Clinical Infectious Diseases 2007;44:159–177

This document presents guidelines for developing institutional programs to enhance antimicrobial stewardship, an activity that includes appropriate selection, dosing, route, and duration of antimicrobial therapy. The multifaceted nature of antimicrobial stewardship has led to collaborative review and support of these recommendations by the following organizations: American Academy of Pediatrics, American Society of Health‐System Pharmacists, Infectious Diseases Society for Obstetrics and Gynecology, Pediatric Infectious Diseases Society, Society for Hospital Medicine, and Society of Infectious Diseases Pharmacists. The primary goal of antimicrobial stewardship is to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use, including toxicity, the selection of pathogenic organisms (such as Clostridium difficile), and the emergence of resistance. Thus, the appropriate use of antimicrobials is an essential part of patient safety and deserves careful oversight and guidance. Given the association between antimicrobial use and the selection of resistant pathogens, the frequency of inappropriate antimicrobial use is often used as a surrogate marker for the avoidable impact on antimicrobial resistance. The combination of effective antimicrobial stewardship with a comprehensive infection control program has been shown to limit the emergence and transmission of antimicrobial‐resistant bacteria. A secondary goal of antimicrobial stewardship is to reduce health care costs without adversely impacting quality of care.

Critical Care 2010;14:205

You are director of a large multi-disciplinary ICU. You have recently read that hospital-wide antibiotic stewardship programs have the potential to improve the quality and safety of care, and to reduce the emergence of multi-drug resistant organisms and overall costs. You are considering starting one of these programs in your ICU, but are concerned about the associated infrastructure costs. You are debating whether it is worth bringing the concept forward to your hospital’s administration to consider investing in.

Statement for debate
Antibiotic stewardship programs improve patient outcomes and cost-effectiveness in critically ill patients in the ICU.

Critical Care 2009, 13:235

Primary influenza pneumonia has a high mortality rate during pandemics, not only in immunocompromised individuals and patients with underlying comorbid conditions, but also in young, healthy adults. Clinicians should maintain a high index of suspicion for this diagnosis in patients presenting with influenza-like symptoms that progress quickly (2-5 days) to respiratory distress and extensive pulmonary involvement. The sensitivity of rapid diagnostic techniques in identifying infections with the pandemic 2009 H1N1v influenza strain is currently suboptimal. The most reliable real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) molecular testing is available in limited clinical settings. Despite 6 months of pandemic circulation, most novel H1N1v pandemic strains remain susceptible to oseltamivir. Ensuring an appropriate oxygenation and ventilation strategy, as well as prompt initiation of antiviral therapy, is essential in management.

Arch Surg 2009;144:359-366;  Click here for Invited critique

To conduct a meta-analysis of randomized controlled trials in which high inspired oxygen concentrations were compared with standard concentrations to assess the effect on the development of surgical site infections (SSIs).

Data sources
A systematic literature search was conducted using the MEDLINE, EMBASE, and Cochrane databases and included a manual search of references of original articles, poster presentations, and abstracts from major meetings (“gray” literature).

Study selection
Twenty-one of 2167 articles met the inclusion criteria. Of these, 5 randomized controlled trials (3001 patients) assessed the effect of perioperative supplemental oxygen use on the SSI rate. Studies used a treatment-inspired oxygen concentration of 80%. Maximum follow-up was 30 days.

Data extraction
Data were abstracted by 3 independent reviewers using a standardized data collection form. Relative risks were reported using a fixed-effects model. Results were subjected to publication bias testing and sensitivity analyses.

Data synthesis
Infection rates were 12.0% in the control group and 9.0% in the hyperoxic group, with relative risk reduction of 25.3% (95% confidence interval [CI], 8.1%-40.1%) and absolute risk reduction of 3.0% (1.1%-5.3%). The overall risk ratio was 0.742 (95% CI, 0.599-0.919; P = .006). The benefit from increasing oxygen concentration was greater in colorectal-specific procedures, with a risk ratio of 0.556 (95% CI, 0.383-0.808; P = .002).

Conclusions
Perioperative supplemental oxygen therapy exerts a significant beneficial effect in the prevention of SSIs. We recommend its use along with maintenance of normothermia, meticulous glycemic control, and preservation of intravascular volume perioperatively in the prevention of SSIs.

Critical Care 2009, 13:R83

The development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment. Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting. Until recently, no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction; however, over the past years, procalcitonin (PCT) is the first among a large array of inflammatory variables that offers this possibility. The present study aimed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients.

Methods
All patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible. Patients were randomly assigned to either a PCT-guided (study group) or a standard (control group) antibiotic regimen. Antibiotic therapy in the PCT-guided group was discontinued, if clinical signs and symptoms of infection improved and PCT decreased to <1 ng/ml or the PCT value was >1 ng/ml, but had dropped to 25 to 35% of the initial value over three days. In the control group antibiotic treatment was applied as standard regimen over eight days.

Results
A total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high-grade suspected infections were enrolled in this study. In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly. The control group comprised 53 patients with a standardized duration of antibiotic therapy over eight days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls (5.9 +/- 1.7 versus 7.9 +/- 0.5 days, P < 0.001) without negative effects on clinical outcome.

Conclusions
Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine.

Crit Care Med 2008; 36:1330-1349

To update the practice parameters for the evaluation of adult patients who develop a new fever in the intensive care unit, for the purpose of guiding clinical practice.

Participants
A task force of 11 experts in the disciplines related to critical care medicine and infectious diseases was convened from the membership of the Society of Critical Care Medicine and the Infectious Diseases Society of America. Specialties represented included critical care medicine, surgery, internal medicine, infectious diseases, neurology, and laboratory medicine/microbiology.

Evidence
The task force members provided personal experience and determined the published literature (MEDLINE articles, textbooks, etc.) from which consensus was obtained. Published literature was reviewed and classified into one of four categories, according to study design and scientific value.

Consensus process
The task force met twice in person, several times by teleconference, and held multiple e-mail discussions during a 2-yr period to identify the pertinent literature and arrive at consensus recommendations. Consideration was given to the relationship between the weight of scientific evidence and the strength of the recommendation. Draft documents were composed and debated by the task force until consensus was reached by nominal group process.

Conclusions
The panel concluded that, because fever can have many infectious and noninfectious etiologies, a new fever in a patient in the intensive care unit should trigger a careful clinical assessment rather than automatic orders for laboratory and radiologic tests. A cost-conscious approach to obtaining cultures and imaging studies should be undertaken if indicated after a clinical evaluation. The goal of such an approach is to determine, in a directed manner, whether infection is present so that additional testing can be avoided and therapeutic decisions can be made.

Crit Care Med 2009;37:1624-1633

To assess the usefulness of the “Candida score” (CS) for discriminating between Candida species colonization and invasive candidiasis (IC) in non-neutropenic critically ill patients. A rate of IC <5% in patients with CS <3 was the primary end point.

Design
Prospective, cohort, observational study.

Setting
Thirty-six medical-surgical intensive care units of Spain, Argentina, and France.

Patients
A total of 1,107 non-neutropenic adult intensive care unit patients admitted for at least 7 days between April 2006 and June 2007.

Measurements and main results
Clinical data, surveillance cultures for fungal growth, and serum levels of (1-3)-beta-d-glucan and anti-Candida antibodies (in a subset of patients) were recorded. The CS was calculated as follows (variables coded as absent = 0, present = 1): total parenteral nutrition x1, plus surgery x1, plus multifocal Candida colonization x1, plus severe sepsis x2. A CS >=3 accurately selected patients at high risk for IC. The colonization index was registered if >=0.5. The rate of IC was 2.3% (95% confidence interval [CI] 1.06-3.54) among patients with CS <3, with a linear association between increasing values of CS and IC rate (p <= 0.001). The area under the receiver operating characteristic curve for CS was 0.774 (95% CI 0.715-0.832) compared with 0.633 (95% CI 0.557-0.709) for CI. (1-3)-Beta-d-glucan was also an independent predictor of IC (odds ratio 1.004, 95% CI 1.0-1.007). The relative risk for developing IC in colonized patients without antifungal treatment was 6.83 (95% CI 3.81-12.45).

Conclusions
In this cohort of colonized patients staying >7 days, with a CS <3 and not receiving antifungal treatment, the rate of IC was <5%. Therefore, IC is highly improbable if a Candida-colonized non-neutropenic critically ill patient has a CS <3.

JAMA. 2009;301:1231-1241

Use of a chlorhexidine gluconate–impregnated sponge (CHGIS) in intravascular catheter dressings may reduce catheter-related infections (CRIs). Changing catheter dressings every 3 days may be more frequent than necessary.

Objective
To assess superiority of CHGIS dressings regarding the rate of major CRIs (clinical sepsis with or without bloodstream infection) and noninferiority (less than 3% colonization-rate increase) of 7-day vs 3-day dressing changes.

Design, setting, and patients
Assessor-blind, 2 x 2 factorial, randomized controlled trial conducted from December 2006 through June 2008 and recruiting patients from 7 intensive care units in 3 university and 2 general hospitals in France. Patients were adults (>18 years) expected to require an arterial catheter, central-vein catheter, or both inserted for 48 hours or longer.

Interventions
Use of CHGIS vs standard dressings (controls). Scheduled change of unsoiled adherent dressings every 3 vs every 7 days, with immediate change of any soiled or leaking dressings.

Main outcome measures
Major CRIs for comparison of CHGIS vs control dressings; colonization rate for comparison of 3- vs 7-day dressing changes.

Results
Of 2095 eligible patients, 1636 (3778 catheters, 28 931 catheter-days) could be evaluated. The median duration of catheter insertion was 6 (interquartile range [IQR], 4-10) days. There was no interaction between the interventions. Use of CHGIS dressings decreased the rates of major CRIs (10/1953 [0.5%], 0.6 per 1000 catheter-days vs 19/1825 [1.1%], 1.4 per 1000 catheter-days; hazard ratio [HR], 0.39 [95% confidence interval {CI}, 0.17-0.93]; P = .03) and catheter-related bloodstream infections (6/1953 catheters, 0.40 per 1000 catheter-days vs 17/1825 catheters, 1.3 per 1000 catheter-days; HR, 0.24 [95% CI, 0.09-0.65]). Use of CHGIS dressings was not associated with greater resistance of bacteria in skin samples at catheter removal. Severe CHGIS-associated contact dermatitis occurred in 8 patients (5.3 per 1000 catheters). Use of CHGIS dressings prevented 1 major CRI per 117 catheters. Catheter colonization rates were 142 of 1657 catheters (7.8%) in the 3-day group (10.4 per 1000 catheter-days) and 168 of 1828 catheters (8.6%) in the 7-day group (11.0 per 1000 catheter-days), a mean absolute difference of 0.8% (95% CI, –1.78% to 2.15%) (HR, 0.99; 95% CI, 0.77-1.28), indicating noninferiority of 7-day changes. The median number of dressing changes per catheter was 4 (IQR, 3-6) in the 3-day group and 3 (IQR, 2-5) in the 7-day group (P < .001).

Conclusions
Use of CHGIS dressings with intravascular catheters in the intensive care unit reduced risk of infection even when background infection rates were low. Reducing the frequency of changing unsoiled adherent dressings from every 3 days to every 7 days modestly reduces the total number of dressing changes and appears safe.

Critical Care Medicine 2009;37:32-38

To compare the incidence of ventilator-associated pneumonia (VAP) with or without isotonic saline instillation before tracheal suctioning. As a secondary objective, we compared the incidence of endotracheal tube occlusion and atelectasis.

Design
Randomized clinical trial.

Setting and patients
The study was conducted in a medical surgical intensive care unit of an oncologic hospital. We selected consecutive patients needing mechanical ventilation for >72 hrs. Patients were allocated into two groups: a saline group that received instillation of 8 mL of saline before tracheal suctioning and a control group which did not. VAP was diagnosed based on clinical suspicion and confirmed by bronchoalveolar lavage quantitative culture. The incidence of atelectasis on daily chest radiography and endotracheal tube occlusions were recorded. The sample size was calculated to a power of 80% and a type I error probability of 5%.

Measurements and main results
One hundred thirty patients were assigned to the saline group and 132 to the control group. The baseline demographic variables were similar between groups. The rate of clinically suspected VAP was similar in both groups. The incidence of microbiological proven VAP was significantly lower in the saline group (23.5% × 10.8%; p = 0.008) (incidence density/1.000 days of ventilation 21.22 × 9.62; p < 0.01). Using the Kaplan-Meier curve analysis, the proportion of patients remaining without VAP was higher in the saline group (p = 0.02, log-rank test). The relative risk reduction of VAP in the saline instillation group was 54% (95% confidence interval, 18%-74%) and the number needed to treat was eight (95% confidence interval, 5-27). The incidence of atelectases and endotracheal tube occlusion were similar between groups.

Conclusions
Instillation of isotonic saline before tracheal suctioning decreases the incidence of microbiological proven VAP.

PNAS 2008; (online before print)

The 1918 influenza pandemic was the most devastating outbreak of infectious disease in human history, accounting for about 50 million deaths worldwide. In addition to a significant number of cases of secondary bacterial pneumonia, this highly pathogenic strain of influenza A virus caused fatal primary viral pneumonia. To identify the viral gene(s) chiefly responsible for the high virulence of the 1918 virus, we generated a series of reassortants between the 1918 virus and a contemporary human H1N1 virus (A/Kawasaki/173/2001; K173) using reverse genetics. We then assessed their virulence properties in ferrets, a model closely resembling humans in terms of sensitivity to influenza virus infection and pattern of spread after intranasal inoculation. Substitution of single genes from the 1918 virus in the genetic background of K173 virus did not markedly alter the pattern of infection. That is, the reassortants grew well in nasal turbinates, but only sporadically (if at all) in the trachea and lungs. One exception was the 1918PB1/K173 reassortant, which replicated efficiently in lung tissues as well as the upper respiratory tract. A reassortant virus expressing the 1918 viral RNA polymerase complex (PA, PB1, and PB2) and nucleoprotein showed virulence properties in the upper and lower respiratory tracts of ferrets that closely resembled those of wild-type 1918 virus. Our findings strongly implicate the viral RNA polymerase complex as a major determinant of the pathogenicity of the 1918 pandemic virus. This new insight may aid in identifying virulence factors in future pandemic viruses that could be targeted with antiviral compounds.

NEJM 2009;360:20-31

Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) are infection-prevention measures used in the treatment of some patients in intensive care, but reported effects on patient outcome are conflicting.

Methods
We evaluated the effectiveness of SDD and SOD in a crossover study using cluster randomization in 13 intensive care units (ICUs), all in the Netherlands. Patients with an expected duration of intubation of more than 48 hours or an expected ICU stay of more than 72 hours were eligible. In each ICU, three regimens (SDD, SOD, and standard care) were applied in random order over the course of 6 months. Mortality at day 28 was the primary end point. SDD consisted of 4 days of intravenous cefotaxime and topical application of tobramycin, colistin, and amphotericin B in the oropharynx and stomach. SOD consisted of oropharyngeal application only of the same antibiotics. Monthly point-prevalence studies were performed to analyze antibiotic resistance.

Results
A total of 5939 patients were enrolled in the study, with 1990 assigned to standard care, 1904 to SOD, and 2045 to SDD; crude mortality in the groups at day 28 was 27.5%, 26.6%, and 26.9%, respectively. In a random-effects logistic-regression model with age, sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, intubation status, and medical specialty used as covariates, odds ratios for death at day 28 in the SOD and SDD groups, as compared with the standard-care group, were 0.86 (95% confidence interval [CI], 0.74 to 0.99) and 0.83 (95% CI, 0.72 to 0.97), respectively.

Conclusions
In an ICU population in which the mortality rate associated with standard care was 27.5% at day 28, the rate was reduced by an estimated 3.5 percentage points with SDD and by 2.9 percentage points with SOD

NEJM 2002;347:1549-1556

Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.

Methods
We conducted a prospective, randomized, double-blind, multicenter trial of adjuvant treatment with dexamethasone, as compared with placebo, in adults with acute bacterial meningitis. Dexamethasone (10 mg) or placebo was administered 15 to 20 minutes before or with the first dose of antibiotic and was given every 6 hours for four days. The primary outcome measure was the score on the Glasgow Outcome Scale at eight weeks (a score of 5, indicating a favorable outcome, vs. a score of 1 to 4, indicating an unfavorable outcome). A subgroup analysis according to the causative organism was performed. Analyses were performed on an intention-to-treat basis.

Results
A total of 301 patients were randomly assigned to a treatment group: 157 to the dexamethasone group and 144 to the placebo group. The base-line characteristics of the two groups were similar. Treatment with dexamethasone was associated with a reduction in the risk of an unfavorable outcome (relative risk, 0.59; 95 percent confidence interval, 0.37 to 0.94; P=0.03). Treatment with dexamethasone was also associated with a reduction in mortality (relative risk of death, 0.48; 95 percent confidence interval, 0.24 to 0.96; P=0.04). Among the patients with pneumococcal meningitis, there were unfavorable outcomes in 26 percent of the dexamethasone group, as compared with 52 percent of the placebo group (relative risk, 0.50; 95 percent confidence interval, 0.30 to 0.83; P=0.006). Gastrointestinal bleeding occurred in two patients in the dexamethasone group and in five patients in the placebo group.

Conclusions
Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of gastrointestinal bleeding.

Critical Care 2007,11

The aim of this study was to compare the early postoperative kinetics of procalcitonin (PCT) and C-reactive protein (CRP) serum levels in patients undergoing orthotopic liver transplantation (OLTx) with different immunosuppressive regimens.

Methods
PCT and CRP serum concentrations were measured in a group of 28 OLTx recipients before induction of anesthesia, at 4 and 8 hours following graft reperfusion, and daily until postoperative day 4. The same parameters were determined in 12 patients undergoing liver resection without conjunctive immunosuppressive therapy. Summary data are expressed as medians and ranges. Two-tailed nonparametric tests were performed and considered significant at p values of less than 0.05.

Results
The highest serum levels of PCT (median 3.0 ng/mL, minimum 1.4 ng/mL, maximum 13.9 ng/mL) were found in patients after OLTx without ATG therapy, on postoperative day 1. In patients with ATG administration, PCT levels were highly increased on postoperative day 1 (median 53.0 ng/mL, minimum 7.9 ng/mL, maximum 249.1 ng/mL). Thereafter, PCT values continuously decreased independently of further ATG administration in both groups of patients. No evidence of infection was present in either group. In 12 patients undergoing liver resection, peak serum PCT levels did not exceed 3.6 ng/mL. CRP serum levels in a group of patients with and without ATG therapy increased significantly on postoperative day 1, followed by a decrease. The highest levels of CRP were found in patients after liver resection on postoperative day 2 and decreased thereafter.

Conclusion
ATG administration to patients with OLTx is associated with an increase in serum PCT levels, with peak values on postoperative day 1, and this was in the absence of any evidence of infection. The results of this study indicate that ATG immunosuppressive therapy is a stimulus for the synthesis of PCT.

Am J Infect Dis. 2007;3:51-61

Surgical site infections (SSIs) are the most common type of nosocomial infection among surgical patients and are commonly caused by the patients own microbial flora. The prevalence of SSI is a major concern because of the associated increase in the incidence of morbidity and mortality, length of hospitalization and cost of care for postoperative patients. Key factors that determine whether patients are at risk for developing SSI include the inherent potential contamination of the surgical site, the duration of the operation and the individual patient susceptibility. Preventive preoperative measures that can reduce the risk of SSIs include administration of antimicrobial prophylaxis, proper utilization of skin antiseptic agents for both the patient and the surgical team, proper patient preoperative hair removal and the policy of canceling elective procedures when remote skin, urinary or pulmonary infections occur. This paper will review the efficacy and safety of available antiseptic agents, as well as discuss patient-specific prevention strategies.

Destruction by oxidation, or oxidative killing, is the most important defense against surgical pathogens and depends on the partial pressure of oxygen in contaminated tissue. An easy method of improving oxygen tension in adequately perfused tissue is to increase the concentration of inspired oxygen. We therefore tested the hypothesis that the supplemental administration of oxygen during the perioperative period decreases the incidence of wound infection.

Methods
We randomly assigned 500 patients undergoing colorectal resection to receive 30 percent or 80 percent inspired oxygen during the operation and for two hours afterward. Anesthetic treatment was standardized, and all patients received prophylactic antibiotic therapy. With use of a double-blind protocol, wounds were evaluated daily until the patient was discharged and then at a clinic visit two weeks after surgery. We considered wounds with culture-positive pus to be infected. The timing of suture removal and the date of discharge were determined by the surgeon, who did not know the patient’s treatment-group assignment.

Results
Arterial oxygen saturation was normal in both groups; however, the arterial and subcutaneous partial pressure of oxygen was significantly higher in the patients given 80 percent oxygen than in those given 30 percent oxygen. Among the 250 patients who received 80 percent oxygen, 13 (5.2 percent; 95 percent confidence interval, 2.4 to 8.0 percent) had surgical-wound infections, as compared with 28 of the 250 patients given 30 percent oxygen (11.2 percent; 95 percent confidence interval, 7.3 to 15.1 percent; P=0.01). The absolute difference between groups was 6.0 percent (95 percent confidence interval, 1.2 to 10.8 percent). The duration of hospitalization was similar in the two groups.

Conclusions
The perioperative administration of supplemental oxygen is a practical method of reducing the incidence of surgical-wound infections.

J Bone Joint Surg Am 2007;89:1605-1618

Surgical site infection is one of the most common complications that a surgeon encounters, with an infection occurring after approximately 780,000 operations in the United States each year. In the era of evidence-based medicine, it is in the best interest of patients and physicians to follow practices backed by basic science and clinical data. Unfortunately, standards of practice, even for the use of prophylactic antibiotics, are frequently not followed. In 2005, this journal made a commitment to present physicians with the literature to support the best available treatment for their patients with use of “recommendations for care” based on grades of recommendation in review articles. Grades of recommendation are intended to guide surgeons in determining whether they should change their practice on the basis of good (Grade-A) or fair (Grade-B) recommendations. Grade-A recommendations are generated from Level-I studies, whereas Grade-B recommendations are derived from Level-II or III research. A proposal is considered to be Grade C when there is poor or conflicting evidence concerning an intervention based on Level-IV or V studies, and Grade I indicates that evidence is inadequate to make a recommendation. We have provided these recommendations in this article, and we have also provided a level-of-evidence grade for individual studies. Methods for determining levels of evidence were introduced in this journal in 2003 and have been shown to be reliable and reproducible.

The current article synthesizes the best available evidence regarding use of preoperative antibiotics before elective and emergent orthopaedic operations, preoperative skin preparation of the patient and surgeon, operating-room issues, wound closure, operative drainage, and use of dressings in the hope that it will help physicians to reduce the incidence of postoperative wound infection. The management and effect of important patient factors such as smoking, nutritional status, immunocompromise, medications, cardiovascular status, obesity, and other major comorbidities will not be addressed here. The reader is instead referred to an excellent review of these topics by Gurkan and Wenz.

author email corresponding author email

Critical Care 2007, 11:R92

The aim of the present study was to evaluate the C-reactive protein level, the body temperature and the white cell count in patients after prescription of antibiotics in order to describe the clinical resolution of severe community-acquired pneumonia.

Methods
A cohort of 53 consecutive patients with severe community-acquired pneumonia was studied. The C-reactive protein levels, body temperature and white cell count were monitored daily.

Results
By day 3 a C-reactive protein level 0.5 times the initial level was a marker of poor outcome (sensitivity, 0.91; specificity, 0.59). Patients were divided according to their C-reactive protein patterns of response to antibiotics, into fast response, slow response, nonresponse, and biphasic response. About 96% of patients with a C-reactive protein pattern of fast response and 74% of patients with a slow response pattern survived, whereas those patients with the patterns of nonresponse and of biphasic response had a mortality rate of 100% and 33%, respectively (P < 0.001). On day 3 of antibiotic therapy, a decrease in C-reactive protein levels by 0.31 or more from the previous day's level was a marker of good prognosis (sensitivity, 0.75; specificity, 0.85).

Conclusion
Daily C-reactive protein measurement after antibiotic prescription is useful in identification, as early as day 3, of severe community-acquired pneumonia patients with poor outcome. The identification of the C-reactive protein pattern of response to antibiotic therapy was useful in the recognition of the individual clinical course, either improving or worsening, as well as the rate of improvement, in patients with severe community-acquired pneumonia.

Critical Care 2007, 11:R35 

The aim of this study was to evaluate the impact of an intensive care unit (ICU)-acquired infection on long-term survival and quality of life.

Methods
Long-term survival was prospectively evaluated among hospital survivors who had stayed in a mixed university level ICU for longer than 48 hours during a 14-month study period in 2002-2003. Health-related quality of life was assessed with the five-dimensional EuroQol (EQ-5D) questionnaire in January 2005.

Results
Of the 272 hospital survivors, 83 (30.5 %) died after discharge during the follow-up period. The median follow-up time after hospital discharge was 22 months. Long-term mortality did not differ between the patients without infection on admission who developed or did not develop an ICU-acquired infection, 21.7 % vs. 26.9 % (p=0.41), or between the patients with infection on admission and with (35.1 %) or without (27.6 %) an ICU-acquired infection (p=0.40). The EQ-5D response rate was 75 %. The patients who developed an ICU-acquired infection had significantly more problems in self-care (50%) than those without an ICU-acquired infection (32%, p= 0.004), while multivariate analysis did not show ICU-acquired infection to be a significant risk factor for diminished self-care; odds ratio (OR) 1.71 (95 % confidence interval: 0.65-4.54), p= 0.28. The general health status did not differ between those with and those without an ICU-acquired infection as measured by EQ-VAS: the mean EQ-VAS value was 60.2 (standard deviation (SD) 21) for the patients without ICU-acquired infection, and 60.6 (SD 22) for those with ICU-acquired infection. The current general level of health compared to the status before ICU admission did not differ between the groups either. Only 36 % of those employed resumed their previous jobs.

Conclusion
ICU-acquired infection did not have an impact on long-term survival. The patients with ICU-acquired infection experienced more often problems in self-care than those without ICU infection, but ICU-acquired infection was not a significant risk factor for diminished self-care in multivariate analysis.

Critical Care 2006, 10:R153

Nosocomial pneumonia is a major source of morbidity and mortality after severe burns. Burned patients suffer trace element deficiencies, depressed antioxidant and immune defences. The study aimed at determining the effect of trace element supplementation on nosocomial or ICU-acquired pneumonia.

Material and methods
Two consecutive, randomised double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21intervention) admitted to the Burn centre of a University hospital were combined. Intervention: intravenous trace element supplements (copper 2.5-3.1 mg/d, selenium 315-380 mcg/d, zinc 26.2-31.4 mg/d) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteremia, wound, urine, other), wound healing, length of ICU stay. Plasma and skin (study 2) concentrations of Se and Zn were determined on days 3, 10 and 20.

Results
The patients, aged 42+/-15 years were burned on 46+/-19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalization of plasma selenium, zinc and glutathione peroxidase concentrations in plasma and skin in the trace element supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5+/-1.2 to 2.0+/-1.0 episodes per patient in placebo group (p <0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus 7 (33%) patients respectively (p<0.001), and of ventilator-associated pneumonia from 13 to 6 episodes respectively (p=0.023).

Conclusions
Enhancing trace element status and antioxidant defences by selenium, zinc and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill severely burned patients.

Critical Care Medicine 2006;34:2758-2765

To identify factors associated with mortality and morbidity among adults admitted to intensive care units (ICUs) for pneumococcal meningitis, particularly the impact of delayed antibiotic administration.

Design
We conducted a prospective, multicenter, observational study of 156 consecutive adults hospitalized for pneumococcal meningitis. We analyzed parameters associated with 3-month survival.

Setting
Fifty-six medical and medical-surgical ICUs in France.

Results
Of the 148 strains isolated, 56 (38%) were nonsusceptible to penicillin G. At 3 months after ICU admission, the mortality rate was 33% (51/156), and 34% of survivors (36/105) had neurologic sequelae. Multivariate analysis identified three variables as independently associated with 3-month mortality: Simplified Acute Physiology Score II (odds ration [OR], 1.12; 95% confidence interval [CI], 1.072-1.153; p = .002); isolation of a nonsusceptible strain (OR, 6.83; 95% CI, 2.94-20.8; p < 10-4), and an interval of >3 hrs between hospital admission and administration of antibiotics (OR, 14.12; 95% CI, 3.93-50.9; p < 10-4). In contrast, a cerebrospinal fluid leukocyte count >103 cells/µL had a protective effect (OR, 0.30; 95% CI, 0.10-0.944; p = 0.04).

Conclusions
Independent of severity at the time of ICU admission, isolation of penicillin-nonsusceptible strains and a delay in antibiotic treatment following admission were predictors of mortality among patients with pneumococcal meningitis.