Current management of SARS-CoV-2 infection in solid organ transplant recipients: Experience derived from an ESGICH-ESOT survey.

OBJECTIVE: Solid organ transplant (SOT) recipients have a poorer SARS-CoV-2 vaccine response and higher risk for COVID-19-associated complications. However, there is no consensus on the current management of COVID-19 and data on persistent COVID-19 rates in SOT recipients are lacking. METHODS: An electronic survey concerning the management of COVID-19 in SOT recipients was distributed among all members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) and of the European Society for Organ Transplantation (ESOT). Four major sections were covered: prevention, early COVID-19, late COVID-19, and persistent COVID-19. We developed a structured questionnaire including eight multiple-choice questions with branching logic in case of positive answers and three open-ended questions related to clinical practice. Questions were asked separately for lung and non-lung transplantation. RESULTS: Thirty-two physicians from 24 different centers participated. Most answers (n = 30) were provided by European physicians. Thirty of 32 (93.75%) physicians managed non-lung transplant recipients and 12 of 32 (33.3%) lung transplant recipients. There was a huge variability in practice regarding the treatment of COVID-19, and particularly noticeable when considering lung and non-lung transplant recipients. Main discordances included the use of nirmatrelvir alone or in combination therapy for early COVID-19, the use of immunomodulatory drugs other than steroids for late COVID-19, and the need for treating asymptomatic viral shedding in persistent COVID-19. There was more similarity in terms of prophylaxis recommendations. CONCLUSION: Despite a low number of respondents, this survey shows that there are many differences on how experts manage SARS-CoV-2 infections in SOT recipients.

Mycoplasma genitalium antibiotic resistance-associated mutations in genital and extragenital samples from men-who-have-sex-with-men attending a STI clinic in Verona, Italy.

Background: Mycoplasma genitalium (MG) is one of the most warning emerging sexually transmitted pathogens also due to its ability in developing resistance to antibiotics. MG causes different conditions ranging from asymptomatic infections to acute mucous inflammation. Resistance-guided therapy has demonstrated the best cure rates and macrolide resistance testing is recommended in many international guidelines. However, diagnostic and resistance testing can only be based on molecular methods, and the gap between genotypic resistance and microbiological clearance has not been fully evaluated yet. This study aims at finding mutations associated with MG antibiotic resistance and investigating the relationship with microbiological clearance amongst MSM. Methods: From 2017 to 2021, genital (urine) and extragenital (pharyngeal and anorectal swabs) biological specimens were provided by men-who-have-sex-with-men (MSM) attending the STI clinic of the Infectious Disease Unit at the Verona University Hospital, Verona, Italy. A total of 1040 MSM were evaluated and 107 samples from 96 subjects resulted positive for MG. Among the MG-positive samples, all those available for further analysis (n=47) were considered for detection of mutations known to be associated with macrolide and quinolone resistance. 23S rRNA, gyrA and parC genes were analyzed by Sanger sequencing and Allplex™ MG and AziR Assay (Seegene). Results: A total of 96/1040 (9.2%) subjects tested positive for MG in at least one anatomical site. MG was detected in 107 specimens: 33 urine samples, 72 rectal swabs and 2 pharyngeal swabs. Among them, 47 samples from 42 MSM were available for investigating the presence of mutations associated with macrolide and quinolone resistance: 30/47 (63.8%) showed mutations in 23S rRNA while 10/47 (21.3%) in parC or gyrA genes. All patients with positive Test of Cure (ToC) after first-line treatment with azithromycin (n=15) were infected with 23S rRNA-mutated MG strains. All patients undergoing second-line moxifloxacin treatment (n=13) resulted negative at ToC, even those carrying MG strains with mutations in parC gene (n=6). Conclusion: Our observations confirm that mutations in 23S rRNA gene are associated with azithromycin treatment failure and that mutations in parC gene alone are not always associated with phenotypic resistance to moxifloxacin. This reinforces the importance of macrolide resistance testing to guide the treatment and reduce antibiotic pressure on MG strains.

Colonisation with Extended-Spectrum Cephalosporin-Resistant Enterobacterales and Infection Risk in Surgical Patients: A Systematic Review and Meta-analysis.

INTRODUCTION: Limited evidence has been reported for surgical site infections (SSIs) in patients undergoing surgery who are carriers of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E). A systematic review and meta-analysis were conducted to evaluate the risk of postoperative infections in adult inpatients colonised with ESCR-E before surgery. METHODS: The Medline, Embase and Cochrane databases were searched between January 2011 and April 2022, following PRISMA indications. Random effects meta-analysis was used to quantify the association between ESCR-E colonisation and infection. RESULTS: Among the 467 articles reviewed, 9 observational studies encompassing 7219 adult patients undergoing surgery were included. The ESCR-E colonisation rate was 13.7% (95% CI 7.7-19.7). The most commonly reported surgeries included abdominal surgery (44%) and liver transplantation (LT; 33%). The SSI rate was 23.2% (95% CI 13.2-33.1). Pooled incidence risk was 0.36 (95% CI 0.22-0.50) vs 0.13 (95% CI 0.02-0.24) for any postoperative infection and 0.28 (95% CI 0.18-0.38) vs 0.17 (95% CI 0.07-0.26) for SSIs in ESCR-E carriers vs noncarriers, respectively. In ESCR-E carriers, the ESCR-E infection ratio was 7 times higher than noncarriers. Postoperative infection risk was higher in carriers versus noncarriers following LT. Sources of detected heterogeneity between studies included ESCR-E colonisation and the geographic region of origin. CONCLUSIONS: Patients colonised with ESCR-E before surgery had increased incidence rates of post-surgical infections and SSIs compared to noncarriers. Our results suggest considering the implementation of pre-surgical screening for detecting ESCR-E colonisation status according to the type of surgery and the local epidemiology.

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.

Dalbavancin in the treatment of acute bacterial skin and skin structure and other infections: a safety evaluation.

INTRODUCTION: Dalbavancin is a second-generation lipoglycopeptide approved since 2014 to treat acute bacterial skin and skin-structure infections (ABSSSI). Dalbavancin is characterized by Gram-positive activity and novel pharmacokinetic properties allowing prolonged terminal half-life andonce weekly dosing . A good safety profile was reported in clinical trials . AREAS COVERED: Dalbavancin safety and tolerability from trials and post-marketing studies were reviewed. While most reports included predominantly ABSSSI, two clinical trials and recent observational studies have explored the use of dalbavancin for off-label indications, mainly including bloodstream and osteoarticular infections. EXPERT OPINION: The occurrence of drug-related adverse effects (AE) was similar between dalbavancin and comparators in clinical trials enrolling patients with ABSSSI. Most common AE included gastrointestinal symptoms, infusion reaction, and hypersensitivity. Low rates of drug discontinuation and serious AE were reported across studies. In the past 5 years, several observational studies have reported safety data on the use of dalbavancin, confirming its favorable safety profile. Nevertheless, data from dalbavancin off-label use, often derived from prolonged (>2 weeks) treatments with variable dosing regimens, were mainly retrospective and lacked comparators. Further research is required to allow a reliable analysis of short- and long-term dalbavancin-related AE in non-ABSSSI.

Determinants of persistence of symptoms and impact on physical and mental wellbeing in Long COVID: A prospective cohort study.

BACKGROUND: Residual symptoms can be detected for several months after COVID-19. To better understand the predictors and impact of symptom persistence we analyzed a prospective cohort of COVID-19 patients. METHODS: Patients were followed for 9 months after COVID-19 onset. Duration and predictors of persistence of symptoms, physical health and psychological distress were assessed. RESULTS: 465 patients (54% males, 51% hospitalized) were included; 37% presented with at least 4 symptoms and 42% complained of symptom lasting more than 28 days. At month 9, 20% of patients were still symptomatic, showing mainly fatigue (11%) and breathlessness (8%). Hospitalization and ICU stay vs. non-hospitalized status increased the median duration of fatigue of 8 weeks. Age > 50 years (OR 2.50), ICU stay (OR 2.35), and presentation with 4 or more symptoms (OR 2.04) were independent predictors of persistence of symptoms at month 9. A total of 18% of patients did not return to optimal pre-COVID physical health, while 19% showed psychological distress at month 9. Hospital admission (OR 2.28) and persistence of symptoms at day 28 (OR 2.21) and month 9 (OR 5.16) were independent predictors of suboptimal physical health, while female gender (OR 5.27) and persistence of symptoms at day 28 (OR 2.42) and month 9 (OR 2.48) were risk factors for psychological distress. CONCLUSIONS: Patients with advanced age, ICU stay and multiple symptoms at onset were more likely to suffer from long-term symptoms, which had a negative impact on both physical and mental wellbeing. This study contributes to identify the target populations and Long COVID consequences for planning long-term recovery interventions.

Assessment of COVID-19 progression on day 5 from symptoms onset.

BACKGROUND: A major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19. METHODS: Prospective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or transfer to ICU and/or respiratory failure (PaO2/FiO2 ratio < 200) within day-11 of symptoms onset. Multivariate regression was performed to identify predictors of COVID-19 progression. A model assessed at day-5 of symptoms onset including male sex, age > 65 years, dyspnoea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) was proposed. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values. RESULTS: A total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. The proposed model showed an AUC of 0.73 (95% CI 0.66-0.81) for predicting disease progression by day-11. CONCLUSION: An easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate clinicians' decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients.