Preparing for 2009 H1N1 Influenza
N Engl J of Medicine Nov 12, 2009 V.361 N.20 p.1991-1993
Editorial
Richard P. Wenzel, M.D., and Michael B. Edmond, M.D., M.P.H.
In 1743, when disease was presumed to be astral in origin, European newspapers reported on a contagious influence (influenza in Italian) that was being visited on the citizens of Rome. Two hundred years later, Wilson Smith and colleagues would isolate an influenza A virus, one of the members of the orthomyxovirus family.1 The key reservoirs of all influenza A viruses are migrating waterfowl, and intermittently, other hosts, such as pigs and people, are infected. Further classification of influenza A viruses is based on the specific hemagglutinin viral attachment spike and neuraminidase disengagement spike; the latter is cleaved when newly minted viruses emerge from infected cells. Smith’s isolate was a variant of the H1N1 agent that caused the pandemic of 1918–1919, and H1N1 progeny persisted until the emergence of the Asian influenza pandemic strain (H2N2) in 1957. However, a new H1N1 strain of swine influenza emerged in 1976, and variants of this virus continue to circulate as one of the seasonal strains.
abstract
http://content.nejm.org/cgi/content/full/361/20/1991?query=TOC
Add comment November 11, 2009
Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus
N Engl J of Medicine Nov 12, 2009 V.361 N.20 p.1945-1952
Kathy Hancock, Ph.D., Vic Veguilla, M.P.H., Xiuhua Lu, M.D., Weimin Zhong, Ph.D., Eboneé N. Butler, M.P.H., Hong Sun, M.D., Feng Liu, M.D., Ph.D., Libo Dong, M.D., Ph.D., Joshua R. DeVos, M.P.H., Paul M. Gargiullo, Ph.D., T. Lynnette Brammer, M.P.H., Nancy J. Cox, Ph.D., Terrence M. Tumpey, Ph.D., and Jacqueline M. Katz, Ph.D.
Background A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups.
Methods Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines.
Results A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults.
Conclusions Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies.
abstract
http://content.nejm.org/cgi/content/full/361/20/1945?query=TOC
Add comment November 11, 2009
Hospitalized Patients with 2009 H1N1 Influenza in the United States, April–June 2009
N Engl J of Medicine Nov 12, 2009 V.361 N.20 p.1935-1944
Seema Jain, M.D., Laurie Kamimoto, M.D., M.P.H., Anna M. Bramley, M.P.H., Ann M. Schmitz, D.V.M., Stephen R. Benoit, M.D., M.P.H., Janice Louie, M.D., M.P.H., David E. Sugerman, M.D., M.P.H., Jean K. Druckenmiller, B.S., S.M.(N.R.M.), Kathleen A. Ritger, M.D., M.P.H., Rashmi Chugh, M.D., M.P.H., Supriya Jasuja, M.D., M.P.H., Meredith Deutscher, M.D., Sanny Chen, Ph.D., M.H.S., John D. Walker, M.D., Jeffrey S. Duchin, M.D., Susan Lett, M.D., M.P.H., Susan Soliva, M.P.H., Eden V. Wells, M.D., M.P.H., David Swerdlow, M.D., Timothy M. Uyeki, M.D., M.P.H., Anthony E. Fiore, M.D., M.P.H., Sonja J. Olsen, Ph.D., Alicia M. Fry, M.D., M.P.H., Carolyn B. Bridges, M.D., Lyn Finelli, Dr.P.H., for the 2009 Pandemic Influenza A (H1N1) Virus Hospitalizations Investigation Team
Background During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics of patients who were hospitalized with 2009 H1N1 influenza in the United States from April 2009 to mid-June 2009.
Methods Using medical charts, we collected data on 272 patients who were hospitalized for at least 24 hours for influenza-like illness and who tested positive for the 2009 H1N1 virus with the use of a real-time reverse-transcriptase–polymerase-chain-reaction assay.
Results Of the 272 patients we studied, 25% were admitted to an intensive care unit and 7% died. Forty-five percent of the patients were children under the age of 18 years, and 5% were 65 years of age or older. Seventy-three percent of the patients had at least one underlying medical condition; these conditions included asthma; diabetes; heart, lung, and neurologic diseases; and pregnancy. Of the 249 patients who underwent chest radiography on admission, 100 (40%) had findings consistent with pneumonia. Of the 268 patients for whom data were available regarding the use of antiviral drugs, such therapy was initiated in 200 patients (75%) at a median of 3 days after the onset of illness. Data suggest that the use of antiviral drugs was beneficial in hospitalized patients, especially when such therapy was initiated early.
Conclusions During the evaluation period, 2009 H1N1 influenza caused severe illness requiring hospitalization, including pneumonia and death. Nearly three quarters of the patients had one or more underlying medical conditions. Few severe illnesses were reported among persons 65 years of age or older. Patients seemed to benefit from antiviral therapy.
abstract
http://content.nejm.org/cgi/content/full/361/20/1935?query=TOC
Add comment November 11, 2009
Critical Care Services and 2009 H1N1 Influenza in Australia and New Zealand
N Engl J of Medicine Nov 12, 2009 V.361 N.20 p.1925-1934
The ANZIC Influenza Investigators
Background Planning for the treatment of infection with the 2009 pandemic influenza A (H1N1) virus through health care systems in developed countries during winter in the Northern Hemisphere is hampered by a lack of information from similar health care systems.
Methods We conducted an inception-cohort study in all Australian and New Zealand intensive care units (ICUs) during the winter of 2009 in the Southern Hemisphere. We calculated, per million inhabitants, the numbers of ICU admissions, bed-days, and days of mechanical ventilation due to infection with the 2009 H1N1 virus. We collected data on demographic and clinical characteristics of the patients and on treatments and outcomes.
Results From June 1 through August 31, 2009, a total of 722 patients with confirmed infection with the 2009 H1N1 virus (28.7 cases per million inhabitants; 95% confidence interval [CI], 26.5 to 30.8) were admitted to an ICU in Australia or New Zealand. Of the 722 patients, 669 (92.7%) were under 65 years of age and 66 (9.1%) were pregnant women; of the 601 adults for whom data were available, 172 (28.6%) had a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 35. Patients infected with the 2009 H1N1 virus were in the ICU for a total of 8815 bed-days (350 per million inhabitants). The median duration of treatment in the ICU was 7.0 days (interquartile range, 2.7 to 13.4); 456 of 706 patients (64.6%) with available data underwent mechanical ventilation for a median of 8 days (interquartile range, 4 to 16). The maximum daily occupancy of the ICU was 7.4 beds (95% CI, 6.3 to 8.5) per million inhabitants. As of September 7, 2009, a total of 103 of the 722 patients (14.3%; 95% CI, 11.7 to 16.9) had died, and 114 (15.8%) remained in the hospital.
Conclusions The 2009 H1N1 virus had a substantial effect on ICUs during the winter in Australia and New Zealand. Our data can assist planning for the treatment of patients during the winter in the Northern Hemisphere
abstract
http://content.nejm.org/cgi/content/full/361/20/1925?query=TOC
Add comment November 11, 2009
From Prolonged Febrile Illness to Fever of Unknown Origin
Archives of Internal Medicine May 12, 2003 V.163 N.9 p.1033-1041
The Challenge Continues
Steven Vanderschueren, MD, PhD; Daniël Knockaert, MD, PhD; Tom Adriaenssens, MD; Wim Demey, MD; Anne Durnez, MD; Daniël Blockmans, MD, PhD; Herman Bobbaers, MD, PhD
From the Department of Internal Medicine, Unit of General Internal Medicine, University Hospital Leuven, Leuven, Belgium. The authors have no relevant financial interest in this article.
Background Epidemiological changes and the ongoing expansion of the diagnostic armamentarium warrant a regular update of the spectrum of diseases that present as prolonged febrile illnesses.
Methods We prospectively collected a series of 290 immunocompetent patients referred to our university hospital between 1990 and 1999 with a febrile illness (temperature >38.3°C) of uncertain cause, lasting at least 3 weeks. Patients were categorized in 4 groups according to the timing of diagnosis: early diagnosis (within 3 in-hospital days or 3 outpatient visits), intermediate diagnosis (between days 4 and 7), late diagnosis (after day 7), and no diagnosis during index contact or follow-up.
Results A final diagnosis was established early in 67 patients (23.1%), intermediate in 38 (13.1%), and late in 87 (30.0%). In the remaining 98 (33.8%), no diagnosis was made. The cause of the fever remained obscure in 50 (47.6%) of 105 patients with episodic fever vs 48 (25.9%) of 185 patients with continuous fever (P<.001). Among the 192 patients with a final diagnosis, noninfectious inflammatory diseases represented the most prevalent diagnostic category (35.4%), surpassing infections (29.7%), miscellaneous causes (19.8%), and malignancies (15.1%). Fourteen disorders accounted for over 59% of diagnoses, whether diagnosis was reached early, intermediate, or late. Hematological malignancies made up 11.5% of diagnoses, but were responsible for 14 (58.3%) of the 24 fatalities related to the febrile illness. Of the 80 patients discharged alive without diagnosis and for whom follow-up was available, 3 died, but the deaths were considered to be unrelated to the feverish illness.
Conclusions Prolonged febrile illnesses remain a diagnostic challenge. Despite the technological progress of the late 20th century, the origin of the fever remains elusive in many patients, especially in those with episodic fevers. Noninfectious inflammatory diseases emerge as the most prevalent diagnostic category.
abstract
http://archinte.ama-assn.org/cgi/content/abstract/163/9/1033
Add comment November 11, 2009
A Comprehensive Evidence-Based Approach to Fever of Unknown Origin
Archives of Internal Medicine Mar 19, 2003 V.163 N.5 p.545-551
Ophyr Mourad, MD, FRCPC; Valerie Palda, MD, MSc; Allan S. Detsky, MD, PhD
From the Departments of Medicine (Drs Mourad, Palda, and Detsky) and Health Policy Management and Evaluation (Drs Palda and Detsky), University of Toronto; and the Division of General Internal Medicine, St Michael’s Hospital (Drs Mourad and Palda) and Mt Sinai Hospital and University Health Network (Dr Detsky), Toronto, Ontario.
Background Fever of unknown origin (FUO) is defined as a temperature higher than 38.3°C on several occasions and lasting longer than 3 weeks, with a diagnosis that remains uncertain after 1 week of investigation.
Methods A systematic review was performed to develop evidence-based recommendations for the diagnostic workup of FUO. MEDLINE database was searched (January 1966 to December 2000) to identify articles related to FUO. Articles were included if the patient population met the criteria for FUO and they addressed the natural history, prognosis, or spectrum of disease or evaluated a diagnostic test in FUO. The quality of retrieved articles was rated as “good,” “fair,” or “poor,” and sensitivity, specificity, and diagnostic yield of tests were calculated. Recommendations were made in accordance with the strength of evidence.
Results The prevalence of FUO in hospitalized patients is reported to be 2.9%. Eleven studies indicate that the spectrum of disease includes “no diagnosis” (19%), infections (28%), inflammatory diseases (21%), and malignancies (17%). Deep vein thrombosis (3%) and temporal arteritis in the elderly (16%-17%) were important considerations. Four good natural history studies indicate that most patients with undiagnosed FUO recover spontaneously (51%-100%). One fair-quality study suggested a high specificity (99%) for the diagnosis of endocarditis in FUO by applying the Duke criteria. One fair-quality study showed that computed tomographic scanning of the abdomen had a diagnostic yield of 19%. Ten studies of nuclear imaging revealed that technetium was the most promising isotope, showing a high specificity (94%), albeit low sensitivity (40%-75%) (2 fair-quality studies). Two fair-quality studies showed liver biopsy to have a high diagnostic yield (14%-17%), but with risk of harm (0.009%-0.12% death). Empiric bone marrow cultures showed a low diagnostic yield of 0% to 2% (2 fair-quality articles).
Conclusions Diagnosis of FUO may be assisted by the Duke criteria for endocarditis, computed tomographic scan of the abdomen, nuclear scanning with a technetium-based isotope, and liver biopsy (fair to good evidence). Routine bone marrow cultures are not recommended.
abstract
http://archinte.ama-assn.org/cgi/content/abstract/163/5/545
Add comment November 11, 2009
Practice Guidelines for Evaluating New Fever in Critically Ill Adult Patients
Clinical Infectious Diseases May 1998 V.26 N.5 p.1042–1059
Naomi P. O’Grady Philip S. Barie John G. Bartlett Thomas Bleck Glenda Garvey Judith Jacobi Peter Linden
Dennis G. Maki Myung Nam William Pasculle Michael D. Pasquale Debra L. Tribett Henry Masur
From the National Institutes of Health, Bethesda, and the Johns Hopkins Hospital and St. Agnes Hospital, Baltimore, Maryland; the New York Hospital, and the Columbia‐Presbyterian Medical Center, New York, New York; the University of Virginia, Charlottesville, and Infectious Disease Physicians, Inc., Annandale, Virginia; the Methodist Hospital of Indiana, Indianapolis, Indiana; and the University of Pittsburgh Medical Center, Pittsburgh, and the Lehigh Valley Hospital, Allentown, Pennsylvania
These practice guidelines have been developed by a Task Force of the Society of Critical Care Medicine in collaboration with the IDSA and are part of a series of updated and new guidelines from the IDSA that will appear in CID.
Add comment November 11, 2009
Effects of Preoperative Skin Preparation on Postoperative Wound Infection Rates: A Prospective Study of 3 Skin Preparation Protocols
Infection Control and Hospital Epidemiology October 2009 V.30 N.10 p.964–971
Brian R. Swenson, MD, MS; Traci L. Hedrick, MD; Rosemarie Metzger, MD; Hugo Bonatti, MD; Timothy L. Pruett, MD; Robert G. Sawyer, MD
From the Departments of Surgery (B.R.S., T.L.H., R.M., H.B., T.L.P., R.G.S.) and Public Health Sciences (R.G.S.), University of Virginia Health System, Charlottesville.
Objective. To compare the effects of different skin preparation solutions on surgical-site infection rates.
Design. Three skin preparations were compared by means of a sequential implementation design. Each agent was adopted as the preferred modality for a 6-month period for all general surgery cases. Period 1 used a povidone-iodine scrub-paint combination (Betadine) with an isopropyl alcohol application between these steps, period 2 used 2% chlorhexidine and 70% isopropyl alcohol (ChloraPrep), and period 3 used iodine povacrylex in isopropyl alcohol (DuraPrep). Surgical-site infections were tracked for 30 days as part of ongoing data collection for the National Surgical Quality Improvement Project initiative. The primary outcome was the overall rate of surgical-site infection by 6-month period performed in an intent-to-treat manner.
Setting. Single large academic medical center.
Patients. All adult general surgery patients.
Results. The study comprised 3,209 operations. The lowest infection rate was seen in period 3, with iodine povacrylex in isopropyl alcohol as the preferred preparation method (3.9%, compared with 6.4% for period 1 and 7.1% for period 2; ). In subgroup analysis, no difference in outcomes was seen between patients prepared with povidone-iodine scrub-paint and those prepared with iodine povacrylex in isopropyl alcohol, but patients in both these groups had significantly lower surgical-site infection rates, compared with rates for patients prepared with 2% chlorhexidine and 70% isopropyl alcohol (4.8% vs 8.2%; ).
Conclusions. Skin preparation solution is an important factor in the prevention of surgical-site infections. Iodophor-based compounds may be superior to chlorhexidine for this purpose in general surgery patients.
Abstract
Add comment November 10, 2009
Long-term follow-up trial of oral rifampin-cotrimoxazole combination versus intravenous cloxacillin in treatment of chronic staphylococcal osteomyelitis.
Antimicrob Agents Chemother. 2009 Jun. V.53 N.6 p.2672-2676.
G. Euba,1* O. Murillo,1 N. Fernández-Sabé,1 J. Mascaró,1, J. Cabo,2 A. Pérez,2 F. Tubau,3 R. Verdaguer,3 F. Gudiol,1 and J. Ariza1
Infectious Diseases Department,1 Orthopedic Surgery Department,2 Microbiology Department, IDIBELL, Hospital Universitari de Bellvitge, Barcelona, Spain3
Oral therapies alternative to fluoroquinolones against staphylococcal chronic osteomyelitis have not been evaluated in comparative studies. Consecutive nonaxial Staphylococcus aureus chronic osteomyelitis cases were included in a comparative trial after debridement. Fifty patients were randomized: group A (n = 22) was treated with cloxacillin for 6 weeks intravenously plus 2 weeks orally (p.o.), and group B (n = 28) was treated with rifampin-cotrimoxazole for 8 weeks p.o. During follow-up (10 years), five relapses occurred: two (10%) in group A and three (11%) in group B. Foreign-body maintenance was associated with relapse (P = 0.016). Oral rifampin-cotrimoxazole treatment showed outcomes comparable to those for intravenous cloxacillin treatment.
Add comment November 10, 2009
Efficacy of daptomycin in implant-associated infection due to methicillin-resistant Staphylococcus aureus: importance of combination with rifampin.
Antimicrob Agents Chemother. 2009 Jul. V.53 N.7 p.2719-2724.
Anne-Kathrin John,1 Daniela Baldoni,1 Manuel Haschke,2 Katharina Rentsch,3 Patrick Schaerli,4 Werner Zimmerli,5 and Andrej Trampuz1,6*
Infectious Diseases, Department of Biomedicine, University Hospital Basel, Basel, Switzerland,1 Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland,2 Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland,3 Infectious Diseases, Transplantation and Immunology, Novartis Pharma Schweiz AG, Bern, Switzerland,4 Basel University Medical Clinic, Kantonsspital, Liestal, Switzerland,5 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland6
Limited treatment options are available for implant-associated infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). We compared the activity of daptomycin (alone and with rifampin [rifampicin]) with the activities of other antimicrobial regimens against MRSA ATCC 43300 in the guinea pig foreign-body infection model. The daptomycin MIC and the minimum bactericidal concentration in logarithmic phase and stationary growth phase of MRSA were 0.625, 0.625, and 20 µg/ml, respectively. In time-kill studies, daptomycin showed rapid and concentration-dependent killing of MRSA in stationary growth phase. At concentrations above 20 µg/ml, daptomycin reduced the counts by >3 log10 CFU/ml in 2 to 4 h. In sterile cage fluid, daptomycin peak concentrations of 23.1, 46.3, and 53.7 µg/ml were reached 4 to 6 h after the administration of single intraperitoneal doses of 20, 30, and 40 mg/kg of body weight, respectively. In treatment studies, daptomycin alone reduced the planktonic MRSA counts by 0.3 log10 CFU/ml, whereas in combination with rifampin, a reduction in the counts of >6 log10 CFU/ml was observed. Vancomycin and daptomycin (at both doses) were unable to cure any cage-associated infection when they were given as
monotherapy, whereas rifampin alone cured the infections in 33% of the cages. In combination with rifampin, daptomycin showed cure rates of 25% (at 20 mg/kg) and 67% (at 30 mg/kg), vancomycin showed a cure rate of 8%, linezolid showed a cure rate of 0%, and levofloxacin showed a cure rate of 58%. In addition, daptomycin at a high dose (30 mg/kg) completely prevented the emergence of rifampin resistance in planktonic and adherent MRSA cells. Daptomycin at a high dose, corresponding to 6 mg/kg in humans, in combination with rifampin showed the highest activity against planktonic and adherent MRSA. Daptomycin plus rifampin is a promising treatment option for implant-associated MRSA infections.
Add comment November 10, 2009
