Archive for February, 2009

Marked increase in the incidence of invasive anal cancer among HIV-infected patients despite treatment with combination antiretroviral therapy

AIDS June 19, 2008 V.22 N.10 p.1203-1211

Piketty, Christophea; Selinger-Leneman, Hanab,c; Grabar, Sophieb,c,d; Duvivier, Claudineb,c,e; Bonmarchand, Manuelaf; Abramowitz, Laurentg; Costagliola, Dominiqueb,c; Mary-Krause, Murielleb,c; on behalf of the FHDH-ANRS CO 4

From the aAP-HP, Department of Clinical Immunology, Georges Pompidou European Hospital, René Descartes University, Paris, France

bINSERM U720, Paris, France

cPierre et Marie Curie University, UMR S720, Paris, France

dAP-HP, Department of Biostatistics, Cochin Hospital, René Descartes University, Paris, France

eAP-HP, Department of Infectious Diseases, Pitié Salpétrière Hospital, Paris, France

fAP-HP, Department of Internal Medicine, Pitié-Salpétrière Hospital, Paris, France

gAP-HP, Department of Gastroenterology and Proctology, Bichat-Claude Bernard Hospital, Paris, France.

Objective: To describe the cases of anal cancer that appeared in the French Hospital Database on HIV between 1992 and 2004 and to study risk factors of anal cancer.

Methods: We examined the incidence rates of anal cancer between 1992 and 2004 and the risk associated among 86 322 HIV-infected patients included in the French Hospital Database on HIV.

Results: We identified 132 cases of anal cancer, including 124 cases in men (94%), of whom 75% had sex with men. Median age at diagnosis was 42.8 years (interquartile range: 36.9-49.4). At diagnosis, 103 patients (78%) were receiving combination antiretroviral therapy for a median of 37.1 months (interquartile range: 4.5-59.8). Median survival after anal cancer diagnosis was 5 years. The respective overall incidence rates of anal cancer per 100 000 person-years between 1992 and March 1996, April 1996 to 1998 and between 1999 and 2004 were 11 (95% confidence interval, 4-17), 18 (95% confidence interval, 10-27) and 40 (95% confidence interval, 32-47). The risk of anal cancer was higher among men who have sex with men. After adjustment for age at inclusion in the study, as well as gender, the HIV transmission group, the nadir CD4 cell count and AIDS status, the incidence was higher in the years 1999-2004 than in between 1992 to March 1996 (hazard ratio, 2.5; 95% confidence interval, 1.2-5.3), with no change in the years 1999-2004.

Conclusion: The incidence of anal cancer has increased among HIV-infected patients in France since 1996. Although an ascertainment bias cannot be excluded, data indicate that combination antiretroviral therapy does not prevent anal cancer in these patients. This supports the urgent need for developing anal cancer screening programs for HIV-infected men who have sex with men.


February 28, 2009 at 6:43 pm Leave a comment

Pneumonia – Criteria for Patient Inestability on Hospital Discharge

Chest Sept 2008 V.134 N.3 p.595-600


Criteria for Patient Inestability on Hospital Discharge

Alberto Capelastegui, MD, PhD*, Pedro P. España, MD, Amaia Bilbao, MSc, Marimar Martinez-Vazquez, MD, Inmaculada Gorordo, MD, Mikel Oribe, MD, Isabel Urrutia, MD, PhD, and José M. Quintana, MD, PhD

From the Pneumology Service (Drs. Capelastegui, España, Gorordo, Oribe, and Urrutia), Department of Emergency Medicine (Dr. Martinez-Vazquez), and Research Unit (Dr. Quintana), Hospital de Galdakao-Usansolo-CIBER Epidemiología y Salud Pública, Galdakao; and the Basque Foundation for Health Innovation and Research-CIBER Epidemiología y Salud Pública (Mrs. Bilbao), Sondika, Bizkaia, Spain.


A study was undertaken to identify and weigh at the time of hospital discharge simple clinical variables that could predict short-term outcomes in patients with pneumonia.


In a prospective observational cohort study of 870 patients discharged alive after hospitalization for pneumonia, we collected oxygenation and vital signs on discharge and assessed mortality and readmission within 30 days. From the β-parameter obtained in a multivariate Cox proportional hazard regression model, a score was assigned to each predictive variable. The effects of instability at discharge on outcomes within 30 days thereafter were examined by adjusted models with use of the pneumonia severity index at hospital admission, the length of stay, the Charlson comorbidity index, or the preillness functional status.


Four variables related to a 30-day mortality rate from all causes were identified in the multivariate model; these included one major criterion (temperature >37.5°C) and three minor criteria (systolic BP < 90 mm Hg or diastolic BP < 60 mm Hg, respiratory rate > 24 breaths/min, and oxygen saturation < 90%). The developed score remained significantly associated with a higher risk-adjusted rate of death. Patients with a score ≥ 2 (one major criterion or two minor criteria) had a sixfold-greater risk-adjusted hazard ratio (HR) of death (HR, 5.8; 95% confidence interval, 2.5 to 13.1).


Four criteria of instability on discharge seem to be related to the mortality rate after discharge, but each of the factors must be weighed differently. The resulting score is a simple alternative that can be used by clinicians in the discharge process.


February 28, 2009 at 6:40 pm Leave a comment

Cytomegalovirus Reactivation in Critically Ill Immunocompetent Patients

JAMA 23 July 2008 V.300 N.4 p.413-422

Ajit P. Limaye, MD; Katharine A. Kirby, MSc; Gordon D. Rubenfeld, MD; Wendy M. Leisenring, ScD; Eileen M. Bulger, MD; Margaret J. Neff, MD; Nicole S. Gibran, MD; Meei-Li Huang, PhD; Tracy K. Santo Hayes, BSc; Lawrence Corey, MD; Michael Boeckh, MD

Departments of Laboratory Medicine (Dr Limaye and Ms Santo), Medicine (Drs Limaye, Rubenfeld, Neff, Corey, and Boeckh), Biostatistics (Dr Leisenring), and Surgery (Drs Bulger and Gibran), University of Washington, and the Programs in Infectious Diseases (Drs Huang, Corey, and Boeckh) and Clinical Statistics (Ms Kirby and Dr Leisenring), Fred Hutchinson Cancer Research Center, Seattle.

Context Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons, but the incidence and association of CMV reactivation with adverse outcomes in critically ill persons lacking evidence of immunosuppression have not been well defined.

Objective To determine the association of CMV reactivation with intensive care unit (ICU) and hospital length of stay in critically ill immunocompetent persons.

Design, Setting, and Participants We prospectively assessed CMV plasma DNAemia by thrice-weekly real-time polymerase chain reaction (PCR) and clinical outcomes in a cohort of 120 CMV-seropositive, immunocompetent adults admitted to 1 of 6 ICUs at 2 separate hospitals at a large US tertiary care academic medical center between 2004 and 2006. Clinical measurements were assessed by personnel blinded to CMV PCR results. Risk factors for CMV reactivation and association with hospital and ICU length of stay were assessed by multivariable logistic regression and proportional odds models.

Main Outcome Measures Association of CMV reactivation with prolonged hospital length of stay or death.

Results The primary composite end point of continued hospitalization (n = 35) or death (n = 10) by 30 days occurred in 45 (35%) of the 120 patients. Cytomegalovirus viremia at any level occurred in 33% (39/120; 95% confidence interval [CI], 24%-41%) at a median of 12 days (range, 3-57 days) and CMV viremia greater than 1000 copies/mL occurred in 20% (24/120; 95% CI, 13%-28%) at a median of 26 days (range, 9-56 days). By logistic regression, CMV infection at any level (adjusted odds ratio [OR], 4.3; 95% CI, 1.6-11.9; P = .005) and at greater than 1000 copies/mL (adjusted OR, 13.9; 95% CI, 3.2-60; P < .001) and the average CMV area under the curve (AUC) in log10 copies per milliliter (adjusted OR, 2.1; 95% CI, 1.3-3.2; P < .001) were independently associated with hospitalization or death by 30 days. In multivariable partial proportional odds models, both CMV 7-day moving average (OR, 5.1; 95% CI, 2.9-9.1; P < .001) and CMV AUC (OR, 3.2; 95% CI, 2.1-4.7; P < .001) were independently associated with a hospital length of stay of at least 14 days.

Conclusions These preliminary findings suggest that reactivation of CMV occurs frequently in critically ill immunocompetent patients and is associated with prolonged hospitalization or death. A controlled trial of CMV prophylaxis in this setting is warranted.



February 28, 2009 at 3:38 pm Leave a comment

Empirical Fluconazole versus Placebo for Intensive Care Unit Patients

Annals of Internal Medicine 15 July 2008 V.149 N.2 p.83-90

A Randomized Trial

Mindy G. Schuster, MD; John E. Edwards, Jr., MD; Jack D. Sobel, MD; Rabih O. Darouiche, MD; Adolf W. Karchmer, MD; Susan Hadley, MD; Gus Slotman, MD; Helene Panzer, PhD; Pinaki Biswas, PhD; and John H. Rex, MD

University of Pennsylvania School of Medicine, Philadelphia Pennsylvania; Harbor-UCLA Medical Center, Torrance, California; Detroit Medical Center, Wayne State University School of Medicine, Detroit, Michigan; Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, and University of Texas Medical School, Houston, Texas; Beth Israel Deaconess Medical Center and Tufts-New England Medical Center, Boston, Massachusetts; University of Medicine and Dentistry of New Jersey, Newark, New Jersey; and Pfizer, New York, New York.

Background: Invasive infection with Candida species is an important cause of morbidity and mortality in intensive care unit (ICU) patients. Optimal preventive strategies have not been clearly defined.

Objective: To see whether empirical fluconazole improves clinical outcomes more than placebo in adult ICU patients at high risk for invasive candidiasis.

Design: Double-blind, placebo-controlled, randomized trial conducted from 1995 to 2000.

Setting: 26 ICUs in the United States.

Patients: 270 adult ICU patients with fever despite administration of broad-spectrum antibiotics. All had central venous catheters and an Acute Physiology and Chronic Health Evaluation II score greater than 16.

Intervention: Patients were randomly assigned to either intravenous fluconazole, 800 mg daily, or placebo for 2 weeks and were followed for 4 weeks thereafter. Two hundred forty-nine participants were available for outcome assessment.

Measurements: A composite primary outcome that defined success as all 4 of the following: resolution of fever; absence of invasive fungal infection; no discontinuation because of toxicity; and no need for a nonstudy, systemic antifungal medication (as assessed by a blinded oversight committee).

Results: Only 44 of 122 (36%) fluconazole recipients and 48 of 127 (38%) placebo recipients had a successful outcome (relative risk, 0.95 [95% CI, 0.69 to 1.32; P = 0.78]). The main reason for failure was lack of resolution of fever (51% for fluconazole and 57% for placebo). Documented invasive candidiasis occurred in 5% of fluconazole recipients and 9% of placebo recipients (relative risk, 0.57 [CI, 0.22 to 1.49]). Seven (5%) fluconazole recipients and 10 (7%) placebo recipients had adverse events resulting in discontinuation of the study drug. Discontinuation because of abnormal liver test results occurred in 3 (2%) fluconazole recipients and 5 (4%) placebo recipients.

Limitations: Twenty-one randomly assigned patients were not included in the analysis because they either did not meet entry criteria or did not have postbaseline assessments. Fewer fungal infections than anticipated occurred in the control group. Confidence bounds were wide and did not exclude potentially important differences in outcomes between groups.

Conclusion: In critically ill adults with risk factors for invasive candidiasis, empirical fluconazole did not clearly improve a composite outcome more than placebo



February 28, 2009 at 3:36 pm Leave a comment

Continued early onset group B streptococcal infections in the era of intrapartum prophylaxis

Journal of Perinatology (2009) 29, 20–25

L S Pulver1, M M Hopfenbeck1, P C Young1, G J Stoddard2, K Korgenski3, J Daly3 and C L Byington1

1. 1Department of Pediatrics, University of Utah, Salt Lake City, UT, USA

2. 2Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

3. 3Microbiology Laboratory, Primary Children’s Medical Center, Salt Lake City, UT, USA

Objective – The objective of the study was to determine the rate of early onset group B streptococcus (EOGBS) infection in Utah and identify potential areas of failure in EOGBS prevention.

Study Design – We queried the microbiology records of Intermountain Healthcare for infants with culture-confirmed EOGBS between 1 January 2002 and 31 May 2006 and calculated rates of EOGBS per 1000 deliveries. We reviewed the infant and maternal records of each EOGBS case to identify possible failures in EOGBS prevention.

Result – There were 54 cases of EOGBS among the 127 205 births (0.42/1000 births). Of all, 12 were preterm. Of the 39 (93%) women prenatally screened for GBS, 31 (79%) had negative results and 7/8 (88%) women with positive prenatal GBS screens either did not receive intrapartum antibiotic prophylaxis (IAP) or received inadequate IAP. Of the 54 infants with EOGBS, 3 (6%) died.

Conclusion – Utah’s rates of EOGBS were higher than the national average. Factors associated with EOGBS include missed screening opportunities, inadequate IAP, and false-negative maternal GBS culture.



February 26, 2009 at 4:32 pm Leave a comment

Practice Guidelines for the Treatment of Candidiasis

Clinical Infectious Diseases April 2000 V.30 N.4 p.662-678


John H. Rex,1 Thomas J. Walsh,2 Jack D. Sobel,3 Scott G. Filler,4 Peter G. Pappas,5 William E. Dismukes,5 John E. Edwards4

From the 1Division of Infectious Diseases, Department of Internal Medicine, Center for the Study of Emerging and Re-emerging Pathogens, University of Texas Medical School, Houston; 2Infectious Diseases Section, Pediatric Branch, National Cancer Institute, Bethesda, Maryland; 3Wayne State University School of Medicine, Detroit, Michigan; 4Harbor-UCLA Medical Center, Torrance, California; 5Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham


February 26, 2009 at 3:50 pm Leave a comment

Oropharyngeal and Esophageal Candidiasis in Immunocompromised Patients: Treatment Issues

Clinical Infectious Diseases February 1998 V.26 N.2 p.259-272

State-of-the-Art Clinical Article

Rabih O. Darouiche

From the Department of Medicine, Infectious Disease Section, Veterans Affairs Medical Center, Houston, Texas


February 26, 2009 at 3:48 pm Leave a comment

Emergence of Ciprofloxacin-Resistant Neisseria meningitidis in North America

N England J of Medicine February 26, 2009 V.360 N.9 p.886-892

Brief Report

Henry M. Wu, M.D., Brian H. Harcourt, Ph.D., Cynthia P. Hatcher, B.S., Stanley C. Wei, M.D., Ryan T. Novak, Ph.D., Xin Wang, Ph.D., Billie A. Juni, M.S., Anita Glennen, B.S., David J. Boxrud, M.S., Jean Rainbow, R.N., M.P.H., Susanna Schmink, B.S., Raydel D. Mair, B.S., M. Jordan Theodore, B.S., Molly A. Sander, M.P.H., Tracy K. Miller, M.P.H., Kirby Kruger, B.S., Amanda C. Cohn, M.D., Thomas A. Clark, M.D., M.P.H., Nancy E. Messonnier, M.D., Leonard W. Mayer, Ph.D., and Ruth Lynfield, M.D.

We report on three cases of meningococcal disease caused by ciprofloxacin-resistant Neisseria meningitidis, one in North Dakota and two in Minnesota. The cases were caused by the same serogroup B strain. To assess local carriage of resistant N. meningitidis, we conducted a pharyngeal-carriage survey and isolated the resistant strain from one asymptomatic carrier. Sequencing of the gene encoding subunit A of DNA gyrase (gyrA) revealed a mutation associated with fluoroquinolone resistance and suggests that the resistance was acquired by means of horizontal gene transfer with the commensal N. lactamica. In susceptibility testing of invasive N. meningitidis isolates from the Active Bacterial Core surveillance system between January 2007 and January 2008, an additional ciprofloxacin-resistant isolate was found, in this case from California. Ciprofloxacin-resistant N. meningitidis has emerged in North America.



February 25, 2009 at 11:15 pm Leave a comment

Eradication of HIV: current challenges and new directions

Journal of Antimicrobial Chemotherapy January 2009 V.63 N.1 p.7-10

Matthew D. Marsden1,2 and Jerome A. Zack1,2,3,*

1 Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA 2 UCLA AIDS Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA 3 Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA

Highly active antiretroviral therapy (HAART) can potently suppress human immunodeficiency virus (HIV) replication and prevent progression to AIDS. However, HAART does not cure infected patients. Instead, HIV persists in latently infected CD4+ T cells and various cryptic cellular reservoirs. Hence, under current therapy regimens, patients must continue taking HAART for the remainder of their lives. Eliminating residual replication-competent virus is critical if eradication of HIV is to be achieved. While this challenge is formidable, we describe here a number of innovative approaches intended to further deplete HIV in HAART-treated patients. New antiretroviral drugs that target different viral proteins and stages of the virus life cycle, compounds that enhance anti-HIV immune responses and novel gene therapy approaches may each play a role in improving long-term suppression of the virus. Moreover, methods for more specifically and efficiently inducing HIV from latency and eliminating the newly activated host cells are also under development.



February 25, 2009 at 4:34 pm Leave a comment

Risk of Herpes Zoster in Patients With Rheumatoid Arthritis Treated With Anti–TNF- αAgents

JAMA February 18, 2009; Vol. 301, No. 7 p.737-744

Anja Strangfeld, MD; Joachim Listing, PhD; Peter Herzer, MD; Anke Liebhaber, MD; Karin Rockwitz, MD; Constanze Richter, MD; Angela Zink, PhD

German Rheumatism Research Centre, Berlin (Drs Strangfeld and Listing); and German Rheumatism Research Centre and Department of Rheumatology and Clinical Immunology, Charité- University Medicine, Berlin (Dr Zink). Drs Herzer, Liebhaber, Rockwitz, and Richter are rheumatologists in private practice in Germany.

Context The risk of bacterial infection is increased in patients treated with drugs that inhibit tumor necrosis factor (TNF-). Little is known about the reactivation of latent viral infections during treatment with TNF- inhibitors.

Objective To investigate whether TNF- inhibitors together as a class, or separately as either monoclonal anti–TNF- antibodies (adalimumab, infliximab) or a fusion protein (etanercept), are related to higher rates of herpes zoster in patients with rheumatoid arthritis.

Design, Setting, and Patients Patients were enrolled in the German biologics register RABBIT, a prospective cohort, between May 2001 and December 2006 at the initiation of treatment with infliximab, etanercept, adalimumab, or anakinra, or when they changed conventional disease-modifying antirheumatic drug (DMARD). Treatment, clinical status, and adverse events were assessed by rheumatologists at fixed points during follow-up.

Main Outcome Measures Hazard ratio (HR) of herpes zoster episodes following anti–TNF- treatment. Study aims were to detect a clinically significant difference (HR, 2.0) between TNF- inhibitors as a class compared with DMARDs and to detect an HR of at least 2.5 for each of 2 types of TNF- inhibitors, the monoclonal antibodies or the fusion protein, compared with conventional DMARDs.

Results Among 5040 patients receiving TNF- inhibitors or conventional DMARDs, 86 episodes of herpes zoster occurred in 82 patients. Thirty-nine occurrences could be attributed to treatment with anti–TNF- antibodies, 23 to etanercept, and 24 to conventional DMARDs. The crude incidence rate per 1000 patient-years was 11.1 (95% confidence interval [CI], 7.9-15.1) for the monoclonal antibodies, 8.9 (95% CI, 5.6-13.3) for etanercept, and 5.6 (95% CI, 3.6-8.3) for conventional DMARDs. Adjusted for age, rheumatoid arthritis severity, and glucocorticoid use, a significantly increased risk was observed for treatment with the monoclonal antibodies (HR, 1.82 [95% CI, 1.05-3.15]), although this risk was lower than the threshold for clinical significance. No significant associations were found for etanercept use (HR, 1.36 [95% CI, 0.73-2.55]) or for anti–TNF- treatment (HR, 1.63 [95% CI, 0.97-2.74]) as a class.

Conclusion Treatment with monoclonal anti–TNF- antibodies may be associated with increased risk of herpes zoster, but this requires further study.


February 25, 2009 at 4:32 pm Leave a comment

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