Showing papers in "Clinical Infectious Diseases in 2009"

Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America

Abstract: The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, “Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews,” and recently issued a “Call to Action” to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure—one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.

Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America.

Abstract: Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.

Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America

Abstract: These updated guidelines replace the previous management guidelines published in 2001. The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them.

Ongoing Revolution in Bacteriology: Routine Identification of Bacteria by Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry

Abstract: Background. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry accurately identifies both selected bacteria and bacteria in select clinical situations. It has not been evaluated for routine use in the clinic. Methods. We prospectively analyzed routine MALDI-TOF mass spectrometry identification in parallel with conventional phenotypic identification of bacteria regardless of phylum or source of isolation. Discrepancies were resolved by 16S ribosomal RNA and rpoB gene sequence-based molecular identification. Colonies (4 spots per isolate directly deposited on the MALDI-TOF plate) were analyzed using an Autoflex II Bruker Daltonik mass spectrometer. Peptidic spectra were compared with the Bruker BioTyper database, version 2.0, and the identification score was noted. Delays and costs of identification were measured. Results. Of 1660 bacterial isolates analyzed, 95.4% were correctly identified by MALDI-TOF mass spectrometry; 84.1% were identified at the species level, and 11.3% were identified at the genus level. In most cases, absence of identification (2.8% of isolates) and erroneous identification (1.7% of isolates) were due to improper database entries. Accurate MALDI-TOF mass spectrometry identification was significantly correlated with having 10 reference spectra in the database (P = .01). The mean time required for MALDI-TOF mass spectrometry identification of 1 isolate was 6 minutes for an estimated 22%-32% cost of current methods of identification. Conclusions. MALDI-TOF mass spectrometry is a cost-effective, accurate method for routine identification of bacterial isolates in <1 h using a database comprising ≥10 reference spectra per bacterial species and a ≥1.9 identification score (Brucker system). It may replace Gram staining and biochemical identification in the near future.

Antimicrobial Susceptibility Testing: A Review of General Principles and Contemporary Practices

Abstract: An important task of the clinical microbiology laboratory is the performance of antimicrobial susceptibility testing of significant bacterial isolates. The goals of testing are to detect possible drug resistance in common pathogens and to assure susceptibility to drugs of choice for particular infections. The most widely used testing methods include broth microdilution or rapid automated instrument methods that use commercially marketed materials and devices. Manual methods that provide flexibility and possible cost savings include the disk diffusion and gradient diffusion methods. Each method has strengths and weaknesses, including organisms that may be accurately tested by the method. Some methods provide quantitative results (eg, minimum inhibitory concentration), and all provide qualitative assessments using the categories susceptible, intermediate, or resistant. In general, current testing methods provide accurate detection of common antimicrobial resistance mechanisms. However, newer or emerging mechanisms of resistance require constant vigilance regarding the ability of each test method to accurately detect resistance.

Epidemiology and Outcomes of Candidemia in 2019 Patients: Data from the Prospective Antifungal Therapy Alliance Registry

Abstract: Background. Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. Methods. Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis. Results. The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P<.001) and were less likely to be neutropenic (5.1%; P<.001) and to receive corticosteroids (33.5%; P<.001) or other immunosuppressive drugs (7.9%; P = .002), compared with patients infected with other Candida species. Candida krusei candidemia was most commonly associated with prior use of antifungal agents (70.6%; P<.001), hematologic malignancy (52.9%; P<.001) or stem cell transplantation (17.7%; P<.001), neutropenia (45.1%; P<.001), and corticosteroid treatment (60.8%; P<.001). Patients with C. krusei candidemia had the highest crude 12-week mortality in this series (52.9%; P<.001). Fluconazole was the most commonly administered antimicrobial, followed by the echinocandins, and amphotericin B products were infrequently administered. Conclusions. The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen.

Google Trends: A Web-Based Tool for Real-Time Surveillance of Disease Outbreaks

Abstract: Google Flu Trends can detect regional outbreaks of influenza 7-10 days before conventional Centers for Disease Control and Prevention surveillance systems. We describe the Google Trends tool, explain how the data are processed, present examples, and discuss its strengths and limitations. Google Trends shows great promise as a timely, robust, and sensitive surveillance system. It is best used for surveillance of epidemics and diseases with high prevalences and is currently better suited to track disease activity in developed countries, because to be most effective, it requires large populations of Web search users. Spikes in search volume are currently hard to interpret but have the benefit of increasing vigilance. Google should work with public health care practitioners to develop specialized tools, using Google Flu Trends as a blueprint, to track infectious diseases. Suitable Web search query proxies for diseases need to be established for specialized tools or syndromic surveillance. This unique and innovative technology takes us one step closer to true real-time outbreak surveillance.

Vancomycin Therapeutic Guidelines: A Summary of Consensus Recommendations from the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists

Abstract: Practice guidelines for therapeutic monitoring of vancomycin treatment for Staphylococcus aureus infection in adult patients were reviewed by an expert panel of the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. A literature review of existing evidence regarding vancomycin dosing and monitoring of serum concentrations, in addition to patient outcomes combined with expert opinion regarding the drug's pharmacokinetic, pharmacodynamic, and safety record, resulted in new recommendations for targeting and adjustment of vancomycin therapy.

Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry.

Abstract: BACKGROUND With use of data from the Prospective Antifungal Therapy (PATH) Alliance registry, we performed this multicenter, prospective, observational study to assess the epidemiologic characters and outcomes of invasive fungal infection (IFI) in hematopoietic stem cell transplant (HSCT) recipients. METHODS Sixteen medical centers from North America reported data on adult HSCT recipients with proven or probable IFI during the period July 2004 through September 2007. The distribution of IFIs and rates of survival at 6 and 12 weeks after diagnosis were studied. We used logistic regression models to determine risk factors associated with 6-week mortality for allogeneic HSCT recipients with invasive aspergillosis (IA). RESULTS Two hundred thirty-four adult HSCT recipients with a total of 250 IFIs were included in this study. IA (59.2%) was the most frequent IFI, followed by invasive candidiasis (24.8%), zygomycosis (7.2%), and IFI due to other molds (6.8%). Voriconazole was the most frequently administered agent (68.4%); amphotericin B deoxycholate was administered to a few patients (2.1%). Ninety-three (46.7%) of 199 HSCT recipients with known outcome had died by week 12. The 6-week survival rate was significantly greater for patients with IA than for those with invasive candidiasis and for those with IFI due to the Zygomycetes or other molds (P < .07). The 6-week mortality rate for HSCT recipients with IA was 21.5%. At 6 weeks, there was a trend toward a worse outcome among allogeneic HSCT recipients with IA who received myeloablative conditioning (P = .07); absence of mechanical ventilation or/and hemodialysis (P = .01) were associated with improved survival. CONCLUSIONS IA remains the most commonly identified IFI among HSCT recipients, but rates of survival in persons with IA appear to have improved, compared with previously reported data. Invasive candidiasis and IFI due to molds other than Aspergillus species remain a significant problem in HSCT recipients.

Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship.

Abstract: Background Organisms resistant to antimicrobials continue to emerge and spread. This study was performed to measure the medical and societal cost attributable to antimicrobial-resistant infection (ARI). Methods A sample of high-risk hospitalized adult patients was selected. Measurements included ARI, total cost, duration of stay, comorbidities, acute pathophysiology, Acute Physiology and Chronic Health Evaluation III score, intensive care unit stay, surgery, health care-acquired infection, and mortality. Hospital services used and outcomes were abstracted from electronic and written medical records. Medical costs were measured from the hospital perspective. A sensitivity analysis including 3 study designs was conducted. Regression was used to adjust for potential confounding in the random sample and in the sample expanded with additional patients with ARI. Propensity scores were used to select matched control subjects for each patient with ARI for a comparison of mean cost for patients with and without ARI. Results In a sample of 1391 patients, 188 (13.5%) had ARI. The medical costs attributable to ARI ranged from $18,588 to $29,069 per patient in the sensitivity analysis. Excess duration of hospital stay was 6.4-12.7 days, and attributable mortality was 6.5%. The societal costs were $10.7-$15.0 million. Using the lowest estimates from the sensitivity analysis resulted in a total cost of $13.35 million in 2008 dollars in this patient cohort. Conclusions The attributable medical and societal costs of ARI are considerable. Data from this analysis could form the basis for a more comprehensive evaluation of the cost of resistance and the potential economic benefits of prevention programs.

Seasonal Influenza in Adults and Children—Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management: Clinical Practice Guidelines of the Infectious Diseases Society of America

Abstract: Guidelines for the treatment of persons with influenza virus infection were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass diagnostic issues, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal (interpandemic) influenza. They are intended for use by physicians in all medical specialties with direct patient care, because influenza virus infection is common in communities during influenza season and may be encountered by practitioners caring for a wide variety of patients.

Chikungunya Fever: An Epidemiological Review of a Re-Emerging Infectious Disease

Abstract: Chikungunya fever is an acute febrile illness associated with severe, often debilitating polyarthralgias. The disease is caused by Chikungunya virus (CHIKV), an arthropod-borne virus that is transmitted to humans primarily via the bite of an infected mosquito. Since a re-emergence of CHIKV in 2004, the virus has spread into novel locations, such as Europe, and has led to millions of cases of disease throughout countries in and around the Indian Ocean. The risk of importation of CHIKV into new areas is ever present because of the high attack rates associated with the recurring epidemics, the high levels of viremia in infected humans, and the worldwide distribution of the vectors responsible for transmitting CHIKV. In this review, we will characterize the epidemiology and global expansion of CHIKV, describe the clinical features and laboratory testing for the disease, and discuss priorities for further studies needed for effective disease control and prevention.

Epidemiology of Extrapulmonary Tuberculosis in the United States, 1993–2006

Abstract: Background Almost one-fifth of United States tuberculosis cases are extrapulmonary; unexplained slower annual case count decreases have occurred in extrapulmonary tuberculosis (EPTB), compared with annual case count decreases in pulmonary tuberculosis (PTB) cases. We describe the epidemiology of EPTB by means of US national tuberculosis surveillance data. Methods US tuberculosis cases reported from 1993 to 2006 were classified as either EPTB or PTB. EPTB encompassed lymphatic, pleural, bone and/or joint, genitourinary, meningeal, peritoneal, and unclassified EPTB cases. We excluded cases with concurrent extrapulmonary-pulmonary tuberculosis and cases of disseminated (miliary) tuberculosis. Demographic characteristics, drug susceptibility test results, and risk factors, including human immunodeficiency virus (HIV) status, were compared for EPTB and PTB cases. Results Among 253,299 cases, 73.6% were PTB and 18.7% were EPTB, including lymphatic (40.4%), pleural (19.8%), bone and/or joint (11.3%), genitourinary (6.5%), meningeal (5.4%), peritoneal (4.9%), and unclassified EPTB (11.8%) cases. Compared with PTB, EPTB was associated with female sex (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.7-1.8) and foreign birth (OR, 1.5; CI, 1.5-1.6), almost equally associated with HIV status (OR, 1.1; CI, 1.1-1.1), and negatively associated with multidrug resistance (OR, 0.6; CI, 0.5-0.6) and several tuberculosis risk factors, especially homelessness (OR, 0.3; CI, 0.3-0.3) and excess alcohol use (OR, 0.3; CI, 0.3-0.3). Slower annual decreases in EPTB case counts, compared with annual decreases in PTB case counts, from 1993 through 2006 have caused EPTB to increase from 15.7% of tuberculosis cases in 1993 to 21.0% in 2006. Conclusions EPTB epidemiology and risk factors differ from those of PTB, and the proportion of EPTB has increased from 1993 through 2006. Further study is needed to identify causes of the proportional increase in EPTB.

An Estimate of the Burden of Chagas Disease in the United States

Abstract: Chagas disease causes the highest burden of any parasitic disease in the Western hemisphere. By applying published seroprevalence figures to immigrant populations, we estimate that 300,167 individuals with Trypanosoma cruzi infection live in the United States, with 30,000-45,000 cardiomyopathy cases and 63-315 congenital infections annually. T. cruzi causes a substantial disease burden in the United States.

Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients.

Abstract: BACKGROUND Data suggest that higher doses of vancomycin can increase the risk of nephrotoxicity. No study has been undertaken to determine the pharmacodynamic index (ie, the area under the curve [AUC] or the trough value) that best describes the relationship between vancomycin exposure and onset of nephrotoxicity. METHODS A retrospective study was conducted among patients who received vancomycin for a suspected or proven gram-positive infection during the period from 1 January 2005 through 31 December 2006 at Albany Medical Center Hospital. Patients were included in our study if they (1) were > or =18 years old, (2) had an absolute neutrophil count of > or =1000 cells/mm(3), (3) received vancomycin for >48 h, (4) had 1 vancomycin trough level collected within 96 h of vancomycin therapy, and (5) had a baseline serum creatinine level of <2.0 mg/dL. Patients were excluded if they (1) had a diagnosis of cystic fibrosis, (2) received intravenous contrast dye within 7 days of starting vancomycin or during therapy, or (3) required vasopressor support during therapy. Demographics, comorbid conditions, and treatment data were collected. The highest observed vancomycin trough value within 96 h of initiation of vancomycin therapy and the estimated vancomycin AUC were analyzed as measures of vancomycin exposure. The vancomycin AUC value from 0 to 24 h at steady state (in units of mg x h/L) for each patient was estimated by use of the maximum a posteriori probability Bayesian procedure in ADAPT II. Nephrotoxicity was defined as an increase in serum creatinine level of 0.5 mg/dL or 50%, whichever was greater, following initiation of vancomycin therapy. Logistic and Cox proportional hazards regression models identified the vancomycin pharmacodynamic index that best describes the relationship between vancomycin exposure and toxicity. RESULTS During the study period, 166 patients met the inclusion criteria. Both initial vancomycin trough values and 0-24-h at steady state AUC values were associated with nephrotoxicity in the bivariate analyses. However, the vancomycin trough value, modeled as a continuous variable, was the only vancomycin exposure variable associated with nephrotoxicity in the multivariate analyses. CONCLUSIONS The results indicate that a vancomycin exposure-toxicity response relationship exists. The vancomycin trough value is the pharmacodynamic index that best describes this association.

A Multinational Survey of Risk Factors for Infection with Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Nonhospitalized Patients

Abstract: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are increasing in frequency and are associated with high mortality rates. Circulation of CTX-M-type ESBLs in the community is of particular concern, because it may confound standard infection-control measures.

Topical Antimicrobial Therapy for Treating Chronic Wounds

Abstract: Various agents have been applied topically to treat infected wounds for millennia, but their proper role remains unclear. Topical therapy affords many potential advantages but also has disadvantages. Opinions differ on which clinical signs define wound infection and on whether quantitative microbiological studies are useful. Clinically infected wounds usually require systemic antibiotic therapy, whereas clinically uninfected wounds that are healing as expected do not require antimicrobials. There is controversy over how to treat poorly healing wounds with "secondary" signs suggesting infection; these may benefit from topical antimicrobial agents. Some evidence supports using topical agents for malodorous or burn wounds. Meta-analyses and systematic reviews suggest there are few proven indications for topical antimicrobials. Use of a newer, relatively nontoxic antiseptic (eg, cadexomer iodine or silver dressings) is preferable to use of topical antibiotics, especially agents that are available for systemic use. We provide clinically relevant information on currently available topical antimicrobial agents.

Missed visits and mortality among patients establishing initial outpatient HIV treatment.

Abstract: BACKGROUND Dramatic increases in the number of patients requiring linkage to treatment for human immunodeficiency virus (HIV) infection are anticipated in response to updated Centers for Disease Control and Prevention HIV testing recommendations that advocate routine, opt-out HIV testing. METHODS A retrospective analysis nested within a prospective HIV clinical cohort study evaluated patients who established initial outpatient treatment for HIV infection at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic from 1 January 2000 through 31 December 2005. Survival methods were used to evaluate the impact of missed visits during the first year of care on subsequent mortality in the context of other baseline sociodemographic, psychosocial, and clinical factors. Mortality was ascertained by query of the Social Security Death Index as of 1 August 2007. RESULTS Among 543 study participants initiating outpatient care for HIV infection, 60% missed a visit within the first year. The mortality rate was 2.3 deaths per 100 person-years for patients who missed visits, compared with 1.0 deaths per 100 person-years for those who attended all scheduled appointments during the first year after establishing outpatient treatment (P = .02). In Cox proportional hazards analysis, higher hazards of death were independently associated with missed visits (hazard ratio, 2.90; 95% confidence interval, 1.28-6.56), older age (hazard ratio, 1.58 per 10 years of age; 95% confidence interval, 1.12-2.22), and baseline CD4+ cell count < 200 cells/mm(3) (hazard ratio, 2.70; 95% confidence interval, 1.00-7.30). CONCLUSIONS Patients who missed visits within the first year after initiating outpatient treatment for HIV infection had more than twice the rate of long-term mortality, compared with those patients who attended all scheduled appointments. We posit that early missed visits are not causally responsible for the higher observed mortality but, rather, identify those patients who are more likely to exhibit health behaviors that portend increased subsequent mortality.

Recent Advances in the Management of Mucormycosis: From Bench to Bedside

Abstract: Recent therapeutic advances have the potential to improve outcomes of mucormycosis. Lipid formulations of amphotericin B (LFAB) have evolved as the cornerstone of primary therapy for mucormycosis. Posaconazole may be useful as salvage therapy, but it cannot be recommended as primary therapy for mucormycosis on the basis of available data. Preclinical and limited retrospective clinical data suggest that combination LFAB-echinocandin therapy may improve survival during mucormycosis. A definitive trial is needed to confirm these results. Combination therapy with LFAB and the iron chelator, deferasirox, also improved outcomes in animal models of mucormycosis. In contrast, combination polyene-posaconazole therapy was of no benefit in preclinical studies. Adjunctive therapy with recombinant cytokines, hyperbaric oxygen, and/or granulocyte transfusions can be considered for selected patients. Early initiation of therapy is critical to maximizing outcomes; recent developments in polymerase chain reaction technology are advancing early diagnostic strategies. Prospective, randomized clinical trials are needed to define optimal management strategies for mucormycosis.

Risk Factors for Toxoplasma gondii Infection in the United States

Abstract: Background. Toxoplasmosis can cause severe ocular and neurological disease. We sought to determine risk factors for Toxoplasma gondii infection in the United States. Methods. We conducted a case-control study of adults recently infected with T. gondii. Case patients were selected from the Palo Alto Medical Foundation Toxoplasma Serology Laboratory from August 2002 through May 2007; control patients were randomly selected from among T. gondii-seronegative persons. Data were obtained from serological testing and patient questionnaires. Results. We evaluated 148 case patients with recent T. gondii infection and 413 control patients. In multivariate analysis, an elevated risk of recent T. gondii infection was associated with the following factors: eating raw ground beef (adjusted odds ratio [aOR], 6.67; 95% confidence limits [CLs], 2.09, 21.24; attributable risk [AR], 7%); eating rare lamb (aOR, 8.39; 95% CLs, 3.68, 19.16; AR, 20%); eating locally produced cured, dried, or smoked meat (aOR, 1.97; 95% CLs, 1.18, 3.28; AR, 22%); working with meat (aOR, 3.15; 95% CLs, 1.09, 9.10 ; AR, 5%); drinking unpasteurized goat's milk (aOR, 5.09; 95% CLs, 1.45, 17.80; AR, 4%); and having 3 or more kittens (aOR, 27.89; 95% CLs, 5.72, 135.86; AR, 10%). Eating raw oysters, clams, or mussels (aOR, 2.22; 95% CLs, 1.07, 4.61; AR, 16%) was significant in a separate model among persons asked this question. Subgroup results are also provided for women and for pregnant women. Conclusions. In the United States, exposure to certain raw or undercooked foods and exposure to kittens are risk factors for T. gondii infection. Knowledge of these risk factors will help to target prevention efforts.

Human Health Consequences of Use of Antimicrobial Agents in Aquaculture

Abstract: Intensive use of antimicrobial agents in aquaculture provides a selective pressure creating reservoirs of drug-resistant bacteria and transferable resistance genes in fish pathogens and other bacteria in the aquatic environment. From these reservoirs, resistance genes may disseminate by horizontal gene transfer and reach human pathogens, or drug-resistant pathogens from the aquatic environment may reach humans directly. Horizontal gene transfer may occur in the aquaculture environment, in the food chain, or in the human intestinal tract. Among the antimicrobial agents commonly used in aquaculture, several are classified by the World Health Organisation as critically important for use in humans. Occurrence of resistance to these antimicrobial agents in human pathogens severely limits the therapeutic options in human infections. Considering the rapid growth and importance of aquaculture industry in many regions of the world and the widespread, intensive, and often unregulated use of antimicrobial agents in this area of animal production, efforts are needed to prevent development and spread of antimicrobial resistance in aquaculture to reduce the risk to human health.

Streptococcus suis: an emerging human pathogen.

Abstract: Streptococcus suis infection is acquired through exposure to contaminated pigs or pig meat. Over the past few years, the number of reported S. suis infections in humans has increased significantly, with most cases originating in Southeast Asia, where there is a high density of pigs. Increased awareness, improved diagnostics, and the occurrence of outbreaks have contributed to this increase. Meningitis and sepsis are the most common clinical manifestations of S. suis infection; hearing loss is a frequent complication. In this article, we provide an overview of the emergence and clinical manifestations of S. suis infection.

Scrub Typhus: The Geographic Distribution of Phenotypic and Genotypic Variants of Orientia tsutsugamushi

Abstract: Orientia tsutsugamushi is the etiological agent of scrub typhus, an acute, mite-borne, febrile illness that occurs in the Asia-Pacific region. Historically, strain characterization used serological analysis and revealed dramatic antigenic diversity. Eyeing a recommendation of potential vaccine candidates for broad protection, we review geographic diversity and serological and DNA prevalences. DNA analysis together with immunological analysis suggest that the prototype Karp strain and closely related strains are the most common throughout the region of endemicity. According to serological analysis, ∼50% of isolates are seroreactive to Karp antisera, and approximately one-quarter of isolates are seroreactive to antisera against the prototype Gilliam strain. Molecular methods reveal greater diversity. By molecular methods, strains phylogenetically similar to Karp make up ∼40% of all genotyped isolates, followed by the JG genotype group (Japan strains serotypically similar to the Gilliam strain but genetically non-Gilliam; 18% of all genotyped isolates). Three other genotype groups (Katorelated, Kawasaki-like, and TA763-like) each represent ∼10% of genotyped isolates. Strains genetically similar to the Gilliam strain make up only 5% of isolates. Strains from these groups should be included in any potential vaccine.

Increasing Burden of Invasive Group B Streptococcal Disease in Nonpregnant Adults, 1990–2007

Abstract: Background. Group B Streptococcus (GBS), traditionally considered to be a neonatal pathogen, is an important cause of morbidity and mortality among older adults and among those with underlying medical conditions. We used population-based surveillance to examine trends in adult GBS disease during the period 1990-2007 and to describe the epidemiology of adult GBS disease to guide prevention efforts. Methods. Active Bacterial Core surveillance was conducted in selected counties in 10 US states. A case was defined as isolation of GBS from a normally sterile site in a nonpregnant resident of a surveillance area who was ≥ 18 years of age. Rates were calculated using US Census data. Demographic and clinical information was abstracted from medical records. Serotyping and susceptibility testing were performed on isolates collected from a subset of case patients. Results. A total of 19,512 GBS cases were identified in nonpregnant adults during 1990-2007 (median patient age, 63 years); the incidence of adult GBS disease doubled from 3.6 cases per 100,000 persons during 1990 to 7.3 cases per 100,000 persons during 2007 (P<.001). The mean difference in incidence between black and white persons was 4.6 cases per 100,000 persons (range, 3.1 cases per 100,000 persons during 1991 to 5.8 cases per 100,000 persons during 1999). Common clinical syndromes in 2007 included bacteremia without focus (39.3%), skin and/or soft-tissue infection (25.6%), and pneumonia (12.6%). Most (88.0%) GBS cases in adults had ≥1 underlying condition; diabetes was present in 44.4% of cases. Serotypes V, la, II, and III accounted for 80.8% of infections during 1998-1999 and 78.5% of infections during 2005-2006. Conclusions. Invasive GBS disease in nonpregnant adults represents a substantial and increasing burden, particularly among older persons, black persons, and adults with diabetes. Prevention strategies are needed.

Campylobacter Genotyping to Determine the Source of Human Infection

Abstract: Campylobacteriosis, caused principally by Campylobacter jejuni and Campylobacter coli, is among the main causes of bacterial gastroenteritis worldwide. In developing countries, campylobacteriosis is primarily a disease that occurs during infancy, because of high levels of early exposure and acquired immunity [1], but in industrialized countries, the epidemiology is characterized by sporadic infection throughout the population at all ages [2]. Campylobacter infection accounts for an estimated 2.5 million cases in the United States and >340,000 cases in the United Kingdom each year [3, 4], which is >3 times the number of cases caused by Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes combined [5]. The estimated annual economic burden of Campylobacter infection is £500 million in the United Kingdom [6] and $8 billion in the United States [7], but despite its significance as a public health problem, the relative contributions of different sources of infection to the human disease burden remain uncertain. Many species of wild and farm animals, particularly birds, carry Campylobacter species as part of their gut microbiota, and contamination of human food can occur at any point from the farm to the consumer. Potential sources of human infection include contaminated meat, poultry, water, and milk and contact with animals [8]. Analytical epidemiology methods, including risk assessment and case-control studies, provide some indirect evidence for the origin of disease, but because the majority of human Campylobacter infections are sporadic with very few recognized outbreaks that indicate a common infection source [9, 10], these approaches are incomplete. Because interventions for controlling Campylobacter transmission are costly and implementation requires consideration of cost-effectiveness, the uncertainty regarding the sources of human infection has inhibited effective public health intervention by government agencies and industry. Molecular typing has enhanced many epidemiological studies, including the identification of food-borne outbreaks of infection due to E. coli O157:H7 [11], Salmonella enterica [12], Campylobacter [13], and L. monocytogenes [14]; early identification of an outbreak source enables effective disease containment [14, 15]. Recent advances in bacterial genetic typing and analysis provide the opportunity to determine the origin of Campylobacter isolates obtained from patients on the basis of their genotypes, because there is sufficient genetic variation within the bacterial population to define host or source-associated genotypes [16]. In this study, we used multilocus sequence typing (MLST) [17], which has several advantages over other microbial typing schemes such as serotyping, PFGE, and flaA typing [18-20]. Because it is based on nucleotide sequence, MLST is inherently reproducible, scalable, and portable between laboratories, with data readily shared via the Internet [21]. We addressed the sources of campylobacteriosis in industrialized countries as part of the national Campylobacter MLST Project in Scotland (CaMPS), which included a comprehensive survey of isolates from all confirmed cases of human campylobacteriosis in Scotland during a 15-month period (from mid-July 2005 through mid-October 2006). To attribute isolates to a source, 4 important resources were exploited: (1) a standardized MLST genotyping protocol, (2) a national-scale contemporaneous comparison data set of MLST genotypes from potential disease sources in Scotland, (3) a substantial data archive of MLST genotypes from other sources and locations, and (4) model-based statistical methods that allow quantitative estimation of the genetic attribution of disease to source.

Nontuberculous mycobacterial disease prevalence and risk factors: a changing epidemiology.

Abstract: Background Nontuberculous mycobacteria (NTM) are important human pathogens, yet little is known about disease prevalence in the United States. Reports suggest prevalence has increased, particularly in women, but population-based data to substantiate this are lacking. We sought to estimate NTM disease prevalence in Oregon, and describe disease by site, species, and patient demographic characteristics. Methods We contacted laboratories that performed mycobacterial cultures on Oregon residents in 2005-2006. For each isolate, we obtained source, collection date, species, and patient demographics. We used the microbiologic component of the American Thoracic Society/Infectious Diseases Society of America's pulmonary NTM disease criteria to define cases of pulmonary NTM, and patients with isolates from a normally sterile site were classified as having extrapulmonary disease. Results We identified 933 patients with > or =1 NTM isolate. Of these, 527 (56%) met the case definition (annualized prevalence, 7.2 cases per 100,000 persons). Pulmonary cases predominated (5.6 cases per 100,000 persons), followed by skin/soft-tissue cases (0.9 cases per 100,000 persons). Mycobacterium avium complex was the most common species identified in pulmonary cases (4.7 cases per 100,000 persons). Pulmonary disease prevalence was significantly higher in women (6.4 cases per 100,000 persons) than men (4.7 cases per 100,000 persons) and was highest in persons aged >50 years (15.5 cases per 100,000 persons). Conclusions NTM are frequently isolated from Oregon residents; more than one-half of all isolates likely represent true disease. Pulmonary NTM is most common among elderly women, and M. avium causes most disease. Future efforts to monitor disease trends should be undertaken, and efforts made to validate the use of the ATS/IDSA microbiologic criteria alone to predict pulmonary NTM disease.

Empirical versus Preemptive Antifungal Therapy for High-Risk, Febrile, Neutropenic Patients: A Randomized, Controlled Trial

Abstract: BACKGROUND: Empirical antifungal therapy is the standard of care for neutropenic patients with hematological malignancies who remain febrile despite broad-spectrum antibacterial treatment. Recent diagnostic improvements may ensure the early diagnosis of potentially invasive fungal disease. Reserving antifungals for this stage may achieve similar survival rates and reduce treatment toxicity and costs. METHODS: In this multicenter, open-label, randomized noninferiority trial, we compared an empirical antifungal strategy with a preemptive one. Empirical treatment was defined as antibacterial treatment of patients who have persistent or recurrent fever. Preemptive treatment was defined as treatment of patients who have clinical, imaging, or galactomannan-antigen-assay evidence suggesting fungal disease. First-line antifungal treatment was amphotericin B deoxycholate (1 mg/kg/day) or liposomal amphotericin (3 mg/kg/day), depending on daily renal function. The primary efficacy outcome was the proportion of patients alive at 14 days after recovery from neutropenia. RESULTS: The median duration of neutropenia (neutrophil count, <500 cells/mm3) for the 293 patients enrolled was 18 days (range, 5-69 days). By intention-to-treat analysis, survival was 97.3% with empirical treatment and 95.1% with preemptive treatment. The lower 95% confidence limit for the difference in mortality was -5.9%, which was within the noninferiority margin of -8%. Probable or proven invasive fungal infections were more common among patients who received preemptive treatment than among patients who received empirical treatment (13 of 143 vs. 4 of 150; P < .05), and most infections occurred during induction therapy (12 of 73 patients in the preemptive treatment group vs. 3 of 78 patients in the empirical treatment group were infected during induction therapy; P < .01). Preemptive treatment did not decrease nephrotoxicity but decreased costs of antifungal therapy by 35%. CONCLUSIONS: Preemptive treatment increased the incidence of invasive fungal disease, without increasing mortality, and decreased the costs of antifungal drugs. Empirical treatment may provide better survival rates for patients receiving induction chemotherapy.

Clinical Relevance of the Pharmacokinetic Interactions of Azole Antifungal Drugs with Other Coadministered Agents

Abstract: There are currently a number of licensed azole antifungal drugs; however; only 4 (namely, fluconazole, itraconazole, posaconazole, and voriconazole) are used frequently in a clinical setting for prophylaxis or treatment of systemic fungal infections. In this article, we review the pharmacokinetic interactions of these azole antifungal drugs with other coadministered agents. We describe these (2-way) interactions and the extent to which metabolic pathways and/or other supposed mechanisms are involved in these interactions. This article provides an overview of all published drug-drug interactions in humans (either healthy volunteers or patients), and on the basis of these findings, we have developed recommendations for managing the specific interactions.

World Health Organization Ranking of Antimicrobials According to Their Importance in Human Medicine: A Critical Step for Developing Risk Management Strategies for the Use of Antimicrobials in Food Production Animals

Abstract: The use of antimicrobials in food animals creates an important source of antimicrobial-resistant bacteria that can spread to humans through the food supply. Improved management of the use of antimicrobials in food animals, particularly reducing the usage of those that are "critically important" for human medicine, is an important step toward preserving the benefits of antimicrobials for people. The World Health Organization has developed and applied criteria to rank antimicrobials according to their relative importance in human medicine. Clinicians, regulatory agencies, policy makers, and other stakeholders can use this ranking when developing risk management strategies for the use of antimicrobials in food production animals. The ranking allows stakeholders to focus risk management efforts on drugs used in food animals that are the most important to human medicine and, thus, need to be addressed most urgently, such as fluoroquinolones, macrolides, and third- and fourth-generation cephalosporins.

Influenza estacional en adultos y niños—Diagnóstico, tratamiento, quimioprofilaxis y control de brotes institucionales: Guías de práctica clínica de la Sociedad de Enfermedades Infecciosas de Estados Unidos de América

Abstract: 14 Universidad de Toronto, Ontario, Canada. Es importante advertir que, en las guo´as, no es posible tener en cuenta siempre las variaciones individuales que se presenten entre pacientes. Las guo´as no intentan reemplazar el criterio del medico respecto de pacientes en particular o cuadros clo´nicos especiales. La Sociedad de Enfermedades Infecciosas de Estados Unidos de America considera que la adhesion a estas guo´as es voluntaria y que la determinacion final sobre su aplicacion corresponde al medico conforme a la situacion individual de cada paciente. Los hallazgos y las conclusiones de este informe pertenecen a los autores y no representan, necesariamente, la postura oficial de los Centros para el Control y Prevencion de Enfermedades.