Efficacy and safety of ceftolozane/tazobactam as therapeutic option for complicated skin and soft tissue infections by MDR/XDR Pseudomonas aeruginosa in patients with impaired renal function: a case series from a single-center experience.

INTRODUCTION: Pseudomonas aeruginosa (PA) is a known cause of skin and soft tissue infections (SSTIs). Therapeutic options against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of PA are limited, especially in patients with impaired renal function. Ceftolozane/tazobactam (C/T) is a novel beta-lactam/beta-lactamase inhibitor with powerful anti-PA activity. Thanks to its characteristics, it appears to be the best available anti-pseudomonal drug in many clinical scenarios. A case series of four adult patients followed between January 2018 and May 2019 is reported. All subjects presented complicated SSTIs by MDR- or XDR-PA and were affected by chronic kidney disease. RESULTS: C/T was used as a monotherapy in three cases and in combination regimen in the remaining case. In two cases, C/T was the first-line option, in the remaining ones was the salvage treatment. All patients were successfully treated without worsening of renal function and without any other adverse events. CONCLUSIONS: C/T may represent a useful option against MDR- and XDR-PA strains responsible of complicated SSTIs in patients affected by impaired renal function.

A large survey among European trainees in clinical microbiology and infectious disease on training systems and training adequacy: identifying the gaps and suggesting improvements.

The purpose of this investigation was to perform a survey among European clinical microbiology (CM) and infectious disease (ID) trainees on training satisfaction, training tools, and competency assessment. An online, anonymous survey in the English language was carried out between April and July 2015. There were 25 questions: seven in a 5-point Likert scale (1: worst scenario, 5: best scenario) and the remainder as closed multiple-choice questions in five areas (satisfaction, adequacy, system, mentorship, and evaluation of training). Included were 419 respondents (215 CM, 159 ID, and 45 combined CM/ID) from 31 European countries [mean age (standard deviation) 32.4 (5.3) years, 65.9 % women]. Regarding satisfaction on the training scheme, CM and ID scored 3.6 (0.9) and 3.2 (1.0), respectively. These scores varied between countries, ranging from 2.5 (1.0) for Italian ID to 4.3 (0.8) for Danish CM trainees. The majority of respondents considered training in management and health economics inadequate and e-learning and continuing medical education programs insufficient. Many trainees (65.3 % of CM and 62.9 % of ID) would like to have more opportunities to spend a part of their training abroad and expected their mentor to be more involved in helping with future career plans (63.5 % of CM and 53.4 % of ID) and practical skills (53.0 % of CM and 61.2 % of ID). Two-thirds of the respondents across the specialties agreed that a European exam should be developed, but half of them thought it should not be made mandatory. This survey shows high heterogeneity in training conditions in European countries, identifies perceived gaps in training, and suggests areas for improvements.

Personal life and working conditions of trainees and young specialists in clinical microbiology and infectious diseases in Europe: a questionnaire survey.

The purpose of this investigation was to assess the balance between the personal and professional lives of trainees and young European specialists in clinical microbiology (CM) and infectious diseases (ID), and determine differences according to gender, country of training, workplace and specialty. The Steering Committee of the Trainee Association of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) devised a questionnaire survey consisting, beyond the demographic questions, of nine yes/no questions, 11 Likert scale self-evaluations and one open-response item on parenthood, working conditions, quality of life, alcohol consumption and burnout. This anonymous survey in English was held between April and July 2015 among European CM/ID trainees and young specialists (<3 years after training completion). Responses from 416 participants with a mean age of 32 years [standard deviation (SD) 5 years] were analysed. Females and physicians from Northern/Western Europe (NWE) benefit more from paternity/maternity leaves even during training than their counterparts. Among all respondents, only half of breastfeeding mothers enjoyed the benefit of working hours flexibility. Only two-thirds of respondents found their working environment stimulating. In comparison to colleagues from other parts of Europe, trainees and young specialists from Southern/Eastern Europe (SEE) had less frequent regular meetings with mentors/supervisors and head of departments where trainees' issues are discussed. Also, physicians from SEE were more frequently victims of workplace mobbing/bullying in comparison to those from other regions. Finally, multivariate analysis showed that female gender, SEE region and ID specialty were associated with burnout feelings. Female gender and country of work from SEE largely determine satisfactory working conditions, the possibility of parenthood leaves, amount of leisure time, mobbing experiences and burnout feelings among European CM/ID trainees and young specialists.

Previous bloodstream infections due to other pathogens as predictors of carbapenem-resistant Klebsiella pneumoniae bacteraemia in colonized patients: results from a retrospective multicentre study.

INTRODUCTION: the purpose of this retrospective multicenter study was to assess whether the risk of developing bloodstream infections (BSI) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) in colonized patients is influenced by the occurrence of BSI due to other pathogens. METHODS: from January 2012 to March 2014, all patients with at least one rectal swab positive for CRKP and at least 30 days of previous hospital stay were included in the study. The primary outcome measure was CRKP BSI, defined as a time-to-event endpoint. The role of potential predictors was evaluated through univariable and multivariable Cox regression analyses, considering previous BSI as a time-dependent variable. RESULTS: during the study period, 353 patients met the inclusion criteria. Thirty-seven developed a CRKP BSI (11%). A higher incidence of CRKP BSI was observed in presence rather than in absence of previous BSI. In the final multivariable model of risk factors for CRKP BSI, multisite colonization (hazard ratio [HR] 13.73, 95% confidence intervals [CI] 3.29-57.32, p < 0.001), ICU stay (HR 3.14, 95% CI 1.19-8.31, p = 0.021), and previous BSI (p = 0.026, with the overall effect being mainly due to Enterococcus spp. BSI vs absence of BSI, HR 6.62, 95% CI 2.11-20.79) were associated with the development of CRKP BSI, while an inverse association was observed for age (HR 0.98, 95% CI 0.95-1.00, p = 0.027). CONCLUSIONS: previous BSI due to other pathogens were associated with an increased risk of CRKP BSI that was independent of other factors in colonized patients with prolonged hospital exposure.

Prevention of hepatitis B virus infection: from the past to the future.

About 3-5 % of the world's population is chronically infected by hepatitis B virus (HBV) and is at risk of developing liver cirrhosis or hepatocellular carcinoma. The risk of dying prematurely because of chronic HBV infection is higher in younger people. The current strategies to prevent HBV infection involve immunization (active and/or passive) and antiviral chemoprophylaxis. The vaccines available for active immunization, containing hepatitis B surface antigen, are safe and confer long-term immunity in most healthy subjects. Since the vaccination is unsatisfactory in some patients, e.g., those with chronic kidney disease, human immunodeficiency virus infection, type I diabetes mellitus, and celiac disease, new strategies of vaccination are required. The neonatal, infant, and adolescent routine program vaccination in about 180 countries has greatly decreased the disease burden. Passive immunization with specific HBV immunoglobulins is recommended after single acute exposure, in infants born to infected mothers, and in HBV-infected patients undergoing liver transplantation combined with nucleoside/nucleotide analogues (chemoprophylaxis). Chemoprophylaxis is also indicated in HBV carrier candidates for immunosuppressive treatment and in patients with occult B infection undergoing immunosuppressive therapy or hematopoietic stem cell transplantation. Since HBV is not eradicable by an immune response or by antiviral drugs developed so far, the only preventive strategy remains global neonatal vaccination in all countries, firstly in HBV-endemic countries.

A systematic review on the effect of diabetes mellitus on the pharmacokinetics of TB drugs.

The coexistence of TB and diabetes mellitus (DM) (TB-DM) is associated with an increased risk of treatment failure, death, delayed culture conversion, and drug resistance. Because plasma concentrations may influence clinical outcomes, we evaluated the evidence on the pharmacokinetic (PK) of TB drugs in individuals with DM to guide management.We performed a systematic review and meta-analysis through searches of major databases from 1946 to 6 July 2023. PROSPERO (CRD42022323566).Of 4,173 potentially relevant articles, we identified 16 studies assessing rifampicin (RIF) PK, 9 on isoniazid (INH), 8 on pyrazinamide (PZA), and 3 on ethambutol (EMB). Two studies reported on second-line anti-TB drugs. According to our meta-analysis, RIF time to maximum concentration (Tmax) was significantly prolonged in patients with DM compared with non-DM patients. We found no significant differences for RIF Cmax, area under the curve (AUC) 0-24 or drug concentration at 2 h (C2h), INH C2h, PZA C2h, PZA Tmax, and EMB Tmax. Although RIF C2h was slightly reduced in patients with TB-DM, this finding was not statistically significant.This review comprehensively examines the impact of DM on the PK of TB drugs. We observed significant heterogeneity among the studies. Given the association between lower plasma concentrations and poor clinical outcomes among patients with DM, we recommend a higher dose limit to compensate for the larger body weight of patients with DM..

Risk factors for candidaemia in hospitalized patients with liver cirrhosis: a multicentre case-control-control study.

OBJECTIVES: The aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis. METHODS: This was a case-control-control (1:2:2) study performed in four Italian tertiary centres from 2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission. RESULTS: During the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (<30 days) acute-on-chronic liver failure (relative risk ratio (RRR) 2.22 (95% confidence interval (CI) 1.09-4.54), p = 0.046), previous(<30 days) gastrointestinal endoscopy (RRR 2.38 (95% CI 1.19-4.78) p = 0.014), previous(<30 days) antibiotic treatment for at least 7 days (RRR 2.74 (95% CI 1.00-7.48), p = 0.049), presence of central venous catheter (RRR 2.77 (95% CI 1.26-6.09, p = 0.011), total parenteral nutrition (RRR 3.90 (95% CI 1.62-9.40), p = 0.002) at infection onset and length of in-hospital stay >15 days (RRR 4.63 (95% CI 2.11-10.18), p <0.001] Conversely, rifaximin treatment was associated with lower rate of candidaemia (RRR 0.38 (95% CI 0.19-0.77), p = 0.007). Multivariable analysis for 30-day mortality showed that patients with isolation of Candida spp. from blood cultures had worse outcome when compared with controls even though the difference did not reach a statistical significance (hazard ratio 1.64 (95% 0.97-2.75) p = 0.06). CONCLUSIONS: We identified previous antibiotic use, gastrointestinal endoscopy or acute-on-chronic liver failure and presence of central venous catheter especially for parenteral nutrition as independent factors associated with candidaemia. Surprisingly, chronic rifaximin use was a protective factor.

A prospective multicentre study of the epidemiology and outcomes of bloodstream infection in cirrhotic patients.

OBJECTIVES: To describe the current epidemiology of bloodstream infection (BSI) in patients with cirrhosis; and to analyse predictors of 30-day mortality and risk factors for antibiotic resistance. METHODS: Cirrhotic patients developing a BSI episode were prospectively included at 19 centres in five countries from September 2014 to December 2015. The discrimination of mortality risk scores for 30-day mortality were compared by area under the receiver operator risk and Cox regression models. Risk factors for multidrug-resistant organisms (MDRO) were assessed with a logistic regression model. RESULTS: We enrolled 312 patients. Gram-negative bacteria, Gram-positive bacteria and Candida spp. were the cause of BSI episodes in 53%, 47% and 7% of cases, respectively. The 30-day mortality rate was 25% and was best predicted by the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure-SOFA (CLIF-SOFA) score. In a Cox regression model, delayed (>24 hours) antibiotic treatment (hazard ratio (HR) 7.58; 95% confidence interval (CI) 3.29-18.67; p < 0.001), inadequate empirical therapy (HR 3.14; 95% CI 1.93-5.12; p < 0.001) and CLIF-SOFA score (HR 1.35; 95% CI 1.28-1.43; p < 0.001) were independently associated with 30-day mortality. Independent risk factors for MDRO (31% of BSIs) were previous antimicrobial exposure (odds ratio (OR) 2.91; 95% CI 1.73-4.88; p < 0.001) and previous invasive procedures (OR 2.51; 95% CI 1.48-4.24; p 0.001), whereas spontaneous bacterial peritonitis as BSI source was associated with a lower odds of MDRO (OR 0.30; 95% CI 0.12-0.73; p 0.008). CONCLUSIONS: MDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates. Our data suggest that improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.