Ventilator-associated Respiratory Infections Research Articles

Ventilator-associated events versus ventilator-associated respiratory infections-moving into a new paradigm or merging both concepts, instead?

Despite ventilator-associated respiratory infections (VARI) are reported as the most common and fatal complications related to mechanical ventilation (MV), they are not the unique occurrences. The new classification of ventilator-associated events (VAE) proposed by the centers for disease control and prevention (CDC) enhance the spectra of complications due to MV including both infection-related and non-infectious events. Both VAEs and VARIs are associated with prolonged duration of MV, longer stay in hospital and in the intensive care unit (ICU) and more antibiotic consumption, nonetheless patients with VAEs have worst outcomes. The VARI and VAE algorithms are focused on different targets and the correlation between both classifications is shown to be poor. The diagnostic criteria of the traditional classification have limited accuracy and the non-infectious complications may be misinterpreted as VARI. While the VAE surveillance enhances the spectra of MV complications but excludes less severe VARIs. Noninfective events explain up to 30% of VAEs, the main causes being atelectasis, acute respiratory distress syndrome, pulmonary edema and pulmonary embolism. The bundles assessing VAE are associated with less incidence of VAP and improved outcomes but they fail to reduce the rates of VAE. Automated VAE surveillance is efficient and useful as a quality indicator in the ICU while the differences in the interpretation of VARI criteria limit its role in the design of global protocols and preventive strategies. We suggest that a more comprehensive strategy should combine both algorithms with emphasis on clinical outcomes.

Excess direct hospital cost of treating adult patients with ventilator associated respiratory infection (VARI) in Vietnam

IntroductionVentilator associated respiratory infections (VARIs) are the most common hospital acquired infections in critical care worldwide. This work aims to estimate the total annual direct hospital cost of treating VARI throughout Vietnam.MethodsA costing model was constructed to evaluate the excess cost of diagnostics and treatment of VARI in Vietnam. Model inputs included costs for extra lengths of stay, diagnostics, VARI incidence, utilisation of ventilators and antibiotic therapy.ResultsWith the current VARI incidence rate of 21.7 episodes per 1000 ventilation-days, we estimated 34,428 VARI episodes in the 577 critical care units in Vietnam per year. The extra cost per VARI episode was $1,174.90 and the total annual excess cost was US$40.4 million. A 1% absolute reduction in VARI incidence density would save US$1.86 million annually. For each episode of VARI, the share of excess cost components was 45.1% for critical care unit stay and ventilation, 3.7% for diagnostics and 51.1% for extra antimicrobial treatment.ConclusionsAt the current annual government health expenditure of US$117 per capita, VARI represents a substantial cost to the health service in Vietnam. Enhanced infection prevention and control and antimicrobial stewardship programmes should be implemented to reduce this.

C-reactive protein and procalcitonin profile in ventilator-associated lower respiratory infections

PurposeVentilator-associated tracheobronchitis (VAT) has been suggested as an intermediate process between tracheobronchial colonization and ventilator-associated pneumonia (VAP) in patients receiving mechanical ventilation. The aim of this study was to evaluate the ability of C-reactive protein (CRP) and procalcitonin (PCT) to differentiate between VAT and VAP. MethodsPre-planned analysis of the prospective multinational TAVeM database, performed on 2960 patients receiving mechanical ventilation for >48 h, including 689 patients with VA-LRTI. Patients with the diagnosis of VAT or VAP microbiologically documented and with one measurement of CRP and/or PCT on the day of diagnosis were included. ResultsFour hundred and four patients (mean age 63 years, 298 men, ICU mortality 40%) were studied, 207 with VAT and 197 with VAP. On the day of infection diagnosis, the median CRP was elevated in both groups but significantly higher in VAP (18 mg/dL vs. 14 mg/dL, p = .001). Median PCT was also significantly higher in VAP (2.1 ng/dL vs. 0.64 ng/d L, p < .001). Both biomarkers could not help distinguish between VAT and VAP. ConclusionAlthough PCT and CRP presented lower values in VAT as compared to VAP, there was a marked overlap of both biomarkers values in both VA-LRTI not allowing adequate discrimination.

Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial

BackgroundVentilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam.Methods/designThis is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admission diagnosis (180 tetanus, 420 non-tetanus) and site and will be randomised in a 1:1 ratio to receive either (1) automated, continuous control of endotracheal cuff pressure or (2) intermittent measurement and control of endotracheal cuff pressure using a manual cuff pressure meter. The primary outcome is the occurrence of VARI, defined as either VAP or VAT during the ICU admission up to a maximum of 90 days after randomisation. Patients in both groups who are at risk for VARI will receive a standardised battery of investigations if their treating physician feels a new infection has occurred, the results of which will be used by an endpoint review committee, blinded to the allocated arm and independent of patient care, to determine the primary outcome. All enrolled patients will be followed for mortality and endotracheal tube cuff-related complications at 28 days and 90 days after randomisation. Other secondary outcomes include antibiotic use; days ventilated, in ICU and in hospital; inpatient mortality; costs of antibiotics in ICU; duration of ICU stay; and duration of hospital stay.DiscussionThis study will provide high-quality evidence concerning the use of continuous endotracheal cuff pressure control as a method to reduce VARI, antibiotic use and hospitalisation costs and to shorten stay.Trial registrationClinicalTrials.gov, NCT02966392. Registered on November 9, 2016. Protocol version: 2.0; issue date March 3, 2017.

Distribution of New Delhi metallo-beta-lactamase producing Acinetobacter baumannii in patients with ventilator associated respiratory tract infection

Background and objectives: Ventilator-associated respiratory tract infection (VARTI) is a major cause of morbidity and mortality among the critically ill patients of intensive care units (ICU). Acinetobacter baumannii, an important offending pathogen in VARTI, has been found to be resistant to several antibiotics including carbapenems. The present study was conducted to determine the rate of New Delhi metallo-β-lactamase 1(NDM-1) producing A. baumannii causing VARTI among the patients admitted in an ICU of a large tertiary care hospital.Methods: The study was conducted from July 2013 to June 2014. Endotracheal aspirates (ETA) were collected from patients with clinically suspected VARTI. Samples were collected from patients who were on mechanical ventilation for more than 48 hours. ETA samples were cultured aerobically and isolated A. baumannii were tested for susceptibility to carbapenem. Presence of NDM-1 encoded by the blaNDM-1 gene was detected by polymerase chain reaction (PCR).Results: A total of 138 VARTI cases were included in the study. Total 107 (77.5%) bacteria were isolated from 138 ETA samples of which 38 were A. baumannii. Out of 38 isolated A. baumannii, 35 (92.1%) were resistant to imipenem/meropenem and 33 (86.8%) were positive for blaNDM-1 gene by PCR.Conclusion: The present study demonstrated that high proportion of A. baumannii isolated from VARTI cases in ICU were carbapenem resistant and blaNDM-1 positive. Careful infection control program should be considered to contain the spread of this multi-resistant organism to other hospital and community.IMC J Med Sci 2018; 12(1): 37-41

New Approaches to Anti-infective Treatment of Ventilator-Associated Respiratory Infections caused by Pseudomonas aeruginosa

Study background: The purpose of this study was to evaluate recent strategies for anti-infective treatment in patients suffering from ventilator-associated respiratory infections caused by P. aeruginosa and to assess the riskbenefit profile of inhaled tobramycin.Methods: Electronic health records of patients suffering from respiratory infections caused by P. aeruginosa from 2011-2014 were retrospectively screened.Results: In 81 patients, P. aeruginosa was found in respiratory secretions, of which 26 patients suffered from ventilator-associated pneumonia (VAP), whereas 55 patients only fulfilled criteria of ventilator-associated tracheitis (VAT). Inhaled tobramycin was used in 14 patients with VAP and 31 patients with VAT. In this context, inhaled tobramycin was shown to be safe (e.g. no bronchoconstriction or systemic toxicity) and did not result in an increase of tobramycin resistant strains in respiratory secretions at 90 days following study inclusion. However, a clear clinical benefit (e.g. reduced need for i.v. antibiotics) could not be shown.\Conclusion: Inhaled tobramycin was shown to be a suitable approach with a favorable risk profile to treat patients suffering from respiratory infections (VAP, VAT) caused by P. aeruginosa. The clinical benefit needs to be reevaluated in a larger prospective investigation.

Ventilator-associated respiratory infection in a resource-restricted setting: impact and etiology

BackgroundVentilator-associated respiratory infection (VARI) is a significant problem in resource-restricted intensive care units (ICUs), but differences in casemix and etiology means VARI in resource-restricted ICUs may be different from that found in resource-rich units. Data from these settings are vital to plan preventative interventions and assess their cost-effectiveness, but few are available.MethodsWe conducted a prospective observational study in four Vietnamese ICUs to assess the incidence and impact of VARI. Patients ≥ 16 years old and expected to be mechanically ventilated > 48 h were enrolled in the study and followed daily for 28 days following ICU admission.ResultsFour hundred fifty eligible patients were enrolled over 24 months, and after exclusions, 374 patients’ data were analyzed. A total of 92/374 cases of VARI (21.7/1000 ventilator days) were diagnosed; 37 (9.9%) of these met ventilator-associated pneumonia (VAP) criteria (8.7/1000 ventilator days). Patients with any VARI, VAP, or VARI without VAP experienced increased hospital and ICU stay, ICU cost, and antibiotic use (p < 0.01 for all). This was also true for all VARI (p < 0.01 for all) with/without tetanus. There was no increased risk of in-hospital death in patients with VARI compared to those without (VAP HR 1.58, 95% CI 0.75–3.33, p = 0.23; VARI without VAP HR 0.40, 95% CI 0.14–1.17, p = 0.09). In patients with positive endotracheal aspirate cultures, most VARI was caused by Gram-negative organisms; the most frequent were Acinetobacter baumannii (32/73, 43.8%) Klebsiella pneumoniae (26/73, 35.6%), and Pseudomonas aeruginosa (24/73, 32.9%). 40/68 (58.8%) patients with positive cultures for these had carbapenem-resistant isolates. Patients with carbapenem-resistant VARI had significantly greater ICU costs than patients with carbapenem-susceptible isolates (6053 USD (IQR 3806–7824) vs 3131 USD (IQR 2108–7551), p = 0.04) and after correction for adequacy of initial antibiotics and APACHE II score, showed a trend towards increased risk of in-hospital death (HR 2.82, 95% CI 0.75–6.75, p = 0.15).ConclusionsVARI in a resource-restricted setting has limited impact on mortality, but shows significant association with increased patient costs, length of stay, and antibiotic use, particularly when caused by carbapenem-resistant bacteria. Evidence-based interventions to reduce VARI in these settings are urgently needed.

Is There a Role for Inhaled Antibiotics in the Treatment of Ventilator-Associated Infections?

The increasing emergence of multidrug-resistant organisms creates a therapeutic challenge for physicians treating ventilator-associated respiratory infections. As the production of new systemic antibiotics lags far behind the emergence of worsening antibiotic resistance, intensivists are turning to inhaled antibiotics to use as adjunctive therapy. When given properly, these drugs can provide high concentrations of drug in the lung that could not be achieved with intravenous antibiotics without significant systemic toxicity. This review summarizes current evidence describing the use of inhaled antibiotics for the treatment of bacterial ventilator-associated infections. Inhaled adjunctive therapy has been described in numerous small nonrandomized studies and in six recent randomized placebo-controlled trials. Inhaled therapy has also been used to treat ventilator-associated tracheobronchitis. These preliminary data suggest aerosolized delivery of antimicrobials may effectively treat resistant pathogens with high minimum inhibitory concentrations when used in time-limited protocols and delivered with devices known to deposit antibiotics in the area of infection. Large, multisite, clinical, randomized placebo-controlled studies are needed to confirm these data.

A prospective study of ventilator-associated tracheobronchitis: Incidence and etiology in intensive care unit of a tertiary care hospital.

Context:Ventilator-associated tracheobronchitis (VAT) is an infective complication of mechanical ventilation and is a part of the spectrum of ventilator-associated respiratory infections. In the Intensive Care Units (ICUs), VAT is a relatively common problem but in comparison to ventilator-associated pneumonia (VAP), much less data are available on VAT and its management.Materials and Methods:Patients ventilated for more than 48 hours were screened daily for the development of VAT. Patients were followed up daily until they were extubated, died or discharged from the hospital. The patient demographics, underlying condition, causative organism and resistance patterns were observed.Results:13.2% of patients developed VAT. The majority patients who developed VAT had underlying neurological problems. The mean time to develop VAT from the time of mechanical ventilation was 7.3 days and from time of ICU admission was 10 days, respectively. Multidrug-resistant (MDR) Acinetobacter sp. and Pseudomonas aeruginosa were the most frequently isolated organisms.Conclusions:VAT is a common healthcare-associated infection caused mostly by MDR Gram-negative bacteria. Monitoring and active surveillance are required to detect VAT at the earliest to institute appropriate isolation measures and therapy.

Is HELICS the Right Way? Lack of Chest Radiography Limits Ventilator-Associated Pneumonia Surveillance in Wales.

Introduction: The reported incidence of ventilator-associated pneumonia (VAP) in Wales is low compared with surveillance data from other European regions. It is unclear whether this reflects success of the Welsh healthcare-associated infection prevention measures or limitations in the application of European VAP surveillance methods. Our primary aim was to investigate episodes of ventilator-associated respiratory tract infection (VARTI), to identify episodes that met established criteria for VAP, and to explore reasons why others did not, according to the Hospitals in Europe Link for Infection Control through Surveillance (HELICS) definitions.Materials and Methods: During two 14-day study periods 2012–2014, investigators reviewed all invasively ventilated patients in all 14 Welsh Intensive Care Units (ICUs). Episodes were identified in which the clinical team had commenced antibiotic therapy because of suspected VARTI. Probability of pneumonia was estimated using a modified Clinical Pulmonary Infection Score (mCPIS). Episodes meeting HELICS definitions of VAP were identified, and reasons for other episodes not meeting definitions examined. In the second period, each patient was also assessed with regards to the development of a ventilator-associated event (VAE), according to recent US definitions.Results: The study included 306 invasively ventilated patients; 282 were admitted to ICU for 48 h or more. 32 (11.3%) patients were commenced on antibiotics for suspected VARTI. Ten of these episodes met HELICS definitions of VAP, an incidence of 4.2 per 1000 intubation days. In 48% VARTI episodes, concurrent chest radiography was not performed, precluding the diagnosis of VAP. Mechanical ventilation (16.0 vs. 8.0 days; p = 0.01) and ICU stay (25.0 vs. 11.0 days; p = 0.01) were significantly longer in patients treated for VARTI compared to those not treated. There was no overlap between episodes of VARTI and of VAE.Discussion: HELICS VAP surveillance definitions identified less than one-third of cases in which antibiotics were commenced for suspected ventilator-associated RTI. Lack of chest radiography precluded nearly 50% cases from meeting the surveillance definition of VAP, and as a consequence we are almost certainly underestimating the incidence of VAP in Wales.

The use of inhaled antibiotic therapy in the treatment of ventilator-associated pneumonia and tracheobronchitis: a systematic review.

BackgroundVentilator-associated respiratory infections (tracheobronchitis, pneumonia) contribute significant morbidity and mortality to adults receiving care in intensive care units (ICU). Administration of broad-spectrum intravenous antibiotics, the current standard of care, may have systemic adverse effects. The efficacy of aerosolized antibiotics for treatment of ventilator-associated respiratory infections remains unclear. Our objective was to conduct a systematic review of the efficacy of aerosolized antibiotics in the treatment of ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT), using the Cochrane Collaboration guidelines.MethodsWe conducted a search of three databases (PubMed, Web of Knowledge and the Cochrane Collaboration) for randomized, controlled trials studying the use of nebulized antibiotics in VAP and VAT that measured clinical cure (e.g., change in Clinical Pulmonary Infection Score) as an outcome measurement. We augmented the electronic searches with hand searches of the references for any narrative review articles as well as any article included in the systematic review. Included studies were examined for risk of bias using the Cochrane Handbook’s “Risk of Bias” assessment tool.ResultsSix studies met full inclusion criteria. For the systemic review’s primary outcome (clinical cure), two studies found clinically and statistically significant improvements in measures of VAP cure while four found no statistically significant difference in measurements of cure. No studies found inferiority of aerosolized antibiotics. The included studies had various degrees of biases, particularly in the performance and detection bias domains. Given that outcome measures of clinical cure were not uniform, we were unable to conduct a meta-analysis.ConclusionsThere is insufficient evidence for the use of inhaled antibiotic therapy as primary or adjuvant treatment of VAP or VAT. Additional, better-powered randomized-controlled trials are needed to assess the efficacy of inhaled antibiotic therapy for VAP and VAT.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0202-8) contains supplementary material, which is available to authorized users.

Natural History, Outcomes and Antibiotic Treatment for Ventilator-Associated Tracheobronchitis in Critical Ill Patients

We assessed incidence and outcomes of patients with ventilator-associated respiratory infections (VARI) due to tracheobronchitis (VAT) and pneumonia (VAP), including length of intensive care unit (ICU) stay and ventilator days. We also examined pathogens, rate of progression from VAT to VAP, and impact of antibiotic therapy for VAT. Data analysis included 234 patients, 100 patients (43%) had at least moderate (+++) bacterial growth in their semi-quantitative endotracheal aspirate (SQ-ETA) cultures. VAT and VAP were each diagnosed in 34 (15%) patients. Staphylococcus aureus was the most common pathogen isolated and had the highest rate of progression from VAT to VAP. Seven (21%) of the 34 patients were diagnosed with VAT that later progressed to VAP in averaged 3 days. Patients diagnosed with VAT had significantly more ventilator days (9 vs 6, p < 0.001), ICU days (17 vs 11, p < 0.001) and hospital days (22 vs 17, p < 0.001). No significant difference was observed in the clinical outcomes of the 25 VAT patients with timely, appropriate antibiotics compared to the 9 VAT patients who did not receive timely appropriate antibiotics. VAT was a risk factor for increased ventilator days, longer length of ICU and hospital stay. The time window from VAT to VAP allowed physicians to identify the pathogens and sensitivity profile needed to treat VAT with appropriate antibiotics. Data from well-designed studies were needed to assess the impact of early, appropriate antibiotic therapy for VAT, the choice of antibiotics, as well as the duration and route of administration.

Ventilator associated- respiratory infections (VARI), are all the same?

Ventilator associated- respiratory infections (VARI) are the most prevalent in the ICU. The differential diagnosis of pneumonia (VAP) and tracheobronchitis (TAV) is overlapping.

Assessment of the intensity of the epidemic process of ventilator-associated respiratory tract infections in patients of surgical intensive care unit

The urgency of the problem of ventilator-associated respiratory tract infections is stipulated by the ever-increasing number of diseases caused by nosocomial polyantibiotic-resistant strains and high mortality rate. Purpose - to give an assessment of the intensity of the epidemic process of ventilator-associated respiratory tract infections in patients of the surgical intensive care unit. In the base of the analysis there were put the results of a comprehensive epidemiological, clinical, and instrumental study of 137 patients (100 patients with severe injuries and 37 patients with diseases of the abdomen and thorax) with ventilator - associated respiratory tract infections received medical treatment in the surgical intensive care unit. The proportion of respiratory tract infections in the structure of nosocomial infections in these patients varies from 34.6 to 58.9 %, in that there was revealed the prevalence of nosocomial pneumonias (63.5 %). When using a ventilator with viral-bacterial filters signs of nosocomial respiratory tract infections were manifested on the 10th day and later in 50.8 % of patients. In cases with the duration of artificial ventilation more than 10 days the risk of the development of these infections in patients with diseases of the abdominal cavity and thorax was 2.1 times higher than in patients with injuries. There was shown the necessity of the development of a set of measures for the prevention of nosocomial infections of the respiratory tract.

Nebulized antibiotics. An adequate option for treating ventilator-associated respiratory infection?

Ventilator-associated tracheobronchitis (VAT) is a frequent complication in critical patients. The 90% of those who develop it receive broad-spectrum antibiotic (ATB) treatment, without any strong evidence of its favorable impact. The use of nebulized ATB could be a valid treatment option, to reduce the use of systemic ATB and the pressure of selection on the local flora. Several studies suggest that an adequate nebulization technique can ensure high levels of ATB even in areas of lung consolidation, and to obtain clinical and microbiological cure. New studies are needed to properly assess the impact of treatment with nebulized ATB on the emergence of resistance.

Characterization of the microflora of ventilator-associated respiratory tract infections in patients with severe trauma

Rationale The relevance of ventilator-associated respiratory tract infections in severe injury patients (SIP) is associated with both features of causative pathogens and the initial severity of the state of patients. Among causative pathogens nosocomial flora is dominant. Purpose - to perform an analysis of the microbiological monitoring of ventilator-associated respiratory tract infections in SIP. The analysis was based on the results of a prospective epidemiological, clinical, and instrumental study of 100 SIP with ventilator-associated respiratory tract infections, stayed in the surgical intensive care unit. The proportion of ventilator-associated respiratory infections in the structure of nosocomial infections in these patients is between 90 - 95%, at that there was revealed the prevalence of nosocomial pneumonia (61%). Ventilator-associated respiratory tract infection most commonly occurs during the first 10 days of mechanical ventilation. The prevailing flora was represented by Gram negative Acinetobacter baumamnnii (40.3 ± 2.1%) and Pseudomonas aeruginosa (38.4% ± 3.2%). Isolated microorganisms possessed multiple antibiotic resistance, with the greatest extent to aminoglycosides - 69.5%, fluoroquinolones - 40.3%, penicillin - 37.6%; cephalosporins (third generation) - 33.8%. There is noted marked preponderance of microbial associations compared with monocultures 57.1 ± 5.3%.

Ventilator-associated respiratory infection following lung transplantation

The medical records of 170 adult patients who underwent lung transplantation between January 2010 and December 2012 were reviewed to assess the incidence, causative organisms, risk factors and outcomes of post-operative pneumonia and tracheobronchitis. 20 (12%) patients suffered 24 episodes of ventilator-associated pneumonia. The condition was associated with mean increases of 43 days in mechanical ventilation and of 35 days in hospital stay, and significantly higher hospital mortality (OR 9.0, 95% CI 3.2-25.1). Pseudomonas aeruginosa (eight out of 12 patients were multidrug-resistant) was the most common pathogen, followed by Enterobacteriaceae (one out of five patients produced extended-spectrum β-lactamases). Gastroparesis occurred in 55 (32%) patients and was significantly associated with pneumonia (OR 6.2, 95% CI 2.2-17.2). Ventilator-associated tracheobronchitis was associated with a mean increase of 28 days in mechanical ventilation and 30.5 days in hospital stay, but was not associated with higher mortality (OR 1.2, 95% CI 0.4-3.2). Pseudomonas aeruginosa (six out of 16 patients were multidrug resistant) was the most common pathogen, followed by Enterobacteriaceae (three out of 14 patients produced extended-spectrum β-lactamase). Patients with gastroparesis also had more episodes of ventilator-associated tracheobronchitis (40% versus 12%, p<0.001). In conclusion, ventilator-associated pneumonia following lung transplantation increased mortality. Preventing gastroparesis probably decreases the risk of pneumonia and tracheobronchitis. Multidrug-resistant bacteria frequently cause post-lung-transplantation pneumonia and tracheobronchitis.

Subglottic secretion drainage and continuous control of cuff pressure used together save health care costs

Preventive strategies to reduce ventilator-associated respiratory infection (VARI) include the use of an endotracheal tube incorporating a lumen for subglottic secretion drainage (SSD) and a system for continuous control of endotracheal tube cuff pressure (CCCP). The health care costs associated with the combined use of these 2 measures aimed at preventing VARI are not known, however. The objective of this study was to determine whether the simultaneous use of these 2 preventive measures for VARI could save health care costs. We performed a prospective observational study of patients who needed mechanical ventilation in an intensive care unit. The health care costs considered here included only the costs of the endotracheal tube, cuff control, and antimicrobials used to treat VARI. The study cohort comprised 656 patients, including 241 with intermittent control of cuff pressure and without SSD (standard group), 260 with CCCP and without SSD (CCCP group), 84 with intermittent control of cuff pressure and with SSD (SSD group), and 71 with CCCP and SSD (CCCP + SSD group). The incidence of VARI and health care costs were lower in the CCCP + SSD group compared with the standard, CCCP, and SSD groups. The combined use of SSD and CCCP reduced the incidence of VARI and saved health care costs.

Ventilator-associated pneumonia and other infections

One of the fundamental elements of therapy in patients hospitalised in the Intensive Care Unit (ICU) is mechanical ventilation (MV). MV enables sufficient gas exchange in patients with severe respiratory insufficiency, thus preserving the proper functioning of organs and systems. However, clinical and experimental studies show that mechanical ventilation may cause severe complications, e.g. lung injury (VALI, VILI), systemic inflammatory response syndrome (SIRS), and, on rare occasions, multiple organ failure (MOF). Mechanical ventilation and especially endotracheal intubation are associated also with higher risk of infectious complications of the respiratory system: ventilator-associated respiratory infection (VARI) and ventilator-associated pneumonia (VAP). The complications of the MV listed above have a significant influence on the length of treatment and also on the increase of the costs of therapy and mortality of patients who stay in an ICU. These negative effects of supported breathing are the reasons for intensive research to find new biological markers of inflammation and lung injury, more sensitive and specific diagnostic instruments, more effective methods of therapy, and programs of prevention. The purpose of this article is the presentation of current knowledge concerning VAP-related infections, to allow pulmonologists and general practitioners to become more familiar with the problem. Basic and the most important data concerning the definition, epidemiology, pathophysiology, microbiology, diagnostics, treatment, and prevention of VAP have been included. Additionally, ventilator-associated tracheobronchitis (VAT) was discussed.

Avoidable statistical pitfalls in analyzing length of stay in intensive care units or hospitals

In a study of ventilated patients in a recent issue of Critical Care, Shahin and colleagues [1] compared the length of stay in ICU between patients who acquired a suspected ventilator-associated respiratory infection (sVARI) and patients who remained free of this infection. There are two basic facts that require special attention in the statistical analysis. First, ventilation is a time-dependent study entry since some patients receive ventilation a few days after the time of admission to the ICU. In keeping with the study design, these patients cannot be discharged between admission and first ventilation; ignoring this fact leads to length bias [2]. Second, sVARI is a time-dependent exposure since sVARI might occur a few days after the start of ventilation; treating sVARI incorrectly as time-fixed (that is, assumed to be known at the time of admission) leads to time-dependent bias [2]. The statistical models used by Shahin and colleagues incorrectly assumed that ventilation and sVARI occurrence already happened at the day of admission. Both types of bias can be substantial in such settings: in a study of patients colonized with methicillin-resistant Staphylococcus aureus (MRSA), the biased extra length of hospital stay of MRSA-infected patients was 24.5 days whereas the correct estimate was only 6 days [2]. Length and time-dependent bias are avoidable types of bias since the chronological order (admission, time of first ventilation, time of sVARI, and time of discharge) can be acknowledged in a multi-state model [2]. Researchers are encouraged to use adequate models to receive valid results for hospital-acquired infections [3]. Authors’ response Jason Shahin and Arnold S Kristof We thank Dr Wolkewitz for indicating the effects of length and time-dependent biases in studies that use survival analyses to infer a causal link between a time-dependent exposure and time-based clinical outcomes. The time-dependent bias in the study attempting to establish S. aureus bacteremia as a cause of increased duration of admission is a good example, especially since the exposure tends to occur later in the ICU course. In our study on sVARIs [1], we looked for an association between sVARI and patient co-morbidities or outcomes common to contemporary ICUs. Although we focused on iatrogenic immunosuppression, there was also an association between sVARI and duration of mechanical ventilation or length of stay. However, we did not wish to imply a causal effect of sVARI on the latter outcomes. As Wolkewitz indicates, this would require a prospective proportional hazards-based analysis accounting for the duration of admission or mechanical ventilation prior to sVARI in a multi-state model. In contrast, our findings also incorporate a potential effect of duration of mechanical ventilation or ICU stay on the prevalence of sVARI and in part describe the nature of the patient who develops sVARI. This observation would likely be lost in a multi-state model. Nonetheless, we agree with Dr Wolkewitz that it would be of interest to incorporate the time to event in a separate statistical analysis that attempts to address a potential causal effect between sVARI and time-dependent clinical outcomes.