Antimicrobial Resistance

J. T. Weber

• Publisher: S. Karger
• Year: 2010
• ISBN:
  9783805593243
• Topic: Medicina
• Subtopic: Sanità, amministrazione e assistenza pubblica

Preventing, controlling and treating drug-resistant infections is one of the major challenges in modern medicine. Antimicrobial Resistance goes beyond simple definitions and microbiological data to fully explore this rapidly changing area, describing evidence for effective interventions, costs, treatment strategies and directions for future research.Each chapter provides essential background and examines the evidence for an important aspect of prevention and control, treatment strategy or policy decision. Prevention and control strategies are analyzed for inappropriate antimicrobial use, fluoroquinolone-resistant organisms, health-care associated infections and parasitic diseases. Furthermore, treatment strategies for changing resistance patterns are explored for community-acquired pneumonia during an influenza pandemic and infections with community-associated MRSA, extended-spectrum beta-lactamase producing organisms and fungi. Data for policy making are presented in articles that detail the costs of antimicrobial-resistant infections in healthcare settings and the threat of resistance with the introduction of antiretroviral therapy for large populations in the developing world. These reviews show where interventions, surveillance and research will be most useful in the future. Antimicrobial Resistance is an invaluable contribution for infectious disease physicians and public health officials who are interested in the prevention of antimicrobial-resistant infections.

Weber JT (ed): Antimicrobial Resistance – Beyond the Breakpoint.
Issues Infect Dis. Basel, Karger, 2010, vol 6, pp 1–20

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Community-Associated Methicillin Resistant Staphylococcus aureus

Loren Gregory Miller

David Geffen School of Medicine at UCLA, Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, Calif., USA

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Abstract

Community-associated methicillin-resistant Staphylococcus aureus has rapidly risen in incidence to become not only very common, but the predominant cause of S. aureus infections in many parts of the world. This bacterium is notable for its predilection to cause infections in healthy persons and be transmitted easily from person to person. Additionally, this organism has the ability to cause severe, life-threatening infections that were previously only rarely, if ever, associated with S. aureus. Optimal methods to treat and prevent this infection are uncertain and will require extensive investigation.

Copyright © 2010 S. Karger AG, Basel

Infections caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) have, in a relatively brief period of time, been transformed from a rare entity worthy of case reports, to a common infection. In many parts of the world CA-MRSA infections are common reasons that patients present to primary care physicians, urgent care clinics, and emergency departments. CA-MRSA infections are also being seen increasingly by subspecialty practitioners, who previously had not encountered or were not aware that community-associated S. aureus infections could be and are caused by MRSA. This chapter will review current understanding of the epidemiology, pathogenesis, treatment and prevention of CA-MRSA infections.

S. aureus, MRSA and Community-Associated Infections: Background

S. aureus is a ubiquitous human pathogen and a common cause of invasive and lifethreatening infections. It is the most common cause of community-associated cellulitis [1, 2] and endocarditis [3], and is a common cause of bacteremia [1, 4, 5]. S. aureus strains were once nearly uniformly susceptible to semi-synthetic penicillinase-resistant β-lactams (e.g. methicillin, oxacillin), the most commonly used class of antibiotics for skin infection. These strains were termed ‘methicillin resistant Staphylococcus aureus,’ or MRSA, a term that implied cross-resistance to all ß-lactams including all penicillins and cephalosporins. By the 1970s, MRSA outbreaks were reported in large, urban, tertiary care hospitals in the United States. Soon MRSA became endemic as a nosocomial pathogen in many hospitals [6]. MRSA infections acquired in the community, however, remained extremely rare.

Defining a ‘community-associated’ infection is challenging. Most experts prefer the term ‘community-associated’ rather than other terms found in the literature (e.g. community-acquired, community-onset). In the past, terms such as ‘nosocomially acquired’ and ‘community-acquired’ were used to describe the locale in which an infection was acquired. More recently, public health officials have emphasized describing the origin of the organism that subsequently caused the infection (community vs. healthcare setting) rather than just where the infection was acquired [7].

Many CA-MRSA definitions have been used [8]. One commonly used definition of community-associated is based on epidemiologic risk factors. The designation of MRSA as CA-MRSA infection reflects that the MRSA culture was obtained in the outpatient setting or isolated during 72 h of hospitalization and the patient did not have exposures associated with healthcare-associated (HA) MRSA infections, such as recent (defined as ‘in the prior 12 months’) hospitalization, receipt of hemodialysis, residence in a chronic care facility, or presence of an indwelling catheter [9].

Others have used molecular characteristics of the MRSA isolate to distinguish CA-MRSA from HA-MRSA strains. CA-MRSA infections are typically caused by strains that carry Staphylococcal Chromosomal Cassette (SCC)mec type IV (or V), whereas HA-MRSA is typically caused by strains that contain SCCmec types I—III (discussed below). However, a molecular definition of CA-MRSA is limiting. The rule that MRSA containing SCCmec type IV causes community-associated infections is increasingly being violated. Many groups have reported SCCmec type IV-containing MRSA strains causing healthcare-associated infections [10–12]. In one hospital in Los Angeles, SCCmec type IV-containing MRSA is now responsible for the majority of HA-MRSA infections, surpassing SCCmec types I—III in prevalence [12]. An epidemiologic definition of CA-MRSA is more advantageous as strains of both community- and healthcare-associated S. aureus are known to evolve over time [13].

Nevertheless, any epidemiologic classification system has limitations. For example, patients with exposures that would categorize their infection as healthcare-associated (e.g. hospitalization in the prior year), but have an MRSA infection almost certainly associated with an outbreak (e.g. in a prison or among football players) would incorrectly have their infection categorized as a HA-MRSA infection. Others have noted that rates of CA-MRSA versus HA-MRSA can vary dramatically depending on the definitions and data source used to determine community-associated status. These miscategorizations may distract investigators from potentially important healthcare sources of infection [14].

Rapid Increase in CA-MRSA Incidence

The incidence of CA-MRSA infections and reported numbers of outbreaks has increased at a rapid rate during the late 1990s and the early 21st century. Retrospective investigations of Native Americans in rural areas of the Midwestern United States [15] and of hospitalized children in Chicago [16] demonstrated 15-fold and 7-fold increases, respectively, in the proportion of community-associated S. aureus isolates that were methicillin-resistant during the 1990s. In the latter study, the proportion of children with S. aureus infections caused by CA-MRSA more than doubled, from 25-67%, over a 5-year period. This rise was due to a 26-fold increase in the incidence of MRSA in infected children with no recognized risk factors for MRSA. Similarly, a retrospective study from Texas found a 7-fold increase in the incidence of CA-MRSA infections from 1997-2000 relative to 1990-1996 [17].

In a similar time period, outbreaks of CA-MRSA infection have been increasingly described. Many populations of healthy persons have been affected. These populations include inmates in jails and prisons [18, 19], athletes participating in contact sports [18, 20], military personnel [21, 22], HIV-infected men who have sex with men [23, 24], and intravenous drug users [8, 25], among other populations. Outbreaks of CA-MRSA are being reported worldwide, including in the United States, Europe, Australia and Asia [26]. In many parts of the world, CA-MRSA infections are endemic and not associated with recognized outbreaks. Several centers have shown that MRSA is responsible for over 50% of community-associated S. aureus infections [27, 28].

Risk Factors, Clinical Manifestations and Transmission

Risk factors for CA-MRSA infection among the general population are incompletely understood. Data on CA-MRSA risk factors often come from outbreak investigations, which typically occur in relatively homogenous patient populations, such as inmates and athletes [28]. Studies on risk factors for endemic CA-MRSA infections (i.e. infections occurring in non-outbreak settings) frequently come from single centers, making findings difficult to extrapolate to other locales. That said, there are a few commonalities in studies of risk factors. Ethnic minorities comprise 50-90% of CA-MRSA patients in several case series [29–31], and lower socioeconomic status has been associated with increased CA-MRSA risk as well [30, 31]. In several investigati...