Archive for August, 2011

Immune Reconstitution Syndrome and Exacerbation of Infections after Pregnancy

CID Nov.1, 2007  V.45 N.9 P.1192-1199

Nina Singh1,2 and John R. Perfect3

1Veterans Affairs Medical Center, Pittsburgh, Pennsylvania

2University of Pittsburgh, Pittsburgh, Pennsylvania

3Duke University, Durham,  North Carolina


Pregnancy is a state of subtle immunosuppression characterized by physiologic suppression of proinflammatory host responses that are meant to promote embryonic implantation. Rapid reversal of these changes and a rebound of inflammatory responses during the postpartum period can result in quiescent or latent infection manifesting as symptomatic disease. Infections due to several microbial pathogens and noninfectious diseases with an autoimmune basis have been shown to worsen or begin during the postpartum period. Awareness that symptoms resulting from immune reconstitution can occur in any host with a rapidly changing immunologic repertoire, including women in the postpartum phase, is a critical first step in fully understanding this phenomenon. Future studies to discern the precise pathophysiologic basis of immune reconstitution, to identify pregnant women at risk, and to determine markers that may be diagnostically helpful have significant implications for optimizing treatment of these patients.



August 29, 2011 at 6:49 pm Leave a comment

Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011

MMWR Aug.18, 2011 V.60 N.30 P.1128-1132 Early Release

This document provides updated guidance for the use of influenza vaccines in the United States for the 2011–12 influenza season. Vaccination of all persons aged ≥6 months continues to be recommended. Although influenza vaccine strains for the 2011–12 season are unchanged from those for the 2010–11 season, annual vaccination is recommended even for those who received the vaccine for the previous season. For issues related to influenza vaccination that are not addressed in this update, refer to the 2010 ACIP statement on prevention and control of influenza with vaccines and associated updates.

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August 27, 2011 at 9:40 pm Leave a comment

HIV: Just another chronic disease

Cleve Clin J Med 1 August 2010  V.77  N.8  p.489

BRIAN F. MANDELL, MD, PhD, Editor-in-Chief

He was about 30 years old, appearing ill although not gaunt, wearing an oxygen mask and nice pajamas, and breathing hard, in a corner room of the Silverstein Pavilion at theUniversityofPennsylvania. We were on resident morning rounds; it was maybe 1981. His partner was holding his hand; both sets of parents were standing between the bed and the window. We had no clue what was going on, why he had pulmonary hypertension, thrombocytopenia, fevers, and more. We did not know human immunodeficiency virus (HIV), the agent that would shortly be the cause of his death …



August 27, 2011 at 5:26 pm Leave a comment

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

Journal of Antimicrobial Chemotherapy Sept 2011 V.66 N.9 P.1963-1971

Dafna Yahav1,2,*, Adi Lador1,2, Mical Paul2,3 and Leonard Leibovici1,2

1Department of Medicine E, Rabin Medical Center, Beilinson Hospital, Petah-Tiqva, Israel

2Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel

3Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, Petah-Tiqva, Israel



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).


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.


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.


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.


August 27, 2011 at 5:24 pm Leave a comment

Effective antibacterials: at what cost? The economics of antibacterial resistance and its control

Journal of Antimicrobial Chemotherapy Sept 2011 V.66 N.9 P.1948-1953

Anthony R. White* and on behalf of the BSAC Working Party on The Urgent Need: Regenerating Antibacterial Drug Discovery and Development†

Tony White Ltd, Newport, Essex CB11 3RS, UK


The original and successful business model of return on investment being sufficiently attractive to the pharmaceutical industry to encourage development of new antibacterial molecules and related diagnostics has been compromised by increasing development costs and regulatory hurdles, resulting in a decreasing chance of success and financial return. The supply of new effective agents is diminishing along with the number of companies engaged in antibacterial research and development. The BSAC Working Party on The Urgent Need:Regenerating Antibacterial Drug Discovery and Development identified the need to establish, communicate and apply the true health and economic value of antibacterials, along with the adoption of meaningful incentives, as part of the future model for antibacterial development. Robust data are needed on the cost of resistance and ineffective treatment of bacterial infection, along with national and local holistic analyses of the cost–benefit of antibacterials. An understanding of the true health and economic value of antibacterials and the cost of resistance across healthcare systems needs to be generated, communicated and used in order to set a pricing and reimbursement structure that is commensurate with value. The development and economic model of antibacterial use needs to be rebuilt based on this value through dialogue with the various stakeholders, including the pharmaceutical industry, and alternative incentives from ‘push’ to ‘pull’ and funding models, such as public/private partnerships, agreed. A research and development model that succeeds in developing and delivering new antibacterial agents that address the health needs of society from start to finish, ‘from cradle to grave’, must be established.




August 27, 2011 at 5:22 pm Leave a comment

Regulatory opportunities to encourage technology solutions to antibacterial drug resistance

Journal of Antimicrobial Chemotherapy Sept 2011 V.66 N.9 P.1945-1947

Roger Finch* and on behalf of the BSAC Working Party on The Urgent Need: Regenerating Antibacterial Drug Discovery and Development†

Nottingham University Hospitals, Department of Microbiology and Infectious Diseases, The Clinical Sciences Building, Hucknall Road, Nottingham NG5 1PB, UK


Regulatory agencies play a critical role in the licensing of new antimicrobial agents. To address the pivotal role played by regulatory agencies, particularly in the context of a paucity of new drugs active against bacteria resistant to currently available drugs, the BSAC formed the ‘Urgent Need’ Working Party to address the regeneration of antibacterial drug discovery and development. The Working Party identified a number of issues, including: increased application of pharmacokinetic/pharmacodynamic principles to expedite drug development; the need to prioritize licensing of drugs (including ‘orphan’ drugs) active in life-threatening infections; and expansion of the use of surrogate markers and rapid point of care diagnostics to facilitate drug development.




August 27, 2011 at 5:21 pm Leave a comment

Hepatitis B & hepatitis C in HIV-infection.

Indian J Med Res. 2005 Apr  V.121 N.4 P.424-50.

Kottilil S, Jackson JO, Polis MA.

Laboratory of Immunoregulation, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Building 10, Rm. 11N204, 9000 Wisconsin Avenue, Bethesda, MD 20892, USA.


Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) are the three most common chronic viral infections seen in the world. All three viruses share modes of transmission and hence co-exist in the same host at significantly high rates. HIV-induced immunosuppression has deleterious effects on the natural history, pathophysiology, diagnosis, therapeutic responses to hepatitis viruses. Responses to HBV vaccination are impaired in persons with HIV infection. Co-infection with the hepatitis viruses and HIV is likely to become a major health care catastrophe in the coming years. This review discusses the current trends in the understanding of the biology of co-infection and implications for treating these viruses effectively.




August 21, 2011 at 3:11 pm Leave a comment

NIH consensus development statement on management of hepatitis B.

NIH Consens State Sci Statements. 2008 Oct 22-24 V.25 N.2 P.1-29.

Belongia EA, Costa J, Gareen IF, Grem JL, Inadomi JM, Kern ER, McHugh JA, Petersen GM, Rein MF, Sorrell MF, Strader DB, Trotter HT.



To provide health care providers, patients, and the general public with a responsible assessment of currently available data on the management of hepatitis B.


A non-DHHS, nonadvocate 12-member panel representing the fields of hepatology and liver transplantation, gastroenterology, public health and epidemiology, infectious diseases, pathology, oncology, family practice, internal medicine, and a public representative. In addition, 22 experts from pertinent fields presented data to the panel and conference audience.


Presentations by experts and a systematic review of the literature prepared by the Minnesota Evidence-basedPracticeCenter, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience.

CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government.


The most important predictors of cirrhosis or hepatocellular carcinoma in persons who have chronic HBV are persistently elevated HBV DNA and ALT levels in blood. Other risk factors include HBV genotype C infection, male sex, older age, family history of hepatocellular carcinoma, and co-infection with HCV or HIV. The major goals of anti-HBV therapy are to prevent the development of progressive disease, specifically cirrhosis and liver failure, as well as hepatocellular carcinoma development and subsequent death. To date, no RCTs of anti-HBV therapies have demonstrated a beneficial impact on overall mortality, liver-specific mortality, or development of hepatocellular carcinoma. Most published reports of hepatitis therapy use changes in short-term virologic, biochemical, and histologic parameters to infer likelihood of long-term benefit. Approved therapies are associated with improvements in intermediate biomarkers, including HBV DNA, HBeAg loss or seroconversion, decreases in ALT levels, and improvement in liver histology (Table). Although various monitoring practices have been recommended, no clear evidence exists for an optimal approach. The most important research needs include representative prospective cohort studies to define the natural history of the disease and large RCTs of monotherapy and combined therapies, including placebo-controlled trials, that measure the effects on clinical health outcomes. Table. Criteria Useful in Determining for Whom Therapy is Indicated: Patients for whom therapy is indicated: Patients who have acute liver failure, cirrhosis and clinical complications, cirrhosis or advanced fibrosis and HBV DNA in serum, or reactivation of chronic HBV after chemotherapy or immunosuppression; Infants born to women who are HBsAg-positive (immunoglobulin and vaccination). Patients for whom therapy may be indicated: Patients in the immune-active phase who do not have advanced fibrosis or cirrhosis. Patients for whom immediate therapy is not routinely indicated: Patients with chronic hepatitis B in the immune-tolerant phase (with high levels of serum HBV DNA but normal serum ALT levels or little activity on liver biopsy); Patients in the inactive carrier or low replicative phase (with low levels of or no detectable HBV DNA in serum and normal serum ALT levels); Patients who have latent HBV infection (HBV DNA without HBsAg). We recommend routine screening for hepatitis B of newly arrived immigrants to theUnited Statesfrom countries where the HBV prevalence rate is greater than 2%. Screening will facilitate the provision of medical and public health services for infected patients and their families and provide public health data on the burden of disease in immigrant populations. The screening test should not be used to prohibit immigration


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August 21, 2011 at 3:09 pm Leave a comment

Discovery research: the scientific challenge of finding new antibiotics

Journal of Antimicrobial Chemotherapy Sept 2011 V.66 N.9 P.1941-1944

David M. Livermore* and on behalf of the British Society for Antimicrobial Chemotherapy Working Party on The Urgent Need: Regenerating Antibacterial Drug Discovery and Development†

Antibiotic Resistance Monitoring & Reference Laboratory, HPA Microbiology Services – Colindale, 61 Colindale Avenue, London NW9 5EQ, UK


The dwindling supply of new antibiotics largely reflects regulatory and commercial challenges, but also a failure of discovery. In the 1990s the pharmaceutical industry abandoned its classical ways of seeking antibiotics and instead adopted a strategy that combined genomics with high-throughput screening of existing compound libraries. Too much emphasis was placed on identifying targets and molecules that bound to them, and too little emphasis was placed on the ability of these molecules to permeate bacteria, evade efflux and avoid mutational resistance; moreover, the compound libraries were systematically biased against antibiotics. The sorry result is that no antibiotic found by this strategy has yet entered clinical use and many major pharmaceutical companies have abandoned antibiotic discovery. Although a raft of start-up companies—variously financed by venture capital, charity or public money—are now finding new antibiotic compounds (some of them very promising in vitro or in early trials), their development through Phase III depends on financial commitments from large pharmaceutical companies, where the discouraging regulatory environment and the poor likely return on investment remain paramount issues.



August 12, 2011 at 6:32 pm Leave a comment

The urgent need for new antibacterial agents

Journal of Antimicrobial Chemotherapy Sept 2011 V.66 N.9 P.1939-1940

Richard Wise* and on behalf of the BSAC Working Party on The Urgent Need: Regenerating Antibacterial Drug Discovery and Development†

British Society for Antimicrobial Chemotherapy, Griffin House, 53 Regent Place, Birmingham B1 3NJ, UK

I find it continually amazing that society as a whole does not recognize the consequences of rising antimicrobial resistance as the threat it most certainly is. This is not for a lack of sustained activity by those who share these concerns. Far from it. Since 1997 there have been a plethora of enquiries, reports and recommendations—many from important bodies in both Europe andNorth America, yet little meaningful action has materialized. Some might consider this to be rather negative and an overstatement, yet can they point out a concrete outcome to all this activity? . . .



August 12, 2011 at 6:31 pm Leave a comment

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