Mario Sarti

Control of carbapenemase-producing Klebsiella pneumoniae: a region-wide intervention

Starting in 2010, there was a sharp increase in infections caused by Klebsiella pneumoniae resistant to carbapenems in the Emilia-Romagna region in Italy. A region-wide intervention to control the spread of carbapenemase-producing K. pneumoniae (CPKP) in Emilia-Romagna was carried out, based on a regional guideline issued in July 2011. The infection control measures recommended to the Health Trusts (HTs) were: phenotypic confirmation of carbapenemase production, active surveillance of asymptomatic carriers and contact isolation precautions for carriers. A specific surveillance system was activated and the implementation of control measures in HTs was followed up. A significant linear increase of incident CPKP cases over time (p<0.001) was observed at regional level in Emilia-Romagna in the pre-intervention period, while the number of cases remained stable after the launch of the intervention (p=0.48). Considering the patients hospitalised in five HTs that provided detailed data on incident cases, a downward trend was observed in incidence after the release of the regional guidelines (from 32 to 15 cases per 100,000 hospital patient days). The spread of CPKP in Emilia-Romagna was contained by a centrally-coordinated intervention. A further reduction in CPKP rates might be achieved by increased compliance with guidelines and specific activities of antibiotic stewardship.

Epidemiology and outcome of candidemia in internal medicine wards: A regional study in Italy.

BACKGROUND More than one-third of candidemia episodes occur in Internal Medicine Wards (IMWs) but only few studies have focused on this setting and specific data about epidemiology, clinical characteristics and risk factors for mortality are scant. OBJECTIVE To describe epidemiology and to assess risk factors for in-hospital mortality among patients with candidemia in IMWs. METHODS Multicenter retrospective cohort study on patients with candidemia cared for in IMWs of an Italian region (Emilia Romagna) from January 2012 to December 2013. Non survivors were compared with survivors; variables with p≤0.1 at univariate analysis were entered into a multivariate Cox regression model. RESULTS 232 patients were included. Overall candidemia incidence was 2.2 cases/1000 admissions. Candida albicans accounted for 59% of cases. Antifungal treatment was started <24h, 24-72h, and >72h from blood cultures in 47%, 27% and 12% of patients, respectively; 13.8% of patients received no antifungal treatment. In-hospital mortality was 40%. At multivariate analysis, chronic-obstructive-pulmonary-disease (HR 2.72, 95%CI 1.66-4.45, p<0.001) and isolation of C. tropicalis (HR 2.18, 95%CI 1.19-3.99, p=0.01) were the independent risk factors for in-hospital mortality; central-venous-catheter removal (HR 0.59, 95%CI 0.36-0.96, p=0.03) and adequate and timely (within 72h from blood drawing) empirical therapy (HR 0.42, 95%CI 0.25-0.69, p=0.001) were protective factors. CONCLUSIONS The present study conducted in a relatively large geographic area confirms high incidence and mortality of candidemia in IMWs, with a worrisome rate of inappropriateness in patient management. Specific interventions aimed to increase awareness of IMWs about candidemia are needed.

Polyclonal diffusion of beta-lactamase producing Enterococcus faecium.

ABSTRACT 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.

Evolving beta-lactamase epidemiology in Enterobacteriaceae from Italian nationwide surveillance, October 2013: KPC-carbapenemase spreading among outpatients

Extended-spectrum beta-lactamases (ESBLs), AmpC-type 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 Proteus mirabilis (n = 275) from an Italian nationwide cross-sectional survey carried out in October 2013. Overall, 15.3% of isolates were non-susceptible to extended-spectrum cephalosporins but susceptible to carbapenems (ESCR-carbaS), while 4.3% were also non-susceptible to carbapenems (ESCR-carbaR). ESCR-carbaS isolates were contributed by all three species, with higher proportions among isolates from inpatients (20.3%) but remarkable proportions also among those from outpatients (11.1%). Most ESCR-carbaS isolates were ESBL-positive (90.5%), and most of them were contributed by E. coli carrying blaCTX-M group 1 genes. Acquired ACBLs were less common and mostly detected in P. mirabilis. ESCR-carbaR isolates were mostly contributed by K. pneumoniae (25.1% and 7.7% among K. pneumoniae isolates from inpatients and outpatients, respectively), with blaKPC as the most common carbapenemase gene. Results showed an increasing trend for both ESBL and carbapenemase producers in comparison with previous Italian surveys, also among outpatients.

Risk factors for colonization with carbapenemase-producing Klebsiella pneumoniae in hospital: a matched case-control study.

The present case-control study aimed to identify the main factors associated with colonization with carbapenemase-producing Klebsiella pneumoniae (CPKP) in acute care facilities. Administration of carbapenems (odds ratio [OR], 3.67; 95% confidence interval [CI], 1.37-9.83) and other antibiotics (OR, 2.83; 95% CI, 1.10-7.31) during the hospital stay was significantly associated with outcome. The design of this study, with concurrent selection of controls and matching by hospital ward and date of screening, provides a more accurate estimation of relative risks for CPKP colonization than previous investigations.

Detection of mcr-4 positive Salmonella enterica serovar Typhimurium in clinical isolates of human origin, Italy, October to November 2016

In this study we report the detection of the recently described mcr-4 gene in two human isolates of Salmonella enterica serovar Typhimurium. The strains were isolated from faecal samples of two Italian patients with gastroenteritis, collected in 2016. The identified mcr-4 genes (variant mcr-4.2) differed from the mcr-4 gene originally described in a Salmonella strain of swine origin from Italy. Salmonella species could represent a hidden reservoir for mcr genes.

Staphylococcus aureus in a northern Italian region: Phenotypic and molecular characterization

Abstract Background: Staphylococcus aureus is a leading cause of community-acquired infections and healthcare-associated infections. Epidemiological data are useful for understanding the dynamics of the diffusion of this pathogen, and to plan control activities and monitor their efficacy. Methods: S. aureus isolates were collected in 13 public hospital laboratories of Emilia-Romagna (northern Italy region) during February–March 2009; phenotypic and molecular characterizations of these isolates were performed. Results: The study sample included 267 isolates, 57 from blood, 81 from respiratory tract, and 129 from wounds; 106 (40%) were methicillin-resistant S. aureus (MRSA). MRSA showed a limited number of circulating clones with 2 predominant spa types – t008 and t041 – accounting for 36% and 27% of MRSA isolates, respectively. The t041 type had a higher prevalence of antimicrobial resistance compared to other spa types and accounted for most of the retrieved hetero-vancomycin-intermediate S. aureus (h-VISA), while t008 was more frequently detected in non-hospital isolates. A higher degree of genetic diversity was observed in methicillin-susceptible S. aureus (MSSA), with no predominant clones and low prevalence of antimicrobial resistance. The occurrence of community-acquired MRSA infection appears to be rare in Emilia-Romagna. Conclusions: In contrast to previous studies reporting Italian data, t008 was the most frequent spa type among MRSA isolates in Emilia-Romagna. The prevalence of antimicrobial resistance of different MRSA spa types could influence their ability to cause infections with hospital onset. The presence of only 2 major MRSA clones circulating in Emilia-Romagna increases the chances that a regional strategy aimed at MRSA prevention will be effective.

Nocardia brasiliensis in Italy: A nine-year experience

In the past, no case reports concerning N. brasiliensis infections were published from Italy. We now report 4 cases observed during 1998–2006 in 4 Italian patients, 1 immunosuppressed and 3 immunocompetent.

Italian nationwide survey on Pseudomonas aeruginosa from invasive infections: activity of ceftolozane/tazobactam and comparators, and molecular epidemiology of carbapenemase producers

Objectives Pseudomonas aeruginosa is a major cause of severe healthcare-associated infections and often shows MDR phenotypes. Ceftolozane/tazobactam is a new cephalosporin/β-lactamase inhibitor combination with potent activity against P. aeruginosa. This survey was carried out to evaluate the susceptibility of P. aeruginosa, circulating in Italy, to ceftolozane/tazobactam and comparators and to investigate the molecular epidemiology of carbapenemase-producing strains. Methods Consecutive non-replicate P. aeruginosa clinical isolates (935) from bloodstream infections and lower respiratory tract infections were collected from 20 centres distributed across Italy from September 2013 to November 2014. Antimicrobial susceptibility testing was performed by broth microdilution and results were interpreted according to the EUCAST breakpoints. Isolates resistant to ceftolozane/tazobactam were investigated for carbapenemase genes by PCR, and for carbapenemase activity by spectrophotometric assay. WGS using an Illumina platform was performed on carbapenemase-producing isolates. Results Ceftolozane/tazobactam was the most active molecule, retaining activity against 90.9% of P. aeruginosa isolates, followed by amikacin (88.0% susceptibility) and colistin (84.7% susceptibility). Overall, 48 isolates (5.1%) were positive for carbapenemase genes, including blaVIM (n = 32), blaIMP (n = 12) and blaGES-5 (n = 4), while the remaining ceftolozane/tazobactam-resistant isolates tested negative for carbapenemase production. Carbapenemase producers belonged to 10 different STs, with ST175 (n = 12) and ST621 (n = 11) being the most common lineages. Genome analysis revealed different trajectories of spread for the different carbapenemase genes. Conclusions Ceftolozane/tazobactam exhibited potent in vitro activity against P. aeruginosa causing invasive infections in Italy. Carbapenemase production was the most common mechanism of resistance to ceftolozane/tazobactam.

Double synergy differential test for detection of plasmid-mediated AmpC-type β-lactamases in Proteus mirabilis

Proteus mirabilis is an important pathogen, being one of the most common enterobacterial species isolated from both community-acquired and health-careassociated infections (Adler et al., 2008; Bret et al., 1998; Endimiani et al., 2005). In addition to extended-spectrum blactamases (ESBLs), acquired AmpC-type b-lactamases represent an important mechanism of resistance to extendedspectrum cephalosporins in P. mirabilis and are emerging in several European countries including France, Poland, Italy and Spain (Decre et al., 2002; Literacka et al., 2004; Luzzaro et al., 2009; Mata et al., 2010).