Archive for June 13, 2011

Hepatic safety of antibiotics used in primary care

Journal of Antimicrobial Chemotherapy July 2011 V.66 N.7 P.1431-1446

Raúl J. Andrade1,2 and Paul M. Tulkens3,4,*

1Hepatology Unit, Gastroenterology Service, Virgen de la Victoria University Hospital Department of Medicine, University of Málaga, Spain

2Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Barcelona, Spain

3Cellular and Molecular Pharmacology & Centre for Clinical Pharmacy, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium

4Human Biochemistry and Biochemical Pathology, Université de Mons, Belgium


Antibiotics used by general practitioners frequently appear in adverse-event reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse reaction cannot be predicted from the drug’s pharmacological profile or from pre-clinical toxicology tests) and occur via an immunological reaction or in response to the presence of hepatotoxic metabolites. With the exception of trovafloxacin and telithromycin (now severely restricted), hepatotoxicity crude incidence remains globally low but variable. Thus, amoxicillin/clavulanate and co-trimoxazole, as well as flucloxacillin, cause hepatotoxic reactions at rates that make them visible in general practice (cases are often isolated, may have a delayed onset, sometimes appear only after cessation of therapy and can produce an array of hepatic lesions that mirror hepatobiliary disease, making causality often difficult to establish). Conversely, hepatotoxic reactions related to macrolides, tetracyclines and fluoroquinolones (in that order, from high to low) are much rarer, and are identifiable only through large-scale studies or worldwide pharmacovigilance reporting. For antibiotics specifically used for tuberculosis, adverse effects range from asymptomatic increases in liver enzymes to acute hepatitis and fulminant hepatic failure. Yet, it is difficult to single out individual drugs, as treatment always entails associations. Patients at risk are mainly those with previous experience of hepatotoxic reaction to antibiotics, the aged or those with impaired hepatic function in the absence of close monitoring, making it important to carefully balance potential risks with expected benefits in primary care. Pharmacogenetic testing using the new genome-wide association studies approach holds promise for better understanding the mechanism(s) underlying hepatotoxicity.



June 13, 2011 at 5:56 pm Leave a comment

Not Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA)! A Clinician’s Guide to Community MRSA – Its Evolving Antimicrobial Resistance and Implications for Therapy

Clin Inf Dis 1 January 2011 V.52 N.1 P.99-101

George M. Eliopoulous, Section Editor

1Infectious Diseases

2Microbiology Departments, Austin Health, Heidelberg

3Department of Microbiology, Monash University, Clayton

4Department of Microbiology and Infectious Diseases, PathWest Laboratory Medicine–WA Royal Perth Hospital, Perth, and Departments of


6Microbiology and Immunology, University of Melbourne, Parkville, Australia

7French National Reference Centre for Staphylococci, Inserm U 851, Hospices Civils de Lyon, University of Lyon, Lyon, France


There is significant diversity in methicillin-resistant Staphylococcus aureus (MRSA) clones arising in the community worldwide, with considerable geographical differences in typical antimicrobial resistance profiles. Many community clones of MRSA have a non–multidrug resistant antimicrobial profile, providing increased options for empirical and directed therapy of infections caused by these strains. However, the recent description of increasing non–β lactam resistance in community clones of MRSA, especially USA300, provides a timely warning for clinicians making decisions about therapy for patients potentially infected with these strains. Continued monitoring of global epidemiology and emerging drug resistance data is critical for the effective management of these infections.


June 13, 2011 at 12:13 pm Leave a comment

Procalcitonin and C-Reactive Protein in Hospitalized Adult Patients With Community-Acquired Pneumonia or Exacerbation of Asthma or COPD

Chest June 2011 V.139 N.6  P.1410-1418

Mona Bafadhel, Tristan W. Clark, Carlene Reid, Marie-jo Medina, Sally Batham, Michael R. Barer, Karl G. Nicholson, and Christopher E. Brightling

From the Institute for Lung Health (Drs Bafadhel and Brightling and Ms Reid), and the Department of Infection, Immunity, and Inflammation (Drs Bafadhel, Barer, Nicholson, and Brightling and Mss Medina and Batham), University of Leicester; and the Department of Infectious Disease (Drs Clark and Nicholson and Ms Batham), University Hospitals of Leicester NHS Trust, Leicester, England.



Antibiotic overuse in respiratory illness is common and is associated with drug resistance and hospital-acquired infection. Biomarkers that can identify bacterial infections may reduce antibiotic prescription. We aimed to compare the usefulness of the biomarkers procalcitonin and C-reactive protein (CRP) in patients with pneumonia or exacerbations of asthma or COPD.


Patients with a diagnosis of community-acquired pneumonia or exacerbation of asthma or COPD were recruited during the winter months of 2006 to 2008. Demographics, clinical data, and blood samples were collected. Procalcitonin and CRP concentrations were measured from available sera.


Sixty-two patients with pneumonia, 96 with asthma, and 161 with COPD were studied. Serum procalcitonin and CRP concentrations were strongly correlated (Spearman rank correlation coefficient [rs] = 0.56, P < .001). Patients with pneumonia had increased procalcitonin and CRP levels (median [interquartile range] 1.27 ng/mL [2.36], 191 mg/L [159]) compared with those with asthma (0.03 ng/mL [0.04], 9 mg/L [21]) and COPD (0.05 ng/mL [0.06], 16 mg/L [34]). The area under the receiver operating characteristic curve (95% CI) for distinguishing between patients with pneumonia (antibiotics required) and exacerbations of asthma (antibiotics not required), for procalcitonin and CRP was 0.93 (0.88-0.98) and 0.96 (0.93-1.00). A CRP value > 48 mg/L had a sensitivity of 91% (95% CI, 80%-97%) and specificity of 93% (95% CI, 86%-98%) for identifying patients with pneumonia.


Procalcitonin and CRP levels can both independently distinguish pneumonia from exacerbations of asthma. CRP levels could be used to guide antibiotic therapy and reduce antibiotic overuse in hospitalized patients with acute respiratory illness.


June 13, 2011 at 12:11 pm Leave a comment

Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial

LANCET June 11, 2011 V.377 N.9782  P.2023 – 2030

Sabine CA Meijvis, Hans Hardeman, Hilde HF Remmelts, Rik Heijligenberg, Ger T Rijkers, Heleen van Velzen-Blad, G Paul Voorn, Ewoudt MW van de Garde, Henrik Endeman, Jan C Grutters, Willem Jan W Bos, Douwe H Biesma 



Whether addition of corticosteroids to antibiotic treatment benefits patients with community-acquired pneumonia who are not in intensive care units is unclear. We aimed to assess effect of addition of dexamethasone on length of stay in this group, which might result in earlier resolution of pneumonia through dampening of systemic inflammation.


In our double-blind, placebo-controlled trial, we randomly assigned adults aged 18 years or older with confirmed community-acquired pneumonia who presented to emergency departments of two teaching hospitals in the Netherlands to receive intravenous dexamethasone (5 mg once a day) or placebo for 4 days from admission. Patients were ineligible if they were immunocompromised, needed immediate transfer to an intensive-care unit, or were already receiving corticosteroids or immunosuppressive drugs. We randomly allocated patients on a one-to-one basis to treatment groups with a computerised randomisation allocation sequence in blocks of 20. The primary outcome was length of hospital stay in all enrolled patients. This study is registered with, number NCT00471640.


Between November, 2007, and September, 2010, we enrolled 304 patients and randomly allocated 153 to the placebo group and 151 to the dexamethasone group. 143 (47%) of 304 enrolled patients had pneumonia of pneumonia severity index class 4—5 (79 [52%] patients in the dexamethasone group and 64 [42%] controls). Median length of stay was 6·5 days (IQR 5·0—9·0) in the dexamethasone group compared with 7·5 days (5·3—11·5) in the placebo group (95% CI of difference in medians 0—2 days; p=0·0480). In-hospital mortality and severe adverse events were infrequent and rates did not differ between groups, although 67 (44%) of 151 patients in the dexamethasone group had hyperglycaemia compared with 35 (23%) of 153 controls (p<0·0001).


Dexamethasone can reduce length of hospital stay when added to antibiotic treatment in non-immunocompromised patients with community-acquired pneumonia.


June 13, 2011 at 12:09 pm Leave a comment


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