Clinical Experience with Drotrecogin Alfa in Treating Gram-Positive and -Negative Pathogens in Patients with Severe Sepsis

BackgroundNewer concepts in the management of severe sepsis and, in particular, in the understanding of the relationship between proinflammatory and procoagulant activities during severe infection have led to the introduction of activated protein C (drotrecogin) into the therapeutic program. The combination of effective antimicrobial therapy, aggressive supportive care, and efforts to antagonize procoagulants and inhibitors of fibrinolysis was used in this study.MethodsWe treated 12 patients with severe sepsis using this combination of antimicrobial agents and drotrecogin. All patients presented with hypotension and organ failure and some with multiple organ failure. Infected patients were separated into those with gram-positive and those with gram-negative infections.ResultsIn contrast to an expected mortality rate of nearly 40% in this group of patients, only 2 (9%) expired. Both deaths were due to infection by gram-negative organisms in patients with complicated abdominal infections and concurrent cancer. All patients with gram-positive organisms survived.ConclusionThose patients with infections caused by gram-positive organisms seemed to have a better prognosis than those with gram-negative infections, perhaps because their illnesses are less complicated by local disease. Although our study is small, it suggests that activated protein C will have a significant beneficial effect on the future treatment of severe sepsis and can reduce the mortality rate significantly. Further improvement in survival rates will require more effective treatment of local disease and associated noninfectious ailments.

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Epidemiology of Sepsis in the Valencian Community (Spain), 1995–2004

Infection Control and Hospital Epidemiology ◽

10.1086/589583 ◽

2008 ◽

Vol 29 (7) ◽

pp. 630-634 ◽

Cited By ~ 44

Author(s):

Juan Carlos Andreu Ballester ◽

Ferran Ballester ◽

Antonio González Sánchez ◽

Amadeo Almela Quilis ◽

Enrique Colomer Rubio ◽

...

Keyword(s):

Severe Sepsis ◽

Mortality Rate ◽

Confidence Interval ◽

Organ Failure ◽

Incidence Rates ◽

Public Hospitals ◽

Polymicrobial Sepsis ◽

Gram Negative Bacteria ◽

Gram Negative

Objective.To study the incidence of sepsis in the Valencian Community (Spain) during a period of 10 years (1995–2004).Methods.We downloaded data on discharge diagnoses of septicemia in all 26 public hospitals in the Valencian Community during the 10-year study period, as well as the additional discharge diagnoses of each patient.Results.We identified 33,767 cases of sepsis during the study period. The age-standardized incidence rates among men increased from 64.11 (95% confidence interval [CI], 60.37–67.85) cases per 100,000 population in 1995 to 114.02 (95% CI, 109.02–118.50) cases per 100,000 population in 2004 (P < .001), and those among women increased from 45.08 (95% CI, 42.01–48.15) cases per 100,000 population in 1995 to 83.62 (95% CI, 79.85–87.39) cases per 100,000 population in 2004 (P < .001). Gram-negative bacteria were the most frequently involved microorganisms (in 21.4% of cases), and there was a significant increase in the number of sepsis cases caused by these organisms from 1999 onward. The mortality rate was approximately 42.5% among patients hospitalized for sepsis, and mortality was associated with organ failure. In addition, mortality was associated with the microorganism responsible not being known, with infection due to fungi, and with polymicrobial sepsis.Conclusions.The rates of hospitalization both for sepsis overall and for severe sepsis in the Valencian Community (Spain) are lower than those in other countries but are increasing, by 5% each year. The increase in the number of cases in which gram-negative bacteria are the cause of sepsis is notable.

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Effect of Human Plasma-Derived Protein C and Murine Recombinant Protein C on Severe Neonatal Sepsis in Mice.

Blood ◽

10.1182/blood.v104.11.689.689 ◽

2004 ◽

Vol 104 (11) ◽

pp. 689-689

Author(s):

Eva-Maria Muchitsch ◽

Hans Peter Schwarz ◽

Katalin Varadi ◽

Charles Esmon ◽

Giuseppe Mancuso ◽

...

Keyword(s):

Severe Sepsis ◽

Mortality Rate ◽

Human Plasma ◽

Neonatal Sepsis ◽

Protein C ◽

Activated Protein C ◽

Risk Of Death ◽

Neonatal Mice ◽

Endogenous Protein ◽

Septic Condition

Abstract Neonatal sepsis is a leading cause of infant morbidity and mortality frequently associated with activation of the coagulation system. Reduced levels of protein C are found in the majority of patients with sepsis and are associated with an increased risk of death. Although activated protein C is indicated for the treatment of severe sepsis in adults, the risk of severe bleeding may limit its use in neonates. Because the likelihood of inducing bleeding with the zymogen form of protein C is reduced we assessed both human and murine protein C zymogen in a murine neonatal sepsis model. In this model neonatal mice were challenged with viable group B streptococci (GBS). The effect of this septic condition on endogenous protein C levels was evaluated and the effect of treatment with either recombinant murine protein C or human plasma-derived (non-activated) protein C (Ceprotin) investigated. During severe GBS sepsis murine endogenous protein C levels decreased over time in neonatal mice, resulting in a maximum decrease of −30 % at 16 hours after GBS challenge and returned towards baseline at 30 hours. Concomitantly, there was an increase in endogenous protein C activation up to 59 % at 6 hours after GBS challenge, returning to baseline levels at 16 hours. Blocking endogenous murine protein C with an anti-mouse monoclonal antibody increased the mortality rate significantly from 62 to 91 %. Treatment of neonatal septic mice (n=36) with 300 U/kg murine protein C subcutaneously 4 hours before GBS challenge decreased the mortality rate significantly in severe sepsis (LD90) to 64 % (p=0.002). Similarly pretreatment with human plasma-derived protein C (200 IU/kg) 4 hours before GBS challenge increased survival rate significantly in severe septic mice. Treatment with 200 IU/kg (Ceprotin) was even effective given 18 hours after GBS challenge, leading to a decrease in the mortality rate in severe sepsis from 87.5 to 48 %. Despite this species difference and the septic condition, human protein C zymogen was activated to activated protein C and detectable in the circulation of mice. This is the first preclinical study were a beneficial effect of a non-activated protein C could be shown in an animal model of severe neonatal sepsis.

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Updates on role of human recombinant activated protein C in patients with sepsis and severe sepsis: Changed scenario after PROWESS SHOCK trial

Indian Journal of Anaesthesia ◽

10.4103/0019-5049.104597 ◽

2012 ◽

Vol 56 (6) ◽

pp. 597 ◽

Cited By ~ 2

Author(s):

Aparna Shukla

Keyword(s):

Severe Sepsis ◽

Protein C ◽

Activated Protein C ◽

Shock Trial

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Effectiveness of ZnO Nano Particles against the Foodborne Microbial Pathogens E. coli and S. aureus

Jordan Journal of Chemistry ◽

10.47014/15.2.4 ◽

2020 ◽

Vol 15 (2) ◽

pp. 87-94

Keyword(s):

Antimicrobial Agents ◽

Inhibitory Concentration ◽

Antimicrobial Effect ◽

Nano Particles ◽

Microbial Pathogens ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Antimicrobial Susceptibility Tests ◽

Susceptibility Tests

In this work, various concentrations of ZnO nano particles, prepared by the coprecipitation method with a size range of 47-68 nm, have been investigated as antimicrobial agents. Dilution antimicrobial susceptibility tests were carried out on two kinds of microbes (Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli) according to the standard method recommended by Clinical and Laboratory Standards Institute, CLSI-2015-M07-A10. The results showed that the antimicrobial effect is larger, the higher the concentration of ZnO nano particles in solution. It was also found that Gram-positive microbes are more sensitive to ZnO nano particles when compared with the Gram-negative ones. The minimum inhibitory concentration (MIC) for E. coli was found to be 50 mg/mL while that for S. aureus was 25 mg/mL. The minimum bactericidal concentration (MBC) was 1600 mg/mL for E. coli and 800 mg/mL for S. aureus.

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Microwave Assisted Synthesis and Antimicrobial Evaluation of Schiff Bases of Indole-3-aldehyde

E-Journal of Chemistry ◽

10.1155/2011/265329 ◽

2011 ◽

Vol 8 (1) ◽

pp. 305-311 ◽

Cited By ~ 6

Author(s):

Priyanka Kamaria ◽

N. Kawathekar ◽

Prerna Chaturvedi

Keyword(s):

Schiff Bases ◽

Antimicrobial Agents ◽

Microwave Assisted Synthesis ◽

Bacterial Strains ◽

Mass Spectral Analysis ◽

Gram Positive ◽

Gram Negative ◽

Mass Spectral ◽

Microwave Assisted ◽

Antimicrobial Evaluation

In order to develop new antimicrobial agents, a series of Schiff bases of indole-3-aldehyde were synthesized by microwave assisted synthesis by takingDMFas solvent and evaluated for their antimicrobial activity. All the synthesized compounds were characterized byIR,1HNMRand mass spectral analysis. All compounds were tested against five gram positive and five gram negative bacterial strains and one fungal strain. All compounds exhibited better activity against gram positive strains than against gram negative strains and the compounds were found more active againstS.aureusandB.subtilis.

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Construction of Leaderless-Bacteriocin-Producing Bacteriophage Targeting E. coli and Neighboring Gram-Positive Pathogens

Microbiology Spectrum ◽

10.1128/spectrum.00141-21 ◽

2021 ◽

Author(s):

Yoshimitsu Masuda ◽

Shun Kawabata ◽

Tatsuya Uedoi ◽

Ken-ichi Honjoh ◽

Takahisa Miyamoto

Keyword(s):

Antimicrobial Agents ◽

Host Strain ◽

Phage Resistance ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Gram Positive Bacteria ◽

T7 Phage

We demonstrated that we could combine LLB and phage to construct promising novel antimicrobial agents, LLB-phage. The first LLB-phage, lnqQ -T7 phage, can control the growth of both the Gram-negative host strain and neighboring Gram-positive bacteria while preventing the emergence of phage resistance in the host strain.

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