Carbapenem-resistant Klebsiella pneumoniae (CR-KP) is becoming a common cause of healthcare-associated infection in Italy, with high morbidity and mortality. Prevalent CR-KP clones and resistance mechanisms vary between regions and over time. Therapeutic approaches and their impact on mortality have to be investigated. We performed a prospective study of patients with CR-KP isolation, hospitalized in nine hospitals of Rome, Italy, from December 2010 to May 2011, to describe the molecular epidemiology, antibiotic treatment and risk factors for mortality. Overall, 97 patients (60% male, median age 69 years) were enrolled. Strains producing blaKPC-3 were identified in 89 patients, blaVIM in three patients and blaCTX-M-15 plus porin defects in the remaining five patients. Inter-hospital spread of two major clones, ST512 and ST258, was found. Overall, 36.1% and 20.4% of strains were also resistant to colistin and tigecycline, respectively. Infection was diagnosed in 91 patients who received appropriate antibiotic treatment, combination therapy and removal of the infectious source in 73.6%, 59.3% and 28.5% of cases, respectively. Overall, 23 different antibiotic regimens were prescribed. In-hospital mortality was 25.8%. Multivariate analysis adjusted for appropriate treatment, combination therapy and infectious-source removal, showed that Charlson comorbidity score, intensive-care unit onset of infection, bacteraemia and infection due to a colistin-resistant CR-KP strain were independent risk factors for mortality. The spread of clones producing K. pneumoniae carbapenemases, mainly ST258, is currently the major cause of CR-KP infection in central Italy. We observed a high rate of resistance to colistin that is independently associated with worse outcome.

BackgroundA common pattern emerging from several studies evaluating the impact of the 2009 A/H1N1 pandemic influenza (A/H1N1pdm) conducted in countries worldwide is the low attack rate observed in elderly compared to that observed in children and young adults. The biological or social mechanisms responsible for the observed age-specific risk of infection are still to be deeply investigated.MethodsThe level of immunity against the A/H1N1pdm in pre and post pandemic sera was determined using left over sera taken for diagnostic purposes or routine ascertainment obtained from clinical laboratories. The antibody titres were measured by the haemagglutination inhibition (HI) assay. To investigate whether certain age groups had higher risk of infection the presence of protective antibody (≥1∶40), was calculated using exact binomial 95% CI on both pre- and post- pandemic serological data in the age groups considered. To estimate age-specific susceptibility to infection we used an age-structured SEIR model.ResultsBy comparing pre- and post-pandemic serological data in Italy we found age- specific attack rates similar to those observed in other countries. Cumulative attack rate at the end of the first A/H1N1pdm season in Italy was estimated to be 16.3% (95% CI 9.4%-23.1%). Modeling results allow ruling out the hypothesis that only age-specific characteristics of the contact network and levels of pre-pandemic immunity are responsible for the observed age-specific risk of infection. This means that age-specific susceptibility to infection, suspected to play an important role in the pandemic, was not only determined by pre-pandemic levels of H1N1pdm antibody measured by HI.ConclusionsOur results claim for new studies to better identify the biological mechanisms, which might have determined the observed pattern of susceptibility with age. Moreover, our results highlight the need to obtain early estimates of differential susceptibility with age in any future pandemics to obtain more reliable real time estimates of critical epidemiological parameters.

Objectives: To analyse the strains collected during a 1-year survey of ceftazidime-avibactam-resistant KPC-producing Klebsiella pneumoniae, in order to investigate the molecular mechanisms potentially responsible for their resistant phenotype. Methods: Clinical KPC-producing K. pneumoniae isolates were collected from 31 patients in six different hospitals in Rome. For eight of the patients, an additional strain grown before the start of treatment was also available, bringing the total of isolates studied to 39. Antimicrobial susceptibility was determined by automated system, broth microdiluition and E-test as appropriate. In silico analysis of acquired resistance genes was achieved by whole-genome sequencing, while multilocus sequence typing and core genome multilocus sequence typing were employed for molecular typing. Mutations associated with ceftazidimeavibactam resistance were identified by Sanger sequencing of the bla KPC gene. Possible mutations in OmpK35 and OmpK36 outer membrane proteins were also investigated. Results: Molecular analyses highlighted the circulation of the ST512, 101 and 307 high-risk clones; 26 of the 31 patients carried a mutated KPC variant, five had a wild-type KPC-3. Among the KPC variants detected, 11 were different mutations within the bla KPC-3 gene, four of which were novel mutational changes. Conclusions: Different mutations including single amino-acid substitutions, insertions or deletions within the bla KPC gene were found in 26/31 ceftazidime-avibactam-resistant KPC-producing K. pneumoniae strains belonging to high-risk clones circulating in Italy. Of note, in 14/31 cases the isolates displayed resistance to both ceftazidime-avibactam and carbapenems, raising concerns for the possible selection of a multidrug-resistant phenotype.

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Introduction: Lactobacilli are currently proposed as probiotic agents in several dietary products. In blood cultures, they are usually considered as contaminants, but in recent years they have been recognized as causal infectious agents of endocarditis, urinary tract infections, meningitis, intraabdominal infections and bacteraemia.