Risk of prostate cancer across different racial/ethnic groups in men with diabetes: a retrospective cohort study.

AIM: To examine the associations between prostate cancer, diabetes and race/ethnicity. METHODS: Using administrative data from British Columbia, Canada for the period 1994 to 2012, we identified men aged ≥50 years with and without diabetes. Validated surname algorithms identified men as Chinese, Indian or of other race/ethnicity. Multivariable Cox regression was used to estimate adjusted risks of prostate cancer according to diabetes status and race/ethnicity. RESULTS: Our cohort of 160 566 men had a mean (sd) age of 64.7 (9.4) years and a median of 9 years' follow-up. The incidence rates of prostate cancer among those with and without diabetes were 177.4 (171.7-183.4) and 216.0 (209.7-222.5) per 1000 person-years, respectively. The incidence among Chinese men was 120.9 (109.2-133.1), among Indian men it was 144.1 (122.8-169.0) and in men of other ethnicity it was 204.8 (200.2-209.5). Diabetes was independently associated with a lower risk of prostate cancer (adjusted hazard ratio 0.82, 95% CI 0.78-0.86), as was Chinese (adjusted hazard ratio 0.54, 95% CI 0.46,0.63) and Indian (adjusted hazard ratio 0.66, 95% CI 0.49,0.89) race/ethnicity; however, there was no statistically significant interaction between diabetes status and race/ethnicity (all P>0.1). CONCLUSION: Diabetes and Chinese and Indian race/ethnicity were each independently associated with a lower risk of prostate cancer.

Risk factors for pneumococcal endocarditis.

Bacteremia is one of the most common manifestations of invasive pneumococcal disease (IPD). One complication of bacteremia is endocarditis; yet, few studies have evaluated the overall incidence and risk factors for IPD-associated endocarditis. Thus, we evaluated the overall incidence and risk factors of endocarditis compared to those without endocarditis in a large population of IPD patients. We prospectively collected all IPD cases from 2000 to 2014 in Northern Alberta, Canada. Descriptive statistics were used to compare sociodemographic variables, clinical characteristics, and IPD-related outcomes between patients with and without endocarditis. Endocarditis complicated the course of only 28 (0.3%) of 3251 adult patients with IPD. Endocarditis patients were more likely to use illicit drugs and have a higher severity of illness at presentation (i.e., higher rate of altered mental status and rate of intensive care unit [ICU] utilization, p < 0.05); however, no other major risk factors were identified. New murmur development among endocarditis patients was common: 39.3% compared to 2.2% of non-endocarditis patients (p < 0.001). The mortality rate of 39.3% was more than twice that of the rate of 14.7% for the patients with IPD but without endocarditis. There was no pneumococcal serotype predilection for endocarditis. Endocarditis is an uncommon complication of IPD, but, when present, is associated with a significantly increased risk of mortality. Overall, few specific risk factors were identified for IPD-related endocarditis, with the exception of illicit drug use.

Risk of new-onset heart failure in patients using sitagliptin: a population-based cohort study.

AIMS: To examine whether patients using sitagliptin at the time of an acute coronary syndrome event are at increased risk of incident heart failure compared with those not exposed. METHODS: Using US claims data, people with diabetes without a history of heart failure in the 3 years before hospitalization for acute coronary syndrome were identified for the period 2004 to 2010. We used a nested case-control design, whereby cases were patients who developed incident heart failure <30 days after admission to hospital for acute coronary syndrome and were matched by age and sex with up to 10 controls with no heart failure. Subjects exposed or not exposed to sitagliptin in the 90 days before acute coronary syndrome admission were compared using conditional logistic regression after adjustment for clinical and laboratory data, healthcare utilization and propensity scores. RESULTS: In total, 457 cases of heart failure developing de novo after diagnosis of acute coronary syndrome were matched to 4570 controls. The average age of the subjects was 55 years and 65% were male. Overall, 11 of 147 (7%) people exposed to sitagliptin developed heart failure compared with 446 of the 4880 people not exposed (9%, adjusted odds ratio 0.75, 95% CI 0.38-1.46; P=0.40). Sitagliptin exposure before acute coronary syndrome was not associated with an increased risk of death or heart failure combined (7% vs 9%, adjusted odds ratio 0.66, 95% CI 0.34-1.28). CONCLUSIONS: In our sample of patients who are at high risk of heart failure after acute coronary syndrome, sitagliptin exposure was not associated with an increased risk of de novo heart failure.

[Expert recommendations: Hepatitis C and transplantation]. / Empfehlungen zur antiviralen Therapie der chronischen Hepatitis C bei Patienten auf der Warteliste und nach Transplantation.

With the approval of new direct acting antiviral agents (DAA), therapeutic options for patients with chronic hepatitis C virus (HCV) infection are now generally available before and after liver transplantation (LT). Interferon-free DAA regimens are highly effective therapies and provide a good safety profile. However, the body of clinical evidence in this patient population is limited and the best treatment strategies for patients on the waiting list with (de)compensated cirrhosis and after LT are not well defined. The following recommendations for antiviral therapy in the context of LT are based on the currently available literature and clinical experience of experts in the field, and have been discussed in an expert meeting. The aim of this article is to guide clinicians in the decision making when treating patients before and after LT with DAAs.

Cardiovascular safety of sulphonylureas: over 40 years of continuous controversy without an answer.

More than 40 years after publication of the University Group Diabetes Program trial, the cardiovascular safety of sulphonylureas is still contentious. Although several hypotheses linking sulphonylureas to adverse cardiovascular effects exist, none provide conclusive evidence. Adding to the controversy, current clinical trials and observational studies provide inconsistent, and sometimes conflicting, evidence for the cardiovascular effects of sulphonylureas. Overall, observational evidence suggests that an increased risk of adverse cardiovascular outcomes is associated with sulphonylureas; however, these data may be subject to residual confounding and bias. Although evidence from randomized controlled trials has suggested a neutral effect, the majority of these studies were not specifically designed to assess the effect of sulphonylureas on adverse cardiovascular event risk. Current ongoing large clinical trials may provide some clarity on the cardiovascular safety of sulphonylureas, but the results are not expected for several years. With the continued uncertainties concerning the cardiovascular safety of all antidiabetic drugs, a clear answer with regard to sulphonylureas is warranted. The objectives of the present article were to provide an overview of the controversy surrounding sulphonylurea-related cardiovascular effects, to discuss the limitations of the current literature, and to provide recommendations for future studies aiming to elucidate the true relationship between sulphonylureas and adverse cardiovascular effects in people with type 2 diabetes.

Rates and risk factors for recurrent pneumonia in patients hospitalized with community-acquired pneumonia: population-based prospective cohort study with 5 years of follow-up.

BACKGROUND: The rates and risk factors for developing recurrent pneumonia following hospitalization with community-acquired pneumonia (CAP) are poorly understood. METHODS: We examined a population-based cohort of patients with CAP who survived hospital admission and who were free of pneumonia for at least 3 months. We collected clinical, functional, and medication-related information and pneumonia severity index (PSI). Using linked databases we followed patients for 5 years and captured any clinical episode of pneumonia 90 days or more post-discharge. We used Cox proportional hazards models (adjusted for age, sex, PSI, functional status, medications) to determine rates and independent correlates of recurrent pneumonia. RESULTS: The final cohort included 2709 inpatients; 43% were 75 years or older, 34% were not fully independent, and 56% had severe pneumonia. Over 5 years of follow-up, 245 (9%; 95% confidence interval [CI], 8%-10%) patients developed recurrent pneumonia, and 156 (64%) of these episodes required hospitalization. Rate of recurrence was 3.0/100 person-years and median time to recurrence was 317 days (interquartile range, 177-569); 32 (13%) patients had 2 or more recurrences. In multivariable analyses only age >75 years (adjusted P = .047) and less than fully independent functional status (12% recurrence rate with impaired functional status vs 7% for fully independent; adjusted hazard ratio, 1.7; 95% CI, 1.3-2.2; P < .001) were significantly associated with recurrent pneumonia. CONCLUSIONS: One of 11 patients who survived CAP hospitalization had recurrent pneumonia over 5 years and those with impaired functional status were at particularly high risk. Recurrent pneumonia is common and more attention to preventive strategies at discharge and closer follow-up over the long-term seem warranted.

Risk of acute coronary events associated with glyburide compared with gliclazide use in patients with type 2 diabetes: a nested case-control study.

AIM: Sulfonylureas might increase the risk of adverse cardiovascular events; however, emerging evidence suggests there may be important differences amongst these drugs. Some, like glyburide, inhibit KATP channels in the heart and pancreas, while others, like gliclazide, are more likely to selectively inhibit KATP channels in the pancreas. We hypothesized that the risk of acute coronary syndrome (ACS) events would be higher in patients using glyburide compared with gliclazide. METHODS: This nested case-control study used administrative health data from Alberta, Canada. New users of glyburide or gliclazide aged ≥66 years between 1998 and 2010 were included. Cases were individuals with an ACS-related hospitalization or death. Up to four controls were matched based on birth year, sex, cohort-entry year and follow-up time. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (OR), controlling for baseline drug use and co-morbidities. RESULTS: Our cohort included 7441 gliclazide and 13 884 glyburide users; 51.4% men, mean (s.d.) age 75.5 (6.6) years and mean (s.d.) duration of follow-up 5.5 (4.0) years. A total of 4239 patients had an ACS-related hospitalization or death and were matched to 16 723 controls. Compared with gliclazide use, glyburide use was associated with a higher risk (adjusted OR 1.14; 95% CI 1.06-1.23) of ACS-related hospitalization or death over 5.5 years (number needed to harm: 50). CONCLUSION: In this observational study, glyburide use was associated with a 14% higher risk of ACS events compared with gliclazide use. Although the difference is small and probably to have implications at the population level rather than the individual patient or clinician, any causal inferences regarding sulfonylurea use and adverse cardiovascular risk should be tested in a large-scale randomized controlled trial.

Biliary complications after liver transplantation: old problems and new challenges.

Due to a vulnerable blood supply of the bile ducts, biliary complications are a major source of morbidity after liver transplantation (LT). Manifestation is either seen at the anastomotic region or at multiple locations of the donor biliary system, termed as nonanastomotic biliary strictures. Major risk factors include old donor age, marginal grafts and prolonged ischemia time. Moreover, partial LT or living donor liver transplantation (LDLT) and donation after cardiac death (DCD) bear a markedly higher risk of biliary complications. Especially accumulation of several risk factors is critical and should be avoided. Prophylaxis is still a major issue; however no gold standard is established so far, since many risk factors cannot be influenced directly. The diagnostic workup is mostly started with noninvasive imaging studies namely MRI and MRCP, but direct cholangiography still remains the gold standard. Especially nonanastomotic strictures require a multidisciplinary treatment approach. The primary management of anastomotic strictures is mainly interventional. However, surgical revision is finally indicated in a significant number of cases. Using adequate treatment algorithms, a very high success rate can be achieved in anastomotic complications, but in nonanastomotic strictures a relevant number of graft failures are still inevitable.

Randomized controlled trial of high-dose intradermal versus standard-dose intramuscular influenza vaccine in organ transplant recipients.

The immunogenicity of standard intramuscular (IM) influenza vaccine is suboptimal in transplant recipients. Also, recent studies suggest that alloantibody may be upregulated due to vaccination. We evaluated a novel high-dose intradermal (ID) vaccine strategy. In conjunction, we assessed alloimmunity. Transplant recipients were randomized to receive IM or high-dose ID vaccine. Strain-specific serology and HLA alloantibody production was determined pre- and postimmunization. In 212 evaluable patients (105 IM, 107 ID), seroprotection to H1N1, H3N2 and B strains was 70.5%, 63.8% and 52.4% in the IM group, and 71.0%, 70.1%, 63.6% in the ID group (p=ns). Seroconversion to ≥1 antigen was 46.7% and 51.4% in the IM and ID groups respectively (p=0.49). Response was more likely in those≥6 months posttransplant (53.2% vs. 19.2%; p=0.001). Use of mycophenolate mofetil was inversely associated with vaccine response in a dose-dependent manner (p<0.001). Certain organ subgroups had higher response rates for influenza B in the ID vaccine group. Differences in anti-HLA antibody production were detected in only 3/212(1.4%) patients with no clinical consequences. High-dose intradermal vaccine is an alternative to standard vaccine and has potential enhanced immunogenicity in certain subgroups. In this large cohort, we also show that seasonal influenza does not result in significant alloantibody production.

Role of mannose-binding lectin-2 polymorphism in the development of acute cellular rejection after transplantation for hepatitis C virus-induced liver disease.

UNLABELLED: The development of liver and graft disease is suspected to be affected by genetic diversity. Mannose-binding lectin-2 (MBL-2) is an important immunomodulatory factor that is involved in complement activation. The aim of our study was to elucidate the role of MBL-2 genotypes after liver transplantation (LT) for hepatitis C virus (HCV)-induced liver disease regarding the incidence of acute cellular rejection (ACR), graft inflammation, fibrosis development, and antiviral treatment response. METHODS: A group of 149 patients who underwent LT for HCV-induced liver disease were genotyped for MBL-2 (rs7096206; G/C) by TaqMan genotyping assay. We evaluated 518 post-LT protocol biopsies and at least 98 urgent liver biopsies regarding graft fibrosis stages, inflammation grades, and evidence for rejection within MBL-2 genotype groups. RESULT: No association of MBL-2 polymorphisms was observed regarding inflammation, fibrosis, and antiviral treatment outcome. However, the C allele of the MBL-2 gene (P = 0.001) and gender compatibility (P = 0.012) were factors significantly associated with the incidence of ACR. CONCLUSION: MBL-2 polymorphisms and gender are involved in the development of ACR after LT. CC genotype and gender match may be regarded as risk factors for ACR in HCV-positive graft recipients. Further studies are needed to confirm and verify this observation in non-HCV groups as well.

Dysglycaemia and 90 day and 1 year risks of death or readmission in patients hospitalised for community-acquired pneumonia.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether dysglycaemia at admission is associated with adverse events at 90 days or 1 year in a population-based cohort of patients hospitalised with community-acquired pneumonia (CAP). METHODS: Clinical and laboratory data were prospectively collected on all 2,366 adults without diabetes admitted with CAP to six hospitals in Edmonton (AB, Canada) and grouped according to admission glucose: 4.0 to <6.1 mmol/l(n=778, reference group), 6.1 to <7.8 mmol/l (n=924); 7.8 to<11.1 mmol/l (n=535); and 11.1 to 20 mmol/l (n=129). Multivariable Cox models were used to examine the relationship between dysglycaemia and mortality or CAP readmission during follow-up. RESULTS: The mean age was 69 (SD 18) years and 48% of participants were female. Compared with those with glucose <6.1 mmol/l (114 [15%] deaths), no differences in 90 day mortality were observed in the dysglycaemia groups: 143 deaths (15%) in the 6.1-7.8 mmol/l group (adjusted HR [aHR] 0.92, 95% CI 0.72-1.18), 111 deaths (21%) in the 7.8-11.1 mmol/l group (aHR 1.05, 0.81-1.37)and 34 deaths (26%) in the 11.1-20 mmol/l group (aHR 1.30, 0.88-1.93). Similarly, compared with those in the <6.1 mmol/l group (198 [25%] deaths), no difference in 1 year mortality was observed: 233 deaths (25%) in the 6.1 to <7.8 mmol/l group (aHR 0.86, 0.71-1.04), 164 deaths (31%) in the 7.8 to <11.1 mmol/l group (aHR 0.92, 0.75-1.14) and 49 deaths (38%) in the 11.1 to 20 mmol/l group (aHR 1.12, 0.81-1.55). Readmissions for CAP were also similar at 1 year: compared with 10% (70/707) in the 6.1 mmol/l group, the frequencies were 8% (66/842), 9% (45/474) and 10% (11/107) in the 6.1 to <7.8 mmol/l, 7.8 to <11.1 mmol/l, and 11.1 to 20 mmol/l groups, respectively (p>0.05 for all comparisons). CONCLUSIONS/INTERPRETATION: Although previously associated with inpatient morbidity and mortality, admission dysglycaemia was not associated with an increased risk of death or CAP readmission at 90 days or 1 year among those who survived hospitalisation for pneumonia.

Insulin use and increased risk of mortality in type 2 diabetes: a cohort study.

AIM: To compare population-based rates of all-cause and cardiovascular (CV) mortality in newly treated patients with type 2 diabetes according to levels of insulin exposure. METHODS: Using the administrative databases of Saskatchewan Health, 12272 new users of oral antidiabetic therapy were identified between 1991 and 1996 and grouped according to cumulative insulin exposure based on total insulin dispensations per year: no exposure (reference group); low exposure (0 to <3); moderate exposure (3 to <12) and high exposure (> or =12). Time-varying multivariable Cox proportional hazards models were used to examine the relationship between insulin exposure and all-cause, CV-related and non-vascular mortality after adjustment for demographics, medications and comorbidities. RESULTS: Average age was 65 (s.d. 13.9) years, 45% were female, and mean follow-up was 5.1 (s.d. 2.2) years. In total, 1443 (12%) subjects started insulin, and 2681 (22%) deaths occurred. The highest mortality rates were in the high exposure group; 95 deaths/1000 person-years compared with 40 deaths/1000 person-years in the no exposure group [unadjusted hazard ratio (HR): 2.32; 95% confidence interval (CI): 1.96-2.73]. After adjustment, we observed a graded risk of mortality associated with increasing exposure to insulin: low exposure [adjusted HR (aHR): 1.75; 95% CI: 1.24-2.47], moderate exposure (aHR: 2.18; 1.82-2.60) and high exposure (aHR: 2.79; 2.36-3.30); p = 0.005 for trend. Analyses restricted to CV-related (p = 0.042 for trend) and non-vascular (p = 0.004 for trend) mortality showed virtually identical results. CONCLUSIONS: We observed a significant and graded association between mortality risk and insulin exposure level in an inception cohort of patients with type 2 diabetes that persisted despite multivariable adjustment.

Acute Graft Dysfunction 17 Years After Liver Transplant: A Challenging Clinical and Histologic Manifestation of Hepatitis E.

Acute hepatitis E virus infection after liver transplant is a challenging clinical phenomenon. Due to its unspecific clinical and histological presentation, the diagnosis of acute or chronic hepatitis E virus infection can be difficult in unclear cases of elevated liver enzymes. Here, we report the case of a 56-year-old male patient who presented to our center for 17-year follow-up after liver transplant with α1-antitrypsin deficiency. The patient was asymptomatic but had remarkably increased transaminases and cholestasis parameters. Blood levels for immunosuppressives were in the normal range, and cholestasis and deteriorated liver perfusion were excluded by ultrasonographic examination. A liver biopsy was performed that was histologically interpreted as acute cellular rejection grade I. Accordingly, the patient was treated with 5-day high-dose intravenous steroids and increased doses of the maintenance immunosuppressive agents, resulting in the slow normalization of the liver enzymes. Extended laboratory examinations revealed presence of acute hepatitis E virus infection, and a retrospectively immunohistologic staining of the liver biopsy was positive for hepatitis E virus antigen. Acute hepatitis E virus infection can be a reason for acute allograft dysfunction after liver transplant. This differential diagnosis should be kept in mind, especially when graft dysfunction occurs long after transplant.

Metformin and the risk of prostate cancer across racial/ethnic groups: a population-based cohort study.

BACKGROUND: Men with diabetes may have a lower risk of prostate cancer than men without diabetes which may be altered by metformin use or race/ethnicity. METHODS: Using administrative databases, from 1994 to 2012, adult (age⩾50 years) men with diabetes were identified. Metformin exposure was defined as a time-dependent variable, stratified first into any use, and into tertiles of cumulative dose. Surname algorithms identified individuals as Chinese or non-Chinese. Multivariable Cox regression estimated the risk of prostate cancer. RESULTS: The cohort of 80 001 had a mean age of 64 years and median follow-up of 9 years. Chinese users of metformin aged 50-59, 60-69 and ⩾70 had similar risks of prostate cancer as non-users. Non-Chinese users aged 50-59 (adjusted hazards ratio (aHR): 0.86, 0.74 to 1.00) had a decreased risk whereas men aged 60-69 and ⩾70 did not. However, when metformin exposure was stratified into tertiles, there was no association in any strata except non-Chinese men aged 50-59 in the first (aHR: 0.68, 95% confidence interval (CI): 0.55, 0.84), second (aHR: 0.75, 95% CI: 0.61, 0.92) and third (aHR: 0.79, 95% CI: 0.64, 0.96) tertiles of metformin exposure and non-Chinese men aged 60-69 in the first (aHR: 0.81, 95% CI: 0.68, 0.95) tertiles of metformin exposure. CONCLUSIONS: There was no clear association between metformin and risk of prostate cancer in men with diabetes in either race/ethnicity. Our findings suggest a consistent relationship between metformin and prostate cancer across race/ethnicity.

The impact of multimorbidity on short-term events in patients with community-acquired pneumonia: prospective cohort study.

The impact of multimorbidity on patients with community-acquired pneumonia has not been well characterised. Thus, our aim was to explore the relationship between multimorbidity and adverse events within 90 days of discharge. Data were prospectively collected for a population-based cohort of all adults discharged from any of the seven emergency departments (ED) or six hospitals in Edmonton (Alberta, Canada) with community-acquired pneumonia. Multivariable Cox regression models were used to examine the independent association between multimorbidity (defined as two or more chronic conditions) and subsequent 90-day mortality, hospitalisation, or ED visits after treatment of pneumonia. The cohort included 5565 patients, mean age was 57 years (SD 20), 54% were male, and 59% were treated as outpatients; 1602 (29%) patients had multimorbidity. Within 90 days, 255 (5%) patients died, 1205 (22%) were hospitalised, 1280 (23%) died or were hospitalised, and 2049 (37%) were admitted to the ED. The presence of multimorbidity was independently associated with an increased risk of death or hospitalisation within 90 days (37% vs. 17% for those without multimorbidity, adjusted hazard ratio: 1.43, 95% confidence interval: 1.26 to 1.62) as well as ED visits (45% vs. 34%, adjusted hazard ratio: 1.40, 95% confidence interval: 1.26 to 1.56). Multimorbidity was present in one-third of all patients with pneumonia in our study, and it was independently associated with death, hospitalisation, or return to ED within 90 days of discharge. Our findings suggest that multimorbidity is strongly related to prognosis and should be considered when making site-of-care decisions in the ED or deciding upon readiness for discharge.

Recurrent pneumonia: a review with focus on clinical epidemiology and modifiable risk factors in elderly patients.

Community-acquired pneumonia (CAP) is one of the most common reasons for physician visits and hospitalizations in North America. Rates of CAP increase with age and CAP is associated with significant morbidity and mortality, especially in the elderly. Though there is much written about the epidemiology and risk factors of incident (first episode) pneumonia, much less is known about recurrent pneumonia. Rates of recurrent pneumonia within 3-5-years of an episode of CAP are 9-12% with a median time to recurrence of 123-317 days and mortality ranging from 4 to 10%. Age ≥65-years-old and impaired functional status are the only patient characteristics that are independently associated with increased risk of recurrence. In terms of modifiable risk factors, only the use of proton-pump inhibitors and systemic and inhaled corticosteroids have consistently been associated with increased risk of recurrent pneumonia, while angiotensin-converting enzyme (ACE) inhibitors may exert a protective effect. Many chronic medical conditions typically associated with increased incident pneumonia-such as chronic obstructive pulmonary disease (COPD), neurological disease (resulting in dysphagia or silent aspiration), and heart failure-were not associated with increased risk of recurrent pneumonia. However, those who are immune-suppressed (e.g., immunoglobulin deficiencies) may be at increased risk of recurrent pneumonia. In summary, among those who survive an episode of pneumonia, recurrence is not uncommon, particularly in the elderly. Following recovery from an episode of pneumonia, patients should be evaluated for risk factors that would predispose to a second episode including seeking evidence of immunosuppression in younger patients and medication optimization, particularly in the elderly.

Impact of guideline-concordant antibiotics and macrolide/ß-lactam combinations in 3203 patients hospitalized with pneumonia: prospective cohort study.

For patients hospitalized with pneumonia, guidelines provide empirical antibiotic recommendations and some studies suggest that macrolide/ß-lactam combinations are preferable. We hypothesized that guideline-concordant regimens, particularly macrolide/ß-lactams, would reduce mortality and ICU admissions. All patients hospitalized with pneumonia in Edmonton, Alberta, Canada, were managed according to a clinical pathway and enrolled in a population-based registry. Clinical data, Pneumonia Severity Index and treatments were collected. Guideline-concordant regimens were macrolides/ß-lactams or respiratory fluoroquinolone monotherapy. The main outcome was in-hospital mortality. The study included 3203 patients and most had severe pneumonia (63% PSI Class IV-V). Three hundred and twenty-one (10.0%) patients died, 306 (9.6%) were admitted to the ICU and 570 (17.8%) achieved the composite of death or ICU admission. Most (n = 2506) patients received guideline-concordant antibiotics. Receipt of guideline-concordant antibiotics was not associated with a reduction in mortality alone (231 (9.2%) vs. 90 (12.9%); adjusted odds ratio (aOR), 0.82; 95% CI, 0.61-1.09; p 0.16), but was associated with decreased death or ICU admission (14.7% vs. 29.0%; aOR, 0.44; 95% CI, 0.36-0.54; p < 0.0001). Within guideline-concordant subgroups, there was no difference in mortality between macrolide/ß-lactams and respiratory fluoroquinolone monotherapy (22 (8.3%) vs. 209 (9.3%); aOR, 1.09; 95% CI, 0.66-1.81; p 0.73) but macrolide/ß-lactams were associated with increased odds of death or ICU admission (17.4% vs. 14.4%; aOR, 1.58; 95% CI, 1.09-2.27; p 0.01). In conclusion, guideline-concordant antibiotics were not associated with decreased mortality for patients hospitalized with pneumonia, but were associated with a decrease in the composite endpoint of death or ICU admission. Our findings do not support any clinical advantage of macrolide/ß-lactam compared with respiratory fluoroquinolone monotherapy.