Loading dose plus continuous/extended infusion versus intermittent bolus of ß-lactams for the treatment of Gram-negative bacteria bloodstream infections: a propensity score-adjusted retrospective cohort study.

BACKGROUND: Optimal ß-lactam dosing for the treatment of Gram-negative bacteria bloodstream infections (GNB-BSIs) remains a debated issue. Herein, the efficacy and safety of a loading dose (LD) followed by extended/continuous infusion (EI/CI) versus intermittent bolus (IB) of these drugs for the treatment of GNB-BSIs was evaluated. METHODS: This is a retrospective observational study enrolling patients with GNB-BSIs treated with ß-lactams from 1 October 2020 to 31 March 2022. The 30 day infection-related mortality rate was assessed with Cox regression, while mortality risk reduction was evaluated by an inverse probability of treatment weighting regression adjustment (IPTW-RA) model. RESULTS: Overall, 224 patients were enrolled: 140 and 84 in the IB and EI/CI groups, respectively. ß-Lactam regimens were chosen according to pathogen antibiogram, clinical judgement and current guidelines. Interestingly, the LD + EI/CI regimen was associated with a significant lower mortality rate (17% versus 32%, P = 0.011). Similarly, ß-lactam LD + EI/CI was significantly associated with a reduced risk of mortality at multivariable Cox regression [adjusted HR (aHR) = 0.46; 95%CI = 0.22-0.98; P = 0.046]. Finally, the IPTW-RA (adjusted for multiple covariates) was performed, showing a significant risk reduction in the overall population [-14% (95% CI = -23% to -5%)]; at the subgroup restricted analysis, a significant risk reduction (>15%) was observed in the case of GNB-BSI in severely immunocompromised patients (P = 0.003), for SOFA score > 6 (P = 0.014) and in septic shock (P = 0.011). CONCLUSIONS: The use of LD + EI/CI of ß-lactams in patients with a GNB-BSI may be associated with reduced mortality; also in patients with severe presentation of infection or with additional risk factors, such as immunodepression.

Impact of Vitamin D in Prophylaxis and Treatment in Tuberculosis Patients.

Vitamin D plays a crucial role in many infectious diseases, such as tuberculosis (TB), that remains one of the world's top infectious killers with 1.5 million deaths from TB in 2021. Vitamin D suppresses the replication of Mycobacterium tuberculosis in vitro and showed a promising role in TB management as a result of its connection with oxidative balance. Our review encourages the possible in vivo benefit of a joint administration with other vitamins, such as vitamin A, which share a known antimycobacterial action with vitamin D. However, considering the low incidence of side effects even at high dosages and its low cost, it would be advisable to assess vitamin D level both in patients with active TB and high-risk groups and administer it, at least to reach sufficiency levels.

Epidemiological evaluation of human papillomavirus genotypes and their associations in multiple infections.

The aim of this study was to determine the frequency of multiple type human papillomavirus (HPV) infections, and whether any types are involved in multiple HPV-type infections (mHPV) more or less frequently than expected. From January 2012 to February 2018, 2848 cervico-vaginal swabs were analysed in the UOC Microbiology and Virology of Policlinico of Bari, Italy. HPV DNA detection was performed using initially nested-polymerase chain reaction (PCR) and subsequently multiplex real-time PCR assay. 1357/2848 samples (47.65%) were HPV DNA positive and 694/1357 (51.14%) showed mHPVs. The median number of mHPVs was 2 (interquartile range: 2-3). HPV-types more frequently detected were 42 (9.97%), 16 (8.92%), 53 (7.23%) and 31 (7.16%). Each detected HPV-type was involved in mHPVs in more than 50% of cases. Statistical analysis showed significant associations for all HPV-types except for 33, 43, 51, 58 and 82 HPV-types. The major number of significant pairwise associations were detected for the types 42 and 70. Only positive associations were detected. Further data are necessary to evaluate the clinical impact of the single combinations.

A Retrospective Study about the Impact of Switching from Nested PCR to Multiplex Real-Time PCR on the Distribution of the Human Papillomavirus (HPV) Genotypes.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) is the most prevalent etiological agent of viral sexually-transmitted infection. This study retrospectively evaluated the impact of a switch to a real-time PCR assay in the HPV prevalence and genotypes distribution by a quasi-experimental before-and-after approach. MATERIALS AND METHODS: In total, 1742 samples collected from 1433 patients were analyzed at the UOC Microbiology and Virology of Policlinico of Bari, Italy. HPV DNA detection was performed using initially nested PCR and subsequently multiplex real-time PCR assay. RESULTS: Statistically significant difference in HPV overall prevalence after the introduction of the real-time assay was not detected (48.97% vs. 50.62%). According to different extraction-DNA amplification methods, differences were observed in the prevalence rates of HPV-45, 68, 40, 42, and 43. The lowest prevalence for HPV-45 was observed in the Magna Pure-Real Time PCR group, while HPV-68, 40, 42, and 43 were less observed in the Qiagen-Real Time PCR group. After, a multivariate logistic regression, an increase in the prevalence of HPV-42 (aOR: 4.08, 95% CI: 1.71-9.73) was associated with the multiplex real-time PCR assay. CONCLUSIONS: Although this study is a not a direct comparison between two diagnostic methods because it has a sequential structure, it serves to verify the impact of a new molecular assay on HPV distribution. Moreover, the stability of HPV prevalence over time suggests that the population composition and the behavioral variables did not likely change during the observation period. Our study proposes that the introduction of a molecular test for HPV detection may be related to changes of HPV genotypes distribution.

Simultaneous detection and identification of STI pathogens by multiplex Real-Time PCR in genital tract specimens in a selected area of Apulia, a region of Southern Italy.

PURPOSE: Genital tract infections are globally a major cause of morbidity in sexually active individuals. The aim of this study was to investigate the prevalence and associations of co-infections of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma hominis (MH), Mycoplasma genitalium, Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP) in specimens collected from female (SF) and male (SM) patients. METHODS: 1575 samples from 1575 individuals from the geographical area around Bari, Apulia region in Southern Italy, were collected and analyzed by a multiplex Real-Time PCR (mRT-PCR) (AnyplexTM II STI-7, Seegene, Inc., Seoul, Korea) assay. RESULTS: 455/1575 (28.89%) samples resulted positive for at least one of the targets named above. Statistically significant differences in prevalence of the pathogens between SF and SM were not detected except for UP (24.92% in SF vs 8.91% in SM). Prevalence of co-infections was 6.84 and 3.96% in SF and SM, respectively. Moreover, MH presence in SF, but not in SM, was associated with UU and UP. CONCLUSIONS: Our data suggest different patterns of infections between females and male and the importance of an increased vigilance of sexually transmitted pathogens to reduce the burden on general population and the sequelae or the complications on reproductive organs.

Prevalence of Clostridium difficile and ribotype 027 infection in patients with nosocomial diarrhoea in Southern Italy.

Clostridium difficile is an emerging cause of healthcare-associated infections. The increasing frequency and severity is attributed to highly virulent ribotypes such as 027. The aim of this study was to retrospectively analyze the prevalence of CDI and ribotype 027 in 481 clinical samples collected from hospitalized patients and sent to the laboratory of molecular biology, UOC Microbiology and Virology, Azienda Ospedaliera-Universitaria, Policlinico of Bari, Italy. Toxins A+B and DNA C. difficile detections were performed using immunochromatographic test and a multiplex real-time PCR assay, respectively. Overall, 37/366 (10.11%) patients were positive at the immunochromatographic assay. This result was confirmed in 31 (8.47%) samples from 31 different patients by molecular assay. Logist regression confirmed age >50 years (adjusted odds ratio [aOR]: 4.29, 95%CI:1.44-18.50) and hospitalization in the Infectious Diseases (aOR: 3.77, 95%CI: 1.34-9.85) ward were risk factors for CDI. The associated 027 ribotype deletion D117tcd was detected in seven (22.58%) of 31 positive patients. Exploratory analysis of monthly prevalence of 027 ribotype suggested a slight increase after August 2015. Our results show that a monitoring program is needed to either better assess the diffusion of CDI and ribotype 027 or also to establish the risk factors associated with the transmission in our healthcare facilities.

Intravenous Fosfomycin as Adjunctive Therapy for Gram-Negative Bacteria Bloodstream Infections: a Propensity Score Adjusted Retrospective Cohort Study.

BACKGROUND: The role of intravenous fosfomycin (iv-FOS), as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI), needs to be evaluated in clinical practice as in vitro data show a potential efficacy. METHODS: All consecutive patients with a GNB-BSI from January 1st, 2021, to April 1st, 2023, were included. Primary outcome was 30-day mortality. A Cox- regression analysis was used to identify predictors of mortality. Moreover, an inverse-probability of treatment-weighting (IPTW) analysis was also performed. RESULTS: Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57-78) years, and a median Charlson-comorbidity index of 5 (3-7). At GNB-BSI onset, median SOFA score was 5 (2-7), 122 (34%) presented with septic shock. Pathogens involved were principally K. pneumoniae (42%), E. coli (28%), and P. aeruginosa (17%); of them 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and beta-lactams/beta-lactamases-inhibitors (19%); combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) gr/daily. Use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, p-value=0.147). However, at multivariable Cox-regression combination therapy with iv-FOS resulted protective for mortality (aHR=0.51, 95%CI=0.28-0.92), but not other combo-therapies (HR=0.69, 95%CI=0.44-1.16). This result was also confirmed at the IPTW-adjusted-Cox-model (aHR=0.52, 95%CI=0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA>6, PITT≥4) and when iv-FOS was initiated within 24 hours from GNB-BSI onset. CONCLUSIONS: Fosfomycin in combination therapy for GNB-BSI may have a role to improve survival. These results justify the development of further clinical trials.

Genotypic and phenotypic characteristics of Candida parapsilosis bloodstream isolates: Health Care Associated Infections in a teaching Hospital in Italy.

BACKGROUND: Candidemia is the most common healthcare associated invasive fungal infection. Over the last few decades, candidemia caused by Candida species other than Candida albicans, particularly the Candida parapsilosis complex, has emerged worldwide. The aims of this study were: to analyze the genotypic and phenotypic characteristics of C. parapsilosis strains isolated from blood cultures and the environment in a hospital in southern Italy, to study the possible source of infection and to correlate the isolated strains. METHODS: From April to October 2022, cases of candidemia due to C. parapsilosis in patients admitted to a hospital in the Apulia region were investigated. However, 119 environmental samples from the intensive care unit were collected for identification of the likely environmental reservoir of infection. Routine antifungal (amphotericin B, anidulafungin, fluconazole) susceptibility was performed on all isolates. Whole genome sequencing was performed to study the genotypic correlation of the isolates. Biofilm biomass and metabolic activity were also quantified for all isolates. RESULTS: A total of 43 C. parapsilosis isolates were cultured from the bloodstream of each patient in different departments, and seven surface samples were positive for C. parapsilosis. Most of the isolated yeasts (41/50; 85 %) were resistant to fluconazole and were genetically related to each other, suggesting an ongoing clonal outbreak of this pathogen. The fluconazole-susceptible isolates produced significantly more biofilm than did the resistant isolates. Metabolic activity was also higher for fluconazole-susceptible than resistant isolates. CONCLUSION: Cross-transmission of the microorganisms is suggested by the phenotypic similarity and genetic correlation between clinical and environmental strains observed in our study.

Human Papillomavirus Carcinogenicity and the Need of New Perspectives: Thoughts from a Retrospective Analysis on Human Papillomavirus Outcomes Conducted at the Hospital University of Bari, Apulia, Italy, between 2011 and 2022.

BACKGROUND: The current manuscript's aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed two hypothetical models of HPV's molecular dynamics, intending to clarify the impact of prevention and therapeutic strategies, explicitly modeled by recent survey data. METHODS: We presented clinical data from 9647 participants tested for either high-risk (HR) or low-risk (LR) HPV at the affiliated Bari Policlinic University Hospital of Bari from 2011 to 2022. HPV DNA detection was performed using nested-polymerase chain reaction (PCR) and multiplex real-time PCR assay. Statistical analysis showed significant associations for all genders and ages and both HR- and LR-HPV types. A major number of significant pairwise associations were detected for the higher-risk types and females and lower-risk types and males. RESULTS: The overall prevalence of HPV was 50.5% (n-4.869) vs. 49.5% (n-4.778) of the study population, of which 74.4% (n-3621) were found to be HPV high-risk (HR-HPV) genotypes and 57.7% (n-2.807) low-risk HPV (LR-HPV) genotypes, of which males were 58% and females 49%; the three most prevalent HR-HPV genotypes were HPV 53 (n707-15%), 16 (n704-14%), and 31 (n589-12%), and for LR-HPV, they were 42 (19%), 6 (16%), and 54 (13%); 56% of patients screened for HPV were ≤ 30 years old, 53% were between 31 and 40 years old, 46% were 41-50 and 51-60 years old, and finally, 44% of subjects were >60 years old. CONCLUSIONS: Our study provided comprehensive epidemiological data on HPV prevalence and genotype distribution among 9647 participants, which could serve as a significant reference for clinical practice, and it implied the necessity for more effective screening methods for HPV carcinogenesis covering the use of more specific molecular investigations. Although this is a predominantly descriptive and epidemiological study, the data obtained offer not only a fairly unique trend compared to other studies of different realities and latitudes but also lead us to focus on the HPV infection within two groups of young people and adults and hypothesize the possible involvement of dysbiosis, stem cells, and the retrotransposition mechanism.

Pannonibacter anstelovis sp. nov. Isolated from Two Cases of Bloodstream Infections in Paediatric Patients.

This study describes two cases of bacteraemia sustained by a new putative Pannonibacter species isolated at the U.O.C. of Microbiology and Virology of the Policlinico of Bari (Bari, Italy) from the blood cultures of two patients admitted to the Paediatric Oncohaematology Unit. Pannonibacter spp. is an environmental Gram-negative bacterium not commonly associated with nosocomial infections. Species identification was performed using Sanger sequencing of the 16S rRNA gene and Whole-Genome Sequencing (WGS) for both strains. Genomic analyses for the two isolates, BLAST similarity search, and phylogeny for the 16S rDNA sequences lead to an assignment to the species Pannonibacter phragmitetus. However, by performing ANIb, ANIm, tetranucleotide correlation, and DNA-DNA digital hybridization, analyses of the two draft genomes showed that they were very different from those of the species P. phragmitetus. MALDI-TOF analysis, assessment of antimicrobial susceptibility by E-test method, and Analytical Profile Index (API) tests were also performed. This result highlights how environmental bacterial species can easily adapt to the human host and, especially in nosocomial environments, also gain pathogenic potential through antimicrobial resistance.

Cardiac Tuberculosis: A Case Series from Ethiopia, Italy, and Uganda and a Literature Review.

Extrapulmonary tuberculosis (TB) is estimated to account for up to 20% of active cases of TB disease, but its prevalence is difficult to ascertain because of the difficulty of diagnosis. Involvement of the heart is uncommon, with constrictive pericarditis being the most common cardiac manifestation. Diagnostic research for cardiac disease is frequently lacking, resulting in a high mortality rate. In addition to direct cardiac involvement, instances of cardiac events during antitubercular therapy are described. This case series describes five cases of TB affecting the heart (cardiac TB) from Italy and high-burden, low-income countries (Ethiopia and Uganda), including a case of Loeffler syndrome manifesting as myocarditis in a patient receiving antitubercular therapy. Our study emphasizes how cardiac TB, rare but important in high-burden areas, is a leading cause of pericardial effusion or pericarditis. Timely diagnosis and a comprehensive approach, including imaging and microbiological tools, are crucial. Implementing high-sensitivity methods and investigating alternative samples, such as detection of tuberculosis lipoarabinomannan or use of the GeneXpert assay with stool, is recommended in TB control programs.

Coinfections in intensive care units. Has anything changed with Covid-19 pandemia?

BACKGROUND AND AIM: Since December 2019, the Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2), has spread from China, becoming a pandemic. Bacterial and fungal co-infections may lead to increase in COVID-19 severity with a decrease in patients survive. The aim of this work was to evaluate bacterial and fungal co-infections in COVID-19 patients admitted to ICU in comparison with patients recovered in ICU in pre-COVID-19 era in order to understand whether the pandemic had changed the incidence of overinfections in patients admitted to ICU. In fact, the epidemiological data should guide the choice of empirical therapy. METHODS: During pandemic, AOUC Policlinico of Bari organized dedicated ICUs for patient with SARS-CoV-2. Blood cultures, urine, and tracheobronchial aspirate were included in the analysis. RESULTS: Specimens of 1905 patients were analysed in this work. Comparing clinical isolates prevalence by material and COVID-19 vs. non-COVID-19 patients statistically significant differences were detected for A. baumannii complex, Aspergillus fumigatus, Escherichia coli, Haemophilus influenzae and Serratia marcescens isolated from tracheobronchial aspirates; C. albicans from urine samples, A. baumannii complex, Enterococcus faecalis and Enterococcus faecium isolated from blood culture. CONCLUSIONS: Although the organisms isolated in COVID-19 patients are consistent with those frequently associated with healthcare associated infection, our data suggest a particular prevalence in COVID-19 patients of A. baumannii, Stenotrophomonas maltophilia and Aspergillus spp. in the respiratory tract, C. albicans in urine and  A. baumannii, E. faecalis and E. faecium in blood cultures.

Looking for Stenotrophomonas maltophilia treatment: in vitro activity of ceftazidime/avibactam alone and in combination with aztreonam.

During the Sars-Cov-2 pandemic, Stenotrophomonas maltophilia (S.maltophilia) secondary pulmonary infections have increased, especially in critically ill patients, highlighting the need for new therapeutic options. Trimethoprim-sulfamethoxazole (SXT) is the treatment of choice but the increase of resistant strains or adverse drug reactions limited its clinical use. Recently ceftazidime/avibactam (CZA) has been approved for the treatment of multi drug resistant (MDR) Gram-negative bacteria infections, including hospital acquired pneumonia. The aim of this study was to evaluate the in vitro activity of ceftazidime/avibactam (CZA) alone and in combination with aztreonam (ATM) against S. maltophilia clinical isolates by E-test method. Susceptibility of SXT and levofloxacin (LEV) was also investigated. Our results showed 22% of resistance to CZA, 2% to SXT and 26% to LEV. CZA in combination with ATM demonstrated synergistic activity against 86% of the strains, including all those resistant to CZA. The combination of CZA with ATM provides a new therapeutic option for the treatment of severe respiratory infections in critically ill patients.

Effectiveness of First-Line Therapy with Old and Novel Antibiotics in Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii: A Real Life, Prospective, Observational, Single-Center Study.

Evidence-based, standard antibiotic therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a relevant unmet clinical need in the intensive care unit (ICU). We aimed to evaluate the effectiveness of first-line therapy with old and novel CRAB active antibiotics in monomicrobial VAP caused by CRAB. A prospective, observational study was performed in a mixed non-COVID-19 ICU. The primary outcome measure was clinical failure upon first-line targeted therapy. Features independently influencing failure occurrence were also investigated via Cox proportional multivariable analysis. To account for the imbalance in antibiotic treatment allocation, a propensity score analysis with an inverse probability treatment weighting approach was adopted. Of the 90 enrolled patients, 34 (38%) experienced clinical failure. Compared to patients who experienced a clinical resolution of VAP, those who had clinical failure were of an older age (median age 71 (IQR 64-78) vs. 62 (IQR 52-69) years), and showed greater burden of comorbidities (median Charlson comorbidity index 8 (IQR 6-8) vs. 4 (IQR 2-6)), higher frequency of immunodepression (44% vs. 21%), and greater clinical severity at VAP onset (median SOFA score 10 (IQR 9-11) vs. 9 (IQR 7-11)). Lower rates of use of fast molecular diagnostics for nosocomial pneumonia (8.8% vs. 30.3%) and of timely CRAB active therapy administration (65% vs. 89%), and higher rates of colistin-based targeted therapy (71% vs. 46%) were also observed in patients who failed first-line therapy. Overall, CRAB active iv regimens were colistin-based in 50 patients and cefiderocol-based in 40 patients, both always combined with inhaled colistin. According to the backbone agent of first-line regimens, clinical failure was lower in the cefiderocol group, compared to that in the colistin group (25% vs. 48%, respectively). In multivariable Cox regression analysis, the burden of comorbid conditions independently predicted clinical failure occurrence (Charlson index aHR = 1.21, 95% CI = 1.04-1.42, p = 0.01), while timely targeted antibiotic treatment (aHR = 0.40, 95% CI = 0.19-0.84, p = 0.01) and cefiderocol-based first-line regimens (aHR = 0.38, 95% CI = 0.17-0.85, p = 0.02) strongly reduced failure risk. In patients with VAP caused by CRAB, timely active therapy improves infection outcomes and cefiderocol holds promise as a first-line therapeutic option.

Cefiderocol Versus Colistin for the Treatment of Carbapenem-Resistant Acinetobacter baumannii Complex Bloodstream Infections: A Retrospective, Propensity-Score Adjusted, Monocentric Cohort Study.

INTRODUCTION: Bloodstream infections (BSI) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are associated with high mortality with limited treatment. The aim of this study is to compare effectiveness and safety of colistin-based versus cefiderocol-based therapies for CRAB-BSI. METHODS: This is a retrospective observational study enrolling patients with monomicrobial CRAB-BSIs treated with colistin or cefiderocol from 1 January 2020, to 31 December 2022. The 30-day all-cause mortality rate was the primary outcome. A Cox regression analysis was performed to identify factors independently associated with mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. RESULTS: Overall 118 patients were enrolled, 75 (63%) and 43 (37%) treated with colistin- and cefiderocol-based regimens. The median (q1-q3) age was 70 (62-79) years; 70 (59%) patients were men. The 30-day all-cause mortality was 52%, significantly lower in the cefiderocol group (40% vs 59%, p = 0.045). By performing a Cox regression model, age (aHR = 1.03, 95% CI 1.00-1.05), septic shock (aHR = 1.93, 95% CI 1.05-3.53), and delayed targeted therapy (aHR = 2.42, 95% CI 1.11-5.25) were independent predictors of mortality, while cefiderocol-based therapy was protective (aHR = 0.49, 95% CI 0.25-0.93). The IPTW-adjusted Cox analysis confirmed the protective effect of cefiderocol (aHR = 0.53, 95% CI 0.27-0.98). CONCLUSIONS: Cefiderocol may be a valuable treatment option for CRAB-BSI, especially in the current context of limited treatment options.

An Artefactual Cluster of Mycobacterium abscessus Pneumonia among Cancer Patients Arising from Contamination.

The Mycobacteriumabscessus complex (MABC) is a group of rapidly growing, nontuberculous mycobacteria that are ubiquitous in soil, urban water pipes, swimming pools, and drinking water. Members of the MABC are considered opportunistic pathogens. The aim of this study was to investigate the origins of MABC detected in broncho-lavage (BL) samples from asymptomatic cancer patients. We turned our attention to washing and disinfection procedures for bronchoscopes; we also assessed water and disinfectant samples. Of 10 BL and 34 environmental samples tested, four BL samples (40%) and seven environmental samples (20.6%) tested positive for MABC. We hypothesized that contamination could arise from the prewashing machine and/or the water used because no patient had clinical or radiological signs consistent with MABC respiratory tract infection. Our study highlights the importance of evaluating cleaning and disinfection procedures for endoscope channels to reduce the potential spread of microorganisms and artefactual results arising from contamination.

Emerging issue of fluconazole-resistant candidemia in a tertiary care hospital of southern italy: time for antifungal stewardship program.

An increased number of patients is at risk of Candida spp. bloodstream infection (CBSI) in modern medicine. Moreover, the rising of antifungal resistance (AR) was recently reported. All consecutive CBSI occurred in our Hospital (consisting of 1,370 beds) between 2015 and 2018, were reviewed. For each case, Candida species, AR pattern, ward involved and demographic data of patients were recorded. Overall, 304 episodes of CBSI occurred, with a median (q1:first-,q3:third quartile) of 77 (71-82) CBSI/year. Over the years, a significant increase of CBSI due to C. albicans compared to non-albicans strains was recorded in medical wards (from 65% to 71%, p=0.030), while this ratio remained stable in others. An increase of resistant strains to multiple antifungals such as C. guillermondii was noticed in recent years (from 0% to 9.8%, p=0.008). Additionally, from 2015 to 2018 an increase in fluconazole-resistance was recorded in our Hospital (from 7.4% to 17.4%, p=0.025) and a slight increase in voriconazole-resistance (from 0% to 7% in 2018, p=0.161) was observed, while resistance to echinocandin and amphotericin B remained firmly below 2%. This study suggests a rapid spread of antifungal resistance in our Hospital; therefore, an appropriate antifungal stewardship programs is urgently warranted.

Predictors for Pulmonary Tuberculosis Outcome and Adverse Events in an Italian Referral Hospital: A Nine-Year Retrospective Study (2013-2021).

Background: The COVID-19 pandemic has undone years of progress in providing essential TB services and controlling the TB burden. Italy, a low TB burden country, has an incidence of 7.1 cases per 100,000 people. To control the TB spreading in Italy is critical to investigate the characteristics of patients with the worst outcomes and the highest risk of adverse events related to antituberculosis therapy. Therefore, we conducted a large retrospective study in TB patients admitted to the Clinic of Infectious Diseases University of Bari, Italy, in order to describe the clinical presentation and the factors associated with adverse events and outcomes. Methods: We retrospectively evaluated the patients admitted to the Clinic of Infectious Diseases from January 2013 to 15 December 2021. We stratified our cohort into two groups: <65 years of age and ≥65 years in order to assess any differences between the two groups. Two logistic regression models were implemented considering the dependent variables as: (I) the adverse events; and (II) the unsuccessful treatments. Results: In total, 206 consecutive patients [60% (n = 124) M, median age 39 years, range 16-92] were diagnosed and admitted with TB at Clinic of Infectious Diseases. Of the whole sample, 151 (74%) were <65 years and 55 (26%) were ≥65. Statistically significant differences between the two groups were detected (p-value < 0.05) for nationality (p-value = 0.01), previous contact with TB patient (p-value = 0.00), type of TB (p-value = 0.00), unsuccessful treatment (p-value = 0.00), length of hospitalization (p-value = 0.02) and diagnostic delay (p-value = 0.01). Adverse events related to TB drug regimen were reported in 24% (n = 49). Age < 65 years (O.R. = 3.91; 95% CI 1.72-4.21), non-Italian nationality (O.R. = 4.45; 95% CI 2.22-4.98.), homeless (O.R. = 3.23; 95% CI 2.58-4.54), presence of respiratory symptoms (O.R. = 1.23; 95% CI 1.10-1.90), diagnostic delay (O.R = 2.55; 95% CI 1.98-3.77) resulted associated with unsuccessful treatment outcome (death, failure or lost to follow up). Finally, age < 65 years (O.R. = 1.73; 95% CI 1.31-2.49), presence of pulmonary TB (O.R. = 1.15; 95% CI 1.02-1.35), length of hospitalization (O.R. = 1.82; 95% CI 1.35-2.57) and TB culture positive (O.R. = 1.35; 95% CI 1.12-1.82) were associated with adverse events in our populations. Conclusions: The pharmacological approach alone seems insufficient to treat and cure a disease whose ethiopathogenesis is not only due to the Mycobacterium tuberculosis, but also to the poverty or the social fragility. Our data suggest that young foreigners, the homeless, and the people with low social and economic status are at higher risk of an unfavorable outcome in low incidence TB countries. Targeted actions to support this highly vulnerable population both in terms of outcome and occurrence of adverse events are needed.

Impact of a Multistep Bundles Intervention in the Management and Outcome of Gram-Negative Bloodstream Infections: A Single-Center "Proof-of-Concept" Study.

Background: This is a "proof-of-concept" study aiming to evaluate the impact of a multistep bundles intervention in the management and outcomes of patients with gram-negative bloodstream infections (GN-BSIs). Methods: This was a single-center, quasi-experimental design study. In the pre-phase (January 2019 to May 2020), patients were retrospectively enrolled. During the post-phase (June 2020 to September 2021), all patients were prospectively enrolled in a nonmandatory 3-step bundles intervention arm including (i) step 1: imaging to detect deep foci of infection, follow-up blood cultures and procalcitonin monitoring; (ii) step 2: early targeted antibiotic treatment and surgical source control; (iii) step 3: discontinuation of antibiotics within 7-10 days in case of uncomplicated BSI. Patients were followed up to 28 days from BSI onset. The primary outcome was 28-day mortality. Results: A total of 271 patients were enrolled: 127 and 144 in the pre- vs post-phase, respectively. Full application of step 1 (67% vs 42%; P < .001), step 2 (83% vs 72%; P = .031), and step 3 (54% vs 2%; P < .001) increased in the post-phase. Overall, the intervention reduced 28-day mortality (22% vs 35%, respectively; P = .016) and the median duration of total (11 vs 15 days; P < .001) and targeted (8 vs 12 days; P = .001) antibiotic therapy. Finally, the multivariate Cox regression confirmed the independent protective effect of adherence to step 1 (adjusted hazard ratio [aHR], 0.36; 95% CI, 0.20-0.63) and step 2 (aHR, 0.48; 95% CI, 0.29-0.81) on risk of 28-day mortality. Conclusions: Clinical management and outcomes of patients with GN-BSIs may be improved by providing a pre-established multistep bundles intervention.

High risk of unsuccessful treatment outcome in migrant population with tuberculosis: Data from three Italian hospitals.

Introduction: Tuberculosis (TB) remains an unresolved global health problem and vulnerable groups such as migrants remain the most affected with a higher risk of worse outcomes. The aim of this study was to evaluate clinical features, outcomes, and adverse events in migrant and native Italian patients admitted to three Italian hospitals in Southern Italy in order to assess differences and targeted strategies. Methods: We performed a retrospective study on TB patients admitted between January 1, 2013, and December 31, 2021, in three Apulia hospitals. Two logistic regression models were used, with the dependent variables being (I) unsuccessful treatment (died, loss to follow-up, and failed treatment) and (II) adverse events. Results: We enrolled 543 consecutive patients admitted at three Italian hospitals with a diagnosis of TB during the study period, of them 323 (59.5%) were migrants and 220 Italian patients. The treatment success rate in the migrant group was 44.9% (137/305), while in the non-migrant group was 97.1% (203/209). Independent factors of unsuccess treatment (death, failure or loss to follow up) were: migrant status (O.R. = 11.31; 95% CI 9.72-14.23), being male (O.R. = 4.63; 95% CI 2.16-6.10), homelessness (O.R. = 3.23; 95% CI 2.58-4.54), having a MDR (Multidrug-resistant) (O.R = 6.44; 95% CI 4.74-8.23), diagnostic delay (O.R. = 3.55; 95% CI 1.98-5.67), and length of hospitalization (O.R. = 3.43; 95% CI 1.88-5.87). While, age >65 ys (O.R. = 3.11; 95% CI 1.42-4.76), presence of extrapulmonary TB (O.R. = 1.51; 95% CI 1.31-2.18), monoresistance (O.R. = 1.45; 95% CI 1.25-3.14) and MDR pattern (O.R. = 2.44; 95% CI 1.74-5.03) resulted associated with adverse events. Conclusion: Migrant population is at high risk of unsuccessful treatment (death, loss to follow-up, and treatment failure). Policies targeted specifically to this group are needed to really impact and improve their health status and also to contain the TB burden.