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Martina Spaziante,1 Carolina Venditti,2 Ornella Butera,2 Francesco Messina,2 Antonino Di Caro,2 Gilda Tonziello,1 Simone Lanini,1 Maria Adriana Cataldo,1 Vincenzo Puro1 1Emerging Infection Unit and Regional Service for Surveillance and Control of Infectious Diseases (SeRESMI), National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, Italy; 2Laboratory of Microbiology, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Rome, ItalyCorrespondence: Maria Adriana Cataldo Tel +39 0655170786Email adriana.cataldo@inmi.itIntroduction: New Delhi metallo-β-lactamase producing Klebsiella pneumoniae (NDM-Kpn) strains have been causing healthcare-associated infections worldwide. The aim of this study was to describe the molecular mechanisms of antimicrobial resistance and to analyze the clonality of NDM-Kpn isolates collected between January 2019 and June 2020 from patients admitted to hospitals from the Lazio region, Italy.Methods: We performed a retrospective cohort study. Whole-genome sequencing (WGS) was performed on all NDM-Kpn strains; clonality and genetic relationships were further investigated.Results: During the surveillance period, 17 NDM-Kpn isolates were obtained from 17 patients admitted to seven different hospitals. Eight different sequence types (STs) were detected: ST147 (n = 4), ST383 (n = 4), ST15 (n = 3), ST11 (n = 2), ST17 (n = 1), ST29 (n = 1), ST307 (n = 1) and the newly identified ST4853 (n = 1). Genetic relationships were further investigated by the WGS-based core genome MLST (cgMLST) scheme, and 5 cluster types (CTs) were identified. Whereas a substantial overall heterogeneity among isolates was detected (8 different STs were identified out of 17 isolates), the strains within each cluster showed a very high level of genome similarity.Discussion: Our study highlights the key role of surveillance, which allowed taking a picture of a part of the NDM-Kpn strains circulating in Italy, adding further insight into their molecular features.Keywords: carbapenem-resistant Klebsiella pneumoniae, New Delhi metallo-β-lactamase, surveillance, healthcare-associated infections

Objectives During the COVID-19 pandemic, several studies described an increased chance of developing pulmonary embolism (PE). Several scores have been used to predict the occurrence of PE. In this systematic review, we aim at summarizing the literature on predicting rules for PE in hospitalized COVID-19 patients (HCPs). Methods PUBMED and EMBASE databases were searched to identify articles (1 January 2020-28 April 2021) presenting data pertaining the use of a prediction rule to assess the risk for PE in adult HCPs. The investigated outcome was the diagnosis of PE. Studies presenting data on the use of a single laboratory assay for PE prediction were excluded. Included studies were appraised for methodological quality using the Newcastle - Ottawa Quality Assessment Scale for Cohort Studies (NOS). Results We obtained a refined pool of 12 studies, for a total of 5 scoring systems (Wells score, Geneva score, CHADS2/CHA2DS2VASc/M-CHA2DS2VASc, CHOD score, Padua Prediction Score), and 4526 patients. Only one score was specifically designed for HCPs. Three and nine included studies were prospective and retrospective cohort studies, respectively. Among the examined scores, CHOD score seems promising in terms of predictive ability. Conclusion New prediction rules, specifically developed and validated for estimating the risk of PE in HCP, differentiating ICU from non-ICU patients, and taking into account anticoagulation prophylaxis, comorbidities and the time from COVID-19 diagnosis are needed.

Diagnosis of spondylodiscitis (SD) may be challenging due to the nonspecific clinical and laboratory findings and the need to perform various diagnostic tests including serologic, imaging, and microbiological examinations. Homogeneous management of SD diagnosis through international, multidisciplinary guidance would improve the sensitivity of diagnosis and lead to better patient outcome. An expert specialist team, comprising nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), neuroradiologists appointed by the European Society of Neuroradiology (ESNR), and infectious diseases specialists appointed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), reviewed the literature from January 2006 to December 2015 and proposed 20 consensus statements in answer to clinical questions regarding SD diagnosis. The statements were graded by level of evidence level according to the 2011 Oxford Centre for Evidence-based Medicine criteria and included in this consensus document for the diagnosis of SD in adults. The consensus statements are the result of literature review according to PICO (P:population/patients, I:intervention/indicator, C:comparator/control, O:outcome) criteria. Evidence-based recommendations on the management of adult patients with SD, with particular attention to radiologic and nuclear medicine diagnosis, were proposed after a systematic review of the literature in the areas of nuclear medicine, radiology, infectious diseases, and microbiology. A diagnostic flow chart was developed based on the 20 consensus statements, scored by level of evidence according to the Oxford Centre for Evidence-based Medicine criteria. This consensus document was developed with a final diagnostic flow chart for SD diagnosis as an aid for professionals in many fields, especially nuclear medicine physicians, radiologists, and orthopaedic and infectious diseases specialists.

The impact of inappropriate empirical antibiotic therapy (IEAT) on the outcome of severe infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-Ent) remains unclear. Current evidence is limited by study design and lack of confounder control. The main objective of this study was to define the outcome of severe infections due to ESBL-Ent according to clinical parameters and place of infection acquisition. Adult hospitalised patients with ESBL-Ent infections were included in a 3-year multicentre prospective study. Primary outcomes were IEAT rates and crude mortality of severe infections, adjusted by place of acquisition [community-acquired infection (CAI), healthcare-associated infection (HCAI) and hospital-acquired infection (HAI)]. Among 729 patients, 519 (71.2%) were diagnosed with HAI, 176 (24.1%) with HCAI and 34 (4.7%) with CAI. Moreover, 32.9% of patients received IEAT; higher rates of IEAT were observed in pneumonia (23%) and deep surgical site infections (19%). HCAIs were more frequently associated with IEAT than HAIs (48.3% vs. 27.9%; OR = 1.7, 95% CI 1.2–2.4). The overall mortality rate for severe infections (n = 264) was 12.1% and was significantly higher in HCAIs (20%) than HAIs (10%) (RR = 2.3, 95% CI 1.01–5.3). IEAT significantly increased the risk of mortality in bloodstream infections (RR = 8.3, 95% CI 2–46.3). Rates of IEAT and overall mortality of ESBL-Ent severe infections were higher in HCAIs than HAIs. Prompt diagnosis of patients with severe HCAIs due to ESBL-Ent is essential since these infections receive high rates of IEAT and significantly higher mortality than HAIs [ClinicalTrials.gov Identifier: NCT00404625].

Background: Limited and wide-ranging data are available on the recurrent Clostridioides difficile infection (rCDI) incidence rate. Methods: We performed a cohort study with the aim to assess the incidence of and risk factors for rCDI. Adult patients with a first CDI, hospitalized in 15 Italian hospitals, were prospectively included and followed-up for 30 d after the end of antimicrobial treatment for their first CDI. A case–control study was performed to identify risk factors associated with 30-day onset rCDI. Results: Three hundred nine patients with a first CDI were included in the study, 32% of the CDI episodes (99/309) were severe/complicated, complete follow-up was available for 288 patients (19 died during the first CDI episode, and 2 were lost during follow-up). At the end of the study, the crude all-cause mortality rate was 10.7% (33 deaths/309 patients). Two hundred seventy-one patients completed the follow-up, rCDI occurred in 21% of patients (56/271) with an incidence rate of 72/10,000 patient-days. Logistic regression analysis identified exposure to cephalosporin as an independent risk factor associated with rCDI (RR: 1.7, 95% CI: 1.1–2.7, p = 0.03). Conclusion: Our study confirms the relevance of rCDI in terms of morbidity and mortality and provides a reliable estimation of its incidence.

Objectives The main aim of this systematic review and meta-analysis was to assess the proportion of confirmed COVID-19 patients with Clostridioides difficile infection (CDI) and to describe risk factors and outcome of these patients. Methods MEDLINE and Cochrane Central Register of Controlled Trials databases were searched up to July 15, 2021. We included studies reporting data on CDI occurring in patients with a confirmed diagnosis of COVID-19. We pooled proportion of CDI patients using a random effects model (DerSimonian–Laird method) stabilising the variances using the Freeman-Tukey double arcsine transformation. Results Thirteen studies were included in the systematic review. All the studies retrospectively collected data between February 2020 and February 2021. The reported CDI incidence rates ranged from 1.4 to 4.4 CDI cases per 10,000 patient-days. Seven studies reported data on the number of COVID-19 patients who developed CDI and the total number of COVID-19 patients in the study period and were included in the meta-analysis, comprising 23,697 COVID-19 patients. The overall pooled proportion of COVID-19 patients who had CDI was 1% [95% confidence interval: 1–2]. Among studies reporting CDI occurrence in patients with and without COVID-19, the majority of them reported reduced or unchanged CDI rates compared to pre-COVID period. Conclusions CDI is a relevant issue for COVID-19 patients. Adherence to infection prevention and control measures and to the antimicrobial stewardship principles is crucial even during the COVID-19 pandemic.

Objectives Peripheral bone infection (PBI) and prosthetic joint infection (PJI) are two different infectious conditions of the musculoskeletal system. They have in common to be quite challenging to be diagnosed and no clear diagnostic flowchart has been established. Thus, a conjoined initiative on these two topics has been initiated by the European Society of Radiology (ESR), the European Association of Nuclear Medicine (EANM), the European Bone and Joint Infection Society (EBJIS), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). The purpose of this work is to provide an overview on the two consensus documents on PBI and PJI that originated by the conjoined work of the ESR, EANM, and EBJIS (with ESCMID endorsement).Methods and results After literature search, a list of 18 statements for PBI and 25 statements for PJI were drafted in consensus on the most debated diagnostic challenges on these two topics, with emphasis on imaging.Conclusions Overall, white blood cell scintigraphy and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities for the diagnosis of PBI and PJI. However, the choice of which advanced diagnostic modality to use first depends on several factors, such as the benefit for the patient, local experience of imaging specialists, costs, and availability. Since robust, comparative studies among most tests do not exist, the proposed flowcharts are based not only on existing literature but also on the opinion of multiple experts involved on these topics.Key PointsFor peripheral bone infection and prosthetic joint infection, white blood cell and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities.Two evidence- and expert-based diagnostic flowcharts involving variable combination of laboratory tests, biopsy methods, and radiological and nuclear medicine imaging modalities are proposed by a multi-society expert panel.Clinical application of these flowcharts depends on several factors, such as the benefit for the patient, local experience, costs, and availability.

Objectives Clostridioides difficile infection (CDI) represents a challenging issue, with an evolving epidemiology. Main objectives of our study were: to assess the frequency of diarrhea of overall etiology, including CDI, as a cause of hospital admission or occurring during hospital stay;- to determine the rate of underdiagnosis of community-acquired (CA-), health care associated (HCA)- and hospital onset (HO-) CDI, and explore factors associated with its clinical suspicion by physicians. Methods A prospective cohort study included all hospitalized patients with diarrhea at two acute-care hospitals. C. difficile (CD) tests were performed on every stool samples, irrespective of the treating physician request. Factors associated with the likelihood of CD test request by physicians were assessed. Results We enrolled 871 (6%) patients with diarrhea. CD test performed on all diarrheic stool samples was positive in 228 cases (26%); 37, 106, 85 cases of CA- (14%), HCA- (42%) and HO- diarrhea (24%), respectively. Treating physicians did not request CD test in 207 (24%) diarrhea cases. The rate of CDI underdiagnosis was 11% (24/228); it was higher in CA-CDI (27%, 10/37). Logistic regression analysis identified age >65 years (RR 1.1; 95 CI 1.06–1.2) and hospitalizations in the previous 3 months (RR 1.2; 95% CI 1.1–1.3) as independent factors associated with the likelihood of requesting the CD test by the physician. These risk factors differed by epidemiological classification of diarrhea and by hospital. Conclusions Our study confirmed the relevance of CDI underdiagnosis and provided new insights in the factors underlying the lack of CDI clinical suspicion.

Despite the large amount of scientific publications exploring the epidemiology and the clinical management of Clostridium difficile (CD) infection, some issues remain unsolved or need further studies. The aim of this review is to give an update on the hot topics on CD prevention, including stewardship programs, and on the non-microbiological treatment of CD infection. Areas covered: This article will review the importance of minimizing the CD spore shedding in the healthcare environment for potentially reducing CD transmission. Moreover, antimicrobial stewardship programs aimed to reduce CD incidence will be reviewed. Finally, new strategies for reducing CD infection recurrence will be described. Expert commentary: Besides the basic infection control and prevention practices, including hand hygiene, contact isolation and environmental cleaning, in the prevention of CD infection other issues should be addressed including minimizing the spread of CD in the healthcare setting, and implementing the best strategy for reducing CD infection occurrence, including tailored antimicrobial stewardship programs. Regarding new advancements in treatment and management of CDI episodes, non-antimicrobial approaches seem to be promising in reducing and managing recurrent CD infection.

Introduction In adults with a suspicion of peripheral bone infection, evidence-based guidelines in choosing the most accurate diagnostic strategy are lacking. Aim and methods To provide an evidence-based, multidisciplinary consensus document on the diagnostic management of adult patients with PBIs, we performed a systematic review of relevant infectious, microbiological, orthopedic, radiological, and nuclear medicine literature. Delegates from four European societies (European Bone and Joint Infection Society, European Society of Microbiology and Infectious Diseases, European Society or Radiology, and European Association of Nuclear Medicine) defined clinical questions to be addressed, thoroughly reviewed the literature pertinent to each of the questions, and thereby evaluated the diagnostic accuracy of each diagnostic technique. Inclusion of the papers per statement was based on a PICO (Population/problem – Intervention/indicator – Comparator – Outcome) question following the strategy reported by the Oxford Centre for Evidence-based Medicine. For each statement, the level of evidence was graded according to the 2011 review of the Oxford Centre for Evidence-based Medicine. All approved statements were addressed taking into consideration the available diagnostic procedures, patient acceptance, tolerability, complications, and costs in Europe. Finally, a commonly agreed-upon diagnostic flowchart was developed. Electronic supplementary material The online version of this article (10.1007/s00259-019-4262-x) contains supplementary material, which is available to authorized users.

The current picture of Clostridium difficile infection (CDI) is alarming with a mortality rate ranging between 3% and 15% and a CDI recurrence rate ranging from 12% to 40%. Despite the great efforts made over the past 10 years to face the CDI burden, there are still gray areas in our knowledge on CDI management. The traditional anti-CDI antimicrobials are not always adequate in addressing the current needs in CDI management. The aim of our review is to give an update on novel antimicrobials for the treatment of CDI, considering the currently available evidences on their efficacy, safety, molecular mechanism of action, and their probability to be successfully introduced into the clinical practice in the near future. We identified, through a PubMed search, 16 novel antimicrobial molecules under study for CDI treatment: cadazolid, surotomycin, ridinilazole, LFF571, ramoplanin, CRS3123, fusidic acid, nitazoxanide, rifampin, rifaximin, tigecycline, auranofin, NVB302, thuricin CD, lacticin 3147, and acyldepsipeptide antimicrobials. In comparison with the traditional anti-CDI antimicrobial treatment, some of the novel antimicrobials reviewed in this study offer several advantages, i.e., the favorable pharmacokinetic and pharmacodynamic profile, the narrow-spectrum activity against CD that implicates a low impact on the gut microbiota composition, the inhibitory activity on CD sporulation and toxins production. Among these novel antimicrobials, the most active compounds in reducing spore production are cadazolid, ridinilazole, CRS3123, ramoplanin and, potentially, the acyldepsipeptide antimicrobials. These antimicrobials may potentially reduce CD environment spread and persistence, thus reducing CDI healthcare-associated acquisition. However, some of them, i.e., surotomycin, fusidic acid, etc., will not be available due to lack of superiority versus standard of treatment. The most CD narrow-spectrum novel antimicrobials that allow to preserve microbiota integrity are cadazolid, ridinilazole, auranofin, and thuricin CD. In conclusion, the novel antimicrobial molecules under development for CDI have promising key features and advancements in comparison to the traditional anti-CDI antimicrobials. In the near future, some of these new molecules might be effective alternatives to fight CDI.

Surgical site infections are among the most common healthcare-associated infections and are linked with increased length of hospitalization, re-admission, mortality and significant financial burden. Risk factors for the occurrence of surgical site infections include variables related to the surgical procedure as well as host factors. Increasing age is associated with the occurrence of surgical site infections. The aim of this review is to give an update on the antibiotic prophylaxis for surgical site infection in elderly people. We focused on specific issues and practical applications, such as the importance of targeting the antimicrobial agent to the susceptibility pattern of colonizing flora in selected cases and the need for dosage modifications.

Objectives Vancomycin-resistant enterococci (VRE) represent a major problem in healthcare settings worldwide. It is still unclear which is the most effective infection control and prevention (ICP) measure to reduce the spread of hospital-acquired VRE. Methods Cochrane databases, MEDLINE, EMBASE and CINAHL were searched until June 2012 to find studies comparing wards/hospitals where ICP measures to prevent VRE transmission were investigated. In the absence of heterogeneity, a fixed-effects model was used to estimate the pooled risk ratio (RR). Study quality was assessed according to Cochrane Effective Practice and Organisation of Care (EPOC) criteria. Results The search strategy retrieved 549 studies and 9 studies (1 randomized clinical trial, 3 controlled clinical trials and 5 interrupted time series) with 30, 949 participants were included. The overall study quality was low. Implementation of hand hygiene was associated with a 47% decrease in the VRE acquisition rate (pooled RR 0.53, 95% CI 0.39-0.73, I(2) 26%) while contact precautions did not significantly reduce the VRE acquisition rate (pooled RR 1.08, 95% CI 0.63-1.83, I(2) 0%). Due to the low number of studies, meta-analysis was not applied for surveillance screening, environmental cleaning and antibiotic formulary interventions. No studies were available on the effectiveness of isolation and cohorting of patients and staff. Conclusions Available evidence on the ICP measures to reduce VRE spread in adult hospitalized patients is poor. This systematic review suggests a significant role for the implementation of hand hygiene. Further studies with appropriate study design are urgently needed to define ICP measures able to reduce the acquisition of VRE among hospitalized patients.

We describe the interspecies transmission of the plasmid-mediated blaKPC-3 gene, which confers carbapenem resistance, between clinically relevant gram-negative bacteria in a single patient. A KPC-3 producing Enterobacter aerogenes was isolated from a hospitalized patient previously colonized and then infected by a Klebsiella pneumoniae ST101 carrying the blaKPC-3 gene. The strains showed identical plasmids. Since intense horizontal exchanges among bacteria can occur in the gut, clinicians should be aware that patients colonized by carbapenem-resistant K. pneumoniae could become carriers of other carbapenem-resistant Enterobacteriaceae.

Objectives To explore the accuracy of application of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) tool in epidemiological studies focused on the evaluation of the role of antibiotics in selecting resistance, and to derive and test an extension of STROBE to improve the suitability of the tool in evaluating the quality of reporting in these area. Methods A three-step study was performed. First, a systematic review of the literature analysing the association between antimicrobial exposure and acquisition of methicillin-resistant Staphylococcus aureus and/or multidrug-resistant Acinetobacter baumannii was performed. Second, articles were reviewed according to the STROBE checklist for epidemiological studies. Third, a set of potential new items focused on antimicrobial-resistance quality indicators was derived through an expert two-round RAND-modified Delphi procedure and tested on the articles selected through the literature review. Results The literature search identified 78 studies. Overall, the quality of reporting appeared to be poor in most areas. Five STROBE items, comprising statistical analysis and study objectives, were satisfactory in

OBJECTIVES To assess risk factors for acquiring extended-spectrum β-lactamase-producing Gram-negative bacteria (ESBL+ GN) causing urinary tract infections (UTIs) in long-term care facilities (LTCFs). METHODS A prospective case-case-control study was carried out. In the first study, cases were defined as patients harbouring ESBL+ GN, while, in the second study, cases were defined as patients harbouring ESBL-negative (ESBL-) GN. Controls were selected by simple random sampling from patients without GN infection. ESBL determinants were characterized by hybridization, and confirmed by PCR and sequencing. RESULTS The study involved 297 LTCF patients (99 with ESBL+ GN UTI, 99 with ESBL- GN UTI and 99 without GN infection). ESBL+ GN UTIs were due to Escherichia coli (64%), Proteus mirabilis (25%) and Klebsiella pneumoniae (11%). The CTX-M-type enzymes were the most prevalent (73% of isolates), whereas TEM- and SHV-type ESBLs and AmpC-type enzymes were less prevalent (10%, 2% and 15% of isolates, respectively). Patients with ESBL+ GN UTI were more likely to have a permanent urinary catheter (OR 15, 95% CI 6.9-30.5) and to have received antimicrobial therapy in the previous 30 days (OR 4, 95% CI 1.2-10.9). After adjusting for type, dosage and duration of antibiotic, exposure to ≥7 days of quinolones and third-generation cephalosporins was associated with the highest risk of ESBL+ GN UTI development (OR 7, 95% CI 1.2-40). Independent risk factors for acquiring ESBL- GN UTIs were previous surgical procedures (OR 2, 95% CI 1.1-4) and the presence of a urinary catheter (OR 8, 95% CI 4-16). No specific antibiotics remained a significant risk for ESBL- GN UTI after adjusting for demographic and clinical risk factors. CONCLUSIONS Exposure to ≥7 days of quinolones and third-generation cephalosporins significantly increases the risk of ESBL+ GN UTI. Interventions aimed at improving compliance with antimicrobial stewardship principles should be further developed and implemented in LTCFs.

Methicillin-resistant Staphylococcus aureus (MRSA), one of the most common causes of infections, has been traditionally recognized as a nosocomial pathogen. However, in recent years, its epidemiology has radically changed, being now observed even more frequently in the community, and accounting for50% of staphylococcal infections in the US outpatient setting. Community-acquired (CA)-MRSA strains typically cause infections among otherwise healthy individuals, with risk factors differing from those of nosocomial MRSA. The clinical manifestations may range from a furuncle to life-threatening infections, such as necrotizing fasciitis and pneumonia. The antibiotic treatment of these infections may also differ because CA-MRSA strains often retain susceptibility to antimicrobials other than glycopeptides and newer agents. Moreover, the production of toxins, such as the Panton-Valentine leukocidin (PVL), should influence the antibiotic choice because in these cases the use of a combination therapy with antimicrobial agents able to decrease toxin production is suggested. There are still many unanswered key questions regarding the epidemiology, prevention, and treatment of CA-MRSA infections. This article reviews current knowledge of CA-MRSA.

Current evidence does not provide a clear definition of the association between methicillin-resistant Staphylococcus aureus (MRSA) isolation and previous antibiotic use. A systematic review was performed to determine whether antibiotic exposure is a risk factor for the isolation of MRSA.MEDLINE and EMBASE databases were searched to identify studies published between 1976 and 2007 on the role of antibiotics as a risk factor for MRSA isolation in adult patients. The outcome of interest was MRSA isolation. Summary statistics were risk ratios (RR) comparing MRSA-positive patients to those without S. aureus isolation or with methicillin-susceptible S. aureus isolation.Seventy-six studies, including a total of 24 230 patients, met the inclusion criteria. Antibiotic exposure was determined in the 126 +/- 184 (mean +/- SD) days preceding MRSA isolation. The risk of acquiring MRSA was increased by 1.8-fold [95% confidence interval (CI), 1.7-1.9; P0.001] in patients who had taken antibiotics. The RR for single classes of antibiotics was 3 (95% CI, 2.5-3.5) for quinolones, 2.9 (95% CI, 2.4-3.5) for glycopeptides, 2.2 (95% CI, 1.7-2.9) for cephalosporins and 1.9 (95% CI, 1.7-2.2) for other beta-lactams. Significant heterogeneity was detected among studies. A regression analysis revealed that the heterogeneity was linked to the length of time in which antibiotic exposure was detected before MRSA isolation (more or less than 180 days).This meta-analysis shows a clear association between exposure to antibiotics and MRSA isolation. This information may be useful for researchers in designing future studies and for policy decision-making on the appropriate management of antibiotic therapies.

Background.Case-control studies analyzing antibiotic exposure as a risk factor for antimicrobial resistance usually assume single-drug resistance in the bacteria under study, even though resistance to multiple antimicrobials may be present. Since antibiotic selection pressures differ depending on the susceptibility profile of the antimicrobial-resistant bacteria, an accurate assessment of whether exposure to an individual antimicrobial is a risk factor for the emergence of resistance should distinguish between single-drug–resistant and multidrug-resistant bacteria.Objective.To determine whether the exposures to individual antibiotics that were identified as independent risk factors in case-control studies differed depending on whether single-drug–resistant or multidrug-resistant bacteria were evaluated.Design.Two retrospective case-control studies were performed with data on patients harboringPseudomonas aeruginosastrains resistant only to ciprofloxacin (CRPA) and patients harboringP. aeruginosastrains resistant to ciprofloxacin and other antibiotics (multidrug-resistantP. aeruginosa[MDR-PA]). These 2 groups were compared with patients not harboringP. aeruginosa.Setting.Two tertiary care hospitals.Results.A total of 41 patients harboring CRPA and 151 patients harboring MDR-PA were identified and matched to 192 control subjects. By conditional logistic regression, independent risk factors associated with presence of CRPA were nonambulatory status (OR, 5.6 [95% confidence interval {CI}, 1.4-23];P= .02) and prior ciprofloxacin exposure (OR, 5.0 [95% CI, 1.2-21];P= .03). Independent risk factors for presence of MDR-PA were a Charlson score greater than 2 (OR, 3.3 [95% CI 1.8-6.0];PP= .001), third- and fourth-generation cephalosporins (OR, 3.5 [95% CI, 1.7-7.1];PP= .02), and/or aminoglycosides (OR, 2.3 [95% CI, 1.04-5.1];P= .04).Conclusion.There were substantial differences in exposure to individual antimicrobials between patients harboring CRPA and patients harboring MDR-PA. Future case-control studies addressing risk factors for single-drug–resistant bacteria should consider the complete susceptibility profile of the bacteria under investigation.

Although resistance to tigecycline has been reported in surveillance studies, very few reports have described the emergence of resistance in vivo . We report two cases of patients with infections due to SHV-12-producing Klebsiella pneumoniae and K. pneumoniae carbapenemase-3 (KPC-3)-producing Escherichia coli , which developed tigecycline resistance in vivo after treatment. The reported limited experience underlines the risk of occurrence of a tigecycline MIC increase under treatment pressure.

Healthcare-associated infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) are a leading cause of morbidity and mortality worldwide. These evidence-based guidelines have been produced after a systematic review of published studies on infection prevention and control interventions aimed at reducing the transmission of MDR-GNB. The recommendations are stratified by type of infection prevention and control intervention and species of MDR-GNB and are presented in the form of ‘basic’ practices, recommended for all acute care facilities, and ‘additional special approaches’ to be considered when there is still clinical and/or epidemiological and/or molecular evidence of ongoing transmission, despite the application of the basic measures. The level of evidence for and strength of each recommendation, were defined according to the GRADE approach.

Reduced circulation of hepatitis A virus lead to an increase of susceptible individuals, and outbreaks occurred recently. In Northern Italy an outbreak is ongoing, attributed to a monophyletic genotype IA strain, with mixed frozen berries as probable source. From 01/01/2013 to 07/15/2013, 30 cases were diagnosed at National Institute for Infectious Diseases, Rome, Italy, representing about twice the number of cases in whole 2012. Phylogenetic analysis indicated that most, although not all, infections were attributable to the same monophyletic genotype IA strain identified in the contemporary Northern Italy outbreak. This strain is also very similar to previous isolates from Venezuela.

Objectives: To summarize available evidence on the effect of continuous infusion (CoI) of vancomycin compared with intermittent infusion (InI) in adult patientswith Gram-positive infections. Methods: MEDLINE, EMBASE and Cochrane databases were searched. Randomized clinical trials (RCTs) and observational studies that comparatively assessed CoI and InI of vancomycin in terms of mortality, clinical cure, toxicity rates and serum drug exposure [trough concentration(Cmin) for InI and steady-state concentration (Css) for CoI; area under the curve at 24 h (AUC24) for both] were included. Meta-analysis was conducted combining and analysing the relative risk (RR) and computing a summary RR of the effects with 95% confidence interval (CI). The standardized mean difference was calculated for continuous outcomes. The I2 test was calculated to assess heterogeneity across studies. Results: One RCT and five observational studies were included in the analysis. Compared with InI, CoI of vancomycin was associated with a significantly lower risk of nephrotoxicity (RR 0.6, 95% CI 0.4-0.9, P=0.02;I2=0). Overall mortality was not different between the two groups (RR 1.03, 95% CI 0.7-1.6, P=0.9; I2=0). Conclusions: Our meta-analysis suggests that administration of vancomycin for the treatment ofGram-positiveinfections by CoI is associated with a significantly lower risk of nephrotoxicity when compared with InI of the drug.RCTs are needed to define the impact on mortality rate and on the pharmacodynamic activity in terms of AUC/MIC ratio. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Selenium is a non-metallic chemical element of great important to human health. Low selenium levels in humans are associated with several pathological conditions and are a common finding in HIV infected individuals. We conducted a review of the literature to assess if selenium deficiency or selenium supplementation could play a role in modifying the clinical course of HIV disease. Several studies investigated the role of selenium in disease progression, morbidity and mortality in HIV infected individuals. Larger studies were conducted in countries with poor economic resources and limited access to HAART. According to the majority of published studies low selenium levels appear to have an association with mortality, and selenium supplementation appears to play a beneficial role on survival or on slowing disease progression among HIV infected individuals. The role of selenium supplementation on preventing hospital admission among HIV outpatients was also noticed. The literature suggests an association between selenium deficiency and development of HIV associated cardiomyopathy and furthermore, selenium supplementation appears to improve the cardiac function in HIV infected individuals with cardiomyopathy. However, there is conflicting evidence regarding the role selenium in modifying HIV viral load and immune status in HIV infection.

Over the past years there has been a significant increase in the number of joint prosthesis replacements worldwide. The most serious complication of joint prosthesis is infection with an incidence of 1.5-2.5% for primary interventions and up to 20% for revision procedures. The mortality rate ranges between 1% and nearly 3%. The economic cost of this complication is up to $50,000 per patient and $250,000 million per year. A major issue in the management of prosthetic joint infection (PJI) is the relative difficulty in making a diagnosis so to cause a significant effect on the prognosis. Goals of the treatment are to eradicate infection, prevent its recurrence and preserve mechanical joint function. In this review we focus on the value of traditional and newer diagnostic tests and we discuss management and preventive strategies. European networks are needed to define the best diagnostic and treatment strategies in order to reduce future challenge posed by PJIs.

Detection and eradication of meticillin-resistant Staphylococcus aureus (MRSA) represents a public health priority worldwide. Our aim was to do a systematic review and meta-analysis of randomised, non-randomised, and observational studies to summarise the available evidence on the effect of MRSA detection by rapid screening tests on hospital-acquired MRSA infections and acquisition rate. Eligible studies were retrieved from Medline, EmBase, Science Citation Index, and the Cochrane database. We judged as eligible those studies that compared hospitals and wards in which active screening for the detection of MRSA carriers was done at hospital admission by use of a rapid molecular test to those in which active screening was done with culture alone or not at all. To account for statistical heterogeneity between studies, random-effects models were used. Ten studies (nine interventional studies and one unblinded, cluster-randomised, crossover trial) were reviewed. Meta-analysis was done for studies reporting data on the same outcome. Primary outcomes included MRSA acquisition rate per 1000 patient-days (four studies); incidence of MRSA bloodstream infections per 1000 patient-days (three studies); and incidence of MRSA surgical-site infections per 100 surgical procedures (five studies). Compared with culture screening, use of rapid screening tests was not associated with a significant decrease in MRSA acquisition rate (risk ratio 0.87, 95% CI 0.61-1.24). Between wards applying rapid screening tests and those not applying screening, we noted a significantly decreased risk for MRSA bloodstream infections (0.54, 95% CI 0.41-0.71), but not for MRSA surgical-site infections (0.69, 95% CI 0.46-1.01). We conclude that active screening for MRSA is more important than the type of test used. Since important and costly decisions, such as mandatory legislation for MRSA universal screening, are under consideration in many countries worldwide, policy makers should be aware of the limits and the heterogeneity of the available evidence.

Systematic review and meta-analysis are assuming greater importance in influencing policy makers and clinical opinion worldwide. Many discussions and publications have considered the merits of meta-analysis of epidemiologic data.50 Some observers suggest that meta-analysis of observational studies should be abandoned altogether. 51 In the authors' opinion, statistical combination of observational studies should not be a primary goal of a review. Analysis of heterogeneity between longitudinal studies, however, would provide more insights than mathematical calculation of the summary risk. Meta-analyses of risk factors for infections should strictly follow guidelines for meta-analyses of observational studies. A study protocol should be written in advance, completed literature searches performed, and studies selected in a reproducible and objective fashion. Biologic plausibility must be addressed. The reported findings should be interpreted with caution, taking into account the limitations of various methodologic aspects of risk factors studies. An important role for meta-analyses in this field would be to clarify hypotheses to be formulated for future Identifying Risk Factors for Infections 221 studies and stress limitations strictly related to studies on risk factors for bacterial and viral infections.

Accurate assessment of risk factors for nosocomial acquisition of colonization by antibiotic-resistant bacteria (ARB) is often confounded by scarce data on antibiotic use. A 12-month, nested, multicenter cohort study was conducted. Target ARB were methicillin (meticillin)-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and ciprofloxacin-resistant Pseudomonas aeruginosa (CR-PA). Nares and rectal swabs were obtained before and after starting antibiotics. Pulsed-field gel electrophoresis was done to define genetic relatedness of the strains. Primary outcomes were (i) the mean time, in days, for acquisition of target ARB colonization in patients previously not colonized; (ii) the rate of acquisition per 1,000 antibiotic-days according to different classes of antibiotics; (iii) the rate of infection caused by the same bacteria as those previously isolated in screening samples; and (iv) the risk factors for ARB acquisition. In total, 6,245 swabs from 864 inpatients were processed. The rate of acquisition was 3%, 2%, and 1% for MRSA, VRE, and CR-PA, respectively. The rate of acquisition of ARB per 1,000 antibiotic-days was 14 for carbapenems, 9 for glycopeptides, and 6 for broad-spectrum cephalosporins and quinolones. The highest rates of acquisition were observed for carbapenems in dialyzed and diabetic patients. Four risk factors were independently associated with acquisition of target ARB: use of carbapenems, age of >70 years, hospitalization for >16 days, and human immunodeficiency virus infection. During the 30-day follow-up, 4 among 42 patients newly colonized by ARB (9%) suffered from an infection due to the same bacteria as those isolated in a previous screening sample. Colonizing and infecting strains from single patients were genotypically identical. Identifying ARB colonization early during antibiotic therapy could target a high-risk hospitalized population that may benefit from intervention to decrease the risk of subsequent nosocomial infections.

Background: The multidrug-resistant (MDR) Acinetobacter baumannii calcoaceticus complex (Abc) has emerged as an important cause of nosocomial infections. The aims of the study were to evaluate risk factors for MDR-Abc in intensive care units (ICUs) as well as in medical and surgical wards, to define the likelihood ratios (LRs) of risk factors and to determine if risk factors differ depending on whether colonization or infections are considered. Methods: Two prospective matched case‐control studies were performed. MDR-Abc was defined as a strain resistant to four or more classes of antibiotics. The two case groups included patients with MDR-Abc infections or colonization. Controls were selected among patients not harbouring Abc. Matching criteria were the number of days from admission to MDR-Abc isolation among cases and the duration of hospitalization among controls. Results: Overall, 514 patients were included in the study. One hundred and thirty-seven patients were infected and 120 colonized. A Charlson score >3 and previous methicillin-resistant Staphylococcus aureus isolation and b-lactam use were independent risk factors for colonization and infection. Bedridden status and previous ICU admission were associated with colonization, while the presence of a central venous catheter and surgery were related to infection. The analysis of LRs showed an association between the presence of more than two risk factors and colonization or infection. The highest predicting value was observed for the presence of more than two risk factors and colonization in patients with no history of ICU admission. Conclusions: This study provides novel information that can be used to identify interventions for different stages of the spread of MDR-Abc.

International guidelines suggest that a high prevalence of meticillin-resistant Staphylococcus aureus (MRSA) infections should influence the use of vancomycin for surgical prophylaxis. In order to compare the efficacy and adverse effects of vancomycin versus cefazolin as antimicrobial prophylaxis for insertion of cerebrospinal fluid (CSF) shunts, a randomised prospective clinical trial was performed. Over a 16-month period, all consecutive adult patients who underwent CSF shunt insertion at a university hospital with a high prevalence of MRSA infections were included. Patients were randomly allocated to receive either vancomycin or cefazolin before surgery and followed-up for four weeks for the development of infections. Of the 176 patients included in the study, 88 received vancomycin and 88 cefazolin. Shunt infections were significantly less likely to be observed in patients who were on vancomycin prophylaxis (4% vs 14%; P=0.03). All isolated staphylococci were resistant to meticillin. Mortality of patients with post-surgical infections was higher in the cefazolin group (P=0.02). Our data suggest that use of vancomycin as prophylactic agent for cerebrospinal shunt placement reduces the rate of shunt infections in the context of high prevalence of MRSA.

Staphylococcus aureus bloodstream infection (BSI) contributes significantly to the morbidity and mortality of in-patients. The optimal therapy for methicillin-susceptible S. aureus BSI consists of penicillins. The efficacy of these drugs is well documented from several published data and supported from a long clinical experience. Methicillin-resistant S. aureus (MRSA) strains are responsible for the majority of nosocomial BSI and are recovered with increasing frequency at hospital admission. Although glycopeptides still represent the drugs of choice, there are several concerns on the treatment of MRSA BSI: reports of clinical failure with vancomycin treatment, regardless of the in vitro susceptibility; increasing reports of MRSA strains with reduced vancomycin susceptibility; difficulty in therapeutic dosage monitoring of teicoplanin; lack of evidence on the efficacy of combination therapy. Recently, new drugs have been introduced in the therapeutic arsenal for MRSA infections, but their clinical use is not yet clearly established for BSI. The review summarises evidence on present therapeutic options for the treatment of S. aureus BSI.

Transmission of vancomycin-resistant enterococci (VRE) can occur through direct contact with colonised or infected patients or through indirect contact via the hands of health-care workers (HCWs), or via contaminated patient care equipment or environmental surfaces. Antibiotic exposure plays an important role in the transmission dynamic of VRE. Until now, the control measures aimed at reducing the incidence of VRE colonisation and infection in hospitals have included: education of HCWs with implementation of hand-washing practices and compliance; wide and targeted surveillance cultures; isolation of VRE-positive patients; pre-emptive isolation of high-risk patients; and restriction of antibiotic use. However, despite these, VRE is still endemic in many hospitals. The causes of this could be non-compliance with infection control interventions, overuse of antibiotics, and insensitive microbiological methods for detecting VRE in stool. A scoring system using point values has been demonstrated to be useful in reducing rates of nosocomial VRE colonisation. Future prospective comparative studies of infection control approaches in different epidemiological situations might be useful.

Risk-scoring systems are utilised in patients with bloodstream infections (BSI) to quantify disease-associated morbidity and mortality based on simple clinical or laboratory data usually obtained early in the course of illness. In order to reduce BSI-associated mortality, specific scores were elaborated to allow early diagnosis and prompt and appropriate antibiotic therapy. Risk scoring was also successfully derived and validated to identify patients at higher risk for antibiotic-resistant BSI, or colonisation, mainly due to methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. However, a major limitation of risk-scoring systems is the relevance to the local epidemiological environment and the difficulty in generalising results from a single study. Intelligence technology recently utilised scores to predict risks for specific pathogens causing BSI. An example of this innovation, the TREAT system, was able to significantly reduce mortality, length of hospitalisation and costs in patients with BSI. New randomised clinical trials are needed to study the efficacy of clinical scores in reducing BSI-associated morbidity and mortality.

The presented study examined the incidence, risk factors and outcome of nosocomial bacterial pneumonia (NBP) in human immunodeficiency virus (HIV)-infected subjects. Forty-two cases of NBP were ascertained by a 5-yr prospective surveillance and were matched to 84 controls. NBP incidence was 10.8 per 10,000 hospital patient-days. In particular, the incidence of NBP was 13.9 per 10,000 patient-days in the period 1994–1996 and 5.6 per 10,000 patient-days in the period 1997–1998 (p=0.01).By using regression analysis, predictors for developing NBP were an increasing value of Acute Physiology and Chronic Health Evaluation (APACHE) III score (pNosocomial bacterial pneumonia is more common in patients with advanced human immunodeficiency virus infection, high Acute Physiology and Chronic Health Evaluation III score and central nervous system diseases. Although the incidence of nosocomial bacterial pneumonia, as well of other opportunistic infections, decreased considerably in the era of highly active antiretroviral therapy, it still represents an important cause of mortality.

The aim of the study was to assess the incidence of hospital and community acquired bacterial pneumonia in HIV-infected subjects prior to and after the introduction of highly active antiretroviral therapy (HAART). We studied 266 patients with bacterial pneumonia over two separate periods, 154 in the first period and 112 in the second period. A statistically significant difference in the incidence of bacterial pneumonia in the two study periods was observed ranging from 13.1 to 8.5 episodes per 100 persons. The incidence of community-acquired bacterial pneumonia decreased from 10.7 to 7.7 ( P =0.01), while that of nosocomial episodes decreased from 2.4 to 0.8 episodes ( P =0.003). Low levels of peripheral CD 4+ cells ( 3 ) and intravenous drug abuse (IVDA) were significantly associated with the development of community-acquired bacterial pneumonia, while an increasing value of APACHE III score and prolonged hospitalisation increased the risk of nosocomial bacterial pneumonia in both study periods.

Maria Adriana Cataldo, Nicola PetrosilloSecond Infectious Diseases Division, National Institute for Infectious Diseases, “Lazzaro Spallanzani”, Rome, ItalyAbstract: Fungi are a frequent cause of nosocomial infections, with an incidence that has increased significantly in recent years, especially among critically ill patients who require intensive care unit (ICU) admission. Among ICU patients, postsurgical patients have a higher risk of Candida infections in the bloodstream. In consideration of the high incidence of fungal infections in these patients, their strong impact on mortality rate, and of the difficulties in Candida diagnosis, some experts suggest the use of antifungal prophylaxis in critically ill surgical patients. A clinical benefit from this strategy has been demonstrated, but the economic impact of the use of antifungal prophylaxis in surgical patients has not been systematically evaluated, and its cost–benefit ratio has not been defined. Whereas the costs associated with treating fungal infections are very high, the cost of antifungal drugs varies from affordable (ie, the older azoles) to expensive (ie, echinocandins, polyenes, and the newer azoles). Adverse drug-related effects and the possibly increased incidence of fluconazole resistance and of isolates other than Candida albicans must also be taken into account. From the published studies of antifungal prophylaxis in surgical patients, a likely economic benefit of this strategy could be inferred, but its usefulness and cost–benefits should be evaluated in light of local data, because the available evidence does not permit general recommendations.Keywords: antifungal prophylaxis, cost-effectiveness, economics, surgery, fungal infection&nbsp

The aim of this study was to evaluate the effect of highly active antiretroviral therapy (HAART) on the incidence of bacterial infections in HIV-infected patients. Two time periods were compared: (A) January 1992-December 1995 (before HAART) and (B) January 1997-December 2000 (after HAART). During the study periods, we observed 931 patients with bacterial infections, i.e. 322 with bacteremia, 369 with bacterial pneumonia and 240 with urinary tract infections, out of 4,242 HIV-infected subjects admitted to the Department of Infectious Diseases of a large university hospital. By comparing the overall incidence of bacterial infections during periods A and B, a statistically significant difference, from 32% to 18% (p

Background In developed countries, Clostridium difficile infection (CDI) represents an emerging threat in terms of morbidity and mortality rates. In our country limited CDI epidemiological data can be found. We have conducted a 6-year retrospective study to evaluate the incidence of CDI in Italian urban hospitals. Methods Stool samples tested for C. difficile toxins from January 2006 to December 2011 in 5 large hospitals in Rome, Italy, were considered in the analysis. Repeated samples taken ≤ 2 months after a positive result were excluded. Results A total of 402 CDI episodes were identified. The incidence of CDI episodes progressively increased from 0.3 in 2006 to 2.3 per 10,000 patient-days in 2011. CDI episodes mostly occurred in patients > 60 years of age (77%). The >80 year-old age class reported the highest percentage of CDI episodes on tested samples (16%). Eighty percent (80%) of CDI episodes occurred in medical wards followed by surgery (10.2%) and intensive care units (9.8%). Conclusions A significant increasing incidence of CDI episodes over the study period was observed during the years (p