Variation in Streptococcus pyogenes NAD+ glycohydrolase is associated with tissue tropism.

Streptococcus pyogenes is an important pathogen that causes a variety of diseases. The most common infections involve the throat (pharyngitis) or skin (impetigo); however, the factors that determine tissue tropism and severity are incompletely understood. The S. pyogenes NAD(+) glycohydrolase (SPN) is a virulence factor that has been implicated in contributing to the pathogenesis of severe infections. However, the role of SPN in determining the bacterium's tissue tropism has not been evaluated. In this report, we examine the sequences of spn and its endogenous inhibitor ifs from a worldwide collection of S. pyogenes strains. Analysis of average pairwise nucleotide diversity, average number of nucleotide differences, and ratio of nonsynonymous to synonymous substitutions revealed significant diversity in spn and ifs. Application of established models of molecular evolution shows that SPN is evolving under positive selection and diverging into NAD(+) glycohydrolase (NADase)-active and -inactive subtypes. Additionally, the NADase-inactive SPN subtypes maintain the characteristics of a functional gene while ifs becomes a pseudogene. Thus, NADase-inactive SPN continues to evolve under functional constraint. Furthermore, NADase activity did not correlate with invasive disease in our collection but was associated with tissue tropism. The ability to cause infection at both the pharynx and the skin ("generalist" strains) is correlated with NADase-active SPN, while the preference for causing infection at either the throat or the skin ("specialist" strains) is associated with NADase-inactive SPN. These findings suggest that SPN has a NADase-independent function and prompt a reevaluation of the role of SPN in streptococcal pathogenesis.

Clostridium difficile infection in the intensive care unit.

Clostridium difficile infection (CDI) is becoming more common worldwide. The morbidity and mortality associated with C difficile is also increasing at an alarming rate. Critically ill patients are at particularly high risk for CDI because of the prevalence of multiple risk factors in this patient population. Treatment of C difficile continues to be a difficult problem in patients with severe or recurrent disease. This article seeks to provide a broad understanding of CDI in the intensive care unit, with special emphasis on risk factor identification, treatment options, and disease prevention.

Trends in Clostridium difficile Disease: Epidemiology and Intervention.

Clostridium difficile is the most common cause of nosocomial infectious diarrhea. The incidence of C difficile infection (CDI) is increasing in both inpatients and outpatients, and outbreaks caused by a hypervirulent strain of C difficile are resulting in more severe disease. Moreover, community-associated CDI is occurring in persons who lack the traditional risk factors, which include antibiotic use, advanced age, and severe underlying disease. The clinical severity of CDI ranges from a mild, self-limited diarrheal illness to a fulminant, life-threatening colitis. Enzyme-linked immunosorbent assay is the most common laboratory method used for detection of C difficile toxins and can confirm the diagnosis within several hours. The choice of treatment should be based on disease severity. Oral metronidazole is generally regarded as the treatment of choice for mild to moderate CDI, while oral vancomycin is recommended for severe disease. Timely surgical intervention is important in patients who have severe complicated CDI.

Clostridium difficile infection in solid organ transplant recipients.

PURPOSE OF REVIEW: To provide a general understanding of Clostridium difficile infection with a focus on recent publications that evaluate the disease in solid organ transplant recipients. RECENT FINDINGS: The incidence of C. difficile infection is increasing worldwide. Epidemics due to a hypervirulent C. difficile strain are associated with an escalating severity of disease. New evidence further supports basing initial treatment choice on disease severity. SUMMARY: C. difficile is a significant pathogen in solid organ transplant recipients. Multiple risk factors are found in this population that may result in more severe disease. A high index of suspicion is necessary for the early diagnosis and treatment of C. difficile infection in transplant recipients. Metronidazole and vancomycin show equivalent efficacy in the treatment for mild-to-moderate disease, but vancomycin has demonstrated superiority in the treatment of severe disease. Surgical intervention is also an important consideration in the treatment of solid organ transplant recipients with severe colitis. Rigorous infection control practices are essential for preventing the spread of C. difficile within the hospital environment.

Tigecycline for treatment of pneumonia and empyema caused by carbapenemase-producing Klebsiella pneumoniae.

Strains of Klebsiella pneumoniae that produce one of three possible carbapenemases--KPC--have recently been identified with increasing frequency among isolates recovered from patients residing along the East Coast of the United States, particularly within the New York City metropolitan region. These strains have exhibited resistance to multiple antibiotic classes, including carbapenem agents. We report a case of nosocomial pneumonia and empyema caused by a KPC-producing isolate of K. pneumoniae at a large midwestern U.S. tertiary care facility in which the patient was treated with tigecycline. Although the pneumonia was treated successfully, the empyema recurred in association with a treatment-emergent tigecycline minimum inhibitory concentration (MIC) increase from 0.75 to 2 microg/ml. Clinicians should be aware of the potential occurrence of this treatment-emergent MIC increase, especially in the setting of sustained tigecycline therapy. In addition, the emergence of carbapenem-resistant Enterobacteriaceae reinforces the importance of antibiotic stewardship and strict infection control practices.