Antibiotic prophylaxis to prevent nosocomial infections in patients in intensive care units: evidence that struggle to convince practising clinicians.

BACKGROUND: Pneumonia is an important cause of mortality in intensive care units. The incidence of pneumonia in such patients ranges between 7 and 40%, and the crude mortality from ventilator associated pneumonia may exceed 50%. Although not all deaths in patients with this form of pneumonia are directly attributable to pneumonia, it has been shown to contribute to mortality in intensive care units independently of other factors that are also strongly associated with such deaths. OBJECTIVES: The objective of this review was to assess the effects of antibiotics for preventing respiratory tract infections and overall mortality in adults receiving intensive care. Search strategy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2003), which contains the Acute Respiratory Infections (ARI) Group specialised trials register; MEDLINE (January 1966 to September 2003); EMBASE (January 1990 to September 2003); proceedings of scientific meetings and reference lists of articles from January 1984 to December 2002. We also contacted investigators in the field. Selection criteria. Randomised trials of antibiotic prophylaxis for respiratory tract infections and deaths among adult intensive care unit patients. Data collection and analysis. At least two reviewers independently extracted data and assessed trial quality. RESULTS: Overall 36 trials involving 6922 people were included. There was variation in the antibiotics used, patient characteristics and risk of respiratory tract infections and mortality in the control groups. In 17 trials (involving 4295 patients) that tested a combination of topical and systemic antibiotic, the average rates of respiratory tract infections and deaths in the control group were 36% and 29% respectively. There was a significant reduction of both respiratory tract infections (odds ratio 0.35, 95% confidence interval [CI] 0.29-0.41) and total mortality (odds ratio 0.78, 95% CI 0.68-0.89) in the treated group. On average 5 patients needed to be treated to prevent one infection and 21 patients to prevent one death. In 17 trials (involving 2664 patients) that tested topical antimicrobials alone (or comparing topical plus systemic versus systemic alone) the rates of respiratory tract infections and deaths in the control groups were 30 and 26% respectively. There was a significant reduction of respiratory tract infections (odds ratio 0.52, 95% CI 0.43-0.63), but not in total mortality (odds ratio 0.97, 95% CI 0.81-1.16) in the treated group. CONCLUSIONS: A combination of topical and systemic prophylactic antibiotics reduces respiratory tract infections and overall mortality in adult patients receiving intensive care. A treatment based on the use of topical prophylaxis alone reduces respiratory infections, but not mortality. The risk of occurrence of resistance as a negative consequence of antibiotic use was appropriately explored only in the most recent trial by de Jonge, which did not show any such effect.

Antibiotics for preventing respiratory tract infections in adults receiving intensive care.

BACKGROUND: Pneumonia is an important cause of mortality in intensive care units. The incidence of pneumonia in such patients ranges between 7% and 40%, and the crude mortality from ventilator associated pneumonia may exceed 50%. Although not all deaths in patients with this form of pneumonia are directly attributable to infections, it has been shown to contribute to mortality in intensive care units independently of other factors that are also strongly associated with such deaths. OBJECTIVES: The objective of this review was to assess the effects of antibiotics for preventing respiratory tract infections and overall mortality in adults receiving intensive care. SEARCH STRATEGY: We searched Medline, the Cochrane Acute Respiratory Infections Group trials register, proceedings of scientific meetings and reference lists of articles from January 1984 to December 1999. We also contacted investigators in the field. SELECTION CRITERIA: Randomised trials of antibiotic prophylaxis for respiratory tract infections and deaths among adult intensive care unit patients. DATA COLLECTION AND ANALYSIS: Investigators were contacted for additional information. At least two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Overall 33 trials involving 5727 people were included. There was variation in the antibiotics used, patient characteristics and risk of respiratory tract infections and mortality in the control groups. In 16 trials (involving 3361 patients) that tested a combination of topical and systemic antibiotic, the average rates of respiratory tract infections and deaths in the control group were 36% and 30% respectively. There was a significant reduction of both respiratory tract infections (odds ratio 0.35, 95% confidence interval 0.29 to 0.41) and total mortality (odds ratio 0.80, 95% confidence interval 0.69 to 0.93) in the treated group. On average 5 patients needed to be treated to prevent one infection and 23 patients to prevent one death. In 17 trials (involving 2366 patients) that tested topical antimicrobials the rates of respiratory tract infections and deaths in the control groups were 28% and 26% respectively. There was a significant reduction of respiratory tract infections (odds ratio 0.56, 95% confidence interval 0.46 to 0.68) but not in total mortality (odds ratio 1.01, 95% confidence interval 0.84 to 1.22) in the treated group. REVIEWER'S CONCLUSIONS: A combination of topical and systemic prophylactic antibiotics can reduce respiratory tract infections and overall mortality in adult patients receiving intensive care. The design of the trials included in this systematic review does not allow to assess whether or not the treatment leads to antimicrobial resistance. Trials with different design are warranted to reliably address this question.

Antibiotics for preventing respiratory tract infections in adults receiving intensive care.

OBJECTIVES: Pneumonia is an important cause of mortality in intensive care units. The objective of this review was to assess the effects of antibiotics for preventing respiratory tract infections and overall mortality in adults receiving intensive care. SEARCH STRATEGY: We searched MEDLINE, proceedings of scientific meetings and reference lists of articles from January 1984 to September 1997. We also contacted investigators in the field. SELECTION CRITERIA: Randomised trials of antibiotic prophylaxis for respiratory tract infections and deaths among adult intensive care unit patients. DATA COLLECTION AND ANALYSIS: Trials were assessed for quality and investigators contacted for additional information. MAIN RESULTS: Overall 33 trials involving 5727 people were included. There was variation in the antibiotics used, patient characteristics and the risk of respiratory tract infections and mortality in the control groups. In 16 trials (involving 3493 patients) of a topical and systemic antibiotic combination, the average rates of respiratory tract infections and deaths in the control group were 33% and 28% respectively. There was a significant reduction of both respiratory tract infections (odds ratio 0.36, 95% confidence interval 0.30 to 0. 43) and total mortality (odds ratio 0.80, 95% confidence interval 0. 68 to 0.93). On average five patients needed to be treated to prevent one infection and 23 treated to prevent one death. In 17 trials (involving 2366 patients) of topical antimicrobials the rates of respiratory tract infections and deaths in the control groups were 30% and 24% respectively. There was a significant reduction of respiratory tract infections (odds ratio 0.57, 95% confidence interval 0.46 to 0.69) but not in total mortality (odds ratio 1.01, 95% confidence interval 0.84 to 1.22). REVIEWER'S CONCLUSIONS: A combination of topical and systemic prophylactic antibiotics can reduce respiratory tract infections and overall mortality in adult patients receiving intensive care. [This abstract has been prepared centrally.]

Antibiotic prophylaxis in intensive care units: meta-analyses versus clinical practice.

OBJECTIVE: At least 7 meta-analyses (MA) have been published since 1991 on the effectiveness of antibiotic prophylaxis in Intensive care units (ICU) patients, but controversy still remains about the overall effectiveness and risk-benefits profile of the treatment. This paper aims to summarise available data on effectiveness and discuss reasons why the controversy is still open and possible directions for future research. DESIGN: Review of available published MA on the effectiveness of various regimens of antibiotic prophylaxis with particular emphasis on the results of the individual patient data analysis published in 1998. SETTING: MA or randomised control trials (RCTs), published and unpublished, conducted anywhere in the world. PATIENTS AND PARTICIPANTS: Unselected adult ICU populations included in studies, published and unpublished, comparing different forms of antibiotic prophylaxis. MAIN OUTCOME MEASURE: Respiratory tract infections (RTIs) - however defined in individual studies - and total mortality. DATA SOURCES: General information from the 7 MAs published between 1991 and 1999 and detailed information from the MA published in the British Medical Journal in 1998 that reported data on 5727 patients enrolled in 33 RCTs; access to individual patients data could be obtained from 25 of 33 RCTs and allowed a confirmatory individual patient MA on 4343 patients. RESULTS: Pooled estimates from 16 RCTs (including 3361 patients) testing the effect of the topical and systemic antibiotic combination indicates a significant reduction of both RTIs (OR=0.35, 95% CI=0.29-0.41) and total mortality (OR=0.80, 95% CI=0.69-0.93). Five and 23 patients need to be treated to prevent one infection and one death, respectively, using this treatment. Pooled data from the 17 RCTs (including 2366 patients) testing the effect of a regimen based on topical antimicrobials indicated a statistically significant reduction in RTIs (OR=0.57, 95% CI=0.46-0.69) but not in total mortality (OR=1.01; 95% CI=0.84-1.22). Individual patient data analyses confirmed these results. CONCLUSIONS: After over 30 RCTs and seven MAs, there is strong evidence that antibiotic prophylaxis can reduce both RTIs and total mortality in ICUs patients in a statistically and clinically significant way. Concerns about the possible occurrence of antimicrobial resistance are not supported by available data but cannot, at the same time, be ruled out due to methodologic inadequacies of the studies carried out so far. Whether new trials are needed, and how they should be designed to answer the question of the potential for antibiotic resistance following widespread use of the treatment, are now the main issues to be settled. Convening an international panel of clinical experts and methodologists could be appropriate, in order to explore the best way to resolve the controversy that seems to be preventing the widespread use of a treatment that the best analysis of available data now indicates is effective.

Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials.

OBJECTIVE: To determine whether antibiotic prophylaxis reduces respiratory tract infections and overall mortality in unselected critically ill adult patients. DESIGN: Meta-analysis of randomised controlled trials from 1984 and 1996 that compared different forms of antibiotic prophylaxis used to reduce respiratory tract infections and mortality with aggregate data and, in a subset of trials, data from individual patients. SUBJECTS: Unselected critically ill adult patients; 5727 patients for aggregate data meta-analysis, 4343 for confirmatory meta-analysis with data from individual patients. MAIN OUTCOME MEASURES: Respiratory tract infections and total mortality. RESULTS: Two categories of eligible trials were defined: topical plus systemic antibiotics versus no treatment and topical preparation with or without a systemic antibiotic versus a systemic agent or placebo. Estimates from aggregate data meta-analysis of 16 trials (3361 patients) that tested combined treatment indicated a strong significant reduction in infection (odds ratio 0.35; 95% confidence interval 0.29 to 0.41) and total mortality (0.80; 0.69 to 0.93). With this treatment five and 23 patients would need to be treated to prevent one infection and one death, respectively. Similar analysis of 17 trials (2366 patients) that tested only topical antibiotics indicated a clear reduction in infection (0.56; 0.46 to 0.68) without a significant effect on total mortality (1.01; 0.84 to 1.22). Analysis of data from individual patients yielded similar results. No significant differences in treatment effect by major subgroups of patients emerged from the analyses. CONCLUSIONS: This meta-analysis of 15 years of clinical research suggests that antibiotic prophylaxis with a combination of topical and systemic drugs can reduce respiratory tract infections and overall mortality in critically ill patients. This effect is significant and worth while, and it should be considered when practice guidelines are defined.

Idebenone induces oxygen consumption rate modifications in aged rat brain mitochondria.

Idebenone effects on oxygen consumption in brain mitochondria, obtained from young and aged rats, were evaluated. Sixty rats (3 and 20 months of age) were treated for 3 months with 30 mg/kg of idebenone and compared to a placebo group. Brain mitochondria oxygen consumption rate was measured by polarographic techniques in basal (State 4), ADP-stimulated (State 3) and uncoupled conditions. When Complex I substrates (pyruvate + malate) were used, aged non-treated rats showed a significant increase in State 4 (175%) and uncoupled (152%) O(2)-uptake rate; no difference was found in State 3 respiration and in ADP/O(2) ratio. Idebenone was able to reverse these age-related effects probably acting on lipid peroxidation and the mitochondrial respiratory chain. No differences were found in mitochondrial enzymatic activities.

[Neurologic prognosis after cardiocirculatory arrest outside the hospital]. / Prognosi neurologica dopo arresto cardiocircolatorio extraospedaliero.

OBJECTIVE: To detect clinical signs and times of evaluation able to identify patients with good neurologic prognosis after out-of-hospital cardiac arrest. EXPERIMENTAL DESIGN: Retrospective study with 6 months-2 years of follow-up. SETTING: General intensive care unit, from 1993 to 1995. PATIENTS: Twenty-three patients aged 18-80 years, admitted with coma after out-of-hospital cardiac arrest, who survived at least 24 hours, without concomitant neurologic disorders. INTERVENTIONS: Neurologic outcome classification in three categories: complete neurologic recovery (A), moderate to severe disability (B), death without regained consciousness (C); A and B groups of patients are considered together as a "good neurologic outcome" group. MEASUREMENTS: Evaluation of some neurological parameters (GCS, motor response to pain, spontaneous motility, cranial nerve reflexes, spontaneous breathing, seizures) 6 hours (t0), 24 hours (t1), 72 hours (t2) and 7 days (t3) after arrest. RESULTS: Patients with good prognosis are identified with 100% sensitivity from the following parameters: at t0 none; at t1 motor response to pain, GCS > 4, absence of seizures; at t2 the former parameters, spontaneous breathing, brain stem reflexes, normal pupils; at t3 all the former parameters and spontaneous motility. Specificity is greater than 50% only for motor response to pain and GCS > 4. CONCLUSIONS: It is mostly impossible to state a neurologic prognosis in the first hours after cardiac arrest. The single predictor with the most reliable prognostic value is motor response to pain which allows, if present, to identify all the patients with a good prognosis as early as 24 hours after arrest.

Diagnosis of bacterial infection in the ICU: general principles.

Diagnosis and treatment of infection is a common procedure in the clinical management of patients in the ICU. Infection in the ICU is an important area for study, but requires well-defined and proven diagnostic criteria. The diagnosis of infection, like any diagnosis, is based on probability, and diagnostic criteria are therefore selected according to the physician's objectives and the acceptable margin of error. It is easier to diagnose correctly a full-blown, severe bacterial infection than one that is just beginning, and the same criteria cannot be used to identify accurately both conditions. We should diagnose an infectious complication at the time it needs treatment, but there is often a lack of clear objectives in the diagnostic process, and up to now, few reliable criteria have been available. Before considering the sensitivity and specificity of single diagnostic procedures it is important to trace the evolution of the infection. The problem may be approached in two steps, by describing or defining (i) the minimum level of severity of a probable infection which requires/justifies specific treatment as the first end-point of the diagnosis, and (ii) the ways the diagnosis may be confirmed using the best available procedure (which might not be always available or applicable in all cases in the short term).

Clinical and biochemical evidence of skeletal muscle involvement in galactose-1-phosphate uridyl transferase deficiency.

An 8-year-old boy with galactose-1-phosphate uridyl transferase (GALT) deficiency presented with hypotonia, muscle hypotrophy, hepatomegaly, bilateral cataract and mild mental retardation. Two brothers showed a GALT activity consistent with a homozygotic condition and both parents were found to be heterozygotes for this defect. Histological and ultrastructural examination of muscle biopsy specimens showed several necrotic fibres. GALT activity was undetectable in skeletal muscle and muscle tissue cultures; myotubes converted galactose to CO2 at a lower rate than controls. Galactose-1-phosphate was increased in the patient's red cells and muscle tissue. GALT deficiency, not previously described in muscle, may be of pathogenic relevance in determining the myopathic features present in GALT deficiency syndrome.