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Prevention and control of nosocomial pneumonia
Pneumonia causes 79% of all infectious deaths in the United States and is a leading cause of death around the world. Although community-acquired pneumonia (CAP) causes most of these deaths, nosocomial pneumonia, both hospital-acquired pneumonia (HAP) in general and the ventilator-associated pneumonia (VAP) subset, remains an important cause of mortality and morbidity in the critically ill. Preventing pneumonia in the critically ill is a daunting task, and even controlling the incidence is difficult. Although complete prevention of nosocomial pneumonia is unlikely, substantial progress has been made.
With a prevalence of 21.8%, pneumonia remains the most common nosocomial infection, including in the intensive care unit (ICU). The incidence varies significantly among different types of ICU patients. Postoperative patients, especially those undergoing cardiothoracic, neurosurgical, and trauma-related surgery, appear to have the highest rates. Coronary care unit patients appear to have the lowest rates; medical, respiratory, and other surgical patients demonstrate intermediate rates.
Despite significant improvements in other important nosocomial infections, the prevalence of nosocomial pneumonia has not decreased. However, prevention strategies discussed in this chapter have substantially changed the clinical presentations of HAP/VAP. VAP rates have decreased as prevention strategies effectively decrease the incidence of early-onset (within 7 days of intubation) VAPs. Conversely, VAP now occurs in a subset of patients who enter a vicious cycle of prolonged ventilation, which increases the risk of pneumonia, leading to further prolongation of ventilation and high risk of recurrent pneumonia. One major factor characterizing these patients is the dramatic increase (from 18.7% to 29.9% over 13 years) in the proportion of pneumonia patients with any immunocompromising condition.
A distinction should be made between prevention of all nosocomial pneumonia and prevention of life-threatening nosocomial pneumonia. Differential effects of prevention strategies have resulted in a shift in the etiology of VAP. For example, methicillin-resistant Staphylococcus aureus (MRSA) caused up to 30% of VAPs in the past, , whereas more recent studies find rates as low as 7%. , Conversely, the frequency of pneumonia multidrug-resistant (MDR) strains of Enterobacterales has progressively increased for both HAP and VAP. Prevention of HAP/VAP due to Pseudomonas aeruginosa, Acinetobacter species, and MDR Enterobacterales, especially carbapenem-resistant Enterobacterales (CRE), is more likely to affect mortality. Unfortunately, the most effective strategies to prevent pneumonia work predominantly or exclusively in early-onset VAP and therefore have not resulted in a significant improvement in mortality. Conversely, one of the most consistent adverse effects of VAP (including early-onset) is a prolonged duration of mechanical ventilation. Because duration of ICU stay is the principal determinant of cost of care, prevention measures may be cost-effective even if they do not result in improved mortality.
The other major shift in nosocomial pneumonia epidemiology in the ICU is that HAP precipitating the need for mechanical ventilation is now more common than VAP. The influence of endotracheal intubation is so dominant that ICU-acquired pneumonia was once considered almost synonymous with VAP. Endotracheal intubation increases the rate of nosocomial pneumonia between 3-fold and 21-fold. HAP associated with mechanical ventilation appears to have an equal risk of MDR pathogens and higher crude mortality rates than VAP. , Even in the ICU, increased use of noninvasive ventilation and high-flow oxygen delivery results in more HAP patients who are not intubated. Therefore prevention strategies need to be extended outside the ICU and to nonintubated patients to make further progress in preventing overall pneumonia rates and associated morbidity and mortality.
Lack of diagnostic accuracy severely compromises efforts to prevent HAP/VAP. , Etiologic diagnosis is particularly difficult in patients who are not intubated. Radiographic interpretation is also problematic. The National Nosocomial Infections Surveillance (NNIS) definition of infectious ventilator-associated complication (IVAC), which does not require a chest radiograph in the definition, is neither sensitive nor specific, and VAP prevention strategies to alter the frequency of this entity have been disappointing. Others ignore the need for abnormal chest radiographs and instead combine VAP with a newly defined ventilator-associated tracheobronchitis (VAT). Whether VAT is an early stage of VAP and progresses to VAP is still debatable.
Pathogenesis
Two keys to prevention and control strategies are a clear understanding of the underlying pathogenesis of nosocomial pneumonia and a comprehensive approach to prevention. The benefit of both is best demonstrated by a study deploying seven interventions to prevent HAP in high-risk patients with an automatically triggered order set in a large integrated healthcare system. These interventions ( Table 106.1 ) were based on the pathogenesis of HAP. Over a 6-year period, HAP rates decreased from 5.9 to 1.79/1000 admissions ( P = 0.003), with mortality decreasing from 1.05 to 0.34/1000 admissions and highly significant decreases in broad-spectrum antibiotics.
TABLE 106.1
Interventions for High-Risk Patients to Prevent Hospital-Acquired Pneumonia
From Lacerna CC, Patey D, Block L, et al. A successful program preventing nonventilator hospital-acquired pneumonia in a large hospital system. Infect Control Hosp Epidemiol . 2020;41(5):547–552.
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The essence of nosocomial pneumonia pathogenesis involves three basic steps:
- 1.
Colonization of the oropharynx with pathogenic microorganisms
- 2.
Aspiration of oropharyngeal contents into the lower respiratory tract
- 3.
Overwhelming of the lower respiratory tract’s host defense mechanisms.
Effective prevention and control measures can be analyzed by their effect on one or more of these steps.
Despite the simplicity of this paradigm, assumption that the pathogenesis of all types of HAP/VAP is the same would be naive and incorrect. An example is the role of gastric colonization preceding oropharyngeal colonization, the basis for attention to enteral feedings and stress ulcer prophylaxis in VAP prevention. Although possibly important for pneumonia caused by Enterobacterales, gastric and enteric colonization has no role in the pathogenesis of S. aureus or P. aeruginosa pneumonia, the two common causes of VAP. Conversely, daily chlorhexidine baths did not prevent VAP in a trauma population but did significantly decrease VAP from MRSA. Therefore prevention strategies should be individualized to the patients, pathogens, and mechanisms prevalent in a specific ICU.
Colonization with pathogenic microorganisms
The major antecedent event to most nosocomial pneumonias is colonization of the oropharynx with pathogenic bacteria. The oropharynx is not sterile, but the character of the normal flora is remarkably constant. A variety of factors alter the normal flora, allowing replacement by more pathogenic microorganisms. The importance of the normal flora is illustrated by the adverse effects of iseganan, an antimicrobial peptide active against almost all bacteria. Oropharyngeal application of iseganan did not significantly decrease VAP rates but was associated with a trend for increased mortality.
Time of exposure to these selective forces within the hospital is critical. Early-onset pneumonia, even early-onset VAP, tends to be caused by less pathogenic microorganisms characteristic of CAP such as streptococci, Hemophilus influenzae, or methicillin-sensitive S. aureus . Most selective forces are introduced in the hospital environment itself, rather than specifically in the ICU. Therefore patients who develop pneumonia during the first few days of ICU admission or mechanical ventilation are at risk for MDR pathogens if preceded by a 3- to 5-day hospital stay. Many of the same factors also operate in skilled-care nursing facilities and lead to the designation of healthcare–associated pneumonia (HCAP). Although this term has been abandoned, the risk factors remain.
Previously, colonization of the oropharynx by gram-negative enteric bacilli, generally from the Enterobacterales order, was emphasized. As part of the normal bowel flora, oropharyngeal colonization occurred by one of two main routes. The first is reflux of bacteria into the stomach from the duodenum, with subsequent gastroesophageal reflux into the esophagus and oropharynx. Colonization and proliferation in the stomach are critical intermediate steps in this pathway. Therefore many prevention strategies logically target the stomach. The other route is self-inoculation by the fecal-oral route, through contamination of equipment or the hands of healthcare providers or the patient.
The pattern with Enterobacterales does not apply to all HAP/VAP pathogens. None of S. aureus , P. aeruginosa , and Acinetobacter species, common causes of VAP, have a typical colonization pattern like that of Enterobacterales. S. aureus is a normal colonizer of the skin and the nasopharynx. Antegrade colonization of the oropharynx from the nose, especially with the use of nasogastric tubes in many critically ill patients, can occur quite easily. Lack of nasal colonization, detected on admission screening, effectively excludes MRSA as a cause of HAP/VAP. Acinetobacter is found on moist body surfaces and in the gingival crevices of patients with poor oral hygiene. P. aeruginosa is usually not part of normal bowel flora but is ubiquitous in the environment. One of the unique aspects of Pseudomonas VAP is the appearance of tracheal colonization before oropharyngeal colonization. Because colonization of the stomach is not an important intermediary step for these pathogens, prevention measures directed at the stomach are not likely to affect pneumonia caused by them. Conversely, both MRSA and Acinetobacter colonization can be decreased with the use of chlorhexidine whole-body bathing.
Recent data from the lung microbiome have suggested that gram-negative pathogens may potentially cause pneumonia without antecedent oropharyngeal colonization. A gut-specific Bacteroides strain was found to be increased in patients with acute respiratory distress syndrome (ARDS) and/or sepsis. This finding may represent hematogenous spread of enteral pathogens to the lung via gut translocation, independent of oropharyngeal colonization, and may explain the association of septic shock and ARDS with the risk of MDR pathogens. Protection of the gastrointestinal (GI) brush border with enteral nutrition or selective decontamination of the digestive tract (SDD) may be more important in some of these patients in addition to those with chemotherapy-induced mucositis.
Avoidance of antibiotics
The single most important factor that leads to colonization of the oropharynx with pathogenic microorganisms is use of systemic antibiotics, especially broad-spectrum, that include coverage of gram-positive pathogens. Antibiotic killing of the usual oropharyngeal flora gives pathogens a selection advantage; at the same time, some pathogens are also eliminated. For this reason, antibiotics function more as amplifying agents rather than as true causes of colonization. The pathogenic microorganisms must still reside in the area normally, such as nasopharyngeal carriage of S. aureus, or be transferred from other sites, including the environment to colonize. Thus pneumonia can still occur despite avoidance of antibiotics. However, the causative microorganisms are more likely to be less virulent pathogens or even normal flora, such as alpha-hemolytic streptococci, and less likely to lead to life-threatening pneumonia.
Diagnostic strategies for fever in the ICU that result in the use of fewer antibiotics have been associated with lower mortality. Shorter courses and fewer antibiotics for documented infections in critically ill patients have also been associated with a decreased risk of superinfection. Although avoiding antibiotics may have only a small effect on the risk of developing the first episode of pneumonia, limiting their usage has a major effect on secondary pneumonia and infection-related death in the ICU.
Topical antibacterial agents
In contrast to systemic antibiotics, the use of topical antibiotics for the prevention of colonization may be beneficial. In general, strategies rely on controlling pathogenic microorganisms at specific sites, despite the effect on normal flora. Topical agents generally do not have the toxicity of systemic agents, and although the use of topical antibiotics can lead to MDR isolates, the risk may not be as great as with systemic antibiotics.
Selective digestive decontamination of the digestive tract
By far the most extensively studied and most aggressive form of topical antibiotic strategy to prevent colonization is SDD. Although the specific agents used in different studies vary, the major focus is on controlling oropharyngeal colonization by sterilizing almost the entire GI tract, including the large bowel. SDD is discussed more extensively in Chapter 110 .
Topical oropharyngeal agents
Controlling colonization of the oropharynx alone has also generated interest because little disruption of the normal bowel flora is expected by treating only the primary area of concern. Oropharyngeal decontamination alone appears to be equivalent to SDD for the prevention of VAP. Chlorhexidine oral rinse has been the most extensively studied. Unfortunately, different concentrations of chlorhexidine have been used and different populations have been compared. The strongest support for efficacy is for the 2% concentration. Chlorhexidine may not be able to prevent infection with MDR pathogens such as Pseudomonas and Acinetobacter . Oral decontamination with other agents, such as povidone/iodine and antimicrobial peptides, has not demonstrated benefit. Universal decolonization of patients with daily chlorhexidine for 5 days and nasopharyngeal mupirocin demonstrated lower MRSA bacteremia and surgical site infection rates but no effect on pneumonia.
Aerosolized antibiotics
The earliest studied form of topical colonization prevention was aerosolized antibiotics. In the early era of mechanical ventilation, daily aerosolized polymyxin B resulted in a dramatic decrease in the rate of gram-negative VAP. Not surprisingly, routine use was soon complicated by the emergence of antibiotic-resistant microorganisms. This feature, combined with a lack of mortality benefit, led to abandonment of this strategy. Aerosolized ceftazidime did not decrease VAP rates in trauma patients but did not increase MDR pathogen colonization either. A recent variation of this practice is to use aerosolized antibiotics for purulent tracheobronchitis, thought to be a precursor to VAP.
Avoidance of increased gastric pH
The normally acidic environment of the gastric lumen is extremely effective in preventing colonization with either swallowed oropharyngeal flora or refluxed enteric flora. Several prevention strategies focus on this aspect of prevention.
Stress ulcer prophylaxis
Because GI bleeding from stress ulceration was at one time a substantial problem in ventilated patients and a major cause of death, prophylaxis against stress ulceration was considered critical for ventilated patients . This generated a debate regarding the optimal GI bleeding prophylaxis , which has evolved over the last few decades. Initially, antacids were found to be inferior to histamine-2 blockers (H2 blockers). In addition to increasing gastric pH, antacids increase gastric volume, probably an independent risk factor for VAP. Subsequently sucralfate was hypothesized to be superior to H2 blockers because it did not affect gastric pH and might have intrinsic antibacterial properties. No clear-cut benefit of sucralfate over H2 blockers in reducing VAP was found, whereas a slight but consistent increase in GI bleeding has been documented. Proton pump inhibitors (PPIs) appear equivalent to H2 blockers.
However, the incidence of stress mucosal ulceration has decreased markedly as a result of better hemodynamic resuscitation, improved ventilatory strategies, and earlier use of enteral nutrition. Several multivariate analyses found PPIs associated with increased pneumonia rates, including HAP/VAP, , HCAP, and even CAP. Based on this concern, the need for stress ulcer prophylaxis at all in most mechanically ventilated patients has been questioned. Multicenter placebo-controlled trials have not found a benefit in either mortality or even GI bleeding , with inconsistent increases in VAP rates. , Ironically, GI prophylaxis had been encouraged as part of a ventilator/VAP bundle in many institutions. A subgroup of patients at increased risk for GI hemorrhage can be identified , and patients without these high - risk factors may not need prophylaxis. ,
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