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Ventilator-associated Pneumonia caused by commensal oropharyngeal Flora: a retrospective Analysis of a prospectively collected Database

An Erratum to this article was published on 17 September 2015



The significance of commensal oropharyngeal flora (COF) as a potential cause of ventilator-associated pneumonia (VAP) is scarcely investigated and consequently unknown. Therefore, the aim of this study was to explore whether COF may cause VAP.


Retrospective clinical, microbiological and radiographic analysis of all prospectively collected suspected VAP cases in which bronchoalveolar lavage fluid exclusively yielded ≥ 104 cfu/ml COF during a 9.5-year period. Characteristics of 899 recent intensive care unit (ICU) admissions were used as a reference population.


Out of the prospectively collected database containing 159 VAP cases, 23 patients were included. In these patients, VAP developed after a median of 8 days of mechanical ventilation. The patients faced a prolonged total ICU length of stay (35 days [P < .001]), hospital length of stay (45 days [P = .001]), and a trend to higher mortality (39 % vs. 26 %, [P = .158]; standardized mortality ratio 1.26 vs. 0.77, [P = .137]) compared to the reference population. After clinical, microbiological and radiographic analysis, COF was the most likely cause of respiratory deterioration in 15 patients (9.4 % of all VAP cases) and a possible cause in 2 patients.


Commensal oropharyngeal flora appears to be a potential cause of VAP in limited numbers of ICU patients as is probably associated with an increased length of stay in both ICU and hospital. As COF-VAP develops late in the course of ICU admission, it is possibly associated with the immunocompromised status of ICU patients.

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Mechanically ventilated patients are at risk for ventilator-associated pneumonia (VAP) [1], which is associated with an increased intensive care unit (ICU) length of stay (LOS), morbidity and mortality [25]. A globally accepted gold standard for the diagnosis of VAP is lacking [68], with the exception of the new surveillance ventilator-associated events definitions [9]. Generally recommended and accepted microbiological diagnostic modalities for VAP are quantitative specimen collection techniques as bronchoalveolar lavage (BAL) [10, 11] and protected specimen brushing obtained bronchoscopically and nonbronchoscopically. The identification of aerobic oropharyngeal flora in BAL fluid (BALF) cultures is commonly considered colonization, contamination from the upper respiratory tract or otherwise regarded clinically irrelevant, regardless of quantity [1113].

Authoritative guidelines remain inconclusive regarding the role of commensal oropharyngeal flora (COF) as a causative agent in VAP, mainly due to a scarcity of studies in this research field [14]. However, there is evidence that COF may cause pulmonary infection, mostly in immunocompromized patients. Examples are Streptococcus oralis/mitis in neutropenic patients [15, 16] and species of the Streptococcus anginosus group in patients with predisposing factors including cancer, alcoholism [17, 18], and cystic fibrosis [19, 20]. Furthermore, aspiration may cause a pneumonia due to both anaerobic and/or aerobic oropharyngeal flora [21]. For the critically ill, several studies demonstrate that the innate immune response is declined due to several different mechanisms [2224]. Therefore, one may hypothesize that ICU patients are likewise at risk for infections by COF. This study explores whether COF can be a cause of VAP.



The study was conducted at the Maastricht University Medical Centre, a 715-bed hospital with approximately 30,000 annual admissions, 18 mixed surgical-medical ICU beds, and 9 post-cardiothoracic surgery beds. Other elective postoperative patients are rarely admitted, due to a 24-h post anaesthesia care unit. When technically possible and safe, a BAL was performed in all mechanically ventilated patients who met the clinical criteria of suspected VAP. These criteria include (≥2 of the following) a rectal temperature > 38.0 °C or < 35.5 °C, white blood cell count > 10,000/μl or < 3,000/μl, purulent sputum, and a new, persistent or progressive infiltrate on chest X-ray [25]. In patients with localized pulmonary lesions, the affected region was sampled, whereas in case of diffuse pulmonary lesions the middle lobe or lingula was lavaged. The BALF was microbiologically evaluated within 15 min after it was obtained. Selective oropharyngeal decontamination (SOD) is used since December 2010, whereas selective digestive tract decontamination (SDD) is used since January 2012. The SOD consists of topical antibiotics (polymyxin E, tobramycin, amphotericin B) applied to the oropharynx, whereas the SDD consists of oropharyngeal and gastric application of the same non-absorbable antibiotics along with a four day course of intravenous cefotaxime. The ethics committee of the institution, the “Medical Research Ethics Committee”, approved the study and informed consent was regarded unnecessary since standard care was provided.


Ventilator-associated pneumonia in clinically suspected cases (for definition, see previous paragraph) was diagnosed if subsequent BALF analysis was indicative for pneumonia: cultures yielding a potentially pathogenic microorganism [12] ≥ 104 cfu/ml and/or if ≥ 2 % BALF cells containing intracellular organisms (ICOs) [10, 26]. In a pneumonia suspected case that was admitted from home less than 3 days prior to diagnosis, community-acquired pneumonia (CAP) was considered, if this case had no recent contact with the healthcare system. A CAP was also considered when the potentially pathogenic microorganism was very unlikely to be nosocomial (e.g. Haemophilus influenzae, Mycoplasma spp.) [27]. When a clinical suspected case was admitted in the hospital for more than 3 days and with positive BALF results, but was not mechanically ventilated for ≥ 48 in the 72 h prior to the pneumonia, hospital-acquired pneumonia (HAP) was diagnosed [14].

Commensal oropharyngeal flora as the cause of VAP was considered in VAP suspected cases if BALF quantitative cultures revealed COF ≥ 104 cfu/ml without significant growth (≥104 cfu/ml) of other potentially pathogenic microorganisms. Commensal oropharyngeal flora included (a combination of) the following bacteria: viridans streptococci, coagulase-negative staphylococci, Haemophilus spp. (excluding H. influenzae if not predominant), Moraxella spp. (if not predominant), Corynebacterium spp., Neisseria spp., Peptostreptococcus spp., Stomatococcus spp., and Prevotella spp. [28]. Whereas Candida spp. may occasionally cause a pneumonia [29], Candida spp. were considered nonpathogenic in this study, consistent with previous studies and guidelines [3032].

Data collection

From January 2005 until January 2014, all results of BALF analyses from patients consecutively admitted to the ICU were prospectively collected. From this database, patients with suspected COF as the cause for VAP were included in the present study. Cases lacking a microbiological BAL report were excluded. Retrospectively, the following clinical data were collected or calculated from the included cases: body temperature, C-reactive protein (CRP), white blood cell count, antibiotic administration, ICU length of stay, hospital length of stay, duration of mechanical ventilation, mortality, acute physiology and chronic health evaluation (APACHE)-II score (to calculate standardized mortality ratio [SMR; observed mortality divided by expected mortality]) [33], sequential organ failure assessment (SOFA) score (to determine the extent of critical illness) [34, 35], clinical pulmonary infection score (CPIS; more than 6 points is indicative of pneumonia) [36], and post-mortem examination, if available.

Reference population

On the advice of the statistical department a reference population was used in order to place the results of suspected cases in perspective. Since June 2013, the hospital participated in the Dutch National Intensive Care Evaluation registry. To experience the possibilities of this registry, the characteristics of all patients admitted from June 2013 to April 2014 in the same ICU were extracted from this database. Post cardiothoracic surgery patients (44 % of all ICU admissions) were excluded. It should be realized that a reference population is not a control group and interpretation of finding should be performed in this perspective.

Microbiological data collection

Bronchoalveolar lavage fluids were initially analysed according to a highly standardized protocol as described elsewhere [37]. From each BALF sample, 6 ml was centrifuged (250 g for 10 min), dividing the sample into cells and supernatant. The supernatant was stored in tubes of 1 ml at −80 °C. The cells were re-suspended in 6 ml of a mixture of Eagle’s Minimal Essential Medium with 2 % Dimethyl Sulfoxide and stored in tubes of 1 ml at −80 °C. Oropharyngeal flora was (formerly) reported on the basis of classical bacteriological phenotypic identification tests. In order to confirm and specify these results, included samples were defrosted and quantitatively cultured on blood agar, chocolate agar, and MacConkey agar. The different colony types were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), a rapid and highly accurate soft ionization technique [38]. Antibiotic susceptibility was assessed for all separate strains when quantitative cultures revealed ≥ 104 cfu/ml. Results of polymerase chain reactions (PCRs) for viruses and Pneumocystis jirovecii, as well as Grocott’s methenamine silver staining, were collected from electronic patient data organisers using SAP. In patients that were both admitted to the hospital less than 8 days prior to BAL procedure and that lacked PCR results, PCRs for the identification of respiratory viruses were performed on the defrosted BALF. These viruses included influenza virus A and B, human respiratory syncytial virus, human metapneumovirus and parainfluenza virus 1–4. Furthermore, results of endotracheal aspirates (ETA) were analysed, preferably from the day of BAL, otherwise one day before or after. Endotracheal aspirates were obtained twice weekly and in case of clinical suspicion of a pulmonary infection. Samples were immediately microbiologically evaluated when obtained during daytime.

Commensal oropharyngeal flora caused ventilator-associated pneumonia likelihood

Based on the collected clinical, radiographic, and microbiological data and subsequent microbiological analyses made, the likelihood of presence of COF caused VAP (COF-VAP) was evaluated by 4 researchers (two consultant ICU physicians, one medical microbiologist, one ICU researcher).


Patient characteristics were analysed using descriptive statistics and presented as the mean ± standard deviation, median including interquartile range, or absolute numbers and percentages of patients, where applicable. Demographic and clinical characteristics of the suspected cases were compared with the reference population using the single sample t-test, the paired samples t-test or the Fisher’s exact test, where appropriate. For the comparison of the observed and expected mortality, a Chi-square test was used. A one-way within-subjects ANOVA was used to analyse the course of the SOFA-score, body temperature, leukocytes and CRP. Statistical significance was defined as P < .05. The IBM SPSS Statistics version 20 for Windows (Chicago, IL, USA) was used for analysis.


The study was conducted between January 2005 and July 2014. During this period, 17,254 patients were admitted to the ICU, of which 159 individuals met the VAP criteria during the study period. Twenty-three patients were considered to have COF-VAP (see Fig. 1 for inclusion flow chart). During the defined period, 899 patients (excluding post cardiothoracic surgery patients) needed ICU admission and consequently, these patients were included in the reference population.

Fig. 1
figure 1

Inclusion flow chart

Basic characteristics including clinical findings, BALF cytological results and outcome of the studied group and the reference population are presented in Table 1. Individual results of the analyses are presented in Table 2. The most common reason for ICU admission was respiratory failure (7/23 [30 %]) followed by multi-trauma (5/23 [22 %]). The reason for ICU admission of the study group was more often surgically related compared to the reference population (13/23 [57 %] vs. 267/899 [30 %], P = .01). Suspected COF-VAP developed after a median of 8 days of mechanical ventilation. Aspiration prior to BAL was considered possible in 3 patients. Five patients were mechanically ventilated for more than 2 days by means of a tracheostomy prior to the suspected VAP.

Table 1 Basic characteristics and clinical findings
Table 2 Characteristics, diagnostic results and outcome in suspected cases of commensal oropharyngeal flora caused ventilator-associated pneumonia

Clinical parameters

On the day of BAL, mean CPIS revealed 6.4 (standard deviation 2.4). An increase in mean SOFA score, white blood cell count, and CRP was observed on the day after the diagnosis compared to the day of diagnosis (See Fig. 2). After this initial increase, a gradual and persistent decrease was observed for all parameters.

Fig. 2
figure 2

Course of clinical and laboratory parameters. Numbers signify mean values in all commensal oropharyngeal flora caused ventilator-associated pneumonia suspected cases. *P value < .05 for the increase/decrease of the value as compared to the previous value


As shown in Table 1, median hospital LOS and ICU LOS in the studied group were significantly longer compared to the reference population (64 days vs. 24 days [P = .001] and 33 vs. 5.7 days [P < .001], respectively). The SMR in the studied group revealed 1.26 compared to 0.77 in the reference population (P = .137).

Microbiological results

Overall cytological BAL findings are presented in Table 1 and an individual overview of cytological and microbiological analysis is provided in Table 2. In 21 patients, a BALF cell count was performed revealing 13 BALF with more than 50 % polymorphonuclear neutrophils. In 11 BALF, 2 % or more BALF cells contained ICOs. Additionally, the percentage of squamous epithelial cells, an indicator of oropharyngeal contamination, was less than 1 % in all patients. In 6 patients, BALF could not be retrieved from storage and in 3 patients, BALF culture yielded no growth. These 3 fluid samples were preserved for 5, 6, and 9 years. In the remaining 14 BALF, MALDI-TOF-MS was able to identify 1 or more bacterial species. In 5 patients, bacteria ≥ 104 cfu/ml were identified, of which 2 types are potential pathogenic pathogens (Citrobacter koseri 106 cfu/ml and H. influenzae 106 cfu/ml) and 1 type possibly pathogenic (E. faecalis 2*104 cfu/ml). In 4 BALF, the presence of exclusively COF according to the definition was confirmed by MALTI-TOF-MS.

Endotracheal aspirates were obtained from all studied cases. Rare, moderate and heavy growth of COF was present in 9, 1, and 4 cases, respectively. Moderate or heavy growth of COF was present in 2 out of 15 patients with probably COF-VAP [sensitivity 13 %]). In 6 cases, moderate or heavy growth of another pathogenic microorganism was identified (S. aureus [twice], P. aeruginosa [twice], H. influenzae [case described above in this section], and M. morganii). Three cases were eventually diagnosed with pneumonia caused by the same microorganism (positive predictive value 50 %). PCR on BALF for viral pathogens was performed in 15 patients. Parainfluenza virus-3 (cycle threshold (ct) 19 [infection likely]) and Cytomegalovirus (ct 37 [probably reactivation]) were identified, each virus in 1 case. In 1 patient, Mycoplasma pneumoniae (ct 23 [infection likely]) was identified by PCR. In 1 case, both BALF Grocott’s staining and PCR were positive for Pneumocystis jirovecii.

Antibiotic treatment

Data concerning the administered antibiotics were available in 22 patients. Eleven of these patients (50 %) received (broad spectrum) antibiotics in the 72 h prior to the BAL. Overall, piperacillin/tazobactam was the most frequently used antibiotic (15/22 [68 %]). Five patients received inadequate treatment for COF-VAP (See Table 2; Patients no. 7, 8, 10, 22, and 23) of which 2 had unfavourable respiratory outcome (patients no. 8 and 10) and 2 died (patients no. 10 and 22), 47 and 3 days after the diagnosis, respectively. Of the 17 patients that received appropriate COF-VAP treatment, 6 patients died after a median of 54 days after the diagnosis.

Post mortem examination

In 4 out of the 9 deceased patients, consent for autopsy was obtained. Pathological evidence of an active pneumonia was found in 3 patients in post-mortem examination, performed at least 22 days after diagnosis. A faecal peritonitis was observed in the fourth patient, probably explaining her respiratory deterioration.

Level of certainty of the presence of commensal oropharyngeal flora ventilator-associated pneumonia

An alternative diagnosis was concerned more likely in 6 patients: Citrobacter koseri VAP, H. influenzae pneumonia, parainfluenza virus-3 CAP or E. faecium HAP, Mycoplasma pneumoniae CAP (all 4 with clinical signs of pneumonia), Pneumocystis jirovecii caused CAP (with CT-thorax suggestive of Pneumocystis pneumonia), and abdominal sepsis (with clinical signs of an ileus the day before the patient deceased). Eleven patients received antibiotics in the three days prior to the (presumed) VAP, making their culture results more difficult to interpret. The cultures in cases number 2 and 18 yielded ≥103 cfu/ml P. aeruginosa and S. aureus, respectively, under appropriate antibiotic treatment, which cannot exclude their causative contribution to VAP. Therefore these 2 cases were considered to have possible COF-VAP. In the remaining 15 cases (9.4 % of all VAP cases), no other infection was found and COF-VAP was considered likely.

Additional findings

Additionally, 3 cases of probable COF-HAP and 1 case of probable COF-HAP were identified in 8 eligible cases (see Appendix). Besides the fact that these 4 positive cases were immunocompromised due to previous used medication or malignancies, further discussion of this subgroup is beyond the scope of this article.


This large retrospective analysis of a prospectively collected case series revealed 23 patients suspected of COF-VAP. In 15 patients (9.4 % of all VAP cases), COF-VAP was the most likely diagnosis.

Previous studies

So far, 1 currently available study investigated the possible role of COF as the cause of VAP [39]. This French group retrospectively investigated 29 episodes of VAP with significant growth of oropharyngeal and cutaneous commensal microorganisms in BALF and protected brush specimen derived from 28 immunocompetent patients. The suspected cases also revealed signs of VAP including a longer ICU LOS. A panel of 3 experts confirmed 14 out of the 29 (48 %) suspected cases as COF-VAP (corresponding to 3.8 % of their VAP cases), whereas in the other cases an alternative diagnosis was considered more likely. The authors concluded that COF may cause VAP in ICU patients with no known prior immunodeficiency, that it has similar clinical features as VAP, and that patients should be treated with antibiotics with the probable exception of stable patients with a high likelihood of an alternative diagnosis [39]. The results of the present study, using more clinical data and microbiological analyses, are in support of their preliminary findings.

Two decades ago, several small studies revealed the presence of COF in post-mortem lung biopsy cultures in previously mechanically ventilated patients [4042] (reported incidences varied from 9 % to 57 %, with not all studies reporting the level of growth), whereas another study found no COF in post-mortem biopsy diagnosed VAP cases [43].


One might perhaps expect a rise in COF-VAP rates after the introduction of SOD/SDD, as it focusses on the elimination of Gram negatives as well as the selection of commensal bacteria [44]. Yet, so far (see Table 2) no diagnosis of COF-VAP was made after the introduction of SOD/SDD, whereas the incidence of VAP per 1,000 ventilator days declined from 4.38 ± 1.64 before to 1.64 ± 0.43 (P = .007) after the introduction of SOD and SDD in our clinic [45].

Results of endotracheal aspirates

Whereas ETA and BALF analysis can both be used to diagnose VAP [14, 30], results of these 2 diagnostic modalities agree only fairly [46]. Overall, the current results confirm the poor agreement between BALF and ETA analyses results.

Re-cultured bronchoalveolar lavage fluid and identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Whereas all 23 BALF samples revealed ≥ 104 cfu/ml COF at the time of the BAL procedure, the repeated microbiological examinations on preserved specimen were frequently not in accordance. The BALF samples that revealed no growth were similar durations as the samples that did reveal growth, suggesting that the time of storage did not cause the disagreement. However, Neisseria spp., Streptococcus spp. (not S. pyogenes), and Haemophilus spp. are known with a limited survival on inanimate surfaces [47], contributing to the absence of growth on re-culturing despite the correct solvents and temperature. The lack of significant growth of microorganism could have been related to the storage-related factors, as well as the presence of antibiotics in the sample before storage. On the other hand, one may doubt if the C. koserii, H. influenzae, and E. faecalis identified by MALDI-TOF-MS were true pathogens or that their presence was caused by contamination before, during, or after the BALF storage and retrieval.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was able to identify all strains that re-grew on any agar plate. Rothia dentocariosa, Capnocytophaga sputigena, and Lactobacillus acidophilus are part of COF, although not included in our definition since these species were not routinely identified before MALDI-TOF-MS use.


Although some results are more difficult to interpret due to previous antibiotic use, identified COF is mostly susceptible to the antibiotics used, but was nonetheless still present in significant numbers in BALF. Furthermore, at least 9 patients that were eventually diagnosed with COF-VAP did not receive antibiotics prior to BAL. In 6 patients, an alternative diagnosis was concerned more likely, although COF as a contributing or the main cause of VAP can neither be established nor excluded with certainty. Remarkably, 3 suspected VAP cases actually had CAP.

Treatment and outcome

Four out of the 15 patients with probable COF-VAP received inappropriate antibiotic treatment. The respiratory outcome was unfavourable in 2 out of 3 cases that survived the VAP episode, suggesting that COF-VAP should be treated appropriately. Commensal oropharyngeal flora is generally susceptible to the antibiotics suggested by authoritative guidelines [14].

Entity or fiction?

Although no hard argument can be provided to state that COF-VAP is an entity, 6 arguments originated from the present study support that COF indeed may cause VAP. First, it is plausible from a pathophysiological point of view. As stated in the introduction section, COF may behave pathogenic in immunocompromised patients. Whereas COF-VAP developed after a median of 8 days of mechanical ventilation, a previously immunocompetent person may already be considered immunocompromised after 48 h of ICU admission [24]. Additionally, many COF-VAP suspected cases revealed positive viral and fungal PCR, which is also associated with a decreased immune status. Finally, COF was able to cause HAP and CAP in immunocompromised patients. Second, scores resulting from generally accepted clinical scoring systems, as well as laboratory results, indicated a significant clinical relevance. Third, cytological analysis of BALF frequently was indicative of a bacterial infection. Fourth, COF was the most likely cause of VAP in 15 cases and possibly the cause in 2 cases. Fifth, inappropriate antibiotic treatment for COF-VAP (n = 4) was associated with unfavourable respiratory outcome. Sixth and last, COF-VAP was associated with increased ICU and hospital LOS including a trend towards increased mortality as compared to a reference population.

Contrariwise, post-mortem examination 4 days after BAL of one patient revealed no signs of pneumonia, indicative of a false positive BALF analysis. However, at the time of BAL, this patient presents with an ileus and abdominal sepsis was the post-mortem diagnosis. Although it is possible that the patient fulfilled all criteria for performing a BAL due to the extrapulmonary problems, BAL should thus only be performed in the absence of an obvious alternative explanation for the patient’s clinical presentation.

The current study demonstrated a probable association between merely significant growth of COF in VAP suspected patients and worse outcome. Similar to VAP caused by other microorganisms [2], it remains unknown whether this association is causal or that COF-VAP results from critical illness and that the outcome is therefore unfavourable.

Limitations of the study

There are several limitations to the study. First, due to the lack of a globally accepted gold standard to diagnose VAP [7, 8, 11], VAP in clinically suspected patients was defined as BALF revealing ≥ 2 % ICOs and/or significant growth (≥ 104 cfu/ml [36]) of a potential pathogenic microorganism. Second, a limited number of clinical and microbiological data were irretrievable in a number of patients. Third, median ICU and hospital LOS of the suspected cases were compared to mean LOS in a recent patient population. Since mean ICU and hospital LOS declined during the studied period (2005–2013), this comparison may be unfair. However, since the mean ICU LOS was 8.6 days in 2005, a median ICU LOS of 33 days in the studied period is still significantly higher. Fourth, enterococci were excluded as a potential cause for VAP, although these microorganisms may possibly also cause VAP in the immunocompromised ICU-patient. Fifth, a reference population is not a control group. In future studies, a control group should preferably consist of “regular” VAP cases to demonstrate that COF behaves like “regular” VAP causative microorganisms. Finally, in the process of BALF storage and re-culturing the occurrence of contamination cannot be ruled out.

Future studies

Since COF-VAP has a low overall incidence (15 out of 6500 ICU admissions [0.23 %]) and VAP incidences decline [45, 48], future research should preferably focus on multi-centre trials. Notwithstanding, when more similar studies become available, a meta-analysis could empower the results of Lambotte et al. and the current study.


As COF was identified as the most likely causative agent in 9.4 % of all VAP episodes, COF is probably an overlooked cause of VAP. The immunocompromised status of the ICU patient may contribute to its origination. Commensal oropharyngeal flora VAP is probably associated with significant clinical signs of bacterial infection, a prolonged ICU and hospital LOS, and a trend towards increased mortality. In the absence of other pulmonary and non-pulmonary explanations for a patient’s pulmonary deterioration, ICU physicians should perhaps acknowledge this entity and treat it accordingly.





Acute physiology and chronic health evaluation


Bbronchoalveolar lavage


Bronchoalveolar lavage fluid


Community-acquired pneumonia


Chronic lymphocytic leukaemia




Coagulase-negative staphylococcus


Continues positive airway pressure


Clinical pulmonary infection score


C-reactive protein


Cycle threshold


Endotracheal aspirate




Hospital-acquired pneumonia


Intracellular organism, in Table, percentage of BAL fluid cells containing intracellular organisms


Intensive care unit


Interquartile range


Length of stay




Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry


Mechanical ventilation


Not performed


Obstructive sleep apnoea syndrome


Pneumocystis pneumonia


Polymerase chain reaction


Parainfluenza virus


Polymorphonuclear neutrophils


Standard deviation


Selective digestive tract decontamination


Standardized mortality ratio


Selective oropharyngeal decontamination


Sequential organ failure assessment


Ventilator-associated pneumonia


  1. Klompas M, Khan Y, Kleinman K, Evans RS, Lloyd JF, Stevenson K, et al. Multicenter evaluation of a novel surveillance paradigm for complications of mechanical ventilation. PLoS One. 2011;6(3), e18062.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med. 2005;33(10):2184–93.

    Article  PubMed  Google Scholar 

  3. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323–9.

    CAS  Article  PubMed  Google Scholar 

  4. Kuti EL, Patel AA, Coleman CI. Impact of inappropriate antibiotic therapy on mortality in patients with ventilator-associated pneumonia and blood stream infection: a meta-analysis. J Crit Care. 2008;23(1):91–100.

    Article  PubMed  Google Scholar 

  5. Melsen WG, Rovers MM, Groenwold RH, Bergmans DC, Camus C, Bauer TT, et al. Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis. 2013;13(8):665–71.

    Article  PubMed  Google Scholar 

  6. Klompas M. Eight initiatives that misleadingly lower ventilator-associated pneumonia rates. Am J Infect Control. 2012;40(5):408–10.

    Article  PubMed  Google Scholar 

  7. Grgurich PE, Hudcova J, Lei Y, Sarwar A, Craven DE. Diagnosis of ventilator-associated pneumonia: controversies and working toward a gold standard. Curr Opin Infect Dis. 2013;26(2):140–50.

    Article  PubMed  Google Scholar 

  8. Novosel TJ, Hodge LA, Weireter LJ, Britt RC, Collins JN, Reed SF, et al. Ventilator-associated pneumonia: depends on your definition. Am Surg. 2012;78(8):851–4.

    PubMed  Google Scholar 

  9. Raoof S, Baumann MH. An official multi-society statement: ventilator-associated events: the new definition. Crit Care Med. 2014;42(1):228–9.

    Article  PubMed  Google Scholar 

  10. Grossman RF, Fein A. Evidence-based assessment of diagnostic tests for ventilator-associated pneumonia. Executive Summary Chest. 2000;117(4 Suppl 2):177S–81S.

    CAS  PubMed  Google Scholar 

  11. Hunter JD. Ventilator associated pneumonia. BMJ. 2012;344, e3325.

    Article  PubMed  Google Scholar 

  12. Rello J, Diaz E, Rodriguez A. Etiology of ventilator-associated pneumonia. Clin Chest Med. 2005;26(1):87–95.

    Article  PubMed  Google Scholar 

  13. Cabello H, Torres A, Celis R, El-Ebiary M, Puig de la Bellacasa J, Xaubet A, et al. Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study. Eur Respir J. 1997;10(5):1137–44.

    CAS  Article  PubMed  Google Scholar 

  14. American Thoracic S, Infectious Diseases Society of A. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388–416.

    Article  Google Scholar 

  15. Carratala J, Roson B, Fernandez-Sevilla A, Alcaide F, Gudiol F. Bacteremic pneumonia in neutropenic patients with cancer: causes, empirical antibiotic therapy, and outcome. Arch Intern Med. 1998;158(8):868–72.

    CAS  Article  PubMed  Google Scholar 

  16. Shenep JL. Viridans-group streptococcal infections in immunocompromised hosts. Int J Antimicrob Agents. 2000;14(2):129–35.

    CAS  Article  PubMed  Google Scholar 

  17. Wong CA, Donald F, Macfarlane JT. Streptococcus milleri pulmonary disease: a review and clinical description of 25 patients. Thorax. 1995;50(10):1093–6.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Shinzato T, Saito A. The Streptococcus milleri group as a cause of pulmonary infections. Clin Infect Dis. 1995;21 Suppl 3:S238–43.

    Article  PubMed  Google Scholar 

  19. Hauser AR, Jain M, Bar-Meir M, McColley SA. Clinical significance of microbial infection and adaptation in cystic fibrosis. Clin Microbiol Rev. 2011;24(1):29–70.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Sibley CD, Parkins MD, Rabin HR, Duan K, Norgaard JC, Surette MG. A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients. Proc Natl Acad Sci U S A. 2008;105(39):15070–5.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. DiBardino DM, Wunderink RG. Aspiration pneumonia: A review of modern trends. J Crit Care. 2015;30(1):40–8.

    Article  PubMed  Google Scholar 

  22. Opal SM. Immunologic alterations and the pathogenesis of organ failure in the ICU. Semin Respir Crit Care Med. 2011;32(5):569–80.

    Article  PubMed  Google Scholar 

  23. Kox M, Vrouwenvelder MQ, Pompe JC, van der Hoeven JG, Pickkers P, Hoedemaekers CW. The effects of brain injury on heart rate variability and the innate immune response in critically ill patients. J Neurotrauma. 2012;29(5):747–55.

    Article  PubMed  Google Scholar 

  24. Conway Morris A, Anderson N, Brittan M, Wilkinson TS, McAuley DF, Antonelli J, et al. Combined dysfunctions of immune cells predict nosocomial infection in critically ill patients. Br J Anaesth. 2013;111(5):778–87.

    CAS  Article  PubMed  Google Scholar 

  25. Bonten MJ, Bergmans DC, Stobberingh EE, van der Geest S, De Leeuw PW, van Tiel FH, et al. Implementation of bronchoscopic techniques in the diagnosis of ventilator-associated pneumonia to reduce antibiotic use. Am J Respir Crit Care Med. 1997;156(6):1820–4.

    CAS  Article  PubMed  Google Scholar 

  26. Linssen CF, Jacobs JA, Schouten JS, van Mook WN, Ramsay G, Drent M. Influence of antibiotic therapy on the cytological diagnosis of ventilator-associated pneumonia. Intensive Care Med. 2008;34(5):865–72.

    Article  PubMed  Google Scholar 

  27. File TM. Community-acquired pneumonia. Lancet. 2003;362(9400):1991–2001.

    Article  PubMed  Google Scholar 

  28. Murray PR, Rosenthal KS, Pfaller MA, editors. Medical Microbiology. Seventh Edition. Elsevier; 2012. ISBN: 978-0-323-08692-9 [].

  29. el-Ebiary M, Torres A, Fabregas N, de la Bellacasa JP, Gonzalez J, Ramirez J, et al. Significance of the isolation of Candida species from respiratory samples in critically ill, non-neutropenic patients. An immediate postmortem histologic study. Am J Respir Crit Care Med. 1997;156(2 Pt 1):583.

    CAS  Article  PubMed  Google Scholar 

  30. Magill SS, Klompas M, Balk R, Burns SM, Deutschman CS, Diekema D, et al. Developing a new, national approach to surveillance for ventilator-associated events*. Crit Care Med. 2013;41(11):2467–75.

    Article  PubMed  Google Scholar 

  31. Medford AR, Husain SA, Turki HM, Millar AB. Diagnosis of ventilator-associated pneumonia. J Crit Care. 2009;24(3):473. e471-476.

    Article  PubMed  Google Scholar 

  32. Canadian Critical Care Trials G. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med. 2006;355(25):2619–30.

    Article  Google Scholar 

  33. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–29.

    CAS  Article  PubMed  Google Scholar 

  34. Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793–800.

    CAS  Article  PubMed  Google Scholar 

  35. Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286(14):1754–8.

    CAS  Article  PubMed  Google Scholar 

  36. Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991;143(5 Pt 1):1121–9.

    CAS  Article  PubMed  Google Scholar 

  37. De Brauwer EI, Jacobs JA, Nieman F, Bruggeman CA, Wagenaar SS, Drent M. Cytocentrifugation conditions affecting the differential cell count in bronchoalveolar lavage fluid. Anal Quant Cytol Histol. 2000;22(5):416–22.

    PubMed  Google Scholar 

  38. Clark AE, Kaleta EJ, Arora A, Wolk DM. Matrix-assisted laser desorption ionization-time of flight mass spectrometry: a fundamental shift in the routine practice of clinical microbiology. Clin Microbiol Rev. 2013;26(3):547–603.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. Lambotte O, Timsit JF, Garrouste-Orgeas M, Misset B, Benali A, Carlet J. The significance of distal bronchial samples with commensals in ventilator-associated pneumonia: colonizer or pathogen? Chest. 2002;122(4):1389–99.

    Article  PubMed  Google Scholar 

  40. Rouby JJ, Martin De Lassale E, Poete P, Nicolas MH, Bodin L, Jarlier V, et al. Nosocomial bronchopneumonia in the critically ill. Histologic and bacteriologic aspects. Am Rev Respir Dis. 1992;146(4):1059–66.

    CAS  Article  PubMed  Google Scholar 

  41. Kirtland SH, Corley DE, Winterbauer RH, Springmeyer SC, Casey KR, Hampson NB, et al. The diagnosis of ventilator-associated pneumonia: a comparison of histologic, microbiologic, and clinical criteria. Chest. 1997;112(2):445–57.

    CAS  Article  PubMed  Google Scholar 

  42. Torres A, el-Ebiary M, Padro L, Gonzalez J, de la Bellacasa JP, Ramirez J, et al. Validation of different techniques for the diagnosis of ventilator-associated pneumonia. Comparison with immediate postmortem pulmonary biopsy. Am J Respir Crit Care Med. 1994;149(2 Pt 1):324–31.

    CAS  Article  PubMed  Google Scholar 

  43. Papazian L, Thomas P, Garbe L, Guignon I, Thirion X, Charrel J, et al. Bronchoscopic or blind sampling techniques for the diagnosis of ventilator-associated pneumonia. Am J Respir Crit Care Med. 1995;152(6 Pt 1):1982–91.

    CAS  Article  PubMed  Google Scholar 

  44. Van de Voort PHJ, van Saene HKF, editors. Selective Digestive Tract Decontamination in Intensive Care Medicine. A Practical Guide to Controlling Infection. 1st Edition. Italy: Springer-Verlag Italia; 2008.

  45. Schnabel RM, Scholte JB, Van Der Velden KE, Roekaerts PM, Bergmans DC. Ventilator-associated pneumonia rates after introducing selective digestive tract decontamination. Infect Dis. 2015;1–4.

  46. Scholte JB, van Dessel HA, Linssen CF, Bergmans DC, Savelkoul PH, Roekaerts PM, et al. Endotracheal aspirate and bronchoalveolar lavage fluid analysis: interchangeable diagnostic modalities in suspected ventilator-associated pneumonia? J Clin Microbiol. 2014;52(10):3597–604.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kramer A, Schwebke I, Kampf G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review BMC Infect Dis. 2006;6:130.

    Article  PubMed  Google Scholar 

  48. Pileggi C, Bianco A, Flotta D, Nobile CG, Pavia M. Prevention of ventilator-associated pneumonia, mortality and all intensive care unit acquired infections by topically applied antimicrobial or antiseptic agents: a meta-analysis of randomized controlled trials in intensive care units. Crit Care. 2011;15(3):R155.

    Article  PubMed  PubMed Central  Google Scholar 

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The advice and support in the statistical analysis by professor R. Vos of the department of statistics and methodology at Maastricht University are very much appreciated.

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Correspondence to Johannes B. J. Scholte.

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Competing interests

The authors declare that they have no competing interest.

Authors’ contributions

CFML initiated the study together with WNKAvM. JBJS, JIMvdV, and CFML prospectively collected and managed the database. JBJS and JIMvdV performed all statistical and initial interpretation of the results, wrote the first drafts of the manuscript and coordinated the implementation of suggestions from the other authors. The COF-VAP likelihood was evaluated by JBJS, JIMvdV, CFML, and WNKAvM. All authors actively participated in discussions on previous drafts and provided multiple qualitative comments resulting in the final approved manuscript.

Authors’ information

JBJS, DCJJB and WNKAvM are all consultants in internal medicine and intensive care medicine. WNKAvM is also an associate professor in medical education and chair of the professional behaviour committee at Maastricht University. JIMvdV is a resistant in anaesthesiology. CFML and HAvD are consultants in medical microbiology. PHMS is professor and chair of the department of medical microbiology and PMHJR is professor and chair of the department of intensive care medicine.

An erratum to this article is available at


Table 3 Individual characteristics, diagnostic results and outcome of the suspected cases of commensal oropharyngeal flora caused hospital-acquired pneumonia and community-acquired pneumonia

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Scholte, J.B.J., van der Velde, J.I.M., Linssen, C.F.M. et al. Ventilator-associated Pneumonia caused by commensal oropharyngeal Flora: a retrospective Analysis of a prospectively collected Database. BMC Pulm Med 15, 86 (2015).

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  • Ventilator-associated pneumonia
  • Bronchoalveolar lavage
  • Commensal oropharyngeal flora
  • Intensive care unit