Aspects of the antimicrobial susceptibility of Streptococcus pyogenes, Streptococcus pneumoniae and Aerococcus urinae

Streptococcus pyogenes and Streptococcus pneumoniae are important human pathogens capable of causing invasive infections which need antimicrobial treatment. Aerococcus urinae is a rare and relatively unknown causative agent in invasive infections but its clinical importance is emerging. Antimicrobial susceptibility testing (AST) is a crucial method to study the usefulness of the clinically used antimicrobial drugs and to observe trends in the prevalence of the resistance or its emergence. This thesis project aimed to analyse the antimicrobial susceptibilities of S. pyogenes and S. pneumoniae towards commonly used antimicrobial drugs and to characterize both species to gain more understanding related to their resistance. The aim was also to study bacteraemic infections caused by A. urinae and to estimate the effectiveness of the given empiric cefuroxime treatment. In addition, the objective was to determine the in vitro susceptibility of A. urinae to benzylpenicillin, cefuroxime and ceftriaxone. Species identification was performed by latex agglutination (S. pyogenes), optochin susceptibility (S. pneumoniae) and/or MALDI-TOF MS (S. pneumoniae and A. urinae). Antimicrobial susceptibilities were determined by disk diffusion, gradient diffusion (Etest) and/or broth microdilution test (Sensititre) according to the EUCAST standards. S. pyogenes isolates were characterized by emm typing and resistance gene analysis was performed by multiplex PCR to detect ermB, ermTR, and/or mefA. S. pneumoniae isolates were serotyped. Clinical bacterial isolates were found from the laboratory database using WHONET or collected particularly for the study project. Clinical data from the patients were collected retrospectively. The patient catchment area was the Helsinki metropolitan area in southern Finland representing nearly a third of the Finnish population. Susceptibility and patient data were analysed statistically by SPSS. In this thesis project we described a skin and soft tissue infection epidemic in the adult population caused by macrolide and clindamycin resistant S. pyogenes emm33 in 2012–2013. Emm33 is a rare and previously unknown emm type in Finland. Epidemic S. pyogenes emm33, a putative clone, harboured the ermTR and expressed a constitutive MLSB phenotype but was susceptible to telithromycin. S. pyogenes emm33 was also susceptible to tetracycline, doxycycline, levofloxacin, moxifloxacin, and vancomycin. Studied patients were mainly 41–60 years old and bacteraemic patients often had alcoholism and/or intravenous drug abuse. The clinicians in the HUS district were informed about the epidemic and advised in empirical treatment choices. We studied the susceptibility patterns of invasive and non-invasive S. pneumoniae isolates in 2009–2014 and showed that S. pneumoniae non-susceptibility to clinically important antimicrobial agents decreased significantly in the Helsinki metropolitan area during the four years after the 10-valent pneumococcal conjugate vaccinate (PCV10) implementation in 2010. This trend was seen especially in non-invasive isolates from <5 years old patients, where non-susceptibility decreased towards penicillin, erythromycin, clindamycin, tetracycline, and trimethoprim–sulfamethoxazole. The proportion of multidrug resistant (MDR) isolates decreased also significantly from 22% in 2009 to 6% in 2014 among these patients. S. pneumoniae serotype distributions showed that the number of the PCV10 serotypes decreased among invasive isolates. In contrast, the non-PCV10 serotypes increased among invasive isolates from ≥5 years old patients and of these, serotypes 19A (38%), 3 (13%), and 6A (13%) were the most frequent. Especially 19A is associated with high prevalence of resistance therefore making the continuous surveillance of pneumococcus essential. We retrospectively studied 141 clinical A. urinae isolates and the clinical data of 77 patients with bacteraemic A. urinae infection from 2013–2018. All A. urinae isolates were susceptible to benzylpenicillin (S ≤0.125, EUCAST breakpoints for aerococci) and cefuroxime (S ≤4, EUCAST PK/PD breakpoints) but 2–3% were resistant to ceftriaxone (R >2, EUCAST PK/PD breakpoints). Bacteraemic A. urinae patients were primarily elderly men harbouring several comorbidities. All but one patient was given antimicrobial therapy and the response was mainly good based on decreased fever and CRP. Thirty-day mortality was 17% and patients who died were on average older compared to survivors. Cefuroxime was the first empiric antimicrobial agent given to 87% of the patients and it was given equally often to patients who survived and did not survive. There were no differences between the cefuroxime MIC values of the survivors versus non-survivors. Based on these findings, A. urinae was clinically susceptible in vitro to cefuroxime and furthermore, empiric cefuroxime treatment likely covers bacteraemic infections caused by A. urinae. The results of this study made A. urinae more familiar to HUS district physicians and have improved the treatment of bacteraemic A. urinae patients.Streptococcus pyogenes eli A-ryhmän streptokokki ja Streptococcus pneumoniae eli pneumokokki ovat merkittäviä ihmisen taudinaiheuttajabakteereita. Ne voivat aiheuttaa vakavia infektioita, joiden hoitoon tarvitaan mikrobilääkkeitä. Aerococcus urinae on harvinainen ja melko tuntematon bakteeri, mutta sen merkitys taudinaiheuttajana on kasvamassa. Mikrobilääkeherkkyysmääritys on keskeinen menetelmä mikrobilääkkeiden hyödyllisyyden selvittämisessä sekä mikrobilääkkeille vastustuskykyisten eli resistenttien bakteerien esiintyvyyden ja resistenssin ilmaantuvuuden seurannassa. Tämän väitöskirjan tavoitteena oli analysoida A-ryhmän streptokokin ja pneumokokin herkkyyttä yleisesti käytetyille mikrobilääkkeille ja tutkia molempia lajeja tarkemmin resistenssiin liittyvien ilmiöiden ymmärtämiseksi. Lisäksi tavoitteena oli tutkia A. urinae -bakteerin aiheuttamia vakavia infektioita sekä niiden hoidossa käytetyn kefuroksiimi-mikrobiläkkeen käyttökelpoisuutta. Kliiniset bakteerikannat haettiin laboratorion tietokannasta tai kerättiin tätä väitöskirjaprojektia varten. Bakteerilajit tunnistettiin ja niiden mikrobilääkeherkkyydet tutkittiin yleisesti hyväksytyillä menetelmillä. Tiedot potilaista haettiin takautuvasti potilastietokannoista. Potilaat olivat kotoisin Helsingin seudulta, joka kattaa noin kolmanneksen koko Suomen väestöstä. Tässä väitöskirjassa kuvattiin makrolidi- ja klindamysiiniresistentin A-ryhmän streptokokin aiheuttama iho- ja pehmytkudosinfektioiden epidemia aikuisväestössä vuosina 2012–2013. Epidemian aiheutti harvinainen ja Suomessa aiemmin tuntematon emm33-tyyppi. HUS-alueen kliinikoita ohjeistettiin välttämään klindamysiinin käyttöä ainoana empiirisenä mikrobilääkkeenä iho- ja pehmytkudosinfektioiden hoidossa. Tutkimme pneumokokin mikrobilääkeherkkyydet vuosilta 2009–2014 ja havaitsimme, että herkkyystilanne Helsingin seudulla on merkittävästi parantunut rokotusohjelmaan vuonna 2010 käyttöönotetun 10-valenttisen pneumokokkikonjugaattirokotteen myötä. Rokotteeseen kuulumattomien pneumokokkiserotyyppien määrä kuitenkin kasvoi tutkimusajanjaksolla, minkä vuoksi pneumokokin herkkyystilannetta tärkeää seurata jatkuvasti. Tutkimme A. urinae -bakteerikantojen mikrobilääkeherkkyyksiä ja vakavaan A. urinae -infektioon sairastuneiden potilaiden kliinisiä tietoja vuosilta 2013–2018. A. urinae -kannat olivat herkkiä kefuroksiimille. Potilaat olivat suurelta osin ikääntyneitä miehiä, joilla oli useita oheissairauksia. Potilaiden vaste mikrobilääkehoidolle oli pääasiassa suotuisaa. Tutkimustulostemme perusteella kefuroksiimi soveltuu tiettyjen vakavien A. urinae -bakteerin aiheuttamien infektioiden empiiriseen hoitoon

Mikrobilääkkeille resistentit bakteerit yleistyvät

English summaryPeer reviewe

Clinical and microbiological characterization of Aerococcus urinae bacteraemias at Helsinki metropolitan area, Finland

Our objective was to assess the incidence of bacteraemic Aerococcus urinae cases at Helsinki metropolitan area, Finland, from a 6-year study period (2013 to 2018) and to further characterize available cases. The study evaluates the outcome of commonly used cefuroxime treatment and determinate a set of A. urinae in vitro antimicrobial susceptibilities for benzylpenicillin, cefuroxime, and ceftriaxone. Clinical records of A. urinae bacteraemic patients were reviewed retrospectively. Antimicrobial susceptibility testing was performed by disk diffusion, gradient test, and broth microdilution for 139-141 clinical A. urinae isolates. Clinical data of 72/77 patients were combined with the in vitro susceptibilities. We found an increasing number of bacteraemic A. urinae cases within 6-year study period (p = 0.01). The patients were mainly elderly males, and all suffered from underlying conditions. A total of 27.3% of cases (21/77) showed polymicrobial blood cultures. Thirty-day mortality was 22.1%. Cefuroxime was the initial empiric antimicrobial agent given for 66/76 of the patients and treatment outcome was favorable for 20/22 patients who received cefuroxime at least up to day 5. All isolates were susceptible to benzylpenicillin and cefuroxime interpreted by EUCAST breakpoints for Aerococci and PK-PD breakpoints, respectively. MIC determinations gave variable results for ceftriaxone, 2.1-2.9% of the isolates were resistant. To conclude, it seems that the number of bacteraemic Aerococcus urinae cases is increasing at Helsinki metropolitan area, Finland, reflecting the growing blood culture sampling. Clinical A. urinae isolates were susceptible to cefuroxime in vitro. Treatment data indicate that empirical cefuroxime started for possibly urinary tract -derived community-acquired bacteraemia covers A. urinae.Peer reviewe

Efficacy of a multicomponent singing intervention on communication and psychosocial functioning in chronic aphasia: A randomized controlled crossover trial

The ability to produce words through singing can be preserved in severe aphasia, but the benefits of group-based singing rehabilitation in aphasia are largely unknown. Our aim was to determine the efficacy of a multicomponent singing intervention on communication and speech production, emotional-social functioning and caregiver well-being in aphasia. Fifty-four patients with acquired brain injury and chronic aphasia and their family caregivers (n = 43) were recruited. Using a crossover randomized controlled trial design, participants were randomized to two groups who received a 4-month singing intervention either during the first or second half of the study in addition to standard care. The intervention comprised weekly group-based training (including choir singing and group-level melodic intonation therapy) and tablet-assisted singing training at home. At baseline, 5- and 9-month stages, patients were assessed with tests and questionnaires on communication and speech production, mood, social functioning, and quality of life and family caregivers with questionnaires on caregiver burden. All participants who participated in the baseline measurement (n = 50) were included in linear mixed model analyses. Compared with standard care, the singing intervention improved everyday communication and responsive speech production from baseline to 5-month stage, and these changes were sustained also longitudinally (baseline to 9-month stage). Additionally, the intervention enhanced patients’ social participation and reduced caregiver burden. This study provides novel evidence that group-based multicomponent singing training can enhance communication and spoken language production in chronic aphasia as well as improve psychosocial wellbeing in patients and caregivers.Peer reviewe

Clinical and microbiological characterization of Aerococcus urinae bacteraemias at Helsinki metropolitan area, Finland

Our objective was to assess the incidence of bacteraemic Aerococcus urinae cases at Helsinki metropolitan area, Finland, from a 6-year study period (2013 to 2018) and to further characterize available cases. The study evaluates the outcome of commonly used cefuroxime treatment and determinate a set of A. urinae in vitro antimicrobial susceptibilities for benzylpenicillin, cefuroxime, and ceftriaxone. Clinical records of A. urinae bacteraemic patients were reviewed retrospectively. Antimicrobial susceptibility testing was performed by disk diffusion, gradient test, and broth microdilution for 139-141 clinical A. urinae isolates. Clinical data of 72/77 patients were combined with the in vitro susceptibilities. We found an increasing number of bacteraemic A. urinae cases within 6-year study period (p = 0.01). The patients were mainly elderly males, and all suffered from underlying conditions. A total of 27.3% of cases (21/77) showed polymicrobial blood cultures. Thirty-day mortality was 22.1%. Cefuroxime was the initial empiric antimicrobial agent given for 66/76 of the patients and treatment outcome was favorable for 20/22 patients who received cefuroxime at least up to day 5. All isolates were susceptible to benzylpenicillin and cefuroxime interpreted by EUCAST breakpoints for Aerococci and PK-PD breakpoints, respectively. MIC determinations gave variable results for ceftriaxone, 2.1-2.9% of the isolates were resistant. To conclude, it seems that the number of bacteraemic Aerococcus urinae cases is increasing at Helsinki metropolitan area, Finland, reflecting the growing blood culture sampling. Clinical A. urinae isolates were susceptible to cefuroxime in vitro. Treatment data indicate that empirical cefuroxime started for possibly urinary tract -derived community-acquired bacteraemia covers A. urinae.</p

Neuroanatomical correlates of speech and singing production in chronic post-stroke aphasia

A classical observation in neurology is that aphasic stroke patients with impairments in speech production can nonetheless sing the same utterances. This preserved ability suggests a distinctive neural architecture for singing that could contribute to speech recovery. However, to date, these structural correlates remain unknown. Here, we combined a multivariate lesion–symptom mapping and voxel-based morphometry approach to analyse the relationship between lesion patterns and grey matter volume and production rate in speech and singing tasks. Lesion patterns for spontaneous speech and cued repetition extended into frontal, temporal and parietal areas typically reported within the speech production network. Impairment in spontaneous singing was associated with damage to the left anterior–posterior superior and middle temporal gyri. Preservation of grey matter volume in the same regions where damage led to poor speech and singing production supported better performance in these tasks. When dividing the patients into fluent and dysfluent singers based on the singing performance from demographically matched controls, we found that the preservation of the left middle temporal gyrus was related to better spontaneous singing. These findings provide insights into the structural correlates of singing in chronic aphasia and may serve as biomarkers to predict treatment response in clinical trials using singing-based interventions for speech rehabilitation.Peer reviewe

Obesity and smoking are factors associated with poor prognosis in patients with bacteraemia

BACKGROUND: Bacteraemia is still a major cause of case fatality in all age groups. Our aim was to identify the major underlying conditions constituting risk factors for case fatality in bacteraemia patients. METHODS: The study involved 149 patients (79 male and 70 female) with bacteraemia caused by Staphylococcus aureus (S. aureus) (41 patients), Streptococcus pneumoniae (Str. pneumoniae) (42 patients), β-hemolytic streptococcae (β-hml str.) (23 patients) and Eschericia coli (E. coli) (43 patients). Underlying diseases, alcohol and tobacco consumption and body mass index (BMI) were registered. Laboratory findings and clinical data were registered on admission and 6 consecutive days and on day 10–14. Case fatality was studied within 30 days after positive blood culture. Associations between underlying conditions and case fatality were studied in univariate analysis and in a multivariate model. RESULTS: Nineteen patients (12.8%) died of bacteraemia. We found obesity (p = 0.002, RR 9.8; 95% CI 2.3 to 41.3), smoking (p < 0.001, RR 16.9; 95% CI 2.1 to 133.5), alcohol abuse (p = 0.008, RR 3.9; 95% CI 1.3 to 11.28), COPD (p = 0.01, RR 8.4; 95% CI 1.9 to 37.1) and rheumatoid arthritis (p = 0.045, RR 5.9; 95% CI 1.2 to 28.8) to be significantly associated with case fatality in bacteraemia in univariate model. The median BMI was significantly higher among those who died compared to survivors (33 vs. 26, p = 0.003). Obesity and smoking also remained independent risk factors for case fatality when their effect was studied together in a multivariate model adjusted with the effect of alcohol abuse, age (continuos variable), sex and causative organism. CONCLUSION: Our results indicate that obesity and smoking are prominent risk factors for case fatality in bacteraemic patients. Identification of risk factors underlying fatal outcome in bacteraemia may allow targeting of preventive efforts to individuals likely to derive greatest potential benefit

"Kaze no naka de sodatta ki wa ne ga tsuyoi" - "Tuulessa kasvavilla puilla on vahvat juuret" : suomalaisen ja japanilaisen sijaishuollon eroja ja yhtäläisyyksiä

Tämän opinnäytetyön tavoitteena on vertailla suomalaisen ja japanilaisen sijaishuollon eroja ja yhtäläisyyksiä ja sitä, millaisia vaikutuksia kulttuurilla on lastensuojelutyöhön. Tutkimuksen taustalla on molempien maiden kiinnostus lastensuojelutyön kehittämiseen sekä aiheen ajankohtaisuus molemmissa yhteiskunnissa. Tutkimus on toteutettu lyhytvaihtona Japanissa ja on osa SOCPEDA-projektia (Empowering Social Pedagogic Child Welfare Training in Finland and Japan 2017–2019). Tutkimuksen tietoperustana on suomalaisen sijaishuollon lainsäädäntö ja suomalaisen lastenkotityön arki ja työkäytännöt, joiden pohjalta vertailu on toteutettu. Tutkimus on laadullinen tutkimus ja tutkimusmenetelminä on käytetty havainnointia, etnografiaa ja haastattelua. Tulokset on analysoitu keskustelemalla. Tutkimuksen tulosten mukaan suomalainen ja japanilainen sijoitusprosessi sekä lastenkotien arki ovat samankaltaisia. Molemmissa maissa sijoituksen tarkoituksena on turvata lapsen kasvu ja kehitys sekä tarjota turvalliset kasvuolosuhteet. Lasten sijoitukseen johtavat syyt sekä lasten ja perheiden ongelmat ovat samanlaisia molemmissa maissa, minkä vuoksi myös lasten tarvitsema tuki ja arki ovat samanlaista. Sekä Japanissa että Suomessa lastenkodeissa tehdään perhetyötä ja yhtenä tärkeänä tavoitteena on perheen jälleenyhdistäminen. Tutkimuksen tulosten perusteella Suomessa sijaishuollon perhetyötä tehdään suunnitelmallisemmin. Väkilukuun suhteutettuna Japanissa on sijoitettuja lapsia ja lastenkoteja huomattavasti vähemmän kuin Suomessa. Molemmissa maissa tavoitteena on, että lapset sijoitettaisiin ensisijaisesti perheisiin. Japanissa suurin osa sijoitetuista lapsista asuu kuitenkin lastenkodeissa ja Suomessa yli puolet lapsista on perhehoidossa. Tutkimuksen tulosten mukaan sijaishuollon ja lastensuojelutyön suurimmat erot maiden välillä tulevat kulttuurin ja yhteiskunnan rakenteiden kautta. Japanissa lasten kasvatus on yhteisön vastuulla, kun taas Suomessa lapsen kasvatuksesta vastaavat ensisijaisesti huoltajat ja tarvittaessa viranomaiset. Japanilainen häpeäkulttuuri tuo haasteita perheiden ongelmien esiin nostamisessa ja niihin puuttumisessa. Suomessakin on paljon puhumattomuutta, mutta lastensuojelutyön ammattilaiset uskaltavat kuitenkin puuttua perheiden ongelmiin. Japanilainen perhekäsitys on laajempi kuin suomalainen ja perheen sekä suvun merkitys korostuvat Japanissa.The aim of this thesis is to compare the differences and similarities between Finnish and Japanese foster care and the impact of culture on child welfare work. There is interest for developing child welfare work both Finland and Japan. Child welfare and foster care are current topics in both societies. The research has been carried out in the exchange and it is part of SOCPEDA-project (Empowering Social Pedagogic Child Welfare Training in Finland and Japan 2017–2019). The research and comparison are based on Finnish Child Welfare Act and working practices and everyday life in Finnish children’s homes. This thesis is a qualitative research and observation, ethnography and interviews have been used as the research methods. The results have been analyzed by discussing. Based on the results it can be concluded that the Finnish and Japanese process of taking child into care and everyday life in foster care are similar. In both countries, the purpose of taking child into care is to secure the child’s growth and development and to provide safe growth milieu of a child. The reasons of placements and the problems of children and their families are similar in both countries, so children need similar support and everyday life. Both in Japan and Finland, one goal is to reunite the family, therefore family work is important part of working in children’s home. On the other hand, family work is more methodical in Finnish foster care. In Japan there is less children’s homes and children in foster care commensurate with population than in Finland. In both countries aim is to place children in foster families but in Japan most children live in children’s homes. In Finland over half of children live in foster family. Based on the results of the research, it can be concluded that culture and societies’ structures create the biggest differences between countries in foster care and child welfare work. In Japan, community has the responsibility for upbringing of children while in Finland parents have the responsibility and ultimately authorities have the responsibility if necessary. Japanese shame culture brings challenges to raise and concern the problems of families. In Finland, there is a lot of speechlessness but nevertheless, child welfare professionals do interventions. In Japan, the concept of family is broader, and family is more important in Japan than in Finland

Toiminnallisuutta kokonaisvaltaisen hyvinvoinnin tukemiseksi – harjoitteita kuntouttavaan työtoimintaan : sosiaalipalvelusäätiö Ote sr:n henkilökunnan työkalu

Opinnäytetyöprosessimme tavoitteena oli luoda Ote-säätiölle kuntouttavaan työtoimintaan toiminnallisia harjoitteita sisältävä opas Ote-säätiön henkilökunnalle. Tuotoksemme oli työkalu, jota voidaan käyttää hyödyksi asiakkaiden kokonaisvaltaisen hyvinvoinnin tukemisessa. Prosessissamme oli neljä vaihetta; ideointi-/aloitusvaihe, suunnitteluvaihe ja sitoutuminen, toteuttamisvaihe sekä kirjoitus- ja tiedotusvaihe. Prosessimme alussa perehdyimme kuntouttavaan työtoimintaan sekä Ote-säätiöön, sekä ihmisen kokonaisvaltaiseen hyvinvointiin. Tämän jälkeen loimme alustavan suunnitelman, jonka kävimme läpi toimeksiantajamme kanssa.Seuraavassa vaiheessa suunnittelimme ja ohjasimme kaiken kaikkiaan neljä toiminnallista ryhmätuokiota. Näiden ohjausten teemoina, sekä koko opinnäytetyömme perustana, toimi ihmisen kokonaisvaltainen hyvinvointi, jonka olimme jakaneet neljään osa-alueeseen: sosiaalinen hyvinvointi, liikunta, ravinto sekä sosiaalinen hyvinvointi. Kehittämismenetelminämme käytimme osallistuvaa havainnointia sekä tarkkailua. Näiden menetelmien avulla muovasimme lopputuotoksemme digitaalisen harjoiteoppaan. Sisällytimme oppaaseen myös liitteenä apukysymyksiä, joiden avulla asiakkaan kehitystä voi seurata.Koimme opinnäyteprosessimme olevan kaiken kaikkiaan onnistunut kokonaisuus, ja olemme tyytyväisiä kehittämistyöhömm

Shiga toxin-producing Escherichia coli (STEC) stool multiplex PCR can replace culture for clinical diagnosis and follow-up

Shiga toxin (stx)-producing Escherichia coli (STEC) causes potentially severe gastrointestinal infections. Due to its public health importance, control measures are required, and carriers may need to refrain from work or daycare when the risk of spread to vulnerable people is high. We evaluated the use of direct stool multiplex PCR compared to culture for primary STEC diagnostics and for follow-up in order to update the national guidelines for STEC monitoring. We analyzed primary and follow-up samples of 236 STEC PCR-positive cases at HUSLAB, Helsinki, Finland in 2016-2017, altogether 858 samples. All STEC PCR-positive samples were inoculated on non-selective chromogenic agar plates. Culture positivity was confirmed from culture sweeps by PCR. 211 (89%) of the cases were culture positive in their primary sample. Of all primary and follow-up samples, 499 were PCR positive and of these 450 (90%) were culture positive. PCR-negative follow-up samples were available from 125 cases. Of these, 88 cases were followed for at least three consecutive PCR-negative samples. Two cases (2%) had culture-positive sample(s) after two consecutive PCR-negative samples. The median time for STEC clearance was 22-23 days. The laboratory-developed multiplex PCR test used in this study is a reliable method for STEC diagnostics and follow-up in a clinical laboratory. When non-selective methodology is used, the majority of PCR-positive samples (90%) are also culture positive. Furthermore, only two cases (2%) in our material had two consecutive PCR-negative samples followed by positive samples. Consequently, to demonstrate the clearance from STEC infection, we consider two PCR-negative follow-up samples sufficient. The Finnish national guidelines for STEC monitoring have been updated accordingly.Peer reviewe