Archive for November, 2010

Vital Signs: HIV Testing and Diagnosis Among Adults — United States, 2001–2009

MMWR  Nov 30, 2010  V.59   Early Release

IV testing and linkage to care are essential to identify persons early in their course of infection to prevent progression to AIDS and death and to reduce transmission. CDC used 2001–2009 data from the National Health Interview Survey to estimate percentages of persons aged 18–64 years who reported ever being tested for HIV in the United States. The results of that analysis indicate that the number of persons in the United States who report ever being tested for HIV is increasing, and fewer persons are being diagnosed late in their infection. However, nearly one third of diagnoses still occur late. Increased testing efforts are needed, particularly among populations that account for most HIV diagnoses.

Full Text


November 30, 2010 at 5:57 pm Leave a comment

Influenza Vaccine — Safe, Effective, and Mistrusted

N Engl J of Med Nov.25, 2010


Katherine M. Harris, Ph.D., Jürgen Maurer, Ph.D., and Arthur L. Kellermann, M.D., M.P.H.

On August 10, 2010, the World Health Organization (WHO) declared an end to the 2009 influenza A (H1N1) pandemic. It is fortunate that the virus that had spread worldwide so quickly turned out to be less severe than was first feared. It is worth remembering, though, that an earlier strain of H1N1 influenza — the one that emerged in 1918 — sparked the worst closely observed and recorded pandemic in history, killing an estimated 20 million to 40 million people worldwide.

The 2009 H1N1 virus did give us one gift of inestimable value: it provided a full-scale test of the ability of the United States to counter pandemic influenza. If we draw the right lessons from the response, we can considerably strengthen our country’s public health preparedness….



November 26, 2010 at 3:40 pm Leave a comment

A new option for complicated skin and skin structure infections: experience with ceftaroline

Journal of Antimicrobial Chemotherapy November 2010  V.65 Suppl 4


Full Text



The problem of complicated skin and skin structure infections: the need for new agents

Robert C. Moellering Jr

Harvard Medical School and Department of Medicine, Beth Israel Deaconess Medical Center, 110 Francis Street, Suite 6A, Boston, MA 02215, USA

Complicated skin and skin structure infections (cSSSIs) continue to pose a significant clinical challenge. The most frequent cause of these infections is Staphylococcus aureus, although other organisms, including Streptococcus pyogenes and, in certain circumstances, Enterobacteriaceae, are also involved. The relentless increase in methicillin resistance among S. aureus isolated in hospitals throughout the world has made it important to provide coverage for these organisms when treating cSSSIs in hospitals. More recently, however, there has been a striking increase in methicillin resistance among staphylococci isolated from infections acquired in the community, particularly in the USA. As a result, previous recommendations for empirical therapy of these important infections are now outdated. The papers in this Supplement detail the properties of a new broad-spectrum cephalosporin that has activity against MRSA and is, thus, an outstanding candidate for empirical therapy of cSSSIs. The papers included provide data on the in vitro activity, pharmacokinetics and pharmacodynamics as well as the clinical efficacy of ceftaroline fosamil, which is a welcome addition to our therapeutic armamentarium against cSSSIs.



Ceftaroline fosamil: a novel broad-spectrum cephalosporin with expanded anti-Gram-positive activity

Donald Biek1,*, Ian A. Critchley1, Todd A. Riccobene2 and Dirk A. Thye1 

1Cerexa, Inc., 2100 Franklin St, Ste 900, Oakland, CA 94612, USA

2Forest Research Institute, Inc., Jersey City, NJ 07311, USA

Ceftaroline fosamil is a novel cephalosporin with broad-spectrum activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae, and common Gram-negative organisms. The activity of ceftaroline against MRSA is attributed to its ability to bind to penicillin-binding protein (PBP) 2a with high affinity and inhibit the biochemical activity of PBP 2a more efficiently than other presently available β-lactams. The activity of ceftaroline against MRSA and the β-haemolytic streptococci makes it an attractive monotherapy agent for the treatment of complicated skin and skin structure infections (cSSSIs). Recent profiling and surveillance studies have shown that ceftaroline is active against contemporary skin pathogens collected from US and European medical centres in 2008. The mean free drug %T > MIC (percentage of time the drug concentration remains above the MIC) needed for stasis ranged from 26% for S. aureus to 39% for S. pneumoniae in the murine thigh infection model. Pharmacokinetic and pharmacodynamic target attainment predictions for 600 mg of ceftaroline fosamil every 12 h showed that the mean %T > MICs for which plasma free-drug concentrations exceeded an MIC of 1 and 2 mg/L were 71% and 51% of the dosing interval, respectively. For a 40% T > MIC target, the predicted attainments for infections due to pathogens for which ceftaroline MICs were 1 or 2 mg/L were 100% and 90%, respectively. Clinical and microbiological successes of ceftaroline fosamil in treating cSSSIs were demonstrated in two Phase III clinical studies, in which 96.8% of all baseline cSSSI isolates from the microbiologically evaluable population were inhibited by ceftaroline at ≤2 mg/L. Ceftaroline fosamil is a promising broad-spectrum agent for the treatment of cSSSIs.



Ceftaroline activity against pathogens associated with complicated skin and skin structure infections: results from an international surveillance study

Ronald N. Jones1,2,*, Rodrigo E. Mendes1 and Helio S. Sader1

1JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA

2Tufts University School of Medicine, Boston, MA 02111, USA


To assess the spectrum and potency of ceftaroline, a novel anti-methicillin-resistant staphylococcal cephalosporin, against a 2008 surveillance collection of clinical isolates from patients in the USA and Europe.


A collection of 14 169 isolates of various bacterial species from complicated skin and skin structure infections (cSSSIs) was tested for susceptibility to ceftaroline and 19 comparator agents in a central reference laboratory using CLSI broth microdilution methods. Organisms were received from 55 medical centres; 27 in the USA and 28 in Europe (12 countries, including Israel). The clonality of isolates of Staphylococcus aureus with elevated ceftaroline MICs (4 mg/L) was determined by PFGE and single and multilocus sequence typing, and the mechanism of ceftaroline non-susceptibility was assessed by molecular methods (PCR amplification and sequencing).


Ceftaroline, the active component of the parenteral prodrug ceftaroline fosamil, was active against 2988 methicillin-resistant S. aureus (MRSA) isolates, with an MIC90 of 1 mg/L. The MIC90 for methicillin-susceptible strains was 0.25–0.5 mg/L. Ceftaroline was additionally active against coagulase-negative staphylococci (MIC90, 0.5–1 mg/L), Enterococcus faecalis (MIC50, 2 mg/L), β-haemolytic and viridans group streptococci (MIC90, 0.015–0.25 mg/L) and three commonly isolated Enterobacteriaceae (Escherichia coli, Klebsiella spp. and Proteus mirabilis; MIC90 values of 0.25 to >16 mg/L). All but four isolates of MRSA (0.13%) had ceftaroline MIC values of ≤2 mg/L. The isolates for which ceftaroline MICs were 4 mg/L were clonal (single Greek hospital) and had detectable mecA mutations (N146K, N204K, E150K and H351N).


The ceftaroline yearly (2008) surveillance for the USA and Europe documented low MIC50/90 values for MRSA isolates at 1/1 and 1/2 mg/L, respectively. Ceftaroline demonstrated promising potency and coverage against Gram-positive and -negative pathogens known to cause cSSSIs, including MRSA and β-haemolytic streptococci.



Pharmacodynamics of ceftaroline fosamil for complicated skin and skin structure infection: rationale for improved anti-methicillin-resistant Staphylococcus aureus activity

George L. Drusano

Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12208, USA

Ceftaroline fosamil is a new β-lactam antibiotic with an altered 3′ side chain that allows it to interact with penicillin-binding protein (PBP) 2a, resulting in lower MIC values for methicillin-resistant Staphylococcus aureus (MRSA). Large MRSA collections repeatedly demonstrate MIC90 values of 1 mg/L. The pharmacokinetics for ceftaroline fosamil are straightforward and reminiscent of many other cephalosporin antibiotics, with a terminal half-life of ∼2.6 h. Pharmacodynamic evaluation demonstrates that relatively short free drug T > MIC results in stasis or 1 log10 cfu/g bacterial kill (mean values for four S. aureus isolates of 26% and 33% of the dosing interval, respectively). Monte Carlo simulation demonstrated high expected target attainment rates (>97%) and clinical trial data showed clinically evaluable and microbiologically evaluable cure rates (96.7%) that are highly concordant with the pharmacodynamic analyses. Clinical trial data for ceftaroline fosamil are in excellent concordance with the pharmacodynamic analysis. Ceftaroline fosamil at a dose of 600 mg administered intravenously every 12 h is highly likely to be successful in clinical practice for treatment of complicated skin and skin structure infections.



– – –

November 26, 2010 at 12:11 pm Leave a comment

Clinical Management of Pandemic 2009 Influenza A(H1N1) Infection

Chest April 2010; Vol. 137, No. 4 p.916-925

David S. Hui, MD, FCCP, Nelson Lee, MD and Paul K. S. Chan, MD

From the Department of Medicine and Therapeutics (Drs Hui and Lee), the Stanley Ho Center for Emerging Infectious Diseases, School of Public Health & Primary Care (Drs Hui, Lee, and Chan), and the Department of Microbiology (Dr Chan), The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.


Antiviral therapy and vaccination are important strategies for controlling pandemic 2009 influenza A(H1N1) but efficacy depends on the timing of administration and is often limited by supply shortage. Patients with dyspnea, tachypnea, evidence of hypoxemia, and pulmonary infiltrates on chest radiograph should be hospitalized. Patients with severe illness or underlying medical conditions that increase the risk of more severe disease should be treated with oseltamivir or zanamivir as soon as possible, without waiting for the results of laboratory tests. Lung-protective ventilation strategy with a low tidal volume and adequate pressure, in addition to a conservative fluid management approach, is recommended when treating adult patients with ARDS. Extracorporeal membrane oxygenation has emerged as an important rescue therapy for critically ill patients. Use of systemic steroids was associated with delayed viral clearance in severe acute respiratory syndrome and H3N2 infection. Low-dose corticosteroids may be considered in the treatment of refractory septic shock. Passive immunotherapy in the form of convalescent plasma or hyperimmune globulin may be explored as rescue therapy. More data are needed to explore the potential role of IV gamma globulin and other drugs with immunomodulating properties, such as statins, gemfibrozil, and N-acetyl-cysteine. Health-care workers must apply strict standard and droplet precautions when dealing with suspected and confirmed case and upgrade to airborne precautions when performing aerosol-generating procedures. Nonpharmacologic measures, such as early case isolation, household quarantine, school/workplace closure, good community hygiene, and restrictions on travel are useful measures in controlling an influenza pandemic at its early phase.



November 24, 2010 at 4:32 pm Leave a comment

HIV-1 Protease Mutations and Protease Inhibitor Cross-Resistance

Antimicrob. Agents Chemother. 1 Oct 2010 V.54 N.10 p.4253-4261

Soo-Yon Rhee,1* Jonathan Taylor,2 W. Jeffrey Fessel,3 David Kaufman,4 William Towner,5 Paolo Troia,6 Peter Ruane,7 James Hellinger,8 Vivian Shirvani,9 Andrew Zolopa,1 and Robert W. Shafer1

Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California,1 Department of Statistics, Stanford University, Stanford, California,2 Kaiser Permanente Medical Care Program-Northern California, San Francisco, California,3 St. Vincent’s Medical Center, New York, New York,4 Department of Infectious Diseases, Kaiser Permanente Los Angeles, Los Angeles, California,5 Division of Infectious and Immunologic Diseases, University of California Davis Medical Center, Sacramento, California,6 Light Source Medical, Los Angeles, California,7 Division of Infectious Diseases, Department of Medicine, Tufts Medical Center, Boston, Massachusetts,8 Cedars-Sinai Hospital, University of California, Los Angeles, California9

The effects of many protease inhibitor (PI)-selected mutations on the susceptibility to individual PIs are unknown. We analyzed in vitro susceptibility test results on 2,725 HIV-1 protease isolates. More than 2,400 isolates had been tested for susceptibility to fosamprenavir, indinavir, nelfinavir, and saquinavir; 2,130 isolates had been tested for susceptibility to lopinavir; 1,644 isolates had been tested for susceptibility to atazanavir; 1,265 isolates had been tested for susceptibility to tipranavir; and 642 isolates had been tested for susceptibility to darunavir. We applied least-angle regression (LARS) to the 200 most common mutations in the data set and identified a set of 46 mutations associated with decreased PI susceptibility of which 40 were not polymorphic in the eight most common HIV-1 group M subtypes. We then used least-squares regression to ascertain the relative contribution of each of these 46 mutations. The median number of mutations associated with decreased susceptibility to each PI was 28 (range, 19 to 32), and the median number of mutations associated with increased susceptibility to each PI was 2.5 (range, 1 to 8). Of the mutations with the greatest effect on PI susceptibility, I84AV was associated with decreased susceptibility to eight PIs; V32I, G48V, I54ALMSTV, V82F, and L90M were associated with decreased susceptibility to six to seven PIs; I47A, G48M, I50V, L76V, V82ST, and N88S were associated with decreased susceptibility to four to five PIs; and D30N, I50L, and V82AL were associated with decreased susceptibility to fewer than four PIs. This study underscores the greater impact of nonpolymorphic mutations compared with polymorphic mutations on decreased PI susceptibility and provides a comprehensive quantitative assessment of the effects of individual mutations on susceptibility to the eight clinically available PIs.



November 24, 2010 at 4:31 pm Leave a comment

Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men

N Engl J of Medicine Nov.23, 2010

Robert M. Grant, M.D., M.P.H., Javier R. Lama, M.D., M.P.H., Peter L. Anderson, Pharm.D., Vanessa McMahan, B.S., Albert Y. Liu, M.D., M.P.H., Lorena Vargas, Pedro Goicochea, M.Sc., Martín Casapía, M.D., M.P.H., Juan Vicente Guanira-Carranza, M.D., M.P.H., Maria E. Ramirez-Cardich, M.D., Orlando Montoya-Herrera, M.Sc., Telmo Fernández, M.D., Valdilea G. Veloso, M.D., Ph.D., Susan P. Buchbinder, M.D., Suwat Chariyalertsak, M.D., Dr.P.H., Mauro Schechter, M.D., Ph.D., Linda-Gail Bekker, M.B., Ch.B., Ph.D., Kenneth H. Mayer, M.D., Esper Georges Kallás, M.D., Ph.D., K. Rivet Amico, Ph.D., Kathleen Mulligan, Ph.D., Lane R. Bushman, B.Chem., Robert J. Hance, A.A., Carmela Ganoza, M.D., Patricia Defechereux, Ph.D., Brian Postle, B.S., Furong Wang, M.D., J. Jeff McConnell, M.A., Jia-Hua Zheng, Ph.D., Jeanny Lee, B.S., James F. Rooney, M.D., Howard S. Jaffe, M.D., Ana I. Martinez, R.Ph., David N. Burns, M.D., M.P.H., and David V. Glidden, Ph.D. for the iPrEx Study Team


Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition.


We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC–TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections.


The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57).


Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; number, NCT00458393.)

Full Text



Oral Preexposure Prophylaxis for HIV — Another Arrow in the Quiver?

Nelson L. Michael, M.D., Ph.D.

Despite the growing global access to life-extending antiretroviral drugs for the more than 33 million persons living with human immunodeficiency virus (HIV) infection, approximately 7000 new infections occur daily. This alarming number speaks to the critical need for effective approaches to HIV prevention. Early approaches to prevention were limited to the consistent use of barrier methods during sex, a reduction in the prevalence of HIV in the blood supply, behavior modification, postexposure prophylaxis, and awareness of HIV-infection status. Antiretroviral drugs that were provided to pregnant women with HIV infection were shown to dramatically reduce the risk of perinatal transmission, with added protection to treated breast-fed infants of HIV-infected mothers. A single study suggested that treatment of intercurrent sexually transmitted infections could decrease the susceptibility to HIV

Full Text


November 23, 2010 at 6:39 pm Leave a comment

Staphylococcus epidermidis: A possible role in the pustules of rosacea

Journal of the American Academy of Dermatology 12/Oct/2010

Margot Whitfeld FACD, MBBSa, b, , , Nishmi Gunasingam MBBSa, Liang Joo Leow MBBSc, Kyoko Shirato MBBSd and Veronica Preda MBBS BSc (Hons)a, b

a Department of Dermatology, St Vincent’s Hospital, Darlinghurst, Sydney, Australia

b Skin and Cancer Foundation of Australia, Darlinghurst, Sydney, Australia

c Peter McCallum Institute Melbourne, Australia

d Royal Adelaide Hospital, Adelaide, Australia


Rosacea is a common skin and ocular disease. Cutaneous rosacea is characterized by facial flushing, telangiectasia, papules, and pustules. It is generally regarded as inflammatory in nature. We believed that the role of bacteria as a contributory factor in pustular and ocular rosacea needed to be revisited.


We sought to ascertain whether there is an increase in the bacteria isolated from the (1) pustules of rosacea; and (2) eyelid margins of persons with cutaneous pustular rosacea.


Bacterial swabs were taken and cultured from an incised rosacea pustule, the ipsilateral cheek skin, and the eyelid margin of 15 patients with pustular rosacea. Swabs were also taken from the cheek skin and ipsilateral eyelid margin of 15 matched control subjects.


A pure growth of Staphylococcus epidermidis was isolated from a pustule of 9 of 15 patients with pustular rosacea, and no pure growth of S epidermidis was isolated from their ipsilateral cheek skin. This was a highly statistically significant increase (P = .0003). A pure growth of S epidermidis was isolated from the eyelid margins of 4 of 15 patients with pustular rosacea, and no pure growth was isolated from the eyelids of age- and sex-matched control subjects. This was a statistically significant increase (P = .05).


This study focuses on the microbial basis of rosacea.


Our findings suggest S epidermidis may play a role in pustular and ocular rosacea.


November 23, 2010 at 12:12 am Leave a comment

Older Posts


November 2010

Posts by Month

Posts by Category