Evaluation of the HANDOC Score and the 2023 International Society of Cardiovascular Infectious Diseases and European Society of Cardiology Duke Clinical Criteria for the Diagnosis of Infective Endocarditis Among Patients With Streptococcal Bacteremia.

BACKGROUND: Streptococci are a common cause of infective endocarditis (IE). We aimed to evaluate the performance of the HANDOC score to identify patients at high risk for IE and the Duke clinical criteria of the European Society of Cardiology (ESC; 2015 and 2023 versions) and the 2023 version from the International Society of Cardiovascular Infectious Diseases (ISCVID) in diagnosing IE among patients with streptococcal bacteremia. METHODS: This retrospective study included adult patients with streptococcal bacteremia hospitalized at Lausanne University Hospital. Episodes were classified as IE by the Endocarditis Team. A HANDOC score >2 classified patients as high risk for IE. RESULTS: Among 851 episodes with streptococcal bacteremia, IE was diagnosed in 171 episodes (20%). Among 607 episodes with non-ß-hemolytic streptococci, 213 (35%) had HANDOC scores >2 points; 132 (22%) had IE. The sensitivity of the HANDOC score to identify episodes at high risk for IE was 95% (95% confidence interval [CI], 90%-98%), the specificity 82% (95% CI, 78%-85%), and the negative predictive value (NPV) 98% (95% CI, 96%-99%). 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria classified 114 (13%), 145 (17%), and 126 (15%) episodes as definite IE, respectively. Sensitivity (95% CI) for the 2015 Duke-ESC, 2023 Duke-ISCVID, and 2023 Duke-ESC clinical criteria was calculated at 65% (57%-72%), 81% (74%-86%), and 73% (65%-79%), respectively, with specificity (95% CI) at 100% (98%-100%), 99% (98%-100%), and 99% (98%-100%), respectively. CONCLUSIONS: The HANDOC score showed an excellent NPV to identify episodes at high risk for IE. Among the different versions of the Duke criteria, the 2023 Duke-ISCVID version fared better for the diagnosis of IE among streptococcal bacteremia.

Genomic evolution of ST228 SCCmec-I MRSA 10 years after a major nosocomial outbreak.

In this study, we investigated the genomic changes in a major methicillin-resistant Staphylococcus aureus (MRSA) clone following a significant outbreak at a hospital. Whole-genome sequencing of MRSA isolates was utilized to explore the genomic evolution of post-outbreak MRSA strains. The epidemicity of the clone declined over time, coinciding with the introduction of multimodal infection control measures. A genome-wide association study (GWAS) identified multiple genes significantly associated with either high or low epidemic success, indicating alterations in mobilome, virulence, and defense mechanisms. Random Forest models pinpointed a gene related to fibrinogen binding as the most influential predictor of epidemicity. The decline of the MRSA clone may be attributed to various factors, including the implementation of new infection control measures, single nucleotide polymorphisms accumulation, and the genetic drift of a given clone. This research underscores the complex dynamics of MRSA clones, emphasizing the multifactorial nature of their evolution. The decline in epidemicity seems linked to alterations in the clone's genetic profile, with a probable shift towards decreased virulence and adaptation to long-term carriage. Understanding the genomic basis for the decline of epidemic clones is crucial to develop effective strategies for their surveillance and management, as well as to gain insights into the evolutionary dynamics of pathogen genomes.

Predictors of mortality of Pseudomonas aeruginosa bacteraemia and the role of infectious diseases consultation and source control; a retrospective cohort study.

PURPOSE: To determine predictors of mortality among patients with Pseudomonas aeruginosa bacteraemia. METHODS: Retrospective study. SETTING: This study conducted at the Lausanne University Hospital, Switzerland included adult patients with P. aeruginosa bacteraemia from 2015 to 2021. RESULTS: During the study period, 278 episodes of P. aeruginosa bacteraemia were included. Twenty (7%) isolates were multidrug-resistant. The most common type of infection was low respiratory tract infection (58 episodes; 21%). Sepsis was present in the majority of episodes (152; 55%). Infectious diseases consultation within 48 h of bacteraemia onset was performed in 203 (73%) episodes. Appropriate antimicrobial treatment was administered within 48 h in 257 (92%) episodes. For most episodes (145; 52%), source control was considered necessary, with 93 (64%) of them undergoing such interventions within 48 h. The 14-day mortality was 15% (42 episodes). The Cox multivariable regression model showed that 14-day mortality was associated with sepsis (P 0.002; aHR 6.58, CI 1.95-22.16), and lower respiratory tract infection (P < 0.001; aHR 4.63, CI 1.78-12.06). Conversely, interventions performed within 48 h of bacteraemia onset, such as infectious diseases consultation (P 0.036; HR 0.51, CI 0.27-0.96), and source control (P 0.009; aHR 0.17, CI 0.47-0.64) were associated with improved outcome. CONCLUSION: Our findings underscore the pivotal role of early infectious diseases consultation in recommending source control interventions and guiding antimicrobial treatment for patients with P. aeruginosa bacteraemia.

Investigations of an increased incidence of non-Aspergillus invasive mould infections in an onco-haematology unit.

AIMS OF THE STUDY: Invasive mould infections are life-threatening complications in patients with haematologic cancer and chemotherapy-induced neutropenia. While invasive aspergillosis represents the main cause of invasive mould infections, non-Aspergillus mould infections, such as mucormycosis, are increasingly reported. Consequently, their local epidemiology should be closely monitored. The aim of this study was to investigate the causes of an increased incidence of non-Aspergillus mould infections in the onco-haematology unit of a Swiss tertiary care hospital. METHODS: All cases of proven and probable invasive mould infections were retrospectively identified via a local registry for the period 2007-2021 and their incidence was calculated per 10,000 patient-days per year. The relative proportion of invasive aspergillosis and non-Aspergillus mould infections was assessed. Factors that may affect invasive mould infections' incidence, such as antifungal drug consumption, environmental contamination and changes in diagnostic approaches, were investigated. RESULTS: A significant increase of the incidence of non-Aspergillus mould infections (mainly mucormycosis) was observed from 2017 onwards (Mann and Kendall test p = 0.0053), peaking in 2020 (8.62 episodes per 10,000 patient-days). The incidence of invasive aspergillosis remained stable across the period of observation. The proportion of non-Aspergillus mould infections increased significantly from 2017 (33% vs 16.8% for the periods 2017-2021 and 2007-2016, respectively, p = 0.02). Building projects on the hospital site were identified as possible contributors of this increase in non-Aspergillus mould infections. However, novel diagnostic procedures may have improved their detection. CONCLUSIONS: We report a significant increase in non-Aspergillus mould infections, and mainly in mucormycosis infections, since 2017. There seems to be a multifactorial origin to this increase. Epidemiological trends of invasive mould infections should be carefully monitored in onco-haematology units in order to implement potential corrective measures.

[Combating antimicrobial resistance: audits of practices to target actions]. / Lutte contre l'antibiorésistance : audits des pratiques pour cibler les actions.

Antibiotic resistance is a public health emergency requiring a concerted approach and motivating the implementation of antibiotic stewardship programmes. As part of an institutional project at the Centre hospitalier universitaire vaudois, we collected data on the appropriateness of antimicrobial prescriptions in various medical and surgical departments in order to identify areas for improvement. The results show that there is room for improvement and that there are differences between departments, particularly regarding surgical prophylaxis administered beyond the operating time, adaptation of the spectrum and duration. Prescribing appropriateness data is an essential complement to consumption data for adapting effective intervention strategies.

L'antibiorésistance constitue une urgence de santé publique justifiant une approche concertée et motivant la mise en place de programmes de gestion des antibiotiques (Antibiotic Stewardship). Dans le cadre d'un projet institutionnel conduit au Centre hospitalier universitaire vaudois, nous avons collecté dans différents services médico-chirurgicaux des données d'adéquation des prescriptions afin d'identifier les domaines d'amélioration. Les résultats obtenus montrent qu'il existe une marge d'amélioration et des différences interservices, en particulier concernant les prophylaxies chirurgicales administrées au-delà du temps opératoire, l'adaptation du spectre et la durée. Les données d'adéquation des prescriptions sont un complément essentiel aux données de consommation pour adapter des stratégies d'intervention efficaces.

Role of source control in critically ill candidemic patients: a multicenter retrospective study.

PURPOSE: Candidemia is associated with high mortality especially in critically ill patients. Our aim was to identify predictors of mortality among critically ill patients with candidemia with a focus on early interventions that can improve prognosis. METHODS: Multicenter retrospective study. SETTING: This retrospective study was conducted in Intensive Care Units from three European university hospitals from 2015 to 2021. Adult patients with at least one positive blood culture for Candida spp. were included. Patients who did not require source control were excluded. Primary outcome was 14-day mortality. RESULTS: A total of 409 episodes of candidemia were included. Most candidemias were catheter related (173; 41%), followed by unknown origin (170; 40%). Septic shock developed in 43% episodes. Overall, 14-day mortality rate was 29%. In Cox proportional hazards regression model, septic shock (P 0.001; HR 2.20, CI 1.38-3.50), SOFA score ≥ 10 points (P 0.008; HR 1.83, CI 1.18-2.86), and prior SARS-CoV-2 infection (P 0.003; HR 1.87, CI 1.23-2.85) were associated with 14-day mortality, while combined early appropriate antifungal treatment and source control (P < 0.001; HR 0.15, CI 0.08-0.28), and early source control without appropriate antifungal treatment (P < 0.001; HR 0.23, CI 0.12-0.47) were associated with better survival compared to those without neither early appropriate antifungal treatment nor source control. CONCLUSION: Early source control was associated with better outcome among candidemic critically ill patients.

Predictors of Mortality of Streptococcal Bacteremia and the Role of Infectious Diseases Consultation: A Retrospective Cohort Study.

BACKGROUND: Streptococcal bacteremia is associated with high mortality. Thia study aims to identify predictors of mortality among patients with streptococcal bacteremia. METHODS: This retrospective study was conducted at the Lausanne University Hospital, Switzerland, and included episodes of streptococcal bacteremia among adult patients from 2015 to 2023. RESULTS: During the study period, 861 episodes of streptococcal bacteremia were included. The majority of episodes were categorized in the Mitis group (348 episodes; 40%), followed by the Pyogenic group (215; 25%). Endocarditis was the most common source of bacteremia (164; 19%). The overall 14-day mortality rate was 8% (65 episodes). The results from the Cox multivariable regression model showed that a Charlson comorbidity index >4 (P .001; hazard ratio [HR], 2.87; confidence interval [CI]: 1.58-5.22), Streptococcus pyogenes (P = .011; HR, 2.54;CI: 1.24-5.21), sepsis (P < .001; HR, 7.48; CI: 3.86-14.47), lower respiratory tract infection (P = .002; HR, 2.62; CI: 1.42-4.81), and absence of source control interventions within 48 hours despite being warranted (P = .002; HR, 2.62; CI: 1.43-4.80) were associated with 14-day mortality. Conversely, interventions performed within 48 hours of bacteremia onset, such as infectious diseases consultation (P < .001; HR, 0.29; CI: .17-.48) and appropriate antimicrobial treatment (P < .001; HR, .28; CI: .14-.57), were associated with improved outcome. CONCLUSIONS: Our findings underscore the pivotal role of infectious diseases consultation in guiding antimicrobial treatment and recommending source control interventions for patients with streptococcal bacteremia.

Prevalence of Infective Endocarditis among Patients with Staphylococcus aureus Bacteraemia and Bone and Joint Infections.

We aimed to evaluate the occurrence of infective endocarditis (IE) among patients with bone and joint infections (BJIs) and Staphylococcus aureus bacteraemia. This observational study was conducted at Lausanne University Hospital, Switzerland, from 2014 to 2023, and included episodes involving BJI, S. aureus bacteraemia, and cardiac imaging studies. The endocarditis team defined IE. Among the 384 included episodes, 289 (75%) involved native BJI (NBJI; 118 septic arthritis, 105 acute vertebral or non-vertebral osteomyelitis, 101 chronic osteitis), and 112 (29%) involved orthopedic implant-associated infection (OIAI; 78 prosthetic joint infection and 35 osteosynthesis/spondylodesis infection). Fifty-one episodes involved two or more types of BJI, with 17 episodes exhibiting both NBJI and OIAI. IE was diagnosed in 102 (27%) episodes. IE prevalence was 31% among patients with NBJI and 13% among patients with OIAI (p < 0.001). The study revealed a high prevalence of IE among S. aureus bacteraemic patients with NBJI, with notably lower prevalence among those with OIAI.

Core genome multilocus sequence typing of Clostridioides difficile to investigate transmission in the hospital setting.

PURPOSE: Traditional epidemiological investigations of healthcare-associated Clostridioides difficile infection (HA-CDI) are often insufficient. This study aimed to evaluate a procedure that includes secondary isolation and genomic typing of single toxigenic colonies using core genome multilocus sequence typing (cgMLST) for the investigation of C. difficile transmission. METHODS: We analyzed retrospectively all toxigenic C. difficile-positive stool samples stored at the Lausanne University Hospital over 6 consecutive months. All isolates were initially typed and classified using a modified double-locus sequence typing (DLST) method. Genome comparison of isolates with the same DLST and clustering were subsequently performed using cgMLST. The electronic administrative records of patients with CDI were investigated for spatiotemporal epidemiological links supporting hospital transmission. A comparative descriptive analysis between genomic and epidemiological data was then performed. RESULTS: From January to June 2021, 86 C. difficile isolates were recovered from thawed samples of 71 patients. Thirteen different DLST types were shared by > 1 patient, and 13 were observed in single patients. A genomic cluster was defined as a set of isolates from different patients with ≤ 3 locus differences, determined by cgMLST. Seven genomic clusters were identified, among which plausible epidemiological links were identified in only 4/7 clusters. CONCLUSION: Among clusters determined by cgMLST analysis, roughly 40% included unexplained HA-CDI acquisitions, which may be explained by unidentified epidemiological links, asymptomatic colonization, and/or shared common community reservoirs. The use of DLST, followed by whole genome sequencing analysis, is a promising and cost-effective stepwise approach for the investigation of CDI transmission in the hospital setting.

Association of antimicrobial perioperative prophylaxis with cefuroxime plus metronidazole or amoxicillin/clavulanic acid and surgical site infections in colorectal surgery.

OBJECTIVE: To compare intravenous (IV) amoxicillin/clavulanic acid (A/CA) to IV cefuroxime plus metronidazole (C + M) for preventing surgical site infections (SSI) in colorectal surgery. BACKGROUND: Given their spectra that include most Enterobacterales and anaerobes, C + M is commonly recommended as prophylaxis of SSI in colorectal surgery. A/CA offers good coverage of Enterobacterales and anaerobes as well, but, in contrast to C + M, it also includes Enterococcus faecalis which is also isolated from patients with SSI and could trigger anastomotic leakage. METHODS: Data from a Swiss SSI surveillance program were used to compare SSI rates after class II (clean contaminated) colorectal surgery between patients who received C + M and those who received A/CA. We employed multivariable logistic regression to adjust for potential confounders, along with propensity score matching to adjust for group imbalance. RESULTS: From 2009 to 2018, 27,922 patients from 127 hospitals were included. SSI was diagnosed in 3132 (11.2%): 278/1835 (15.1%) in those who received A/CA and 2854/26,087 (10.9%) in those who received C + M (p < 0.001). The crude OR for SSI in the A/CA group as compared to C + M was 1.45 [CI 95% 1.21-1.75]. The adjusted OR was 1.49 [1.24-1.78]. This finding persisted in a 1:1 propensity score matched cohort of 1835 patients pairs with an OR of 1.60 [1.28-2.00]. Other factors independently associated with SSI were an ASA score > 2, a longer duration of operation, and a reoperation for a non-infectious complication. Protective factors were female sex, older age, antibiotic prophylaxis received 60 to 30 min before surgery, elective operation, and endoscopic approach. CONCLUSIONS: Despite its activity against enterococci, A/CA was less effective than C + M for preventing SSI, suggesting that it should not be a first choice antibiotic prophylaxis for colorectal surgery.

Clinical significance of concomitant bacteriuria in patients with Staphylococcus aureus bacteraemia.

This retrospective study, conducted at Lausanne University Hospital (2015-2021), compared Staphylococcus aureus bacteraemia (SABA) patients with or without concomitant bacteriuria (SABU). Among 448 included bacteraemic patients, 62 (13.8%) had S. aureus concurrently isolated from urine. In multivariate analysis, there was a significant difference in the odds of community-onset bacteraemia (P 0.030), malignancy (P 0.002), > 1 pair of positive blood cultures (P 0.037), and persistent bacteraemia for at least 48 h (P 0.045) in patients with concurrent SABU. No difference concerning mortality was found. On the other hand, SABU was associated with higher rates of SABA recurrence after antibiotic cessation.

Predictors of mortality of Staphylococcus aureus bacteremia among patients hospitalized in a Swiss University Hospital and the role of early source control; a retrospective cohort study.

S. aureus bacteremia is associated with high mortality. The aim was to identify predictors of mortality among patients with S. aureus bacteremia and evaluate the role of early source control. This retrospective study was conducted at the Lausanne University Hospital, Switzerland. All episodes of S. aureus bacteremia among adult patients from 2015 to 2021 were included. During the study period, 839 episodes of S. aureus bacteremia were included, of which 7.9% were due to methicillin-resistant isolates. Bacteremias were related to bone or joint infections (268; 31.9%), followed by bacteremia of unknown origin (158; 18.8%), proven endocarditis (118; 14.1%) and lower-respiratory tract infections (79; 9.4%). Overall 28-day mortality was 14.5%. Cox multivariate regression model showed that Charlson comorbidity index > 5 (P < 0.001), nosocomial bacteremia (P 0.019), time to blood culture positivity ≤ 13 h (P 0.004), persistent bacteremia for ≥ 48 h (P 0.004), sepsis (P < 0.001), bacteremia of unknown origin (P 0.036) and lower respiratory tract infection (P < 0.001) were associated with 28-day mortality, while infectious diseases consultation within 48 h from infection onset (P < 0.001) was associated with better survival. Source control was warranted in 575 episodes and performed in 345 episodes (60.0%) within 48 h from infection onset. Results from a second multivariate analysis confirmed that early source control (P < 0.001) was associated with better survival. Mortality among patients with S. aureus bacteremia was high and early source control was a key determinant of outcome. Infectious diseases consultation within 48 h played an important role in reducing mortality.

Impact of selective reporting of antibiotic susceptibility testing results on meropenem prescriptions for the treatment of Pseudomonas aeruginosa infections after 2020 EUCAST criteria update: an observational study in a university hospital.

BACKGROUND: We previously reported an increase in meropenem prescriptions for Pseudomonas aeruginosa infections in our hospital after the implementation of the 10th version of the EUCAST breakpoints table for P. aeruginosa in January 2020. As a consequence, antibiotic susceptibility testing results were adapted by masking meropenem for P. aeruginosa isolates susceptible to either ceftazidime, cefepime or piperacillin-tazobactam. We aimed to assess the changes in meropenem prescriptions after the implementation of the selective reporting. METHODS: In this retrospective single-centre observational study, we analysed antimicrobial therapies prescribed for P. aeruginosa infections after the susceptibility testing results have been made available over three periods: "before EUCAST update", "after EUCAST update without selective reporting" and "after EUCAST update with selective reporting", at Lausanne University Hospital, Switzerland. We collected epidemiological, microbiological and clinical data. The primary outcome was the prescription of meropenem to treat P. aeruginosa infections after the release of susceptibility testing results. Secondary outcomes were the use of increased dosage of non-meropenem anti-pseudomonal drugs, and IDs' consultations rates after the release of susceptibility testing results. RESULTS: Among the 457 patients included, 65 (14.2%) received meropenem: 5/148 (3.4%) before EUCAST update, 51/202 (25.3%) after EUCAST update without selective reporting, and 9/107 (8.4%) after EUCAST update with selective reporting. Supervision and counselling from IDs as well as the use of increased dosages of non-carbapenem antibiotics increased in both periods after EUCAST update, compared to the first period, respectively: 40.5% (60/148) versus 61.4% (124/202) versus 51.4% (55/107) (P < 0.001), and 57.9% (84/148) versus 91.1% (183/202) versus 90.7% (97/107) (P < 0.001). CONCLUSIONS: Selective reporting of antibiotic susceptibility testing results might decrease unnecessary meropenem prescriptions for the treatment of P. aeruginosa infections and could be part of multimodal antibiotic stewardship interventions.

The LAUsanne STAPHylococcus aureus ENdocarditis (LAUSTAPHEN) score: A prediction score to estimate initial risk for infective endocarditis in patients with S. aureus bacteremia.

Introduction: Infective endocarditis (IE) is a common complication of Staphylococcus aureus bacteremia (SAB). The study aimed to develop and validate a prediction score to determine IE risk among SAB. Methods: This retrospective study included adults with SAB (2015-2021) and divided them into derivation and validation cohorts. Using the modified 2015 European Society of Cardiology modified Duke Criteria for definite IE, the LAUSTAPHEN score was compared to previous scores. Results: Among 821 SAB episodes, 419 and 402 were divided into derivation and validation cohorts, respectively. Transthoracic and transoesophageal echocardiography (TOE) were performed in 77.5 and 42.1% of episodes, respectively. Definite IE was diagnosed in 118 episodes (14.4%). Derivation cohort established that cardiac predisposing factors, such as cardiac implantable electronic devices, prolonged bacteremia ≥48 h, and vascular phenomena were independently associated with IE. In addition to those parameters, native bone and joint infections were used to constitute the LAUSTAPHEN score. LAUSTAPHEN and VIRSTA scores misclassified <4% of IE cases as low risk. Misclassification using POSITIVE and PREDICT scores was >10%. The number of TOEs required to safely exclude IE were 66.9 and 51.6% with VIRSTA and LAUSTAPHEN, respectively. Discussion: LAUSTAPHEN and VIRSTA scores exhibited the lowest misclassification rate of IE cases to the low-risk group. However, the number of patients requiring TOE was higher for VIRSTA than for LAUSTAPHEN.

Prevalence and Factors Associated with Prosthetic Joint Infections in Patients with Staphylococcus aureus Bacteraemia: A 7-Year Retrospective Study.

Background: Staphylococcus aureus is the main cause of haematogenous prosthetic joint infections (PJI). We aimed to describe the prevalence and factors associated with PJI in patients with documented S. aureus bacteraemia. Methods: Adult patients with S. aureus bacteraemia and presence of prosthetic joint hospitalized in Lausanne University Hospital during a seven-year period (2015−2021) were included. Results: Among 135 patients with S. aureus bacteraemia and prosthetic joints, 38 (28%) had PJI. Multivariate analysis revealed that the presence of PJI was associated with knee arthroplasty (P 0.029; aOR 3.00, 95% CI 1.12−8.05), prior arthroplasty revision (P 0.034; aOR 3.59, 95% CI 1.10−11.74), community-acquired bacteraemia (P 0.005; aOR 4.74, 95% CI 1.61−14.01) and age < 70 years (P 0.007; aOR 9.39, 95% CI 1.84−47.85). Conclusions: PJI was common among patients with documented S. aureus bacteraemia. PJI was associated with characteristics of the prosthesis, such as prior arthroplasty revisions and knee prosthesis.

Κey Role of Early Source Control in Candidemic Patients With Sepsis or Septic Shock.

Background: Despite advances in diagnostic and therapeutic approaches, candidemia remains associated with high mortality rates. This study aimed at identifying predictors of mortality among patients with candidemia, with a focus on early interventions that can improve prognosis. Methods: This was a single-center retrospective study including all adult patients with at least 1 positive blood culture for Candida species from 2014 to 2021. Results: A total of 222 episodes of candidemia were included. Most candidemias were of unknown origin (36%) or vascular catheter related (29%). Septic shock developed in 29% episodes. Overall, 14-day mortality rate was 23%. In univariate analyses, septic shock was associated with higher 14-day mortality, whereas catheter-related candidemia and early (<72 hours) interventions, such as appropriate antifungal therapy, source control, and infectious diseases consultation, were associated with improved survival. In a Cox multivariate regression model, septic shock (odds ratio [OR], 3.62 [95% confidence interval {CI}, 2.05-6.38]) was associated with higher mortality. While the impact of early antifungal therapy did not reach statistical significance, early (<72 hours) infectious diseases consultation (OR, 0.46 [95% CI, .23-.91]) and early source control (OR, 0.15 [95% CI, .08-.31]) were associated with better survival. Subanalyses showed that the benefits of early source control, specifically catheter removal, were significant among patients with sepsis or septic shock, but not among those without sepsis. These associations remained significant after exclusion of patients who died prematurely or were in palliative care. Conclusions: Early source control, in particular catheter removal, was a key determinant of outcome among candidemic patients with sepsis or septic shock.

Molecular typing of Clostridioides difficile from frozen stool samples to investigate cross-transmissions: A proof of concept.

PURPOSE: Toxigenic Clostridioides difficile is responsible for up to one third of post antibiotic diarrhea and for more than 95% of pseudomembranous colitis. Nowadays, diagnosis relies on the documentation of the presence of the toxin in stools by specific antigenic or PCR tests. Stool cultures have been mostly abandoned, leading to the absence of isolates for further epidemiological analyses. METHODS: Aliquots of stool samples, frozen for up to two years, were thawed and inoculated onto commercial C. difficile media. Eighteen stools were recovered from patients hospitalized in the pediatric ward where at that time a chain of transmission was suspected. Eleven stools were recovered from patients hospitalized in a medical ward over a three months period with no suspected transmission event. Up to 16 characteristic colonies were isolates per culture. PCR of toxins genes and molecular typing by Double Locus Sequence Typing (DLST) were performed on these colonies. Whole genome multi locus sequence typing (wgMLST) was performed on selected isolates. RESULTS: Among the 29 stool specimens, no growth was observed for four stools and only one colony grew for one stool. Except the latter, all 16 colonies of the 24 stools showed identical toxin genes profiles than the original stool. However, variant DLST genotypes was observed within 20% of investigated stools. The majority of variants were single locus variant due to an IN/DEL of the repeat in one of the two DLST locus. Despite this variation, results of molecular typing overrule the putative transmission chain in the pediatric ward and revealed undetected chains of transmission in the medical ward. These results were confirmed with wgMLST. CONCLUSIONS: The developed protocol allows prospective and retrospective molecular and genomic epidemiological investigation of C. difficile infections for infection control purpose.

Management of Beta-Lactam Antibiotics Allergy: A Real-Life Study.

Beta-lactam allergy is a common problem in everyday medical practice and is recognized as a major public health issue. Carrying this label frequently leads to the avoidance of all beta-lactam antibiotics, favoring the use of other less preferred classes of antibiotics, that are more expensive and associated with more side effects and increased antimicrobial resistance. Therefore, delabeling a beta-lactam allergy is part of antimicrobial stewardship programs. Herein, we retrospectively examined the clinical records of 576 patients who were referred to our center for a label of allergy to beta-lactam antibiotics and were systematically investigated following a standardized algorithm. Our main aim was to evaluate the frequency of confirmed immediate- and delayed-type allergy to commonly prescribed subclasses of beta-lactam antibiotics (penicillin and cephalosporin), as well as the negative predictive value (NPV) and the sensitivity of skin tests. Our secondary aims were to examine the safety of beta-lactam skin testing and drug challenge. We identified that 260 patients reported a history of immediate reactions, 131 of delayed reactions, and 114 of unknown timing or mechanism of reactions. Following assessment and testing, 86 (18.3%) patients had a confirmed allergy to any beta-lactam antibiotics; 63 (13.4%) with an immediate- and 23 (4.9%) with a delayed-type reaction. Most frequently identified confirmed allergy was to penicillins (65 patients), followed by cephalosporins (21 patients). When immediate-type reactions were examined, NPV of skin tests were 96.3% and 100% for penicillins and cephalosporins, respectively. When delayed reactions were considered, NPV were 91.9 and 87.5% for penicillins and cephalosporins, respectively. Evaluation of the safety of skin tests according to the standardized procedure showed that systemic allergic reactions occurred in only 0.7% of skin tests and in 3.1% of drug challenges. Overall, our data indicate that only 18.3% of patients with a beta-lactam allergy label have a confirmed allergy and non-allergic patients can be safely delabeled through allergic workup based on skin tests and drug challenge. This approach supports the policy of saving second-line antibiotics through a standardized allergy workup.

Point prevalence study of antibiotic appropriateness and possibility of early discharge from hospital among patients treated with antibiotics in a Swiss University Hospital.

BACKGROUND: The growing threat of multidrug resistant organisms have led to increasingly promote prudent and rational use of antimicrobials as well as early hospital discharge plan. Antibiotic stewardship programs (ASP) have been developed as multifaceted approaches to improve use of current antibiotics and are now widely applied through different strategies. Proactive interventions are still limited in Switzerland and data on antimicrobial appropriateness and early discharge strategies are lacking. We aimed to describe the opportunities of antibiotics prescriptions optimization at Lausanne University Hospital, Switzerland and evaluate the suitability for early discharge among patients receiving antibiotics. The need for outpatient medical structures was also assessed. METHODS: We conducted a point prevalence survey of antibiotic prescriptions in adult medical and surgical units with exclusion of intermediate and intensive care units. All hospitalized patients receiving a systemic antibiotic on the day of evaluation were included. An infectious diseases specialist evaluated antimicrobial appropriateness and assessed suitability for discharge according to medical and nursing observations. The need of flexible additional outpatient facility for a close medical follow-up was evaluated concomitantly. RESULTS: A total of 564 patients' files were reviewed. 182 (32%) patients received one or more systemic antibiotic: 62 (34%) as a prophylaxis and 120 (66%) as a treatment with or without concomitant prophylaxis. 37/62 (60%) patients receiving prophylaxis had no indication to continue the antibacterial. Regarding the patients treated with antibiotics, 69/120 (58%) presented at least one opportunity for treatment optimization, mainly interruption of treatment. A previous ID consultation was recorded for 55/120 (46%) patients, of whom 21 (38%) could have benefited from antimicrobial therapy optimization on the day of the point assessment. 9.2% patients were eligible for discharge of whom 64% could leave the hospital with a close outpatient follow-up for infectious issues. CONCLUSIONS: This point prevalence study offers precious indicators for tailoring future antibiotic stewardship interventions that can be combined with early discharge. Any centre considering implementing ASP should conduct this type of analysis with a pragmatic approach to gain insight into local practices and needed resources.