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In Vitro Activities of Mupirocin, Tigecycline, Ceftaroline, Vancomycin, Linezolid and Daptomycin in Clinical Isolates of Methicillin-Resistant Staphylococcus aureus by E-Test Methodology  [PDF]
Priyal Chadha, Noriel Mariano, Vincent LaBombardi, Sorana Segal-Maurer, Carl Urban
Open Journal of Medical Microbiology (OJMM) , 2015, DOI: 10.4236/ojmm.2015.51002
Abstract: Introduction: In 2013, the Center for Disease Control (CDC) designated methicillin-resistant Staphylococcus aureus (MRSA) as a serious threat. In addition to its intrinsic virulence, MRSA has become resistant to numerous antibacterial agents. In many instances, mupirocin is used empirically to decolonize patients harboring MRSA to decrease the possibility of progression to disease. In vitro susceptibility information is critical to identify patients who would benefit from use of mupirocin for decolonization and treatment of infections caused by MRSA. Methods: One-hundred and sixty-three recent MRSA single patient clinical isolates were collected from the Clinical Microbiology Laboratory. In-vitro susceptibility testing was performed using E-test methodology for tigecycline, ceftaroline, daptomycin, vancomycin, linezolid, and mupirocin. Results: Of the 163 MRSA isolates tested, >99% demonstrated susceptibility to tigecycline, ceftaroline, daptomycin, vancomycin, and linezolid. Seventy (43%) had vancomycin MICs ≥ 1.5 μg/ml, twenty-four isolates (15%) were resistant to mupirocin, and three appeared to express mupirocin hetero-resistance. Conclusion: While antibiotic susceptibility to mupirocin is not routinely performed in clinical microbiology laboratories, the level of resistance to mupirocin identified in this surveillance study suggests that susceptibility testing should be added to routine MRSA panels.
Economic burden of inpatient and outpatient antibiotic treatment for methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections: a comparison of linezolid, vancomycin, and daptomycin  [cached]
Stephens JM,Gao X,Patel DA,Verheggen BG
ClinicoEconomics and Outcomes Research , 2013,
Abstract: Jennifer M Stephens,1 Xin Gao,1 Dipen A Patel,1 Bram G Verheggen,2 Ahmed Shelbaya,3,5 Seema Haider4 1Pharmerit North America, Bethesda, MD, USA; 2Pharmerit Europe, Rotterdam, The Netherlands; 3Pfizer Inc, New York, NY, USA; 4Pfizer Inc, Groton, CT, USA; 5Mailman School of Public Health, Columbia University, NY, USA Background: Previous economic analyses evaluating treatment of methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections (cSSTI) failed to include all direct treatment costs such as outpatient parenteral antibiotic therapy (OPAT). Our objective was to develop an economic model from a US payer perspective that includes all direct inpatient and outpatient costs incurred by patients with MRSA cSSTI receiving linezolid, vancomycin, or daptomycin. Methods: A 4-week decision model was developed for this economic analysis. Published literature and database analyses with validation by experts provided clinical, resource use, and cost inputs on data such as efficacy rate, length of stay, adverse events, and OPAT services. Base-case analysis assumed equal efficacy and equal length of stay for treatments. We conducted several sensitivity analyses where assumptions on resource use or efficacy were varied. Costs were reported in year-end 2011 US dollars. Results: Total treatment costs in the base-case were lower for linezolid ($10,571) than vancomycin ($11,096), and daptomycin ($13,612). Inpatient treatment costs were $740 more, but outpatient costs, $1,266 less with linezolid than vancomycin therapy due to a switch to oral linezolid when the patient was discharged. Compared with daptomycin, both inpatient and outpatient treatment costs were lower with linezolid by $87 and $2,954 respectively. In sensitivity analyses, linezolid had lower costs compared with vancomycin and daptomycin when using differential length of stay data from a clinical trial, and using success rates from a meta-analysis. In a scenario without peripherally inserted central catheter line costs, linezolid became slightly more expensive than vancomycin (by $285), but remained less costly than daptomycin (by $2,316). Conclusion: Outpatient costs of managing MRSA cSSTI may be reduced by 30%–50% with oral linezolid compared with vancomycin or daptomycin. Results from this analysis support potential economic benefit and cost savings of using linezolid versus traditional OPAT when total inpatient and outpatient medical costs are evaluated. Keywords: economic model, OPAT, cost
Retrospective Analysis of Clinical and Cost Outcomes Associated with Methicillin-Resistant Staphylococcus aureus Complicated Skin and Skin Structure Infections Treated with Daptomycin, Vancomycin, or Linezolid  [PDF]
Bradley M. Wright,Edward H. Eiland III
Journal of Pathogens , 2011, DOI: 10.4061/2011/347969
Abstract: Objective. The objective of this analysis was to compare clinical and cost outcomes associated with patients who had suspected or documented methicillin-resistant Staphylococcus aureus (MRSA) infections treated with daptomycin, vancomycin, or linezolid in complicated skin and skin structure infections (cSSSIs). Design. This was a retrospective analysis conducted from February to June of 2007. Appropriate data was collected, collated, and subsequently evaluated with the purpose of quantifying length of stay, antibiotic therapy duration, clinical cure rates, adverse drug events, and cost of hospitalization. Results. All 82 patients included in the analysis experienced clinical cure. The duration of antibiotic therapy was similar among the three groups yet the length of hospitalization was slightly shorter in the daptomycin group. Conclusions. The incidence of resistant staphylococcal infections is increasing; therefore, judicious use of MRSA active agents is paramount. Future studies are necessary to determine if MRSA treatment options can be stratified based on the severity of the infectious process. 1. Introduction Skin and skin structure infections (SSSIs) are common within the hospital setting as well as in the community. Some common examples of SSSIs include abscesses, cellulitis, diabetic foot infections, and surgical site infections. Oral antibiotics can often be used to safely manage many SSSIs; however, complicated SSSIs (cSSSIs) may be life threatening and often involve deeper layers of skin and more severe symptoms which will often necessitate hospitalization, intravenous antibiotics, and may also require surgical intervention. Although a variety of gram-positive and gram-negative pathogens may cause SSSIs, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as the most common pathogen [1, 2] A study of 265 community hospitals in the Southeastern United States found the prevalence of MRSA as the causative pathogen for surgical site infections increased from 0.12 infections per 100 procedures to 0.23 infections per 100 procedures from 2000 to 2005 [3] In addition, a retrospective analysis of 288 patients managed with operative debridement for SSSIs found that the incidence of MRSA increased from 34 percent to 77 percent from 2000 to 2006. The percentage of MRSA isolates with an MIC ≤ 0.5?mcg/mL to vancomycin decreased from 100 percent in 2000 to 62 percent in 2006 [4]. This increasing prevalence of MRSA infection within the hospital and the community further complicates the treatment of SSSIs as MRSA infections are also known to be
Comparison of the pharmacokinetic properties of vancomycin, linezolid, tigecyclin, and daptomycin
Kerry S Estes, Hartmut Derendorf
European Journal of Medical Research , 2010, DOI: 10.1186/2047-783x-15-12-533
Abstract: Appropriate treatment for serious infections caused by drug resistant Staphylococcus aureus represents a major challenge for clinicians where failure can result in patient mortality. Although newer antibiotic agents have been developed, vancomycin continues to be the most commonly preferred drug for treating serious gram-positive infections involving methicillin-resistant S. aureus (MRSA) and is often administered empirically to patients with serious infections due to methicillin sensitive S. aureus (MSSA) prior to microbiological characterization. While numerous reports are available that address vancomycin treatment outcomes in various populations of hospitalized patients, optimized dosing strategies elude consensus at the same time that treatment failure rates are high [1-3]. This report compares pharmacokinetic properties of vancomycin and selected newer agents available for treating patients with serious MRSA infections. The respective pharmacokinetic properties are first presented for each compound and then compared.Vancomycin is indicated for susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci [4]. It is indicated for penicillin-allergic patients, for patients who cannot receive or who have failed to respond to other drugs, including the penicillins or cephalosporins, and for infections caused by vancomycin-susceptible organisms that are resistant to other antimicrobial drugs. Vancomycin is indicated for initial therapy when MRSA are suspected, but after susceptibility data are available, therapy should be adjusted accordingly.Vancomycin is effective in the treatment of staphylococcal endocarditis. Its effectiveness has been documented in other infections due to staphylococci, including septicemia, bone infections, lower respiratory tract infections, skin and skin structure infections. When staphylococcal infections are localized and purulent, antibiotics are used as adjuncts to appropriate surgical measures.Vancomycin has been
The Prevalence of Methicillin-Resistant Staphylococcus aureus Colonization in Patients with Complicated Skin and Skin Structure Infections after Treatment with Linezolid or Vancomycin  [PDF]
Laura A. Puzniak, Kimbal D. Ford, David B. Huang
Advances in Infectious Diseases (AID) , 2014, DOI: 10.4236/aid.2014.44026
Abstract: Background: Complicated skin and skin structure infections (cSSSIs) due to Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), are associated with significant morbidity. Re-ducing MRSA carriage has been a focus of infection control interventions. The prevalence of MRSA colonization after successful treatment of a MRSA cSSSI is unknown. Methods: Secondary analysis of a randomized controlled trial comparing linezolid and vancomycin for the treatment of MRSA cSSSI. Adult patients that had a colonization culture, confirmed MRSA cSSSI, received at least one dose of study treatment, and had an outcome recorded at end of study. Patient, clinical characteristics and prevalence of colonization were compared by treatment regimens. A multivariate regression model identified predictors of MRSA colonization at EOS. Results: There were 456 patients evaluated. The prevalence of MRSA colonization was higher for vancomycin treated patients compared to linezolid treated patients at end of treatment (EOT) (28% vs. 5%, p < 0.001) and EOS (34% vs. 22%, p < 0.01). Independent predictors of colonization at EOS after treatment for a MRSA cSSSI included diagnosis, primarily driven by abscess, black race, treatment with vancomycin, MRSA mixed infection and male gender. Conclusion: Patients treated with linezolid for a cSSSI had less MRSA colonization at EOT and EOS compared to those treated with vancomycin. Multiple independent predictors of MRSA colonization were identified. Additional studies evaluating the relationship of MRSA colonization after treatment of cSSSI are needed.
Evaluation of tigecycline activity in clinical isolates among Indian medical centers  [cached]
Manoharan Anand,Chatterjee Saradiya,Madhan S,Mathai Dilip
Indian Journal of Pathology and Microbiology , 2010,
Abstract: Background: Resistance to multiple antibiotics among Gram-positive cocci (GPC) and Gram negative bacilli (GNB) is high in India. Tigecycline, a glycylcycline antibiotic is a newer treatment option for emerging single or multidrug-resistant (MDR) GPC and GNB. Material and Method: We evaluated the in vitro activity of tigecycline and compared it against other antimicrobials. Between 2005-2007, seven Indian medical centers from diverse geographic regions forwarded 727 isolates [Escherichia coli (166), Staphylococcus aureus (125), Klebsiella spp (120), Streptococcus pneumoniae (102), Enterococcus spp. (100), Pseudomonas aeruginosa (50), Acinetobacter spp. (50) and Enterobacter spp. (14)] from patients with blood stream (BSI), skin and soft tissue (SSTI) including surgical site, urinary tract and respiratory infections to our reference laboratory. Susceptibility to 11 antimicrobials besides tigecycline included: vancomycin, linezolid, teicoplanin, quinopristin-dalfopristin, daptomycin, amikacin, imipenem, levofloxacin, meropenem, and piperacillin/tazobactam was determined by agar dilution and Etest method. Result: Tigecycline was active against all GPC (MIC 90 < 0.25 μg/ml), E. coli and Klebsiella spp. (MIC 90 ≤1 μg/ml). MDR Acinetobacter spp. showed lower susceptibility (70.6%) to tigecycline. Tigecycline MIC 90 values were not influenced by oxacillin resistance among S. aureus, S. pneumoniae, vancomycin resistance in Enterococci (VRE) and ESBL producing E. coli, Klebsiella spp. and Enterobacter spp. Increased resistance was seen to other antimicrobials among ESBL producing E. coli, Klebsiella spp., Metallo Beta Lactamase (MBL) producing P. aeruginosa and VRE. Conclusion: Tigecycline is an alternative option for emerging multidrug-resistant (MDR) pathogens exhibiting promising spectrum/potency exceeding currently available agents seen in India.
Successful treatment of a neonate with persistent vancomycin-resistant enterococcal bacteremia with a daptomycin-containing regimen
Christy A Beneri, David P Nicolau, Howard S Seiden, Lorry G Rubin
Infection and Drug Resistance , 2008, DOI: http://dx.doi.org/10.2147/IDR.S3649
Abstract: ccessful treatment of a neonate with persistent vancomycin-resistant enterococcal bacteremia with a daptomycin-containing regimen Case report (5192) Total Article Views Authors: Christy A Beneri, David P Nicolau, Howard S Seiden, Lorry G Rubin Published Date August 2008 Volume 2008:1 Pages 9 - 11 DOI: http://dx.doi.org/10.2147/IDR.S3649 Christy A Beneri1, David P Nicolau2, Howard S Seiden3, Lorry G Rubin1 1Pediatric Infectious Diseases, Schneider Children’s Hospital - North Shore-LIJ Health System, New Hyde Park, New York, USA; 2Center for Anti-Infective Research and Development - Hartford Hospital, Hartford, Connecticut, USA; 3Pediatric Cardiology, Schneider Children’s Hospital - North Shore-LIJ Health System, New Hyde Park, New York, USA Abstract: Infections caused by vancomycin-resistant enterococci (VRE) may be difficult to treat because of the limited armamentarium of antimicrobial agents. The difficulty is compounded in pediatric patients in general and neonates in particular because many of the newer antimicrobials have not been studied or approved for children. We report a 3-week-old infant who developed enterococcal bacteremia on post-operative day 10 after a surgical palliation for complex congenital heart disease that was complicated by acute renal failure. Despite removal of vascular catheters and antimicrobial regimens that included linezolid, quinupristin/dalfopristin, ampicillin/sulbactam, rifampin, and gentamicin, bacteremia persisted. It was not cleared until daptomycin (in combination with doxycycline) was started. This is the first case of successful treatment of probable endocarditis due to VRE in a neonate using a daptomycin-containing regimen.
Tigeciclina versus vancomycin más aztreonam en el tratamiento de infecciones complicadas de piel y tejidos blandos: Experiencia en Latinoamérica Tigecycline as effective as vancomycin plus aztreonam in the treatment of complicated skin and skin structure infections: Experience in Latin America
M. Isabel Campos B,Daniel Curcio J,Carlos Seas R,Abel Jasovich
Revista chilena de infectología , 2009,
Abstract: Introducción: El tratamiento de infecciones complicadas de piel y tejidos blandos (ICPTB) puede representar un desafío. Se comparó la eficacia de tigeciclina versus vancomicina/aztreonam en pacientes con ICPTB en un estudio multicéntrico; este artículo se refiere a la experiencia en Latinoamérica (LA). Método: Se asignaron, en forma randomizada, los pacientes a dos grupos de tratamiento: tigeciclina o vancomicina/aztreonam. La meta a evaluar (outcome) primaria fue la curación clínica, denominada test de curación (TC). Se establecieron, además, metas secundarias y la evaluación de seguridad del fármaco. Resultados: Un subtotal de 167 pacientes procedentes de LA, de un estudio multinacional que incluyó 573 pacientes, recibieron ≥ 1 dosis del fármaco en estudio. Al TC, los porcentajes de curación fueron similares entre tigeciclina y vanco-micina/aztreonam en los pacientes clínicamente evaluables). La no inferioridad de tigeciclina no pudo ser demostrada (tama o de muestra insuficiente). Los pacientes tratados con tigeciclina tuvieron mayor incidencia de náuseas, vómitos y anorexia; los pacientes que recibieron vancomicina/aztreonam tuvieron mayor incidencia de prurito y rash. Conclusiones: Los resultados de eficacia en LA fueron consistentes con el estudio multinacional sugiriendo que tigeciclina no es inferior a vancomicina/aztreonam en el tratamiento de pacientes con ICPTB. Background: Treating complicated skin and skin structure infections (cSSSIs) can be challenging. Tigecycline was compared to vancomycin/aztreonam in patients with cSSSIs in a multinational trial; this article reports on the Latin American (LA) population. Methods: Patients were randomly assigned to receive tigecycline or vancomycin/ aztreonam. Primary endpoint was clinical cure rate at test-of-cure (TOC). Several secondary endpoints and safety were also assessed. Results: A subtotal of 167 LA patients from the multinational trial (N = 573) received ≥ 1 dose of study drug. At TOC, cure rates were similar between tigecycline and vancomycin/aztreonam in the clinically evaluable population.) Noninferiority of tigecycline could not be demonstrated (insufficient sample sizes). Tigecycline-treated patients had higher incidences of nausea, vomiting, anorexia; vancomycin/aztreonam-treated patients had higher incidences of pruritus and rash. Conclusions: Efficacy results in the LA population were consistent with the multinational study suggesting that tigecycline is noninferior to vancomycin/aztreonam in treating patients with cSSSI.
Daptomycin for Treatment of Complicated Skin and Skin Structure Infections
Maximillian Jahng and Jennifer Le
Healthy Aging & Clinical Care in the Elderly , 2012, DOI: 10.4137/HACCE.S7655
Abstract: Acute bacterial skin and skin structure infections (ABSSSI) are common in the elderly and are often complicated due to several factors, including higher prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and presence of comorbidities compared to younger patients. Daptomycin, a cyclic lipopeptide, exhibits excellent in vitro bactericidal activity against MRSA and other Gram-positive bacteria associated with complicated skin and skin structure infections (cSSSI). Daptomycin achieves adequate drug penetration into inflamed soft tissues, and is primarily cleared by the kidneys. Typical daptomycin dosing for cSSSI is 4 mg/kg, using actual body weight. While some data are available for the safety and efficacy of doses up 12 mg/kg, higher doses should be reserved for serious and invasive infections. In comparative studies daptomycin was non-inferior to comparator drugs (including vancomycin or penicillinase-resistant penicillins) for treatment of cSSSI. The overall response rate for daptomycin was greater than 80%. Post-marketing analyses of daptomycin therapy for cSSSI have shown similar clinical success of greater than 80%, even in older patients. Daptomycin was generally well-tolerated. The most common side effects were constipation, nausea, and headaches. The incidences of muscle toxicity were similar between daptomycin and comparator antibiotics (less than 5%). However, the risk of skeletal muscle toxicity may increase when higher doses of daptomycin are used. As such, creatinine phosphokinase should be monitored regularly while a patient is on daptomycin therapy. If possible, daptomycin susceptibility should be performed at baseline and when treatment failure is suspected. Based on the current available data, daptomycin appears to be a viable alternative to standard treatment options for cSSSI.
Re?at ?zaras,Fehmi Tabak
Klimik Journal , 2010,
Abstract: Infections due to Gram-positive microorganisms are increasing all over the world. Treatment options in infections caused by resistant Gram-positive bacteria are limited. Daptomycin is the first member of cyclic lipopeptide agents. Its spectrum of activity is the Gram-positive organisms, including resistant species such as methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, vancomycin-resistant S. aureus, and vancomycin-resistant enterococci. Daptomycin has been approved for the treatment of complicated skin and soft tissue infections, S. aureus bacteremia and right-sided infective endocarditis. The recommended dosing regimen is 4-6 mg/kg IV once daily. Dose adjustment is necessary in renal failure. Primary toxicity of daptomycin is reversible dose-related myalgias and weakness.
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