Genomic epidemiology and characterisation of penicillin-sensitive Staphylococcus aureus isolates from invasive bloodstream infections in China: an increasing prevalence and higher diversity in genetic typing be revealed

Staphylococcus aureus is one of the major causes of bloodstream infections. The aim of our study was to characterize methicillin-resistant Staphylococcus aureus (MRSA) isolates from blood of patients hospitalized in the Czech Republic between 2016 and 2018. All MRSA strains were tested for antibiotic susceptibility, analyzed by spa typing and clustered using a Based Upon Repeat Pattern (BURP) algorithm. The representative isolates of the four most common spa types and representative isolates of all spa clonal complexes were further typed by multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. The majority of MRSA strains were resistant to ciprofloxacin (94%), erythromycin (95.5%) and clindamycin (95.6%). Among the 618 strains analyzed, 52 different spa types were detected. BURP analysis divided them into six different clusters. The most common spa types were t003, t586, t014 and t002, all belonging to the CC5 (clonal complex). CC5 was the most abundant MLST CC of our study, comprising of 91.7% (n = 565) of spa-typeable isolates. Other CCs present in our study were CC398, CC22, CC8, CC45 and CC97. To our knowledge, this is the biggest nationwide study aimed at typing MRSA blood isolates from the Czech Republic.

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286. Exploratory Cost-Effectiveness Analysis for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: Are Daptomycin and Linezolid Favored over Vancomycin and Other Antibiotics?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.330 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S143-S144

Author(s):

Michelle Vu ◽

Kenneth Smith ◽

Sherrie L Aspinall ◽

Cornelius J Clancy ◽

Deanna Buehrle

Keyword(s):

Staphylococcus Aureus ◽

Cost Effectiveness ◽

Methicillin Resistant Staphylococcus Aureus ◽

Bloodstream Infections ◽

Sensitivity Analyses ◽

Drug Event ◽

Base Case ◽

Health Administration ◽

Research Support ◽

Methicillin Resistant

Abstract Background Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSAB) cause significant mortality and often require extended antibiotic therapy. Vancomycin, the most common initial MRSAB treatment, carries significant monitoring burden and nephrotoxicity risks. We compared cost-effectiveness of vancomycin and other antibiotic regimens as MRSAB treatment. Methods We estimated cost-effectiveness of intravenous antibiotics (vancomycin, daptomycin, linezolid, ceftaroline/daptomycin, dalbavancin) for Veterans Health Administration (VA) patients with MRSAB using an exploratory decision-tree model. Primary effectiveness outcome was composite of microbiological failure and adverse drug event (ADE)-related discontinuation at 7-days. Results In base-case analyses, linezolid and daptomycin were less expensive and had fewer treatment failures than other regimens at 4 and 6-weeks. Compared to linezolid, daptomycin incremental cost-effectiveness ratios were ~$45,000 (4-weeks) and ~$61,000 (6-weeks) per composite failure avoided, respectively. In one-way sensitivity analyses, daptomycin (4-weeks) was favored over linezolid if linezolid microbiological failure or ADE-related discontinuation rates were >14.8% (base case: 14.0%) or >14.3% (base case: 14.0%), respectively, assuming a willingness to pay (WTP) threshold of $40,000/ composite treatment failure avoided. Vancomycin was favored if its microbiological failure risk was < 16.4% (base case: 27.2%). In two-way sensitivity analyses, daptomycin was favored if linezolid microbiological failure and ADE-related discontinuation rates were >19% and > 16%, respectively. Linezolid, daptomycin and vancomycin were favored in 47%, 39%, and 11% of 4-week probabilistic iterations, respectively, at $40,000 WTP. Conclusion Daptomycin or linezolid are likely less expensive and more effective than vancomycin or other initial regimens for MRSAB. More data are needed to support safety of linezolid in MRSAB patients. Disclosures Cornelius J. Clancy, MD, Astellas (Consultant, Grant/Research Support)Cidara (Consultant, Research Grant or Support)Melinta (Grant/Research Support)Merck (Consultant, Grant/Research Support)Needham Associates (Consultant)Qpex (Consultant)Scynexis (Consultant)Shionogi (Consultant)

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Genomic Epidemiology of Invasive Methicillin-Resistant Staphylococcus aureus Infections Among Hospitalized Individuals in Ontario, Canada

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa147 ◽

2020 ◽

Vol 222 (12) ◽

pp. 2071-2081 ◽

Cited By ~ 2

Author(s):

Jennifer L Guthrie ◽

Sarah Teatero ◽

Sotaro Hirai ◽

Alex Fortuna ◽

Daniel Rosen ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Demographic Data ◽

Public Health Practice ◽

Acid Resistance ◽

Fold Increase ◽

High Genetic Diversity ◽

Methicillin Resistant ◽

Genomic Epidemiology ◽

Healthcare Settings

Abstract Background Prevention and control of methicillin-resistant Staphylococcus aureus (MRSA) infections remain challenging. In-depth surveillance integrating patient and isolate data can provide evidence to better inform infection control and public health practice. Methods We analyzed MRSA cases diagnosed in 2010 (n = 212) and 2016 (n = 214) by hospitals in Ontario, Canada. Case-level clinical and demographic data were integrated with isolate characteristics, including antimicrobial resistance (AMR), classic genotyping, and whole-genome sequencing results. Results Community-associated MRSA (epidemiologically defined) increased significantly from 23.6% in 2010 to 43.0% in 2016 (P < .001). The MRSA population structure changed over time, with a 1.5× increase in clonal complex (CC)8 strains and a concomitant decrease in CC5. The clonal shift was reflected in AMR patterns, with a decrease in erythromycin (86.7% to 78.4%, P = .036) and clindamycin resistance (84.3% to 47.9%, P < .001) and a >2-fold increase in fusidic acid resistance (9.0% to 22.5%, P < .001). Isolates within both CC5 and CC8 were relatively genetically diverse. We identified 6 small genomic clusters—3 potentially related to transmission in healthcare settings. Conclusions Community-associated MRSA is increasing among hospitalized individuals in Ontario. Clonal shifting from CC5 to CC8 has impacted AMR. We identified a relatively high genetic diversity and limited genomic clustering within these dominant CCs.

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Evaluation of Fixed-Dose Daptomycin in Obese Patients With Bloodstream Infections Caused by Staphylococcus aureus

Annals of Pharmacotherapy ◽

10.1177/1060028019883810 ◽

2019 ◽

Vol 54 (3) ◽

pp. 290-291 ◽

Cited By ~ 1

Author(s):

Michael P. Lorenzo ◽

Erica L. Housman ◽

Seth T. Housman

Keyword(s):

Staphylococcus Aureus ◽

Bloodstream Infections ◽

Fixed Dose ◽

Obese Patients

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Effect of Statin Therapy in the Outcome of Bloodstream Infections Due to Staphylococcus aureus: A Prospective Cohort Study

PLoS ONE ◽

10.1371/journal.pone.0082958 ◽

2013 ◽

Vol 8 (12) ◽

pp. e82958 ◽

Cited By ~ 18

Author(s):

Luis E. López-Cortés ◽

Juan Gálvez-Acebal ◽

María D. del Toro ◽

Carmen Velasco ◽

Marina de Cueto ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Cohort Study ◽

Statin Therapy ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Bloodstream Infections

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Evaluation of Ceftaroline Alone and in Combination against Biofilm-Producing Methicillin-Resistant Staphylococcus aureus with Reduced Susceptibility to Daptomycin and Vancomycin in anIn VitroPharmacokinetic/Pharmacodynamic Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00386-15 ◽

2015 ◽

Vol 59 (8) ◽

pp. 4497-4503 ◽

Cited By ~ 23

Author(s):

Katie E. Barber ◽

Jordan R. Smith ◽

Cortney E. Ireland ◽

Blaise R. Boles ◽

Warren E. Rose ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Medical Device ◽

Bloodstream Infections ◽

Methicillin Resistant ◽

Content Type ◽

Elimination Half ◽

Antimicrobial Protection ◽

Mrsa Strains ◽

Post Hoc

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.

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Activity of Oritavancin Against Gram-positive Pathogens Causing Bloodstream Infections in the United States Over 10 Years: Focus on Drug-Resistant Enterococcal Subsets (2010-2019)

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01667-21 ◽

2021 ◽

Author(s):

Cecilia G. Carvalhaes ◽

Helio S. Sader ◽

Jennifer M. Streit ◽

Mariana Castanheira ◽

Rodrigo E. Mendes

Keyword(s):

United States ◽

Staphylococcus Aureus ◽

Enterococcus Faecium ◽

Bloodstream Infections ◽

The United States ◽

Drug Resistant ◽

Gram Positive ◽

Methicillin Resistant ◽

Vancomycin Resistant ◽

Over Time

Oritavancin displayed potent and stable activity (MIC 90 range, 0.06-0.5 mg/L) over time (2010-2019) against Gram-positive pathogens causing bloodstream infections, including methicillin-resistant Staphylococcus aureus and resistant subsets of Enterococcus spp. Daptomycin and linezolid were also active against methicillin-resistant S. aureus and vancomycin-resistant Enterococcus . Only oritavancin and linezolid remained active against Enterococcus faecium isolates displaying an elevated daptomycin MIC (i.e., 2-4 mg/L). Proportions of methicillin-resistant S. aureus and vancomycin-resistant Enterococcus within the respective S. aureus and enterococcal populations decreased over this period.

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SEPSIS MARKERS AND SENSITIVITY OF STAPHYLOCOCCUS AUREUS AND ESCHERICHIA COLI ISOLATES IN A GENERAL HOSPITAL SETTING

Vestnik ◽

10.53065/kaznmu.2021.86.69.013 ◽

2021 ◽

pp. 68-74

Author(s):

М.Е. Рамазанов ◽

В.Н. Сон ◽

М.Р. Рысулы ◽

С.Т. Турсуналиев ◽

Е.Б. Еспенбетов

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Hospital Setting ◽

Bloodstream Infections ◽

High Sensitivity ◽

Clinical Isolates ◽

Empiric Antibiotic Therapy ◽

E Coli ◽

Number Of Patients ◽

Empiric Antibiotic

Представлены результаты проспективного обследования 80 больных ГКБ №7 с бактериемией с октября 2019 года по февраль 2021 года из различных отделений госпиталя. Производилась оценки показателей маркеров сепсиса - пресепсина, прокальцитонина и С-реактивного белка (СРБ) в крови больных в динамике эмпирической терапии антимикробными препаратами (АМП). Наибольшее число больных с выявленной бактериемией находилось в отделении ОАРИТ - 39 пациентов, у 25 из них был диагностирован сепсис по шкале СЕПСИС III, вызванный известными патогенами Staphylococcus aureus (46,6%) и Escherichia coli (36,6%). Для эмпирического лечения применялись различные антибиотики: ампенициллин, амикацин, меропенем, цефотаксим, метрид, ципрофлоксацин, ципрокс, цефлокс, цефазолин, цефтриаксон, левофлоксацин. Уровни прокальцитонина составляют для больных с клиническими изолятами E. coli 20,8±3,1нг/мл, а для изолятов St. aureus 15,7±1,8 нг/мл. После терапии АМП наблюдается значительное снижение показателей до 1,43±0,6 и 2,3±0,9 нг/мл., что позволяет признать эффективность эмпирической антибиотикотерапии при инфекциях кровотока. Высокая чувствительность клинических изолятов Escherichia coli отмечена к препаратам группы карбапенемов - имипенему и меропенему (90,9%), низкая к эртапенему (72,7%). 100% чувствительность все изоляты показали по отношению к АМП из группы глицилциклинов - тигециклину, который структурно сходен с тетрациклинами. Высокой резистеностью клинические изоляты Staphylococcus aureus обладают к пенициллину (92,9%), липопептиду природного происхождения даптомицину (85,8%) и препарату из группы линкозамидов - клиндамицину (64,3%). The results of a prospective examination of 80 patients with bacteremia from October 2019 to February 2021 from various departments of the hospital are presented. The largest number of patients with detected bacteremia were in the OARIT department - 39 patients, 25 of them were diagnosed with sepsis according to the SEPSIS III scale, caused by known pathogens Staphylococcus aureus (46.6%) and Escherichia coli (36.6%). For empirical treatment, various antibiotics were used: ampenicillin, amikacin, meropenem, cefotaxime, metrid, ciprofloxacin, ciprox, ceflox, cefazolin, ceftriaxone, levofloxacin. Procalcitonin levels for patients with clinical E. coli isolates are 20.8 ± 3.1 ng / ml, and for St. aureus 15.7 ± 1.8 ng / ml. After AMP therapy, there is a significant decrease in indicators to 1.43 ± 0.6 and 2.3 ± 0.9 ng / ml, which makes it possible to recognize the effectiveness of empiric antibiotic therapy for bloodstream infections. High sensitivity of clinical isolates of Escherichia coli was noted to drugs of the carbapenem group - imipenem and meropenem (90.9%), low to ertapenem (72.7%). All isolates showed 100% sensitivity to AMPs from the glycylcycline group - tigecycline, which is structurally similar to tetracyclines. Clinical isolates of Staphylococcus aureus are highly resistant to penicillin (92.9%), natural lipopeptide daptomycin (85.8%), and a drug from the lincosamide group - clindamycin (64.3%).

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