Henry F. Chambers

Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children

Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

Practice Guidelines for the Diagnosis and Management of Skin and Soft-Tissue Infections

EXECUTIVE SUMMARYSoft-tissue infections are common, generally of mild tomodest severity, and are easily treated with a variety ofagents. An etiologic diagnosis of simple cellulitis is fre-quently difficult and generally unnecessary for patientswith mild signs and symptoms of illness. Clinical as-sessment of the severity of infection is crucial, and sev-eral classification schemes and algorithms have beenproposed to guide the clinician [1]. However, mostclinical assessments have been developed from eitherretrospective studies or from an author’s own “clinicalexperience,” illustrating the need for prospectivestudieswith defined measurements of severity coupled to man-agement issues and outcomes.Until then, it is the recommendation of this com-mittee that patients with soft-tissue infection accom-panied by signs and symptoms of systemic toxicity (e.g.,fever or hypothermia, tachycardia [heart rate,

Waves of Resistance: Staphylococcus aureus in the Antibiotic Era

Staphylococcus aureus is notorious for its ability to become resistant to antibiotics. Infections that are caused by antibiotic-resistant strains often occur in epidemic waves that are initiated by one or a few successful clones. Methicillin-resistant S. aureus (MRSA) features prominently in these epidemics. Historically associated with hospitals and other health care settings, MRSA has now emerged as a widespread cause of community infections. Community or community-associated MRSA (CA-MRSA) can spread rapidly among healthy individuals. Outbreaks of CA-MRSA infections have been reported worldwide, and CA-MRSA strains are now epidemic in the United States. Here, we review the molecular epidemiology of the epidemic waves of penicillin- and methicillin-resistant strains of S. aureus that have occurred since 1940, with a focus on the clinical and molecular epidemiology of CA-MRSA.

Community-associated meticillin-resistant Staphylococcus aureus

Meticillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals worldwide, and causes substantial morbidity and mortality. Health-care-associated MRSA infections arise in individuals with predisposing risk factors, such as surgery or presence of an indwelling medical device. By contrast, many community-associated MRSA (CA-MRSA) infections arise in otherwise healthy individuals who do not have such risk factors. Additionally, CA-MRSA infections are epidemic in some countries. These features suggest that CA-MRSA strains are more virulent and transmissible than are traditional hospital-associated MRSA strains. The restricted treatment options for CA-MRSA infections compound the effect of enhanced virulence and transmission. Although progress has been made towards understanding emergence of CA-MRSA, virulence, and treatment of infections, our knowledge remains incomplete. Here we review the most up-to-date knowledge and provide a perspective for the future prophylaxis or new treatments for CA-MRSA infections.

Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America

A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panels recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

SeminarCommunity-associated meticillin-resistant Staphylococcus aureus

Meticillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals worldwide, and causes substantial morbidity and mortality. Health-care-associated MRSA infections arise in individuals with predisposing risk factors, such as surgery or presence of an indwelling medical device. By contrast, many community-associated MRSA (CA-MRSA) infections arise in otherwise healthy individuals who do not have such risk factors. Additionally, CA-MRSA infections are epidemic in some countries. These features suggest that CA-MRSA strains are more virulent and transmissible than are traditional hospital-associated MRSA strains. The restricted treatment options for CA-MRSA infections compound the effect of enhanced virulence and transmission. Although progress has been made towards understanding emergence of CA-MRSA, virulence, and treatment of infections, our knowledge remains incomplete. Here we review the most up-to-date knowledge and provide a perspective for the future prophylaxis or new treatments for CA-MRSA infections.

Diagnosis and Management of Infective Endocarditis and Its Complications

Infective endocarditis (IE) carries a high risk of morbidity and mortality. Rapid diagnosis, effective treatment, and prompt recognition of complications are essential to good patient outcome. Therapy of IE caused by the more commonly encountered organisms, including streptococci, enterococci, staphylococci, and the HACEK organisms ( Hemophilus parainfluenzae, Hemophilus aphrophilus, Actinobacillus [Hemophilus] actinomycetemcomitans, Cardiobacterium hominis, Eikenella species , and Kingella species), has been addressed previously by this committee.1 Likewise, the antimicrobial prevention of endocarditis has also been previously addressed.2 In this article, we review and update the current literature with respect to diagnostic challenges and strategies, difficult therapeutic situations, and management choices in patients with IE. This article focuses predominantly on adults with IE. A separate article, currently in preparation, will address the issues of IE in childhood. ### Clinical Criteria The diagnosis of IE is straightforward in those patients with classic oslerian manifestations: bacteremia or fungemia, evidence of active valvulitis, peripheral emboli, and immunologic vascular phenomena. In other patients, however, the classic peripheral stigmata may be few or absent.3 This may occur during acute courses of IE, particularly among intravenous drug abuse (IVDA) patients in whom IE is often due to Staphylococcus aureus infection of right-sided heart valves, or in patients with IE caused by microorganisms such as HACEK. Acute IE evolves too quickly for the development of immunologic vascular phenomena, which are more characteristic of subacute IE. In addition, acute right-sided IE valve lesions do not create the peripheral emboli and immunologic vascular phenomena that can result from left-sided valvular involvement.3 The variability in the clinical presentation of IE requires a diagnostic strategy that will be both sensitive for disease detection and specific for its exclusion across all the forms of the disease. In 1981, von Reyn et al4 proposed a scheme for strict case definitions of IE …

Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users.

The clinical courses of 13 consecutive intravenous drug users with Staphylococcus aureus endocarditis treated principally with vancomycin were reviewed. Two patients, one with only right-sided endocarditis and the other with tricuspid and mitral valve endocarditis, had recurrences of positive blood cultures 2 days after completing a 4-week course of vancomycin. Two patients, both of whom eventually were cured, had modifications of therapy because of bacteremia persisting 7 and 16 days into therapy. One patient required an operation for recurrent fevers, and the resected vegetation showed evidence of active infection. Time-kill studies performed with nafcillin and vancomycin for 10 isolates of S. aureus showed that vancomycin was less rapidly bactericidal than nafcillin. Although vancomycin is used as an alternative to penicillinase-resistant penicillins for treatment of staphylococcal endocarditis, these findings raise the question of whether it is equivalent to these drugs in efficacy.

National trends in ambulatory visits and antibiotic prescribing for skin and soft-tissue infections.

BACKGROUND Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a common cause of skin and soft-tissue infections (SSTIs) in the United States. It is unknown whether this development has affected the national rate of visits to primary care practices and emergency departments (EDs) and whether changes in antibiotic prescribing have occurred. METHODS We examined visits by patients with SSTIs to physician offices, hospital outpatient departments, and EDs using the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey from 1997 to 2005. We estimated annual visit rates for all SSTIs and a subset classified as abscess/cellulitis. For abscess/cellulitis visits, we examined trends in characteristics of patients and clinical settings and in antibiotic prescribing. RESULTS Overall rate of visits for SSTIs increased from 32.1 to 48.1 visits per 1000 population (50%; P = .003 for trend), reaching 14.2 million by 2005. More than 95% of this change was attributable to visits for abscess/cellulitis, which increased from 17.3 to 32.5 visits per 1000 population (88% increase; P < .001 for trend). The largest relative increases occurred in EDs (especially in high safety-net-status EDs and in the South), among black patients, and among patients younger than 18 years. Use of antibiotics recommended for CA-MRSA increased from 7% to 28% of visits (P < .001) during the study period. Independent predictors of treatment with these antibiotics included being younger than 45 years, living in the South, and an ED setting. CONCLUSIONS The incidence of SSTIs has rapidly increased nationwide in the CA-MRSA era and appears to disproportionately affect certain populations. Although physicians are beginning to modify antibiotic prescribing practices, opportunities for improvement exist, targeting physicians caring for patients who are at high risk.

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged worldwide. The United States, in particular, is experiencing a serious epidemic of CA-MRSA that is almost entirely caused by an extraordinarily infectious strain named USA300. However, the molecular determinants underlying the pathogenic success of CA-MRSA are mostly unknown. To gain insight into the evolution of the exceptional potential of USA300 to cause disease, we compared the phylogeny and virulence of USA300 with that of closely related MRSA clones. We discovered that the sublineage from which USA300 evolved is characterized by a phenotype of high virulence that is clearly distinct from other MRSA strains. Namely, USA300 and its progenitor, USA500, had high virulence in animal infection models and the capacity to evade innate host defense mechanisms. Furthermore, our results indicate that increased virulence in the USA300/USA500 sublineage is attributable to differential expression of core genome-encoded virulence determinants, such as phenol-soluble modulins and α-toxin. Notably, the fact that the virulence phenotype of USA300 was already established in its progenitor indicates that acquisition of mobile genetic elements has played a limited role in the evolution of USA300 virulence and points to a possibly different role of those elements. Thus, our results highlight the importance of differential gene expression in the evolution of USA300 virulence. This finding calls for a profound revision of our notion about CA-MRSA pathogenesis at the molecular level and has important implications for design of therapeutics directed against CA-MRSA.