Co-amoxiclav induces proliferation and cytotoxin production of Clostridium difficile ribotype 027 in a human gut model.

J Antimicrob Chemother. 2012 Jan 25;

Authors: Chilton CH, Freeman J, Crowther GS, Todhunter SL, Nicholson S, Wilcox MH

Abstract
OBJECTIVES: Co-amoxiclav is widely prescribed in hospitals. Although reports have suggested it may be linked to onset of Clostridium difficile infection (CDI), data on the risk of CDI associated with specific antibiotics is difficult to obtain, due to confounding clinical factors. We have examined the propensity of co-amoxiclav to induce CDI using a human gut model. METHODS: We used a triple-stage chemostat human gut model to study the effects of co-amoxiclav on indigenous gut microorganisms and C. difficile PCR ribotype 027. C. difficile viable counts and spores were evaluated, and cytotoxin titres were assayed. Co-amoxiclav concentrations were measured using a large plate bioassay. RESULTS: Co-amoxiclav induced rapid C. difficile germination and high toxin production in the gut model, from 5 days after commencement of instillation. Cell proliferation and toxin production were prolonged and continued throughout the duration of the experiment. Only very low levels of co-amoxiclav antimicrobial activity could be detected within the gut model, despite having a marked effect on gut flora microorganisms. CONCLUSIONS: Co-amoxiclav induced CDI within the gut model, supporting clinical observations linking co-amoxiclav treatment with CDI onset. This reinforces the value of the gut model as a clinically relevant means of studying CDI. Caution should be exercised in the prescription of co-amoxiclav to patients in high CDI risk settings.

PMID: 22279183 [PubMed - as supplied by publisher]

Prospective study of severity assessment and management of acute medical admissions with skin and soft tissue infection.

J Antimicrob Chemother. 2012 Jan 9;

Authors: Marwick C, Rae N, Irvine N, Davey P

Abstract
BACKGROUND: Several severity scoring systems have been proposed for skin and soft tissue infections (SSTIs), but none has been tested prospectively. METHODS: We prospectively enrolled adult, acute medical admissions with SSTI between April 2009 and June 2010. Severity was assessed using two proposed SSTI scoring systems, one based on a generic sepsis definition. Antimicrobial prescribing was compared with guideline recommendations. RESULTS: We enrolled 79 patients. One of the scoring systems classified 47% into class I (no sepsis or comorbidity), 5% into class II (no sepsis, but comorbidity), 34% into class III [sepsis, but standardized early warning system (SEWS) <4], and 14% into class IV (sepsis with SEWS ?4). The other system classified 39% as mild and 61% as moderate/severe. There were significant discrepancies between the two scoring systems. Using the worst clinical observations in the first 24 h, 19% of patients had more severe disease than was apparent on admission. Under-treatment of patients with sepsis occurred in 13% of patients according to admission observations, increasing to 22% according to the worst observations. Seventy-nine percent of patients with sepsis received antibiotics within 4 h of admission. This was associated with fewer adverse outcomes (P?=?0.05). CONCLUSIONS: There is significant room for improvement in the management of SSTIs presenting to acute medical units. The added value of specific SSTI severity scores over generic sepsis assessment requires validation in a larger prospective study. We have changed our antibiotics policy for SSTI to use generic sepsis scores, and we emphasize the need to reassess patients on the day of admission.

PMID: 22232513 [PubMed - as supplied by publisher]

Mandatory surveillance of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in England: the first 10 years.

J Antimicrob Chemother. 2012 Jan 4;

Authors: Johnson AP, Davies J, Guy R, Abernethy J, Sheridan E, Pearson A, Duckworth G

Abstract
Since 2001 it has been mandatory for acute hospital Trusts (groups of hospitals under the same management) in England to report all cases of bacteraemia due to Staphylococcus aureus together with information on their susceptibility or resistance to methicillin. This allowed the incidence of methicillin-resistant S. aureus (MRSA) bacteraemia (expressed as the number of cases per 1000 occupied bed days) to be determined for each Trust. In late 2005, the scheme was enhanced to collect demographic, clinical and epidemiological information on each case using a web-based data collection system. Analysis of this mandatory dataset has provided important information on the trends in MRSA bacteraemia in England and has documented a year-on-year decrease in incidence since 2006, following a government initiative in which Trusts were tasked with halving their MRSA bacteraemia rates over a 3year period. In addition, the enhanced mandatory surveillance scheme has captured a wealth of data that have helped to further define the epidemiology of MRSA bacteraemia. It is to be hoped that based on the English experience of mandatory surveillance, other countries will consider the implementation of similar schemes, not only for MRSA but for other pathogens of public health importance.

PMID: 22223229 [PubMed - as supplied by publisher]

A comparative evaluation of adverse platelet outcomes among Veterans' Affairs patients receiving linezolid or vancomycin.

J Antimicrob Chemother. 2011 Dec 15;

Authors: Patel N, Vandewall H, Tristani L, Rivera A, Woo B, Dihmess A, Li HK, Smith R, Lodise TP

Abstract
OBJECTIVES: The primary objectives were to compare the incidences of severe thrombocytopenia, critical thrombocytopenia and a relative decline in platelets from baseline (?50% decline) between patients receiving linezolid and those receiving vancomycin. The secondary objective was to assess the relationship between vancomycin trough concentration and adverse platelet outcomes. METHODS: A matched cohort study was performed at the Upstate New York Veterans' Affairs Healthcare Network from January 2005 until February 2008. Eligibility criteria were: (i) receipt of linezolid or vancomycin therapy for ?48 h; (ii) initiation of therapy as an inpatient; and (iii) baseline platelets available for evaluation. Patients who received linezolid were matched 1?:?1 to patients who received vancomycin. Cumulative incidences and times to event for (i) platelet count ?50?000 cells/mm(3), (ii) platelet count ?20?000 cells/mm(3) and (iii) ?50% decline in platelets from baseline were evaluated. Multivariate analyses were performed. RESULTS: The study included 502 patients (251 matched pairs). The occurrences of platelet counts ?50?000 cells/mm(3) and ?20?000 cells/mm(3) did not differ significantly between linezolid and vancomycin patients. A ?50% decline in platelets from baseline was observed in 78 (31.1%) patients receiving vancomycin and 43 (17.1%) patients receiving linezolid (risk ratio 0.55; 95% CI 0.40-0.77). A clear exposure-response relationship was observed between vancomycin trough concentration and ?50% decline in platelets from baseline. CONCLUSIONS: The incidence of thrombocytopenia was low and did not differ significantly among vancomycin and linezolid patients.

PMID: 22174041 [PubMed - as supplied by publisher]

Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics.

J Antimicrob Chemother. 2011 Dec 6;

Authors: Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ

Abstract
BackgroundClostridium difficile infections (CDIs) are common in developed countries and affect >250?000 hospitalized patients annually in the USA. The most important risk factor for the disease is antibiotic therapy.MethodsTo determine the period at risk for CDI after cessation of antibiotics, we performed a multicentre case-control study in the Netherlands between March 2006 and May 2009. Three hundred and thirty-seven hospitalized patients with diarrhoea and a positive toxin test were compared with 337 patients without diarrhoea. Additionally, a control group of patients with diarrhoea due to a cause other than CDI (n?=?227) was included.ResultsIn the month prior to the date of inclusion, CDI patients more frequently used an antibiotic compared with non-diarrhoeal patients (77% versus 49%). During antibiotic therapy and in the first month after cessation of the therapy, patients had a 7-10-fold increased risk for CDI (OR 6.7-10.4). This risk declined in the period between 1 and 3 months after the antibiotic was stopped (OR 2.7). Similar results were observed when the second control group was used. All antibiotic classes, except first-generation cephalosporins and macrolides, were associated with CDI. Second- and third-generation cephalosporins (OR 3.3 and 5.3, respectively) and carbapenems (OR 4.7) were the strongest risk factors for CDI. Patients with CDI used more antibiotic classes and more defined daily doses, compared with non-diarrhoeal patients.ConclusionsAntibiotic use increases the risk for CDI during therapy and in the period of 3 months after cessation of antibiotic therapy. The highest risk for CDI was found during and in the first month after antibiotic use. Our study will aid clinicians to identify high-risk patients.

PMID: 22146873 [PubMed - as supplied by publisher]

Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis.

J Antimicrob Chemother. 2011 Oct 25;

Authors: Cataldo MA, Tacconelli E, Grilli E, Pea F, Petrosillo N

Abstract
ObjectivesTo summarize available evidence on the effect of continuous infusion (CoI) of vancomycin compared with intermittent infusion (InI) in adult patients with Gram-positive infections.MethodsMEDLINE, EMBASE and Cochrane databases were searched. Randomized clinical trials (RCTs) and observational studies that comparatively assessed CoI and InI of vancomycin in terms of mortality, clinical cure, toxicity rates and serum drug exposure [trough concentration (C(min)) for InI and steady-state concentration (C(ss)) for CoI; area under the curve at 24 h (AUC(24)) for both] were included. Meta-analysis was conducted combining and analysing the relative risk (RR) and computing a summary RR of the effects with 95% confidence interval (CI). The standardized mean difference was calculated for continuous outcomes. The I(2) test was calculated to assess heterogeneity across studies.ResultsOne RCT and five observational studies were included in the analysis. Compared with InI, CoI of vancomycin was associated with a significantly lower risk of nephrotoxicity (RR 0.6, 95% CI 0.4-0.9, P?=?0.02; I(2?)=?0). Overall mortality was not different between the two groups (RR 1.03, 95% CI 0.7-1.6, P?=?0.9; I(2?)=?0).ConclusionsOur meta-analysis suggests that administration of vancomycin for the treatment of Gram-positive infections by CoI is associated with a significantly lower risk of nephrotoxicity when compared with InI of the drug. RCTs are needed to define the impact on mortality rate and on the pharmacodynamic activity in terms of AUC/MIC ratio.

PMID: 22028203 [PubMed - as supplied by publisher]

A randomized, double-blind, placebo-controlled pilot study to assess the ability of rifaximin to prevent recurrent diarrhoea in patients with Clostridium difficile infection.

J Antimicrob Chemother. 2011 Sep 21;

Authors: Garey KW, Ghantoji SS, Shah DN, Habib M, Arora V, Jiang ZD, Dupont HL

Abstract
BackgroundUncontrolled case series have demonstrated decreased Clostridium difficile infection (CDI) recurrence in patients given rifaximin after standard antibiotic therapy. However, clinical trials assessing whether rifaximin decreases recurrent diarrhoea in patients with CDI have not been performed. The purpose of this study was to assess rates of recurrent diarrhoea in patients with CDI given rifaximin versus placebo immediately after standard therapy.MethodsThis was a randomized, double-blind, placebo-controlled pilot study. Patients with CDI and a Horn's index ?1 were randomized to receive rifaximin 400 mg three times daily or placebo for 20 days given immediately after finishing standard anti-CDI antibiotics. Patients were followed for 3 months and assessed for recurrent diarrhoea that included CDI recurrence (return of diarrhoea with a positive toxin test) and patient self-reported return of non-CDI diarrhoea after a period of wellness.ResultsSixty-eight patients aged 61?±?18 years (50% male) were given rifaximin (n?=?33) or placebo (n?=?35). Twenty-four of 68 (35%) patients had recurrent diarrhoea either due to recurrent CDI (23.5%) or self-reported diarrhoea (11.5%). Recurrent diarrhoea occurred in 17 of 35 (49%) patients given placebo and 7 of 33 (21%) given rifaximin (P?=?0.018). CDI recurrence occurred in 11 of 35 (31%) patients given placebo and 5 of 33 (15%) patients given rifaximin (P?=?0.11). Self-reported diarrhoea occurred in 6 of 35 (17%) of patients given placebo and 2 of 33 (6%) given rifaximin (P?=?0.15).ConclusionsPatients with CDI given a rifaximin chaser regimen experienced a decreased incidence of recurrent diarrhoea compared with placebo.

PMID: 21948965 [PubMed - as supplied by publisher]

Empirical management of community-acquired pneumonia: impact of concurrent A/H1N1 influenza pandemic on guideline implementation.

J Antimicrob Chemother. 2011 Sep 15;

Authors: Cortoos PJ, Gilissen C, Mol PG, Van den Bossche F, Simoens S, Willems L, Leenaers H, Vandorpe L, Peetermans WE, Laekeman G

Abstract
BackgroundGuideline-concordant therapies have been proven to be associated with improved health and economic outcomes in the treatment of community-acquired pneumonia (CAP). However, actual use of CAP guidelines remains poor, but using tailored interventions looks promising. Based on local observations, we assessed the impact of low-intensity interventions to improve guideline use.MethodsPre-and post-intervention study with segmented regression analysis in a large tertiary care centre [University Hospitals Leuven (UZL)] and a smaller secondary care control hospital [Ziekenhuis Oost-Limburg (ZOL)] from October 2007 through to June 2010 in Belgium.ResultsA total of 477 patients were included in UZL, with 58.5% of the patients treated according to local guidelines. Guideline adherence remained stable, but a decrease (-28.6%; P?=?0.021) was observed during guideline re-introduction in October 2009. Further analysis showed a high correlation with the concurrent A/H1N1 influenza pandemic (r(point-biserial)?=?0.683; P?=?0.045) and with suspected influenza infection (odds ratio = 2.70; P?=?0.038). In ZOL, 326 patients were enrolled, with 69.3% being treated concordantly. A similar, non-significant decrease in guideline adherence was observed after October 2009.ConclusionsOur interventions did not lead to a higher proportion of CAP patients receiving guideline-compliant therapy. Instead, a compliance decrease was observed, coinciding with the peak in the A/H1N1 pandemic in the population. Similar observations could be made in ZOL. The widespread attention for this pandemic may have altered the perception of needed antibiotic therapy for pulmonary infections, bypassing our interventions and decreasing actual guideline compliance. Increased vigilance and follow-up is needed when epidemics with similar impact occur in the future.

PMID: 21926079 [PubMed - as supplied by publisher]

A randomized trial of the efficacy and safety of sequential intravenous/oral moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and skin structure infections.

J Antimicrob Chemother. 2011 Sep 6;

Authors: Gyssens IC, Dryden M, Kujath P, Nathwani D, Schaper N, Hampel B, Reimnitz P, Alder J, Arvis P

Abstract
OBJECTIVES: moxifloxacin iv/oral versus piperacillin/tazobactam (TZP) iv followed by oral amoxicillin/clavulanate (AMC). PATIENTS AND METHODS: NCT 00402727. RESULTS: 432/497 (86.9%) versus TZP-AMC: 370/429 (86.2%), microbiologically valid (MBV) population]. Moxifloxacin was non-inferior to TZP-AMC at TOC in both the MBV and the ITT populations. Both treatments were well tolerated.ConclusionsOnce-daily iv/oral moxifloxacin monotherapy was clinically and bacteriologically non-inferior to iv TZP thrice daily followed by oral AMC twice daily in patients with cSSSIs.

PMID: 21896561 [PubMed - as supplied by publisher]

Impact of antimicrobial stewardship programme changes on unnecessary double anaerobic coverage therapy.

J Antimicrob Chemother. 2011 Jul 29;

Authors: Rattanaumpawan P, Morales KH, Binkley S, Synnestvedt M, Weiner MG, Gasink LB, Fishman NO, Lautenbach E

Background Concern has been raised over the practice of unnecessary double anaerobic coverage therapy (DACT) in the hospital setting. However, the incidence of and risk factors for unnecessary DACT are not well studied. On 8 September 2008, the antimicrobial stewardship programme (ASP) at our institution was modified such that several antibiotics, including ampicillin/sulbactam and metronidazole, no longer required pre-approval. We anticipated that this change would increase both unnecessary DACT and target antibiotic consumption. Methods A nested case-control study was conducted to determine the cumulative incidence of and risk factors for unnecessary DACT. Cases were subjects who received unnecessary DACT while controls were subjects who did not receive DACT or who received necessary DACT. Segmented regression analysis was subsequently performed to evaluate the impact of ASP changes on unnecessary DACT and consumption of target antibiotics. Results From October 2007 to September 2009, the cumulative incidence of unnecessary DACT was 2.3% [95% confidence interval (CI) 1.7-3.1]. Independent risk factors for unnecessary DACT [adjusted odds ratio (95% CI); P value] included hospitalization on a surgical ward [3.51 (1.03-12.02); P?=?0.002], hospitalization on an obstetrics and gynaecology ward [9.07 (2.54-32.40); P?=?0.002] and underlying metastatic malignancy [3.18 (1.38-7.09); P?=?0.006]. The ASP change was associated with an increase in ampicillin/sulbactam and metronidazole consumption. However, there was no significant impact on unnecessary DACT prescribing. Conclusions Although uncommon, unnecessary DACT is more prevalent in specific services. Future qualitative studies focusing on these specific subgroups would be useful in elucidating this problem more clearly. The ASP changes were not associated with increases in unnecessary DACT.

PMID: 21803769 [PubMed - as supplied by publisher]

Is methicillin-resistant Staphylococcus aureus replacing methicillin-susceptible S. aureus?

J Antimicrob Chemother. 2011 Jul 7;

Authors: Mostofsky E, Lipsitch M, Regev-Yochay G

Despite extensive research on the emergence of and treatments for methicillin-resistant Staphylococcus aureus (MRSA), prior studies have not rigorously evaluated the impact of methicillin resistance on the overall incidence of S. aureus infections. Yet, there are direct clinical and research implications of determining whether methicillin-susceptible S. aureus (MSSA) infection rates remain stable in the face of increasing MRSA prevalence or whether MSSA will be replaced over time. A synthesis of prior studies indicates that the emergence of healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) has led to an increase in the overall incidence of S. aureus infections, with MRSA principally adding to, rather than replacing, MSSA. However, colonization with CA-MRSA may at least partially replace colonization with MSSA. So far, evidence indicates that MSSA still accounts for many infections. Therefore, eradication of MRSA alone is not sufficient to address the public health burden of S. aureus.

PMID: 21737459 [PubMed - as supplied by publisher]

Efficacy and safety of tigecycline: a systematic review and meta-analysis.

J Antimicrob Chemother. 2011 Jun 18;

Authors: Yahav D, Lador A, Paul M, Leibovici L

Background Tigecycline is a novel glycylcycline that exhibits broad-spectrum antibacterial activity. Recently, the US FDA issued a warning concerning increased mortality with tigecycline in randomized controlled trials (RCTs). Methods We conducted a systematic review and meta-analysis of RCTs that compared tigecycline with any other antibiotic regimen for the treatment of any infection. A comprehensive search, without publication status or other restrictions, was conducted. The primary outcome was overall 30 day mortality. The secondary outcome included clinical and microbiological failure, superinfections and adverse events (AEs). The trials' risks of bias and their effects on results were assessed. Two reviewers independently extracted the data. Individual trials' relative risks (RRs) were pooled using a fixed effect meta-analysis. Results Fifteen trials (7654 patients) were included. Overall mortality was higher with tigecycline compared with other regimens [RR 1.29, 95% confidence interval (CI) 1.02-1.64, without heterogeneity]. The type of infection assessed and the trials' reported risks of bias did not affect this result. Clinical failure was significantly higher with tigecycline (RR 1.16, 95% CI 1.06-1.27) and non-statistically significant higher rates of microbiological failure were demonstrated (RR 1.13, 95% CI 0.99-1.30). Development of septic shock was significantly more frequent with tigecycline (RR 7.01, 95% CI 1.27-38.66). Superinfections were significantly more common with tigecycline and so were AEs, including all AEs and AEs requiring discontinuation. Conclusions In the light of the increased mortality, probably explained by decreased clinical and microbiological efficacy, clinicians should avoid tigecycline monotherapy in the treatment of severe infections and reserve it as a last-resort drug.

PMID: 21685488 [PubMed - as supplied by publisher]

Changing epidemiology of central venous catheter-related bloodstream infections: increasing prevalence of Gram-negative pathogens.

J Antimicrob Chemother. 2011 Jun 10;

Authors: Marcos M, Soriano A, Iñurrieta A, Martínez JA, Romero A, Cobos N, Hernández C, Almela M, Marco F, Mensa J

Objectives Gram-positive microorganisms have been the predominant pathogens in central venous catheter-related bloodstream infections (CRBSIs). Recent guidelines recommend empirical therapy according to this and restrict coverage for Gram-negatives to specific circumstances. This study aimed to analyse the epidemiological changes in CRBSIs over the 1991-2008 period and to analyse predictors of Gram-negative CRBSIs. Patients and methods A prospectively collected cohort of patients with confirmed CRBSIs was analysed. Strains isolated and antimicrobial susceptibility, as well as clinical and demographic variables were recorded. Differences observed during the study period were analysed by means of a ?(2) trend test and factors associated with Gram-negative CRBSIs by means of multivariable analysis. Results Between 1991 and 2008, 1129 episodes of monomicrobial CRBSIs were recorded. There was an increase in the incidence of CRBSIs, from 0.10 (1991-92) to 0.31 (2007-08) episodes/1000 patient-days. A significant increase in the number of Gram-negative strains among the total isolates was also found, from 3 (4.7%) in 1991-92 to 70 (40.23%) in 2007-08, with a parallel decrease in the percentage of Gram-positives. Solid organ transplantation, prior use of penicillins and hospital stay longer than 11 days were independently associated with a significantly higher risk of Gram-negative CRBSIs, while cirrhosis, diabetes and use of quinolones were associated with a higher risk of Gram-positives. Conclusions Gram-negative strains are an increasing cause of CRBSIs, reaching a prevalence of 40% in the 2007-08 period in our hospital. If this trend is confirmed in other centres, a broad-spectrum empirical therapy should be considered in managing these infections.

PMID: 21665905 [PubMed - as supplied by publisher]

Cost-effectiveness analysis of anidulafungin versus fluconazole for the treatment of invasive candidiasis.

J Antimicrob Chemother. 2011 May 30;

Authors: Neoh CF, Liew D, Slavin M, Marriott D, Chen SC, Morrissey O, Stewart K, Kong DC

Background Anidulafungin was found to be non-inferior to and possibly more efficacious than fluconazole for treatment of invasive candidiasis (IC) in a major randomized clinical trial (RCT). There are no data comparing the cost-effectiveness between azoles and echinocandins in treating IC. This economic analysis investigated the cost-effectiveness of anidulafungin compared with fluconazole for treatment of IC in an Australian setting. Methods A decision analytic model was constructed to capture downstream consequences of using either agent for treatment of IC. The main outcomes analysed in the model were treatment success and treatment failure (observed and indeterminate). Outcome probabilities and treatment pathways were derived from a published RCT. Resources used were estimated by an expert panel and cost inputs were derived from the latest Australian resources. The analysis was based on an Australian hospital perspective. Sensitivity analyses were conducted using Monte Carlo simulation. Results Anidulafungin (AU$74?587) had a higher total cost than fluconazole (AU$60?945) per successfully treated patient, primarily due to its higher acquisition cost. Hospitalization was the main cost driver for both comparators. However, when the rates of mortality in both treatment arms were considered, treatment with anidulafungin was expected to save an additional 0.53 life-years, with an incremental cost-effectiveness ratio (ICER) of AU$25?740 per life-years saved, which was below the implicit ICER threshold value for Australia. The results were robust over a wide range of variables. Conclusions This is the first economic evaluation of anidulafungin versus fluconazole in the treatment of IC in Australia. Anidulafungin appears to be a cost-effective option.

PMID: 21628305 [PubMed - as supplied by publisher]

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

J Antimicrob Chemother. 2011 May 17;

Authors: Grenier C, Pépin J, Nault V, Howson J, Fournier X, Poirier MS, Cabana J, Craig C, Beaudoin M, Valiquette L

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 multidrug-resistant (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 2008. 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%); P?=?0.01]. 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 (0.4-0.8); 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; P?=?0.4]. However, 30 day mortality tended to be higher when the empirical treatment was microbiologically ineffective [4/22 (18%) versus 17/187 (9%) when effective; P?=?0.3]. 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.

PMID: 21586592 [PubMed - as supplied by publisher]