Meningococcal disease deaths and the frequency of antibiotic administration delays

Lala, Hamish M; Mills, Graham; Barratt, K; Bonning, John; Manikkam, Noel E.; Martin, Diana

doi:10.1016/j.jinf.2006.10.050

Cited by 18 publications

(7 citation statements)

References 15 publications

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“…One study has demonstrated that increasing severity of the clinical syndrome (fulminant septic shock vs. meningitis or sepsis without shock) is associated with a higher burden of neisserial DNA and LPS in plasma of patients with meningococcal disease 39 . In another study, logistic regression analysis demonstrated that blood bacterial load predicted outcome of meningococcal shock 40 . Delays in antimicrobial therapy were associated with outcome only in univariate analysis and all deaths were associated with blood bacterial loads of >10 5 cfu/mL bacteria.…”

Section: A New Composite Model: Integrating Shockmentioning

confidence: 99%

An alternate pathophysiologic paradigm of sepsis and septic shock

Kumar

2013

Virulence

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The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role.

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Section: A New Composite Model: Integrating Shockmentioning

confidence: 99%

An alternate pathophysiologic paradigm of sepsis and septic shock

Kumar

2013

Virulence

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“…The two central themes to this new paradigm are: septic shock represents a unique clinical entity to other forms of sepsis, and the duration of hypotension prior to the administration of appropriate antimicrobial therapy is a surrogate marker for increasing microbial burden of the organism. In both animal models and people with critical illness related infections it has been demonstrated the longer the duration of hypotension prior to antimicrobial administration the greater the bacterial load and, consequently, a higher bacterial load is associated with increased morbidity and mortality in the presence of septic shock . Kumar proposes the rapid clearance of bacterial pathogens is a key determinant affecting patient outcomes in septic shock.…”

Section: Introductionmentioning

confidence: 99%

The role of antimicrobials in the treatment of sepsis and critical illness‐related bacterial infections: Examination of the evidence

Keir

Dickinson²

2015

J Vet Emergen Crit Care

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“…The evidence for this proposal lay in stark clinical features (hypotension, lactic acidosis, substantial exhaustion of compensatory physiologic responses) and high (>50%) mortality in septic shock, in contrast to the milder clinical features and lower mortality (15%) of sepsis or severe sepsis, 28 the different profiles of inflammatory mediators in these conditions 29,30 and evidence of immune dysfunction in septic shock compared with sepsis without shock. 31 The second major implication is that delays in initiation of appropriate antimicrobial therapy is associated with a higher microbial load, [32][33][34] and that organism burden is associated with increased morbidity and mortality in serious infections. 6,[35][36][37][38][39][40][41] Hence, early appropriate antimicrobial therapy with acceleration of the speed of bacterial clearance should be associated with both improved morbidity and mortality.…”

Section: A Composite Model: Integrating Infection and Shockmentioning

confidence: 99%

Optimizing Antimicrobial Therapy of Sepsis and Septic Shock: Focus on Antibiotic Combination Therapy

Vázquez-Grande

Kumar

2015

Semin Respir Crit Care Med

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Severe sepsis and septic shock with sepsis-associated multiple organ failure represent the major causes of infection-associated mortality and remain the most common cause of death in intensive care units (ICUs) of developed countries. They account for 10 to 15% of all ICU admissions and 25% of sepsis cases 1 ; up to 50 to 75% of severe sepsis cases progress to septic shock. 2 Septic shock alone represents 5 to 8% of all ICU admissions. 3 Historically, the mortality associated with sepsis and septic shock has been 50 to 75%. [4][5][6] This decreased after the development of modern antimicrobial therapies, starting with penicillin in the early 1940s. Since then sepsis-associated mortality has fallen to the 30 to 50% range. 4,5 Since the development of modern antimicrobials, bacterial pathogens have continuously evolved under their selective pressure. There has also been a gradual increase in the incidence of sepsis over the intervening decades. 7 Current estimates suggest a doubling of total cases of severe sepsis in United States by 2050 (from the actual 800,000 cases per year AbstractThere has been little improvement in septic shock mortality in the past 70 years, despite ever more broad-spectrum and potent antimicrobials. In the past, resuscitative elements have been the primary area of clinical septic shock management and research. The question of the optimal use of antimicrobial therapy was relatively ignored in recent decades. This review explores the pathophysiology of sepsis in an attempt to produce a better understanding and define key determinants of antimicrobial therapy response in septic shock. Optimizing existing antimicrobials delivery can drive significant improvements in the outcome of sepsis and septic shock. Inappropriate antimicrobial selection and dosing or delays in the administration substantially increase mortality and morbidity in life-threatening infections. Definitive combination therapy (where a pathogen known to be susceptible to a given agent is additionally covered by another agent) remains controversial. Although some in vitro studies, animal models, and clinical studies of infection including endocarditis, gram-negative bacteremia, and neutropenic infections have supported combination therapy, the potential clinical benefit in other severe infections has been questioned. Several meta-analyses have failed to demonstrate improvement of outcome with combination therapy in immunocompetent patients with sepsis and/or gram-negative bacteremia. These meta-analyses did not undertake subgroup analyses of the septic shock population. This article reviews the existing evidence supporting combination therapy for severe infections, sepsis, and septic shock.

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Meningococcal disease deaths and the frequency of antibiotic administration delays

Cited by 18 publications

References 15 publications

An alternate pathophysiologic paradigm of sepsis and septic shock

An alternate pathophysiologic paradigm of sepsis and septic shock

The role of antimicrobials in the treatment of sepsis and critical illness‐related bacterial infections: Examination of the evidence

Optimizing Antimicrobial Therapy of Sepsis and Septic Shock: Focus on Antibiotic Combination Therapy

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