Incidence

Nosocomial tracheobronchitis occurs in 3% to 10% of tracheally intubated patients and often precedes the development of VAP. Nosocomial pneumonia is the second most common nosocomial infection and the leading cause of death from hospital-acquired infections in critically ill patients. Most recent studies report a VAP density rate of approximately 9 to 10 cases per 1000 ventilator days; nevertheless, those rates differ greatly according to the characteristics of the studied population. The risk of VAP is approximately 1% per day on mechanical ventilation and changes over time, being 3% the first 5 days on mechanical ventilation, 2% from days 5 to 10, and 1% for the remaining days.

Impact on Outcomes

Nosocomial tracheobronchitis in hospitalized patients is associated with longer duration of mechanical ventilation and intensive care unit (ICU) stay. Indeed, tracheobronchitis is associated with increased sputum production, which often leads to weaning difficulties and extubation failure. Nevertheless, tracheobronchitis is not associated with worse survival.

The crude mortality rate for nosocomial pneumonia may be as high as 30% to 70%, although several cofactors influence mortality, making it extremely difficult to determine the true disease-attributable mortality. Indeed, the heterogeneity between patient populations, microbial patterns, antibiotic treatment, and diagnostic methods challenge precise estimate of mortality. Several case-matching studies have estimated that one third to one half of all VAP-related deaths are a direct result of the infection, with a higher mortality rate in cases caused by Pseudomonas aeruginosa or Acinetobacter spp. and associated with bacteremia. Higher mortality is associated in particular with late-onset VAP, specifically when the initial empirical antimicrobial therapy regimen is inadequate.

Role of Endotracheal Tube

Pulmonary aspiration of colonized oropharyngeal secretions across the tracheal tube cuff is the main pathogenic mechanism for development of tracheobronchitis and VAP. The endotracheal tube (ETT), commonly used in the ICU for long-term mechanically ventilated patients, includes a high-volume, low-pressure (HVLP) cuff, which is approximately two to three times larger than the trachea; hence, when the cuff is inflated within the trachea, folds invariably form along the cuff surface, which leads to aspiration of oropharyngeal secretions. Several respiratory defense mechanisms are severely impaired after tracheal intubation: (1) The ETT completely bypasses the anatomic barrier provided by laryngeal structures, creating a direct conduit by which bacteria can be aspirated and reach lower airways; (2) presence of the tube hinders cough; and (3) inflation of the ETT cuff within the trachea drastically lowers mucociliary velocity.

Additionally, the ETT is commonly made of polyvinylchloride (PVC). With this material, bacteria easily adhere to the internal surface of the tube to form a complex structure called biofilm. Bacteria present within the biofilm have survival advantages and may be a source of persistent infection.

Sources of Colonization

General Prophylactic Measures

Maintaining high levels of current knowledge on pathophysiology of nosocomial infections and preventive strategies in clinical health care personnel can be effective in reducing incidence of those diseases. Respiratory care practitioners and nurses should be the primary recipients of ongoing education programs, and frequent performance feedback and compliance assessment should be undertaken.

The World Health Organization (WHO) has endorsed hand hygiene as the single most important element of strategies to prevent health care–associated infections. Overall, most of the studies conducted in ICUs have shown consistent reduction in nosocomial infection rates through implementation of alcohol-based hand hygiene.

Daily interruption or lightening of sedation, as a strategy to avoid consistent impairment of respiratory defenses, as well as the avoidance of paralytic agents, is highly recommended.

Diagnostic Strategies for Nosocomial Respiratory Infection

An ideal diagnostic strategy for patients suspected on clinical grounds to have nosocomial respiratory infection should achieve the following objectives:

The diagnosis of nosocomial pneumonia begins with clinical suspicion triggered by suggestive findings. The presence of a new or progressively worsening radiographic infiltrate plus clinical criteria constitutes a firm basis for further investigation. Either of two diagnostic algorithms can be used: clinical or bacteriologic. The clinical approach recommends treating every patient suspected to have a pulmonary infection with new antibiotics even when the likelihood of infection is low (Figure 27-1). Nevertheless, samples of respiratory secretions such as endotracheal aspirate or sputum should be obtained before the initiation of antibiotic treatment. In this strategy, the selection of appropriate empirical therapy is based on risk factors and local resistance patterns. The etiology in each case of pneumonia is defined by semiquantitative cultures of endotracheal aspirates or sputum, often with additional microscopic examination of the Gram stain. Antimicrobial therapy is adjusted according to culture results or clinical response. Semiquantitative culture of tracheal aspirates has the advantage that no specialized microbiologic techniques are required, and the sensitivity is high. This clinical strategy provides antimicrobial treatment to a majority of the patients with suspected pneumonia and yields a low rate of false-negative results. Still, if the tracheal aspirate culture does not demonstrate pathogens and the patient has not received new antibiotics within the previous 72 hours, the diagnosis of pneumonia is unlikely. The main drawback of this strategy is that the high sensitivity of semiquantitative cultures of tracheal aspirates leads to overtreatment, with institution of unnecessary antibiotics in patients with false-positive results.

Figure 27-1 Clinical noninvasive strategy for the diagnosis and management of ventilator-associated pneumonia (VAP). LRT, lower respiratory tract.

(Modified from American Thoracic Society: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, Am J Respir Crit Care Med 171:388–416, 2005.)

The bacteriologic strategy is based on the results of quantitative cultures of lower respiratory secretions (Figure 27-2). The procedure used to collect the samples (endotracheal aspirate, BAL fluid, or PSB) may be invasive (bronchoscopic) or noninvasive (blind procedures). The strategy reduces risks for overuse of antibiotics, because quantitative cultures yield fewer microorganisms above the threshold in comparison with semiquantitative cultures. Among the disadvantages of the bacteriologic strategy is the possibility of obtaining false-negative results, which leads to delayed antibiotic treatment in patients with pneumonia. Moreover, results obtained using the microbiology strategy may lack reproducibility, and often no microbiologic information is available at the time of initiation of empirical antibiotic therapy.

Figure 27-2 Invasive and quantitative culturing strategy for the diagnosis and management of ventilator-associated pneumonia (VAP). ATB, antibiotic; BAL, bronchoalveolar lavage; BAS, bronchial aspiration; PSB, protected specimen brushing.

(Modified from American Thoracic Society: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, Am J Respir Crit Care Med 171:388–416, 2005.)

Practical Implementation of A Diagnostic Strategy in Suspected Nosocomial Respiratory Infection

In practice, the development of local clinical guidelines can combine both clinical and bacteriologic strategies. In mechanically ventilated patients, the presence of an infiltrate on the chest radiograph differentiates between the possible presence of pneumonia and tracheobronchitis. The next step is to obtain samples from the lower respiratory tract, before initiation of antibiotic treatment or change in regimen, even though it should not delay the administration of antibiotic therapy, particularly for septic patients. When indicated, additional samples should be collected for microbiologic analyses, such as blood, pleural fluid, and, in case L. pneumophila or S. pneumoniae infections are suspected, urine should be obtained. With clinical findings suggestive of pneumonia, CPIS should be calculated, to improve objective assessment of the clinical parameters (see Table 27-1).

The Likely Etiologic Microorganisms

The selection of initial antimicrobial therapy needs to be tailored to the local prevalence of pathogens and antimicrobial patterns of resistance of the institution. The dynamics of change of oropharyngeal flora during hospital stay is depicted in Figure 27-3. Changes in oropharyngeal flora tend to occur progressively, so that the presence of microorganisms during one stage often overlaps with the next stage.

Figure 27-3 Evolution of the potentially pathogenic microorganisms present in the oropharyngeal flora, related to comorbidity, antibiotic treatment, and colonization pressure. Implicated species include Neisseria influenzae, Neisseria meningitidis, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Streptococcus pyogenes, as well as drug-resistant/susceptible staphylococci. ESBL, extended-spectrum beta-lactamase; GNB, gram-negative bacilli; ICU, intensive care unit; MDR, multidrug-resistant; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive S. aureus. *Transiently present in healthy carriers. †Producers of extended-spectrum beta-lactamase or with type ampC chromosomal beta-lactamases. ‡P. aeruginosa, Stenotrophomonas spp., Acinetobacter spp., Burkholderia spp.

Choice of the Empirical Antimicrobials Likely to be Active Against Causative Microorganisms

The latest guidelines of the American Thoracic Society and the Infectious Diseases Society of America (ATS/IDSA) for the management of adult patients with nosocomial pneumonia recommend that the selection of empirical antibiotic therapy for each patient should be based on the timing of onset and presence of risk factors for MDR pathogens—antimicrobial therapy in preceding 90 days; current hospitalization of 5 days or more; high frequency of antibiotic resistance in the community or in the specific hospital unit; hospitalization for 2 days or longer within the preceding 90-day period; residence in a nursing home or extended care facility; home infusion therapy (including antibiotics); chronic dialysis within 30 days; home wound care; MDR pathogen carrier status or infection in a family member; and immunosuppressive disease and/or therapy. The antibiotics recommended in the current ATS/IDSA guidelines are shown in Tables 27-2 and 27-3. Broad-spectrum empirical antibiotic therapy should be rapidly deescalated as soon as microbiologic data become available, to limit the emergence of resistance in the hospital.

Table 27-2 Initial Empirical Antibiotic Treatment in Nosocomial and Ventilator-Associated Pneumonia of Early Onset in Patients Without Risk Factors for Infection by Multidrug-Resistant Pathogens

Modified from American Thoracic Society: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, Am J Respir Crit Care Med 171:388–416, 2005.

Table 27-3 Initial Empirical Antibiotic Treatment for Nosocomial and Ventilator-Associated Pneumonia of Late Onset or in Patients with Risk Factors for Infection by Multidrug-Resistant Pathogens and Any Degree of Severity

ESBL, extended-spectrum beta-lactamase; GNB, gram-negative bacilli; ICU, intensive care unit.

* If an ESBL-positive strain such as K. pneumoniae, or Acinetobacter, is suspected, a carbepenem is the agent of first choice.

† If L. pneumophila is the suspected pathogen, the combination antibiotic regimen should include a macrolide (e.g., azithromycin), or a fluoroquinolone (e.g., ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside.

‡ The choice of beta-lactam is made as follows: Patients who have not received any antipseudomonal beta-lactam within the last 30 days should be administered piperacillin-tazobactam or an antipseudomonal cephalosporin. Patients who have received these drugs should be given empirical therapy with a carbapenem. Patients with infection by ESBL-producing microorganisms should be treated with carbapenem regardless of the results of the antibiogram.

§ For combined empirical therapy for multidrug-resistant GNB, an antipseudomonal fluoroquinolone should be given in cases of renal failure or with concomitant use of vancomycin. In other settings, combined empirical therapy with amikacin is initiated and maintained for a 5-day period.

¶ Empirical therapy aimed against MRSA is initiated in patients with proven colonization, previous infection by this microorganism, or implementation of mechanical ventilation for more than 6 days. The antibiotic of choice is either vancomycin (except in persons allergic to this medication, those with serum creatinine values of 1.6 mg/dL or greater, or patients presenting with signs of empirical treatment failure after 48 hours of antibiotic therapy) or linezolid. NOTE: For epidemiologic surveillance, nasal and perineal cultures should be performed on admission and at 1-week intervals thereafter during the ICU stay.

Antimicrobial Therapy in Special Situations

The addition of antibiotics with activity against MRSA depends on the local prevalence of MRSA, the presence of risk factors for MRSA, and the severity of infection. In geographic areas with documented presence of community-acquired MRSA, severe pneumonia with radiologic images of cavitation and presence of gram-positive cocci in respiratory secretions, empirical treatment with linezolid or vancomycin may be appropriate. Infections by L. pneumophila serogroup 1 can be diagnosed by a Legionella urinary antigen test. A fluoroquinolone or a macrolide would be an appropriate agent for treatment of L. pneumophila infection.

Modifications of Therapy and Duration of Treatment

After 72 hours, treatment should be adjusted in accordance with the microbiologic results. The initial beta-lactam should be continued if the microorganism is susceptible to the empirical beta-lactam originally prescribed. If it is not, another beta-lactam, possibly a carbapenem, may be introduced. The empirical antibiotic active against MRSA should be discontinued if the presence of this pathogen is not confirmed by cultures. Discontinuation of the fluoroquinolone and especially the aminoglycoside should be considered after 3 to 5 days of treatment. The bactericidal activity of aminoglycosides and fluoroquinolones leads to a rapid reduction in the bacterial load during the first days of treatment. Thereafter, monotherapy may be sufficient. This approach would decrease emergence of resistant mutants and minimize nephrotoxicity caused by aminoglycosides.

A majority of infections can be effectively treated with regimens lasting up to 8 days. Four special situations may justify prolonged treatment: (1) infection by microorganisms that may multiply in the cellular cytoplasm, such as Legionella spp.; (2) the presence of biofilms or prosthetic devices; (3) the development of tissue necrosis, the formation of abscesses, or infection within a closed cavity, such as empyema; and (4) persistence of the original infection (such as with perforation or endocarditis). If the clinical course from the pneumonia is favorable within the first 3 to 5 days of antimicrobial therapy, treatment may be withdrawn after the completion of 8 days. In cases of pneumonia produced by nonfermenting gram-negative bacilli, the eradication of these microorganisms from the bronchial secretion can be achieved with a longer regimen of up to 14 days.

In patients originally suspected on clinical grounds to have ICU-acquired pneumonia but whose CPIS is lower than 6 on the third day of drug therapy, treatment may be withdrawn. In this setting, the patient probably did not have pneumonia, or the pneumonia was sufficiently mild that prolonged antibiotic treatment is not required (Figure 27-4).

Figure 27-4 Suggested flowchart for follow-up evaluation in patients with nosocomial pneumonia and ventilator-associated pneumonia (VAP). *Criteria of treatment failure. †In cases in which the etiologic agent is Pseudomonas aeruginosa or Acinetobacter spp., the treatment should be maintained for 14 days. ‡Patients with criteria for treatment failure and in whom methicillin-resistant S. aureus (MRSA) is isolated should be administered linezolid. If a gram-negative bacillus is isolated, consultation with an infectious diseases specialist is recommended.

(Modified from American Thoracic Society: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, Am J Respir Crit Care Med 171:388–416, 2005.)

Important Insights for Treatment of Nosocomial Respiratory Infections

Studies have proved beneficial effects of antimicrobial treatment for patients with nosocomial tracheobronchitis being cared for in an ICU. In these patients, antibiotics can have an impact on ICU mortality rate, duration of mechanical ventilation, and ICU stay and ultimately hinder progression of the infection to VAP. Of importance, patients with airway colonization but without local and systemic signs of infection should not be treated. Additionally, aerosolized antibiotics can be a feasible option in such patients.

There is evidence that appropriate and timely antibiotic treatment can improve outcome in patients with VAP. Guidelines can play a significant role in accomplishing this aim. To achieve significant reductions in morbidity and mortality, however, two important principles should be followed: (1) the guidelines should be implemented in specific clinical settings, and (2) antibiotic treatment regimens should be tailored to specific risk factors for acquiring MDR pathogens. Although implementation of such guidelines is difficult, the available evidence demonstrates improvement in both management and outcome.