John G. Bartlett

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.

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.

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.

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 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.

There is a surge of new interest in C. difficile infection (CDI) reflecting substantial increases in cases and fatalities. The new challenges by this now old pathogen have brought renewed interest in all facets of the disease. Particularly important are the role of fluoroquinolones as inducing agents, the new polymerase chain reaction test to detect toxigenic strains in stools, the important role of the NAP‐1 strain, recent evidence favoring oral vancomycin over metronidazole in seriously ill patients, and new guidelines for management.

There has been a recent surge of interest in Clostridium difficile infection, which reflects an impressive increase in the number and severity of these infections. This review addresses some of the newer methods for detection of C. difficile infection at the bedside and in the laboratory. Particularly important are the new rapid diagnostic tests that detect toxigenic C. difficile using polymerase chain reaction and the combination tests that, either simultaneously or sequentially, screen for C. difficile and test for toxins A and B. It is expected that these new testing methods will largely supplant the enzyme immunoassays for toxins, which are used by most laboratories, departments, and divisions. The present goal is to combine clinical, laboratory, and animal research related to C. difficile that reflects issues that are considered to be major contemporary challenges. Among this work is the pursuit of studies of immune mechanisms to better control this disease.

The escalating rate of antibiotic resistance and the dearth of new antibiotics in development, as summarized by reviews from the Infectious Diseases Society of