We searched PubMed using the terms “CA-MRSA”, “Europe and CA-MRSA”, “Panton-Valentine leukocidin”, and “USA300”, without any language restrictions. We selected references mainly from the past 5 years, including cross-references, although landmark or highly regarded references were also included. Review articles were cited when appropriate for further detail about a specific topic. We also included references on the basis of comments from peer reviewers.
SeminarCommunity-associated meticillin-resistant Staphylococcus aureus
Introduction
Staphylococcus aureus is a leading cause of human bacterial infections worldwide.1 The severity of these infections varies widely—from minor skin infections to fatal necrotising pneumonia. The pathogen is also a commensal organism in people, and about 30% of healthy individuals who are not in institutions are colonised asymptomatically with S aureus in the nostrils.2 These findings are noteworthy because nasal carriage of S aureus has been associated with subsequent infection.3
S aureus has outstanding ability to acquire resistance to antibiotics. Epidemics or pandemics of antibiotic-resistant S aureus have arisen in the past 60 years.4, 5 Benzylpenicillin was no longer effective for treatment of most S aureus infections within 10 years after its introduction for use in people because of the acquisition of plasmid-encoded β lactamase.6 Penicillin-resistant S aureus became pandemic throughout the late 1950s and early 1960s.7 Meticillin-resistant S aureus (MRSA) was first reported in 1961, 2 years after the antibiotic was introduced to treat the penicillin-resistant strain.8 MRSA spread worldwide over the next several decades and is now endemic in most hospitals and health-care facilities in industrialised countries. In the USA, MRSA is among the leading causes of death by any single infectious agent.4, 9 A major concern for treatment of MRSA infections is the increasing prevalence of resistance to several antibiotics (multidrug resistance).
By contrast with health-care-associated MRSA (HA-MRSA) infections, for which there is a predisposing risk factor or illness, community-associated MRSA (CA-MRSA) infections can occur in otherwise healthy individuals,10 suggesting that these bacterial strains have greater virulence than do traditional HA-MRSA strains. In addition to enhanced virulence, some CA-MRSA strains, such as USA300, have the ability to spread readily. These characteristics perhaps partly explain why CA-MRSA is present in many countries (figure 1).11, 12
In this Seminar, we review our current understanding of CA-MRSA emergence, the basis for enhanced transmission and virulence, and provide an update of the most recent strategies for diagnosis and treatment of CA-MRSA infections.
Section snippets
Epidemiology
Since MRSA was first described in 1961, it has been regarded as a nosocomial pathogen that is not normally present in the community. However, this notion has changed greatly in the past 15 years, and CA-MRSA infections are now prevalent and widespread (figure 1). Although MRSA infections acquired from the community were reported in Detroit, MI, USA, in 1982, all patients had predisposing risk factors for infection, such as previous hospital admission or intravenous drug abuse.13 The first
S aureus immune evasion
The ability of bacteria to cause disease in human beings is due largely to evasion of innate immunity, which includes resistance to killing by phagocytic leucocytes. S aureus produces several molecules—some on the cell surface and others freely secreted—that together elicit a robust inflammatory response. In as much as neutrophils are a key component of the inflammatory response and are the most prominent cellular defence against S aureus infections, the pathogen has evolved means to circumvent
Diagnosis
S aureus infection is diagnosed readily by isolating the organism from cultures of blood, tissue, or pus. The organism will grow in virtually any non-selective bacterial culture medium. Unless a patient has been previously treated with an effective antistaphylococcal drug (and generally several days of effective treatment are needed to render a site culture-negative), failure to culture S aureus is strong evidence against staphylococcal infection. If the bacterium is isolated from blood or
Antimicrobial therapy
Emergence of CA-MRSA has profoundly affected the choice of empirical treatment for suspected staphylococcal infection, particularly common skin and soft-tissue infections. β-lactams, which are inexpensive, not toxic, and highly effective, have been the drugs of choice for treatment of such infections, but, like HA-MRSA, CA-MRSA strains are broadly resistant to almost all β-lactam antibiotics, making these an undesirable option when the prevalence of CA-MRSA strains is high. Clinical evidence
Conclusions and future
S aureus has been a cause of human disease throughout recorded history. The antibiotic era was perhaps largely expected to eliminate S aureus (and other bacterial pathogens) as a leading cause of human infections. However, S aureus has extraordinary ability to develop resistance to antibiotics, which have been the impetus for waves of antibiotic resistance over the past 60 years.5 This resistance is perplexing, because antibiotics are absolutely crucial for treatment of many types of bacterial
Search strategy and selection criteria
References (156)
- et al.
Genetic analysis of community isolates of methicillin-resistant Staphylococcus aureus in Western Australia
J Hosp Infect
(1993) - et al.
Genome and virulence determinants of high virulence community-acquired MRSA
Lancet
(2002) - et al.
Meticillin-resistant Staphylococcus aureus among US prisoners and military personnel: review and recommendations for future studies
Lancet Infect Dis
(2006) - et al.
Methicillin-resistant Staphylococcus aureus producing Panton-Valentine leukocidin in a retrospective case series from 12 French hospital laboratories, 2000–2003
Clin Microbiol Infect
(2005) - et al.
Structure and specific detection of staphylococcal cassette chromosome mec type VII
Biochem Biophys Res Commun
(2008) - et al.
Fifteen-year study of the changing epidemiology of methicillin-resistant Staphylococcus aureus
Am J Med
(2006) - et al.
Host defense and pathogenesis in Staphylococcus aureus infections
Infect Dis Clin North Am
(2009) - et al.
Bacterial complement evasion
Mol Immunol
(2007) - et al.
Leukocidal toxins of staphylococci
Zentralbl Bakteriol
(1999) - et al.
The Panton-Valentine leukocidin vaccine protects mice against lung and skin infections caused by Staphylococcus aureus USA300
Clin Microbiol Infect
(2009)
Effect of staphylococcal leukocidin on mouse leukocyte system
Zentralbl Bakteriol Mikrobiol Hyg [A]
Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients
Lancet
Analyses of clonality and the evolution of bacterial pathogens
Curr Opin Microbiol
Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997–1999
Clin Infect Dis
Changes in the prevalence of nasal colonization with Staphylococcus aureus in the United States, 2001–2004
J Infect Dis
Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group
N Engl J Med
Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era
J Clin Invest
Waves of resistance: Staphylococcus aureus in the antibiotic era
Nat Rev Microbiol
Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci
Science
Infections caused by a particular phage type of Staphylococcus aureus
Med J Aust
“Celbenin”-resistant staphylococci
BMJ
Invasive methicillin-resistant Staphylococcus aureus infections in the United States
JAMA
Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk
JAMA
Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence
Emerg Infect Dis
Global distribution of Panton-Valentine leukocidin—positive methicillin-resistant Staphylococcus aureus, 2006
Emerg Infect Dis
Community-acquired methicillin-resistant Staphylococcus aureus infections: a new source for nosocomial outbreaks
Ann Intern Med
Methicillin-resistant Staphylococcus aureus clones, Western Australia
Emerg Infect Dis
Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus—Minnesota and North Dakota, 1997–1999
JAMA
Novel type of staphylococcal cassette chromosome mec identified in community-acquired methicillin-resistant Staphylococcus aureus strains
Antimicrob Agents Chemother
The emergence and importation of diverse genotypes of methicillin-resistant Staphylococcus aureus (MRSA) harboring the Panton-Valentine leukocidin gene (pvl) reveal that pvl is a poor marker for community-acquired MRSA strains in Ireland
J Clin Microbiol
Diversity among community isolates of methicillin-resistant Staphylococcus aureus in Australia
J Clin Microbiol
A survey of community-associated methicillin-resistant Staphylococcus aureus in Korea
J Antimicrob Chemother
Coexistence of Panton-Valentine leukocidin-positive and -negative community-associated methicillin-resistant Staphylococcus aureus USA400 sibling strains in a large Canadian health-care region
J Infect Dis
Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database
J Clin Microbiol
Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus
J Clin Microbiol
Shift in Staphylococcus aureus clone linked to an infected tattoo
Emerg Infect Dis
Methicillin-resistant Staphylococcus aureus in two child care centers
J Infect Dis
Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men
Ann Intern Med
A high-morbidity outbreak of methicillin-resistant Staphylococcus aureus among players on a college football team, facilitated by cosmetic body shaving and turf burns
Clin Infect Dis
Community-onset methicillin-resistant Staphylococcus aureus associated with antibiotic use and the cytotoxin Panton-Valentine leukocidin during a furunculosis outbreak in rural Alaska
J Infect Dis
Clinical practice: colonization, fomites, and virulence: rethinking the pathogenesis of community-associated methicillin-resistant Staphylococcus aureus infection
Clin Infect Dis
Epidemic community-associated methicillin-resistant Staphylococcus aureus: recent clonal expansion and diversification
Proc Natl Acad Sci USA
Methicillin-resistant S. aureus infections among patients in the emergency department
N Engl J Med
Emergence of two populations of methicillin-resistant Staphylococcus aureus with distinct epidemiological, clinical and biological features, isolated from patients with community-acquired skin infections
Br J Dermatol
Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains
J Clin Microbiol
The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA)
Proc Natl Acad Sci USA
A novel methicillin-resistance cassette in community-acquired methicillin-resistant Staphylococcus aureus isolates of diverse genetic backgrounds
J Infect Dis
Fitness cost of staphylococcal cassette chromosome mec in methicillin-resistant Staphylococcus aureus by way of continuous culture
Antimicrob Agents Chemother
Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community
J Clin Microbiol
Cited by (1055)
Current status of development and biomedical applications of peptide-based antimicrobial hydrogels
2024, Advances in Colloid and Interface Science