Burden of primary influenza and respiratory syncytial virus pneumonia in hospitalised adults: insights from a 2-year multi-centre cohort study (2017-2018).

BACKGROUND: Viral community-acquired pneumonia (CAP) is a potentially serious illness, particularly in adult patients with underlying chronic conditions. In addition to the most recent SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) are considered the most relevant causes of viral CAP. AIMS: To describe the clinical features of hospitalised adults admitted for influenza-A/B and RSV pneumonia and analyse, according to aetiology, factors associated with non-invasive ventilation (NIV) failure and in-hospital death (IHD). METHODS: This was a retrospective and multi-centre study of all adults who were admitted for laboratory-confirmed influenza-A/B or RSV pneumonia, during two consecutive winter seasons (October-April 2017-2018 and 2018-2019) in three tertiary hospitals in Portugal, Italy and Cyprus. RESULTS: A total of 356 adults were included in the study. Influenza-A, influenza-B and RSV were deemed to cause pneumonia in 197 (55.3%), 85 (23.9%) and 74 (20.8%) patients, respectively. Patients with both obstructive sleep apnoea or obesity hypoventilation syndrome and influenza-A virus pneumonia showed a higher risk for NIV failure (odds ratio (OR) 4.66; 95% confidence interval (CI) 1.42-15.30). Patients submitted to NIV showed a higher risk for IHD, regardless of comorbidities (influenza-A OR 3.00; 95% CI 1.35-6.65, influenza-B OR 4.52; 95% CI 1.13-18.01, RSV OR 5.61; 95% CI 1.26-24.93). CONCLUSION: The increased knowledge of influenza-A/B and RSV pneumonia burden may contribute to a better management of patients with viral CAP.

Distribution of serotypes and antibiotic resistance of invasive Pseudomonas aeruginosa in a multi-country collection.

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections and is frequently associated with healthcare-associated infections. Because of its ability to rapidly acquire resistance to antibiotics, P. aeruginosa infections are difficult to treat. Alternative strategies, such as a vaccine, are needed to prevent infections. We collected a total of 413 P. aeruginosa isolates from the blood and cerebrospinal fluid of patients from 10 countries located on 4 continents during 2005-2017 and characterized these isolates to inform vaccine development efforts. We determined the diversity and distribution of O antigen and flagellin types and antibiotic susceptibility of the invasive P. aeruginosa. We used an antibody-based agglutination assay and PCR for O antigen typing and PCR for flagellin typing. We determined antibiotic susceptibility using the Kirby-Bauer disk diffusion method. RESULTS: Of the 413 isolates, 314 (95%) were typed by an antibody-based agglutination assay or PCR (n = 99). Among the 20 serotypes of P. aeruginosa, the most common serotypes were O1, O2, O3, O4, O5, O6, O8, O9, O10 and O11; a vaccine that targets these 10 serotypes would confer protection against more than 80% of invasive P. aeruginosa infections. The most common flagellin type among 386 isolates was FlaB (41%). Resistance to aztreonam (56%) was most common, followed by levofloxacin (42%). We also found that 22% of strains were non-susceptible to meropenem and piperacillin-tazobactam. Ninety-nine (27%) of our collected isolates were resistant to multiple antibiotics. Isolates with FlaA2 flagellin were more commonly multidrug resistant (p = 0.04). CONCLUSIONS: Vaccines targeting common O antigens and two flagellin antigens, FlaB and FlaA2, would offer an excellent strategy to prevent P. aeruginosa invasive infections.

Gut Microbiota Modulation and Prevention of Dysbiosis as an Alternative Approach to Antimicrobial Resistance: A Narrative Review.

Background: The importance of gut microbiota in human health is being increasingly studied. Imbalances in gut microbiota have been associated with infection, inflammation, and obesity. Antibiotic use is the most common and significant cause of major alterations in the composition and function of the gut microbiota and can result in colonization with multidrug-resistant bacteria. Methods: The purpose of this review is to present existing evidence on how microbiota modulation and prevention of gut dysbiosis can serve as tools to combat antimicrobial resistance. Results: While the spread of antibiotic-resistant pathogens requires antibiotics with novel mechanisms of action, the number of newly discovered antimicrobial classes remains very low. For this reason, the application of alternative modalities to combat antimicrobial resistance is necessary. Diet, probiotics/prebiotics, selective oropharyngeal or digestive decontamination, and especially fecal microbiota transplantation (FMT) are under investigation with FMT being the most studied. But, as prevention is better than cure, the implementation of antimicrobial stewardship programs and strict infection control measures along with newly developed chelating agents could also play a crucial role in decreasing colonization with multidrug resistant organisms. Conclusion: New alternative tools to fight antimicrobial resistance via gut microbiota modulation, seem to be effective and should remain the focus of further research and development.

Severity of RSV infection in Southern European elderly patients during two consecutive winter seasons (2017-2018).

In Europe, the respiratory syncytial virus (RSV) surveillance system is very heterogeneous and there is growing evidence of the importance of RSV infections resulting in hospitalization of elderly patients. The aim of this study was to assess the severity of RSV infection in the elderly living in the aged Southern European countries. We conducted a retrospective study of elderly patients ( ≥65-year old) admitted for laboratory-confirmed RSV infection in three tertiary hospitals in Portugal, Italy, and Cyprus over two consecutive winter seasons (2017-2018). Uni-multivariable analyses were carried out to evaluate the effect of clinical variables on radiologically confirmed pneumonia, use of noninvasive ventilation (NIV), and in-hospital death (IHD). A total of 166 elderly patients were included. Pneumonia was evident in 29.5%. NIV was implemented in 16.3%, length of stay was 11.8 ± 12.2 days, and IHD occurred in 12.1%. Multivariable analyses revealed that the risk of pneumonia was higher in patients with chronic kidney disease (CKD) (odds ratio [OR]: 2.57; 95% confidence interval [CI]: 1.12-5.91); the use of NIV was higher in patients with obstructive sleep apnea or obesity hypoventilation syndrome (OSA or OHS) (OR: 5.38; 95% CI: 1.67-17.35) and CKD (OR: 2.52; 95% CI: 1.01-6.23); the risk of IHD was higher in males (OR: 3.30; 95% CI: 1.07-10.10) and in patients with solid neoplasm (OR: 9.06; 95% CI: 2.44-33.54) and OSA or OHS (OR: 8.39; 95% CI: 2.14-32.89). Knowledge of factors associated with RSV infection severity may aid clinicians to set priorities and reduce disease burden. Development of effective antiviral treatment and vaccine against RSV is highly desirable.

Comparative virulence of seasonal viruses responsible for lower respiratory tract infections: a southern European multi-centre cohort study of hospital admissions.

OBJECTIVES: Our study aimed to compare the clinical severity of lower respiratory tract infections (LRTI's) caused by Influenza and Respiratory Syncytial Virus (RSV). METHODS: We conducted a retrospective cohort study of LRTI admissions with positive PCR results for Influenza or RSV from 2017 to 2019 in three teaching hospitals in southern Europe. Data on clinical characteristics, viral agents and disease outcome were collected. Nosocomial infection was excluded. Main outcomes were invasive mechanical ventilation and in-hospital death. RESULTS: A total of 984 patients were included. Median age was 75 years. Influenza A was the most frequently identified virus (56.5%), of which 27.1% were subtype H1N1 and 53.0% H3N2. Influenza B was isolated in 22.3% and RSV in 21.0%. There were 10.5% of patients who died during admission and 8.3% submitted to IMV. Influenza A H1N1 was associated with lower age and less co-morbidity, while the opposite was observed for RSV. Influenza A H1N1 was independently associated with both higher risk of death (adjusted odds ratio 2.0 [1.2-3.4] p = 0.008) and IMV (adjusted odds ratio 5.1 [3.0-8.5] p < 0.001). CONCLUSION: Influenza A H1N1 was an independent predictor of mortality and IMV. These findings may have implications on hospital resource planning and vaccination policies.

Effect of public health interventions during the first epidemic wave of COVID-19 in Cyprus: a modelling study.

BACKGROUND: Cyprus addressed the first wave of SARS CoV-2 (COVID-19) by implementing non-pharmaceutical interventions (NPIs). The aims of this study were: a) to estimate epidemiological parameters of this wave including infection attack ratio, infection fatality ratio, and case ascertainment ratio, b) to assess the impact of public health interventions and examine what would have happened if those interventions had not been implemented. METHODS: A dynamic, stochastic, individual-based Susceptible-Exposed-Infected-Recovered (SEIR) model was developed to simulate COVID-19 transmission and progression in the population of the Republic of Cyprus. The model was fitted to the observed trends in COVID-19 deaths and intensive care unit (ICU) bed use. RESULTS: By May 8th, 2020, the infection attack ratio was 0.31% (95% Credible Interval [CrI]: 0.15, 0.54%), the infection fatality ratio was 0.71% (95% CrI: 0.44, 1.61%), and the case ascertainment ratio was 33.2% (95% CrI: 19.7, 68.7%). If Cyprus had not implemented any public health measure, the healthcare system would have been overwhelmed by April 14th. The interventions averted 715 (95% CrI: 339, 1235) deaths. If Cyprus had only increased ICU beds, without any social distancing measure, the healthcare system would have been overwhelmed by April 19th. CONCLUSIONS: The decision of the Cypriot authorities to launch early NPIs limited the burden of the first wave of COVID-19. The findings of these analyses could help address the next waves of COVID-19 in Cyprus and other similar settings.

Sociometric Risk Network Structure, HIV Prevalence, and Drug Injection-Related Norms among People Who Inject Drugs (PWID) in Athens, Greece.

Background: Structural properties of sociometric networks have been associated with behaviors related to HIV transmission. Very few studies, however, have explored the correlation between sociometric network factors and drug injection-related norms. Methods: This exploratory work: (i) describes basic structural qualities of a sociometric risk network of participants in the Transmission Reduction Intervention Project (TRIP) in Athens, Greece, in the context of a large HIV outbreak among people who inject drugs (PWID); (ii) measures HIV prevalence within specific structures within the sociometric risk network of PWID in TRIP; and (iii) explores the association of structural properties of the sociometric risk network in TRIP with drug injection-related norms. Results: The sociometric risk network in TRIP consisted of a large component (n = 241, 67.8%), a few small components (n = 36, 10.1%) with 2-10 individuals each, and some isolates (n = 79, 22.2%). HIV prevalence was significantly higher in the large component (55.6%), the 2-core (59.1%) and 3-core (66.3%) of the large component, and the 3-cliques of the cores. Drug injection-related norms were significantly associated with structural characteristics of the sociometric risk network. A safe behavioral pattern (use of unclean cooker/filter/rinse water was never encouraged) was significantly (p = 0.03) less normative among people who TRIP participants of the 2-core injected with (40.5%) than among network contacts of TRIP participants outside the 2-core (55.6%). On the contrary, at drug-using venues, 2-core members reported that safer behaviors were normative compared to what was reported by those without 2-core membership. Conclusions: Sociometric network data can give useful insights into HIV transmission dynamics and inform prevention strategies.Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2021.1914103 .

Antimicrobial Resistance in Bacteria: Mechanisms, Evolution, and Persistence.

In recent years, we have seen antimicrobial resistance rapidly emerge at a global scale and spread from one country to the other faster than previously thought. Superbugs and multidrug-resistant bacteria are endemic in many parts of the world. There is no question that the widespread use, overuse, and misuse of antimicrobials during the last 80 years have been associated with the explosion of antimicrobial resistance. On the other hand, the molecular pathways behind the emergence of antimicrobial resistance in bacteria were present since ancient times. Some of these mechanisms are the ancestors of current resistance determinants. Evidently, there are plenty of putative resistance genes in the environment, however, we cannot yet predict which ones would be able to be expressed as phenotypes in pathogenic bacteria and cause clinical disease. In addition, in the presence of inhibitory and sub-inhibitory concentrations of antibiotics in natural habitats, one could assume that novel resistance mechanisms will arise against antimicrobial compounds. This review presents an overview of antimicrobial resistance mechanisms, and describes how these have evolved and how they continue to emerge. As antimicrobial strategies able to bypass the development of resistance are urgently needed, a better understanding of the critical factors that contribute to the persistence and spread of antimicrobial resistance may yield innovative perspectives on the design of such new therapeutic targets.

Influenza and respiratory syncytial virus infections in the oldest-old continent.

SARS-CoV-2 dramatically revealed the sudden impact of respiratory viruses in our lives. Influenza and respiratory syncytial virus (RSV) infections are associated with high rates of morbidity, mortality, and an important burden on healthcare systems worldwide, especially in elderly patients. The aim of this study was to identify severity predictors in the oldest-old admitted with influenza and/or RSV infections. This is a multicenter, retrospective study of all oldest-old patients (≥ 85 years old) admitted for laboratory-confirmed influenza and/or RSV infection in three tertiary hospitals in Portugal, Italy, and Cyprus over two consecutive winter seasons. The outcomes included the following: pneumonia on infection presentation, use of non-invasive ventilation (NIV), and in-hospital death (IHD). The association with possible predictors, including clinical features and type of virus infection, was assessed using uni- and multivariable analyses. A total of 251 oldest-old patients were included in the study. Pneumonia was evident in 32.3% (n = 81). NIV was implemented in 8.8% (n = 22), and IHD occurred in 13.9% (n = 35). Multivariable analyses revealed that chronic obstructive pulmonary disease (COPD) or asthma was associated with pneumonia (OR 1.86; 95% CI 1.02-3.43; p = 0.045). COPD or asthma (OR 4.4; 95% CI 1.67-11.6; p = 0.003), RSV (OR 3.12; 95% CI 1.09-8.92; p = 0.023), and influenza B infections (OR 3.77; 95% CI 1.06-13.5; p = 0.041) were associated with NIV use, respectively, while chronic kidney disease was associated with IHD (OR 2.50; 95% CI 1.14-5.51; p = 0.023). Among the oldest-old, chronic organ failure, such as COPD or asthma, and CKD predicted pneumonia and IHD, respectively, beyond the importance of viral virulence itself. These findings could impact on public health policies, such as fostering influenza immunization campaigns, home-based care programs, and end-of-life care. Filling knowledge gaps is crucial to set priorities and advise on transition model of care that best fits the oldest-old.

Hair cortisol concentrations exhibit a positive association with salivary cortisol profiles and are increased in obese prepubertal girls.

Cortisol, a key mediator of the stress response, has been associated with obesity and metabolic syndrome manifestations as early as in childhood. Scalp hair cortisol has been proposed as a reliable index of long-term circulating cortisol. We aimed to investigate whether obese prepubertal girls have higher scalp hair cortisol than normal-weight controls and whether hair cortisol levels are correlated with salivary cortisol concentrations in these groups. In this cross-sectional study, 25 obese girls and 25 normal-weighted, age-matched girls were enrolled. Anthropometric evaluation, blood chemistry and salivary cortisol measurements were performed, and body mass index (BMI) and areas under the curve with respect to ground (AUCg) were calculated. Hair cortisol determination was performed with liquid chromatography-tandem mass spectrometry. Both hair cortisol concentrations and salivary cortisol AUCs were higher in the obese than the normal-weight girls (p < .001 and p = .002, respectively). A positive correlation between hair cortisol and BMI Z-score was found (rho = .327, p = .025), while hair cortisol correlated positively with salivary cortisol AUCg (rho = .3, p = .048). We conclude that obese prepubertal girls have higher hair and salivary cortisol concentrations than their age-matched lean counterparts. Hair cortisol assessment seems to be a sensitive method of evaluating systemic cortisol exposure, which is supported by our finding that hair cortisol is associated with salivary concentrations of the hormone. Lay Summary: Cortisol is the key hormone of the stress response. Childhood obesity has been associated with cortisol production dysregulation. Our findings suggest a positive association between obesity in prepubertal girls and elevated cortisol concentrations, measured in saliva and hair.

Antimicrobial Use during the SARS-CoV-2 Pandemic in a Greek Tertiary University Hospital.

In cases of SARS-CoV-2 hospitalization, despite low bacterial co-infection rates, antimicrobial use may be disproportionately high. Our aim was to quantify such usage in COVID-19 patients and identify factors linked to increased antibiotic use. We retrospectively studied patients with SARS-CoV-2 infection who were hospitalized at our institution during the pandemic. In the initial two waves of the pandemic, antimicrobial use was notably high (89% in the first wave and 92% in the second), but it decreased in subsequent waves. Elevated procalcitonin (>0.5 µg/mL) and C-reactive protein (>100 mg/L) levels were linked to antibiotic usage, while prior vaccination reduced antibiotic incidence. Antimicrobial use decreased in the pandemic, suggesting enhanced comprehension of SARS-CoV-2's natural course. Additionally, it was correlated with heightened SARS-CoV-2 severity, elevated procalcitonin, and C-reactive protein levels.

Enterobacterales carrying chromosomal AmpC ß-lactamases in Europe (EuESCPM): Epidemiology and antimicrobial resistance burden from a cohort of 27 hospitals, 2020-2022.

INTRODUCTION: The ESCPM group (Enterobacter species including Klebsiella aerogenes - formerly Enterobacter aerogenes, Serratia species, Citrobacter freundii complex, Providencia species and Morganella morganii) has not yet been incorporated into systematic surveillance programs. METHODS: We conducted a multicentre retrospective observational study analysing all ESCPM strains isolated from blood cultures in 27 European hospitals over a 3-year period (2020-2022). Diagnostic approach, epidemiology, and antimicrobial susceptibility were investigated. RESULTS: Our study comprised 6,774 ESCPM isolates. MALDI-TOF coupled to mass spectrometry was the predominant technique for bacterial identification. Susceptibility to new ß-lactam/ß-lactamase inhibitor combinations and confirmation of AmpC overproduction were routinely tested in 33.3% and 29.6% of the centres, respectively. The most prevalent species were E. cloacae complex (44.8%) and S. marcescens (22.7%). Overall, third-generation cephalosporins (3GC), combined third- and fourth-generation cephalosporins (3GC + 4GC) and carbapenems resistance phenotypes were observed in 15.7%, 4.6%, and 9.5% of the isolates, respectively. AmpC overproduction was the most prevalent resistance mechanism detected (15.8%). Among carbapenemase-producers, carbapenemase type was provided in 44.4% of the isolates, VIM- (22.9%) and OXA-48-enzyme (16%) being the most frequently detected. E. cloacae complex, K. aerogenes and Providencia species exhibited the most notable cumulative antimicrobial resistance profiles, with the former displaying 3GC, combined 3GC + 4GC and carbapenems resistance phenotypes in 15.2%, 7.4%, and 12.8% of the isolates, respectively. K. aerogenes showed the highest rate of both 3GC resistant phenotype (29.8%) and AmpC overproduction (32.1%), while Providencia species those of both carbapenems resistance phenotype (42.7%) and carbapenemase production (29.4%). ESCPM isolates exhibiting both 3GC and combined 3GC + 4GC resistance phenotypes displayed high susceptibility to ceftazidime/avibactam (98.2% and 95.7%, respectively) and colistin (90.3% and 90.7%, respectively). Colistin emerged as the most active drug against ESCPM species (except those intrinsically resistant) displaying both carbapenems resistance phenotype (85.8%) and carbapenemase production (97.8%). CONCLUSIONS: This study presented a current analysis of ESCPM species epidemiology in Europe, providing insights to inform current antibiotic treatments and guide strategies for antimicrobial stewardship and diagnostics.

Recurrent Scedosporium apiospermum Cutaneous Infection in a Patient with Rheumatoid Arthritis: The Potent Role of IL-6 Signaling Pathway Blockade: A Case-Based Review.

Rheumatoid arthritis (RA) patients deal with a higher risk of bacterial and fungal infections compared to the general population because of their dysregulated immune system as well as the immunosuppressive therapy they usually receive. Scedosporium spp. is a fungal pathogen responsible for cutaneous, lung, central nervous system, and eye infections, mostly in immunocompromised patients, leading to death in disseminated cases. We report the case of an 81-year-old woman with rheumatoid arthritis treated with steroids and an IL-6 inhibitor who was diagnosed with scedosporiosis of the upper limb. She was treated with voriconazole for one month, which was discontinued due to adverse events, and when scedosporiosis relapsed, she switched to itraconazole. We also reviewed the current literature on RA patients presenting with Scedosporium infections. Early and accurate diagnosis of scedosporiosis has therapeutic and prognostic implications, as traditionally this fungus is resistant to commonly used antifungals. Clinical alertness regarding uncommon infections, including fungal, in patients with autoimmune diseases on immunomodulatory agents is essential for effective treatment.

The Role of Probiotics in Inflammation Associated with Major Surgery: A Narrative Review.

BACKGROUND: Gut microbiota is well-known for its ability to maintain intestinal homeostasis. However, the disruption of this homeostasis, known as dysbiosis, leads to multiple consequences, including local and systemic inflammation. Surgery-induced inflammation is a major concern for patients, as it leads to many infectious and non-infectious complications. OBJECTIVE: The purpose of this review was to explore the role of probiotics and symbiotics in surgery-induced inflammation and to determine if their use is effective in combatting inflammation and its complications Methods and Materials: A literature search was conducted, and articles published only in English, until December 2022 were included. The results are reported in the form of a narrative review. RESULTS: The perioperative use of probiotics and/or symbiotics results in lower risk of infectious complications, including reduced rates of surgical site infections, respiratory and urinary tract infections, shorter hospital stays, and fewer days of antibiotic administration. It also contributes to reducing non-infectious complications, as it mitigates systemic and local inflammation via maintenance of the intestinal barrier, improves intestinal mobility, and is associated with lower rates of postoperative pain and anastomotic leak. CONCLUSIONS: Restoring gut microbiota after disruptions caused by surgery may accelerate local healing processes, attenuate systemic inflammation, and may thus prove beneficial to certain populations.

Mycobacterium marinum: A Case-Based Narrative Review of Diagnosis and Management.

Skin and soft tissue infections caused by non-tuberculous mycobacteria are occurring more frequently in recent years. However, chronic skin and soft tissue lesions present a challenge for clinicians, as the diagnostic work-up and definitive diagnosis require knowledge and available laboratory resources. We present here the case of a 66-year-old male patient who presented with painful abscess-like nodules on his right hand and forearm, which worsened after treatment with an anti-TNF-a agent. The fluid specimen taken from the lesion was positive for mycobacteria according to the acid-fast stain. Mycobacterium marinum was identified, first by next-generation sequencing and finally grown on culture, after eight weeks. Acknowledging the complexity of diagnosing and managing infections by non-tuberculous mycobacteria, and especially Mycobacterium marinum, we provide a review of the current epidemiology, clinical characteristics, diagnosis and management of Mycobacterium marinum infection.

Factors Associated with Extended-Spectrum ß-Lactamases and Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections: A Five-Year Retrospective Study.

Klebsiella pneumoniae is one of the leading causes of nosocomial infections. It has been estimated that nosocomial infection by Klebsiella pneumoniae comprises 3-8% of all nosocomial infections. Klebsiella pneumoniae bloodstream infections (BSIs) occur worldwide with varying mortality. Resistant strains, like those producing extended-spectrum beta-lactamases (ESBL) and carbapenemases, are becoming increasingly common, especially in hospital settings, posing therapeutic challenges. In this article, we aimed to study the epidemiology and risk factors of BSIs due to resistant Klebsiella pneumoniae strains in the period 1 January 2014-31 December 2018 at the Nicosia General Hospital, the largest tertiary hospital in Cyprus. Data on demographics, co-morbidities, prior hospitalization, prior intensive care unit (ICU) admission, previous antimicrobial use, nosocomial acquisition of the infection, the presence of a prosthetic device or surgery, and the primary site of infection were retrospectively recorded. Associations between the detection of ESBL Klebsiella pneumoniae BSIs and factors/covariates were examined using logistic regression. This study involved 175 patients with BSI caused by Klebsiella pneumoniae. Of these, 61 BSIs were caused by ESBL strains, 101 by non-ESBL, and 13 by carbapenem-resistant (CR) strains. In univariable analyses, age, sex, heart disease, antimicrobial use during current admission, previous hospitalization (ward or ICU), and primary BSI were associated with the presence of an ESBL strain. Antibiotic use during current admission and heart disease remained statistically significantly associated with ESBL Klebsiella pneumoniae BSI in multivariable models. Antibiotic use during current admission, respiratory infection, and a recent history of surgery were more prevalent among CR Klebsiella pneumoniae BSI patients than among non-CR Klebsiella pneumoniae BSI patients. Our study showed that recent antimicrobial use and heart disease were associated with BSI due to ESBL-producing Klebsiella pneumoniae. This finding could inform clinical practice in hospital settings.

Glycemic Dysregulation, Inflammation and Disease Outcomes in Patients Hospitalized with COVID-19: Beyond Diabetes and Obesity.

INTRODUCTION: During the COVID-19 pandemic, diabetes mellitus (DM) and obesity were associated with high rates of morbidity and mortality. The aim of this study was to investigate the relationship between markers of inflammation, disease severity, insulin resistance, hyperglycemia, and outcomes in COVID-19 patients with and without diabetes and obesity. MATERIALS AND METHODS: Epidemiological, clinical, and laboratory data were collected from the University Hospital of Ioannina COVID-19 Registry and included hospitalized patients from March 2020 to December 2022. The study cohort was divided into three subgroups based on the presence of DM, obesity, or the absence of both. RESULTS: In diabetic patients, elevated CRP, IL-6, TRG/HDL-C ratio, and TyG index, severe pneumonia, and hyperglycemia were associated with extended hospitalization. Increased IL-6, NLR, and decreased PFR were associated with a higher risk of death. In the obese subgroup, lower levels of PFR were associated with longer hospitalization and a higher risk of death, while severe lung disease and hyperglycemia were associated with extended hospitalization. In patients without DM or obesity severe pneumonia, NLR, CRP, IL-6, insulin resistance indices, and hyperglycemia during hospitalization were associated with longer hospitalization. CONCLUSION: Inflammatory markers and disease severity indices were strongly associated with disease outcomes and hyperglycemia across all subgroups.

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.