SDD is a prophylactic measure using selected antimicrobials to control gut overgrowth, thereby reducing the 4 harmful side effects, including restoration of suppressed systemic immunity and reduction of severe infections of lower airways. In conclusion, severity of underlying disease promoting oropharyngeal overgrowth and subsequent lower airway infection following migration is the major determinant factor for developing pneumonia, rather than factors associated with translaryngeal intubation.
Ventilator associated pneumonia: perspectives on the burden of illness.
Zandstra and colleagues make this case very cogently in their argument for selective decontamination of the digestive track as a VAP-preventive measure. We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.
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Ventilator associated pneumonia: perspectives on the burden of illness. - PubMed - NCBI
New endotracheal tubes designed to prevent ventilator-associated pneumonia: Respir Care ; 55 8: Defining, treating and preventing hospital acquired pneumonia: Intensive Care Med ; 35 1: Nosocomial pneumonia in ventilated patients: Am J Med ; 94 3: Hospital-acquired pneumonia in adults: A consensus statement of the American Thoracic Society. Over the years, since the publication of the initial RCT, there have been various international initiatives to implement this preventive strategy against VAP.
Different guidelines recommend several strategies for VAP prevention. However, these American guidelines have not yet recommended the prophylactic use of systemic antibiotics for all intubated patients, which awaits the availability of further data. These current guidelines mention no prevention measures for nosocomial pneumonia..
End Points From Previous Trials Of HAP And/Or VAP
In , the Brain Trauma Foundation published the 3rd edition of its Guidelines for the management of severe traumatic brain injury, 9 describing the results of this initial RCT, and suggests the immediate application of this pharmacological measure to reduce VAP incidence in intubated traumatic brain injury patients.. From a European perspective, guidelines published in 10 present the short course of IV antibiotics as a strategy that requires further study to be systematically recommended in intubated patients for VAP prevention..
The implementation of the guidelines aims at reducing VAP to less than 9 episodes per days of mechanical ventilation. A total of 35 preventive measures were initially selected. A group of experts have generated a list of 7 basic mandatory recommendations: After a review of literature and the international guidelines that have been published since the publication of the initial work, the question that we make is: The answer is simple.
Since the single RCT study performed twenty years ago, the current clinical practice has changed and there is no uniform management of intubated patients with coma. The fact that the type and dose of IV antibiotic was different in all the aforementioned studies suggests that the positive effect of IV antibiotic prophylaxis depends more on immediate administration upon intubation — to counteract bacterial inoculum in the upper airways — than on antibiotic type and dose. This preventive measure may now be obsolete due to changes in the colonizing microorganisms of the population or due to a multifactorial behaviour in VAP development in coma patients.
It is surprising that, throughout all these years, no research has been focused on this hypothesis and tested this or any other antibiotic using a large randomized clinical trial.. Patients with structural coma, usually due to traumatic head injury, are nearly always intubated in emergency conditions outside the hospital, where the lack of aseptic conditions makes it easier for microorganisms to enter the respiratory tract.
Furthermore, high oxygen tension in ventilated patients is enough to kill anaerobes and — in this situation of new microbiology patterns of VAP — we and others propose the use of other antibiotics rather than cefuroxime for prophylaxis and for treatment of aspiration pneumonia, 11 which is the pathogenic basis of EO-VAP in intubated patients with altered level of consciousness.. Consequently, we believe that it is time to risk a change to an antibiotic prophylaxis which is likely to be more effective against aerobic gram-positive and enteric gram-negative bacilli, as well as a change in terms of pharmacokinetics and pharmacodynamics with a more adequate spectrum to the current aetiology of EO-VAP in recently-intubated coma patients.
However, the effect of this prophylactic measure on the development of bacterial resistance must always be monitored periodically to detect prophilaxis-related bacterial resistance if its use is not appropriate. After 20 years of the IV antibiotic prophylaxis for VAP prevention in intubated coma patients, perhaps it is time to launch a large RCT to evaluate other types of antibiotic prophylaxis with no effect on normal anaerobic microbiota and with a broad-spectrum to Gram-positive and enteric Gram-negative bacilli.
However, attention must be paid to the evolution of resistant micro-organisms, and maintaining this antibiotic prophylaxis for more days than planned should be avoided.. The authors declare no conflict of interest..
The author thanks the team of physicians and nurses in our ICU for their professional care of critically-ill patients and their families. I also thank Dr. Previous Article Vol May Next article. Antibiotic prophylaxis against ventilator-associated pneumonia in patients with coma: Where are we now?. Thirty-nine published articles were identified, but none described placebocontrolled or dose-ranging studies. The end point evaluated in these studies was all-cause mortality. Of these studies, 12 were nonrandomized, observational studies evaluating all-cause mortality with use of a placebo substitute of inadequate, inappropriate, or delayed initial therapy.
Very limited to no placebo- controlled literature on clinical response or other non-mortality-related end points was discovered during the literature review. Although many different end points have been suggested as clinically relevant and important to health care providers and patients, the problem remains that there are few data other than those for all-cause mortality to establish the treatment effect of antibacterial therapy.
Perspectives on Critical Care Infectious Diseases: Ventilator-Associated Pneumonia
Certainly, these end points may be used in a superiority trial or as secondary end points in noninferiority trials. Such end points include clinical response, time to event eg, hospital discharge, extubation, normalization of temperature and white blood cell count, oxygen saturation, respiratory rate, and pulse , radiologic and microbiologic outcome, and change in Clinical Pulmonary Infection Score or other scoring systems [ 7 , 8 ]. However, none of these have been validated as surrogate markers, nor has any correlation between them and either clinical response or all-cause mortality been evaluated in prior registrational trials.
A related issue is the timing of assessment of end points, which likely will depend on the end point that is selected. Options include at the end of treatment, during the course of treatment to evaluate improvement, at the test-of-cure visit, or at the first time of determination of clinical failure h after initiation of therapy. Of the 23 studies used in the analysis by Sorbello et al [ 6 ], more than half did not specify when the mortality end point was assessed, and a few used days as the time of assessment. For a mortality end point, there are some issues to consider. Mortality, although not difficult to define, is not a clean end point, because determining attributability is in the eye of the beholder and may be unclear even when an autopsy is performed.
All-cause mortality may be related to underlying comorbidities and gives a false impression that, somehow, the antibacterial treatment is related to the deaths.
Another question pertains to the amount of the treatment effect of antibacterial therapy on a given end point that is reasonable to health care providers and patients to sacrifice when selecting a noninferiority margin. Preserving more of the effect is desirable for an end point, such as mortality; however, sample sizes may become quite large with very small margins. For other end points to be used as primary in noninferiority trials, the historical evidence of treatment effect, compared with placebo, must be established for the study results to be interpretable and fulfill the requirements of the Code of Federal Regulations.
Sound scientific data and justification must be the rationale for the final design of trials for these significant and common infections. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
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End Points For Future Trials. US Food and Drug Administration.