Microbiological Diagnosis of Ventilator-associated Pneumonia: Using the Data to Optimize Clinical Outcomes

In this issue of the Journal (pp. 1229-1232), Afessa and colleagues (1) report that a simple calibrated loop culture method applied to bronchoalveolar lavage (BAL) specimens yielded results that were concordant with the serial dilution culture technique for the microbiological diagnosis of ventilator-associated pneumonia (VAP). The calibrated loop culture method allows quantification of bacterial populations in BAL samples to be performed in a more time-efficient and less costly manner than serial dilutions. Although the results from these two techniques were found to be highly concordant, this study does not address the important question of whether quantitative culture methods applied to distal respiratory secretions should be routinely employed in the management of clinically suspected VAP. To answer this key clinical question requires an understanding of the potential impact of such sampling, and the culture methods on the two key outcomes associated with the treatment of VAP-that is, hospital mortality and the emergence of antibiotic resistance.

All currently available microbiological techniques applied to lower respiratory tract samples require a fixed amount of time to obtain and process the specimens before the results of special stains and cultures become available. Therefore, there is the potential for delaying antimicrobial therapy if antibiotic decision making in clinically suspected VAP is predicated solely on the findings from such measures. Delayed administration of appropriate antibiotic therapy in patients with VAP has been associated with excess hospital mortality (2). Similarly, the timely prescription of an initial antibiotic regimen that is inappropriate for the microorganism(s) causing VAP (i.e., an antibiotic regimen to which the pathogen is resistant based on in vitro susceptibility testing) has also been associated with a significantly greater risk of death (3, 4). This association has been demonstrated for other serious infections, including bloodstream infection, severe sepsis, and community-acquired pneumonia (5). Therefore, initial appropriate antibiotic selection should be regarded as a primary determinant of hospital outcome for patients with life-threatening infections, including VAP. Such initial therapy should be selected according to the presence or absence of risk factors for health care-associated infection (e.g., prior hospitalization, admission from a nursing home, current hemodialysis, wound or infusion therapy), suggesting a high likelihood that the underlying infection will be attributed to potentially antibiotic-resistant bacteria (6).

Unfortunately, the imperative to treat an increasingly compromised patient population in the hospital setting, often colonized or infected with antibiotic-resistant pathogens, has resulted in clinicians lowering their threshold for the administration of empiric antibiotics. Prior antibiotic exposure has been shown to be an important risk factor for the subsequent administration of inappropriate antimicrobial treatment (7). In addition, excess antibiotic use patterns, especially durations of antibiotic administration beyond 7 or 8 days in mechanically ventilated patients, have been linked with subsequent infections caused by potentially antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species, and extended-spectrum ß-lactamase-producing gramnegative bacteria (8-10). These findings suggest that clinicians managing patients with suspected VAP should employ antimicrobial treatment strategies that minimize the use of prolonged and potentially unnecessary antibiotic exposure to curtail resistance.

The upper airway of mechanically ventilated patients (e.g., oropharynx, endotracheal tube, tracheostomy tube, trachea, sinuses) is commonly colonized with potentially pathogenic bacteria, as well as yeast (11). Consequently, secretions obtained from an endotracheal tube or a tracheostomy tube cannot consistently differentiate between upper airway colonization and lower respiratory tract infection, even when quantitative culture techniques are applied to the specimens (11, 12). Sampling methods that minimize contamination from the upper airway (e.g., bronchoscopic or catheter BAL and brushing) offer the potential advantage of establishing a more precise microbiologic diagnosis of VAP (11). One practical clinical impaction from employing techniques that minimize upper airway colonization is that antibiotic regimens are more likely to be modified once the special stain and culture results become available (13, 14). Presumably, this is related to the greater confidence clinicians have in the culture results reflecting the presence or absence of VAP (11, 14).

The recently published Infectious Diseases Society of America/ American Thoracic Society guidelines for the management of nosocomial pneumonia attempt to address the need for balancing appropriate initial antimicrobial therapy and resistance with the proposed de-escalation approach to antibiotic treatment (15). In patients with clinically suspected VAP, the guideline recommends that respiratory specimens for microbiological processing be obtained followed by timely administration of an empiric antibiotic regimen based on the presence or absence of risk factors for infection with multidrug-resistant bacteria (15). The subsequent availability of microorganism identification and antibiotic susceptibility testing allows for modification or deescalation of the initially applied, often broad-spectrum, antimicrobial regimen. Regrettably, this treatment algorithm often is not adhered to in daily clinical practice. Hindrances to its utilization include highly restricted hospital formularies promoting initial inappropriate antibiotic treatment in patients at high risk for infection with multidrug-resistant bacteria, failure to identify patient risk factors for the presence of health care-associated infections, and the inability to obtain uncontaminated respiratory specimens for microbiological processing (11).

The primary advantage associated with obtaining properly collected and processed lower respiratory tract samples in patients with suspected VAP is to permit more specific modification of the initially prescribed antibiotic regimen (11, 13-15). This has been demonstrated for both medical and surgical patients, including the early, complete discontinuation of empirically prescribed antibiotics (16, 17). Given the complexity of patients in the intensive care unit with a possible diagnosis of VAP, the use of calibrated loop cultures of lower respiratory tract samples should be considered a clinical tool primarily aimed at reducing the unnecessary administration of antibiotics. Future advances in our ability to more rapidly establish or exclude the diagnosis of VAP using BAL or serum biomarkers and more rapid identification of pathogens and their antimicrobial susceptibilities could lead to further refinements in our current practices. Until then, clinicians ought to manage clinically suspected VAP in a manner that attempts to balance the patient's need to receive appropriate initial antibiotic treatment with the need to minimize the emergence of antimicrobial resistance by avoiding unnecessary antibiotic use.

Conflict of Interest Statement: M.H.K. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.