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.

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.

Lyme disease presenting as multiple ischaemic strokes.

A 46-year-old man presented with recurrent left hemiparesis and headache. MRI of brain showed an acute right pontine and subacute right thalamic infarcts and MR angiogram showed multiple intracranial arterial stenoses, suggesting cerebral vasculopathy. There was a cerebrospinal fluid lymphocytic pleocytosis with Borrelia burgdorferi antibodies. Central nervous system Lyme disease occasionally presents with ischaemic strokes; this case is unusual in showing vasculopathy on brain imaging, supporting meningovasculitis as the likely mechanism.

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.

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.

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.

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.

Management and prevention of ventilator-associated pneumonia caused by multidrug-resistant pathogens.

Ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) pathogens is a leading healthcare-associated infection in mechanically ventilated patients. The incidence of VAP due to MDR pathogens has increased significantly in the last decade. Risk factors for VAP due to MDR organisms include advanced age, immunosuppression, broad-spectrum antibiotic exposure, increased severity of illness, previous hospitalization or residence in a chronic care facility and prolonged duration of invasive mechanical ventilation. Methicillin-resistant Staphylococcus aureus and several different species of Gram-negative bacteria can cause MDR VAP. Especially difficult Gram-negative bacteria include Pseudomonas aeruginosa, Acinetobacter baumannii, carbapenemase-producing Enterobacteraciae and extended-spectrum ß-lactamase producing bacteria. Proper management includes selecting appropriate antibiotics, optimizing dosing and using timely de-escalation based on antiimicrobial sensitivity data. Evidence-based strategies to prevent VAP that incorporate multidisciplinary staff education and collaboration are essential to reduce the burden of this disease and associated healthcare costs.

Strategies for prevention of ventilator-associated pneumonia: bundles, devices, and medications for improved patient outcomes.

Ventilator-associated pneumonia is associated with significant patient morbidity, mortality, and increased health care costs. In the current economic climate, it is crucial to implement cost-effective prevention strategies that have proven efficacy. Multiple prevention measures have been proposed by various expert panels. Global strategies have focused on infection control, and reduction of lower airway colonization with bacterial pathogens, intubation, duration of mechanical ventilation, and length of stay in the intensive care unit. Routine use of the Institute for Healthcare Improvement ventilator care bundle is widespread, and has been clearly demonstrated to be an effective method for reducing the incidence of ventilator-associated pneumonia. In this article, we examine specific aspects of the Institute for Healthcare Improvement bundle, better-designed endotracheal tubes, use of antibiotics and probiotics, and treatment of ventilator-associated tracheobronchitis to prevent ventilator-associated pneumonia.

Diagnosis of ventilator-associated respiratory infections (VARI): microbiologic clues for tracheobronchitis (VAT) and pneumonia (VAP).

Intubated patients are at risk of bacterial colonization and ventilator-associated respiratory infection (VARI). VARI includes tracheobronchitis (VAT) or pneumonia (VAP). VAT and VAP caused by multidrug-resistant (MDR) pathogens are increasing in the United States and Europe. In patients with risk factors for MDR pathogens, empiric antibiotics are often initiated for 48 to 72 hours pending the availability of pathogen identification and antibiotic sensitivity data. Extensive data indicate that early, appropriate antibiotic therapy improves outcomes for patients with VAP. Recognizing and treating VARI may allow earlier appropriate therapy and improved patient outcomes.

Ventilator-associated tracheobronchitis and pneumonia: thinking outside the box.

Lower respiratory tract infections in intubated patients include ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). These infections are increasingly caused by multidrug-resistant bacteria, which colonize the patient's oropharynx and enter the lower respiratory tract around the endotracheal tube cuff or through the lumen. Progression of colonization to VAT and, in some patients, to VAP is related to the quantity, types, and virulence of invading bacteria versus containment by host defenses. Diagnostic criteria for VAT and VAP overlap in terms of clinical signs and symptoms, and they share similar microbiologic criteria when endotracheal sputum aspirate samples are used. In addition, the diagnosis of VAP requires a new and persistent infiltrate on a chest radiograph, which may be difficult to assess in critically ill patients, and a significant bacterial culture of a endtotracheal aspirate or bronchoalveolar lavage specimen. Current guidelines for the management of VAP strongly recommend the use of early, appropriate empirical antibiotic therapy based on patient risk factors for multidrug-resistant pathogens. An alternative model focused on VAT, using serial surveillance of endotracheal aspirate specimens to identify multidrug-resistant pathogens and their antibiotic susceptibilities, would allow earlier, targeted antibiotic treatment that could improve outcomes in patients, prevent VAP, and provide an attractive model for clinical research trials.

Association between a silver-coated endotracheal tube and reduced mortality in patients with ventilator-associated pneumonia.

BACKGROUND: A silver-coated endotracheal tube (ETT) reduced the incidence of ventilator-associated pneumonia (VAP) compared with an uncoated ETT in the North American Silver-Coated Endotracheal Tube (NASCENT) study. METHODS: To evaluate the effect of an ETT and risk factors on mortality, we performed a retrospective cohort analysis in patients who developed VAP in the NASCENT study. We determined causes of death and VAP due to potentially multidrug-resistant bacteria (eg, Pseudomonas, Acinetobacter) and performed stepwise multivariate logistic regression with the following predefined variables: treatment group, Acute Physiology and Chronic Health Evaluation (APACHE) II score, continuous sedation, coma, COPD, emergency surgery/trauma, immunodeficiency, potentially multidrug-resistant bacteria, and inappropriate initial antibiotics. RESULTS: The silver-coated ETT was associated with reduced mortality in patients with VAP (silver vs control, 5/37 [14%] vs 20/56 [36%], P = .03), but not in those without VAP (228/729 [31%] vs 178/687 [26%], P = .03). The only between-group difference in leading causes of death was respiratory failure (silver vs control, 45/233 [19%] vs 22/198 [11%], P = .02). Of the VAP-related deaths, one in the silver group was caused by Acinetobacter sepsis. In the control group, six deaths were caused by sepsis and three by pneumonia; six of nine pathogens were potentially multidrug resistant. In multivariate analysis, the treatment group was a predictor of mortality (odds ratio, silver vs control, 0.28; 95% CI, 0.09-0.89; P = .03). APACHE II > or = 20 and inappropriate antibiotics also remained in the model (P < .1). CONCLUSIONS: These findings suggest that a silver-coated ETT was associated with reduced mortality in patients who developed VAP in the NASCENT study. Studies are needed to confirm these exploratory findings.

Ventilator-associated tracheobronchitis: the impact of targeted antibiotic therapy on patient outcomes.

Nosocomial lower respiratory tract infections are a common cause of morbidity and mortality in ICU patients receiving mechanical ventilation. Many studies have investigated the management and prevention of ventilator-associated pneumonia (VAP), but few have focused on the role of ventilator-associated tracheobronchitis (VAT). The pathogenesis of lower respiratory tract infections often begins with tracheal colonization that may progress to VAT, and in selected patients to VAP. Since there is no well-established definition of VAT, discrimination between VAT and VAP can be challenging. VAT is a localized disease with clinical signs (fever, leukocytosis, and purulent sputum), microbiologic information (Gram stain with bacteria and leukocytes, with either a positive semiquantitative or a quantitative sputum culture), and the absence of a new infiltrate on chest radiograph. Monitoring endotracheal aspirates has been used to identify and quantify pathogens colonizing the lower airway, to diagnose VAT or VAP, and to initiate early, targeted antibiotic therapy. Recent data suggest that VAT appears to be an important risk factor for VAP and that targeted antibiotic therapy for VAT may be a new paradigm for VAP prevention and better patient outcomes.

Predictors of treatment for hepatitis C virus (HCV) infection in drug users.

Documented treatment rates for Hepatitis C virus (HCV) infection are low. Within this cohort of HCV-infected patients (N = 373), participants who were not actively injecting drugs or not co-infected with HIV were most likely to initiate HCV treatment. Persons of white race and HIV-infected participants with a CD4 count above 200 were also more likely to have initiated HCV treatment. We defined five factors as potentially modifiable, and found almost all (90%) of the cohort had at least one such factor. Participants with more than one of these factors were least likely to initiate treatment. The proportion of patients receiving treatment increased as their number of modifiable risk factors decreased (p < 0.01, for trend). Focused strategies to overcome these potentially modifiable factors may be indicated to increase HCV treatment in affected populations.

Molecular typing of Mycobacterium chelonae isolates from a pseudo-outbreak involving an automated bronchoscope washer.

We describe a pseudo-outbreak of Mycobacterium chelonae infection in bronchoalveolar lavage fluid from 9 patients that was traced to contamination of an automated bronchoscope washer. Molecular typing using repetitive extragenic palindromic polymerase chain reaction was helpful in confirming epidemiologic and clinical findings.