Abstract
Pneumonia is the leading cause of morbidity and mortality, particularly in old adults. The incidence and etiologic distribution of community-acquired pneumonia is variable both geographically and temporally, and epidemiology might evolve with the change of population characteristics and vaccine uptake rates. With the increasing prevalence of chronic medical conditions, a wide spectrum of healthcare-associated pneumonia could also affect the epidemiology of community-acquired pneumonia. Here, we provide an overview of the epidemiological changes associated with community-acquired pneumonia over the decades since pneumococcal conjugate vaccine introduction.
Keywords: Pneumonia, Incidence, Mortality, Epidemiology, Pneumococcal conjugate vaccine
Introduction
Pneumonia is the leading infectious disease and is ranked the fourth most common cause of death in South Korea as of 2017 [1]. Globally, three million people die annually due to pneumonia, exceeding all other infectious causes including tuberculosis, malaria, and human immunodeficiency virus (HIV) infection [2]. With the increase in elderly population with chronic disease, long-term care facilities (LTCF) have expanded in South Korea in the recent decade, and this increase in elderly people living in LTCF could be contributing to the rise in pneumonia-related morbidity and mortality.
Prior to 2005, pneumonia was classified as either community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). Since 2005, healthcare-associated pneumonia (HCAP) was first incorporated into the HAP guidelines of the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA), considering that HCAP patients might be at high risk for multi-drug resistant (MDR) pathogens through repeated contact with the healthcare system [3]. However, HCAP was removed from the revised HAP guidelines again in 2016, and was supposed to be included in the upcoming CAP guidelines [4]. Similar to patients with CAP, most HCAP cases present from the community followed by frequent emergency room visits during acute disease phase. Furthermore, increasing evidence shows that the causative pathogens of HCAP cases are more closely related to pathogens associated with CAP than HAP [5,6,7,8,9].
In the beginning of the new millennium, pneumococcal conjugate vaccine (PCV) was developed and is now in widespread use. In children, PCV7 was first licensed in 2000, and extended to PCV10/PCV13 later in 2010 [10]. In turn, PCV13 was additionally licensed for adults in 2012 as the first conjugate vaccine for adults. PCV13 showed 45% efficacy against vaccine-type non-invasive pneumococcal pneumonia in the community-acquired pneumonia immunization trial in adults (CAPiTA), and 70% real world effectiveness [11,12]. Vaccine efficacy could be variable depending on pneumonia types because of different vaccine uptake rates and host factors; therefore, PCVs might affect the epidemiology of pneumonia differentially for CAP and HCAP. This review focuses on the change of epidemiology and etiologic distribution of pneumonia over time after the introduction of PCVs.
Incidence and case-fatality rate of community-acquired pneumonia
The incidence of CAP in adults varies worldwide by country, age, gender, and study period; however, reliable data on the incidence of CAP over a prolonged time period exists only for a few countries in North America and Europe, including the United States (107–370 cases per 100,000 persons aged 18–64 years, 630–5, 697 cases per 100,000 persons aged ≥65 years), the United Kingdom (52–106 cases per 100,000 persons aged 16–64 years, 275–1,006 cases per 100,000 persons aged ≥65 years), and Spain (68–320 cases per 100,000 persons aged 18–64 years, 237–1,400 cases per 100,000 persons aged ≥65 years) (Table 1) [13,14,15,16,17,18,19,20,21,22,23,24,25]. A wide variation of CAP incidence, even within the same country, results from distinctions in several factors such as inclusion of HCAP or outpatient pneumonia, and data sources of pneumonia assessment. Among these factors, CAP burden revealed a sharp divergence based on whether the study definition included HCAP. As for retrospective studies, it is difficult to differentiate HCAP from CAP cases by diagnostic codes alone. Thus, the burden in defining CAP using the International Classification of Diseases (ICD) code, which inevitably includes HCAP cases, is generally higher than those defined using clinical and radiological criteria. For example, Jain et al. reported that an annual incidence of CAP in the United States excluding patients with HCAP was 248 cases per 100,000 persons [17]. This result was substantially lower than 649 cases per 100,000 persons in another study by Ramirez et al., which included patients with HCAP [23]. Similarly, two Korean studies showed a large difference in the annual incidence of CAP regarding the inclusion of HCAP: 626 cases per 100,000 persons in one study defined by ICD codes vs. 308 cases per 100,000 persons in another study defined by physician assessment [1,2]. Both studies included HCAP cases. However, the former study might include most HCAP cases, while the latter study excluded LTCF-associated HCAP cases. Although there was a substantial gap in the burden of CAP based on study method, the incidence of CAP increased consistently with age and is higher in men than in women in all studies. The CAP incidence for persons aged 65 years and older was at least three-fold higher compared to those under the age of 65.
Table 1. Incidence and case fatality rate of community-acquired pneumonia in adults.
| Period | Authors [reference] | Study years | Country | Incidencea | Case-fatality rate | HCAP inclusion | Outpatient inclusion | Pneumonia assessment | Study type |
|---|---|---|---|---|---|---|---|---|---|
| Pre-PCV7 period | Kaplan et al. [18] | 1997 | US | ≥65 years: 1,830 | 10.6 | Inclusion | Exclusion | ICD code | Retrospective |
| Jackson et al. [16] | 1998–2001 | US | ≥65 years: 2,840 | 3.6 | Inclusion | Inclusion | ICD code | Retrospective | |
| Griffin et al. [14] | 1997–1999 | US | 18–64 years: 107–336 | NA | Inclusion | Exclusion | ICD code | Retrospective | |
| ≥65 years: 1,293–5,697 | |||||||||
| Lovering et al. [19] | 1994–1996 | UK | 16–59 years: 52–106 | 18.9 | Inclusion | Inclusion | Physician assessment | Prospective | |
| ≥60 years: 275–720 | |||||||||
| Millett at al. [20] | 1997–2005 | UK | ≥65 years: 630–793 | NA | Inclusion | Inclusion | ICD code | Retrospective | |
| Monge et al. [21] | 1995–1996 | Spain | <65 years: 93 | <65 years: 2.7 | Inclusion | Exclusion | ICD code | Retrospective | |
| ≥65 years: 523 | ≥65 years: 11.6 | ||||||||
| Gutierrez et al. [15] | 1999–2001 | Spain | 15–64 years: 68–108 | NA | Inclusion | Inclusion | Physician assessment | Prospective | |
| ≥65 years: 237–526 | |||||||||
| Post-PCV7 period | Takaki et al. [32] | 2008–2010 | Japan | 15–64 years: 340 | NA | Exclusion | Inclusion | Physician assessment | Prospective |
| 65–74 years: 1,070 | |||||||||
| ≥75 years: 4,290 | |||||||||
| Griffin et al. [14] | 2001–2009 | US | 18–64 years: 89–370 | NA | Inclusion | Exclusion | ICD code | Retrospective | |
| ≥65 years: 1,208–5,209 | |||||||||
| Simonsen et al. [31] | 2007–2009 | US | 18–64 years: 86.4–267.7 | NA | Inclusion | Exclusion | ICD code | Retrospective | |
| ≥65 years: 1,438.4 | |||||||||
| Millett et al. [20] | 2006–2010 | UK | ≥65 years: 1,375.2 | NA | Inclusion | Inclusion | ICD code | Retrospective | |
| Schnoor et al. [30] | 2003–2004 | German | ≥18 years: 370–1,010 | 3.6 | Inclusion | Inclusion | Physician assessment | Prospective | |
| Vila-Corcoles et al. [33] | 2002–2005 | Spain | ≥65 years: 1,050 | 15.0 | Inclusion | Exclusion | Physician assessment | Prospective | |
| Sicras et al. [24] | 2008–2009 | Spain | 18–64 years: 180–320 | 2.5 | Inclusion | Inclusion | ICD code | Retrospective | |
| ≥65 years: 510–810 | |||||||||
| Ochoa et al. [22] | 2002–2005 | Spain | ≥65 years: 1,400 | 13.0 | Inclusion | Inclusion | ICD, physician assessment | Prospective | |
| Gil-Prieto et al. [13] | 2003–2007 | Spain | ≥50 years: 627 | 17.0 | Inclusion | Exclusion | ICD code | Retrospective | |
| ≥65 years: 1,029 | |||||||||
| Post-PCV13 period | Choi et al. [1] | 2009–2013 | South Korea | 50–64 years: 477–600 | NA | Inclusion | Exclusion | ICD code | Retrospective |
| 65–74 years: 1,557–1,801 | |||||||||
| ≥75 years: 3,679–4,935 | |||||||||
| Heo et al. [2] | 2011–2014 | South Korea | 50–69 years: 369 | 6.2 | Inclusion | Exclusion | Physician assessment | Retrospective | |
| 70–79 years: 1,679 | |||||||||
| ≥80 years: 4,865 | |||||||||
| Morimoto et al. [29] | 2011–2013 | Japan | 55–64 years: 650 | 8.0 | Inclusion | Exclusion | Physician assessment | Prospective | |
| 65–74 years: 1,690 | |||||||||
| 75–84 years: 4,340 | |||||||||
| Simonsen et al. [25] | 2011–2012 | US | 18–64 years: 80.1–258.2 | NA | Inclusion | Exclusion | ICD code | Retrospective | |
| ≥65 years: 1,375.2 | |||||||||
| Jain et al. [17] | 2010–2012 | US | 50–64 years: 263 | NA | Exclusion | Exclusion | Physician assessment | Prospective | |
| 65–79 years: 630 | |||||||||
| ≥80 years: 1,643 | |||||||||
| Ramirez et al. [23] | 2014–2016 | US | 18–64 years: 327 | 6.5 | Inclusion | Exclusion | Physician assessment | Prospective | |
| ≥65 years: 2,093 | |||||||||
| Lopardo et al. [28] | 2012–2015 | Argentina | 18–64 years: 228–1,100 | 12.1 | Inclusion | Inclusion | Physician assessment | Prospective | |
| ≥65 years: 2,949 | |||||||||
| Uruguay | 18–64 years: 270–612 | ||||||||
| ≥65 years: 1,981 | |||||||||
| Paraguay | 18–64 years: 48–293 | ||||||||
| ≥65 years: 1,090 |
HCAP, healthcare-associated pneumonia; PCV7, 7-valent pneumococcal conjugate vaccine; ICD, International Classification of Diseases; NA, not available; PCV13, 13-valent pneumococcal conjugate vaccine
aCases/100,000 person-year.
Given the importance of pneumococcal pneumonia in the burden of CAP, both direct and indirect herd effect of PCVs should be considered in predicting the change of CAP incidence among adults. Since the introduction of pediatric PCV vaccination in national immunization programs (NIPs) in several countries, the incidence of invasive pneumococcal disease (IPD) was substantially decreased in both children and adults [26,27]. However, although lots of studies were conducted to evaluate the incidence of CAP since the introduction of PCVs, indirect effects on adult CAP have not been conclusively determined [1,2,13,14,17,20,22,23,24,25,28,29,30,31,32,33]. Previous reports in the United States have suggested that the incidence of hospitalized CAP among older adults showed a significant reduction in the last decade [14,25,31]. On the other hand, other studies have not shown any significant decrease in CAP rate in adults [20,34]. These inconsistent results might be related to the diverse degree of indirect herd effect on older adults with respect to PCV coverage rates and time interval following PCV NIP implementation.
The case-fatality rate (CFR) of CAP has been published much more than those presented in table 1. Overall CFR ranged from 2.5% to 20%, reaching up to 50% in patients admitted to intensive care unit [35,36]. CFR is influenced by several factors including age, sex, treatment regimen, vaccination status, and underlying comorbidities [37]. Although varied by country, approximately 10% of patients required intensive care, and 14% (median) died among hospitalized patients with CAP [38].
Etiologic distribution of causative pathogens in community-acquired pneumonia
Because the causative pathogen of CAP is unknown on initial presentation, it is important to know the distribution of CAP etiologic agents for the selection of appropriate empirical antibiotics. Streptococcus pneumoniae has been recognized as the most common identifiable pathogen of CAP, followed by Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, Mycoplasma pneumoniae, and Chlamydophila pneumoniae in varying order (Table 2). Traditionally, causative agents of CAP were identified using conventional culture methods, so microorganisms were identified in less than 30% of CAP cases during the pre-PCV7 period [39,40,41,42,43]. With advances in serological and molecular diagnostic tests, the diagnostic yield has improved by up to 40-50%, yet around 50% of CAP pathogens are still unidentified (Table 2) [7,44,45,46,47]. Prior antibiotic use is one of the important reasons for test-negative results. It is unclear to what degree viral pathogens and oral streptococci contribute to the development of pneumonia, and these are points to be further clarified in the future.
Table 2. Etiological distribution of community-acquired pneumonia in South Korea.
| Period | Authors [reference] | Study years (population age) | No. of cases | No. of cases with identified bacteria (%) | Gram-positive (%)a | Gram-negative (%)a | Atypical organisms (%)a |
|---|---|---|---|---|---|---|---|
| Pre-PCV7 period | Yu et al. [43] | 1994–1997 (≥16 years) | 214 | 81 (37.9) | Streptococcus pneumoniae (33.3) | Klebsiella pneumoniae (14.8) | Mycoplasma pneumoniae (6.2) |
| Staphylococcus aureus (16.0) | Pseudomonas aeruginosa (6.2) | ||||||
| Haemophilus influenzae (13.6) | |||||||
| Chung et al. [39] | 1995–1996 (≥15 years) | 246 | 54 (22.0) | Streptococcus pneumoniae (35.2) | Klebsiella pneumoniae (14.8) | Mycoplasma pneumoniae (2.0) | |
| Streptococcus spp. (7.5) | Pseudomonas aeruginosa (1.9) | ||||||
| Staphylococcus aureus (9.3) | Haemophilus influenzae (22.2) | ||||||
| Woo et al. [42] | 1997–2000 (≥16 years) | 585 | 219 (37.4) | Streptococcus pneumoniae (26.9) | Klebsiella pneumoniae (20.0) | - | |
| Streptococcus spp. (6.0) | Pseudomonas aeruginosa (12.8) | ||||||
| Staphylococcus aureus (11.4) | Haemophilus influenzae (5.0) | ||||||
| Sohn et al. [40] | 2001–2002 (≥16 years) | 202 | 39 (19.3) | Streptococcus pneumoniae (43.6) | Klebsiella pneumoniae (10.3) | Mycoplasma pneumoniae (7.4) | |
| Streptococcus spp. (10.3) | Pseudomonas aeruginosa (10.3) | Chlamydia pneumoniae (8.3) | |||||
| Staphylococcus aureus (2.6) | Haemophilus influenzae (2.6) | Legionella pneumophila (2.8) | |||||
| Song et al. [41] | 2002–2004 (≥18 years) | 955 | 108 (11.3) | Streptococcus pneumoniae (35.2) | Klebsiella pneumoniae (11.1) | Mycoplasma pneumoniae (11.0) | |
| Streptococcus spp. (8.3) | Pseudomonas aeruginosa (6.5) | Chlamydia pneumoniae (13.4) | |||||
| Staphylococcus aureus (11.1) | Haemophilus influenzae (2.8) | Legionella pneumophila (1.1) | |||||
| Post-PCV7 period | Jeon et al. [54] | 2007–2008 (≥60 years) | 175 | 63 (36.0) | Streptococcus pneumoniae (33.3) | Klebsiella pneumoniae (20.6) | Mycoplasma pneumoniae (3.2) |
| Staphylococcus aureus (14.3) | Pseudomonas aeruginosa (6.3) | ||||||
| Haemophilus influenzae (11.1) | |||||||
| Choi et al. [52] | 2007–2013 (≥18 years) | 2,221 | 568 (25.6) | Streptococcus pneumoniae (48.6) | Klebsiella pneumoniae (18.5) | Mycoplasma pneumoniae (0.9) | |
| Streptococcus spp. (1.6) | Pseudomonas aeruginosa (14.6) | ||||||
| Staphylococcus aureus (19.2) | Haemophilus influenzae (18.5) | ||||||
| Jeong et al. [5] | 2008–2010 (≥50 years) | 519 | 122 (23.5) | Streptococcus pneumoniae (48.4) | Klebsiella pneumoniae (11.5) | - | |
| Streptococcus spp. (6.6) | Pseudomonas aeruginosa (9.0) | ||||||
| Staphylococcus aureus (10.7) | Haemophilus influenzae (5.7) | ||||||
| Yoo et al. [56] | 2008–2010 (≥50 years) | 693 | 220 (31.7) | Streptococcus pneumoniae (23.2) | Klebsiella pneumoniae (7.7) | Mycoplasma pneumoniae (25.5) | |
| Streptococcus spp. (2.3) | Pseudomonas aeruginosa (10.0) | Chlamydia pneumoniae (1.4) | |||||
| Staphylococcus aureus (9.5) | Haemophilus influenzae (4.5) | Legionella pneumophila (1.4) | |||||
| Chong et al. [53] | 2009–2010 (≥18 years) | 619 | 131 (21.2) | Streptococcus pneumoniae (39.7) | Klebsiella pneumoniae (19.8) | Mycoplasma pneumoniae (31.3) | |
| Streptococcus spp. (0.8) | Pseudomonas aeruginosa (8.4) | ||||||
| Staphylococcus aureus (6.1) | Haemophilus influenzae (0.8) | ||||||
| Seong et al. [55] | 2010–2011 (≥18 years) | 275 | 105 (38.2) | Streptococcus pneumoniae (41.9) | Klebsiella pneumoniae (5.7) | Mycoplasma pneumoniae (6.7) | |
| Streptococcus spp. (4.8) | Pseudomonas aeruginosa (9.5) | ||||||
| Staphylococcus aureus (9.5) | Haemophilus influenzae (1.0) | ||||||
| Kang et al. [49] | 2008–2014 (≥65 years) | 212 | 62 (29.2) | Streptococcus pneumoniae (69.4) | Klebsiella pneumoniae (4.8) | ||
| Staphylococcus aureus (12.9) | Pseudomonas aeruginosa (3.2) | ||||||
| Haemophilus influenzae (11.3) | |||||||
| Post-PCV13 period | Lee et al. [46]b | 2011–2013 (≥18 years) | 75 | 37 (49.3) | Streptococcus pneumoniae (13.5) | Klebsiella pneumoniae (23.3) | |
| Streptococcus spp. (8.1) | Pseudomonas aeruginosa (10.8) | ||||||
| Staphylococcus aureus (37.8) | Haemophilus influenzae (0.0) | ||||||
| Seo et al. [47] | 2011–2016 (≥18 years) | 1,665 | 832 (50.0) | Streptococcus pneumoniae (21.4) | Klebsiella pneumoniae (13.6) | Mycoplasma pneumoniae (19.8) | |
| Streptococcus spp. (3.6) | Pseudomonas aeruginosa (2.9) | Chlamydia pneumoniae (26.9) | |||||
| Staphylococcus aureus (4.8) | Haemophilus influenzae (1.2) | Legionella pneumophila (1.1) | |||||
| Koh et al. [7] | 2012–2013 (≥65 years) | 151 | 62 (41.1) | Streptococcus pneumoniae (46.8) | Klebsiella pneumoniae (14.5) | Mycoplasma pneumoniae (8.1) | |
| Staphylococcus aureus (14.5) | Pseudomonas aeruginosa (6.5) | ||||||
| Haemophilus influenzae (3.2) | |||||||
| Ahn et al. [44] | 2012–2014 (≥18 years) | 647 | 177 (27.4) | Streptococcus pneumoniae (32.8) | Klebsiella pneumoniae (19.8) | Mycoplasma pneumoniae (14.7) | |
| Streptococcus spp. (0.6) | Pseudomonas aeruginosa (14.5) | ||||||
| Staphylococcus aureus (5.7) | |||||||
| Kim et al. [45] | 2016 (≥18 years) | 101 | 47 (46.5) | Streptococcus pneumoniae (38.3) | Klebsiella pneumoniae (21.3) | Mycoplasma pneumoniae (4.3) | |
| Staphylococcus aureus (23.4) | Pseudomonas aeruginosa (8.5) | ||||||
| Haemophilus influenzae (2.1) |
PCV7, 7-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine.
aProportion among cases with identified bacteria.
bCases requiring intensive care unit (ICU) care.
Among CAP cases caused by identified bacterial pathogens, S. pneumoniae is the most important causative species, accounting for 26.9–69.4% of pneumonia cases in South Korea (Table 2) [48], and the proportion of pneumococcal pneumonia was higher in studies confined to older adults [7,49]. However, in a study of severe CAP cases admitted to intensive care units (ICUs), S. aureus infection was more common compared to S. pneumoniae (37.8% vs. 13.5%) [46]. Etiologic distribution might be affected by disease severity, age, and underlying medical conditions.
Although IPDs were already reported as markedly decreased in both children and adults in the PCV13 era, data on pneumococcal CAP is still insufficient [50,51]. The introduction of PCVs was expected to affect the etiologic distribution of CAP; however, significant change was not observed after the introduction of the pediatric PCV7 conjugate vaccine [5,49,52,53,54,55,56]. Even in the early period of PCV13 use, S. pneumoniae still remained as the predominant agent causing CAP in South Korea, at 26.9–43.6% in the pre-PCV7 period, 23.2–69.4% in the post-PCV7 period, and 13.5–46.8% in the post-PCV13 period (Table 2) [7,44,45,46,47]. Similarly, in the etiology of pneumonia in the community study conducted in the United States during the early PCV13 period (2011-2012), S. pneumoniae was the most common causative pathogen of community-acquired bacterial pneumonia (30.1%, 115 cases), followed by S. aureus (9.7%, 37 cases) among the total 382 bacterial pneumonia cases [17]. Considering that about 65% of pediatric PCV13 immunization is required to expect a herd effect in adults and a seven year time period may be required to get the maximal herd effect from childhood immunization, subsequent studies are required to see the PCV13 herd effect [57,58]; however, there are several unpredictable uncertainties. First, it is not clear whether pediatric herd effect is enough to decrease non-invasive pneumococcal pneumonia in adults, not confined to IPDs. Second, depending on the degree of serotype replacement, the disease burden of pneumococcal pneumonia would be either persistent or decreased.
Comparison of etiologic distribution between community-acquired pneumonia vs. healthcare-associated pneumonia
During the early 2000s, several studies in the United States reported a high prevalence of MDR pathogens including methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa in HCAP cases, who had recent contact with healthcare systems through nursing homes, hemodialysis, chronic wound care, or recent hospitalization as examples [59,60]. Based on this evidence, the 2005 ATS/IDSA guidelines for nosocomial pneumonia included recommendations for HCAP treatment, suggesting empirical coverage of MDR pathogens [3]. Since then, subsequent studies were conducted in South Korea, Japan, and Spain, but most studies showed that S. pneumoniae is the most common causative agent of HCAP, similar to CAP (Table 3) [5,6,7,8,9,44,45,46,49,54,55,61,62,63,64,65]. In addition, although the proportion of MDR pathogens is higher in HCAP, some studies revealed indistinguishable etiologic distribution of causative agents between HCAP and CAP [5,6,7,8,9]. Prior meta-analysis suggested that higher mortality of HCAP might not be associated with higher frequency of resistant pathogens [66]. Moreover, empirical antibiotic therapy based on HAP guidelines did not show better clinical outcomes compared to CAP regimen, and resulted in higher mortality with inadequate coverage for atypical pathogens in some studies [67,68,69]. Accordingly, HCAP treatment will be covered in the next revised ATS/IDSA CAP guidelines. Given that the HCAP population is heterogeneous and overlaps with that of CAP and HAP, HCAP needs to be further sub-classified, and empirical antibiotic therapy for HCAP should be stratified based on the risk of MDR infection in each subgroup.
Table 3. Etiologic distribution of pneumonia: community-acquired pneumonia vs. healthcare-associated pneumonia.
| Country | Authors [reference] | Study periods/age | CAPa | HCAPa | ||
|---|---|---|---|---|---|---|
| US | Kollef et al. [59] | 2002–2003 year/≥18 years | Streptococcus pneumoniae (16.6) | Streptococcus pneumoniae (5.5) | ||
| Staphylococcus aureus (25.5) | Staphylococcus aureus (46.7) | |||||
| MSSA (12.0) | MSSA (20.2) | |||||
| MRSA (6.2) | MRSA (26.5) | |||||
| Haemophilus influenzae (16.6) | Haemophilus influenzae (5.8) | |||||
| Klebsiella spp. (9.5) | Klebsiella spp. (7.6) | |||||
| Pseudomonas aeruginosa (17.1) | Pseudomonas aeruginosa (25.3) | |||||
| Escherichia coli (4.8) | Escherichia coli (5.2) | |||||
| Micek et al. [60] | 2003–2005 year/≥18 years | Streptococcus pneumoniae (40.9) | Streptococcus pneumoniae (10.4) | |||
| Staphylococcus aureus (25.5) | Staphylococcus aureus (46.7) | |||||
| MSSA (16.6) | MSSA (14.3) | |||||
| MRSA (8.9) | MRSA (18.3) | |||||
| Haemophilus influenzae (17.3) | Haemophilus influenzae (4.2) | |||||
| Klebsiella spp. (3.4) | Klebsiella spp. (6.5) | |||||
| Pseudomonas aeruginosa (4.8) | Pseudomonas aeruginosa (25.5) | |||||
| Escherichia coli (5.8) | Escherichia coli (4.2) | |||||
| Atypical pathogens (3.4) | Atypical pathogens (0.2) | |||||
| South Korea | Jeon et al. [54] | 2007–2008 year/≥60 years | Streptococcus pneumoniae (33.3) | Streptococcus pneumoniae (6.7) | ||
| Staphylococcus aureus (11.1) | Staphylococcus aureus (40.0) | |||||
| MSSA (4.8) | MSSA (10.0) | |||||
| MRSA (6.3) | MRSA (30.0) | |||||
| Haemophilus influenzae (11.1) | Haemophilus influenzae (3.3) | |||||
| Klebsiella pneumoniae (20.6) | Klebsiella pneumoniae (26.7) | |||||
| Pseudomonas aeruginosa (6.3) | Pseudomonas aeruginosa (26.7) | |||||
| Mycoplasma pneumoniae (3.2) | Mycoplasma pneumoniae (0.0) | |||||
| Jeong et al. [5] | 2008–2010 year/≥18 years | Streptococcus pneumoniae (48.4) | Streptococcus pneumoniae (30.8) | |||
| Staphylococcus aureus (10.7) | Staphylococcus aureus (19.2) | |||||
| MSSA (9.0) | MSSA (9.2) | |||||
| MRSA (1.6) | MRSA (10.0) | |||||
| Haemophilus influenzae (5.7) | Haemophilus influenzae (6.9) | |||||
| Klebsiella pneumoniae (11.5) | Klebsiella pneumoniae (16.9) | |||||
| Pseudomonas aeruginosa (9.0) | Pseudomonas aeruginosa (15.4) | |||||
| Escherichia coli (0.8) | Escherichia coli (3.8) | |||||
| Kang et al. [49] | 2008–2014 year/≥65 years | Streptococcus pneumoniae (69.4) | Streptococcus pneumoniae (35.2) | |||
| Staphylococcus aureus (12.9) | Staphylococcus aureus (24.1) | |||||
| MSSA (11.3) | MSSA (3.7) | |||||
| MRSA (1.6) | MRSA (20.4) | |||||
| Haemophilus influenzae (11.3) | Haemophilus influenzae (0.0) | |||||
| Klebsiella spp. (4.8) | Klebsiella spp. (14.8) | |||||
| ESBL-producer (0.0) | ESBL-producer (7.4) | |||||
| Pseudomonas spp. (3.2) | Pseudomonas spp. (13.0) | |||||
| Escherichia coli (0.0) | Escherichia coli (9.3) | |||||
| ESBL-producer (0.0) | ESBL-producer (1.9) | |||||
| Seong et al. [55] | 2010–2011 year/≥18 years | Streptococcus pneumoniae (41.9) | Streptococcus pneumoniae (33.3) | |||
| Staphylococcus aureus (9.5) | Staphylococcus aureus (31.4) | |||||
| MSSA (6.7) | MSSA (15.7) | |||||
| MRSA (2.9) | MRSA (15.7) | |||||
| Haemophilus influenzae (1.0) | Haemophilus influenzae (0.0) | |||||
| Klebsiella spp. (5.7) | Klebsiella spp. (3.9) | |||||
| ESBL-producer (1.0) | ESBL-producer (2.0) | |||||
| Pseudomonas spp. (9.5) | Pseudomonas spp. (18.6) | |||||
| Mycoplasma pneumoniae (6.7) | Mycoplasma pneumoniae (0.0) | |||||
| Lee et al. [46]b | 2011–2013 year/≥18 years | Streptococcus pneumoniae (13.5) | Streptococcus pneumoniae (6.5) | |||
| Staphylococcus aureus (37.8) | Staphylococcus aureus (26.1) | |||||
| MSSA (29.7) | MSSA (8.7) | |||||
| MRSA (8.1) | MRSA (19.6) | |||||
| Haemophilus influenzae (0.0) | Haemophilus influenzae (0.0) | |||||
| Klebsiella pneumoniae (23.3) | Klebsiella pneumoniae (45.6) | |||||
| Pseudomonas aeruginosa (10.8) | Pseudomonas aeruginosa (10.9) | |||||
| Escherichia coli (5.4) | Escherichia coli (15.3) | |||||
| Koh et al. [7]c | 2012–2013 year/≥65 years | Streptococcus pneumoniae (46.8) | Streptococcus pneumoniae (46.7) | |||
| Staphylococcus aureus (14.5) | Staphylococcus aureus (23.3) | |||||
| MSSA (3.2) | MSSA (3.3) | |||||
| MRSA (11.3) | MRSA (20.0) | |||||
| Haemophilus influenzae (3.2) | Haemophilus influenzae (0.0) | |||||
| Klebsiella pneumoniae (14.5) | Klebsiella pneumoniae (16.7) | |||||
| Pseudomonas aeruginosa (6.5) | Pseudomonas aeruginosa (16.7) | |||||
| Mycoplasma pneumoniae (8.1) | Mycoplasma pneumoniae (20.0) | |||||
| Ahn et al. [44] | 2012–2014 year/≥18 years | Streptococcus pneumoniae (32.8) | Streptococcus pneumoniae (17.0) | |||
| Staphylococcus aureus (5.7) | Staphylococcus aureus (18.9) | |||||
| MSSA (1.7) | MSSA (2.6) | |||||
| MRSA (4.0) | MRSA (16.3) | |||||
| Klebsiella pneumoniae (19.8) | Klebsiella pneumoniae (21.6) | |||||
| Pseudomonas aeruginosa (14.5) | Pseudomonas aeruginosa (19.6) | |||||
| ESBL-producing Enterobacteriaceae (2.3) | ESBL-producing Enterobacteriaceae (17.6) | |||||
| Mycoplasma pneumoniae (14.7) | Mycoplasma pneumoniae (6.5) | |||||
| Kim et al. [45] | 2016 year/≥18 years | Streptococcus pneumoniae (38.3) | Streptococcus pneumoniae (21.8) | |||
| Staphylococcus aureus (23.4) | Staphylococcus aureus (25.7) | |||||
| MSSA (17.0) | MSSA (7.9) | |||||
| MRSA (6.4) | MRSA (17.8) | |||||
| Haemophilus influenzae (2.1) | Haemophilus influenzae (6.9) | |||||
| Klebsiella pneumoniae (21.3) | Klebsiella pneumoniae (21.8) | |||||
| Pseudomonas aeruginosa (8.5) | Pseudomonas aeruginosa (19.8) | |||||
| Escherichia coli (4.3) | Escherichia coli (9.9) | |||||
| Mycoplasma pneumoniae (4.3) | Mycoplasma pneumoniae (0.0) | |||||
| Japan | Ishida et al. [62] | 2008–2010 year/≥18 years | Streptococcus pneumoniae (58.2) | Streptococcus pneumoniae (31.8) | ||
| Staphylococcus aureus (0.0) | Staphylococcus aureus (19.1) | |||||
| MSSA (0.0) | MSSA (11.0) | |||||
| MRSA (0.0) | MRSA (8.1) | |||||
| Haemophilus influenzae (14.9) | Haemophilus influenzae (9.2) | |||||
| Klebsiella pneumoniae (5.0) | Klebsiella pneumoniae (11.6) | |||||
| Pseudomonas aeruginosa (3.0) | Pseudomonas aeruginosa (13.3) | |||||
| Escherichia coli (1.0) | Escherichia coli (7.5) | |||||
| Mycoplasma pneumoniae (3.5) | Mycoplasma pneumoniae (0.6) | |||||
| Maruyama et al. [9] | 2009–2011 year/≥18 years | Streptococcus pneumoniae (58.5) | Streptococcus pneumoniae (54.4) | |||
| Staphylococcus aureus (1.9) | Staphylococcus aureus (19.0) | |||||
| MSSA (1.9) | MSSA (7.7) | |||||
| MRSA (0.0) | MRSA (11.3) | |||||
| Haemophilus influenzae (15.1) | Haemophilus influenzae (5.6) | |||||
| Klebsiella pneumoniae (3.8) | Klebsiella pneumoniae (6.2) | |||||
| Pseudomonas aeruginosa (1.9) | Pseudomonas aeruginosa (11.3) | |||||
| Escherichia coli (1.9) | Escherichia coli (3.6) | |||||
| Mycoplasma pneumoniae (20.8) | Mycoplasma pneumoniae (6.7) | |||||
| Kosai et al. [8] | 2009–2012 year/≥18 years | Streptococcus pneumoniae (54.4) | Streptococcus pneumoniae (45.7) | |||
| Staphylococcus aureus (15.8) | Staphylococcus aureus (28.6) | |||||
| MSSA (8.8) | MSSA (5.7) | |||||
| MRSA (7.0) | MRSA (14.0) | |||||
| Haemophilus influenzae (19.3) | Haemophilus influenzae (8.6) | |||||
| Klebsiella pneumoniae (3.5) | Klebsiella pneumoniae (17.1) | |||||
| Pseudomonas aeruginosa (3.5) | Pseudomonas aeruginosa (8.6) | |||||
| Escherichia coli (1.8) | Escherichia coli (5.7) | |||||
| Mycoplasma pneumoniae (33.3) | Mycoplasma pneumoniae (28.6) | |||||
| Fukuyama et al. [61] | 2010–2012 year/≥18 years | Streptococcus pneumoniae (36.9) | Streptococcus pneumoniae (29.9) | |||
| Staphylococcus aureus (1.0) | Staphylococcus aureus (4.3) | |||||
| Haemophilus influenzae (29.6) | Haemophilus influenzae (28.9) | |||||
| Klebsiella pneumoniae (5.3) | Klebsiella pneumoniae (15.2) | |||||
| Pseudomonas aeruginosa (5.8) | Pseudomonas aeruginosa (8.1) | |||||
| Mycoplasma pneumoniae (4.4) | Mycoplasma pneumoniae (0.5) | |||||
| Kamata et al. [6] | 2010–2013 year/≥18 years | Streptococcus pneumoniae (40.6) | Streptococcus pneumoniae (59.2) | |||
| Staphylococcus aureus (7.5) | Staphylococcus aureus (26.2) | |||||
| MSSA (7.5) | MSSA (14.6) | |||||
| MRSA (0.0) | MRSA (11.6) | |||||
| Haemophilus influenzae (7.5) | Haemophilus influenzae (10.7) | |||||
| Klebsiella pneumoniae (1.0) | Klebsiella pneumoniae (16.5) | |||||
| Pseudomonas aeruginosa (2.8) | Pseudomonas aeruginosa (20.4) | |||||
| Mycoplasma pneumoniae (15.1) | Mycoplasma pneumoniae (6.8) | |||||
| Parrott et al. [63] | 2011–2013 year/≥18 years | Streptococcus pneumoniae (35.2) | Streptococcus pneumoniae (29.5) | |||
| Staphylococcus aureus (9.3) | Staphylococcus aureus (11.4) | |||||
| MSSA (7.4) | MSSA (6.8) | |||||
| MRSA (1.9) | MRSA (4.5) | |||||
| Haemophilus influenzae (25.9) | Haemophilus influenzae (18.2) | |||||
| Klebsiella pneumoniae (3.7) | Klebsiella pneumoniae (15.9) | |||||
| Pseudomonas aeruginosa (3.7) | Pseudomonas aeruginosa (15.9) | |||||
| Escherichia coli (0.0) | Escherichia coli (9.1) | |||||
| ESBL-producer (0.0) | ESBL-producer (4.5) | |||||
| Mycoplasma pneumoniae (3.7) | Mycoplasma pneumoniae (0.0) | |||||
| Spain | Polverino et al. [64] | 2008–2010 year/≥18 years | Streptococcus pneumoniae (70.8) | Streptococcus pneumoniae (62.7) | ||
| Staphylococcus aureus (2.8) | Staphylococcus aureus (2.4) | |||||
| Haemophilus influenzae (1.4) | Haemophilus influenzae (1.2) | |||||
| Pseudomonas aeruginosa (1.4) | Pseudomonas aeruginosa (4.8) | |||||
| Gram-negative bacilli (5.6) | Gram-negative bacilli (7.2) | |||||
| Atypical pathogens (4.2) | Atypical pathogens (2.4) | |||||
| Valles et al. [65] | 2011–2012 year/≥18 years | Streptococcus pneumoniae (63.6) | Streptococcus pneumoniae (44.8) | |||
| Staphylococcus aureus (4.1) | Staphylococcus aureus (10.3) | |||||
| MSSA (3.7) | MSSA (5.2) | |||||
| MRSA (0.4) | MRSA (5.2) | |||||
| Haemophilus influenzae (3.3) | Haemophilus influenzae (8.6) | |||||
| Pseudomonas aeruginosa (2.9) | Pseudomonas aeruginosa (6.9) | |||||
| Enterobacteriaceae (7.0) | Enterobacteriaceae (10.3) | |||||
| Atypical pathogens (2.5) | Atypical pathogens (3.4) | |||||
CAP, community-acquired pneumonia; HCAP, healthcare-associated pneumonia; MSSA, methicillin-susceptible Staphylococcus aureus; MRSA, methicillin-resistant Staphylococcus aureus; ESBL, extended-spectrum beta-lactamases.
aProportion (%) among cases with identified bacteria.
bCases requiring intensive care unit (ICU) care.
cComparison between community-acquired pneumonia vs. nursing home-acquired pneumonia.
Since the introduction of PCV13, community-acquired pneumococcal pneumonia was expected to gradually decrease. In comparison, the disease burden of pneumococcal pneumonia might be persistent among at-risk HCAP populations particularly residing in LTCF with missed opportunity of vaccination [70], as pneumococcal pneumonia outbreaks have been reported among unvaccinated nursing home residents [71,72]. In some studies conducted in Japan, the proportion of pneumococcal pneumonia in HCAP was similar or rather higher compared to that of CAP (Table 3) [6,8,9]. The concerning point is that MDR S. pneumoniae might be transmitted among LTCF residents with repeated antibiotic exposure. Actually, levofloxacin and ceftriaxone-resistant pneumococcal HCAP cases were recently reported in South Korea [73,74,75] and these MDR pneumococcal pneumonia cases were related to underlying neurological diseases and LTCF residence[73,74,75]. Pneumococcal disease burden among these high-risk populations should be monitored, and targeted vaccination strategy could be considered.
Conclusions
In this review, we summarized the incidence, CFR, and etiologic distribution of CAP since the introduction of PCV use. The incidence and etiologic distribution of this disease might be variable based on study population characteristics (density and age distribution), vaccine uptake rate, and case definitions as whether to include HCAP in the analysis. In the future, pneumonia-related morbidity and mortality could increase with our increasing aged population, and the proportion of HCAP might be higher with the rising prevalence of coexisting medical conditions. The current HCAP definition should be better clarified and further categorized to avoid overtreatment or undertreatment for MDR pathogens. Considering recent reports of MDR pneumococcal HCAP cases in South Korea, pneumococcal vaccination strategy should be tailored to minimize the missed vaccination opportunity in patients with chronic medical conditions [73,74,75].
Footnotes
Conflict of Interest: No conflicts of interest.
- Conceptualization: JYS.
- Data curation: JYH, JYS.
- Resources: JYH, JYS.
- Software: JYH, JYS.
- Supervision: JYS.
- Writing - original draft: JYH, JYS.
- Writing - review & editing: JYH, JYS.
References
- 1.Choi MJ, Song JY, Noh JY, Yoon JG, Lee SN, Heo JY, Yoon JW, Jo YM, Cheong HJ, Kim WJ. Disease burden of hospitalized community-acquired pneumonia in South Korea: Analysis based on age and underlying medical conditions. Medicine (Baltimore) 2017;96:e8429. doi: 10.1097/MD.0000000000008429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Heo JY, Seo YB, Choi WS, Lee J, Yoon JG, Lee SN, Choi MJ, Noh JY, Ahn JY, Jeong HW, Cheong HJ, Kim WJ, Lee HY, Song JY. Incidence and case fatality rates of community-acquired pneumonia and pneumococcal diseases among Korean adults: Catchment population-based analysis. PLoS One. 2018;13:e0194598. doi: 10.1371/journal.pone.0194598. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388–416. doi: 10.1164/rccm.200405-644ST. [DOI] [PubMed] [Google Scholar]
- 4.Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratalà J, El Solh AA, Ewig S, Fey PD, File TM, Jr., Restrepo MI, Roberts JA, Waterer GW, Cruse P, Knight SL, Brozek JL. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63:e61–e111. doi: 10.1093/cid/ciw353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Jeong BH, Koh WJ, Yoo H, Um SW, Suh GY, Chung MP, Kim H, Kwon OJ, Jeon K. Performances of prognostic scoring systems in patients with healthcare-associated pneumonia. Clin Infect Dis. 2013;56:625–632. doi: 10.1093/cid/cis970. [DOI] [PubMed] [Google Scholar]
- 6.Kamata K, Suzuki H, Kanemoto K, Tokuda Y, Shiotani S, Hirose Y, Suzuki M, Ishikawa H. Clinical evaluation of the need for carbapenems to treat community-acquired and healthcare-associated pneumonia. J Infect Chemother. 2015;21:596–603. doi: 10.1016/j.jiac.2015.05.002. [DOI] [PubMed] [Google Scholar]
- 7.Koh SJ, Lee JH. Clinical characteristics of nursing home-acquired pneumonia in elderly patients admitted to a Korean teaching hospital. Korean J Intern Med. 2015;30:638–647. doi: 10.3904/kjim.2015.30.5.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Kosai K, Izumikawa K, Imamura Y, Tanaka H, Tsukamoto M, Kurihara S, Takazono T, Morinaga Y, Nakamura S, Miyazaki T, Yanagihara K, Tashiro T, Kohno S. Importance of functional assessment in the management of community-acquired and healthcare-associated pneumonia. Intern Med. 2014;53:1613–1620. doi: 10.2169/internalmedicine.53.2499. [DOI] [PubMed] [Google Scholar]
- 9.Maruyama T, Fujisawa T, Okuno M, Toyoshima H, Tsutsui K, Maeda H, Yuda H, Yoshida M, Kobayashi H, Taguchi O, Gabazza EC, Takei Y, Miyashita N, Ihara T, Brito V, Niederman MS. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57:1373–1383. doi: 10.1093/cid/cit571. [DOI] [PubMed] [Google Scholar]
- 10.Geno KA, Gilbert GL, Song JY, Skovsted IC, Klugman KP, Jones C, Konradsen HB, Nahm MH. Pneumococcal Capsules and Their Types: Past, Present, and Future. Clin Microbiol Rev. 2015;28:871–899. doi: 10.1128/CMR.00024-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Bonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, van Werkhoven CH, van Deursen AM, Sanders EA, Verheij TJ, Patton M, McDonough A, Moradoghli-Haftvani A, Smith H, Mellelieu T, Pride MW, Crowther G, Schmoele-Thoma B, Scott DA, Jansen KU, Lobatto R, Oosterman B, Visser N, Caspers E, Smorenburg A, Emini EA, Gruber WC, Grobbee DE. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med. 2015;372:1114–1125. doi: 10.1056/NEJMoa1408544. [DOI] [PubMed] [Google Scholar]
- 12.McLaughlin JM, Jiang Q, Isturiz RE, Sings HL, Swerdlow DL, Gessner BD, Carrico RM, Peyrani P, Wiemken TL, Mattingly WA, Ramirez JA, Jodar L. Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Hospitalization for Community-Acquired Pneumonia in Older US Adults: A Test-Negative Design. Clin Infect Dis. 2018;67:1498–1506. doi: 10.1093/cid/ciy312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Gil-Prieto R, Garcìa-Garcìa L, Alvaro-Meca A, Méndez C, García A, de Miguel AG. The burden of hospitalisations for community-acquired pneumonia (CAP) and pneumococcal pneumonia in adults in Spain (2003-2007) Vaccine. 2011;29:412–416. doi: 10.1016/j.vaccine.2010.11.025. [DOI] [PubMed] [Google Scholar]
- 14.Griffin MR, Zhu Y, Moore MR, Whitney CG, Grijalva CG. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. N Engl J Med. 2013;369:155–163. doi: 10.1056/NEJMoa1209165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Gutiérrez F, Masiá M, Rodríguez JC, Mirete C, Soldán B, Padilla S, Hernández I, De Ory F, Royo G, Hidalgo AM. Epidemiology of community-acquired pneumonia in adult patients at the dawn of the 21st century: a prospective study on the Mediterranean coast of Spain. Clin Microbiol Infect. 2005;11:788–800. doi: 10.1111/j.1469-0691.2005.01226.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Jackson ML, Neuzil KM, Thompson WW, Shay DK, Yu O, Hanson CA, Jackson LA. The burden of community-acquired pneumonia in seniors: results of a population-based study. Clin Infect Dis. 2004;39:1642–1650. doi: 10.1086/425615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L, Team CE CDC EPIC Study Team. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015;373:415–427. doi: 10.1056/NEJMoa1500245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Kaplan V, Angus DC, Griffin MF, Clermont G, Scott Watson R, Linde-Zwirble WT. Hospitalized community-acquired pneumonia in the elderly: age- and sex-related patterns of care and outcome in the United States. Am J Respir Crit Care Med. 2002;165:766–772. doi: 10.1164/ajrccm.165.6.2103038. [DOI] [PubMed] [Google Scholar]
- 19.Lovering AM, MacGowan AP, Anderson P, Irwin D. Epidemiology and resource utilization for patients hospitalized for lower respiratory tract infection. Clin Microbiol Infect. 2001;7:666–670. doi: 10.1046/j.1469-0691.2001.00350.x. [DOI] [PubMed] [Google Scholar]
- 20.Millett ER, Quint JK, Smeeth L, Daniel RM, Thomas SL. Incidence of community-acquired lower respiratory tract infections and pneumonia among older adults in the United Kingdom: a population-based study. PLoS One. 2013;8:e75131. doi: 10.1371/journal.pone.0075131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Monge V, González A. Hospital admissions for pneumonia in Spain. Infection. 2001;29:3–6. doi: 10.1007/s15010-001-0024-2. [DOI] [PubMed] [Google Scholar]
- 22.Ochoa-Gondar O, Vila-Córcoles A, de Diego C, Arija V, Maxenchs M, Grive M, Martin E, Pinyol JL EVAN-65 Study Group. The burden of community-acquired pneumonia in the elderly: the Spanish EVAN-65 study. BMC Public Health. 2008;8:222. doi: 10.1186/1471-2458-8-222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Ramirez JA, Wiemken TL, Peyrani P, Arnold FW, Kelley R, Mattingly WA, Nakamatsu R, Pena S, Guinn BE, Furmanek SP, Persaud AK, Raghuram A, Fernandez F, Beavin L, Bosson R, Fernandez-Botran R, Cavallazzi R, Bordon J, Valdivieso C, Schulte J, Carrico RM University of Louisville Pneumonia Study Group. Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality. Clin Infect Dis. 2017;65:1806–1812. doi: 10.1093/cid/cix647. [DOI] [PubMed] [Google Scholar]
- 24.Sicras-Mainar A, Ibáñez-Nolla J, Cifuentes I, Guijarro P, Navarro-Artieda R, Aguilar L. Retrospective epidemiological study for the characterization of community- acquired pneumonia and pneumococcal pneumonia in adults in a well-defined area of Badalona (Barcelona, Spain) BMC Infect Dis. 2012;12:283. doi: 10.1186/1471-2334-12-283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Simonsen L, Taylor RJ, Schuck-Paim C, Lustig R, Haber M, Klugman KP. Effect of 13-valent pneumococcal conjugate vaccine on admissions to hospital 2 years after its introduction in the USA: a time series analysis. Lancet Respir Med. 2014;2:387–394. doi: 10.1016/S2213-2600(14)70032-3. [DOI] [PubMed] [Google Scholar]
- 26.Fitzwater SP, Chandran A, Santosham M, Johnson HL. The worldwide impact of the seven-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2012;31:501–508. doi: 10.1097/INF.0b013e31824de9f6. [DOI] [PubMed] [Google Scholar]
- 27.Tsaban G, Ben-Shimol S. Indirect (herd) protection, following pneumococcal conjugated vaccines introduction: A systematic review of the literature. Vaccine. 2017;35:2882–2891. doi: 10.1016/j.vaccine.2017.04.032. [DOI] [PubMed] [Google Scholar]
- 28.Lopardo GD, Fridman D, Raimondo E, Albornoz H, Lopardo A, Bagnulo H, Goleniuk D, Sanabria M, Stamboulian D. Incidence rate of community-acquired pneumonia in adults: a population-based prospective active surveillance study in three cities in South America. BMJ Open. 2018;8:e019439. doi: 10.1136/bmjopen-2017-019439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Morimoto K, Suzuki M, Ishifuji T, Yaegashi M, Asoh N, Hamashige N, Abe M, Aoshima M, Ariyoshi K Adult Pneumonia Study Group-Japan (APSG-J) The burden and etiology of community-onset pneumonia in the aging Japanese population: a multicenter prospective study. PLoS One. 2015;10:e0122247. doi: 10.1371/journal.pone.0122247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Schnoor M, Hedicke J, Dalhoff K, Raspe H, Schäfer T CAPNETZ study group. Approaches to estimate the population-based incidence of community acquired pneumonia. J Infect. 2007;55:233–239. doi: 10.1016/j.jinf.2007.04.355. [DOI] [PubMed] [Google Scholar]
- 31.Simonsen L, Taylor RJ, Young-Xu Y, Haber M, May L, Klugman KP. Impact of pneumococcal conjugate vaccination of infants on pneumonia and influenza hospitalization and mortality in all age groups in the United States. MBio. 2011;2:e00309–10. doi: 10.1128/mBio.00309-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Takaki M, Nakama T, Ishida M, Morimoto H, Nagasaki Y, Shiramizu R, Hamashige N, Chikamori M, Yoshida L, Ariyoshi K, Suzuki M, Morimoto K. High incidence of community-acquired pneumonia among rapidly aging population in Japan: a prospective hospital-based surveillance. Jpn J Infect Dis. 2014;67:269–275. doi: 10.7883/yoken.67.269. [DOI] [PubMed] [Google Scholar]
- 33.Vila-Corcoles A, Ochoa-Gondar O, Rodriguez-Blanco T, Raga-Luria X, Gomez-Bertomeu F EPIVAC Study Group. Epidemiology of community-acquired pneumonia in older adults: a population-based study. Respir Med. 2009;103:309–316. doi: 10.1016/j.rmed.2008.08.006. [DOI] [PubMed] [Google Scholar]
- 34.Grijalva CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR. Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet. 2007;369:1179–1186. doi: 10.1016/S0140-6736(07)60564-9. [DOI] [PubMed] [Google Scholar]
- 35.Welte T, Köhnlein T. Global and local epidemiology of community-acquired pneumonia: the experience of the CAPNETZ Network. Semin Respir Crit Care Med. 2009;30:127–135. doi: 10.1055/s-0029-1202941. [DOI] [PubMed] [Google Scholar]
- 36.Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012;67:71–79. doi: 10.1136/thx.2009.129502. [DOI] [PubMed] [Google Scholar]
- 37.Arnold FW, Wiemken TL, Peyrani P, Ramirez JA, Brock GN. Mortality differences among hospitalized patients with community-acquired pneumonia in three world regions: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study. Respir Med. 2013;107:1101–1111. doi: 10.1016/j.rmed.2013.04.003. [DOI] [PubMed] [Google Scholar]
- 38.Anevlavis S, Bouros D. Community acquired bacterial pneumonia. Expert Opin Pharmacother. 2010;11:361–374. doi: 10.1517/14656560903508770. [DOI] [PubMed] [Google Scholar]
- 39.Chung MH, Shin WS, Kim YR, Kang MW, Kim MJ, Jung HJ, Park SC, Pai H, Choi HJ, Shin HS, Kim EC, Choe KW, Kim S, Peck KR, Song JH, Lee K, Kim JM, Chong Y, Han SW, Lee KM. Etiology of communityacquired pneumonia surveyed by 7 university hospitals. Korean J Infect Dis. 1997;29:339–359. [Google Scholar]
- 40.Sohn JW, Park SC, Choi YH, Woo HJ, Cho YK, Lee JS, Sim HS, Kim MJ. Atypical pathogens as etiologic agents in hospitalized patients with community-acquired pneumonia in Korea: a prospective multi-center study. J Korean Med Sci. 2006;21:602–607. doi: 10.3346/jkms.2006.21.4.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Song JH, Oh WS, Kang CI, Chung DR, Peck KR, Ko KS, Yeom JS, Kim CK, Kim SW, Chang HH, Kim YS, Jung SI, Tong Z, Wang Q, Huang SG, Liu JW, Lalitha MK, Tan BH, Van PH, Carlos CC, So T Asian Network for Surveillance of Resistant Pathogens Study Group. Epidemiology and clinical outcomes of community-acquired pneumonia in adult patients in Asian countries: a prospective study by the Asian network for surveillance of resistant pathogens. Int J Antimicrob Agents. 2008;31:107–114. doi: 10.1016/j.ijantimicag.2007.09.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Woo JH, Kang JM, Kim YS, Shin WS, Ryu JH, Choi JH, Kim YR, Cheong HJ, Uh ST, Park CS, Chung MH, Chung KS, Lee CJ, Ryu J. A prospective multicenter study of community-acquired pneumonia in adults with emphasis on bacterial etiology. Korean J Infect Dis. 2001;33:1–7. [Google Scholar]
- 43.Yu CW, Park CW, Hwang BY, Song JY, Park O, Sohn JW, Cheong HJ, Kim WJ, Kim MJ, Park SC. Clinical Features and Prognosis of Community-acquired Pneumonia in the Elderly Patients. Korean J Infect Dis. 2000;32:212–218. [Google Scholar]
- 44.Ahn JH, Lee KH, Chung JH, Shin KC, Lee CK, Kim HJ, Choi EY. Clinical characteristics and prognostic risk factors of healthcare-associated pneumonia in a Korean tertiary teaching hospital. Medicine (Baltimore) 2017;96:e8243. doi: 10.1097/MD.0000000000008243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Kim ES, Park KU, Lee SH, Lee YJ, Park JS, Cho YJ, Yoon HI, Lee CT, Lee JH. Comparison of viral infection in healthcare-associated pneumonia (HCAP) and community-acquired pneumonia (CAP) PLoS One. 2018;13:e0192893. doi: 10.1371/journal.pone.0192893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Lee H, Park JY, Lee T, Lee YJ, Lim HJ, Park JS, Yoon HI, Lee JH, Lee CT, Cho YJ. Intermediate risk of multidrug-resistant organisms in patients who admitted intensive care unit with healthcare-associated pneumonia. Korean J Intern Med. 2016;31:525–534. doi: 10.3904/kjim.2015.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Seo H, Cha SI, Shin KM, Lim JK, Yoo SS, Lee SY, Lee J, Kim CH, Park JY. Relationship Between Clinical Features and Computed Tomographic Findings in Hospitalized Adult Patients With Community-Acquired Pneumonia. Am J Med Sci. 2018;356:30–38. doi: 10.1016/j.amjms.2018.03.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Lee MS, Oh JY, Kang CI, Kim ES, Park S, Rhee CK, Jung JY, Jo KW, Heo EY, Park DA, Suh GY, Kiem S. Guideline for Antibiotic Use in Adults with Community-acquired Pneumonia. Infect Chemother. 2018;50:160–198. doi: 10.3947/ic.2018.50.2.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Kang YS, Ryoo SR, Byun SJ, Jeong YJ, Oh JY, Yoon YS. Antimicrobial Resistance and Clinical Outcomes in Nursing Home-Acquired Pneumonia, Compared to Community-Acquired Pneumonia. Yonsei Med J. 2017;58:180–186. doi: 10.3349/ymj.2017.58.1.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50.Ladhani SN, Collins S, Djennad A, Sheppard CL, Borrow R, Fry NK, Andrews NJ, Miller E, Ramsay ME. Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000-17: a prospective national observational cohort study. Lancet Infect Dis. 2018;18:441–451. doi: 10.1016/S1473-3099(18)30052-5. [DOI] [PubMed] [Google Scholar]
- 51.Pelton SI, Bornheimer R, Doroff R, Shea KM, Sato R, Weycker D. Decline in Pneumococcal Disease Attenuated in Older Adults and Those with Comorbidities Following Universal Childhood PCV13 Immunization. Clin Infect Dis. 2018 doi: 10.1093/cid/ciy800. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Choi MJ, Song JY, Cheong HJ, Jeon JH, Kang SH, Jung EJ, Noh JY, Kim WJ. Clinical usefulness of pneumococcal urinary antigen test, stratified by disease severity and serotypes. J Infect Chemother. 2015;21:672–679. doi: 10.1016/j.jiac.2015.06.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Chong YP, Jung KS, Lee KH, Kim MN, Moon SM, Park S, Hur J, Kim DM, Jeon MH, Woo JH. The bacterial etiology of community-acquired pneumonia in Korea: A nationwide prospective multicenter study. Infect Chemother. 2010;42:397–403. [Google Scholar]
- 54.Jeon EJ, Cho SG, Shin JW, Kim JY, Park IW, Choi BW, Choi JC. The difference in clinical presentations between healthcare-associated and community-acquired pneumonia in university-affiliated hospital in Korea. Yonsei Med J. 2011;52:282–287. doi: 10.3349/ymj.2011.52.2.282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Seong GM, Kim M, Lee J, Lee JH, Jeong SY, Choi Y, Kim WJ. Healthcare-Associated Pneumonia among Hospitalized Patients: Is It Different from Community Acquired Pneumonia? Tuberc Respir Dis (Seoul) 2014;76:66–74. doi: 10.4046/trd.2014.76.2.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56.Yoo KH, Yoo CG, Kim SK, Jung JY, Lee MG, Uh ST, Shim TS, Jeon K, Shim JJ, Lee HB, Chung CR, Kang KW, Jung KS. Economic burden and epidemiology of pneumonia in Korean adults aged over 50 years. J Korean Med Sci. 2013;28:888–895. doi: 10.3346/jkms.2013.28.6.888. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57.Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH, Bennett NM, Reingold A, Thomas A, Schaffner W, Craig AS, Smith PJ, Beall BW, Whitney CG, Moore MR Active Bacterial Core Surveillance/Emerging Infections Program Network. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis. 2010;201:32–41. doi: 10.1086/648593. [DOI] [PubMed] [Google Scholar]
- 58.Klugman KP. Herd protection induced by pneumococcal conjugate vaccine. Lancet Glob Health. 2014;2:e365–6. doi: 10.1016/S2214-109X(14)70241-4. [DOI] [PubMed] [Google Scholar]
- 59.Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest. 2005;128:3854–3862. doi: 10.1378/chest.128.6.3854. [DOI] [PubMed] [Google Scholar]
- 60.Micek ST, Kollef KE, Reichley RM, Roubinian N, Kollef MH. Health care-associated pneumonia and community-acquired pneumonia: a single-center experience. Antimicrob Agents Chemother. 2007;51:3568–3573. doi: 10.1128/AAC.00851-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 61.Fukuyama H, Yamashiro S, Kinjo K, Tamaki H, Kishaba T. Validation of sputum Gram stain for treatment of community-acquired pneumonia and healthcare-associated pneumonia: a prospective observational study. BMC Infect Dis. 2014;14:534. doi: 10.1186/1471-2334-14-534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62.Ishida T, Tachibana H, Ito A, Yoshioka H, Arita M, Hashimoto T. Clinical characteristics of nursing and healthcare-associated pneumonia: a Japanese variant of healthcare-associated pneumonia. Intern Med. 2012;51:2537–2544. doi: 10.2169/internalmedicine.51.7987. [DOI] [PubMed] [Google Scholar]
- 63.Parrott G, Nebeya D, Kinjo T, Miyagi K, Haranaga S, Higa F, Tateyama M, Fujita J. Etiological analysis and epidemiological comparison among adult CAP and NHCAP patients in Okinawa, Japan. J Infect Chemother. 2017;23:452–458. doi: 10.1016/j.jiac.2017.03.018. [DOI] [PubMed] [Google Scholar]
- 64.Polverino E, Torres A, Menendez R, Cillóniz C, Valles JM, Capelastegui A, Marcos MA, Alfageme I, Zalacain R, Almirall J, Molinos L, Bello S, Rodríguez F, Blanquer J, Dorado A, Llevat N, Rello J HCAP Study investigators. Microbial aetiology of healthcare associated pneumonia in Spain: a prospective, multicentre, case-control study. Thorax. 2013;68:1007–1014. doi: 10.1136/thoraxjnl-2013-203828. [DOI] [PubMed] [Google Scholar]
- 65.Vallés J, Martin-Loeches I, Torres A, Diaz E, Seijas I, López MJ, Garro P, Castillo C, Garnacho-Montero J, Martin MM, de la Torre MV, Olaechea P, Cilloniz C, Almirall J, García F, Jiménez R, Seoane E, Soriano C, Mesalles E, Posada P. Epidemiology, antibiotic therapy and clinical outcomes of healthcare-associated pneumonia in critically ill patients: a Spanish cohort study. Intensive Care Med. 2014;40:572–581. doi: 10.1007/s00134-014-3239-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 66.Chalmers JD, Rother C, Salih W, Ewig S. Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. Clin Infect Dis. 2014;58:330–339. doi: 10.1093/cid/cit734. [DOI] [PubMed] [Google Scholar]
- 67.Chen JI, Slater LN, Kurdgelashvili G, Husain KO, Gentry CA. Outcomes of health care-associated pneumonia empirically treated with guideline-concordant regimens versus community-acquired pneumonia guideline-concordant regimens for patients admitted to acute care wards from home. Ann Pharmacother. 2013;47:9–19. doi: 10.1345/aph.1R322. [DOI] [PubMed] [Google Scholar]
- 68.Webb BJ, Dangerfield BS, Pasha JS, Agrwal N, Vikram HR. Guideline-concordant antibiotic therapy and clinical outcomes in healthcare-associated pneumonia. Respir Med. 2012;106:1606–1612. doi: 10.1016/j.rmed.2012.08.003. [DOI] [PubMed] [Google Scholar]
- 69.Grenier C, Pépin J, Nault V, Howson J, Fournier X, Poirier MS, Cabana J, Craig C, Beaudoin M, Valiquette L. Impact of guideline-consistent therapy on outcome of patients with healthcare-associated and community-acquired pneumonia. J Antimicrob Chemother. 2011;66:1617–1624. doi: 10.1093/jac/dkr176. [DOI] [PubMed] [Google Scholar]
- 70.Yang TU, Song JY, Noh JY, Cheong HJ, Kim WJ. Influenza and Pneumococcal Vaccine Coverage Rates among Patients Admitted to a Teaching Hospital in South Korea. Infect Chemother. 2015;47:41–48. doi: 10.3947/ic.2015.47.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 71.Tan CG, Ostrawski S, Bresnitz EA. A preventable outbreak of pneumococcal pneumonia among unvaccinated nursing home residents in New Jersey during 2001. Infect Control Hosp Epidemiol. 2003;24:848–852. doi: 10.1086/502148. [DOI] [PubMed] [Google Scholar]
- 72.Nuorti JP, Butler JC, Crutcher JM, Guevara R, Welch D, Holder P, Elliott JA. An outbreak of multidrug-resistant pneumococcal pneumonia and bacteremia among unvaccinated nursing home residents. N Engl J Med. 1998;338:1861–1868. doi: 10.1056/NEJM199806253382601. [DOI] [PubMed] [Google Scholar]
- 73.Baek JY, Kang CI, Kim SH, Ko KS, Chung DR, Peck KR, Lee NY, Song JH. Emergence of multidrug-resistant clones in levofloxacin-nonsusceptible Streptococcus pneumoniae isolates in Korea. Diagn Microbiol Infect Dis. 2018;91:287–290. doi: 10.1016/j.diagmicrobio.2018.02.010. [DOI] [PubMed] [Google Scholar]
- 74.Choi MJ, Noh JY, Cheong HJ, Kim WJ, Kim MJ, Jang YS, Song JY. Spread of ceftriaxone non-susceptible pneumococci in South Korea: Long-term care facilities as a potential reservoir. PLoS One. 2018 doi: 10.1371/journal.pone.0210520. [In press] [DOI] [PMC free article] [PubMed] [Google Scholar]
- 75.Park M, Kim HS, Kim HS, Park JY, Song W, Cho HC, Kim JS. Novel Levofloxacin-Resistant Multidrug-Resistant Streptococcus pneumoniae Serotype 11A Isolates, South Korea. Emerg Infect Dis. 2016;22:1978–1980. doi: 10.3201/eid2211.151450. [DOI] [PMC free article] [PubMed] [Google Scholar]