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Antimicrobial susceptibilities, drug resistance gene arrays and epidemic potential of Enterobacteriaceae and other Gram negative clinical isolates: novel diagnostic and therapeutic strategies
Full text linkAntibiotic resistance can be horizontally acquired through transfer of antibiotic resistance plasmids or determinants between bacteria, or can be due to a mutational event in a target site in response of antibiotics excessive use/misuse for treatment of infections in human and veterinary medicine. Consequently the proliferation of Extended Spectrum β-lactamases (ESBLs)- among Gram negative bacteria, mediated through promiscuous conjugative plasmids, transposons and integrons increased the volume of carbapenems into clinical medicine worldwide.
Within this decade, four molecular classes of carbapenemases have emerged throughout the world:
Chromosomal encoded Class A carbapenemases (IMI, NMC-A and SME);
Non chromosomal encoded Class A such as KPC in Enterobacteriaceae;
Class B enzymes MBLs with the most prevalent IMP-and VIM- and NDM-type;
Class D acquired, as OXA-23, OXA-58 and OXA-48-like.
The thesis work was on:
1.Characterizing ESBLs and Class B carbapenemases:
i)CASE STUDY: A 62-year-old patient was transferred to the cardiac rehabilitation unit of the I.R.C.C.S. Fondazione S. Maugeri after undergoing heart transplantation. On 1 August 2013 and during hospitalization in the rehabilitation unit, Klebsiella oxytoca and Citrobacter koseri clinical isolates were simultaneously recovered from the patient’s preputial swab. Molecular characterization confirmed the presence of blaCMY-4 and blaVIM-4 determinants in a 150 Kb transferable plasmid of IncA/C group. This case is the first detection in Italy of the K. oxytoca and C. koseri clinical isolates co-producing the CMY-4 and VIM-4 enzymes.
ii) ESBL OUTBREAK by Klebsiella pneumoniae at a Neonatal Intensive Care Unit (NICU).We report an outbreak of an extended spectrum beta-lactamase Klebsiella pneumoniae (ESBL-Kp) clones in a NICU in northern Italy. Colonization of patients was assessed by cultures of rectal swabs sampled once a week. ESBL production was investigated by phenotypic and molecular tests. Plasmid characterization and whole-genome sequencing were performed. Molecular typing was carried out by PFGE and MLST.
2.Characterizing Class A carbapenemases:
i)CASE STUDY: Aim of the study was to characterize KPC-producing Escherichia coli clinical isolates among a Northern Italy Long-Term Care and Rehabilitation Facility (LTCRF) residents.
Here we report a LTCRF outbreak caused by an ST131-B2 E. coli associated with blaKPC-2 and blaKPC-8 genes, and the emergence of the new ST3948.
3.Characterizing Class B carbapenemases
ST405 NDM-5-positive Escherichia coli strains were isolated from two inpatients at an Italian Hospital in 2014-2015. Bacterial typing was performed and the entire plasmid content was fully sequenced. An IncFII plasmid harboring blaNDM-5, rmtB, blaTEM-1b, dfrA12, aadA2, mphA, sul1 genes and an IncI1 plasmid, harboring the blaCMY-42 gene were co-resident within the ST405 strains. The emergence of an hidden ST405 local reservoir cannot be excluded, even if foreign origin of the MDR ST405 clone was hypothesized.
4.Characterizing Class D carbapenemases.
The aim was to assess by NGS the Antimicrobial-resistance evolution in a collection of A. baumannii strains belonging to ST78 lineage and responsible for outbreaks in Italy since 2002. The genomic evolution of these strains in 10 years period and the detection of their genomic characterization, also associated with Italian ST78 clone, were also investigated.
Our results suggest that isolates belonging to ST78 acquired novel antibiotic resistance genes. To our knowledge, this is the first study on the genomic evolution in an epidemic A. baumannii genotype (i.e. ST78) beside the three main ICs.Antibiotic resistance can be horizontally acquired through transfer of antibiotic resistance plasmids or determinants between bacteria, or can be due to a mutational event in a target site in response of antibiotics excessive use/misuse for treatment of infections in human and veterinary medicine. Consequently the proliferation of Extended Spectrum β-lactamases (ESBLs)- among Gram negative bacteria, mediated through promiscuous conjugative plasmids, transposons and integrons increased the volume of carbapenems into clinical medicine worldwide.
Within this decade, four molecular classes of carbapenemases have emerged throughout the world:
Chromosomal encoded Class A carbapenemases (IMI, NMC-A and SME);
Non chromosomal encoded Class A such as KPC in Enterobacteriaceae;
Class B enzymes MBLs with the most prevalent IMP-and VIM- and NDM-type;
Class D acquired, as OXA-23, OXA-58 and OXA-48-like.
The thesis work was on:
1.Characterizing ESBLs and Class B carbapenemases:
i)CASE STUDY: A 62-year-old patient was transferred to the cardiac rehabilitation unit of the I.R.C.C.S. Fondazione S. Maugeri after undergoing heart transplantation. On 1 August 2013 and during hospitalization in the rehabilitation unit, Klebsiella oxytoca and Citrobacter koseri clinical isolates were simultaneously recovered from the patient’s preputial swab. Molecular characterization confirmed the presence of blaCMY-4 and blaVIM-4 determinants in a 150 Kb transferable plasmid of IncA/C group. This case is the first detection in Italy of the K. oxytoca and C. koseri clinical isolates co-producing the CMY-4 and VIM-4 enzymes.
ii) ESBL OUTBREAK by Klebsiella pneumoniae at a Neonatal Intensive Care Unit (NICU).We report an outbreak of an extended spectrum beta-lactamase Klebsiella pneumoniae (ESBL-Kp) clones in a NICU in northern Italy. Colonization of patients was assessed by cultures of rectal swabs sampled once a week. ESBL production was investigated by phenotypic and molecular tests. Plasmid characterization and whole-genome sequencing were performed. Molecular typing was carried out by PFGE and MLST.
2.Characterizing Class A carbapenemases:
i)CASE STUDY: Aim of the study was to characterize KPC-producing Escherichia coli clinical isolates among a Northern Italy Long-Term Care and Rehabilitation Facility (LTCRF) residents.
Here we report a LTCRF outbreak caused by an ST131-B2 E. coli associated with blaKPC-2 and blaKPC-8 genes, and the emergence of the new ST3948.
3.Characterizing Class B carbapenemases
ST405 NDM-5-positive Escherichia coli strains were isolated from two inpatients at an Italian Hospital in 2014-2015. Bacterial typing was performed and the entire plasmid content was fully sequenced. An IncFII plasmid harboring blaNDM-5, rmtB, blaTEM-1b, dfrA12, aadA2, mphA, sul1 genes and an IncI1 plasmid, harboring the blaCMY-42 gene were co-resident within the ST405 strains. The emergence of an hidden ST405 local reservoir cannot be excluded, even if foreign origin of the MDR ST405 clone was hypothesized.
4.Characterizing Class D carbapenemases.
The aim was to assess by NGS the Antimicrobial-resistance evolution in a collection of A. baumannii strains belonging to ST78 lineage and responsible for outbreaks in Italy since 2002. The genomic evolution of these strains in 10 years period and the detection of their genomic characterization, also associated with Italian ST78 clone, were also investigated.
Our results suggest that isolates belonging to ST78 acquired novel antibiotic resistance genes. To our knowledge, this is the first study on the genomic evolution in an epidemic A. baumannii genotype (i.e. ST78) beside the three main ICs
Fosfomycin resistance mechanisms in Enterobacterales: an increasing threat
No full textAntimicrobial resistance is well-known to be a global health and development threat. Due to the decrease of effective antimicrobials, re-evaluation in clinical practice of old antibiotics, as fosfomycin (FOS), have been necessary. FOS is a phosphonic acid derivate that regained interest in clinical practice for the treatment of complicated infection by multi-drug resistant (MDR) bacteria. Globally, FOS resistant Gram-negative pathogens are raising, affecting the public health, and compromising the use of the antibiotic. In particular, the increased prevalence of FOS resistance (FOSR) profiles among Enterobacterales family is concerning. Decrease in FOS effectiveness can be caused by i) alteration of FOS influx inside bacterial cell or ii) acquiring antimicrobial resistance genes. In this review, we investigate the main components implicated in FOS flow and report specific mutations that affect FOS influx inside bacterial cell and, thus, its effectiveness. FosA enzymes were identified in 1980 from Serratia marcescens but only in recent years the scientific community has started studying their spread. We summarize the global epidemiology of FosA/ C2/L1-2 enzymes among Enterobacterales family. To date, 11 different variants of FosA have been reported globally. Among acquired mechanisms, FosA3 is the most spread variant in Enterobacterales, followed by FosA7 and FosA5. Based on recently published studies, we clarify and represent the molecular and genetic composition of fosA/C2 genes enviroment, analyzing the mechanisms by which such genes are slowly transmitting in emerging and high-risk clones, such as E. coli ST69 and ST131, and K. pneumoniae ST11. FOS is indicated as first line option against uncomplicated urinary tract infections and shows remarkable qualities in combination with other antibiotics. A rapid and accurate identification of FOSR type in Enterobacterales is difficult to achieve due to the lack of commercial phenotypic susceptibility tests and of rapid systems for MIC detection
FosA8-producing E. coli ST131: clinical cases in Italy, February 2023
No full text: Fosfomycin-resistant FosA8-producing Enterobacterales are uncommon strains with extremely low incidence in Europe, based on only three reports in the literature. We detected FosA8-producing Escherichia coli ST131 in clinical isolates from two patients admitted in February 2023 to a rehabilitation unit in Italy. The occurrence of rare fosA-like genes in the high-risk clone ST131 is of clinical relevance. The dissemination of FosA-producing E. coli, although still at low levels, should be continuously monitored
Detection of an IncA/C plasmid encoding VIM-4 and CMY-4 β-lactamases in Klebsiella oxytoca and Citrobacter koseri from an inpatient in a cardiac rehabilitation unit
Full text linkA 62-year-old patient was transferred to the cardiac rehabilitation unit of the I.R.C.C.S. Fondazione S. Maugeri after undergoing a heart transplantation at the Acute Care Hospital I.R.C.C.S. S. Matteo of Pavia. On 1 August 2013 and during hospitalization in the rehabilitation unit, Klebsiella oxytoca and Citrobacter koseri clinical isolates were simultaneously recovered from the patient's preputial swab. Both the K. oxytoca and C. koseri strains were carbapenem- resistant by MicroScan System (Beckman Coulter). Carbapenem-resistant K. pneumoniae had previously been reported in the same rehabilitation facility. The aim of the study was to identify the carbapenem resistance mechanisms among the enterobacterial species recovered. Phenotypic screening tests useful to detect the β-lactamases/carbapenemases were performed. Carbapenem MICs were obtained by Etest. AmpC and MBL encoding genes were identified by PCR and sequencing. Conjugation assays and plasmid characterization were performed. Both of the K. oxytoca and C. koseri isolates were multi drug resistant, showing resistance to amoxicillin-clavulanic acid, three generation cephalosporins, ertapenem (K. oxytoca MIC, >32 mg/L; C. koseri MIC, 4 mg/L), imipenem (K. oxytoca MIC, 4 mg/L; C. koseri MIC, 12 mg/L), thrimethoprim sulphamethoxazole and gentamicin. Susceptibility was retained to fluoroquinolones, colistin and tigecycline. Molecular characterization confirmed the co-presence of blaCMY-4 and blaVIM-4 determinants in a 150 Kb transferable plasmid of IncA/C group. This case is the first detection in Italy of the K. oxytoca and C. koseri clinical isolates co-producing the CMY-4 and VIM-4 enzymes
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Clinical isolation of an Enterobacter cloacae strain producing the novel plasmid-borne AmpC ACT-24 variant
No full textAppropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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