Marco Milanese

Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial

This study was undertaken to assess whether oropharyngeal vancomycin may control oropharyngeal carriage and lower airway infection due to methicillin‐resistant Staphylococcus aureus (MRSA) acquired in the intensive care unit (ICU). Secondary endpoints were the emergence of vancomycin-resistant enterococci, vancomycin-intermediate S. aureus and vancomycin consumption. A total of 84 patients, admitted to a medical/surgical ICU and mechanically ventilated for >72u2005h, were randomly assigned to control (n=42) or test (n=42) group. Both groups received the protocol of selective decontamination of the digestive tract, including polymyxin E, tobramycin and amphotericin B. Patients in the test group received 0.5u2005g of a 4% vancomycin gel at 6‐h intervals in the oropharynx. Lower airway infections due to MRSA acquired on the ICU were reduced in the test group, as was oropharyngeal carriage. Neither vancomycin-resistant enterococci nor vancomycin-intermediate S. aureus were isolated from either surveillance or diagnostic samples during the study period. The vancomycin costs were lower in the test group. This study demonstrates that oropharyngeal vancomycin, which controls intensive care unit‐acquired lower airway infections and secondary carriage due to methicillin-resistant Staphylococcus aureus, is cost-effective and safe in terms of vancomycin-resistant enterococci and vancomycin-intermediate Staphylococcus aureus.

Impact of selective decontamination of the digestive tract on fungal carriage and infection: systematic review of randomized controlled trials

ObjectiveTo determine the impact of the antifungal component of selective decontamination of the digestive tract on fungal carriage, infection and fungaemia.DesignMeta-analysis of randomized controlled trials of selective decontamination of the digestive tractStudy selectionData sources included Medline, Embase, Cochrane Register of Controlled Trials, previous meta-analyses, personal communications and conference proceedings, without restriction of language or publication status. All randomized trials were selected that compared oropharyngeal and/or intestinal administration of antifungals amphotericin B or nystatin, as part of selective decontamination protocol, with no treatment in the controls. There were 42 randomized controlled trials with a total of 6,075 critically ill patients.MethodsThree reviewers independently applied selection criteria, performed quality assessment and extracted the data. The main outcome measures were patients with fungal carriage, patients with fungal infections and patients with fungaemia. Odds ratios were pooled with the random effect model.Measurements and resultsEnteral antifungals significantly reduced fungal carriage (odds ratio 0.32, 95% confidence interval 0.19–0.53) and overall fungal infections (0.30, 0.17–0.53). Fungaemia was not significantly reduced in the treatment group (0.89, 0.16–4.95).ConclusionsAntifungals, as part of selective decontamination of the digestive tract, reduce fungal carriage and infection but not fungaemia in critically ill patients and may justify the inclusion of an antifungal component in the decontamination protocol.

Prevention of ventilator-associated pneumonia by use of oral chlorhexidine.

To the Editor—We read with interest the article by Tantipong et al. on the use of oral decontamination with 2% chlorhexidine solution for the prevention of ventilator-associated pneumonia (VAP). We believe that their study has some important limitations and that the authors conclusion that oral chlorhexidine is an effective and safe method for VAP prevention is not supported by the results. In their study, some patients received ventilation for less than 48 hours, the population was not homogeneous, and the randomization procedure was not adequate. The mean duration of mechanical ventilation was approximately 5 days, but only 43% of patients in the test group and 50% of patients in the control group received ventilation for more than 48 hours, a period that, if not completed, is usually considered an exclusion criterion in the majority of trials on VAP prevention. Approximately 60% of patients admitted to their study were adults who received ventilation in intensive care units (ICUs) (mainly surgical ICUs), whereas 40% received ventilation in general medical wards. Although the mean Acute Physiology and Chronic Health Evaluation II score was not significantly different among the 2 arms, it is highly likely that patients who received ventilation in general medical wards were in less critical condition than those treated in ICUs. Moreover, the care of a patient who receives ventilation may be different in the general ward than in the ICU, all wards did not change their regular protocols, parenteral antibiotic policy was not reported, semirecumbency was maintained only if possible, and the degree of semirecumbency was not assessed. Therefore, the study results seem to not be generalizable to the high-risk ICU population. Finally, randomization according to patient sex is not an adequate method of randomization, the study was not blinded, and it is not clear whether consecutive patients were enrolled. All these issues may have influenced the results and should be acknowledged by the authors. The authors claim that oral decontamination with 2% chlorhexidine solution is an effective method for reducing VAP is not supported by the results and may be misleading for the reader. Although use of chlorhexidine reduced the risk of VAP by approximately 55% in the overall population and among patients who received mechanical ventilation for more than 2 days, this reduction was not statistically significant, because both relative-risk (RR) calculations had large 95% confidence intervals (CIs) (RR, 0.43 [95% CI, 0.16-1.17] for study patients who received mechanical ventilation and oral decontamination and RR, 0.45 [95% CI, 0.16-1.23] for patients who received mechanical ventilation for more than 2 days). The study showed a significant, albeit borderline (P = .04), reduction in the number of episodes of pneumonia per 1,000 ventilator-days, but this reduction was not statistically significant (P = .06) when the authors evaluated only patients who received mechanical ventilation for more than 48 hours, which is an acceptable period for the diagnosis of VAP.

Selective digestive decontamination reduces ventilator-associated tracheobronchitis

We read with interest the systematic review and metaanalysis on frequency, prevention, outcome and treatment of ventilator-associated tracheobronchitis (VAT) by Agrafiotis et al. We are surprised by the authors’ finding that selective digestive decontamination (SDD) does not prevent VAT (odds ratio [OR]: 0.62, 95% confidence interval [CI]: 0.31e1.26). We believe that an inadequate literature search is the reason for this result. The authors found five randomized controlled trials (RCTs) of SDD including about 800 patients. Remarkably, sixteen years ago Kollef analysed seven RCTs including 1043 patients and

Parenteral antibiotics are not enough to prevent pneumonia in stroke

The Preventive Antibiotics in Stroke Study (PASS; April 18, p 1519) reported that parenteral ceftriaxone did not significantly reduce pneumonia. We would like to comment on these results. Post-stroke pneumonia is mainly due to aspiration of oropharyngeal secretions promoted by dysphagia, impaired swallowing, and reduced or ineff ective cough. Most pneumonias are primary endogenous; they develop early, within the first 4–7 days of treatment, and are caused by microorganisms carried in the oropharynx on hospital admission. Microorganisms belong to normal flora (eg, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, and meticillinsensitive Staphylococcus aureus) and so-called abnormal flora (eg, aerbic Gram-negative bacilli and metici l l in-resistant S aureus). Pneumonia is also secondary endogenous; it develops late, after 1 week, and is invariably caused by abnormal flora acquired in the oropharynx during the patient’s hospital stay, causing secondary oropharyngeal carriage, overgrowth, and subsequent infection. Prevention of primary endogenous pneumonia requires the early administration of parenteral anti biotics, whereas secondary endogenous pneumonia is controlled by topical oropharyngeal antibiotics (eg, polymyxin E and tobramycin). This is termed selective digestive decontamination, or, its variant, selective oropharyngeal decontamination, and has been shown to reduce pneumonia in critically ill patients and in stroke. PASS was designed to prevent only primary endogenous pneumonia, as the study used parenteral ceftriaxone. Therefore, the information that parenteral antibiotics do not reduce pneumonia is inaccurate because the authors lumped together both primary and secondary endogenous pneumonia; the secondary form cannot be prevented by a 4-day course of parenteral antibiotic.

Selective digestive decontamination is superior to oropharyngeal chlorhexidine in preventing pneumonia and reducing mortality in critically ill patients

full SDD protocol with parenteral and enteral antimicrobials, assuming that the sample size was sufficient. Opinion leaders have expressed concerns regarding resistance, and, despite the fact that those concerns are based on low level evidence, this has hindered the implementation of SDD. Resistance was not a clinically relevant problem in the 60 RCTs evaluating SDD.