European Society of Clinical Microbiology and Infectious Diseases/European Committee on infection control clinical guidelines on pre-operative decolonization and targeted prophylaxis in patients colonized by multidrug-resistant Gram-positive bacteria before surgery.

SCOPE: The aim of these guidelines is to provide recommendations for decolonization and perioperative antibiotic prophylaxis (PAP) in multidrug-resistant Gram-positive bacteria (MDR-GPB) adult carriers before inpatient surgery. METHODS: These European Society of Clinical Microbiology and Infectious Diseases/European Committee on Infection Control guidelines were developed following a systematic review of published studies targeting methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, methicillin-resistant coagulase-negative Staphylococci, and pan-drug-resistant-GPB. Critical outcomes were the occurrence of surgical site infections (SSIs) caused by the colonizing MDR-GPB and SSIs-attributable mortality. Important outcomes included the occurrence of SSIs caused by any pathogen, hospital-acquired infections, all-cause mortality, and adverse events associated with the interventions, including resistance development to the agents used and the incidence of Clostridioides difficile infections. The last search of all databases was performed on 1 November 2023. The level of evidence and the strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included. RECOMMENDATIONS: The guideline panel reviewed the impact of decolonization, targeted PAP, and combined interventions (e.g. decolonization and targeted PAP) on the risk of SSIs and other outcomes in MDR-GPB carriers, according to the type of bacteria and type of surgery. We recommend screening for S. aureus before high-risk operations, such as cardiothoracic and orthopaedic surgery. Decolonization with intranasal mupirocin with or without a chlorhexidine bath is recommended in patients colonized with S. aureus before cardiothoracic and orthopaedic surgery and suggested in other surgeries. The addition of vancomycin to standard prophylaxis is suggested for MRSA carriers in cardiothoracic surgery, orthopaedic surgery, and neurosurgery. Combined interventions (e.g. decolonization and targeted prophylaxis) are suggested for MRSA carriers undergoing cardiothoracic and orthopaedic surgery. No recommendation could be made regarding screening, decolonization and targeted prophylaxis for vancomycin-resistant enterococci because of the lack of data. No evidence was retrieved for methicillin-resistant coagulase-negative Staphylococci and pan-drug-resistant-GPB. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship and infection control teams are warranted before implementing screening procedures or performing changes in PAP policy. Future research should focus on novel decolonizing techniques, on the monitoring of resistance to decolonizing agents and PAP regimens, and on standardized combined interventions in high-quality studies.

Microbial Therapy and Breast Cancer Management: Exploring Mechanisms, Clinical Efficacy, and Integration within the One Health Approach.

This comprehensive review elucidates the profound relationship between the human microbiome and breast cancer management. Recent findings highlight the significance of microbial alterations in tissue, such as the gut and the breast, and their role in influencing the breast cancer risk, development, progression, and treatment outcomes. We delve into how the gut microbiome can modulate systemic inflammatory responses and estrogen levels, thereby impacting cancer initiation and therapeutic drug efficacy. Furthermore, we explore the unique microbial diversity within breast tissue, indicating potential imbalances brought about by cancer and highlighting specific microbes as promising therapeutic targets. Emphasizing a holistic One Health approach, this review underscores the importance of integrating insights from human, animal, and environmental health to gain a deeper understanding of the complex microbe-cancer interplay. As the field advances, the strategic manipulation of the microbiome and its metabolites presents innovative prospects for the enhancement of cancer diagnostics and therapeutics. However, rigorous clinical trials remain essential to confirm the potential of microbiota-based interventions in breast cancer management.

Immune Checkpoint Inhibitors and Infection: What Is the Interplay?

Immune checkpoint molecules are receptors expressed on immune cells, especially T-cells, which activate immunosuppressive pathways and lead them to a state known as T-cell exhaustion. Immune checkpoint inhibitors (ICIs) constitute a group of specific antibodies that target these molecules, restoring T-cell effector function. Several ICIs have already been approved by the FDA as therapeutic options for certain malignancies. However, evidence in the literature remains unclear regarding the possible risk of infection in patients receiving this treatment. A thorough examination of existing literature was carried out to investigate whether the use of ICIs increases the likelihood of specific infections and to explore the potential beneficial effects of ICIs on the treatment of infections. Our review found most infectious complications are related to immunosuppressive therapy for immune-related adverse events caused by checkpoint blockade. Current evidence shows that ICIs per se do not seem to generally increase the risk of infection, yet they might increase susceptibility to certain infections, such as tuberculosis. On the other hand, reinvigoration of immune responses triggered by ICIs might play a significant role in pathogen clearance, establishing a possible positive impact of ICIs, especially on chronic infectious diseases, such as HIV infection. Data from preclinical models are limited and larger clinical trials are warranted to shed more light on the effect of immune checkpoint blockade on specific pathogens.

Statins in Children with Neurofibromatosis Type 1: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Statins, apart from their plasma-cholesterol-lowering ability, exert several pleiotropic effects, making them a potential treatment for other diseases. Animal studies have showed that statins, through the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, can affect the Ras/MAPK pathway, thus providing impetus to examine the efficacy of statins in the pediatric population with neurofibromatosis type 1 (NF1). We aimed to systematically address all relevant evidence of statin treatment in children with NF1. METHODS: We searched PubMed and Cochrane Library resources up to 2 June 2023 for randomized controlled trials (RCTs) written in English and evaluating statins versus placebo in children with NF1 (PROSPERO registration number: CRD42023439424). RESULTS: Seven RCTs were suitable to be included in this qualitative synthesis, with a total participation of 336 children with NF1. The duration of the studies ranged from 12 to 52 weeks. The mean age of the pediatric population was 10.9 years old. Three studies investigated the role of simvastatin, while four studies examined lovastatin. According to our analysis, neither simvastatin nor lovastatin improved cognitive function, full-scale intelligence, school performance, attention problems, or internalizing behavioral problems when compared with placebo in children with NF1. Statins were well tolerated in all included RCTs. CONCLUSION: Although safe, current evidence demonstrates that statins exert no beneficial effect in cognitive function and behavioral problems in children with NF1.

The Effect of Statins on the Incidence and Prognosis of Bladder Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Statins are widely used due to their ability to lower plasma cholesterol and offer protection from the effects of atherosclerosis. However, their role in urology and specifically bladder cancer remains unclear. We aimed to systematically address this issue in the literature and determine any possible effects of statin therapy on bladder cancer. METHODS: We searched MEDLINE (PubMed) and Cochrane Library databases for records up to 26 March 2023, for studies evaluating the effects of statins on urinary bladder cancer (UBC). We included all randomized controlled trials (RCTs), cohorts, and case-control studies that were conducted on the adult population. PROSPERO registration number: CRD42023407795. RESULTS: Database searches returned 2251 reports, and after thorough investigation and assessment for eligibility, 32 reports were included in the analysis. Of them, 4 were RCTs, 6 were case-control studies, and 22 were cohort studies. Our qualitative analysis demonstrated no association between statin administration and UBC local control, recurrence, survival, or mortality, or between statin administration and bacille Calmette-Guérin (BCG) immunotherapy effectiveness. A meta-analysis of 10 trials revealed a non-significant reduction of 11% in UBC risk among users compared with non-users in RCTs (RR: 0.89, 95% CI 0.68-1.16, p = 0.37) and a non-significant increase of 32% of UBC risk among statin users compared with non-users in the analysis of the cohort studies (RR: 1.32, 95% CI 0.76-2.30, p = 0.33). CONCLUSIONS: Our results provide strong evidence to support the neutral effect of statins on UBC local control, recurrence, survival, and mortality, and on BCG immunotherapy. Our meta-analysis revealed a non-significant effect on UBC risk among statin users when compared with non-users, indicating no statin effect on UBC incidence and overall prognosis.

ESCMID/EUCIC clinical practice guidelines on perioperative antibiotic prophylaxis in patients colonized by multidrug-resistant Gram-negative bacteria before surgery.

SCOPE: The aim of the guidelines is to provide recommendations on perioperative antibiotic prophylaxis (PAP) in adult inpatients who are carriers of multidrug-resistant Gram-negative bacteria (MDR-GNB) before surgery. METHODS: These evidence-based guidelines were developed after a systematic review of published studies on PAP targeting the following MDR-GNB: extended-spectrum cephalosporin-resistant Enterobacterales, carbapenem-resistant Enterobacterales (CRE), aminoglycoside-resistant Enterobacterales, fluoroquinolone-resistant Enterobacterales, cotrimoxazole-resistant Stenotrophomonas maltophilia, carbapenem-resistant Acinetobacter baumannii (CRAB), extremely drug-resistant Pseudomonas aeruginosa, colistin-resistant Gram-negative bacteria, and pan-drug-resistant Gram-negative bacteria. The critical outcomes were the occurrence of surgical site infections (SSIs) caused by any bacteria and/or by the colonizing MDR-GNB, and SSI-attributable mortality. Important outcomes included the occurrence of any type of postsurgical infectious complication, all-cause mortality, and adverse events of PAP, including development of resistance to targeted (culture-based) PAP after surgery and incidence of Clostridioides difficile infections. The last search of all databases was performed until April 30, 2022. The level of evidence and strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included in the recommendation development. RECOMMENDATIONS: The guideline panel reviewed the evidence, per bacteria, of the risk of SSIs in patients colonized with MDR-GNB before surgery and critically appraised the existing studies. Significant knowledge gaps were identified, and most questions were addressed by observational studies. Moderate to high risk of bias was identified in the retrieved studies, and the majority of the recommendations were supported by low level of evidence. The panel conditionally recommends rectal screening and targeted PAP for fluoroquinolone-resistant Enterobacterales before transrectal ultrasound-guided prostate biopsy and for extended-spectrum cephalosporin-resistant Enterobacterales in patients undergoing colorectal surgery and solid organ transplantation. Screening for CRE and CRAB is suggested before transplant surgery after assessment of the local epidemiology. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship teams before implementing the screening procedures or performing changes in PAP are warranted. High-quality prospective studies to assess the impact of PAP among CRE and CRAB carriers performing high-risk surgeries are advocated. Future well-designed clinical trials should assess the effectiveness of targeted PAP, including the monitoring of MDR-GNB colonization through postoperative cultures using European Committee on Antimicrobial Susceptibility Testing clinical breakpoints.

Lomentospora prolificans Disseminated Infections: A Systematic Review of Reported Cases.

BACKGROUND: Lomentospora prolificans, a rare, highly virulent filamentous fungus with high rates of intrinsic resistance to antifungals, has been associated with different types of infections in immunocompromised as well as immunocompetent individuals. OBJECTIVE: To systematically address all relevant evidence regarding L. prolificans disseminated infections in the literature. METHODS: We searched Medline via PubMed and Scopus databases through July 2022. We performed a qualitative synthesis of published articles reporting disseminated infections from L. prolificans in humans. RESULTS: A total of 87 studies describing 142 cases were included in our systematic review. The pathogen was most frequently reported in disseminated infections in Spain (n = 47), Australia (n = 33), the USA (n = 21), and Germany (n = 10). Among 142 reported cases, 48.5% were males. Underlying conditions identified for the majority of patients included malignancy (72.5%), hemopoietic stem cell transplantation (23.2%), solid organ transplantation (16%), and AIDS (2%). Lungs, central nervous system, skin, eyes, heart and bones/joints were the most commonly affected organs. Neutropenia was recorded in 52% of patients. The mortality rate was as high as 87.3%. CONCLUSIONS: To the best of our knowledge, this is the first systematic review conducted on disseminated infections due to this rare microorganism. Physicians should be aware that L. prolificans can cause a diversity of infections with high mortality and primarily affects immunocompromised and neutropenic patients.

Clinical significance of P-class pumps in cancer.

P-class pumps are specific ion transporters involved in maintaining intracellular/extracellular ion homeostasis, gene transcription, and cell proliferation and migration in all eukaryotic cells. The present review aimed to evaluate the role of P-type pumps [Na+/K+ ATPase (NKA), H+/K+ ATPase (HKA) and Ca2+-ATPase] in cancer cells across three fronts, namely structure, function and genetic expression. It has been shown that administration of specific P-class pumps inhibitors can have different effects by: i) Altering pump function; ii) inhibiting cell proliferation; iii) inducing apoptosis; iv) modifying metabolic pathways; and v) induce sensitivity to chemotherapy and lead to antitumor effects. For example, the NKA ß2 subunit can be downregulated by gemcitabine, resulting in increased apoptosis of cancer cells. The sarcoendoplasmic reticulum calcium ATPase can be inhibited by thapsigargin resulting in decreased prostate tumor volume, whereas the HKA α subunit can be affected by proton pump inhibitors in gastric cancer cell lines, inducing apoptosis. In conclusion, the present review highlighted the central role of P-class pumps and their possible use and role as anticancer cellular targets for novel therapeutic chemical agents.

Age, Comorbidities and Fear of Fall: mortality predictors associated with fall-related fractures.

Objectives: To determine mortality predictors following fall related fractures in older patients. Materials and methods: Patients aged ≥ 70 years hospitalized for fall related fractures were prospectively evaluated. Mortality was the main outcome. Age, functional-cognitive function, medications, comorbidities, fall history, fear of falls were also assessed. Outcomes: A total of 100 patients were enrolled. Ninety-one out of 100 (91%) suffered a hip fracture; 92 (92%) had surgery. The one-year post-discharge mortality was 20%. Univariate analysis revealed that older age, increased Charlson comorbidity index, low abbreviated mental test on admission, low modified Barthel index (MBI), fear of falls and delirium were significantly correlated with one-year post discharge mortality (p=.03, p=.003, p=.04, p=.005, p=.004, p=.015, respectively). Conclusion: Age, fear of falls and Charlson comorbidity index are predictors of one-year mortality after hospitalization for fracture. It is of utmost importance to identify older patients suffering from fracture at risk of dying that may benefit from patient-centered care.

Is brucellosis a great mimic of tuberculosis? A case report.

Tuberculosis (TB) can manifest prolonged fever or fever of unknown origin, especially when it is located extrapulmonary. We report a case of disseminated TB complicated by iliac bone osteolysis and a gluteal abscess in a 75-year-old female patient with fever and bone marrow dysplasia. Diagnosis of TB was made despite transient false-positive high-titer agglutination tests and ELISA antibodies to Brucella. The case presented shows that in a highly suggestive case of TB, positive agglutination tests or ELISA antibodies to Brucella should be interpreted with caution, and repeated testing should be performed to assess their persistence and fluctuation over time.

Fungal infections in patients with inflammatory bowel disease: A systematic review.

BACKGROUND: Despite reports of fungal infections in patients with inflammatory bowel disease (IBD), their clinical and microbiological characteristics remain unknown. OBJECTIVES: The aim of this systematic review was to examine all available evidence regarding fungal infections in patients with IBD. METHODS: Systematic search of PubMed (through 27 May 2017) for studies providing data on clinical, microbiological, treatment and outcome data of fungal infections in patients with IBD. The primary study outcome was to record the most common fungal species in patients with IBD. Secondary outcomes were classified into 3 categories: (i) characteristics of fungal infections; (ii) data on IBD and (iii) treatment and outcomes of fungal infections in patients with IBD. RESULTS: Fourteen studies with data on 1524 patients were included in final analysis. The most common fungal infections in patients with IBD were caused by Candida species (903 infections); the most commonly reported site of Candida infection was the gastrointestinal tract. Available evidence shows that most fungal infections occur within 12 months of IBD treatment and within 6 months when anti-TNFa agents are used. CONCLUSIONS: This systematic review thoroughly describes fungal infections in patients with IBD and provides important information for the early detection and management of these infections.

Factors Associated with HIV Testing and HIV Treatment Adherence: A Systematic Review.

BACKGROUND: The impact of the global economic crisis on HIV-related access and care remains unclear. The objective of this systematic review of the literature was to evaluate the association between socioeconomic factors and HIV diagnosis, and adherence to treatment, following the 2008 global economic crisis. METHOD: A systematic search of PubMed and Scopus for studies published between January 2008 and October 2016 was conducted. Studies providing data on social, demographic, economic and cultural barriers associated with HIV diagnosis and treatment were included. RESULTS: Of 33 studies included, 22 evaluated HIV testing and 11 evaluated treatment adherence. Medical history of a sexually transmitted disease, knowledge of HIV-related risks, and age, were significantly associated with HIV testing in most of the included studies. Absence of social support, and alcohol or substance use, were the most common factors associated with adherence. Financial factors were not as commonly found to be related to access to HIV diagnosis and HIV treatment adherence, compared to knowledge of HIV-related risks and social support. CONCLUSION: The identification of persons who are less likely to test for HIV, and to adhere to HIV treatment, may serve as a guide for public health interventions, especially in resource-limited areas.

Surveillance of surgical site infections at a tertiary care hospital in Greece: incidence, risk factors, microbiology, and impact.

BACKGROUND: In this first attempt to implement a standardized surveillance system of surgical site infections (SSI) in a Greek hospital, our objective was to identify areas for improvement by comparing main epidemiologic and microbiologic features of SSI with international data. METHODS: The National Nosocomial Infections Surveillance (NNIS) system protocols were employed to prospectively collect data for patients in 8 surgical wards who underwent surgery during a 9-month period. SSI rates were benchmarked with international data using standardized infection ratios. Risk factors were evaluated by multivariate logistic regression. RESULTS: A total of 129 SSI was identified in 2420 operations (5.3%), of which 47.3% developed after discharge. SSI rates were higher for 2 of 20 operation categories compared with Spanish and Italian data and for 12 of 20 categories compared with NNIS data. Gram-positive microorganisms accounted for 52.1% of SSI isolates, and Enterococci were predominant. Alarming resistance patterns for Enterococcus faecium and Acinetobacter baumannii were recorded. Potentially modifiable risk factors for SSI included multiple procedures, extended duration of operation, and antibiotic prophylaxis. SSI was associated with prolongation of postoperative stay but not with mortality. CONCLUSION: Comparisons of surveillance data in our hospital with international benchmarks provided useful information for infection control interventions to reduce the incidence of SSI.