Nasal carriage of <i><scp>S</scp>taphylococcus aureus</i> in patients undergoing <scp>M</scp>ohs micrographic surgery is an important risk factor for postoperative surgical site infection: A prospective randomised study

Tai, Yee J; Borchard, Kate; Gunson, Todd H.; Smith, Harvey R.; Vinciullo, Carl

doi:10.1111/ajd.12028

Cited by 51 publications

(46 citation statements)

References 16 publications

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“…The quinoline-derived cationic antimicrobial HT61 [1] was initially developed to improve the success of nasal decolonisation interventions aimed at decreasing the risk of post-operative surgical site infections (SSI) posed by carriage of methicillin resistant Staphylococcus aureus (MRSA) [2,3] . However, more recently it has been proposed as a resistance breaker to be used in conjunction with other more established antimicrobials [4] .…”

Section: Introductionmentioning

confidence: 99%

“…In bilayers containing 25 mol% phosphatidylglycerol, neutron reflectometry data suggests that exposure to HT61 increases the level of solvent in the hydrophobic region of the membrane, which is indicative of gross structural damage. Increasing the proportion of PG elicits a concomitant level of membrane damage resulting in almost total destruction when 75 mol% phosphatidylglycerol is present.We therefore propose that HT61's primary action is directed towards the cytoplasmic membrane of Gram positive bacteria.The quinoline-derived cationic antimicrobial HT61 [1] was initially developed to improve the success of nasal decolonisation interventions aimed at decreasing the risk of post-operative surgical site infections (SSI) posed by carriage of methicillin resistant Staphylococcus aureus (MRSA) [2,3] . However, more recently it has been proposed as a resistance breaker to be used in conjunction with other more established antimicrobials [4] .…”

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confidence: 99%

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Mechanism of Action of a Membrane-Active Quinoline-Based Antimicrobial on Natural and Model Bacterial Membranes

et al. 2017

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self-assembled monolayers; SLD, scattering length density; SMW, silicon matched water; SSI, surgical site infections; SRS, standard reaction solution; TMPA, 3-(trimethoxysilyl)propyl acrylate; TSA, tryptone soya agar. ABSTRACTHT61 is a quinoline-derived antimicrobial, which exhibits bactericidal potency against both multiplying and quiescent methicillin resistant and sensitive Staphylococcus aureus, and has been proposed as an adjunct for other antimicrobials in order to extend their usefulness in the face of increasing antimicrobial resistance. In this study we have examined HT61's effect on the permeability of Staphylococcus aureus membranes and whether this putative activity can be attributed to an interaction with lipid bilayers. Using membrane potential and ATP release assays, we have shown that HT61 disrupts the membrane enough to results in depolarisation of the membrane and release of intercellular constituents at concentrations above and below the minimum inhibitory concentration of the drug. Utilising both monolayer subphase injection and neutron reflectometry we have shown that increasing the anionic lipid content of the membrane leads to a more marked effect of the drug. In bilayers containing 25 mol% phosphatidylglycerol, neutron reflectometry data suggests that exposure to HT61 increases the level of solvent in the hydrophobic region of the membrane, which is indicative of gross structural damage. Increasing the proportion of PG elicits a concomitant level of membrane damage resulting in almost total destruction when 75 mol% phosphatidylglycerol is present.We therefore propose that HT61's primary action is directed towards the cytoplasmic membrane of Gram positive bacteria.The quinoline-derived cationic antimicrobial HT61 [1] was initially developed to improve the success of nasal decolonisation interventions aimed at decreasing the risk of post-operative surgical site infections (SSI) posed by carriage of methicillin resistant Staphylococcus aureus (MRSA) [2,3] . However, more recently it has been proposed as a resistance breaker to be used in conjunction with other more established antimicrobials [4] . Although the protein synthesis inhibitor mupirocin is currently widely used for anti-MRSA nasal decolonisation, it is not active against non-multiplying persister bacteria which constitute a reservoir for recolonisation [5] . In addition to this, an increased prevalence of mupirocin resistant MRSA [6] has led to the development of more effective alternatives, including the experimental antimicrobials LTX-109 [7] and XF-73 [8] in addition to HT61 [1] .The mode of action of HT61 has not hitherto been thoroughly investigated, however initial cell-based assays showed that HT61 is capable of depolarising the cytoplasmic membrane ofGram positives with further evidence from electron microscopy suggesting that HT61 causes lysis of either the membrane or cell wall [1,4] . The putative membrane-targeting of HT61 may provide some explanation for its potency against non-multiplying MRSA [9] , and suggests that...

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Mechanism of Action of a Membrane-Active Quinoline-Based Antimicrobial on Natural and Model Bacterial Membranes

et al. 2017

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“…23,[27][28][29] However, recent reviews have been unable to show definitive evidence that preoperative showering reduces SSI. [33][34][35][36][37] Investigations from various surgical disciplines have shown a reduction in SSI to a rate comparable with noncarriers with the use of protocols to identify and decolonize carriers of S. aureus before surgery. It has been shown that nasal carriage of S. aureus is an independent risk factor for the development of SSI in multiple surgical settings, including dermatologic surgery.…”

Section: Preoperative Decolonizationmentioning

confidence: 99%

“…It has been shown that nasal carriage of S. aureus is an independent risk factor for the development of SSI in multiple surgical settings, including dermatologic surgery. 37 A variety of decolonization protocols have been described, usually consisting of topical agents used [38][39][40][41] It remains to be seen if these interventions are beneficial in a dermatologic surgery setting, but a recent prospective randomized study demonstrated a significant reduction in SSI after Mohs surgery among nasal S. aureus carriers with the use of a topical decolonization regimen.…”

Section: Preoperative Decolonizationmentioning

confidence: 99%

Role of Antiseptics in the Prevention of Surgical Site Infections

Echols

Graves

LeBlanc³

et al. 2015

Dermatologic Surgery

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More randomized controlled trials will be needed to determine if any specific regimen is most effective. At this point in time, product usage should be based on specific attributes relating to the products, such as iodophors around the eyes and/or ears to avoid irritation and aqueous-based solutions in hair bearing areas because of concern for flammability. Ultimately, it is up to the individual surgeon to tailor the optimal antiseptic regimen for their specific scope of practice.

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“…The most well-established regimen recommended in several national guidelines (e.g., in the 1998 United Kingdom guideline and the upcoming U.S. CDC guideline) is using a combination of 5 to 7 days of treatment with nasal mupirocin ointment and chlorhexidine soap (4,5,(10)(11)(12). This treatment has been shown to reduce the incidence of nosocomial infections (5).…”

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confidence: 99%

LTX-109 Is a Novel Agent for Nasal Decolonization of Methicillin-Resistant and -Sensitive Staphylococcus aureus

Nilsson

Janson

Wold

et al. 2015

Antimicrob Agents Chemother

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Nasal decolonization has a proven effect on the prevention of severe Staphylococcus aureus infections and the control of methicillin-resistant S. aureus (MRSA). However, rising rates of resistance to antibiotics highlight the need for new substances for nasal decolonization. LTX-109 is a broad-spectrum, fast-acting bactericidal antimicrobial drug for topical treatment, which causes membrane disruption and cell lysis. This mechanism of action is not associated with cross-resistance and has a low propensity for development of resistance. In the present study, persistent nasal MRSA and methicillin-sensitive S. aureus (MSSA) carriers were treated for 3 days with vehicle or with 1%, 2%, or 5% LTX-109. A significant effect on nasal decolonization was observed already after 2 days of LTX-109 treatment in subjects treated with 2% or 5% LTX-109 compared to vehicle (P < 0.0012 by Dunnett=s test). No safety issues were noted during the 9-week follow-up period. Minimal reversible epithelial lesions were observed in the nasal cavity. The systemic exposure was very low, with a maximum concentration of drug in plasma (C max ) at 1 to 2 h postdosing (3.72 to 11.7 ng/ml). One week after treatment initiation, LTX-109 was not detectable in any subject. Intranasal treatment of S. aureus with LTX-109 is safe and reduces the bacterial load already after a single day of treatment. Hence, LTX-109 has potential as a new and effective antimicrobial agent with a low propensity of resistance development that can prevent infections by MSSA/MRSA during hospitalization. (This study has been registered at ClinicalTrials.gov under registration no. NCT01158235.) N asal carriage of Staphylococcus aureus is considered a marker of extended skin carriage and colonization by S. aureus. The colonization is often asymptomatic, but most severe S. aureus infections are caused by endogenous strains from the patient (1-5).Persistent nasal colonization by S. aureus, including methicillin-resistant S. aureus (MRSA) strains, has shown to be a major risk factor for surgical-site (6) and renal dialysis (5, 7) infections. Such individuals have a substantially increased risk for S. aureus hospital-acquired infections (8), with up to as many as 11 to 22% of methicillin-sensitive and -resistant S. aureus carriers developing nosocomial infections during hospital admission (9). In addition, patients carrying S. aureus can be a source of transmission to noncarriers, which subsequently can lead to health care-related exogenous infections.The spread of S. aureus remains unquestionably a serious challenge in infection control in hospitals, and in an attempt to reduce the S. aureus infection rates, prevention programs aiming at decolonizing individual nasal S. aureus carriers have been implemented. The most well-established regimen recommended in several national guidelines (e.g., in the 1998 United Kingdom guideline and the upcoming U.S. CDC guideline) is using a combination of 5 to 7 days of treatment with nasal mupirocin ointment and chlorhexidine soap (4,5,(10)(11)(12...

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Nasal carriage of Staphylococcus aureus in patients undergoing Mohs micrographic surgery is an important risk factor for postoperative surgical site infection: A prospective randomised study

Cited by 51 publications

References 16 publications

Mechanism of Action of a Membrane-Active Quinoline-Based Antimicrobial on Natural and Model Bacterial Membranes

Mechanism of Action of a Membrane-Active Quinoline-Based Antimicrobial on Natural and Model Bacterial Membranes

Role of Antiseptics in the Prevention of Surgical Site Infections

LTX-109 Is a Novel Agent for Nasal Decolonization of Methicillin-Resistant and -Sensitive Staphylococcus aureus

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