Publications by authors named "Floriana Campanile"

40 Publications

Diagnostic stewardship based on patient profiles: differential approaches in acute versus chronic infectious syndromes.

Expert Rev Anti Infect Ther 2021 May 14:1-11. Epub 2021 May 14.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

: New diagnostics may be useful in clinical practice, especially in contexts of high prevalence of multidrug-resistant organisms (MDRO). However, misuse of diagnostic tools may lead to increased costs and worse patient outcome. Conventional and new techniques should be appropriately positioned in diagnostic algorithms to guide an appropriate use of antimicrobial therapy.: A panel of experts identified 4 main areas in which the implementation of diagnostic stewardship is needed. Among chronic infections, bone and prosthetic joint infections and subacute-chronic intravascular infections and endocarditis represent common challenges for clinicians. Among acute infections, bloodstream infections and community-acquired pneumonia may be associated with high mortality and require appropriate diagnostic approach.: Diagnostic stewardship aims to improve the appropriate use of microbiological diagnostics to guide therapeutic decisions through appropriate and timely diagnostic testing. Here, diagnostic algorithms based on different patient profiles are proposed for chronic and acute clinical syndromes. In each clinical scenario, combining conventional and new diagnostic techniques is crucial to make a rapid and accurate diagnosis and to guide the selection of antimicrobial therapy. Barriers related to the implementation of new rapid diagnostic tools, such as high initial costs, may be overcome through their rational and structured use.
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http://dx.doi.org/10.1080/14787210.2021.1926986DOI Listing
May 2021

Staphylococcus aureus ST228 and ST239 as models for expression studies of diverse markers during osteoblast infection and persistence.

Microbiologyopen 2021 03;10(2):e1178

Department of Biomedical and Biotechnological Sciences (BIOMETEC), Medical Molecular Microbiology and Antibiotic Resistance laboratory (MMARLab, University of Catania, Catania, Italy.

The ability of S. aureus to infect bone and osteoblasts is correlated with its incredible virulence armamentarium that can mediate the invasion/internalization process, cytotoxicity, membrane damage, and intracellular persistence. We comparatively analyzed the interaction, persistence, and modulation of expression of selected genes and cell viability in an ex vivo model using human MG-63 osteoblasts of two previously studied and well-characterized S. aureus clinical strains belonging to the ST239-SCCmecIII-t037 and ST228-SCCmecI-t041 clones at 3 h and 24 h post-infection (p.i). S. aureus ATCC12598 ST30-t076 was used as a control strain. Using imaging flow cytometry (IFC), we found that these strains invaded and persisted in MG-63 osteoblasts to different extents. The invasion was evaluated at 3 h p.i and persistence at 24 h p.i., in particular: ATCC12598 internalized in 70% and persisted in 50% of MG-63 cells; ST239-SCCmecIII internalized in 50% and persisted in 45% of MG-63 cells; and ST228-SCCmecI internalized in 30% and persisted in 20% of MG-63 cells. During the infection period, ST239-III exerted significant cytotoxic activity resulting from overexpression of hla and psmA and increased expression of the genes involved in adhesion, probably due to the release and re-entry of bacteria inside MG-63 cells at 24 h p.i. The lower invasiveness of ST228-I was also associated with non-cytotoxic activity inside osteoblasts. This clone was unable to activate sufficient cellular reaction and succumbed inside MG-63 cells. Our findings support the idea of considering new strategies, based on a translational approach-eukaryotic host-pathogen interaction (EHPI)-and to be applied on a large scale, to predict S. aureus /osteoblast interaction and treat bone infections. Such strategies rely on the study of the genetic and biochemical basis of both pathogen and host.
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http://dx.doi.org/10.1002/mbo3.1178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087985PMC
March 2021

Different Modulatory Effects of Four Methicillin-Resistant Clones on MG-63 Osteoblast-Like Cells.

Biomolecules 2021 01 7;11(1). Epub 2021 Jan 7.

Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95125 Catania, Italy.

is a Gram-positive bacterium responsible for a variety of mild to life-threatening infections including bone infections such as osteomyelitis. This bacterium is able to invade and persist within non-professional phagocytic cells such as osteoblasts. In the present study, four different strains, namely, 2SA-ST239-III (ST239), 5SA-ST5-II (ST5), 10SA-ST228-I (ST228), and 14SA-ST22-IVh (ST22), were tested for their ability to modulate cell viability in MG-63 osteoblast-like cells following successful invasion and persistence. Methicillin-sensitive (MSSA) ATCC-12598-ST30 (ST30) was used as control strain. Despite being proven that ST30, ST239, and ST22 have a similar ability to internalize and persist in MG-63 osteoblast-like cells under our experimental conditions, we demonstrated that the observed decrease in cell viability was due to the different behavior of the considered strains, rather than the number of intracellular bacteria. We focused our attention on different biochemical cell functions related to inflammation, cell metabolism, and oxidative stress during osteoblast infections. We were able to show the following: (1) ST30 and ST239 were the only two clones able to persist and maintain their number in the hostile environment of the cell during the entire period of infection; (2) ST239 was the only clone able to significantly increase gene expression (3 and 24 h post-infection (p.i.)) and protein secretion (24 h p.i.) of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in MG-63 osteoblast-like cells; (3) the same clone determined a significant up-regulation of the transforming growth factorbeta 1 (TGF-β1) and of the metabolic marker glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNAs at 24 h p.i.; and (4) neither the MSSA nor the four methicillin-resistant (MRSA) strains induced oxidative stress phenomena in MG-63 cells, although a high degree of variability was observed for the different clones with regard to the expression pattern of nuclear factor E2-related factor 2 (Nrf2) and its downstream gene heme oxygenase 1 (HO-1) activation. Our results may pave the way for an approach to -induced damage, moving towards individualized therapeutic strategies that take into account the differences between MSSA and MRSA as well as the distinctive features of the different clones. This approach is based on a change of paradigm in antibiotic therapy involving a case-based use of molecules able to counteract pro-inflammatory cytokines activity such as selective cytokine signaling inhibitors (IL-6, TNF-α).
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http://dx.doi.org/10.3390/biom11010072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825699PMC
January 2021

In Vitro Activity of Dalbavancin against Refractory Multidrug-Resistant (MDR) Isolates.

Antibiotics (Basel) 2020 Dec 3;9(12). Epub 2020 Dec 3.

Department of Biomedical and Biotechnological Sciences (BIOMETEC)-Medical Molecular Microbiology and Antibiotic Resistance Laboratory (MMARLab), University of Catania, 95123 Catania, Italy.

The high prevalence of methicillin-resistant (MRSA) infections, always treated with vancomycin and daptomycin, has led to the emergence of vancomycin-intermediate (VISA), heteroresistant vancomycin-intermediate (hVISA) and daptomycin non-susceptible (DNS) . Even if glycopeptides and daptomycin remain the keystone for treatment of resistant , the need for alternative therapies that target MRSA has now become imperative. The in vitro antibacterial and bactericidal activity of dalbavancin was evaluated against clinically relevant showing raised antibiotic resistance levels, from methicillin-susceptible to Multidrug-Resistant (MDR) MRSA, including hVISA, DNS and rifampicin-resistant (RIF-R) strains. A total of 124 strains were tested for dalbavancin susceptibility, by the broth microdilution method. Two VISA and 2 hVISA reference strains, as well as a vancomycin-resistant (VRSA) reference strain and a methicillin-susceptible (MSSA) reference strain, were included as controls. Time-kill curves were assayed to assess bactericidal activity. Dalbavancin demonstrated excellent in vitro antibacterial and bactericidal activity against all resistance classes, including hVISA and DNS isolates. The RIF-R strains showed the highest percentage of isolates with non-susceptibility, reflecting the correlation between B mutations and VISA/hVISA emergence. Our observations suggest that dalbavancin can be considered as an effective alternative for the management of severe MRSA infections also sustained by refractory phenotypes.
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http://dx.doi.org/10.3390/antibiotics9120865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761838PMC
December 2020

Gold standard susceptibility testing of fosfomycin in Staphylococcus aureus and Enterobacterales using a new agar dilution panel®.

J Glob Antimicrob Resist 2020 12 27;23:334-337. Epub 2020 Oct 27.

Department of Biomedical and Biotechnological Sciences, section of Microbiology, University of Catania, Italy.

Objectives: Many clinical laboratories have difficulty in routinely performing in vitro fosfomycin susceptibility testing using the agar dilution (AD) method, considered to be the gold standard method. The objective of our work was to evaluate a rapid commercial fosfomycin agar dilution panel against clinical Staphylococcus aureus and Enterobacterales strains, in two different centres located in Italy and in the UK.

Methods: A total of 99 Enterobacterales (mostly Escherichia coli and Klebsiella pneumoniae) and 80 S. aureus clinical isolates was used to evaluate the commercial device, a 12-well panel containing fosfomycin incorporated into CA-MH agar supplemented with 25mg/L of glucose-6-phosphate (Liofilchem S.r.l., Roseto degli Abruzzi, Italy). Testing was performed in two centres (Italy and UK) and kit results were compared against the gold standard in-house AD MIC method.

Results: According to the EUCAST breakpoints, fosfomycin inhibited 61% of the S. aureus strains, and 76% of the Enterobacterales isolates tested by the AD reference method. There was a Categorical Agreement (CA) of 100% and an Essential Agreement (EA) of 91.25% for S. aureus; while the Enterobacterales strains showed a CA of 94% and an EA of 97%. No evaluation errors were observed among S. aureus, while 5% Major Error and 1% Very Major Error were observed for the Enterobacterales.

Conclusions: Our results confirmed the feasibility of determining fosfomycin susceptibility using a commercial AD panel as a routine substitution for the AD test. The few differences observed were only in strains with MICs around the breakpoint used.
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http://dx.doi.org/10.1016/j.jgar.2020.08.025DOI Listing
December 2020

Fluoroquinolone Metalloantibiotics: A Promising Approach against Methicillin-Resistant .

Int J Environ Res Public Health 2020 04 30;17(9). Epub 2020 Apr 30.

REQUIMTE-LAQV (Rede de Química e Tecnologia - Laboratório Associado para a Química Verde), Departamento de Química e Bioquímica da Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, s/n, 4169-007 Porto, Portugal.

Fluoroquinolones (FQs) are antibiotics commonly used in clinical practice, although nowadays they are becoming ineffective due to the emergence of several mechanisms of resistance in most bacteria. The complexation of FQs with divalent metal ions and phenanthroline (phen) is a possible approach to circumvent antimicrobial resistance, since it forms very stable complexes known as metalloantibiotics. This work is aimed at determining the antimicrobial activity of metalloantibiotics of Cu(II)FQphen against a panel of multidrug‑resistant (MDR) clinical isolates and to clarify their mechanism of action. Minimum inhibitory concentrations (MICs) were determined against MDR isolates of and methicillin-resistant (MRSA). Metalloantibiotics showed improved antimicrobial activity against several clinical isolates, especially MRSA. Synergistic activity was evaluated in combination with ciprofloxacin and ampicillin by the disk diffusion and checkerboard methods. Synergistic and additive effects were shown against MRSA isolates. The mechanism of action was studied though enzymatic assays and atomic force microscopy (AFM) experiments. The results indicate a similar mechanism of action for FQs and metalloantibiotics. In summary, metalloantibiotics seem to be an effective alternative to pure FQs against MRSA. The results obtained in this work open the way to the screening of metalloantibiotics against other Gram‑positive bacteria.
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http://dx.doi.org/10.3390/ijerph17093127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246690PMC
April 2020

Detection of methicillin-resistant Staphylococcus aureus persistence in osteoblasts using imaging flow cytometry.

Microbiologyopen 2020 05 1;9(5):e1017. Epub 2020 Apr 1.

Department of Biomedical and Biotechnological Sciences (BIOMETEC), Medical Molecular Microbiology and Antibiotic Resistance Laboratory (MMARLab), University of Catania, Catania, Italy.

Methicillin-resistant S. aureus has been reported as the main pathogen involved in chronic infections, osteomyelitis, and prosthetic joint infections. The host/pathogen interaction is dynamic and requires several changes to promote bacterial survival. Here, we focused on the internalization and persistence behavior of well-characterized Staphylococcus aureus invasive strains belonging to the main ST-MRSA-SCCmec clones. To overcome the limitations of the cell culture method, we comparatively analyzed the ability of internalization within human MG-63 osteoblasts with imaging flow cytometry (IFC). After evaluation by cell culture assay, the MRSA clones in the study were all able to readily internalize at 3h postinfection, the persistence of intracellular bacteria was evaluated at 24h both by routine cell culture and IFC assay, after vancomycin-BODIPY staining. A statistical difference of persistence was found in ST5-SCCmecII (26.59%), ST228-SCCmecI (20.25%), ST8-SCCmecIV (19.52%), ST239-SCCmecIII (47.82%), and ST22-SCCmecIVh (50.55%) showing the same ability to internalize as ATCC12598 (51%), the invasive isolate used as control strain for invasion and persistence assays. We demonstrated that the intracellular persistence process depends on the total number of infected cells. Comparing our data obtained by IFC with those of the cell culture assay, we obtained greater reproducibility rates and a number of intracellular bacteria, with the advantage of analyzing live host cells. Moreover, with some limitations related to the lack of whole-genome sequencing analysis, we validated the different proclivities to persist in the main Italian HA-MRSA invasive isolates and our results highlighted the heterogeneity of the different clones to persist during cell infection.
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http://dx.doi.org/10.1002/mbo3.1017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221431PMC
May 2020

Prevalence of meticillin-resistant and -susceptible coagulase-negative staphylococci with the first detection of the mecC gene among cows, humans and manure in Tunisia.

Int J Antimicrob Agents 2020 Jan 18;55(1):105826. Epub 2019 Oct 18.

University of Manouba, ISBST, BVBGR-LR11ES31, Biotechpole Sidi Thabet, Ariana, Tunisia. Electronic address:

In Europe, a novel mecA homologue - mecC (formerly mecA) - has emerged recently in staphylococci from animals, humans and the environment. This paper reports the first occurrence of the mecC gene in Staphylococcus sciuri from cows and manure in Tunisia and Africa. Forty-nine coagulase-negative staphylococci (CNS) were isolated from the milk of cows with mastitis (n=20), manure (n=20) and human nares (n=9), including 16 Staphylococcus equoruim (32.6%), 12 S. xylosus (24.5%), 12 S. sciuri (24.5%), two S. saprophyticus (4.1%), two S. haemolyticus (4.1%), two S. lentus (4.1%), two S. vitulinus (4.1%) and one S. cohnii (2%). CNS from the three origins carried various resistance genes [mecA, blaZ, tet(K), erm(A), erm(B), msr(A)], suggesting an ongoing genetic exchange among CNS from the three niches. The mecA gene was detected in CNS (n=11) recovered from cows, manure and humans, whereas the mecC gene (n=3) was only detected in CNS from cows and manure. Various staphylococcal cassette chromosome mec (SCCmec) - SCCmec type I (n=1), II (n=3), IV (n=2), V/VII (n=2) and untypeable (n=3) - and diverse pulsed-field gel electrophoresis (PFGE) patterns were observed in mecA-positive CNS. Otherwise, similar SCCmec types and PFGE patterns were found in meticillin-resistant CNS within different farms and origins, showing the potential of SCCmec interspecies exchange and circulation of the same clones of meticillin-resistant CNS in the human-animal-environment interface. This study provides baseline data to support clonal dissemination of CNS between cows, humans and manure, and indicates the possible transmission of the mecC gene to humans in contact with cows and manure.
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http://dx.doi.org/10.1016/j.ijantimicag.2019.10.007DOI Listing
January 2020

Genotypic analysis of Italian MRSA strains exhibiting low-level ceftaroline and ceftobiprole resistance.

Diagn Microbiol Infect Dis 2019 11 15;95(3):114852. Epub 2019 Jun 15.

Department of Biomedical and Biotechnological Sciences (BIOMETEC) - Medical Molecular Microbiology and Antibiotic Resistance laboratory (MMARLab), - University of Catania, Italy. Electronic address:

The aim of this study was to address the involvement of PBP mutations in the bactericidal activity to novel cephalosporins, alone and in combination with daptomycin, in not-related multidrug-resistant methicillin-resistant Staphylococcus aureus strains isolated during a nationwide Italian survey. MICs determination and time-killing assays were performed and mecA, pbp1, pbp2, pbp3, pbp4, and gdpP genes were sequenced. Ten strains showed low-level resistance to ceftaroline and ceftobiprole. PBP2a sequence analysis identified four different mutations (N146K; N204K; T235I; E239K) uniquely present in the non-penicillin-binding domain (nPBD). Epidemiologically, this resistance was associated with the most widespread MDR Italian clone ST228-SCCmecI-t001/t041, confirming its proclivity to accumulate mutations, and it is also associated to substitutions in the GdpP signaling protein, involved in the maintenance of di-AMP balance, recently associated with resistance to beta-lactams. Despite these mutations, both drugs retained their potent in vitro bactericidal activity and showed a synergistic effect towards difficult-to-treat isolates.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.06.004DOI Listing
November 2019

Spread of Vancomycin-Resistant Enterococcus faecium Isolates Despite Validated Infection Control Measures in an Italian Hospital: Antibiotic Resistance and Genotypic Characterization of the Endemic Strain.

Microb Drug Resist 2018 Oct 26;24(8):1148-1155. Epub 2018 Jan 26.

1 Department of Life Sciences, University of Trieste , Trieste, Italy .

An alarming increase of vancomycin-resistant Enterococcus faecium (VREfm) isolates was detected in an Italian referral hospital subjected to policies of infection control validated by the Joint Commission International. Analysis of the population structure of 122 consecutive, nonreplicate VREfm isolates collected over an 18-month period identified a single major clone that spread around the whole hospital, rapidly establishing an endemic state. It belonged to sequence type (ST) 17 and showed a highly multidrug-resistant phenotype, being resistant to all antimicrobial classes for the carriage of several resistance determinants. Furthermore, some strains with decreased susceptibility to daptomycin were detected. Eighteen out of the 122 isolates did not group in the major clone. They showed a low spreading potential inside the hospital wards, even if most of them displayed a multidrug-resistant phenotype and belonged to a hospital-adapted lineage. Causes that led to the VREfm endemic state have not been fully elucidated. However, it is conceivable that the increase in systemic antibiotic consumption and the use of selective digestive tract decontamination, including vancomycin in critically ill patients during the period before 2014, may have played a role in the ST17 clone dissemination, but additional traits conferring high fitness in hospital environment cannot be excluded.
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http://dx.doi.org/10.1089/mdr.2017.0314DOI Listing
October 2018

Burden of Rifampicin- and Methicillin-Resistant Staphylococcus aureus in Italy.

Microb Drug Resist 2018 Jul/Aug;24(6):732-738. Epub 2017 Nov 29.

Medical Molecular Microbiology and Antibiotic Resistance Laboratory (MMAR Lab), Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania , Catania, Italy .

Rifampicin is one of the major drugs used on its own and also in combination to treat numerous infections sustained by methicillin-resistant Staphylococcus aureus (MRSA). In Italy, rifampicin resistance (RIF-R) is increasing in multidrug-resistant-MRSA isolates (16.4%), with respect to Europe (5.7%). In our study, the relationship between clones, rpoB mutations, and susceptibility profiles in 50 RIF-R MRSA isolated from hospitalized patients was evaluated. Antimicrobial susceptibility testing was performed by the broth microdilution method. Isolates were typed by MLST/SCCmec/spa-typing. The rpoB gene was analyzed by PCR and sequence analysis. RIF-R isolates were 60% heterogeneous vancomycin-intermediate S. aureus (hVISA) and 22% daptomycin nonsusceptible and belonged to the major MRSA clones: ST228-SCCmec I (44%), ST8-SCCmec IV (18%), ST239-SCCmec III (16%), ST5-SCCmec II (14%), and ST22-SCCmec IVh (4%). Thirteen diverse RpoB amino acid substitutions were identified. Half of the strains harbored the H481N substitution, conferring low-level resistance. Different single mutations at the equivalent locus (H481D; H481Y) or in other loci, and multiple mutations conferred high-level resistance. In conclusion, this study investigated the nature of RIF-R in Italy among RIF-R-MRSA strains, finding a prevalence of ST228, strongly associated with reduced susceptibility to glycopeptides (hVISA). The spread of RIF-R strains in clinical settings represents a serious threat, due to their complex resistance nature even to new anti-Gram-positive drugs, making these infections particularly difficult to treat.
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http://dx.doi.org/10.1089/mdr.2017.0299DOI Listing
October 2018

Rapid containment of nosocomial transmission of a rare community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clone, responsible for the Staphylococcal Scalded Skin Syndrome (SSSS).

Ital J Pediatr 2017 Jan 6;43(1). Epub 2017 Jan 6.

MMARLab - Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Via Santa Sofia 97, 95123, Catania, Italy.

Background: The aims of this study were to identify the source and the transmission pathway for a Staphylococcal Scalded Skin Syndrome (SSSS) outbreak in a maternity setting in Italy over 2 months, during 2014; to implement appropriate control measures in order to prevent the epidemic spread within the maternity ward; and to identify the Methicillin-Resistant Staphylococcus aureus (MRSA) epidemic clone.

Methods: Epidemiological and microbiological investigations, based on phenotyping and genotyping methods, were performed. All neonates involved in the outbreak underwent clinical and microbiological investigations to detect the cause of illness. Parents and healthcare workers were screened for Staphylococcus aureus to identify asymptomatic carriers.

Results: The SSSS outbreak was due to the cross-transmission of a rare clone of ST5-CA-MRSA-SCCmecV-spa type t311, exfoliative toxin A-producer, isolated from three neonates, one mother (from her nose and from dermatological lesions due to pre-existing hand eczema) and from a nurse (colonized in her nose by this microorganism). The epidemiological and microbiological investigation confirmed these as two potential carriers.

Conclusions: A rapid containment of these infections was obtained only after implementation of robust swabbing of mothers and healthcare workers. The use of molecular methodologies for typing was able to identify all carriers and to trace the transmission.
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http://dx.doi.org/10.1186/s13052-016-0323-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217574PMC
January 2017

Epidemiology of Staphylococcus aureus in Italy: First nationwide survey, 2012.

J Glob Antimicrob Resist 2015 Dec 29;3(4):247-254. Epub 2015 Jul 29.

Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Catania, Italy.

A 3-month epidemiological study to determine the prevalence and antibiotic resistance of Staphylococcus aureus nosocomial infections was performed in 52 centres throughout Italy in 2012. A total of 21,873 pathogens were analysed. The prevalence of S. aureus among all nosocomial pathogens isolated in that period was 11.6% (n=2541), whilst the prevalence of methicillin-resistant S. aureus (MRSA) among the S. aureus was 35.8% (n=910). All tested antimicrobials demonstrated ≥92.2% susceptibility against methicillin-susceptible S. aureus, with the exception of clindamycin (89.7%) and erythromycin (84.2%). Among MRSA, percentages of resistance ranged from 12.6% to >39% for tetracycline, rifampicin, clindamycin and gentamicin; higher percentages were found for erythromycin (65.4%) and fluoroquinolones (72.3-85.8%). Overall, the glycopeptide minimum inhibitory concentration (MIC) distribution showed that 58.3% of strains possessed MICs of 1-2mg/L and few strains were linezolid- or daptomycin-resistant. Molecular characterisation was performed on 102 MRSA selected from Northern, Central and Southern regions. Five major clones were found: Italian/ST228-I (t001-t023-t041-t1686-t3217), 33.3%; USA500/ST8-IV (t008), 17.6%; E-MRSA15/ST22-IVh (t020-t025-t032-t223), 16.7%; USA100/ST5-II (t002-t653-t1349-t2164-t3217-t388), 14.7%; and Brazilian/ST239/241-III (t030-t037), 3.9%. Five PVL-positive CA-MRSA isolates, belonging to USA300 and minor clones, were also identified. In conclusion, this first nationwide surveillance study showed that in Italy, S. aureus infections accounted for 11.6% of all nosocomial infections; MRSA accounted for approximately one-third of the S. aureus isolates and these were multidrug-resistant organisms. Five major MRSA epidemic clones were observed and were inter-regionally distributed, with ST228-SCCmecI becoming predominant.
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http://dx.doi.org/10.1016/j.jgar.2015.06.006DOI Listing
December 2015

High Resolution Melting-Typing (HRMT) of methicillin-resistant Staphylococcus aureus (MRSA): The new frontier to replace multi-locus sequence typing (MLST) for epidemiological surveillance studies.

J Microbiol Methods 2015 Oct 5;117:136-8. Epub 2015 Aug 5.

Medical Molecular Microbiology and Antibiotic Resistance laboratory (MMAR Lab), Department of Biomedical and Biotechnological Sciences, University of Catania, Italy. Electronic address:

We report an implemented molecular-typing-method based on HRMA to detect SNPs within MLST loci, characterizing 100 clinical MRSA and 11 control strains, representative of Italian clones. The results provide solid evidence that HRMT could be a fast, cost-effective and reliable alternative to MLST, for MRSA molecular epidemiology.
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http://dx.doi.org/10.1016/j.mimet.2015.08.001DOI Listing
October 2015

Insights and clinical perspectives of daptomycin resistance in Staphylococcus aureus: A review of the available evidence.

Int J Antimicrob Agents 2015 Sep 19;46(3):278-89. Epub 2015 Jun 19.

Medical Department, Novartis Farma SpA, Largo U. Boccioni 1, 21040 Origgio, Italy.

The emergence of glycopeptide reduced susceptibility and resistance in Staphylococcus aureus strains is a growing clinical problem that poses significant clinical challenges in treatment. Its development is a complex and novel process involving many subtle physiological changes in the micro-organism. Daptomycin is the first cyclic lipopeptide approved for clinical use. Unlike most other antimicrobials, a trend towards increased daptomycin resistance has not been reported, although several cases of daptomycin non-susceptibility have been reported. The present review will present the available evidence on daptomycin resistance of S. aureus, with particular attention to its development. In addition to a literature overview, we have compiled the reported cases of daptomycin non-susceptibility to shed light on possible clinical mechanisms of resistance. In the 36 reports describing 62 clinical cases, infections caused by meticillin-resistant S. aureus (MRSA) strains with a vancomycin minimum inhibitory concentration (MIC) between 1mg/L and 2mg/L often led to vancomycin treatment failure, which may be associated with the development of non-susceptibility to daptomycin. Additional evidence suggests that underdosage of daptomycin is an important clinical aspect that merits further study. The current analysis highlights the importance of determining the MIC when using vancomycin to treat patients with severe S. aureus infections and that when failure is suspected, testing for heterogeneous vancomycin-intermediate S. aureus (hVISA) may also be necessary. Whilst further investigation is needed, it can be hypothesised that MRSA strains become hVISA during prolonged bacteraemia, which may predispose to the development of daptomycin resistance.
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http://dx.doi.org/10.1016/j.ijantimicag.2015.05.008DOI Listing
September 2015

Linezolid-resistant staphylococcal bacteraemia: A multicentre case-case-control study in Italy.

Int J Antimicrob Agents 2015 Mar 30;45(3):255-61. Epub 2014 Dec 30.

Department of Public Health and Infectious Diseases, Policlinico Umberto I, 'Sapienza' University of Rome, Viale dell'Università 37, 00161 Rome, Italy. Electronic address:

The aim of this multicentre study was to analyse the characteristics of patients with bloodstream infections due to staphylococcal strains resistant to linezolid. This was a retrospective case-case-control study of patients hospitalised in three large teaching hospitals in Italy. A linezolid-resistant (LIN-R) Staphylococcus spp. group and a linezolid-susceptible (LIN-S) Staphylococcus spp. group were compared with control patients to determine the clinical features and factors associated with isolation of LIN-R strains. All LIN-R Staphylococcus spp. strains underwent molecular typing. Compared with the LIN-S group, central venous catheters were the main source of infection in the LIN-R group. The LIN-R and LIN-S groups showed a similar incidence of severe sepsis or septic shock, and both showed a higher incidence of these compared with the control group. Overall, patients in the LIN-R group had a higher 30-day mortality rate. Multivariate analysis found previous linezolid therapy, linezolid therapy >14 days, antibiotic therapy in the previous 30 days, antibiotic therapy >14 days, previous use of at least two antibiotics and hospitalisation in the previous 90 days as independent risk factors associated with isolation of a LIN-R strain. The G2576T mutation in domain V of 23S rRNA was the principal mechanism of resistance; only one strain of Staphylococcus epidermidis carried the cfr methylase gene (A2503), together with L4 insertion (71GGR72) and L3 substitution (H146Q). LIN-R strains are associated with severe impairment of clinical conditions and unfavourable patient outcomes. Reinforcement of infection control measures may have an important role in preventing these infections.
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http://dx.doi.org/10.1016/j.ijantimicag.2014.12.008DOI Listing
March 2015

Antibiotics promote aggregation within aquatic bacterial communities.

Front Microbiol 2014 1;5:297. Epub 2014 Jul 1.

Laboratory of Molecular Microbiology and Antibiotic Resistance, Department of Bio-Medical Sciences, University of Catania Catania, Italy.

The release of antibiotics (AB) into the environment poses several threats for human health due to potential development of AB-resistant natural bacteria. Even though the use of low-dose antibiotics has been promoted in health care and farming, significant amounts of AB are observed in aquatic environments. Knowledge on the impact of AB on natural bacterial communities is missing both in terms of spread and evolution of resistance mechanisms, and of modifications of community composition and productivity. New approaches are required to study the response of microbial communities rather than individual resistance genes. In this study a chemostat-based experiment with 4 coexisting bacterial strains has been performed to mimicking the response of a freshwater bacterial community to the presence of antibiotics in low and high doses. Bacterial abundance rapidly decreased by 75% in the presence of AB, independently of their concentration, and remained constant until the end of the experiment. The bacterial community was mainly dominated by Aeromonas hydrophila and Brevundimonas intermedia while the other two strains, Micrococcus luteus and Rhodococcus sp. never exceed 10%. Interestingly, the bacterial strains, which were isolated at the end of the experiment, were not AB-resistant, while reassembled communities composed of the 4 strains, isolated from treatments under AB stress, significantly raised their performance (growth rate, abundance) in the presence of AB compared to the communities reassembled with strains isolated from the treatment without AB. By investigating the phenotypic adaptations of the communities subjected to the different treatments, we found that the presence of AB significantly increased co-aggregation by 5-6 fold. These results represent the first observation of co-aggregation as a successful strategy of AB resistance based on phenotype in aquatic bacterial communities, and can represent a fundamental step in the understanding of the effects of AB in aquatic ecosystems.
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http://dx.doi.org/10.3389/fmicb.2014.00297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077313PMC
July 2014

Molecular epidemiology of methicillin-resistant S. aureus in the ICU setting.

Intensive Care Med 2014 May 14;40(5):759-60. Epub 2014 Mar 14.

Department of Medical Sciences, Infectious Diseases, Amedeo di Savoia Hospital, University of Turin, Corso Svizzera 164, 10149, Turin, Italy.

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http://dx.doi.org/10.1007/s00134-014-3257-0DOI Listing
May 2014

Methicillin-resistant Staphylococcus aureus nasal colonization in a department of pediatrics: a cross-sectional study.

Ital J Pediatr 2014 Jan 10;40. Epub 2014 Jan 10.

Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

Background: We describe methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage at admission in patients admitted to a Department of Pediatrics.

Methods: All patients received a nasal swab at admission. A questionnaire was administered and molecular genetics analyses were performed on all identified MRSA isolates.

Results: We enrolled 785 patients, affected with both acute and chronic diseases. MRSA nasal colonization prevalence was 1.15% (CI: 0.5607%-2.093%). Methicillin-sensitive Staphylococcus aureus (MSSA) nasal colonization prevalence at admission was 19.75% (CI 17.07%-22.64%). Only one MRSA isolate carried the SCCmec V variant; all other isolates carried the SCCmecIV variant. Five out of 9 MRSA-colonized patients had an underlying condition. Antibiotic therapy in the previous 6 months was a protective factor for both MRSA (OR 0,66; 95% CI: 0,46-0,96) and MSSA (OR 0,65; 95% CI: 0,45-0,97) colonization. A tendency to statistical significance was seen in the association between hospitalization in the 6 months prior to admission and MRSA colonization at admission (OR 4,92; 95% CI: 0,97-24,83). No patient was diagnosed with an S. aureus infection during hospitalization.

Conclusions: The majority of our MRSA colonizing isolates have community origins. Nevertheless, most MRSA-colonized patients had been hospitalized previously, suggesting that strains that circulate in the community also circulate in hospital settings. Further studies should elucidate the role of children with frequent contact with health care institutions in the circulation of antibiotic resistant strains between the hospital and the community.
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http://dx.doi.org/10.1186/1824-7288-40-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896672PMC
January 2014

dltA overexpression: A strain-independent keystone of daptomycin resistance in methicillin-resistant Staphylococcus aureus.

Int J Antimicrob Agents 2014 Jan 16;43(1):26-31. Epub 2013 Oct 16.

Department of Biomedical Sciences-Microbiology, University of Catania, Via Androne 81, 95124 Catania, Italy. Electronic address:

The mechanisms leading to reduced susceptibility to daptomycin (DAP) are multifactorial and have not been fully elucidated. We analysed, by sequencing and expression studies, the role of the major molecular targets (cell-envelope charge genes, dltA, mprF, cls2; cell-wall turnover and autolysis genes, sceD, atl) involved in the emergence of DAP resistance in three series of isogenic clinical methicillin-resistant Staphylococcus aureus (MRSA) in which DAP resistance emerged after a heterogeneous glycopeptide-intermediate S. aureus (hGISA) step under teicoplanin and DAP therapy. All of the isolates had different genotypes and were δ-haemolysin negative, reflecting a strain proclivity to acquire DAP/glycopeptide non-susceptibility under antibiotic pressure. DAP exposure led to the emergence of DAP resistance after an hGISA step probably in parallel with the timing of the two antimicrobial administrations and, in two of three cases, in conditions of DAP underdosage. Real-time qPCR data revealed that all DAP-resistant (DAP-R) isolates had dltA overexpression, whereas mprF upregulation was found only in DAP-R strains with the S295L and T345I amino acid substitutions. Strains that were heteroresistant to DAP did not possess DAP-R-like characteristics. DAP-R strains presented high cls2 expression and no known cls2 mutations, and moreover exhibited sceD and atl upregulation. In conclusion, these findings highlight that dltA overexpression is the common pathway of resistance among genotypically different series of isolates and may represent the keystone of DAP resistance in MRSA, leading to electrostatic repulsion and, indirectly, to a reduction of autolysin activity. mprF mutations related to increased transcription may play a role in this complex phenomenon.
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http://dx.doi.org/10.1016/j.ijantimicag.2013.10.001DOI Listing
January 2014

Daptomycin plus trimethoprim/sulfamethoxazole combination therapy in post-neurosurgical meningitis caused by linezolid-resistant Staphylococcus epidermidis.

Diagn Microbiol Infect Dis 2013 May 26;76(1):99-102. Epub 2013 Feb 26.

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Post-neurosurgical infection is a serious complication that occurs in approx. 4% of all patients undergoing neurosurgical procedures and is associated with high morbidity and mortality rates and prolonged length of intensive care unit (ICU) stay. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are the most frequent pathogens involved in CNS post-neurosurgical meningitis. Treatment is challenging especially in patients with meningitis due to multidrug- resistant (MDR) CONS. Herein, we report a unique case of post-neurosurgical meningitis due to MRSE resistant to linezolid (a molecular analysis revealed the presence of the mutation G2576T on domain V of the 23S rRNA gene) and with reduced susceptibility to glycopeptides, successfully treated with a combination of daptomycin at 10 mg/kg daily plus trimethoprim/sulfamethoxazole (TMP/SMX). This antibiotic combination showed an indifferent interaction in in vitro studies. Daptomycin serum and cerebrospinal fluid (CSF) concentrations, determined through blood and CSF samples drawn just prior to and 4 h after the third dose, were 18.9-0.78 and 51.65-3.1 mg/L, respectively. These values allowed us to approximate a 5-6% penetration rate of the drug through an inflamed blood-brain barrier. In conclusion, although further studies are needed, combination of high-dose daptomycin plus TMP/SMX is a reasonable option for treatment of meningitis caused by multidrug-resistant S. epidermidis.
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http://dx.doi.org/10.1016/j.diagmicrobio.2013.01.021DOI Listing
May 2013

Worrisome trend of new multiple mechanisms of linezolid resistance in staphylococcal clones diffused in Italy.

J Clin Microbiol 2013 Apr 23;51(4):1256-9. Epub 2013 Jan 23.

University of Catania, Catania, Italy.

In order to assess the frequency of clinically relevant linezolid-resistant staphylococcal isolates, and the role of linezolid in maintaining and coselecting multiple resistance mechanisms (cfr, 23S rRNA, L3/L4 mutations), a prospective Italian study was performed from 2010 to 2011 to confirm the diffusion of three major multidrug-resistant clones (ST2, ST5, ST23).
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http://dx.doi.org/10.1128/JCM.00098-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666802PMC
April 2013

Daptomycin efficacy in the central nervous system of a patient with disseminated methicillin-resistant Staphylococcus aureus infection: a case report.

J Med Case Rep 2012 Aug 31;6:264. Epub 2012 Aug 31.

Second Infectious Diseases Division, National Institute for Infectious Diseases "LazzaroSpallanzani", Via Portuense, 292-00149, Rome, Italy.

Introduction: Staphylococcus aureus has emerged as a major nosocomial pathogen in the last decades and also represents the second most common pathogen isolated from patients in outpatient settings. Although methicillin-resistant S.aureus infections were traditionally limited to hospitals, community-associated cases of methicillin-resistant S.aureus infections have been reported. In our case, we observed an unexpected event during treatment.

Case Presentation: A 60-year-old Caucasian man developed fever and multiple muscle and brain abscesses caused by Panton-Valentine leukocidin-negative community-associated methicillin-resistant S. aureus.

Conclusion: Although our patient was given antimicrobials active against the isolated methicillin-resistant S. aureus strain, it was only after the introduction of daptomycin that his skin, soft tissue and muscle lesions and also brain manifestations improved.
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http://dx.doi.org/10.1186/1752-1947-6-264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470956PMC
August 2012

Genomic diversification of enterococci in hosts: the role of the mobilome.

Front Microbiol 2012 14;3:95. Epub 2012 Mar 14.

Molecular Microbiology and Antibiotic Resistance Lab, Department of Microbiology, University of Catania Catania, Italy.

Enterococci are ubiquitous lactic acid bacteria, possessing a flexible nature that allows them to colonize various environments and hosts but also to be opportunistic pathogens. Many papers have contributed to a better understanding of: (i) the taxonomy of this complex group of microorganisms; (ii) intra-species variability; (iii) the role of different pathogenicity traits; and (iv) some markers related to the character of host-specificity, but the reasons of such incredible success of adaptability is still far from being fully explained. Recently, genomic-based studies have improved our understanding of the genome diversity of the most studied species, i.e., E. faecalis and E. faecium. From these studies, what is becoming evident is the role of the mobilome in adding new abilities to colonize new hosts and environments, and eventually in driving their evolution: specific clones associated with human infections or specific hosts can exist, but probably the consideration of these populations as strictly clonal groups is only partially correct. The variable presence of mobile genetic elements may, indeed, be one of the factors involved in the evolution of one specific group in a specific host and/or environment. Certainly more extensive studies using new high throughput technologies are mandatory to fully understand the evolution of predominant clones and species in different hosts and environments.
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http://dx.doi.org/10.3389/fmicb.2012.00095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303144PMC
October 2012

Modulating activity of vancomycin and daptomycin on the expression of autolysis cell-wall turnover and membrane charge genes in hVISA and VISA strains.

PLoS One 2012 9;7(1):e29573. Epub 2012 Jan 9.

Unit of Microbiology, Department of Bio-Medical Sciences University of Catania, Catania, Italy.

Glycopeptides are still the gold standard to treat MRSA (Methicillin Resistant Staphylococcus aureus) infections, but their widespread use has led to vancomycin-reduced susceptibility [heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA) and Vancomycin-Intermediate-Staphylococcus aureus (VISA)], in which different genetic loci (regulatory, autolytic, cell-wall turnover and cell-envelope positive charge genes) are involved. In addition, reduced susceptibility to vancomycin can influence the development of resistance to daptomycin. Although the phenotypic and molecular changes of hVISA/VISA have been the focus of different papers, the molecular mechanisms responsible for these different phenotypes and for the vancomycin and daptomycin cross-resistance are not clearly understood. The aim of our study was to investigate, by real time RT-PCR, the relative quantitative expression of genes involved in autolysis (atl-lytM), cell-wall turnover (sceD), membrane charges (mprF-dltA) and regulatory mechanisms (agr-locus-graRS-walKR), in hVISA and VISA cultured with or without vancomycin and daptomycin, in order to better understand the molecular basis of vancomycin-reduced susceptibility and the modulating activity of vancomycin and daptomycin on the expression of genes implicated in their reduced susceptibility mechanisms. Our results show that hVISA and VISA present common features that distinguish them from Vancomycin-Susceptible Staphylococcus aureus (VSSA), responsible for the intermediate glycopeptide resistance i.e. an increased cell-wall turnover, an increased positive cell-wall charge responsible for a repulsion mechanism towards vancomycin and daptomycin, and reduced agr-functionality. Indeed, VISA emerges from hVISA when VISA acquires a reduced autolysis caused by a down-regulation of autolysin genes, atl/lytM, and a reduction of the net negative cell-envelope charge via dltA over-expression. Vancomycin and daptomycin, acting in a similar manner in hVISA and VISA, can influence their cross-resistance mechanisms promoting VISA behavior in hVISA and enhancing the cell-wall pathways responsible for the intermediate vancomycin resistance in VISA. Daptomycin can also induce a charge repulsion mechanism both in hVISA and VISA increasing the activity of the mprF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029573PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253798PMC
May 2012

Polyclonal diffusion of beta-lactamase-producing Enterococcus faecium.

J Clin Microbiol 2012 Jan 9;50(1):169-72. Epub 2011 Nov 9.

Clinical Microbiology, S. Agostino-Estense Hospital, Baggiovara, Modena, Italy.

We describe here the isolation of 8 beta-lactamase-producing multidrug-resistant Enterococcus faecium isolates in 2010. All strains showed diverse pulsed-field gel electrophoresis (PFGE) profiles, all belonging to the same clonal complex, CC17. By PCR and hybridization experiments, the entire blaZ-blaI-blaR1 operon was found. The beta-lactamase activity was demonstrated at a high inoculum and in the presence of methicillin after overnight incubation.
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http://dx.doi.org/10.1128/JCM.05640-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256721PMC
January 2012

DNA methylase modifications and other linezolid resistance mutations in coagulase-negative staphylococci in Italy.

J Antimicrob Chemother 2010 Nov 18;65(11):2336-40. Epub 2010 Sep 18.

Department of Microbiology, University of Catania, Via Androne 81, 95124 Catania, Italy.

Background: Despite 10 years of clinical use, linezolid resistance in Staphylococcus aureus and coagulase-negative staphylococci (CoNS) is still a rare phenomenon. This study reports the mechanisms of resistance and strain types seen in clusters of linezolid-resistant CoNS from two different hospitals in Italy during the period 2008-09.

Methods: Genes associated with linezolid resistance were subjected to molecular analysis and isolates were characterized by PFGE macrorestriction analysis using SmaI.

Results: Thirty-three linezolid-resistant isolates of methicillin-resistant CoNS comprising Staphylococcus epidermidis (24), Staphylococcus hominis (5) and Staphylococcus simulans (4) were studied. The isolates showed varying levels of linezolid resistance. Almost all isolates for which linezolid MICs were 64 mg/L possessed point mutations in domain V of 23S rRNA, while isolates for which the MICs were 256 mg/L expressed methylase activity at position A2503 mediated by the cfr gene. Overall, the isolates showed reduced susceptibility to vancomycin (MICs 1-2 mg/L) and 11 of the 33 isolates showed no susceptibility to teicoplanin. These strains were also resistant to chloramphenicol (28 of 33), lincomycin (24 of 33), erythromycin (17 of 33) and quinupristin/dalfopristin (13 of 33). S. epidermidis isolates, showing mutations or methylase modifications, belonged to different PFGE profiles and to two different sequence types (ST2 and ST23), in which the cfr gene was carried on a plasmid of ∼50 kb.

Conclusions: Clinical CoNS strains with resistance to linezolid and other second-line antibiotics, as well as reduced susceptibility to glycopeptides, have emerged in Italy.
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http://dx.doi.org/10.1093/jac/dkq344DOI Listing
November 2010

Heteroresistance to glycopeptides in Italian meticillin-resistant Staphylococcus aureus (MRSA) isolates.

Int J Antimicrob Agents 2010 Nov 19;36(5):415-9. Epub 2010 Aug 19.

Department of Microbiology, University of Catania (I), Catania, Italy.

The prevalence and molecular characterisation of heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) strains were determined in a large group of Italian strains isolated between 2005 and mid 2007. Amongst the 1284 strains isolated from documented infections in hospitalised patients (bloodstream infection, pneumonia, and skin and skin-structure infections), 139 S. aureus with vancomycin minimum inhibitory concentrations (MICs) between 1 mg/L and 2 mg/L were screened for the presence of hVISA using three different methods and were confirmed by population analysis profile (PAP). Thirty-six hVISA strains (25.9%) were detected. Amongst the three screening methods used, the macro Etest (MET) demonstrated 100% specificity and 75% sensitivity. hVISA strains were accessory gene regulator (agr) types I and II and belonged to the major nosocomial clones circulating in Italy (ST8, ST239, ST247 and ST228). All strains were susceptible to quinupristin/dalfopristin, linezolid, daptomycin, tigecycline and dalbavancin. In conclusion, we have demonstrated that hVISA isolates are common amongst MRSA isolates with MICs between 1 mg/L and 2 mg/L in Italy. MET, with its high sensitivity and specificity, should be used for early detection of hVISA, especially in patients with serious or prolonged infections sustained by MRSA. Finally, the most recent anti-Gram-positive drugs maintained their full spectrum of in vitro activity against these strains.
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http://dx.doi.org/10.1016/j.ijantimicag.2010.06.044DOI Listing
November 2010

Linezolid Resistance in Staphylococci.

Pharmaceuticals (Basel) 2010 Jun 24;3(7):1988-2006. Epub 2010 Jun 24.

Department of Microbiology, University of Catania, Via Androne 81, 95124 Catania, Italy.

Linezolid, the first oxazolidinone to be used clinically, is effective in the treatment of infections caused by various Gram-positive pathogens, including multidrug resistant enterococci and methicillin-resistant Staphylococus aureus. It has been used successfully for the treatment of patients with endocarditis and bacteraemia, osteomyelitis, joint infections and tuberculosis and it is often used for treatment of complicated infections when other therapies have failed. Linezolid resistance in Gram-positive cocci has been encountered clinically as well as in vitro, but it is still a rare phenomenon. The resistance to this antibiotic has been, until now, entirely associated with distinct nucleotide substitutions in domain V of the 23S rRNA genes. The number of mutated rRNA genes depends on the dose and duration of linezolid exposure and has been shown to influence the level of linezolid resistance. Mutations in associated ribosomal proteins also affect linezolid activity. A new phenicol and clindamycin resistance phenotype has recently been found to be caused by an RNA methyltransferase designated Cfr. This gene confers resistance to lincosamides, oxazolidinones, streptogramin A, phenicols and pleuromutilins, decrease the susceptibility of S. aureus to tylosin, to josamycin and spiramycin and thus differs from erm rRNA methylase genes. Research into new oxazolidinones with improved characteristics is ongoing. Data reported in patent applications demonstrated that some oxazolidinone derivatives, also with improved characteristics with respect to linezolid, are presently under study: at least three of them are in an advanced phase of development.
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http://dx.doi.org/10.3390/ph3071988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036669PMC
June 2010
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