Highly pathogenic avian influenza A(H5N1) virus infections on fur farms connected to mass mortalities of black-headed gulls, Finland, July to October 2023.

Highly pathogenic avian influenza (HPAI) has caused widespread mortality in both wild and domestic birds in Europe 2020-2023. In July 2023, HPAI A(H5N1) was detected on 27 fur farms in Finland. In total, infections in silver and blue foxes, American minks and raccoon dogs were confirmed by RT-PCR. The pathological findings in the animals include widespread inflammatory lesions in the lungs, brain and liver, indicating efficient systemic dissemination of the virus. Phylogenetic analysis of Finnish A(H5N1) strains from fur animals and wild birds has identified three clusters (Finland I-III), and molecular analyses revealed emergence of mutations known to facilitate viral adaptation to mammals in the PB2 and NA proteins. Findings of avian influenza in fur animals were spatially and temporally connected with mass mortalities in wild birds. The mechanisms of virus transmission within and between farms have not been conclusively identified, but several different routes relating to limited biosecurity on the farms are implicated. The outbreak was managed in close collaboration between animal and human health authorities to mitigate and monitor the impact for both animal and human health.

Increasing proportions of extended-spectrum ß-lactamase-producing isolates among Escherichia coli from urine and bloodstream infections: results from a nationwide surveillance network, Finland, 2008 to 2019.

BackgroundEscherichia coli is the leading cause of urinary tract infections (UTI) and bloodstream infections (BSI), and the emergence of antimicrobial resistance (AMR) in E. coli causes concern.AimTo investigate changes in the proportion of extended-spectrum ß-lactamase (ESBL) producing isolates among E. coli isolated from urine and blood in Finland during 2008-2019.MethodsSusceptibility testing of 1,568,488 urine (90% female, 10% male) and 47,927 blood E. coli isolates (61% female, 39% male) from all Finnish clinical microbiology laboratories during 2008-2019 was performed according to guidelines from the Clinical and Laboratory Standard Institute during 2008-2010 and the European Committee on Antimicrobial Susceptibility Testing during 2011-2019. A binomial regression model with log link compared observed trends over time and by age group and sex.ResultsThe annual proportion of ESBL-producing E. coli isolates among E. coli from blood cultures increased from 2.4% (23/966) to 8.6% (190/2,197) among males (average annual increase 7.7%; 95% CI: 4.4-11.0%, p < 0.01) and from 1.6% (28/1,806) to 6.4% (207/3,218) among females (9.3%; 95% CI: 4.8-14.0%, p < 0.01). In urine cultures, the proportion of ESBL-producing E. coli isolates increased from 2.2% (239/10,806) to 7.2% (1,098/15,297) among males (8.8%; 95% CI: 6.5-11.3%, p < 0.01) and from 1.0% (1,045/108,390) to 3.1% (3,717/120,671) among females (8.6%; 95% CI: 6.3-11.0%, p < 0.01). A significant increase was observed within most age groups.ConclusionsConsidering the ageing population and their risk of E. coli BSI and UTI, the increase in the annual proportions of ESBL-producing E. coli is concerning, and these increasing trends should be carefully monitored.

Highly pathogenic avian influenza A(H5N1) virus infection on multiple fur farms in the South and Central Ostrobothnia regions of Finland, July 2023.

Since mid-July 2023, an outbreak caused by highly pathogenic avian influenza A(H5N1) virus clade 2.3.4.4b genotype BB is ongoing among farmed animals in South and Central Ostrobothnia, Finland. Infections in foxes, American minks and raccoon dogs have been confirmed on 20 farms. Genetic analysis suggests introductions from wild birds scavenging for food in farm areas. Investigations point to direct transmission between animals. While no human infections have been detected, control measures are being implemented to limit spread and human exposure.

Three clusters of carbapenemase-producing Citrobacter freundii in Finland, 2016-20.

OBJECTIVES: Carbapenemase-producing Enterobacterales (CPE) have spread widely into health care facilities (HCF) but clusters caused by carbapenemase-producing (CP) Citrobacter freundii have been uncommon until recent years. Here we describe CP C. freundii clusters detected in Finland during 2016-20. METHODS: As a part of the national CPE surveillance, clinical microbiology laboratories send potential CP C. freundii isolates to the reference laboratory for confirmation and further characterization. Whole genome sequencing (WGS) with Illumina MiSeq sequencer was used to detect clusters. Resistance genes and STs were analysed using SRST2 and typing with core genome (cg) MLST. A case was defined as a patient with a CP C. freundii isolate belonging to one of the detected clusters. RESULTS: We detected three CP C. freundii clusters: cluster 1 included 16 cases in five HCFs during 2016-20, cluster 2 had two cases in two HCFs during 2018-19 and cluster 3 had two cases in one HCF in 2020. The isolates (11 clinical and 5 screening) in cluster 1 had KPC-2 carbapenemase and were sequence type (ST)18. Cluster 2 (2 clinical isolates) had OXA-181/GES-5 carbapenemases and were ST604 and cluster 3 (two screening isolates) had KPC-3 carbapenemase and were ST116. None of the cases had a history of recent travel abroad. CONCLUSIONS: CP C. freundii also causes outbreaks and can be a reservoir of carbapenemase genes. The long intervals between successive cases, mostly found in clinical specimens in two clusters, suggest that besides unknown carriers, environmental contamination may play a role in transmission.

Molecular epidemiology of carbapenemase-producing Enterobacterales in Finland, 2012-2018.

Carbapenemase-producing Enterobacterales (CPE) pose an increasing threat to patient safety and healthcare systems globally. We present molecular epidemiology of CPE in Finland during 2012-2018 with detailed characteristics of CPE strains causing clusters during the same time period. All Finnish clinical microbiology laboratories send Enterobacterales isolates with reduced susceptibility to carbapenems or isolates producing carbapenemase to the reference laboratory for further characterization by whole genome sequencing (WGS). In total, 231 CPE strains from 202 patients were identified during 2012-2018. Of the strains, 59% were found by screening and 32% from clinical specimens, the latter were most commonly urine. Travel and/or hospitalization history abroad was reported for 108/171 strains (63%). The most common species were Klebsiella pneumoniae (45%), Escherichia coli (40%), and Citrobacter freundii (6%), and the most common carbapenemase genes blaNDM-like (35%), blaOXA-48-like (33%), and blaKPC-like (31%). During 2012-2018, the annual number of CPE strains increased from 9 to 70 and different sequence types from 7 to 33, and blaOXA-48-like genes became the most prevalent. Of the clusters, 3/8 were linked to traveling or hospitalization abroad and 5/8 were caused by K. pneumoniae clone clonal complex 258. Most of the clusters were caused by K. pneumoniae producing KPC. High variety among different sequence types indicates that majority of CPE cases detected in Finland are likely imported from foreign countries. Nearly one-third of the cases are not found by screening suggesting that there is hidden transmission occurring in the healthcare settings.

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.

Emergence of ceftazidime-avibactam-resistant Klebsiella pneumoniae during treatment, Finland, December 2018.

In December 2018, a ceftazidime-avibactam (CAZ-AVI)-resistant KPC-2-producing Klebsiella pneumoniae strain was isolated in Finland. CAZ-AVI resistance was observed 34 days after CAZ-AVI treatment in a trauma patient transferred from a hospital in Greece who had been colonised with blaKPC-2-producing K. pneumoniae ST39, and later developed a bloodstream infection. The CAZ-AVI-resistant strain contained a novel 15 amino acid insertion in the KPC-2 protein causing structural changes proximal to the KPC-2 active site.

Tracing local and regional clusters of carbapenemase-producing Klebsiella pneumoniae ST512 with whole genome sequencing, Finland, 2013 to 2018.

BackgroundTwo epidemiologically-unrelated clusters of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae were detected among several healthcare facilities (HCF) in Finland by routine surveillance using whole genome sequencing (WGS).AimThe objective was to investigate transmission chains to stop further spread of the responsible strain.MethodsIn this observational retrospective study, cases were defined as patients with K. pneumoniae KPC-3 sequence type (ST)512 strain detected in Finland from August 2013 to May 2018. Environmental specimens were obtained from surfaces, sinks and toilets in affected wards. WGS was performed on K. pneumoniae cultures using Illumina MiSeq platform and data were analysed using Ridom SeqShere software K. pneumoniae core genome multilocus sequence typing (cgMLST) scheme. Epidemiological information of the cases was provided by HCFs.ResultsWe identified 20 cases in six HCFs: cluster 1 included 18 cases in five HCFs and cluster 2 two cases in one HCF. In cluster 1, a link with a foreign country was unclear, 6/18 cases without overlapping stay had occupied the same room in one of the five HCFs within > 3 years. In cluster 2, the index case was transferred from abroad, both cases occupied the same room 8 months apart. A strain identical to that of the two cases in cgMLST was isolated from the toilet of the room, suggesting a clonal origin.ConclusionsThe clusters were mostly related to case transfer between facilities and likely involved environmental transmission. We show that CPE surveillance using WGS and collaboration between hospitals are crucial to identify clusters and trace transmission chains.

Impact of Antimicrobial Treatment for Acute Otitis Media on Carriage Dynamics of Penicillin-Susceptible and Penicillin-Nonsusceptible Streptococcus pneumoniae.

Background: Despite concerns that antimicrobial treatment of prevalent infections may select for drug-resistant bacteria, the effects of antimicrobial treatment on colonization dynamics have not been well quantified. Methods: We measured impacts of antimicrobial treatment on nasopharyngeal carriage of penicillin-susceptible Streptococcus pneumoniae (PSSP) and penicillin-nonsusceptible (PNSP) lineages at the end of treatment and 15, 30, and 60 days after treatment in a previously conducted randomized, double-blinded, placebo-controlled trial of amoxicillin-clavulanate for stringently defined acute otitis media. Results: In intention-to-treat analyses, immediate treatment with amoxicillin-clavulanate reduced PSSP carriage prevalence by 88% (95% confidence interval [CI], 76%-96%) at the end of treatment and by 27% (-3%-49%) after 60 days but did not alter PNSP carriage prevalence. By the end of treatment, 7% of children who carried PSSP at enrollment remained colonized in the amoxicillin-clavulanate arm, compared with 61% of PSSP carriers who received placebo; impacts of amoxicillin-clavulanate persisted at least 60 days after treatment among children who carried PSSP at enrollment. Amoxicillin-clavulanate therapy reduced PSSP acquisition by >80% over 15 days. Among children who carried PNSP at enrollment, no impacts on carriage prevalence of S. pneumoniae, PSSP, or PNSP were evident at follow-up visits. Conclusions: Although the absolute risk of carrying PNSP was unaffected by treatment, antimicrobial therapy conferred a selective impact on colonizing pneumococci by accelerating clearance and delaying acquisition of PSSP.

Sharing more than friendship - transmission of NDM-5 ST167 and CTX-M-9 ST69 Escherichia coli between dogs and humans in a family, Finland, 2015.

IntroductionCarbapenemase-producing Enterobacteriaceae (CPE) have rarely been reported in dogs, and never in animals in Finland. However, in April 2015, two meropenem-resistant Escherichia coli were identified from two dogs in one family. Both dogs suffered from chronic otitis externa. Methods: Epidemiological and molecular investigations (pulsed-field gel electrophoresis (PFGE), multilocus sequence typing) were conducted to investigate the source of infection and transmission routes. Results: In both dogs and one family member New Delhi metallo-beta-lactamase (NDM-5)-producing multidrug-resistant ST167 E. coli was found. Whole genome sequencing confirmed that the isolates were identical or only had one or two allelic differences. Additionally, the dogs and humans of the family carried an identical extended-spectrum beta-lactamase (ESBL) CTX-M-group 9 E. coli ST69 strain, indicating interspecies transmission. While the original source remains unclear, human-to-canine transmission is possible. No carbapenems had been administered to the dogs, but exposure to numerous other antimicrobials likely sustained the bacteria and supported its propagation in the canine host. Conclusion: To our knowledge, canine clinical NDM-5 E. coli in Europe, and confirmed CPE transmission between dogs and humans have not been previously reported. The screening of veterinary Enterobacteriaceae isolates for carbapenem resistance is highly recommended.

Genomic Characteristics Behind the Spread of Bacteremic Group A Streptococcus Type emm89 in Finland, 2004-2014.

BACKGROUND: Many countries worldwide have reported increasing numbers of emm89 group A Streptococcus (GAS) infections during last decade. Pathogen genetic factors linked to this increase need assessment. METHODS: We investigated epidemiological characteristics of emm89 GAS bacteremic infections, including 7-day and 30-day case-fatality rates, in Finland during 2004-2014 and linked them to whole-genome sequencing data obtained from corresponding strains. The Fisher exact test and exact logistic regression were used to compare differences between bacteremic infections due to emm89 GAS belonging to different genetic clades and subclades. RESULTS: Out of 1928 cases of GAS bacteremic infection, 278 were caused by emm89 GAS. We identified 2 genetically distinct clades, arbitrarily designated clade 2 and clade 3. Both clades were present during 2004-2008, but clade 3 increased rapidly from 2009 onward. Six subclades (designated subclades A-F) were identified within clade 3, based on phylogenetic core genome analysis. The case-fatality rate differed significantly between subclades (P < .05), with subclade D having the highest 30-day estimated case-fatality rate (19% vs 3%-14%). CONCLUSIONS: A new emm89 clone, clade 3, emerged in 2009 and spread rapidly in Finland. Patients infected with certain subclades of clade 3 were significantly more likely to die. A specific polymerase chain reaction assay was developed to follow the spread of subclade D in 2015.

Cefotaxime-resistant Salmonella enterica in travelers returning from Thailand to Finland.

During 1993-2011, cefotaxime resistance among Salmonella enterica isolates from patients in Finland increased substantially. Most of these infections originated in Thailand; many were qnr positive and belonged to S. enterica serovar Typhimurium and S. enterica monophasic serovar 4,[5],12:i:-. Although cefotaxime-resistant salmonellae mainly originate in discrete geographic areas, they represent a global threat.

Evaluation of the Carba NP test for carbapenemase detection.

The Carba NP test was evaluated against a panel of 61 carbapenemase-producing bacterial species (15 producing class A carbapenemases, 15 producing class D carbapenemases, and 31 producing metallo-ß-lactamases) and against 111 isolates with non-wild-type carbapenem susceptibility but not producing carbapenemase. Carbapenemase production was verified by PCR and UV-spectrophotometric measurement of imipenem hydrolysis. No false positives were seen, but there were consistent problems with the detection of OXA-48-like enzymes and also some rarer class A enzymes.

A placebo-controlled trial of antimicrobial treatment for acute otitis media.

BACKGROUND: The efficacy of antimicrobial treatment in children with acute otitis media remains controversial. METHODS: In this randomized, double-blind trial, children 6 to 35 months of age with acute otitis media, diagnosed with the use of strict criteria, received amoxicillin-clavulanate (161 children) or placebo (158 children) for 7 days. The primary outcome was the time to treatment failure from the first dose until the end-of-treatment visit on day 8. The definition of treatment failure was based on the overall condition of the child (including adverse events) and otoscopic signs of acute otitis media. RESULTS: Treatment failure occurred in 18.6% of the children who received amoxicillin-clavulanate, as compared with 44.9% of the children who received placebo (P<0.001). The difference between the groups was already apparent at the first scheduled visit (day 3), at which time 13.7% of the children who received amoxicillin-clavulanate, as compared with 25.3% of those who received placebo, had treatment failure. Overall, amoxicillin-clavulanate reduced the progression to treatment failure by 62% (hazard ratio, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P<0.001) and the need for rescue treatment by 81% (6.8% vs. 33.5%; hazard ratio, 0.19; 95% CI, 0.10 to 0.36; P<0.001). Analgesic or antipyretic agents were given to 84.2% and 85.9% of the children in the amoxicillin-clavulanate and placebo groups, respectively. Adverse events were significantly more common in the amoxicillin-clavulanate group than in the placebo group. A total of 47.8% of the children in the amoxicillin-clavulanate group had diarrhea, as compared with 26.6% in the placebo group (P<0.001); 8.7% and 3.2% of the children in the respective groups had eczema (P=0.04). CONCLUSIONS: Children with acute otitis media benefit from antimicrobial treatment as compared with placebo, although they have more side effects. Future studies should identify patients who may derive the greatest benefit, in order to minimize unnecessary antimicrobial treatment and the development of bacterial resistance. (Funded by the Foundation for Paediatric Research and others; ClinicalTrials.gov number, NCT00299455.).

An outbreak of CTX-M-15 -producing Escherichia coli, Enterobacter cloacae, and Klebsiella in a children's hospital in Finland.

Four different extended-spectrum ß -lactamase (ESBL)-producing bacteria from a pediatric surgery ward were studied. The presence of TEM-, SHV-, and CTX-M-type ß -lactamases was analyzed and the relatedness of the isolates studied with a repetitive PCR system (DiversiLab) and pulsed-fi eld gel electrophoresis (PFGE). Molecular analysis showed that a clonal dissemination of CTX-M-15-producing Escherichia coli and Enterobacter cloacae had occurred.

Impact of the COVID-19 pandemic on extended-spectrum ß-lactamase producing Escherichia coli in urinary tract and blood stream infections: results from a nationwide surveillance network, Finland, 2018 to 2022.

BACKGROUND: Before the COVID-19 pandemic there has been a constant increase in antimicrobial resistance (AMR) of Escherichia coli, the most common cause of urinary tract infections and bloodstream infections. The aim of this study was to investigate the impact of the COVID-19 pandemic on extended-spectrum ß-lactamase (ESBL) production in urine and blood E. coli isolates in Finland to improve our understanding on the source attribution of this major multidrug-resistant pathogen. METHODS: Susceptibility test results of 564,233 urine (88.3% from females) and 23,860 blood E. coli isolates (58.8% from females) were obtained from the nationwide surveillance database of Finnish clinical microbiology laboratories. Susceptibility testing was performed according to EUCAST guidelines. We compared ESBL-producing E. coli proportions and incidence before (2018-2019), during (2020-2021), and after (2022) the pandemic and stratified these by age groups and sex. RESULTS: The annual number of urine E. coli isolates tested for antimicrobial susceptibility decreased 23.3% during 2018-2022 whereas the number of blood E. coli isolates increased 1.1%. The annual proportion of ESBL-producing E. coli in urine E. coli isolates decreased 28.7% among males, from 6.9% (average during 2018-2019) to 4.9% in 2022, and 28.7% among females, from 3.0 to 2.1%. In blood E. coli isolates, the proportion decreased 32.9% among males, from 9.3 to 6.2%, and 26.6% among females, from 6.2 to 4.6%. A significant decreasing trend was also observed in most age groups, but risk remained highest among persons aged ≥ 60 years. CONCLUSIONS: The reduction in the proportions of ESBL-producing E. coli was comprehensive, covering both specimen types, both sexes, and all age groups, showing that the continuously increasing trends could be reversed. Decrease in international travel and antimicrobial use were likely behind this reduction, suggesting that informing travellers about the risk of multidrug-resistant bacteria, hygiene measures, and appropriate antimicrobial use is crucial in prevention. Evaluation of infection control measures in healthcare settings could be beneficial, especially in long-term care.

Clostridium difficile contamination of public tap water distribution system during a waterborne outbreak in Finland.

AIMS: In November through December 2007, the drinking water distribution system in the town of Nokia, Finland, was contaminated with treated sewage effluent that resulted in a large gastroenteritis outbreak in the community. The aim of the present study was to investigate if the contaminated water in this outbreak was also a potential source of Clostridium difficile infections. METHODS: Samples from the contaminated tap water and treated sewage effluent were collected. Stool samples from a portion of patients that fell ill during the outbreak were examined for C. difficile. PCR ribotyping was performed on toxin positive C. difficile isolates and the genetic profiles of the water and patient isolates were compared. RESULTS: Twelve toxin-positive C. difficile isolates were found in water samples: five from contaminated tap water and seven from treated sewage effluent. Among these, four and five distinct PCR ribotype profiles were identified, respectively. Four PCR ribotype profiles were found among nine human faecal C. difficile isolates. Two isolates, one from tap water and one from a patient, had an indistinguishable PCR ribotype profile. CONCLUSIONS: Our findings demonstrate for the first time C. difficile contamination of a tap water distribution system and waterborne transmission of toxigenic C. difficile seems possible.

Genomic epidemiology of nosocomial carbapenemase-producing Citrobacter freundii in sewerage systems in the Helsinki metropolitan area, Finland.

Multi-drug resistance is emerging in Citrobacter freundii, which is the third most common carbapenemase-producing (CP) Enterobacteriaceae in humans in Finland due to recent outbreaks. The objective of this study was to determine if wastewater surveillance (WWS) could detect CP C. freundii strains causing infections in humans. Selective culturing was used to isolate CP C. freundii from the hospital environment, hospital wastewater, and untreated municipal wastewater in Helsinki, Finland, between 2019 and 2022. Species were identified using MALDI-TOF, and presumptive CP C. freundii isolates were subjected to antimicrobial susceptibility testing and further characterized by whole genome sequencing. A genomic comparison was conducted to compare isolates collected from the hospital environment, untreated municipal wastewater, and a selection of isolates from human specimens from two hospitals in the same city. We also examined the persistence of CP C. freundii in the hospital environment and the impact of our attempts to eradicate it. Overall, 27 blaKPC - 2-carrying C. freundii were detected in the hospital environment (ST18; n = 23 and ST8; n = 4), while 13 blaKPC - 2-carrying C. freundii (ST8) and five blaVIM - 1-carrying (ST421) C. freundii were identified in untreated municipal wastewater. CP C. freundii was not identified in hospital wastewater. We found three clusters (cluster distance threshold ≤ 10 allelic difference) after comparing the recovered isolates and a selection of isolates from human specimens. The first cluster consisted of ST18 isolates from the hospital environment (n = 23) and human specimens (n = 4), the second consisted of ST8 isolates from the hospital environment (n = 4), untreated municipal wastewater (n = 6), and human specimens (n = 2), and the third consisted of ST421 isolates from the untreated municipal wastewater (n = 5). Our results support previous studies suggesting that the hospital environment could act as a source of transmission of CP C. freundii in clinical settings. Furthermore, the eradication of CP Enterobacteriaceae from the hospital environment is challenging. Our findings also showed that CP C. freundii is persistent throughout the sewerage system and demonstrate the potential of WWS for detecting CP C. freundii.

Carbapenemase-producing Enterobacteriaceae in Finland: the first years (2008-11).

OBJECTIVES: Carbapenemase-producing Enterobacteriaceae (CPE) are becoming a global problem; they are often resistant to nearly all available antibiotics. Here we report details on all Finnish CPE isolates found until the end of 2011: carbapenemase genes, travel history and multilocus sequence typing (MLST) data. METHODS: Enterobacteriaceae sent to the Antimicrobial Resistance Unit of the National Institute for Health and Welfare were tested for susceptibility to carbapenems, screened for carbapenemases by PCR and isolates with decreased susceptibility to carbapenems were tested for hydrolysis of imipenem. Carbapenemase-producing Escherichia coli and Klebsiella pneumoniae isolates were typed by MLST. RESULTS: In all, 26 CPE strains were found from 25 patients: 10 with OXA-48-like enzymes, 5 with KPC, 4 with VIM, 3 with NDM, 3 with IMI/NMC-A and 1 with GES-14. The species were K. pneumoniae (n = 16), E. coli (n = 6), Enterobacter cloacae (n = 3) and Raoultella planticola (n = 1). Of the 25 patients, 18 had a known travel history/hospital transfer from abroad. Local spread/transmission was suspected in 2011, but there were no hospital outbreaks. The K. pneumoniae multilocus sequence types ST258, ST182, ST147, ST244, ST14, ST13, ST383, ST101 and ST15, and the E. coli sequence types ST38 and ST90 were found. Many of these are global epidemic clones. CONCLUSIONS: CPE strains are increasingly found in Finland, but still at a very low prevalence.