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Background. Screening inpatients for diabetes mellitus may be a good opportunity to detect undiagnosed cases and several studies have demonstrated the feasibility and usefulness of this practice. HbA1c has been suggested as the method of choice due to the effects of acute illness on glucose. The aim of this study was to evaluate a screening protocol based on HbA1c to identify inpatients with undiagnosed diabetes mellitus in an internal medicine department.

Introduction. Several diagnoses have been associated with leukemoid reaction (LR). In patients with LR the diagnostic and prognostic value of detailed manual blood smear counts (such as the percentage of band cells or grading of neutrophil toxic changes) has not been studied previously.

Introduction. Eosinopenia has been previously investigated as a marker to differentiate infectious from non-infectious diagnoses and as a prognostic marker. Most previous studies were conducted in intensive care unit patients. Our study focuses on the value of eosinopenia in patients admitted to the Internal Medicine department.

Background: Increasing incidence of carbapenem-resistant Gram-negative bacteraemia (CR-GNB) has triggered increased use of polymyxins, likely fuelling the emergence and spread of colistin resistance., Aim: To estimate the excess clinical burden of colistin resistance in intensive care patients with CR-GNB., Methods: A cohort was constructed of patients with CR-GNB during their stay in the intensive care unit (ICU) of a university hospital in Greece, over a 4-year period (2020-2023). Competing risks survival analysis was performed to estimate the burden associated with colistin resistance., Findings: In 177 ICU patients with CR-GNB, 134 (76%) had colistin-resistant isolates, predominantly Acinetobacter baumannii (79%), identified by broth microdilution. Patients with colistin resistant infection were similar to those with colistin susceptible with respect to age, sex, APACHE II score, Charlson comorbidity index, Pitt bacteraemia score, prior surgery and the occurrence of polymicrobial cultures. However, patients in the colistin resistant group had lower mortality risk compared to the colistin susceptible (31% vs. 44%, P = 0.004 at 14 days; 46% vs. 56% at 28 days, P = 0.173; respectively). Multivariable regression analysis confirmed that colistin resistant CR-GNB was associated with significantly lower hazard of inpatient death compared to colistin susceptible infection at 14 days (cause-specific hazard ratio [csHR], 0.53; 95% CI 0.28 - 1.01) and 28 days (csHR, 0.55; 95% CI 0.31 - 0.95) of infection onset., Conclusion: Limited impact of colistin resistance on mortality was demonstrated in a large contemporary cohort of ICU patients with CR-GNB, possibly reflecting the recent shift away from colistin-based treatment regimens., (Copyright © 2024. Published by Elsevier Ltd.)

T-cell prolymphocytic leukemia (T-PLL) presents unique treatment challenges because of its rarity and aggressiveness. Allogeneic hematopoietic stem cell transplantation offers a potentially curative option, but its safety in patients with concurrent invasive fungal infections and solid malignancies remains uncertain. We present a case of a 68-year-old male with T-PLL who developed disseminated cryptococcal disease with prostate involvement and concurrent prostate cancer (PCa). Despite the challenges, successful control of the infection and radical prostatectomy enabled the patient to proceed safely to allogeneic transplantation. The case highlights the importance of vigilance for unusual infections, such as Cryptococcus, in immunocompromised patients presenting with lower urinary tract symptoms. Clinicians should consider the possibility of PCa in this population, particularly in the context of chronic leukemia. Concurrently, the potential association between fungal prostate infections and PCa warrants further investigation., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ioannidis et al.)

Acinetobacter baumannii has emerged as a pressing challenge in clinical practice, mainly due to the development of resistance to multiple antibiotics, including colistin, one of the last-resort treatments. This review highlights all the possible mechanisms of colistin resistance and the genetic basis contributing to this resistance, such as modifications to lipopolysaccharide or lipid A structures, alterations in outer membrane permeability via porins and heteroresistance. In light of this escalating threat, the review also evaluates available treatment options. The development of new antibiotics (cefiderocol, sulbactam/durlobactam) although not available everywhere, and the use of various combinations and synergistic drug combinations (including two or more of the following: a polymyxin, ampicillin/sulbactam, carbapenems, fosfomycin, tigecycline/minocycline, a rifamycin, and aminoglycosides) are discussed in the context of overcoming colistin resistance of A. baumannii infections. Although most studied combinations are polymyxin-based combinations, non-polymyxin-based combinations have been emerging as promising options. However, clinical data remain limited and continued investigation is essential to determine optimal therapeutic strategies against colistin-resistant A. baumannii .

Background: Cefiderocol is a last resort option for carbapenem-resistant (CR) Gram-negative bacteria, especially metallo-β-lactamase-producing Pseudomonas aeruginosa and CR Acinetobacter baumannii. Monitoring global levels of cefiderocol non-susceptibility (CFDC-NS) is important., Objectives: To systematically collate and examine studies investigating in vitro CFDC-NS and estimate the global prevalence of CFDC-NS against major Gram-negative pathogens., Data Sources: PubMed and Scopus, up to May 2023., Study Eligibility Criteria: Eligible were studies reporting CFDC-NS in Enterobacterales, P. aeruginosa, A. baumannii, or Stenotrophomonas maltophilia clinical isolates., Risk-Of-Bias Assessment: Two independent reviewers extracted study data and assessed the risk of bias on the population, setting, and measurement (susceptibility testing) domains., Data Synthesis: Binomial-Normal mixed-effects models were applied to estimate CFDC-NS prevalence by species, coresistance phenotype, and breakpoint definition (EUCAST, CLSI, and FDA). Sources of heterogeneity were investigated by subgroup and meta-regression analyses., Results: In all, 78 studies reporting 82 035 clinical isolates were analysed (87% published between 2020 and 2023). CFDC-NS prevalence (EUCAST breakpoints) was low overall but varied by species (S. maltophilia 0.4% [95% CI 0.2-0.7%], Enterobacterales 3.0% [95% CI 1.5-6.0%], P. aeruginosa 1.4% [95% CI 0.5-4.0%]) and was highest for A. baumannii (8.8%, 95% CI 4.9-15.2%). CFDC-NS was much higher in CR Enterobacterales (12.4%, 95% CI 7.3-20.0%) and CR A. baumannii (13.2%, 95% CI 7.8-21.5%), but relatively low for CR P. aeruginosa (3.5%, 95% CI 1.6-7.8%). CFDC-NS was exceedingly high in New Delhi metallo-β-lactamase-producing Enterobacterales (38.8%, 95% CI 22.6-58.0%), New Delhi metallo-β-lactamase-producing A. baumannii (44.7%, 95% CI 34.5-55.4%), and ceftazidime/avibactam-resistant Enterobacterales (36.6%, 95% CI 22.7-53.1%). CFDC-NS varied considerably with breakpoint definition, predominantly among CR bacteria. Additional sources of heterogeneity were single-centre investigations and geographical regions., Conclusions: CFDC-NS prevalence is low overall, but alarmingly high for specific CR phenotypes circulating in some institutions or regions. Continuous surveillance and updating of global CFDC-NS estimates are imperative while cefiderocol is increasingly introduced into clinical practice. The need to harmonize EUCAST and CLSI breakpoints was evident., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Aim: To review preclinical and clinical data relevant to daptomycin lock therapy in catheter-related bloodstream infection (CRBSI). Methods: Systematic review in PubMed, Scopus and clinical trial registries. Results: Preclinical data demonstrate daptomycin lock solution stability and compatibility with heparin, good biofilm penetration, bactericidal activity against biofilm-embedded bacteria, and high efficacy in vitro and in animal catheter infection models. Clinical data remain limited (two case reports and five case series totaling n = 65 CRBSI episodes), albeit promising (successful catheter salvage in about 80% of cases). Conclusion: Despite theoretical advantages of daptomycin, clinical data remain scarce. Comparative studies versus alternative lock solutions are needed, as well as studies to define optimal daptomycin lock regimen (including optimal concentration, dwell time and lock duration).

Staphylococcus aureus bacteremia (SAB) is a severe infection frequently associated with significant morbidity and mortality. Recent studies have shown that SAB mortality has decreased during the last decades. However, about 25% of patients suffering from the disease will ultimately die. Hence, there is an urgent need for more timely and efficient treatment of patients with SAB. The aim of the present study was to retrospectively evaluate a cohort of SAB patients hospitalized in a tertiary hospital and to identify factors independently associated with mortality. All 256 SAB patients hospitalized from January 2005 to December 2021 in the University Hospital of Heraklion, Greece, were evaluated. Their median age was 72 years, while 101 (39.5%) were female. Most SAB patients were cared for in medical wards (80.5%). The infection was community-acquired in 49.5%. Among all strains 37.9% were methicillin-resistant S. aureus (MRSA), however, definite treatment with an antistaphylococcal penicillin was given only in 22% of patients. Only 14.4% of patients had a repeat blood culture after the initiation of antimicrobial treatment. Infective endocarditis was present in 8%. In-hospital mortality has reached 15.9%. Female gender, older age, higher McCabe score, previous antimicrobial use, presence of a central venous catheter, neutropenia, severe sepsis, septic shock, and MRSA SAB were positively associated with in-hospital mortality, while monomicrobial bacteremia was negatively associated. The multivariate logistic regression model identified only severe sepsis ( p = 0.05, odds ratio = 12.294) and septic shock ( p = 0.007, odds ratio 57.18) to be independently positively associated with in-hospital mortality. The evaluation revealed high rates of inappropriate empirical antimicrobial treatment and non-adherence to guidelines, as shown, by the lack of repeat blood cultures. These data underline the urgent need for interventions with antimicrobial stewardship, increased involvement of infectious diseases physicians, educational sessions, and creation and implementation of local guidelines for improvement of the necessary steps for timely and efficient SAB treatment. Optimization of diagnostic techniques is needed to overcome challenges such as heteroresistance that may affect treatment. Clinicians should be aware of the factors associated with mortality in patients with SAB to identify those who are at a higher risk and optimize medical management.

Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Background: In the last decades, solid organ transplantation (SOT) has emerged as an important method in the management of chronic kidney, liver, heart, and lung failure. Antimicrobial use has led to a significant reduction of morbidity and mortality due to infectious complications among patients with SOT; however, it can lead to adverse events and drive the development of antimicrobial resistance; thus, antimicrobial stewardship is of extreme importance. Even though there are ongoing efforts of transplant societies to implement principles of antimicrobial stewardship in everyday practice in SOT, there is still a lack of guidelines in this patient population., Aim: The aim of this study was to review the status of antimicrobial stewardship in patients with SOT, highlight its importance from the perspective of an ongoing vivid dialogue among ESCMID experts in the field of antimicrobial stewardship, and depict opportunities for future study in the field., Review: Antimicrobial stewardship programs are important in order to allow appropriate initiation and termination of antimicrobials in SOT recipients, and also aid in the most appropriate dosing and choosing of the route of administration of antimicrobials. Application of already known antimicrobial stewardship principles and application of currently used biomarkers and newly developed molecular rapid diagnostic testing tools can aid to the rationalization of antimicrobial prescribing and to a more targeted treatment of infections. Finally, physicians caring for SOT recipients should be actively involved in antimicrobial stewardship in order to assure optimization of antimicrobial prescribing and become familiar with the principles of antimicrobial stewardship., (© 2022 Wiley Periodicals LLC.)

Background: Both healthcare-associated infections (HAIs) and antimicrobial resistance are associated with an increased length of stay and hospital costs, while they have also been linked to high morbidity and mortality rates. In 2016 and 2017, the latest point prevalence survey (PPS) of HAIs and antimicrobial use in European acute care hospitals highlighted an HAI prevalence of 6.5%, while Greece had a higher HAI prevalence of 10%. The aim of this PPS was to record the prevalence of HAIs and antimicrobial use in all eight public acute care hospitals in Crete, Greece during the COVID-19 pandemic in order to highlight the types of infections and antimicrobial practices that need to be prioritized for infection control initiatives., Methods: The PPS was conducted between 30 March and 15 April 2022, according to the ECDC standardized relevant protocol (version 5.3). Statistics were extracted using the ECDC Helics.Win.Net application (software version 4.1.0)., Results: A total of 1188 patients were included. The overall point prevalence of patients with at least one HAI was 10.6%. The most frequent types of infections were pneumonia (34.3%), bloodstream infections (10.5%), systemic infections and urinary tract infections (10.5% and 9.1%, respectively). In 14 (12.4%) cases, the pathogen responsible for HAI was SARS-CoV-2 following onsite spread, accounting for almost 10% of all HAIs. Microorganisms were identified in 60.1% of HAIs. Antimicrobials were administered in 711 (59.8%) patients, with 1.59 antimicrobials used per patient., Conclusion: The prevalence of HAI and antimicrobial use among hospitalized patients in Crete, Greece was similar to the national HAI prevalence in 2016 despite the enormous pressure on public hospitals due to the COVID-19 pandemic. Nevertheless, both HAI prevalence and antimicrobial use remain high, underlining the need to implement adequate infection control and antimicrobial stewardship interventions.

Purpose: Pending approval of new antimicrobials, synergistic combinations are the only treatment option against pandrug-resistant A. baumannii (PDRAB). Considering the lack of a standardized methodology, the aim of this manuscript is to systematically review the methodology and discuss unique considerations for assessing antimicrobial combinations against PDRAB., Methods: Post-hoc analysis of a systematic review (conducted in PubMed and Scopus from inception to April 2021) of studies evaluating antimicrobial combination against A. baumannii, based on antimicrobials that are inactive in vitro alone., Results: Eighty-four publications were reviewed, using a variety of synergy testing methods, including; gradient-based methods (n = 11), disk-based methods (n = 6), agar dilution (n = 2), checkerboard assay (n = 44), time-kill assay (n = 50), dynamic in vitro PK/PD models (n = 6), semi-mechanistic PK/PD models (n = 5), and in vivo animal models (n = 11). Several variations in definitions of synergy and interpretation of each method were observed and are discussed. Challenges related to testing combinations of antimicrobials that are inactive alone (with regards to concentrations at which the combinations are assessed), as well as other considerations (assessment of stasis vs killing, clinical relevance of re-growth in vitro after initial killing, role of in vitro vs in vivo conditions, challenges of clinical testing of antimicrobial combinations against PDRAB infections) are discussed., Conclusion: This review demonstrates the need for consensus on a standardized methodology and clinically relevant definitions for synergy. Modifications in the methodology and definitions of synergy as well as a roadmap for further development of antimicrobial combinations against PDRAB are proposed., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Cefiderocol appears promising, as it can overcome most β-lactam resistance mechanisms (including β-lactamases, porin mutations, and efflux pumps). Resistance is uncommon according to large multinational cohorts, including against isolates resistant to carbapenems, ceftazidime/avibactam, ceftolozane/tazobactam, and colistin. However, alarming proportions of resistance have been reported in some recent cohorts (up to 50%). A systematic review was conducted in PubMed and Scopus from inception to May 2022 to review mechanisms of resistance, prevalence of heteroresistance, and in vivo emergence of resistance to cefiderocol during treatment. A variety of mechanisms, typically acting in concert, have been reported to confer resistance to cefiderocol: β-lactamases (especially NDM, KPC and AmpC variants conferring resistance to ceftazidime/avibactam, OXA-427, and PER- and SHV-type ESBLs), porin mutations, and mutations affecting siderophore receptors, efflux pumps, and target (PBP-3) modifications. Coexpression of multiple β-lactamases, often in combination with permeability defects, appears to be the main mechanism of resistance. Heteroresistance is highly prevalent (especially in A. baumannii ), but its clinical impact is unclear, considering that in vivo emergence of resistance appears to be low in clinical studies. Nevertheless, cases of in vivo emerging cefiderocol resistance are increasingly being reported. Continued surveillance of cefiderocol's activity is important as this agent is introduced in clinical practice.

Background. Acinetobacter baumannii complex (ABC) infections are commonly polymicrobial. Examining which pathogens are most commonly co-isolated with ABC is an important first step for assessing disease potential due to pathogen-pathogen interactions. Methods. Based on a systematic search of PubMed, Scopus and CENTRAL, we estimated percent proportions of co-isolates in polymicrobial pulmonary and bloodstream ABC infections using random-effects meta-analysis., Results: Twenty-eight eligible studies were analysed reporting 575 polymicrobial bloodstream and 290 polymicrobial pulmonary infections. Common co-isolates in pulmonary infections were P. aeruginosa (36%, 95% CI 24-49%, I 2 71%), S. aureus (28%, 95% CI 19-38%, I 2 44%) and Klebsiella spp. (11%, 95% CI 6-20 %, I 2 56%), while the prevalence of other co-pathogens did not exceed 5%. Most common co-isolates in bloodstream infections were coagulase-negative Staphylococci (21%, 95% CI 12-34 %, I 2 84%), Enterococci (15%, 95% CI 9-26%, I 2 73%), P. aeruginosa (12%, 95% CI 6-22%, I 2 74%), Klebsiella spp. (10%, 95% CI 6-16%, I 2 42%), Enterobacter spp. (10%, 95% CI 6-16 %, I 2 38%) and S. aureus (8%, 95% CI 4-15%, I 2 58%)., Conclusion: The common co-isolation of certain pathogens (especially P. aeruginosa ) with ABC suggests potential beneficial between-pathogen interactions, which may have treatment implications for polymicrobial infections and requires further study., Competing Interests: The authors declare that there are no conflicts of interest., (© 2022 The Authors.)

Background: Most of the antimicrobial stewardship (AMS) literature has focused on antimicrobial consumption for the treatment of infections, for the prophylaxis of surgical site infection and for the prevention of endocarditis. The role of AMS for medical antibiotic prophylaxis (AP) has not been adequately addressed., Aims: To identify targets for AMS interventions for medical AP in adult patients., Sources: Targeted searches were conducted in PubMed., Content: The various indications for medical AP and relevant evidence from practice guidelines are outlined. The following were identified as potential targets for AMS interventions: (a) addressing under-utilization of antibiotic-sparing strategies (e.g. for recurrent urinary tract infections, recurrent soft-tissue infections, recurrent exacerbations associated with bronchiectasis or chronic obstructive pulmonary disease), (b) reducing unnecessary AP beyond recommended indications (e.g. for acute pancreatitis, bite wounds, or urinary catheter manipulations), (c) reducing the use of AP with a broader spectrum than necessary, (d) reducing the use of AP for longer than the recommended duration (e.g. AP for prevention of osteomyelitis in open fractures or AP in high-risk neutropenia), (e) evaluating the role of antibiotic cycling to prevent the emergence of resistance during prolonged AP (e.g. in recurrent urinary tract infections or prophylaxis for spontaneous bacterial peritonitis), and (f) addressing research gaps regarding appropriate indications or antibiotic regimens for medical prophylaxis., Implications: This review summarizes current trends in AP and proposes targets for AMS interventions., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Differentiating Acinetobacter baumannii complex (ABC) infection from colonization remains difficult and further complicated in polymicrobial infections., Purpose: To assess the frequency of polymicrobial ABC infections and associated mortality. We hypothesized a lower mortality in polymicrobial infections if ABC isolation reflects colonization in some polymicrobial infections., Methods: A systematic review was conducted in PubMed, Scopus and CENTRAL for studies reporting ABC pulmonary and bloodstream infections. The proportion of infections that were polymicrobial and the magnitude of the association between polymicrobial (vs monomicrobial) infection and mortality were estimated with meta-analyses., Results: Based on 80 studies (9759 infections) from 23 countries, the pooled proportion of polymicrobial infection was 27% (95% CI 22-31%) and was similarly high for bloodstream and pulmonary infections. Polymicrobial infection was variably and insufficiently defined in most (95%) studies. Considerable heterogeneity (I 2  = 95%) was observed that persisted in subgroup analyses and meta-regressions. Based on 17 studies (2675 infections), polymicrobial infection was associated with lower 28-day mortality (OR = 0.75, 95% CI 0.58-0.98, I 2  = 36%). However, polymicrobial infection was not associated with in-hospital mortality (OR = 0.97, 95% CI 0.69-1.35, I 2  = 0%) based on 14 studies (953 infections). The quality of evidence (GRADE) for the association of polymicrobial (vs monomicrobial) infection with mortality was low and at high risk of bias., Conclusion: Polymicrobial ABC infections are common and may be associated with lower 28-day mortality. Considering the heterogeneity of polymicrobial infections and limitations of the available literature, more research is required to clarify the clinical impact of polymicrobial (vs monomicrobial) ABC infection., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Antimicrobial combinations are at the moment the only potential treatment option for pandrug-resistant A. baumannii . A systematic review was conducted in PubMed and Scopus for studies reporting the activity of antimicrobial combinations against A. baumannii resistant to all components of the combination. The clinical relevance of synergistic combinations was assessed based on concentrations achieving synergy and PK/PD models. Eighty-four studies were retrieved including 818 eligible isolates. A variety of combinations ( n = 141 double, n = 9 triple) were tested, with a variety of methods. Polymyxin-based combinations were the most studied, either as double or triple combinations with cell-wall acting agents (including sulbactam, carbapenems, glycopeptides), rifamycins and fosfomycin. Non-polymyxin combinations were predominantly based on rifampicin, fosfomycin, sulbactam and avibactam. Several combinations were synergistic at clinically relevant concentrations, while triple combinations appeared more active than the double ones. However, no combination was consistently synergistic against all strains tested. Notably, several studies reported synergy but at concentrations unlikely to be clinically relevant, or the concentration that synergy was observed was unclear. Selecting the most appropriate combinations is likely strain-specific and should be guided by in vitro synergy evaluation. Furthermore, there is an urgent need for clinical studies on the efficacy and safety of such combinations.

Background: Vaccination against COVID-19 is among the most effective measures to stop the spread of the disease. However, acceptance of vaccination against COVID-19 among HCWs has not been universal and emergence of new variants with increased transmissibility, reduced neutralization by BNT162b2 vaccine-elicited sera and ability to cause breakthrough infections in vaccinated individuals is concerning. The aim of this study was to compare viral load, clinical presentation at diagnosis and type of exposure among vaccinated (with BNT162b2) and non-vaccinated healthcare workers (HCWs)., Methods: Prospective cohort of HWCs diagnosed with COVID-19 by nasopharyngeal PCR from 4 January to 14 April. Viral loads were expressed by the cycle threshold (Ct) in PCR., Results: During the study period 55 HCWs were found positive for SARS-CoV-2, most of whom (44/55) were identified from March 28 to April 14 during an in-hospital COVID-19 outbreak. Of the 55 HCWs, 21 were fully vaccinated and another three had received one dose. Most cases (54/55) were due to variant B.1.1.7. Vaccinated and unvaccinated HCWs did not differ significantly in regards to age, gender, site of acquisition, presence of symptoms at diagnosis and viral load., Conclusions: This study found a similar viral load in vaccinated and non-vaccinated HCWs infected by SARS-CoV-2 variant B.1.1.7, suggesting potentially reduced efficacy of BNT162b2 in preventing transmission of B.1.1.7.

Pandrug-resistant A. baumannii (PDRAB) is increasingly being reported but remains rare. Several case studies show that A. baumannii can acquire resistance to last resort antibiotics during treatment by single-step chromosomal mutations. However, re-emergence of the ancestral susceptible strain after withdrawal of antibiotics has been described, possibly due to fitness cost associated with acquired resistance. Therefore, PDRAB may be a transient phenotype. Epidemiological data to show this process in larger cohorts are currently lacking. In this study of 91 hospitalized patients with PDRAB we showed the frequent (60%) isolation of non-PDRAB, often susceptible only to colistin, aminoglycosides and/or tigecycline, preceding and/or following PDRAB isolation. However, the isolation of PDRAB in two outpatients, 25 and 36 days after their discharge from the hospital, suggests the potential of some PDRAB strains to persist even in the absence of antimicrobial pressure.

Health care workers (HCWs) face a higher risk of infection, since they work at the front line of COVID-19 patients' management. Misinterpretations of current scientific evidence among HCWs may impact the delivery of appropriate care to COVID-19 patients and increase the risk of SARS-CoV-2 transmission in the hospital setting. Moreover, knowledge may affect HCWs perceptions depending on their broad beliefs and past experiences. The aim of this study was to explore the knowledge and perceptions of HCWs regarding COVID-19 issues during the second wave of the pandemic. A cross-sectional survey, involving a printed questionnaire, was conducted from 21 October 2020 to 31 January 2021 in four tertiary care hospitals located at four distant geographical regions in Greece. In total, 294 HCWs participated in this study. The majority of HCWs provided precise responses regarding general knowledge, perceptions, and practices concerning the COVID-19 pandemic. However, responses on hand hygiene and antimicrobial use in HCWs with COVID-19 were mistaken. This study reveals a certain degree of misconceptions and knowledge gaps in HCWs everyday practice, especially regarding hand hygiene and antimicrobial use in COVID-19 patients.

The potential of A. baumannii for acquired resistance to last resort antibiotics (colistin and tigecycline) during treatment has important clinical implications, especially when dealing with patients failing to improve despite treatment with an active antimicrobial. However, the relevant literature remains scattered. Therefore, a systematic search was conducted in PubMed and Scopus. Several studies reported emergence of resistance to colistin or tigecycline during treatment, in most cases (86%) resulting in persistent or recurrent infections, especially in cases of emergent resistance without fitness cost. Lipopolysaccharide modification in the case of colistin and overexpression of efflux pumps in the case of tigecycline were the main mechanisms of resistance. Emergent colistin resistance is often associated with fitness cost which may result in re-emergence of the fitter and more virulent colistin susceptible strain after cessation of antibiotic pressure. Prospective studies are needed to determine the frequency of emergent resistance during treatment and its impact on patient outcomes.

The management of carbapenem-resistant infections is often based on polymyxins, tigecycline, aminoglycosides and their combinations. However, in a recent systematic review, we found that Gram-negative bacteria (GNB) co-resistant to carbapanems, aminoglycosides, polymyxins and tigecycline (CAPT-resistant) are increasingly being reported worldwide. Clinical data to guide the treatment of CAPT-resistant GNB are scarce and based exclusively on few case reports and small case series, but seem to indicate that appropriate (in vitro active) antimicrobial regimens, including newer antibiotics and synergistic combinations, may be associated with lower mortality. In this review, we consolidate the available literature to inform clinicians dealing with CAPT-resistant GNB about treatment options by considering the mechanisms of resistance to carbapenems. In combination with rapid diagnostic methods that allow fast detection of carbapenemase production, the approach proposed in this review may guide a timely and targeted treatment of patients with infections by CAPT-resistant GNB. Specifically, we focus on the three most problematic species, namely Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Several treatment options are currently available for CAPT-resistant K. pneumonia. Newer β-lactam-β-lactamase combinations, including the combination of ceftazidime/avibactam with aztreonam against metallo-β-lactamase-producing isolates, appear to be more effective compared to combinations of older agents. Options for P. aeruginosa (especially metallo-β-lactamase-producing strains) and A. baumannii remain limited. Synergistic combination of older agents (e.g., polymyxin- or fosfomycin-based synergistic combinations) may represent a last resort option, but their use against CAPT-resistant GNB requires further study.

Background: Colistin is one of the few remaining options for carbapenem-resistant Acinetobacter baumannii (A. baumannii); however, emergence of resistance from heteroresistant populations is possible. This review aimed to systematically search and consolidate the literature on the prevalence, mechanisms and therapeutic implications of colistin heteroresistance in Acinetobacter spp., Methods: A systematic search was conducted in PubMed and Scopus. The pooled prevalence of colistin heteroresistance was calculated using meta-analysis of proportions with the Freeman-Tukey transformation and the random-effects (DerSimonian and Laird) method., Results: Based on 15 studies the prevalence of colistin heteroresistance was 33% (95% CI 16-53%) but considerable heterogeneity was observed (I 2  = 96%, P < 0.001). Prior exposure to colistin was associated with a higher proportion of resistant subpopulations. Colistin heteroresistance may result from chromosomal mutations in resistant subpopulations (predominantly in PmrAB and lpx genes) resulting in lipopolysaccharide modification or loss, or overexpression of efflux pumps. No dosage scheme of colistin monotherapy can prevent the emergence of resistant subpopulations in vitro, but few studies have reported in vivo emergence of resistance from heteroresistant A. baumannii during treatment, and studies examining the correlation between heteroresistance and clinical/microbiological outcomes are lacking. Several colistin-based combinations have been shown in vitro to prevent the emergence of the resistant subpopulations but none have been translated so far into clinical benefit. Reasons for this discrepancy are discussed., Conclusions: Colistin heteroresistance was common but highly variable between studies. The impact of colistin heteroresistance (frequency of emergent resistance during treatment and correlation with treatment outcomes) requires further study., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Wernicke encephalopathy (WE) predominantly occurs in alcoholic patients. Few case reports have described this diagnosis as a result of dieting. The diagnosis is often missed or delayed resulting in permanent and severe neurologic sequelae and even death. The typical neurological signs may be absent or missed during the early stages of thiamine deficiency., Case Report: A 23-year-old female presented to the hospital with confusion, bilateral lateral rectus palsy, and ataxia. Based on the typical neurological triad, WE was suspected. The brain MRI was also typical for WE. Prompt clinical improvement was seen within days after intravenous thiamine supplementation. A detailed medical history revealed that during the past 3 months she had been following a liquid-only diet and had lost about 30 kg. During that time, she had visited the emergency department on multiple occasions due to fatigue, nausea, and vomiting., Conclusion: A high level of suspicion is required by physicians to recognize that fatigue, nausea, and vomiting may represent early signs of thiamine deficiency in patients at risk for nutritional deficiencies. Empirical thiamine supplementation may be reasonable in such cases.

Background: Empirical treatment of patients with cellulitis/erysipelas usually targets both streptococci and methicillin-sensitive S. aureus (MSSA). However, the recommendation to empirically cover MSSA is weak and based on low-quality evidence., Methods and Objective: A systematic review was conducted in PubMed and clinical trial registries to assess the role of S. aureus in cellulitis/erysipelas and the need for empirical MSSA coverage., Results: Combined microbiological and serological data, and response to penicillin monotherapy suggest that streptococci are responsible for the vast majority of cases of cellulitis/erysipelas. However, most cases are non-culturable and the specificity of microbiological and serological studies is questionable based on recent studies using molecular techniques. According to epidemiological data and three randomized controlled trials, empirical coverage of methicillin-resistant S. aureus (MRSA) is not recommended for most patients, despite the high prevalence of MRSA in many areas. If MRSA is indeed not an important cause of uncomplicated cellulitis/erysipelas, then the same may apply to MSSA. Based on indirect comparison of data from clinical studies, cure rates with penicillin monotherapy (to which most MSSA are resistant) are comparable to the cure rates reported in many studies using wider-spectrum antibiotics., Conclusion: Considering the limitations of microbiological studies in identifying the pathogens responsible for cellulitis/erysipelas, treatment needs to be guided by clinical trials. Trials comparing penicillin or amoxicillin monotherapy to MSSA-covering regimens are needed to definitively answer whether empirical coverage of MSSA is needed and to identify the subset of patients that can be safely treated with penicillin or amoxicillin monotherapy.

Background: The literature on the epidemiology, mortality and treatment of pandrug-resistant (PDR) Gram-negative bacteria (GNB) is scarce, scattered and controversial., Objectives: To consolidate the relevant literature and identify treatment options for PDR GNB infections., Methods: A systematic search in MEDLINE, Scopus and clinical trial registries was conducted. Studies reporting PDR clinical isolates were eligible for review if susceptibility testing for all major antimicrobials had been performed. Characteristics and findings of retrieved studies were qualitatively synthesized., Results: Of 81 studies reviewed, 47 (58%) were published in the last 5 years. The reports reflected a worldwide dissemination of PDR GNB in 25 countries in 5 continents. Of 526 PDR isolates reported, Pseudomonas aeruginosa (n=175), Acinetobacter baumannii (n=172) and Klebsiella pneumoniae (n=125) were most common. PDR GNB were typically isolated in ICUs, but several studies demonstrated wider outbreak potential, including dissemination to long-term care facilities and international spread. All-cause mortality was high (range 20%-71%), but appeared to be substantially reduced in studies reporting treatment regimens active in vitro. No controlled trial has been performed to date, but several case reports and series noted successful use of various regimens, predominantly synergistic combinations, and in selected patients increased exposure regimens and newer antibiotics., Conclusions: PDR GNB are increasingly being reported worldwide and are associated with high mortality. Several treatment regimens have been successfully used, of which synergistic combinations appear to be most promising and often the only available option. More pharmacokinetic/pharmacodynamic and outcome studies are needed to guide the use of synergistic combinations., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Both antimicrobial consumption and antimicrobial resistance are very high in Greece, ranking among the highest of Europe. The link between antimicrobial consumption and resistance is well-known. Here, we discuss the reasons of antimicrobial overuse in Greece in the community (such as self-medication, dispersion of antibiotics by pharmacies without prescription, over-prescription by physicians, patient expectations and liability pressure) and we explore the misuse of antibiotics for common community infections. Furthermore, we discuss how such overuse/misuse can drive antimicrobial resistance, using methicillin-resistance in Staphylococcus aureus as an example. S. aureus is one of the pathogens with high rates of resistance in Greece. Comparing the rate of antimicrobial susceptibility to non-beta lactams between methicillin-resistant and methicillin-sensitive S. aureus we highlight the antibiotics that have the potential to drive methicillin-resistance through co-selection. Based on the above we identify targets for intervention in order to reduce antimicrobial overuse/misuse in the community in Greece., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Prior studies have shown that young people "not in education, employment or training" ("NEET") are at higher risk for psychopathology and substance abuse. Similar studies are lacking in Southern European populations. We aimed to examine the associations of anxiety and depressive symptoms, and substance use with NEET status in a large, randomized population-based sample in Greece., Methods: A telephone structured questionnaire was conducted in a representative sample of 2771 young Greeks aged 15-24 years. Anxiety and depressive symptoms were assessed with GAD-7 and PHQ-9 scales, respectively. Substances use and several sociodemographic parameters were also examined., Results: In our sample 16.4% were NEETs. In multivariate analyses, NEETs compared to non-NEETs were older, with lower family income, without insurance and more likely to be married and smoke. Furthermore, NEET status was associated with a higher GAD-7 score among older NEETs and long-term NEETs (NEETs unemployed for more than a year). Moreover, being NEET among older participants was associated with severe symptoms of anxiety and moderate/severe symptoms of depression., Limitations: This was a telephone survey and a clinical evaluation of the patients was not performed. Furthermore, the structured interview was not designed to detect the level of substance use or the reasons for being NEET., Conclusions: NEET status is frequent among young Greeks. Older, and long-term NEETs appear to be at higher risk for presenting anxiety/depression symptoms. Whether NEET status is associated with adverse outcomes later in life requires longitudinal studies., (Copyright © 2019. Published by Elsevier B.V.)