Chapter 27 Nosocomial Respiratory Infections
The designation nosocomial respiratory infection refers to tracheobronchitis and pneumonia caused by pathogens highly prevalent in hospital settings and developing at least 48 hours after hospital admission. Nosocomial tracheobronchitis is characterized by signs of respiratory infection, such as an increase in the volume and purulence of respiratory secretions, fever, and leukocytosis, without radiologic infiltrates suggestive of consolidation on the chest film. Nosocomial pneumonia comprises pneumonia developing in nonintubated patients, ventilator-associated pneumonia (VAP), and health care–associated pneumonia (HCAP). VAP commonly develops in patients who receive invasive mechanical ventilation. HCAP is a more recently recognized clinical entity that is defined in the latest guidelines of the American Thoracic Society for the diagnosis and treatment of nosocomial pneumonia. HCAP develops in patients who are not hospitalized but are at risk for colonization by pathogens present in hospital settings, including multiple drug–resistant (MDR) microorganisms.
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.
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.
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.
Patients can be colonized exogenously by contaminated respiratory equipment, the hospital environment, and the hands of the attending staff. Thus, health care personnel should be adequately trained in infection control and preventive strategies; strict sterilization protocols and hand washing with alcohol-based solutions should be implemented; and finally, lower patient-nurse ratios can be expected to promote optimal care with consequent lower colonization rates.
Nevertheless, endogenous colonization is believed to be the primary pathogenic mechanism for nosocomial respiratory infection development. In the hospitalized patient, the oral flora may shift to a predominance of aerobic gram-negative pathogens, P. aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA). After aspiration of bacteria-laden oropharyngeal secretions and colonization of the airways, the occurrence of respiratory infection depends on the size of the inoculum, the patient’s functional status, and the competency of host defenses.
According to the gastropulmonary hypothesis of colonization, the stomach of patients being treated in ICUs often is colonized by pathogens as a consequence of alkalinization of gastric contents by enteral nutrition and drugs. Continuous gastroesophageal reflux facilitates translocation of microbes into the oropharynx, which are then aspirated across the ETT cuff. Early studies have shown that in tracheally intubated patients, gastric pH higher than 4 is consistently associated with pathogenic colonization of the stomach. Conclusive evidence is still lacking, however, for an association of gastric colonization with increased risk of pneumonia, and some investigators have not found a relationship with bacteria causing lung infection as first originating in the stomach.
Nosocomial respiratory infections may be caused by a variety of pathogens, and often more than one pathogen may be isolated. Microorganisms responsible for those infections differ according to the studied population, the duration of hospital stay, and the specific diagnostic methods used. Nosocomial respiratory infections are commonly caused by aerobic, gram-negative bacilli, such as P. aeruginosa, Escherichia coli, Klebsiella pneumoniae, or Acinetobacter spp., whereas Streptococcus aureus is the predominant isolated gram-positive pathogen. In a recent report by Esperatti and colleagues, the etiology of nosocomial pneumonia was investigated for invasively versus noninvasively ventilated patients managed in the ICU. Of interest, no significant differences were found, except for a higher proportion of S. pneumoniae in the noninvasively ventilated patients. These results imply that prevalence rates for nosocomial pathogens are similar in intubated and nonintubated patients, and that the use of empirical therapy likely to be active against them is warranted.
Underlying diseases may predispose patients to infection with specific organisms. For instance, patients with chronic obstructive pulmonary disease (COPD) are at increased risk for Haemophilus influenzae, Moraxella catarrhalis, P. aeruginosa, or S. pneumoniae infections; patients with acute respiratory distress syndrome (ARDS) are at higher risk for development of VAP caused by S. aureus, P. aeruginosa, and Acinetobacter baumannii. Finally, patients with traumatic injuries and neurologic disorders are at increased risk for S. aureus, Haemophilus, and S. pneumoniae infections.
Identification of pathogens resistant to multiple drugs is extremely important, in order to guide appropriate antibiotic treatment. Potential MDR pathogens are P. aeruginosa, MRSA, Acinetobacter spp., Stenotrophomonas maltophilia, Burkholderia cepacia, and extended-spectrum beta-lactamase–producing (ESBL-positive) K. pneumoniae. Conversely, S. pneumoniae, H. influenzae, methicillin-sensitive S. aureus, and antibiotic-sensitive Enterobacteriaceae organisms are not considered to be MDR pathogens. The incidence of MDR pathogens is closely linked to local factors and varies widely from one hospital to another. Accordingly, practitioners must be aware of the most prevalent microorganisms in their own clinical facilities and geographic regions to avoid the administration of initial inadequate antimicrobial therapy.
Legionella pneumophila as a cause of nosocomial pneumonia should be considered, particularly in immunocompromised patients. Anaerobes may potentially cause nosocomial infections, but often those pathogens are identified in association with aerobic pathogens, and their role is still considered controversial. Nosocomial infections are rarely caused by a fungus. Candida spp. and Aspergillus fumigatus are the most common isolated fungi, predominantly in immunocompromised patients. Finally, herpes simplex virus type 1 and cytomegalovirus (CMV) are the most common viruses identified as a cause of respiratory infections in hospitalized patients; of note, CMV pneumonia was found to be consistently associated with worse outcomes in patients managed in the ICU.
Nosocomial respiratory infections are associated with high morbidity and mortality and constitute an important burden for the health care system; therefore, appropriate preventive strategies, summarized in Box 27-1, should be implemented to reduce overall incidence of those diseases. Approaches with proven efficacy in reduction of nosocomial respiratory infections should be grouped and implemented as a bundle, because together they are expected to result in a better outcome than when implemented individually.
Preventive Strategies for Nosocomial Pneumonia
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.
Tracheal intubation and mechanical ventilation constitute the main risk for nosocomial respiratory infections and should be avoided whenever possible. Noninvasive ventilation is an attractive alternative for patients with acute exacerbations of COPD or acute hypoxemic respiratory failure, and for some immunocompromised patients with pulmonary infiltrates and respiratory failure.