Newer Antistaphylococcal Agents: In-Vitro Studies and Emerging Trends in Staphylococcus aureus Resistance
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Staphylococcus aureus became known as a causative agent of infection when Alexander Ogston identified its role in sepsis and abscess formation.1 It continues to be one of the commonest human pathogens and is most frequently isolated in community and hospital-acquired infections. S aureus causes a broad spectrum of diseases, including superficial lesions, such as wound infections; systemic and life-threatening conditions, such as endocarditis, osteomyelitis, pneumonia, brain abscesses, meningitis, and bacteremia; and toxinoses, such as food poisoning, scalded skin syndrome, and toxic shock syndrome.2
The discovery of penicillin in the 1940s and many antibiotics in the 1950s to the 1970s (known as the “Golden Age of Antibiotics”) created a sense of euphoria in the medical community, as it perceived that bacterial infections were curable. However, the bright prospect of antimicrobial therapy began to dim when it became obvious that disease-causing bacteria possess a repertoire of strategies against antimicrobial agents. The emergence of S aureus strains with resistance to penicillin and methicillin was reported in 1948 and 1961, respectively.3,4 In both cases, resistance developed within a few years of the introduction of the antibiotics into clinical medicine. For many years, methicillin-resistant S aureus (MRSA) was considered a multi-drug- resistant pathogen that has been historically associated with hospitals and healthcare facilities.5 However, in addition to having established itself as a major hospital pathogen, MRSA has now been documented in the healthy community affecting persons without established risk factors for MRSA acquisition.6 Following the spread of MRSA, parenteral glycopeptides (vancomycin and teicoplanin) became the mainstay of therapy for MRSA infections. However, the first vancomycin-intermediately resistant S aureus (VISA) isolate was identified in Japan in 1997, and these strains have been reported worldwide.7–10 VISA strains were found to adapt and develop intermediate resistance by thickening of their cell walls. To date, 4 vancomycin-resistant S aureus (VRSA) isolates have been identified in the United States—2 from Michigan and 1 each from Pennsylvania and New York.11–14 Vancomycin-resistant enterococci were isolated from 3 of the 4 patients with VRSA, and it is postulated that in-vivo transfer of the vanA gene could have occurred.15 The authors have observed 4 major trends in the epidemiology of S aureus, especially MRSA. In many countries, infections caused by multiresistant strains (especially MRSA) are of great concern. In other countries, the frequency of MRSA is low. The third trend is the emergence of MRSA in the community, and the final trend is the recent reporting of vancomycin-intermediate and -resistant S aureus.
Over the years, there has been growing concern surrounding the increased prevalence of antimicrobial resistance in S aureus, especially hospital-associated MRSA (HA-MRSA), which limits drug options. This has led to the development of new drugs targeted against this pathogen. However, S aureus continues to demonstrate resistance to a wide range of antimicrobial agents. This review describes the newly developed drugs, their mechanism of action, in-vitro effectiveness based on recent studies conducted in various countries, and emerging trends in S aureus resistance (especially HA-MRSA) to new antibacterial agents.
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