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Health-CareAssociated PneumoniaAmong Hospitalized Patients in aJapanese Community Hospital*

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; and Yoshinori Hasegawa, MD, PhD, FCCP

Background: Health-careassociated pneumonia (HCAP) is a relatively new concept. Epidemio-logic studies are limited, and initial empirical antibiotic treatment is still under discussion. Thisstudy 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 ofHCAP.Methods: We conducted a retrospective observational study of patients with HCAP and CAP whowere hospitalized between November 2005 and January 2007, and compared baseline charac-teristics, 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 mortal-ity and occurrence of potentially drug-resistant (PDR) pathogens.Results: A total of 371 patients (141 HCAP patients, 230 CAP patients) were evaluated. Theproportion of patients in the severe class was higher in the HCAP patients than in CAP patients. Inthe moderate class, the in-hospital mortality proportion of HCAP patients was significantly higherthan 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 patientsthan 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 fromCAP, and suggests that the therapeutic strategy for HCAP in the moderate class holds the key toimproving mortality. Physicians may need to consider PDR pathogens in selecting the initial empiricalantibiotic treatment of HCAP. (CHEST 2009; 135:633640)

Key words: antibiotics; drug resistance; mortality; pathogens; severity

Abbreviations: A-DROP age, dehydration, respiratory failure, orientation disturbance, low BP; ATS American ThoracicSociety; CAP community-acquired pneumonia; CI confidence interval; ESBL extended-spectrum -lactamase;HAP hospital-acquired pneumonia; HCAP health-careassociated pneumonia; IDSA Infectious Diseases Society ofAmerica; MDRmultidrug-resistant; MRSAmethicillin-resistant Staphylococcus aureus; NHAP nursing home-acquired pneumonia; PDR potentially drug-resistant

Health-careassociated pneumonia (HCAP) is arelatively new concept and has been docu-

mented in the 2005 American Thoracic Society(ATS)/Infectious Diseases Society of America(IDSA) guidelines.1 Previously, HCAP substantiallyoverlapped community-acquired pneumonia (CAP).However, HCAP has been excluded from CAPbecause the epidemiologic pattern of HCAP is sim-

ilar to that of hospital-acquired pneumonia (HAP).2

Although a number of studies35 regarding nursinghome-acquired pneumonia (NHAP) and pneumoniain residents of long-term care facilities have beenpublished in the past decade, those studies onHCAP, as newly defined by the 2005 ATS/IDSAguidelines,1 are inadequate, and further evidence isrequired.

CHEST Original ResearchRESPIRATORY INFECTION

www.chestjournal.org CHEST / 135 / 3 / MARCH, 2009 633

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For the initial empirical treatment of patientswith HCAP, the 2005 ATS/IDSA guidelines1 rec-ommended the administration of broad-spectrumantibiotics. This is the same strategy as that rec-ommended for patients with HAP and ventilator-associated pneumonia, who had risk factors for

For editorial comment see page 594

multidrug-resistant (MDR) pathogens. However,practice guidelines1,611 for NHAP have recom-mended a different strategy using an antibacterialregimen. The differences are encapsulated in thefollowing questions: (1) should we follow the strategyfor CAP or HAP? and (2) should we routinely considerMDR pathogens in determining the empirical treat-ment? The British Thoracic Society guidelines10,12

have documented that patients with NHAP shouldbe treated as having CAP because there is nodifference in the distribution of causative pathogensbetween patients with NHAP and other older adults

with CAP. Carratala and Garcia-Vidal13 reportedthat broad-spectrum antibiotic therapy should beadministered to patients with HCAP having riskfactors for resistant pathogens. Consequently, theselection of antibiotics for the initial empirical treat-ment of HCAP is still under discussion.

The 2007 IDSA/ATS guidelines2 for CAP recom-mend empirical antibiotic treatment in each severityclass because of the differences in infecting patho-gens. On the other hand, the 2005 ATS/IDSA guide-lines1 for HAP, ventilator-associated pneumonia, andHCAP recommend considering risk factors for MDR

pathogens, not the severity of the patients disease, inselecting empirical antibiotic agents. However, thedifferences in mortality and infecting pathogens ineach severity class among patients with HCAP havenot been clearly demonstrated in previous studies.1416

We consider that a description of mortality and infect-ing pathogens in each severity class would be useful asa means of outlining the differences between HCAP

and CAP. The objective of this study was to determinethe differences in baseline characteristics, mortality,and pathogens between HCAP and CAP patients, andto clarify the strategy for the treatment of HCAP. Inparticular, we focused on in-hospital mortality andidentified pathogens in each severity class.

Materials and Methods

Study Design and Patient Population

We conducted a retrospective observational study of patientswith pneumonia hospitalized at Handa City Hospital (a 500-bedcommunity hospital in Handa City, Aichi, Japan) between No-

vember 1, 2005, and January 31, 2007. Patients with HAP wereexcluded. We categorized the study patients into HCAP or CAPgroups, and compared baseline characteristics, disease severity,pathogen distribution, antibiotic regimens, and outcomes be-tween the pneumonia groups. We adhered to the Japaneseethical guidelines for epidemiologic studies, and our study pro-tocol was approved by the Institutional Review Boards of NagoyaUniversity Graduate School of Medicine and Handa City Hospital.

Definitions

HCAP and CAP were defined according to ATS/IDSA guide-lines.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) homeinfusion therapy (including antibiotics); (4) long-term dialysis(including hemodialysis and peritoneal dialysis) within 30 days ofentering the study; and (5) home wound care. Comorbidities

were defined as described previously.17 The outcome measuresevaluated were 30-day survival or discharge from the hospital within30 days, in-hospital mortality, initial treatment failure, and inappro-priate initial antibiotic treatment. Initial treatment failure was de-fined as death during initial treatment or change of therapeuticagents from initial agents to others after 48 h due to clinicalinstability (eg, lack of response or worsening of fever pattern,respiratory condition, and/or radiographic status; requiring mechan-ical ventilation; and requiring aggressive fluid resuscitation or vaso-pressors). Initial antibiotic treatment was classified as being inappro-priate if the initially prescribed antibiotics were not active against theidentified pathogens based on in vitro susceptibility testing.16 Pre-dicted theoretical susceptibility was applied for atypical pathogens(Mycoplasma pneumoniae, Chlamydophila species, and Legionellaspecies), 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 cul-tured in sheep blood agar, chocolate agar, and potato dextroseagar in a semiquantitative manner. Positive bacterial cultureresults for respiratory tracts, except the normal flora, are de-scribed in the table of microbial identification. Serologic methodsusing single or paired sera were used to detect antibodies againstM pneumoniae and Chlamydophila pneumoniae.19,20 Legionella

pneumophila serogroup 1 antigen in urine was detected byimmunochromatography. The antibiotic sensitivity of microbes

was determined using a microdilution panel (MicroScan; DadeBehring Inc; Tokyo, Japan) according to the National Committee

*From the Department of Respiratory Medicine (Drs. Shindo,Hashimoto, Imaizumi, and Hasegawa), Nagoya University Grad-uate School of Medicine, Nagoya, Japan; the Department ofRespiratory Medicine (Drs. S. Sato, Maruyama, Ohashi, and

Ogawa), Handa City Hospital, Aichi, Japan; and the Departmentof Biostatistics (Dr. T. Sato), Kyoto University School of PublicHealth, Kyoto, Japan.The authors have reported to the ACCP that no significantconflicts of interest exist with any companies/organizations whoseproducts or services may be discussed in this article.Manuscript received June 8, 2008; revision accepted October 2,2008.Reproduction of this article is prohibited without written permissionfrom the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).Correspondence to: Yuichiro Shindo, MD, Department of Respi-ratory Medicine, Nagoya University Graduate School of Medi-cine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan;e-mail: [email protected]: 10.1378/chest.08-1357

634 Original Research



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for Clinical Laboratory Standards guidelines.21 The results ob-tained with ciprofloxacin were used to predict results for pazu-floxacin because their efficacies were similar.22

In a previous study,23 methicillin-resistant Staphylococcusaureus (MRSA), Pseudomonas aeruginosa, Acinetobacter bau-

mannii, and Stenotrophomonas maltophilia were reported aspotentially drug-resistant (PDR) bacteria. These bacteria weredocumented as MDR pathogens in the 2005 ATS/IDSAguidelines.1 Moreover, it is problematic that extended-spectrum

-lactamase (ESBL)-producing Enterobacteriaceae (eg, Kleb-siella species and Escherichia coli) have been increasing.24 In thepresent study, MRSA, Pseudomonas species, Acinetobacter spe-cies, S maltophilia, and ESBL-producing Enterobacteriaceae

were considered as PDR pathogens.

Severity Evaluation

The severity of pneumonia was evaluated using the predictiverule for CAP; that is, the A-DROP (age, dehydration, respiratoryfailure, orientation disturbance, and low BP) scoring system ofthe 6-point scoring system proposed by the Japanese RespiratorySociety, 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 followingparameters: (1) age (men, 70 years; women, 75 years); (2)dehydration (BUN concentration 21 mg/dL); (3) respiratoryfailure (pulse oximetric saturation 90%; PAo2 60 mm Hg, orPao2/fraction of inspired oxygen ratio 300); (4) orientationdisturbance (confusion); and (5) low BP (systolic BP 90 mmHg).17,25,26 According to the A-DROP scores, we divided thepatients into three severity classes (mild, 0; moderate, 1 or 2; andsevere, 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 severityclass, we described the proportion of in-hospital mortality andoccurrence of PDR pathogens for both pneumonia groups.

Statistical Analysis

A statistical software package (SPSS for Windows, version16.0J; SPSS Inc; Chicago, IL) was used for all statisticalcomparisons. The level for significance was 0.05. Baselinecharacteristics, the proportion of 30-day survival or hospitaldischarge within 30 days, the proportion of in-hospital mor-tality, initial treatment failure, and the occurrence of PDRpathogens were compared between the two groups. The 2

test was used for analyzing discrete variables, the Wilcoxontest for continuous variables, and the trend test for an ordinal

variable. In the analyses to assess the relationship betweenPDR pathogens and possible risk factors, and that amonginitial treatment failure, inappropriate initial antibiotic treat-

ment, and PDR pathogens among HCAP patients, we calcu-lated risk ratios and associated 95% confidence intervals (CIs).

Results

Patient Characteristics

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

Pathogen Distribution

The microbes identified in the HCAP and CAPgroups are shown in Table 3. Laboratory cultureswere obtained from the respiratory tracts of 132 of141 HCAP patients (93.6%) and 224 of 230 CAPpatients (97.4%). The number of sputum samplesevaluated for infecting pathogens was 132 of 132 inthe HCAP group (100%) and 220 of 224 in the CAP

group (98.2%). Streptococcus pneumoniae and Saureus were the most frequently isolated pathogensin both groups. Gram-negative pathogens, strepto-cocci other than S pneumoniae, P aeruginosa, andMRSA were isolated more frequently in HCAPpatients than in CAP patients.

Antibiotic Treatment and Clinical Outcomes

Table 4 shows the initial antibiotic treatments andclinical outcomes of patients with HCAP and CAP.HCAP patients received antibiotic monotherapy as

the initial treatment more frequently than CAPpatients. The proportion of 30-day survival or hospi-tal discharge within 30 days was significantly lower,while the proportion of in-hospital mortality andinappropriate initial antibiotic treatment were signif-icantly higher among HCAP patients than amongCAP patients. Although the proportion of initialtreatment failure was higher among HCAP patientsthan among CAP patients, the difference betweenthe two groups was not significant.

Mortality and Occurrence of PDR Pathogens

According to Severity ClassificationDifferences in the proportion of in-hospital mor-

tality and occurrence of PDR pathogens in eachseverity class, as assessed by A-DROP, are presentedin Table 5. As shown in Table 2, age distributiondiffered between the HCAP and CAP groups. Theminimum age was 15 years in patients with CAP but53 years in patients with HCAP. Therefore, we limitedour study to patients with CAP aged 53 years toreduce the effect of age distribution. As a result, 27patients with CAP, including 1 patient with initialtreatment failure, were excluded, and there was no

Table 1Backgrounds of 141 Patients With HCAP*

Backgrounds No. (%)

Hospitalization for 2 d in the preceding 90 d 55 (39.0)Residence in a nursing home or extended care

facility86 (61.0)

Home infusion therapy (including antibiotics) 23 (16.3)Long-term dialysis within 30 d 10 (7.1)Home wound care 3 (2.1)

*Including overlapping cases.




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in-hospital death and no occurrence of PDR pathogensamong these 27 patients. In addition, we evaluatedpatients with identified pathogens by comparing thefrequency of PDR pathogen occurrence among pa-tients aged 53 years between the pneumonia groups.

First, 141 HCAP patients and 203 CAP patientswere evaluated for in-hospital mortality according toseverity classification. The in-hospital mortality propor-

tion of HCAP patients was significantly higher than thatof CAP patients, especially in the moderate class(11.1% vs 1.9%, respectively; p 0.008). Although theobserved in-hospital mortality proportion was highamong patients in the severe class, there was nosignificant difference between the groups.

Second, 77 HCAP patients and 101 CAP patientswere evaluated for the occurrence of PDR patho-

Table 2Baseline Characteristics of Patients With HCAP and CAP*

Variables HCAP Patients (n 141) CAP Patients (n 230) p Value

Male gender 78 (55.3) 145 (63.0) 0.140Age, yr 81.3 9.8 69.7 16.9 0.001

Age 65 yr 131 (92.9) 167 (72.6) 0.001Male 70 yr 63/78 (80.8) 85/145 (58.6) 0.001Female 75 yr 60/63 (95.2) 42/85 (49.4) 0.001

Comorbidities

Neoplastic disease 20 (14.2) 34 (14.8) 0.874Chronic lung disease 38 (27.0) 82 (35.7) 0.082Congestive heart failure 22 (15.6) 21 (9.1) 0.059Chronic renal disease 14 (9.9) 5 (2.2) 0.001Chronic liver disease 0 (0) 8 (3.5) 0.025Central nervous system disorder 59 (41.8) 46 (20.0) 0.001Diabetes 25 (17.7) 40 (17.4) 0.934Immunosuppression 13 (9.2) 17 (7.4) 0.531Two or more comorbidities 54 (38.3) 72 (31.3) 0.167

Clinical parametersOrientation disturbance (confusion) 60 (42.6) 32 (13.9) 0.001Systolic BP 90 mm Hg or diastolic BP 60 mm Hg 43 (30.5) 66 (28.7) 0.712Pulse rate 125 beats/min 14 (9.9) 23 (10.0) 0.982Respiratory rate 30 breaths/min 42 (32.3) 41 (20.6) 0.017

Spo2

90%, Pao2

60 mm Hg, or Pao2/F

io2

300 85 (60.3) 106 (46.1) 0.008Laboratory findingsBUN 21 mg/dL 69 (48.9) 73 (31.7) 0.001pH 7.35 18 (14.9) 10 (5.2) 0.003Na 130 mmol/L 12 (8.5) 8 (3.5) 0.037Glucose 250 mg/dL 7 (5.0) 12 (5.2) 0.915Hematocrit 30% 22 (15.6) 15 (6.5) 0.005

Radiographic findingsBilateral lung involvement 41 (29.1) 64 (27.8) 0.795Involvement of two or more zones 59 (41.8) 80 (34.8) 0.173Pleural effusion 22 (15.6) 27 (11.7) 0.286

Use of antibiotics within the previous 90 d 89# (63.1) 48 (20.9) 0.001Probable aspiration** 82 (58.2) 42 (18.3) 0.001Tube feeding 14 (9.9) 1 (0.4) 0.001Poor functional status 81 (57.4) 25 (10.9) 0.001

A-DROP severity class 0.001Mild (score, 0) 4 (2.8) 60 (26.1)Moderate (score, 1 or 2) 72 (51.1) 116 (50.4)Severe (score, 35) 65 (46.1) 54 (23.5)

*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 cephalo-

sporins, 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.




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gens. In the severe class, there was no significantdifference in the occurrence of PDR pathogensbetween HCAP and CAP patients. However, PDRpathogens were more frequently isolated amongHCAP patients than among CAP patients in themoderate class (22.2% vs 1.9%, respectively;p 0.002). The frequency of PDR pathogens was

almost the same in the moderate and severe classesof HCAP patients, whereas it was dependent on theseverity of pneumonia in CAP patients. The in-hospital mortality proportion among HCAP and CAPpatients with PDR pathogens was 12.5% (one ofeight patients) and 0% (zero of one patient), respec-tively, in the moderate class, and 44.4% (four of ninepatients) and 40.0% (two of five patients), respec-tively, in the severe class.

Third, we assessed the roles of initial treatmentfailure and inappropriate initial antibiotic treatment.The in-hospital mortality proportion among HCAP

patients with and without initial treatment failurewas 62.9% (22 of 35 patients) and 7.5% (8 of 106patients), respectively (p 0.001); that among CAPpatients with and without initial treatment failurewas 32.5% (13 of 40 patients) and 2.5% (4 of 163patients), respectively (p 0.001). The in-hospitalmortality proportion among HCAP patients with andwithout inappropriate initial antibiotic treatment was33.3% (5 of 15 patients) and 17.5% (10 of 57patients), respectively (p 0.180); that among CAPpatients with and without inappropriate initial anti-

biotic treatment was 30.0% (3 of 10 patients) and11.4% (10 of 88 patients), respectively (p 0.100).Furthermore, the proportion of initial treatmentfailure among HCAP patients without PDR patho-gens was 16.7% (10 of 60 patients) and that forHCAP patients with PDR pathogens was 70.6% (12of 17 patients). The proportion of inappropriateinitial antibiotic treatment among HCAP patientswithout PDR pathogens was 5.4% (3 of 56 patients)and that for HCAP patients with PDR pathogens was75.0% (12 of 16 patients). As described above,HCAP patients with PDR pathogens had a risk ratio

Table 4Antibiotic Treatment and Clinical Outcomesof Patients With HCAP and CAP*

Therapy and OutcomesHCAP Patients

(n 141)CAP Patients

(n 230) p Value

Initial antibiotic treatmentMonotherapy 60 (42.6) 23 (10.0)-Lactams 56 (39.7) 23 (10.0)Quinolones 3 (2.1) 0 (0)

Other 1 (0.7) 0 (0)Combination therapy 81 (57.4) 207 (90.0)-Lactams

quinolones10 (7.1) 7 (3.0)

-Lactams aminoglycosides

5 (3.5) 0 (0)

-Lactams macrolides

29 (20.6) 186 (80.9)

-Lactams clindamycin

35 (24.8) 13 (5.7)

Other combinations 2 (1.4) 1 (0.4)30-d survival or hospital

discharge within30 d

119 (84.4) 219 (95.2) 0.001

In-hospital mortality 30 (21.3) 17 (7.4) 0.001Initial treatment failure 35 (24.8) 41 (17.8) 0.105Inappropriate initial

antibiotictreatment

15/72 (20.8) 10/103 (9.7) 0.038

*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 medicalrecords indicating that they had died and were discharged fromthe hospital with improvement of signs and symptoms.

Among patients in whom pathogens were identified, we could notevaluate the appropriateness of antibiotic treatment in five patientswith HCAP and four patients with CAP.

Table 3Microbes Identified in HCAP and CAP Patients*

Microbes

HCAPPatients

(n 141)

CAPPatients

(n 230)

Gram-negativepathogens

34 (24.1) 30 (13.0)

Klebsiella species 10 (7.1) 4 (1.7)ESBLs 0 (0) 0 (0)

Pseudomonas species 8 (5.7) 4 (1.7)E coli 5 (3.5) 1 (0.4)

ESBLs 1 (0.7) 0 (0)Haemophilus

influenzae4 (2.8) 17 (7.4)

Proteus mirabilis 4 (2.8) 1 (0.4)Acinetobacter species 3 (2.1) 0 (0)S maltophilia 0 (0) 0 (0)Other Gram-negative

bacteria4 (2.8) 3 (1.3)

Gram-positivepathogens

44 (31.2) 72 (31.3)

S pneumoniae 19 (13.5) 44 (19.1)S aureus 14 (9.9) 14 (6.1)

MSSA 9 (6.4) 12 (5.2)MRSA 5 (3.5) 2 (0.9)Streptococci other

than Spneumoniae

10 (7.1) 12 (5.2)

Other Gram-positivebacteria

4 (2.8) 3 (1.3)

Atypical pathogens 1 (0.7) 16 (7.0)C pneumoniae 1 (0.7) 13 (5.7)M pneumoniae 0 (0) 2 (0.9)L pneumophila 0 (0) 1 (0.4)

Nocardia species 1 (0.7) 0 (0)No pathogen identified 64 (45.4) 121 (52.6)

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

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




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thermore, in-hospital death tended to occur morefrequently in patients who received inappropriateinitial antibiotic treatment compared with those whoreceived appropriate initial antibiotic treatment.

Therefore, HCAP should be identified as a distinctentity in determining the initial empirical antibiotictreatment, as stated in recent reports.30,31

In the present study, PDR pathogens occurredmore frequently among HCAP patients than amongCAP patients (Table 5). We found that the propor-tion of initial treatment failure and inappropriateinitial antibiotic treatment was markedly higheramong HCAP patients with PDR pathogens thanamong those without. More specifically, HCAP pa-tients with PDR pathogens were 4.2 and 14.0 timesas likely, respectively, to have initial treatment failure

and inappropriate initial antibiotic treatment thanthose without PDR pathogens. Therefore, we sug-gest that physicians should give more considerationto PDR pathogens in choosing the initial empiricalantibiotic treatment of HCAP patients to improvetheir management.

What population among HCAP patients should betargeted for treatment with broad-spectrum antibi-otics? As shown in Table 5, the frequency of PDRpathogens was not dependent on the severity ofpneumonia in HCAP patients; in this respect, thesepatients 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 tubefeeding were found to be significant risk factors.Therefore, we suggest that HCAP patients withthese risk factors for PDR pathogens should betreated with broad-spectrum antibiotics (an anti-pseudomonal -lactam plus a fluoroquinolone or anaminoglycoside plus vancomycin or linezolid), asrecommended by the 2005 ATS/IDSA guidelines,1

even if the patients are not classified as having asevere disease.

The present study has several limitations. First,the data were retrospectively collected from a singleinstitution. Second, the identified pathogens in-cluded oropharyngeal colonizers and were not defi-nite causes of pneumonia since most of the resultswere obtained from sputum cultures; Gram stainingwas not performed in some cases; and the cultureswere semiquantitative rather than quantitative.However, previous reports11,32,33 have indicated acorrelation between oropharyngeal colonization andpathogenesis for most episodes of NHAP or pneu-monia occurring 4 days after intubation. Third,evaluation for atypical pathogens was inadequatebecause of the small quantity of data.

In summary, we found that in the moderate

severity class the in-hospital mortality proportion ofHCAP patients was significantly higher than that ofCAP patients. Moreover, in the moderate class, PDRpathogens were identified more frequently amongHCAP than among CAP patients. On the other hand,in the severe class, there were no significant differ-ences between HCAP and CAP patients in in-hospital mortality and occurrence of PDR patho-gens. These results provide additional evidence thatHCAP should be distinguished from CAP. More-over, we showed that the occurrence of PDR patho-gens among HCAP patients was associated with ahigher proportion of initial treatment failure andinappropriate initial antibiotic treatment. We suggestthat the therapeutic strategy for the moderate classholds the key to improving mortality in HCAPpatients, and that physicians may need to considerPDR pathogens in choosing the initial empiricalantibiotic treatment of HCAP patients in order toimprove their management.

ACKNOWLEDGMENT: We thank Professor Michio Ohta(Department of Molecular Bacteriology, Nagoya UniversityGraduate School of Medicine, Nagoya, Japan) for his commentson the microbiological evaluation.

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

Risk Factors Yes No Risk Ratio 95% CI p Value

Use of antibiotics within the previous 90 d 14/50 (28.0) 3/27 (11.1) 2.5 0.88.0 0.088Use of broad-spectrum antibiotics for 2 d within the

previous 90 d11/31 (35.5) 5/44 (11.4) 3.1 1.28.1 0.012

Chronic lung disease 5/22 (22.7) 12/55 (21.8) 1.0 0.42.6 0.931Probable aspiration 14/54 (25.9) 3/23 (13.0) 2.0 0.66.3 0.212Tube feeding 5/11 (45.5) 12/66 (18.2) 2.5 1.15.7 0.044

Poor functional status 14/49 (28.6) 3/28 (10.7) 2.7 0.88.5 0.069Immunosuppression 0/5 (0.0) 17/72 (23.6) 0.218

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

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




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