Search

Vancomycin-resistant Enterococcus faecium (VREF) and methicillin-resistant Staphylococcus aureus (MRSA) are associated with significant health burden. We investigated linezolid and daptomycin resistance among VREF and MRSA in the EU/EEA between 2014 and 2018. Descriptive statistics and multivariable logistic regression were used to analyze 6,949 VREF and 35,131 MRSA blood isolates from patients with bloodstream infection. The population-weighted mean proportion of linezolid resistance in VREF and MRSA between 2014 and 2018 was 1.6% (95% CI 1.33–2.03%) and 0.28% (95% CI 0.32–0.38%), respectively. Daptomycin resistance in MRSA isolates was similarly low [1.1% (95% CI 0.75–1.6%)]. On the European level, there was no temporal change of daptomycin and linezolid resistance in MRSA and VREF. Multivariable regression analyses showed that there was a higher likelihood of linezolid and daptomycin resistance in MRSA (aOR: 2.74, p < 0.001; aOR: 2.25, p < 0.001) and linezolid in VREF (aOR: 1.99, p < 0.001) compared to their sensitive isolates. The low proportion of linezolid and daptomycin resistance in VREF and MRSA suggests that these last-resort antibiotics remain effective and will continue to play an important role in the clinical management of these infections in Europe. However, regional and national efforts to contain antimicrobial resistance should continue to monitor the trend through strengthened surveillance that includes genomic surveillance for early warning and action. [ABSTRACT FROM AUTHOR]

Background Despite the advances in current healthcare, bone and joint infections (BJIs) are a major clinical challenge that frequently involve prolonged systemic antibiotic use. Healthcare providers consider tedizolid an attractive candidate for therapy in adults and children with BJI. Objectives We tested tedizolid against a US and European collection of Gram-positive BJI isolates (n =  797) consecutively collected from 2014 to 2017. Methods Organisms were tested by broth microdilution susceptibility methods following current CLSI guidelines and interpreted by both CLSI and EUCAST breakpoint criteria. Results Staphylococcus aureus (59.3%; 58.6% in the USA and 60.4% in Europe) was the most common pathogen with a 29.6% MRSA rate and tedizolid MIC50/90 of 0.12/0.25 mg/L (100% susceptible). CoNS (15.0% of BJI in adults and <5% in children) had tedizolid MIC50/90 values of 0.12/0.12 mg/L (99.1% susceptible). Tedizolid exhibited MIC50/90 values of 0.12/0.25 mg/L for all streptococci and enterococci. Overall, high susceptibility rates (>95%) for vancomycin, daptomycin and linezolid were observed and, based on MIC90 values, tedizolid (MIC90 0.12–0.25 mg/L) was 4- to 8-fold more potent than linezolid (MIC90 0.5–2  mg/L) against this collection of Gram-positive pathogens causing BJI. Conclusions This study showed that tedizolid had potent in vitro activity against contemporary Gram-positive cocci causing BJI in adults and children in US and European hospitals. [ABSTRACT FROM AUTHOR]

Background: Many infections due to Gram-positive cocci (GPC; staphylococci, streptococci and enterococci) regularly involve prolonged systemic antibiotic use. Dalbavancin has demonstrated activity against GPC isolates and has been approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) in adults.Objectives: To evaluate the activity of dalbavancin against GPC isolated from a variety of infection types in the USA and Europe.Methods: A total of 14 319 Staphylococcus aureus, 1992 CoNS, 3269 β-haemolytic streptococci (BHS), 2071 Enterococcus faecalis, 936 Enterococcus faecium, 71 Enterococcus gallinarum/casseliflavus and other Enterococcus spp., 3487 Streptococcus pneumoniae and 1063 viridans group streptococci (VGS) causing clinical infections were consecutively collected (2015-16) and tested for susceptibility by broth microdilution methods.Results: All S. aureus (36.4% MRSA) isolates were susceptible to dalbavancin, teicoplanin and vancomycin, while daptomycin and linezolid showed susceptibility rates of >99.9% (according to CLSI criteria). Dalbavancin MIC results were at least 16-fold lower than these comparators against all S. aureus. Dalbavancin was the most potent agent against CoNS [62.2%/59.6% methicillin-resistant (CLSI/EUCAST)], followed by daptomycin, linezolid and vancomycin. All vancomycin-susceptible E. faecalis isolates were inhibited by dalbavancin at ≤0.25 mg/L (FDA susceptible breakpoint). Dalbavancin was very active against BHS (MIC90 0.03 mg/L) and the most active agent against S. pneumoniae and VGS (highest MIC 0.25 mg/L). Ceftriaxone, daptomycin, levofloxacin and vancomycin were also active (93.5%-100.0% susceptible) against VGS, whereas clindamycin, erythromycin, penicillin and tetracycline had lower activity.Conclusions: Dalbavancin appears to be a viable candidate for treating serious infections caused by GPC. [ABSTRACT FROM AUTHOR]

Background: Daptomycin is an optimal choice for outpatient parenteral antibiotic therapy (OPAT) because of its safety, once-daily administration and its activity against Gram-positive bacteria. Although daptomycin is increasingly being used in OPAT, limited information about its safety in this scenario is available. Methods: We performed a prospective multicentre pilot study to evaluate the safety of daptomycin in outpatients with proved or suspected Gram-positive infections (DAPTODOM). The primary objective was to evaluate the safety and the secondary objective to evaluate the efficacy in OPAT. We also looked at the development of daptomycin resistance in those cases with microbiological failure. Results: We included 54 patients from 12 Spanish hospitals, 67% male with a mean age of 67.1 years. Most patients (87%) had chronic underlying diseases. The main reason for inclusion was skin and soft-tissue infections in 52%, followed by bacteremia or endocarditis in 34%. Staphylococcus aureus accounted for 44% of the isolates (24% were methicillin-resistant), coagulase-negative staphylococci 15% and enterococci 7%. Two patients (4%) had to be readmitted because of complications; only one patient had an adverse effect related to daptomycin (increase in serum creatine kinase levels), which disappeared after discontinuation (2%). At the end of follow-up, 96% of patients had good outcome and only 4% of patients did not have a clinical or microbiological cure. The use of a 2-minute bolus in 18 cases was not associated with adverse effects. Conclusions: Daptomycin was safe and efficacious in outpatients with Gram-positive bacterial infections and can be administered in 2-minute bolus infusion. [ABSTRACT FROM AUTHOR]

Introduction: Daptomycin, a rapid concentration-dependent bactericidal antibiotic, is approved at a dose of 4 mg/kg/day for the treatment of complicated skin and soft tissue infections (cSSTI) and at a dose of 6 mg/kg/day for the treatment of Staphylococcus aureus right-sided infective endocarditis (RIE) and bacteremia associated with cSSTI and RIE. Studies have reported the successful use of high-dose daptomycin (>6 mg/kg/day) in patients with difficult-to-treat infections. The present analysis evaluated the effectiveness and safety of high doses (>6 mg/kg/day) of daptomycin for the treatment of different Gram-positive infections.Methods: European Cubicin(®) Outcomes Registry and Experience (EU-CORE) is a non-interventional, multicenter, retrospective, patient registry designed to collect real-world data from patients treated with daptomycin between 2006 and 2012. Clinical outcomes were assessed at the end of daptomycin treatment for three dose groups: ≤6, >6 to <8, and ≥8 mg/kg/day. Safety was assessed for up to 30 days post-daptomycin treatment.Results: Of the 6075 patients enrolled in EU-CORE, 4892 patients received daptomycin doses ≤6 mg/kg/day, while 1097 patients received high doses (>6 mg/kg/day). The primary infections with the largest proportion of patients treated with a high dose (>6 mg/kg/day) were osteomyelitis (37.1%), foreign body/prosthetic infection (31.6%), and endocarditis (27.6%). S. aureus was identified in 42.9% of patients with positive cultures treated with either ≤6 or >6 mg/kg/day. The overall clinical success rate was 82.0% (899/1097) with high doses (>6 mg/kg/day) and 80.3% (3928/4890) with doses ≤6 mg/kg/day. Numerically higher clinical success rate was observed for endocarditis and foreign body/prosthetic infection, as well as for coagulase-negative staphylococcal and enterococcal infections, with high-dose daptomycin treatment. There were no new or unexpected safety findings at doses >6 mg/kg/day.Conclusion: These results suggested that daptomycin at doses >6 mg/kg/day was effective and well tolerated. High-dose daptomycin is a potential therapeutic option in patients with difficult-to-treat Gram-positive infections.Funding: This study was funded by Novartis Pharma AG. [ABSTRACT FROM AUTHOR]

Abstract: We report the results of the international daptomycin surveillance programs for Europe, Latin America, and selected Asia-Pacific nations. A total of 7948 consecutive Gram-positive organisms of clinical significance were collected in 2011 and susceptibility tested against daptomycin and various comparator agents by Clinical and Laboratory Standards Institute (Clinical and Laboratory Standards Institute. M07-A9. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard: ninth edition Wayne, PA: CLSI. 2012.; Cubicin Package Insert 2012. Cubist Pharmaceuticals, Inc, Lexington, MA. Available at http://www.cubicin.com/pdf/PrescribingInformation.pdf. Accessed January 1, 2012.) broth microdilution methods. The test medium was adjusted to contain physiological levels of calcium (50 mg/L) when testing daptomycin. Daptomycin exhibited potent activity against methicillin-susceptible and -resistant Staphylococcus aureus overall and for each region (MIC50/90, 0.25–0.5/0.5 μg/mL), with susceptibility rates at 100.0% in Latin America, Australia/New Zealand, and India, and at 99.9% in Europe. The daptomycin MIC50/90 for coagulase-negative staphylococci was also at 0.25–0.5/0.5 μg/mL, and only 1 isolate was considered nonsusceptible with a MIC value at 2 μg/mL. Daptomycin was also highly active against Enterococcus faecalis (MIC50/90, 1/1–2 μg/mL) and E. faecium (MIC50/90, 2/2 μg/mL for both vancomycin-susceptible and -resistant isolates). All enterococcal isolates were susceptible to daptomycin (MIC, ≤4 μg/mL) and tigecycline. Susceptibility to linezolid for E. faecalis was at 100.0%, while for E. faecium regional susceptibility rates were at 100.0% except in Europe (99.0%). Viridans group streptococci (MIC50/90, 0.25/1 μg/mL) and β-haemolytic streptococci (MIC50/90, ≤0.06/0.25 μg/mL) continue to be very susceptible to daptomycin. In summary, the results of this investigation document the high potency and wide spectrum of daptomycin when tested against a large resistance-surveillance collection of Gram-positive pathogens and indicate that daptomycin nonsusceptibility remains rare among indicated species after many years of clinical use worldwide. [Copyright &y& Elsevier]

Abstract: Bacteraemia has not been recognised as a therapeutic indication in Europe since the publication of the Note for Guidance on Evaluation of Medicinal Products for Treatment of Bacterial Infections in 1997 by the European Medicines Agency (EMEA). This standpoint is in sharp contrast to the labelling decisions taken by the US Food and Drug Administration (FDA). In Europe, a site-specific indication, such as treatment of complicated skin and soft tissue infections is considered to cover cases with bacteraemia, but not vice versa. Only cautionary information is presented in the labelling, e.g. if the number of bacteraemia cases in clinical trials has been low enough to be of concern or if the pharmacokinetic characteristics of the drug may not secure sufficient concentrations in blood. Primary bacteraemia is potentially a situation where the described regulatory paradigm may not apply, but this has yet to be tested. The European approach is likely to be increasingly challenged due to the increasing incidence of bloodstream infections, particularly due to resistant pathogens, and the associated high morbidity and mortality. [Copyright &y& Elsevier]

The antimicrobial susceptibility patterns of 9322 contemporary (2002–2004) Gram-positive bacterial isolates collected from 31 medical centres in 14 countries in Europe were evaluated by broth microdilution methods according to CLSI guidelines. The isolates collected comprised Staphylococcus aureus (4842 isolates), coagulase-negative staphylococci (CoNS; 1942 isolates), Enterococcus faecalis (1147 isolates), Enterococcus faecium (391 isolates), β-haemolytic streptococci (660 isolates) and viridans group streptococci (340 isolates). The organisms were tested against daptomycin and more than 20 comparator agents in Mueller–Hinton broth, supplemented with calcium to 50 mg/L when testing daptomycin. Overall, methicillin (oxacillin) resistance rates were 26.7% and 77.0% for S. aureus (MRSA) and CoNS, respectively, and the vancomycin resistance rate among enterococci was 6.1%. MRSA rates varied from 0.6% in Sweden to 40.2–43.0% in Belgium, Greece, Ireland, the UK and Israel, and VRE rates varied from 0% in Switzerland to 21.2% in Ireland. More than 99.9% of isolates tested were considered susceptible to daptomycin according to breakpoints established by the United States Food and Drug Administration and the CLSI. Daptomycin was active against all Gram-positive species, with the highest MIC being 2, 8, 0.5 and 2 mg/L for staphylococci, enterococci, β-haemolytic streptococci and viridans group streptococci, respectively. Daptomycin activity was not influenced adversely by resistance to other agents among staphylococci or enterococci . This novel lipopeptide (daptomycin) appears to be an excellent alternative therapeutic option for serious infections caused by multidrug-resistant Gram-positive organisms isolated in Europe. [ABSTRACT FROM AUTHOR]

We aimed to characterize real-world dosing of weight-based intravenous (IV) antibiotic therapy in patients hospitalized for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections (cSSTIs). This was a subgroup analysis of a retrospective chart review that captured data from 12 European countries. The study included patients ≥18 years old, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Patients treated with IV vancomycin, teicoplanin or daptomycin at any stage during hospitalization were included in this analysis. Analyses were conducted at the regimen level (dosing in mg/kg or in mg, frequency, and total daily dose (TDD)), with potentially multiple regimens per patient, and the patient level, categorizing patients into low, standard (labelled) and high dosing groups according to their initial MRSA-targeted regimen. Among the 1502 patients in the parent study, 998 patients contributed a total of 1050 daptomycin, teicoplanin or vancomycin regimens. Across all regimens, the mean initial TDDs were 6.3 ± 1.9 mg/kg for daptomycin, 10.5 ± 4.9 mg/kg for teicoplanin and 28.5 ± 11.5 mg/kg for vancomycin. A total of 789 patients received first-line therapy with one of the above antibiotics. The majority of patients receiving first-line teicoplanin and daptomycin (96% and 80%, respectively) received higher than labelled cSSTI doses, whereas vancomycin doses were lower than labelled doses in >40% of patients. These real-world data reveal significant deviation from labelled antibiotic dosing in 12 European countries and the potential for suboptimal outcomes in patients with MRSA cSSTIs., (Copyright © 2015. Published by Elsevier Ltd.)