Tracheobronchial Colonization Research Articles

Evolution of Tracheobronchial Colonization Following Tracheal Intubation in Patients With Neurologic Injury Who Are Ventilated: The INSPIRE Study

BackgroundCharacteristics and course of endotracheal secretions have scarcely been studied in patients under mechanical ventilation (MV) at risk of developing ventilator-associated pneumonia (VAP). Research questionExhaustive description of endotracheal secretions and determination of their predictive value for the diagnosis of VAP during MV. Study design and methodsSingle-center prospective study in neuro-injured patients requiring MV for at least 7 days. Patients with pulmonary and infectious diseases were ineligible. All endotracheal aspirates (ETA) collected between tracheal intubation and Day7 were analyzed. Macroscopic characteristics and microbiology were assessed. CPIS was calculated daily. A blinded adjudication committee validated all VAP events. ResultsForty-eight patients and 1544 ETAs were analyzed. Overall, 81% of the ETA were purulent and 50% were thick. Culture results showed high inter- and intra-individual variability. Ten patients (21%) developed an early VAP. Eight patients (80%) with VAP and 14 (37%) without had a CPIS>6. The day before VAP diagnosis, a 20-mL increase in ETA volume detected a VAP with a sensitivity of 67% and a specificity of 93%. InterpretationOur study provides new information on the course of respiratory colonization in mechanically ventilated patients and suggests that ETA color and aspect, and pathogens kinetics cannot predict VAP. Traditional VAP criteria (CPIS and bacterial load) had also a low diagnostic specificity. Contrariwise, an increase in secretion volume should alert for VAP development.

Aerosolized Antibiotics to Manage Ventilator-Associated Infections: A Comprehensive Review.

Ventilator-associated lower respiratory tract infectious complications in critically ill patients cover a wide spectrum of one disease process (respiratory infection), initiating from tracheal tube and/or tracheobronchial colonization, to ventilator associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). VAP occurence has been associated with increased intensive care unit (ICU) morbidity (ventilator days, as well as length of ICU and hospital stay) and ICU mortality. Therefore, treatments that aim at VAP/VAT incidence reduction are a high priority. The aim of the present review is to discuss the current literature concerning two major aspects: (a) can aerosolized antibiotics (AA) administered in a pre-emptive way prevent the occurrence of ventilator-associated infections? and (b) can VAT treatment with aerosolized avert the potential evolution to VAP? There were identified eight studies that provided data on the use of aerosolized antibiotics for the prevention of VAT/VAP. Most of them report favorable data on reducing the colonisation rate and the progression to VAP/VAT. Another four studies dealt with the treatment of VAT/VAP. The results support the decrease in the incidence to VAP transition and/or the improvement in signs and symptoms of VAP. Moreover, there are concise reports on higher cure rates and microbiological eradication in patients treated with aerosolized antibiotics. Yet, differences in the delivery modality adopted and resistance emergence issues preclude the generalisability of the results. Aerosolized antibiotic therapy can be used to manage ventilator-associated infections, especially those with difficult to treat resistance. The limited clinical data raise the need for large randomized controlled trials to confirm the benefits of AA and to evaluate the impact on antibiotic selection pressure.

1065. Efficacy of Cefiderocol in Experimental Stenotrophomonas maltophilia Pneumonia in Persistently Neutropenic Rabbits

Background Stenotrophomonas maltophilia causes lethal pneumonia, bacteremia, and sepsis in immunocompromised patients. As a standard of care, trimethoprim-sulfamethoxazole (T/S) is considered to be the first-line therapy for Stenotrophomonas pneumonia. Cefiderocol (CFDC) is a new parenteral siderophore cephalosporin that is transported through the outer cell membrane as a siderophore mimic that then inhibits Gram-negative cell wall biosynthesis. CFDC has potent activity in vitro against S. maltophilia; however, little is known about its in vivo activity against Stenotrophomonas pneumonia in immunocompromised hosts. We therefore studied CFDC in comparison to TS in the persistently neutropenic rabbit model of Stenotrophomonas pneumonia. This rabbit model, in contrast to conventional murine models, reflects the human pattern of infection more accurately over time.MethodsWe initially studied the plasma pharmacokinetics of CFDC in non-infected and infected animals. Stenotrophomonas pneumonia was established by direct endotracheal inoculation of S. maltophilia 1×1010 CFUs for tracheobronchial colonization that evolved into bronchopneumonia. Experimental groups consisted of CFDC, T/S, and untreated controls (UC). Rabbits received CFDC at 120 mg/kg IV Q8h and T/S at 5 mg/kg IV Q12h. Profound persistent neutropenia was maintained with cytosine arabinoside. Treatment was continued for 10 days.ResultsThere were no significant differences between non-infected and infected rabbits in CFDC pharmacokinetics. Rabbits treated with CFDC and T/S demonstrated significant decreases of residual pulmonary and BAL bacterial burden vs UC (p≤0.001). CFDC achieved full clearance of S. maltophilia from lung tissue and BAL. This antibacterial activity coincided with significant reduction of lung weights (marker of organism-mediated pulmonary injury) in the CFDC group vs T/S and UC (p< 0.01). Survival was prolonged in the CFDC treatment group with 87% survival in comparison to that of T/S (25%) and UC (0%) (p< 0.01). Table 1. Efficacy of Cefiderocol in Experimental Stenotrophomonas maltophilia Pneumonia in Persistency Neutropenic Rabbits ConclusionCefiderocol is highly active in treatment of experimental S. maltophilia pneumonia in persistently neutropenic rabbits, thus laying the foundation for future clinical investigations against this lethal infection. Disclosures Naoki Ishibashi, MD, Shionogi, Inc. (Employee) Benjamin Georgiades, n/a, Shionogi, Inc. (Consultant) Roger Echols, MD, Shionogi (Consultant) Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support) Yoshinori Yamano, PhD, Shionogi (Employee) Thomas J. Walsh, MD, PhD (hon), Scynexis (Consultant, Grant/Research Support)Shionogi (Consultant, Grant/Research Support)

Effect of Nebulized Amphotericin B in Critically ill Patients With Respiratory Candida spp. De-colonization: A Retrospective Analysis.

The potential relationship among airway Candida spp. de-colonization, nebulized amphotericin B (NAB), and occurrence of ventilator-associated pneumonia (VAP) in patients who are critically ill has not been fully investigated, especially concerning effects on survival. In this observational, retrospective, cohort study in a 22-bed central intensive care unit, we included patients aged >18 years who required mechanical ventilation (MV) for >48 h, with at least two consecutive positive Candida spp. test results. Patients were categorized into NAB and no NAB (control) groups. Propensity matching at 1:1 was performed according to strict standards, and multiple Cox proportional hazard model and multivariate analyses were performed to evaluate the effects of NAB treatment. Throughout an 8-year study period, 526 patients had received MV and had positive respiratory tract Candida spp. cultures. Of these, we included 275 patients and excluded 251 patients. In total, we successfully matched 110 patients from the two groups (each group, n = 55; total population median age, 64 years; Acute Physiology and Chronic Health Evaluation II [APACHE II] score, 25.5; sequential organ failure assessment score, 9). The Candida spp. de-colonization rate was 69.1% in patients treated with NAB. VAP incidence did not differ significantly between the NAB (10.91%) and control (16.36%) groups (P = 0.405). Pseudomonas aeruginosa-related VAP rates differed significantly between the NAB (10.91%) and control (25.45%) groups (P = 0.048). Five (9.1%) patients in the NAB group died during hospitalization compared with 17 (30.9%) controls (P = 0.014). At 28 days, 9 (16.4%) and 16 (29.1%) deaths occurred in the NAB and control groups, respectively, (P = 0.088). The cumulative 90-day mortality rate differed significantly between the two groups (23.6 vs. 43.6%, P = 0.015). Multivariate logistic regression analyses indicated a decreased 90-day mortality in the NAB group (adjusted odds ratio 0.413; 95% confidence interval 0.210–0.812; P = 0.01). In subgroup analyses, the NAB-associated decreased risk of death at 90 days was consistent across subgroups of patients with a Candida score of 2, younger age (<64 years), a higher APACHE II score (≥25), fewer Candida sites (<2), or MV at admission. NAB treatment contributed to Candida spp. airway de-colonization, was associated with a reduced risk of P. aeruginosa-related VAP, and improved 90-day mortality in patients critically ill with Candida spp. tracheobronchial colonization who had received MV for >2 days. NAB may be an alternative treatment option for critically ill patients with VAP.

2381. Ceftolozane/Tazobactam in the Treatment of Experimental Pseudomonas aeruginosa Pneumonia in Persistently Neutropenic Rabbits: Impact on Strains With Genetically Defined Resistance

Background Pseudomonas pneumonia is a life-threatening infection with high mortality, particularly in neutropenic patients. The efficacy of current antimicrobial therapy with extended spectrum penicillins (ESPs) and anti-pseudomonal cephalosporins (ASCs) is limited by emergence of resistance. Ceftolozane/tazobactam is a novel cephalosporin with in vitro activity against isolates of Pseudomonas aeruginosa that are resistant to ESPs and ASCs. In order to assess the antimicrobial effect of ceftolozane/tazobactam in treatment of Pseudomonas pneumonia, we investigated this new agent in the treatment of experimental Pseudomonas pneumonia in persistently neutropenic rabbits infected with different strains of genetically defined mechanisms of resistance.Methods Pseudomonas pneumonia was established in a rabbit model by direct endotracheal inoculation of P. aeruginosa 1 × 108–109 CFUs for tracheobronchial colonization that evolves into bronchopneumonia. Four treatment groups were studied: ceftolozane/tazobactam, ceftazidime (CTZ), piperacillin/tazobactam (TZP), and untreated controls (UC). Rabbits were dosed IV to achieve humanized doses of ceftolozane/tazobactam 3g (2g/1g) Q8h, CTZ 2g Q8h, and TZP 4.5g Q8h. Four isolates of P. aeruginosa were studied: pan-susceptible (PS), OPRD porin loss (OPRDPL), efflux pump expression (EPE), and AmpC hyperexpression (ACHE). Profound, persistent neutropenia was maintained with cytosine arabinoside and methylprednisolone. Treatment was continued for 12 days.ResultsTreatment with ceftolozane/tazobactam resulted in ≥105 reduction in residual pulmonary bacterial burden caused by all 4 strains (P ≤ 0.01). This antibacterial activity coincided with reduction of lung weight (P < 0.05), which is a marker of organism-mediated pulmonary injury. CTZ was less active in ACHE-infected rabbits, while TZP had less activity in EPE, ACHE, and OPRDPL strains. Survival was prolonged in ceftolozane/tazobactam and CTZ treatment groups in comparison to that of TZP and UC (P < 0.001).ConclusionCeftolozane/tazobactam is highly active in treatment of experimental P. aeruginosa pneumonia in persistently neutropenic rabbits, including infections caused by strains with the most common resistant mechanisms.Disclosures C. A. DeRyke, Merck: Employee, Salary. D. L. Culshaw, Merck: Employee, Salary. L. Caro, Merck: Employee and Shareholder, Salary and stock options. M. J. Satlin, Hardy Diagnostics: Grant Investigator, Research support. Allergan: Grant Investigator, Grant recipient. Merck: Grant Investigator, Grant recipient. Biomerieux: Grant Investigator, Grant recipient. Achaogen: Consultant, Consulting fee. T. J. Walsh, Merck: Grant Investigator, Research grant. Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Gilead: Scientific Advisor, Consulting fee. Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Scynexis: Grant Investigator, Research grant. Amplyx: Grant Investigator, Research grant. Shionogi: Scientific Advisor, Consulting fee.

Are tracheal surveillance cultures useful in the intensive care unit?

Endotracheal aspirate (ETA) surveillance cultures have been used to predict the microorganisms responsible for ventilator associated pneumonia (VAP) in intensive care unit (ICU) patients for 3 decades. However, although more than a dozen studies have been performed, the usefulness and the safety of this strategy are still debated. Tracheobronchial bacterial colonization often precedes the occurrence of VAP, and it has been postulated that the microbes present in the tracheal secretions a few days before VAP might be the same as those retrieved in the lower respiratory tract. A large number of studies, with heterogeneous designs and variable results, have questioned the possibility of predicting, by regular ETA cultures after the 48th hour of mechanical ventilation (MV), the microbiology of VAP and therefore of determining the adequate antibiotic therapy to limit the over-prescription of broad spectrum molecules when following guidelines. Although it has shown some promising results, the strategy has not achieved unanimity because of some discordant data. The aim of this review is to provide an updated overview of the literature available in the field and to attempt to determine the strengths and weaknesses of antibiotic stewardship based on ETA surveillance cultures in VAP, particularly in the global context of drug resistant microorganism emergence and the crucial necessity of broad spectrum molecule preservation.

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.

Impact of tapered-cuff tracheal tube on microaspiration of gastric contents in intubated critically ill patients: a multicenter cluster-randomized cross-over controlled trial.

Studies on the impact of tapered-cuff tracheal tubes on rates of microaspiration and ventilator-associated pneumonia (VAP) in intubated patients have reported conflicting results. The aim of this study was to determine the influence of this shape of tracheal cuff on abundant microaspiration of gastric contents in critically ill patients. All patients intubated in the intensive care unit (ICU) and requiring mechanical ventilation for at least 48h were eligible for this multicenter cluster-randomized controlled cross-over open-label study. The primary outcome was abundant microaspiration of gastric contents, defined by the presence of pepsin at significant level in>30% of tracheal aspirates. Quantitative measurement of pepsin and salivary amylase was performed in all tracheal aspirates during the 48h following enrollment. A total of 326 patients were enrolled in the ten participating ICUs (162 in the PVC tapered-cuff group and 164 in the standard-cuff group). Patient characteristics were similar in the two study groups. The proportion of patients with abundant microaspiration of gastric contents was 53.5% in the tapered-cuff and 51.0% in the standard-cuff group (odds ratio 1.14, 95% CI 0.72-1.82). While abundant microaspiration of oropharyngeal secretions was not significantly different (77.4 vs 68.6%, p=0.095), the proportion of patients with tracheobronchial colonization was significantly lower (29.6 vs 43.3%, p=0.01) in the tapered-cuff than in the standard-cuff group. No significant difference between the two groups was found for other secondary outcomes, including ventilator-associated events and VAP. This trial showed no significant impact of tapered-cuff tracheal tubes on abundant microaspiration of gastric contents. ClinicalTrials.gov, number NCT01948635.

Impact of tracheal cuff shape on microaspiration of gastric contents in intubated critically ill patients: study protocol for a randomized controlled trial.

BackgroundVentilator-associated pneumonia (VAP) is the most common infection in intubated critically ill patients. Microaspiration of the contaminated gastric and oropharyngeal secretions is the main mechanism involved in the pathophysiology of VAP. Tracheal cuff plays an important role in stopping the progression of contaminated secretions into the lower respiratory tract. Previous in vitro studies suggested that conical cuff shape might be helpful in improving tracheal sealing. However, clinical studies found conflicting results. The aim of this study is to determine the impact of conical tracheal cuff shape on the microaspiration of gastric contents in critically ill patients.Methods/DesignThis prospective cluster randomized controlled crossover open-label trial is currently being conducted in ten French intensive care units (ICUs). Patients are allocated to intubation with a polyvinyl chloride (PVC) standard (barrel)-shaped or a PVC conical-shaped tracheal tube. The primary objective is to determine the impact of the conical shaped tracheal cuff on abundant microaspiration of gastric contents. Secondary outcomes include the incidence of microaspiration of oropharyngeal secretions, tracheobronchial colonization, VAP and ventilator-associated events. Abundant microaspiration is defined as the presence of pepsin at significant level (>200 ng/ml) in at least 30 % of the tracheal aspirates. Pepsin and amylase are quantitatively measured in all tracheal aspirates during the 48 h following inclusion. Quantitative tracheal aspirate culture is performed at inclusion and twice weekly. We plan to recruit 312 patients in the participating ICUs.DiscussionBEST Cuff is the first randomized controlled study evaluating the impact of PVC tracheal-cuff shape on gastric microaspirations in patients receiving invasive mechanical ventilation. Enrollment began in June 2014 and is expected to end in October 2015.Trial registrationClinicalTrials.gov Identifier: NCT01948635 (registered 31 August 2013).

Continuous control of tracheal cuff pressure and ventilator-associated pneumonia

Intubation is performed in a large proportion of critically ill patients. Underinflation (< 20 cmH2O) and overinflation (> 30 cmH2O) of tracheal cuff were identified as risk factors for microaspiration and tracheal ischemic lesions, respectively. Maintaining cuff pressure (Pcuff) around 25 cmH2O is recommended to prevent these complications. Periodic adjustment of Pcuff using a manual manometer might be helpful in preventing severe tracheal ischemic lesions. However, despite manual control of Pcuff, patients spend a large amount of time with underinflation of Pcuff. Two randomized controlled studies evaluated the impact of continuous control of Pcuff on microaspiration of gastric contents and ventilation-acquired pneumonia (VAP) incidence. The first study using an electronic device failed to demonstrate any impact of continuous control of Pcuff on VAP rate (15% in the two groups). However, the second one found the pneumatic device to be associated with significantly reduced microaspiration of gastric contents, tracheobronchial colonization, and VAP rate (9.8% vs. 26.2%, p = 0.032, odds ratio [95%confidence interval] 0.30 [0.11–0.84]). Different devices and different patient characteristics might explain the different results found in these studies. Further randomized controlled multicenter trials are needed to determine the impact of continuous control of Pcuff on VAP incidence, and to compare the different available devices.

Tracheobroncial colonization in coronary care unit intubated patients

Tracheobronchial tree colonization is considered an important risk factor for the development of ventilator-associated pneumonia (VAP). The aim of the present study was to examine microbiologically the respiratory tract flora of mechanically ventilated patients hospitalized in the Coronary Care Unit (CCU) of our institution for the detection of colonization with important bacterial pathogens.

Alcohol-based hand rub and ventilator-associated pneumonia after elective neurosurgery: An interventional study

Background:Interventional studies on the effect of alcohol-based hand rub on ventilator-associated pneumonia (VAP) among neurosurgical patients are scarce.Aim:To observe the effect of alcohol-based hand rub on tracheobronchial colonization and VAP after elective neurosurgical procedures.Materials and Methods:An interventional study using a “before–after” design in a tertiary care center in Kerala. Two 9-month study periods were compared; between these periods, an infection control protocol incorporating an alcohol-based hand rub was implemented for a period of 3 months and continued thereafter. Consecutive patients who required mechanical ventilation after neurosurgery between January and September 2006 and 2007, respectively, were included. Outcome measures included VAP rate, tracheobronchial colonization rate, profile of microorganisms and patient survival.Results:A total of 352 patients were on mechanical ventilator for a varying period of 1–125 days. The patients in the control and intervention groups were similar with regard to sex, age and type of neurosurgery. Tracheobronchial colonization was seen in 86 (48.6%) of 177 in the control group and 73 (41.7%) of 175 among the intervention group (P = 0.195). The VAP rates in the control and intervention groups were 14.03 and 6.48 per 1000 ventilator days (P = 0.08). The predominant organisms causing VAP and tracheobronchial colonization were Klebsiella and Pseudomonas aeruginosa, respectively, in both groups. Patient survival rates were 87.6% (control) and 92% (intervention).Conclusion:Clinical results indicated a better outcome, showing a reduction in tracheobronchial colonization rate and VAP rate, although this was not statistically significant.

Short term Candida albicans colonization reduces Pseudomonas aeruginosa-related lung injury and bacterial burden in a murine model

IntroductionPseudomonas aeruginosa is a frequent cause of ventilator-acquired pneumonia (VAP). Candida tracheobronchial colonization is associated with higher rates of VAP related to P. aeruginosa. This study was designed to investigate whether prior short term Candida albicans airway colonization modulates the pathogenicity of P. aeruginosa in a murine model of pneumonia and to evaluate the effect of fungicidal drug caspofungin.MethodsBALB/c mice received a single or a combined intratracheal administration of C. albicans (1 × 105 CFU/mouse) and P. aeruginosa (1 × 107 CFU/mouse) at time 0 (T0) upon C. albicans colonization, and Day 2. To evaluate the effect of antifungal therapy, mice received caspofungin intraperitoneally daily, either from T0 or from Day 1 post-colonization. After sacrifice at Day 4, lungs were analyzed for histological scoring, measurement of endothelial injury, and quantification of live P. aeruginosa and C. albicans. Blood samples were cultured for dissemination.ResultsA significant decrease in lung endothelial permeability, the amount of P. aeruginosa, and bronchiole inflammation was observed in case of prior C. albicans colonization. Mortality rate and bacterial dissemination were unchanged by prior C. albicans colonization. Caspofungin treatment from T0 (not from Day 1) increased their levels of endothelial permeability and lung P. aeruginosa load similarly to mice receiving P. aeruginosa alone.ConclusionsP. aeruginosa-induced lung injury is reduced when preceded by short term C. albicans airway colonization. Antifungal drug caspofungin reverses that effect when used from T0 and not from Day 1.

Interaction Between Pseudomonas aeruginosa and Candida albicans in the Respiratory Tract of Critically Ill Patients

Pseudomonas aeruginosa is one of the most frequent causative microorganisms of ventilator-acquired pneumonia (VAP). Tracheobronchial colonization (TBC) by Candida species is frequent ventilated patients. Clinical studies have found evidence of interactions between Candida and Pseudomonas, with Candida colonization possibly increasing the risk for Pseudomonas VAP. Very few animal studies have been performed stating either an indifferent or a facilitating role of previous C. albicans TBC on the development of murine P. aeruginosa pneumonia. In vitro, P. aeruginosa forms a biofilm on C. albicans filaments and ultimately kills them. In contrast, P. aeruginosa neither binds to nor kills yeast-forms C. albicans. In the presence of P. aeruginosa, C. albicans grows essentially as a yeast-form to avoid P. aeruginosa-dependant killing. This strategy of resistance operates through the detection of P. aeruginosa quorumsensing (QS) molecule 3OC12-HSL. Moreover, C. albicans produces farnesol, a cell-cell signaling molecule that induces decreased production of the QS molecule, Pseudomonas quinolone (PQS) signal and the virulence factor pyocyanin in addition to inhibit P. aeruginosa swarming mobility. By reviewing the advances made in the understanding of context-specific interactions of C. albicans and P. aeruginosa, we get an understanding on how these microorganisms mutually influence their lifestyle in the respiratory tract of critically ill patients.

Bacteremic community-acquired pneumonia due to Pasteurella multocida

An 87-year-old man was admitted to hospital because of fever, productive cough, dyspnea and altered consciousness. His medical history was significant for chronic obstructive pulmonary disease. He owned several pets. Physical examination and a chest radiograph revealed right upper lobe pneumonia. Blood cultures taken on admission yielded Pasteurella multocida and antimicrobial susceptibility testing showed susceptibility to beta-lactams. The fever subsided four days after treatment with intravenous ceftriaxone and the patient was discharged in a very good clinical condition after two weeks of treatment. Although no history of bites or scratches was documented, it is likely that our patient was exposed to the secretions of his many pets through inhalation of contaminated aerosols. This resulted in tracheobronchial tree colonization by P. multocida, which later developed into pneumonia. Close animal contact should be avoided by frail, elderly patients with chronic pulmonary diseases, as it is a risk factor for pneumonia due to Pasteurella spp.

Interaction de Pseudomonas aeruginosa avec Candida albicans dans les voies respiratoires: de la physiopathologie à une perspective thérapeutique

Several studies evidenced a pathogenic interaction between P. aeruginosa and C. albicans. P. aeruginosa is one of the most frequent microorganisms responsible for ventilator-associated pneumonia (VAP) and C. albicans usually colonize tracheo-bronchial tract of patients undergoing mechanical ventilation in the intensive care unit. In vitro, P. aeruginosa exploits filamentous fungi resulting in fungal killing and limitation of C. albicans growth in the host. Biofilm also play an important role as a persistent source of infectious material for recurrent episodes of VAP. Indeed, Candida spp and P. aeruginosa are the most common pathogens retrieved from endotracheal tube biofilm and tracheal secretions in patients with VAP. Finally, it has been demonstrated that previous tracheo-bronchial C. albicans colonization enhanced the incidence of P. aeruginosa pneumonia in a murine model. A recent study performed in patients requiring intubation and mechanical ventilation identified Candida spp tracheo-bronchial colonization as a risk factor for P. aeruginosa VAP. In addition, a retrospective study suggested that antifungal treatment might reduce P. aeruginosa VAP or tracheo-bronchial colonization in intubated patients with Candida spp tracheo-bronchial colonization. These interactions have major environmental and medical consequences. Experimental studies providing a better understanding of the mechanisms of interaction and clinical studies evaluating the necessity of a antifungal treatment might improve the management of these opportunistic infections.

Diagnostic Characteristics of Routine Surveillance Cultures of Endotracheal Aspirate Samples in Cases of Late-Onset Ventilator-Associated Pneumonia Due to Acinetobacter baumannii

Of 20 consecutive episodes of ventilator-associated pneumonia due to Acinetobacter baumannii, 18 were preceded by tracheobronchial colonization with strains ofA. baumannii that had the same antibiotic susceptibility pattern. When the results of routine surveillance cultures of endotracheal aspirate samples were compared with the results of bronchoalveolar lavage fluid cultures performed for patients who developed late-onset ventilator-associated pneumonia, the sensitivity of the surveillance cultures was 90%, and the negative predictive value was 96%. The positive predictive value of surveillance cultures for identifying causative pathogens in cases of pneumonia due to A. baumannii was good.

Increased Plasminogen Activator Inhibitor-1 Concentrations in Bronchoalveolar Lavage Fluids Are Associated with Increased Mortality in a Cohort of Patients with Pseudomonas aeruginosa

Increased plasminogen activator inhibitor-1 (PAI-1) concentrations are found in bronchoalveolar lavage (BAL) fluids from patients with ventilator-associated pneumonia or acute respiratory distress syndrome. The authors hypothesized that PAI-1 concentrations were associated with increased mortality in patients with either Pseudomonas aeruginosa-induced ventilator-associated pneumonia or tracheobronchial colonization. In a prospective cohort study, daily aspirates from intubated patients were cultured for P. aeruginosa. Positive patients had blind BAL (bBAL) that was processed for biomarker concentrations. Secretion of type III secretion cytotoxins were also analyzed from the P. aeruginosa strains. Thirty-three patients were enrolled. Ten of the 33 patients died. bBAL PAI-1 concentrations were significantly increased in nonsurvivors compared with survivors (31.7 vs. 3.4 ng/ml, P = 0.001 for hospital mortality; 35.9 vs. 4.7 ng/ml, P = 0.02 for 28-day mortality). Even when acute respiratory distress syndrome patients were excluded, there was a significant difference between the survivors and nonsurvivors for bBAL PAI-1 concentrations (P = 0.005). Eighty-three percent of P. aeruginosa strains isolated from patients with high concentrations of bBAL PAI-1 also had strains that secreted cytotoxins. PAI-1 concentrations in bBALs correlated with mortality in ventilated patients with positive cultures for P. aeruginosa. Elevated bBAL PAI-1 concentrations also correlated with the secretion of type III exotoxins by P. aeruginosa.

Impact of antifungal treatment on Candida–Pseudomonas interaction: a preliminary retrospective case–control study

ObjectiveA pathogenic interaction between Candida albicans and Pseudomonas aeruginosa has recently been demonstrated. In addition, experimental and clinical studies identified Candida spp. tracheobronchial colonization as a risk factor for P. aeruginosa pneumonia. The aim of this study was to determine the impact of antifungal treatment on ventilator-associated pneumonia (VAP) or tracheobronchial colonization due to P. aeruginosa.Design and settingRetrospective observational case–control study conducted in a 30-bed ICU during a 1-year period.Patients and methodsOne hundred and two patients intubated and ventilated for longer than 48 h with tracheobronchial colonization by Candida spp. Routine screening for Candida spp. and P. aeruginosa was performed at ICU admission and weekly. Antifungal treatment was based on medical staff decisions. Patients with P. aeruginosa VAP or tracheobronchial colonization were matched (1:2) with patients without P. aeruginosa VAP or tracheobronchial colonization. In case and control patients, risk factors for P. aeruginosa VAP or tracheobronchial colonization were determined using univariate and multivariate analyses.ResultsThirty-six patients (35%) received antifungal treatment. Nineteen patients (18%) developed a P. aeruginosa VAP or tracheobronchial colonization, and all were successfully matched. Antifungal treatment [31% vs 60%; p = 0.037, OR (95% CI) = 0.67 (0.45–0.90)], and duration of antifungal treatment (7 ± 11 vs 14 ± 14 days; p = 0.045, in case and control patients respectively) were significantly associated with reduced risk for P. aeruginosa VAP or tracheobronchial colonization. Antifungal treatment was the only variable independently associated with P. aeruginosa VAP or tracheobronchial colonization (OR = 0.68, 95% CI = 0.49–0.90, p = 0.046).ConclusionIn patients with Candida spp. tracheobronchial colonization, antifungal treatment may be associated with reduced risk for P. aeruginosa VAP or tracheobronchial colonization.Electronic supplementary materialSupplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-006-0422-0 and is accessible for authorized users.

TRACHEOSTOMY IN CRITICALLY ILL NEUROSURGICAL PATIENTS

Objective: To determine the value of early tracheostomy in ventilated neurosurgical patients.Methods:Retrospective review of intubated patients in the Neurosurgical Intensive Care Unit who underwent elective open tracheostomies for prolonged ventilation.Results:Thirty patients over a 2‐year period were analyzed. There were 19 males and 11 females, mean age 53.9 ± 18.1 years (range 14–89), and mean Glasgow Coma Scale (GCS) score on admission, 7.1 ± 3.8 (range 3–15). The underlying disease etiology was cerebrovascular disease in 53% of patients, head trauma in 33% and tumor or infection in 13%. Tracheostomy was performed after a mean period of 8.5 ± 3.5 days (range 2–18), with patients requiring ventilation for a mean duration of 13.5 ± 6.3 days (range 3–31). Complications were minimal; 1 wound infection (3.3%) and 4 tube obstructions (13.3%). Patients who underwent elective early tracheostomy (Group I = within 7 days) had poorer GCS on admission (6.3 ± 2.9 vs 7.7 ± 4.3 in Group II, P = 0.271). Tracheostomy was performed after a mean of 5.3 ± 1.7 days in Group I vs 10.6 ± 2.7 days in Group II. Group I patients had faster recovery from nosocomial pneumonia (12.3 ± 6.2 vs 17.9 ± 12.5 days, P = 0.168), shorter duration of ventilation (9.8 ± 5.9 vs 16.0 ± 5.4 days, P = 0.007), and reduced incidence of multibacterial tracheobronchial colonization (42%vs 72%, P = 0.098). The most prevalent organisms were Acinetobacter baumanii (43.3%), Pseudomonas (40%), Methicillin resistant Staphylococcus Aureus (MRSA) (33%), Klebsiella (30%) and Staphylococcus Aureus (26.7%).Conclusion:Early tracheostomy in selected neurosurgical patients with poor GCS scores was associated with reduced incidence of tracheobronchial colonization by multiple pathogens, improvement in chest infections, and rapid weaning from ventilatory support.