Emergence of OXA-48-producing Klebsiella pneumoniae in Lithuania, 2023: a multi-cluster, multi-hospital outbreak.

In 2023, an increase of OXA-48-producing Klebsiella pneumoniae was noticed by the Lithuanian National Public Health Surveillance Laboratory. Whole genome sequencing (WGS) of 106 OXA-48-producing K. pneumoniae isolates revealed three distinct clusters of carbapenemase-producing K. pneumoniae high-risk clones, including sequence type (ST) 45 (n = 35 isolates), ST392 (n = 32) and ST395 (n = 28), involving six, six and nine hospitals in different regions, respectively. These results enabled targeted investigation and control, and underscore the value of national WGS-based surveillance for antimicrobial resistance.

Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023.

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-ß-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1-carrying-P. stuartii and the third bla NDM-5-carrying-P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10, bla CMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.

Emergence and persistent spread of carbapenemase-producing Klebsiella pneumoniae high-risk clones in Greek hospitals, 2013 to 2022.

BackgroundPreliminary unpublished results of the survey of carbapenem- and/or colistin-resistant Enterobacterales (CCRE survey) showed the expansion of carbapenemase-producing Klebsiella pneumoniae (CPKP) sequence type (ST) 39 in 12 of 15 participating Greek hospitals in 2019.AimWe conducted a rapid survey to determine the extent of spread of CPKP high-risk clones in Greek hospitals in 2022 and compare the distribution of circulating CPKP clones in these hospitals since 2013.MethodsWe analysed whole genome sequences and epidemiological data of 310 K. pneumoniae isolates that were carbapenem-resistant or 'susceptible, increased exposure' from Greek hospitals that participated in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE, 2013-2014), in the CCRE survey (2019) and in a national follow-up survey (2022) including, for the latter, an estimation of transmission events.ResultsFive K. pneumoniae STs including ST258/512 (n = 101 isolates), ST11 (n = 93), ST39 (n = 56), ST147 (n = 21) and ST323 (n = 13) accounted for more than 90% of CPKP isolates in the dataset. While ST11, ST147 and ST258/512 have been detected in participating hospitals since 2013 and 2014, KPC-2-producing ST39 and ST323 emerged in 2019 and 2022, respectively. Based on the defined genetic relatedness cut-off, 44 within-hospital transmission events were identified in the 2022 survey dataset, with 12 of 15 participating hospitals having at least one within-hospital transmission event.ConclusionThe recent emergence and rapid spread of new high-risk K. pneumoniae clones in the Greek healthcare system related to within-hospital transmission is of concern and highlights the need for molecular surveillance and enhanced infection prevention and control measures.

Rapid cross-border emergence of NDM-5-producing Escherichia coli in the European Union/European Economic Area, 2012 to June 2022.

Whole genome sequencing data of 874 Escherichia coli isolates carrying bla NDM-5 from 13 European Union/European Economic Area countries between 2012 and June 2022 showed the predominance of sequence types ST167, ST405, ST410, ST361 and ST648, and an increasing frequency of detection. Nearly a third (30.6%) of these isolates were associated with infections and more than half (58.2%) were predicted to be multidrug-resistant. Further spread of E. coli carrying bla NDM-5 would leave limited treatment options for serious E. coli infections.

Increasing number of cases and outbreaks caused by Candida auris in the EU/EEA, 2020 to 2021.

The number of cases of Candida auris infection or carriage and of countries reporting cases and outbreaks increased in the European Union and European Economic Area during 2020 and 2021. Eight countries reported 335 such cases in 2020 and 13 countries 655 cases in 2021. Five countries experienced outbreaks while one country reported regional endemicity. These findings highlight the need for adequate laboratory capacity and surveillance for early detection of C. auris and rapid implementation of control measures.

Candida auris: epidemiological situation, laboratory capacity and preparedness in the European Union and European Economic Area*, January 2018 to May 2019.

Between January 2018 and May 2019, 349 cases of Candida auris were reported in the European Union/European Economic Area*, 257 (73.6%) colonisations, 84 (24.1%) bloodstream infections, seven (2.0%) other infections and one case of unknown infection/colonisation status (0.3%). Most cases (97.1%, n = 339) were reported from Spain or the United Kingdom, but also for the first time in Greece, the Netherlands and Poland. Laboratory capacity and preparedness has improved since January 2018.

Epidemiological situation, laboratory capacity and preparedness for carbapenem-resistant Acinetobacter baumannii in Europe, 2019.

To update information on the epidemiological situation and national capacity for detection, surveillance and containment of carbapenem-resistant Acinetobacter baumannii (CRAb) in Europe, we performed a survey in 37 countries. Nine countries reported regional or inter-regional spread and seven an endemic situation. Laboratories with a reference function, surveillance systems, and a national containment plan for CRAb existed in 30, 23 and eight countries, respectively. A pan-European molecular survey would provide in-depth understanding of the CRAb epidemiology.

Cross-border spread of blaNDM-1- and blaOXA-48-positive Klebsiella pneumoniae: a European collaborative analysis of whole genome sequencing and epidemiological data, 2014 to 2019.

Analysis of sequencing data for 143 blaNDM-1- and blaOXA-48-positive Klebsiella pneumoniae isolates from 13 European national collections and the public domain resulted in the identification of 15 previously undetected multi-country transmission clusters. For 10 clusters, cases had prior travel/hospitalisation history in countries outside of the European Union including Egypt, Iran, Morocco, Russia, Serbia, Tunisia and Turkey. These findings highlight the benefit of European whole genome sequencing-based surveillance and data sharing for control of antimicrobial resistance.

Worsening epidemiological situation of carbapenemase-producing Enterobacteriaceae in Europe, assessment by national experts from 37 countries, July 2018.

A survey on the epidemiological situation, surveillance and containment activities for carbapenemase-producing Enterobacteriaceae (CPE) was conducted in European countries in 2018. All 37 participating countries reported CPE cases. Since 2015, the epidemiological stage of CPE expansion has increased in 11 countries. Reference laboratory capability, dedicated surveillance and a specific national containment plan are in existence in 33, 27 and 14 countries, respectively. Enhanced control efforts are needed for CPE containment in Europe.

Isoniazid (INH) mono-resistance and tuberculosis (TB) treatment success: analysis of European surveillance data, 2002 to 2014.

INTRODUCTION: Isoniazid (INH) is an essential drug for tuberculosis (TB) treatment. Resistance to INH may increase the likelihood of negative treatment outcome. AIM: We aimed to determine the impact of INH mono-resistance on TB treatment outcome in the European Union/European Economic Area and to identify risk factors for unsuccessful outcome in cases with INH mono-resistant TB. METHODS: In this observational study, we retrospectively analysed TB cases that were diagnosed in 2002-14 and included in the European Surveillance System (TESSy). Multilevel logistic regression models were applied to identify risk factors and correct for clustering of cases within countries. RESULTS: A total of 187,370 susceptible and 7,578 INH mono-resistant TB cases from 24 countries were included in the outcome analysis. Treatment was successful in 74.0% of INH mono-resistant and 77.4% of susceptible TB cases. In the final model, treatment success was lower among INH mono-resistant cases (Odds ratio (OR): 0.7; 95% confidence interval (CI): 0.6-0.9; adjusted absolute difference in treatment success: 5.3%). Among INH mono-resistant TB cases, unsuccessful treatment outcome was associated with age above median (OR: 1.3; 95% CI: 1.2-1.5), male sex (OR: 1.3; 95% CI: 1.1-1.4), positive smear microscopy (OR: 1.3; 95% CI: 1.1-1.4), positive HIV status (OR: 3.3; 95% CI: 1.6-6.5) and a prior TB history (OR: 1.8; 95% CI: 1.5-2.2). CONCLUSIONS: This study provides evidence for an association between INH mono-resistance and a lower likelihood of TB treatment success. Increased attention should be paid to timely detection and management of INH mono-resistant TB.

Candida auris: epidemiological situation, laboratory capacity and preparedness in European Union and European Economic Area countries, 2013 to 2017.

During 2013-2017, 620 cases of Candida auris were reported in the European Union/European Economic Area - 466 (75.2%) colonisations, 110 (17.7%) bloodstream infections, 40 (6.5%) other infections and four cases (0.6%) of unknown colonisation/infection status - the majority from four large outbreaks. Survey results showed that several countries lacked laboratory capacity and/or information on the occurrence of cases at national level. To prevent further spread, adequate laboratory capacity and infection control preparedness is required in Europe.

The relationship between Mycobacterium tuberculosis MGIT time to positivity and cfu in sputum samples demonstrates changing bacterial phenotypes potentially reflecting the impact of chemotherapy on critical sub-populations.

OBJECTIVES: The relationship between cfu and Mycobacterial Growth Indicator Tube (MGIT) time to positivity (TTP) is uncertain. We attempted to understand this relationship and create a mathematical model to relate these two methods of determining mycobacterial load. METHODS: Sequential bacteriological load data from clinical trials determined by MGIT and cfu were collected and mathematical models derived. All model fittings were conducted in the R statistical software environment (version 3.0.2), using the lm and nls functions. RESULTS: TTP showed a negative correlation with log10 cfu on all 14 days of the study. There was an increasing gradient of the regression line and y-intercept as treatment progressed. There was also a trend towards an increasing gradient with higher doses of rifampicin. CONCLUSIONS: These data suggest that there is a population of mycobacterial cells that are more numerous when detected in liquid than on solid medium. Increasing doses of rifampicin differentially kill this group of organisms. These findings support the idea that increased doses of rifampicin are more effective.

The molecular bacterial load assay replaces solid culture for measuring early bactericidal response to antituberculosis treatment.

We evaluated the use of the molecular bacterial load (MBL) assay, for measuring viable Mycobacterium tuberculosis in sputum, in comparison with solid agar and liquid culture. The MBL assay provides early information on the rate of decline in bacterial load and has technical advantages over culture in either form.

Evaluation of quantitative antibiotic susceptibility testing by Vitek 2 as a routine method to predict strain relatedness of coagulase-negative staphylococci isolated from blood cultures.

To test the hypothesis that the strain relatedness of coagulase-negative staphylococci (CoNS) recovered from blood cultures can be inferred from automated antibiotic susceptibility testing (AST) results generated by Vitek 2, concordant or discordant AST results were compared with pulsed-field gel electrophoresis (PFGE) typing results for 119 CoNS blood culture isolate pairs. Concordant AST results were highly predictive of the strain relatedness of CoNS isolates.

Neurosyphilis manifesting with unilateral visual loss and hyponatremia: a case report.

BACKGROUND: Syphilis is called the chameleon of the diseases due to its variety of its clinical presentations, potentially affecting every organ of the body. Incidence of this ancient disease is once again on the increase worldwide. CASE PRESENTATION: We here report an unusual case of neurosyphilis manifesting with unilateral visual loss and hyponatremia. The patient also had primary syphilitic lesions and was concomitantly diagnosed with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Treatment with ceftriaxone and prednisolone, completely resolved the hyponatremia and visual acuity was partially restored. CONCLUSION: Awareness of syphilis as a differential diagnosis is important as previously unreported presentations of neurosyphilis can arise, especially in HIV infected patients.

Screening and control of methicillin-resistant Staphylococcus aureus in 186 intensive care units: different situations and individual solutions.

INTRODUCTION: Controversy exists about the benefit of screening for prevention of methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units (ICUs) and recent studies have shown conflicting results. The aim of this observational study was to describe and evaluate the association between MRSA incidence densities (IDs) and screening and control measures in ICUs participating in the German Nosocomial Infection Surveillance System. METHODS: The surveillance module for multidrug-resistant bacteria collects data on MRSA cases in ICUs with the aim to provide a national reference and a tool for evaluation of infection control management. The median IDs of MRSA cases per 1000 patient-days (pd) with the interquartile range (IQR) were calculated from the pooled data of 186 ICUs and correlated with parameters derived from a detailed questionnaire regarding ICU structure, microbiological diagnostics and MRSA screening and control measures. The association between questionnaire results and MRSA cases was evaluated by generalized linear regression models. RESULTS: One hundred eighty-six ICUs submitted data on MRSA cases for 2007 and 2008 and completed the questionnaire. During the period of analysis, 4935 MRSA cases occurred in these ICUs; of these, 3928 (79.6%) were imported and 1007 MRSA cases (20.4%) were ICU-acquired. Median MRSA IDs were 3.23 (IQR 1.24-5.73), 2.24 (IQR 0.63-4.30) and 0.64 (IQR 0.17-1.39) per 1000 pd for all cases, imported and ICU-acquired MRSA cases, respectively. MRSA IDs as well as implemented MRSA screening and control measures varied widely between ICUs. ICUs performing universal admission screening had significantly higher MRSA IDs than ICUs performing targeted or no screening. Separate regression models for ICUs with different screening strategies included the incidence of imported MRSA cases, the type of ICU, and the length of stay in independent association with the number of ICU-acquired MRSA cases. CONCLUSIONS: The analysis shows that MRSA IDs and structural parameters differ considerably between ICUs. In response, ICUs have combined screening and control measures in many ways to achieve various individual solutions. The incidence of imported MRSA cases might be helpful for consideration in the planning of MRSA control programmes.

European intensive care physicians' experience of infections due to antibiotic-resistant bacteria.

Background: Antimicrobial resistance (AMR) compromises the treatment of patients with serious infections in intensive care units (ICUs), and intensive care physicians are increasingly facing patients with bacterial infections with limited or no adequate therapeutic options. A survey was conducted to assess the intensive care physicians' perception of the AMR situation in the European Union/European Economic Area (EU/EEA). Methods: Between May and July 2017, physicians working in European ICUs were invited to complete an online questionnaire hosted by the European Society of Intensive Care Medicine. The survey included 20 questions on hospital and ICU characteristics, frequency of infections with multidrug-resistant (MDR) bacteria and relevance of AMR in the respondent's ICU, management of antimicrobial treatment as well as the use of last-line antibiotics in the six months preceding the survey. For the analysis of regional differences, EU/EEA countries were grouped into the four sub-regions of Eastern, Northern, Southern and Western Europe. Results: Overall, 1062 responses from four European sub-regions were analysed. Infections with MDR bacteria in their ICU were rated as a major problem by 257 (24.2%), moderate problem by 360 (33.9%) and minor problem by 391 (36.8%) respondents. Third-generation cephalosporin-resistant Enterobacteriaceae were the most frequently encountered MDR bacteria followed by, in order of decreasing frequency, meticillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and vancomycin-resistant enterococci. Perception of the relevance of the AMR problem and the frequency of specific MDR bacteria varied by European sub-region. Bacteria resistant to all or almost all available antibiotics were encountered by 132 (12.4%) respondents. Many physicians reported not having access to specific last-line antibiotics. Conclusions: The percentage of European ICU physicians perceiving AMR as a substantial problem in their ICU is high with variation by sub-region in line with epidemiological studies. The reports of bacteria resistant to almost all available antibiotics and the limited availability of last-line antibiotics in ICUs in the EU/EEA are of concern.

Pneumonia associated with invasive and noninvasive ventilation: an analysis of the German nosocomial infection surveillance system database.

PURPOSE: Pneumonia associated with invasive mechanical ventilation (IMV) is one of the indicator infections of the German Nosocomial Infection Surveillance System. In 2005 surveillance was extended to include pneumonia associated with noninvasive ventilation (NIV). The aim of this study was to determine the utilization of IMV and NIV and the associated incidence densities (IDs) of pneumonia and to compare the characteristics of pneumonia cases and the spectrum of associated pathogens. METHODS: We analyzed the pooled data of 400 intensive care units (ICUs) with respect to three categories of pneumonia: pneumonia associated with IMV and NIV and pneumonia not associated with ventilation. Pooled ventilation utilization rates and pneumonia IDs were calculated in total and stratified by hospital size, hospital type and ICU type. RESULTS: Four hundred ICUs with 779,500 admitted patients, 1,068,472 IMV days and 101,569 NIV days reported 6,869 cases of pneumonia between 2005 and 2007. Of these, 5,811 cases were associated with IMV, 160 with NIV and 898 were not associated with ventilation. The mean pneumonia IDs were 1.58 and 5.44 cases per 1,000 ventilator days for NIV and IMV, respectively. Pneumonia cases associated with IMV were younger, had a longer ICU stay before onset of pneumonia and were more often associated with gram-negative bacteria than cases associated with NIV; however, there were no differences in the proportion of secondary sepsis and death. CONCLUSIONS: This surveillance study including pneumonia associated with IMV and NIV and pneumonia not associated with ventilation shows significant differences of pneumonia IDs, patient characteristics and the spectrum of associated pathogens.

Outbreak of carbapenem-resistant Acinetobacter baumannii carrying the carbapenemase OXA-23 in a German university medical centre.

A prolonged outbreak of carbapenem-resistant Acinetobacter baumannii in a German university medical centre in 2006 was investigated; the investigation included a descriptive epidemiological analysis, a case-control study, environmental sampling, molecular typing of A. baumannii isolates using PFGE and repetitive-sequence-based PCR (rep-PCR) typing, and detection of OXA-type carbapenemases by multiplex PCR. Thirty-two patients acquired the outbreak strain in five intensive care units (ICUs) and two regular wards at a tertiary care hospital within 10 months. The outbreak strain was resistant to penicillins, cephalosporins, ciprofloxacin, gentamicin, tobramycin, imipenem and meropenem, and carried the bla(OXA-23)-like gene. Based on PFGE and rep-PCR typing, it was shown to be related to the pan-European A. baumannii clone II. The most likely mode of transmission was cross-transmission from colonized or infected patients via the hands of health-care workers, with the severity of disease and intensity of care (therapeutic intervention scoring system 28 score >median) being independently associated with acquisition of the outbreak strain (odds ratio 6.67, 95 % confidence interval 1.55-36.56). Control of the outbreak was achieved by enforcement of standard precautions, education of personnel, screening of ICU patients for carbapenem-resistant A. baumannii and cohorting of patients. This is believed to be the first report of an outbreak of A. baumannii carrying the carbapenemase OXA-23 in Germany.