Archive for May 15, 2006

ARTICLE – Long-Term Cardiac Outcomes of Treating Chronic Chagas Disease with Benznidazole versus No Treatment – A Nonrandomized Trial

Source: Annals of Internal Medicine 16 May 2006 Vol.144 N.10 p.724-734

Rodolfo Viotti, MD; Carlos Vigliano, MD; Bruno Lococo, MD; Graciela Bertocchi, MD; Marcos Petti, MD; María Gabriela Alvarez, MD; Miriam Postan, MD, PhD; and Alejandro Armenti, MD

Background: Benznidazole is effective for treating acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain.

Objective: To compare long-term outcomes of patients with nonacute Chagas disease treated with benznidazole versus outcomes of those who did not receive treatment.

Design: Clinical trial with unblinded, nonrandom assignment of patients to intervention or control groups.

Setting: Chagas disease center in Buenos Aires, Argentina.

Patients: 566 patients 30 to 50 years of age with 3 positive results on serologic tests and without heart failure.

Measurements: The primary outcome was disease progression, defined as a change to a more advanced Kuschnir group or death. Secondary outcomes included new abnormalities on electrocardiography and serologic reactivity.

Intervention: Oral benznidazole, 5 mg/kg of body weight per day for 30 days (283 patients), or no treatment (283 patients).

Results: Fewer treated patients had progression of disease (12 of 283 [4%] vs. 40 of 283 [14%]; adjusted hazard ratio, 0.24 [95% CI, 0.10 to 0.59]; P = 0.002) or developed abnormalities on electrocardiography (15 of 283 [5%] vs. 45 of 283 [16%]; adjusted hazard ratio, 0.27 [CI, 0.13 to 0.57]; P = 0.001) compared with untreated patients. Left ventricular ejection fraction (hazard ratio, 0.97 [CI, 0.94 to 0.99]; P < 0.002) and left ventricular diastolic diameter (hazard ratio, 2.45 [CI, 1.53 to 3.95]; P < 0.001) were also associated with disease progression. Conversion to negative results on serologic testing was more frequent in treated patients than in untreated patients (32 of 218 [15%] vs. 12 of 212 [6%]; adjusted hazard ratio, 2.1 [CI, 1.06 to 4.06]; P = 0.034).

Limitations: Nonrandom, unblinded treatment assignment was used, and follow-up data were missing for 20% of patients. Loss to follow-up was more common among patients who were less sick. Two uncontrolled interim analyses were conducted.

Conclusions: Compared with no treatment, benznidazole treatment was associated with reduced progression of Chagas disease and increased negative seroconversion for patients presenting with nonacute disease and no heart failure. These observations indicate that a randomized, controlled trial should now be conducted.

Editors' Notes – Context

The effect of antitrypanosomal drug therapy on progression of heart involvement in patients with chronic Chagas disease is uncertain.

Contribution

The authors assigned alternating patients with 3 positive results on serologic tests for Trypanosoma cruzi and no evidence of heart failure to receive benznidazole for 30 consecutive days (n = 283) or no treatment (n = 283). After a median follow-up of 9.8 years, 14.1% of untreated patients and 4.2% of treated patients (P = 0.002) had progression of heart disease.

Cautions

Assignment of patients was not randomized. Twenty percent of patients from both groups were lost to follow-up.

Implications

Treatment during the chronic phase of Chagas disease may reduce the risk for progression of heart disease.

The Editors

Author and Article Information

From Hospital Interzonal General de Agudos Eva Perón and Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, Buenos Aires, Argentina.

Acknowledgments: The authors thank the directors at Hospital Eva Perón for providing a suitable setting for this research. Dr. Postan is a fellow of CONICET, Argentina.

Grant Support: None.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Rodolfo Viotti, MD, José Hernández 3440, Villa Ballester, Gral. San Martín, Buenos Aires ZC 1653, Argentina; e-mail, peron@millicom.com.ar.

Current Author Addresses: Dr. Viotti: José Hernández 3440, Villa Ballester, Gral. San Martín, Buenos Aires ZC 1653, Argentina.

Drs. Vigliano, Lococo, Bertocchi, Petti, Alvarez, and Armenti: Avenue Ricardo Balbin 900, San Martín, Buenos Aires ZC 1650, Argentina.

Dr. Postan: Avenue Paseo Colón 568, Buenos Aires ZC 1063, Argentina.

Author Contributions: Conception and design: R. Viotti, C. Vigliano, A. Armenti.

Analysis and interpretation of the data: R. Viotti, C. Vigliano, M. Petti, A. Armenti.

Drafting of the article: R. Viotti, C. Vigliano, G. Bertocchi, M. Postan.

Critical revision of the article for important intellectual content: B. Lococo, G. Bertocchi, M. Petti, M.G. Alvarez, M. Postan, A. Armenti.

Final approval of the article: R. Viotti, C. Vigliano, B. Lococo, G. Bertocchi, M. Petti, M. Postan, A. Armenti.

Provision of study materials or patients: R. Viotti, C. Vigliano, B. Lococo, M. Petti, M.G. Alvarez.

Statistical expertise: R. Viotti.

Administrative, technical, or logistic support: B. Lococo, G. Bertocchi, M.G. Alvarez, M. Postan.

Collection and assembly of data: R. Viotti, C. Vigliano, B. Lococo, G. Bertocchi, M. Petti, M.G. Alvarez, M. Postan.

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May 15, 2006 at 11:49 pm Leave a comment

ARTICLE – The Prevalence of Hepatitis C Virus Infection in the United States, 1999 through 2002

Source: Annals of Internal Medicine 16 May 2006 Vol.144 N.10 p.705-714

Gregory L. Armstrong, MD; Annemarie Wasley, ScD; Edgar P. Simard, MPH; Geraldine M. McQuillan, PhD; Wendi L. Kuhnert, PhD; and Miriam J. Alter, PhD

Background: Defining the primary characteristics of persons infected with hepatitis C virus (HCV) enables physicians to more easily identify persons who are most likely to benefit from testing for the disease.

Objective: To describe the HCV-infected population in the United States.

Design: Nationally representative household survey.

Setting: U.S. civilian, noninstitutionalized population.

Participants: 15 079 participants in the National Health and Nutrition Examination Survey between 1999 and 2002.

Measurements: All participants provided medical histories, and those who were 20 to 59 years of age provided histories of drug use and sexual practices. Participants were tested for antibodies to HCV (anti-HCV) and HCV RNA, and their serum alanine aminotransferase (ALT) levels were measured.

Results: The prevalence of anti-HCV in the United States was 1.6% (95% CI, 1.3% to 1.9%), equating to an estimated 4.1 million (CI, 3.4 million to 4.9 million) anti-HCV–positive persons nationwide; 1.3% or 3.2 million (CI, 2.7 million to 3.9 million) persons had chronic HCV infection. Peak prevalence of anti-HCV (4.3%) was observed among persons 40 to 49 years of age. A total of 48.4% of anti-HCV–positive persons between 20 and 59 years of age reported a history of injection drug use, the strongest risk factor for HCV infection. Of all persons reporting such a history, 83.3% had not used injection drugs for at least 1 year before the survey. Other significant risk factors included 20 or more lifetime sex partners and blood transfusion before 1992. Abnormal serum ALT levels were found in 58.7% of HCV RNA–positive persons. Three characteristics (abnormal serum ALT level, any history of injection drug use, and history of blood transfusion before 1992) identified 85.1% of HCV RNA–positive participants between 20 and 59 years of age.

Limitations: Incarcerated and homeless persons were not included in the survey.

Conclusions: Many Americans are infected with HCV. Most were born between 1945 and 1964 and can be identified with current screening criteria. History of injection drug use is the strongest risk factor for infection.

Editors' Notes – Context

The Third National Health and Nutrition Examination Survey (NHANES III), conducted between 1988 and 1994, indicated that 1.8% of people in the United States had been infected with hepatitis C virus (HCV), 70% of whom had chronic infection. Most anti-HCV–positive individuals were between 30 and 49 years of age.

Contribution

Data from the recent NHANES (1999–2002) show little change in anti-HCV prevalence, but peak prevalence has shifted to individuals between 40 and 49 years of age. More than 85% of HCV RNA–positive individuals may be identified through targeted testing of 18% of adults between 20 and 59 years of age: persons with abnormal serum alanine aminotransferase levels, those who have used injection drugs, and those who received blood transfusions before 1992.

Cautions

Incarcerated and homeless people were not included in the survey.

Implications

Despite a decrease in new HCV infections, aging of chronically infected individuals may presage an imminent increase in complications.

The Editors

Author and Article Information

From National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Maryland.

Grant Support: None.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Gregory L. Armstrong, MD, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Mailstop G-37, 1600 Clifton Road NE, Atlanta, GA 30333; e-mail, GArmstrong@cdc.gov.

Current Author Addresses: Drs. Armstrong and Wasley and Mr. Simard: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Mailstop G-37, 1600 Clifton Road NE, Atlanta, GA 30333.

Dr. McQuillan: Centers for Disease Control and Prevention, National Center for Health Statistics, Division of Health and Nutrition Examination Surveys, 3311 Toledo Road, Room 4204, Hyattsville, MD 20782.

Dr. Kuhnert: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Mailstop A-33, 1600 Clifton Road NE, Atlanta, GA 30333.

Dr. Alter: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Mailstop D-66, 1600 Clifton Road NE, Atlanta, GA 30333.

Author Contributions: Conception and design: G.L. Armstrong, G.M. McQuillan, M.J. Alter.

Analysis and interpretation of the data: G.L. Armstrong, A. Wasley, E.P. Simard, G.M. McQuillan, W.L. Kuhnert, M.J. Alter.

Drafting of the article: G.L. Armstrong, G.M. McQuillan.

Critical revision of the article for important intellectual content: G.L. Armstrong, A. Wasley, E.P. Simard, G.M. McQuillan, M.J. Alter.

Final approval of the article: G.L. Armstrong, A. Wasley, E.P. Simard, G.M. McQuillan, M.J. Alter.

Provision of study materials or patients: G.M. McQuillan.

Statistical expertise: G.L. Armstrong.

Obtaining of funding: M.J. Alter.

Administrative, technical, or logistic support: W.L. Kuhnert.

Collection and assembly of data: A. Wasley, E.P. Simard, G.M. McQuillan.

May 15, 2006 at 11:47 pm Leave a comment

REVIEWS OF ANTI-INFECTIVE AGENTS INVITED ARTICLE – Fluoroquinolones and Anaerobes

Source: Clinical Infectious Diseases 1 June 2006 Vol.42 .11 p.1598-1607

Louis D. Saravolatz, Section Editor

Gary E. Stein1,2 and Ellie J. C. Goldstein3,4

Departments of 1Medicine and 2Pharmacology, Michigan State University, East Lansing, Michigan; and 3Department of Medicine, University of California–Los Angeles School of Medicine, and 4R. M. Alden Research Laboratory, Santa Monica, California

The usefulness of fluoroquinolones for the treatment of mixed aerobic and anaerobic infections has been investigated since these agents started being used in clinical practice. Newer compounds have increased in vitro activity against anaerobes, but clinically relevant susceptibility breakpoints for these bacteria have not been established. Pharmacodynamic analyses and corroboration by new data from clinical trials have enhanced our knowledge concerning the use of fluoroquinolones to treat selective anaerobic pathogens. These studies suggest that newer agents could be useful in the treatment of several types of mixed aerobic and anaerobic infections, including skin and soft-tissue, intra-abdominal, and respiratory infections.

The major concerns with expanding the use of fluoroquinolones to treat anaerobic infections have been reports of increasing resistance in Bacteroides group isolates and the impact of these antibiotics on the incidence of Clostridium difficile–associated disease.

Received 21 November 2005; accepted 18 February 2006; electronically published 24 April 2006.

May 15, 2006 at 4:42 pm Leave a comment

MAJOR ARTICLE – Serotonin Toxicity Associated with the Use of Linezolid: A Review of Postmarketing Data

Source: Clinical Infectious Diseases 1 June 2006 Vol.42 .11 p.1578-1583

Kenneth R. Lawrence,1 May Adra,1 and P. Ken Gillman2,3

1Tufts–New England Medical Center, Department of Pharmacy, Boston, Massachusetts; and 2Department of Clinical Neuropharmacology, Pioneer Valley Private Hospital, and 3Department of Clinical Neuropharmacology, James Cook University, Mount Pleasant, Queensland, Australia

Background. Linezolid is the first oxazolidinone antimicrobial marketed in the United States. It exhibits monoamine oxidase (MAO) type A and MAO type B inhibitory effects. The concomitant administration of nonselective MAO inhibitors or MAO-A inhibitors with drugs that increase serotonin concentrations is associated with serotonin toxicity.

Methods. We requested from the US Food and Drug Administration all postmarketing adverse event reports regarding linezolid that included serotonin toxicity or any report describing cognitive or behavioral symptoms and autonomic and neuromuscular excitability. We assessed the case summaries obtained from the Adverse Event Reporting System database for serotonin toxicity. A case of serotonin toxicity was defined as having the following: (1) linezolid as the primary suspect drug; (2) concurrent administration of 1 secondary suspect drug known to increase serotonin concentrations in the central nervous system; and (3) serotonin toxicity, as defined by the modified Hunter Serotonin Toxicity Criteria or by the reporter.

Results. Twenty-nine cases were classified as serotonin toxicity. Patients’ ages ranged from 17–83 years, and the ratio of females to males was 1:1. The most common class of drugs received concurrently with linezolid was selective serotonin reuptake inhibitors (26 of 43 patients). Thirteen patients required an intervention to prevent permanent impairment or required hospitalization for the adverse event.

Conclusion. The use of linezolid with medications that increase concentrations of serotonin in the central nervous system may result in serotonin toxicity. Prescribers must weigh risks and benefits of this combination. Patients and prescribers should be cognizant of signs and symptoms of serotonin toxicity and should initiate appropriate measures if such symptoms develop.

Received 31 October 2005; accepted 1 February 2006; electronically published 27 April 2006.

May 15, 2006 at 4:40 pm Leave a comment

MAJOR ARTICLE – Reduction in Acquisition of Vancomycin-Resistant Enterococcus after Enforcement of Routine Environmental Cleaning Measures

Source: Clinical Infectious Diseases 1 June 2006 Vol.42 .11 p.1552-1560

Mary K. Hayden,1 Marc J. M. Bonten,3 Donald W. Blom,1 Elizabeth A. Lyle,1 David A. M. C. van de Vijver,3 and Robert A. Weinstein1,2

1Rush University Medical Center and 2Stroger (Cook County) Hospital, Chicago, Illinois; and 3University Medical Center Utrecht, Utrecht, The Netherlands

Background. The role of environmental contamination in nosocomial cross-transmission of antibiotic-resistant bacteria has been unresolved.

Using vancomycin-resistant enterococci (VRE) as a marker organism, we investigated the effects of improved environmental cleaning with and without promotion of hand hygiene adherence on the spread of VRE in a medical intensive care unit.

Methods. The study comprised a baseline period (period 1), a period of educational intervention to improve environmental cleaning (period 2), a "washout" period without any specific intervention (period 3), and a period of multimodal hand hygiene intervention (period 4). We performed cultures for VRE of rectal swab samples obtained from patients at admission to the intensive care unit and daily thereafter, and we performed cultures of environmental samples and samples from the hands of health care workers twice weekly. We measured patient clinical and demographic variables and monitored intervention adherence frequently.

Results. Our study included 748 admissions to the intensive care unit over a 9-month period. VRE acquisition rates were 33.47 cases per 1000 patient-days at risk for period 1 and 16.84, 12.09, and 10.40 cases per 1000 patient-days at risk for periods 2, 3, and 4, respectively. The mean (±SD) weekly rate of environmental sites cleaned increased from 0.48 ± 0.08 at baseline to 0.87 ± 0.08 in period 2; similarly high cleaning rates persisted in periods 3 and 4. Mean (±SD) weekly hand hygiene adherence rate was 0.40 ± 0.01 at baseline and increased to 0.57 ± 0.11 in period 2, without a specific intervention to improve adherence, but decreased to 0.29 ± 0.26 in period 3 and 0.43 ± 0.1 in period 4. Mean proportions of positive results of cultures of environmental and hand samples decreased in period 2 and remained low thereafter. In a Cox proportional hazards model, the hazard ratio for acquiring VRE during periods 2–4 was 0.36 (95% confidence interval, 0.19–0.68); the only determinant explaining the difference in VRE acquisition was admission to the intensive care unit during period 1.

Conclusions. Decreasing environmental contamination may help to control the spread of some antibiotic-resistant bacteria in hospitals.

Received 23 December 2005; accepted 1 February 2006; electronically published 27 April 2006.

May 15, 2006 at 4:38 pm Leave a comment

MAJOR ARTICLE – Reduction of Urinary Tract Infection and Antibiotic Use after Surgery: A Controlled, Prospective, Before-After Intervention Study

Source: Clinical Infectious Diseases 1 June 2006 Vol.42 .11 p.1544-1551

François Stéphan,1,2,a Hugo Sax,2 Maud Wachsmuth,1,2 Pierre Hoffmeyer,3 François Clergue,1 and Didier Pittet2

1Division of Anesthesiology, Department of Anesthesiology, Pharmacology, and Surgical Intensive Care, 2Infection Control Program, Department of Internal Medicine, and 3Clinic of Orthopedic Surgery, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland

Background. Urinary tract infection is the most frequent health care–associated complication. We hypothesized that the implementation of a multifaceted prevention strategy could decrease its incidence after surgery.

Methods. In a controlled, prospective, before-after intervention trial with 1328 adult patients scheduled for orthopedic or abdominal surgery, nosocomial infection surveillance was conducted until hospital discharge. A multifaceted intervention including specifically tailored, locally developed guidelines for the prevention of urinary tract infection was implemented for orthopedic surgery patients, and abdominal surgery patients served as control subjects. Infectious and noninfectious complications, adherence to guidelines, and antibiotic use were monitored before and after the intervention and again 2 years later.

Results.  The incidence of urinary tract infection decreased from 10.4 to 3.9 episodes per 100 patients in the intervention group (incidence-density ratio, 0.41; 95% CI, 0.20–0.79; P = .004). Adherence to guidelines was 82.2%. Both the frequency and the duration of urinary catheterization decreased following the intervention. Recourse to antibiotic therapy after surgery dropped in the intervention group from 17.9 to 15.6 defined daily doses per 100 patient-days (P < .005) because of a reduced need for the treatment of urinary tract infection (P < .001). Follow-up after 2 years revealed a sustained impact of the strategy and a subsequent low use of antibiotics, consistent with stable adherence to guidelines (80.8%).

Conclusions. A multifaceted prevention strategy can dramatically decrease postoperative urinary tract infection and contribute to the reduction of the overall use of antibiotics after surgery.

Received 23 September 2005; accepted 1 February 2006; electronically published 25 April 2006.
a Present affiliation: Department of Anesthesiology-Critical Care Medicine, Point-à-Pitre Hospital, University of Antilles-Guyane, Pointe-à-Pitre Cedex, France.

May 15, 2006 at 4:35 pm Leave a comment

MAJOR ARTICLE – Clinical and Virological Improvement of Hepatitis B Virus–Related or Hepatitis C Virus–Related Chronic Hepatitis with Concomitant Hepatitis A Virus Infection

Source: Clinical Infectious Diseases 1 June 2006 Vol.42 .11 p.1536-1543

Evangelista Sagnelli,1,2 Nicola Coppola,1,2 Mariantonietta Pisaturo,1,2 Raffaella Pisapia,1,2 Mirella Onofrio,1,2 Caterina Sagnelli,2 Antonio Catuogno,1 Carlo Scolastico,2 Felice Piccinino,2 and Pietro Filippini2

1Division of Infectious Diseases, Azienda Ospedaliera San Sebastiano, Caserta, and 2Department of Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy

Background. We evaluated the clinical and virological characteristics of hepatitis A virus infection in persons concomitantly infected with hepatitis B virus (HBV) or hepatitis C virus (HCV).

Methods. We enrolled 21 patients with acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13 patients who were positive for hepatitis B surface antigen (case B group), 8 patients who were anti-HCV positive (case C group), and 21 patients with acute hepatitis A without a preexisting liver disease (control A group). Two control groups of patients with chronic hepatitis B (control B group) or C (control C group) were also chosen. All control groups were pair-matched by age and sex with the corresponding case group.

Results. Fulminant hepatitis A was never observed, and hepatitis A had a severe course in 1 patient in the case B group and in 1 patient in the control A group. Both patients recovered.

On admission, HBV DNA was detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in the control B group; HCV RNA was found in no patient in the case C group and in 16 patients (81.2%) in the control C group. Of 9 patients in the case B group who were followed up for 6 months, 3 became negative for hepatitis B surface antigen and positive for hepatitis B surface antibody, 2 remained positive for hepatitis A surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA with a low viral load. Of 6 patients in the case C group who were followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently low viral loads.

Conclusion. Concomitant hepatitis A was always self-limited, associated with a marked inhibition of HBV and HCV genomes, and possibly had a good prognosis for the underlying chronic hepatitis.

Received 3 November 2005; accepted 24 January 2006; electronically published 26 April 2006.

May 15, 2006 at 4:33 pm Leave a comment

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