Assessment of the Activity of Tigecycline against Gram-Positive and Gram-Negative Organisms Collected from Italy between 2012 and 2014, as Part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.)
1
Department of Bio-Medical Sciences, University of Catania, Via Androne 81, Catania 95124, Italy
2
Pfizer Inc., Collegeville, PA 19426, USA
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2016, 9(4), 74; https://doi.org/10.3390/ph9040074
Submission received: 25 August 2016
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Revised: 15 November 2016
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Accepted: 22 November 2016
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Published: 26 November 2016
Abstract
:As part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T) we report the in vitro activity of tigecycline and its comparators against Gram-negative and Gram-positive organisms collected from Italian centers between 2012 and 2014. Minimum inhibitory concentrations were determined according to the broth microdilution methodology of the Clinical and Laboratory Standards Institute, and antimicrobial resistance was determined using the European Committee on Antimicrobial Susceptibility Testing interpretive criteria. Among the Enterobacteriaceae, 31% of Escherichia coli isolates, 22% of Klebsiella pneumoniae, and 1% of Klebsiella oxytoca were extended-spectrum β-lactamase producers (ESBLs). Resistance rates among ESBL-K. pneumoniae and ESBL-E. coli to meropenem were 24% and <1%, respectively. Thirty-seven percent of K. pneumoniae were multidrug resistant (MDR) strains. Resistance rates among isolates of Acinetobacter baumannii to amikacin, levofloxacin and meropenem were between 84% and 94%. Eighty percent of A. baumannii isolates were MDR strains. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 38% of S. aureus isolates. No isolates of MRSA were resistant to linezolid, tigecycline or vancomycin. Antimicrobial resistance remains a problem in Italy with increasing numbers of MDR organisms. Despite high levels, MRSA rates appear to be stabilising. Tigecycline retains its in vitro activity against the majority of organisms, including those with multidrug resistance.
1. Introduction
Across Europe the overuse and misuse of antibiotics has led to increasing rates of antimicrobial resistance, particularly in the southern and eastern areas [1]. Contributing factors include varying rates of infection control, incorrect prescribing behavior, and a lack of patient knowledge and understanding [2,3]. In recent years many healthcare facilities in Europe have implemented infection control programs to combat antimicrobial resistance [1]. Following this, rates of methicillin-resistant Staphylococcus aureus (MRSA) have stabilized in some areas and have decreased in others [1]. Italy is no exception to this, with reports of decreasing rates of MRSA over recent years [4].
A recent report by the European Antimicrobial Resistance Surveillance Network (EARS-Net) showed that in Italy there were increasing rates of resistance among isolates of Klebsiella pneumoniae, Escherichia coli and Acinetobacter spp. to a range of antimicrobial agents, including fluoroquinolones, third-generation cephalosporins, aminoglycosides and carbapenems, alone, or in combination [1]. This rise in multidrug resistance has increased the use of carbapenems resulting in escalating numbers of carbapenem-resistant bacteria [5]. Rates of penicillin- and macrolide-non-susceptibility among Streptococcus pneumoniae also remain high in Italy [1].
Tigecycline is a broad-spectrum antimicrobial agent with in vitro activity against Gram-positive, Gram-negative and multidrug-resistant (MDR) pathogens. It is licensed to treat complicated skin and skin structure infections and complicated intra-abdominal infections in the USA and Europe, and also community-acquired bacterial pneumonia in the USA [6]. The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a global surveillance study which has been ongoing since 2004 and monitors the in vitro antibacterial activity of tigecycline and comparator agents against a range of clinically important Gram-positive and Gram-negative organisms. This paper serves as an update of the one by Stefani et al., which covered the period 2004 to 2011 [7]. Here, we report on antimicrobial resistance among isolates of Gram-positive and Gram-negative organisms and their resistant phenotypes collected from Italian T.E.S.T. centers between 2012 and 2014. We also discuss the 2012 to 2014 data in comparison to the 2004 to 2011 data published in the earlier paper by Stefani et al. [7].
2. Results
Between 2012 and 2014 a total of 6605 isolates were examined as part of the T.E.S.T. Italy study; 4535 Gram-negative and 2070 Gram-positive isolates.
2.1. Gram-Negative Organisms
Among isolates of K. pneumoniae, 52%–57% were resistant to amoxicillin/clavulanate, cefepime, ceftriaxone, or levofloxacin (Table 1). Resistance to amikacin, meropenem and piperacillin/tazobactam decreased by 10%–13% between 2012 and 2014. Resistance to tigecycline was seen among 6% of K. pneumoniae isolates. Among Klebsiella oxytoca isolates, resistance to amoxicillin/clavulanate, ceftriaxone or piperacillin/tazobactam decreased by 15%–21% between 2012 and 2013, and 17%–26% between 2012 and 2014. Although, K. oxytoca isolates resistant to levofloxacin, cefepime and meropenem were detected in 2012 and 2013 no resistant isolates were detected in 2014. Between 2012 and 2014 only one K. oxytoca isolate was resistant to tigecycline.
Resistance among isolates of E. coli to the majority of antimicrobials in the T.E.S.T. panel remained consistent between 2012 and 2014 (Table 1). Resistance was highest to ampicillin (77%). No E. coli isolates were resistant to tigecycline and only one isolate (collected in 2013) was resistant to meropenem.
Isolates of Enterobacter spp. and Serratia marcescens show similar results; ≤5% of isolates were resistant to amikacin, meropenem or tigecycline (Table 1). Among isolates of Enterobacter spp., percentage resistance to cefepime, ceftriaxone and levofloxacin was ≥10% higher than that for S. marcescens. Twenty-nine percent of Enterobacter spp. and 8% of S. marcescens were resistant to piperacillin/tazobactam.
Breakpoints were only available for three of the antimicrobials in the T.E.S.T. panel against A. baumannii: amikacin, levofloxacin, and meropenem. Between 2012 and 2014 resistance to each of these antimicrobials was ≥84% (Table 1). Resistance among Psuedomonas aeruginosa isolates to amikacin, cefepime, ceftazidime, levofloxacin, meropenem or piperacillin/tazobactam remained below 41% in 2012, 2013 and 2014.
Between 2012 and 2014, ≤10% of Haemophilus influenzae isolates were resistant to amoxicillin/clavulanate, ampicillin and ceftriaxone (Table 1). Less than 1% of isolates were resistant to levofloxacin, meropenem and minocycline.
2.2. Gram-Negative Phenotypes
Between 2012 and 2014, 22% of K. pneumoniae were extended-spectrum β-lactamase (ESBL)-producers and 37% were MDR (Table 2). High percentages of resistance among ESBL-K. pneumoniae were reported for ceftriaxone (99%) and cefepime (93%) (Table 3). Resistance to amikacin, amoxicillin/clavulanate and meropenem decreased by 10%–12% between 2012 and 2014. Resistance to piperacillin/tazobactam reduced from 70% in 2012 to 44% in 2014. Between 2012 and 2014 a 10% increase in resistance among ESBL-K. pneumoniae to cefepime was seen. Tigecycline showed the lowest percentage resistance (8%) between 2012 and 2014. Between 2012 and 2014 ≥94% of MDR K. pneumoniae isolates were resistant to amoxicillin/clavulanate, cefepime, ceftriaxone, levofloxacin and piperacillin/tazobactam; 88% of isolates were resistant to meropenem. Twelve percent of MDR K. pneumoniae were resistant to tigecycline.
Thirty-one percent of E. coli isolates collected between 2012 and 2014 were ESBL-producers (Table 2). Resistance among ESBL-producing E. coli to the majority of antimicrobials in the T.E.S.T. panel remained constant between 2012 and 2014 (Table 3). One exception to this was amoxicillin/clavulanate, which showed a decrease in resistance from 71% in 2012, to 55% in 2013, and 65% in 2014. Cefepime resistance also decreased from 88% in 2012 to 67% in 2014. No isolates of ESBL-E. coli were resistant to tigecycline.
Of the A. baumannii isolates submitted between 2012 and 2014, 80% were MDR strains (Table 2). Among P. aeruginosa, 19% of isolates were MDR strains (Table 2). Among MDR P. aeruginosa, ≥82% of isolates were resistant to cefepime, levofloxacin, meropenem and piperacillin/tazobactam. Resistance among MDR P. aeruginosa to amikacin fluctuated from 51% in 2012, to 44% in 2013 and increased to 61% in 2014. Resistance to ceftazidime decreased by 15% between 2012 and 2014 (Table 3).
Fewer than 10 isolates of ESBL-K. oxytoca, β-lactamase positive H. influenzae (βLPos H. influenzae) and β-lactamase negative ampicillin-resistant H. influenzae (BLNAR H. influenzae) were submitted in any one year between 2012 and 2014 (Table 2).
2.3. Gram-Positive Organisms
Among S. aureus isolates, 62% were methicillin-susceptible (MSSA) and 8% of these isolates were resistant to levofloxacin and 2% were resistant to minocycline (Table 4). No MSSA isolates were resistant to linezolid, tigecycline and vancomycin.
No Enterococcus faecalis isolates were resistant to ampicillin, linezolid or tigecycline (Table 4). Among E. faecium isolates, 86% were resistant to ampicillin. No isolates of E. faecium were resistant to linezolid and only one isolate (in 2013) was resistant to tigecycline.
Among S. pneumoniae isolates the highest rates of resistance were to the macrolides (36%–37%) (Table 4). Between 2012 and 2014 resistance to azithromycin, erythromycin and clarithromycin decreased by 16%–17%. Resistance to clindamycin reduced from 36% in 2012 to 26% in 2014. No isolates of S. pneumoniae were resistant to ceftriaxone, linezolid, meropenem or vancomycin.
Between 2012 and 2014, 84% of Streptococcus agalactiae isolates were resistant to minocycline, 2% were resistant to levofloxacin; no isolates were resistant to linezolid, penicillin, tigecycline or vancomycin (Table 4).
2.4. Gram-Positive Phenotypes
Methicillin-resistant S. aureus accounted for 38% of S. aureus isolates collected between 2012 and 2014 (Table 2). No isolates of MRSA were resistant to linezolid, tigecycline or vancomycin; 83% of isolates were resistant to levofloxacin (Table 5). Data analysis of vancomycin against MRSA showed a downward shift in minimum inhibitory concentration (MICs) between 2004 and 2014 (Figure 1). Between 2012 and 2014, 20% of E. faecium isolates were vancomycin-resistant (Table 2); none of these isolates were resistant to linezolid or tigecycline (Table 5). Ten isolates of vancomycin-resistant E. faecalis and six isolates of penicillin-resistant S. pneumoniae were identified between 2012 and 2014 (Table 2).
3. Discussion
Italy has relatively high rates of antimicrobial resistance compared to other parts of Europe [1]. Reports show that despite an improvement in infection control in Italy, more effort is needed to standardize infection control procedures between regions and hospitals, as well as to ensure their effective operation [9,10]. This report on T.E.S.T. data from Italy between 2012 and 2014 is an update of the previous publication by Stefani et al. which presented data from the 2004 to 2011 time period [7]. Comparisons between the two studies are limited because the current report uses the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria for determining susceptibility and resistance and the previous publication used the Clinical and Laboratory Standards Institute (CLSI) interpretive criteria [8,11]. Both guidelines use different methods for determining clinical breakpoints: CLSI use a variant of the error-rate-bounded method which incorporates an intermediate zone [12], whereas EUCAST define MIC breakpoints on the basis of epidemiological cut-off values, pharmacokinetic/pharmacodynamic parameters, and by correlating MIC breakpoints to zone diameter values using the “MIC-coloured zone diameter histogram technique” [13]. EUCAST breakpoints do not define an intermediate category which Marchese et al. [14], and Hombach et al. [15,16] conclude will lead to increasing numbers of resistant bacteria being reported in countries that shift from using CLSI to EUCAST criteria, such as Italy. Generally, for the organisms included in this study breakpoints are different between CLSI and EUCAST, with EUCAST typically having lower susceptibility breakpoints. The decision was taken to use the EUCAST criteria in this report as these breakpoints are now considered the European standard and their use would allow the comparison of data from this study with other contemporary studies, it was also felt that the data would be more meaningful to healthcare providers currently practicing.
Our report shows comparable rates of ESBL-producing K. pneumoniae between 2012 and 2014 to that reported in the earlier study by Stefani et al. (22% and 24% respectively) [7]. However, the number of ESBL-producing E. coli isolates has increased between the two studies, from 25% (2004–2011), to 31% (2012–2014) [7]. Tigecycline and meropenem were the most active agents against E. coli and its resistant phenotype (≥98% susceptible); this result is comparable with that by Stefani et al. [7]. A surveillance study by Jones et al. monitored antimicrobial resistance in 21 European countries, including Italy, in 2011. Similarly they also reported elevated levels of ESBL-producing E. coli and Klebsiella spp. (20.1% and 45.7%, respectively) in Europe, as well as comparable rates of susceptibility among ESBL-E. coli to tigecycline and carbapenems (>99%) [17].
Increasing numbers of carbapenem-resistant Enterobacteriaceae are a major global health concern and Italy has one of the highest levels of carbapenem resistance in Europe [1,5,17,18,19,20]. A survey conducted in Italy by Giani et al. in 2011 identified that 2% of all Enterobacteriaceae were carbapenem-resistant, and the majority of these were K. pneumoniae (86.7%) [5]. In 2012 the European Center for Disease Prevention and Control (ECDC) launched the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE) which aimed to monitor epidemiology, undertake surveillance and enhance laboratory capacity and diagnostics [20,21]. A recent report by Albiger et al. on data collected from the EuSCAPE project in 2015 identified that Italy was one of four European countries that classified carbapenemase-producing Enterobacteriaceae as an endemic situation [20]. A Spanish study by Palacios-Baena et al. also reported that K. pneumoniae isolates accounted for a large proportion of carbapenemase-producing Enterobacteriaceae (74%) [22]. Our report shows similar results; in total we report 8.8% (268/3053) of Enterobacteriaceae isolates were meropenem-resistant; 93.3% (250/268) of these were K. pneumoniae isolates.
Jones et al. reported increasing rates of carbapenem resistance among Klebsiella spp. in 2011 from Bulgaria, Greece, Israel, Italy, Poland, Romania, Russia and Turkey [17]. The results from the recent EARS-Net report show that in 2014, Greece, Italy and Romania had the highest levels of carbapenem resistance among K. pneumoniae isolates (62.3%, 32.9% and 31.5%, respectively). Other European countries report <10% of K. pneumoniae isolates were resistant to carbapenems [1]. A report by Magiorakos et al. on invasive K. pneumoniae isolates collected as part of the EARS-Net study between 2005 and 2010 identified there were 18 European countries that reported at least one carbapenem-resistant K. pneumoniae isolate [19]. In 2010 Greece reported the highest rate of carbapenem-resistant K. pneumoniae (49.8%), followed by Cyprus (16.4%), Italy (12.5%), Hungary (5.9%) and Portugal (2.2%) [19]. Percentages of carbapenem-resistant K. pneumoniae continue to increase in Italy, from 15% in 2010, to 27% in 2011 and up to 33% in 2014 [1,23]. This is consistent with our report which shows 33% of K. pneumoniae isolates were resistant to meropenem between 2012 and 2014.
The previous paper by Stefani et al. did not present data on MDR K. pneumoniae [1]. In our analysis, rates of meropenem resistance among MDR K. pneumoniae were 86%–90% between 2012 and 2014. However, statistical analysis using the Cochrane-Armitage trend test shows a significant (p < 0.0001) increase in resistance to meropenem among MDR K. pneumoniae isolates collected between 2004 and 2014; 4.5% (2/44) in 2008, 46.7% (14/30) in 2009, 60% (42/70) in 2010 to 89.4% (101/113) in 2011. These results must be treated with caution due to low n values, although this demonstrates how quickly antimicrobial resistance can become a problem. Conversely, rates of resistance to amikacin among MDR K. pneumoniae decreased significantly (p < 0.0001) over the course of the study from 68.8% (11/16) in 2006 to 21.1% (12/57) in 2014.
Acinetobacter baumannii and P.aeruginosa and their MDR strains are serious nosocomial pathogens and are intrinsically resistant to many antimicrobials [24,25]. Isolates of Acinetobacter spp. are reported more frequently in eastern and southern areas of Europe [1]. Our report identifies 80% of A. baumannii isolates collected in Italy were MDR; this is comparable with results from EARS-Net (>87% of Acinetobacter spp. from Italy were resistant to fluoroquinolones, aminoglycosides and/or carbapenems) [1]. Tigecycline remains active against A. baumannii with an MIC90 of 2 mg/L, which is comparable with data reported by Stefani et al. [7], as well as those from other Italian studies by Mezzatesta et al. and Jones et al. [17,26].
Our report shows that rates of MRSA remain high in Italy (2012–2014, 38% of S. aureus isolates were methicillin-resistant) however rates appear to be stabilizing. Rates of MRSA fluctuated between 34% and 41% between 2012 and 2014 and these results are comparable with those previously published by Stefani et al. [7]. Similarly, an Italian study by Campanile et al. in 2012 identified 35.8% of S. aureus isolates as MRSA [4]. The EARS-Net report shows that Italy was one of seven European countries to have percentages of MRSA >25%. However, there was a decrease in rates of MRSA in Italy between 2011 and 2014 (38.2% and 33.6%, respectively) [1].
As with other studies, both from Italy and other European countries, linezolid, tigecycline and vancomycin were the most active agents against S. aureus, including MRSA [7,17,27,28]. There were no MRSA or enterococci isolates that were resistant to linezolid despite other European reports showing outbreaks of linezolid-resistant MRSA and linezolid-resistant enterococci [17,29,30,31]. Vancomycin-resistant S. aureus remains rare with only a few cases reported globally, mainly in the USA [32]; however there has been a recent report of the first vancomycin-resistant S. aureus strain in Portugal [33]. A cumulative plot of S. aureus MICs over time showed a downward shift in MICs in Italy between 2004 and 2014. Several studies have evaluated vancomycin MIC creep (defined as the progressive increase in vancomycin MICs within a susceptible range) in S. aureus over time [34,35,36]; however our study appears to shown the opposite, with MICs decreasing.
Rates of vancomycin-resistant E. faecalis remain low (3%), with less than 10 isolates submitted in any one year, which is comparable with other parts Europe [1]. Our report shows that 20% of E. faecium isolates were vancomycin-resistant. However, EARS-Net reported lower percentages of vancomycin-resistant E. faecium in Italy (8.5% in 2014) [1].
Tigecycline retained good in vitro activity, with low rates of resistance among Gram-positive (<1%) and Gram-negative organisms (≤6%). Resistance rates among Gram-positive organisms to tigecycline are similar to that reported by Stefani et al. and Jones et al. [7,17]. Similar to our study, Jones et al. use EUCAST breakpoints to determine antimicrobial resistance [17]. Both reports identify there were no isolates of E. coli resistant to tigecycline. Our study reports marginally higher rates of resistance among K. pneumoniae (6%) and Enterobacter spp. (5%) isolates to tigecycline compared to that reported by Jones et al. for Klebsiella spp. (1%) and Enterobacter spp. (1.2%) [17]. Tigecycline is not active in vitro against P. aeruginosa. We report that 90% of A. baumannii isolates were inhibited by tigecycline at a concentration of 2 mg/L. This is comparable with reports from Italy [26], Eastern Europe [27] and Spain [28].
Limitations of this study include the varying number of participating centers and isolates submitted between years, which may cause fluctuations in antimicrobial resistance. It should be noted that despite efforts of Magiorakos et al. to standardize methodology to define MDR, variations in definitions between studies exists, which may cause limitations when comparing rates of MDR between studies [37]. We report the in vitro activity of antimicrobial agents, which limits the ability to compare the relationship of serum levels to dose and resistance at the site of infection.
This report shows that antimicrobial resistance in Italy continues to be major public health concern. There are increasing numbers of MDR organisms, particularly MDR A. baumannii. Despite levels of MRSA remaining high, this appears to have stabilized over recent years. The escalation of carbapenem-resistant Enterobacteriaceae in Italy gives cause for concern and it is therefore essential to monitor these organisms. Tigecycline continues to retain its in vitro activity against the majority of organisms including those with multidrug resistance. The results of this study show the importance of continuing surveillance of antimicrobial resistance and susceptibility to help to reduce the incidence of infection and optimize the use of antimicrobial agents.
4. Materials and Methods
Between 2012 and 2014 a total of 19 Italian centers submitted isolates as part of the T.E.S.T. study. All centers did not participate in all years. Ten centers participated for 3 years, four centers for 2 years, and five centers for 1 year. Details of the isolate collection and antimicrobial susceptibility testing have been previously published (e.g., Stefani et al. [7]). Minimum inhibitory concentrations were determined using broth microdilution methodology described by the CLSI [38]. Antimicrobial susceptibility was determined according to EUCAST interpretive criteria [8]. Methicillin resistance in S. aureus and ESBL-production among E. coli and Klebsiella spp. were determined by IHMA according to CLSI guidelines [39].
In this study multidrug resistance was defined as resistance to three or more classes of antimicrobial agents. Classes used to define MDR Acinetobacter baumannii and P. aeruginosa were the same as previously described by Stefani et al. [7]. Classes used to define MDR K. pneumoniae were aminoglycosides (amikacin), β-lactams (ampicillin, amoxicillin/clavulanate, cefepime, ceftriaxone or piperacillin/tazobactam), carbapenems (imipenem/meropenem), glycylcycline (tigecycline) and quinolones (levofloxacin).
Acknowledgments
The authors would like to thank all Tigecycline Evaluation and Surveillance Trial (T.E.S.T). Italy investigators and laboratories for their participation in the study and would also like to thank the staff at IHMA for their coordination of T.E.S.T. T.E.S.T. is funded by Pfizer Inc. This study was sponsored by Pfizer Inc. Medical writing support was provided by Wendy Hartley and Rachel Beeby, employees of Micron Research Ltd., Ely, UK, which received financial support from Pfizer in connection with the study and development of this manuscript. Micron Research Ltd. also provided data management services which were funded by Pfizer Inc.
Author Contributions
S.S. participated in data collection and interpretation as well as drafting and reviewing the manuscript. M.J.D. was involved in the study design and participated in data interpretation and drafting and review of the manuscript. All authors read and approved the final manuscript.
Conflicts of Interest
S.S. has no competing interests to declare. M.J.D. is an employee of Pfizer, Inc.
References
- European Center for Disease Prevention and Control. Antimicrobial Resistance Surveillance in Europe 2014; Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net); ECDC: Stockholm, Sweden, 2015. [Google Scholar]
- Hulscher, M.E.; van der Meer, J.W.; Grol, R.P. Antibiotic use: How to improve it? Int. J. Med. Microbiol. 2010, 300, 351–356. [Google Scholar] [CrossRef] [PubMed]
- Gualano, M.R.; Gili, R.; Scaioli, G.; Bert, F.; Siliquini, R. General population’s knowledge and attitudes about antibiotics: A systematic review and meta-analysis. Pharmacoepidemiol. Drug Saf. 2015, 24, 2–10. [Google Scholar] [CrossRef] [PubMed]
- Campanile, F.; Bongiorno, D.; Perez, M.; Mongelli, G.; Sesssa, L.; Benvenuto, S.; Gona, F.; AMCLI–S. aureus Survey Participants; Varaldo, P.E.; Stefani, S. Epidemiology of Staphylococcus aureus in Italy: First nationwide survey, 2012. J. Glob. Antimicrob. Resist. 2015, 3, 247–254. [Google Scholar] [CrossRef] [PubMed]
- Giani, T.; Pini, B.; Arena, F.; Conte, V.; Bracco, S.; Migliavacca, R.; AMCLI-CRE Survey Participants; Pantosti, A.; Pagani, L.; Luzzaro, F.; et al. Epidemic diffusion of KPC carbapenemase-producing Klebsiella pneumoniae in Italy: Results of the first countrywide survey, 15 May to 30 June 2011. Euro Surveill. 2013, 18, 1–9. [Google Scholar]
- Pfizer Inc. (Wyeth Pharmaceuticals). Tygacil® Package Insert; Pfizer Inc.: Philadelphia, PA, USA, 2013. Available online: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021821s026s031lbl.pdf (accessed on 15 April 2016).
- Stefani, S.; Dowzicky, M.J. Longitudinal assessment of antimicrobial susceptibility among Gram-negative and Gram-positive organisms collected from Italy as part of the Tigecycline Evaluation and Surveillance Trial between 2004 and 2011. Pharmaceuticals 2013, 6, 1381–1406. [Google Scholar] [CrossRef] [PubMed]
- The European Committee on Antimicrobial Susceptibility Testing. Breakpoint Tables for Interpretation of MICs and Zone Diameters, version 6.0; European Society of Clinical Microbiology and Infectious Disease: Stockholm, Sweden, 2016; Available online: http://www.eucast.org/clinical_breakpoints/ (accessed on 15 April 2016).
- Moro, M.L.; Marchi, M.; Buttazzi, R.; Nascetti, S.; INF-OSS Project Group. Progress in infection prevention and control in Italy: A nationwide survey. J. Hosp. Infect. 2011, 77, 52–57. [Google Scholar] [CrossRef] [PubMed]
- Charrier, L.; Argentero, P.A.; Farina, E.C.; Serra, R.; Mana, F.; Zotti, C.M. Surveillance of healthcare-associated infections in Piemonte, Italy: Results from a second regional prevalence study. BMC Public Health 2014, 14, 558. [Google Scholar] [CrossRef] [PubMed]
- Clinical Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing, 20th ed.; CLSI Supplement M100-S23; CLSI: Wayne, PA, USA, 2013. [Google Scholar]
- Clinical Laboratory Standards Institute (CLSI). Development of in Vitro Susceptibility Testing Criteria and Quality Control Parameters, Approved Guideline, 3rd ed.; CLSI Document M23-A3; CLSI: Wayne, PA, USA, 2008. [Google Scholar]
- European Committee on Antimicrobial Susceptibility Testing. Setting Breakpoints for New Antimicrobial Agents, EUCAST SOP 1.1, 2013. Available online: http://www.eucast.org/documents/sops/ (accessed on 27 October 2016).
- Marchese, A.; Esposito, S.; Barbieri, R.; Bassetti, M.; Debbia, E. Does the adoption of EUCAST susceptibility breakpoints affect the selection of antimicrobials to treat acute community-acquired respiratory tract infections? BMC Infect. Dis. 2012, 12, 181–189. [Google Scholar] [CrossRef] [PubMed]
- Hombach, M.; Bloemberg, G.V.; Böttger, E.C. Effects of clinical breakpoint changes in CLSI guidelines 2010/2011 and EUCAST guidelines 2011 on antibiotic susceptibility test reporting Gram-negative bacilli. J. Antimicrob. Chemother. 2012, 67, 622–632. [Google Scholar] [CrossRef] [PubMed]
- Hombach, M.; Böttger, E.C.; Roos, M. The critical influence of the intermediate category on interpretation errors in revised EUCAST and CLSI antimicrobial susceptibility testing guidleines. Clin. Microbiol. Infect. 2013, 19, E59–E71. [Google Scholar] [CrossRef] [PubMed]
- Jones, R.N.; Flonta, M.; Gurler, N.; Cepparulo, M.; Mendes, R.E.; Castanheira, M. Resistance surveillance program report for selected European nations (2011). Diagn. Microbiol. Infect. Dis. 2014, 78, 429–436. [Google Scholar] [CrossRef] [PubMed]
- Cantón, R.; Akóva, M.; Carmeli, Y.; Giske, C.G.; Glupczynski, Y.; Gniadkowski, M.; Livermore, D.M.; Miriagou, V.; Naas, T.; Rossolini, G.M.; et al. Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe. Clin. Microbiol. Infect. 2012, 18, 413–431. [Google Scholar] [CrossRef] [PubMed]
- Magiorakos, A.P.; Suetens, C.; Monnet, D.L.; Gagliotti, C.; Heuer, O.E.; EARS-Net Coordination Group and EARS-Net Participants. The rise in carbapenem resistance in Europe: Just the tip of the iceberg? Antimicrob. Resist. Infect. Control 2013, 2, 6. [Google Scholar] [PubMed]
- Albiger, B.; Glasner, C.; Struelens, M.J.; Grundmann, H.; Monnet, D.L.; European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) Working Group. Carbapenemase-producing Enterobacteriaceae in Europe: Assessment by national experts from 38 countries, May 2015. Euro Surveill. 2015, 20, 1–18. [Google Scholar]
- European Center for Disease Prevention and Control. Carbapenemase-Producing Bacteria in Europe: Interim Results from the European Survey on Carbapenemases-Producing Enterobacteriaceae (EuSCAPE) Project; ECDC: Stockholm, Sweden, 2013. [Google Scholar]
- Palacios-Baena, Z.R.; Oteo, J.; Conejo, C.; Larrosa, M.N.; Bou, G.; Fernández-Martínez, M.; González-López, J.J.; Martínez-Martínez, L.; Merino, M.; Pomar, V.; et al. Comprehensive clinical and epidemiological assessment of colonization and infection due to carbapenemase-producing Enterobacteriaceae in Spain. J. Infect. 2016, 72, 152–160. [Google Scholar] [CrossRef] [PubMed]
- European Center for Disease Prevention and Control. Antimicrobial Resistance Surveillance in Europe 2013; Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net); ECDC: Stockholm, Sweden, 2014. [Google Scholar]
- Peleg, A.Y.; Seifert, H.; Paterson, D.L. Acinetobacter baumannii: Emergence of a successful pathogen. Clin. Microbiol. Rev. 2008, 21, 538–582. [Google Scholar] [CrossRef] [PubMed]
- Zavascki, A.P.; Carvalhaes, C.G.; Picão, R.C.; Gales, A.C. Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: Resistance mechanisms and implications for therapy. Expert Rev. Anti-Infect. Ther. 2010, 8, 71–93. [Google Scholar] [CrossRef] [PubMed]
- Mezzatesta, M.L.; Trovato, G.; Gona, F.; Nicolosi, V.M.; Nicolosi, D.; Carattoli, A.; Fadda, G.; Nicoletti, G.; Stefani, S. In vitro activity of tigecycline and comparators against carbapenem-susceptible and resistant Acinetobacter baumannii clinical isolates in Italy. Ann. Clin. Microbiol. Antimicrob. 2008, 7, 4. [Google Scholar] [CrossRef] [PubMed]
- Balode, A.; Punda-Polic, V.; Dowzicky, M.J. Antimicrobial susceptibility of Gram-negative and Gram-positive bacteria collected from countries in Eastern Europe: Results from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) 2004–2010. Int. J. Antimicrob. Agents 2013, 41, 527–535. [Google Scholar] [CrossRef] [PubMed]
- Marco, F.; Dowzicky, M.J. Antimicrobial susceptibility among important pathogens collected as part of the Tigecycline Evaluation and Surveillance Trial (T. E.S.T.) in Spain, 2004–2014. J. Glob. Antimicrob. Resist. 2016, 6, 50–56. [Google Scholar] [CrossRef] [PubMed]
- Jones, R.N.; Kohno, S.; Ono, Y.; Ross, J.E.; Yanagihara, K. ZAPPS International Surveillance Program (2007) for linezolid resistance: Results from 5591 Gram-positive clinical isolates in 23 countries. Diagn. Microbiol. Infect. Dis. 2009, 64, 191–201. [Google Scholar] [CrossRef] [PubMed]
- Sánchez García, M.; De la Torre, M.A.; Morales, G.; Peláez, B.; Tolón, M.J.; Domingo, S.; Candel, F.J.; Andrade, R.; Arribi, A.; García, N.; et al. Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit. JAMA 2010, 303, 2260–2264. [Google Scholar] [CrossRef] [PubMed]
- Ross, J.E.; Farrell, D.J.; Mendes, R.E.; Sader, H.S.; Jones, R.N. Eight-year (2002–2009) summary of the linezolid (Zyvox® Annual Appraisal of Potency and Spectrum; ZAAPS) program in European countries. J. Chemother. 2011, 23, 71–76. [Google Scholar] [CrossRef] [PubMed]
- Limbago, B.M.; Kallen, A.J.; Zhu, W.; Eggers, P.; McDougal, L.K.; Albrecht, V.S. Report of the 13th vancomycin-resistant Staphylococcus aureus isolate from the United States. J. Clin. Microbiol. 2014, 52, 998–1102. [Google Scholar] [CrossRef] [PubMed]
- Melo-Cristino, J.; Resina, C.; Manuel, V.; Lito, L.; Ramirez, M. First case of infection with vancomycin-resistant Staphylococcus aureus in Europe. Lancet 2013, 382, 205. [Google Scholar] [CrossRef]
- Wang, G.; Hindler, J.F.; Ward, K.W.; Bruckner, D.A. Increased vancomycin MICs for Staphylococcus aureus clinical isolates from a University Hospital during a 5-year period. J. Clin. Microbiol. 2006, 44, 3883–3886. [Google Scholar] [CrossRef] [PubMed]
- Steinkraus, G.; White, R.; Friedrich, L. Vancomycin MIC creep in non-vancomycin-intermediate Staphylococcus aureus (VISA), vancomycin-susceptible clinical methicillin-resistant (MRSA) blood isolates from 2001 to 2005. J. Antimicrob. Chemother. 2007, 60, 788–794. [Google Scholar] [CrossRef] [PubMed]
- Sader, H.S.; Fey, P.D.; Limaye, A.P.; Madinger, N.; Pankey, G.; Rahal, J.; Rybak, M.J.; Snydman, D.R.; Steed, L.L.; Waites, K.; et al. Evaluation of vancomycin and daptomycin potency trends (MIC creep) against methicillin-resistant Staphylococcus aureus isolates collected in nine U.S. medical centers from 2002 to 2006. Antimicrob. Agents Chemother. 2009, 53, 4127–4132. [Google Scholar] [CrossRef] [PubMed]
- Magiorakos, A.P.; Srinivasan, A.; Carey, R.B.; Carmeli, Y.; Falagas, M.E.; Giske, C.G.; Harbarth, S.; Hindler, J.F.; Kahlmeter, G.; Olsson-Liljequist, B.; et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect. 2012, 18, 268–281. [Google Scholar] [CrossRef] [PubMed]
- Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, Approved Standard 10th ed.; Document MO7-A10; CLSI: Wayne, PA, USA, 2015. [Google Scholar]
- Clinical Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing, 26th ed.; CLSI Supplement M100S; CLSI: Wayne, PA, USA, 2016. [Google Scholar]
Figure 1.
Cumulative minimum inhibitory concentration (MIC) distribution of vancomycin against methicillin-resistant Staphylococcus aureus, Italy 2004 to 2014.
Figure 1.
Cumulative minimum inhibitory concentration (MIC) distribution of vancomycin against methicillin-resistant Staphylococcus aureus, Italy 2004 to 2014.
Table 1.
Antimicrobial activity among Gram-negative organisms collected in Italy between 2012 and 2014.
| 2012 | 2013 | 2014 | 2012–2014 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | |
| Klebsiella pneumoniae | ||||||||||||||||
| N = 297 | N = 304 | N = 154 | N = 755 | |||||||||||||
| AMK | 4 | 32 | 56.2 | 21.2 | 2 | 32 | 73.7 | 11.2 | 4 | 16 | 70.8 | 9.1 | 4 | 32 | 66.2 | 14.7 |
| AMC | 32 | ≥64 | 38.0 | 62.0 | 16 | ≥64 | 46.1 | 53.9 | 16 | ≥64 | 44.2 | 55.8 | 16 | ≥64 | 42.5 | 57.5 |
| FEP | 32 | ≥64 | 42.4 | 55.2 | 2 | ≥64 | 48.7 | 48.0 | 16 | ≥64 | 42.2 | 55.8 | 16 | ≥64 | 44.9 | 52.5 |
| CRO | 64 | 64 | 40.4 | 58.9 | 8 | 64 | 48.7 | 51.3 | 32 | 64 | 42.2 | 57.1 | 32 | 64 | 44.1 | 55.5 |
| LVX | ≥16 | ≥16 | 39.7 | 58.6 | 2 | ≥16 | 48.7 | 49.0 | 8 | ≥16 | 42.9 | 56.5 | 8 | ≥16 | 44.0 | 54.3 |
| MEM | 0.12 | ≥32 | 57.2 | 41.4 | ≤0.06 | ≥32 | 70.7 | 25.7 | ≤0.06 | ≥32 | 68.2 | 31.8 | 0.12 | ≥32 | 64.9 | 33.1 |
| MIN | 4 | 8 | - | - | 2 | 16 | - | - | 2 | 8 | - | - | 4 | 8 | - | - |
| TZP | 128 | ≥256 | 43.1 | 54.5 | 8 | ≥256 | 53.3 | 40.8 | 8 | ≥256 | 53.9 | 41.6 | 16 | ≥256 | 49.4 | 46.4 |
| TGC | 1 | 2 | 82.2 | 4.7 | 0.5 | 2 | 79.6 | 6.3 | 1 | 2 | 76.6 | 6.5 | 1 | 2 | 80.0 | 5.7 |
| Klebsiella oxytoca | ||||||||||||||||
| N = 54 | N = 73 | N = 26 | N = 153 | |||||||||||||
| AMK | 2 | 4 | 98.1 | 0.0 | 2 | 4 | 98.6 | 0.0 | 2 | 2 | 100 | 0.0 | 2 | 4 | 98.7 | 0.0 |
| AMC | 4 | ≥64 | 70.4 | 29.6 | 2 | 8 | 91.8 | 8.2 | 2 | 4 | 96.2 | 3.8 | 2 | 32 | 85.0 | 15.0 |
| FEP | ≤0.5 | 4 | 81.5 | 9.3 | ≤0.5 | ≤0.5 | 95.9 | 2.7 | ≤0.5 | ≤0.5 | 100 | 0.0 | ≤0.5 | 1 | 91.5 | 4.6 |
| CRO | ≤0.06 | 16 | 79.6 | 20.4 | ≤0.06 | 0.25 | 93.2 | 5.5 | ≤0.06 | 0.12 | 96.2 | 3.8 | ≤0.06 | 4 | 88.9 | 10.5 |
| LVX | 0.06 | 8 | 88.9 | 11.1 | 0.03 | 0.12 | 94.5 | 2.7 | 0.03 | 0.06 | 100 | 0.0 | 0.03 | 0.25 | 93.5 | 5.2 |
| MEM | ≤0.06 | 0.12 | 98.1 | 1.9 | ≤0.06 | ≤0.06 | 98.6 | 1.4 | ≤0.06 | ≤0.06 | 100 | 0.0 | ≤0.06 | 0.12 | 98.7 | 1.3 |
| MIN | 1 | 2 | - | - | 1 | 4 | - | - | 1 | 1 | - | - | 1 | 2 | - | - |
| TZP | 2 | ≥256 | 75.9 | 24.1 | 1 | 4 | 97.3 | 2.7 | 1 | 2 | 96.2 | 3.8 | 1 | 32 | 89.5 | 10.5 |
| TGC | 0.25 | 0.5 | 98.1 | 0.0 | 0.25 | 1 | 94.5 | 1.4 | 0.25 | 0.5 | 100 | 0.0 | 0.25 | 0.5 | 96.7 | 0.7 |
| Escherichia coli | ||||||||||||||||
| N = 332 | N = 428 | N = 226 | N = 986 | |||||||||||||
| AMK | 2 | 8 | 97.0 | 0.9 | 2 | 8 | 95.8 | 1.4 | 2 | 8 | 95.6 | 1.3 | 2 | 8 | 96.1 | 1.2 |
| AMC | 8 | 32 | 53.6 | 46.4 | 8 | 32 | 61.0 | 39.0 | 8 | 32 | 59.3 | 40.7 | 8 | 32 | 58.1 | 41.9 |
| AMP | ≥64 | ≥64 | 20.8 | 79.2 | ≥64 | ≥64 | 24.1 | 75.9 | ≥64 | ≥64 | 24.3 | 75.7 | ≥64 | ≥64 | 23.0 | 77.0 |
| FEP | ≤0.5 | ≥64 | 60.2 | 34.0 | ≤0.5 | ≥64 | 61.4 | 31.8 | ≤0.5 | 32 | 63.3 | 26.5 | ≤0.5 | ≥64 | 61.5 | 31.3 |
| CRO | 0.12 | 64 | 59.9 | 38.9 | 0.12 | 64 | 61.9 | 37.6 | ≤0.06 | 64 | 60.6 | 38.1 | 0.12 | 64 | 61.0 | 38.1 |
| LVX | 8 | ≥16 | 43.4 | 55.4 | 8 | ≥16 | 45.6 | 54.2 | 8 | ≥16 | 38.1 | 60.6 | 8 | ≥16 | 43.1 | 56.1 |
| MEM | ≤0.06 | 0.12 | 100 | 0.0 | ≤0.06 | 0.12 | 99.5 | 0.2 | ≤0.06 | ≤0.06 | 98.7 | 0.0 | ≤0.06 | 0.12 | 99.5 | 0.1 |
| MIN | 2 | 16 | - | - | 1 | 16 | - | - | 1 | 8 | - | - | 1 | 8 | - | - |
| TZP | 2 | 32 | 84.0 | 11.4 | 2 | 64 | 83.2 | 12.4 | 2 | 16 | 88.9 | 7.5 | 2 | 32 | 84.8 | 11.0 |
| TGC | 0.12 | 0.5 | 100 | 0.0 | 0.12 | 0.5 | 97.4 | 0.0 | 0.12 | 0.5 | 99.6 | 0.0 | 0.12 | 0.5 | 98.8 | 0.0 |
| Enterobacter spp. | ||||||||||||||||
| N = 268 | N = 389 | N = 190 | N = 847 | |||||||||||||
| AMK | 2 | 4 | 96.6 | 1.5 | 2 | 4 | 97.4 | 1.0 | 2 | 4 | 96.3 | 2.1 | 2 | 4 | 96.9 | 1.4 |
| FEP | ≤0.5 | 16 | 66.0 | 19.4 | ≤0.5 | 16 | 71.2 | 16.7 | ≤0.5 | 16 | 72.6 | 15.3 | ≤0.5 | 16 | 69.9 | 17.2 |
| CRO | 1 | 64 | 51.5 | 47.0 | 0.5 | 64 | 58.4 | 38.8 | 0.5 | 64 | 54.7 | 40.5 | 0.5 | 64 | 55.4 | 41.8 |
| LVX | 0.06 | 8 | 78.0 | 19.8 | 0.06 | ≥16 | 77.1 | 21.1 | 0.06 | ≥16 | 83.7 | 15.8 | 0.06 | ≥16 | 78.9 | 19.5 |
| MEM | ≤0.06 | 0.5 | 96.6 | 0.7 | ≤0.06 | 0.25 | 96.1 | 1.5 | ≤0.06 | 0.25 | 97.4 | 0.5 | ≤0.06 | 0.25 | 96.6 | 1.1 |
| MIN | 2 | 8 | - | - | 2 | 8 | - | - | 2 | 8 | - | - | 2 | 8 | - | - |
| TZP | 4 | 128 | 57.8 | 36.9 | 2 | 128 | 65.8 | 24.9 | 2 | 128 | 67.9 | 26.8 | 4 | 128 | 63.8 | 29.2 |
| TGC | 0.5 | 2 | 89.2 | 4.5 | 0.5 | 2 | 90.0 | 4.9 | 0.5 | 2 | 86.8 | 6.8 | 0.5 | 2 | 89.0 | 5.2 |
| Serratia marcescens | ||||||||||||||||
| N = 107 | N = 131 | N = 74 | N = 312 | |||||||||||||
| AMK a | 2 | 8 | 92.5 | 4.7 | 2 | 4 | 96.2 | 3.1 | 2 | 8 | 94.6 | 0.0 | 2 | 8 | 94.6 | 2.9 |
| FEP | ≤0.5 | 4 | 84.1 | 9.3 | ≤0.5 | 1 | 90.8 | 3.8 | ≤0.5 | 2 | 89.2 | 4.1 | ≤0.5 | 2 | 88.1 | 5.8 |
| CRO | 0.25 | 32 | 76.6 | 19.6 | 0.25 | 4 | 86.3 | 11.5 | 0.25 | 8 | 79.7 | 17.6 | 0.25 | 16 | 81.4 | 15.7 |
| LVX | 0.12 | 2 | 88.8 | 9.3 | 0.12 | 1 | 94.7 | 4.6 | 0.12 | 0.5 | 93.2 | 2.7 | 0.12 | 1 | 92.3 | 5.8 |
| MEM | 0.12 | 1 | 93.5 | 4.7 | 0.12 | 0.25 | 98.5 | 0.8 | ≤0.06 | 0.12 | 98.6 | 0.0 | 0.12 | 0.25 | 96.8 | 1.9 |
| MIN | 4 | 8 | - | - | 4 | 8 | - | - | 2 | 4 | - | - | 4 | 4 | - | - |
| TZP | 2 | 16 | 86.0 | 9.3 | 1 | 4 | 92.4 | 5.3 | 1 | 32 | 82.4 | 10.8 | 1 | 16 | 87.8 | 8.0 |
| TGC | 1 | 2 | 78.5 | 4.7 | 1 | 2 | 74.8 | 1.5 | 1 | 2 | 85.1 | 0.0 | 1 | 2 | 78.5 | 2.2 |
| Acinetobacter baumannii | ||||||||||||||||
| N = 182 | N = 183 | N = 107 | N = 472 | |||||||||||||
| AMK | ≥128 | ≥128 | 14.3 | 84.1 | ≥128 | ≥128 | 11.5 | 86.9 | ≥128 | ≥128 | 15.0 | 79.4 | ≥128 | ≥128 | 13.3 | 84.1 |
| FEP | 32 | ≥64 | - | - | ≥64 | ≥64 | - | - | 32 | ≥64 | - | - | ≥64 | ≥64 | - | - |
| CAZ | 32 | 32 | - | - | 32 | 32 | - | - | 32 | 32 | - | - | 32 | 32 | - | - |
| CRO | 64 | 64 | - | - | 64 | 64 | - | - | 64 | 64 | - | - | 64 | 64 | - | - |
| LVX | ≥16 | ≥16 | 7.1 | 92.9 | ≥16 | ≥16 | 4.4 | 95.6 | ≥16 | ≥16 | 4.7 | 94.4 | ≥16 | ≥16 | 5.5 | 94.3 |
| MEM | ≥32 | ≥32 | 12.6 | 84.6 | ≥32 | ≥32 | 5.5 | 94.5 | ≥32 | ≥32 | 7.5 | 87.9 | ≥32 | ≥32 | 8.7 | 89.2 |
| MIN | 8 | 16 | - | - | 8 | 16 | - | - | 4 | 16 | - | - | 4 | 16 | - | - |
| TZP | ≥256 | ≥256 | - | - | ≥256 | ≥256 | - | - | ≥256 | ≥256 | - | - | ≥256 | ≥256 | - | - |
| TGC | 0.5 | 2 | - | - | 1 | 2 | - | - | 0.5 | 2 | - | - | 0.5 | 2 | - | - |
| Pseudomonas aeruginosa | ||||||||||||||||
| N = 268 | N = 298 | N = 173 | N = 739 | |||||||||||||
| AMK | 4 | 32 | 79.9 | 15.3 | 4 | 16 | 87.6 | 7.4 | 4 | 32 | 81.5 | 12.7 | 4 | 32 | 83.4 | 11.5 |
| FEP | 8 | 32 | 65.3 | 34.7 | 4 | 16 | 69.8 | 30.2 | 8 | 32 | 72.8 | 27.2 | 8 | 32 | 68.9 | 31.1 |
| CAZ | 4 | 32 | 70.1 | 29.9 | 2 | 32 | 76.5 | 23.5 | 2 | 32 | 78.0 | 22.0 | 4 | 32 | 74.6 | 25.4 |
| LVX | 2 | ≥16 | 47.0 | 41.4 | 1 | ≥16 | 58.1 | 31.9 | 1 | ≥16 | 51.4 | 41.0 | 1 | ≥16 | 52.5 | 37.5 |
| MEM | 1 | ≥32 | 59.7 | 26.5 | 1 | 16 | 72.5 | 17.1 | 1 | ≥32 | 59.5 | 27.2 | 1 | ≥32 | 64.8 | 22.9 |
| TZP | 8 | 128 | 67.2 | 32.8 | 4 | 128 | 72.8 | 27.2 | 8 | 64 | 75.1 | 24.9 | 8 | 128 | 71.3 | 28.7 |
| TGC | 8 | 16 | - | - | 8 | 16 | - | - | 8 | 16 | - | - | 8 | 16 | - | - |
| Haemophilus influenzae | ||||||||||||||||
| N = 98 | N = 101 | N = 72 | N = 271 | |||||||||||||
| AMK | 4 | 16 | - | - | 4 | 8 | - | - | 4 | 8 | - | - | 4 | 8 | - | - |
| AMC | 0.5 | 2 | 98.0 | 2.0 | 0.5 | 1 | 99.0 | 1.0 | 0.5 | 2 | 95.8 | 4.2 | 0.5 | 1 | 97.8 | 2.2 |
| AMP | ≤0.5 | 1 | 91.8 | 8.2 | ≤0.5 | 1 | 91.1 | 8.9 | ≤0.5 | 4 | 84.7 | 15.3 | ≤0.5 | 2 | 89.7 | 10.3 |
| FEP | ≤0.5 | ≤0.5 | - | - | ≤0.5 | ≤0.5 | - | - | ≤0.5 | 1 | - | - | ≤0.5 | ≤0.5 | - | - |
| CRO | ≤0.06 | ≤0.06 | 98.0 | 2.0 | ≤0.06 | ≤0.06 | 98.0 | 2.0 | ≤0.06 | 0.12 | 91.7 | 8.3 | ≤0.06 | ≤0.06 | 96.3 | 3.7 |
| LVX | 0.015 | 0.03 | 100 | 0.0 | 0.015 | 0.015 | 100 | 0.0 | 0.015 | 0.25 | 98.6 | 1.4 | 0.015 | 0.03 | 99.6 | 0.4 |
| MEM | ≤0.06 | 0.25 | 100 | 0.0 | ≤0.06 | 0.25 | 100 | 0.0 | 0.12 | 0.25 | 100 | 0.0 | ≤0.06 | 0.25 | 100 | 0.0 |
| MIN | ≤0.5 | 1 | 98.0 | 0.0 | ≤0.5 | 1 | 96.0 | 0.0 | ≤0.5 | 1 | 98.6 | 1.4 | ≤0.5 | 1 | 97.4 | 0.4 |
| TZP | ≤0.06 | ≤0.06 | - | - | ≤0.06 | ≤0.06 | - | - | ≤0.06 | 0.12 | - | - | ≤0.06 | ≤0.06 | - | - |
| TGC | 0.12 | 0.25 | - | - | 0.12 | 0.25 | - | - | 0.12 | 0.25 | - | - | 0.12 | 0.25 | - | - |
MIC50, minimum inhibitory concentration required to inhibit growth of 50% of isolates (mg/L); MIC90, minimum inhibitory concentration required to inhibit growth of 90% of isolates (mg/L); R, resistance; S, susceptibility; AMK, amikacin; AMC, amoxicillin/clavulanate; AMP, ampicillin; FEP, cefepime; CAZ, ceftazidime; CRO, ceftriaxone; LVX, levofloxacin; MEM, meropenem; MIN, minocycline; TZP, piperacillin/tazobactam; TGC, tigecycline; N = total number of isolates. a S. marcescens produces a chromosomal AAC(6′)-Ic enzyme that affects the activity of clinically available aminoglycosides, except streptomycin, gentamicin and arbekacin. “-” no EUCAST resistance or susceptibility breakpoints available.
Table 2.
Rates of Gram-positive and Gram-negative phenotypes collected from Italy between 2012 and 2014.
| 2012 | 2013 | 2014 | 2012–2014 | |||||
|---|---|---|---|---|---|---|---|---|
| n/N | % | n/N | % | n/N | % | n/N | % | |
| Gram-negative | ||||||||
| ESBL-K. pneumoniae | 57/297 | 19.2 | 68/304 | 22.4 | 41/154 | 26.6 | 166/755 | 22.0 |
| MDR K. pneumoniae | 136/297 | 45.8 | 89/304 | 29.3 | 57/154 | 37.0 | 282/755 | 37.4 |
| ESBL-K. oxytoca | 1/54 | 1.9 | 1/73 | 1.4 | 0/26 | 0.0 | 2/153 | 1.3 |
| ESBL-E. coli | 108/332 | 32.5 | 121/428 | 28.3 | 78/226 | 34.5 | 307/986 | 31.1 |
| MDR A. baumannii | 140/182 | 76.9 | 157/183 | 85.8 | 81/107 | 75.7 | 378/472 | 80.1 |
| MDR P. aeruginosa | 69/268 | 25.7 | 41/298 | 13.8 | 33/173 | 19.1 | 143/739 | 19.4 |
| βLPos H. influenzae | 6/98 | 6.1 | 8/101 | 7.9 | 9/72 | 12.5 | 23/271 | 8.5 |
| BLNAR H. influenzae | 2/98 | 2.0 | 1/101 | 1.0 | 2/72 | 2.8 | 5/271 | 1.8 |
| Gram-positive | ||||||||
| Methicillin-resistant S. aureus | 114/331 | 34.4 | 163/398 | 41.0 | 85/214 | 39.7 | 362/943 | 38.4 |
| Van-R E. faecalis | 2/142 | 1.4 | 6/170 | 3.5 | 2/76 | 2.6 | 10/388 | 2.6 |
| Van-R E. faecium | 13/57 | 22.8 | 6/68 | 8.8 | 16/53 | 30.2 | 35/178 | 19.7 |
| Pen-R S. pneumoniae | 1/92 | 1.1 | 3/81 | 3.7 | 2/72 | 2.8 | 6/245 | 2.4 |
ESBL, extended-spectrum β-lactamase; MDR, multidrug-resistant; βLPos, β-lactamase positive; BLNAR, β-lactamase negative ampicillin resistant; Van-R, vancomycin-resistant; Pen-R, penicillin-resistant. N = total number of isolates; n = number of resistant isolates.
Table 3.
Antimicrobial activity among resistant phenotypes of Gram-negative organisms collected from Italy between 2012 to 2014 a.
| 2012 | 2013 | 2014 | 2012–2014 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | |
| ESBL-Klebsiella pneumoniae | ||||||||||||||||
| N = 57 | N = 68 | N = 41 | N = 166 | |||||||||||||
| AMK | 4 | 32 | 61.4 | 17.5 | 4 | 16 | 83.8 | 4.4 | 4 | 16 | 82.9 | 7.3 | 4 | 16 | 75.9 | 9.6 |
| AMC | 32 | ≥64 | 5.3 | 94.7 | 16 | ≥64 | 10.3 | 89.7 | 16 | ≥64 | 17.1 | 82.9 | 32 | ≥64 | 10.2 | 89.8 |
| FEP | ≥64 | ≥64 | 8.8 | 87.7 | ≥64 | ≥64 | 2.9 | 95.6 | 32 | ≥64 | 2.4 | 97.6 | ≥64 | ≥64 | 4.8 | 93.4 |
| CRO | 64 | 64 | 0.0 | 98.2 | 64 | 64 | 0.0 | 100 | 64 | 64 | 2.4 | 97.6 | 64 | 64 | 0.6 | 98.8 |
| LVX | ≥16 | ≥16 | 15.8 | 82.5 | ≥16 | ≥16 | 13.2 | 85.3 | 8 | ≥16 | 12.2 | 87.8 | ≥16 | ≥16 | 13.9 | 84.9 |
| MEM | 0.25 | ≥32 | 64.9 | 29.8 | 0.12 | ≥32 | 75.0 | 22.1 | ≤0.06 | ≥32 | 80.5 | 19.5 | 0.12 | ≥32 | 72.9 | 24.1 |
| MIN | 4 | 8 | - | - | 4 | 8 | - | - | 4 | 8 | - | - | 4 | 8 | - | - |
| TZP | ≥256 | ≥256 | 21.1 | 70.2 | 16 | ≥256 | 35.3 | 44.1 | 16 | ≥256 | 41.5 | 43.9 | 32 | ≥256 | 31.9 | 53.0 |
| TGC | 1 | 2 | 82.5 | 7.0 | 1 | 2 | 73.5 | 8.8 | 1 | 2 | 70.7 | 9.8 | 1 | 2 | 75.9 | 8.4 |
| MDR Klebsiella pneumoniae | ||||||||||||||||
| N = 136 | N = 89 | N = 57 | N = 282 | |||||||||||||
| AMK | 16 | 32 | 11.0 | 45.6 | 16 | ≥128 | 24.7 | 38.2 | 16 | 32 | 29.8 | 21.1 | 16 | 32 | 19.1 | 38.3 |
| AMC | ≥64 | ≥64 | 3.7 | 96.3 | ≥64 | ≥64 | 3.4 | 96.6 | ≥64 | ≥64 | 5.3 | 94.7 | ≥64 | ≥64 | 3.9 | 96.1 |
| FEP | ≥64 | ≥64 | 3.7 | 94.9 | ≥64 | ≥64 | 3.4 | 95.5 | ≥64 | ≥64 | 5.3 | 94.7 | ≥64 | ≥64 | 3.9 | 95.0 |
| CRO | 64 | 64 | 4.4 | 95.6 | 64 | 64 | 4.5 | 95.5 | 64 | 64 | 5.3 | 94.7 | 64 | 64 | 4.6 | 95.4 |
| LVX | ≥16 | ≥16 | 0.0 | 100 | ≥16 | ≥16 | 0.0 | 100 | ≥16 | ≥16 | 0.0 | 100 | ≥16 | ≥16 | 0.0 | 100 |
| MEM | ≥32 | ≥32 | 9.6 | 89.7 | ≥32 | ≥32 | 11.2 | 86.5 | ≥32 | ≥32 | 14.0 | 86.0 | ≥32 | ≥32 | 11.0 | 87.9 |
| MIN | 4 | 8 | - | - | 4 | 16 | - | - | 4 | 8 | - | - | 4 | 8 | - | - |
| TZP | ≥256 | ≥256 | 4.4 | 95.6 | ≥256 | ≥256 | 4.5 | 93.3 | ≥256 | ≥256 | 5.3 | 91.2 | ≥256 | ≥256 | 4.6 | 94.0 |
| TGC | 1 | 2 | 69.9 | 7.4 | 1 | 4 | 57.3 | 15.7 | 1 | 4 | 52.6 | 15.8 | 1 | 4 | 62.4 | 11.7 |
| ESBL-Escherichia coli | ||||||||||||||||
| N = 108 | N = 121 | N = 78 | N = 307 | |||||||||||||
| AMK | 4 | 8 | 94.4 | 0.9 | 4 | 8 | 93.4 | 2.5 | 4 | 16 | 87.2 | 3.8 | 4 | 8 | 92.2 | 2.3 |
| AMC | 16 | 32 | 28.7 | 71.3 | 16 | 32 | 44.6 | 55.4 | 16 | 32 | 34.6 | 65.4 | 16 | 32 | 36.5 | 63.5 |
| AMP | ≥64 | ≥64 | 0.0 | 100 | ≥64 | ≥64 | 0.0 | 100 | ≥64 | ≥64 | 1.3 | 98.7 | ≥64 | ≥64 | 0.3 | 99.7 |
| FEP | 32 | ≥64 | 2.8 | 88.0 | 32 | ≥64 | 1.7 | 83.5 | 16 | ≥64 | 7.7 | 66.7 | 32 | ≥64 | 3.6 | 80.8 |
| CRO | 64 | 64 | 0.0 | 98.1 | 64 | 64 | 2.5 | 96.7 | 64 | 64 | 1.3 | 97.4 | 64 | 64 | 1.3 | 97.4 |
| LVX | 8 | ≥16 | 7.4 | 92.6 | 8 | ≥16 | 5.8 | 94.2 | 8 | ≥16 | 5.1 | 93.6 | 8 | ≥16 | 6.2 | 93.5 |
| MEM | ≤0.06 | 0.12 | 100 | 0.0 | ≤0.06 | 0.12 | 99.2 | 0.8 | ≤0.06 | 0.12 | 97.4 | 0.0 | ≤0.06 | 0.12 | 99.0 | 0.3 |
| MIN | 2 | 16 | - | - | 1 | 8 | - | - | 1 | 8 | - | - | 2 | 8 | - | - |
| TZP | 4 | 32 | 75.9 | 16.7 | 4 | 64 | 79.3 | 12.4 | 2 | 64 | 78.2 | 12.8 | 4 | 64 | 77.9 | 14.0 |
| TGC | 0.12 | 0.5 | 100 | 0.0 | 0.12 | 0.5 | 98.3 | 0.0 | 0.12 | 0.5 | 98.7 | 0.0 | 0.12 | 0.5 | 99.0 | 0.0 |
| MDR Acinetobacter baumannii | ||||||||||||||||
| N = 140 | N = 157 | N = 81 | N = 378 | |||||||||||||
| AMK | ≥128 | ≥128 | 0.0 | 100 | ≥128 | ≥128 | 0.0 | 100 | ≥128 | ≥128 | 0.0 | 100 | ≥128 | ≥128 | 0.0 | 100 |
| FEP | ≥64 | ≥64 | - | - | ≥64 | ≥64 | - | - | ≥64 | ≥64 | - | - | ≥64 | ≥64 | - | - |
| CAZ | 32 | 32 | - | - | 32 | 32 | - | - | 32 | 32 | - | - | 32 | 32 | - | - |
| CRO | 64 | 64 | - | - | 64 | 64 | - | - | 64 | 64 | - | - | 64 | 64 | - | - |
| LVX | ≥16 | ≥16 | 0.0 | 100 | ≥16 | ≥16 | 0.0 | 100 | ≥16 | ≥16 | 0.0 | 100 | ≥16 | ≥16 | 0.0 | 100 |
| MEM | ≥32 | ≥32 | 0.0 | 100 | ≥32 | ≥32 | 0.0 | 100 | ≥32 | ≥32 | 0.0 | 100 | ≥32 | ≥32 | 0.0 | 100 |
| MIN | 8 | 16 | - | - | 8 | 16 | - | - | 8 | 16 | - | - | 8 | 16 | - | - |
| TZP | ≥256 | ≥256 | - | - | ≥256 | ≥256 | - | - | ≥256 | ≥256 | - | - | ≥256 | ≥256 | - | - |
| TGC | 1 | 2 | - | - | 1 | 2 | - | - | 1 | 2 | - | - | 1 | 2 | - | - |
| MDR Pseudomonas aeruginosa | ||||||||||||||||
| N = 69 | N = 41 | N = 33 | N = 143 | |||||||||||||
| AMK | 32 | ≥128 | 36.2 | 50.7 | 8 | 64 | 51.2 | 43.9 | 32 | 64 | 30.3 | 60.6 | 32 | 64 | 39.2 | 51.0 |
| FEP | 32 | ≥64 | 13.0 | 87.0 | 16 | ≥64 | 4.9 | 95.1 | 16 | ≥64 | 18.2 | 81.8 | 16 | ≥64 | 11.9 | 88.1 |
| CAZ | 32 | 32 | 27.5 | 72.5 | 32 | 32 | 24.4 | 75.6 | 16 | 32 | 42.4 | 57.6 | 16 | 32 | 30.1 | 69.9 |
| LVX | ≥16 | ≥16 | 2.9 | 95.7 | ≥16 | ≥16 | 2.4 | 95.1 | ≥16 | ≥16 | 0.0 | 100 | ≥16 | ≥16 | 2.1 | 96.5 |
| MEM | ≥32 | ≥32 | 10.1 | 87.0 | 16 | ≥32 | 7.3 | 87.8 | 16 | ≥32 | 9.1 | 87.9 | 16 | ≥32 | 9.1 | 87.4 |
| TZP | 64 | ≥256 | 15.9 | 84.1 | 64 | ≥256 | 14.6 | 85.4 | 32 | 128 | 27.3 | 72.7 | 64 | ≥256 | 18.2 | 81.8 |
| TGC | 16 | 16 | - | - | 16 | 16 | - | - | 16 | 16 | - | - | 16 | 16 | - | - |
MIC50, minimum inhibitory concentration required to inhibit growth of 50% of isolates (mg/L); MIC90, minimum inhibitory concentration required to inhibit growth of 90% of isolates (mg/L); R, resistance; S, susceptibility; AMK, amikacin; AMC, amoxicillin/clavulanate; AMP, ampicillin; FEP, cefepime; CAZ, ceftazidime; CRO, ceftriaxone; LVX, levofloxacin; MEM, meropenem; MIN, minocycline; TZP, piperacillin/tazobactam; TGC, tigecycline; ESBL, extended-spectrum β-lactamase; MDR, multidrug-resistant; N = total number of isolates. a Data not shown for ESBL-K. oxytoca, β-lactamase positive H. influenzae and β-lactamase negative ampicillin-resistant H. influenzae as the number of isolates submitted was <10 in each year of collection. “-” no EUCAST resistance or susceptibility breakpoints available.
Table 4.
Antimicrobial activity among Gram-positive organisms collected in Italy between 2012 and 2014.
| 2012 | 2013 | 2014 | 2012–2014 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | |
| Methicillin susceptible Staphylococcus aureus | ||||||||||||||||
| N = 217 | N = 235 | N = 129 | N = 581 | |||||||||||||
| AMC | 1 | 2 | - | - | 0.5 | 2 | - | - | 1 | 2 | - | - | 1 | 2 | - | - |
| AMP | 2 | 8 | - | - | 2 | 16 | - | - | 1 | 8 | - | - | 2 | 16 | - | - |
| CRO | 2 | 4 | - | - | 2 | 4 | - | - | 2 | 4 | - | - | 2 | 4 | - | - |
| LVX | 0.25 | 4 | 87.1 | 12.0 | 0.25 | 0.5 | 94.5 | 5.1 | 0.12 | 0.5 | 93.0 | 6.2 | 0.12 | 1 | 91.4 | 7.9 |
| LZD | 2 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 |
| MEM | 0.25 | 0.5 | - | - | ≤0.12 | 0.25 | - | - | ≤0.12 | 0.25 | - | - | ≤0.12 | 0.25 | - | - |
| MIN | ≤0.25 | 0.5 | 96.8 | 1.4 | ≤0.25 | ≤0.25 | 98.3 | 1.7 | ≤0.25 | ≤0.25 | 95.3 | 3.9 | ≤0.25 | ≤0.25 | 97.1 | 2.1 |
| PEN | 2 | ≥16 | 18.9 | 81.1 | 2 | ≥16 | 24.7 | 75.3 | 2 | ≥16 | 24.0 | 76.0 | 2 | ≥16 | 22.4 | 77.6 |
| TZP | 0.5 | 1 | - | - | 0.5 | 1 | - | - | 0.5 | 1 | - | - | 0.5 | 1 | - | - |
| TGC | 0.12 | 0.12 | 100 | 0.0 | 0.12 | 0.12 | 100 | 0.0 | 0.12 | 0.12 | 100 | 0.0 | 0.12 | 0.12 | 100 | 0.0 |
| VAN | 0.5 | 1 | 100 | 0.0 | 0.5 | 1 | 100 | 0.0 | 0.5 | 1 | 100 | 0.0 | 0.5 | 1 | 100 | 0.0 |
| Enterococcus faecalis | ||||||||||||||||
| N = 142 | N = 170 | N = 76 | N = 388 | |||||||||||||
| AMP a | 1 | 2 | 99.3 | 0.0 | 1 | 1 | 100 | 0.0 | 0.5 | 2 | 100 | 0.0 | 1 | 2 | 99.7 | 0.0 |
| LVX | 1 | ≥64 | - | - | 1 | ≥64 | - | - | 1 | ≥64 | - | - | 1 | ≥64 | - | - |
| LZD | 1 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 | 1 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 |
| MEM | 4 | 8 | - | - | 4 | 8 | - | - | 4 | 8 | - | - | 4 | 8 | - | - |
| MIN | 8 | 8 | - | - | 8 | 8 | - | - | 8 | 8 | - | - | 8 | 8 | - | - |
| PEN | 2 | 8 | - | - | 2 | 8 | - | - | 2 | 4 | - | - | 2 | 8 | - | - |
| TZP | 2 | 8 | - | - | 2 | 8 | - | - | 2 | 8 | - | - | 2 | 8 | - | - |
| TGC | 0.06 | 0.12 | 100 | 0.0 | 0.12 | 0.12 | 100 | 0.0 | 0.06 | 0.12 | 100 | 0.0 | 0.06 | 0.12 | 100 | 0.0 |
| VAN | 1 | 2 | 98.6 | 1.4 | 1 | 2 | 96.5 | 3.5 | 1 | 2 | 97.4 | 2.6 | 1 | 2 | 97.4 | 2.6 |
| Enterococcus faecium | ||||||||||||||||
| N = 57 | N = 68 | N = 53 | N = 178 | |||||||||||||
| AMP a | ≥32 | ≥32 | 5.3 | 93.0 | ≥32 | ≥32 | 17.6 | 80.9 | ≥32 | ≥32 | 15.1 | 84.9 | ≥32 | ≥32 | 12.9 | 86.0 |
| LVX | ≥64 | ≥64 | - | - | ≥64 | ≥64 | - | - | ≥64 | ≥64 | - | - | ≥64 | ≥64 | - | - |
| LZD | 2 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 |
| MEM | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - |
| MIN | 4 | 8 | - | - | 1 | 8 | - | - | 4 | 8 | - | - | 4 | 8 | - | - |
| PEN | ≥16 | ≥16 | - | - | ≥16 | ≥16 | - | - | ≥16 | ≥16 | - | - | ≥16 | ≥16 | - | - |
| TZP | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - |
| TGC | 0.06 | 0.06 | 100 | 0.0 | 0.06 | 0.12 | 98.5 | 1.5 | 0.06 | 0.25 | 100 | 0.0 | 0.06 | 0.12 | 99.4 | 0.6 |
| VAN | 1 | ≥64 | 77.2 | 22.8 | 1 | 2 | 91.2 | 8.8 | 1 | ≥64 | 69.8 | 30.2 | 1 | ≥64 | 80.3 | 19.7 |
| Streptococcus pneumoniae | ||||||||||||||||
| N = 92 | N = 81 | N = 72 | N = 245 | |||||||||||||
| AMC | ≤0.03 | 0.12 | - | - | ≤0.03 | 1 | - | - | ≤0.03 | 0.5 | - | - | ≤0.03 | 0.25 | - | - |
| AMP | ≤0.06 | 0.25 | 95.7 | 1.1 | ≤0.06 | 1 | 88.9 | 3.7 | ≤0.06 | 1 | 87.5 | 5.6 | ≤0.06 | 0.5 | 91.0 | 3.3 |
| AZI | 0.12 | 64 | 55.6 | 44.4 | 0.12 | ≥128 | 64.1 | 33.3 | 0.12 | 64 | 72.9 | 27.1 | 0.12 | 64 | 63.4 | 35.7 |
| CRO | ≤0.03 | 0.25 | 96.7 | 0.0 | ≤0.03 | 0.5 | 93.8 | 0.0 | ≤0.03 | 1 | 87.5 | 0.0 | ≤0.03 | 0.5 | 93.1 | 0.0 |
| CLI | 0.03 | 64 | 55.6 | 44.4 | 0.03 | ≥128 | 61.5 | 38.5 | 0.03 | ≥128 | 72.9 | 27.1 | 0.03 | ≥128 | 62.6 | 37.4 |
| CLN | 0.03 | ≥128 | 64.4 | 35.6 | 0.06 | ≥128 | 70.5 | 29.5 | 0.06 | ≥128 | 74.3 | 25.7 | 0.06 | ≥128 | 69.3 | 30.7 |
| ERY | 0.03 | 64 | 56.7 | 43.3 | 0.03 | ≥128 | 64.1 | 35.9 | 0.06 | ≥128 | 72.9 | 27.1 | 0.03 | 64 | 63.9 | 36.1 |
| LVX | 1 | 1 | 100 | 0.0 | 1 | 1 | 95.1 | 4.9 | 0.5 | 1 | 100 | 0.0 | 1 | 1 | 98.4 | 1.6 |
| LZD | ≤0.5 | 1 | 100 | 0.0 | ≤0.5 | 1 | 100 | 0.0 | ≤0.5 | 1 | 100 | 0.0 | ≤0.5 | 1 | 100 | 0.0 |
| MEM | ≤0.12 | 0.25 | 100 | 0.0 | ≤0.12 | 0.25 | 100 | 0.0 | ≤0.12 | 0.5 | 100 | 0.0 | ≤0.12 | 0.25 | 100 | 0.0 |
| MIN | 1 | 8 | 43.5 | 31.5 | 1 | 8 | 32.1 | 32.1 | 0.5 | 4 | 56.9 | 26.4 | 1 | 8 | 43.7 | 30.2 |
| PEN | ≤0.06 | 0.25 | 64.1 | 1.1 | ≤0.06 | 0.5 | 66.7 | 3.7 | ≤0.06 | 1 | 76.4 | 2.8 | ≤0.06 | 0.5 | 68.6 | 2.4 |
| TZP | ≤0.25 | ≤0.25 | - | - | ≤0.25 | 1 | - | - | ≤0.25 | 2 | - | - | ≤0.25 | 1 | - | - |
| TGC | 0.015 | 0.03 | - | - | 0.015 | 0.03 | - | - | 0.015 | 0.03 | - | - | 0.015 | 0.03 | - | - |
| VAN | 0.25 | 0.5 | 100 | 0.0 | 0.25 | 0.5 | 100 | 0.0 | 0.25 | 0.5 | 100 | 0.0 | 0.25 | 0.5 | 100 | 0.0 |
| Streptococcus agalactiae | ||||||||||||||||
| N = 111 | N = 125 | N = 80 | N = 316 | |||||||||||||
| AMC | 0.06 | 0.12 | - | - | 0.06 | 0.12 | - | - | 0.06 | 0.12 | - | - | 0.06 | 0.12 | - | - |
| AMP | ≤0.06 | 0.12 | - | - | 0.12 | 0.12 | - | - | ≤0.06 | 0.12 | - | - | 0.12 | 0.12 | - | - |
| CRO | 0.06 | 0.12 | - | - | 0.06 | 0.12 | - | - | 0.06 | 0.12 | - | - | 0.06 | 0.12 | - | - |
| LVX | 0.5 | 1 | 96.4 | 3.6 | 0.5 | 1 | 96.0 | 2.4 | 0.5 | 1 | 100 | 0.0 | 0.5 | 1 | 97.2 | 2.2 |
| LZD | 1 | 1 | 100 | 0.0 | 1 | 1 | 100 | 0.0 | 1 | 1 | 100 | 0.0 | 1 | 1 | 100 | 0.0 |
| MEM | ≤0.12 | ≤0.12 | - | - | ≤0.12 | ≤0.12 | - | - | ≤0.12 | ≤0.12 | - | - | ≤0.12 | ≤0.12 | - | - |
| MIN | 8 | 8 | 17.1 | 82.0 | 8 | ≥16 | 12.8 | 86.4 | 8 | 8 | 12.5 | 83.8 | 8 | 8 | 14.2 | 84.2 |
| PEN | ≤0.06 | 0.12 | 100 | 0.0 | 0.12 | 0.12 | 100 | 0.0 | ≤0.06 | ≤0.06 | 100 | 0.0 | ≤0.06 | 0.12 | 100 | 0.0 |
| TZP | ≤0.25 | ≤0.25 | - | - | ≤0.25 | ≤0.25 | - | - | ≤0.25 | ≤0.25 | - | - | ≤0.25 | ≤0.25 | - | - |
| TGC | 0.03 | 0.06 | 100 | 0.0 | 0.03 | 0.03 | 100 | 0.0 | 0.03 | 0.06 | 100 | 0.0 | 0.03 | 0.06 | 100 | 0.0 |
| VAN | 0.25 | 0.5 | 100 | 0.0 | 0.5 | 0.5 | 100 | 0.0 | 0.5 | 0.5 | 100 | 0.0 | 0.5 | 0.5 | 100 | 0.0 |
MIC50, minimum inhibitory concentration required to inhibit growth of 50% of isolates (mg/L); MIC90, minimum inhibitory concentration required to inhibit growth of 90% of isolates (mg/L); R, resistance; S, susceptibility; AMK, amikacin; AMC, amoxicillin-clavulanate; AMP, ampicillin; AZI, azithromycin; FEP, cefepime; CRO, ceftriaxone; CLI, clarithromycin; CLN, clindamycin; ERY, erythromycin; LVX, levofloxacin; LZD, linezolid; MEM, meropenem; MIN, minocycline; PEN, penicillin; TZP, piperacillin-tazobactam; TGC, tigecycline; VAN, vancomycin; N = total number of isolates. a Susceptibility to amoxicillin with and without β-lactamase inhibitor can be inferred from ampicillin [8]. “-” no EUCAST resistance or susceptibility breakpoints available.
Table 5.
Antimicrobial activity among resistant phenotypes of Gram-positive organisms collected from Italy between 2012 to 2014 a.
| 2012 | 2013 | 2014 | 2012–2014 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | MIC50 | MIC90 | %S | %R | |
| Methicillin-resistant Staphylococcus aureus | ||||||||||||||||
| N = 114 | N = 163 | N = 85 | N = 362 | |||||||||||||
| AMC | 8 | ≥16 | - | - | 8 | ≥16 | - | - | 4 | ≥16 | - | - | 8 | ≥16 | - | - |
| AMP | 16 | ≥32 | - | - | 16 | ≥32 | - | - | 16 | ≥32 | - | - | 16 | ≥32 | - | - |
| CRO | 32 | ≥128 | - | - | 64 | ≥128 | - | - | 16 | ≥128 | - | - | 32 | ≥128 | - | - |
| LVX | 16 | ≥64 | 14.0 | 84.2 | 16 | 32 | 16.6 | 82.2 | 16 | ≥64 | 12.9 | 84.7 | 16 | ≥64 | 14.9 | 83.4 |
| LZD | 2 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 |
| MEM | 4 | ≥32 | - | - | 4 | ≥32 | - | - | 2 | ≥32 | - | - | 4 | ≥32 | - | - |
| MIN | ≤0.25 | ≤0.25 | 95.6 | 3.5 | ≤0.25 | 0.5 | 96.9 | 1.8 | ≤0.25 | ≤0.25 | 98.8 | 1.2 | ≤0.25 | ≤0.25 | 97.0 | 2.2 |
| PEN | ≥16 | ≥16 | 0.0 | 100 | ≥16 | ≥16 | 0.0 | 100 | 8 | ≥16 | 0.0 | 100 | ≥16 | ≥16 | 0.0 | 100 |
| TZP | 16 | ≥32 | - | - | 16 | ≥32 | - | - | 8 | ≥32 | - | - | 16 | ≥32 | - | - |
| TGC | 0.12 | 0.25 | 100 | 0.0 | 0.12 | 0.25 | 100 | 0.0 | 0.12 | 0.12 | 100 | 0.0 | 0.12 | 0.25 | 100 | 0.0 |
| VAN | 0.5 | 1 | 100 | 0.0 | 0.5 | 1 | 100 | 0.0 | 0.5 | 1 | 100 | 0.0 | 0.5 | 1 | 100 | 0.0 |
| Vancomycin-resistant Enterococcus faecium | ||||||||||||||||
| N = 13 | N = 6 | N = 16 | N = 35 | |||||||||||||
| AMP b | ≥32 | ≥32 | 0.0 | 100 | ≥32 | ≥32 | [0] | [6] | ≥32 | ≥32 | 0.0 | 100 | ≥32 | ≥32 | 0.0 | 100 |
| LVX | ≥64 | ≥64 | - | - | ≥64 | ≥64 | - | - | ≥64 | ≥64 | - | - | ≥64 | ≥64 | - | - |
| LZD | 2 | 2 | 100 | 0.0 | 2 | 2 | [6] | [0] | 2 | 2 | 100 | 0.0 | 2 | 2 | 100 | 0.0 |
| MEM | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - |
| MIN | 4 | 8 | - | - | 1 | 8 | - | - | 2 | 8 | - | - | 4 | 8 | - | - |
| PEN | ≥16 | ≥16 | - | - | ≥16 | ≥16 | - | - | ≥16 | ≥16 | - | - | ≥16 | ≥16 | - | - |
| TZP | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - | ≥32 | ≥32 | - | - |
| TGC | 0.06 | 0.25 | 100 | 0.0 | 0.06 | 0.12 | [6] | [0] | 0.03 | 0.12 | 100 | 0.0 | 0.06 | 0.12 | 100 | 0.0 |
| VAN | ≥64 | ≥64 | 0.0 | 100 | 32 | ≥64 | [0] | [6] | ≥64 | ≥64 | 0.0 | 100 | ≥64 | ≥64 | 0.0 | 100 |
MIC50, minimum inhibitory concentration required to inhibit growth of 50% of isolates (mg/L); MIC90, minimum inhibitory concentration required to inhibit growth of 90% of isolates (mg/L); R, resistance; S, susceptibility; AMC, amoxicillin/clavulanate; AMP, ampicillin; CRO; ceftriaxone; LVX, levofloxacin; LZD, linezolid; MEM, meropenem; MIN, minocycline; PEN, penicillin; TZP, piperacillin/tazobactam; TGC, tigecycline; VAN, vancomycin. a Data not shown for vancomycin-resistant Enterococcus faecalis and penicillin-resistant Streptococcus pneumoniae as the number of resistant isolates submitted was <10 in each year of collection. b Susceptibility to amoxicillin with and without beta-lactamase inhibitor can be inferred from ampicillin [8]. Percentage susceptible or resistant not calculated when <10 isolates. In these cases total number of isolates susceptible to resistant are given in square brackets. “-” no EUCAST resistance or susceptibility breakpoints available.
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Stefani, S.; Dowzicky, M.J. Assessment of the Activity of Tigecycline against Gram-Positive and Gram-Negative Organisms Collected from Italy between 2012 and 2014, as Part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Pharmaceuticals 2016, 9, 74. https://doi.org/10.3390/ph9040074
AMA Style
Stefani S, Dowzicky MJ. Assessment of the Activity of Tigecycline against Gram-Positive and Gram-Negative Organisms Collected from Italy between 2012 and 2014, as Part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Pharmaceuticals. 2016; 9(4):74. https://doi.org/10.3390/ph9040074
Chicago/Turabian StyleStefani, Stefania, and Michael J. Dowzicky. 2016. "Assessment of the Activity of Tigecycline against Gram-Positive and Gram-Negative Organisms Collected from Italy between 2012 and 2014, as Part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.)" Pharmaceuticals 9, no. 4: 74. https://doi.org/10.3390/ph9040074
APA StyleStefani, S., & Dowzicky, M. J. (2016). Assessment of the Activity of Tigecycline against Gram-Positive and Gram-Negative Organisms Collected from Italy between 2012 and 2014, as Part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Pharmaceuticals, 9(4), 74. https://doi.org/10.3390/ph9040074
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