Control and Eradication of Methicillin-Resistant<i>Staphylococcus aureus</i>on a Surgical Unit

Bartzokas, C. A.; Paton, James; Gibson, M.F.; Graham, Robert H.; McLoughlin, Gráinne; Croton, R.

doi:10.1056/nejm198411293112207

Cited by 147 publications

(43 citation statements)

References 16 publications

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“…Specific inhibitors of the FAS-II pathway include triclosan and thiolactomycin. Triclosan, a specific inhibitor of FAS-II trans-2-enoyl-ACP reductase (ENR, also known as inhA or FabI) is effective against a broad spectrum of bacteria (20), including Escherichia coli (21,22), mycobacteria (23), and multidrug-resistant Staphylococcus aureus (24,25) and is widely used as an antimicrobial in household formulations, including soaps and toothpaste. Recently, triclosan was found to inhibit P. falciparum growth with an IC 50 of ϳ1 M (19,26).…”

mentioning

confidence: 99%

Structural Elucidation of the Specificity of the Antibacterial Agent Triclosan for Malarial Enoyl Acyl Carrier Protein Reductase

Perozzo

Kuo

Sidhu

et al. 2002

Journal of Biological Chemistry

204

228

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The human malaria parasite Plasmodium falciparum synthesizes fatty acids using a type II pathway that is absent in humans. The final step in fatty acid elongation is catalyzed by enoyl acyl carrier protein reductase, a validated antimicrobial drug target. Here, we report the cloning and expression of the P. falciparum enoyl acyl carrier protein reductase gene, which encodes a 50-kDa protein (PfENR) predicted to target to the unique parasite apicoplast. Purified PfENR was crystallized, and its structure resolved as a binary complex with NADH, a ternary complex with triclosan and NAD ؉ , and as ternary complexes bound to the triclosan analogs 1 and 2 with NADH. Novel structural features were identified in the PfENR binding loop region that most closely resembled bacterial homologs; elsewhere the protein was similar to ENR from the plant Brassica napus (root mean square for C␣s, 0.30 Å). Triclosan and its analogs 1 and 2 killed multidrug-resistant strains of intra-erythrocytic P. falciparum parasites at sub to low micromolar concentrations in vitro. These data define the structural basis of triclosan binding to PfENR and will facilitate structure-based optimization of PfENR inhibitors.Treatment of Plasmodium falciparum malaria has depended for decades on the use of the aminoquinoline chloroquine or the synergistic antifolate combination pyrimethamine-sulfadoxine. These drugs were characterized by their potency against the P. falciparum asexual intra-erythrocytic stages (responsible for malaria pathogenesis), their affordability and their safety. The occurrence and spread of drug-resistant strains of P. falciparum have largely contributed to a recent resurgence of malaria, which claims 1 to 3 million lives annually and which is endemic in inter-tropical areas representing 40% of the world's population (1). The current situation of antimalarial chemotherapy and resistance, in conjunction with the reappearance of malaria in formerly well-controlled areas, reinforces the need for new, highly potent antimalarials.Recent investigations into Apicomplexan parasites, including Plasmodium and Toxoplasma, have uncovered the existence of a unique organelle, the apicoplast (2-4). The finding that ciprofloxacin-mediated inhibition of plastid replication in Toxoplasma gondii tachyzoites blocked parasite propagation provided evidence for the indispensable nature of this nonphotosynthetic plastid organelle (5). Studies of plastid inhibitors and apicoplast mis-segregation mutants confirmed the essential requirement of this organelle for normal parasite development and indicated that inhibition of apicoplast function or loss of this organelle resulted in parasite death following reinvasion of host cells (5-7). This organelle appears to derive ultimately from a cyanobacterial endosymbiont (4,8,9) and as such was postulated to contain prokaryotic-type metabolic pathways, of significant interest from the perspective of developing antiparasitic drugs (10). Recent studies indicate that these pathways include fatty acid and isoprenoid bios...

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mentioning

confidence: 99%

Structural Elucidation of the Specificity of the Antibacterial Agent Triclosan for Malarial Enoyl Acyl Carrier Protein Reductase

Perozzo

Kuo

Sidhu

et al. 2002

Journal of Biological Chemistry

204

228

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“…In contrast, screening high risk patients for the presence of MRSA followed by implementation of isolation or barrier precautions for those found to be infected or colonized has been shown to be effective in controlling MRSA outbreaks in hospitals and long term care facilities (115)(116)(117)(118)(119), and in reducing nosocomial transmission and overall prevalence in facilities where MRSA is endemic (11,110,(120)(121)(122)(123)(124)(125). Jernigan et al (118,121) reported a 15-fold decrease in transmission of MRSA in a hospital when colonized patients were recognized by a screening program and then cared for with isolation precautions, compared with when isolation precautions were used only in patients recognized to have MRSA from clinical specimens.…”

Section: Screening and Surveillancementioning

confidence: 99%

The Management of Infection and Colonization due to Methicillin‐Resistant Staphylococcus aureus: A CIDS/CAMM Position Paper

Simor

Loeb²

2004

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Methicillin-resistantStaphylococcus aureus(MRSA) is being seen with greater frequency in most hospitals and other health care facilities across Canada. The organism may cause life-threatening infections and has been associated with institutional outbreaks. Several studies have confirmed that MRSA infection is associated with increased morbidity and mortality compared with infections caused by susceptible strains, even when the presence of comorbidities is accounted for. Treatment of MRSA infection is complicated by the fact that these organisms are resistant to multiple antimicrobial agents, so treatment options are limited. The effectiveness of decolonization therapy (attempting to eradicate MRSA carriage) is also uncertain. This paper reviews the medical management of MRSA infections, discusses the potential role of decolonization and provides an overview of evidence to support recommended infection control practices.

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“…Preoperative shaving of the surgical site the night before an operation is associated with a significantly higher SSI risk than either the use of depilatory agents or no hair removal [16,[33][34][35][36][37][38][39][40][41][42][43][44]. In one study, SSI rates were 5.6% in patients who had hair removed by razor shave compared to a 0.6% rate among those who had hair removed by depilatory or who had no hair removed [45].…”

Section: Preoperative Hair Removalmentioning

confidence: 99%

Surgical Site Infections in Relation to the Timing of Shaving among the Gastrointestinal Emergency Patients through the Midline Incisions- A Randomized Controlled Clinical Trial

Hossain¹

2012

J Med Microb Diagn

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Control and Eradication of Methicillin-ResistantStaphylococcus aureuson a Surgical Unit

Cited by 147 publications

References 16 publications

Structural Elucidation of the Specificity of the Antibacterial Agent Triclosan for Malarial Enoyl Acyl Carrier Protein Reductase

Structural Elucidation of the Specificity of the Antibacterial Agent Triclosan for Malarial Enoyl Acyl Carrier Protein Reductase

The Management of Infection and Colonization due to Methicillin‐Resistant Staphylococcus aureus: A CIDS/CAMM Position Paper

Surgical Site Infections in Relation to the Timing of Shaving among the Gastrointestinal Emergency Patients through the Midline Incisions- A Randomized Controlled Clinical Trial

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