ABSTRACT
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.
ABSTRACT
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.
