Organ specific apoptosis following polymicrobial intraperitoneal infection

Franklin, Glen A.; Turina, Matthias; Kuhn, John F; Turpen, R.; Peyton, James C.; Cheadle, William G.

doi:10.1007/s00011-006-0063-3

Cited by 4 publications

(1 citation statement)

References 45 publications

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“…Coinfection or polymicrobial infection is known to impair or alter the host immune mechanisms (2), which may contribute to the observed synergistic effect on mortality. Polymicrobial sepsis has been shown to impair leukocyte migration, suppress polymorphonuclear leukocyte function (27,33), alter cytokine and chemokine expression (24), alter dendritic cell function (13), and induce organ-specific apoptosis (14), as well as increase the level of inducible apoptosis of CD4 ϩ lymphocytes (3). In our neonatal model of coinfection, the mechanisms contributing to synergistic effects on mortality were very likely the physical interaction between C. albicans and S. epidermidis, even though they were administered at different subcutaneous sites, and the immune dysfunction induced by the coinfection.…”

Section: Vol 51 2007 Fluconazole Prophylaxis In Neonatal Coinfectiomentioning

confidence: 99%

Neonatal Coinfection Model of Coagulase-Negative Staphylococcus ( Staphylococcus epidermidis ) and Candida albicans : Fluconazole Prophylaxis Enhances Survival and Growth

Venkatesh

Pham

Fein

et al. 2007

Antimicrob Agents Chemother

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Coagulase-negative staphylococci (CoNS) and Candida are among the most common causes of single infections and coinfections in neonates after 72 h of age. In neonates, coinfection increases the rate of mortality threefold and results in significantly greater morbidity compared to those that result from single infections. In an effort to better understand this phenomenon, we developed the first neonatal animal model of coinfection (with CoNS and Candida) and evaluated its effects on mortality and morbidity and the impact of antifungal prophylaxis with fluconazole. Neonatal Wistar rats were infected with Candida albicans and/or Staphylococcus epidermidis with doses of 2 ؋ 10 8 and 2 ؋ 10 6 CFU subcutaneously in different combinations and were monitored for mortality, weight gain, and bacteremia. The in vitro sensitivity of C. albicans to fluconazole was evaluated and the MIC was determined. A subset of rats in these experiments received fluconazole at 10 mg/kg of body weight/dose intraperitoneally starting 24 h before infection for 4 days, and the serum trough levels of fluconazole were measured. Coinfection in the suckling rat significantly increased the rate of mortality compared to that after infection with a single species (P < 0.001) and resulted in deaths even at sublethal doses. Coinfection also impaired weight gain significantly in severely infected pups compared to that achieved after infection with a single species (P < 0.001). Fluconazole prophylaxis significantly reduced mortality by 30% in the Candida group and 36% in the coinfection group and improved weight gain in this neonatal model of coinfection (P < 0.001). We developed a neonatal model of coinfection with Candida and CoNS, observed significantly greater mortality and morbidity with coinfection, and found that fluconazole prophylaxis significantly reduced the rates of both mortality and morbidity. Further research on neonatal coinfection is urgently needed to improve clinical outcomes.

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Section: Vol 51 2007 Fluconazole Prophylaxis In Neonatal Coinfectiomentioning

confidence: 99%

Neonatal Coinfection Model of Coagulase-Negative Staphylococcus ( Staphylococcus epidermidis ) and Candida albicans : Fluconazole Prophylaxis Enhances Survival and Growth

Venkatesh

Pham

Fein

et al. 2007

Antimicrob Agents Chemother

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Prophylaxis with lactoferrin, a novel antimicrobial agent, in a neonatal rat model of coinfection

et al. 2007

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Lactoferrin has broad-spectrum antimicrobial activity, and the authors hypothesized that recombinant human lactoferrin (Talactoferrin alfa [TLF]) would reduce mortality and morbidity in a coinfection model. The MIC 50 (minimum inhibitory concentration required to inhibit the growth of 50% of organisms) of TLF against Candida albicans and Staphylococcus epidermidis was determined. Neonatal Wistar rats were infected with C albicans or S epidermidis or both, at doses of 2 x10(8) colony-forming units (CFUs) given subcutaneously. Rat pups in each group were randomly given TLF intraperitoneally at 40 mg/kg/dose or 300 mg/kg/dose, or saline in 0.2 mL, once a day for 4 d and were monitored for mortality, weight gain, and blood culture positivity. Trough serum levels of TLF were measured at 24, 48, 72, 96, and 144 h. MIC 50 of TLF was 30 microg/mL and 500 microg/mL for C albicans and S epidermidis, respectively. TLF prophylaxis significantly improved survival in the coinfection group at 40 mg/kg/dose (by 16.1%; P=.019) and at 300 mg/kg/dose (by 15.1%; P=.027) and in the S epidermidis group at a dose of 40 mg/kg/dose (by 18.6%; P=.04). Weight gain was not affected by TLF prophylaxis. Serum trough levels of TLF were 1000-fold lower than in vitro MIC 50. The authors conclude that lactoferrin prophylaxis significantly enhanced survival in coinfection and in the subgroup of S epidermidis infection (40 mg/kg/dose) through indirect mechanisms.

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Decreased Neutrophil Response in a Model of Chronic IntraperitonealKlebsiellaInfection

Woods

Peyton

Franklin

et al. 2007

Surgical Infections

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Despite persistent intra-abdominal infection, gentamicin treatment significantly prolonged survival in this uniformly lethal model. Although antibiotic treatment did not suppress bacteremia, it did diminish bacterial spread from the blood to the lung. This procedure produced a clinically relevant, novel model of antibiotic-treated chronic intraperitoneal infection, which will allow future study of specific host defense mechanisms.

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Organ specific apoptosis following polymicrobial intraperitoneal infection

Abstract: The distribution of apoptotic cells during intraperitoneal infection occurs in an organ specific manner, with significant increases in the spleen and liver. This distribution likely reflected the clearance of apoptotic cells as the inflammatory focus became contained.

Cited by 4 publications

References 45 publications

Neonatal Coinfection Model of Coagulase-Negative Staphylococcus ( Staphylococcus epidermidis ) and Candida albicans : Fluconazole Prophylaxis Enhances Survival and Growth

Neonatal Coinfection Model of Coagulase-Negative Staphylococcus ( Staphylococcus epidermidis ) and Candida albicans : Fluconazole Prophylaxis Enhances Survival and Growth

Prophylaxis with lactoferrin, a novel antimicrobial agent, in a neonatal rat model of coinfection

Decreased Neutrophil Response in a Model of Chronic IntraperitonealKlebsiellaInfection

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