Evolving Understanding of the Causes of Pneumonia in Adults, With Special Attention to the Role of Pneumococcus.

Before 1945, Streptococcus pneumoniae caused more than 90% of cases of pneumonia in adults. After 1950, the proportion of pneumonia caused by pneumococcus began to decline. Pneumococcus has continued to decline; at present, this organism is identified in fewer than fewer10%-15% of cases. This proportion is higher in Europe, a finding likely related to differences in vaccination practices and smoking. Gram-negative bacilli, Staphylococcus aureus, Chlamydia, Mycoplasma, and Legionella are each identified in 2%-5% of patients with pneumonia who require hospitalization. Viruses are found in 25% of patients, up to one-third of these have bacterial coinfection. Recent studies fail to identify a causative organism in more than 50% of cases, which remains the most important challenge to understanding lower respiratory infection. Our findings have important implications for antibiotic stewardship and should be considered as new policies for empiric pneumonia management are developed.

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 patient's 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 panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.

Executive Summary: 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 patient's 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 panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.

Biology of Clostridium difficile: implications for epidemiology and diagnosis.

Clostridium difficile is an anaerobic, spore-forming, gram-positive rod that causes a spectrum of antibiotic-associated colitis through the elaboration of two large clostridial toxins and other virulence factors. Since its discovery in 1978 as the agent responsible for pseudomembranous colitis, the organism has continued to evolve into an adaptable, aggressive, hypervirulent strain. Advances in molecular methods and improved animal models have facilitated an understanding of how this organism survives in the environment, adapts to the gastrointestinal tract of animals and humans, and accomplishes its unique pathogenesis. The advances in microbiology have been accompanied by some important clinical observations including increased rates of C. difficile infection, increased virulence, and multiple outbreaks. The major new risk is fluoroquinolone use; there is also an association with proton pump inhibitors and increased recognition of cases in outpatients, pediatric patients, and patients without recent antibiotic use. The combination of more aggressive strains with mobile genomes in a setting of an expanded pool of individuals at risk has refocused attention on and challenged assumptions regarding diagnostic gold standards. Future research is likely to build upon the advancements in phylogenetics to create novel strategies for diagnosis, treatment, and prevention.

Why infectious diseases.

Infectious diseases is a broad discipline that is almost unique in contemporary medicine with its ability to cure and prevent disease, to identify specific disease causes (microbes), and to deal with diverse, sometimes massive outbreaks. The value of the infectious disease practitioner is now magnified by the crisis of antibiotic resistance, the expanding consequences of international travel, the introduction of completely new pathogen diagnostics, and healthcare reform with emphasis on infection prevention and cost in dollars and lives. Infectious disease careers have great personal rewards to the practitioner based on these observations. It is unfortunate that we have been so effective in our work, but relatively ineffective in convincing the healthcare system of this value.

Antibacterial resistance leadership group: open for business.

Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance.

Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile Infection.

The prevalence of recurrent Clostridium difficile infection (RCDI) is increasing; fecal microbiota transplantation (FMT) is an effective therapy. However, there have been no studies of the efficacy of a single session of combined enteral and colonic FMT or characterizations of changes in the microbiota between donors and recipients. We performed a study of 27 patients with RCDI who were given a fixed volume of processed fecal filtrate via enteroscopy and colonoscopy in a single session. Patients were closely monitored, and fecal samples were collected from 2 patient-donor pairs for 16S rRNA analysis. All patients had reduced stool frequency, abdominal pain, white blood cell counts, and elimination of fecal C difficile toxin (P < .05). FMT increased microbial diversity, increasing proportions of Lachnospiraceae (phylum Firmicutes) and reducing proportions of Enterobacteriaceae. FMT was associated with marked changes in the composition of fecal microbiota in 2 patients with RCDI.

Seven ways to preserve the miracle of antibiotics.

Antibiotic resistance is a well-acknowledged crisis with no clearly defined comprehensive, national corrective plan. We propose a number of interventions that, collectively, could make a large difference. These include collection of data to inform decisions, efforts to reduce antibiotic abuse in people and animals, great emphasis on antibiotic stewardship, performance incentives, optimal use of newer diagnostics, better support for clinical and basic resistance-related research, and novel methods to foster new antibiotic development.

Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: evidence-based recommendations from an International Association of Physicians in AIDS Care panel.

DESCRIPTION: After HIV diagnosis, timely entry into HIV medical care and retention in that care are essential to the provision of effective antiretroviral therapy (ART). Adherence to ART is among the key determinants of successful HIV treatment outcome and is essential to minimize the emergence of drug resistance. The International Association of Physicians in AIDS Care convened a panel to develop evidence-based recommendations to optimize entry into and retention in care and ART adherence for people with HIV. METHODS: A systematic literature search was conducted to produce an evidence base restricted to randomized, controlled trials and observational studies with comparators that had at least 1 measured biological or behavioral end point. A total of 325 studies met the criteria. Two reviewers independently extracted and coded data from each study using a standardized data extraction form. Panel members drafted recommendations based on the body of evidence for each method or intervention and then graded the overall quality of the body of evidence and the strength for each recommendation. RECOMMENDATIONS: Recommendations are provided for monitoring entry into and retention in care, interventions to improve entry and retention, and monitoring of and interventions to improve ART adherence. Recommendations cover ART strategies, adherence tools, education and counseling, and health system and service delivery interventions. In addition, they cover specific issues pertaining to pregnant women, incarcerated individuals, homeless and marginally housed individuals, and children and adolescents, as well as substance use and mental health disorders. Recommendations for future research in all areas are also provided.

Improvement in the health of HIV-infected persons in care: reducing disparities.

BACKGROUND: Despite advances in human immunodeficiency virus (HIV) treatment, major challenges remain in achieving access, retention, and adherence. Our inner-city HIV clinical practice in Baltimore has a diverse patient population with high rates of poverty, black race, and injection drug use (IDU), providing us the opportunity to compare health process and outcomes. METHODS: Using data collected in a clinical HIV cohort in Baltimore, we compared receipt of combination antiretroviral therapy (ART), HIV type 1 (HIV-1) RNA, CD4, incidence of opportunistic illness, and mortality from 1995 to 2010. Comparisons were made of these outcomes by HIV risk group, sex, and race (black, white). RESULTS: From 1995 to 2010, we followed 6366 patients comprising 27 941 person-years (PY) of follow-up. By 2010, 87% of patients were receiving ART; median HIV-1 RNA was <200 copies/mL, median CD4 was 475 cells/mm(3), opportunistic illness rates were 2.4 per 100 PY, and mortality rates were 2.1 per 100 PY, with no differences by demographic or HIV risk group. The only differences were that the IDU risk group had a median CD4 that was 79 cells/mm(3) lower and HIV-1 RNA 0.16 log(10 )copies/mL higher compared with other risk groups (P < .01). In 2009 a 28-year-old HIV-infected person was estimated to have 45.4 years of life remaining, which did not differ by demographic or behavioral risk group. DISCUSSION: Our results emphasize that advances in HIV treatment have had a positive impact on all affected demographic and behavioral risk groups in an HIV clinical setting, with an expected longevity for HIV-infected patients that is now 73 years.

Provisional guidance on the use of hepatitis C virus protease inhibitors for treatment of hepatitis C in HIV-infected persons.

In May 2011, hepatitis C virus (HCV) protease inhibitors (PIs) were approved by the US Food and Drug Administration to treat persons with genotype 1 chronic hepatitis C virus (HCV) infection, but not those dually infected with human immunodeficiency virus (HIV). Although critical safety and efficacy data are lacking, the availability of the drugs and substantial medical need justify the off-label use of HCV PIs in select HIV/HCV-coinfected persons. Pending results of ongoing investigations, this article represents provisional guidance on the use of HCV PIs in HIV-infected persons.

Impact of an antimicrobial stewardship intervention on shortening the duration of therapy for community-acquired pneumonia.

BACKGROUND: Initial management of community-acquired pneumonia (CAP) has been a Centers for Medicare and Medicaid Services performance measure for a decade. We hypothesized that an intervention directed at management of CAP that assesses areas not covered by the performance measures-treatment duration and antimicrobial selection after additional microbiology data are available--would further improve CAP management. METHODS: We performed a single-center, prospective study to compare management of adult inpatients with presumed CAP before (from 1 January 2008 through 31 March 2008) and after (from 1 February 2010 through 10 May 2010) an intervention consisting of education and prospective feedback to teams regarding antibiotic choice and duration. The primary outcome measure was duration of antibiotic therapy in the 2 periods. RESULTS: There were 62 patients in the preintervention period and 65 patients in the intervention period. The duration of antibiotic therapy decreased from a median of 10 to 7 days (P < .001), with 148 fewer days of antibiotic therapy. The median lengths of stay were similar in the 2 groups (4 vs 5 days). A causative pathogen was identified less frequently during the intervention period (14% vs 34%); however, antibiotics were more frequently narrowed or modified on the basis of susceptibility results during the intervention period (67% vs 19%). Fewer patients received duplicate therapy within 24 hours in the intervention period (90% vs 55%). CONCLUSIONS: The duration of therapy for CAP was excessive at our institution and was decreased with a stewardship intervention. Confirmatory studies at other institutions are needed; efforts to assess and reduce duration of therapy for CAP should be strongly considered.

Anaerobic bacterial infection of the lung.

Anaerobic bacteria are relatively frequent pathogens in pulmonary infections that are associated with aspiration and its associated complications including aspiration pneumonitis, lung abscess, necrotizing pneumonia and empyema. These conditions have been studied since the early 1900's and substantial data with important clinical and microbiologic information are now readily available. However, the reports of these infections in the past 20 years have been sparse in number and much of the previous information relevant to this topic seems much less visible or apparent. The purpose of this report is to summarize the previous data and to celebrate the enormous contributions of Dr. Sydney Finegold to this topic.

A call to arms: the imperative for antimicrobial stewardship.

Antimicrobial resistance is a major public health crisis. The prevalence of drug-resistant organisms, such as the emerging NAP1 strain of Clostridium difficile, now highly resistant to fluoroquinolones, Acinetobacter species, Klebsiella pneumoniae carbapenemase-producing organisms, and methicillin-resistant Staphylococcus aureus, is increasing nationwide. The sources of antimicrobial resistance are manifold, but there is a well-documented causal relationship between antimicrobial use and misuse and the emergence of antimicrobial-resistant pathogens. As the development of new antimicrobial agents is on the decline, the medical community, across all specialties and in conjunction with public health services, must develop and implement programs and strategies designed to preserve the integrity and effectiveness of the existing antimicrobial armamentarium. Such strategies are collectively known as antimicrobial stewardship programs and have the potential to minimize the emergence of resistant pathogens.

Diagnostic tests for agents of community-acquired pneumonia.

Lower respiratory infections are the major cause of death due to infectious disease in the United States and worldwide. Most forms of community-acquired pneumonia (CAP) are treatable, and there is consensus that the selection of antimicrobial agents is notably simplified if the pathogen is defined. The rich history of CAP studies in the prepenicillin era showed that an etiologic diagnosis was established in >90% of cases, but the 2009 data from Medicare indicate that a probable pathogen is now detected in <10% according to a review of the records of >17,000 patients hospitalized with CAP. This review addresses the issue of the state of the art of microbiological studies of CAP in terms of the realities of current-day practice. Unfortunately, the desire for better data to achieve pathogen-directed treatment clashes with a multitude of harsh realities, including cost, Centers for Medicare and Medicaid Services (CMS) requirements for antibiotics to be administered within 6 h of disease onset, guidelines that discourage any microbiological studies in most cases, belief in empiricism that is well supported by at least 1 prospective study, the decline of microbiological analysis standards in most laboratories, and the devastating impact of the Clinical Laboratory Improvement Amendments (CLIA) regulations that led to the demise of "the house staff laboratory" and the distancing of microbiological analysis from the site of care. Microbiological principles are reviewed, with emphasis on specimen source, pathogenic potential of isolates, concentrations, impact of antecedent antibiotics, and the "Washington criteria" for expectorated sputum. The recommendation is that the high-quality microbiological analysis that is still achieved in some places should be retained but that to advance the field on the basis of the contemporary realities, two goals should be adopted: First is the broad use of antigen tests for Streptococcus pneumoniae and Legionella pneumophila with interpretation by clinical staff under the CLIA waiver for low-complexity tests. The second and more ambitious recommendation is the adoption of molecular techniques, with particular emphasis on nucleic acid detection, which is rapid and sensitive and has already been developed for virtually all recognized pulmonary pathogens. This may be the ultimate solution for many laboratories, and it is likely to have selected use.

Dramatic decline in the HIV-1 RNA level over calendar time in a large urban HIV practice.

BACKGROUND: We have previously showed that as antiretroviral therapy has improved over time since 1995-1996, the likelihood of achieving virologic suppression has also improved. Antiretroviral therapy and antiretroviral therapy guidelines have continued to evolve, and we wished to determine the trend in human immunodeficiency virus (HIV-1) RNA levels over time in HIV-infected persons receiving care in our large urban HIV clinical practice in Baltimore, Maryland. METHODS: The HIV-1 RNA level was assessed each year from 1996 through 2010 at the date closest to 1 July for all patients in care and followed up in the Johns Hopkins HIV Clinical Cohort. The clinic population's median HIV-1 RNA level and stratified threshold levels were plotted. The demographic characteristics of the population were also assessed over time. RESULTS: From 1996 (shortly after highly active antiretroviral therapy [HAART] was introduced) to 2010, the median HIV-1 RNA level decreased from 10,400 to <200 copies/mL. The proportion of patients with an HIV-1 RNA level >500 copies/mL decreased from 75% to only 16% during this same period. The population itself became older, had a higher proportion of women, and a lower proportion of patients with injection drug use as a transmission risk, but it was geographically stable. There was an increase in HAART use over time. DISCUSSION: Our results demonstrate the remarkable impact of increased use of and improved management with HAART in this urban HIV-infected population.