until now , it has usually been considered that the best way to diagnose and appropriately treat bacterial infection was to identify the bacteria(s ) responsible for the infection . this statement is accepted without debate for nearly all infections , whether they are severe ( such as meningitis ) or not ( such as urinary tract infection ) . the only question is about the delay for obtaining results with the necessity , in some cases , of initiating urgent empirical antibiotic treatment . curiously , an endless debate exists with the best technique or procedure for dignosing ventilator - associated pneumonia ( vap ) : clinical evaluation alone , microbiological confirmation with discussion on a lot of different diagnostic techniques or procedures ; recently biomarkers have been proposed and tested [ 1 - 4 ] . vap is difficult to diagnose in the critically ill patient because of the presence of underlying cardiopulmonary disorders ( for example , atelectasis , acute respiratory distress syndrome , congestive heart failure , pulmonary contusion , and pulmonary hemorrhage ) , the nonspecific radiographic and clinical signs associated with this infection , and the rapid invasion of the normally sterile lower respiratory tract by microorganisms in all patients with an endotracheal tube , requiring that colonization be differentiated from true infection . actually , there is little information about actual clinical practice ; individual studies indicate that practice often differs from recommendations in the literature . in contrast , recommended design features of future clinical trials of antimicrobial agents for vap - elaborated by the infectious disease society of america , the american thoracic society , the society of critical care medicine , and the american college of chest physicians - stress the requirement of appropriate microbiological confirmation of infection by deep lower respiratory tract culture for inclusion in the intention - to - treat popula - tion of such trials . these difficulties for diagnosing vap and identifying responsible pathogen(s ) lead to potential over- or under - prescription of antibiotics and misguided treatment . the strong associations between delayed diagnosis and subsequent delayed initiation of treatment or between inappropriate initial antibiotic therapy and worse outcome are well documented . on the other hand , a recent observational study conducted in 303 patients at risk for multidrug - resistant pneumonia suggests that guideline - compliant antibiotic treatment was associated with increased mortality in comparison with nonguideline - compliant treatment . the major potential advantage of biomarkers is not to diagnose vap by itself but to po - tentially improve the rapidity and performance of current diagnostic procedures . the rationale is to identify and , if necessary , to dose specific markers of alveolar infection ( not of bron - chial colonization ) : either endogenous mediators released locally by alveolar macrophages activated by microbial products or direct products of parenchymal destruction . a number of biomarkers - including soluble triggering receptor expressed on myeloid cells-1 ( strem-1 ) , procalcitonin ( pct ) , copeptin , c - reactive protein ( crp ) , interleukin-1-beta , granulocyte colony - stimulating factor , macrophage inflammatory protein-1-alpha , plasminogen activation inhibitor-1 , surfactant protein d , receptor of advanced glycation end - products , midregional proatrial natriuretic peptide , and endotoxin   or elastin   fibers - have been tested recently for use in determining the diagnosis and prognosis for patients with suspected or confirmed vap . globally , the results of studies evaluating the value of biomarkers in diagnosing vap are contradictory . initially , biomarkers - particularly crp , pct , and strem-1 - were considered to be promising markers for improving diagnostic strategies of vap . today , the results of recent studies suggest that the measurement of biomarkers in bronchoalveolar lavage ( bal ) fluid appears to have minimal diagnostic value for vap . the article by vanspauwen and colleagues   in the previous issue of critical care adds new data to the search for a biomarker for vap . the investigators evaluated a low - molecular - weight protein secreted in the alveoli , the clara cell protein 10 ( cc-10 ) , which has a possible anti - inflammatory role in humans . bronchoscopy with bal was performed in 196 patients who were treated with mechanical ventilation for more than 48 hours and who had clinical suspicion of vap . the authors found , in the microbiologically confirmed vap group , a median cc-10 concentration that was significantly higher than in the non - vap group ( 3,019 , range 282 to 65,546 versus 2,054 , range 62 to 30,240 ng / ml ; p = 0.03 ) , but such cc-10 levels are not discriminative for diagnosing vap . no difference between patients with corticosteroids or antibiotic therapy and those without or between patients with gram - positive and those with gram - negative bacteria as responsible pathogens was observed . in this well - conducted study , some strengths and weaknesses are worth mentioning . first , to evaluate new diagnostic techniques , a reference standard is required . for vap , because histological confirmation is not a practical reference , quantitative cultures of bal fluid are the best possible alternatives . second , bronchoscopy and lavage may be contraindicated in some patients and remain operator - dependent and time - consuming ; in addition , high variability in the use of bronchoscopic sampling across intensive care units exists . third , an ideal diagnostic test for vap would involve a highly discriminatory , easy - to - sample blood test . in fact , biomarkers potentially used in diagnosing vap , including cc-10 , are bal - based techniques , just like quantitative cultures and direct examination of bal fluid . consequently , such a new technique is probably an extension of bal fluid analysis in addition to microbiological techniques rather than a simplification of diagnostic procedures for vap . fourth , as usual in this type of study , the precise timing of sampling may influence the diagnosis of vap . results of cc-10 dosage in the group of non - vap patients with a distinction between patients with negative cultures and those with more than 0 and less than 10colony - forming units per milliliter ( or less than 2% intracellular organisms ) and data concerning the follow - up of such patients ( particularly the occurrence of subsequent pneumonia ) could give additional information about the ability of cc-10 dosage to predict vap . finally , this study did not include sequential cc-10 measurements , although recent data concerning pct suggest that serial dosages may be used as a marker to monitor response and possibly to terminate antibiotic therapy . today , even if interest in surrogate markers ( that is , bal fluid biomarker dosage ) to resolve the question of diagnosing or predicting vap is not demonstrated , interest in the continuing story of biomarkers and vap is certain . bal : bronchoalveolar lavage ; cc-10 : clara cell protein 10 ; crp : c - reactive protein ; pct : procalcitonin ; strem-1 : soluble triggering receptor expressed on myeloid cells-1 ; vap : ventilator - associated pneumonia . the author has received research support from astellas ( tokyo , japan ) and kalobios ( south san francisco , ca , usa ) and served on an advisory board for sanofi - aventis ( paris , france ) .
evaluation of a new biomarker from bronchoalveolar fluid , the clara cell protein 10 , adds data to the search for a diagnostic marker for ventilator - associated pneumonia ( vap ) . for more than 15 years , investigators tried to identify such a marker for predicting or diagnosing vap . 
 unfortunately , the results of a number of these studies are disappointing . for optimal management of critically ill , ventilated patients with clinical suspicion of vap , clinicians need accurate microbiological information to decide to treat in case of confirmed infection and to guide the initial choice of antibiotic therapy with identification of the responsible pathogen(s ) . 
 thus , today , the potential advantages of biomarkers are to improve the rapidity and performance of current diagnostic procedures and to reduce antibiotic exposure and selective pressure .