Recurrent Methicillin-Resistant Staphylococcus aureus Cutaneous Abscesses and Selection of Reduced Chlorhexidine Susceptibility during Chlorhexidine Use

Johnson, Ryan C.; Schlett, Carey D.; Crawford, Katrina B.; Lanier, Jeffrey; Ellis, Michael W.

doi:10.1128/jcm.01771-15

Cited by 25 publications

(28 citation statements)

References 41 publications

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“…The effectiveness and widespread use of chlorhexidine has led to some concerns regarding the emergence of bacterial resistance (Edmiston et al, 2013;Horner et al, 2012), including MRSA resistance (Johnson et al, 2015). However, reported levels of susceptibility of the bacterial isolates are still several orders of magnitude below the clinically applied dosages (Horner et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…in sutures and central venous and urinary tract catheters, antibiotic release coatings for orthopaedic devices remain mainly experimental. A study in rabbits with titanium fixation plates coated with poly-L -lactide (PLLA), containing a combination of rifampicin and fusidic acid, placed on the tibia, showed a significant reduction in S. aureus infection after 28 d (Kälicke et al, 2006). Direct application of rifampicin and minocycline on titanium significantly reduced S. aureus colonisation of femoral medullary nails and device-related osteomyelitis in rabbits after 1 week (Darouiche, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Chlorhexidine is an important agent in the prevention of the spread of antibiotic resistant organisms and hospital-acquired infections (Johnson et al, 2015). The effectiveness and widespread use of chlorhexidine has led to some concerns regarding the emergence of bacterial resistance (Edmiston et al, 2013;Horner et al, 2012), including MRSA resistance (Johnson et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…One of the most frequently used antiseptics is chlorhexidine, with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and yeasts, and with acceptable tolerability and a good safety record (McDonnell and Russell, 1999). Chlorhexidine has been approved by the American Food and Drug Administration (FDA) for application to intracorporally used medical devices, such as surgical meshes (Choe et al, 2000;Pérez-Köhler et al, 2015) and intravenous catheters (Maki, 1997) and has a history of successful clinical (Karpanen et al, 2016) and experimental use in preventing biomaterial-associated and other infections (Darouiche et al, 2008;Sjollema et al, 2014). Chlorhexidine combined with chloroxylenol in a dip-coating on rabbit tibia intramedullary nails prevented experimental S. aureus osteomyelitis (Darouiche et al, 1998a;Darouiche et al, 1998b).…”

Section: Discussionmentioning

confidence: 99%

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A chlorhexidine-releasing epoxy-based coating on titanium implants prevents Staphylococcus aureus experimental biomaterial-associated infection

Riool,

Dirks,

Jaspers

et al. 2107

eCM

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Prevention of biomaterial-associated infections (BAI) remains a challenging problem, in particular due to the increased risk of resistance development with the current antibiotic-based strategies. Metallic orthopaedic devices, such as non-cemented implants, are often inserted under high mechanical stress. These non-cemented implants cannot be protected by e.g. antibiotic-releasing bone cement or other antimicrobial approaches, such as the use of bioactive glass. Therefore, in order to avoid abrasion during implantation procedures, we developed an antimicrobial coating with great mechanical stability for orthopaedic implants, to prevent Staphylococcus aureus BAI. We incorporated 5 and 10 wt % chlorhexidine in a novel mechanically stable epoxy-based coating, designated CHX 5 and CHX 10 , respectively. The coatings displayed potent bactericidal activity in vitro against S. aureus, with over 80 % of the release (19 µg/cm 2 for CHX 5 and 41 µg/ cm 2 for CHX 10 ) occurring within the first 24 h. In mice, the CHX 10 coating significantly reduced the number of CFU (colony forming units), both on the implants and in the peri-implant tissues, 1 d after S. aureus challenge. The CHX 10 -coated implants were well-tolerated by the animals, with no signs of toxicity observed by histological analysis. Moreover, the coating significantly reduced the frequency of culture-positive tissues 1 d, and of culturepositive implants 1 and 4 d after challenge. In summary, the chlorhexidine-releasing mechanically stable epoxybased CHX 10 coating prevented implant colonisation and S. aureus BAI in mice and has good prospects for clinical development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A chlorhexidine-releasing epoxy-based coating on titanium implants prevents Staphylococcus aureus experimental biomaterial-associated infection

Riool,

Dirks,

Jaspers

et al. 2107

eCM

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“…CHG has been used widely in health care for more than 50 years, and reduced susceptibility as measured by in vitro methods has been reported across the globe (18,(20)(21)(22)(23)(24)46), yet decolonization failure related to nonsusceptibility has been described only rarely (16,25,26). Of note, topical concentrations of CHG used for decolonization remain Ͼ200-fold higher than the highest CHG MICs and minimum bactericidal concentrations (MBCs) recorded for staphylococci (15,25).…”

mentioning

confidence: 99%

Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial

et al. 2016

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h Whether targeted or universal decolonization strategies for the control of methicillin-resistant Staphylococcus aureus (MRSA) select for resistance to decolonizing agents is unresolved. The REDUCE-MRSA trial (ClinicalTrials registration no. NCT00980980) provided an opportunity to investigate this question. REDUCE-MRSA was a 3-arm, cluster-randomized trial of either screening and isolation without decolonization, targeted decolonization with chlorhexidine and mupirocin, or universal decolonization without screening to prevent MRSA infection in intensive-care unit (ICU) patients. Isolates from the baseline and intervention periods were collected and tested for susceptibility to chlorhexidine gluconate (CHG) by microtiter dilution; mupirocin susceptibility was tested by Etest. The presence of the qacA or qacB gene was determined by PCR and DNA sequence analysis. A total of 3,173 isolates were analyzed; 2 were nonsusceptible to CHG (MICs, 8 g/ ml), and 5/814 (0.6%) carried qacA or qacB. At baseline, 7.1% of MRSA isolates expressed low-level mupirocin resistance, and 7.5% expressed high-level mupirocin resistance. In a mixed-effects generalized logistic regression model, the odds of mupirocin resistance among clinical MRSA isolates or MRSA isolates acquired in an ICU in intervention versus baseline periods did not differ across arms, although estimates were imprecise due to small numbers. Reduced susceptibility to chlorhexidine and carriage of qacA or qacB were rare among MRSA isolates in the REDUCE-MRSA trial. The odds of mupirocin resistance were no different in the intervention versus baseline periods across arms, but the confidence limits were broad, and the results should be interpreted with caution.

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Fitness costs associated with carriage of a large staphylococcal plasmid are reduced by subinhibitory concentrations of antiseptics

LaBreck

Merrell

2020

MicrobiologyOpen

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Staphylococcus aureus carries a collection of mobile genetic elements that often harbor virulence and antimicrobial resistance genes. Since the introduction of antibiotics, plasmids have become a major genetic element responsible for the distribution of antimicrobial resistance. Under antimicrobial selection, resistance plasmids are maintained within bacterial populations as a means to ensure survival. However, in the absence of selection, large plasmids can be lost due to the fitness costs associated with harboring these genetic elements. pC02 is a previously identified multidrug resistance, conjugative plasmid that is found in S. aureus. In addition to antibiotic resistance, pC02 also carries genes known to be associated with antiseptic resistance.Among these, we previously characterized the contribution of qacA to pC02 mediated reduced chlorhexidine susceptibility. Herein, we demonstrate that pC02 also mediates triclosan resistance, likely due to the presence of fabI, a known triclosan resistance gene. Moreover, we demonstrate that conjugative transfer of pC02 increases triclosan resistance in recipient cells. Competition assays demonstrated a fitness cost associated with carriage of the large pC02 plasmid. However, subinhibitory concentrations of either chlorhexidine or triclosan abrogated this fitness cost. Given the widespread use of these antiseptics, both of which accumulate in wastewater and other environmental reservoirs, indiscriminate use of antiseptics likely imposes a constant selective pressure that promotes maintenance of antimicrobial resistance factors within S. aureus. K E Y W O R D Santibiotic resistance, bacterial plasmids, mobile genetic elements, Staphylococcus

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Recurrent Methicillin-Resistant Staphylococcus aureus Cutaneous Abscesses and Selection of Reduced Chlorhexidine Susceptibility during Chlorhexidine Use

Cited by 25 publications

References 41 publications

A chlorhexidine-releasing epoxy-based coating on titanium implants prevents Staphylococcus aureus experimental biomaterial-associated infection

A chlorhexidine-releasing epoxy-based coating on titanium implants prevents Staphylococcus aureus experimental biomaterial-associated infection

Chlorhexidine and Mupirocin Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolates in the REDUCE-MRSA Trial

Fitness costs associated with carriage of a large staphylococcal plasmid are reduced by subinhibitory concentrations of antiseptics

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