Access the full text.
Sign up today, get DeepDyve free for 14 days.
Background: Rationale and aims of the study were to compare colonization frequencies with MDR bacteria isolated from LTCF residents in three different Northern Italian regions, to investigate risk factors for colonization and the genotypic characteristics of isolates. The screening included Enterobacteriaceae expressing extended-spectrum β-lactamases (ESβLs) and high-level AmpC cephalosporinases, carbapenemase-producing Enterobacteriaceae, Pseudomonas aeruginosa or Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Methods: Urine samples and rectal, inguinal, oropharyngeal and nasal swabs were plated on selective agar; resistance genes were sought by PCR and sequencing. Demographic and clinical data were collected. Results: Among the LTCF residents, 75.0% (78/104), 69.4% (84/121) and 66.1% (76/115) were colonized with at least one of the target organisms in LTCFs located in Milan, Piacenza and Bolzano, respectively. ESβL producers (60.5, 66.1 and 53.0%) were highly predominant, mainly belonging to Escherichia coli expressing CTX-M group-1 enzymes. Carbapenemase-producing enterobacteria were found in 7.6, 0.0 and 1.6% of residents; carbapemenase-producing P. aeruginosa and A. baumannii were also detected. Colonization by MRSA (24.0, 5.7 and 14.8%) and VRE (20.2, 0.8 and 0. 8%) was highly variable. Several risk factors for colonization by ESβL-producing Enterobacteriaceae and MRSA were found and compared among LTCFs in the three Provinces. Colonization differences among the enrolled LTCFs can be partially explained by variation in risk factors, resident populations and staff/resident ratios, applied hygiene measures and especially the local antibiotic resistance epidemiology. Conclusions: The widespread diffusion of MDR bacteria in LTCFs within three Italian Provinces confirms that LTCFs are an important reservoir of MDR organisms in Italy and suggests that future efforts should focus on MDR screening, improved implementation of infection control strategies and antibiotic stewardship programs targeting the complex aspects of LTCFs. Keywords: Long-term care facilities, Multicenter study, ESβL, AmpC, Carbapenemases, MRSA, VRE * Correspondence: email@example.com; firstname.lastname@example.org Department of Clinical Surgical Diagnostic and Pediatric Sciences, Laboratory of Microbiology and Clinical Microbiology, University of Pavia, Via Brambilla 74, 27100 Pavia, Italy Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Nucleo et al. Antimicrobial Resistance and Infection Control (2018) 7:33 Page 2 of 11 Background four LTCFs were eligible to participate, and the study Life expectancy in Italy is rapidly increasing, with present was approved by the Ethics Committees of the three refer- values of 80.1 years for males and 84.7 for females . Due ring hospitals; informed written consent was obtained to the ageing population, long-term care facilities (LTCFs), from the residents or, if they were unable to consent, from which provide ongoing skilled nursing care to residents their relatives. and help meet both the medical and non-medical needs of elderly individuals with a chronic illness or disability, play Microbiological methods an important role in the Italian healthcare system. Sample processing, microbial identification and antibiotic Residents in LTCFs have a variety of risk factors for susceptibility testing were carried out in the clinical colonization with multidrug-resistant (MDR) bacteria; microbiology laboratories of the referral hospitals. Micro- therefore, these facilities represent reservoirs of: i) Entero- biological methods for the LTCF screening study in bacteriaceae expressing extended-spectrum β-lactamases Bolzano were previously described . Similar methods (ESβLs), derepressed/acquired high-level AmpC cephalos- were used in the epidemiological studies of Milan and porinases or carbapenemases, ii) Pseudomonas aeruginosa Piacenza LTCFs, with minor modifications. or Acinetobacter baumannii producing carbapenemases For the screening of MDR bacteria from LTCF residents and iii) methicillin-resistant Staphylococcus aureus (MRSA) in Milan midstream or catheter urine samples were cultured and vancomycin-resistant enterococci (VRE) [2–4]. on Oxoid Brilliance™ ESβL plates (Thermo Scientific, UK), To promote detailed studies of various microbiological applying a 10 μgimipenem(IMP) disc (Oxoid, Thermo aspects related to LTCFs in Italy, the Association of Italian Scientific, UK), and on Oxoid Brilliance™ VRE (Thermo Sci- Clinical Microbiologists (Associazione Microbiologi Clinici entific, UK). Inguinal, oropharyngeal and rectal swabs were Italiani; AMCLI) in 2016 has set up a new working group seeded on Oxoid Brilliance™ ESβL, applying a 10 μgIMP consisting of Clinical Microbiologists (Gruppo di Lavoro disc, on Oxoid Brilliance™ VRE and on CHROMagar™ per lo Studio delle Infezioni nelle Residenze Sanitarie MRSA (BD Diagnostics, MD). Nasal swabs were plated on Assistite e Strutture assimilabili; GLISTer); one of the main CHROMagar™ MRSA. All plates were incubated at 35 ± 2 ° objectives of this working group is the study of the distri- C under aerobic conditions for 24–48 h. Isolate identifica- bution and prevalence of MDR organisms in Italian LTCFs tion and antibiotic susceptibility testing were performed by and therefore a multicenter point-prevalence survey, the BD Phoenix™ System (BD Diagnostics, MD), according including the main MDR bacteria as described above, was to European Committee on Antimicrobial Susceptibility performed in 2016 on residents of LTCFs, located in three Testing (EUCAST) criteria , using PHOENIX NMIC/ Northern Italian cities. ID402 for non-urinary Gram-negative bacteria, PHOENIX UNMIC/ID403 for Gram-negative isolates from urine cul- Methods tures, and PHOENIX PMIC/ID88 for MRSA and VRE. The The aim strains were phenotypically confirmed for β-lactamase pro- Rationale and aims of the study were to compare duction by the ESBL+AMPC Screen Kit and the KPC + colonization frequencies with MDR bacteria of LTCF MBL Confirm ID Kit (Rosco Diagnostica A/S, Denmark). residents in three different Northern Italian cities, lo- Similarly, for screening of MDR bacteria from LTCF cated in different Italian regions, and to investigate their residents in Piacenza, midstream or catheter urine sam- genotypic characteristics. Moreover, risk factors for ples were seeded on ChromID CPS agar (BioMèrieux, colonization were compared between LTCFs and Marcy l’Etoile, France); rectal swabs on ChromID ESBL colonization prevalence was correlated with the local Agar (BioMèrieux, Marcy l’Etoile, France), on ChromID epidemiology of invasive MDR isolates. VRE Agar (BioMèrieux, Marcy l’Etoile, France) and on Mac Conkey agar applying a 10 μg meropenem (MER) Facilities, patient characteristics and survey design disc (Oxoid, Thermo Scientific, UK); nasal swabs on In October–November 2016, a multicenter point- Chapman Agar (Oxoid, Thermo Scientific, UK), on prevalence screening study was conducted in four LTCFs ChromID ESBL and on MacConkey agar applying a concerning i) Enterobacteriaceae with ESβLs, 10 μg MER disc; and inguinal swabs on Mannite salt carbapenemases or high-level AmpCs, ii) P. aeruginosa agar (Oxoid, Thermo Scientific, UK). Plates were incu- or A. baumannii with carbapenemases, iii) MRSA and bated at 35 ± 2 °C under aerobic conditions for 24–48 h. VRE. The four facilities, located in the Northern Italian Isolate identification and antibiotic susceptibility testing Provinces of Milan (n = 1), Piacenza (n = 2) and Bolzano were performed using the Vitek 2 System (BioMèrieux, (n = 1), offer high skilled 24 h nursing care. Marcy l’Etoile, France), calibrated against EUCAST cri- Although the overall study was performed over a teria , with AST-N202 cards (including an ESβL test) period of 2 months, the sampling interval in each facility for Gram-negative bacteria, AST-P632 cards (with both lasted for a maximum of 1 week. All residents of the oxacillin and cefoxitin) for MRSA and AST-P586 cards Nucleo et al. Antimicrobial Resistance and Infection Control (2018) 7:33 Page 3 of 11 for VRE. Identification of β-lactamase types was based one site with ESβL producers and MRSA as dependent on Vitek 2 results and on the synergistic effects obtained variables, first as univariate and then as multivariate by the ESβL+AMPC Screen Kit and the KPC + MBL models, including predictors with p <0.05 in the univariate Confirm ID Kit (Rosco Diagnostica A/S, Denmark). VRE analysis, comprising the specific LTCF of residence, using were confirmed by vancomycin and teicoplanin Etest stepwise logistic selection. Analysis were performed using strips (BioMèrieux, Marcy l’Etoile, France). the Medcalc® software version 15.11.4 (MedCalc software, Ostend, Belgium). Molecular characterization of resistance genes Molecular characterization of all MDR isolates was per- Results formed in a common reference laboratory, located at the A variable percentage of LTCF residents, present during the University of Pavia. Total DNA was extracted by the au- point-prevalence survey in the four LTCFs, agreed to par- tomated Puro extraction system (DID, Milan, Italy), ticipate: 104/310 (34%) in Milan, 121/326 (37%) in Piacenza using the DNA tissue kit, according to manufacturer’s (2 LTCFs, with 71/216 and 50/110 participating residents, instructions. The presence of ESβL and carbapenemase respectively), and all 115 (100%) residents in the LTCF in genes was investigated by PCR, targeting bla -, Bolzano; no specific LTCF resident selection criteria were CTX-M bla - bla - bla -, bla - bla -, bla - used in Milan and Piacenza and resident characteristics of SHV KPC , VIM IMP , OXA-48 NDM and bla -type genes, and using published primers and enrolled and not-enrolled residents were similar. The me- GES conditions [7–15], summarized in Additional file 1: dian age of LTCF residents in Milan, Piacenza and Bolzano Table S1. A. baumannii isolates were screened for the was 82 years (range: 65–96 years), 86 years (range: 63– presence of the following carbapenemase genes: bla 102 years) and 77 years (range: 30–94 years) for males, and OXA- -like, bla -like, bla -like and bla -like 90 years (range: 71–102 years), 88 years (69–105 years) and 23 OXA-24 OXA-51 OXA-58 [16–18]. The presence of ISAba1 elements adjacent to 84 years (24–96 years) for females, respectively. The me- bla -like genes was determined as previously dian length of stay of residents in the LTCFs in Milan, OXA-51 described ; AmpC genes were detected by a Piacenza and Bolzano was 23 months (range: 1– multiplex PCR . 199 months), 34 months (range: 1–172 months) and Bacterial isolates collected from the LTCF in Milan 19 months (range: 1–174 months), respectively. Various were screened for bla -, bla - bla - and healthcare staff/resident ratios were found in the LTCFs in KPC VIM , OXA-48 bla -type genes by the Cepheid GeneXpert System Milan (ratio: 0.62; 193/310), Piacenza (ratio: 0.61; 201/326; NDM and confirmed by PCR. Check-MDR CT103 XL array corresponding to 73/110 and 128/216 in the two enrolled (Check points Health B.V., Wageningen, The LTCFs, respectively) and Bolzano (ratio: 0.79; 91/115). Netherlands) has been used to investigate the bla gene Demographic and clinical details of the enrolled LTCF resi- content of a carbapenem-resistant P. aeruginosa strain dents are summarized in Table 1. obtained from an oropharyngeal swab, which tested Isolation frequencies and molecular characterization of negative by previous molecular assays. the antibiotic resistance determinants are shown in For gene sequencing, PCR products were purified Table 2. A high percentage of LTCF residents were colo- using the quantum Wizard® SV Gel and PCR Clean-Up nized with at least one of the target MDR organisms in System (Promega, Madison, WT, USA) and subjected to Milan (75.0%; 78/104), Piacenza (69.4%; 84/121) and double-strand Sanger sequencing. Sequences were ana- Bolzano (66.1%; 76/115); moreover, many residents from lyzed according to the BLAST software . Milan (37.5%; 39/104), Piacenza (19.8%; 24/121) and Bolzano (30.4%; 35/115) were colonized with more than Statistical analysis one MDR organism. A significance level of p ≤ 0.05 was used. In-house physi- ESβL-producing E. coli expressing bla -like CTX-M cians reviewed hospital records and, using a standard genes were highly predominant in Milan (80.4%), questionnaire, recorded demographic and clinical data Piacenza (97.0%) and Bolzano (80.3%) and CTX-M- as follows: patient age, gender, length of stay, Barthel im- type determinants were also identified in Proteus mobility score, coma, comorbidities (dementia, urinary mirabilis, Klebsiella pneumoniae, Citrobacter koseri, incontinence, diabetes, cancer, vascular diseases, chronic Enterobacter cloacae complex and Serratia marces- obstructive pulmonary disease, decubitus ulcer), pres- cens.Most bla genes belonged to group-1 CTX-M- ence of infection, antibiotic treatment in the preceding 3 (72.4%), followed by group-9 (14.8%) and other months and the presence of indwelling medical devices. groups (12.8%). A bla -like gene was detected in a BEL The significance of differences in risk factors and P. aeruginosa strain from the LTCF in Milan. colonization proportions was calculated using the pro- In total, ten carbapenemase-producing Enterobacte- portion comparison test. Logistic regression analyses riaceae were detected: n =7 KPC-producing K. pneu- were developed to investigate colonization of at least moniae and n = 1 VIM-1-producing E. cloacae Nucleo et al. Antimicrobial Resistance and Infection Control (2018) 7:33 Page 4 of 11 Table 1 Demographic and clinical details of LTCF residents from three Italian Provinces Milan (M), % Piacenza (P), % Bolzano (B), % Significant differences (p-value) (n = 104) (n = 121) (n = 115) Male sex 30.7 26.4 43.4 M vs. B (0.05); P vs. B (0.006) Age ≥ 86 years 58.7 60.3 35.6 M vs. B (< 0.001); P vs. B (< 0.001) Antibiotics in preceding 3 months 24.0 50.4 23.4 M vs. P (< 0.001); P vs. B (< 0.001) Fluoroquinolones 8.6 7.4 5.2 Penicillins 2.8 1.6 12.1 M vs. B (0.01); P vs. B (0.001) Cephalosporins 5.7 24.8 1.7 M vs. P (< 0.001); P vs. B (< 0.001) Dementia 42.3 79.3 68.7 M vs. P (< 0.001); M vs. B (< 0.001) Peripheral vascular disease 59.6 47.1 71.3 P vs. B (< 0.001) Urinary incontinence 74.0 84.3 85.2 M vs. P (0.05); M vs. B (0.04) Diabetes 19.2 16.5 20.8 Cancer 8.6 8.2 9.5 Decubitus ulcer 6.7 5.7 11.3 Chronic obstructive pulmonary disease 11.5 9.1 18.2 P vs. B (0.04) Physical disability (Barthel immobility score of 0) 10.4 41.3 67.8 M vs. P (< 0.001); M vs. B (< 0.001); P vs. B (< 0.001) Coma 0.0 0.0 17.4 M vs. B (< 0.001); P vs. B (< 0.001) Any medical device 10.5 23.9 38.2 M vs. P (0.009); M vs. B (< 0.001); P vs. B (0.01) Percutaneous enteral gastrostomy tube 2.8 11.5 20.8 M vs. P (0.01); M vs. B (< 0.001); P vs. B (0.05) Tracheostomy tube 0.0 1.6 9.5 M vs. B (0.001); P vs. B (0.007) Urinary catheter 8.6 6.6 18.2 M vs. B (0.04); P vs. B (0.006) Nasogastric tube 0.0 9.1 1.7 M vs. P (0.001); P vs. B (0.01) Length of stay in LTCF < 6 months 17.7 8.2 17.3 M vs. P (0.03); P vs. B (0.03) Hospital admission in previous 12 months, 22.3 15.8 38.2 M vs. B (0.01); M vs. P (< 0.001) any department P vs. B (< 0.001) Geriatrics 0.0 1.6 9.5 M vs. B (p = 0.001); P vs. B (p = 0.007) Medicine 4.8 5.7 6.0 Orthopedics 3.8 3.3 4.3 a b c Infection 3.8 5.7 0.8 P vs. B (0.03) Urinary tract infection - UTI (2), respiratory tract infection - RTI (1), infected prosthesis (1) RTI (6), UTI (1), skin and soft tissue infection (1) UTI (1) complex were isolated from LTCF residents in Milan, Colonization of LTCF residents with ESβL-producing and n = 2 VIM-1 producers (one E. coli and one enterobacteria and MRSA was associated with several Citrobacter amalonaticus) from residents in Bolzano. risk factors in univariate and multivariate analysis Two carbapenemase-positive P. aeruginosa were (Table 3). In multivariate analysis, the LTCF of residence isolated from LTCF residents in Piacenza: in one case was an independent risk factor for ESβL(p ≤ 0.03 for all a bla and in the other a bla -likegenewere comparisons, except p = 0.53 for the comparison of GES-5 VIM identified. Moreover, two P. aeruginosa isolates col- Milan vs. Piacenza) and MRSA (p ≤ 0.02 for all compari- lected in Milan and Piacenza presented a bla sons) colonization. Risk factors for MRSA colonization GES-1 ESβL. Nine bla -positive A. baumannii were iso- were also associated with resident’s gender; for the OXA-23 lated from two and seven LTCF residents in Milan following risk factors significant differences between and Piacenza, respectively. male (n = 226) and female (n = 114) residents were MRSA strains were most frequently isolated from found: age > 85 years (M: 34.5%; F: 20.4%; p < 0.001), LTCF residents in Milan and Bolzano, whereas VRE iso- hospitalization within the previous 12 months (M: lates were highly prevalent in Milan (n =21 Enterococcus 35.0%; F: 20.4%; p = 0.03), administration of any anti- faecalis), but rare in Piacenza (n =1 E. faecalis) and Bol- biotic within the previous 3 months (M: 40.3%; F: 29.6%; zano (n =1 Enterococcus faecium). p = 0.04) and coma (M: 10.5%; F: 3.5%; p = 0.009). Nucleo et al. Antimicrobial Resistance and Infection Control (2018) 7:33 Page 5 of 11 Table 2 Colonization percentages in residents from LTCFs of three Italian Provinces % of LTCF residents colonized with specific resistance phenotype and genotype and significant differences (p ≤ 0.05) Milan Piacenza Bolzano Significant differences (n = 104) (n = 121) (n = 115) (p ≤ 0.05) All resistance groups (MRSA; VRE; ESβL-/AmpC-producing enterobacteria; 75.0 69.4 66.1 carbapenemase-producing enterobacteria, Pseudomonas aeruginosa and Acinetobacter baumannii) All ESβL-positive enterobacteria 60.5 66.1 53.0 P vs. B (0.04) Escherichia coli,ESβL-positive 48.0 55.3 45.2 blaCTX-M-group-1 33.6 41.3 28.7 P vs. B (0.04) blaCTX-M-group-9 6.7 5.7 9.5 blaCTX-M-group, other than 1 or 9 4.8 9.9 0.0 P vs. B (< 0.001) Proteus mirabilis,ESβL-positive 14.4 9.1 7.0 blaCTX-M-group-1 3.8 4.1 0.0 M vs. B (0.04); P vs. B (0.03) blaCTX-M-group-9 1.9 0.0 0.0 Klebsiella pneumoniae, ESBL-positive 6.7 5.7 6.1 blaCTX-M-group-1 5.7 4.1 1.7 blaCTX-M-group-9 0.9 0.8 0.0 blaCTX-M-group, other than 1 or 9 0.0 0.0 2.7 Morganella morganii,ESβL-positive 1.9 1.6 2.6 Citrobacter koseri,ESβL-positive 0.0 3.3 0.8 blaCTX-M-group other than 1 or 9 0.0 3.3 0.0 Enterobacter cloacae complex,ESβL-positive 0.9 0.8 0.0 blaCTX-M-group-1 0.0 0.8 0.0 blaCTX-M-group other than 1 or 9 0.9 0.0 0.0 Serratia marcescens,ESβL-positive 0.0 0.8 0.0 blaCTX-M-group-1, blaCTX-M-15-like 0.0 0.8 0.0 Providencia stuartii 1.9 0.0 0.0 All high-level AmpC-positive enterobacteria 5.7 3.3 25.2 M vs. B (< 0.001); P vs. B (< 0.001) Enterobacter cloacae complex, high-level AmpC 0.0 0.8 0.0 Morganella morganii, high-level AmpC 3.8 0.8 24.3 M vs. B (< 0.001); P vs. B (< 0.001) blaDHA-type 3.8 0.8 8.7 P vs. B (0.004) Citrobacter freundii, high-level AmpC 0.0 0.8 0.0 Proteus mirabilis, high-level AmpC 1.9 0.0 0.8 blaCMY-type 0.0 0.0 0.8 Serratia marcescens, high-level AmpC 0.0 0.8 0.0 Providencia rustigianii, high-level AmpC 0.9 0.0 0.0 All carbapenemase-positive enterobacteria 7.6 0.0 1.6 M vs. P (0.002); M vs. B (0.03) Klebsiella pneumoniae, blaKPC-type 6.7 0.0 0.0 M vs. P (0.004); M vs. B (0.05) Escherichia coli, blaVIM-1 0.0 0.0 0.8 Enterobacter cloacae complex, blaVIM-1 0.9 0.0 0.0 Citrobacter amalonaticus, blaVIM-1 0.0 0.0 0.8 Carbapenemase-positive Pseudomonas aeruginosa 0.0 1.6 0.0 blaVIM-type 0.0 0.8 0.0 blaGES-5 0.0 0.8 0.0 Carbapenemase-positive Acinetobacter baumannii 1.9 5.8 0.0 P vs. B (0.009) blaOXA-23-like 1.9 5.8 0.0 P vs. B (0.009) Nucleo et al. Antimicrobial Resistance and Infection Control (2018) 7:33 Page 6 of 11 Table 2 Colonization percentages in residents from LTCFs of three Italian Provinces (Continued) % of LTCF residents colonized with specific resistance phenotype and genotype and significant differences (p ≤ 0.05) Milan Piacenza Bolzano Significant differences (n = 104) (n = 121) (n = 115) (p ≤ 0.05) MRSA 24.0 5.7 14.8 M vs. P (< 0.001); P vs. B (0.02) a a b VRE 20.2 0.8 0.8 M vs. P (< 0.001); M vs. B (< 0.001) a b Notes: Enterococcus faecalis; Enterococcus faecium Discussion previous studies of carbapenemase-producing Enterobac- The study evaluated the degree of colonization with drug- teriaceae from Bolzano [22, 23, 31], the VIM-1- resistant bacteria among residents of LTCFs located in producing E. coli and C. amalonaticus isolates from resi- three Northern Italian Provinces, finding high dents in this study were also positive for bla .In SHV-12 colonization of residents in Milan (75.0%), Piacenza the present study, all carbapenemase producers from (69.4%) and Bolzano (66.1%). Many residents had more Milan, except an E. cloacae complex isolate expressing a than one target organism, underscoring the role of LTCFs bla gene, had KPC-type enzymes; similar results VIM-1 as a reservoir for these isolates [2–4]. have been reported by other Italian studies in LTCF resi- Colonization of LTCF residents with ESβL-producing dents [25, 32, 33]. Carbapenemase-producing enterobac- enterobacteria was highly prevalent in all the surveyed teria, especially KPC-producing K. pneumoniae, are LTCFs (60.5% in Milan, 66.1% in Piacenza and 53.0% in epidemically spread in Italy  and the emergence of Bolzano), and group-1 CTX-M-type enzymes were highly this MDR phenotype in LTCFs is worrying, expanding predominant, especially in E. coli (80–97% of isolates). the reservoir of this health care threat. Nevertheless, as Notably, about 82% of K. pneumoniae and 32% of P. mir- previously summarized , carbapenemase-producing abilis isolates also harbored a bla -type gene. In the Enterobacteriaceae are still rare in Italian LTCF resi- CTX-M same Bolzano LTCF, here screened for ESβL-producing dents; the reasons are probably multifactorial, compris- enterobacteria, high colonization percentages, equal to ing clinical characteristics of the enrolled residents  64.0 and 49.0%, were previously found in 2008 and and the low carbapenem selective pressure in LTCFs. On 2012 , respectively; the latter survey also screened a average, only 1.1% of residents enrolled in our screening second LTCF in the Province of Bolzano, showing a study received carbapenems within the previous 3 colonization prevalence of 56.0%. In an Italian study car- months (data not shown). Nevertheless, a ried out in 2006, a colonization prevalence of 54.0% was carbapenemase-producing enterobacteria prevalence of found in LTCF residents bearing a urinary catheter , 7.6% (mainly KPC-producing K. pneumoniae), reported while a more recent multicenter study, performed in 2015 here for the LTCF in Milan, gives rise to concern and and involving 12 Italian LTCFs, reported a mean ESβL has to be addressed by future hygiene and antibiotic colonization of 57.3% (range: 32.8–81.5%) . In all these stewardship measures. Italian studies, CTX-M enzymes were the predominantly This study shows the emergence of carbapenemase- produced ESβLs. The high ESβL colonization rates of > producing P. aeruginosa in LTCF residents in Piacenza, 50% in Italian LTCF residents are paralleled by high ESβL identifying single isolates with bla -type and bla VIM GES-5 prevalence in invasive E. coli isolates . Generally, ESβL determinants. P. aeruginosa expressing bla -type de- VIM carriage in most European countries is strikingly lower terminants is widely spread in Italy , and an outbreak than that found in Italy , with exceptions reported from of GES-5-producing P. aeruginosa was reported from a Ireland [27, 28] and Portugal . LTCF in Japan . Moreover, the ESβL genes bla GES-1 In our screening study, high-level AmpC-producing and bla -like were found in two and one P. aeruginosa BEL Enterobacteriaceae were rarely isolated in LTCF resi- isolates, respectively; the latter rarely detected β- dents in Milan and Piacenza, but 24.3% of LTCF resi- lactamase was previously recovered in P. aeruginosa dents in Bolzano were colonized by M. morganii strains from Belgium . A. baumannii producing expressing a high-level DHA-AmpC phenotype; bla - OXA-23 carbapenemases have an epidemic diffusion in DHA type genes in LTCF isolates have previously been found Italy , reflected in the present study by the isolation in a few E. coli and K. pneumoniae strains from Korea of this resistance type from LTCF residents in Milan , but to our knowledge have not yet been reported in (1.9%) and Piacenza (5.8%). Italian LTCFs. MRSA colonization prevalence here reported ranged Carbapenemase-producing enterobacteria were not widely in the surveyed LTCFs (5.7, 14.8 and 24.0% in found in LTCF residents in Piacenza, rarely in Bolzano Milan, Piacenza and Bolzano, respectively), similar to (1.6%) and more frequently in Milan (7.6%). As found in other Italian studies [25, 39, 40]. Varying MRSA Nucleo et al. Antimicrobial Resistance and Infection Control (2018) 7:33 Page 7 of 11 Table 3 Resident’s risk factors for ESβL and MRSA colonization (cumulative data: Milan, Piacenza, Bolzano) Univariate Multivariate Univariate Multivariate analysis analysis analysis analysis ESBL, % No ESBL, % OR pOR p MRSA, % No MRSA, % OR pOR p (n = 203) (n = 137) (CI 95%) (CI 95%) (n = 45) (n = 295) (CI 95%) (CI 95%) Male sex 34.9 31.3 1.17 0.49 51.1 30.8 2.34 0.008 2.31 0.01 (0.74–1.86) (1.24–4.42) (1.16–4.59) Age ≥ 86 years 52.7 49.2 1.15 0.53 39.0 53.0 0.56 0.09 (0.74–1.78) (0.29–1.10) Antibiotics in preceding 39.9 23.3 2.17 0.001 1.74 0.04 37.7 32.5 1.25 0.48 3 months (1.34–3.54) (1.02–2.98) (0.65–2.41) Fluoroquinolones 7.8 5.8 1.38 0.47 15.5 5.7 3.01 0.02 3.59 0.01 (0.57–3.32) (1.17–7.73) (1.26–10.25) Penicillins 7.3 2.9 2.65 0.09 11.1 4.7 2.50 0.09 (0.86–8.17) (0.85–7.34) Cephalosporins 14.2 6.5 2.37 0.03 4.4 12.2 0.33 0.14 (1.08–5.18) (0.07–1.44) Dementia 63.0 66.4 0.86 (0.54– 0.52 62.2 64.7 0.89 0.74 1.36) (0.47–1.71) Peripheral vascular 62.5 59.1 1.15 0.52 62.2 61.0 1.05 0.87 disease (0.74–1.80) (0.55–2.00) Urinary incontinence 83.2 78.8 1.33 0.30 82.2 81.3 1.06 0.89 (0.77–2.31) (0.46–2.40) Diabetes 18.7 18.9 0.98 0.30 26.6 17.6 1.69 0.15 (0.56–1,71) (0.82–3.51) Cancer 11.8 4.3 2.92 0.02 3.47 0.01 4.4 9.5 0.44 0.27 (1.16–7.36) (1.32–9.16) (0.10–1.93) Decubitus ulcer 9.8 5.1 2.03 0.12 6.6 8.1 0.80 0.73 (0.83–4.94) (0.23–2.79) Chronic obstructive 11.8 14.6 0.78 0.45 15.5 12.5 1.28 0.57 pulmonary disease (0.41–1.48) (0.53–3.08) Physical disability 47.7 32.3 1.91 0.005 2.10 0.01 37.7 41.0 0.87 0.67 (Barthel immobility (1.21–3.02) (1.15–3.83) (0.45–1.66) score of 0) Coma 6.9 4.3 1.61 0.33 6.6 5.7 1.16 0.81 (0.60–4.31) (0.32–4.15) Any medical device 32.5 13.1 3.18 < 2.81 0.002 33.3 23.3 1.63 0.15 (1.79–5.66) 0.001 (1.44–5.47) (0.83–3.21) Percutaneous enteral 15.7 6.5 2.66 0.01 11.1 12.2 0.89 0.83 gastrostomy tube (1.22–5.77) (0.33–2.42) Tracheostomy tube 4.9 2.1 2.31 0.21 4.4 3.7 1.20 0.81 (0.62–8.56) (0.25–5.60) Urinary catheter 15.7 4.3 4.08 0.002 20.0 9.8 2.29 0.04 2.61 0.03 (1.66–10.06) (1.00–5.23) (0.06–6.43) Nasogastric tube 5.9 0.7 8.54 0.04 4.4 3.7 1.20 0.81 (1.09–66.49) (0.25–5.60) Length of stay in 15.6 11.9 1.36 0.34 16.6 13.7 1.25 0.61 LTCF < 6 months (0.71–2.61) (0.51–3.00) Hospital admission in 24.2 27.0 0.87 0.58 37.7 23.4 1.97 0.04 previous 12 months (0.53–1.43) (1.02–3.81) Infection 5.4 2.9 1.90 0.27 8.8 3.7 2.51 0.12 (0.59–6.11) (0.76–8.28) ND: not determined; factors included in multivariate analysis are in italics. For multivariate analysis only significant values are shown Nucleo et al. Antimicrobial Resistance and Infection Control (2018) 7:33 Page 8 of 11 colonization prevalence, ranging from close to zero up follow hygiene, infection prevention and control measures to levels higher than 37%, has been reported in Euro- according to guidelines of The Society for Healthcare Epi- pean studies . demiology of America (SHEA) and The Association for Colonization by VRE in the present study was highly Professionals in Infection Control and Epidemiology variable, ranging from 0.8 to 20.2%. VRE-carriage in (APIC) . Nonetheless, the Bolzano LTCF had intro- European LTCF residents was found to be low, ranging duced enforced hygiene measures, according to the World from 0.0–3% [28, 41, 42]. Health Organization guidelines , after the 2008 For Enterobacteriaceae significant differences in screening study, showing an ESβL colonization prevalence colonization frequencies of LTCF residents were found: i) of 64.0% in LTCF residents ; colonization frequency for CTX-M-type ESβL-producing E. coli between Piacenza decreased significantly to 49.0% (p = 0.02) in 2012 , (highest prevalence) and Bolzano, ii) for high-level AmpC- arriving at a slightly higher percentage of 53.0% in 2016, producing M. morganii (highest prevalence in Bolzano), but other factors such as changed case mixes and risk iii) for carbapenemase producers, with highest prevalence factors may also have contributed to this decrease in ESβL in Milan, iv) for carbapenemase-producing A. baumannii, prevalence . showing highest prevalence in Piacenza, and v) for MRSA Significant differences in antibiotic resistance epidemi- and VRE, most prevalent in Milan. Therefore, no clear ology of blood culture isolates, used as a proxy for the gen- picture of general colonization differences can be deduced eral local antibiotic resistance epidemiology, were registered, from overall colonization prevalence data. as derived from European Antimicrobial Resistance Surveil- A variety of risk factors for MRSA and ESβL lance Network (EARS-Net) data for 2016 . Specifically, colonization have previously been reported ; many of we found the following antibiotic resistance data referred to these have also been analyzed in the present survey. the geographic regions of Milan, Piacenza and Bolzano, Interestingly, male residents carried a more than double respectively: E. coli third generation cephalosporin-resistant: risk for MRSA carriage when compared with female res- 22.1% (29/131), 29.4% (71/259) and 17.8% (56/314); K. pneu- idents, probably because of the higher frequencies of moniae carbapenem-resistant: 29.2% (7/24), 13.5% (10/74) other risk factors in males (administration of any anti- and 6.2% (4/64); A. baumannii carbapenem-resistant: 50.0% biotic within the previous 3 months, hospitalization (1/2,) 100.0% (24/24) and 0.0% (0/2); MRSA: 36.0% (18/50), within the previous 12 months and coma), predisposing 49.7% (82/165) and 14.6% (20/137); E. faecalis VRE: 0.0% (0/ men rather than women to MRSA acquisition. More- 20), 2.4% (2/83) and 0.0% (0/41); E. faecium VRE: 10.0% (1/ over, in our study the trend for an inverse correlation (p 10), 22.2% (6/27) and 8.0% (2/25). This data for blood = 0.09) between age > 85 years and MRSA prevalence culture isolates, compared with our LTCF screening data, was associated with a significantly lower percentage of correlates well for ESβL-producing E. coli, carbapenem- male residents > 85 years, compared to females; similar resistant K. pneumoniae and A. baumannii; on the other results have been found by other authors . In the hand, no correlation for MRSA and VRE can be derived. present survey, administration of cephalosporins during Patient transfer between acute-care facilities and LTCFs the previous 3 months resulted to be an independent contribute to the diffusion of MDR organisms in both risk factor for ESβL colonization; the LTCFs in Piacenza settings; such bi-directional movement of MDR bacteria, registered the highest consumption of cephalosporins, related to acute systemic infections, might be more signifi- correlating with highest ESβL prevalence in LTCF resi- cant for Enterobacteriaceae and A. baumannii than for dents from Piacenza. Other independent risk factors for MRSA and VRE. ESβL colonization were physical disability, the presence Moreover, the snapshot approach used in this study of any invasive medical device and cancer. Whereas no might lead to the sudden increase in prevalence of a spe- significant differences were found between residents in cific resistance phenotype, as shown for high-level the three Provinces for cancer as risk factor, physical dis- AmpC-producing M. morganii detected in 2016 from ability and the presence of any medical device showed Bolzano LTCF residents , which could be a transient highest prevalence in the LTCF in Bolzano; nonetheless, phenomenon. Similarly, the high prevalence of VRE in LTCF residents in Bolzano had the lowest ESβL preva- LTCF residents from Milan could be due to a transitory lence in the present screening study. local epidemic event. Therefore, further factors may have contributed to the Finally, the local circulation of highly transmissible observed differences, comprising staff/resident ratio and clones, for example ESβL-producing E. coli,KPC- practiced hygiene and infection control measures . producing K. pneumoniae and OXA-23-producing A. The LTCF in Bolzano showed the highest staff/resident baumannii could contribute to the explanation of the ratio, and understaffing has been shown to be a risk fac- here reported screening results [38, 47]. tor for colonization of LTCF residents by MDR organ- This study has some limitations. First, it has been done isms . All of the surveyed LTCFs in the present study in only four LTCFs, located in three different Provinces Nucleo et al. Antimicrobial Resistance and Infection Control (2018) 7:33 Page 9 of 11 in Northern Italy, and therefore data may not be extrap- Pneumoniae Carbapenemase; LTCF: Long-Term Care Facility; MBL: Metallo-β- Lactamase; MDR: Multidrug-Resistant; MRSA: Methicillin-Resistant olated to other Italian LTCFs with differing characteris- Staphylococcus aureus; PCR: Polymerase Chain Reaction; PFGE: Pulsed-Field tics. Second, the number of LTCF residents participating Gel Electrophoresis; SHEA: The Society for Healthcare Epidemiology of in the study was variable, ranging from 34% in Milan up America; ST: Sequence Typing; VIM: Verona Integron-Encoded Metallo-β- Lactamase; VRE: Vancomycin-Resistant Enterococci to 100% in Bolzano. Third, we did not use an enrich- ment step during the laboratory analysis; this limitation Acknowledgements is partially compensated by using 4–5 different specimen We wish to thank the residents and their relatives who agreed to participate in this study, the managements and staff of the long-term care facilities and the types for the screening of MDR bacteria. Fourth, microbiology laboratories for excellent advice and technical assistance. We are different sample types, types of media and laboratory grateful to Dr. Francesco Luzzaro, Lecco, for providing regional EARS-Net methodologies have been used in the three laboratories antimicrobial resistance data from the geographic region of Milan. Members of the GLISTer group are kindly acknowledged: Laura Pagani, processing the samples from the different LTCFs. Fifth, Massimo Confalonieri, Richard Aschbacher, Claudio Farina, Paolo Fazii, molecular characterization and typing of isolates in the Francesco Luzzaro, Pier Giorgio Montanera. 2016 study was limited, not including pulsed-field gel Prof. Roberta Migliavacca is a member of the European Society of Clinical Microbiology and Infectious Diseases - Study Group for Infections in the electrophoresis (PFGE) and sequence typing (ST) of iso- Elderly (ESGIE) and would like to thank ESGIE members for their stimulating lates and therefore not permitting the identification of support to write this manuscript. epidemic clusters. Finally, screening of healthcare Funding workers has been done only in one of the enrolled The microbiological work was partially funded by a research grant of the LTCFs , but not in the other surveyed facilities. “Fondo Ricerca e Giovani 2016” -University of Pavia and by an unconditional Despite these limitations, the strength of our study is the grant of Cepheid. comparison of colonization prevalence between LTCFs Availability of data and materials located in three different Provinces, comparing it also The datasets generated during and/or analysed during the current study are with differences in risk factors for colonization and in available from the corresponding author on reasonable request. the local epidemiology of invasive isolates. Authors’ contributions 1 3 EN, MC, VMM, RM performed molecular analysis; RDA, MC, EP, AM, FS, GS Conclusions provided patient′s sample data; EF, CR, RA performed and interpreted We performed a multicenter point-prevalence study in phenotypic investigations; RA, RM, LP analyzed and interpreted results; RA was a major contributor in writing the manuscript. All authors read and LTCFs located in three different Provinces in Northern approved the final manuscript. Italy and found high colonization prevalence of LTCF resi- dents for MDR organisms, especially ESβL-producing E. Ethics approval and consent to participate The study was approved by the Ethics Committees of the three referring coli. Variability between the different facilities was notice- hospitals. able also for other MDR organisms. Differences can be partially explained by i) differences in risk factors for Consent for publication Not applicable. colonization by MDR organisms, ii) changes in resident populations and staff/resident ratios, iii) applied hygiene Competing interests measures and iv) differences in the local epidemiology of The authors declare that they have no competing interests. antibiotic resistance of clinical isolates. This widespread diffusion of MDR bacteria in LTCFs of three Italian Publisher’sNote Provinces confirms that these healthcare facilities are an Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. important reservoir for MDR organisms. Future efforts should focus on screening activities, infection control Author details strategies tailored on the complex aspects of LTCFs and Department of Clinical Surgical Diagnostic and Pediatric Sciences, Laboratory of Microbiology and Clinical Microbiology, University of Pavia, Via implementation of antibiotic stewardship programs. Brambilla 74, 27100 Pavia, Italy. Laboratory of Clinical Microbiology, ASP “Golgi-Redaelli”, via Bartolomeo d’Alviano 78, 20146 Milan, Italy. O.U. of Additional file Microbiology, Azienda Sanitaria Locale di Piacenza, Piacenza, Italy. Geriatric Unit, Comprensorio Sanitario di Bolzano, Bolzano, Italy. Microbiology and Virology Laboratory, Comprensorio Sanitario di Bolzano, Bolzano, Italy. Additional file 1: Table S1. Oligonucleotides used for PCR and sequencing. (DOCX 17 kb) Received: 19 December 2017 Accepted: 20 February 2018 Abbreviations AMCLI: Association of Italian Clinical Microbiologist; APIC: The Association for References Professionals in Infection Control and Epidemiology; CTX-M: Cefotaximase- 1. Istituto nazionale di statistica. http://www.istat.it/. Accessed 24 July 2017. Munich type Extended-Spectrum β-Lactamase; EARS-Net: European 2. Moro ML, Gagliotti C. Antimicrobial resistance and stewardship in long-term Antimicrobial Resistance Surveillance Network; ESβL: Extended-Spectrum β- care settings. Future Med. 2013;8:1011–25. Lactamase; EUCAST: European Committee on Antimicrobial Susceptibility 3. Cassone M, Mody L. Colonization with multi-drug resistant organisms in Testing; GLISTer: Gruppo di Lavoro per lo Studio delle Infezioni nelle nursing homes: scope, importance, and management. Curr Geriatr Rep. Residenze Sanitarie Assistite e Strutture Assimilabili; KPC: Klebsiella 2015;4:87–95. Nucleo et al. Antimicrobial Resistance and Infection Control (2018) 7:33 Page 10 of 11 4. Aschbacher R, Pagani E, Confalonieri M, Farina C, Fazii P, Luzzaro F, et al. Enterobacteriaceae among catheterised inpatients in Italian long-term care Review on colonization of residents and staff in Italian long-term care facilities. BMC Infect Dis. 2013;13:124. facilities by multidrug-resistant bacteria compared with other European 25. Giufrè M, Ricchizzi E, Accogli M, Barbanti F, Monaco M, Pimentel de Araujo F, et countries. Antimicrob Resist Infect Control. 2016;5:33. al. Colonization by multidrug-resistant organisms in long-term care facilities in 5. March A, Aschbacher R, Sleghel F, Soelva S, Kaczor M, Migliavacca R, et al. Italy: a point-prevalence study. Clin Microbiol Infect. 2017;23:961–7. Colonization of residents and staff of an Italian long-term care facility and 26. European Centre for Disease Prevention and Control. https://ecdc.europa. an adjacent acute-care hospital geriatric unit by multidrug-resistant bacteria. eu/. Accessed 24 July 2017. New Microbiol. 2017;40:258–63. 27. Rooney PJ, O'Leary MC, Loughrey AC, McCalmont M, Smyth B, Donaghy P, 6. The European Committee on Antimicrobial Susceptibility Testing. et al. Nursing homes as a reservoir of extended-spectrum beta-lactamase Breakpoint tables for interpretation of MICs and zone diameters. Version 6.0, (ESBL)-producing ciprofloxacin-resistant Escherichia coli. J Antimicrob 2016. http://www.eucast.org Chemother. 2009;64:635–41. 7. Pagani L, Dell’Amico E, Migliavacca R, D’Andrea MM, Giacobone E, 28. Ludden C, Cormican M, Vellinga A, Johnson JR, Austin B, Morris D. Amicosante G, et al. Multiple CTX-M-type extended-spectrum-lactamases in Colonisation with ESBL-producing and carbapenemase-producing nosocomial isolates of Enterobacteriaceae from a hospital in Northern Italy. J Enterobacteriaceae, vancomycin-resistant enterococci, and meticillin-resistant Clin Microbiol. 2003;41:4264–9. Staphylococcus aureus in a long-term care facility over one year. BMC Infect 8. Eckert C, Gautier V, Arlet G. DNA sequence analysis of the genetic environment Dis. 2015;15:168. of various blaCTX-M genes. J Antimicrob Chemother 2006; 57:14–23. 29. Rodrigues C, Mendes AC, Sima F, Bavlovič J, Machado E, Novais Â, et al. Long- 9. Perilli M, Dell’Amico E, Segatore B, De Massis RR, Bianchi C, Luzzaro F, et al. term care facility (LTCF) residents colonized with multidrug-resistant (MDR) Molecular characterization of extended-spectrum β-lactamases produced by Klebsiella pneumoniae lineages frequently causing infections in Portuguese nosocomial isolates of Enterobacteriaceae from an Italian nationwide survey. clinical institutions. Infect Control Hosp Epidemiol. 2017;38:1127–30. J Clin Microbiol. 2002;40:611–4. 30. Yoo JS, Byeon J, Yang J, Yoo JI, Chung GT, Lee YS. High prevalence of 10. Rasheed JK, Jay C, Metchock B, Berkowitz F, Weigel L, Crellin J, et al. extended-spectrum beta-lactamases and plasmid-mediated AmpC beta- Evolution of extended-spectrum beta-lactam resistance (SHV-8) in a strain of lactamases in Enterobacteriaceae isolated from long-term care facilities in Escherichia coli during multiple episodes of bacteremia. Antimicrob Agents Korea. Diagn Microbiol Infect Dis. 2010;67:261–5. Chemother. 1997;41:647–53. 31. Carattoli A, Aschbacher R, March A, Larcher C, Livermore DM, Woodford N. 11. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Complete nucleotide sequence of the IncN plasmid pKOX105 encoding Steward CD, et al. Novel carbapenem-hydrolyzing-lactamase, KPC-1, from a VIM-1, QnrS1 and SHV-12 proteins in Enterobacteriaceae from Bolzano, Italy carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents compared with IncN plasmids encoding KPC enzymes in the USA. J Chemother. 2001;45:1151–61. Antimicrob Chemother. 2010;65:2070–5. 12. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of 32. Del Franco M, Paone L, Novati R, Giacomazzi CG, Bagattini M, Galotto C, et al. acquired carbapenemase genes. Diagn Microbiol Infect Dis. 2011;70:119–23. Molecular epidemiology of carbapenem resistant Enterobacteriaceae in Valle d'Aosta region, Italy, shows the emergence of KPC-2 producing Klebsiella 13. Migliavacca R, Docquier JD, Mugnaioli C, Amicosante G, Daturi R, Lee K. pneumoniae clonal complex 101 (ST101 and ST1789). BMC Microbiol. 2015;15:260. Simple microdilution test for detection of metallo-beta-lactamase production in Pseudomonas aeruginosa. J Clin Microbiol. 2002;40:4388–90. 33. Piazza A, Caltagirone M, Bitar I, Nucleo E, Spalla M, Fogato E, et al. Emergence 14. Lagatolla C, Tonin EA, Monti-Bragadin C, Dolzani L, Gombac F, Bearzi C, et of Escherichia coli sequence type 131 (ST131) and ST3948 with KPC-2, KPC-3 al. Endemic carbapenem-resistant Pseudomonas aeruginosa with acquired and KPC-8 carbapenemases from a long-term care and rehabilitation facility metallo-β-lactamase determinants in European hospital. Emerg Infect Dis. (LTCRF) in northern Italy. Adv Exp Med Biol. 2016;901:77–89. 2004;10:535–8. 34. Giani T, Pini B, Arena F, Conte V, Bracco S, Migliavacca R, et al. 15. Poirel L, Le Thomas I, Naas T, Karim A, Nordmann P. Biochemical sequence Epidemic diffusion of KPC carbapenemase-producing Klebsiella analyses of GES-1, a novel class a extended-spectrum β-lactamase, and the pneumoniae in Italy: results of the first countrywide survey, 15 may to class 1 integron In52 from Klebsiella pneumoniae. Antimicrob Agents 30 June 2011. Euro Surveill. 2013;18(22) Chemother. 2000;44:622–32. 35. Prasad N, Labaze G, Kopacz J, Chwa S, Platis D, Pan CX, et al. Asymptomatic rectal colonization with carbapenem-resistant Enterobacteriaceae and 16. Woodford N, Ellington MJ, Coelho JM, Turton JF, Ward ME, Brown S, et al. Clostridium difficile among residents of a long-term care facility in New York Multiplex PCR for genes encoding prevalent OXA carbapenemases in City. Am J Infect Control. 2016;44:525–32. Acinetobacter spp. Int J Antimicrob Agents. 2006;27:351–3. 17. Poirel L, Docquier J-D, De Luca F, Verlinde A, Ide L, Rossolini GM, et al. BEL- 36. Rossolini GM, Luzzaro F, Migliavacca R, Mugnaioli C, Pini B, De Luca F, et al. 2, an extended-Spectrum β-lactamase with increased activity toward First countrywide survey of acquired metallo-beta-lactamases in gram- expanded-Spectrum Cephalosporins in Pseudomonas aeruginosa. negative pathogens in Italy. Antimicrob Agents Chemother. 2008;52:4023–9. Antimicrob Agents Chemother. 2010;54:533–5. 37. Kanayama A, Kawahara R, Yamagishi T, Goto K, Kobaru Y, Takano M, 18. Higgins PG, Lehmann M, Seifert H. Inclusion of OXA-143 primers in a multiplex Morisada K, et al. Successful control of an outbreak of GES-5 extended- polymerase chain reaction (PCR) for genes encoding prevalent OXA spectrum β-lactamase-producing Pseudomonas aeruginosa in a long-term carbapenemases in Acinetobacter spp. Int J Antimicrob Agents. 2010;35:305. care facility in Japan. J Hosp Infect. 2016;93:35–41. 19. Turton JF, Ward ME, Woodford N, Kaufmann ME, Pike R, Livermore DM, et al. 38. Principe L, Piazza A, Giani T, Bracco S, Caltagirone MS, Arena F, et al. The role of ISAba1 in expression of OXA carbapenemase genes in Epidemic diffusion of OXA-23-producing Acinetobacter baumannii Acinetobacter baumannii. FEMS Microbiol Lett. 2006;258:72–7. isolates in Italy: results of the first cross-sectional countrywide survey. J Clin Microbiol. 2014;52:3004–10. 20. D’Andrea MM, Nucleo E, Luzzaro F, Giani T, Migliavacca R, Vailati F. CMY-16, 39. Brugnaro P, Fedeli U, Pellizzer G, Buonfrate D, Rassu M, Boldrin C, et al. a novel acquired AmpC-type β-lactamase of the CMY/LAT lineage in Clustering and risk factors of methicillin-resistant Staphylococcus aureus multifocal monophyletic isolates of Proteus mirabilis from northern Italy. carriage in two Italian long-term care facilities. Infection. 2009;37:216–21. Antimicrob Agents Chemother. 2006;50:618–24. 21. National Center for Biotechnology Information (NCBI). Basic Local Alignment 40. Monaco M, Bombana E, Trezzi L, Regattin L, Brusaferro S, Pantosti A, et al. Search Tool (BLAST). http://blast.ncbi.nlm.nih.gov/Blast.cgi. Accessed 24 July 2017. Methicillin-resistant Staphylococcus aureus colonizing residents and staff members 22. March A, Aschbacher R, Dhanji H, Livermore DM, Böttcher A, Sleghel F, et al. in a nursing home in northern Italy. J Hosp Infect. 2009;73:182–4. Colonization of residents and staff of a long-term-care facility and adjacent 41. Jans B, Schoevaerdts D, Huang TD, Berhin C, Latour K, Bogaerts P, et acute-care hospital geriatric unit by multiresistant bacteria. Clin Microbiol al. Epidemiology of multidrug-resistant microorganisms among Infect. 2010;16:934–44. nursing home residents in Belgium. PLoS One. 2013;8:e64908. 42. Hogardt M, Proba P, Mischler D, Cuny C, Kempf VA, Heudorf U. Current 23. March A, Aschbacher R, Pagani E, Sleghel F, Soelva G, Hopkins KL, et al. prevalence of multidrug-resistant organisms in long-term care facilities in Changes in colonization of residents and staff of a long-term care facility the Rhine-main district, Germany, 2013. Euro Surveill. 2015;20(26) and an adjacent acute-care hospital geriatric unit by multidrug-resistant bacteria over a four-year period. Scand J Infect Dis. 2014;46:114–22. 43. Nillius D, von Müller L, Wagenpfeil S, Klein R, Herrmann M. Methicillin- 24. Arnoldo L, Migliavacca R, Regattin L, Raglio A, Pagani L, Nucleo E, et al. resistant Staphylococcus aureus in Saarland, Germany: the long-term care Prevalence of urinary colonization by extended spectrum-beta-lactamase facility study. PLoS One. 2016; https://doi.org/10.1371/journal.pone.0153030. Nucleo et al. Antimicrobial Resistance and Infection Control (2018) 7:33 Page 11 of 11 44. Dyar OJ, Pagani L, Pulcini C. Strategies and challenges of antimicrobial stewardship in long-term care facilities. Clin Microbiol Infect. 2015;21:10–9. 45. Smith PW, Bennett G, Bradley S, Drinka P, Lautenbach E, Marx J, et al. SHEA/ APIC guideline: infection prevention and control in the long-term care facility. Infect Control Hosp Epidemiol. 2008;29:785–814. 46. http://apps.who.int/iris/bitstream/10665/44102/1/9789241597906_eng.pdf. Accessed 24 July 2017. 47. Mathers AJ, Peirano G, Pitout JD. The role of epidemic resistance plasmids and international high-risk clones in the spread of multidrug-resistant Enterobacteriaceae. Clin Microbiol Rev. 2015;28:565–91. Submit your next manuscript to BioMed Central and we will help you at every step: • We accept pre-submission inquiries � Our selector tool helps you to ﬁnd the most relevant journal � We provide round the clock customer support � Convenient online submission � Thorough peer review � Inclusion in PubMed and all major indexing services � Maximum visibility for your research Submit your manuscript at www.biomedcentral.com/submit
Antimicrobial Resistance and Infection Control – Springer Journals
Published: Mar 6, 2018
Keywords: Long-term care facilities; Multicenter study; ESβL; AmpC; Carbapenemases; MRSA; VRE
Access the full text.
Sign up today, get DeepDyve free for 14 days.