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Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-year period (2008–2012)
Diagnostic Microbiology and Infectious Disease xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Diagnostic Microbiology and Infectious Disease journal homepage: www.elsevier.com/locate/diagmicrobio
Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-year period (2008–2012) Matthaios Papadimitriou-Olivgeris a, Fevronia Kolonitsiou b, Loukia Zerva c, Evangelia Lebessi d, Chryssa Koutsia e, Eleanna Drougka b, Styliani Sarrou f, Nikolaos Giormezis b, Sofia Vourli c, Anastassios Doudoulakakis d, Christos Konsolakis e, Markos Marangos a, Evangelos D. Anastassiou b, Efthimia Petinaki f, Iris Spiliopoulou b,⁎ a
Division of Infectious Diseases, School of Medicine, University of Patras, Patras, Greece Department of Microbiology, School of Medicine, University of Patras, Patras, Greece Department of Microbiology, Attikon University Hospital, Athens, Greece d Department of Microbiology, ‘P&A Kyriakou’ Children's Hospital, Athens, Greece e Department of Microbiology, “Asclepeion” General Hospital, Athens, Greece f Department of Microbiology, University General Hospital of Larissa, Larissa, Greece b c
a r t i c l e
i n f o
Article history: Received 8 June 2015 Received in revised form 30 July 2015 Accepted 2 August 2015 Available online xxxx
a b s t r a c t The tendency of vancomycin, linezolid, and daptomycin MICs was investigated among 6920 staphylococci and enterococci during a 5-year period. Antimicrobial consumption was determined. Decrease of vancomycin MIC was detected associated with reduction in consumption. Linezolid and daptomycin remained active. An upward trend of linezolid MIC for methicillin-resistant staphylococci was observed. © 2015 Elsevier Inc. All rights reserved.
Keywords: MIC Creep Methicillin-resistant Staphylococcus aureus (MRSA) Vancomycin-resistant Enterococcus (VRE)
The prevalence of multidrug-resistant Gram-positive cocci in Greek hospitals is high and has led to an increase usage of vancomycin and newer antibiotics with anti-Gram positive action such as linezolid and daptomycin (ECDC, 2013). Previous studies have demonstrated an increase of vancomycin MIC among methicillin-resistant Staphylococcus aureus (MRSA) during a period of time, a phenomenon known as MIC creep (Sader et al., 2009; Yeh et al., 2012) Other reports failed to find such an association (Sancak et al., 2013), rendering the issue of vancomycin MIC creep controversial (Dhand and Sakoulas, 2012). Antibiotic administration remains one of the most important risk factors for the selection and dissemination of multidrug-resistant bacteria (Papadimitriou-Olivgeris et al., 2013, 2014). The most commonly utilized method for assessing antimicrobial consumption is the ATC/DDD index (anatomical therapeutic chemical/defined daily dose), which calculates the DDD per-100-patient-days (WHO, 2014). The aim of this study was to assess the tendency of vancomycin, linezolid, and daptomycin MIC levels among staphylococci (S. aureus ⁎ Corresponding author. Tel.: +30-2610-996111; fax: +30-2610-994922. E-mail address: [email protected] (I. Spiliopoulou).
and coagulase-negative staphylococci, CNS) and enterococci (E. faecium and E. faecalis) recovered from clinically significant specimens (blood, pus, skin, and soft tissue infections, intravenous catheter related infections, urine, pleural, synovial, and peritoneal fluids) of patients hospitalized in five Greek tertiary care Hospitals during a 5-year period (January 2008 to December 2012) and to examine the temporal relationship of the aforementioned antimicrobial consumption. Five tertiary care Greek hospitals (University General Hospital of Patras, University General Hospital of Larissa, Attikon University General Hospital of Athens, General Hospital Asklepieion Voulas and ‘P&A Kyriakou’ Children's Hospital, Athens) located in 3 different areas of the country, participated in the study. Isolates were identified to species level by the Vitek 2 Advanced Expert System (bioMérieux, Marcy l'Etoile, France). MICs of vancomycin, linezolid, and daptomycin were determined by Etest (bioMérieux) and interpreted according to EUCAST criteria (EUCAST, 2015). Methicillin resistance was determined among staphylococci by the disk diffusion method with cefoxitin verified by PCR for mecA gene, whereas, vancomycin resistance among enterococci was identified by Etest and PCR for the presence of vanA and vanB genes (Bell et al., 1998; EUCAST, 2015; Petinaki et al., 2001). As controls were used the strains: S. aureus ATCC29213 (susceptible) and
http://dx.doi.org/10.1016/j.diagmicrobio.2015.08.002 0732-8893/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Papadimitriou-Olivgeris M, et al, Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-y..., Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.08.002
2
M. Papadimitriou-Olivgeris et al. / Diagnostic Microbiology and Infectious Disease xxx (2015) xxx–xxx
BB270 (mecA-positive), E. faecalis ATCC29212 (susceptible), ATCC51559 (vanA-positive) and ATCC51299 (vanB-positive). The antimicrobial consumption was calculated using the DDDs per 100-patient-days, as described by the WHO ATC/DDD (WHO, 2014). Antibiotic consumption data were collected from the corresponding Pharmacology Department of each participating hospital. Statistical analysis was performed with SPSS version 19.0 (SPSS, Chicago, IL, USA). The MIC trends and the antibiotic consumption over the 5 years were assessed using Spearman's correlation analysis, and a P value b0.05 was considered significant. A total of 6920 Gram-positive cocci were analyzed. Of these strains 3751 were S. aureus (1684 methicillin-susceptible, MSSA and 2067 MRSA), 2129 enterococci (1818 vancomycin-susceptible, VSE and 311 vancomycinresistant, VRE) and 1040 CNS (238 methicillin-susceptible, MS-CNS and 802 methicillin-resistant, MR-CNS). The MICs50 and MICs90 of the isolates during the studied period are depicted in Table 1. The MICs of vancomycin showed a significant reduction for MSSA (r = −0.495, P b 0.001), MRSA (r = −0.251, P b 0.001), S. aureus in total (r = −0.339, P b 0.001), MSCNS (r = −0.228, P b 0.001), MR-CNS (r = −0.450, P b 0.001), CNS in total (r = −0.397, P b 0.001), VSE (r = −0.321, P b 0.001) and enterococci in total (r = −0.222, P b 0.001) during the study period. Staphylococci with reduced susceptibility or resistance to vancomycin were not detected. Linezolid MIC showed a significant increase for MRSA (r = 0.208, P b 0.001) and MR-CNS (r = 0.097, P b 0.001). Daptomycin MIC showed a significant decrease for MSSA (r = −0.137, P b 0.001), MRSA (r -0.072, P b 0.001) and S. aureus in total (r = −0.084, P b 0.001). The yearly consumption for each of the three antibiotics is shown in Fig. 1. A statistically significant decrease in vancomycin consumption (r = −0.863, P b 0.001) was observed during the study, whereas, linezolid (r = 0.481, P b 0.001) and daptomycin consumption (r = 0.995, P b 0.001) increased. No differences in antibiotic consumption and MIC levels were observed among participating hospitals. The prevalence of multidrug-resistant Gram-positive cocci in Greek hospitals remains high, even after the emergence of multiresistant Gram-negative pathogens, resulting to increased consumption of vancomycin and newer antibiotics, such as linezolid and daptomycin. This is the first multicenter study conducted in Greek hospitals in order to determine the MIC trends in the aforementioned antimicrobials for the clinically important Gram-positive cocci during a 5-year period. The present study underlines the steady decrease of vancomycin MIC among S. aureus isolates (MRSA and MSSA). Our findings contradict
Fig. 1. Yearly consumption of vancomycin, linezolid, and daptomycin.
the results of other investigators reporting a MIC creep phenomenon in S. aureus (Dhand and Sakoulas, 2012; Yeh et al., 2012). Van Hal et al. (2011) showed that MIC creep is dependent on testing methodology, and it was observed only if the Etest was used, a method applied also in our study. In a study from nine USA medical centers, no yearly tendency towards vancomycin MIC increase during a ten years period among MRSA was revealed and the occurrence of isolates with MIC N1 mg/L was due to clonal dissemination (Sader et al., 2009). Even though no molecular typing of isolates was performed in the present study, ST80 was the predominant clone (1647 of 2410; 68.3%) during the studied period among Greek MRSA isolates, as published (Drougka, et al., 2014). The reported vancomycin MIC decrease in Greek hospitals correlates with the reduction in vancomycin consumption, resulting to lesser pressure in bacteria. Even though all S. aureus isolates were susceptible, 46.7% of the MRSA and 19.7% of the MSSA had an MIC N1 mg/L. Higher vancomycin MIC levels were associated with poorer outcome when vancomycin was used as treatment option (Soriano et al., 2008), leading to an increase in linezolid and daptomycin consumption. An increase of linezolid MIC among MRSA and MR-CNS was also observed in this study and is probably due to increased linezolid consumption. Clonal dissemination of linezolid-resistant MR-CNS isolates (43 of 802; 5.4%) may also play a role in the increase of linezolid MIC levels among this population
Table 1 Evolution of MICs50 and MICs90 among studied isolates. Number
Vancomycin MIC50
MIC90
Linezolid MIC50
Daptomycin MIC90
MIC50
Number
Vancomycin
Linezolid
MIC90
MIC50
MIC90
MIC50
MIC90
MIC50
MIC90
2 2 2 2 2 2
1.5 1.5 1.5 1 1.5 1.5
2 1.5 2 1.5 1.5 1.5
0.25 0.25 0.5 0.5 0.25 0.25
1 0.75 1 1 0.75 1
2 2 1.5 1.5 1 2
1.5 1.5 1.5 1.5 1.5 1.5
1.5 1.5 1.5 1.5 1.5 1.5
0.25 0.25 0.25 0.25 0.25 0.25
0.5 0.5 0.5 0.38 0.38 0.38
338 340 710 369 310 2067
MRSA 2 1 1.5 1 1 1
Daptomycin
2008 2009 2010 2011 2012 Total
354 331 396 283 320 1684
MSSA 1 1 1 1 0.5 1
2008 2009 2010 2011 2012 Total
18 34 34 62 25 238
MS-CNS 1 1.5 1.5 1.5 1 1.5
2 2 2 2 2 2
0.5 0.5 0.5 1 1 1
1 1 1 1 2 2
0.25 0.25 0.25 0.25 0.25 0.25
0.5 0.5 0.5 0.5 0.5 0.5
98 173 117 306 109 802
MR-CNS 2 2 2 1 1.5 2
3 2 4 3 2 3
1 1 1 1 1 1
2 2 2 4 4 2
0.25 0.5 0.5 0.5 0.5 0.38
1 0.75 0.75 0.75 0.75 0.5
2008 2009 2010 2011 2012 Total
300 311 361 582 264 1818
VSE 2 1 1 1 1 1
2 2 2 2 2 2
2 2 2 2 2 2
2 2 2 2 2 2
1 0.5 0.75 0.5 1 0.5
2 1 1.5 1.5 2 2
50 39 84 95 43 311
VRE 256 256 256 256 256 256
256 256 256 256 256 256
1 1 1.5 1.5 2 1.5
2 2 3 2 2 2
1 1.5 1.5 1.5 1.5 1.5
2 2 2 3 4 2
MICs are depicted in mg/L.
Please cite this article as: Papadimitriou-Olivgeris M, et al, Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-y..., Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.08.002
M. Papadimitriou-Olivgeris et al. / Diagnostic Microbiology and Infectious Disease xxx (2015) xxx–xxx
(Liakopoulos et al., 2010; Papadimitriou-Olivgeris et al., 2013). Even though results concerning daptomycin MIC differ among studied isolates, daptomycin retains high activity against tested Gram-positive cocci. Our collection of MR-CNS and MRSA showed higher daptomycin MIC levels than those reported in a previous study from Greek hospitals during 2006–2007 (Malli et al., 2008). Our study has some limitations. We did not analyze clonal transmission, nor comparison of clinical outcomes and MIC was included. Moreover, Etest was the only method used for MIC determination. In conclusion, a decrease in vancomycin MIC among staphylococci isolated from Greek hospitals was detected, that may be explained by its reduction of consumption. Linezolid and daptomycin remain active against Gram-positive cocci, even though an upward trend of linezolid MIC was observed among several bacterial populations. The emergence of linezolid-resistant MR-CNS combined with a clonal spread may pose a serious threat for the future.
Acknowledgements There was no external financial support received in order to complete the present study and only institutional funds were used.
References Bell J, Turnidge J, Coombs G, O'Brien F. Emergence and epidemiology of vancomycinresistant enterococci in Australia. Commun Dis Intell 1998;22:249–52. Dhand A, Sakoulas G. Reduced vancomycin susceptibility among clinical Staphylococcus aureus isolates (‘the MIC Creep’): implications for therapy. F1000 Med Rep 2012;4:4. Drougka E, Foka A, Liakopoulos A, Doudoulakakis A, Jelastopulu E, Chini V, et al. A 12-year survey of methicillin-resistant Staphylococcus aureus infections in Greece: ST80-IV epidemic? Clin Microbiol Infect 2014;20:O796–803.
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European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe 2012. Annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Stockholm: ECDC; 2013. Liakopoulos A, Spiliopoulou I, Damani A, Kanellopoulou M, Schoina S, Papafragas E, et al. Dissemination of two international linezolid-resistant Staphylococcus epidermidis clones in Greek hospitals. J Antimicrob Chemother 2010;65:1070–1. Malli E, Spiliopoulou I, Kolonitsiou F, Klapsa D, Giannitsioti E, Pantelidi K, et al. In vitro activity of daptomycin against Gram-positive cocci: the first multicentre study in Greece. Int J Antimicrob Agents 2008;32:525–8. Papadimitriou-Olivgeris M, Giormezis N, Fligou F, Liakopoulos A, Marangos M, Anastassiou ED, et al. Factors influencing linezolid-nonsusceptible coagulasenegative staphylococci dissemination among patients in the intensive care unit: a retrospective cohort study. Chemotherapy 2013;59:420–6. Papadimitriou-Olivgeris M, Drougka E, Fligou F, Kolonitsiou F, Liakopoulos A, Dodou V, et al. Risk factors for enterococcal infection and colonization by vancomycinresistant enterococci in critically ill patients. Infection 2014;42:1013–22. Petinaki E, Arvaniti A, Dimitracopoulos G, Spiliopoulou I. Detection of mecA, mecR1 and mecI genes among clinical isolates of methicillin-resistant staphylococci by combined polymerase chain reactions. J Antimicrob Chemother 2001;47:297–304. Sader HS, Fey PD, Limaye AP, Madinger N, Pankey G, Rahal J, et al. Evaluation of vancomycin and daptomycin potency trends (MIC creep) against methicillinresistant Staphylococcus aureus isolates collected in nine U.S. medical centers from 2002 to 2006. Antimicrob Agents Chemother 2009;53:4127–32. Sancak B, Yagci S, Mirza HC, Hascelik G. Evaluation of vancomycin and daptomycin MIC trends for methicillin-resistant Staphylococcus aureus blood isolates over an 11 year period. J Antimicrob Chemother 2013;68:2689–91. Soriano A, Marco F, Martinez JA, Pisos E, Almela M, Dimova VP, et al. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis 2008;46:193–200. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 5.0; 2015 (http://www.eucast.org). van Hal SJ, Barbagiannakos T, Jones M, Wehrhahn MC, Mercer J, Chen D, et al. Methicillinresistant Staphylococcus aureus vancomycin susceptibility testing: methodology correlations, temporal trends and clonal patterns. J Antimicrob Chemother 2011;66:2284–7. WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment, 2015. Oslo, Norway; 2014 (www.whocc.no/atc_ddd_ index/). Yeh YC, Yeh KM, Lin TY, Chiu SK, Yang YS, Wang YC, et al. Impact of vancomycin MIC creep on patients with methicillin-resistant Staphylococcus aureus bacteremia. J Microbiol Immunol Infect 2012;45:214–20.
Please cite this article as: Papadimitriou-Olivgeris M, et al, Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-y..., Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.08.002
Contents lists available at ScienceDirect
Diagnostic Microbiology and Infectious Disease journal homepage: www.elsevier.com/locate/diagmicrobio
Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-year period (2008–2012) Matthaios Papadimitriou-Olivgeris a, Fevronia Kolonitsiou b, Loukia Zerva c, Evangelia Lebessi d, Chryssa Koutsia e, Eleanna Drougka b, Styliani Sarrou f, Nikolaos Giormezis b, Sofia Vourli c, Anastassios Doudoulakakis d, Christos Konsolakis e, Markos Marangos a, Evangelos D. Anastassiou b, Efthimia Petinaki f, Iris Spiliopoulou b,⁎ a
Division of Infectious Diseases, School of Medicine, University of Patras, Patras, Greece Department of Microbiology, School of Medicine, University of Patras, Patras, Greece Department of Microbiology, Attikon University Hospital, Athens, Greece d Department of Microbiology, ‘P&A Kyriakou’ Children's Hospital, Athens, Greece e Department of Microbiology, “Asclepeion” General Hospital, Athens, Greece f Department of Microbiology, University General Hospital of Larissa, Larissa, Greece b c
a r t i c l e
i n f o
Article history: Received 8 June 2015 Received in revised form 30 July 2015 Accepted 2 August 2015 Available online xxxx
a b s t r a c t The tendency of vancomycin, linezolid, and daptomycin MICs was investigated among 6920 staphylococci and enterococci during a 5-year period. Antimicrobial consumption was determined. Decrease of vancomycin MIC was detected associated with reduction in consumption. Linezolid and daptomycin remained active. An upward trend of linezolid MIC for methicillin-resistant staphylococci was observed. © 2015 Elsevier Inc. All rights reserved.
Keywords: MIC Creep Methicillin-resistant Staphylococcus aureus (MRSA) Vancomycin-resistant Enterococcus (VRE)
The prevalence of multidrug-resistant Gram-positive cocci in Greek hospitals is high and has led to an increase usage of vancomycin and newer antibiotics with anti-Gram positive action such as linezolid and daptomycin (ECDC, 2013). Previous studies have demonstrated an increase of vancomycin MIC among methicillin-resistant Staphylococcus aureus (MRSA) during a period of time, a phenomenon known as MIC creep (Sader et al., 2009; Yeh et al., 2012) Other reports failed to find such an association (Sancak et al., 2013), rendering the issue of vancomycin MIC creep controversial (Dhand and Sakoulas, 2012). Antibiotic administration remains one of the most important risk factors for the selection and dissemination of multidrug-resistant bacteria (Papadimitriou-Olivgeris et al., 2013, 2014). The most commonly utilized method for assessing antimicrobial consumption is the ATC/DDD index (anatomical therapeutic chemical/defined daily dose), which calculates the DDD per-100-patient-days (WHO, 2014). The aim of this study was to assess the tendency of vancomycin, linezolid, and daptomycin MIC levels among staphylococci (S. aureus ⁎ Corresponding author. Tel.: +30-2610-996111; fax: +30-2610-994922. E-mail address: [email protected] (I. Spiliopoulou).
and coagulase-negative staphylococci, CNS) and enterococci (E. faecium and E. faecalis) recovered from clinically significant specimens (blood, pus, skin, and soft tissue infections, intravenous catheter related infections, urine, pleural, synovial, and peritoneal fluids) of patients hospitalized in five Greek tertiary care Hospitals during a 5-year period (January 2008 to December 2012) and to examine the temporal relationship of the aforementioned antimicrobial consumption. Five tertiary care Greek hospitals (University General Hospital of Patras, University General Hospital of Larissa, Attikon University General Hospital of Athens, General Hospital Asklepieion Voulas and ‘P&A Kyriakou’ Children's Hospital, Athens) located in 3 different areas of the country, participated in the study. Isolates were identified to species level by the Vitek 2 Advanced Expert System (bioMérieux, Marcy l'Etoile, France). MICs of vancomycin, linezolid, and daptomycin were determined by Etest (bioMérieux) and interpreted according to EUCAST criteria (EUCAST, 2015). Methicillin resistance was determined among staphylococci by the disk diffusion method with cefoxitin verified by PCR for mecA gene, whereas, vancomycin resistance among enterococci was identified by Etest and PCR for the presence of vanA and vanB genes (Bell et al., 1998; EUCAST, 2015; Petinaki et al., 2001). As controls were used the strains: S. aureus ATCC29213 (susceptible) and
http://dx.doi.org/10.1016/j.diagmicrobio.2015.08.002 0732-8893/© 2015 Elsevier Inc. All rights reserved.
Please cite this article as: Papadimitriou-Olivgeris M, et al, Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-y..., Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.08.002
2
M. Papadimitriou-Olivgeris et al. / Diagnostic Microbiology and Infectious Disease xxx (2015) xxx–xxx
BB270 (mecA-positive), E. faecalis ATCC29212 (susceptible), ATCC51559 (vanA-positive) and ATCC51299 (vanB-positive). The antimicrobial consumption was calculated using the DDDs per 100-patient-days, as described by the WHO ATC/DDD (WHO, 2014). Antibiotic consumption data were collected from the corresponding Pharmacology Department of each participating hospital. Statistical analysis was performed with SPSS version 19.0 (SPSS, Chicago, IL, USA). The MIC trends and the antibiotic consumption over the 5 years were assessed using Spearman's correlation analysis, and a P value b0.05 was considered significant. A total of 6920 Gram-positive cocci were analyzed. Of these strains 3751 were S. aureus (1684 methicillin-susceptible, MSSA and 2067 MRSA), 2129 enterococci (1818 vancomycin-susceptible, VSE and 311 vancomycinresistant, VRE) and 1040 CNS (238 methicillin-susceptible, MS-CNS and 802 methicillin-resistant, MR-CNS). The MICs50 and MICs90 of the isolates during the studied period are depicted in Table 1. The MICs of vancomycin showed a significant reduction for MSSA (r = −0.495, P b 0.001), MRSA (r = −0.251, P b 0.001), S. aureus in total (r = −0.339, P b 0.001), MSCNS (r = −0.228, P b 0.001), MR-CNS (r = −0.450, P b 0.001), CNS in total (r = −0.397, P b 0.001), VSE (r = −0.321, P b 0.001) and enterococci in total (r = −0.222, P b 0.001) during the study period. Staphylococci with reduced susceptibility or resistance to vancomycin were not detected. Linezolid MIC showed a significant increase for MRSA (r = 0.208, P b 0.001) and MR-CNS (r = 0.097, P b 0.001). Daptomycin MIC showed a significant decrease for MSSA (r = −0.137, P b 0.001), MRSA (r -0.072, P b 0.001) and S. aureus in total (r = −0.084, P b 0.001). The yearly consumption for each of the three antibiotics is shown in Fig. 1. A statistically significant decrease in vancomycin consumption (r = −0.863, P b 0.001) was observed during the study, whereas, linezolid (r = 0.481, P b 0.001) and daptomycin consumption (r = 0.995, P b 0.001) increased. No differences in antibiotic consumption and MIC levels were observed among participating hospitals. The prevalence of multidrug-resistant Gram-positive cocci in Greek hospitals remains high, even after the emergence of multiresistant Gram-negative pathogens, resulting to increased consumption of vancomycin and newer antibiotics, such as linezolid and daptomycin. This is the first multicenter study conducted in Greek hospitals in order to determine the MIC trends in the aforementioned antimicrobials for the clinically important Gram-positive cocci during a 5-year period. The present study underlines the steady decrease of vancomycin MIC among S. aureus isolates (MRSA and MSSA). Our findings contradict
Fig. 1. Yearly consumption of vancomycin, linezolid, and daptomycin.
the results of other investigators reporting a MIC creep phenomenon in S. aureus (Dhand and Sakoulas, 2012; Yeh et al., 2012). Van Hal et al. (2011) showed that MIC creep is dependent on testing methodology, and it was observed only if the Etest was used, a method applied also in our study. In a study from nine USA medical centers, no yearly tendency towards vancomycin MIC increase during a ten years period among MRSA was revealed and the occurrence of isolates with MIC N1 mg/L was due to clonal dissemination (Sader et al., 2009). Even though no molecular typing of isolates was performed in the present study, ST80 was the predominant clone (1647 of 2410; 68.3%) during the studied period among Greek MRSA isolates, as published (Drougka, et al., 2014). The reported vancomycin MIC decrease in Greek hospitals correlates with the reduction in vancomycin consumption, resulting to lesser pressure in bacteria. Even though all S. aureus isolates were susceptible, 46.7% of the MRSA and 19.7% of the MSSA had an MIC N1 mg/L. Higher vancomycin MIC levels were associated with poorer outcome when vancomycin was used as treatment option (Soriano et al., 2008), leading to an increase in linezolid and daptomycin consumption. An increase of linezolid MIC among MRSA and MR-CNS was also observed in this study and is probably due to increased linezolid consumption. Clonal dissemination of linezolid-resistant MR-CNS isolates (43 of 802; 5.4%) may also play a role in the increase of linezolid MIC levels among this population
Table 1 Evolution of MICs50 and MICs90 among studied isolates. Number
Vancomycin MIC50
MIC90
Linezolid MIC50
Daptomycin MIC90
MIC50
Number
Vancomycin
Linezolid
MIC90
MIC50
MIC90
MIC50
MIC90
MIC50
MIC90
2 2 2 2 2 2
1.5 1.5 1.5 1 1.5 1.5
2 1.5 2 1.5 1.5 1.5
0.25 0.25 0.5 0.5 0.25 0.25
1 0.75 1 1 0.75 1
2 2 1.5 1.5 1 2
1.5 1.5 1.5 1.5 1.5 1.5
1.5 1.5 1.5 1.5 1.5 1.5
0.25 0.25 0.25 0.25 0.25 0.25
0.5 0.5 0.5 0.38 0.38 0.38
338 340 710 369 310 2067
MRSA 2 1 1.5 1 1 1
Daptomycin
2008 2009 2010 2011 2012 Total
354 331 396 283 320 1684
MSSA 1 1 1 1 0.5 1
2008 2009 2010 2011 2012 Total
18 34 34 62 25 238
MS-CNS 1 1.5 1.5 1.5 1 1.5
2 2 2 2 2 2
0.5 0.5 0.5 1 1 1
1 1 1 1 2 2
0.25 0.25 0.25 0.25 0.25 0.25
0.5 0.5 0.5 0.5 0.5 0.5
98 173 117 306 109 802
MR-CNS 2 2 2 1 1.5 2
3 2 4 3 2 3
1 1 1 1 1 1
2 2 2 4 4 2
0.25 0.5 0.5 0.5 0.5 0.38
1 0.75 0.75 0.75 0.75 0.5
2008 2009 2010 2011 2012 Total
300 311 361 582 264 1818
VSE 2 1 1 1 1 1
2 2 2 2 2 2
2 2 2 2 2 2
2 2 2 2 2 2
1 0.5 0.75 0.5 1 0.5
2 1 1.5 1.5 2 2
50 39 84 95 43 311
VRE 256 256 256 256 256 256
256 256 256 256 256 256
1 1 1.5 1.5 2 1.5
2 2 3 2 2 2
1 1.5 1.5 1.5 1.5 1.5
2 2 2 3 4 2
MICs are depicted in mg/L.
Please cite this article as: Papadimitriou-Olivgeris M, et al, Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-y..., Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.08.002
M. Papadimitriou-Olivgeris et al. / Diagnostic Microbiology and Infectious Disease xxx (2015) xxx–xxx
(Liakopoulos et al., 2010; Papadimitriou-Olivgeris et al., 2013). Even though results concerning daptomycin MIC differ among studied isolates, daptomycin retains high activity against tested Gram-positive cocci. Our collection of MR-CNS and MRSA showed higher daptomycin MIC levels than those reported in a previous study from Greek hospitals during 2006–2007 (Malli et al., 2008). Our study has some limitations. We did not analyze clonal transmission, nor comparison of clinical outcomes and MIC was included. Moreover, Etest was the only method used for MIC determination. In conclusion, a decrease in vancomycin MIC among staphylococci isolated from Greek hospitals was detected, that may be explained by its reduction of consumption. Linezolid and daptomycin remain active against Gram-positive cocci, even though an upward trend of linezolid MIC was observed among several bacterial populations. The emergence of linezolid-resistant MR-CNS combined with a clonal spread may pose a serious threat for the future.
Acknowledgements There was no external financial support received in order to complete the present study and only institutional funds were used.
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Please cite this article as: Papadimitriou-Olivgeris M, et al, Activity of vancomycin, linezolid, and daptomycin against staphylococci and enterococci isolated in 5 Greek hospitals during a 5-y..., Diagn Microbiol Infect Dis (2015), http://dx.doi.org/10.1016/j.diagmicrobio.2015.08.002