Multidrug resistant Pseudomonas aeruginosa in Estonian hospitals.

BACKGROUND: We aimed to identify the main spreading clones, describe the resistance mechanisms associated with carbapenem- and/or multidrug-resistant P. aeruginosa and characterize patients at risk of acquiring these strains in Estonian hospitals. METHODS: Ninety-two non-duplicated carbapenem- and/or multidrug-resistant P. aeruginosa strains were collected between 27th March 2012 and 30th April 2013. Clinical data of the patients was obtained retrospectively from the medical charts. Clonal relationships of the strains were determined by whole genome sequencing and analyzed by multi-locus sequence typing. The presence of resistance genes and beta-lactamases and their origin was determined. Combined-disk method and PCR was used to evaluate carbapenemase and metallo-beta-lactamase production. RESULTS: Forty-three strains were carbapenem-resistant, 11 were multidrug-resistant and 38 were both carbapenem- and multidrug-resistant. Most strains (54%) were isolated from respiratory secretions and caused an infection (74%). Over half of the patients (57%) were ≥ 65 years old and 85% had ≥1 co-morbidity; 96% had contacts with healthcare and/or had received antimicrobial treatment in the previous 90 days. Clinically relevant beta-lactamases (OXA-101, OXA-2 and GES-5) were found in 12% of strains, 27% of which were located in plasmids. No Ambler class B beta-lactamases were detected. Aminoglycoside modifying enzymes were found in 15% of the strains. OprD was defective in 13% of the strains (all with CR phenotype); carbapenem resistance triggering mutations (F170 L, W277X, S403P) were present in 29% of the strains. Ciprofloxacin resistance correlated well with mutations in topoisomerase genes gyrA (T83I, D87N) and parC (S87 L). Almost all strains (97%) with these mutations showed ciprofloxacin-resistant phenotype. Multi-locus sequence type analysis indicated high diversity at the strain level - 36 different sequence types being detected. Two sequence types (ST108 (n = 23) and ST260 (n = 18)) predominated. Whereas ST108 was associated with localized spread in one hospital and mostly carbapenem-resistant phenotype, ST260 strains occurred in all hospitals, mostly with multi-resistant phenotype and carried different resistance genotype/machinery. CONCLUSIONS: Diverse spread of local rather than international P. aeruginosa strains harboring multiple chromosomal mutations, but not plasmid-mediated Ambler class B beta-lactamases, were found in Estonian hospitals. TRIAL REGISTRATION: This trial was registered retrospectively in ClinicalTrials.gov ( NCT03343119 ).

Prolonged outbreak of Serratia marcescens in Tartu University Hospital: a case-control study.

BACKGROUND: The aim of our study was to investigate and control an outbreak and identify risk factors for colonization and infection with Serratia marcescens in two departments in Tartu University Hospital. METHODS: The retrospective case-control study was conducted from July 2005 to December 2006. Molecular typing by pulsed field gel electrophoresis was used to confirm the relatedness of Serratia marcescens strains. Samples from the environment and from the hands of personnel were cultured. RESULTS: The outbreak involved 210 patients, 61 (29%) developed an infection, among them 16 were invasive infections. Multivariate analysis identified gestational age, arterial catheter use and antibiotic treatment as independent risk factors for colonization and infection with Serratia marcescens. Molecular typing was performed on 83 Serratia marcescens strains, 81 of them were identical and 2 strains were different. CONCLUSIONS: Given the occasionally severe consequences of Serratia marcescens in infants, early implementation of aggressive infection control measures involving patients and mothers as well as the personnel is of utmost importance.

Characteristics of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae and Contact to Animals in Estonia.

We have attempted to define the prevalence and risk factors of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-Enterobacteriaceae) carriage, and to characterize antimicrobial susceptibility, beta-lactamase genes, and major types of isolated strains in volunteers, with a specific focus on humans in contact with animals. Samples were collected from 207 volunteers (veterinarians, pig farmers, dog owners, etc.) and cultured on selective agar. Clonal relationships of the isolated ESBL-Enterobacteriaceae were determined by whole genome sequencing and multi-locus sequence typing. Beta-lactamases were detected using a homology search. Subjects filled in questionnaires analyzed by univariate and multiple logistic regression. Colonization with ESBL-Enterobacteriaceae was found in fecal samples of 14 individuals (6.8%; 95%CI: 3.75-11.09%). In multiple regression analysis, working as a pig farmer was a significant risk factor for ESBL-Enterobacteriaceae carriage (OR 4.8; 95%CI 1.2-19.1). The only species isolated was Escherichia coli that distributed into 11 sequence types. All ESBL-Enterobacteriaceae isolates were of CTX-M genotype, with the blaCTX-M-1 being the most prevalent and more common in pig farmers than in other groups. Despite the generally low prevalence of ESBL-Enterobacteriaceae in Estonia, the pig farmers may still pose a threat to transfer resistant microorganisms. The clinical relevance of predominant blaCTX-M-1 carrying E. coli is still unclear and needs further studies.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe.

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Surgical-site infections following cesarean section in an Estonian university hospital: postdischarge surveillance and analysis of risk factors.

OBJECTIVES: To evaluate a multi-method approach to postdischarge surveillance of surgical-site infections (SSIs) and to identify infection rates and risk factors associated with SSI following cesarean section. DESIGN: Cross-sectional survey. SETTING: Academic tertiary-care obstetric and gynecology center with 54 beds. PATIENTS: All women who delivered by cesarean section in Tartu University Women's Clinic during 2002. METHODS: Infections were identified during hospital stay or by postdischarge survey using a combination of telephone calls, healthcare worker questionnaire, and outpatient medical records review. SSI was diagnosed according to the criteria of the Centers for Disease Control and Prevention National Nosocomial Infections Surveillance System. RESULTS: The multi-method approach gave a follow-up rate of 94.8%. Of 305 patients, 19 (6.2%; 95% confidence interval [CI95], 3.8-9.6) had SSIs. Forty-two percent of these SSIs were detected during postdischarge surveillance. We found three variables associated with increased risk for developing SSI: internal fetal monitoring (odds ratio [OR], 16.6; CI95, 2.2-125.8; P = .007), chorioamnionitis (OR, 8.8; CI95, 1.1-69.6; P = .04), and surgical wound classes III and IV (OR, 3.8; CI95, 1.2-11.8; P = .02). CONCLUSIONS: The high response rate validated the effectiveness of this kind of surveillance method and was most suitable in current circumstances. A challenge exists to decrease the frequency of internal fetal monitoring and to treat chorioamnionitis as soon as possible.

Design and structure of the Estonian HIV Cohort Study (E-HIV).

BACKGROUND: Estonia is experiencing the new Eastern Europe human immunodeficiency virus (HIV) epidemic, with the highest incidence of new infections in the EU. We describe demographic changes, HIV-related laboratory parameters and co-infections during the concentrated HIV epidemic using the Estonian HIV Cohort Study (E-HIV) database, founded in 2009. METHODS: All 3750 subjects in the E-HIV database on December 31, 2013 were included. Subjects were divided into risk groups: people who inject drugs (PWIDs), sexual transmission (heterosexual/homosexual), and other (perinatal) or unknown risk group. Subjects diagnosed before 2009 (first period) and after (second period) were analyzed separately. RESULTS: The mean age at diagnosis has increased from 22.8 years (interquartile range (IQR) = 19.5-27.2) to 29.7 years (IQR = 25.3-36.2) (p < 0.001) between the first and second periods. PWIDs were younger than other transmission groups (23.2 vs 27.1; p < 0.001). There is a statistical difference in the route of transmission among genders, with overall increasing sexual transmission. The most common AIDS-defining illness was tuberculosis (0.5%). HIV/hepatitis C (HCV) co-infection was diagnosed in 42% of cases. The population median CD4 + cell count at diagnosis has declined over the years; in total 53% have been late presenters. Half of the patients are receiving antiretroviral treatment (cART). The most common combinations are nucleoside reverse transcriptase inhibitor (NRTI) backbone plus protease inhibitors (PIs) (57%) or NRTI backbone + non-NRTIs (42%). CONCLUSION: The E-HIV enables us to fill the gap in the lack of data on the course of the new Eastern European HIV epidemic. These data demonstrate that the HIV epidemic in Estonia is moving from PWIDs to the general population, suggesting that prevention measures and testing guidelines should be revised.