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Introduction Diabetic patients may develop acute lung injury less often than non-diabetics; a fact that could be partially ascribed to the usage of antidiabetic drugs, including metformin. Metformin exhibits pleiotropic properties which make it potentially beneficial against lung injury. We hypothesized that pretreatment with metformin preserves alveolar capillary permeability and, thus, prevents ventilator-induced lung injury. Methods Twenty-four rabbits were randomly assigned to pretreatment with metformin (250 mg/Kg body weight/day per os) or no medication for two days. Explanted lungs were perfused at constant flow rate (300 mL/min) and ventilated with injurious (peak airway pressure 23 cmH2O, tidal volume ≈17 mL/Kg) or protective (peak airway pressure 11 cmH2O, tidal volume ≈7 mL/Kg) settings for 1 hour. Alveolar capillary permeability was assessed by ultrafiltration coefficient, total protein concentration in bronchoalveolar lavage fluid (BALF) and angiotensin-converting enzyme (ACE) activity in BALF. Results High-pressure ventilation of the ex-vivo lung preparation resulted in increased microvascular permeability, edema formation and microhemorrhage compared to protective ventilation. Compared to no medication, pretreatment with metformin was associated with a 2.9-fold reduction in ultrafiltration coefficient, a 2.5-fold reduction in pulmonary edema formation, lower protein concentration in BALF, lower ACE activity in BALF, and fewer histological lesions upon challenge of the lung preparation with injurious ventilation. In contrast, no differences regarding pulmonary artery pressure and BALF total cell number were noted. Administration of metformin did not impact on outcomes of lungs subjected to protective ventilation. Conclusions Pretreatment with metformin preserves alveolar capillary permeability and, thus, decreases the severity of ventilator-induced lung injury in this model.

We compliment Dr Muller and colleagues [1] for their experiment on the protective role of simvastatin against ventilator-induced lung injury (VILI). Their results are in line with those of a relevant study published recently by our research team; we also showed that pretreatment with statins (specifically atorvastatin) attenuates VILI [2]. By synthesizing the findings of the above contributions [1,2], one could make several points. First, given that Muller and colleagues administered simvastatin [1] while we chose atorvastatin [2], it seems that the observed benefit is a class-specific rather than a drug-specific effect; that is, it may apply to the whole class of statins. Second, the prevention of VILI by statins seems not to be species-specific; indeed, our colleagues employed mice [1], while we preferred rabbits [2]. Third, while the first study used female animals [1] and the second study used male animals [2], there were no differences in the produced results; thus, statins seem to be useful for the prevention of VILI in both sexes. This observation is important given the ongoing interest in the possibility that drug responses may differ by sex [3]. Fourth, by using different markers, both studies noted that administration of statins reduced VILI-associated hyperpermeability [1,2]. Indeed, the German group [1] used as a marker of lung permeability the human-serum-albumin bronchoalveolar lavage/plasma ratio, while we used both lung edema and ultrafiltration coefficient (Kf, c). Finally, Muller and colleagues implemented a 6-hour model of injurious mechanical ventilation to show that statins ameliorate pulmonary inflammation [1], whereas we focused on the very acute phase of lung injury, when mechanical phenomena rather than inflammation may best explain the injury [2]. In conclusion, we believe that the two papers [1,2] combined provide strong experimental evidence that a dose of statin as high as 20 mg/kg body weight administered before the induction of mechanical ventilation may protect against VILI and relevant clinical trials are thus fully justified.

Previous animal studies revealed that administration of statins ameliorates lung injury following endotoxin exposure or ischemia-reperfusion. In this experiment, we endeavored to investigate whether pretreatment with atorvastatin confers protection from lung injury caused by high-pressure/high-tidal-volume ventilation.

Nosocomial infections are a major worldwide cause of death and disability, infection control programs are effective in limiting these infections, especially those acquired in the intensive care unit. The development of the world wide web has provided health care professionals with immediate access to continuously updated information in the field of infection control. We sought to identify websites that contain information on nosocomial infection control by using popular internet search engines, such as Google, Yahoo and AltaVista, and by reviewing relevant publications identified in the PubMed and Current Contents databases. Only those sites that were English language, open access, and developed by a government, academic institution, or national or international scientific association were eligible for inclusion. From a vast number of internet sites initially identified, we selected 49 that provide information on infection control for inclusion in our list of practical and relevant internet resources. Several sites provide general information on infection control practices, whereas others focus on one or a few specific infection(s). We provide health care professionals with a timely and succinct list of open access internet resources that contain information regarding the prevention and control of nosocomial infections in order to help in the dissemination of relevant information and so contribute to the limitation of such hazards.

Introduction The administration of prophylactic antibiotics via the respiratory tract is one of several strategies for the prevention of intensive care unit (ICU)-acquired pneumonia. We systematically examined the available evidence regarding the effect of prophylactic antibiotics administered via the respiratory tract on the development of ICU-acquired pneumonia, mortality, colonization of the respiratory tract, emergence of antimicrobial resistance, and toxicity. Methods We searched the PubMed database (January 1950 to September 2005) and references from relevant articles to identify trials that provided comparative data regarding the above-mentioned outcomes. Two investigators independently performed the data extraction to calculate the effect of the studied intervention on clinically relevant outcomes. Results Our meta-analysis includes 8 comparative trials (5 randomized controlled trials (RCTs) and 3 non-randomized trials) studying gentamicin (3 trials), polymyxins (3 trials), tobramycin (1 trial), and ceftazidime (1 trial) that studied 1,877 patients. Our primary analysis, which included the 5 RCTs, revealed that ICU-acquired pneumonia was less common in the group of patients that received the antibiotic prophylaxis (odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.32–0.76). No difference in mortality was found between the compared groups (OR = 0.86, 95% CI 0.55–1.32). Data were too limited to permit an analysis of colonization with Pseudomonas aeruginosa. A secondary analysis, adding the three non-randomized comparative trials, did not reveal substantially different results regarding ICU-acquired pneumonia and mortality, while fewer patients were colonized with P. aeruginosa in the group that received prophylaxis, compared to the group of patients that received no prophylaxis (OR = 0.51, 95% CI 0.30–0.86). No serious drug-related toxicity was noted. No meaningful systematic analysis of the evidence regarding the emergence of resistance could be performed in the studies included in our meta-analysis. Conclusion The limited available evidence supports that prophylactic administration of antibiotics via the respiratory tract is associated with reduction of occurrence of ICU-acquired pneumonia. However, there is evidence from non-comparative studies that this preventive strategy may lead to an increase in the emergence of resistant bacteria. Thus, further investigation, at least in ICU patients at high risk for development of ICU-acquired pneumonia, is warranted, including a more systematic evaluation of issues related to the emergence of resistance.

Introduction There has been a continuing controversy about whether infection with Acinetobacter baumannii increases morbidity and mortality independently of the effect of other confounding factors. Methods We performed a systematic review of matched casecontrol and cohort studies examining the mortality attributable to infection with or acquisition of A. baumannii (infection or colonization). We included in our review studies that compared mortality and/or morbidity of patients with acquisition of or infection with A. baumannii (cases) with the outcomes of matched patients without A. baumannii isolation from clinical specimens (controls). The relevant studies were identified from searches of the PubMed and the Cochrane Library databases. Two independent reviewers performed the literature search, study selection, and data extraction from nine identified relevant studies. Results The attributable mortalities, in the hospital and in the intensive care unit, of patients with A. baumannii infection in six matched case-control studies included in our review ranged from 7.8% to 23% and from 10% to 43%, respectively. In addition, a statistically significantly higher mortality was reported for patients with A. baumannii acquisition; that is, colonization or infection (cases) compared with controls without such an acquisition in all four reviewed studies that reported data on this comparison.

Pineda and colleagues [1] published a well-performed metaanalysis of four randomized controlled trials (RCTs) [2-5] exploring the effect of oral chlorhexidine (CHX) application on the incidence of nosocomial pneumonia (NP) in mechanically ventilated patients. They concluded that oral CHX decontamination did not reduce the incidence of NP in such patients; however, they clearly stated that the combined sample size of the four RCTs included may be inadequate for detecting important differences. Meanwhile, additional important data on this issue have been published; updating the findings of the above meta-analysis [1] is therefore warranted. In detail, Koeman and colleagues [6] enrolled intensive care unit patients requiring mechanical ventilation in a large, multicenter, double-blind, three-arm RCT. Ventilator-associated pneumonia developed in 13 out of 127 (10%) patients treated with 2% CHX paste, in 16 out of 128 (13%) subjects treated with 2% CHX and 2% colistin paste, and in 23 out of 130 (18%) placebo recipients. One additional RCT (in fact, a pilot study) conducted by Bopp and colleagues [7] in patients intubated in the intensive care unit reported that neither of two (0%) patients treated with 0.12% CHX gluconate and one out of three (33%) patients who received standard oral care (with soft foam swab and hydrogen peroxide) developed NP.

The administration of prophylactic antibiotics via the respiratory tract is one of several strategies for the prevention of intensive care unit (ICU)-acquired pneumonia. We systematically examined the available evidence regarding the effect of prophylactic antibiotics administered via the respiratory tract on the development of ICU-acquired pneumonia, mortality, colonization of the respiratory tract, emergence of antimicrobial resistance, and toxicity. We searched the PubMed database (January 1950 to September 2005) and references from relevant articles to identify trials that provided comparative data regarding the above-mentioned outcomes. Two investigators independently performed the data extraction to calculate the effect of the studied intervention on clinically relevant outcomes. Our meta-analysis includes 8 comparative trials (5 randomized controlled trials (RCTs) and 3 non-randomized trials) studying gentamicin (3 trials), polymyxins (3 trials), tobramycin (1 trial), and ceftazidime (1 trial) that studied 1,877 patients. Our primary analysis, which included the 5 RCTs, revealed that ICU-acquired pneumonia was less common in the group of patients that received the antibiotic prophylaxis (odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.32–0.76). No difference in mortality was found between the compared groups (OR = 0.86, 95% CI 0.55–1.32). Data were too limited to permit an analysis of colonization with Pseudomonas aeruginosa. A secondary analysis, adding the three non-randomized comparative trials, did not reveal substantially different results regarding ICU-acquired pneumonia and mortality, while fewer patients were colonized with P. aeruginosa in the group that received prophylaxis, compared to the group of patients that received no prophylaxis (OR = 0.51, 95% CI 0.30–0.86). No serious drug-related toxicity was noted. No meaningful systematic analysis of the evidence regarding the emergence of resistance could be performed in the studies included in our meta-analysis. The limited available evidence supports that prophylactic administration of antibiotics via the respiratory tract is associated with reduction of occurrence of ICU-acquired pneumonia. However, there is evidence from non-comparative studies that this preventive strategy may lead to an increase in the emergence of resistant bacteria. Thus, further investigation, at least in ICU patients at high risk for development of ICU-acquired pneumonia, is warranted, including a more systematic evaluation of issues related to the emergence of resistance.