Archive for December 16, 2005

ARTICLE – Transmission of Hepatitis C Virus to Several Organ and Tissue Recipients from an Antibody-Negative Donor

Source: Annals of Inter Med  1 Nov 2005 Vol 143 N.9 P.648-654

Barna D. Tugwell, MD; Priti R. Patel, MD, MPH; Ian T. Williams, PhD, MS; Katrina Hedberg, MD, MPH; Feng Chai, PhD; Omana V. Nainan, PhD; Ann R. Thomas, MD, MPH; Judith E. Woll, MD; Beth P. Bell, MD, MPH; and Paul R. Cieslak, MD

Background: Although hepatitis C virus (HCV) transmission through tissue transplantation has been rarely reported, a donor with undetected viremia may infect several recipients. A patient developed acute hepatitis C shortly after tissue transplantation. Ninety-one tissues or organs had been recovered from the donor.

Objective: To determine whether the donor was the source of infection and the extent of transmission to other organ and tissue recipients.

Design: Descriptive epidemiologic study; serum testing for HCV infection.

Setting: Recipients were located in 16 states and 2 other countries.

Participants: Donor and graft recipients.

Measurements: Hepatitis C virus infection was defined as the presence of anti-HCV or HCV RNA. The authors determined the genetic relatedness of viral isolates from the donor and recipients by genotype comparison and quasi-species analysis.

Results: The donor was anti-HCV–negative but was HCV RNA–positive (genotype 1a). Forty persons received transplants during 22 months. Five persons were HCV-infected before transplantation or had a genotype other than 1a, and 5 persons had no post-transplantation serum specimens available. Of the remaining 30 recipients, HCV infection occurred in 8 recipients: 3 of 3 organ recipients, 1 of 2 saphenous vein recipients, 1 of 3 tendon recipients, and 3 of 3 tendon with bone recipients. These 8 recipients had viral isolates genetically related to those of the donor. No cases occurred in recipients of skin (n = 2), cornea (n = 1), or irradiated bone (n = 16).

Limitations: Post-transplantation serum specimens were unavailable for 5 recipients.

Conclusions: An anti-HCV–negative donor was the source of HCV infection for 8 recipients of organs or tissues. Although HCV transmission from anti-HCV–negative donors is probably uncommon, changes in donor screening to include routine testing for HCV RNA merit further consideration to improve the safety of transplantation.

 

 

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December 16, 2005 at 3:57 pm Leave a comment

Optimal Duration of IV and Oral Antibiotics in the Treatment of Thoracic Actinomycosis*

Source: Chest. 2005;128:2211-2217

JaeChol Choi, MD; Won-Jung Koh, MD; Tae Sung Kim, MD; Kyung Soo Lee, MD; Joungho Han, MD; Hojoong Kim, MD and O Jung Kwon, MD

* From the Division of Pulmonary and Critical Care Medicine, Department of Medicine (Drs. Choi, Koh, H. Kim, and Kwon), Department of Radiology (Drs. T. S. Kim and Lee), and Department of Pathology (Dr. Han), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Correspondence to: Won-Jung Koh, MD, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Republic of Korea; e-mail: wjkoh@smc.samsung.co.kr

Study objective: IV antibiotic therapy for 2 to 6 weeks followed by 6 to 12 months of oral antibiotic therapy is usually recommended for the treatment of thoracic actinomycosis. The objective of this study was to evaluate the duration of IV and oral antibiotic therapy for thoracic actinomycosis.

Methods: We present a retrospective case series of 28 patients with thoracic actinomycosis as confirmed by histopathology from October 1994 through December 2003.

Results: After diagnosis of actinomycosis, 54% (15 of 28 patients) received antibiotic therapy alone. The duration of IV antibiotic therapy ranged from 0 to 18 days (median, 2 days; interquartile range [IQR], 0 to 3 days), and the duration of oral antibiotic treatment ranged from 76 to 412 days (median, 167 days; IQR, 142 to 214 days) in patients who received antibiotics alone. Combination surgical and antibiotic therapy occurred in 46% (13 of 28 patients). The duration of IV antibiotic therapy ranged from 3 to 17 days (median, 8 days; IQR, 5 to 13 days), and the duration of oral antibiotic therapy ranged from 0 to 534 days (median, 150 days; IQR, 3.5 to 289 days) in these patients. Clinical cures were achieved in 96% (27 of 28 patients). There was no clinical evidence of recurrence during follow-up period at our hospital (median, 23 months; IQR, 9 to 44 months) in 21 patients, excluding 7 patients who were transferred to referring hospitals after completion of antibiotic therapy (n = 6) or during antibiotic therapy (n = 1).

Conclusions: Thoracic actinomycosis is best treated with individualized therapeutic modalities, depending on factors such as the initial burden of disease, the performance of resectional surgery, and the clinical and radiologic responses to therapy. The traditional recommendation of IV antibiotic therapy for 2 to 6 weeks followed by oral antibiotic therapy for 6 to 12 months is not always necessary for all thoracic actinomycosis patients.

 

December 16, 2005 at 3:55 pm Leave a comment

Original Investigation – Risk Factors for Fluoroquinolone Resistance in Nosocomial Escherichia coli and Klebsiella pneumoniae Infections

Source: Arch Intern Med Vol. 162 N.21, Nov 25, 2002 p.2469-2477.

Ebbing Lautenbach, MD,MPH; Neil O. Fishman, MD; Warren B. Bilker, PhD; Analia Castiglioni, MD; Joshua P. Metlay, MD,PhD; Paul H. Edelstein, MD; Brian L. Strom, MD,MPH

Background  The incidence of fluoroquinolone (FQ) resistance has increased markedly in recent years. Even in the common nosocomial pathogens Escherichia coli and Klebsiella pneumoniae, in which the emergence of FQ resistance was believed to be unlikely, increasing resistance to these agents has been noted. Risk factors for FQ resistance in these pathogens remain unknown. Although FQs are important components of the present antimicrobial arsenal, their continued usefulness is threatened by rising FQ resistance.

Objective  To identify risk factors for nosocomial FQ resistance.

Methods  A case-control study of hospitalized patients with infections due to FQ-resistant and FQ-susceptible E coli and K pneumoniae occurring between January 1, 1998, and June 30, 1999.

Results  We included 123 patients with nosocomial FQ-resistant infections and 70 randomly selected patients with nosocomial FQ-susceptible infections. Independent risk factors (adjusted odds ratio [95% confidence interval]) for FQ resistance were (1) recent FQ use (5.25 [1.81-15.26]); (2) residence in a long-term care facility (3.65 [1.64-8.15]); (3) recent aminoglycoside use (8.86 [1.71-45.99]); and (4) older age (1.03 [1.01-1.06]).

Conclusions  Recent FQ use, residence in a long-term care facility, recent aminoglycoside use, and older age were all noted to be independent risk factors for FQ resistance among patients with nosocomial E coli and K pneumoniae infections. Efforts should be directed at recognition and modification of these risk factors to curb the rise in FQ resistance and preserve the utility of these agents in the treatment of common nosocomial gram-negative infections.

From the Divisions of Infectious Diseases (Drs Lautenbach and Fishman) and General Internal Medicine (Drs Castiglioni, Metlay, and Strom) of the Department of Medicine, the Department of Biostatistics and Epidemiology (Drs Lautenbach, Bilker, Metlay, and Strom), the Department of Pathology and Laboratory Medicine (Dr Edelstein), the Center for Clinical Epidemiology and Biostatistics (Drs Lautenbach, Bilker, Metlay, and Strom), and the University of Pennsylvania Centers for Research and Education on Therapeutics (Drs Lautenbach, Metlay, and Strom), University of Pennsylvania School of Medicine, Philadelphia.

 

 

December 16, 2005 at 3:52 pm Leave a comment

MAJOR ARTICLE – Association between Fluoroquinolone Resistance and Mortality in Escherichia coli and Klebsiella pneumoniae Infections: The Role of Inadequate Empirical Antimicrobial Therapy

Source: Clinical Infectious Diseases 2005;41:923-929

Ebbing Lautenbach,1,3,5,6 Joshua P. Metlay,2,3,5,6,7 Warren B. Bilker,3,5,6 Paul H. Edelstein,4 and Neil O. Fishman1

Divisions of 1Infectious Diseases and 2General Internal Medicine, Department of Medicine, 3Department of Biostatistics and Epidemiology, 4Department of Pathology and Laboratory Medicine, 5Center for Clinical Epidemiology and Biostatistics, and 6Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, and 7Department of Veterans Affairs, Philadelphia, Pennsylvania

Background. The prevalence of fluoroquinolone (FQ) resistance among Escherichia coli and Klebsiella pneumoniae has increased markedly in recent years. However, the impact of FQ resistance on mortality remains unknown.

Methods. To identify the association between FQ resistance and mortality, we conducted a retrospective cohort study of hospitalized patients with infections due to FQ-resistant strains and FQ-susceptible strains of E. coli and K. pneumoniae between 1 January 1998 and 30 June 1999.

Results. Of 123 patients with FQ-resistant infection, 16 (13.0%) died, compared with 4 (5.7%) of 70 patients with FQ-susceptible infection (odds ratio [OR], 2.47; 95% confidence interval [CI], 0.7510.53). After adjustment for other significant risk factors and confounders, there remained an independent association between FQ-resistant infection and mortality (adjusted OR, 4.41; 95% CI, 1.0318.81). Patients with FQ-resistant infection were significantly less likely to have received antimicrobial therapy with activity against the infecting pathogen within the first 24 h and 48 h of infection (P = .002 and P Conclusions. FQ resistance is an independent risk factor for mortality in patients with health careacquired E. coli and K. pneumoniae infections. This may be explained, at least in part, by a delay in the initiation of appropriate antimicrobial therapy in patients with FQ-resistant infection. These results highlight the grave clinical consequences of FQ resistance and emphasize the importance of efforts designed to curb the increase in the prevalence of resistance to these agents.

Presented in part: 12th Annual Meeting of the Society for Healthcare Epidemiology of America, Salt Lake City, Utah, April 2002 (abstract 114).

December 16, 2005 at 3:49 pm Leave a comment

MEDICAL SCIENCES – Pivotal role of Harakiri in the induction and prevention of gentamicin-induced hearing loss

Source: Proc Natl Acad Sci USA Nov 1, 2005 vol.102 N.44 p.16019-16024

Gilda M. Kalinec * , Martin E. Fernandez-Zapico , , Raul Urrutia , Nora Esteban-Cruciani , Shanping Chen * and Federico Kalinec *, ¶, ||

*Gonda Department of Cell and Molecular Biology, House Ear Institute, Los Angeles, CA 90057; Gastroenterology Research Unit, Mayo Clinic College of Medicine, Rochester, MN 55905; Children’s Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY 10461; and ¶Departments of Otolaryngology and Cell and Neurobiology, University of Southern California, Los Angeles, CA 90089

Communicated by Thomas S. Reese, National Institutes of Health, Bethesda, MD, September 14, 2005 (received for review January 5, 2005)

Gentamicin is a widely used ototoxic agent. In this study, we shed light on the mechanisms underlying gentamicin-induced hearing loss. More importantly, we demonstrate in vivo and in vitro the effectiveness of a strategy for preventing drug-induced hearing loss using L-carnitine (LCAR), a safe micronutrient that plays a key role in energy metabolism and detoxification [Rebouche, C. J. & Seim, H. (1998) Annu. Rev. Nutr. 18, 39-61]. We show that LCAR prevents changes in hearing threshold and cochlear damage in newborn guinea pigs exposed to gentamicin in utero. Mechanistically, gentamicin-induced apoptosis of auditory cells is mediated by the extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK) pathway through up-regulation of the proapoptotic factor Harakiri (Hrk). Most important, small interfering RNA (siRNA) experiments demonstrate that Hrk up-regulation is crucial for gentamicin-induced apoptosis. LCAR, in contrast, prevents both gentamicin-induced Hrk up-regulation and apoptosis acting by means of c-Jun N-terminal kinase (JNK). Together, these results outline pathways for gentamicin-induced hearing loss and its prevention and assign a key role to Hrk in these processes. Thus, our data offer a conceptual framework for designing clinical trials using a safe micronutrient, LCAR, as a simple preventive strategy for iatrogenically induced ototoxicity.
Author contributions: G.M.K., M.E.F.-Z., S.C., and F.K. performed research; G.M.K., M.E.F.-Z., R.U., and F.K. analyzed data; R.U. contributed new reagents/analytic tools; N.E.-C. and F.K. designed research; and R.U. and F.K. wrote the paper.
Conflict of interest statement: No conflicts declared.

Abbreviations: LCAR, L-carnitine; Hrk, Harakiri; ABR, auditory brainstem response; SEM, scanning electron microscopy; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; siRNA, small interfering RNA; OHC, outer hair cell; MAPK, mitogen-activated protein kinase; p, phosphorylated; I, inhibitor.

G.M.K. and M.E.F.-Z. contributed equally to this work.

To whom correspondence should be addressed at: Department of Cell and Molecular Biology, House Ear Institute, 2100 West Third Street, Los Angeles, CA 90057. E-mail: fkalinec@hei.org.

© 2005 by The National Academy of Sciences of the USA
 

December 16, 2005 at 2:19 pm Leave a comment

SUPPLEMENT ARTICLE – The Role of Antimicrobial Management Programs in Optimizing Antibiotic Prescribing within Hospitals

Source: Clinical Infectious Diseases Jan.15, 2006;42:SS90-S95

David L. Paterson

Antibiotic Management Program and Transplant Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Managing serious infections is a balance between providing timely and appropriate broad-spectrum empirical therapy for individual patients, which has been consistently shown to improve outcomes, and reducing unnecessary use of antimicrobial agents, which may contribute to the development of antimicrobial resistance. To control the spread of antimicrobial resistance, hospitals commonly implement programs designed to optimize antimicrobial use, supported by infection-control measures. Hospital-based antimicrobial management programsalso called “antimicrobial stewardship programs”are primarily based on education coupled with a “front-end” approach (i.e., restricting the availability of selected antimicrobial agents) or a “back-end” approach (i.e., reviewing broad-spectrum empirical therapy and then streamlining or discontinuing therapy, as indicated, on the basis of culture and susceptibility testing results and clinical response). Institutional efforts to optimize antimicrobial use should concentrate on patient outcomes, should have multidisciplinary support, and should use a combination of interventions customized to the needs, resources, and information technology infrastructure of the health care institution.

December 16, 2005 at 1:55 pm Leave a comment

SUPPLEMENT ARTICLE – The Relationship between Antimicrobial Resistance and Patient Outcomes: Mortality, Length of Hospital Stay, and Health Care Costs

Source: Clinical Infectious Diseases Jan.15, 2006;42:SS82-S89

Sara E. Cosgrove

Division of Infectious Diseases, The Johns Hopkins Medical Institutions, Baltimore, Maryland

There is an association between the development of antimicrobial resistance in Staphylococcus aureus, enterococci, and gram-negative bacilli and increases in mortality, morbidity, length of hospitalization, and cost of health care. For many patients, inadequate or delayed therapy and severe underlying disease are primarily responsible for the adverse outcomes of infections caused by antimicrobial-resistant organisms. Patients with infections due to antimicrobial-resistant organisms have higher costs ($6,000$30,000) than do patients with infections due to antimicrobial-susceptible organisms; the difference in cost is even greater when patients infected with antimicrobial-resistant organisms are compared with patients without infection. Strategies to prevent nosocomial emergence and spread of antimicrobial-resistant organisms are essential.
 

December 16, 2005 at 1:53 pm Leave a comment

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