To our knowledge, we are the first to describe the concept of gradual VAP. Establishment of gradual VAP is a common process, mainly in the case of late pneumonia. More importantly, our data support the need to initiate proper antibiotic treatment in the early stages of infection without waiting for all the diagnostic criteria for VAP to be met. However, in this study, we were unable to identify effective diagnostic tools for gradual VAP, apart from the usual clinical criteria.
In line with the idea proposed by Craven and Hjalmarson , our study supports the hypothesis of a continuum between airway colonization, an intermediate process (called ventilator-associated tracheobronchitis in their study), and VAP. During this developing period, the patient’s immune system will attempt to prevent the spread of the organism, and signs of this confrontation will be observable in the form of fever, leukocytosis, and purulent bronchial secretions. This process is typical in late-onset VAP (76 % of late VAP cases in our series were gradual VAP), and its absence is probably justified by the presence of a sudden and large bacterial inoculum into the lung (inoculate at intubation in early VAP, and due to accidental aspiration of subglottic secretions in late VAP).
Our results do not support a nosological separation between VAP and VAT. As described in the literature, VAP and VAT are distinguishable only by the presence of visible lung infiltrate on a chest x-ray. However, the discriminative ability of a portable chest x-ray is more than doubtful. In fact, even in community-acquired pneumonia, plain radiography has shown a diagnostic inaccuracy of 17 % compared with chest computed tomography . Nonetheless, the value of studying VAP development lies in antibiotic prescription rather than in a diagnostic disquisition.
In our study, appropriate antibiotic treatment introduced in the developing period in gradual VAP was associated with a higher rate of early clinical response. Therefore, identifying the right moment to start antibiotics in this continuum between colonization and VAP seems to be a challenge. PCT may be a valuable tool in this context. Stolz et al. showed a safety algorithm for antibiotic discontinuation based on serum PCT after 72 h of antibiotic treatment in 101 patients with VAP . In our study, gradual VAP showed serum PCT greater than or equal to 0.5 ng/ml during the developing period in 65 % of cases, but this was also true for nongradual VAP in 60 % of cases.
According to our results, in the event of suspected VAP, a mCPIS score higher than 5 could indicate antibiotic initiation. However, the lack of sensitivity of mCPIS in our study precludes a safe use of this tool to rule out the existence of an ongoing infectious process. Using a different methodological approach, Singh et al. demonstrated the usefulness of CPIS to safely withdraw antibiotics after 72 h of treatment in patients with an initial but incomplete diagnosis of VAP (CPIS ≤6 points at inclusion) .
Our study has several limitations. The sample size is not large and could be responsible for the observed negative results. However, our sample size is not too far removed from that used in studies by Stolz et al.  and Singh et al. . Gradual VAP definition is roughly equal to VAT criteria, but in our case it systematically preceded the diagnosis of VAP. In any case, we avoid discussion of labeling of patients, as our objective is to analyze the correct time for starting antibiotic treatment. In this sense, the progression to VAP is marked, despite an appropriate antibiotic treatment. Although this phenomenon has already been described , we would need to analyze the characteristics of patients in similar clinical conditions, but without progression to VAP, to get convincing explanations. We believe that nongradual late VAP may be due to accidental inoculation of heavily colonized oropharynx secretions. However, we had little knowledge regarding the existence of this type of incident in such cases. Finally, we must assume that demonstration of the clinical importance of the concept of gradual VAP requires additional studies based on therapeutic interventions. Since this type of intervention may lead to a greater consumption of antibiotics, it should always be associated with an antimicrobial stewardship program.