0
Original Research: RESPIRATORY INFECTION |

Health-Care–Associated Pneumonia Among Hospitalized Patients in a Japanese Community Hospital FREE TO VIEW

Yuichiro Shindo, MD; Shinji Sato, MD, PhD; Eiichi Maruyama, MD; Takamasa Ohashi, MD, PhD; Masahiro Ogawa, MD; Naozumi Hashimoto, MD, PhD; Kazuyoshi Imaizumi, MD, PhD; Tosiya Sato, PhD; Yoshinori Hasegawa, MD, PhD, FCCP
Author and Funding Information

*From the Department of Respiratory Medicine (Drs. Shindo, Hashimoto, Imaizumi, and Hasegawa), Nagoya University Graduate School of Medicine, Nagoya, Japan; the Department of Respiratory Medicine (Drs. S. Sato, Maruyama, Ohashi, and Ogawa), Handa City Hospital, Aichi, Japan; and the Department of Biostatistics (Dr. T. Sato), Kyoto University School of Public Health, Kyoto, Japan.

Correspondence to: Yuichiro Shindo, MD, Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; e-mail: yshindo@med.nagoya-u.ac.jp


The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

For editorial comment see page 594


Chest. 2009;135(3):633-640. doi:10.1378/chest.08-1357
Text Size: A A A
Published online

Background:  Health-care–associated pneumonia (HCAP) is a relatively new concept. Epidemiologic studies are limited, and initial empirical antibiotic treatment is still under discussion. This study aimed to reveal the differences in mortality and pathogens between HCAP and community-acquired pneumonia (CAP) in each severity class, and to clarify the strategy for the treatment of HCAP.

Methods:  We conducted a retrospective observational study of patients with HCAP and CAP who were hospitalized between November 2005 and January 2007, and compared baseline characteristics, severity, pathogen distribution, antibiotic regimens, and outcomes. In each severity class (mild, moderate, and severe) assessed using the A-DROP scoring system (ie, age, dehydration, respiratory failure, orientation disturbance, and low BP), we investigated the in-hospital mortality and occurrence of potentially drug-resistant (PDR) pathogens.

Results:  A total of 371 patients (141 HCAP patients, 230 CAP patients) were evaluated. The proportion of patients in the severe class was higher in the HCAP patients than in CAP patients. In the moderate class, the in-hospital mortality proportion of HCAP patients was significantly higher than that of CAP patients (11.1% vs 1.9%, respectively; p = 0.008). In moderate-class patients in whom pathogens were identified, PDR pathogens were isolated more frequently from HCAP patients than from CAP patients (22.2% vs 1.9%, respectively; p = 0.002). The occurrence of PDR pathogens was associated with initial treatment failure and inappropriate initial antibiotic treatment.

Conclusions:  The present study provides additional evidence that HCAP should be distinguished from CAP, and suggests that the therapeutic strategy for HCAP in the moderate class holds the key to improving mortality. Physicians may need to consider PDR pathogens in selecting the initial empirical antibiotic treatment of HCAP.

Health-care–associated pneumonia (HCAP) is a relatively new concept and has been documented in the 2005 American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines.1 Previously, HCAP substantially overlapped community-acquired pneumonia (CAP). However, HCAP has been excluded from CAP because the epidemiologic pattern of HCAP is similar to that of hospital-acquired pneumonia (HAP).2 Although a number of studies35 regarding nursing home-acquired pneumonia (NHAP) and pneumonia in residents of long-term care facilities have been published in the past decade, those studies on HCAP, as newly defined by the 2005 ATS/IDSA guidelines,1 are inadequate, and further evidence is required.

For the initial empirical treatment of patients with HCAP, the 2005 ATS/IDSA guidelines1 recommended the administration of broad-spectrum antibiotics. This is the same strategy as that recommended for patients with HAP and ventilator-associated pneumonia, who had risk factors for multidrug-resistant (MDR) pathogens. However, practice guidelines1,611 for NHAP have recommended a different strategy using an antibacterial regimen. The differences are encapsulated in the following questions: (1) should we follow the strategy for CAP or HAP? and (2) should we routinely consider MDR pathogens in determining the empirical treatment? The British Thoracic Society guidelines10,12 have documented that patients with NHAP should be treated as having CAP because there is no difference in the distribution of causative pathogens between patients with NHAP and other older adults with CAP. Carratalà and Garcia-Vidal13 reported that broad-spectrum antibiotic therapy should be administered to patients with HCAP having risk factors for resistant pathogens. Consequently, the selection of antibiotics for the initial empirical treatment of HCAP is still under discussion.

The 2007 IDSA/ATS guidelines2 for CAP recommend empirical antibiotic treatment in each severity class because of the differences in infecting pathogens. On the other hand, the 2005 ATS/IDSA guidelines1 for HAP, ventilator-associated pneumonia, and HCAP recommend considering risk factors for MDR pathogens, not the severity of the patient's disease, in selecting empirical antibiotic agents. However, the differences in mortality and infecting pathogens in each severity class among patients with HCAP have not been clearly demonstrated in previous studies.1416 We consider that a description of mortality and infecting pathogens in each severity class would be useful as a means of outlining the differences between HCAP and CAP. The objective of this study was to determine the differences in baseline characteristics, mortality, and pathogens between HCAP and CAP patients, and to clarify the strategy for the treatment of HCAP. In particular, we focused on in-hospital mortality and identified pathogens in each severity class.

Study Design and Patient Population

We conducted a retrospective observational study of patients with pneumonia hospitalized at Handa City Hospital (a 500-bed community hospital in Handa City, Aichi, Japan) between November 1, 2005, and January 31, 2007. Patients with HAP were excluded. We categorized the study patients into HCAP or CAP groups, and compared baseline characteristics, disease severity, pathogen distribution, antibiotic regimens, and outcomes between the pneumonia groups. We adhered to the Japanese ethical guidelines for epidemiologic studies, and our study protocol was approved by the Institutional Review Boards of Nagoya University Graduate School of Medicine and Handa City Hospital.

Definitions

HCAP and CAP were defined according to ATS/IDSA guidelines.1,2 HCAP included patients with any of the following: (1) hospitalization for ≥ 2 days in the preceding 90 days; (2) residence in a nursing home or extended care facility; (3) home infusion therapy (including antibiotics); (4) long-term dialysis (including hemodialysis and peritoneal dialysis) within 30 days of entering the study; and (5) home wound care. Comorbidities were defined as described previously.17 The outcome measures evaluated were 30-day survival or discharge from the hospital within 30 days, in-hospital mortality, initial treatment failure, and inappropriate initial antibiotic treatment. Initial treatment failure was defined as death during initial treatment or change of therapeutic agents from initial agents to others after 48 h due to clinical instability (eg, lack of response or worsening of fever pattern, respiratory condition, and/or radiographic status; requiring mechanical ventilation; and requiring aggressive fluid resuscitation or vasopressors). Initial antibiotic treatment was classified as being inappropriate if the initially prescribed antibiotics were not active against the identified pathogens based on in vitro susceptibility testing.16 Predicted theoretical susceptibility was applied for atypical pathogens (Mycoplasma pneumoniae, Chlamydophila species, and Legionella species), which were considered to be fully susceptible to therapy with macrolides and fluoroquinolones.18

Microbiological Evaluation

Pathogens in samples obtained from respiratory tracts, blood, and other samples were investigated. These samples were cultured in sheep blood agar, chocolate agar, and potato dextrose agar in a semiquantitative manner. Positive bacterial culture results for respiratory tracts, except the normal flora, are described in the table of microbial identification. Serologic methods using single or paired sera were used to detect antibodies against M pneumoniae and Chlamydophila pneumoniae.19,20Legionella pneumophila serogroup 1 antigen in urine was detected by immunochromatography. The antibiotic sensitivity of microbes was determined using a microdilution panel (MicroScan; Dade Behring Inc; Tokyo, Japan) according to the National Committee for Clinical Laboratory Standards guidelines.21 The results obtained with ciprofloxacin were used to predict results for pazufloxacin because their efficacies were similar.22

In a previous study,23 methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia were reported as potentially drug-resistant (PDR) bacteria. These bacteria were documented as MDR pathogens in the 2005 ATS/IDSA guidelines.1 Moreover, it is problematic that extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (eg, Klebsiella species and Escherichia coli) have been increasing.24 In the present study, MRSA, Pseudomonas species, Acinetobacter species, S maltophilia, and ESBL-producing Enterobacteriaceae were considered as PDR pathogens.

Severity Evaluation

The severity of pneumonia was evaluated using the predictive rule for CAP; that is, the A-DROP (age, dehydration, respiratory failure, orientation disturbance, and low BP) scoring system of the 6-point scoring system proposed by the Japanese Respiratory Society, which is a modified version of the CURB-65 (ie, confusion, BUN > 20 mg/dL, respiratory rate ≥ 30 breaths/min, systolic BP < 90 mm Hg or diastolic BP ≤ 60 mm Hg, and age ≥ 65 years) clinical prediction rule and assesses the following parameters: (1) age (men, ≥ 70 years; women, ≥ 75 years); (2) dehydration (BUN concentration ≥ 21 mg/dL); (3) respiratory failure (pulse oximetric saturation ≤ 90%; PAo2 ≤ 60 mm Hg, or Pao2/fraction of inspired oxygen ratio ≤ 300); (4) orientation disturbance (confusion); and (5) low BP (systolic BP ≤ 90 mm Hg).17,25,26 According to the A-DROP scores, we divided the patients into three severity classes (mild, 0; moderate, 1 or 2; and severe, 3 to 5). The predicted 30-day mortality proportion, which was reported in our recent study,17 was categorized as follows: mild, 0%; moderate, 2.5%; and severe, 23.3%. In each severity class, we described the proportion of in-hospital mortality and occurrence of PDR pathogens for both pneumonia groups.

Statistical Analysis

A statistical software package (SPSS for Windows, version 16.0J; SPSS Inc; Chicago, IL) was used for all statistical comparisons. The α level for significance was < 0.05. Baseline characteristics, the proportion of 30-day survival or hospital discharge within 30 days, the proportion of in-hospital mortality, initial treatment failure, and the occurrence of PDR pathogens were compared between the two groups. The χ2 test was used for analyzing discrete variables, the Wilcoxon test for continuous variables, and the trend test for an ordinal variable. In the analyses to assess the relationship between PDR pathogens and possible risk factors, and that among initial treatment failure, inappropriate initial antibiotic treatment, and PDR pathogens among HCAP patients, we calculated risk ratios and associated 95% confidence intervals (CIs).

Patient Characteristics

A total of 371 patients were evaluated during the study period, comprising 141 patients with HCAP (38.0%) and 230 patients with CAP (62.0%). The backgrounds of the 141 HCAP patients are shown in Table 1, and the baseline characteristics of patients with HCAP and CAP are presented in Table 2.

Table Graphic Jump Location
Table 1 Backgrounds of 141 Patients With HCAP*

*Including overlapping cases.

Table Graphic Jump Location
Table 2 Baseline Characteristics of Patients With HCAP and CAP*

*Data are presented as No. (%) or mean ± SD, unless otherwise indicated. Spo2 = pulse oximetric saturation; Fio2 = fraction of inspired oxygen.

†Values are No. of patients/total No. of patients (%).

‡Respiratory rate was evaluated in 329 of all study patients (88.7%) on arrival at the hospital.

§One patient with Spo2 94% and Fio2 0.28 was included because oxygen status was not confirmed while breathing room air.

‖Arterial blood gas analysis was performed in 314 of the study patients (84.6%) on arrival at the hospital.

¶Lungs were divided artificially into six zones on the radiograph: right and left, upper, middle, and lower zones.

#Of 89 patients, 52 received broad-spectrum antibiotics, which included antipseudomonal penicillins, IV third- or fourth-generation cephalosporins, carbapenems, and fluoroquinolones, on > 2 days within the previous 90 days.

**Probable aspiration was defined as any witnessed aspiration before hospital admission or aspiration confirmed by the fluid-drinking test on hospital admission.

††Patients with poor functional status were defined as being bedridden or those who used a wheelchair and had difficulty walking.

‡‡Trend test.

Pathogen Distribution

The microbes identified in the HCAP and CAP groups are shown in Table 3. Laboratory cultures were obtained from the respiratory tracts of 132 of 141 HCAP patients (93.6%) and 224 of 230 CAP patients (97.4%). The number of sputum samples evaluated for infecting pathogens was 132 of 132 in the HCAP group (100%) and 220 of 224 in the CAP group (98.2%). Streptococcus pneumoniae and S aureus were the most frequently isolated pathogens in both groups. Gram-negative pathogens, streptococci other than S pneumoniae, P aeruginosa, and MRSA were isolated more frequently in HCAP patients than in CAP patients.

Table Graphic Jump Location
Table 3 Microbes Identified in HCAP and CAP Patients*

*Data are presented as No. (%). MSSA = methicillin-sensitive Staphylococcus aureus.

†One suspected case in the HCAP group. One definitive and 12 suspected cases in the CAP group.

Antibiotic Treatment and Clinical Outcomes

Table 4 shows the initial antibiotic treatments and clinical outcomes of patients with HCAP and CAP. HCAP patients received antibiotic monotherapy as the initial treatment more frequently than CAP patients. The proportion of 30-day survival or hospital discharge within 30 days was significantly lower, while the proportion of in-hospital mortality and inappropriate initial antibiotic treatment were significantly higher among HCAP patients than among CAP patients. Although the proportion of initial treatment failure was higher among HCAP patients than among CAP patients, the difference between the two groups was not significant.

Table Graphic Jump Location
Table 4 Antibiotic Treatment and Clinical Outcomes of Patients With HCAP and CAP*

*Values are given as No. (%), unless otherwise indicated.

†We calculated the proportion of hospital discharge within 30 days instead of the 30-day survival in patients who had no medical records indicating that they had died and were discharged from the hospital with improvement of signs and symptoms.

‡Among patients in whom pathogens were identified, we could not evaluate the appropriateness of antibiotic treatment in five patients with HCAP and four patients with CAP.

Mortality and Occurrence of PDR Pathogens According to Severity Classification

Differences in the proportion of in-hospital mortality and occurrence of PDR pathogens in each severity class, as assessed by A-DROP, are presented in Table 5. As shown in Table 2, age distribution differed between the HCAP and CAP groups. The minimum age was 15 years in patients with CAP but 53 years in patients with HCAP. Therefore, we limited our study to patients with CAP aged ≥ 53 years to reduce the effect of age distribution. As a result, 27 patients with CAP, including 1 patient with initial treatment failure, were excluded, and there was no in-hospital death and no occurrence of PDR pathogens among these 27 patients. In addition, we evaluated patients with identified pathogens by comparing the frequency of PDR pathogen occurrence among patients aged ≥ 53 years between the pneumonia groups.

Table Graphic Jump Location
Table 5 In-hospital Mortality and Occurrence of PDR Pathogens in Each Severity Class Assessed by A-DROP (Excluding Patients Aged < 53 yr)*

*Values are given as % (No. of patients/total No. of patients), unless otherwise indicated.

†Twenty-seven patients with CAP who were < 53 years old (minimum age of patients with HCAP) were excluded to reduce the effect of age distribution.

‡Causes of death in the moderate class were as follows: among patients with HCAP, worsening of pneumonia in four patients and relapse of pneumonia in four patients; among patients with CAP, worsening of pneumonia in one patient and pancreatic cancer in another patient. Among the dead patients in whom pathogens were isolated in the moderate class, PDR pathogens were isolated in one of three patients (33.3%) with HCAP and zero of one patient with CAP. Causes of death in the severe class were as follows: among patients with HCAP, worsening of pneumonia in 17 patients and relapse of pneumonia in 5 patients; among patients with CAP, worsening of pneumonia in 7 patients, relapse of pneumonia in 6 patients, and other diseases (myocardial infarction and adult T-cell leukemia) in 2 patients. Among dead patients in whom pathogens were isolated in the severe class, PDR pathogens were isolated in 4 of 13 patients (30.8%) with HCAP and 2 of 12 patients (16.7%) with CAP.

§We evaluated patients in whom pathogens were identified; CAP patients < 53 years old were excluded. HCAP patients, n = 77; CAP patients, n = 101.

First, 141 HCAP patients and 203 CAP patients were evaluated for in-hospital mortality according to severity classification. The in-hospital mortality proportion of HCAP patients was significantly higher than that of CAP patients, especially in the moderate class (11.1% vs 1.9%, respectively; p = 0.008). Although the observed in-hospital mortality proportion was high among patients in the severe class, there was no significant difference between the groups.

Second, 77 HCAP patients and 101 CAP patients were evaluated for the occurrence of PDR pathogens. In the severe class, there was no significant difference in the occurrence of PDR pathogens between HCAP and CAP patients. However, PDR pathogens were more frequently isolated among HCAP patients than among CAP patients in the moderate class (22.2% vs 1.9%, respectively; p = 0.002). The frequency of PDR pathogens was almost the same in the moderate and severe classes of HCAP patients, whereas it was dependent on the severity of pneumonia in CAP patients. The in-hospital mortality proportion among HCAP and CAP patients with PDR pathogens was 12.5% (one of eight patients) and 0% (zero of one patient), respectively, in the moderate class, and 44.4% (four of nine patients) and 40.0% (two of five patients), respectively, in the severe class.

Third, we assessed the roles of initial treatment failure and inappropriate initial antibiotic treatment. The in-hospital mortality proportion among HCAP patients with and without initial treatment failure was 62.9% (22 of 35 patients) and 7.5% (8 of 106 patients), respectively (p < 0.001); that among CAP patients with and without initial treatment failure was 32.5% (13 of 40 patients) and 2.5% (4 of 163 patients), respectively (p < 0.001). The in-hospital mortality proportion among HCAP patients with and without inappropriate initial antibiotic treatment was 33.3% (5 of 15 patients) and 17.5% (10 of 57 patients), respectively (p = 0.180); that among CAP patients with and without inappropriate initial antibiotic treatment was 30.0% (3 of 10 patients) and 11.4% (10 of 88 patients), respectively (p = 0.100). Furthermore, the proportion of initial treatment failure among HCAP patients without PDR pathogens was 16.7% (10 of 60 patients) and that for HCAP patients with PDR pathogens was 70.6% (12 of 17 patients). The proportion of inappropriate initial antibiotic treatment among HCAP patients without PDR pathogens was 5.4% (3 of 56 patients) and that for HCAP patients with PDR pathogens was 75.0% (12 of 16 patients). As described above, HCAP patients with PDR pathogens had a risk ratio of 4.2 (95% CI, 2.2 to 8.1; p < 0.001) with respect to initial treatment failure and 14.0 (95% CI, 4.5 to 43.6; p < 0.001) with respect to inappropriate initial antibiotic treatment.

Risk Factors for Occurrence of PDR Pathogens Among HCAP Patients

Table 6 shows risk ratios of the possible risk factors for the occurrence of PDR pathogens by univariate analyses. Of these factors, the use of broad-spectrum antibiotics on > 2 days within the previous 90 days and tube feeding were significant; the corresponding risk ratios were 3.1 and 2.5.

Table Graphic Jump Location
Table 6 Risk Factors for Occurrence of PDR Pathogens Among HCAP Patients*

*Values are given as No. of patients/total No. of patients (%), unless otherwise indicated. We evaluated 77 patients in whom pathogens were identified.

†Broad-spectrum antibiotics comprised antipseudomonal penicillins, IV third- or fourth-generation cephalosporins, carbapenems, and fluoroquinolones. Details of the antibiotics used were not evaluated in two patients, and these patients were excluded from the study.

This retrospective study has shown differences in baseline characteristics, disease severity, identified pathogens, initial antibiotic regimens, and clinical outcomes between HCAP and CAP patients. We especially focused on differences in mortality and identified pathogens in each severity class between HCAP and CAP patients. We found significant differences in the in-hospital mortality and occurrence of PDR pathogens in the moderate class between HCAP and CAP patients, but not in the severe class.

Previously, a substantial number of HCAP patients were defined as having CAP.2 In order to determine the differences between HCAP and CAP patients, we evaluated the severity of HCAP using the A-DROP scoring system, which has been found to be useful in assessing the severity of CAP.17

We found no significant difference between HCAP and CAP patients in the in-hospital mortality and occurrence of PDR pathogens in the severe class. In contrast, in the moderate class the in-hospital mortality proportion of HCAP patients was significantly higher than that of CAP patients. These results suggest that the therapeutic strategy for the moderate class holds the key to improving mortality in HCAP patients.

In the moderate class, the occurrence of PDR pathogens among HCAP patients was significantly higher than that among CAP patients. Although an association between the occurrence of PDR pathogens and the in-hospital mortality was not found in the present study, the in-hospital mortality proportion among HCAP patients with initial treatment failure was markedly higher than that among CAP patients. Our findings suggest that the initial treatment failure among HCAP patients was more fatal than that among CAP patients, and they indicate that physicians should pay careful attention to the initial treatment of HCAP.

Micek et al16 alerted physicians to the greater likelihood of HCAP patients receiving inappropriate initial antibiotic treatment and their greater risk of in-hospital mortality. Kollef et al27 reported that inadequate antimicrobial treatment of infection was the most important independent determinant of hospital mortality. In addition, Craven28 and Zilberberg et al29 emphasized that the early initiation of appropriate and adequate antibiotic therapy was important for improving the outcomes of patients with HCAP. In the present study, HCAP patients were more likely to receive β-lactam monotherapy or β-lactams in combination with clindamycin than CAP patients. This might reflect the fact that the use of these antibiotics has been accepted in Japan for the initial empirical therapy of patients with aspiration pneumonia and NHAP.8,9,25 As a result, HCAP patients have been receiving inappropriate initial antibiotic treatment more frequently than CAP patients. Furthermore, in-hospital death tended to occur more frequently in patients who received inappropriate initial antibiotic treatment compared with those who received appropriate initial antibiotic treatment. Therefore, HCAP should be identified as a distinct entity in determining the initial empirical antibiotic treatment, as stated in recent reports.30,31

In the present study, PDR pathogens occurred more frequently among HCAP patients than among CAP patients (Table 5). We found that the proportion of initial treatment failure and inappropriate initial antibiotic treatment was markedly higher among HCAP patients with PDR pathogens than among those without. More specifically, HCAP patients with PDR pathogens were 4.2 and 14.0 times as likely, respectively, to have initial treatment failure and inappropriate initial antibiotic treatment than those without PDR pathogens. Therefore, we suggest that physicians should give more consideration to PDR pathogens in choosing the initial empirical antibiotic treatment of HCAP patients to improve their management.

What population among HCAP patients should be targeted for treatment with broad-spectrum antibiotics? As shown in Table 5, the frequency of PDR pathogens was not dependent on the severity of pneumonia in HCAP patients; in this respect, these patients differed from CAP patients. In the analysis of risk factors for the occurrence of PDR pathogens (Table 6), the use of broad-spectrum antibiotics on > 2 days within the previous 90 days and tube feeding were found to be significant risk factors. Therefore, we suggest that HCAP patients with these risk factors for PDR pathogens should be treated with broad-spectrum antibiotics (an antipseudomonal β-lactam plus a fluoroquinolone or an aminoglycoside plus vancomycin or linezolid), as recommended by the 2005 ATS/IDSA guidelines,1 even if the patients are not classified as having a severe disease.

The present study has several limitations. First, the data were retrospectively collected from a single institution. Second, the identified pathogens included oropharyngeal colonizers and were not definite causes of pneumonia since most of the results were obtained from sputum cultures; Gram staining was not performed in some cases; and the cultures were semiquantitative rather than quantitative. However, previous reports11,32,33 have indicated a correlation between oropharyngeal colonization and pathogenesis for most episodes of NHAP or pneumonia occurring > 4 days after intubation. Third, evaluation for atypical pathogens was inadequate because of the small quantity of data.

In summary, we found that in the moderate severity class the in-hospital mortality proportion of HCAP patients was significantly higher than that of CAP patients. Moreover, in the moderate class, PDR pathogens were identified more frequently among HCAP than among CAP patients. On the other hand, in the severe class, there were no significant differences between HCAP and CAP patients in in-hospital mortality and occurrence of PDR pathogens. These results provide additional evidence that HCAP should be distinguished from CAP. Moreover, we showed that the occurrence of PDR pathogens among HCAP patients was associated with a higher proportion of initial treatment failure and inappropriate initial antibiotic treatment. We suggest that the therapeutic strategy for the moderate class holds the key to improving mortality in HCAP patients, and that physicians may need to consider PDR pathogens in choosing the initial empirical antibiotic treatment of HCAP patients in order to improve their management.

A-DROP

age, dehydration, respiratory failure, orientation disturbance, low BP

ATS

American Thoracic Society

CAP

community-acquired pneumonia

CI

confidence interval

ESBL

extended-spectrum β-lactamase

HAP

hospital-acquired pneumonia

HCAP

health-care–associated pneumonia

IDSA

Infectious Diseases Society of America

MDR

multidrug-resistant

MRSA

methicillin-resistant Staphylococcus aureus

NHAP

nursing home- acquired pneumonia

PDR

potentially drug-resistant

We thank Professor Michio Ohta (Department of Molecular Bacteriology, Nagoya University Graduate School of Medicine, Nagoya, Japan) for his comments on the microbiological evaluation.

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. [PubMed] [CrossRef]
 
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44suppl:S27-S72. [PubMed]
 
Muder RR. Pneumonia in residents of long-term care facilities: epidemiology, etiology, management, and prevention. Am J Med. 1998;105:319-330. [PubMed]
 
Marrie TJ. Pneumonia in the long-term-care facility. Infect Control Hosp Epidemiol. 2002;23:159-164. [PubMed]
 
Furman CD, Rayner AV, Tobin EP. Pneumonia in older residents of long-term care facilities. Am Fam Physician. 2004;70:1495-1500. [PubMed]
 
Mandell LA, Marrie TJ, Grossman RF, et al. Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society; the Canadian Community-Acquired Pneumonia Working Group. Clin Infect Dis. 2000;31:383-421. [PubMed]
 
Mandell LA, Bartlett JG, Dowell SF, et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003;37:1405-1433. [PubMed]
 
Committee for the Japanese Respiratory Society Guidelines for the Management of Respiratory Infections. Antibacterial therapy of hospital-acquired pneumonia. Respirology. 2004;9suppl:S16-S24. [PubMed]
 
Committee for the Japanese Respiratory Society Guidelines for the Management of Respiratory Infections. Appendix I: nursing-home acquired pneumonia. Respirology. 2004;9suppl:S51-S55. [PubMed]
 
British Thoracic Society Guidelines for the management of community-acquired pneumonia in adults: 2004 Update.Accessed October 22, 2008 Available at:http://www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/Pneumonia/Guidelines/MACAPrevisedApr04.pdf.
 
Mylotte JM. Nursing home-acquired pneumonia: update on treatment options. Drugs Aging. 2006;23:377-390. [PubMed]
 
Lim WS, Macfarlane JT. A prospective comparison of nursing home acquired pneumonia with community acquired pneumonia. Eur Respir J. 2001;18:362-368. [PubMed]
 
Carratalà J, Garcia-Vidal C. What is healthcare-associated pneumonia and how is it managed? Curr Opin Infect Dis. 2008;21:168-173. [PubMed]
 
Kollef MH, Shorr A, Tabak YP, et al. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest. 2005;128:3854-3862. [PubMed]
 
Carratalà J, Mykietiuk A, Fernandez-Sabe N, et al. Health care-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes. Arch Intern Med. 2007;167:1393-1399. [PubMed]
 
Micek ST, Kollef KE, Reichley RM, et al. Health care-associated pneumonia and community-acquired pneumonia: a single-center experience. Antimicrob Agents Chemother. 2007;51:3568-3573. [PubMed]
 
Shindo Y, Sato S, Maruyama E, et al. Comparison of severity scoring systems A-DROP and CURB-65 for community-acquired pneumonia. Respirology. 2008;13:731-735. [PubMed]
 
Roson B, Carratalà J, Fernandez-Sabe N, et al. Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia. Arch Intern Med. 2004;164:502-508. [PubMed]
 
Ishida T, Hashimoto T, Arita M, et al. Etiology of community-acquired pneumonia in hospitalized patients: a 3-year prospective study in Japan. Chest. 1998;114:1588-1593. [PubMed]
 
Miyashita N, Ouchi K, Kawasaki K, et al. Comparison of serological tests for detection of immunoglobulin M antibodies toChlamydophila pneumoniaeRespirology. 2008;13:427-431. [PubMed]
 
National Committee for Clinical Laboratory Standards Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 2003;6th ed Wayne, PA National Committee for Clinical Laboratory Standards document M7–A6; supplemental tables M100–S13 (M7).
 
Fukuoka Y, Ikeda Y, Yamashiro Y, et al. In vitroandin vivoantibacterial activities of T-3761, a new quinolone derivative. Antimicrob Agents Chemother. 1993;37:384-392. [PubMed]
 
Trouillet JL, Chastre J, Vuagnat A, et al. Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med. 1998;157:531-539. [PubMed]
 
Bradford PA. Extended-spectrum β-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev. 2001;14:933-951. [PubMed]
 
Committee for the Japanese Respiratory Society Guidelines for the Management of Respiratory Infections. The Japanese Respiratory Society guidelines for the management of community-acquired pneumonia in adults. Respirology. 2006;11suppl:S1-S133. [PubMed]
 
Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003;58:377-382. [PubMed]
 
Kollef MH, Sherman G, Ward S, et al. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999;115:462-474. [PubMed]
 
Craven DE. What is healthcare-associated pneumonia, and how should it be treated? Curr Opin Infect Dis. 2006;19:153-160. [PubMed]
 
Zilberberg MD, Shorr AF, Micek ST, et al. Antimicrobial therapy escalation and hospital mortality among patients with HCAP: a single center experience.Accessed on October 22, 2008 Available at:http://www.chestjournal.org/papbyrecent.dtl.
 
Abrahamian FM, Deblieux PM, Emerman CL, et al. Health care-associated pneumonia: identification and initial management in the ED. Am J Emerg Med. 2008;26:1-11. [PubMed]
 
Kollef MH, Morrow LE, Baughman RP, et al. Health care-associated pneumonia (HCAP): a critical appraisal to improve identification, management, and outcomes; proceedings of the HCAP Summit. Clin Infect Dis. 2008;46suppl:S296-S334. [PubMed]
 
Verghese A, Berk SL. Bacterial pneumonia in the elderly. Medicine (Baltimore). 1983;62:271-285. [PubMed]
 
Ewig S, Torres A, El-Ebiary M, et al. Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury: incidence, risk factors, and association with ventilator-associated pneumonia. Am J Respir Crit Care Med. 1999;159:188-198. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1 Backgrounds of 141 Patients With HCAP*

*Including overlapping cases.

Table Graphic Jump Location
Table 2 Baseline Characteristics of Patients With HCAP and CAP*

*Data are presented as No. (%) or mean ± SD, unless otherwise indicated. Spo2 = pulse oximetric saturation; Fio2 = fraction of inspired oxygen.

†Values are No. of patients/total No. of patients (%).

‡Respiratory rate was evaluated in 329 of all study patients (88.7%) on arrival at the hospital.

§One patient with Spo2 94% and Fio2 0.28 was included because oxygen status was not confirmed while breathing room air.

‖Arterial blood gas analysis was performed in 314 of the study patients (84.6%) on arrival at the hospital.

¶Lungs were divided artificially into six zones on the radiograph: right and left, upper, middle, and lower zones.

#Of 89 patients, 52 received broad-spectrum antibiotics, which included antipseudomonal penicillins, IV third- or fourth-generation cephalosporins, carbapenems, and fluoroquinolones, on > 2 days within the previous 90 days.

**Probable aspiration was defined as any witnessed aspiration before hospital admission or aspiration confirmed by the fluid-drinking test on hospital admission.

††Patients with poor functional status were defined as being bedridden or those who used a wheelchair and had difficulty walking.

‡‡Trend test.

Table Graphic Jump Location
Table 3 Microbes Identified in HCAP and CAP Patients*

*Data are presented as No. (%). MSSA = methicillin-sensitive Staphylococcus aureus.

†One suspected case in the HCAP group. One definitive and 12 suspected cases in the CAP group.

Table Graphic Jump Location
Table 4 Antibiotic Treatment and Clinical Outcomes of Patients With HCAP and CAP*

*Values are given as No. (%), unless otherwise indicated.

†We calculated the proportion of hospital discharge within 30 days instead of the 30-day survival in patients who had no medical records indicating that they had died and were discharged from the hospital with improvement of signs and symptoms.

‡Among patients in whom pathogens were identified, we could not evaluate the appropriateness of antibiotic treatment in five patients with HCAP and four patients with CAP.

Table Graphic Jump Location
Table 5 In-hospital Mortality and Occurrence of PDR Pathogens in Each Severity Class Assessed by A-DROP (Excluding Patients Aged < 53 yr)*

*Values are given as % (No. of patients/total No. of patients), unless otherwise indicated.

†Twenty-seven patients with CAP who were < 53 years old (minimum age of patients with HCAP) were excluded to reduce the effect of age distribution.

‡Causes of death in the moderate class were as follows: among patients with HCAP, worsening of pneumonia in four patients and relapse of pneumonia in four patients; among patients with CAP, worsening of pneumonia in one patient and pancreatic cancer in another patient. Among the dead patients in whom pathogens were isolated in the moderate class, PDR pathogens were isolated in one of three patients (33.3%) with HCAP and zero of one patient with CAP. Causes of death in the severe class were as follows: among patients with HCAP, worsening of pneumonia in 17 patients and relapse of pneumonia in 5 patients; among patients with CAP, worsening of pneumonia in 7 patients, relapse of pneumonia in 6 patients, and other diseases (myocardial infarction and adult T-cell leukemia) in 2 patients. Among dead patients in whom pathogens were isolated in the severe class, PDR pathogens were isolated in 4 of 13 patients (30.8%) with HCAP and 2 of 12 patients (16.7%) with CAP.

§We evaluated patients in whom pathogens were identified; CAP patients < 53 years old were excluded. HCAP patients, n = 77; CAP patients, n = 101.

Table Graphic Jump Location
Table 6 Risk Factors for Occurrence of PDR Pathogens Among HCAP Patients*

*Values are given as No. of patients/total No. of patients (%), unless otherwise indicated. We evaluated 77 patients in whom pathogens were identified.

†Broad-spectrum antibiotics comprised antipseudomonal penicillins, IV third- or fourth-generation cephalosporins, carbapenems, and fluoroquinolones. Details of the antibiotics used were not evaluated in two patients, and these patients were excluded from the study.

References

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. [PubMed] [CrossRef]
 
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44suppl:S27-S72. [PubMed]
 
Muder RR. Pneumonia in residents of long-term care facilities: epidemiology, etiology, management, and prevention. Am J Med. 1998;105:319-330. [PubMed]
 
Marrie TJ. Pneumonia in the long-term-care facility. Infect Control Hosp Epidemiol. 2002;23:159-164. [PubMed]
 
Furman CD, Rayner AV, Tobin EP. Pneumonia in older residents of long-term care facilities. Am Fam Physician. 2004;70:1495-1500. [PubMed]
 
Mandell LA, Marrie TJ, Grossman RF, et al. Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society; the Canadian Community-Acquired Pneumonia Working Group. Clin Infect Dis. 2000;31:383-421. [PubMed]
 
Mandell LA, Bartlett JG, Dowell SF, et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003;37:1405-1433. [PubMed]
 
Committee for the Japanese Respiratory Society Guidelines for the Management of Respiratory Infections. Antibacterial therapy of hospital-acquired pneumonia. Respirology. 2004;9suppl:S16-S24. [PubMed]
 
Committee for the Japanese Respiratory Society Guidelines for the Management of Respiratory Infections. Appendix I: nursing-home acquired pneumonia. Respirology. 2004;9suppl:S51-S55. [PubMed]
 
British Thoracic Society Guidelines for the management of community-acquired pneumonia in adults: 2004 Update.Accessed October 22, 2008 Available at:http://www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/Pneumonia/Guidelines/MACAPrevisedApr04.pdf.
 
Mylotte JM. Nursing home-acquired pneumonia: update on treatment options. Drugs Aging. 2006;23:377-390. [PubMed]
 
Lim WS, Macfarlane JT. A prospective comparison of nursing home acquired pneumonia with community acquired pneumonia. Eur Respir J. 2001;18:362-368. [PubMed]
 
Carratalà J, Garcia-Vidal C. What is healthcare-associated pneumonia and how is it managed? Curr Opin Infect Dis. 2008;21:168-173. [PubMed]
 
Kollef MH, Shorr A, Tabak YP, et al. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest. 2005;128:3854-3862. [PubMed]
 
Carratalà J, Mykietiuk A, Fernandez-Sabe N, et al. Health care-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes. Arch Intern Med. 2007;167:1393-1399. [PubMed]
 
Micek ST, Kollef KE, Reichley RM, et al. Health care-associated pneumonia and community-acquired pneumonia: a single-center experience. Antimicrob Agents Chemother. 2007;51:3568-3573. [PubMed]
 
Shindo Y, Sato S, Maruyama E, et al. Comparison of severity scoring systems A-DROP and CURB-65 for community-acquired pneumonia. Respirology. 2008;13:731-735. [PubMed]
 
Roson B, Carratalà J, Fernandez-Sabe N, et al. Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia. Arch Intern Med. 2004;164:502-508. [PubMed]
 
Ishida T, Hashimoto T, Arita M, et al. Etiology of community-acquired pneumonia in hospitalized patients: a 3-year prospective study in Japan. Chest. 1998;114:1588-1593. [PubMed]
 
Miyashita N, Ouchi K, Kawasaki K, et al. Comparison of serological tests for detection of immunoglobulin M antibodies toChlamydophila pneumoniaeRespirology. 2008;13:427-431. [PubMed]
 
National Committee for Clinical Laboratory Standards Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 2003;6th ed Wayne, PA National Committee for Clinical Laboratory Standards document M7–A6; supplemental tables M100–S13 (M7).
 
Fukuoka Y, Ikeda Y, Yamashiro Y, et al. In vitroandin vivoantibacterial activities of T-3761, a new quinolone derivative. Antimicrob Agents Chemother. 1993;37:384-392. [PubMed]
 
Trouillet JL, Chastre J, Vuagnat A, et al. Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med. 1998;157:531-539. [PubMed]
 
Bradford PA. Extended-spectrum β-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev. 2001;14:933-951. [PubMed]
 
Committee for the Japanese Respiratory Society Guidelines for the Management of Respiratory Infections. The Japanese Respiratory Society guidelines for the management of community-acquired pneumonia in adults. Respirology. 2006;11suppl:S1-S133. [PubMed]
 
Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003;58:377-382. [PubMed]
 
Kollef MH, Sherman G, Ward S, et al. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999;115:462-474. [PubMed]
 
Craven DE. What is healthcare-associated pneumonia, and how should it be treated? Curr Opin Infect Dis. 2006;19:153-160. [PubMed]
 
Zilberberg MD, Shorr AF, Micek ST, et al. Antimicrobial therapy escalation and hospital mortality among patients with HCAP: a single center experience.Accessed on October 22, 2008 Available at:http://www.chestjournal.org/papbyrecent.dtl.
 
Abrahamian FM, Deblieux PM, Emerman CL, et al. Health care-associated pneumonia: identification and initial management in the ED. Am J Emerg Med. 2008;26:1-11. [PubMed]
 
Kollef MH, Morrow LE, Baughman RP, et al. Health care-associated pneumonia (HCAP): a critical appraisal to improve identification, management, and outcomes; proceedings of the HCAP Summit. Clin Infect Dis. 2008;46suppl:S296-S334. [PubMed]
 
Verghese A, Berk SL. Bacterial pneumonia in the elderly. Medicine (Baltimore). 1983;62:271-285. [PubMed]
 
Ewig S, Torres A, El-Ebiary M, et al. Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury: incidence, risk factors, and association with ventilator-associated pneumonia. Am J Respir Crit Care Med. 1999;159:188-198. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
Guidelines
Feverish illness in children: assessment and initial management in children younger than 5 years.
National Collaborating Centre for Women's and Children's Health | 8/28/2009
Blepharitis.
American Academy of Ophthalmology | 6/5/2009
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543