Clinical Characteristics of Nursing and Healthcare-Associated Pneumonia: A Japanese Variant of Healthcare-Associated Pneumonia

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1 ORIGINAL ARTICLE Clinical Characteristics of Nursing and Healthcare-Associated Pneumonia: A Japanese Variant of Healthcare-Associated Pneumonia Tadashi Ishida, Hiromasa Tachibana, Akihiro Ito, Hiroshige Yoshioka, Machiko Arita and Toru Hashimoto Abstract Objective The aim of this study was to describe the epidemiology, clinical features, antimicrobial treatment, and outcomes of patients with nursing and healthcare-associated pneumonia (NHCAP); a new category of pneumonia proposed by the Japanese Respiratory Society. Methods We conducted a retrospective analysis of a prospectively collected database of patients with NHCAP and community-acquired pneumonia (CAP) hospitalized at a single center between January 2008 and December 2010, and compared their clinical characteristics. The criteria for NHCAP were as follows: (1) residence in a nursing home or an extended-care ward, (2) a discharge from a hospital in the preceding 90 days, (3) an elderly or handicapped patient who needs long-term care, (4) a patient who regularly requires vascular access in an outpatient setting. Results A total of 442 NHCAP patients and 451 CAP patients were evaluated. The NHCAP patients were older and had a higher frequency of underlying diseases. Aspiration was thought to be associated with the NHCAP in 63% of patients. Streptococcus pneumoniae was the leading pathogen in both groups, whereas the frequency of multidrug-resistant pathogens was higher in the NHCAP patients. The most frequently used antimicrobials in NHCAP patients were penicillins with beta-lactamase inhibitors. The in-hospital mortality and recurrence rates were significantly higher in NHCAP patients than in CAP patients (13.1% vs. 5.1%, p<0.001 and 18.8% vs. 5.5%, p<0.001). Conclusion The clinical picture of NHCAP is consistent with that of HCAP described in the past. It is thought to be of benefit to modify the healthcare-associated pneumonia (HCAP) criteria considering the healthcare and social health insurance system in Japan. Key words: nursing and healthcare-associated pneumonia, community-acquired pneumonia, aspiration, antimicrobials (Intern Med 51: , 2012) () Introduction Pneumonia has traditionally been classified as either community- or hospital-acquired, depending whether the pneumonia developed in an outpatient setting or in an inpatient setting. This classification reflects differences in the pathogens, severities, and outcomes among the two pneumonia categories, and forms the basis for treatment decisions and antimicrobial selections. In 2005, in the joint guidelines proposed by the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA), a new category of pneumonia, healthcare-associated pneumonia (HCAP) was defined (1). The criteria for HCAP were identified as any one of the following; 1) hospitalization for two days or more in the preceding 90 days, 2) residence in a nursing home or extended-care facility, 3) home infusion therapy including antibiotics, 4) chronic dialysis within 30 Department of Respiratory Medicine, Kurashiki Central Hospital, Japan Received for publication April 18, 2012; Accepted for publication June 25, 2012 Correspondence to Dr. Tadashi Ishida, ishidat@kchnet.or.jp 2537

2 Table 1. Criteria for NHCAP according to the JRS 2011 Guidelines (9) Any of the Following Residence in a nursing home or an extended-care ward Discharge from a hospital in the preceding 90 days An elderly or handicapped patient who needs long-term care with an ECOG PS of 3 or 4 A patient who regularly requires vascular access for dialysis, antimicrobial treatment, chemotherapy, or immunosuppressive therapy in an outpatient setting ECOG: Eastern Cooperative Oncology Group (10), PS: performance status days, 5) home wound care, 6) exposure to a family member infected with a multi-drug resistant (MDR) pathogen. The original ATS/IDSA guidelines stated that all patients with HCAP should receive empiric antimicrobials directed at MDR pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. After the ATS/IDSA guidelines were published, many studies from various countries have reported the epidemiology and outcomes of HCAP (2-7). These studies revealed that HCAP was a clinically heterogeneous disease (8), and the populations of patients with HCAP varied among countries depending on the healthcare environment, including the social health insurance system. The Japanese Respiratory Society (JRS) was planning to report HCAP guidelines in Japan in However, during the discussion of these guidelines, the necessity of defining original criteria to adjust the concept of HCAP for Japanese situations became apparent. First, in Japan, extended-care beds exist in community hospitals, and many patients are hospitalized for a long time. Second, since the number of nursing homes per capita is smaller in Japan than in Western countries, many elderly people who are candidates for nursing home placement are cared for by their family members at home. Taking these situations into consideration, the JRS Committee proposed the new term nursing and healthcareassociated pneumonia (NHCAP) and defined the criteria listed in Table 1 in the guidelines for a diagnosis of this disease (9). The aim of this study was to describe the epidemiology, clinical features, antimicrobial treatment, and outcomes of this new category of pneumonia patients. Study population Materials and Methods We conducted a retrospective analysis of a prospectively collected database of adult hospitalized patients with pneumonia at Kurashiki Central Hospital (a 1,150-bed community hospital in Kurashiki City, Okayama, Japan) between January 2008 and December Pneumonia was diagnosed as a disease presenting with new infiltrative shadows on chest X-rays, and symptoms of acute respiratory infection, such as cough, fever, purulent sputum, dyspnea and chest pain. Patients with hospital-acquired pneumonia (HAP) were excluded. The study patients were classified into the following two groups: NHCAP and CAP. The NHCAP patients were defined according to the criteria in the JRS NHCAP guidelines (Table 1) as meeting any one of the following: 1) residence in a nursing home or an extended-care ward, 2) a discharge from a hospital in the preceding 90 days, 3) an elderly or handicapped patient who needs longterm care with an Eastern Cooperative Oncology Group performance status of 3 or 4 (10), 4) a patient who regularly requires vascular access for dialysis, antimicrobial treatment, chemotherapy, or immunosuppressive therapy in an outpatient setting. The patients were classified into the CAP group if they did not meet the criteria for NHCAP. The study was approved by the Kurashiki Central Hospital ethics committee (approval number 363). Data collection Data for the study were obtained from the database of hospitalized patients with pneumonia at the Department of Respiratory Medicine in Kurashiki Central Hospital. The baseline demographic and clinical data in all hospitalized patients with pneumonia were prospectively collected by chest physicians. Data included the patient characteristics (age, sex, comorbid diseases, previously used antimicrobials, and presence of aspiration), vital signs, severity of pneumonia, laboratory data, percutaneous oxygen saturation or arterial blood gases, chest roentgenograms, microbiological examinations, antimicrobials used, and clinical outcomes. The outcome measures evaluated were the 30-day survival or discharge from the hospital within 30 days. Initial treatment failure was defined as death during the initial treatment or a change to other antimicrobials due to a lack of response to the initial ones. Recurrence was defined as the emergence of new pneumonia after remission of the proceeding pneumonia. The length of the hospital stay, length of intravenous therapy, and number of hospital days until the body temperature had decreased to 37.8 (100 F) and remained 37.8 for 16 hours were recorded. The severity of pneumonia was evaluated using the pneumonia severity index (PSI) system (11). Microbiological examination Blood cultures were performed on admission in all patients. If sputum was available, Gram staining and a quantitative culture of sputum were performed. Sputum data were only evaluated when the Gram staining revealed numerous leukocytes (>25 in a 100 microscopic field) and few epithelial cells. An organism exhibiting heavy growth ( 10 7 colony forming units (CFU)/mL) of a predominant bacterium on sputum culture was considered to be a presumptive pathogen. Moderate growth (10 5 or 10 6 CFU/mL) on the sputum culture was also considered as evidence of a presumptive pathogen if the Gram staining revealed a bacterium compatible with the culture results. Streptococcus pneumoniae and Legionella pneumophila serogroup 1 were detected using a rapid immunochromatographic assay, the 2538

3 Table 2. Baseline Characteristics of Patients with NHCAP and CAP Variables NHCAP CAP (n=442) (n=451) p value Age (IQR) 82 (73-89) 76 (67-82) < 0.05 Gender, male 275 (62.2%) 324 (71.8%) < 0.01 Comorbidities Congestive heart failure 187 (42.3%) 111 (24.6%) < Chronic lung disease 153 (34.6%) 156 (34.6%) Chronic liver disease 35 (7.9%) 21 (4.7%) < 0.05 Chronic renal failure 63 (14.3%) 33 (7.3%) < Cerebrovascular disease 192 (43.4%) 78 (17.3%) < Diabetes 91 (20.6%) 95 (21.1%) Neoplastic disease 81 (18.3%) 25 (2.2%) < PSI, median (IQR) 126 ( ) 97 (81-120) < 0.05 Probable aspiration 280 (63.3%) 96 (21.3%) < Previous antibiotic treatment, n (%) 129 (29.2%) 138 (30.6%) IQR: interquartile range, PSI: pneumonia severity index Binax NOW (Binax Inc., Portland, ME, USA). Mycoplasma pneumoniae was detected by culturing sputum samples or pharyngeal swabs in PPLO (pleuropneumonia-like organism) medium and/or by the PA method for measuring serum antibodies. Chlamydophila pneumoniae was detected by antibody measurement by ELISA, singly or in combination. Standard serological methods using single or paired sera were used to determine whether there was elevation of antibodies against M. pneumoniae (a single increase 320 or a four-fold increase in the paired sera) and C. pneumoniae (a single increase up to 3.0 as the cut-off index or a 1.3 cut-off index increase in the paired sera). When plural pathogens satisfied the above criteria in one patient, the pneumonia was defined as polymicrobial. In the present study, MRSA, Pseudomonas aeruginosa and extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae were considered to be MDR pathogens. Aspiration assessment All patients were screened for swallowing function on admission. Trained nurses checked three items as follows: past history of aspiration pneumonia, choking sensation with a wet cough during meals, and the presence of massive fur on the tongue. If at least one item was recognized, the patient was judged to have a risk of aspiration, and consulted a speech-language-hearing therapist (ST). The ST assessed the swallowing function using the water swallowing test, repetitive saliva swallowing test, video endoscopic examination and videofluorography according to the Japan Study Group on Aspiration Pulmonary Disease guidelines (12). Statistical analysis The data were analyzed using the SPSS software program version 18.0 (SPSS Inc., Chicago, IL, USA). The chisquare test was used to compare categorical data, and Fisher s exact test was used when any parameter numbered less than 10. The Mann-Whitney U test was used for comparison of two groups for continuous data. A p value <0.05 was considered to be statistically significant. Patient characteristics Results A total of 442 patients with NHCAP and 451 patients with CAP were evaluated during the study period. The backgrounds of the 442 patients with NHCAP were as follows: 128 patients (29.0%) were residents of a nursing home or those who were hospitalized in extended-care beds, 241 patients (54.5%) were discharged from hospitals in the preceding 90 days, 197 patients (44.6%) were elderly or handicapped individuals who needed care, 51 patients (11.5%) regularly required vascular access in outpatient settings (hemodialysis 27, antimicrobial therapy 4, chemotherapy 15, immunosuppressive therapy 8). Among the 197 patients who needed long-term care, 87 patients (44.2%) were cared for at home. One hundred and thirty-five patients met two or more criteria for a diagnosis of NHCAP. The baseline characteristics of the patients are shown in Table 2. The patients with NHCAP were older, and had a higher frequency of congestive heart failure, chronic liver disease, chronic renal failure, cerebrovascular disease, and neoplastic disease than patients with CAP. In addition, patients with NHCAP had a significantly higher tendency to experience aspiration. Pathogen distribution An etiological diagnosis was made in 173 patients 2539

4 Table 3. Microbiological Results in the Patients with NHCAP and CAP Pathogen NHCAP (n=173) CAP (n=201) Streptococcus pneumoniae 55 (31.8%) 117 (58.2%) Streptococcus anginosus group 7 (4.0%) 5 (2.5%) Streptococcus spp. 10 (5.8%) 0 (0%) MSSA 19 (11.0%) 0 (0%) MRSA 14 (8.1%) 0 (0%) Moraxella catarrhalis 12 (6.9%) 11 (5.5%) Haemophilus influenzae 16 (9.2%) 30 (14.9%) Klebsiella spp. 20 (11.6%) 10 (5.0%) Pseudomonas aeruginosa 23 (13.3%) 6 (3.0%) Escherichia coli 12 (7.5%) 2 (1.0%) Mycoplasma pneumoniae 1 (0.6%) 7 (3.5%) Chlamydophila pneumoniae 9 (5.2%) 21 (10.4%) Legionella spp. 0 (0%) 10 (5.0%) anaerobes 5 (2.9%) 5 (2.5%) viruses 1 (0.6%) 2 (1.0%) other organisms 6 (3.5%) 3 (1.5%) polymicrobial 34 (19.7%) 21 (10.4%) MSSA: methicillin-susceptible Staphylococcus aureus, MRSA: methicillin-resistant Staphylococcus aureus Table 4. Microbiological Results in Patients with NHCAP Classified according to Probable Aspiration Pathogen Aspiration (+) Aspiration (-) (n=100) (n=73) Streptococcus pneumoniae 26 (26.0%) 29 (39.7%) Streptococcus anginosus group 5 (5.0%) 2 (2.7%) Streptococcus spp. 6 (6.0%) 4 (5.5%) MSSA 10 (10.0%) 9 (12.3%) MRSA 13 (13.0%) 1 (1.4%) Moraxella catarrhalis 8 (8.0%) 4 (5.5%) Haemophilus influenzae 7 (7.0%) 9 (12.3%) Klebsiella spp. 14 (14.0%) 6 (6.8%) Pseudomonas aeruginosa 12 (12.0%) 11 (15.1%) Escherichia coli 11 (11.0%) 1 (1.4%) Chlamydophila pneumoniae 6 (6.0%) 3 (4.1%) anaerobes 2 (2.0%) 3 (4.1%) other organisms 0 (0%) 2 (2.7%) polymicrobial 20 (20.0%) 14 (19.2%) MSSA: methicillin-susceptible Staphylococcus aureus, MRSA: methicillin-resistant Staphylococcus aureus (39.1%) with NHCAP compared with 201 patents (44.6%) with CAP. The frequencies of the organisms isolated are shown in Table 3. S. pneumoniae was the most common pathogen in both groups. The frequencies of detection of S. anginosus and other streptococci that are commonly found in the oral cavity were higher in patients with NHCAP. S. aureus, including MRSA, was prevalent in patients with NHCAP, but was not detected in patients with CAP. Klebsiella spp., Escherichia coli, andp. aeruginosa were isolated more frequently in NHCAP patients than in CAP patients. Atypical pathogens such as M. pneumoniae, C. pneumoniae and Legionella spp. were more frequently detected in CAP patients than in NHCAP patients. With regard to MDR pathogens, MRSA and P. aeruginosa were detected in 14 and 23 patients with NHCAP, respectively. An ESBLproducing pathogen was found in only one patient (E.coli). Polymicrobial infection was more commonly observed in NHCAP patients. The predominant combinations of pathogens were S. pneumoniae + S. aureus, 7;S. pneumoniae+ Klebsiella spp., 5; S. pneumoniae + P. aeruginosa, 3; and anaerobe + anaerobe, 3. The microbiological results in the patients with and without probable aspiration are shown in Table 4. MRSA and E. coli were detected significantly more often in patients with probable aspiration. Antimicrobial treatment Table 5 shows the initial antimicrobial treatments for patients with NHCAP and CAP. The patients with NHCAP more frequently received monotherapy as the initial treatment than patients with CAP. The most frequently used antimicrobials in patients with both NHCAP and CAP were 2540

5 Table 5. Initial Antimicrobial Treatment for Patients with NHCAP and CAP Antimicrobials NHCAP (n=442) CAP (n=451) Penicillins 13 (2.9%) 44 (9.8%) Penicillins / beta-lactamase 327 (74.0%) 266 (59.0%) inhibitors Cephalosporins 56 (12.7%) 97 (21.5%) Carbapenems 39 (8.8%) 24 (5.3%) Macrolides 52 (11.8%) 136 (30.2%) Tetracyclines 17 (3.8%) 47 (10.4%) Fluoroquinolones 22 (5.0%) 50 (11.1%) Lincomycins 4 (0.9%) 3 (0.7%) Combination therapy 82 (18.6%) 221 (49.0%) penicillins with beta-lactamase inhibitors (sulbactam/ampicillin in 317 and 263, tazobactam/piperacillin in 12 and 3, respectively). The use of cephalosporins, macrolides, tetracyclines, and fluoroquinolones as the initial regimen was less common in patients with NHCAP than in those with CAP. On the other hand, carbapenems were more frequently used in NHCAP patients. Six of 23 patients in whom P. aeruginosa was detected, and 5 of 14 patients in whom MRSA was detected, were cured without using anti-pseudomonas and anti-mrsa antimicrobials. Clinical outcomes Table 6 shows the clinical outcomes of patients with NHCAP and CAP. The in-hospital mortality in patients with NHCAP was 13.1%, which was significantly higher than that in patients with CAP (5.1%, p<0.001). The in-hospital mortality and the predominant pathogens based on each criteria of NHCAP are indicated in Table 7. The incidences of initial treatment failure, recurrence within 30 days after remission of pneumonia, and readmission within 30 days were also higher in patients with NHCAP. In the 64 patients with initial treatment failure, the predominant pathogens were as follows: S. pneumoniae, 7; Klebsiella spp., 5; P. aeruginosa, 5; E. coli, 4;andS. aureus, 4. The length of the hospital stay and intravenous therapy were significantly longer in NHCAP patients. Nevertheless, the rate of admission to the ICU was lower in patients with NHCAP than in patients with CAP, although the difference was not significant. Discussion NHCAP is a new category of pneumonia that the JRS has defined in its guidelines. Thus, there have only been a few reports describing the clinical characteristics of NHCAP. The corresponding author (T.I.) attended the meeting of the writing committee for the NHCAP guidelines. The biggest issue discussed by the guideline writing committee was the differences in the healthcare and social health insurance systems between Japan and Western countries, especially the United States. In Japan, general hospitals have extended-care wards, and patients tend to stay longer in hospitals than in Western countries (13). Since the number of nursing homes is insufficient for those who need nursing care, many patients who should be cared for in nursing homes stay in their own homes and receive care from their family members, visiting nurses and/or caregivers. As a measure of the aging society, the Japanese government established the nursing insurance system in 2000, and criteria for certification of those in need of long-term care. According to the data of the Ministry of Health, Labor and Welfare of Japan (14), a total of 3,494,000 individuals have been certified as individuals who require nursing care as of July 2011, and 2,634,000 of them (75.4%) are staying in their homes. Most of them regularly visit clinics or hospitals or are visited by healthcare professionals. Although cases of pneumonia developing in individuals receiving nursing care at home have been dealt with as CAP, our survey of bedridden patients at home who contracted pneumonia (15) has revealed significant similarities in terms of the patient characteristics, causative organisms, and clinical course of pneumonia, between them and patients with HCAP. It thus appears that we should include cases of pneumonia among individuals receiving nursing care in their homes as a separate category to better cover the concept of HCAP. For this reason, a separate definition for NHCAP was developed. The present survey indicated that NHCAP was common, and the number of patients hospitalized for NHCAP was almost identical to that of patients hospitalized with CAP. Of the patients classified into the NHCAP group in this survey, 24.3% would have been classified as having CAP according to conventional criteria. However, the patients with NHCAP were older and had underlying diseases more frequently than those with CAP. In addition, the patients with NHCAP had more severe pneumonia, higher in-hospital mortality rates, higher incidences of initial treatment failure, recurrence of pneumonia, and a longer duration of hospitalization compared with patients with CAP. Although severe pneumonia was more common among patients with NHCAP, the ICU admission rate did not differ significantly between NHCAP and CAP patients. This finding may represent treatment biases, in which attending physicians, patients and their family members tend to avoid intensive treatment such as artificial ventilation because of the social background of NHCAP patients. A similar tendency has been reported in patients with HCAP (16). Even if the same criteria are used, the clinical picture of HCAP differs significantly between countries with different healthcare and medical insurance systems. For example, the etiology and mortality of HCAP patients in Spain are similar to those of CAP patients (3), while those in the United States are similar to those of patients with HAP (2, 17), and those in Japan (5) appear to fall between the cases in Spain and the United States. It is known that HCAP is a heterogeneous disease with a broad clinical spectrum (8, 18, 19). We believe that the definition of HCAP should be appropriately 2541

6 Table 6. Clinical Outcomes in the Patients with NHCAP and CAP NHCAP CAP Variables p value (n=442) (n=451) ICU admission, n (%) 19 (4.3%) 31 (6.9%) Initial treatment failure* 1, n (%) 64 (14.5%) 43 (9.5%) < 0.05 Recurrence* 2, n (%) 83(18.8%) 25 (5.5%) < In-hospital mortality, n (%) 58 (13.1%) 23 (5.1%) < Readmission within 30 days, n (%) 57 (12.9%) 17 (3.8%) < Length of hospital stay, median (IQR) 15 (9-26) 10 (7-16) < Length of intravenous therapy, median (IQR) 9 (6-13) 7 (5-9) < Days to defervescence ( 37.8 C) * 3, median (IQR) 2 (2-3) 2 (2-3) ICU: intensive care unit, IQR: interquartile range * 1 Death during initial treatment or change to other antimicrobials for reason of lack of response to initial ones. * 2 Recurrence within 30 days, after remission of pneumonia. * 3 Number of hospital days until the body temperature had decreased to 37.8 C (100 F) and remained 7.8 C for 16 hours. Table 7. Mortality and Pathogens in Each Criteria of NHCAP Residence in Discharge in the Patients with Patients requiring a nursing home preceding 90 days PS 3 or 4 vascular access n In Hospital Mortality, n (%) 17 (13.3) 25 (10.4) 31 (12.9) 8 (15.7) Pathogen (n) 1st S. pneumoniae (19) S. pneumoniae (31) S. pneumoniae (30) S. pneumoniae (4) 2nd P. aeruginosa (7) P. aeruginosa (14) P. aeruginosa (12) C. pneumoniae (4) 3rd K. pneumoniae (6) MSSA (12) K. pneumoniae (10) P. aeruginosa (2) 4th H.influenzae (5) K. pneumoniae (8) H.influenzae (8) H.influenzae (2) 5th Streptococcus spp. (5) M. catarrhalis (8) Streptococcus spp. (8) K. pneumoniae (2) 6th MRSA (4) H.iIfluenzae (7) E.coli (7) E.coli (1) 7th E.coli (4) MRSA (7) MSSA (7) MSSA (1) Polymicrobial Unknown 62.5% 60.6% 60.4% 66.7% MSSA: methicillin-susceptible Staphylococcus aureus, MRSA: methicillin-resistant Staphylococcus aureus modified according to the social circumstances and healthcare environment of the country where it will be used. An outstanding feature of the patients with NHCAP in the present study was the frequency of aspiration. In the present survey, aspiration was suspected in 63% of the patients with NHCAP. This finding is consistent with a report on HCAP where aspiration was suspected to be involved in the development of disease in many patients (19-21). We screened all hospitalized patients for swallowing function, and found that patients with NHCAP, especially those with a poor performance status, had a significantly higher risk of aspiration than patients with CAP. The longer duration of hospitalization among NHCAP patients is largely explained by the necessity of swallowing training and assessment for nutritional treatment in patients who are at risk of aspiration, in addition to the antimicrobial treatment for pneumonia. The etiological factors in the present survey were similar to those in published reports on HCAP (2-7, 16). S. pneumoniae was the most common pathogen, and streptococci normally found in the oral cavity, Gram-negative rods, and MRSA were more frequently observed in the NHCAP patients than in the CAP patients. The higher prevalence of streptococcal infection and polymicrobial infection further suggest the involvement of aspiration in the development of NHCAP. Based on the reports of HCAP in Japan by Shindo and colleagues (5), the patient characteristics and pathogens in NHCAP were similar to those in HCAP patients. However, the rates of initial treatment failure and in-hospital mortality in Shindo s study were significantly higher than those in our study. This is thought to be due to differences in the patient populations. In Shindo s study, most of the patients were 2542

7 residents in nursing homes or extended-care facilities, whereas in our study, patients with recent hospitalization were the largest population. In this survey, we encountered a substantial number of patients in whom microbiologically meaningful amounts of P. aeruginosa and MRSA were detected, but who improved clinically without antimicrobial treatment against P. aeruginosa and MRSA. Since the pathogens causing pneumonia may have been replaced by other bacteria, it is advised that the pneumonia s actual causal organism should be confirmed. Cultures may detect meaningful amounts of bacterial colonization in the airway in patients with NHCAP who often have many other underlying diseases; therefore, we should carefully consider whether the detected bacteria are the true cause of the pneumonia (22-24). Further studies should be performed regarding this possibility. This is supported by the fact that a report has described that the prognosis was poor in HAP and HCAP patients with risk factors for infection with multi-resistant strains who received antimicrobial agents sufficiently covering drug-resistant strains according to the ATS/IDSA guidelines (25). We have treated patients with pneumonia empirically without using strict criteria for selection of antimicrobial agents. Patients with NHCAP were often treated with penicillins with beta-lactamase inhibitors, because physicians try to cover range of potential pathogens that can lead to aspiration pneumonia. Combination therapy was less common among patients with NHCAP, which suggests that physicians did not try to cover atypical pathogens in many cases. Although the ATS/IDSA guidelines recommend that patients with HCAP be treated with antimicrobial agents covering drug-resistant strains, because all patients with HCAP have a risk for infection with drug-resistant strains, studies have reported that treatment according to these guidelines does not improve the survival in this patient population (24, 25). Our data also indicated that monotherapy is sufficiently effective for patients with mild or moderate pneumonia. In conclusion, the clinical picture of NHCAP delineated in this survey was largely consistent with that of HCAP described in the past. Since HCAP is a disease category significantly affected by the healthcare and social insurance system of each country, we believe it is of significance that we created NHCAP as a variant of HCAP in Japan. However, there might be controversy about whether pneumonia in patients who are bedridden at home should be included under the category of HCAP or not. Placing cases of pneumonia occurring in institutions and those at home into the same category may be inappropriate, since the etiology and outcome of pneumonia depend not only on the characteristics of the patients, but also the surrounding environment. Our study is limited because it was a retrospective study in a single institution. Further prospective multi-center examinations should be conducted to perform sub-analyses of the different categories of NHCAP and assess the validity of the categorization. Author s disclosure of potential Conflicts of Interest (COI). Ishida T: Honoraria, Abott, Taisyo-Toyama and Daiichi-Sankyo. Acknowledgement Author contributions: Dr. Ishida: contributed to the study conception and design, analysis and interpretation of data, and preparation and revision of the manuscript. Dr. Tachibana: contributed to the study conception and design, and acquisition and tabulation of data. 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