The utility of endotracheal aspirate bacteriology in identifying mechanically ventilated patients at risk for ventilator associated pneumonia: a single-center prospective observational study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a well-known, life-threatening disease that persists despite preventative measures and approved antibiotic therapies. This prospective observational study investigated bacterial airway colonization, and whether its detection and quantification in the endotracheal aspirate (ETA) is useful for identifying mechanically ventilated ICU patients who are at risk of developing VAP. METHODS: 240 patients admitted to 3 ICUs at the Lahey Hospital and Medical Center (Burlington, MA) between June 2014 and June 2015 and mechanically ventilated for > 2 days were included. ETA samples and clinical data were collected. Airway colonization was assessed, and subsequently categorized into "heavy" and "light" by semi-quantitative microbiological analysis of ETAs. VAP was diagnosed retrospectively by the study sponsor according to a pre-specified pneumonia definition. RESULTS: Pathogenic bacteria were isolated from ETAs of 125 patients. The most common species isolated was S. aureus (56.8%), followed by K. pneumoniae, P. aeruginosa, and E. coli (35.2% combined). VAP was diagnosed in 85 patients, 44 (51.7%) with no bacterial pathogen, 18 associated with S. aureus and 18 Gram-negative-only cases, and 5 associated with other Gram-positive or mixed species. A higher proportion of patients who were heavily colonized with S. aureus developed VAP (32.4%) associated with S. aureus compared to those lightly colonized (17.6%). The same tendency was seen for patients heavily and lightly colonized with Gram-negative pathogens (30.0 and 0.0%, respectively). Detection of S. aureus in the ETA preceded S. aureus VAP by approximately 4 days, while Gram-negative organisms were first detected 2.5 days prior to Gram-negative VAP. VAP was associated with significantly longer duration of mechanical ventilation and hospitalization regardless of microbiologic cause when compared to patients who did not develop VAP. CONCLUSIONS: The overall VAP rate was 35%. Heavy tracheal colonization supported identification of patients at higher risk of developing a corresponding S. aureus or Gram-negative VAP. Detection of bacterial ETA-positivity tended to precede VAP.

Low Efficacy of Antibiotics Against Staphylococcus aureus Airway Colonization in Ventilated Patients.

Background: Airway-colonization by Staphylococcus aureus predisposes to the development of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). Despite extensive antibiotic treatment of intensive care unit patients, limited data are available on the efficacy of antibiotics on bacterial airway colonization and/or prevention of infections. Therefore, microbiologic responses to antibiotic treatment were evaluated in ventilated patients. Methods: Results of semiquantitative analyses of S. aureus burden in serial endotracheal-aspirate (ETA) samples and VAT/VAP diagnosis were correlated to antibiotic treatment. Minimum inhibitory concentrations of relevant antibiotics using serially collected isolates were evaluated. Results: Forty-eight mechanically ventilated patients who were S. aureus positive by ETA samples and treated with relevant antibiotics for at least 2 consecutive days were included in the study. Vancomycin failed to reduce methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) burden in the airways. Oxacillin was ineffective for MSSA colonization in approximately 30% of the patients, and responders were typically coadministered additional antibiotics. Despite antibiotic exposure, 15 of the 39 patients (approximately 38%) colonized only by S. aureus and treated with appropriate antibiotic for at least 2 days still progressed to VAP. Importantly, no change in antibiotic susceptibility of S. aureus isolates was observed during treatment. Staphylococcus aureus colonization levels inversely correlated with the presence of normal respiratory flora. Conclusions: Antibiotic treatment is ineffective in reducing S. aureus colonization in the lower airways and preventing VAT or VAP. Staphylococcus aureus is in competition for colonization with the normal respiratory flora. To improve patient outcomes, alternatives to antibiotics are urgently needed.

Effect of early allograft dysfunction on outcomes following liver transplantation.

Early allograft dysfunction (EAD) following liver transplantation (LT) remains a challenge for patients and clinicians. We retrospectively analyzed the effect of pre-defined EAD on outcomes in a 10-year cohort of deceased-donor LT recipients with clearly defined exclusion criteria. EAD was defined by at least one of the following: AST or ALT >2000 IU/L within first-week post-LT, total bilirubin ≥10 mg/dL, and/or INR ≥1.6 on post-operative day 7. Ten patients developed primary graft failure and were analyzed separately. EAD occurred in 86 (36%) recipients in a final cohort of 239 patients. In univariate and multivariate analyses, EAD was significantly associated with mechanical ventilation ≥2 days or death on days 0, 1, PACU/SICU stay >2 days or death on days 0-2 and renal failure (RF) at time of hospital discharge (all P<.05). EAD was also significantly associated with higher one-year graft loss in both uni- and multivariate Cox hazard analyses (P=.0203 and .0248, respectively). There was no difference in patient mortality between groups in either of the Cox proportional hazard models. In conclusion, we observed significant effects of EAD on short-term post-LT outcomes and lower graft survival.

Pre-emptive antibiotic therapy to reduce ventilator-associated pneumonia: "thinking outside the box".

Mechanically ventilated, intubated patients are at increased risk for tracheal colonization with bacterial pathogens that may progress to heavy bacterial colonization, ventilator-associated tracheobronchitis (VAT), and/or ventilator-associated pneumonia (VAP). Previous studies report that 10 to 30 % of patients with VAT progress to VAP, resulting in increased morbidity and significant acute and chronic healthcare costs. Several natural history studies, randomized, controlled trials, and a meta-analysis have reported antibiotic treatment for VAT can reduce VAP, ventilator days, length of intensive care unit (ICU) stay, and patient morbidity and mortality. We discuss early diagnostic criteria, etiologic agents, and benefits of initiating, early, appropriate intravenous or aerosolized antibiotic(s) to treat VAT and reduce VAP, to improve patient outcomes by reducing lung damage, length of ICU stay, and healthcare costs.

Antibiotic therapy for ventilator-associated tracheobronchitis: a standard of care to reduce pneumonia, morbidity and costs?

PURPOSE OF REVIEW: The present review draws our attention to ventilator-associated tracheobronchitis (VAT) as a distinct clinical entity that has been associated with progression to ventilator-associated pneumonia (VAP) and worse patient outcomes. In contrast to VAP, which has been extensively investigated for over the past 30 years, most VAT studies have been conducted in the past decade. There are ample data which demonstrate that VAT may progress to VAP, have more ventilator days, and have longer ICU stay that may translate into higher healthcare costs. RECENT FINDINGS: The article focuses on the diagnostic criteria for VAT, causative agents, and studies analyzing associations between VAT and patient outcomes in relation to early, appropriate intravenous, and/or aerosolized antibiotic therapy. Aerosolized antibiotic treatment delivered by improved device technology is a novel approach that has proved to be effective for the treatment and eradication of multidrug-resistant bacterial pathogens. Aerosolized antibiotics are effective in decreasing the use of systemic antibiotics, reducing bacterial resistance, and may also facilitate clinical resolution of infection. SUMMARY: Evidence presented in this review supports treatment of VAT with early and appropriate antibiotic therapy as a standard of care to reduce VAP, ventilator days, and duration of ICU stay in high-risk patient population.

Patient controlled opioid analgesia versus non-patient controlled opioid analgesia for postoperative pain.

BACKGROUND: This is an updated version of the original Cochrane review published in Issue 4, 2006. Patients may control postoperative pain by self administration of intravenous opioids using devices designed for this purpose (patient controlled analgesia or PCA). A 1992 meta-analysis by Ballantyne et al found a strong patient preference for PCA over non-patient controlled analgesia, but disclosed no differences in analgesic consumption or length of postoperative hospital stay. Although Ballantyne's meta-analysis found that PCA did have a small but statistically significant benefit upon pain intensity, a 2001 review by Walder et al did not find statistically significant differences in pain intensity or pain relief between PCA and groups treated with non-patient controlled analgesia. OBJECTIVES: To evaluate the efficacy and safety of patient controlled intravenous opioid analgesia (termed PCA in this review) versus non-patient controlled opioid analgesia of as-needed opioid analgesia for postoperative pain relief. SEARCH METHODS: We ran the search for the previous review in November 2004. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 12), MEDLINE (1966 to 28 January 2015), and EMBASE (1980 to 28 January 2015) for randomized controlled trials (RCTs) in any language, and reference lists of reviews and retrieved articles. SELECTION CRITERIA: We selected RCTs that assessed pain intensity as a primary or secondary outcome. These studies compared PCA without a continuous background infusion with non-patient controlled opioid analgesic regimens. We excluded studies that explicitly stated they involved patients with chronic pain. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, which included demographic variables, type of surgery, interventions, efficacy, and adverse events. We graded each included study for methodological quality by assessing risk of bias and employed the GRADE approach to assess the overall quality of the evidence. We performed meta-analysis of outcomes that included pain intensity assessed by a 0 to 100 visual analog scale (VAS), opioid consumption, patient satisfaction, length of stay, and adverse events. MAIN RESULTS: Forty-nine studies with 1725 participants receiving PCA and 1687 participants assigned to a control group met the inclusion criteria. The original review included 55 studies with 2023 patients receiving PCA and 1838 patients assigned to a control group. There were fewer included studies in our updated review due to the revised exclusion criteria. For the primary outcome, participants receiving PCA had lower VAS pain intensity scores versus non-patient controlled analgesia over most time intervals, e.g., scores over 0 to 24 hours were nine points lower (95% confidence interval (CI) -13 to -5, moderate quality evidence) and over 0 to 48 hours were 10 points lower (95% CI -12 to -7, low quality evidence). Among the secondary outcomes, participants were more satisfied with PCA (81% versus 61%, P value = 0.002) and consumed higher amounts of opioids than controls (0 to 24 hours, 7 mg more of intravenous morphine equivalents, 95% CI 1 mg to 13 mg). Those receiving PCA had a higher incidence of pruritus (15% versus 8%, P value = 0.01) but had a similar incidence of other adverse events. There was no difference in the length of hospital stay. AUTHORS' CONCLUSIONS: Since the last version of this review, we have found new studies providing additional information. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides moderate to low quality evidence that PCA is an efficacious alternative to non-patient controlled systemic analgesia for postoperative pain control.

α-Hemolysin activity of methicillin-susceptible Staphylococcus aureus predicts ventilator-associated pneumonia.

RATIONALE: Colonization of lower airways by Staphylococcus aureus is a risk factor for the development of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). However, little is known about the virulence factors of methicillin-sensitive and -resistant S. aureus (MSSA and MRSA) that may influence host colonization and progression to VAT and VAP. OBJECTIVES: We evaluated MRSA and MSSA endotracheal aspirates (ETA) for genotype and α-hemolysin activity in relation to the development of VAT and VAP. METHODS: Serial S. aureus ETA isolates from ventilated patients were analyzed for methicillin resistance, molecular type by Multi-Locus Sequence Typing and spa-typing, and α-hemolysin activity by semiquantitative analysis of hemolysis on sheep blood agar and quantitative measurement of cytolysis of human lung epithelial cells. The virulence of selected strains was assessed in mice by intranasal challenge. MEASUREMENTS AND MAIN RESULTS: We detected S. aureus from ETA samples in a quarter of the 231 ventilated patients analyzed; one-third of them developed VAP. VAP patients (n = 15) were mainly infected by MSSA strains (87%), whereas colonized individuals (n = 18) not progressing to disease mainly carried MRSA strains (68%). MSSA isolates from colonized or VAT patients exhibited significantly lower α-hemolysin activity than those from VAP cases; however, no such relationship was found with MRSA strains. α-Hemolysin activity of S. aureus isolates was predictive for virulence in mouse pneumonia model. CONCLUSIONS: MSSA strains with strong blood agar hemolysis and high α-hemolysin activity are markers for VAP, but not VAT, and might be considered in differential diagnosis and initiation of therapy.

Antibiotic treatment of ventilator-associated tracheobronchitis: to treat or not to treat?

PURPOSE OF REVIEW: To evaluate the data on antimicrobial therapy for ventilator-associated tracheobronchitis (VAT) to prevent ventilator-associated pneumonia (VAP), and its impact on patient outcomes. RECENT FINDINGS: Mechanically ventilated patients are at increased risk for tracheal colonization with bacterial pathogens that may progress to VAT and/or VAP. Previous studies suggest that 10-30% of patients with VAT progress to VAP, which results in increased morbidity but not mortality. Several natural history studies and small randomized controlled trials and a meta-analysis reported that appropriate, pre-emptive antibiotic treatment for VAT reduces VAP, duration of intubation and length of ICU stay. SUMMARY: This review focuses on diagnostic criteria for VAT and VAP, etiologic agents, rationale and benefits of initiating pre-emptive, appropriate antibiotic treatment for VAT to prevent VAP, improve patient outcomes and associated acute and chronic healthcare costs.

Ventilator-associated tracheobronchitis: pre-emptive, appropriate antibiotic therapy recommended.

Nseir and colleagues presented data from a large multicenter study of patients with ventilator-associated tracheobronchitis (VAT), demonstrating that appropriate antibiotic therapy for VAT was an independent predictor for reducing transition to pneumonia (ventilator-associated pneumonia, or VAP). These data added to the growing evidence supporting the use of appropriate antibiotic therapy for VAT as a standard of care to prevent VAP and improve patient outcomes.

Sodium homeostasis during liver transplantation and correlation with outcomes.

BACKGROUND: Reports of perioperative serum sodium increase in liver transplant (LT) recipients are mostly restricted to unintentional rapid serum sodium overcorrection with subsequent development of central pontine myelinolysis. We examined intraoperative serum sodium changes and their effect on short-term outcomes after LT. METHODS: We retrospectively analyzed data of all LT recipients over a period of 3.5 years. Collected information included preoperative and postoperative serum sodium (Napre and Napost), delta sodium (ΔNa), intraoperative serum sodium peak and trough with corresponding maximum ΔNa, intraoperative peak blood glucose, history of hepatic encephalopathy, perioperative diuretics, intraoperative administration of vasopressin, dopaminergic agents, alkalizing drugs (sodium bicarbonate [NaHCO3], tromethamine), crystalloids, colloids, fresh frozen plasma (FFP), and packed red blood cells (PRBC). The delta of serum osmolality (ΔOsm) was calculated from Napre and Napost, blood urea nitrogen, and blood glucose values, and the correlation between ΔNa and ΔOsm was examined. Outcomes analyzed included intubation for ≥2 days, postanesthesia care unit/surgical intensive care unit (PACU/SICU) length of stay (LOS) for ≥2 days, need of SICU admission, hospital LOS, postoperative neurological complications, and mortality. Univariate and multivariate analyses were performed to test associations between ΔNa and outcomes. A P value <0.005 was considered significant. RESULTS: Data of 164 patients were analyzed. Their ΔNa was 5.3 ± 4.5 (mean ± SD) mEq/L. A lower Napre was associated with greater ΔNa, a relationship likely due to the regression to the mean. In a subgroup of patients with Napre < 130 mEq/L, ΔNa was 11.0 ± 3.6 mEq/L, significantly higher than in normonatremic patients (P < 0.0001). Mortality and neurologic complications were not affected by changes in ΔNa (all P ≥ 0.41). An increase in ΔNa was associated with higher odds of prolonged intubation and prolonged PACU/SICU LOS in univariate and multivariate regression analyses (P = 0.0003 and P = 0.0049, respectively, for adjusted odds ratios). The odds ratios for associations of ΔNa with those outcomes did not differ between patients treated versus not treated with NaHCO3. The intraoperative ΔNa was significantly higher in patients with intraoperative hyperglycemia (P < 0.0001). Intraoperative administration of NaHCO3 and the number of transfused FFP and PRBC units were also associated with a significantly higher ΔNa (P = 0.0001). The ΔNa correlated significantly with ΔOsm. CONCLUSIONS: A larger intraoperative increase in ΔNa is associated with worse recipient short-term outcomes. Patients with preoperative hyponatremia may be at particular risk. ΔNa increases with the intraoperative use of NaHCO3, quantity of FFP, and PRBCs transfused, as well as with intraoperative hyperglycemia. Potential differences on sodium homeostasis between NaHCO3 and tromethamine use for intraoperative pH adjustment should be prospectively investigated.

Diagnosis of ventilator-associated pneumonia: controversies and working toward a gold standard.

PURPOSE OF REVIEW: The aim is to discuss the clinical, microbiologic, and radiological criteria used in the diagnosis of ventilator-associated pneumonia (VAP), distinguish between ventilator-associated tracheobronchitis (VAT) and VAP, and reconcile the proposed Centers for Disease Control surveillance criteria with clinical practice. RECENT FINDINGS: Numerous ventilator-associated complications (VACs), including VAP and VAT, may occur in critically ill, intubated patients. A variety of definitions for identifying VAP have been proposed, but there is no diagnostic gold standard. The proposed surveillance definition will identify infectious and noninfectious VAC, including VAP and VAT, but this definition may be inadequate for clinical practice. SUMMARY: The clinical characteristics of VAP and VAT are similar and include fever, leukocytosis, and purulent sputum. An infiltrate on chest radiograph is consistent with VAP but lacks diagnostic precision, so it is not a criterion in the proposed surveillance definition and should be interpreted cautiously by clinicians. Microbiologically, quantitative and semiquantitative endotracheal aspirate cultures may be employed to diagnose VAP and VAT. Positive bronchoalveolar lavage and protected specimen brush cultures are useful only for the diagnosis of VAP. Experts should collaborate to develop consensus definitions for VAP and VAT that can be applied in practice.

Early Allograft Dysfunction Following Liver Transplant: Impact of Obesity, Diabetes, and Red Blood Cell Transfusion.

PURPOSE: We examined the role of obesity and intraoperative red blood cell (RBC) and platelet transfusion in early allograft dysfunction (EAD) following liver transplantation (LT). METHODS: This is a retrospective analysis of 239 adult deceased-donor LT recipients over a 10-year period. EAD was defined by Olthoff's criteria. Data collection included donor (D) and recipient (R) age, body mass index (BMI) ≥ 35 kg/m2, diabetes mellitus, allograft macrosteatosis, and intraoperative (RBC) and platelet administration. We employed logistic regression to evaluate associations of these factors with EAD. Results are presented as odds ratios (OR) and 95% confidence intervals (CI) with corresponding P values. A P ≤ .05 was considered statistically significant. RESULTS: EAD occurred in 85 recipients (36%). Macrosteatosis data were available for 199 donors. In the multivariate analyses, BMI-D ≥ 35 kg/m2 increased the odds of developing EAD by 156% in the entire cohort (OR 2.56, 95% CI 1.09-6.01) and by 187% in recipients with macrosteatosis data (n = 199, OR 2.87, 95% CI 1.15-7.15). Each unit of RBCs increased the odds for EAD by 8% (OR 1.08, 95% CI 1.02-1.14) and, for the subgroup of 238 recipients with macrosteatosis data, by 9% (OR 1.09, 95% CI 1.02-1.16). CONCLUSION: We found a significant independent association of donor obesity and intraoperative RBC transfusion with EAD but no such association for platelet administration, MELD score, age, recipient obesity, and diabetes.

Adjusting the pH of lidocaine for reducing pain on injection.

BACKGROUND: Lidocaine administration produces pain due to its acidic pH. OBJECTIVES: The objective of this review was to determine if adjusting the pH of lidocaine had any effect on pain resulting from non-intravascular injections in adults and children. We tested the hypothesis that adjusting the pH of lidocaine solution to a level closer to the physiologic pH reduces this pain. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, to June 2010); Ovid MEDLINE (1966 to June 2010); EMBASE (1988 to June 2010); LILACS (1982 to June 2010); CINAHL (1982 to June 2010); ISI Web of Science (1999 to June 2010); and abstracts of the meetings of the American Society of Anesthesiologists (ASA). We checked the full articles of selected titles. We did not apply any language restrictions. SELECTION CRITERIA: We included double-blinded, randomized controlled trials that compared pH-adjusted lidocaine with unadjusted lidocaine. We evaluated pain at the injection site, satisfaction and adverse events. We excluded studies in healthy volunteers. DATA COLLECTION AND ANALYSIS: We separately analysed parallel-group and crossover trials; trials that evaluated lidocaine with or without epinephrine; and trials with pH-adjusted lidocaine solutions < 7.35 and ≥ 7.35. To explain heterogeneity, we separately analysed studies with a low and higher risk of bias due to the level of allocation concealment; studies that employed a low and a higher volume of injection; and studies that used lidocaine for different types of procedures. MAIN RESULTS: We included 23 studies of which 10 had a parallel design and 13 were crossover studies. Eight of the 23 studies had moderate to high risk of bias due to the level of allocation concealment.Pain associated with the infiltration of buffered lidocaine was less than the pain associated with infiltration of unbuffered lidocaine in both parallel and crossover trials. In the crossover studies, the difference was -1.98 units (95% confidence interval (CI) -2.62 to -1.34) and in the parallel-group studies it was -0.98 units (95% CI -1.49 to -0.47) on a 0 to 10 scale. The magnitude of the pain decrease associated with buffered lidocaine was larger when the solution contained epinephrine. The risk of bias, volume of injection, and type of procedure failed to explain the heterogeneity of the results.Patients preferred buffered lidocaine (odds ratio 3.01, 95% CI 2.19 to 4.15). No adverse events or toxicity were reported. AUTHORS' CONCLUSIONS: Increasing the pH of lidocaine decreased pain on injection and augmented patient comfort and satisfaction.

Prospective Observational Study Comparing Sepsis-2 and Sepsis-3 Definitions in Predicting Mortality in Critically Ill Patients.

BACKGROUND: Sepsis definitions have evolved, but there is a lack of consensus over adoption of the most recent definition, Sepsis-3. We sought to compare Sepsis-2 and Sepsis-3 in the classification of patients with sepsis and mortality risk at 30 days. METHODS: We used the following definitions: Sepsis-2 (≥2 systemic inflammatory response syndrome criteria + infection), Sepsis-3 (prescreening by quick Sequential Organ Failure Assessment [qSOFA] of ≥2 of 3 criteria followed by the complete score change ≥2 + infection), and an amended Sepsis-3 definition, iqSOFA (qSOFA ≥2 + infection). We used χ 2 or Wilcoxon rank-sum tests, receiver-operator characteristic curves, and survival analysis. RESULTS: We enrolled 176 patients (95% in an intensive care unit, 38.6% female, median age 61.4 years). Of 105 patients classified by Sepsis-2 as having sepsis, 80 had sepsis per Sepsis-3 or iqSOFA (kappa = 0.72; 95% confidence interval [CI], 0.62-0.82). Twenty-five (14.8%) died (20 of 100 with sepsis per Sepsis-2 [20%], and 20 of 77 [26.0%] with sepsis per Sepsis-3 or iqSOFA). Results for Sepsis-3 and iqSOFA were identical. The area under the curve of receiver-operator characteristic (ROC) curves for identifying those who died were 0.54 (95% CI, 0.41-0.68) for Sepsis-2, 0.84 (95% CI, 0.74-0.93) for Sepsis-3, and 0.69 (95% CI, 0.60-0.79) for iqSOFA (P < .01). Hazard ratios for death associated with sepsis were greatest for sepsis or septic shock per Sepsis-3. CONCLUSIONS: Sepsis-3 and iqSOFA were better at predicting death than Sepsis-2. Using the SOFA score might add little advantage compared with the simpler iqSOFA score.

Electroconvulsive therapy complicated by life-threatening hyperkalemia in a catatonic patient.

Electroconvulsive therapy (ECT) requires brief general anesthesia, and succinylcholine is a depolarizing neuromuscular blocking agent that is frequently used for this procedure. Its use leads to intracellular potassium release into the extracellular space, usually increasing the serum potassium level by 0.5-1 mEq/L, with little clinical significance. However, long-term immobilization has been associated with changes at the neuromuscular junction (up-regulation of nicotinic cholinergic receptors) and subsequent serious hyperkalemia following succinylcholine administration. We report the case of a severely obese patient, immobilized due to her catatonic state, who developed life-threatening ventricular tachycardia after succinylcholine administration for ECT. Resumption of normal physical activity reverses these neuromuscular junctional changes, allowing subsequent safe succinylcholine administration. Current drug development may eliminate the need for succinylcholine use during ECT.

Incidence and outcomes of ventilator-associated tracheobronchitis and pneumonia.

BACKGROUND: Prolonged intubation with mechanical ventilation carries a risk for ventilator-associated respiratory infections manifest as tracheobronchitis or pneumonia. This study analyzed natural history, incidence, and outcomes of patients developing ventilator-associated tracheobronchitis and pneumonia. METHODS: We studied 188 mixed intensive care unit (ICU) patients intubated ≥48 hours for the development of tracheobronchitis defined as quantitative endotracheal aspirate ≥10(5) cfu/mL plus at least 2 clinical criteria (fever, leukocytosis, or purulent sputum). Pneumonia was defined as microbiologic criteria for tracheobronchitis and a new and persistent infiltrate on chest radiograph. RESULTS: Airways of 41 (22%) patients became heavily colonized with a bacterial pathogen(s) at a concentration of ≥10(5) cfu/mL. Tracheobronchitis developed in 21 (11%) study patients, of which 6 (29%) later progressed to pneumonia. Including these 6 patients, 28 (15%) study patients developed pneumonia. Multidrug-resistant pathogens were isolated in 39% of pneumonia patients. Patients with tracheobronchitis and pneumonia had significantly more ventilator days and longer stays in the ICU (P ≤.02). CONCLUSIONS: Approximately one third of tracheobronchitis patients later developed pneumonia. Patients with tracheobronchitis or pneumonia experienced significantly more ventilator days and longer ICU stays, but had no difference in mortality. Better patient outcomes and reduced health care costs may be achieved by earlier treatment of ventilator-associated respiratory infections, manifest as tracheobronchitis or pneumonia.