Literature Review |

Top Ten List in Ventilator-Associated Pneumonia* FREE TO VIEW

Gonzalo Hernández; Jordi Rello
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*From the Critical Care Department (Dr. Hernández), 12 de Octubre University Hospital, University Complutense, Madrid, Spain; and Critical Care Department (Dr. Rello), Joan XXIII University Hospital, University Rovira i Virgili, Tarragona, Spain.

Correspondence to: Jordi Rello, MD, PhD, Critical Care Department, Joan XXIII University Hospital, Carrer Mallafré Guasch 4, 43007 Tarragona, Spain; e-mail: jrc@hjxxiii.scs.es

Chest. 2003;124(4):1580-1583. doi:10.1378/chest.124.4.1580
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1. Hubmayr RD. Statement of the Fourth International Consensus Conference in Critical Care on ICU-Acquired Pneumonia, Chicago, Illinois, May 2002. Intensive Care Med 2002; 28:1521–1536

This international consensus conference was sponsored by the American Thoracic Society, the European Respiratory Society, the European Society of Intensive Care Medicine, and the Société de Réanimation de Langue Française. It reviewed the actual knowledge on the habitual questions in ventilator-associated pneumonia (VAP), remarking on the unresolved controversies. Interestingly, the consensus conference reports a wide range of incidence, from 1 to > 20 episodes per 1,000 ventilator days, with a low average of seven VAP cases per 1,000 ventilator days. It concludes that the diagnostic method of choice depends on local expertise and availability, but what is really important is always to obtain any kind of respiratory sample. The therapeutic approach emphasizes the clinical importance of the initial empiric treatment, supporting the start of antibiotic therapy only with clinical suspicion. A patient-based therapy, targeted on local microbiological patterns is recommended. The relevance of the direct examination of pulmonary secretions and drug characteristics is emphasized in choosing the initial empiric antibiotic therapy. There is not evidence enough to make strong recommendations on decisions like withholding empiric treatment, choosing definitive antibiotic therapy, and duration of treatment.

2. Trouillet JL, Vuagnat A, Combes A, et al. Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant vs piperacillin-susceptible organism. Clin Infect Dis 2002; 34:1047–1054

Pseudomonas aeruginosa is one of the leading pathogens causing VAP and is identified as the causative agent in 15 to 20% of cases. In addition, P aeruginosa is one of the bacteria associated with attributable mortality in VAP patients. This is the first article documenting epidemiologic, clinical, and prognostic differences between piperacillin-resistant P aeruginosa and piperacillin-susceptible P aeruginosa (PSPA). The authors reported an elevated percentage of resistant strains (25%) that is similar to that obtained in other European countries. Up to 50% of resistant strains associated resistance to other antipseudomonal antibiotics, especially β-lactam agents, aminoglucoside agents, and ciprofloxacin. Prior use of fluoroquinolone agents appears to be one of the most important causal factors for piperacillin-resistant P aeruginosa infections. The 70% of recurrent episodes were due to PSPA with an elevated percentage (85%) of changes in the resistance pattern. All episodes appeared after 7 days of mechanical ventilation. The related mortality rate was 59% for resistant strains. There were no statistical differences compared with PSPA.

3. Hauser A, Cobb E, Bodi M, et al. Type III protein secretion is associated with a poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Crit Care Med 2002; 30:521–528

Little is known about the clinical and virulence patterns of P aeruginosa in intubated patients. The genetic variability of P aeruginosa in respiratory secretion cultures is very high between patients, but significant differences have not been demonstrated. This was the first study showing increased virulence and worse outcome in patients with pneumonia caused by P aeruginosa. Those strains associated with relapse or death produced detectable in vitro amounts of type III proteins. Type III proteins were detectable in 77% of the isolates in this series, with 81% in patients with severe episodes, reflecting their clinical relevance. The exact mechanism of virulence of these proteins remains unclear, although they operate on cell internalization of bacteria. In addition, this discovery opens a new line of investigation on future therapeutic agents. Antibodies against type III proteins have demonstrated a protective effect in animal models.

4. Olson M, Harmon B, Kollef MH, et al. Silver-coated endotracheal tubes associated with reduced bacterial burden in the lungs of mechanically ventilated dogs. Chest 2002; 121:863–870

The accumulation of respiratory secretions on the internal surface of orotracheal tubes harbors a large amount of bacteria. The most important mechanism of VAP development is the aspiration of colonized aerodigestive tract secretions from the external side of the endotracheal tube, while the second most important mechanism is aspiration through the inner side. Silver has bactericidal effects and is nontoxic, and bacterial resistance has not been described. Olson et al reported that silver-coated tubes reduce the biofilm formation, with a significant lumen-narrowing difference between both tubes. Eighty-three percent of noncoated tubes compared to 0% of coated ones had a narrowing of > 50%. Coated tubes not only reduced the bacterial burden, with a statistically minor risk of colonization but also delayed the mean (± SD) duration of internal face colonization from 1.8 ± 0.4 to 3.2 ± 0.8 days. This beneficial effect was correlated with a decline in the degree of histologic grade of lung parenchyma inflammation. The use of silver-coated urinary catheters has demonstrated a reduction in urinary tract infections in humans. Clinical trials regarding silver-coated endotracheal tubes in humans as VAP prevention therapy are warranted.

5. Rello J, Lorente C, Bodi M, et al. Why do physicians not follow evidence-based guidelines for preventing ventilator-associated pneumonia? Chest 2002; 122:656–661

The article reflects the need to improve medical and nursing staff adherence to guidelines. A total of 110 opinion leaders on VAP from 22 countries were interviewed for their personal opinions on different VAP prevention measures. Scientific evidence published alone has been shown to be ineffective in improving guideline implementation because the degree of adherence is independent of the strength of evidence and the grade of effectiveness, at least in part because of the disagreement of opinion leaders about the interpretation of reported trials. However, the most important reason why recommendations are not followed is the lack of technological availability, which has been cited by 78% of the interviewed opinion leaders. Pharmacologic strategies had worse adherence than nonpharmacologic ones, which were predominantly conditioned for excessive antibiotic employment. This report highlighted the great importance of educational measures in improving VAP prevention, remarking on the need for a multidisciplinary approach.

6. Zack JE, Garrison T, Trovillion E, et al. Effect of an education program aimed at reducing the occurrence of ventilator-associated pneumonia. Crit Care Med 2002; 30:2407–2412

This interesting article confirms the huge importance of implementing scientific data with educational programs, and is directed to physicians and nurses in an effort to improve VAP prevention. The reduction in the VAP rate reported is 57.6% (range, 12.6 to 5.7 episodes per 1,000 ventilator days). The program included a theoretical module, with self-study and practice modifications, with staff meetings and didactic lectures. The authors reinforced the programs with continuous visual support throughout the ICU, contributing to the adherence to the guidelines. These strategies require constant reinforcement by continuous updating and feedback based on results. It is important to point out that the combination of different measures is an important way to reduce the incidence of VAP. As can be inferred from the study, not only the incidence of VAP can be reduced with educational programs, but also the costs and patient morbidity attributed to nosocomial infections.

7. Lambotte O, Timsit JF, Garrouste-Orgeas M, et al. The significance of distal bronchial samples with commensals in ventilator-associated pneumonia: colonizer or pathogen? Chest 2002; 122:1389–1399

This expert group investigated the potential role of nonpathogenic microorganisms in VAP. Three hundred sixty-nine VAP patients were identified during the study period. Only 29 episodes were considered to have been caused by commensal pathogens. The percentage of pathogens of unknown etiology was not reported. Polymicrobial VAP was found in 77 patients, and these patients were excluded from the study. Most patients had risk factors for more virulent or resistant pathogens like COPD, glucocorticoid therapy, or immunosuppression. Although the onset of 10 cases occurred before the sixth ICU day, all Gram-negative commensal pathogens that were isolated were sensitive to therapy with a third-generation cephalosporin or amoxicillin/clavulanic acid. Seven of 29 patients did not receive adequate treatment, and mortality did not increase significantly. Although the authors attribute a pathogenic role to commensal bacteria, they did not find any difference in mortality rate between patients with or without VAP. In addition, besides the limited relevance to mortality, only 20% of patients who died had received histologic confirmation of a diagnosis of pneumonia. Commensal pathogens can produce fulminant infections in immunocompromised patients, but this is the first study that has suggested the need to treat commensal isolates in patients with VAP. Future investigations are needed to define the pathogenic role of commensal agents in these kinds of patients.

8. Iregui M, Ward S, Sherman G, et al. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 2002; 122:262–268

The occurrence of and effect on prognosis of delays in the beginning of the treatment of VAP have not been reported before, to our knowledge. Appropriate initial antibiotic treatment has been reported to reduce in-hospital mortality. Iregui et al have found an increase in the hospital mortality rate with delayed initial treatment. Adequate initial treatment usually has been defined as an antibiotic with in vitro susceptibility to the pathogen isolated in respiratory samples. This definition needs the addition of onset timing in antibiotic administration. The most common cause of inadequate initial treatment was a delay in writing the medical orders. The presence of a resistant organism accounted for < 20% of cases. It is important to note that diagnostic delays were not counted, although radiologic criteria included an infiltrate persistence of > 72 h. Inadequate clinical evaluation and waiting for microbiological results were reasons of delayed empiric treatments.

9. Hayon J, Figliolini C, Combes A, et al. Role of serial routine microbiologic culture results in the initial management of ventilator-associated pneumonia. Am J Respir Crit Care Med 2002; 165:41–46

This study tested the potential value of routine microbiological cultures before VAP onset in predicting the causative pathogen of VAP and in anticipating the correct antibiotic choice. Authors cultured blood, respiratory secretions, catheter-tips, urine, and others substances, and found that there was no relationship between the colonization of tissues other than from the lungs and the etiology of VAP. High-quality distal bronchial samples obtained by BAL and protected-specimen brush, if cultured in the previous 72 h, had positive predictive values of 25% and 28%, respectively. Only distal respiratory secretions, when repeated at intervals between 48 and 72 h, might have a role in predicting the causative bacteria of VAP. Special attention is required for potentially drug-resistant bacteria like methicillin- resistant Staphylococcus aureus, P aeruginosa, and Acinetobacter baumannii with positive predictive values of 62%, 52%, and 24%, respectively. Previous colonization with any of these pathogens implies a high risk for subsequent pneumonia, allowing for an adequate empiric antibiotic selection.

10. Rello J, Ollendorf D, Oster G, et al. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 2002; 122:2115–2121

The authors present the largest study performed in the United States, comprising 842 VAP patients and 2,243 control subjects. The mean interval between intubation and the identification of VAP was 3.3 ± 6.6 days. A crude incidence of 9.3% was found in ventilated patients. The authors also reported morbidity and economic variables resulting in an increase in mean ICU and hospital stays (6.1 days), mean period of mechanical ventilation (9.6 days), and a mean doubled increase in hospital charges ($41,294). P aeruginosa was isolated most frequently in patients with VAP, occurring > 4 days after the start of mechanical ventilation (19.7%), while S aureus was isolated most frequently in patients in whom VAP was diagnosed before the fourth day of onset of mechanical ventilation (23.7%). They found no attributable mortality at 30 days. An outstanding conclusion is that intermediate underlying illness severity is one of the independent risk factors for developing VAP, as reported previously for late-onset VAP episodes caused by P aeruginosa. The main goal of this study concerned the impact on the design of future studies aimed at VAP prevention.

Abbreviations: PSPA = piperacillin susceptible Pseudomonas aeruginosa; VAP = ventilator-associated pneumonia

This research was supported in part by Comissió Interdepartamental de Recerca i Tecnología (SGR 2001/414) and Distinció a la Recerca Universitaria (JR).

We wish to thank Jordi Vallés for a critical review of the manuscript.




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