How to 'SAVE' antibiotics: effectiveness and sustainability of a new model of antibiotic stewardship intervention in the internal medicine area.

BACKGROUND: Antibiotic stewardship (AS) is a cornerstone of the fight against antimicrobial resistance; however, evidence on the best practice to improve antibiotic prescription in various hospital settings is still scarce. This study aimed to measure the efficacy of a non-restrictive AS intervention in the internal medicine area of a tertiary-care hospital across a 3-year period. METHODS: The intervention comprised a 3-month 'intensive phase' based on education and guidelines provision, followed by 9 months of audits and feedback activities. The primary outcome was the overall antibiotic consumption measured as days of therapy (DOTs) and defined daily doses (DDDs). Secondary outcomes were carbapenem and fluoroquinolone consumption, all-cause in-hospital mortality, length of stay, incidence of Clostridioides difficile and carbapenem-resistant Enterobacterales bloodstream infections (CRE-BSIs). All outcomes were measured in the intervention wards comparing the pre-phase with the post-phase using an interrupted time-series model. RESULTS: A total of 145 337 patient days (PDs) and 14 159 admissions were included in the analysis. The intervention was associated with reduced DOTs*1000PDs (-162.2/P = 0.005) and DDDs*1000PDs (-183.6/P ≤ 0.001). A sustained decrease in ward-related antibiotic consumption was also detected during the post-intervention phase and in the carbapenem/fluoroquinolone classes. The intervention was associated with an immediate reduction in length of stay (-1.72 days/P < 0.001) and all-cause mortality (-3.71 deaths*100 admissions/P = 0.002), with a decreasing trend over time. Rates of Clostridioides difficile infections and CRE-BSIs were not significantly impacted by the intervention. CONCLUSIONS: The AS intervention was effective and safe in decreasing antibiotic consumption and length of stay in the internal medicine area. Enabling prescribers to judicious use of antimicrobials through active participation in AS initiatives is key to reach sustained results over time.

Characteristics and Outcomes of Bloodstream Infections in a Tertiary-Care Pediatric Hematology-Oncology Unit: A 10-Year Study.

Bloodstream infections (BSIs) after chemotherapy or hematopoietic stem cell transplantation (HSCT) are a leading cause of morbidity and mortality. Data on 154 BSIs that occurred in 111 onco-hematological patients (57 hematological malignancies, 28 solid tumors, and 26 non-malignant hematological diseases) were retrospectively collected and analyzed. Monomicrobial Gram-positive (GP), Gram-negative (GN), and fungal BSIs accounted for 50% (77/154), 38.3% (59/144), and 3.2% (5/154) of all episodes. Polymicrobial infections were 7.8% (12/154), while mixed bacterial-fungal infections were 0.6% (1/154). The most frequent GN isolates were Escherichia coli (46.9%), followed by Pseudomonas aeruginosa (21.9%), Klebsiella species (18.8%), and Enterobacter species (6.3%). Overall, 18.8% (12/64) of GN organisms were multidrug-resistant (seven Escherichia coli, three Klebsiella pneumoniae, and two Enterobacter cloacae), whereas GP resistance to glycopeptides was observed in 1% (1/97). Initial empirical antibiotic therapy was deemed inappropriate in 12.3% of BSIs (19/154). The 30-day mortality was 7.1% (11/154), while the bacteremia-attributable mortality was 3.9% (6/154). In multivariate analysis, septic shock was significantly associated with 30-day mortality (p = 0.0001). Attentive analysis of epidemiology and continuous microbiological surveillance are essential for the appropriate treatment of bacterial infections in pediatric onco-hematological patients.

Resistome and Virulome of Multi-Drug Resistant E. coli ST131 Isolated from Residents of Long-Term Care Facilities in the Northern Italian Region.

Long-term care facilities (LTCFs) are important reservoirs of antimicrobial-resistant (AMR) bacteria which colonize patients transferred from the hospital, or they may emerge in the facility as a result of mutation or gene transfer. In the present study, we characterized, from a molecular point of view, 43 E. coli strains collected from residents of LTCFs in Northern Italy. The most common lineage found was ST131, followed by sporadic presence of ST12, ST69, ST48, ST95, ST410 and ST1193. All strains were incubators of several virulence factors, with iss, sat, iha and senB being found in 84%, 72%, 63% and 51% of E. coli, respectively. Thirty of the ST131 analyzed were of the O25b:H4 serotype and H30 subclone. The ST131 isolates were found to be mainly associated with IncF plasmids, CTX-M-1, CTX-M-3, CTX-M-15, CTX-M-27 and gyrA/parC/parE mutations. Metallo-ß-lactamases were not found in ST131, whereas KPC-3 carbapenemase was found only in two ST131 and one ST1193. In conclusion, we confirmed the spread of extended-spectrum ß-lactamase genes in E. coli ST131 isolated from colonized residents living inside LTCFs. The ST131 represents an incubator of fluoroquinolones, aminoglycosides and other antibiotic resistance genes in addition to different virulence factors.

Whole-Genome Sequencing (WGS) of Carbapenem-Resistant K. pneumoniae Isolated in Long-Term Care Facilities in the Northern Italian Region.

K. pneumoniae (KPN) is one of the widest spread bacteria in which combined resistance to several antimicrobial groups is frequent. The most common ß-lactamases found in K. pneumoniae are class A carbapenemases, both chromosomal-encoded (i.e., NMCA, IMI-1) and plasmid-encoded (i.e., GES-enzymes, IMI-2), VIM, IMP, NDM, OXA-48, and extended-spectrum ß-lactamases (ESBLs) such as CTX-M enzymes. In the present study, a total of 68 carbapenem-resistant KPN were collected from twelve long-term care facilities (LTCFs) in the Northern Italian region. The whole-genome sequencing (WGS) of each KPN strain was determined using a MiSeq Illumina sequencing platform and analysed by a bacterial analysis pipeline (BAP) tool. The WGS analysis showed the prevalence of ST307, ST512, and ST37 as major lineages diffused among the twelve LTCFs. The other lineages found were: ST11, ST16, ST35, ST253, ST273, ST321, ST416, ST1519, ST2623, and ST3227. The blaKPC-2, blaKPC-3, blaKPC-9, blaSHV-11, blaSHV-28, blaCTX-M-15, blaOXA-1, blaOXA-9, blaOXA-23, qnrS1, qnrB19, qnrB66, aac(6')-Ib-cr, and fosA were the resistance genes widespread in most LTCFs. In this study, we demonstrated the spreading of thirteen KPN lineages among the LTCFs. Additionally, KPC carbapenemases are the most widespread ß-lactamase.

Outbreak of Saprochaete clavata Sepsis in Hematology Patients: Combined Use of MALDI-TOF and Sequencing Strategy to Identify and Correlate the Episodes.

INTRODUCTION: New fungal species are increasingly reported in immunocompromised patients. Saprochaete clavata (S. clavata), an ascomycetous fungus formerly called Geotrichum clavatum, is intrinsically resistant to echinocandins and is often misidentified. OBJECTIVE: We describe a cluster of seven S. clavata infections in hospitalized hematology patients who developed this rare fungemia within a span of 11 months. Three of the seven patients died. Identification of the isolates was determined only with the Saramis database of VitekMS system and sequencing of the internal transcribed spacer (ITS) region. Clonal relatedness of the isolates was determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) analysis; clonal correlation between the strains was investigated by means of phylogenetic analysis, based on single-nucleotide variants (SNPs). Clinical presentation, 1-3 ß-D-glucan (BG) and galactomannan (GM) antigen results and analysis of possible sources of contamination are also described with a prospective case-control study of the outbreak. RESULTS: MALDI-TOF MS-Vitek (bioMerieux, Marcy l'Etoile, France) failed to identify the six isolates, while SARAMIS (bioMerieux, Marcy l'Etoile, France) identified the isolates as S. clavata. Initially, Vitek 2 identified the strains as Geotrichum capitatum in two of the seven cases. Molecular identification gave 99% homology with S. clavata. BG was positive in three out of six patients (range 159 to >523 pg/ml), GM results were always negative. All the isolates were resistant to echinocandins (anidulafungin, micafungin, and caspofungin) and Fluconazole, but susceptible to Flucytosine and Voriconazole. One isolate showed acquired resistance to Flucytosine and Amphotericin B during treatment. Both the correlation-based dendrograms obtained by MALDI-TOF MS (Bruker Daltonics) and MS-Vitek not only clustered six of the seven bloodstream infection (BSI) isolates in the same group, but also showed their strong relatedness. Phylogenetic analysis using SNPrelate showed that the seven samples recorded during the investigation period clustered together. We observed a split between one case and the remainder with a node supported by a z-score of 2.3 (p-value = 0.021) and 16 mutations unique to each branch. CONCLUSION: The use of proteomics for identification and evaluation of strain clonality in outbreaks of rare pathogens is a promising alternative to laborious and time-consuming molecular methods, even if molecular whole-genome sequencing (WGS) typing will still remain the reference method for rare emergent pathogens.

Molecular characterization of carbapenem-resistant Klebsiella pneumoniae ST14 and ST512 causing bloodstream infections in ICU and surgery wards of a tertiary university hospital of Verona (northern Italy): co-production of KPC-3, OXA-48, and CTX-M-15 ß-lactamases.

Klebsiella pneumoniae strain is an important opportunistic pathogen that causes severe nosocomial infections. In the present study a molecular characterization of carbapenem resistant K. pneumoniae, isolated from blood samples of hospitalized patients of Verona University Hospital, was performed. The simultaneous presence of SHV-1/CTX-M-15/KPC-3 and SHV-1/CTX-M-15/OXA-48 serin-ß-lactamases was ascertained in the 89% and 11% of K. pneumoniae ST512 and K. pneumoniae ST14, respectively. Molecular characterization of bla genes showed that blaKPC-3 was found in Tn4401a transposon with the tnpR, tnpA, ISKpn6, and ISKpn7 mobile elements whereas blaCTX-M-15 was detected downstream ISEcp1 genetic element. A class 1 integron with a gene cassette of 780 bp corresponding to aadA2 gene was identified in 33 K. pneumoniae ST512 isolates.

Nocardia infection over 5 years (2011-2015) in an Italian tertiary care hospital.

This study was conducted reviewing clinical records of 14 patients affected by nocardiosis over 5 years in a tertiary care hospital. Nocardia abscessus was responsible for one third of infections, deviating significantly from the results reported by other epidemiological investigations and highlighting the key role of molecular identification tests. Indeed, a precise identification of species is crucial for the determination of antibiotic sensitivity patterns and, consequently, for the choice of antibiotic treatment. Noteworthy, 40% of isolates of N. abscessus (formerly N. asteroides complex) showed resistance to carbapenems, which are usually recommended for empirical therapy.