Risk Factors and Outcomes of Candidemia Caused by Biofilm-Forming Isolates in a Tertiary Care Hospital

Very few data exist on risk factors for developing biofilm-forming Candida bloodstream infection (CBSI) or on variables associated with the outcome of patients treated for this infection. METHODS AND FINDINGS: We identified 207 patients with CBSI, from whom 84 biofilm-forming and 123 non biofilm-forming Candida isolates were recovered. A case-case-control study to identify risk factors and a cohort study to analyze outcomes were conducted. In addition, two sub-groups of case patients were analyzed after matching for age, sex, APACHE III score, and receipt of adequate antifungal therapy. Independent predictors of biofilm-forming CBSI were presence of central venous catheter (odds ratio [OR], 6.44; 95% confidence interval [95% CI], 3.21-12.92) or urinary catheter (OR, 2.40; 95% CI, 1.18-4.91), use of total parenteral nutrition (OR, 5.21; 95% CI, 2.59-10.48), and diabetes mellitus (OR, 4.47; 95% CI, 2.03-9.83). Hospital mortality, post-CBSI hospital length of stay (LOS) (calculated only among survivors), and costs of antifungal therapy were significantly greater among patients infected by biofilm-forming isolates than those infected by non-biofilm-forming isolates. Among biofilm-forming CBSI patients receiving adequate antifungal therapy, those treated with highly active anti-biofilm (HAAB) agents (e.g., caspofungin) had significantly shorter post-CBSI hospital LOS than those treated with non-HAAB antifungal agents (e.g., fluconazole); this difference was confirmed when this analysis was conducted only among survivors. After matching, all the outcomes were still favorable for patients with non-biofilm-forming CBSI. Furthermore, the biofilm-forming CBSI was significantly associated with a matched excess risk for hospital death of 1.77 compared to non-biofilm-forming CBSI. CONCLUSIONS: Our data show that biofilm growth by Candida has an adverse impact on clinical and economic outcomes of CBSI. Of note, better outcomes were seen for those CBSI patients who received HAAB antifungal therapy

Management of KPC-Producing Klebsiella pneumoniae Infections

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas

Systemic antifungal treatment after posaconazole prophylaxis: results from the SEIFEM 2010-C survey.

OBJECTIVES: To investigate the incidence, treatment and outcome of breakthrough invasive fungal infections (IFIs) in adult acute myeloid leukaemia (AML) patients after posaconazole prophylaxis. METHODS: From January 2010 to April 2012, all consecutive patients with newly diagnosed AML were prospectively registered at 33 participating Italian centres. All cases of IFIs occurring within 30 days after the end of the first induction chemotherapy were recorded. The strategy of antifungal treatment (empirical, pre-emptive or targeted) and the drugs used were analysed. ClinicalTrials.gov code: NCT01315925. RESULTS: In total, 1192 patients with newly diagnosed AML were enrolled in the study, of whom 510 received posaconazole prophylaxis and were included in the present analysis. Of these patients, 140 (27%) needed systemic antifungal treatment. Among the 127 evaluable cases, an empirical approach was utilized in 102 patients (80%), a pre-emptive approach in 19 patients (15%) and targeted therapy in 6 patients (5%). Only five patients died of IFIs (three in the empirical group and two in the targeted group; 4%). A critical review of IFI diagnoses at 30 days demonstrated that among the patients treated empirically, ∼30% were not affected by IFIs but rather only by fever of unidentified origin. A comparison between the empirical and the pre-emptive groups showed no significant differences regarding the attributable and overall mortalities. CONCLUSIONS: This study confirms that posaconazole prophylaxis reduces the incidence of breakthrough IFIs and does not modify the efficacy of subsequent systemic antifungal treatment, regardless of the approach (empirical or pre-emptive) or the antifungal drug used

Diagnosis and management of infections caused by multidrug-resistant bacteria: guideline endorsed by the Italian Society of Infection and Tropical Diseases (SIMIT), the Italian Society of Anti-Infective Therapy (SITA), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Association of Clinical Microbiologists (AMCLI) and the Italian Society of Microbiology (SIM)

Management of patients with infections caused by multidrug-resistant organisms is challenging and requires a multidisciplinary approach to achieve successful clinical outcomes. The aim of this paper is to provide recommendations for the diagnosis and optimal management of these infections, with a focus on targeted antibiotic therapy. The document was produced by a panel of experts nominated by the five endorsing Italian societies, namely the Italian Association of Clinical Microbiologists (AMCLI), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Society of Microbiology (SIM), the Italian Society of Infectious and Tropical Diseases (SIMIT) and the Italian Society of Anti-Infective Therapy (SITA). Population, Intervention, Comparison and Outcomes (PICO) questions about microbiological diagnosis, pharmacological strategies and targeted antibiotic therapy were addressed for the following pathogens: carbapenem-resistant Enterobacterales; carbapenem-resistant Pseudomonas aeruginosa; carbapenem-resistant Acinetobacter baumannii; and methicillin-resistant Staphylococcus aureus. A systematic review of the literature published from January 2011 to November 2020 was guided by the PICO strategy. As data from randomised controlled trials (RCTs) were expected to be limited, observational studies were also reviewed. The certainty of evidence was classified using the GRADE approach. Recommendations were classified as strong or conditional. Detailed recommendations were formulated for each pathogen. The majority of available RCTs have serious risk of bias, and many observational studies have several limitations, including small sample size, retrospective design and presence of confounders. Thus, some recommendations are based on low or very-low certainty of evidence. Importantly, these recommendations should be continually updated to reflect emerging evidence from clinical studies and real-world experience

Epidemiological and clinical features, response to HAART, and survival in HIV-infected patients diagnosed at the age of 50 or more

BACKGROUND: Over the last years, the mean age of subjects with HIV infection and AIDS is increasing. Moreover, some epidemiological and clinical differences between younger and older HIV-infected individuals have been observed. However, since introduction of HAART therapy, there are controversial results regarding their response to HAART. The aim of the present study is to evaluate epidemiological and clinical features, response to HAART, and survival in elderly HIV-infected patients with regard to younger HIV-infected patients. METHODS: A prospective cohort study (1998–2003) was performed on patients from Sabadell Hospital, in Northeast of Spain. The cohort includes newly attended HIV-infected patients since January 1, 1998. For the purpose of this analysis, data was censured at December 31, 2003. Taking into account age at time of diagnosis, it was considered 36 HIV-positive people aged 50 years or more (Group 1, G1) and 419 HIV-positive people aged 13–40 years (Group 2, G2). Epidemiological, clinical, biological and therapy data are recorded. Statistical analysis was performed using Chi-squared test and Fisher exact test, Mann-Whitney U test, Kaplan-Meier, Log Rank test, and Two-Way ANOVA from random factors. RESULTS: G1 showed higher proportion of men than G2. The most common risk factors in G1 were heterosexual transmission (P = 0.01) and having sex with men or women (P < 0.001). G1 and G2 show parallel profiles through the time regarding immunological response (P = 0.989) and virological response (P = 0.074). However, older people showed lower CD4 cell counts at first clinic visit (P < 0.001) and, eventually, they did not achieve the same counts as G2. G1 presented faster progression to AIDS (P < 0.001) and shorter survival (P < 0.001). CONCLUSION: Older patients have different epidemiological features. Their immunological and virological responses are good. However, older patients do not achieve the same CD4 cell counts likely due to they have lower counts at first clinic visit. Thus, it is essential physicians know older HIV-infected patients features to consider the possibility of HIV infection in these patients with the aim of treatment would not be delayed

Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience

This study describes the largest clinical experience using ceftolozane/tazobactam (C/T) for different Pseudomonas aeruginosa infections. A retrospective study was performed at 22 hospitals in Italy (June 2016\u2013March 2018). All adult patients treated with 654 days of C/T were enrolled. Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to P. aeruginosa infection and lack of microbiological evidence of infection. C/T treatment was documented in 101 patients with diverse infections, including nosocomial pneumonia (31.7%), acute bacterial skin and skin-structure infection (20.8%), complicated UTI (13.9%), complicated IAI (12.9%), bone infection (8.9%) and primary bacteraemia (5.9%). Over one-half of P. aeruginosa strains were XDR (50.5%), with 78.2% of isolates resistant to at least one carbapenem. C/T was used as first-line therapy in 39 patients (38.6%). When used as second-line or later, the most common reasons for discontinuation of previous antibiotics were in vitro resistance of P. aeruginosa and clinical failure of previous therapy. Concomitant antibiotics were reported in 35.6% of patients. C/T doses were 1.5 g q8h in 70 patients (69.3%) and 3 g q8h in 31 patients (30.7%); median duration of C/T therapy was 14 days. Overall clinical success was 83.2%. Significant lower success rates were observed in patients with sepsis or receiving continuous renal replacement therapy (CRRT). Mild adverse events were reported in only three patients. C/T demonstrated a favourable safety and tolerability profile regardless of the infection type. Clinicians should be aware of the risk of clinical failure with C/T therapy in septic patients receiving CRRT

Proline-Rich Tyrosine Kinase 2 (Pyk2) Promotes Cell Motility of Hepatocellular Carcinoma through Induction of Epithelial to Mesenchymal Transition

Aims: Proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine kinase of the focal adhesion kinase (FAK) family, is up-regulated in more than 60% of the tumors of hepatocellular carcinoma (HCC) patients. Forced overexpression of Pyk2 can promote the proliferation and invasion of HCC cells. In this study, we aimed to explore the underlying molecular mechanism of Pyk2-mediated cell migration of HCC cells. Methodology/Principal Findings: We demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization. Conclusion: These data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT. © 2011 Sun et al.published_or_final_versio

The Relationship between Gram-Negative Colonisation and Bloodstream Infections in Neonates: A Systematic Review and Meta-Analysis.

OBJECTIVES: Neonates admitted to Neonatal Intensive Care Units (NICU) are at significant risk of developing bloodstream infections (BSIs). Gram-negative bacteria (GNB) both colonise and infect, but the association between these entities is unclear. By conducting a systematic literature review, we aimed to explore the impact of factors on the association between GN colonisation and GN-BSI at both baby level and unit level. METHODS: We searched Medline, Embase, and Cochrane Library. Observational cohort studies published after 2000 up to June 2016 reporting data on the total number of neonates (0-28 days) colonised with GNB assessed by rectal/skin swab culture and the total number of neonates with GN-BSI (same bacteria) were included. Studies were excluded if data on skin/rectal colonisation, neonates, and GNB could not been identified separately. The meta-analyses along with multivariate meta-regression with random-effect model were performed to investigate factors associated with the GN colonisation and GN-BSI at baby-level and unit-level. RESULTS: 27 studies fulfilled our inclusion criteria, 15 for the baby-level and 12 for the unit-level analysis. Study heterogeneity was high, with suboptimal overall quality of reporting assessed by the STROBE-NI statement (44.8% of items adequately reported). In 1,984 colonised neonates, 157 (7.9%) developed GN-BSI compared with 85 of 3,583 (2.4%) non-colonised neonates. Considerable heterogeneity across studies was observed. Four factors were included in the meta-regression model: Gross domestic product (GDP), pathogen, outbreak, and frequency of screening. There was no statistically significant impact of these factors on GN colonisation and GN-BSI in baby level. We were unable to perform the multivariate meta-regression due to the insufficient reported data for unit level. CONCLUSIONS: Study limitations include the small number and the high heterogeneity of the included studies. While this report shows a correlation between colonisation and BSI risk, this data currently doesn't support routinely screening for GNB. The analysis of large cohorts of colonised neonates with clinical outcomes is still needed to define the major determinants leading from colonisation to infection

Antimicrobial use and microbiological testing in district general hospital ICUs of the Veneto region of north-east Italy

International - predominantly American - studies undertaken in the ICUs of teaching centres show that inadequate antibiotic therapy increases mortality and length of stay. We sought to ascertain whether this also pertains to smaller ICUs in the Veneto region of north-east Italy. To the best of our knowledge, this is the first such survey in the Veneto area or in Italy as a whole. A retrospective, observational study was performed across five general-hospital ICUs to examine appropriateness of microbiological sampling, empirical antibiotic adequacy, and outcomes. Among 911 patients (mean age, 65.8 years ± 16.2 SD; median ICU stay, 17.0 days [IQR, 8.0–29.0]), 757 (83.1 %) were given empirical antibiotics. Treatment adequacy could be fully assessed in only 212 patients (28.0 %), who received empirical treatment and who had a relevant clinical sample collected at the initiation of this antibiotic (T0). Many other patients only had delayed microbiological investigation of their infections between day 1 and day 10 of therapy. Mortality was significantly higher among the 34.9 % of patients receiving inadequate treatment (48.6 % vs 18.80 %; p < 0.001). Only 32.5 % of combination regimens comprised a broad-spectrum Gram-negative β-lactam plus an anti-MRSA agent, and many combinations were irrational. Inadequate treatment was frequent and was strongly associated with mortality; moreover, there was delayed microbiological investigation of many infections, precluding appropriate treatment modification and de-escalation. Improvements in these aspects and in antibiotic stewardship are being sought