Association between the number of symptomatic mpox cases and the detection of mpox virus DNA in wastewater in Switzerland: an observational surveillance study.

AIM OF THE STUDY: The COVID-19 pandemic has drawn attention to the benefit of wastewater-based epidemiology, particularly when case numbers are underreported. Underreporting may be an issue with mpox, where biological reasons and stigma may prevent patients from getting tested. Therefore, we aimed to assess the validity of wastewater surveillance for monitoring mpox virus DNA in wastewater of a Central European city and its association with official case numbers. METHODS: Wastewater samples were collected between 1 July and 28 August 2022 in the catchment area of Basel, Switzerland, and the number of mpox virus genome copies they contained was determined by real-time quantitative PCR. Logistic regression analyses were used to determine the odds of detectability of mpox virus DNA in wastewater, categorised as detectable or undetectable. Mann-Whitney U tests were used to determine associations between samples that tested positive for the mpox virus and officially reported cases and patients' recorded symptomatic phases. RESULTS: Mpox virus DNA was detected in 15 of 39 wastewater samples. The number of positive wastewater samples was associated with the number of symptomatic cases (odds ratio [OR] = 2.18, 95% confidence interval (CI) = 1.38-3.43, p = 0.001). The number of symptomatic cases differed significantly between days with positive versus negative wastewater results (median = 11 and 8, respectively, p = 0.0024). CONCLUSION: Mpox virus DNA was detectable in wastewater, even when officially reported case numbers were low (0-3 newly reported mpox cases corresponding to 6-12 symptomatic patients). Detectability in wastewater was significantly associated with the number of symptomatic patients within the catchment area. These findings illustrate the value of wastewater-based surveillance systems when assessing the prevalence of emerging and circulating infectious diseases.

Influenza transmission dynamics quantified from RNA in wastewater in Switzerland.

INTRODUCTION: Influenza infections are challenging to monitor at the population level due to many mild and asymptomatic cases and similar symptoms to other common circulating respiratory diseases, including COVID-19. Methods for tracking cases outside of typical reporting infrastructure could improve monitoring of influenza transmission dynamics. Influenza shedding into wastewater represents a promising source of information where quantification is unbiased by testing or treatment-seeking behaviours. METHODS: We quantified influenza A and B virus loads from influent at Switzerland's three largest wastewater treatment plants, serving about 14% of the Swiss population (1.2 million individuals). We estimated trends in infection incidence and the effective reproductive number (Re) in these catchments during a 2021/22 epidemic and compared our estimates to typical influenza surveillance data. RESULTS: Wastewater data captured the same overall trends in infection incidence as laboratory-confirmed case data at the catchment level. However, the wastewater data were more sensitive in capturing a transient peak in incidence in December 2021 than the case data. The Re estimated from the wastewater data was roughly at or below the epidemic threshold of 1 during work-from-home measures in December 2021 but increased to at or above the epidemic threshold in two of the three catchments after the relaxation of these measures. The third catchment yielded qualitatively the same results but with wider confidence intervals. The confirmed case data at the catchment level yielded comparatively less precise R_e estimates before and during the work-from-home period, with confidence intervals that included one before and during the work-from-home period. DISCUSSION: Overall, we show that influenza RNA in wastewater can help monitor nationwide influenza transmission dynamics. Based on this research, we developed an online dashboard for ongoing wastewater-based influenza surveillance in Switzerland.

Factors associated with non-carbapenemase mediated carbapenem resistance of Gram-negative bacteria: a retrospective case-control study

Infections with carbapenemase-producing Gram-negative bacteria are related to increased morbidity and mortality, yet little is known regarding infections caused by non-beta-lactamase mediated carbapenem-resistant bacteria. Our objective was to identify risk factors for, and the clinical impact of infections caused by carbapenem-resistant carbapenemase-negative Enterobacterales and Pseudomonas aeruginosa. This retrospective matched case-control study was performed at the University Hospital of Basel, Switzerland, in 2016. We focused on other resistance mechanisms by excluding laboratory-confirmed carbapenemase-positive cases. Carbapenem resistance was set as the primary endpoint, and important risk factors were investigated by conditional logistic regression. The clinical impact of carbapenem resistance was estimated using regression models containing the resistance indicator as explanatory factor and adjusting for potential confounders. Seventy-five cases of infections with carbapenem-resistant, carbapenemase-negative bacteria were identified and matched with 75 controls with carbapenem-susceptible infections. The matched data set was well-balanced regarding age, gender, and comorbidity. Duration of prior carbapenem treatment (OR 1.15, [1.01, 1.31]) correlated with resistance to carbapenems. Our study showed that patients with carbapenem-resistant bacteria stayed 1.59 times (CI [0.81, 3.14]) longer in an ICU. The analyzed dataset did not provide evidence for strong clinical implications of resistance to carbapenems or increased mortality. The duration of prior carbapenem treatment seems to be a strong risk factor for the development of carbapenem resistance. The higher risk for a longer ICU stay could be a consequence of a carbapenem resistance. In contrast to carbapenemase-producers, the clinical impact of carbapenamase-negative, carbapenem-resistant strains may be limited... (AU)

Assessing the rationale of prescribing carbapenems among hospitalized patients with documented penicillin allergy: implications for stewardship.

Background: A reported history of penicillin allergy frequently leads to the prescription of carbapenems as a substitute for penicillin to avoid allergic reactions. Such self-reported allergies need to be accurately characterized to identify targeted antibiotic stewardship interventions that potentially minimize unnecessary carbapenem use. Design: Retrospective cohort study. Method: The proportion of hospitalized patients with penicillin allergy history receiving carbapenem prescriptions was evaluated between January 1st, 2017 and December 31st, 2018 at the University Hospital Basel, Switzerland. The appropriateness of carbapenem prescription of each patient was evaluated using institutional guidelines based on previously published recommendations. Results: Our analysis revealed that among 212 patients with recorded penicillin allergy, of the 247 carbapenem treatment episodes, 79 (32%) were unjustified. Abdominal and lower respiratory tract infections were most frequently associated with inappropriate carbapenem use (OR 2.64, 95% CI 1.22-5.71, P = .014 and OR 2.26, 95% CI 1.08-4.73, P = .031). The recorded allergy type was not documented or unclear in 153 patients (72%) and penicillin allergy was only confirmed in 2 patients (0.9%). Inconsistencies in allergic symptom documentation and allergy types were found between the institution's two software programs. Conclusion: While a multimodal approach to identify and accurately label penicillin allergies remains essential to reduce inappropriate carbapenem use, our findings highlight the need for comprehensive and easily accessible guidelines for carbapenem utilization and structured history-based allergy assessment as an initial screening tool, embedded in a tailored digital allergy record template.

Systematic scoping review of automated systems for the surveillance of healthcare-associated bloodstream infections related to intravascular catheters.

INTRODUCTION: Intravascular catheters are crucial devices in medical practice that increase the risk of healthcare-associated infections (HAIs), and related health-economic adverse outcomes. This scoping review aims to provide a comprehensive overview of published automated algorithms for surveillance of catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI). METHODS: We performed a scoping review based on a systematic search of the literature in PubMed and EMBASE from 1 January 2000 to 31 December 2021. Studies were included if they evaluated predictive performance of automated surveillance algorithms for CLABSI/CRBSI detection and used manually collected surveillance data as reference. We assessed the design of the automated systems, including the definitions used to develop algorithms (CLABSI versus CRBSI), the datasets and denominators used, and the algorithms evaluated in each of the studies. RESULTS: We screened 586 studies based on title and abstract, and 99 were assessed based on full text. Nine studies were included in the scoping review. Most studies were monocentric (n = 5), and they identified CLABSI (n = 7) as an outcome. The majority of the studies used administrative and microbiological data (n = 9) and five studies included the presence of a vascular central line in their automated system. Six studies explained the denominator they selected, five of which chose central line-days. The most common rules and steps used in the algorithms were categorized as hospital-acquired rules, infection rules (infection versus contamination), deduplication, episode grouping, secondary BSI rules (secondary versus primary BSI), and catheter-associated rules. CONCLUSION: The automated surveillance systems that we identified were heterogeneous in terms of definitions, datasets and denominators used, with a combination of rules in each algorithm. Further guidelines and studies are needed to develop and implement algorithms to detect CLABSI/CRBSI, with standardized definitions, appropriate data sources and suitable denominators.

Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

Cefepime versus carbapenems for treatment of AmpC beta-lactamase-producing Enterobacterales bloodstream infections.

PURPOSE: Cefepime is recommended for treating infections caused by AmpC beta-lactamase-producing Enterobacterales (AmpC-PE), though supporting evidence is limited. Therefore, this study compared outcomes associated with cefepime versus carbapenem therapy for bloodstream infections (BSIs) caused by AmpC-PE after phenotypic exclusion of ESBL-co-producing isolates. METHODS: This retrospective cohort study compared definite cefepime versus carbapenem treatment for AmpC-PE BSI in hospitalized patients of the University Hospital Basel, Switzerland, between 01/2015 and 07/2020. Primary outcomes included in-hospital death, renal impairment and neurologic adverse events; secondary outcomes included length of hospital stay and recurrent infection. RESULTS: Two hundred and seventy episodes of AmpC-PE BSI were included, 162, 77 and 31 were treated with a carbapenem, cefepime and other antibiotics, respectively. Patients treated with carbapenems were more likely to be transferred to the ICU on admission and more frequently had central venous catheter as a source of infection. In uni- and multivariable analyses, primary and secondary outcomes did not differ between the two treatment groups, except for more frequent occurrence of neurological adverse events among patients treated with carbapenems and shorter length of hospital stay among survivors treated with cefepime. CONCLUSION: After excluding isolates with phenotypic ESBL-co-production, cefepime was not associated with adverse outcomes compared to carbapenems when used to treat BSIs caused by AmpC-PE. Our study provides evidence to support the use of cefepime as a safe treatment strategy for AmpC-PE BSI, particularly in clinically stable patients without initial renal impairment or increased susceptibility to neurological adverse events.

Extended-spectrum ß-lactamase-producing Enterobacterales in diverse foodstuffs: a prospective, longitudinal study in the city of Basel, Switzerland.

Background: The involvement of non-human-to-human transmission of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) remains elusive. Foodstuffs may serve as reservoirs for ESBL-PE and contribute to their spread. Aim: We aimed to systematically investigate the presence and spatiotemporal distribution of ESBL-PE in diverse unprocessed foodstuffs of different origin purchased in a central European city. Methods: Chicken and green (herbs, salad, sprouts, vegetables) samples were collected monthly for two consecutive years, from June 2017 to June 2019, from large supermarket chains and small local food retailers, representing all ten postcode areas of the City of Basel (Switzerland), and the kitchen of the University Hospital Basel (Basel, Switzerland). After enrichment, presumptive ESBL-PE were isolated by selective culture methods and identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ESBL production was confirmed by phenotypic testing. Results: Among 947 food samples, 14.8% were positive for ESBL-PE isolate/s belonging to eight different ESBL-producing bacterial species. Escherichia coli and Serratia fonticola were predominant across samples (9 and 2%, respectively). Higher ESBL-PE prevalence was observed in chicken (25.9%) than in green (3.8%) samples (p < 0.001). Among greens, ESBL-PE were most frequently isolated from sprouts (15.2%). High ESBL-PE species diversity was observed among chicken samples, with E. coli as predominant (17.6%). ESBL-producing Enterobacter cloacae was detected among different greens. Yet, ESBL-producing Klebsiella pneumoniae was predominant in sprouts (12.1%). In total, 20.5% of samples from organic farming and 14.2% of samples from conventionally raised animals harbored an ESBL-producing isolate. Detection of ESBL-PE across samples differed between organic and non-organic when stratified by food source (p < 0.001), particularly among greens (12.5% organic, 2.4% conventional). High proportion of organic chicken samples was positive for ESBL-E. coli (33.3%), while the detection of several species characterized the conventional chicken samples. No significant differences in ESBL-PE frequences were detected between national (13.4%) and international samples (8.0%) (p = 0.122). Instead, differences were observed between regions of food production and countries (p < 0.001). No significant differences were found when comparing the proportion of ESBL-PE positive samples across districts, shop sizes and the hospital kitchen. The percentage of ESBL-PE positive samples did not differ monthly across the two-year sampling period (p = 0.107). Conclusion: Our findings indicate moderate dissemination of ESBL-PE in foodstuffs, especially between chicken products and sprouts. Chicken meat represents a source for several ESBL-producing Enterobacterales, especially E. coli, while greens are more prone to carry ESBL-K. pneumoniae and E. cloacae. We disclose the importance of food type, food production system and production origin when assessing the risk of contamination with different ESBL-PE species.

Within-host genetic diversity of extended-spectrum beta-lactamase-producing Enterobacterales in long-term colonized patients.

Despite recognition of the immediate impact of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) on human health, essential aspects of their molecular epidemiology remain under-investigated. This includes knowledge on the potential of a particular strain to persist in a host, mutational events during colonization, and the genetic diversity in individual patients over time. To investigate long-term genetic diversity of colonizing and infecting ESBL-Klebsiella pneumoniae species complex and ESBL-Escherichia coli in individual patients over time, we performed a ten-year longitudinal retrospective study and extracted clinical and microbiological data from electronic health records. In this investigation, 76 ESBL-K. pneumoniae species complex and 284 ESBL-E. coli isolates were recovered from 19 and 61 patients. Strain persistence was detected in all patients colonized with ESBL-K. pneumoniae species complex, and 83.6% of patients colonized with ESBL-E. coli. We frequently observed isolates of the same strain recovered from different body sites associated with either colonization or infection. Antimicrobial resistance genes, plasmid replicons, and whole ESBL-plasmids were shared between isolates regardless of chromosomal relatedness. Our study suggests that patients colonized with ESBL-producers may act as durable reservoirs for ongoing transmission of ESBLs, and that they are at prolonged risk of recurrent infection with colonizing strains.

EAES, SAGES, and ESCP rapid guideline: bowel preparation for minimally invasive colorectal resection.

BACKGROUND: Variation exists in practice pertaining to bowel preparation before minimally invasive colorectal surgery. A survey of EAES members prioritized this topic to be addressed by a clinical practice guideline. OBJECTIVE: The aim of the study was to develop evidence-informed clinical practice recommendations on the use of bowel preparation before minimally invasive colorectal surgery, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders. METHODS: This is a collaborative project of EAES, SAGES, and ESCP. We updated a previous systematic review and performed a network meta-analysis of interventions. We appraised the certainty of the evidence for each comparison, using the GRADE and CINeMA methods. A panel of general and colorectal surgeons, infectious diseases specialists, an anesthetist, and a patient representative discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost, and use of resources, moderated by a GIN-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey. RESULTS: The panel suggests either oral antibiotics alone prior to minimally invasive right colon resection or mechanical bowel preparation (MBP) plus oral antibiotics; MBP plus oral antibiotics prior to minimally invasive left colon and sigmoid resection, and prior to minimally invasive right colon resection when there is an intention to perform intracorporeal anastomosis; and MBP plus oral antibiotics plus enema prior to minimally invasive rectal surgery (conditional recommendations); and recommends MBP plus oral antibiotics prior to minimally invasive colorectal surgery, when there is an intention to localize the lesion intraoperatively (strong recommendation). The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/LwvKej . CONCLUSION: This guideline provides recommendations on bowel preparation prior to minimally invasive colorectal surgery for different procedures, using highest methodological standards, through a structured framework informed by key stakeholders. Guideline registration number PREPARE-2023CN045.

Bacterial genome-wide association study substantiates papGII of Escherichia coli as a major risk factor for urosepsis.

BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, often caused by uropathogenic Escherichia coli. Multiple bacterial virulence factors or patient characteristics have been linked separately to progressive, more invasive infections. In this study, we aim to identify pathogen- and patient-specific factors that drive the progression to urosepsis by jointly analysing bacterial and host characteristics. METHODS: We analysed 1076 E. coli strains isolated from 825 clinical cases with UTI and/or bacteraemia by whole-genome sequencing (Illumina). Sequence types (STs) were determined via srst2 and capsule loci via fastKaptive. We compared the isolates from urine and blood to confirm clonality. Furthermore, we performed a bacterial genome-wide association study (bGWAS) (pyseer) using bacteraemia as the primary clinical outcome. Clinical data were collected by an electronic patient chart review. We concurrently analysed the association of the most significant bGWAS hit and important patient characteristics with the clinical endpoint bacteraemia using a generalised linear model (GLM). Finally, we designed qPCR primers and probes to detect papGII-positive E. coli strains and prospectively screened E. coli from urine samples (n = 1657) at two healthcare centres. RESULTS: Our patient cohort had a median age of 75.3 years (range: 18.00-103.1) and was predominantly female (574/825, 69.6%). The bacterial phylogroups B2 (60.6%; 500/825) and D (16.6%; 137/825), which are associated with extraintestinal infections, represent the majority of the strains in our collection, many of which encode a polysaccharide capsule (63.4%; 525/825). The most frequently observed STs were ST131 (12.7%; 105/825), ST69 (11.0%; 91/825), and ST73 (10.2%; 84/825). Of interest, in 12.3% (13/106) of cases, the E. coli pairs in urine and blood were only distantly related. In line with previous bGWAS studies, we identified the gene papGII (p-value < 0.001), which encodes the adhesin subunit of the E. coli P-pilus, to be associated with 'bacteraemia' in our bGWAS. In our GLM, correcting for patient characteristics, papGII remained highly significant (odds ratio = 5.27, 95% confidence interval = [3.48, 7.97], p-value < 0.001). An independent cohort of cases which we screened for papGII-carrying E. coli at two healthcare centres further confirmed the increased relative frequency of papGII-positive strains causing invasive infection, compared to papGII-negative strains (p-value = 0.033, chi-squared test). CONCLUSIONS: This study builds on previous work linking papGII with invasive infection by showing that it is a major risk factor for progression from UTI to bacteraemia that has diagnostic potential.

Identification of microorganisms by a rapid PCR panel from positive blood cultures leads to faster optimal antimicrobial therapy - a before-after study.

BACKGROUND: The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) - a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification. METHODS: In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions. RESULTS: Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0-31.2) hours with BF-FA-BCIP compared to 45.7 (37.7-51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes. CONCLUSIONS: Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04156633, registered on November 5, 2019.

Treatment effect of remdesivir on the mortality of hospitalised COVID-19 patients in Switzerland across different patient groups: a tree-based model analysis.

AIMS OF THE STUDY: Remdesivir has shown benefits against COVID-19. However, it remains unclear whether, to what extent, and among whom remdesivir can reduce COVID-19-related mortality. We explored whether the treatment response to remdesivir differed by patient characteristics. METHODS: We analysed data collected from a hospital surveillance study conducted in 21 referral hospitals in Switzerland between 2020 and 2022. We applied model-based recursive partitioning to group patients by the association between treatment levels and mortality. We included either treatment (levels: none, remdesivir within 7 days of symptom onset, remdesivir after 7 days, or another treatment), age and sex, or treatment only as regression variables. Candidate partitioning variables included a range of risk factors and comorbidities (and age and sex unless included in regression). We repeated the analyses using local centring to correct the results for the propensity to receive treatment. RESULTS: Overall (n = 21,790 patients), remdesivir within 7 days was associated with increased mortality (adjusted hazard ratios 1.28-1.54 versus no treatment). The CURB-65 score caused the most instability in the regression parameters of the model. When adjusted for age and sex, patients receiving remdesivir within 7 days of onset had higher mortality than those not treated in all identified eight patient groups. When age and sex were included as partitioning variables instead, the number of groups increased to 19-20; in five to six of those branches, mortality was lower among patients who received early remdesivir. Factors determining the groups where remdesivir was potentially beneficial included the presence of oncological comorbidities, male sex, and high age. CONCLUSIONS: Some subgroups of patients, such as individuals with oncological comorbidities or elderly males, may benefit from remdesivir.

Predictive performance of automated surveillance algorithms for intravascular catheter bloodstream infections: a systematic review and meta-analysis.

BACKGROUND: Intravascular catheter infections are associated with adverse clinical outcomes. However, a significant proportion of these infections are preventable. Evaluations of the performance of automated surveillance systems for adequate monitoring of central-line associated bloodstream infection (CLABSI) or catheter-related bloodstream infection (CRBSI) are limited. OBJECTIVES: We evaluated the predictive performance of automated algorithms for CLABSI/CRBSI detection, and investigated which parameters included in automated algorithms provide the greatest accuracy for CLABSI/CRBSI detection. METHODS: We performed a meta-analysis based on a systematic search of published studies in PubMed and EMBASE from 1 January 2000 to 31 December 2021. We included studies that evaluated predictive performance of automated surveillance algorithms for CLABSI/CRBSI detection and used manually collected surveillance data as reference. We estimated the pooled sensitivity and specificity of algorithms for accuracy and performed a univariable meta-regression of the different parameters used across algorithms. RESULTS: The search identified five full text studies and 32 different algorithms or study populations were included in the meta-analysis. All studies analysed central venous catheters and identified CLABSI or CRBSI as an outcome. Pooled sensitivity and specificity of automated surveillance algorithm were 0.88 [95%CI 0.84-0.91] and 0.86 [95%CI 0.79-0.92] with significant heterogeneity (I2 = 91.9, p < 0.001 and I2 = 99.2, p < 0.001, respectively). In meta-regression, algorithms that include results of microbiological cultures from specific specimens (respiratory, urine and wound) to exclude non-CRBSI had higher specificity estimates (0.92, 95%CI 0.88-0.96) than algorithms that include results of microbiological cultures from any other body sites (0.88, 95% CI 0.81-0.95). The addition of clinical signs as a predictor did not improve performance of these algorithms with similar specificity estimates (0.92, 95%CI 0.88-0.96). CONCLUSIONS: Performance of automated algorithms for detection of intravascular catheter infections in comparison to manual surveillance seems encouraging. The development of automated algorithms should consider the inclusion of results of microbiological cultures from specific specimens to exclude non-CRBSI, while the inclusion of clinical data may not have an added-value. Trail Registration Prospectively registered with International prospective register of systematic reviews (PROSPERO ID CRD42022299641; January 21, 2022). https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022299641.

Factors associated with non-carbapenemase mediated carbapenem resistance of Gram-negative bacteria: a retrospective case-control study.

Infections with carbapenemase-producing Gram-negative bacteria are related to increased morbidity and mortality, yet little is known regarding infections caused by non-beta-lactamase mediated carbapenem-resistant bacteria. Our objective was to identify risk factors for, and the clinical impact of infections caused by carbapenem-resistant carbapenemase-negative Enterobacterales and Pseudomonas aeruginosa. This retrospective matched case-control study was performed at the University Hospital of Basel, Switzerland, in 2016. We focused on other resistance mechanisms by excluding laboratory-confirmed carbapenemase-positive cases. Carbapenem resistance was set as the primary endpoint, and important risk factors were investigated by conditional logistic regression. The clinical impact of carbapenem resistance was estimated using regression models containing the resistance indicator as explanatory factor and adjusting for potential confounders. Seventy-five cases of infections with carbapenem-resistant, carbapenemase-negative bacteria were identified and matched with 75 controls with carbapenem-susceptible infections. The matched data set was well-balanced regarding age, gender, and comorbidity. Duration of prior carbapenem treatment (OR 1.15, [1.01, 1.31]) correlated with resistance to carbapenems. Our study showed that patients with carbapenem-resistant bacteria stayed 1.59 times (CI [0.81, 3.14]) longer in an ICU. The analyzed dataset did not provide evidence for strong clinical implications of resistance to carbapenems or increased mortality. The duration of prior carbapenem treatment seems to be a strong risk factor for the development of carbapenem resistance. The higher risk for a longer ICU stay could be a consequence of a carbapenem resistance. In contrast to carbapenemase-producers, the clinical impact of carbapenamase-negative, carbapenem-resistant strains may be limited. Trial registration: The study design was prospectively approved by the local Ethics Commission on 10.08.2017 (EKNZ BASEC 2017-00222).

Epidemiology of patients harboring carbapenemase-producing bacteria and comparison with patients with detection of extended-spectrum beta-lactamase-producing Enterobacterales-A retrospective cohort study.

OBJECTIVE: We evaluated the epidemiology of carbapenemase-producing bacteria (CPB) in Switzerland by comparing risk factors between patients colonized with CPB and patients colonized with extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE). METHODS: This retrospective cohort study was conducted at the University Hospital Basel in Switzerland. Hospitalized patients with CPB in any sample between January 2008 and July 2019 were included. The ESBL-PE group consisted of hospitalized patients with detection of ESBL-PE from any sample between January 2016 and December 2018. Comparisons of risk factors for acquisition of CPB and ESBL-PE were performed by logistic regression. RESULTS: Inclusion criteria were met for 50 patients in the CPB group and 572 in the ESBL-PE group. In the CPB group, 62% had a travel history and 60% had been hospitalized abroad. When comparing the CPB group to the ESBL-PE group, hospitalization abroad (odds ratio [OR], 25.33; 95% confidence interval [CI], 11.07-57.98) and prior antibiotic therapy (OR, 4.76; 95% CI, 2.15-10.55) remained independently associated with CPB colonization. Hospitalization abroad (P < .001) and prior antibiotic therapy (P < .001) predicted CPB in the comparison of CPB with ESBL Escherichia coli, whereas hospitalization abroad was associated with CPB in comparison to ESBL Klebsiella pneumoniae. CONCLUSIONS: Although CPB still seem to be mainly imported from areas of higher endemicity, local acquisition of CPB is emerging, especially in patients with close and/or frequent contact with healthcare services. This trend resembles the epidemiology of ESBL K. pneumoniae, supporting mainly healthcare-associated transmission. Frequent evaluation of CPB epidemiology is required to improve detection of patients at risk of CPB carriage.