Serious Infections in Intensive Care Units

Jean Chastre, M.D., Jean-Louis Teboul, M.D., Ph.D.

In recent years, serious infections, including those caused by multidrug-resistant and/or difficult-to-treat microorganisms, have assumed increasing importance in the intensive care setting and have been described in outbreaks in association with intravenous catheters, mechanical ventilation, and other invasive devices. This increased incidence is due, in part, to the dramatic differences in the profile of patients admitted and cared for in intensive care units (ICUs) over the past 20 years: patients are now older with more severe underlying disease, and medical care is more likely to include invasive devices, major surgery, prolonged antimicrobial treatment, and/or immunosuppressive therapy, which increase host susceptibility to bacterial infection and mortality. This issue of Seminars in Respiratory and Critical Care Medicine includes contributions from world-renowned experts in the field of infectious diseases, who have provided state-of-the-art information on important aspects of the clinical management of these dreadful diseases.

In the first article, Dr. Doyle and colleagues describe contemporary rates, sites, and pathogens responsible for common ICU-acquired infections. Emerging pathogens are outlined, including a systematic review of published ICU infection outbreaks from 2005 to 2010. Finally, the authors examine how interventions and antibiotic usage within ICUs can influence the epidemiology of infection.

Central venous catheters (CVCs) are inserted in about half of the ICU patients, leading to a rate of more than three bloodstream infections for 1000 CVC-days in many hospitals. In contrast to other nosocomial infections, many of the risk factors are device related, suggesting that catheter-related bloodstream infections are preventable if rigorous policies are adopted, as reviewed in depth by Dr. Timsit and colleagues. Unfortunately, cross-sectional surveys performed recently have found that very simple recommendations, such as cutaneous antisepsis with alcoholic preparation, maximal barrier precaution, a strict policy of catheter maintenance, and ablation of useless catheters, are not systematically followed, particularly outside the ICUs.

Multidrug-resistant, nonfermenting gram-negative bacilli, especially Pseudomonas aeruginosa and Acinetobacter baumannii, have emerged in the last decades as a major cause of health care–associated infections and nosocomial outbreaks. In some recent surveys, approximately one quarter of P. aeruginosa isolates and one third of A. baumannii isolates that caused ventilator-associated pneumonia (VAP) were resistant to carbapenems, with some strains being resistant to all antibiotics. New options for treating these infections include improved modalities of administration based on pharmacokinetic/pharmacodynamic properties of antimicrobial agents. As underlined by Drs. Sánchez, Gattarello, and Rello, achieving adequate therapy requires using not only the correct antibiotic but also the optimal dose and the correct route of administration (oral, intravenous, or aerosol). Many antibiotics in the ICU are incorrectly used, being administered at too low doses, promoting the emergence of resistant strains and decreasing their potential efficacy.

In the next article, Drs. Echeverria, Kett, and Azoulay provide up-to-date information regarding how to improve the diagnosis and management of Candida infection in the ICU. Because blood culture sensitivity for identifying Candida is low, systemic antifungal therapy should probably be utilized in patients at increased risk for invasive candidiasis and those with unresolving sepsis despite appropriate management.

Although infectious complications in severe, acute pancreatitis are associated with considerable morbidity and mortality, their diagnosis and treatment are difficult. As underlined by Dr. De Waele, overprescription of prophylactic antibiotics is not only ineffective but also may lead to the emergence of resistant strains that are ultimately more difficult to treat. Only patients with documented infected pancreatic necrosis should typically be treated with antibiotics.

In the following article, Dr. Luyt and colleagues make a strong case for shortening the duration of antimicrobial therapy in most patients with VAP, based on serial measurements of the procalcitonin level in the blood. As demonstrated by two randomized, controlled trials, early antibiotic discontinuation should be considered for VAP patients whose serum procalcitonin concentrations have decreased to <0.5 ng/mL or by ≥80%, compared with the first peak concentration.

In 2009, the influenza A(H1N1) pandemic spread worldwide in a few weeks, being responsible for acute respiratory failure and acute respiratory distress syndrome (ARDS) in many patients. Despite attempts to optimize ventilator settings, some patients developed refractory hypoxemia or hypercapnia and received extracorporeal membrane oxygenation (ECMO) as a rescue therapy. The indications, modalities, and results of this therapy are detailed in the article by Drs. Combes and Pellegrino.

The mortality rate of severe sepsis and septic shock remains high despite the impressive technological and pharmacological progress made over the last 2 decades. Recent studies emphasize the major role of early recognition of severe sepsis and of rapid introduction of aggressive hemodynamic therapy (fluids, vasopressors) in addition to early antibiotic therapy. In this issue, Drs. Levinson, Casserly, and Levy discuss how implementation of the Surviving Sepsis Campaign guidelines in the first (“golden”) hours of the development of sepsis can significantly decrease morbidity and mortality of this disease.

A large proportion of patients with severe sepsis or septic shock develop myocardial dysfunction during the early phase of the disease. In their article, Dr. Jozwiak and colleagues review the major mechanisms responsible for the development of sepsis-related myocardial dysfunction and the methods used at the bedside for diagnosing and monitoring this specific abnormality. They also propose a decision tree regarding the appropriateness of treatment with an inotropic agent such as dobutamine.

Implementation of active antibiotic stewardship programs has emerged as an important way to optimize antimicrobial use and reduce costs and bacterial resistance in the ICU. Dr. Arnold and colleagues detail how some new molecular diagnostic techniques aimed at more rapidly detecting microorganisms may help in selecting initially appropriate antimicrobial therapy and facilitate deescalation.

Infections due to P. aeruginosa and MRSA are common in critically ill patients. Both bacteria contain a variety of virulence products or systems that render treatment of infections due to these organisms difficult. Because of the limited possibilities to kill P. aeruginosa and MRSA with antibiotics, there is growing interest in treating infections due to these microorganisms by targeting specific virulence products or systems. Potential interests of these new developments are reviewed in depth by Drs. Wiener-Kronish and Pittet.

Considerable debate persists about the effectiveness of selective decontamination of the digestive tract (SDD) and selective oral decontamination (SOD) to prevent infection in mechanically ventilated patients and about the potential risk of increased antibiotic resistance. Reviewing all the literature dealing with these issues, Drs. van Essen and de Jonge clearly show that in areas with low prevalence of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE), SDD/SOD should be advocated as standard treatments of mechanically ventilated patients. In contrast, in areas where MRSA and VRE are endemic, SDD/SOD should still be considered experimental treatments.

In summary, we are convinced that the information presented in this issue of Seminars in Respiratory and Critical Care Medicine will be instructive and of practical value to our readers and a valuable resource for clinicians providing care for patients with serious infections.