Laura Pagani

• Full Professor of Microbiology and Clincal Microbiology
• University of Pavia

Long-term care facilities (LTCFs) are an important reservoir of multidrug-resistant organisms (MDROs). Colonization of LTCF residents by MDROs is generally higher in Italy compared to other European countries. The present review by the working group for the study of infections in LTCFs (GLISTer) of the Italian Association of Clinical Microbiologist...

Antimicrobial consumption in veterinary medicine has led to the spread of multi drug-resistance in clinically important bacteria, with the companion animals and their environment involved as emerging reservoirs. While CTX-M-15 and CMY-2 acquired β-lactamases have been widely detected in the bacterial population of companion and breeding animals in...

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-lactamase...

Background The emergence of the plasmid-mediated colistin resistance mechanism in Escherichia coli has raised concern among public health experts as colistin is a last-line antimicrobial resort. The primary aim of the study was to investigate the prevalence of this resistance trait in E. coli isolates circulating in the Lombardy region, Northern It...

Nanotechnology is a promising approach both for restoring or enhancing activity of old and conventional antimicrobial agents and for treating intracellular infections by providing intracellular targeting and sustained release of drug inside infected cells. The present paper introduces a formulation study of gentamicin loaded biodegradable nanoparti...

To evaluate the water compartment antibiotic-resistance contamination rates, 11 wells, five streams, and four treatment plants located in the Oltrepò Pavese area were screened for the presence of third generation cephalosporins resistant Gram-negative bacteria. Enterobacteriaceae were also characterized for the Extended-Spectrum-β-Lactamases (ESBLs...

In 2016, we undertook a point prevalence screening study for Enterobacteriaceae with extended-spectrum β-lactamases (ESBLs), high-level AmpC cephalosporinases and carbapenemases, and also methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE) in a long-term care facility (LTCF) and the associated acute care ho...

Extended-spectrum beta-lactamases (ESBLs), AmpCtype beta-lactamases (ACBLs) and carbapenemases are among the most important resistance mechanisms in Enterobacteriaceae. This study investigated the presence of these resistance mechanisms in consecutive non-replicate isolates of Escherichia coli (n = 2,352), Klebsiella pneumoniae (n = 697), and Prote...

Background Rates of colonization and infection with multidrug-resistant (MDR) bacteria are increasing worldwide, in both acute care hospitals and long-term care facilities (LTCFs). Italy has one of the highest prevalence of MDR bacteria in European countries, especially with regard to methicillin-resistant Staphylococcus aureus (MRSA) and extended-...

Aim of the study was to characterize KPC-producing Escherichia coli (KPC-Ec) clinical isolates among a Northern Italy Long-Term Care and Rehabilitation Facility (LTCRF) residents. Thirteen consecutive non repeated MDR E. coli isolates showing ertapenem Minimum Inhibitory Concentrations (MICs) >0.5 mg/L, collected during the period March 2011 – May...

Introduction. This paper reports measures of surveillance and control adopted for the containment of an ESβL producing Klebsiella pneumoniae (KP-ESβL) outbreak of infections/colonizations occurred in the Neonatal intensive-care unit (NICU) and Neonatology division of the Fondazione IRCCS Policlinico San Matteo of Pavia between April and August 2013...

Carbapenem-resistant Acinetobacter baumannii (CRAb) is emerging worldwide as a public health problem in various settings. The aim of this study was to investigate the prevalence of CRAb isolates in Italy and to characterize their resistance mechanisms and genetic relatedness. A countrywide cross-sectional survey was carried out at 25 centers in mid...

The aim of this study was the rapid identification of bla KPC gene in 38 Klebsiella pneumoniae clinical isolates with reduced susceptibility to carbapenems. The modified Hodge Test (MHT) was carried out to phenotypically determine whether resistance to carbapenems was mediated by a carbapenemase. The detection of the bla KPC gene was performed by r...

Aim of the study was the evaluation of the in vitro activity of ceftaroline and its potential against a collection of Hospital-Acquired Methicillin-Resistant Staphylococcus aureus (HA-MRSA) and Hospital-Acquired Methicillin-Susceptible S. aureus (HA-MSSA) isolates. S. aureus isolates from outpatients were also examined. A total of 30 MSSA and 50 MR...

Carbapenem-resistant Enterobacteriaceae (CRE) are emerging as a public health problem in various set-tings. In Italy, a rapid and remarkable increase of carbapenem-non-susceptible Klebsiella pneumoniae has been reported since 2010. Here we report on the results of a countrywide cross-sectional survey, car-ried out from 15 May to 30June 2011 to inve...

Background Long Term Care Facilities (LTCFs) play a key role in guaranteeing care to patients in developed countries. Many patients, mostly elderly, access LTCFs at some time in their lives, and their healthcare pathways often require them to move back and forth between hospital and outpatient settings. These patterns bring about new challenges reg...

Introduction. The dissemination of carbapenemase-producing Klebsiella pneumoniae strains is an increasing problem worldwide. KPC ß-lactamases are Ambler class A enzymes mostly plasmid-encoded; their global spread represents a threat to clinical patients care and public health. Multi locus sequence type (ST)258 is currently the most spread K. pneumo...

The worldwide rapid spread of KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) represents an increasing problem in clinical settings. Reports on KPC-Kp epidemic spread in Italian hospitals began to appear since 2010; colistin (COL) represents one of the few remaining therapeutic options available for the treatment of such multi drug-resis...

Acinetobacter baumannii is a Gram-negative organism reported worldwide as a cause of health-care-associated infections, particularly in intensive care units (ICUs). The aim of this study is to describe the emergence and spread of carbapenem-resistant A. baumannii (CRAB) isolates in hospitalized patients. From March to November 2009, multidrug-resis...

The study aimed to evaluate the ability of NBC45, NBC46 and NB40 Microscan (MS) panels, updated to 2010 EUCAST breakpoints, to identify at species level and to correctly define the susceptibility to ß-lactams of 61 ß-lactamases (BLs) producing Gram-negative isolates. A collection of 73 fully identified strains was analyzed: 21 Klebsiella spp., 17 E...

Little data are available on the frequency and risk factors for infection in patients in rehabilitation units. This was a 2-year retrospective cohort study conducted in 131 rehabilitation units (RUs) of the Lombardy Region, including those for patients requiring musculoskeletal, cardiac, respiratory, neurological and general geriatric rehabilitatio...

Clin Microbiol Infect 2012; 18: 160–166 This study was aimed at tracing the molecular characteristics of carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates in Italy with both pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Two hundred and two CRAB isolates were collected during 2004–2009, in two dif...

Detection of ESBL production by Enterobacteriaceae remains a challenge for microbiologists. Although recent changes in the breakpoints of third-generation cephalosporins decreased the likelihood of reporting ESBL producers as susceptible to these compounds, ESBL detection is of interest for prevention of dissemination of ESBL-producers by cross-tra...

Acinetobacter baumannii is a pathogenic organism that posesses a serious health threat because of the occurrence of the large number of (multi)drug-resistant strains. It can persist for prolonged periods in the hospital environment, infecting debilitated or immune-compromised patients. In this context, the endotoxin portion of the lipopolysaccharid...

Biofilm formation of multidrug resistant (MDR) extended-spectrum beta-lactamase (ES beta L) producing Proteus mirabilis isolates from a long-term care and rehabilitation facility (LTCRF) in Northern Italy was evaluated. A total of 10 strains, 4/10 producing the acquired Amp beta-lactamase CMY-16, 3/10 producing the ES beta L TEM-92 and the remainin...

The new antitubercular drug candidate 2-[2-S-methyl-1,4-dioxa-8-azaspiro[4.5]dec-8-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one (BTZ043) targets the DprE1 (Rv3790) subunit of the enzyme decaprenylphosphoryl-β-d-ribose 2′-epimerase. To monitor the potential development of benzothiazinone (BTZ) resistance, a total of 240 sensitive and mu...

Biofilm formation of multidrug resistant (MDR) extended-spectrum beta-lactamase (ESbetaL) producing Proteus mirabilis isolates from a long-term care and rehabilitation facility (LTCRF) in Northern Italy was evaluated. A total of 10 strains, 4/10 producing the acquired AmpC beta-lactamase CMY-16, 3/10 producing the ESbetaL TEM-92 and the remaining n...

Acinetobacter baumannii is emerging as an important nosocomial pathogen. Multidrug resistance, as well as ability to withstand environmental stresses, makes eradication of A. baumannii difficult, particularly from hospital settings. Over a six-year period, 73 isolates of A. baumannii were collected from infected patients in two hospitals in Italy....

Vulvovaginal candidiasis is a common mucosal infection caused by saprophytic and opportunistic yeasts belonging to the Candida genus. 518 vaginal swabs, with positive fungal culture were collected from unselected women attending the Sexually Transmitted Disease clinic of an Italian tertiary care hospital over a six year period to determine the path...

During the period March 2003 – May 2004 at the Laboratory of Clinical Microbiology “Redaelli” LTCRF in Milan, Italy, a total of 529 E. coli, obtained from inpatients of 3 different Long Term Care Rehabilitation Facilities (LTCRFs) in Northern Italy, were processed and 77 ESßLs producers (14.5%) were identified by Vitek System. The results were conf...

Metallo-β-lactamases (MBLs) can confer resistance to most β-lactams, including carbapenems. Their emergence in gram-negative pathogens is a matter of major concern. Italy was the first European country to report the presence of acquired MBLs in gram-negative pathogens and is one of the countries where MBL producers have been detected repeatedly. He...

Serratia marcescens is a recognized cause of outbreaks in neonatal intensive care units (NICUs). The aim of the present study was to investigate two nosocomial outbreaks of S. marcescens that occurred in an NICU in Northern Italy. In order to determine the origin of the outbreaks and the associated morbidity and mortality of S. marcescens infection...

We report the multiple detection of Proteus mirabilis isolates, from 4 different long-term care and rehabilitation facilities (LTCRFs) of Northern Italy, resistant to expanded-spectrum cephalosporins and cephamycins and producing an acquired ampC-like beta-lactamase, named CMY-16. Genotyping by PFGE showed that isolates were clonally related to eac...

Invasive candidiasis in neonates has become an increasing problem over the past decade in Neonatal Intensive Care Units (NICUs). From August 2005 to January 2006, six invasive candidiasis occurred in neonates in NICU of the S. Matteo hospital of Pavia. The study focused on the species involved and their in vitro antifungal susceptibility. Genotypin...

We report the detection of multidrug resistant ESbetaL producing Proteus mirabilis isolates from a long-term care and rehabilitation facility (LTCRF) in Northern Italy. 53% of the collected P. mirabilis strains were ESbetaL producers. PCR and sequencing techniques confirmed the presence of the bla(TEM-92) and bla(CMY-16) resistance genes in 23/26 (...

The rapid spread of acquired metallo-beta-lactamases (MBLs) among major Gram-negative pathogens is a matter of particular concern worldwide and primarily in Europe, one of first continents where the emergence of acquired MBLs has been reported and possibly the geographical area where the increasing diversity of these enzymes and the number of bacte...

The prevalence, antimicrobial susceptibility, and production of extended-spectrum beta-lactamases (ESBLs) of Salmonella collected from several hospitals in Apulia (southern Italy) were evaluated. The most common Salmonella isolates were Salmonella enterica serovar Typhimurium (44.6%), S. enterica serovar Enteritidis (33.4 %), S. enterica serovar In...

Clinical isolates of Acinetobacter baumannii (n = 470) were collected during a 7-year period and investigated for the genetic determinants of resistance to expanded-spectrum β-lactams. Thirty-one isolates produced the TEM-92 extended-spectrum β-lactamase (ESBL) and were clonally related. This is the first report of A. baumannii producing a TEM-type...

We evaluated the ability of 60 Italian clinical microbiology laboratories in detecting and reporting beta-lactam resistance phenotypes in Enterobacteriaceae. Laboratories received 5 well-characterized isolates producing extended-spectrum beta-lactamases (ESBLs), 2 hyperproducers of chromosomal enzymes, and 3 quality control strains. The performance...

The VIM- and IMP-type metallo-ß-lactamases (MBLs) are clinically relevant emerging resistance determinants in Gram-negative nosocomial pathogens. To date, MBLs have been reported in acute care hospitals, but their epidemiology in Rehabilitation Facilities (RF) - the largest reservoirs of patients colonized by multidrug-resistant isolates - is large...

Ten multidrug-resistant Pseudomonas aeruginosa strains producing VIM-1-like acquired metallo-beta-lactamases (MBLs), isolated from four European countries (Greece, Hungary, Italy, and Sweden), were analyzed for genetic relatedness by several methodologies, including fliC sequence analysis, macrorestriction profiling of genomic DNA by pulsed-field g...

We report multifocal detection (four different cities in northern Italy) of Proteus mirabilis isolates resistant to both oxyimino- and 7-α-methoxy-cephalosporins and producing a novel acquired AmpC-like β-lactamase. The enzyme, named CMY-16, is a variant of the CMY/LAT lineage, which differs from the closest homologues, CMY-4 and CMY-12, by a singl...

S. marcescens is a recognized nosocomial pathogen especially in NICU. We describe the course and related measures of containment of two outbreaks (I-II) of S. marcescens in a 30-bed NICU. Two patients developed sepsis by S. marcescens in June 2003 following this active surveillance was established to detect infected/colonized patients and the sourc...

A novel OXA-type enzyme, named OXA-46, was found to be encoded by a gene cassette inserted into a class 1 integron from a multidrug-resistant Pseudomonas aeruginosa clinical isolate. The variable region of the integron also contained a blaVIM-1 metallo-β-lactamase cassette and a duplicated aacA4 aminoglycoside acetyltransferase cassette. OXA-46 bel...

An outbreak of Pseudomonas aeruginosa showing a multidrug-resistant (MDR) phenotype (including carbapenems, ceftazidime, cefepime, gentamicin, tobramycin, and fluoroquinolones) was observed, during a 5-month period, in a general intensive care unit of a large tertiary care and clinical research hospital in southern Italy. The outbreak involved 15 p...

Three epidemiologically independent Pseudomonas aeruginosa isolates, representative of the first VIM-1 metallo-β-lactamase producers detected at three different hospitals in northern Italy, were investigated to determine their genomic relatedness and to compare the structures of the genetic supports for the VIM-1 determinants. The three isolates, a...

Forty-four nonreplicate clinical isolates of Pseudomonas aeruginosa that were resistant to extended-spectrum cephalosporins (ceftazidime and cefepime) and aztreonam, that putatively produced an acquired extended- spectrum β-lactamase (ESBL), according to the results of a double-disk synergy test, and that had been involved in nosocomial outbreaks w...

Twelve isolates of Enterobacteriaceae (1 of Klebsiella pneumoniae, 8 of Escherichia coli, 1 of Proteus mirabilis, and 2 of Proteus vulgaris) classified as extended-spectrum β-lactamase (ESBL) producers according to the ESBL screen flow application of the BD-Phoenix automatic system and for which the cefotaxime MICs were higher than those of ceftazi...

A blaTEM-92 gene was cloned from a Proteus mirabilis isolate and expressed in Escherichia coli. Production of the enzyme caused reduction of susceptibility to penicillins and narrow- to expanded-spectrum cephalosporins but not to moxalactam and cephamycins. Determination of kinetic parameters with the purified enzyme revealed hydrolysis of expanded...

A microdilution test measuring imipenem MICs in the presence or absence of a mixture of EDTA plus 1,10-phenanthroline was developed and tested on 190 Pseudomonas aeruginosa isolates, including 18 VIM- and 4 IMP-type metallo-β-lactamase (MBL) producers. The chelator mixture reduced by fourfold or more the imipenem MICs for MBL producers, while a low...

β-Lactamase production was detected in 147 (52%) of 282 consecutive nonduplicate Proteus mirabilis isolates obtained over a 1-year period from the S. Matteo Hospital of Pavia (northern Italy). Seventy isolates (48% of the β-lactamase producers) were found to produce extended-spectrum β-lactamases (ESBLs), identified as PER-1 (first report in this s...

The aim of the present study was to investigate the production of extended-spectrum beta-lactamases (ESbetaLs) and the epidemiological correlations in a total of 107 Klebsiella pneumoniae strains resistant to third- and fourth-generation cephalosporins. The strains were collected from patients in four intensive care units (3 neonatal and 1 general)...

β-Lactam resistance on the part of the Enterobacteriaceae causes serious therapeutic problems in our institutions due to their production of extended-spectrum β-lactamases (ESβLs). We studied the in vitro activity of β-lactam/β-lactamase inhibitor combinations and third-generation cephalosporins and monobactams against 71 clinically relevant Entero...

An outbreak of Serratia marcescens involving 42 patients admitted to the general intensive care unit of the Hospital of Varese, Italy, occurred from March 1994 to August 1995. The causative strains were resistant to oxyimino-cephalosporins and monobactams due to their production of an extended-spectrum beta-lactamase. Another outbreak caused by Ser...

A natural TEM variant beta-lactamase was isolated from an epidemic strain of Serratia marcescens. Nucleotide gene sequencing revealed multiple point mutations located in the 42-to-44 tripeptide and positions 145 to 146, 178, and 238. In addition, a glutamic acid 212 deletion was also found. The purified enzyme was studied from a kinetic point of vi...

We studied antibiotic resistance patterns and extended-spectrum beta-lactamases (ES beta Ls) production in Serratia marcescens strains isolated in our hospital during 1993. We examined 210 S. marcescens isolates. Of these, 172 were obtained from 49 patients admitted to an intensive care ward; 157 out of 172 were obtained from February to October an...

β-Lactamases-mediated, resistance to β-lactam antibiotics, including oxyimino cephalosporins, monobactams and carbapenems, has been studied in clinical isolates of Enterobacteriaceae and Pseudomonas aeruginosa. The results of these studies allowed us to evaluate the role played by β-lactamases in resistance and their prevalence in our geographic ar...

Serratia marcescens has recently been identified as an important etiological agent in nosocomial infections, and is considered to be an opportunistic pathogen agent in immunosuppressed patients undergoing long periods of intensive care. Research carried out in 1991 and 1992 showed that it was of epidemiological relevance in only 1-2% of clinical is...

Eighteen strains of Klebsiella pneumoniae recently isolated from hospitalized patients were resistant or moderately resistant to oxyimino-cephalosporins (ceftazidime and/or cefotaxime), aztreonam, cefoxitin and all but one were susceptible to imipenem. Analysis of enzymes produced by these clinical isolates revealed a wide pattern of extended-spect...

Serratia marcescens has recently been identified as an important etiological agent in nosocomial infections, and is considered to be an opportunistic pathogen agent in immunosuppressed patients undergoing long periods of intensive care. Research carried out in 1991 and 1992 showed that it was of epidemiological relevance in only 1–% of clinical iso...