Antimicrobial Susceptibility Profiles of Klebsiella pneumoniae Strains Collected from Clinical Samples in a Hospital in Southern Italy.

Infections caused by antibiotic-resistant bacteria represent a serious threat to global public health. Recently, due to its increased resistance to carbapenems and ß-lactams, Klebsiella pneumoniae has become one of the main causes of septicemia, pneumonia, and urinary tract infections. It is crucial to take immediate action and implement effective measures to prevent further spread of this issue. This study aims to report the prevalence and antibiotic resistance rates of K. pneumoniae strains isolated from clinical specimens from 2015 to 2020 at the University Hospital of Salerno, Italy. More than 3,800 isolates were collected from urine cultures, blood cultures, respiratory samples, and others. K. pneumoniae isolates showed broad resistance to penicillin and cephalosporins, and increased susceptibility to fosfomycin and gentamicin. Extended spectrum beta-lactamase (ESBL) isolates accounted for 20-22%. A high percentage of strains tested were resistant to carbapenems, with an average of 40% to meropenem and 44% to ertapenem. The production of ESBLs and resistance to carbapenems is one of the major public health problems. Constant monitoring of drug-resistant isolates is crucial for developing practical approaches in implementing antimicrobial therapy and reducing the spread of K. pneumoniae in nosocomial environments.

Circulating vitamin D level before initiating chemotherapy impacts on the time-to-outcome in metastatic colorectal cancer patients: systematic review and meta-analysis.

BACKGROUND: Vitamin D (VD) is implicated in various health conditions, including colorectal cancer (CRC). To investigate potential relationships between pre-chemotherapy VD levels and the time-to-outcome in metastatic CRC patients, we conducted a systematic review and meta-analysis. METHODS: Following the PRISMA 2020 guidelines, we performed thorough searches in PubMed/MEDLINE and Scopus/ELSEVIER databases (covering the years 2002 to 2022). Inclusion criteria mandated studies to report on individuals aged 18 years and above with histologically confirmed stage IV CRC. Additionally, studies needed to provide data on VD levels before chemotherapy, along with hazard ratios (HR) and 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS). Five articles were identified with the aim of establishing a combined risk estimate for death and progression based on pre-chemotherapy VD levels. Heterogeneity among studies and publication bias were evaluated using Tau2, I2 statistics, and a Funnel plot. RESULTS: Although no significant heterogeneity was observed in time-to-outcome among the selected studies, variations in technical assessments and serum VD concentration measurements were noted. The pooled analysis, involving 1712 patients for OS and 1264 patients for PFS, revealed a 47% increased risk of death (HR: 1.47, 95% CI: 1.21-1.79) and a 38% increased risk of progression (HR: 1.38, 95% CI: 1.13-1.70) for patients with lower VD levels, as indicated by fixed-effects models. CONCLUSIONS: Our results emphasize the adverse effects of low VD concentration on the time-to-outcome in metastatic CRC patients. This underscores the importance of investigating VD supplementation as an innovative approach in this clinical setting to enhance patient outcomes.

Antimicrobial Resistance in Pseudomonas aeruginosa before and during the COVID-19 Pandemic.

Pseudomonas aeruginosa (PA) is a major Gram-negative opportunistic pathogen causing several serious acute and chronic infections in the nosocomial and community settings. PA eradication has become increasingly difficult due to its remarkable ability to evade antibiotics. Therefore, epidemiological studies are needed to limit the infection and aim for the correct treatment. The present retrospective study focused on PA presence among samples collected at the San Giovanni di Dio and Ruggi D'Aragona University Hospital in Salerno, Italy; its resistance profile and relative variations over the eight years were analyzed. Bacterial identification and antibiotic susceptibility tests were performed by VITEK® 2. In the 2015-2019 and 2020-2022 timeframes, respectively, 1739 and 1307 isolates of PA were obtained from respiratory samples, wound swabs, urine cultures, cultural swabs, blood, liquor, catheter cultures, vaginal swabs, and others. During 2015-2019, PA strains exhibited low resistance against amikacin (17.2%), gentamicin (25.2%), and cefepime (28.3%); moderate resistance against ceftazidime (34.4%), imipenem (34.6%), and piperacillin/tazobactam (37.7%); and high resistance against ciprofloxacin (42.4%) and levofloxacin (50.6%). Conversely, during the 2020-2022 era, PA showed 11.7, 21.1, 26.9, 32.6, 33.1, 38.7, and 39.8% resistance to amikacin, tobramycin, cefepime, imipenem, ceftazidime, ciprofloxacin, and piperacillin/tazobactam, respectively. An overall resistance-decreasing trend was observed for imipenem and gentamicin during 2015-2019. Instead, a significant increase in resistance was recorded for cefepime, ceftazidime, and imipenem in the second set of years investigated. Monitoring sentinel germs represents a key factor in optimizing empirical therapy to minimize the spread of antimicrobial resistance.

Circulating Vitamin D Level and Its Impact on Mortality and Recurrence in Stage III Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Vitamin D (VD) has been implicated in several diseases, including colorectal cancer (CRC). This study aimed to determine whether there is an association between VD levels and time-to-outcome in stage III CRC patients through a systematic review and meta-analysis. METHODS: The study adhered to the PRISMA 2020 statement. Articles were searched in PubMed/MEDLINE and Scopus/ELSEVIER. Four articles were selected, with the primary objective of providing a pooled estimate of the risk of death specifically in stage III CRC patients based on pre-operative VD levels. Study heterogeneity and publication bias were analyzed using Tau2 statistics and funnel plots. RESULTS: The selected studies showed significant heterogeneity regarding time-to-outcome, technical assessments, and serum VD concentration measures. The pooled analysis of 2628 and 2024 patients revealed a 38% and 13% increase in the risk of death (HR: 1.38, 95% CI: 0.71-2.71) and recurrence (HR: 1.13; 95% CI: 0.84-1.53), respectively, for random-effects models among patients with lower levels of VD. CONCLUSIONS: Our findings suggest that a low concentration of VD has a significant negative impact on time-to-outcome in stage III CRC.

The Impact of O6-Methylguanine-DNA Methyltransferase (MGMT) Promoter Methylation on the Outcomes of Patients with Leiomyosarcoma Treated with Dacarbazine.

Dacarbazine is an important drug in the therapeutic landscape of leiomyosarcoma (LMS). Alkylating agents are subjected to resistance mechanisms based on anti-apoptotic pathways and repair mechanisms, including the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). In this retrospective study, the methylation status of the MGMT promoter in histological tumor samples from patients with LMS, dacarbazine-based regimens-treated, was measured and correlated with clinical outcomes aimed at optimizing the use of dacarbazine in soft tissue sarcomas. The patients with unmethylated MGMT had better outcomes than those with methylated MGMT. Patients without MGMT methylation had better Progression Free Survival (PFS) when aged ≥62 years compared to those aged <62 years, while PFS of patients with methylated MGMT was less favorable independently of age (p = 0.0054). The patients without a methylated MGMT gene had higher Disease control rate (DCR). These results are not in agreement with the role of the methylated MGMT gene in other tumors, and with this study, we demonstrated the correlation between methylated MGMT and poor prognosis; despite that, sample smallness, heterogeneity of LMS and of treatment history could be selection bias. Predictive markers of response to chemotherapies in sarcomas remain an unmet need.

The prognostic role of p53 mutations in metastatic colorectal cancer: A systematic review and meta-analysis.

INTRODUCTION: P53 is one of the most frequently mutated genes in colorectal cancer (CRC). The present study was undertaken to provide a solid estimate of the prognostic value of p53 mutations in metastatic CRC patients. METHODS: This meta-analysis was done in accordance to the Preferred Reporting Item For Systematic Reviews and Meta-Analysis 2020 guidelines. Studies in English published in the last ten years were searched through PubMed and Google Scholar. Final selection criteria were: 1) association with overall survival, 2) presence of Hazard Ratios (HRs) with 95% Confidence Intervals (CIs). The articles were evaluated for quality and risk of bias using the Newcastle-Ottawa Scale and QUIPS tool, respectively. The meta-analysis was conducted with random-effects model according to the Hartung-Knapp-Sidik-Jonkman method and results were depicted in classical Forest plots. Studies heterogeneity was determined by I2 and Tau2 statistics. The relationship between p53 mutation and clinic-pathological variables was examined using the χ2 test. RESULTS: Nine articles met the eligibility criteria and went to the final analysis. Sample size ranged from 51 to 1043 patients. All studies were retrospective. The Newcastle Ottawa Scale score was > 6 in all studies, QUIPS risk of bias was low in 6, moderate in 3 studies. Only three studies analysed the entire p53 gene coding region. The DNA sequencing technological platforms varied from Sanger to NGS sequencing techniques. The p53 mutational frequencies ranged from 35.0 % to 73.0 %. A strong association (p < 0.0001) emerged between p53 alteration and left-sided CRC. The final pooled HR (p53 mutated vs p53 wild-type tumors) for overall survival was 1.30 (95 % CI: 0.75-2.25) at random-effects model. CONCLUSIONS: The available evidence does not support a prognostic role for p53 in metastatic CRC patients. Prospective studies, with larger sample sizes and consistent and harmonized methodology, are needed to explore the prognostic role of p53 in metastatic CRC patients.

Prevalence and Distribution of High- and Low- Risk HPV Genotypes in Women Living in the Metropolitan Area of Naples: A Recent Update.

INTRODUCTION: Human papillomavirus (HPV) can infect both male and female genitals, skin, and mucous membranes, causing benign or malignant lesions. HPV is a common sexually transmitted infection and it is the main cause of cervical cancer. The present retrospective study updated the previously published data on HPV genotypes distribution among women living in Naples. MATERIALS AND METHODS: In this study, 502 cervical scrape specimens were collected from women with abnormal cytological indication and analyzed for HPV DNA identification by Linear Array HPV genotyping test. RESULTS: The HPV infection rate was 24.1%. HPV-16 (14.6%) was the most representative HR-HPV genotypes, followed by HPV-31 (13.8%), -18 (9.2%), and HPV-51 (8.5%). In addition, HPV-42 (16.4%) was the most prevalent genotype among LR-HPV  genotypes (low-risk human papillomavirus). It was also found that women at the age group of 23-29 years (42.5%) were at the highest risk of HPV infection. It was found that the HPV-16 frequency decreased, but HPV-31 and -18 frequency increased a little. The LR HPV-53 frequency decreased, leaving the first place for abundance to the LR HPV-42. HPV-6 frequency did not change. LR HPV -11 was no more present. Merging <23 and 23-29 age classes into one class followed the same result. CONCLUSION: HPV prevalence declined in comparison to the previous data. A frequency variation was recorded for several genotypes in this study.  Data can be useful to implement the preventative strategies and to promote HPV vaccination.

Response to Peptide Receptor Radionuclide Therapy in Pheocromocytomas and Paragangliomas: A Systematic Review and Meta-Analysis.

INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC showed efficacy in the metastatic setting of pheocromocytomas (PCCs) and paragangliomas (PGLs) where no standard therapies have been established. BACKGROUND: A search of peer-reviewed and English articles reporting on 177Lu-DOTATATE and 90Y-DOTATOC efficacy was performed through Medline and Scopus. A subsequent meta-analysis was performed to evaluate the pooled effect size on disease control rate (DCR) with PRRT. Secondary endpoints were description of patients' genetic characteristics, hematologic toxicity, and time-to-outcome. The pooled effect was estimated with both a mixed-effects model and a random-effects model. RESULTS: Twelve studies met the criteria for this meta-analysis: ten with 177Lu- and two with 90Y-PRRTs (213 patients). The largest one included 46 patients. Median ages ranged from 32.5 to 60.4 years. When reported, mutations of SDHB were the most frequent genetic alterations. The pooled DCRs were 0.83 (95% CI: 0.75-0.88) and 0.76 (95% CI: 0.56-0.89) for 177Lu- and 90Y-PRRT, respectively. The pooled DCR for PRRT was 0.81 (95% CI: 0.74-0.87). CONCLUSIONS: We report an updated and solid estimate of DCR achieved with 177Lu- and 90Y-PRRT in PCCs and PGLs, showing that these therapies can be considered in the multidisciplinary treatment of PCCs and PGLs as alternatives to I-131 MIBG and chemotherapy.

Prevalence and Antibiotic Resistance Profile of Bacterial Pathogens in Aerobic Vaginitis: A Retrospective Study in Italy.

Aerobic vaginitis (AV) is a vaginal infectious condition, characterized by a high inflammatory response and/or signs of epithelial atrophy, a decrease in the amount of Lactobacillus spp. and an increase in enteric origin bacteria. AV, often misdiagnosed, is difficult to treat due to the emerging spread of multi-drug resistant bacterial strains. The present study aimed to define the prevalence of AV, to detect causative bacteria and their antimicrobial resistance pattern. Women 10-95 years old, admitted to San Giovanni di Dio e Ruggi d'Aragona Hospital, Salerno, Italy (in the years 2015-2019) are included in the study. Bacterial identification and antibiotic susceptibility tests were carried out by VITEK® 2. Among 2069 patients, 1176 tested positive for microbial growth. A higher incidence of infection was found in the 55-64 age group. Among the pathogenic strains, 50.4% were Gram-negative, and 49.6% were Gram-positive. Escherichia coli (E. coli) (32.5%) was the most representative strain, followed by Enterococcus faecalis (E. faecalis) (29.4%), Klebsiella pneumoniae (K. pneumoniae) (7.8%) and Enterococcus faecium (E. faecium) (7.7%). E. coli showed high sensitivity to carbapenems and amikacin. K. pneumoniae carbapenems resistance was fluctuating over time. Alarming resistance to vancomycin was not recorded for Enterococci. Both strains were sensitive to teicoplanin, linezolid and tigecycline. Proper diagnosis and an effective therapeutic approach are needed to improve AV management.

Lower Respiratory Tract Pathogens and Their Antimicrobial Susceptibility Pattern: A 5-Year Study.

Lower respiratory tract infections (LRTIs) are the most common infections in humans. It is estimated that 2.74 million deaths worldwide occur each year due to LRTIs. The aim of the study was to determine the frequency and antibiotic susceptibility pattern of microorganisms isolated from respiratory samples of patients with LRTIs. Between January 2015 and December 2019, a total of 7038 sputum and bronchoaspirate samples from suspected LRTI patients were collected. Among them, 2753 samples (39.1%) showed significant microbial growth on culture media. The LRTI rate was higher in patients with male gender (67.1%) and with age between 40-59 years (48.6%). The microorganism identification and antibiotic susceptibility testing were performed with Vitek 2. Out of 4278 isolates species, 3102 (72.5%) were Gram-negative bacteria, 1048 (24.5%) were Gram-positive bacteria, and 128 (3.0%) were Candida spp. Major microorganisms isolated were Acinetobacter baumannii (18.6%), Staphylococcus aureus (15.2%), Pseudomonas aeruginosa (14.2%), and Klebsiella pneumoniae (10.9%). In antimicrobial susceptibility testing, Staphylococcus aureus isolates were mostly resistant to Penicillin G (84.1%) and Oxacillin (48.1%), whereas they demonstrated maximum sensitivity to Tigecycline (100%) and Linezolid (99.5%). Among Gram-negative isolates, Acinetobacter baumannii showed maximum sensitivity to Colistin but was resistant to other antibiotics (95-99%). Klebsiella pneumoniae isolates were mostly resistant to Cefotaxime (72.7%) and sensitive to Gentamicin (54.3%), and Pseudomonas aeruginosa was resistant to Ciprofloxacin (40.3%) and sensitive to Amikacin (85.9%). Gram-negative bacteria represented the species most commonly isolated. A high rate of antimicrobial resistance was observed in this study. In conclusion, the correct identification of causative microorganisms and their susceptibility patterns to antibiotics is crucial for choosing targeted and effective antibiotic therapy in LRTIs, and to prevent the emergence of multidrug-resistant bacteria.