Treatment Of Methicillin-resistant Staphylococcus Aureus Bacteremia Research Articles

Combination of Antistaphylococcal β-Lactam With Standard Therapy Compared to Standard Therapy Alone for the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia: A Post Hoc Analysis of the CAMERA2 Trial Using a Desirability of Outcome Ranking Approach.

Desirability of outcome ranking (DOOR) is an emerging approach to clinical trial outcome measurement using an ordinal scale to incorporate efficacy and safety endpoints. We applied a previously validated DOOR endpoint to a cohort of CAMERA2 trial participants with methicillin-resistant Staphylococcus aureus bacteremia (MRSAB). Participants were randomly assigned to standard therapy, or to standard therapy plus an antistaphylococcal β-lactam (combination therapy). Each participant was assigned a DOOR category, within which they were further ranked according to their hospital length of stay (LOS) and duration of intravenous antibiotic treatment. We calculated the probability and the generalized odds ratio of participants receiving combination therapy having worse outcomes than those receiving standard therapy. Participants assigned combination therapy had a 54.5% (95% confidence interval [CI], 48.9%-60.1%; P = .11) probability and a 1.2-fold odds (95% CI, .95-1.50; P = .12) of having a worse outcome than participants on standard therapy. When further ranked according to LOS and duration of antibiotic treatment, participants in the combination group had a 55.6% (95% CI, 49.5%-61.7%) and 55.3% (95% CI, 49.2%-61.4%) probability of having a worse outcome than participants in the standard treatment group, respectively. When considering both efficacy and safety, treatment of MRSAB with a combination of standard therapy and a β-lactam likely results in a worse clinical outcome than standard therapy. However, a small benefit of combination therapy cannot be excluded. Most likely the toxicity of combination therapy outweighed any benefit from faster clearance of bacteremia.

310. The Impact of Microscan versus Vitek-2 for Automated Susceptibility Testing on the Utilization of Vancomycin Alternatives for the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

BackgroundAutomated susceptibility testing (AST) provides minimum inhibitory concentrations (MIC) to guide effective antibiotic therapy. AST is critical for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, as susceptible MIC values ≥ 1.5 µg/mL are associated with vancomycin (VAN) failure. The Microscan (MS) instrument may report elevated MIC values compared to Vitek-2 (VTK), thus impacting treatment. This study aimed to evaluate the impact of MS versus VTK on VAN alternative use in the treatment of MRSA bacteremia in a Texas health system.MethodsThis was a retrospective cohort study of patients admitted to the Ascension Seton health system in Austin, TX. Patient eligibility included: age ≥18 years, ≥1 positive MRSA blood culture, ≥72 hours of MRSA therapy, and VAN use within 48 hours of positive culture. Patients were stratified into the MS group (May 2013-Dec 2016) and VTK group (Jun 2017-Mar 2020). The primary outcome was therapy switch from VAN to VAN alternatives. Secondary endpoints include S. aureus MIC, 30-day all-cause mortality, 30 and 90-day readmission, and length of hospital stay (LOS). Outcomes were compared between groups using appropriate bivariable comparisons, as well as multivariable logistic regression and propensity score-adjusted logistic regression.ResultsA total of 199 patients were included: 91 in the MS group and 108 in the VTK group. Switch to VAN alternative was 56% vs. 19% (p< 0.0001) for MS and VTK, respectively. The median (interquartile range) MIC value reported was 2 μg/mL (2 – 2) and 1 μg/mL (0.5 – 1) for MS and VTK, respectively (p< 0.0001). Thirty-day readmission (19% vs. 20%, p=0.7647) and 30-day mortality (10% vs. 9%, p=0.5262) were comparable between MS and VTK groups, respectively. Hospital LOS significantly decreased in the VTK period (16 days vs. 12 days, p=0.0153). The MS group was the only independent positive predictor of VAN alternative therapy: logistic regression, OR 5.64 (95% CI 1.67–18.99) and propensity score adjusted, OR 4.21 (95% CI 1.32–13.48).ConclusionSince implementation of VTK from MS, Ascension Seton hospitals experienced a decreased median VAN MIC for MRSA bacteremia as well as therapy switches from VAN to VAN alternatives without affecting other patient health outcomes.Disclosures All Authors: No reported disclosures

Durable Control of Mycosis Fungoides after Sepsis: “Coley’s Toxin?” Case Report and Review of the Literature

Mycosis fungoides, along with Sezary syndrome, is the most common subtype of cutaneous T-cell lymphoma. In this report, we present a patient with advanced-stage mycosis fungoides, who after successful treatment of methicillin-resistant Staphylococcus aureus bacteremia had prolonged disease control off systemic therapy. While this may have been due to single-agent gemcitabine, which can result in long remission, we hypothesize that our patient's durable response was in part due to the immune response elicited after treatment of her severe infection.

Daptomycin versus teicoplanin for bloodstream infection due to methicillin-resistant Staphylococcus aureus with a high teicoplanin minimal inhibitory concentration ≥1.5 mg/L: a propensity score-based analysis.

BackgroundRecent reports have described decreased effectiveness of teicoplanin in the treatment of bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) with teicoplanin minimal inhibitory concentration (MIC) ≥1.5 mg/L. Consensus guidelines recommend considering use of alternative agents for MRSA infections involving a higher teicoplanin MIC, despite of limited data to support this recommendation.Patients and methodsTo compare the clinical outcome among patients with bacteremia due to MRSA with teicoplanin MIC ≥1.5 mg/L, we included patients who received high-dose daptomycin (≥8 mg/kg/day) and those who received standard-dose (6 mg/kg/day) or high-dose (6 mg/kg/12 hours) maintenance teicoplanin. The primary endpoint was a favorable outcome, defined as the resolution of clinical signs and symptoms and a negative culture report at the end of therapy. Adjusted analyses were performed by multivariate analysis and propensity score-based matching.ResultsOf 142 patients eligible for inclusion, 28 (19.7%) were treated with high-dose daptomycin, 27 (19.0%) with high-dose teicoplanin, and 87 (61.3%) with standard-dose teicoplanin. In multivariate regression analysis, Pittsburgh bacteremia score ≥4 (OR, 5.3; 95%CI, 1.9–14.5) was independently associated with an unfavorable outcome. After propensity-score matching with age and Pittsburgh bacteremia score ≥4, patients on high-dose daptomycin were more likely to have favorable outcomes than those on standard-dose teicoplanin (74.1% vs 42.6%; P=0.02). However, there was no significant difference in terms of favorable outcomes (P=0.12) between patients receiving high-dose daptomycin and those receiving high-dose teicoplanin after the same propensity-score matching.ConclusionTreatment with high-dose daptomycin resulted in significantly better outcomes than with standard-dose teicoplanin in the treatment of MRSA bacteremia with teicoplanin MIC ≥1.5 mg/L. However, the clinical outcome of the patients receiving high-dose teicoplanin was similar to that of the patients receiving high-dose daptomycin.

Methicillin-resistant Staphylococcus aureus infections: A review of the currently available treatment options.

This review is the result of discussions that took place at the 5th MRSA Working Group Consensus Meeting and explores the possible treatment options available for different types of infections due to methicillin-resistant Staphylococcus aureus (MRSA), focusing on those antibiotics that could represent a valid alternative to vancomycin. In fact, whilst vancomycin remains a viable option, its therapy is moving towards individualised dosing. Other drugs, such as the new lipoglycopeptides (oritavancin, dalbavancin and telavancin) and fifth-generation cephalosporins (ceftaroline and ceftobiprole), are showing good in vitro potency and in vivo efficacy, especially for patients infected with micro-organisms with higher vancomycin minimum inhibitory concentrations (MICs). Tedizolid is an attractive agent for use both in hospital and community settings, but the post-marketing data will better clarify its potential. Daptomycin and linezolid have shown non-inferiority to vancomycin in the treatment of MRSA bacteraemia and non-inferiority/superiority to vancomycin in the treatment of hospital-acquired pneumonia. Thus, several options are available, but more data from clinical practice, especially for invasive infections, are needed to assign specific roles to each antibiotic and to definitely include them in the new antibacterial armamentarium.

Telavancin for refractory methicillin-resistant Staphylococcus aureus bacteremia and infective endocarditis

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and infective endocarditis (IE) have become increasingly difficult to treat over the past decade, with suboptimal response rates of less than 50%. Although vancomycin and daptomycin are standard therapeutic options, treatment failures with either or both agents are common. Telavancin is a lipoglycopeptide antibiotic with activity against MRSA. In vitro, telavancin displays bactericidal activity and has lower minimum inhibitory concentrations to MRSA than vancomycin. Methods: We present a retrospective, case-series report of 14 patients treated with telavancin for refractory MRSA bacteremia with and without IE at our institution from 9 September 2010 to 2 April 2012. Results: Of the 14 patients who received telavancin for refractory MRSA bacteremia and IE, eight survived their inpatient admission and were able to be followed for 30 days. The overall survival rate was 57% (n = 8). Of the eight surviving patients, five were diagnosed with MRSA IE and the remaining three were diagnosed with complicated MRSA bacteremia. All six patients who did not survive the inpatient admission were diagnosed with left-sided IE involving the mitral valves. Conclusions: This retrospective case series provides clinical evidence for the use of telavancin as a treatment option for refractory MRSA bacteremia and IE. With limited effective agents in the treatment of MRSA-complicated bacteremia and IE, telavancin represents a potential treatment option. Further randomized, controlled trials are necessary to define the optimal role of telavancin in the treatment of MRSA bacteremia and IE.

Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial

IntroductionDespite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an...

Treatment of methicillin-resistant Staphylococcus aureus: vancomycin and beyond.

There has been a welcome increase in the number of agents available for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin remains an acceptable treatment option, with moves toward individualized dosing to a pharmacokinetic/pharmacodynamic (PK/PD) target. Numerous practicalities, however, would need to be resolved before implementation. Lipoglycopeptides as a class show excellent in vitro potency. Their long half-lives and complex PKs may preclude these agents being used in critically ill patients. Anti-MRSA cephalosporins provide great promise in the treatment of MRSA. These agents, despite broad-spectrum activity, should be reserved for patients with MRSA infections as it is likely that usage will be associated with increased rates of resistance. Daptomycin is currently the only antibiotic to have shown noninferiority to vancomycin in the treatment of MRSA bacteremia. The results of an open-labeled trial to address the superiority of daptomycin compared with vancomycin in reduced vancomycin susceptibility infections are eagerly anticipated. No drug to date has shown superiority to vancomycin in the treatment of MRSA infections with the possible exception of linezolid in hospital-acquired pneumonia (HAP), making linezolid an important option in the treatment of MRSA-proven HAP. Whether these strengths and features are agent or class specific are unclear but will likely be answered with the marketing of tedizolid. There are insufficient data to recommend either quinupristin/dalfopristin or tigecycline, as first line in the treatment of severe MRSA infections. These agents however remain options in patients with no other alternatives.

Ceftaroline—An Anti-MRSA Cephalosporin and Its Implications for Singapore

Ceftaroline is a fifth-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) that was recently launched in Singapore. It received approval from the United States (US) Food Drug Administration (FDA) and European Commission for the treatment of adult patients with community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (cSSTI). This study aimed to review current published data and determine its clinical role, particularly in the local setting. A literature review on published articles in English on ceftaroline, focusing in particular on clinical trials and other clinical reports. Susceptibility testing was also performed on a limited sample of local MRSA and Streptococcus pneumoniae isolates. Ceftaroline has an extensive spectrum of activity, including coverage of MRSA and multidrug-resistant S. pneumoniae. However, it has limited activity against non-fermenting Gram-negative bacteria and is susceptible to hydrolysis by extended spectrum beta-lactamases. It is only available for intravenous delivery, with a reconstituted stability of just 6 hours, rendering it unavailable for use for outpatient antibiotic therapy. Clinical trials demonstrate non-inferiority compared to first-line comparators in the treatment of CAP and cSSTI. Published case reports/series suggest a potential greater role in the treatment of MRSA bacteremia and endocarditis. No resistance was found among local archived MRSA and S. pneumoniae isolates. We believe ceftaroline will occupy primarily niche roles for culture-directed treatment of various infections--in particular those caused by MRSA--until further clinical trial data become available. A variety of factors render it less useful or appealing for empirical treatment of CAP or healthcare-associated infections.

Successful treatment of right-sided native valve methicillin-resistant Staphylococcus aureus endocarditis and septicaemia with teicoplanin and rifampicin: A case report

Vancomycin is the drug of choice in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. However, the presence of certain clinical complications like renal failure alters vancomycin pharmacokinetics, leading to drug accumulation and toxicity. This highlights the need to identify an effective substitute for treating MRSA infections when vancomycin cannot be used. We report the case of a 57-y-old Indian male diagnosed with tricuspid valve endocarditis with septicaemia and a right upper lobe cavity caused by MRSA. The patient also presented with renal failure, which precluded the use of vancomycin for treatment. A 6-week regimen of teicoplanin and rifampicin was used instead, and the infection was successfully treated. This case report provides evidence of the effectiveness of teicoplanin and rifampicin in the treatment of MRSA bacteraemia in situations where the use of vancomycin is contraindicated.

Methicillin-resistant Staphylococcus aureus bacteremia in children.

We reviewed the records of 20 patients with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) and 49 patients with methicillin-susceptible S. aureus (MSSA) bacteremia occurring during a 39-month period. Sixteen of the MRSA bacteremias were clinically significant, as were 42 of the MSSA bacteremias. MRSA bacteremia was almost always nosocomial and occurred mainly in very young patients who were often prematurely born and severely compromised by underlying diseases. In contrast patients with MSSA bacteremia were frequently older children who had no underlying disease and acquired their bacteremic illness in the community. The seven patients with nosocomial MSSA bacteremia had characteristics similar to those of the patients with MRSA bacteremia. Fatality rates for patients with clinically significant bacteremia were 50% for MRSA and 2% for MSSA. Treatment of MRSA bacteremia with vancomycin was effective, provided it was begun early. At hospitals with endemic MRSA it may be necessary to use vacomycin in the initial treatment of nosocomial bacteremia in high risk patients until the identity and antimicrobial susceptibility of the bloodstream pathogen can be determined.