John G. Bartlett

Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults

Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia.

A substance producing cytotoxicity in tissue culture was detected in stool specimens from all of four patients with pseudomembranous colitis due to antibiotics and in one of 54 with antibiotic-associated diarrhea. These stools also caused enterocolitis when injected intracecally into hamsters. On each occasion, cytotoxicity in tissue culture and enterocolitis in hamsters were neutralized by pretreatment with gas-gangrene antitoxin. The toxicity in both tissue cultures and hamsters could be reproduced with broth cultures of clostridia strains isolated from four of the five stools. These results suggest that toxin-producing clostridia are responsible for antibiotic-associated pseudomembranous colitis.

Update of Practice Guidelines for the Management of Community-Acquired Pneumonia in Immunocompetent Adults

The Infectious Diseases Society of America (IDSA) produced guidelines for community-acquired pneumonia (CAP) in immunocompetent adults in 1998 and again in 2000 [1, 2]. Because of evolving resistance to antimicrobials and other advances, it was felt that an update should be provided every few years so that important developments could be highlighted and pressing questions answered. We addressed those issues that the committee believed were important to the practicing physician, including suggestions for initial empiric therapy for CAP. In some cases, only a few paragraphs were needed, whereas, in others, a somewhat more in-depth discussion was provided. Because many physicians focus on the tables rather than on the text of guidelines, it was decided that all of the information dealing with the initial empiric treatment regimens should be in tabular format with footnotes (tables 1–3). The topics selected for updating have been organized according to the headings used in the August 2000 CAP guidelines pub-

Diagnosis and Management of Complicated Intra-abdominal Infection in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America

Evidence-based guidelines for managing patients with intra-abdominal infection were prepared by an Expert Panel of the Surgical Infection Society and the Infectious Diseases Society of America. These updated guidelines replace those previously published in 2002 and 2003. The guidelines are intended for treating patients who either have these infections or may be at risk for them. New information, based on publications from the period 2003-2008, is incorporated into this guideline document. The panel has also added recommendations for managing intra-abdominal infection in children, particularly where such management differs from that of adults; for appendicitis in patients of all ages; and for necrotizing enterocolitis in neonates.

Community-Acquired Pneumonia in Adults: Guidelines for Management

This is part of the series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians in the diagnosis and treatment of community-acquired pneumonia. The targeted providers are internists and family practitioners. The targeted groups are immunocompetent adult patients. Criteria are specified for determining whether the inpatient or outpatient setting is appropriate for treatment. Differences from other guidelines written on this topic include use of laboratory criteria for diagnosis and approach to antimicrobial therapy. Panel members and consultants are experts in adult infectious diseases. The guidelines are evidence based where possible. A standard ranking system is used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary and tables highlight the major recommendations. The guidelines will be listed on the IDSA home page at http://www.idsociety.org.

Narrative Review: The New Epidemic of Clostridium difficile–Associated Enteric Disease

Key Summary Points Clostridium difficile is the most common identifiable bacterial cause of diarrhea in the United States. Tissue culture assay is the best diagnostic test to detect the cytotoxin; enzyme immunoassay is the test used in most hospitals, but it has a sensitivity of only about 75%. A new epidemic strain of C. difficile has emerged that causes more frequent and more serious disease. Features of severe disease include ileus, toxic megacolon, pseudomembrane formation, leukemoid reactions, hyperalbuminemia, requirement for colectomy, sepsis, and death. Risk factors are use of antibiotics (especially broad-spectrum cephalosporins and fluoroquinolones), advanced age, hospitalization, and gastrointestinal surgery or gastrointestinal procedures. Oral vancomycin is the preferred treatment for seriously ill patients. Infection control and antibiotic control are important preventive measures. Diarrhea and colitis due to Clostridium difficile are well-recognized and extensively studied iatrogenic complications of antibiotic use and have been for nearly 30 years. Important risks for infection include hospitalization, advanced age, gastrointestinal surgery or gastrointestinal procedures, and antibiotic exposure. The most common inducing agents have been clindamycin or broad-spectrum cephalosporins, but nearly all agents with an antibacterial spectrum may be responsible. The cytotoxin assay that originally led to the detection of C. difficile in 1978 remains the most sensitive diagnostic test, but the enzyme immunoassay is now used by most laboratories because of ease of processing, cost, and speed of results. Standard treatment of C. difficile infection includes withdrawal of the inducing agent and use of oral metronidazole or oral vancomycin; metronidazole is preferred in guidelines, but vancomycin is probably more effective, especially in seriously ill patients. The major complications of treatment are failure to respond, primarily because of advanced disease with ileus, and relapse or reinfection after treatment is discontinued. Prevention principles include hospital infection control and antibiotic restraint. Against this background, there is a new epidemic of C. difficile infection that is occurring more frequently and is more serious and more refractory to therapy. Evidence of the severity of the infection includes high rates of toxic megacolon, leukemoid reactions, severe hypoalbuminemia, requirement for colectomy, shock, and death. These complications are most common in elderly patients, and the inducing agents are often fluoroquinolones and cephalosporins. Analysis of outbreaks in North America implicates a unique strain of C. difficile that produces large amounts of toxin in vitro, produces a binary toxin of uncertain clinical significance, and is resistant to fluoroquinolones in vitro. Successful management of patients with this strain requires early detection of infection, rapid treatment, and implementation of infection control, sometimes including antibiotic control. Clostridium difficile was identified as the major cause of antibiotic-associated diarrhea and the nearly exclusive cause of pseudomembranous colitis in 1978. Subsequent work in the following 2 years defined the clinical features, methods of laboratory diagnosis, epidemiology, principles of infection control, and treatment of C. difficileassociated disease. Clostridium difficile infection is an important and frequent iatrogenic complication, but it has been relatively easy to manage, with the exception of occasional institutional outbreaks and a nagging problem of relapsing disease following treatment. However, during the past 5 years, an unanticipated increase in infection has been recognized, particularly in some locations where C. difficileassociated disease has become more frequent, more serious, and more refractory to standard therapy. It now seems that this change is explained by a unique strain of C. difficile that has unusual virulence factors, which may account for increased severity, and fluoroquinolone resistance, which may account for increased frequency. These recent observations have resulted in renewed interest in an old pathogen. This review updates the status of C. difficileassociated enteric disease and its management in light of these new observations. Initial Studies (1974 to 2003) Antibiotic-associated enterocolitis was generally attributed to Staphylococcus aureus in the first 25 years of the antibiotic era (1, 2). In 1974, Tedesco and colleagues (3) reported results of a prospective study of 200 patients given clindamycin who underwent endoscopy after reporting diarrhea. In this study, 41 (20.5%) patients had diarrhea and 20 (10%) had pseudomembranous colitis (3). Despite the ease of recovering S. aureus in stool, tests to detect the organism yielded negative results. This led our group and others to pursue an alternative putative agent by using the hamster model (4) for correlations with observations in patients. Clostridium difficile was reported as the agent of antibiotic-associated pseudomembranous colitis in 1978 (5). During the ensuing 25 years, researchers established essential data documenting associated risks, clinical features, diagnosis, and management of C. difficileassociated diarrhea that became widely accepted. Risk Factors Almost all studies include the 3 major risks for infection with C. difficile: antibiotic exposure, advanced age, and hospitalization (68). With regard to antibiotic exposure, any antimicrobial agent with an antibacterial spectrum can be the cause, but there is a hierarchical list of agents that has been subject to change. Clindamycin followed by ampicillin or amoxicillin played prominent roles in the 1970s, but these were largely supplanted by cephalosporins in the 1980s (9, 10). Researchers from Sweden showed that advanced age was a risk in population-based analyses indicating that the rate per 100000 persons older than 65 years of age was 20 times higher than that in persons younger than 20 years of age (11). The risk associated with hospitalization and chronic care facilities is attributed to high rates of C. difficile colonization. Studies have shown a 20% to 40% rate of colonization in hospitalized adults compared with 2% to 3% in healthy adults (12, 13), reflecting widespread contamination of hospital environments, especially in areas associated with infection (6, 7, 14, 15). Gastrointestinal surgery and gastrointestinal procedures are also risks. Clinical Expression Clinical disease and C. difficile toxin are present almost exclusively in patients with recent antibiotic exposure (6, 7, 12, 16), with rare exceptions (17, 18). A recent report implicates gastric acidsuppressive agents as a risk for disease (19), but this has not been consistently observed (20). Clinical expression of infection almost always includes diarrhea, but severity of this and constitutional symptoms (68, 16, 17) varies widely. Common findings in patients with infection include colitis with cramps, fever, fecal leukocytes, and inflammation on colonic biopsy. Pseudomembranous colitis represents an advanced stage of disease, and although considered nonspecific, it is nearly diagnostic of C. difficile infection (17). The disease is almost always restricted to the colon (21). Clostridium difficile infection is a protein-losing enteropathy that is often associated with hypoalbuminemia and sometimes with anasarca (3). Most patients have leukocytosis, and this infection is now recognized as a prominent cause of leukemoid reactions (22). Diagnosis The standard test for infection is detection of C. difficile toxin in stool. The initial report in 1978 (5) used the tissue culture assay, and no subsequent test has proven superior in terms of sensitivity or specificity (2325). The main limitations of the test are the 24 to 48 hours required for results, work intensity, and cost (25). Most laboratories now use enzyme immunoassay to detect toxin A or toxins A and B, but several studies show that these are only about 75% sensitive compared with tissue culture assays (2325) so that repeated tests or empirical treatment may be required (26). Alternative methods of detection include detection of C. difficile by culture, by polymerase chain reaction testing, or by analysis for the common antigen of C. difficile (25, 27, 28). An inherent problem with detection of the organism rather than the toxin is that 10% to 30% of hospitalized patients are colonized without disease (13). Some laboratories use 1 of these last methods to screen stool samples, with subsequent testing for the cytotoxin in samples with positive results (25, 28). Infection Control Standard recommendations of the Society for Healthcare Epidemiology of America for infection control include the following: patient isolation in a single room, preferably with a bathroom; contact precautions; room cleansing with a 1:10 dilution of bleach; avoidance of rectal thermometers; and soap and water for handwashing rather than alcohol-based hand hygiene (14). Alcohol-based hand cleaning is considered inferior because clostridia spores survive alcohol. This is important because health care workers can transmit C. difficile via their hands. Antibiotic control of clindamycin or cephalosporins has sometimes been necessary during epidemics (29, 30). Attempts to prevent infection with prophylactic metronidazole or oral vancomycin may actually increase the rate of C. difficile carriage (31). Treatment Recommendations for treatment are supportive care, withdrawal of the implicated antibiotic, and avoidance of unnecessary use of drugs with antiperistaltic activity (Table). When continued antibiotic treatment is necessary, it is best to use agents with a low probability of causing C. difficileassociated disease, such as urinary antiseptics, tetracyclines, narrow-spectrum betalactams, macrolides, sulfonamides, aminoglycosides, vancomycin, metronidazole, and trimethoprimsulfamethoxa

Guidelines for preventing opportunistic infections among HIV-infected persons - 2002

Introduction In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) among persons infected with human immunodeficiency virus (HIV) (1-3). These guidelines, which are intended for clinicians and health-care providers and their HIV-infected patients, were revised in 1997 (4) and again in 1999 (5), and have been published in MMWR (1, 4, 5), Clinical Infectious Diseases (2, 6, 7), Annals of Internal Medicine (3, 8), American Family Physician (9, 10), and Pediatrics (11); accompanying editorials have appeared in JAMA (12, 13). Response to these guidelines (e.g., a substantial number of requests for reprints, website contacts, and observations from health-care providers) demonstrates that they have served as a valuable reference for HIV health-care providers. Because the 1995, 1997, and 1999 guidelines included ratings indicating the strength of each recommendation and the quality of supporting evidence, readers have been able to assess the relative importance of each recommendation. Since acquired immunodeficiency syndrome (AIDS) was first recognized 20 years ago, remarkable progress has been made in improving the quality and duration of life for HIV-infected persons in the industrialized world. During the first decade of the epidemic, this improvement occurred because of improved recognition of opportunistic disease processes, improved therapy for acute and chronic complications, and introduction of chemoprophylaxis against key opportunistic pathogens. The second decade of the epidemic has witnessed extraordinary progress in developing highly active antiretroviral therapies (HAART) as well as continuing progress in preventing and treating OIs. HAART has reduced the incidence of OIs and extended life substantially (14-16). HAART is the most effective approach to preventing OIs and should be considered for all HIV-infected persons who qualify for such therapy (14-16). However, certain patients are not ready or able to take HAART, and others have tried HAART regimens but therapy failed. Such patients will benefit from prophylaxis against OIs (15). In addition, prophylaxis against specific OIs continues to provide survival benefits even among persons who are receiving HAART (15). Clearly, since HAART was introduced in the United States in 1995, chemoprophylaxis for OIs need not be lifelong. Antiretroviral therapy can restore immune function. The period of susceptibility to opportunistic processes continues to be accurately indicated by CD4+ T lymphocyte counts for patients who are receiving HAART. Thus, a strategy of stopping primary or secondary prophylaxis for certain patients whose immunity has improved as a consequence of HAART is logical. Stopping prophylactic regimens can simplify treatment, reduce toxicity and drug interactions, lower cost of care, and potentially facilitate adherence to antiretroviral regimens. In 1999, the USPHS/IDSA guidelines reported that stopping primary or secondary prophylaxis for certain pathogens was safe if HAART has led to an increase in CD4+ T lymphocyte counts above specified threshold levels. Recommendations were made for only those pathogens for which adequate clinical data were available. Data generated since 1999 continue to support these recommendations and allow additional recommendations to be made concerning the safety of stopping primary or secondary prophylaxis for other pathogens. For recommendations regarding discontinuing chemoprophylaxis, readers will note that criteria vary by such factors as duration of CD4+ T lymphocyte count increase, and, in the case of secondary prophylaxis, duration of treatment of the initial episode of disease. These differences reflect the criteria used in specific studies. Therefore, certain inconsistencies in the format of these criteria are unavoidable. Although considerable data are now available concerning discontinuing primary and secondary OI prophylaxis, essentially no data are available regarding restarting prophylaxis when the CD4+ T lymphocyte count decreases again to levels at which the patient is likely to again be at risk for OIs. For primary prophylaxis, whether to use the same threshold at which prophylaxis can be stopped (derived from data in studies addressing prophylaxis discontinuation) or to use the threshold below which initial prophylaxis is recommended, is unknown. Therefore, in this revision of the guidelines, in certain cases, ranges are provided for restarting primary or secondary prophylaxis. For prophylaxis against Pneumocystis carinii pneumonia (PCP), the indicated threshold for restarting both primary and secondary prophylaxis is 200 cells/L. For all these recommendations, the Roman numeral ratings reflect the lack of data available to assist in making these decisions (Box). Table. System Used to Rate the Strength of Recommendations and Quality of Supporting Evidence During the development of these revised guidelines, working group members reviewed published manuscripts as well as abstracts and material presented at professional meetings. Periodic teleconferences were held to develop the revisions. Major Changes in These Recommendations Major changes in the guidelines since 1999 include the following: Higher level ratings have been provided for discontinuing primary prophylaxis for PCP and Mycobacterium avium complex (MAC) when CD4+ T lymphocytes have increased to >200 cells/L and >100 cells/L, respectively, for 3 months in response to HAART (AI), and a new recommendation to discontinue primary toxoplasmosis prophylaxis has been provided when the CD4+ T lymphocyte count has increased to >200 cells/L for 3 months (AI). Secondary PCP prophylaxis should be discontinued among patients whose CD4+ T lymphocyte counts have increased to >200 cells/L for 3 months as a consequence of HAART (BII). Secondary prophylaxis for disseminated MAC can be discontinued among patients with a sustained (e.g., 6-month) increase in CD4+ count to >100 cells/L in response to HAART, if they have completed 12 months of MAC therapy and have no symptoms or signs attributable to MAC (CIII). Secondary prophylaxis for toxoplasmosis and cryptococcosis can be discontinued among patients with a sustained increase in CD4+ counts (e.g. 6 months) to >200 cells/L and >100200 cells/L, respectively, in response to HAART, if they have completed their initial therapy and have no symptoms or signs attributable to these pathogens (CIII). The importance of screening all HIV-infected persons for hepatitis C virus (HCV) is emphasized (BIII). Additional information concerning transmission of human herpesvirus 8 infection (HHV-8) is provided. New information regarding drug interactions is provided, chiefly related to rifamycins and antiretroviral drugs. Revised recommendations for vaccinating HIV-infected adults and HIV-exposed or infected children are provided. Using the Information in This Report For each of the 19 diseases covered in this report, specific recommendations are provided that address 1) preventing exposure to opportunistic pathogens, 2) preventing first episodes of disease, and 3) preventing disease recurrences. Recommendations are rated by a revised version of the IDSA rating system (17). In this system, the letters AE signify the strength of the recommendation for or against a preventive measure, and Roman numerals IIII indicate the quality of evidence supporting the recommendation (Box). Because of their length and complexity, tables in this report are grouped together and follow the references. Tables appear in the following order: Table 1 Dosages for prophylaxis to prevent first episode of opportunistic disease among infected adults and adolescents; Table 1. Prophylaxis to Prevent First Episode of Opportunistic Disease among Adults and Adolescents Infected with Human Immunodeficiency Virus (HIV) Table 2 Dosages for prophylaxis to prevent recurrence of opportunistic disease among HIV-infected adults and adolescents; Table 2. Prophylaxis to Prevent Recurrence of Opportunistic Disease, after Chemotherapy for Acute Disease, among Adults and Adolescents Infected with Human Immunodeficiency Virus (HIV) Table 3 Effects of food on drugs used to treat OIs; Table 3. Effects of Food on Drugs Used to Prevent Opportunistic Infections Table 4 Effects of medications on drugs used to treat OIs; Table 4. Effects of Medications on Drugs Used to Prevent Opportunistic Infections Table 5 Effects of OI medications on drugs commonly administered to HIV-infected persons; Table 5. Effects of Opportunistic Infection Medications on Antiretroviral Drugs Commonly Administered to Persons Infected with Human Immunodeficiency Virus (HIV) Table 6 Adverse effects of drugs used to prevent OIs; Table 6. Adverse Effects of Drugs Used in Preventing Opportunistic Infections Table 7 Dosages of drugs for preventing OIs for persons with renal insufficiency; Table 7. Dosing of Drugs for Primary Prevention of or Maintenance Therapy for Opportunistic Infections Related to Renal Insufficiency Table 8 Costs of agents recommended for preventing OIs among adults with HIV infection; Table 8. Wholesale Acquisition Costs of Agents Recommended for Preventing Opportunistic Infections among Adults Infected with Human Immunodeficiency Virus Table 9 Immunologic categories for HIV-infected children; Table 9. Immunologic Categories for Human Immunodeficiency Virus-Infected Children, Based on Age-Specific CD4+ T Lymphocyte Counts and Percentage of Total Lymphocytes Table 10 Immunization schedule for HIV-infected children; Table 10. Recommended Immunization Schedule for Human Immunodeficiency Virus (HIV)-Infected Children Table 11 Dosages for prophylaxis to prevent first episode of opportunistic disease among HIV-infected infants and children; Table 11. Prophylaxis to Prevent First Episode of Opportunistic Disease among Infants and Children Infected with Human Immunodeficiency Virus Tabl

Recommendations for use of antiretroviral drugs in pregnant hiv-1-infected women for maternal health and interventions to reduce perinatal hiv-1 transmission in the United States

Associations: Most common: S. aureus Foreign body: Coagulase-negative Staphylococcus or P. acnes Nosocomial: Enterobacteraceae, P. aeruginosa, Candida Bites, diabetic foot lesions, and decubitus ulcers: Streptococci and anaerobes Sickle cell disease: Salmonella or S. pneumonia HIV: Bartonella Bites, human or animal: P. multocida, E. corrodens Immunosuppressed: Aspergillis, C. albicans, Mycobacteria Populations where these organisms are prevalent: Brucella, TB, Coxiella burnetti, endemic fungi Microbiology and histology. The preferred culture sources are blood cultures (which are usually positive only with hematogenous osteomyelitis) or bone biopsy. Cultures from sinus tracts are often misleading. Tissue specimens showing more than 5 neutrophils/HPF show a sensitivity of 43% to 84% in specificity of 93% to 97% (AbdulKarim FW. Mod Pathol. 1998;11:427).

Guidelines for the Selection of Anti-infective Agents for Complicated Intra-abdominal Infections

Joseph S. Solomkin, John E. Mazuski, Ellen J. Baron, Robert G. Sawyer, Avery B. Nathens, Joseph T. DiPiro, Timothy Buchman, E. Patchen Dellinger, John Jernigan, Sherwood Gorbach, Anthony W. Chow, and John Bartlett Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio; Department of Surgery, Washington University School of Medicine, St. Louis, Missouri; Department of Microbiology, Stanford University School of Medicine, Palo Alto, California; Department of Surgery, University of Virginia, Charlottesville; Department of Surgery, University of Washington, Seattle; University of Georgia College of Pharmacy, Department of Surgery, Medical College of Georgia, Augusta, and Centers for Disease Control and Prevention, Atlanta; Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patients individual circumstances.These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panels recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.