REVIEW URRENT C OPINION

Antibiotic therapy for ventilator-associated tracheobronchitis: a standard of care to reduce pneumonia, morbidity and costs? Donald E. Craven a,c, Jana Hudcova b,c, and Jawad Rashid b,d

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. Keywords aerosolized antibiotics, bacterial pathogens, early appropriate therapy, improved patient outcomes, intravenous antibiotics, length of ICU stay, multidrug-resistant, prevention, ventilator days, ventilatorassociated pneumonia

INTRODUCTION Lower respiratory tract infections in mechanically ventilated patients include ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) [1–3,4 ,5,6 ,7 ,8–10]. VAT and VAP have similar clinical presentations and microbiologic diagnostic criteria, except that VAP requires a new and persistent infiltrate on chest radiograph (Fig. 1, Table 1) [7 ,8]. VAT and VAP are caused by a wide spectrum of bacterial pathogens, which vary in virulence and antibiotic resistance (Table 2). The 2005 American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) guidelines recommended early, appropriate intravenous antibiotic therapy for VAP to improve patient outcomes [11]. Recent data by Muscedere et al. [12] confirmed that inadequate antibiotic therapy in &&

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clinically suspected VAP leads to increased ICU mortality (35.1 versus 11.8%; P ¼ 0.001), hospital mortality (48.7 versus 19.5%; P < 0.0001), more ventilator days (15.8 versus 6.8 days; P ¼ 0.0005), ICU days (13.5 versus 8.4 days; P ¼ 0.02), and hospital days (42.2 versus 27.9 days; P ¼ 0.04).

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Center for Infectious Diseases Research & Prevention, bDepartment of Surgical Critical Care, Lahey Hospital & Medical Center, Burlington, c Tufts University School of Medicine and dTufts School of Medicine Public Health Program, Boston, Massachusetts, USA Correspondence to Donald E. Craven, MD, Center for Infectious Diseases Research & Prevention, Lahey Hospital & Medical Center, 31 Mall Road, Burlington, MA 01805, USA. Tel: +1 781 744 8037; fax: +1 781 744 5226; e-mail: [email protected] Curr Opin Pulm Med 2015, 21:250–259 DOI:10.1097/MCP.0000000000000158 Volume 21  Number 3  May 2015

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Antibiotic therapy for VAT Craven et al.

KEY POINTS

consequently may reduce healthcare costs, it is not currently considered a standard of care [1–3,7 ]. In this study, we review data on the epidemiology, pathogenesis, and outcomes of patients with VAT, which support early, appropriate treatment with intravenous and/or aerosolized antibiotic therapy. Benefits reported include improved patient outcomes manifested by reduced progression to VAP, fewer ventilator days, and shorter ICU and hospital length of stay. Considering studies conducted in critically ill mechanically ventilated patients, prolonged mechanical ventilation may adversely affect quality of life and drive up healthcare costs [13,14 ]. These data underscore the importance of early, appropriate antibiotic therapy for patients developing ventilator-associated infections due to VAT and/or VAP, and suggest that antibiotic treatment for VAT should be considered the standard of care. &&

 Intubated, ventilated patients have ‘descending, primarily one-way’ entrance of bacteria into the tracheobronchial tree and alveoli that increase lung burden and may progress to VAT and/or VAP.  Data support early, appropriate antibiotic treatment for VAT, as a ‘standard of care’ to prevent VAP, and reduce ventilator days, length of ICU, and hospital stay.  Larger, randomized, multicenter clinical trials are needed to assess the risks and benefits of early or preemptive intravenous and/or aerosolized antibiotic therapy for VAT and/or VAP.  Delaying early, appropriate antibiotic therapy for VAT and/or VAP seems contradictive to the Hippocrates principle ’Do No Harm’, and seems ‘penny wise and pound foolish’, if our goal is to improve patient outcomes, and reduce debility and associated acute and chronic healthcare costs.

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EPIDEMIOLOGY &&

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A recent study of VAT by Nseir et al. [6 ] and a systematic review by Agrafiotis et al. [4 ] of randomized controlled trials demonstrated that patients treated for VAT were less likely to progress to VAP. Although treatment of VAT prevents development of VAP, reduces ventilator and ICU days, facilitates weaning from the ventilator, and &&

Incidence of VAT ranges from 2.7 to 11.5% [4 ,5]. Pseudomonas aeruginosa, Acinetobacter species, and methicillin-resistant Staphylococcus aureus (MRSA) are the most common organisms isolated [4 ,6 ]. Of note is that Gram-negative bacilli (GNB) are the responsible pathogens in 75% of the VAT episodes [4 ]. Data also demonstrated that 7–30% of patients developing VAT progressed to VAP, and that VAT patients also had worse outcomes [6 ,7 ,15]. Agrafiotis et al. [4 ] reviewed attributable and crude mortality in patients with VAT, and reported no difference in attributable mortality, but noted a higher crude mortality rate. In our natural history study of 234 patients ventilated for at least 48 h, VAT was diagnosed in 34 (15%) patients, of which 7/34 (21%) progressed to VAP [7 ]. VAT patients experienced significantly more ventilator days (P < 0.001) and longer ICU stay (P < 0.001) when compared to those without VAT. Similar results have been reported by other investigators [1,16–18,19 ]. Karvouniaris et al. [19 ] also demonstrated longer hospital stays in patients developing VAT. &&

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Oropharynx 8

10 –10

10

orgs/ml

Orogastric tube Endotracheal tube

ET tube

VAT or VAP SQ-ETA ≥ +++ 5 Q-ETA ≥ 10 /ml VAP 4 BAL ≥ 10 CFU/ml 3 PSB ≥ 10 CFU/ml

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Subglottic secretions ET cuff

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Biofilm

FIGURE 1. Intubated patient with nasopharyngeal colonization and subglottic secretions pooled above the endotracheal (ET) tube cuff. Semiquantitative endotracheal aspirate (SQ-ETA) culture with moderate (þþþ) growth or a quantitative-ETA (Q-ETA) with at least 105 cfu/ml of pathogen are microbiological criteria used for the diagnosis of ventilator-associated tracheobronchitis (VAT) or ventilatorassociated pneumonia (VAP). VAP can also be diagnosed by bronchoscopic or nonbronchoscopic bronchoalveolar lavage (BAL), or protected specimen brush technique (PSB). Reproduced with permission from Craven and Hudcova [8].

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PATHOGENESIS OF VENTILATORASSOCIATED TRACHEOBRONCHITIS AND VENTILATOR-ASSOCIATED PNEUMONIA In intubated patients, the tracheobronchial tree is initially sterile, under normal circumstances, may become colonized with bacterial pathogens at the time of or following intubation, and colonization rates usually increase over time. In some individuals, colonization may progress to VAT and/or VAP,

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Infectious diseases Table 1. Diagnostic criteria for ventilator-associated tracheobronchitis and ventilator-associated pneumonia Clinical signs and symptoms VAT

VAP

Temperature >388 WBC >12 000/ml or 388 WBC >12 000/ml or

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

The present review draws our attention to ventilator-associated tracheobronchitis (VAT) as a distinct clinical entity that has been associated with pr...
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