Poster

70 Sequence types of Staphylococcus epidermidis associated with prosthetic joint infections are not present in the laminar flow during prosthetic joint surgery(Emeli Månsson)

71 Genotypic relatedness between clinical and environmental isolates of Staphylococcus pettenkoferi(Emeli Månsson)

72 Jämförelse av fem olika metoder för påvisande av toxinproducerande C. difficile(Emeli Månsson)

74 Assessing cervical intraepithelial neoplasia as an indicator disease for HIV in a low endemic setting: a population-based register study(Christina Carlander)

75 Suppressive art associated with effective treatment of cervical precancer(Christina Carlander)

76 High incidence of high-grade cervical neoplasia among HIV-infected immigrants: a population based cohort study (Christina Carlander)

78 PCR with electrospray ionization-mass spectrometry on bronchoalveolar lavage for detection of invasive mold infections in hematological patients(Anders Krifors)

79 Rätt val av trumhinnerör minskar komplikationsrisken(Johan Knutsson)

80 Infektionsfokus och etiologi vid neutropen feber i Västmanland(Torbjörn Larsson)

81 Erfarenheter från 5 års användande av Xpert MTB/RIF i Västmanland(Ingrid Selmeryd)

82 Staphylococcus aureus bacteremia in patients with cardiac implantable electronic devices (Jonas Selmeryd)

83 Risk factors for severe malaria in travellers and migrants(Andreas Wångdahl)

Postrar 70 – 83

Sequence types of Staphylococcus epidermidis associated with prosthetic joint infections are not present in the laminar flow during prosthetic joint surgery

Conclusion:  Micrococcus  luteus  and  coagulase-­‐nega-ve  staphylococci  cons-tuted  the  majority  of  iden-fied  microorganisms  in  the  laminar  air  flow  in  the  opera-ng  room  during  prosthe-c  joint  surgery.    ST2  and  ST215  of  S.  epidermidis  were  not  found  to  be  present  in  the  laminar  air  flow  and  other  

routes  of  transmission  of  these  healthcare-­‐associated  strains  thus  seems  more  probable.  

E.Månsson  1,2,  B.Hellmark  3,  M.Sundqvist  3,  B.Söderquist  1,3    1.  Örebro  University,  Sweden    2.  Center  of  clinical  research,  Västmanland  county  hospital,  Sweden  3.  Dept  of  microbiology,  Örebro  university  hospital,  Sweden  

Introduction

Materials and Methods

Correspondence

ResultsStaphylococcus  epidermidis  is  a  ubiquitous  skin  commensal,  but  also  a  common  cause  of  prosthe-c  joint  infec-ons  (PJIs).    Molecular  characteriza-on  of  S.  epidermidis  has  indicated  that  pa-ents  acquire  specific  healthcare-­‐associated,  mul--­‐drug  resistant  strains  (ST2  and  ST215)  that  cause  PJIs  and  that  these  differs  from  commensal  isolates.  Our  aim  was  to  inves-gate  if  such  strains  could  be  iden-fied  in  the  laminar  air  flow  (LAF)  in  the  opera-ng  room  during  prosthe-c  joint  surgery.  !

Air  sampling  was  performed  with  ac-ve  technique  (Sartorius  MD8  AirScan)  during  17  hip/knee  arthroplas-es  at  Västmanlands  sjukhus,  Västerås,  Sweden  from  November  2010  to  January  2011.  A  filter  was  placed  in  the  LAF  in  close  proximity  to  the  wound  and  was  replaced  acer  each  m3  air  sampled  (=  every  10  min).  Filters  were  immediately  placed  on  Mueller  Hinton  agar  and  incubated  overnight.  The  CFU  per  filter  was  calculated  and  isolates  were  subsequently  stored  at  –70°C.    Species  iden-fica-on  was  performed  using  MALDI-­‐TOF  MS  (Bruker  Daltonics).  When  no  reliable  result  was  obtained,  extrac-on  was  performed  and  MALDI-­‐TOF  MS  was  repeated.  Isolates  iden-fied  as  S.  epidermidis  was  further  characterized  by  mul-  locus  sequence  typing  (MLST)  and  an-bio-c  suscep-bility  tes-ng  using  EUCAST  methodology.  

Sequence  types  and  antibiotic  susceptibility  patterns  for  S.  epidermidis  (n=32)  

732042086867

54617054754754754754713013032454822754913027855055154722754754754722755054552

Cefoxi-n

Fucidic

 acid

Clindam

ycin

Erythrom

ycin

Genta

micin

Norflo

xacin

TMP-­‐S

MX

Rifam

picin

ST

Red  =  isolate  resistant.  Black  =  MecA  posi-ve

MALDI-­‐TOF  analysis  of  n=735  isolatesMicrococcus  sp. 303Coagulase  nega-ve  staphylococci 217Corynebact  sp. 37Staphylococcus  sp. 29Kocuria  sp. 17Dietzia  sp 9Stenotrophomonas  maltophilia 7Brevibacterium  sp 5Arthrobacter  sp 5Dermacoccus  sp 5Miscellanous 33No  reliable  ID 68

MALDI-­‐TOF  MS  resulted  in  accurate  species-­‐level  iden-fica-on  (score  ≥  2,0) of  543/735  isolates  (74%).  In  addi-on,  124  isolates  were  iden-fied  to  genus  level.  

All  but  one  S.  epidermidis  (n=32)  isolate  were  sensi-ve  to  cefoxi-n.  MLST  of    S.  epidermidis  demonstrated  18  different  sequence  types,  but  no  ST2  or  ST215.  

Emeli  Månsson  (MD):  emeli.mansson@ltv.se

A BC RF

Gel-like image

CONCLUSION

S. pettenkoferi should most often be regarded as a contamination in blood

cultures. Isolates obtained from the air of the operation room and blood culture

isolates are genetically related, implicating a common origin, probably human

skin flora. The significance of this species in clinical samples must be judged

together with clinical information.

Genotypic relatedness between clinical and environmental isolates of Staphylococcus pettenkoferi

Emeli Månsson1,2, Bengt Hellmark1, Martin Sundqvist1, Bo Söderquist1

1) School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Sweden; 2) Centre for Clinical Research, Uppsala University, County Hospital, Västerås, Sweden.

BACKGROUND

Staphylococcus pettenkoferi was first proposed as

a novel staphylococcal species in 2002. Species

identification of S. pettenkoferi in clinical practice

has become straightforward with MALDI-TOF MS,

and hence reporting of this novel staphylococcal

species is believed to increase. Case reports of S. pettenkoferi infections include osteomyelitis, blood

stream infections in immunocompromised hosts and

bursitis, but little is known about the ecological niche

of S. pettenkoferi. We investigated the genotypic relatedness and

antibiotic susceptibility profiles of 25 isolates of S. pettenkoferi, collected from blood cultures and intra-

operative air sampling, to further characterize this

species.

MATERIALS & METHODS

The clinical isolates (n=16) originated from blood

cultures at the Departments of Clinical Microbiology

in Växjö and Örebro (Sweden), and from the

worldwide SENTRY Antimicrobial Surveillance

Program (JMI Laboratories). The microbiological

relevance of the isolates was determined as significant

if S. pettenkoferi was isolated from ≥ 2 blood culture

bottles. The environmental isolates were collected by

active air sampling during prosthetic joint surgery at

the Department of Orthopaedics, Västerås (Sweden).

Species identification of clinical and

environmental isolates was performed using MALDI-

Fig 1. DiversiLab rep-PCR profiles of 26 S. pettenkoferi isolates. Profiles and corresponding dendrogram obtained using Kullback-Leibner method for correlation analysis. The similarity line (95%) is presented as a light grey vertical line. Each color represents a single pattern (indistinguishable profiles).

RESULTS

Key

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

50 60 70 80 90 100

% similarity

Pattern Alternate id

1 Vasteras 17:2

1 Vasteras 17:1

8 CCUG51270

3 JMI 16

3 JMI 15

4 Vaxjo 9

4 Vaxjo 6

9 Vaxjo 2

10 Vasteras 18:1

12 Vaxjo 3

11 Vaxjo 8

13 Vaxjo 5

14 Vaxjo 12

15 Vaxjo 13

5 Vaxjo 1

5 Vaxjo 11

6 Vasteras 17:5

6 Vasteras 17:3

16 Vaxjo 4

7 Vasteras 17:6

7 Vasteras 17:7

7 Vasteras 17:8

7 Vaxjo 10

17 Vasteras 17:4

18 Orebro 14

19 Vaxjo 7

Source

Air

Air

Ref. strain

Blood culture

Blood culture

Blood culture

Blood culture

Blood culture

Air

Blood culture

Blood culture

Blood culture

Blood culture

Blood culture

Blood culture

Blood culture

Air

Air

Blood culture

Air

Air

Air

Blood culture

Air

Blood culture

Blood culture

Fig 2. Scatter plot of 26 S. pettenkoferi isolates. Each isolate is represented by its number corresponding to the DL profile, as presented in Fig. 1 (“key”). Color represents different origin of isolates (blue = air sampling, green = blood culture, pink = reference strain).

SCATTERPLOT. Gridline spacing: 5 % similarity.

Source: Air Blood culture Ref. strain

TOF MS (Bruker Daltonics) and verified by rpoB gene sequencing. Repetitive-sequence-based PCR was

performed using the DiversiLab Staphylococcus DNA

fingerprinting kit (bioMérieux) with the inclusion

of reference strain CCUG 51270 T. Antibiotic

susceptibility testing was performed with EUCAST-

methodology. In addition all isolates were tested for

presence of the mecA gene using a real-time PCR

system (Light Cycler 2.0)

Only two of the clinical isolates were isolated from

2 blood culture bottles, and hence regarded as

clinically significant findings; Vaxjo_9 and Orebro_14.

Repetitive-sequence-based PCR demonstrated close

relatedness of these isolates to both non-significant

blood culture isolates and to environmental isolates

(Fig. 1 and Fig. 2). Antibiotic susceptibility testing

demonstrated over-all low level of antimicrobial

resistance. The mecA gene was present in two out of

three cefoxitin-resistant isolates.

CORRESPONDENCE emeli.mansson@ltv.se

CL

UST

ER

A

CL

UST

ER

B

26 9

14

1 3

1 1 12

1 0

Cluste r B

23 22 2 5 16

21 7

Clus ter A

20 6

24 19 1 8 17 4 1 2 3

8

15 5

Material och metod27 fecesprov från 26 patienter med frågeställning Clostridium difficile anlayseradesmed:• ImmunoCard (immunkromatografisktsnabbtest från Meridian Diagnostics)

• PREMIER Cl difficile Toxins A&B (EIA frånMeridian Diagnostics)

• GeneXpert, Xpert C.difficile (realtids-PCR från Cepheid)

• C.DIFF CHEK –60 (glutamatdehydrogenas, GDH, EIA från TechLab)

• Odling på CCFA med efterföljande toxintest (PREMIER Cl difficile Toxins A&B)

Prov:

ImmunoCard

(Meridian Diagnostics)

GeneXpert, Xpert

C.difficile (Cepheid)

PREMIER Toxins A&B

(Meridian Diagnostics)

C. DIFF CHEK-60

(Techlab)

Odling

(CCFA)

PREMIER

Toxins A&B

(Meridian

Diagnostics)

1 neg neg neg neg

2 neg neg pos pos

3 neg neg neg neg

4 neg neg neg neg

5 neg neg neg neg

6 neg neg neg neg

7 neg neg neg neg

8 neg neg neg neg växt neg

9 neg neg neg neg växt neg

10 neg neg neg neg

11 pos pos pos pos växt pos

12 neg neg neg pos

13 neg neg neg neg

14 neg neg neg pos växt neg

15 pos pos neg pos växt pos

16 pos pos pos pos växt pos

17 neg neg pos pos växt neg

18 neg neg pos pos

19 neg pos pos pos växt pos

20 pos pos pos pos växt pos

21 neg neg pos neg

22 pos pos pos pos växt pos

23 neg neg pos neg

24 pos pos pos pos växt ej utförd

25 pos pos pos pos växt pos

26 neg pos pos pos växt pos

27 pos pos pos pos växt pos

Cut off 0,150 Cut off 0,08

neg

neg

neg

neg

neg

neg

neg

neg

neg

neg

neg

neg

neg

1,192

0,083

3,014 3,035

0,496 3,347

0,246 0,315

0,989 3,176

2,849 3,052

0,746 0,005

2,291 3,062

0,280 0,014

1,758 2,991

2,780 3,083

0,331 3,013

2,851 3,328

3,135

2,615 3,081

0,138

0,461 0,106

Jämförelse av fem olika metoder för påvisande av toxinproducerande C. difficile

Emeli Månsson, Infektionskliniken Västerås, Magnus Thore Mikrobiologen Västerås och Smittskyddsinstitutet

BakgrundVid mikrobiologiska laboratoriet i Västerås analyseras fecesprov med frågeställning Clostridium difficile med ELISA toxintest samt odling på CCFA. Vid akuta frågeställningar främst helgtid finns snabbtest tillgängligt.

Behandlande läkare upplever att det ibland krävs många fecesprov innan toxinproducerande Clostridium difficile kan påvisas. Det finns även ett önskemål om ett snabbtest med högre diagnostisk träffsäkerhet.

Syftet med denna undersökning var att som ett pilotprojekt jämföra befintlig metodik med en ny kommersiell PCR-metod för påvisande av toxingener och en ELISA test för påvisning av Clostridium difficile antigen.

Resultat och diskussionRealtids-PCR är en enkel och snabb metod som förefaller ha mycket god sensitivitet och specificitet (100% överensstämmelse med odling och toxintest). GDH-ELISA förefaller också ha hög sensitivitet, dock var två fecesprovnegativa i GDH-ELISA där växt påvisades på CCFA. Snabbtestet förefaller ha god specificitet men något sämre sensitivitet (samtliga fecesprov som utföll positiva i snabbtest (n=8) var även positiva i PCR och GDH-ELISA, däremot var 2/19 negativa prov senare positiva i realtids-PCR, toxin-ELISA, GDH-ELISA och odling).

SlutsatsRealtids-PCR (GeneXpert) är i denna pilotstudie tillförlitlig med resultat talande för mycket god sensitivitet och specificitet och är därmed ett alternativ vid akuta frågeställningar. Med nuvarande analysregim där Clostridium difficile inkluderas i allmän fecesodling tillför inte GDH ELISA (C. DIFF CHEK -60) något mervärde men kan teoretiskt övervägas som steg före odling. Toxin-ELISA förefaller ha specificitetsproblem som dock kan minimeras med kompletterande tester inom vissa OD-intervall. Snabbtest (ImmunoCard) har god specificitet men sämre sensitivitet.

Korrespondens: magnus.thore@smi.se

Tabell 1: 27 fecesprov analyserade med snabbtest, realtids-PCR, toxin-ELISA, GDH-ELISA och odling med efterföljande toxin-ELISA

RESULTS •  The proportion of undiagnosed HIV was higher

among all women with CIN2+ than among those without CIN2+ (0.06% (95% CI 0.04-0.08) vs. 0.04% (95% CI 0.04-0.04); p = 0.017)).

•  Among migrant women proportion of undiagnosed HIV was higher among those with CIN2+ than among those without (0.30% (95% CI 0.20-0.43) vs. 0.08 % (95% CI 0.07-0.10); p < 0.001) and exceeded 0.1%, suggested cost-effective for HIV-testing.

•  Women with undiagnosed HIV at time of CIN2+ had a significantly lower nadir CD4+T-cell count, compared to women without CIN2+ before HIV-diagnosis.

OBJECTIVES •  To analyze if the prevalence of undiagnosed HIV

among; 1) all women in Sweden, 2) migrant women in Sweden, diagnosed with CIN2+, reaches >0.1%, which has been suggested cost-effective for HIV-

testing.

METHODS •  All women, born between 1940 and 1990, living in

the Counties of Stockholm and Gothenburg, Sweden, with at least one cervical cytology or histology registered in the Swedish National Cervical Screening Register (NKCx) were included.

•  Data was collected from the NKCx and the Swedish National HIV register.

•  The proportion of women with undiagnosed HIV among women with CIN2+ compared to women with a normal/mildly abnormal cytology/histology was assessed.

CONCLUSIONS •  HIV-testing should be performed in migrant women in Europe with

unknown HIV status diagnosed with cervical intraepithelial neoplasia grade 2 or worse (CIN2+).

•  HIV-testing all migrant women in Europe at time of cervical screening/gynaecologic check-up irrespective of cervical cytology results may be justified.

•  HIV-testing all women in Europe diagnosed with CIN2+ may be considered. •  Updated calculations of cost-effectiveness of HIV-screening in low endemic settings,

such as Europe, are needed.

Christina.Carlander@ki.se

Assessing cervical intraepithelial neoplasia as an indicator disease for HIV in a low endemic setting:

a population-based register study Christina Carlander1,2, Gaetano Marrone1, Johanna Brännström1,3, Aylin Yilmaz4, Kristina Elfgren5, Pär Sparén6, Anders Sönnerborg1, 7

1 Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden, 2 Centre for Clinical Research, Västmanland County hospital, Västerås, Sweden, 3Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden, 4Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 5 CLINTEC, Department of Obstetrics and Gynaecology, Karolinska University Hospital Huddinge, Stockholm, Sweden, 6Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, 7Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

CROI 2018 657

SUPPRESSIVE ART ASSOCIATED WITH EFFECTIVE TREATMENT OF CERVICAL PRECANCER

CONCLUSIONS

•  Suppressive ART and CD4 counts ≥500 are both associated with an effective treatment of CIN2+ among women living with HIV.

•  An early HIV diagnosis, immediate ART and continuum of care are all essential to reach successful CIN2+ treatment.

BACKGROUND It is uncertain what effect suppressive antiretroviral therapy (HIV-RNA<50 copies/mL) has on the results of treatment of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women living with HIV (WLWH). AIM: To assess predictors of effective treatment of CIN2+ among women living with and without HIV DESIGN: Population-based cohort study with follow-up between 1983 and 2015. METHODS •  Registry linking of the Swedish National HIV

Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry.

•  All women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ sometime between 1983 and 2014 were identified (n=179).

•  For each WLWH, two HIV-negative women resident in the same counties and matched for country of birth, diagnosed with CIN2+, were chosen as controls.

•  Treatment failure was defined as the presence of

1) ASCUS+ or 2) CIN2+, at initial follow-up.

•  Recurrence was defined as the presence of CIN1+ subsequent to an initial normal follow-up.

Christina Carlander (1,2), Philippe Wagner (2), Astrid van Beirs (3), Aylin Yilmaz (4), Kristina Elfgren (5), Joakim Dillner (6), Anders Sönnerborg (1,6) Pär Sparén (7)

christina.carlander@ki.se

1 Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, St1) Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden. 2) Centre for Clinical Research,Västmanland County Hospital, Västerås, Sweden. 3) Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden. 4) Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 5) CLINTEC, Department of Obstetrics and Gynaecology, Karolinska University Hospital Huddinge, Stockholm, Sweden. 6) Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. 7) Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

All women living with HIV, born between 1942 and

1989, living in the counties of Stockholm and

Gothenburg sometime between 1983 and 2014

(n=1926)

No CIN2+ diagnosis

1983-2014 (n=1747)

Diagnosed with CIN2+ 1983-2014 (n=179)

No follow-up within one year of CIN2+

treatment (n=36)) At least one follow-up within one year of CIN2+ treatment (n=140)

Treated with hysterectomy (n=3)

Abnormal cytology/histology at first follow up (n=63)

ASCUS (n=7) CIN1 (n=26) CIN2 (n=16) CIN3 (n=14)

Normal cytology/histology at first follow-up (n=77)

No recurrence (n=64)

Recurrence (n=13) CIN1 (n=8) CIN2 (n=3) CIN3 (n=2)

Selection of study population living with HIV

RESULTS •  WLWH were three times more likely to have

treatment failure (odds ratio (OR) for ASCUS+: 3.3 [95% CI 2.1-5.2] OR for CIN2+: 3.7 [95% CI 2.0-6.8]) than HIV-negative women.

•  WLWH were five times more likely to recur (hazard ratio 5.0 [95% CI 2.1-11.6] than HIV-negative women.

•  Suppressive ART was associated with reduced odds of treatment failure (OR for ASCUS+: 0.4 [95% CI 0.2-0.8] OR for CIN2+: 0.3 [95% CI 0.1-0.8]).

•  Immunosuppression (CD4 count <200 cells/µL) associated strongly with treatment failure (compared to CD4 count ≥500: OR for ASCUS+: 8.9 [95% CI 2.9-27.7], OR for CIN2+: 8.5 [95%CI 2.3-30.7]).

High incidence of high-grade cervical neoplasia among

HIV-infected immigrants: a population based cohort study

Christina Carlander (1), Anders Sönnerborg (2), Anders Berglund (3), Katarina Westling (2), Kristina Elfgren (4), Veronica S-Johansson (2), Pär Sparén (5)

1. Center for Clinical Research, Västmanland County Hospital, 2. Department of Medicine, Karolinska Insitutet (KI), 3.Center for Clinical Research,

Uppsala University, 4. Department of Obstetrics and Gynecology, KI. 5. Department of Medical Epidemiology and Biostatistiscs, KI, Sweden

Conclusion

Our results confirm the high incidence of CIN 2+ among HIV-infected women,

increasing with immunosuppression.

In our study, HIV-infected immigrants had a higher incidence of CIN 2+ than

HIV-infected born in Sweden.

Early HIV-diagnosis and attendance to cervical screening, with special focus

on immigrants, is of crucial importance to minimize the incidence of CIN 2+.

Objectives

To assess the incidence of high-

grade cervical intraepithelial

neoplasia and invasive cervical

cancer (CIN 2+), in HIV-infected

women compared to HIV-negative

women.

Methods

A cohort of 1154 HIV-infected

women from the Swedish national

HIV register InfCare HIV and 263

262 HIV-negative controls were

frequency matched on region of

birth and age.

Data was collected between 1993

and 2011 by linking the cohort with

the Swedish National Cervical

Screening Register (NSCR),

collecting all cytological and

histological results.

Results

The cumulative incidence (CuI)

of CIN 2+ after 15 years of

follow up was 15 % for HIV-

infected and 2% for HIV-

negative.

After 10 years of follow-up HIV-

infected women born in Eastern

Europe and Asia, Subsaharan

Africa and Sweden had a CuI of

20 %, 11% and 7% respectively

E-mail: christina.carlander@ltv.se

mediabyran.kib.ki.se

PCR with electrospray ionization-mass spectrometry on bronchoalveolar lavage for detection of invasive mold infections

in hematological patients

Kontakt

Namn Anders Krifors anders.krifors@regionvastmanland.se

Anders Krifors, specialistläkare Infektionskliniken, Doktorand Karolinska Institutet

Conclusion

The PCR/ESI-MS results had a clinical impact on antifungal therapy in 12 (44%) of the patients: modification

of treatment in 6 (22%) patients and discontinuation in 6 (22%) patients. This study provides proof of

concept that routine use of a broad-spectrum PCR for molds in bronchoalveolar lavage in

immunocompromised patients is sensitive, fast, and has an impact on clinical decision-making.

Background

Invasive mold infections are life-threatening

complications in patients with hematological

malignancies, and adequate early treatment has

been shown to be essential for a successful

outcome. Identification of non-aspergillus molds,

especially molds from the order Mucorales causing

mucormycosis, is of particular concern because of

their intrinsic resistance to antifungal agents and

the often aggressive course of the infections.

Conventional microbiological methods for

diagnosing invasive pulmonary mold infections

have low sensitivity, and molecular methods are

being developed. Detection of molds using PCR

with a narrow spectrum has been reported, but

data with broad-spectrum PCR are lacking.

Method

Between February 2016 and May 2017, PCR/ESI-

MS was available as a routine diagnostic method at

Karolinska University Hospital, as one of only two

hospitals worldwide. In this study, the diagnostic

performance and utility of a broad-spectrum PCR

(broad-spectrum PCR with subsequent electrospray

ionization-mass spectrometry, PCR/ESI-MS) for

detection of molds in bronchoalveolar lavage (BAL)

in 27 hematological patients with a new pulmonary

infiltrate was analyzed.

Results

Using the revised EORTC/MSG criteria, PCR/ESI-

MS was the only positive microbiological test in

patients with proven invasive mold infection (n = 2)

and correctly identified all cases of probable

invasive pulmonary aspergillosis (n = 5). In patients

with a possible invasive mold infection (n = 5),

PCR/ESI-MS was positive in three patients.

Mucorales was identified with PCR/ESI-MS in four

patients that were all culture negative.

The PCR/ESI-MS results had a clinical impact on

antifungal therapy in 12 (44%) of the patients:

modification of treatment in 6 (22%) patients and

discontinuation in 6 (22%) patients.

Rätt val av trumhinnerör minskar komplikationsrisken

Kontaktuppgifter

Johan Knutsson, docent, överläkare, ÖNH-kliniken

johan.knutsson@regionvastmanland.se

Johan Knutsson, MD, PhD*; Claudia Priwin MD, PhD; Anne-Charlotte Hessén-Söderman MD, PhD;

Andreas Rosenblad, PhD; Magnus von Unge, MD, PhD*

*Öron-näsa-halskliniken, Västmanlands sjukhus och Centrum för Klinisk Forskning,

Region Västmanland – Uppsala Universitet

SlutsatsTrumhinnerör av silikon ger betydligt lägre risk för infektionsproblem jämfört med rör av Fluoroplast. Silikonrör av

Donaldsontyp resulterar i minst antal infektioner. Trumhinnerör av lång typ har betydligt mindre benägenhet att

stötas ut från trumhinnan än korta rör. Långa rör av Armstrong-typ sitter kvar längst av alla. Infektioner påverkar

inte risken att röret stöts ut för tidigt.

MetodVi inkluderade 400 barn i en randomiserad studie där

barnen lottades till att få en typ av rör insatt genom

ena trumhinnan och en annan typ av rör genom

andra trumhinnan. Fyra olika typer av rör användes i

studien.

Efter operationen gick barnen på kontroll hos

öronläkare var tredje månad, samt hade extra besök

vid behov, tills båda rören var utstötta och

trumhinnan läkt. Vid besöken noterade öronläkaren

om röret var kvar, om det fanns tecken till rörinfektion

samt om trumhinnan läkt när röret stötts ut.

ResultatBarnens medelålder vid operationstillfället var 35,3

månader. Det var vanligare att pojkar opererades

med trumhinnerör; 63,8 procent av studiedeltagarna

var pojkar.

• Rörinfektioner drabbade 13,8% av patienterna.

• Silikonrör resulterade i avsevärt längre tid till

första infektion.

• Det var nästan dubbelt så vanligt att ett

Fluoroplaströr drabbades av rörinfektion.

• Donaldsonrören hade den längsta tiden till första

infektionen.

• Infektioner ökade inte risken för rören att stötas ut.

• Korta rör lossnade tidigare än långa rör.

• Långa Armstrongrör satt längst.

BakgrundAtt operera in rör genom trumhinnorna är en av de

allra vanligaste operationerna som görs på barn.

Operationen görs dels om ett barn drabbas av

många akuta öroninflammationer och dels om det

samlats vätska i örat som nedsätter hörseln.

Det finns en uppsjö av olika typer av rör. Trots detta

finns det väldigt lite kunskap kring eventuella

skillnader avseende komplikationsfrekvens. Den

vanligaste komplikationen är rörinfektion vilket brukar

antibiotikabehandlas. En annan vanlig komplikation

är att röret stöts ur för tidigt vilket kan kräva att en ny

röroperation behöver göras.

SyfteStudiens syfte var att jämföra fyra olika typer av rör

avseende komplikationsfrekvens.

De fyra rörtyperna som användes i studien.

Shepard (kort, Fluoroplastic), Donaldson (kort, silikon)

Armstrong (långt, silikon), Straight tube (långt, Fluoroplastic)

Infektionsfokus och etiologi vid neutropen feber i Västmanland

Torbjörn Larsson torbjorn.c.larsson@regionvastmanland.se

Torbjörn Larsson, Infektionskliniken Västmanlands sjukhus Västerås

Handledare: Göran Åkerblom, Christina Carlander, Tomas Vikerfors

SlutsatsBland patienter med neutropen feber (NF) i Region Västmanland var lungan mest frekvent förekommande

infektionsfokus i de fall detta kunde fastställas. Andelen positiva blododlingar var hög,

kinolonresistensen relativt låg och förekomsten av ESBL-producerande E. coli förhållandevis hög jämfört

med tidigare studier. Ciprofloxacinprofylax har till synes ännu en plats i vården vid NF i Region

Västmanland men med ökande resistens kan läget snart förändras. Den kliniska presentationen vid debut

av NF lämnar viktig prognostisk information.

MetodRetrospektiv kohortstudie baserad på uppgifter från

patientjournaler, kliniskt kemiskt laboratorium och

kliniskt mikrobiologiskt laboratorium.

Studiepopulationen (n=113) inkluderade vuxna

patienter med läkemedelsorsakad neutropeni

(neutrofila <1,0 x 109/L) och samtidig feber på

Västmanlands sjukhus Västerås under perioden

1 jan 2011 till 31 dec 2012.

ResultatMajoriteten av patienterna hade hematologiska maligniteter (72 %). Infektionsfokus kunde fastställas i 2/3 av

fallen och vanligast var lungfokus (17%). Etiologin fastställdes i 45 % av fallen och via blododlingar i 34 % av

fallen. KNS och alfahemolyserande streptokocker var de vanligaste blododlingsfynden följt av E. coli, Klebsiella

och S. aureus. Två fynd av ciprofloxacinresistenta E. coli, varav en i blododling. Av nio E. coli i blodet var två

stammar ESBL-producerande. Av tre blododlingar med S. aureus var en meticillinresistent (MRSA). Mortaliteten

var högre bland de med positiva blododlingar (24%) än negativa blododlingar (11 %); p=0,04. Mortaliteten vid

gramnegativ sepsis var högre (35 %) än vid grampositiv sepsis (15 %); p=0,11. Mortaliteten var hög hos patienter

med organpåverkan (42 %) och låg hos patienter med feber utan andra infektionstecken (5 %).

BakgrundNeutropen feber (NF) är associerat med hög

mortalitet. Aktuella studier visar att andelen

gramnegativa bakteremier ökar hos patienter med

NF och likaså förekomsten av antibiotikaresistenta

bakterier, främst mot kinolonpreparat. Den

mikrobiologiska epidemiologin kring patienter med

NF i region Västmanland är inte tidigare studerad.

SyfteStudiens syfte var att kartlägga infektionsfokus,

etiologi och förekomsten av resistenta bakterier hos

patienter med NF.

Tabell 1. Studiepopulation och resultat.

* I sex fall växte två olika agens i blododlingar.

** Stenotrophomonas maltophilia, Proteus vulgaris, Listeria, Clostridium perfringens, Citrobacter

freundii, Enterobacter spp., Bacteroides fragilis, Leptotrichia buccalis, Pseudomonas aeruginosa,

obestämbar anaerob gramnegativ stav.

Samtliga Endast

feber

Feber och andra

infektionstecken

Sepsis (svår)

Antal 145 59 (41 %) 50 (34 %) 36 (25 %)

Ålder (medelvärde) 65 år (19–91) 66 år 65 år 65 år

Kvinnor 60 (53 %) - - -

Mortalitet 23 (16 %) 3 (5 %) 5 (10 %) 15 (42 %)

Antimikrobiell kemoprofylaxCiprofloxacin 48 (33 %) 16 (27 %) 22 (44 %) 10 (28 %)

PCP-profylax 23 (16 %) 10 (17 %) 8 (16 %) 5 (14 %)

Svampprofylax 83 (57 %) 27 (46 %) 30 (60 %) 26 (72 %)

Aciklovir 80 (55 %) 28 (47 %) 31 (62 %) 21 (58 %)

Bakomliggande sjukdomarHematologiska

maligniteter

104 (72 %) 38 (64 %) 38 (76 %) 28 (78 %)

Tumörsjukdomar 35 (24 %) 18 (31 %) 10 (20 %) 7 (19 %)

Icke-maligniteter 6 (4 %) 3 (5 %) 2 (4 %) 1 (3 %)

InfektionsfokusOkänt 55 (38 %) 32 (54 %) 11 (22 %) 12 (33 %)

Lungor 25 (17 %) 5 (8 %) 14 (28 %) 6 (17 %)

Blod utan annat fokus 18 (12 %) 6 (10 %) 6 (12 %) 6 (17 %)

Tarm/rektum 13 (9 %) 2 (3 %) 6 (12 %) 5 (14 %)

Urinvägar 11 (8 %) 3 (5 %) 6 (12 %) 2 (6 %)

Venös infart 11 (8 %) 1 (2 %) 6 (12 %) 4 11 %)

Svalg 7 (5 %) 7 (12 %) 0 0

Hud/mjukdelar 4 (3 %) 2 (3 %) 1 (2 %) 1 (3 %)

Tänder 1 (<1%) 1 (2 %) 0 0

Agens i blododlingarPositiva blododlingar 49* (34 %) 10 (17%) 23 (46%) 16 (44 %)

KNS 12 (8 %) 3 (5 %) 7 (14 %) 2 (6 %)

Alfa-streptokocker 11 (8 %) 3 (5 %) 5 (10 %) 3 (8 %)

E. coli 9 (6 %) 1 (2%) 5 (10 %) 3 (8 %)

Klebsiella spp. 5 (3 %) 1 (2 %) 1 (2 %) 3 (8 %)

S. aureus (1 MRSA) 3 (2 %) 0 2 (4 %) 1 (3 %)

Enterococcus faecium 3 (2 %) 0 1 (2 %) 2 (6 %)

Candida spp. 2 (1 %) 0 1 (2 %) 1 (3 %)

Övriga arter** 10 2 4 4

Empirisk antibiotikaMeropenem 123 (85 %) 53 (89%) 43 (86 %) 27 (75 %)

Piperacillin-tazobactam 18 (13 %) 6 (10 %) 5 (10 %) 7 (19 %)

Ciprofloxacin 2 (1 %) 0 2 (4 %) 0

Ingen behandling given 2 (1 %) 0 0 2 (6 %)

Erfarenheter från 5 års användande av Xpert MTB/RIF i Västmanland

Emeli Månsson emeli.mansson@regionvastmanland.se

Ingrid Selmeryd ingrid.selmeryd@regionvastmanland.se

•Ingrid Selmeryd, överläkare, Infektionsklinken Västmanlands sjukhus, Västerås

•Emeli Månsson, överläkare, Infektionskliniken Västmanlands sjukhus, Västerås

SlutsatsVi bedömer att vår region har haft stor nytta av tillgång till lokalt utförd PCR för detektion av M. tuberculosis. På 5

år har tiden till behandlingsstart förkortats med totalt 390 dygn, vilket har medfört kortare inneliggande

isoleringsvård än om vi väntat på svar från Karolinska sjukhuset, Solna (KS). Om prov- och provsvarslogistik

mellan vårdavdelning i Västerås och mikrobiologiska laboratoriet på KS förbättrades skulle dock värdet av lokal

PCR för detektion av M. tuberculosis inte vara lika stort.

Resultat

Under dessa 5 år analyserades 450 prov på

misstanke om tuberkulos med lokal PCR.

M. tuberculosis detekterades i prov från 29 patienter

(22 luftvägsprov, 2 ventrikelsköljvätska, 4

abscesspunktat, 1 empyem) (Tabell 1).

27/29 patienter bekräftades sedermera

odlingspositiva. De två odlingsnegativa patienterna

bedömdes kliniskt som otvetydig aktiv tuberkulos

(baserat på symtom, status och behandlingssvar). Av

de 29 patienterna med aktiv tuberkulos var 14

mikroskopinegativa. Prov från 6 av de 14

mikroskopinegativa patienterna var negativa i KS

PCR.

Baserat på resultat från lokal PCR kunde adekvat

behandling sättas in på dessa 29 patienter i medeltal

sex dagar tidigare (median 6, IQR 3-24) än om vi

inväntat svar från KS.

Tidsvinsten var mindre för patienter med

mikroskopipositiva luftvägsprov jämfört med icke eller

lågsmittsamma. Två patienter diagnosticerades med

misstänkt MDR-tuberkulos. Dessa patienter fick

adekvat MDR-regim 10 respektive 24 dagar tidigare

än om vi inväntat resultat från KS. Av samtliga prov

med svaret ”M. tuberculosis ej påvisad” utföll endast

ett positivt i KS PCR.

BakgrundVärdet av PCR för diagnostik av Mycobacterium

tuberculosis har ifrågasatts (1).

I Västmanland har vi sedan 2013 tillgång till lokal

PCR för detektion av M.tuberculosis samt

mutationer i rpoB-genen associerade med

rifampicinresistens (Xpert MTB/RIF, Cepheid, CA,

USA).

Analyskostnaden är 1295kr/prov. Analysen ersätter

inte ordinarie diagnostik med mikroskopi, PCR och

odling på KS.

MetodFör att utvärdera nyttan med lokal tillgång till M.

tuberculosis PCR genomfördes en retrospektiv

analys samt journalgenomgång av samtliga

analyserade prov under åren 2013-2017.

Tabell 1: Datum då svar togs emot från respektive analys och

antal dagar som patienten fick adekvat behandling innan första

svar från Karolinska sjukhuset.

Figur 1 - Tid räknat i dagar från svar på lokal PCR till första

positiva besked (mikroskopi, PCR eller odling) mottaget per telefon

eller skriftligt från Karolinska tuberkuloslaboratorium.

MaterialKS Mikroskopi*

Lokal PCR KS PCR* Odling*Vunnen behandlingstid i dagar

Kommentar

Sputum neg 130430 130508 130528 8

Bronksekret neg 130624 130710 neg 16Klinik som TB. Gott beh. svar

Bronksekret neg 130801 neg 130924 53

Sputum 140224 140220 140224 140320 4

Sputum 140521 140516 140528 140619 5 (10 för MDRbeh)

Sputum 140904 140903 140911 140915 1

Empyem neg 141205 141208 Neg 3Klinik som TB. Gott beh. svar

Sputum 150318 150312 150318 150320 6

Sputum 150430 150429 150504 160518 2

Sputum neg 150529 150611 150709 13

Sputum neg 150618 neg 150722 34

Abscesspunktat neg 151201 neg 151229 28

Sputum 160316 160311 160318 160401 5

Sputum neg 160430 Neg 160531 31

Sputum 160516 160509 160516 160531 7

Sputum 160629 160623 160630 160802 6

Abcscesspunktat 160629 160627 160707 160711 1 INHr

Abscesspunktat neg 160723 160727 160809 3

Abscesspunktat 160913 160907 160913 160922 4

Bronksekret 160927 160926 160927 161012 0Beh. insatt empiriskt efter bronkoskopi

Kräkning (VSK) 161230 161221 161230 170120 8

Sputum 170214 170213 170215 170222 1

Sputum Neg 170316 Ej tagits 170419 31

Sputum Neg 170405 170411 170505 6

VSK Neg 170427 Neg 170613 47

Sputum Neg 170503 Ej tagits 170612 40

Sputum 170628 170626 170628 170725 2

Bronksekret Neg 170818 Neg 170911 24 (MDR)

Sputum 171026 171025 171026 171103 1

*Första datum då svaret togs emot på infektionskliniken i Västerås antingen per telefon eller papper.

Staphylococcus aureus bacteremia in patients with cardiac implantable

electronic devices

Jonas Selmeryd (jonas.selmeryd@regionvastmanland.se)

Sara Pichtchoulin1; Ingrid Selmeryd2; Pär Hedberg1,3; Jonas Selmeryd1,3

1Department of Clinical Physiology , Västmanland County Hospital, Västerås, Sweden 2Department of Infectious Diseases , Västmanland County Hospital, Västerås, Sweden

3Centre for Clinical Research, Uppsala University, Västmanland County Hospital, Västerås, Sweden

Conclusions• Subjects presenting with SAB and concomitant CIED became increasingly more common during the study period.• Subjects were older than observed in previous studies and severely comorbid. This was particularly evident among subjects dying during hospital care

and among discharged patients where the CIED was left in place.• The awareness of possible CIED infection was low and transesophageal echocardiography was rarely used which is a limitation of the present study.• The prevalence of diagnosed CIED endocarditis, as well as extraction frequency, was lower in our study compared with previous studies.• The relapse and mortality rates were, however, similar to previous studies, indicating that few cases of CIED endocarditis were missed.• The low relapse rate despite a low extraction frequency might suggest that an individual risk/benefit-analysis might be preferable to an “extraction for

all”-policy in these elderly and diseased patients.

MethodAll subjects with SAB and concomitant CIEDin Västmanland during 2010-2016 wereretrospectively reviewed. Pocket infectionswere excluded. Data on clinical course andoutcome (death or relapse in SAB within 90days of discharge) were collected.

ResultsWe identified 46 cases of SAB in patients withconcomitant CIED. Stratified by in-hospitaldeath and CIED extraction status, outcomedata, relationship between age andcomorbidity, and treatment duration areshown in Figure 1-3. The yearly frequency ofsubjects presenting with SAB andconcomitant CIED is shown in Figure 4.Comparison between our results and previousstudies on similar cohorts are shown in Table1. Characteristics of study population isshown in Supplementary Table 1.

BackgroundPrevious studies have reported a prevalenceof 34-45 % for Cardiac Implantable ElectronicDevice (CIED) associated infection amongpatients with S. aureus bacteremia (SAB).Due to poor outcome with conservativetreatment, diagnostic difficulties, and highprevalence of CIED infection with SAB, recentSwedish guidelines advocate CIED extractionin all subjects with SAB, if possible. The aimof this study was to investigate the clinicalcourse of SAB in patients with CIED.

Full study populationsSubset of subjects without clinical pocket infection

Author n Age Male sex MRSAPocket

infection Echocardiography TEECommunity acquisition Extraction

In-hospital death

All death during follow-up Relapse n

Duke based diagnosis of CIED endocarditis

Clinical diagnosis of CIED endocarditis

Chamis et.al.1 33 70 (median) 61% 55% 18% 85% 67% 48% 36% N.A. 36% 6% 27 33% N.A.Uslan et.al.2 62 72 (mean) 81% 39% 11% 77% 65% 13% N.A. 32% N.A. N.A. 55 27% N.A.Sohail et.al.3 131 73 (median) 77% 39% 0% 85% 64% 31% N.A. N.A. N.A. N.A. 131 34% N.A.Current study 46 80 (median) 63% 0% 0% 67% 11% 26% 11% 30% 41% 7% 46 N.A. 15%

In-hospital Death (n=14)

Discharged with CIED left (n=27)

Discharged with CIED extracted (n=5)

No events recorded (n=5)

Discharged from hospital (n=32)

SAB in subjects with CIED without clinical pocket infection (n=46)

No events recorded (n=19)

Death not obviously attributable to SAB (n=5)

SAB relapse (n=3)

Successfully managed SAB relapse (n=2)

Fatal SAB relapse (n=1)

Figure 1 Outcome stratified by in-hospital death and CIED extraction status Figure 2 Age and Charlson comorbidity index stratified by in-hospital death and CIED

extraction status. Boxplots with median, interquartile range, 5th percentile, and 95th

percentile indicated. Differences between groups were tested with Wilcoxon two-

sample test.

Table 1 Descriptives and outcomes in similar studies on cohorts with SAB and concomitant CIED MRSA – Methicillin resistant Staphylococcus aureus; TEE – Transesophageal echocardiography. References: 1Circulation 2001;104, 2Pacing Clin

Electrophysiol 2010;33, and 3Circ Arrhythm Electrophysiol American Heart Association, Inc.; 2015;8

Figure 3 Treatment duration in study subjects grouped by in-hospital death and CIED

extraction status. Filled staples indicate treatment duration with intravenous antibiotics

and striped boxes follow up treatment with per oral antibiotics. Time of death and

relapse of SAB within 90 days of discharge are indicated where applicable.

Figure 4 Yearly frequency of study subjects with SAB and concomitant CIED in

Västmanland.

Risk factors for severe malaria in travellers and migrants

Andreas Wångdahl andreas.wangdahl@regionvastmanland.se

Andreas Wångdahl1,2, Katja Wyss2,3, Dashti Saduddin2, Matteo Bottai4, Elsie Ydring5, Tomas Vikerfors1, Anna Färnert2,3

1. Department of Infectious Diseases, Västerås Hospital; Västerås, Sweden

2. Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet; Stockholm, Sweden

3. Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden

4. Unit of Biostatistics, Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

5. Public Health Agency of Sweden, Solna, Sweden

ConclusionSevere malaria was observed in both P. falciparum and non-falciparum episodes. Several risk factors were

described, where young and older age as well as health care delay showed the strongest association to severe

malaria. Furthermore, P. falciparum episodes with parasitemia >2% started on oral treatment showed an

increased risk of developing severe malaria. Current WHO criteria for severe malaria need to be optimized to

better guide the management of malaria in travellers and migrants.

In non-falciparum, age >60y, health care delay and

endemic origin were identified as risk factors for

severe disease.

In P. falciparum episodes with parasitemia ≥2%

without severe signs at presentation, oral treatment

was associated with progress to severe malaria (OR

8.7 [95% CI 1.9-39.3]; P=0.005).

Risk factors associated with severe P. falciparum

malaria are presented in Figure 1.

BackgroundMalaria is caused by Plasmodium falciparum, P.

vivax, P. ovale, P. malariae and P. knowlesi.

Severe malaria involves dysfunction in one or

several organs and can be caused by all species.

Prompt diagnosis and effective treatment are crucial

for the outcome. Risk factors for severe malaria

needs to be acknowledged to improve management

of imported malaria.

AimThe aim was to describe clinical aspects and

outcome of imported malaria and to assess factors

that affect disease severity in different parasite

species.

MethodRetrospective review of medical records including

2793/3260 (85.7%) of all malaria episodes in

Sweden notified to the National Surveillance

Database between 1 January 1995 and 31

December 2015. Demographic, epidemiological and

clinical data were collected and analyzed using

multivariable logistic regression.

ResultsSevere malaria according to WHO 2015 criteria was

found in P. falciparum (9.4%), P. vivax (7.7%), P.

ovale (5.3%), P. malariae (3.3%) and mixed P.

falciparum episodes (21.1%).

Figure 3. P. falciparum parasitemia in episodes deteriorating to

severe malaria after initiation of oral treatment.

Figure 2. Adjusted odds ratio for severe P. falciparum malaria in

travellers and migrants in Sweden.

Figure 1. Causative species of severe malaria in travellers and

migrants .