Not surprising: a rebound in antibacterial consumption in Europe, with Cyprus and Greece on the podium.

Recent European-wide data place Cyprus and Greece in the highest positions of total antimicrobial consumption. While this level of consumption might be partly attributed to the high rates of infections due to MDR bacteria in these countries, several other reasons should be sought to help apply local measures, to decrease inappropriate and excess antimicrobial use. The present viewpoint aims to provide a roadmap for interventions, by briefly discussing the various factors that underlie antimicrobial use and prescribing practices in Greece and Cyprus.

A carbapenem-focused antimicrobial stewardship programme implemented during the COVID-19 pandemic in a setting of high endemicity for multidrug-resistant Gram-negative bacteria.

BACKGROUND: Greece is among the countries characterized by high rates of antimicrobial resistance and high consumption of antibiotics, including carbapenems. OBJECTIVES: To measure the impact of a carbapenem-focused antimicrobial stewardship programme (ASP) on the antibiotic consumption and patient outcomes in a Greek tertiary hospital during the COVID-19 pandemic. METHODS: A quasi-experimental, before-after study, comparing a 12 month pre-intervention period with a 12 month intervention period in which a carbapenem-focused ASP was implemented. RESULTS: A total of 1268 patients were enrolled. The proportion of admitted patients who received carbapenems decreased from 4.1% (842 of 20 629) to 2.3% (426 of 18 245) (-1.8%; P < 0.001). A decrease of -4.9 DDD/100 patient-days (PD) (95% CI -7.3 to -2.6; P = 0.007) in carbapenem use and an increase in the use of piperacillin/tazobactam [+2.1 DDD/100 PD (95% CI 1.0-3.3; P = 0.010)] were observed. Thirty-day mortality following initiation of carbapenem treatment and all-cause in-hospital mortality remained unaltered after ASP implementation. In contrast, length of hospital stay increased (median 17.0 versus 19.0 days; P < 0.001), while the risk of infection-related readmission within 30 days of hospital discharge decreased (24.6% versus 16.8%; P = 0.007). In the post-implementation period, acceptance of the ASP intervention was associated with lower daily hazard of in-hospital death [cause-specific HR (csHR) 0.49; 95% CI 0.30-0.80], lower odds of 30 day mortality (OR 0.36; 95% CI 0.18-0.70) and higher rate of treatment success (csHR 2.45; 95% CI 1.59-3.77). CONCLUSIONS: Implementing and maintaining a carbapenem-focused ASP is feasible, effective and safe in settings with high rates of antimicrobial resistance, even during the COVID-19 pandemic.

Skin manifestations of Pseudomonas aeruginosa infections.

PURPOSE OF REVIEW: Pseudomonas aeruginosa is an opportunistic pathogen with considerable morbidity and mortality, particularly in vulnerable hosts. Skin manifestations are common, either representing local inoculation or secondary skin seeding following bloodstream infections. As patients with various predisposing conditions are expanding, we sought to review the most recent published evidence regarding epidemiology, risk factors and diagnosis of skin manifestations of P. aeruginosa. RECENT FINDINGS: New data exist on epidemiology and diagnosis of skin infections; systemic infections are impacted by multidrug-resistance issues and host immune status. SUMMARY: Green nail syndrome, toe web infection, hot tub folliculitis, hot hand-foot infection and external otitis are the most common infections originating from the skin per se. Local treatments are the cornerstone and prognosis is favorable in immunocompetent hosts. Ecthyma gangrenosum and P. aeruginosa subcutaneous nodules are usually associated with bloodstream infections and occur primarily in immunocompromised hosts. Necrotizing skin and soft tissue infections occur in diabetic, alcoholic and immunocompromised patients; management requires a multidisciplinary team with surgical approach. Burn wound infections may also be challenging, requiring a specialized team. In all the four latter types of P. aeruginosa skin infections portending significant morbidity and mortality, systemic antibiotics are an integral part of the treatment.

Factors Influencing Non-albicans Candidemia: A Case-Case-Control Study.

The study identified factors predisposing to non-albicans candidemia with special interest to prior antimicrobial treatment. A retrospective, case-case-control study was performed at the University Hospital of Heraklion, Greece, from November 2007 through September 2011 including adult patients. The study had three groups. The first included 58 patients with non-albicans candidemia, the second 48 with C. albicans candidemia, while the third (control) 104 without candidemia. Each of the two candidemia groups was compared with the control using multivariate logistic regression model. The mean (SD) age of the non-albicans, the albicans and the control patients was 67 (12), 67 (18) and 59 (19) years, respectively. The most common non-albicans Candida spp. isolated were C. parapsilosis in 19 patients (33%), C. glabrata in 17 (29%) and C. tropicalis in 15 (26%). Independent risk factors for non-albicans candidemia were prior treatment with quinolones (p < 0.001), b-lactam-b-lactamase inhibitors (p = 0.011) and presence of central venous catheter (p = 0.05), while for C. albicans candidemia were prior treatment with quinolones (p < 0.001), carbapenems (p = 0.003) along with cardiac disease (p < 0.001). Neither duration of hospitalization nor in-hospital mortality [41% for the non-albicans vs 29% for C. albicans group (p = 0.192)] was significantly different between the two candidemia groups. The study reveals the role of antimicrobial exposure as a risk factor for candidemia caused by different species. Prior treatment with b-lactam-b-lactamase inhibitors was associated with non-albicans, while with carbapenems with C. albicans candidemia. Prior use of quinolones was associated with candidemia in general.

Antifungal pipeline: Is there light at the end of the tunnel?

The misuse and overuse of classic antifungals have accelerated the development of resistance mechanisms, diminishing the efficacy of established therapeutic pathways and necessitating a shift towards alternative targets. Despite this pressing need for new treatments, the antifungal drug pipeline has been largely stagnant for the past three decades, primarily due to the high risks and costs associated with antifungal drug development, compounded by uncertain market returns. Extensive research durations, special patient populations and rigorous regulatory demands pose significant barriers to bringing novel antifungal agents to market. In response, the "push-pull" incentive model has emerged as a vital strategy to invigorate the pipeline and encourage innovation. This editorial critically examines the current clinical landscape and spotlights emerging antifungal agents, such as Fosmanogepix, Ibrexafungerp, and Olorofim, while also unraveling the multifaceted challenges faced in new antifungal drug development. The generation of novel antifungals offers a beacon of hope in the battle against antimicrobial resistance, but it is premature to declare them as definitive solutions. Their future role hinges on thorough clinical validation, cost-effectiveness assessments, and continuous post-marketing surveillance. Only through strategic implementation and integration with market strategies we can transform the landscape of antifungal development, addressing both the resistance crisis and the treatment challenges.

Brucella Spondylitis: Current Knowledge and Recent Advances.

The most prevalent zoonotic disease is brucellosis, which poses a significant threat for worldwide public health. Particularly in endemic areas, spinal involvement is a major source of morbidity and mortality and can complicate the course of the disease. The diagnosis of Brucella spondylitis is challenging and should be suspected in the appropriate epidemiological and clinical context, in correlation with microbiological and radiological findings. Treatment depends largely on the affected parts of the body. Available treatment options include antibiotic administration for an adequate period of time and, when appropriate, surgical intervention. In this article, we examined the most recent data on the pathophysiology, clinical manifestation, diagnosis, and management of spinal brucellosis in adults.

Antibiotics and Lipid-Modifying Agents: Potential Drug-Drug Interactions and Their Clinical Implications.

Evidence-based prescribing requires taking into consideration the many aspects of optimal drug administration (e.g., dosage, comorbidities, co-administered drugs, etc.). A key issue is the administration of drugs for acute disorders that may potentially interfere with previously prescribed long-term medications. Initiating an antibiotic for an acute bacterial infection constitutes a common example. Hence, appropriate knowledge and awareness of the potential DDIs of antibiotics would lead to proper adjustments, thus preventing over- or under-treatment. For example, some statins, which are the most prescribed lipid-modifying agent (LMA), can lead to clinically important drug-drug interactions (DDIs) with the concurrent administration of antibiotics, e.g., macrolides. This review discusses the clinically significant DDIs of antibiotics associated with co-administrated lipid-lowering therapy and highlights common cases where regimen modifications may or may not be necessary.

Preventing Multidrug-Resistant Bacterial Transmission in the Intensive Care Unit with a Comprehensive Approach: A Policymaking Manual.

Patients referred to intensive care units (ICU) commonly contract infections caused by multidrug-resistant (MDR) bacteria, which are typically linked to complications and high mortality. There are numerous independent factors that are associated with the transmission of these pathogens in the ICU. Preventive multilevel measures that target these factors are of great importance in order to break the chain of transmission. In this review, we aim to provide essential guidance for the development of robust prevention strategies, ultimately ensuring the safety and well-being of patients and healthcare workers in the ICU. We discuss the role of ICU personnel in cross-contamination, existing preventative measures, novel technologies, and strategies employed, along with antimicrobial surveillance and stewardship (AMSS) programs, to construct effective and thoroughly described policy recommendations. By adopting a multifaceted approach that combines targeted interventions with broader preventive strategies, healthcare facilities can create a more coherent line of defense against the spread of MDR pathogens. These recommendations are evidence-based, practical, and aligned with the needs and realities of the ICU setting. In conclusion, this comprehensive review offers a blueprint for mitigating the risk of MDR bacterial transmission in the ICU, advocating for an evidence-based, multifaceted approach.

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.

Oral Molnupiravir and Nirmatrelvir/Ritonavir for the Treatment of COVID-19: A Literature Review with a Focus on Real-World Evidence.

Vaccines remain the cornerstone of medical prevention and are highly effective in reducing the risk of severe disease and death due to coronavirus disease 2019 (COVID-19). In the context of expanding the therapeutic armamentarium against COVID-19, molnupiravir (Lagevrio) and ritonavir-boosted nirmatrelvir (Paxlovid) were developed, constituting the first effective oral treatments against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this narrative review, we retrospectively inquired into the clinical trials and real-world studies investigating the efficacy of these agents. Overall, clinical trials and real-world studies have demonstrated the efficacy of both agents in reducing hospitalization and death rates in COVID-19 patients. As per current recommendations, their use is suggested in patients with mild to moderate symptoms who are at high risk of developing severe disease. Nevertheless, limited data exist regarding their efficacy in specific subpopulations, such as immunocompromised patients, those with severe kidney disease, pregnant women, and children.

Real-World Data Regarding Dalbavancin Use before and during the COVID-19 Pandemic-A Single-Center Retrospective Study.

Dalbavancin is a semisynthetic lipoglycopeptide, which possesses great potential for bactericidal activity similar to antimicrobials with the same mechanism of action, such as vancomycin and teicoplanin. Due to its very prolonged half-life, it can be used in a single or two-dose regimen to treat infections by Gram-positive microorganisms, even resistant ones, such as methicillin-resistant Staphylococcus aureus (MRSA). Currently, it is approved only for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). The aim of this study was to investigate the clinical and microbiological characteristics of patients to whom dalbavancin was administered at the University Hospital of Heraklion and evaluate its use in regard to the COVID-19 pandemic. In total, 146 patients were included in this retrospective cohort study evaluating the use of dalbavancin from the first time it was used in 2017 until the end of 2022. The median age was 68 years (range: 21-96 years), and 86 (59%) patients were male. The most common indications for dalbavancin use were osteoarticular infections in 43%, followed by ABSSSIs in 37%, and cardiovascular infections in 10%. Dalbavancin was used empirically in one out of three patients, most commonly with the indication of ABSSSIs, and most commonly in the post-COVID-19 era. The most frequently isolated pathogens were coagulase-negative staphylococci in 70%, S. aureus in 27%, Enterococcus spp. in 22%, and Streptococcus spp. in 8%, while one out of three infections were polymicrobial. In 12% of patients, the infection was not cured, but no patients died. For patients with ABSSSIs, endocarditis and vascular infections, and bacteremia, the cure rates were more than 90%, and in osteoarticular infections, the cure rate was 76%. Thus, dalbavancin has great potential for use in complicated and invasive infections that may require prolonged intravenous antimicrobial treatment. However, further studies are required to formally investigate its role in such infections.

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.

Endophthalmitis caused by Enterococcus casseliflavus: a systematic review of literature.

Introduction: Enterococcus casseliflavus is a rare pathogen in human infections, despite being widely distributed in natural environments. This systematic review aims to evaluate the evidence related to endophthalmitis caused by E. casseliflavus. Methods: A thorough search of PubMed, PubMed Central, and Scopus databases was conducted, covering the period up to October 2022. Results: A total of 53 records were identified, with 8 studies reporting a total of 21 cases meeting the inclusion criteria. Among these studies, 7 described isolated case reports, while 1 study described 14 cases. The overall quality of the reports was good, as all articles were determined to have low risk of bias. Vancomycin susceptibility was reported in only one case of isolated case reports, while the remaining cases were all vancomycin resistant. With regard to management, in most cases intravenous ampicillin and linezolid were administered, while only one study reported administration of vancomycin. Conclusions: Ophthalmologists should be aware of the potential for E. casseliflavus to cause endophthalmitis infections and the challenges associated with its intrinsic resistance to vancomycin.

The impact of seasonal influenza vaccination uptake on COVID-19 vaccination attitudes in a rural area in Greece.

INTRODUCTION: Promoting vaccination for coronavirus disease 2019 (COVID-19), especially for high-risk groups such as the elderly and persons with comorbidities, is important for reducing the incidence of severe disease and death. METHODS: Retrospective cross-sectional study of factors associated with COVID-19 vaccination, including previous influenza vaccination, among all persons who received medical services in a rural area in Crete, Greece, between October 2020-May 2021. RESULTS: Among 3129 participants, receipt of influenza vaccination in 2020-21 was strongly associated with COVID-19 vaccination, as was influenza vaccination in 2019-20, albeit to a lesser extent. In addition, persons older than 59 years (with exception of those 90 + years old) and those who lived closer to the hospital/health center, were more likely to vaccinate for COVID-19. Persons younger than 40 years of age, females, persons with mental illness or neurologic disease, were also less likely to vaccinate for COVID-19 (all p < 0.001). CONCLUSIONS: COVID-19 vaccination was more likely among those who were vaccinated for influenza before and during the pandemic. Access to healthcare services and specific comorbidities, were important influencers for vaccination, underlying the importance of tailored interventions to enforce vaccination in high-risk groups.

The Burden of COVID-19 in Adult Patients With Hematological Malignancies: A Single-center Experience After the Implementation of Mass-vaccination Programs Against SARS-CoV-2.

BACKGROUND/AIM: Despite the widespread mass-vaccination programs worldwide and the continuing evolution of COVID-19 therapeutics, the burden of SARS-CoV-2 infection in patients with hematological malignancies (HM) remains elusive. The aim of the present study was to assess the clinical characteristics, outcomes and therapeutic strategies applied in HM patients hospitalized during the post-vaccine period in Greece. PATIENTS AND METHODS: From June 2021 to October 2022, 60 HM patients with COVID-19 were retrospectively analyzed. Exploratory end-points included the incidence of intubation, probability of recovery, mortality, and duration of remdesivir (RDV) administration. RESULTS: Overall, mechanical ventilation (MV) was required for five patients and crude mortality was 8.3%. HM of lymphocytic origin (p=0.035) and obesity (p=0.03) were the main determinants of the risk of intubation and among several laboratory markers, only LDH>520 IU/l was proven to be an independent MV predictor (p=0.038). The number of co-existing comorbidities (p=0.05) and disease severity on admission (p<0.001) were found to rule the probability of recovery, and dexamethasone was associated with worse prognosis, particularly in patients with mild/moderate COVID-19. RDV was administered to the entire cohort, of whom 38 were managed with an extended course. In the multivariate analysis, patients with HM of lymphocytic origin were more likely to receive RDV for more than five days (p=0.002). CONCLUSION: Our study emphasizes the frailty of HM patients, even in the era of Omicron-variant predominance, and underlines the need to optimize therapy.

In vitro study on the transmission of multidrug-resistant bacteria from textiles to pig skin.

BACKGROUND: The survival of microorganisms on textiles and specifically on healthcare professionals' (HCP) attire has been demonstrated in several studies. The ability of microorganisms to adhere and remain on textiles for up to hours or days raises questions as to their possible role in transmission from textile to skin via HCP to patients. AIM: To evaluate the presence, survival and transmission of different multidrug-resistant bacteria (MDRB) from HCP attire onto skin. METHODS: Three MDRB [methicillin-resistant Staphylococcus aureus (MRSA); vancomycin-resistant Enterococcus faecium (VRE); carbapenem-resistant Klebsiella pneumoniae, CRKP)] were inoculated on textiles from scrubs (60% cotton-40% polyester) and white coat (100% cotton) at concentrations of 108 colony-forming units (CFU), 105 CFU, and 103 CFU per mL. The inoculation of swatches was divided in time intervals of 1 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, and 6 h. At the end of each period, textiles were imprinted onto pig skins and each skin square was inverted onto three different selective chromogenic media. Growth from the pig skin squares was recorded for the 3 MDRB at the three above concentrations, for the whole length of the 6-h experiment. RESULTS: MRSA was recovered from pig skins at all concentrations for the whole duration of the 6-h study. VRE was recovered from the concentration of 108 CFU/mL for 6 h and from 105 CFU/mL for up to 3 h, while showing no growth at 103 CFU/mL. CRKP was recovered from 108 CFU/mL for 6 h, up to 30 min from 105 CFU/mL and for 1 min from the concentration of 103 CFU/mL. CONCLUSION: Evidence from the current study shows that MRSA can persist on textiles and transmit to skin for 6 h even at low concentrations. The fact that all MDRB can be sustained and transferred to skin even at lower concentrations, supports that textiles are implicated as vectors of bacterial spread.

Emerging and Re-Emerging Infectious Diseases: Humankind's Companions and Competitors.

Infectious disease outbreaks had a significant impact on shaping the societies and cultures throughout human history [...].

Transition beyond the acute phase of the COVID-19 pandemic: Need to address the long-term health impacts of COVID-19.

Despite gaps in knowledge, long-term sequelae of coronavirus disease 2019 (COVID-19) infections are globally acknowledged and thus require special attention by public health organizations and services. Therefore, it is necessary to support and promote public health initiatives that address long-term disability due to COVID-19.

Infections Caused by Moellerella wisconsensis: A Case Report and a Systematic Review of the Literature.

BACKGROUND: Moellerella wisconsensis, a member of the family of Enterobacteriaceae, although isolated widely in nature, rarely causes infections in humans. Herein, we report a case of isolation of M. wisconsensis from pigtail end culture, urine culture and blood culture in a 76-year-old patient. OBJECTIVE: To systematically address all the relevant information regarding M. wisconsensis through literature. METHODS: We searched PubMed and Scopus databases up to January 2022 and performed a qualitative synthesis of published articles reporting infection from M. wisconsensis in humans. RESULTS: We identified 25 records on PubMed and 43 additional records on Scopus. After removing duplicates, we examined in detail 15 articles. Ten studies with a total of 17 cases were included in our systematic review. Nine studies described isolated case reports, while 1 study described 8 cases. The origin of the infection was the alimentary tract in 9 cases, gallbladder in 4 cases, peritoneal cavity in 2 cases, respiratory tract in 1 case and hemodialysis catheter insertion site in 1 case. In 3 of the aforementioned cases M. wisconsensis was also isolated in blood cultures. CONCLUSION: Physicians should be aware that M. wisconsensis can be present in multiple clinical specimens and that the antibiotic resistance profile of the isolates may pose significant challenges.