Archive for September, 2010

New Delhi metallo-beta-lactamase (NDM-1): towards a new pandemia?

Clinical Microbiology and Infection Sept. 2010

Jean Marc Rolain1,*, Philippe Parola1,2, Giuseppe Cornaglia3

1. URMITE UMR CNRS-IRD 6236, IFR48, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France

2. EuroTravNet, The ECDC collaborative Network for Tropical and Travel Medicine

3. Department of Pathology and Diagnostics, University of Verona, Italy

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September 30, 2010 at 4:03 pm Leave a comment

Current and Potential Usefulness of Pneumococcal Urinary Antigen Detection in Hospitalized Patients With Community-Acquired Pneumonia to Guide Antimicrobial Therapy

Archives of Internal Medicine September 27, 2010

Roger Sordé, MD; Vicenç Falcó, MD; Michael Lowak, MD; Eva Domingo, MD; Adelaida Ferrer, MD; Joaquin Burgos, MD; Mireia Puig, MD; Evelyn Cabral, MD; Oscar Len, MD; Albert Pahissa, MD

Departments of Infectious Diseases (Drs Sordé, Falcó, Burgos, Puig, Cabral, Len, and Pahissa), Microbiology (Drs Lowak and Ferrer), and Emergency Medicine (Dr Domingo), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, and the Spanish Network for Research in Infectious Diseases (REIPI) (Drs Sordé, Cabral, Len, and Pahissa), Spain.


The role of pneumococcal urinary antigen detection in the treatment of adults with community-acquired pneumonia (CAP) is not well defined. We assessed the usefulness of pneumococcal urinary antigen detection in the diagnosis and antimicrobial guidance in patients hospitalized with CAP.


A prospective study of all adults hospitalized with CAP was performed from February 2007 through January 2008. To evaluate the accuracy of the test, we calculated its sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. The gold standard used for diagnosis of pneumococcal pneumonia was isolation in blood or pleural fluid (definite diagnosis) and isolation in sputum (probable diagnosis). Antibiotic modifications, complications, and mortality were analyzed.


A total of 474 episodes of CAP were included. Streptococcus pneumoniae was the causative pathogen in 171 cases (36.1%). It was detected exclusively by urinary antigen test in 75 cases (43.8%). Sixty-nine patients had CAP caused by a pathogen other than S pneumoniae. Specificity was 96%, positive predictive value ranged from 88.8% to 96.5%, and the positive likelihood ratio ranged from 14.6 to 19.9. The results of the test led the clinicians to reduce the spectrum of antibiotics in 41 patients. Pneumonia was cured in all of them. Potentially, this optimization would be possible in the 75 patients diagnosed exclusively by the test.


When its findings are positive, the pneumococcal urinary antigen test is a useful tool in the treatment of hospitalized adult patients with CAP because it may allow the clinician to optimize antimicrobial therapy with good clinical outcomes.


September 30, 2010 at 4:00 pm Leave a comment

The Renaissance in HIV Vaccine Development — Future Directions

New England Journal of Medicine, July 29, 2010 V.363


From July 18 through July 23, 2010, delegates from around the globe will convene for the biennial International AIDS Conference in Vienna. They will discuss our current risk of losing the war against the human immunodeficiency virus (HIV). Despite an unprecedented outpouring of resources and proliferation of programs, today, for every two patients who begin receiving treatment for HIV, five people are newly infected. Furthermore, new guidelines from the World Health Organization recommending that infected persons begin receiving treatment earlier will significantly increase the number of patients targeted for therapy. If we are to control this pandemic, we must recognize the urgent need to develop and deploy better prevention tools and, most important, a safe and effective HIV vaccine….

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September 27, 2010 at 11:52 pm Leave a comment

More Challenges in the Prevention and Management of Community-Associated, Methicillin-Resistant Staphylococcus aureus Skin Disease

Annals Intern Med  17 January 2008


Rachel Gorwitz, Scott K. Fridkin, and Kimberly A. Workowski

From the Centers for Disease Control and Prevention and Emory University, Atlanta, GA 30333.

Staphylococcus aureus is and has long been a common cause of community-associated skin infections, transmitted mainly by close (skin-to-skin) contact. Methicillin-resistant S. aureus (MRSA), previously seen almost exclusively in association with health care, emerged in the 1990s as a cause of community-associated skin infection (1). In the United States, a single pulsed-field gel electrophoresis type, USA300, has caused most community-associated MRSA infections…

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September 27, 2010 at 11:50 pm Leave a comment

Re-treatment of Patients With Chronic Hepatitis C Who Do Not Respond to Peginterferon-{alpha}2b: A Randomized Trial

Ann Intern Med  21 April 2009   V.150  N.8  p.28-54


Donald M. Jensen, Patrick Marcellin, Bradley Freilich, Pietro Andreone, Adrian Di Bisceglie, Carlos E. Brandao-Mello, K. Rajender Reddy, Antonio Craxi, Antonio Olveira Martin, Gerlinde Teuber, Diethelm Messinger, James A. Thommes, and Andreas Tietz

From the Center for Liver Diseases, University of Chicago Hospitals, Chicago, Illinois; Centre de Recherche Biologique Bichat-Beaujon CRB3, Hôpital Beaujon, Clichy, France; Liver and Pancreas Institute of Kansas City, Kansas City, Missouri; University of Bologna, Bologna, Italy; Saint Louis University Liver Center, Saint Louis University School of Medicine, Saint Louis, Missouri; University of Rio de Janeiro, Rio de Janeiro, Brazil; University of Pennsylvania, Philadelphia, Pennsylvania; University of Palermo, Palermo, Italy; Hospital La Paz, Madrid, Spain; J.W. Goethe University Hospital, Frankfurt, Germany; IST, Mannheim, Germany; Roche, Nutley, New Jersey; and Roche, Basel, Switzerland.



Many patients with chronic hepatitis C have not responded to therapy with pegylated interferon plus ribavirin.


To evaluate use of peginterferon-α2a plus ribavirin to re-treat nonresponders to peginterferon-α2b plus ribavirin.


Randomized, parallel-group trial conducted between September 2003 and February 2007. Patients and researchers were not blinded to intervention assignment. Random assignment was centralized, computer-generated, and stratified by geographic region, hepatitis C virus (HCV) genotype, and histologic diagnosis.


106 international centers.


950 nonresponders to 12 or more weeks of therapy with peginterferon-α2b plus ribavirin.


Peginterferon-α2a, 360 µg/wk, for 12 weeks, then 180 µg/wk to complete 72 weeks (group A) or 48 weeks (group B), or peginterferon-α2a, 180 µg/wk for 72 weeks (group C) or 48 weeks (group D). All patients received ribavirin, 1000 or 1200 mg/d.


Sustained virologic response (SVR), defined as undetectable (<50 IU/mL) HCV RNA levels 24 weeks after the end of treatment.


The SVR rates in groups A (n = 317), B (n = 156), C (n = 156), and D (n = 313) were 16%, 7%, 14%, and 9%, respectively (relative risk [RR] for group A vs. group D [the primary comparison], 1.80 [95% CI, 1.17 to 2.77]; P = 0.006). Extended treatment duration increased SVR rates (16% for 72 weeks [groups A and C] vs. 8% for 48 weeks [groups B and D]; RR, 2.00 [CI, 1.32 to 3.02]; P < 0.001). Complete viral suppression (HCV RNA level <50 IU/mL)at week 12 was achieved in 21% of patients in groups A and B and 13% of those in groups C and D. Rates of SVR were 49% (77 of 157 patients) and 4% (32 of 719 patients) among those with and without complete viral suppression at week 12, respectively.


Nonresponders to peginterferon-α2a plus ribavirin were not evaluated.


Re-treating nonresponders to therapy with peginterferon-α2b plus ribavirin for 72 weeks significantly increases SVR rates compared with re-treating them for 48 weeks. The overall SVR rate was low, but patients who are most likely to respond to re-treatment can be identified at week 12.



September 27, 2010 at 11:48 pm Leave a comment

Safety and Efficacy of Extended-Duration Antiviral Chemoprophylaxis Against Pandemic and Seasonal Influenza

Ann Intern Med  6 Oct 2009 V.151 N.7 p.464-473


Nayer Khazeni, Dena M. Bravata, Jon-Erik C. Holty, Timothy M. Uyeki, Christopher D. Stave, and Michael K. Gould

From Stanford University Medical Center, Center for Health Policy and Center for Primary Care and Outcomes Research, Stanford Sleep Disorders Center, and Lane Medical Library, Stanford, California; Centers for Disease Control and Prevention, Atlanta, Georgia; and Veterans Affairs Palo Alto Health Care System, Palo Alto, California.



Neuraminidase inhibitors (NAIs) are stockpiled internationally for extended use in an influenza pandemic.


To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza.

Data Sources

Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries.

Study Selection

Randomized, placebo-controlled, double-blind human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events.

Data Extraction

2 reviewers independently assessed study quality and abstracted information from eligible studies.

Data Synthesis

Of 1876 potentially relevant citations, 7 trials involving 7021 unique participants met inclusion criteria. Data were pooled by using random-effects models. Chemoprophylaxis with NAIs decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], −3.9 percentage points [CI, −5.8 to −1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, −0.4 percentage point [CI, −1.6 to 0.9 percentage point]). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, −0.2 to 0.4 percentage point]), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir.


All trials were industry-sponsored. No study was powered to detect rare adverse events, and none included diverse racial groups, children, immunocompromised patients, or individuals who received live attenuated influenza virus vaccine.


Extended-duration zanamivir and oseltamivir chemoprophylaxis seems to be highly efficacious for preventing symptomatic influenza among immunocompetent white and Japanese adults. Extended-duration oseltamivir is associated with increased nausea and vomiting. Safety and efficacy in several subpopulations that might receive extended-duration influenza chemoprophylaxis are unknown.



September 27, 2010 at 11:46 pm Leave a comment

Cryptosporidiosis: environmental, therapeutic, and preventive challenges

Europ J of Clinical Microb & Infec Dis  August 2010 V.29  N.8  p.927 – 935

 S. Collinet-Adler1, 2, 3  and H. D. Ward1, 2

 (1) Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA, USA

(2) Tufts University, Boston, MA, USA

(3) Tufts Medical Center, Box #41, 800, Washington Street, Boston, MA 02111, USA


Cryptosporidium spp. are responsible for endemic and epidemic disease worldwide. Clinical manifestations may include acute, persistent, or chronic diarrhea, biliary, and pulmonary disease. Disease severity ranges from asymptomatic or mild to severe, intractable diarrhea with wasting depending on immune status, nutrition, and age. Transmission is fecal–oral with both human and animal reservoirs. Disease is often self limited in healthy individuals, but therapy remains a challenge in the immune-compromised. Prevention currently depends on appropriate hygiene and proper water management and treatment.


September 27, 2010 at 11:44 pm Leave a comment

Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study.

Clin Infect Dis. 1 Oct 2010 V.51 N.7  p.855-64.

Puls RL, Srasuebkul P, Petoumenos K, Boesecke C, Duncombe C, Belloso WH, Molina JM, Li L, Avihingsanon A, Gazzard B, Cooper DA, Emery S; Altair Study Group.

Collaborators (129)Belloso WH, Cooper D, Emery S, Gazzard B, Hung CC, Jessen H, Kamarulazaman A, Li L, Li P, Losso M, Sierra-Madero J, Mallon P, Mason B, Molina JM, Petoumenos K, Phanuphak KP, Pollack S, Puls R, Rooney J, Walmsley S, Winston A, Wolff M, Emery S, Puls RL, Boesecke C, Lazovski J, Petoumenos K, Delfino M, Drummond F, rriaga M, Dazo C, Haskelberg H, Srasuebkul P, Courtney-Vega K, Berilazic M, Vulcao A, Merlin K, Belloso WH, Benetucci J, Bittar V, Casiro A, Corral J, David D, Laplume H, Losso M, Lupo S, Angel B, Crinejo A, Daciuk L, Elias C, Sanchez M, Guaragna G, Miglioranza C, Oliva SM, Trape L, Anderson J, Cooper DA, Doong N, Dwyer D, French M, Hoy J, Konecny P, Moore R, Quin J, Pett S, Read T, Rotty J, Street A, Dever R, Edward S, Forsdyke C, Giddings E, Hudson J, Kent H, Macrae K, Magill C, Newell S, Norris R, Piper M, Roney J, Silvers J, Skett J, Gill J, Harris M, Montaner J, Walmsley S, Beckthold B, d’Aquila A, Jahnke N, Northland R, Wolff M, Allendes G, Molina JM, Ferret S, Jessen H, Jessen A, Khaykin P, Stephan C, Mantzsch K, Zedlack C, Li P, Lee MP, Sze-Nga C, Yee CW, Mallon P, Breiden J, O’Connor E, Pollack S, Kedem E, Shpilman R, Kamrulazaman A, Tan M, Sierra-Madero J, Brena R, Ortiz A, Li L, Chia E, Hung CC, Chun Liu W, Avihingsanon A, Duncomb C, Phanuphak P, Pussadee K, Gazzard B, Waters L, Winston A, Collister C, Higgs C, Legg K.

National Centre in HIV Epidemiology and Clinical Research, Faculty of Medicine, University of New South Wales, 45 Beach St, Coogee, New South Wales, Australia, 2034.



Antiretroviral therapy is complicated by drug interactions and contraindications. Novel regimens are needed.


This open label study randomly assigned treatment-naive, human immunodeficiency virus (HIV)-infected subjects to receive tenofovir-emtricitabine with efavirenz (Arm I), with ritonavir-boosted atazanavir (Arm II), or with zidovudine/abacavir (Arm III). Pair-wise comparisons of differences in time-weighted mean change from baseline plasma HIV-RNA to week 48 formed the primary analysis. Treatment arms were noninferior if the upper limit of the 95% confidence interval (CI) was <0.5 log(10) copies/mL. Secondary objectives included virologic, immunologic and safety end points.


The intention-to-treat population comprised 322 patients (Arm I, n = 114; Arm II, n = 105; and Arm III, n = 103). Noninferiority for the primary end point was established. Analysis for superiority showed that Arm III was significantly less potent than Arm I (-0.20 log(10) copies/mL; 95% CI, -0.39 to -0.01 log(10) copies/mL; P = .038). The proportions of patients on each of Arm I (95%) and Arm II (96%) with <200 copies/mL were not different (P = .75), but the percentage of patients in Arm III with <200 copies/mL (82%) was significantly lower (P = .005). CD4+ cell counts did not differ. Serious adverse events were more frequent in Arm III (n = 30) than in Arm I or Arm II (n = 15 for each; P = .062).


A novel quadruple nucleo(t)side combination demonstrated significantly less suppression of HIV replication, compared with the suppression demonstrated by standard antiretroviral therapy regimens, although it did meet the predetermined formal definition of noninferiority. Secondary analyses indicated statistically inferior virologic and safety performance. Efavirenz and ritonavir-boosted atazanavir arms were equivalent in viral suppression and safety.


September 25, 2010 at 3:21 pm Leave a comment

Survival of hepatitis C virus in syringes: implication for transmission among injection drug users.

J Infect Dis. 1 Oct 2010 V.202 N.7  p.984-90.

Paintsil E, He H, Peters C, Lindenbach BD, Heimer R.

Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Comment in:

J Infect Dis. 2010 Oct 1;202(7):981-3.



We hypothesized that the high prevalence of hepatitis C virus (HCV) among injection drug users might be due to prolonged virus survival in contaminated syringes.


We developed a microculture assay to examine the viability of HCV. Syringes were loaded with blood spiked with HCV reporter virus (Jc1/GLuc2A) to simulate 2 scenarios of residual volumes: low void volume (2 microL) for 1-mL insulin syringes and high void volume (32 microL) for 1-mL tuberculin syringes. Syringes were stored at 4 degrees C, 22 degrees C, and 37 degrees C for up to 63 days before testing for HCV infectivity by using luciferase activity.


The virus decay rate was biphasic (t1/2alpha= 0.4 h and t1/2beta = 28 hh). Insulin syringes failed to yield viable HCV beyond day 1 at all storage temperatures except 4 degrees , in which 5% of syringes yielded viable virus on day 7. Tuberculin syringes yielded viable virus from 96%, 71%, and 52% of syringes after storage at 4 degrees, 22 degrees, and 37 degrees for 7 days, respectively, and yielded viable virus up to day 63.


The high prevalence of HCV among injection drug users may be partly due to the resilience of the virus and the syringe type. Our findings may be used to guide prevention strategies.


J Infect Dis. 1 Oct 2010 V.202 N.7  p.981-3.

The beginning of a new era in understanding hepatitis C virus prevention.

Rich JD, Taylor LE.

Comment on:

J Infect Dis. 2010 Oct 1;202(7):984-90.


September 25, 2010 at 3:19 pm Leave a comment

Comparison of Changes in Bone Density and Turnover with Abacavir-Lamivudine versus Tenofovir-Emtricitabine in HIV-Infected Adults: 48-Week Results from the ASSERT Study

Clinical Infectious Diseases 15 Oct 2010 V.51  N.8 p.963–972

 Hans-Jürgen Stellbrink,1 Chloe Orkin,2 Jose Ramon Arribas,6 Juliet Compston,5 Jan Gerstoft,7 Eric Van Wijngaerden,8 Adriano Lazzarin,9 Giuliano Rizzardini,10 Herman G. Sprenger,11 John Lambert,12 Gunta Sture,13 David Leather,3 Sara Hughes,4 Patrizia Zucchi,14 and Helen Pearce,3 on behalf of the ASSERT Study Group

1Infektions Medizinisches Centrum Hamburg Study Center, Hamburg, Germany; 2St Bartholomew’s Hospital, 3GlaxoSmithKline, and 4ViiV Healthcare, London, and 5University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; 6Instituto de Investigacion (IdiPAZ), Hospital La Paz, Madrid, Spain; 7Rigshospitalet, Copenhagen, Denmark; 8UZ Leuven, Leuven, Belgium; 9Ospedale San Raffaele and 10Ospedale Luigi Sacco, Milan, Italy; 11University Medical Center Groningen, Groningen, the Netherlands; 12Mater Misericordiae University Hospital and University College Dublin, Dublin, Ireland; 13Latvijas Infektologijas Centrs, Riga, Latvia; and 14GlaxoSmithKline, Verona, Italy


Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. However, few studies have comprehensively compared their relative safety profiles.


In this European, multicenter, open-label, 96-week study, antiretroviral-naive adult subjects with human immunodeficiency virus (HIV) infection were randomized to receive either abacavir-lamivudine or tenofovir-emtricitabine with efavirenz. Primary analyses were conducted after 48 weeks of treatment. Bone mineral density (BMD), a powered secondary end point, was assessed by dual energy x-ray absorptiometry. Bone turnover markers (osteocalcin, procollagen 1 N-terminal propeptide, bone specific alkaline phosphatase, and type 1 collagen cross-linked C telopeptide [CTx]) were assessed in an exploratory analysis.


A total of 385 subjects were enrolled in the study. BMD loss was observed in both treatment groups, with a significant difference in the change from baseline in both total hip (abacavir-lamivudine group, −1.9%; tenofovir-emtricitabine group, −3.6%;  ) and lumbar spine (abacavir-lamivudine group, −1.6%; tenofovir-emtricitabine group, −2.4%;  ). BMD loss of 6% was more common in the tenofovir-emtricitabine group (13% of the tenofovir-emtricitabine group vs 3% of the abacavir-lamivudine group had a loss of 6% in the hip; 15% vs 5% had a loss of 6% in the spine). Bone turnover markers increased in both treatment groups over the first 24 weeks, stabilizing or decreasing thereafter. Increases in all markers were significantly greater in the tenofovir-emtricitabine treatment group than in the abacavir-lamivudine group at week 24. All but CTx remained significantly different at week 48 (eg, osteocalcin: abacavir-lamivudine group, +8.07 mg/L; tenofovir-emtricitabine group, +11.92 mg/L;  ).


This study demonstrated the impact of first-line treatment regimens on bone. Greater increases in bone turnover and decreases in BMD were observed in subjects treated with tenofovir-emtricitabine than were observed in subjects treated with abacavir-lamivudine.





Low Bone Mineral Density with Tenofovir: Does Statistically Significant Mean Clinically Significant?

Andrew Carr1 and  Jennifer Hoy2

1HIV, Immunology and Infectious Diseases Unit and Centre for Applied Medical Research, St Vincent’s Hospital, University of New South Wales, Sydney, and 2Infectious Diseases Unit, Alfred Hospital and Monash University, Melbourne, Australia



September 24, 2010 at 11:34 am Leave a comment

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