Early and Adequate Antibiotic Therapy in the Treatment of Severe Sepsis and Septic Shock

Severe sepsis and septic shock are conditions that pose difficult challenges to physicians and the health care system. In the past 10 years, a number of retrospective and prospective observational studies have shed light on the importance of a rapid and systematic approach to treatment of these conditions. A key component is early and appropriate use of antibiotics. Delay of even 6 h can dramatically increase hospital mortality. In addition, multivariate analyses have demonstrated that inappropriate initial antibiotics lead to worse outcomes. The treating physician can rapidly identify risk factors for initial inappropriate antibiotics at the bedside, such as recent antibiotic therapy or recent hospitalization. Organized antibiotic order sets have been shown to significantly improve timely appropriate antibiotic administration in septic patients. Finally, emerging laboratory data suggest that early in the course of septic shock, the pharmacokinetics of common broad spectrum antibiotics may be significantly altered due to increased volumes of distribution having dosing implications for antibiotics in septic shock.     

Early Antimicrobial Therapy in Severe Sepsis and Septic Shock

The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in the case fatality rates of serious infections, including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure, resulting in a lack of additional significant improvement in clinical effectiveness of antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money were expended on the development of novel nonantimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This article explores the possibility that the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials. Recognizing the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort.     

Appropriate Antibiotic Dosage Levels in the Treatment of Severe Sepsis and Septic Shock

Antibiotic treatment of critically ill patients remains a significant challenge. Optimal antibacterial strategy should achieve therapeutic drug concentration in the blood as well as the infected site. Achieving therapeutic drug concentrations is particularly difficult when infections are caused by some pathogens, such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative rods, because of their low susceptibility to antimicrobials. In sepsis, pharmacokinetics (PKs) of antibiotics are profoundly altered and may result in inadequate drug concentrations, even when recommended regimens are used, which potentially contribute to increased mortality and spread of resistance. The wide inter-individual PK variability observed in septic patients strongly limits the a priori prediction of the optimal dose that should be administered. Higher than standard dosages are necessary for the drugs, such as β-lactams, aminoglycosides, and glycopeptides, that are commonly used as first-line therapy in these patients to maximize their antibacterial activity. However, the benefit of reaching adequate drug concentrations on clinical outcome needs to be further determined.     

Immunoglobulins in Adult Sepsis and Septic Shock

For more than 30?years, intravenously administered immunoglobulins (ivIG) have been used to treat primary and secondary syndromes of immune deficiency. Increasing insight into pathomechanisms of severe sepsis and septic shock have led to the implementation of ivIG therapy in the strategies for adjunctive therapy in sepsis in both adults and children. Direct antitoxic effects, as well as indirect immunomodulatory mechanisms of ivIG have been described in the literature and were the basis for the rationale to use these substances in life-threatening infections and hyperinflammatory states. Several clinical trials have been performed, most of them as minor, investigator-initiated protocols. This review summarizes the results of clinical investigations and systematic meta-analyses that have implications for the development of therapeutic strategies, and international guidelines for the management of severe sepsis and septic shock in adult patients.     

Determinants of Hospital Mortality Among Patients with Sepsis or Septic Shock Receiving Appropriate Antibiotic Treatment

Septic shock affects 750,000 people annually, and accounts for 10 % of all deaths annually in the US. In recent years, outcomes in patients with septic shock have improved; however, mortality still remains high at 40 – 50 %. The use of early protocolized resuscitation goals have been associated with reduced mortality in septic shock. However, strong evidenced-based recommendations for the continued management of patients with septic shock in the ICU setting are currently lacking. Appropriate antibiotic therapy is the cornerstone of management in septic shock. Inappropriate antibiotic therapy can lead to treatment failures and adverse outcomes, including high risk of mortality. This article outlines other key factors that contribute to outcome in septic shock. It is challenging for physicians to optimize therapy when fixed patient features such as age and underlying comorbidity can negatively influence mortality. However, outcomes can also potentially be affected by physician management decisions including fluid balance, corticosteroid use, glucose control and adherence to protocols including early goal-directed therapy and infection-control measures. Certain pathogen virulence characteristics also adversely affect outcomes. We give an overview of the determinants of outcome in septic shock in the setting of appropriate antibiotic use.     

感染性休克急性肺损伤与CD11b表达相关性研究

目的探讨感染性休克急性肺损伤（ALI）患儿粒细胞（PMN）表面CD11b表达的变化及意义。方法用流式细胞术检测感染性休克ALI（观察组）患儿25例中性粒细胞CD11b,并与对照组20例和正常组20例进行比较。结果观察组中性粒细胞CD11b表达为（99.58±2.25）%,与对照组（86.30±6.33）%,和正常组（69.59±9.98）%比较,差异有统计学意义（P〈0.05）。重症期进展期9例患者与恢复的15例重症患者比较,差异无统计学意义（P〉0.05）。重症进展期患者的PMN绝对值与重症恢复期患者和正常组患者比较差异有统计学意义（P〈0.05）。结论CD11b作为白细胞激活的表面标记物,与肺组织的损伤密切相关,其表达水平可反映ALI患者病情的发展趋势。     

Cardiovascular Management of Septic Shock in 2012

Septic shock is a major cause of morbidity and mortality throughout the world. Source control, antimicrobial therapy, early goal-directed fluid resuscitation, and infusion of vasoactive pharmaceuticals remain the cornerstones of treatment. However, the cardiovascular management of septic shock is evolving. Basic science and clinical researchers have identified novel drug targets and are testing the efficacy of new therapeutic agents. For example, prevention of microvascular leak during septic shock is the focus of active investigations and may soon provide considerable benefit to patients. Among the important topics that will be discussed in this review are the following: the role of vascular endothelial dysfunction in microvascular leak, the impact of cytokines upon structural and functional proteins within the endothelial barrier and within the heart, and the ability of selective vasopressin 1a receptor agonists to minimize tissue edema and improve hemodynamic status.     

Timing for Initiation of Continuous Renal Replacement Therapy in Patients With Septic Shock and Acute Kidney Injury

The optimal timing for renal replacement therapy initiation in septic acute kidney injury (AKI) remains controversial. This study investigates the impact of early versus late initiation of continuous renal replacement therapy (CRRT) on organ dysfunction among patients with septic shock and AKI. Patients were dichotomized into “early” (simplified RIFLE Risk) or “late” (simplified RIFLE Injury or Failure) CRRT initiation. Patients with chronic kidney disease stage 5 or those on long‐term dialysis were excluded. Organ dysfunction was quantified by Sequential Organ Failure Assessment (SOFA) score. From January 2008 to June 2011, 120 patients fulfilled the inclusion criteria. Thirty‐one (26%) underwent “early” while 89 (74%) had “late” CRRT. No significant difference was noted between groups on improvement of total SOFA/non‐renal SOFA score or noradrenaline equivalent in the first 24 and 48 h after CRRT initiation. Dialysis requirement and mortality (at 28 days, 3 months and 6 months) did not differ. In conclusion, improvement of non‐renal SOFA score 48 h after CRRT correlated with SOFA score on CRRT initiation (P = 0.040) and APACHE IV risk of death (P = 0.000), but not estimated glomerular filtration rate on CRRT initiation (P = 0.377). Improvement of non‐renal SOFA score correlated with SOFA score on CRRT initiation and APACHE IV risk of death. However, this retrospective review cannot identify any significant clinical benefit of early CRRT initiation in patients presenting with septic shock and AKI.     

Pericardial Tamponade Masquerading as Septic Shock

A 53-year-old man with steroid dependent rheumatoid arthritis presented with fever and serous articular drainage. Oral antibiotics were initially prescribed. Subsequent hemodynamic instability was attributed to septic shock. Further evaluation revealed a pericardial effusion with tamponade. Pericardiocentesis of purulent fluid promptly corrected the hypotension. Proteus mirabilis was later isolated from both the infected joint and the pericardial fluid. This is the first report of combined Proteus mirabilis septic arthritis and purulent pericarditis. It documents the potential for atypical transmission of Gram-negative pathogens, to the pericardium, in patients with a high likelihood of preexisting pericardial disease. In immunocompromised patients, the typical signs and symptoms of pericarditis may be absent, and the clinical presentation of pericardial tamponade may be misinterpreted as one of septic shock. This case underscores the value of a careful physical examination and proper interpretation of ancillary studies. It further illustrates the importance of initial antibiotic selection and the need for definitive treatment of septic arthritis in immunocompromised patients. Potential Financial Conflicts of Interest: The authors do not have any potential financial conflicts of interest to disclose.