key: cord-0037723-q965ge1k authors: Torres, Antoni; Cillóniz, Catia title: Epidemiology, etiology, and risk factors of bacterial pneumonia date: 2015-10-15 journal: Clinical Management of Bacterial Pneumonia DOI: 10.1007/978-3-319-22062-8_2 sha: dd140bd29e5c33744f00454a2771ccf4793e4659 doc_id: 37723 cord_uid: q965ge1k Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection after urinary tract infections. The incidence of HAP ranges from 5 to 15 cases per 1000 hospital admissions, and is a frequent problem in general wards (incidence ranging from 1.6 to 3.67 cases per 1000 admissions). Torres et al [10] Spain/1991 The most frequent Gram-negative pathogens associated with HAP include: • P. aeruginosa; • Acinetobacter baumannii; • Haemophilus influenzae; and • Enterobacteriaceae (Klebsiella pneumoniae, E. coli, Enterobacter species, Serratia species, Proteus species, etc). Gram-negative bacteria are implicated in 50 to 80% of the cases of HAP in an ICU [10] . The most common Gram-positive pathogens isolated from patients with Antibiotic resistance among S. pneumoniae, the most common cause of CAP, has increased worldwide in the last two decades [52] [53] [54] . However, mortality rates related to antibiotic-resistant S. pneumoniae have not increased due to interventions such as conjugated pneumococcal vaccine, which covers the serotypes that are most likely to express resistance [55] . In a study of macrolide-resistant S. pneumoniae, Daneman et al [56] found that resistance, and therefore risk of macrolide failure, was independent of the underlying resistance mechanism. [73] . A. baumannii exhibits a high level of antimicrobial resistance but with a low virulence [74] and can cause CAP and HAP. A. baumannii is a frequent cause of pneumonia in Southeast Asia; hot climates especially dry [75] and humid [76, 77] are the preferred environment of this pathogen. Infections caused by A. baumannii presented similar epidemiologic patterns in CAP and HAP, with a seasonal variation and a peak in the late summer. CAP caused by A. baumannii has a mortality rate of 50% [76] , and in the case of HAP the severity of the underlying disease determines the fatality rate. Garnacho-Montero et al [74] noted that antibiotic exposure was the only independent risk factor associated with VAP caused by A. baumannii. The mortality rate of VAP caused by A. baumannii infection was no higher than VAP caused by other pathogens. Factors that increase the risk of HAP include two main categories and are detailed in Table 2 .5. Intubation and mechanical ventilation increases the risk of VAP by 6-to 21-fold, and the risk is greatest in the first 5 days of intubation [38]. The endotracheal tube allows direct entry of bacteria into the lower respiratory tract, interferes with normal host defense mechanisms, and becomes a reservoir for pathogenic microorganisms. Oropharyngeal colonization is the main mechanism responsible for development of HAP; colonization will be present upon admission or acquired in the ICU. Feldman et al [59] found that colonization and biofilm formation were present within 12 hours of patient intubation and present in almost all patients after 96 hours. In the same study it was also demonstrated that colonization in patients undergoing mechanical ventilation occurred first in the oropharynx and stomach, then lower respiratory tract, and finally in the endotracheal tube [59] . Male sex Pneumonia can occur at any age, but its incidence increases significantly with advanced age. Old age is therefore an important risk factor for pneumonia, which is a leading cause of illness and death in the elderly. A recent study that investigated the influence of age and comorbidity on microbial patterns in patients over 65 years of age with CAP found that age does not significantly affect pathogen patterns, whereas comorbidities were associated with specific causes [23] . The main factors associated with mortality in this analysis were neurologic diseases, the presence of potential MDR pathogens, and very advanced age (>85 years) [23] . Advanced age is associated with a decline in the integrity of physical barriers and protection against invading pathogens, as well as age-related changes in the immune system. Declines in the sensitivities of airway protective cough and swallowing reflexes are age-related and important risk factors for the development of pneumonia [79] . The difference of susceptibility to infections such as pneumonia between males and females is multifactorial. During the development of infection there is an interaction between sex-specific immune responses and immune responses to specific pathogens. A clear example of this relationship is the sex differences in the incidence and outcome of influenza virus A infections. In 2010 the WHO published a report detailing evidence that sex and gender should be considered when evaluating exposure to and the outcome of influenza virus infection [80] . The report concluded that the outcome of pandemic influenza H1N1 is generally worse for young adult females. The number of patients who receive care outside the hospital setting (eg, in nursing homes) is increasing with the aging population, implying an increase in the risk of pneumonia [22, 81, 82] . In addition, 10 to 18% of all patients hospitalized for pneumonia are nursing home residents, with mortality rates potentially as high as 55% [81, 83] . Chronic obstructive pulmonary disease COPD is one of the most common comorbidities associated with CAP. Patients with COPD have a 2-to 4-fold increased risk of CAP [22] . Data from a Spanish study conducted in patients with CAP compared the outcome of patients with and without COPD and revealed that the presence of COPD was an independent risk factor for mortality [84] . The prevalence of diabetes is increasing rapidly and is predicted to increase further, in parallel with the trends observed for obesity [85, 86] . Diabetic patients may have increased susceptibility to pneumonia for several reasons: increased risk of aspiration, hyperglycemia, decreased immunity and impaired lung function, and coexisting morbidity. Kornum et al [87] reported that Type 1 and Type 2 diabetes were risk factors for pneumonia-related hospitalization in a cohort of 34,239 patients with pneumonia in Denmark [87] . Similarly, Yende et al [88] reported that pre-existing diabetes was associated with a higher risk of death after hospitalization for CAP compared to those hospitalized for noninfectious illnesses. Furthermore, the risk of developing severe pneumococcal bacteremia is higher in diabetic patients [89] . Several studies have demonstrated that chronic renal failure is a significant risk factor for mortality in patients with CAP [90, 91] . In patients on dialysis, the mortality rate from pneumonia is 14-to 16-fold higher than in the general population [92] . Bacterial infections occur in 32 to 34% of patients with cirrhosis who are admitted to the hospital, of which approximately 15% are pneumonia (the third leading cause of infection in these patients). Cillóniz et al [93] reported that chronic liver disease was a risk factor for pulmonary complication in patients hospitalized due to pneumococcal pneumonia [93] . CAP is a frequent respiratory complication in patients infected with human immunodeficiency virus (HIV), even in the highly active antiretroviral therapy era [94] [95] [96] . Patients infected with HIV are 25 times more likely to develop pneumonia than uninfected patients; the depletion of CD4+ lymphocytes and high levels of HIV-RNA in HIV-infected persons occurs in parallel to the risk of developing pulmonary infections [97] . Smoking is associated with colonization by pathogenic bacteria and an increased risk of lung infections, especially in the case of pneumococcal pneumonia [98] . In a study of bacterial pneumonia in patients with HIV, current smokers had a >80% higher risk of developing pneumonia compared with never-smokers [33, 99] . Bello et al [100] showed that current smokers with pneumococcal CAP often develop severe sepsis and require hospitalization at a younger age despite having fewer comorbid conditions. Almirall et al [101] found that passive smoking at home is a risk factor for CAP in older adults (65 years of age or more). Samokhvalov et al [102] performed a meta-analysis that showed that the consumption of 24, 60, and 120 g of pure alcohol daily resulted in a relative risk for incident CAP of 1.12 (95% CI 1.02-1.23), 1.33 (95% CI 1.06-1.67), and 1.76 (95% CI 1.13-2.77), respectively, relative to non-drinkers. A hundred million bacteria (oral and respiratory bacteria) are contained in every cubic millimeter of dental plaque. Oral and respiratory bacteria in the dental plaque are shed into the saliva and are then aspirated into the lower respiratory tract and the lungs to cause infection. Aspiration pneumonia is one of the most serious problems in the elderly population. Regular contact with children is associated with an increased risk of developing CAP [103] . Two studies have reported that the presence of children in the household increased the adjusted odds ratio (OR) from 1.0 for 'no children' to 3.2 [104] or 3.41 [105] for three or more children. • CAP is a serious health problem associated with high morbidity and mortality in all age groups worldwide. • HAP is the second most frequent nosocomial infection and is associated with significant impact on patient morbidity and mortality. • Streptococcus pneumoniae remains the most common cause of CAP across all severities. • Six pathogens cause approximately 80% of HAP: S. aureus, P. aeruginosa, Klebsiella species, E. coli, Acinetobacter species, and Enterobacter species. • Pathogens involved in HAP differ significantly from those typically responsible for CAP. • The etiological microorganisms associated with early-onset and late-onset HAP in patients with no prior antibiotic exposure are often the same as those responsible for CAP. • MDR pathogens (P. aeruginosa, A. baumannii, and MRSA) are the most common pathogens in patients with late-onset HAP with prior antibiotic exposure. • Older age, male sex, chronic comorbidities, exposure to cigarette smoke, alcohol abuse, malnutrition, conditions that promote pulmonary aspiration or inhibit coughing, and exposure to contaminated respiratory equipment are the principal risk factors for pneumonia. 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