound Infection ◽

Bacterial Load ◽

Surgical Wound Infection ◽

Vaccine Antigen ◽

Infection Model ◽

Surgical Wound ◽

Log Reduction ◽

Efficacy Trials ◽

Attractive Option

Abstract Vaccines against Staphylococcus aureus have eluded researchers for over three decades while the burden of staphylococcal diseases has increased. Early vaccine attempts mainly used rodents to characterize preclinical efficacy, and all subsequently failed in human clinical efficacy trials. More recently, the leukocidin LukAB has gained interest as a vaccine antigen. We developed a minipig deep surgical wound infection model offering three independent efficacy readouts: bacterial load at the superficial and at the deep-seated surgical site, and dissemination of bacteria. Due to similarities with humans, minipigs are an attractive option to study novel vaccine candidates. With this model, we characterized the efficacy of a LukAB toxoid as vaccine candidate. Compared to control animals, a 3-log reduction of bacteria at the deep-seated surgical site was observed in LukAB-treated minipigs and dissemination of bacteria was dramatically reduced. Therefore, LukAB toxoids may be a useful addition to S. aureus vaccines and warrant further study.

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Use of the Surgical Wound Infection Model To Determine the Efficacious Dosing Regimen of Retapamulin, a Novel Topical Antibiotic

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00183-06 ◽

2006 ◽

Vol 50 (11) ◽

pp. 3886-3888 ◽

Cited By ~ 27

Author(s):

Stephen Rittenhouse ◽

Christine Singley ◽

Jennifer Hoover ◽

Roni Page ◽

David Payne

Keyword(s):

Staphylococcus Aureus ◽

Clinical Trials ◽

Wound Infection ◽

Streptococcus Pyogenes ◽

Surgical Wound Infection ◽

Infection Model ◽

Surgical Wound ◽

Dosing Regimen ◽

Topical Antibiotic ◽

Dosing Regimens

ABSTRACT The effect of topically applied retapamulin ointment was evaluated using various dosing regimens in the Staphylococcus aureus and Streptococcus pyogenes wound infection model. Retapamulin (1%, wt/wt) was efficacious using twice-daily (b.i.d.) applications for 4 or 5 days. These data underpinned the decision to evaluate 1% retapamulin b.i.d. in clinical trials.

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