scholarly journals Activity of Daptomycin with or without 25 Percent Ethanol Compared to Combinations of Minocycline, EDTA, and 25 Percent Ethanol against Methicillin-Resistant Staphylococcus aureus Isolates Embedded in Biofilm

2013 ◽  
Vol 57 (4) ◽  
pp. 1998-2000 ◽  
Author(s):  
R. Estes ◽  
J. Theusch ◽  
A. Beck ◽  
D. Pitrak ◽  
Kathleen M. Mullane

ABSTRACTCentral venous catheters commonly develop central line-associated bloodstream infections.In vitroantibiotic lock therapy (ALT) was simulated on 10 methicillin-resistantStaphylococcus aureus(MRSA) clinical isolates imbedded in biofilm-coated silicon disks. Five days of 4-h daily exposures to daptomycin (2.5 mg/ml) in 25% ethanol or minocycline (3 mg/ml) plus 25% ethanol and 30 mg/ml EDTA resulted in significantly greater elimination of MRSA colonization than treatment with minocycline alone.

2015 ◽  
Vol 59 (8) ◽  
pp. 4497-4503 ◽  
Author(s):  
Katie E. Barber ◽  
Jordan R. Smith ◽  
Cortney E. Ireland ◽  
Blaise R. Boles ◽  
Warren E. Rose ◽  
...  

ABSTRACTAnnually, medical device infections are associated with >250,000 catheter-associated bloodstream infections (CLABSI), with up to 25% mortality.Staphylococcus aureus, a primary pathogen in these infections, is capable of biofilm production, allowing organism persistence in harsh environments, offering antimicrobial protection. With increases inS. aureusisolates with reduced susceptibility to current agents, ceftaroline (CPT) offers a therapeutic alternative. Therefore, we evaluated whether CPT would have a role against biofilm-producing methicillin-resistantS. aureus(MRSA), including those with decreased susceptibilities to alternative agents. In this study, we investigated CPT activity alone or combined with daptomycin (DAP) or rifampin (RIF) against 3 clinical biofilm-producing MRSA strains in anin vitrobiofilm pharmacokinetic/pharmacodynamic (PK/PD) model. Simulated antimicrobial regimens were as follows: 600 mg of CPT every 8 h (q8h) (free maximum concentration of drug [fCmax], 17.04 mg/liter; elimination half-life [t1/2], 2.66 h), 12 mg/kg of body weight/day of DAP (fCmax, 14.7 mg/liter;t1/2, 8 h), and 450 mg of RIF q12h (fCmax, 3.5 mg/liter;t1/2, 3.4 h), CPT plus DAP, and CPT plus RIF. Samples were obtained and plated to determine colony counts. Differences in log10CFU/cm2were evaluated by analysis of variance with Tukey'spost hoctest. The strains were CPT and vancomycin susceptible and DAP nonsusceptible (DNS). CPT displayed activity throughout the experiment. DAP demonstrated initial activity with regrowth at 24 h in all strains. RIF was comparable to the drug-free control, and little benefit was observed when combined with CPT. CPT plus DAP displayed potent activity, with an average log10CFU/cm2reduction of 3.33 ± 1.01 from baseline. CPT demonstrated activity against biofilm-producing DNS MRSA. CPT plus DAP displayed therapeutic enhancement over monotherapy, providing a potential option for difficult-to-treat medical device infections.


2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Sara Ceballos ◽  
Choon Kim ◽  
Yuanyuan Qian ◽  
Shahriar Mobashery ◽  
Mayland Chang ◽  
...  

ABSTRACT The in vitro activities of five quinazolinone antibacterials, compounds Q1 to Q5, were tested against 210 strains of methicillin-resistant Staphylococcus aureus (MRSA). The MIC50/MIC90 values (in μg/ml) were as follows: Q1, 0.5/2; Q2, 1/4; Q3, 2/4; Q4, 0.06/0.25; and Q5, 0.125/0.5. Several strains with high MIC values (from 8 to >32 μg/ml) for some of these compounds exhibited amino acid changes in the penicillin-binding proteins, which are targeted by these antibacterials.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S769-S769
Author(s):  
Sarah C J Jorgensen ◽  
Trang D Trinh ◽  
Evan J Zasowski ◽  
Sara Alosaimy ◽  
Sarah Melvin ◽  
...  

Abstract Background Combination β-lactam and vancomycin (VAN) prevent the emergence of resistance and result in synergistic antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. We sought to provide clinical translation to these data and determine if patients with MRSA bloodstream infection (BSI) treated with VAN + cefazolin (VAN/CFZ) via our MRSA BSI clinical pathway had improved clinical outcomes compared VAN alone. Methods Multicenter, retrospective, comparative cohort study from 2006 to 2019 in adults with MRSA BSI treated with VAN for ≥ 72 hours. VAN/CFZ was defined as VAN + CFZ within ≤ 72 hours of index culture for ≥ 24 hours. Other β-lactams were allowed for < 48 h in the VAN/CFZ group. The VAN alone group could not have other β-lactams within 7 days of treatment initiation. The primary outcome was clinical failure defined as a composite of 30-d all-cause mortality, 60-day recurrence, and persistent BSI (≥ 7 days). The independent effect of VAN/CFZ on clinical failure was evaluated with multivariable logistic regression. The primary safety endpoint was nephrotoxicity within 7 days of treatment initiation. Results A total of 237 patients were included (104 VAN/CFZ, 133 VAN). The most common BSI sources were skin/soft tissue (29.1%), IV catheter (21.9%), osteoarticular (20.3%) and infective endocarditis (16.0%). Demographic and clinical characteristics were similar between groups except VAN/CFZ had a higher median APACHE II score (18 vs. 13, P = 0.011). VAN/CFZ patients were also more likely to have received an infectious disease consult (100% vs. 81.2%, P < 0.001). Median (IQR) duration of CFZ was 115 (87–164) hours. After controlling for age, APACHE II score, ID consult and infection source, VAN/CFZ was associated with reduced odds of clinical failure (aOR 0.425, 95% CI 0.228, 0.792). Bivariate outcomes are shown in the table: Conclusion Patients with MRSA BSI treated with VAN/CFZ vs. VAN experienced fewer clinical failures, supporting additional studies evaluating the role of adjuvant CFZ for MRSA BSI. Disclosures All authors: No reported disclosures.


2016 ◽  
Vol 60 (7) ◽  
pp. 4342-4345 ◽  
Author(s):  
Adam Belley ◽  
David Lalonde Seguin ◽  
Francis Arhin ◽  
Greg Moeck

ABSTRACTAntibacterial agents that kill nondividing bacteria may be of utility in treating persistent infections. Oritavancin and dalbavancin are bactericidal lipoglycopeptides that are approved for acute bacterial skin and skin structure infections in adults caused by susceptible Gram-positive pathogens. Using time-kill methodology, we demonstrate that oritavancin exerts bactericidal activity against methicillin-resistantStaphylococcus aureus(MRSA) isolates that are maintained in a nondividing statein vitro, whereas dalbavancin and the glycopeptide vancomycin do not.


2012 ◽  
Vol 78 (11) ◽  
pp. 4046-4047 ◽  
Author(s):  
Robin Köck ◽  
Bea Loth ◽  
Mahir Köksal ◽  
Josef Schulte-Wülwer ◽  
Jürgen Harlizius ◽  
...  

ABSTRACTLivestock-associated methicillin-resistantStaphylococcus aureus(LA-MRSA) is frequently transmitted from pigs to farmers. This study analyzed whether an absence from direct contact with pigs during holidays had an impact on nasal MRSA colonization rates of pig farmers. Overall, 59% of the farmers did not clear MRSA colonization during their leave.


Author(s):  
Sara Alosaimy ◽  
Abdalhamid M Lagnf ◽  
Taylor Morrisette ◽  
Sarah C J Jorgensen ◽  
Trang D Trinh ◽  
...  

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) management remains challenging for clinicians. Numerous in vitro studies report synergy when vancomycin (VAN)/daptomycin (DAP) were combined with beta-lactams (BL), which has led to clinical implementation of these combinations. While shorter durations of bacteremia have often been reported, there has been no significant impact on mortality. Methods The Detroit Medical Center (DMC) developed and implemented a clinical pathway algorithm for MRSA BSI treatment in 2016 that included the early use of BL combination therapy with standard-of-care (VAN or DAP) and a mandatory infectious diseases consultation. This was a retrospective, quasi-experimental study at the DMC between 2013-2020. Multivariable logistic regression was used to assess the independent association between pathway implementation and 30-day mortality while adjusting for confounding variables. Results Overall, 813 adult patients treated for MRSA BSI were evaluated. Compared to pre-pathway (PRE) patients (n=379), those treated post-pathway (POST) (n=434) had a significant reduction in 30-day and 90-day mortality; 9.7% in POST vs. 15.6% in PRE (p=0.011) and 12.2% in POST vs. 19.0% in PRE (p=0.007), respectively. The incidence of acute kidney injury (AKI) was higher in the PRE compared to POST; 9.6% vs. 7.2% (p=0.282), respectively. After adjusting for confounding variables including infectious diseases consult, POST was independently associated with a reduction in 30-day mortality (adjusted odds ratio [aOR], 0.608; 95% confidence interval [CI], 0.375-0.986). Conclusions Implementation of a MRSA BSI treatment pathway with early use of BL reduced mortality with no increased in AKI. Further prospective evaluation of this pathway approach is warranted.


2016 ◽  
Vol 61 (2) ◽  
Author(s):  
George Sakoulas ◽  
Warren Rose ◽  
Andrew Berti ◽  
Joshua Olson ◽  
Jason Munguia ◽  
...  

ABSTRACT We asked whether beta-lactamase inhibitors (BLIs) increased the activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA), the peptide antibiotic colistin (COL) against the emerging Gram-negative nosocomial pathogen Acinetobacter baumannii, and the human host defense peptide cathelicidin LL37 against either pathogen. DAP and LL37 kill curves were performed with or without BLIs against MRSA, vancomycin-intermediate S. aureus (VISA), and heterogeneous VISA (hVISA). COL and LL37 kill curves were performed against A. baumannii. Boron-dipyrromethene (BODIPY)-labeled DAP binding to MRSA grown with the BLI tazobactam (TAZ) was assessed microscopically. The combination of COL plus TAZ was studied in a murine model of A. baumannii pneumonia. TAZ alone lacked in vitro activity against MRSA or A. baumannii. The addition of TAZ to DAP resulted in a 2- to 5-log10 reduction in recoverable MRSA CFU at 24 h compared to the recoverable CFU with DAP alone. TAZ plus COL showed synergy by kill curves for 4 of 5 strains of A. baumannii tested. Growth with 20 mg/liter TAZ resulted in 2- to 2.5-fold increases in the intensity of BODIPY-DAP binding to MRSA and hVISA strains. TAZ significantly increased the killing of MRSA and A. baumannii by LL37 in vitro. TAZ increased the activity of COL in a murine model of A. baumannii pneumonia. Classical BLIs demonstrate synergy with peptide antibiotics. Since BLIs have scant antimicrobial activity on their own and are thus not expected to increase selective pressure toward antibiotic resistance, their use in combination with peptide antibiotics warrants further study.


Author(s):  
Gaby Scheunemann ◽  
Bruna N. Fortes ◽  
Nilton Lincopan ◽  
Kelly Ishida

Infections by microorganisms resistant to antimicrobials is a major challenge that leads to high morbidity and mortality rates and increased time and cost with hospitalization. It was estimated that 27 to 56% of bloodstream infections by C. albicans are polymicrobial, with S. aureus being one of the microorganisms commonly coisolated worldwide.


Author(s):  
Rahmathulla Safiyul Rahman ◽  
Badr Mohammed Beyari ◽  
Kawlah Essam Samarin ◽  
Khalid Mohammed Alamri ◽  
Marwan Abdulaziz Bader ◽  
...  

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen of clinical significance within the community and healthcare settings. It has been reported with a variety of infections, including endocarditis, bloodstream infections, pneumonia, joint and bone infections, and soft tissue and skin infections. Although many efforts have been exerted to eradicate the rates of infections and studies have reported a decreasing pattern in the prevalence rates over the years, it has been demonstrated that MRSA represents a significant challenge to the healthcare systems and the affected patients. In this literature review, we have provided a discussion regarding the risk factors, screening, and treatment of MRSA among healthcare workers (HCWs) based on the evidence obtained from the current relevant studies in the literature. HCWs are at increased risk of MRSA colonization, and many risk factors have been identified. These mainly include poor hygiene practices, chronic skin diseases, and having a history of working in an MRSA-endemic country. Decolonization practices are the main line of treatment of MRSA colonization among HCWs because antibiotic therapy is usually of limited use because of the increasing resistance to a wide range of antibiotics. Applying adequate interventions as taking care of hand hygiene and using alcohol-based disinfectants is recommended to achieve better outcomes. Increasing awareness among HCWs is also a potential approach to achieve better management.


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