Impact of guideline-consistent therapy on outcome of patients with healthcare-associated and community-acquired pneumonia

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1 Journal of Antimicrobial Chemotherapy Advance Access published May 17, 2011 J Antimicrob Chemother doi: /jac/dkr176 Impact of guideline-consistent therapy on outcome of patients with healthcare-associated and community-acquired pneumonia Cynthia Grenier, Jacques Pépin, Vincent Nault, Jessika Howson, Xavier Fournier, Marie-Sol Poirier, Jérôme Cabana, Camille Craig, Mathieu Beaudoin and Louis Valiquette* Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Québec, Canada *Corresponding author. Tel: , ext ; Fax: ; louis.valiquette@usherbrooke.ca Received 21 December 2010; returned 29 January 2011; revised 29 March 2011; accepted 8 April 2011 Background: A new category of healthcare-associated pneumonia (HCAP) has been added in the most recent American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines, since multidrugresistant (MDR) pathogens are more common in patients with HCAP than in those with community-acquired pneumonia (CAP). The optimal empirical management of patients with HCAP remains controversial and adherence to guidelines is inconsistent. Methods: A retrospective cohort study of 3295 adults admitted for pneumonia in an academic centre of Canada, between 1997 and Results: MDR pathogens were more common among patients with HCAP than in those with CAP, but less so than in other studies. Compared with patients with CAP, those with HCAP had a higher all-cause 30 day mortality [68/563 (12%) versus 201/2732 (7%); P, 0.001] and more frequent need for mechanical ventilation [78/563 (14%) versus 276/2732 (10%); P¼0.01]. In patients with CAP, mortality was lower when treatment was concordant with guidelines [86/1557 (6%) versus 109/1097 (10%) if discordant; adjusted odds ratio 0.6 ( ); P, 0.001]. In HCAP, mortality was similar whether or not empirical treatment was concordant with guidelines [6/35 (17%) versus 18/148 (12%) if discordant; P¼0.4]. However, 30 day mortality tended to be higher when the empirical treatment was microbiologically ineffective [4/22 (18%) versus 17/187 (9%) when effective; P¼0.3]. Conclusions: HCAP is associated with worse outcomes than CAP. MDR pathogens were implicated in only a small fraction of HCAP cases. In our study, unlike CAP, non-respect of current HCAP guidelines had no adverse effect on the ultimate outcome. Strategies for the empirical management of HCAP should be tailored to the local epidemiological context. Keywords: HCAP, CAP, antibacterials Introduction Healthcare-associated infections are a relatively new concept reflecting the shift of many traditional inpatient services towards outpatient settings. 1,2 Consequently, a new category of pneumonia, healthcare-associated pneumonia (HCAP), has been added to the two traditional entities [community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP)] in the most recent American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines. 3 HCAP is defined by exposures (living in a nursing home, receiving long-term dialysis or outpatient intravenous therapy, etc.) which, despite not fulfilling the criteria for HAP, correlate with an increased risk of being infected by multidrug-resistant (MDR) pathogens [Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum b-lactamase (ESBL)-producing Enterobacteriaceae, etc.]. 3 Compared with CAP, HCAP has been associated with more severe disease, higher mortality and longer hospital stay. 4 8 Consequently, broader-spectrum antibacterials are recommended for its empirical treatment. 3 However, the contribution of MDR pathogens in the aetiology of HCAP and its optimal empirical treatment remain debated. Thus, the utility of the HCAP categorization in its present format has been questioned and HCAP guidelines are not consistently followed To address these issues, we undertook the current study, which aimed to compare the clinical characteristics, microbiology, antibacterial therapy and outcomes of patients with CAP and HCAP in a region of Canada between # The Author Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please journals.permissions@oup.com 1of8

2 Grenier et al and Furthermore, we evaluated to what extent empirical treatments were in line with various iterations of management guidelines for CAP and HCAP, as well as effective against the pathogens subsequently documented. Methods Population and study design We carried out a retrospective cohort study of all adults ( 18 years old) with a primary discharge diagnosis of pneumonia (International Classification of Diseases, ninth and tenth revisions, codes and J09 J18.9) hospitalized between January 1997 and December 2008 at the Centre Hospitalier Universitaire de Sherbrooke (CHUS), a 686-bed academic, tertiary-care centre in south-east Québec, Canada. About half of the inhabitants of the Estrie region live in Sherbrooke. As the CHUS holds 92% of the acute care beds of the region, the ascertainment rate for pneumonia necessitating a hospital admission must be of the same order of magnitude. Subjects were included if they had been admitted with a primary diagnosis of pneumonia and had findings consistent with pneumonia on chest X-ray (CXR) within 48 h of admission. Patients discharged from an acute care facility within 14 days of current admission, transferred from another hospital or with a diagnosis of pneumonia made.48 h after admission were excluded. When patients had more than one admission for pneumonia during the study period, only the first episode was considered. The study protocol was approved by the CHUS Ethics Committee (# P2). HCAP and CAP were defined according to ATS/IDSA guidelines. 3 HCAP included patients meeting any of the following criteria: residence in a nursing home or long-term care facility; hospitalization for 2 days in the preceding 90 days but not within the last 14 days; long-term dialysis; or outpatient intravenous therapy or cancer chemotherapy within the previous month. All others were considered to have had CAP. Computerized medical records were reviewed using a standardized form. Variables included demographic characteristics, co-morbidities, symptoms, signs, radiographic and laboratory results (within 48 h of admission), antibacterials administered prior to and during hospitalization and outcomes [intensive care unit (ICU) admission, intubation/mechanical ventilation and 30 day all-cause mortality]. Immunosuppression was defined as the presence of leukaemia, lymphoma, HIV infection, neutropenia, organ transplantation or use of immunosuppressive drugs. Disease severity upon presentation was evaluated through the pneumonia severity index (PSI). 12 Microbiological evaluation Pathogens identified in respiratory samples and blood cultures were reviewed. Only grade 4 and 5 sputum specimens were analysed. 13 Our microbiology laboratory routinely reports the presence of Haemophilus parainfluenzae, considered by some as part of the normal oral flora, by others as a respiratory pathogen; it was included only when found as the sole pathogen with a compatible Gram s stain. Blood cultures with skin organisms were not considered. When requested, Legionella pneumophila serogroup 1 antigen in urine was detected with an immunochromatography kit (Binax, Portland, ME, USA), and antibodies against Mycoplasma pneumoniae, Chlamydophila pneumoniae and L. pneumophila were detected using single or paired sera. Influenza A and B detection was performed by viral culture ( ), antigen detection ( ) and RT PCR ( ). Antimicrobial susceptibility was determined using agar dilution for Gramnegative bacilli, disc diffusion and Etest for Streptococcus pneumoniae, Haemophilus influenzae and S. aureus. 17,18 Patients at high risk for MRSA colonization were screened on admission, as per the hospital s routine infection control procedures. Appropriateness of empirical therapy The appropriateness of empirical antibacterial treatment administered within 24 h of admission was evaluated by two approaches. Firstly, we assessed initial antibacterial regimen agreement with published ATS/IDSA guidelines. For CAP patients, we used the 1993 (ATS), 1998 (IDSA), 2000 (IDSA), 2003 (IDSA) and 2007 ATS/IDSA guidelines for the management of patients requiring hospitalization or ICU admission For HCAP patients, we evaluated whether the empirical antibacterial therapy included coverage of MDR pathogens according to the 2005 ATS/IDSA guidelines for management of adults with HAP, ventilatorassociated pneumonia (VAP) and HCAP (but we considered MRSA coverage as optional, since MRSA colonization and infection are relatively uncommon in our centre). 3,24 We based our analyses on American guidelines since no Canadian HCAP guidelines were available, and the only Canadian CAP guidelines, published in 2000, were almost identical to the American ones. We considered that guidelines should start being applied 6 months after their publication. Secondly, for patients with a confirmed microbial aetiology, we verified whether the initial antibacterial regimen had been effective against the offending pathogen based on in vitro susceptibility testing. Antibacterial treatments were classified as concordant or discordant with guidelines, and as microbiologically effective or ineffective. Patients who did not receive any antibacterial therapy during the first 24 h of hospital admission were considered as discordant and ineffective. Statistical analyses Data were analysed with SAS version 9.1 (SAS Institute) and statistical significance was established at a¼0.05. Continuous variables were compared with the Student s t-test or the Wilcoxon rank-sum test. Proportions were compared with the x 2 or Fisher s exact test when appropriate. Logistic regression was used for multivariate analysis of the impact of guideline concordance on all-cause 30 day mortality, and results are presented as adjusted odds ratios (AORs) with their 95% confidence intervals (CIs). Models were built up sequentially, starting with the variable most strongly associated with the outcome and continuing until no other variable reached significance or altered the odds ratios of variables already in the model. When the final model was reached, each variable was dropped in turn to assess its effect. Different models were compared with the likelihood ratio test. Results During the study period, 5974 episodes of pneumonia in adults were identified with appropriate discharge codes as primary diagnosis but 387 occurred after a first episode and were excluded. From these 5587 episodes, 3295 episodes met eligibility criteria (1631 were excluded because they did not have a pulmonary infiltrate evident on CXR within 48 h of admission, 428 had been hospitalized within 14 days, 165 were transferred from another hospital and 68 for other reasons). Of these episodes, 2732 (83%) were categorized as CAP and 563 (17%) as HCAP. The most common criterion that defined HCAP was hospitalization for 2 days within the preceding days (403 patients, 72%), followed by residence in a long-term care facility (118 patients, 21%), outpatient intravenous anticancer or antimicrobial therapy (50 patients, 9%) and long-term dialysis 2of8

3 HCAP versus CAP in Canada JAC (42 patients, 7%). Only 49 (9%) patients had more than one criterion. Patients with HCAP were older, had more numerous co-morbidities, were more frequently colonized with MRSA and were much more likely to have received antibacterials within the preceding 90 days than patients with CAP (see Table 1). Even though the frequency of multilobar involvement was similar in both groups, those with HCAP were more likely to be hypoxaemic and had higher PSI than those with CAP. Out of 1991 patients able to provide a respiratory specimen, 1463 (73%) were deemed acceptable by the laboratory. In 2769 patients, at least one blood culture set was drawn within 48 h of admission; 239 (9%) patients had at least one positive blood culture with a recognized pathogen [HCAP 41/456 (9%), CAP 198/2313 (9%)]. A bacterial aetiological agent was detected in 1011 (37%) patients with CAP and 209 (37%) patients with HCAP. The microbiological diagnosis was provided by sputum culture alone in 959 (79%) patients, by blood cultures alone in 164 (13%) and by both in 75 (6%) patients. Compared with those without a microbiological diagnosis, patients with an aetiological agent documented were younger, more likely to be male, to have chronic obstructive pulmonary disease (COPD) or to have pulse oximetric saturation (SpO 2 ),90% on admission (data not shown). Regarding outcomes, patients with HCAP experienced a higher all-cause 30 day mortality, longer hospital stay and more frequent need for mechanical ventilation (Table 1). The distribution of pathogens is summarized in Table 2. In both CAP and HCAP, the most frequent pathogens were S. pneumoniae, H. influenzae and H. parainfluenzae. Enterobacteriaceae, MRSA and P. aeruginosa were more frequent while S. pneumoniae and H. influenzae were less common in HCAP than in CAP patients. No EBSL-producing bacteria were identified in either group. A polymicrobial infection was reported in 64 (2%) patients with CAP versus 13 (2%) with HCAP. S. pneumoniae was the most common blood pathogen in both groups [HCAP 27/41 (66%), CAP 161/198 (81%); P¼0.05]. All four cases of HCAP caused by MRSA were known to be colonized with this pathogen prior to developing pneumonia. Among 17 cases of P. aeruginosa HCAP, 9 occurred in patients known to be colonized. Viral pathogens were identified in 153 (5%) patients: influenza A in 115 cases, influenza B in 21, respiratory syncytial virus in 12 and other respiratory viruses in 5 cases. No significant differences in viral aetiology were identified when comparing CAP versus HCAP patients. A virus was identified as the sole pathogen in 105 cases. Table 3 summarizes the empirical antibacterials used within the first 24 h. Monotherapy was used in most patients admitted to the ward and combination therapy in most patients admitted to the ICU, whether it was CAP or HCAP. Apart from an important increase in fluoroquinolone use from 2004 to 2008, no other temporal trends were observed (data not shown). For the analysis of antibacterial concordance with ATS/IDSA guidelines and microbial effectiveness against the identified pathogen, we excluded patients in whom only a viral pathogen was identified (105). Concordance of empirical antibacterial therapy with guidelines is presented in Table 4. Overall, 59% of patients with CAP received empirical treatment consistent with the contemporary IDSA guidelines. The proportion was lower in patients admitted to the ICU. Monotherapy with a second- or third-generation cephalosporin was the main reason explaining the low concordance (25%) in patients with CAP in , as addition of a macrolide was then deemed necessary for all patients given a b-lactam. Overall compliance was poor (19%) in HCAP patients, among whom the main reason for nonconcordance was failure to include two agents active against P. aeruginosa. Antibacterial effectiveness of therapy administered within the first 24 h of admission is also presented in Table 4. Effective antibacterials were administered in 912 (91%) patients with CAP and 187 (89%) patients with HCAP. Antimicrobial effectiveness against the aetiological pathogen changed little over time, in contrast to concordance with guidelines, which fluctuated markedly. Among both non-icu and ICU CAP cases, the most frequent cause of in vitro ineffectiveness was the presence of drug-resistant S. pneumoniae, in nine and four cases, respectively. Among HCAP cases, in vitro ineffectiveness was related to a diversity of pathogens, which included only two MRSA. Among patients with CAP, 30 day mortality was identical whether an aetiological agent was demonstrated [76/1011 (8%)] or not [125/1721 (7%)]; P¼0.8. Mortality was lower when patients were receiving empirical treatment concordant with guidelines [86/1557 (6%) versus 109/1097 (10%) if discordant; P, 0.001]. In a multivariate analysis that adjusted for several independent correlates of mortality displayed in Table 5, receiving empirical treatment concordant with guidelines halved the risk of mortality (AOR 0.6, 95% CI ; P,0.001). Among patients with HCAP, 30 day mortality was similar whether an aetiological agent was demonstrated [21/209 (10%)] or not [47/354 (13%)] (P¼0.3) and whether or not empirical treatment was concordant with guidelines [6/35 (17%)] versus 18/148 (12%) if discordant; P¼0.4]. Adjustment for potential confounding factors did not alter this conclusion (data not shown). Within the subgroup of CAP patients with confirmed aetiology (n¼1008), 30 day mortality was similar whether the empirical treatment had been microbiologically effective [70/916 (8%)] or ineffective [6/92 (7%)]; P¼0.7. Within the subgroup of HCAP patients with confirmed aetiology (n¼209), 30 day mortality was twice as high if the empirical treatment had been microbiologically ineffective [4/22 (18%) versus 17/187 (9%)], but this did not reach statistical significance (P¼0.3). Discussion This study compared the epidemiology and outcomes between CAP and HCAP in a single Canadian centre and evaluated treatment concordance with HCAP guidelines. Overall, compared with CAP patients, HCAP cases experienced a more severe pneumonia: they were more often hypoxaemic on admission, they had a higher pneumonia severity index, stayed longer in hospital, were more likely to need ventilatory support and to die within 30 days of diagnosis of pneumonia, confirming previous observations from other countries. 4 8 This higher severity had multiple causes. HCAP cases were marginally older than their CAP counterparts, and had experienced far more numerous co-morbidities, which at the same time led them to fulfil the HCAP criteria and decreased their likelihood of surviving the acute episode of pneumonia. MRSA, 3of8

4 Grenier et al. Table 1. Characteristics of patients with CAP versus HCAP Variables CAP (n¼2732) HCAP (n¼563) P value Age, years, median (IQR) 72 (57 81) 74 (62 82),0.001 Sex 0.2 female 1268 (46) 245 (44) male 1464 (54) 318 (56) Pre-existing co-morbid conditions COPD 1012 (37) 281 (50),0.001 cancer 490 (18) 185 (33),0.001 diabetes 505 (18) 140 (25),0.001 neurological disease 489 (18) 167 (30),0.001 immunosuppression 405 (15) 183 (33),0.001 congestive heart failure 289 (11) 94 (17),0.001 chronic renal failure 133 (5) 90 (16),0.001 Colonization with MRSA 39 (1) 30 (5),0.001 Cigarette smoking (active) 754 (28) 114 (20),0.001 Clinical parameters upon admission altered mental state 285 (10) 75 (13) NS respiratory rate, breaths/min, median (IQR) 22 (20 28) 24 (20 28) 0.02 SpO 2,0.001,90% 453 (17) 136 (24) 90% 95% 1522 (56) 299 (53) 96% 757 (28) 128 (23) Laboratory findings upon admission leucocytes, 10 9 /L, median (IQR) 13.3 ( ) 12.5 ( ) creatinine, mmol/l, median (IQR) 94 (77 122) 102 (79 147),0.001 haematocrit, %, mean+sd ,0.001 Radiographic findings alveolar infiltrate only unilobar 1809 (66) 370 (66) multilobar 810 (30) 158 (28) others 18 (0.7) 4 (0.8) interstitial infiltrate only 49 (2) 17 (3) alveolar+interstitial infiltrates 46 (2) 14 (2) Probable aspiration 118 (4) 30 (5) NS PSI risk classes low risk (I II) 765 (28) 61 (11) intermediate risk (III) 582 (21) 105 (19) high risk (IV V) 1374 (51) 395 (70) NS,0.001 Antibacterials in the preceding 3 months 179 (7) 213 (38),0.001 Outcomes all-cause 30 day mortality 201 (7) 68 (12),0.001 hospital length of stay, days, median (IQR) 7 (4 12) 6 (4 10),0.001 need for mechanical ventilation 276 (10) 78 (14) 0.01 IQR, interquartile range; NS, not significant. Data are presented as number (%), unless otherwise indicated. P. aeruginosa and Enterobacteriaceae were all more common as aetiological agents among patients with HCAP than in those with CAP, which may also have contributed to the unfavourable outcomes. Thus, our data support the usefulness of the HCAP categorization, at least to identify patients at higher risk of complications and higher risk of infections with MDR pathogens. 4of8

5 HCAP versus CAP in Canada JAC Table 2. Distribution of bacterial pathogens in patients with CAP versus HCAP Pathogens CAP (n¼1103) HCAP (n¼226) P value Gram-positive S. pneumoniae 437 (40) 72 (32) 0.03 methicillin-susceptible S. aureus 40 (4) 10 (4) NS MRSA 6 (0.5) 4 (2) NS other Gram-positive pathogens a 46 (4) 8 (4) NS Gram-negative H. influenzae 273 (25) 35 (15) H. parainfluenzae 152 (14) 37 (16) NS Moraxella catarrhalis 40 (4) 10 (4) NS Enterobacteriaceae b 45 (4) 28 (12),0.001 P. aeruginosa 36 (3) 17 (8) other Gram-negative pathogens c 5 (0.5) 2 (0.9) NS Atypical pathogens d 21 (2) 2 (0.9) NS Others e 2 (0.2) 1 (0.4) NS NS, not significant. Data are presented as number (%). Aetiological agents are more numerous than patients owing to 64 patients with CAP and 13 patients with HCAP who had mixed infections. a b-haemolytic streptococci (groups A, B, C and G) (33), Corynebacterium pseudodiphtheriticum (21). b Escherichia coli (25), Klebsiella sp. (20), Enterobacter sp. (12), Serratia sp. (8), Proteus mirabilis (4), Morganella morganii (2), Proteus vulgaris (1), Hafnia alvei (1) and Citrobacter koseri (1). c Stenotrophomonas maltophilia (4) and Acinetobacter sp. (3). d Legionella pneumophila (19), M. pneumoniae (3) and Chlamydophila psittaci (1). e Pasteurella multocida (1) Bacteroides fragilis (1) and Fusobacterium nucleatum (1). However, even if P. aeruginosa and MRSA were more common in our HCAP patients than amongst our CAP patients, their frequency was much lower than that found in the USA among similar patients (25% 26% for P. aeruginosa and 26% 31% for MRSA) but comparable to reports from Japan and Spain. 6,7 We found few differences between CAP and HCAP cases in the selection of empirical antimicrobial therapy by their attending physicians. Given the low prevalence of MDR pathogens, CAP and HCAP cases did not differ for the in vitro efficacy of this initial therapy against the pathogens subsequently documented, even if adherence to the ATS/IDSA recommendations for the empirical management of HCAP was inconsistent after their publication in Our data concerning patients with CAP demonstrated substantial year-to-year variations in the frequency of concordance with guidelines, not mirrored by changes in the in vitro efficacy against the aetiological agents. The drop in concordance in corresponded to the recommendation, made in both the American and Canadian 2000 guidelines, of always adding a macrolide to a cephalosporin or using a respiratory fluoroquinolone as monotherapy. 21,25 Concordance increased when fluoroquinolones subsequently became more popular. For each period, microbiological efficacy was higher than concordance with guidelines. These discrepancies question the advisability of issuing numerous iterations of CAP treatment guidelines, unless they are justified by substantial changes in the antibacterials available, the distribution of aetiological agents or their resistance to antibacterials. For CAP cases, as previously demonstrated in other different settings, compliance with guidelines was independently associated with lower mortality and shorter hospital stay We failed to demonstrate an association between in vitro activity against subsequently documented pathogen and mortality, but power was hampered by the relatively low mortality and the low proportion of CAP patients with a confirmed aetiology. For HCAP cases, non-concordance of the initial empirical regimen with guidelines was not a risk factor for mortality. The current HCAP guidelines were not adapted to our local distribution of pathogens and their resistance patterns. In regions such as ours where MRSA remains uncommon, it is safe to include vancomycin or linezolid in the empirical management of HCAP only when the patient is known to be colonized with this pathogen. Even using a liberal interpretation of the HCAP guidelines (MRSA coverage as optional rather than compulsory), we found a low concordance rate driven by the failure to include two antipseudomonal agents. This could potentially be detrimental to at most 3% of our HCAP cases, those caused by P. aeruginosa in patients not known to be colonized with this pathogen. Our study demonstrates the importance of adapting HCAP guidelines to local epidemiology and of identifying more specific predictors of MDR pathogens in patients with pneumonia. The ATS/IDSA guidelines include an algorithm to favour the utilization of limited-spectrum antibacterials for HAP and VAP. 3 Patients with early-onset HAP/VAP and absence of risk factors for MDR organisms can be treated empirically with ceftriaxone or fluoroquinolone monotherapy. However, suggested risk factors include the HCAP criteria so that all HCAP patients need to be treated with broad-spectrum antibacterials. In our centre, this was not necessary. Our study had several strengths. We collected data on a large number of cases of pneumonia in adults over a long period, with a near-complete ascertainment of cases within a well-defined population, thus avoiding selection biases. Data were extracted manually from computerized hospital records and were more comprehensive and reliable than what can be obtained from administrative databases designed for other purposes. Since our study spanned a 12 year period, we evaluated guidelines concordance based on those guidelines valid at the time of the patient s admission. This provides a more appropriate evaluation of concordance since bacterial resistance patterns may change over time. Limitations were those inherent to retrospective studies in which the information is by necessity incomplete. For instance, the identification of cases caused by atypical pathogens or viruses was imperfect, as the appropriate assays were not routinely requested. An aetiological agent could be identified in only 37% of cases. Although mortality did not differ between those with and without an aetiological agent identified, other characteristics did vary, notably the presence of COPD (presumably because such patients could more easily produce a sputum sample accepted by the laboratory) and its correlates (male gender), potentially generating biases in our measurements of 5of8

6 Grenier et al. Table 3. Empirical antibacterial therapy in patients with CAP versus HCAP CAP HCAP non-icu (n¼2254) ICU (n¼477) non-icu (n¼457) ICU (n¼106) Monotherapy 1668 (74) 227 (48) 307 (67) 40 (38) cephalosporins Ceph (29) 66 (14) 115 (25) 14 (13) Ceph (6) 29 (6) 37 (8) 8 (8) others 31 (1) 11 (2) 4 (0.9) 1 (0.9) fluoroquinolones 655 (29) 82 (17) 119 (26) 9 (9) other b-lactams 83 (4) 27 (6) 23 (5) 5 (5) macrolides 94 (4) 9 (2) 6 (1) 2 (2) others 17 (0.8) 3 (0.6) 3 (0.7) 1 (0.9) Combination therapy 461 (21) 233 (49) 124 (27) 61 (58) Ceph-2/Ceph-3+macrolides 155 (7) 55 (12) 19 (4) 10 (9) Ceph-2/Ceph-3+fluoroquinolones 95 (4) 45 (9) 21 (5) 8 (8) other b-lactams+fluoroquinolones 55 (2) 51 (11) 30 (7) 16 (15) others 156 (7) 82 (17) 54 (12) 27 (26) None 125 (6) 17 (4) 26 (6) 5 (5) Ceph-2, second-generation cephalosporins; Ceph-3, third-generation cephalosporins. Data are presented as number (%). Table 4. Concordance of empirical antibacterial therapy (within the first 24 h) with guidelines and microbiological effectiveness in patients with CAP versus HCAP Non-ICU CAP a HCAP b P value CAP a HCAP b P value Empirical antibacterial therapy concordant with guidelines January 1997 to June /261 (80) NA 0/38 (0) NA July 1998 to February /535 (85) NA 7/80 (9) NA March 2001 to April /533 (25) NA 39/119 (33) NA May 2004 to April /555 (74) 7/68 (10) c, /142 (24) 5/12 (42) c NS May 2007 to December /309 (77) 15/81 (19), /82 (37) 8/22 (36) NS total 1447/2193 (66) 22/149 (15), /461 (24) 13/34 (38) NS Empirical antibacterial therapy microbiologically effective January 1997 to June /118 (89) 15/19 (79) NS 20/22 (91) 4/5 (80) NS July 1998 to February /182 (93) 27/32 (84) NS 37/42 (88) 12/13 (92) NS March 2001 to April /210 (88) 35/40 (88) NS 54/61 (89) 12/14 (86) NS May 2004 to April /200 (93) 37/40 (93) NS 66/70 (94) 14/14 (100) NS May 2007 to December /69 (87) 25/26 (96) NS 30/30 (100) 6/6 (100) NA total 705/779 (91) 139/157 (89) NS 207/225 (92) 48/52 (92) NS ICU NS, not significant; NA, not available. Data are presented as number (%). a According to ATS/IDSA guidelines on CAP published in 1993, 1998, 2000, 2003 and b Empirical antibacterial therapy against MDR pathogens according to ATS/IDSA guidelines on HCAP, HAP and VAP published in c This period begins in July 2005 for HCAP patients. the distribution of aetiological agents and of the in vitro efficacy of empirical regimens. Implementation of updated versions of guidelines must be a gradual process, but we had to determine an arbitrary cut-off and we elected to do so 6 months after their publication. Finally, our study was performed in a single institution with a relatively low rate of MDR pathogens, and its results cannot be generalized to centres harbouring a more resistant flora. 6of8

7 HCAP versus CAP in Canada JAC Table 5. Independent correlates for all-cause 30 day mortality among patients with CAP (n¼2646) a Variable AOR (95% CI) P value Age 1.05 ( ) b,0.001 Neurological disease 1.7 ( ) Congestive heart failure 1.9 ( ) Altered mental state 2.1 ( ) SpO 2 96% % 95% 0.9 ( ) 0.5,90% 1.8 ( ) 0.02 Increased respiratory rate 1.9 ( ),0.001 (.30 breaths/min ) Multilobar pneumonia 1.6 ( ) Bacteraemia 3.3 ( ),0.001 Concordance with CAP guidelines 0.6 ( ),0.001 a Patients with a viral CAP were excluded from this analysis. b For each additional year of age. In conclusion, this study confirms that HCAP is associated with a worse outcome than CAP. Albeit more frequent than among cases of CAP, MDR pathogens were implicated in only a small fraction of HCAP cases. In this study, non-respect of current HCAP guidelines had no adverse effect on the ultimate outcome. Strategies for the empirical management of HCAP should be tailored to the local epidemiological context and more specific criteria for the empirical coverage of MDR organisms need to be considered when appropriate. Acknowledgements We are indebted to the staff of the medical records department of the CHUS for their patience and collaboration. We thank Annie Chiquette-Pomar, Joanie Gaudreau-Michel, Aïda Lalla-Guindo and Marie-Claude Joseph for chart review and data entry. Funding This study was supported by departmental funding. Transparency declarations J. P. has been on the speakers bureau for Wyeth and Merck, and has served on advisory boards for Pfizer, Wyeth, Ortho, Merck, Acambis, Iroko and The Medicines Company. L. V. has been on the speakers bureau for Wyeth, has served on advisory boards for Oryx, Iroko, Abbott and Wyeth, and has received compensation to conduct clinical trials involving antibacterials from Genzyme, Wyeth, Pfizer, BioCryst, Trius, Cempra, Optimer and Arpida. 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