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  • # 1226 Clinical outcomes of Achromobacter species in adult ... · (1984 – 2013) 306 CF Patients 34 (11%) Patients ≥ 1 sputum (+) with Achromobacter 24 Transient Colonizers 10
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(1984 – 2013) 306 CF Patients 34 (11%) Patients ≥ 1 sputum (+) with Achromobacter 24 Transient Colonizers 10 (3.3%) Persistent colonizers ≥ 50% of all cultures in a 1-year period (minimum of 3 cultures) ≥ 1 positive culture and not meeting criteria for “persistent” Clinical outcomes of Achromobacter species in adult cystic fibrosis patients: A cohort study Edwards BD, 1 Somayaji R, 1, Greysson-Wong J, 2 Storey DG, 3 Rabin HR, 1,2 Surette MG, 2,4.5 Parkins MD 1,2 Background • Achromobacter species are emerging pathogens in cystic fibrosis (CF) with reported prevalence ranging from 5-29% • There is a paucity of knowledge regarding the pathogenicity, transmission characteristics, and clinical impact of this organism Methods • Patients attending the Southern Alberta Adult CF clinic between 1984 – 2013 with ≥ 1 sputum culture positive for Achromobacter species were included • Patients were categorized into transient and persistent for analysis (Figure 1); those with persistent infection were also matched 1:2 with a sex and age-matched control CF cohort for analysis • Data was collected through chart review two years pre- and post- initial Achromobacter infection • Achromobacter isolates were characterized with 16s rRNA, PFGE, and nrdA gene sequencing for speciation and detection of clonality • Outcomes of pulmonary exacerbation (PEx) risk at initial acquisition compared with pre- and post-infection, lung function decline (FEV 1 %/year) and PEx risk pre- and post-infection were assessed with regression models using STATA 14.1 (College Stn, TX) • A total of 34/306 patients (11%) with a median age of 24.8 years were identified with Achromobacter infection in the study period (Figure 1) • Of those with Achromobacter infection, 10/306 (3.3%) developed persistent infection and A. xylosoxidans was the most common species (50.0%) (Figure 2) • Patients were more likely to experience PEx at initial isolation (OR 2.7; [95% CI 1.2 – 6.7]; p=0.03) compared with the prior or subsequent visit • Baseline characteristics of patients with Achromobacter infections and controls were similar (Table 1) • There was no difference in annual lung function decline (-1.08% [95% CI -2.73-0.57] vs. -2.74% [95% CI -4.02 - -1.46]; p=0.12) or odds of PEx (OR 1.21 [95% CI 0.45-3.28]; p=0.70) following persistent Achromobacter infection • Two patients (A182 – a persistent colonizer and A184 – a transient colonizer) cultured Achromobacter xylosoxidans with matching PFGE and nrdA profiles (Figure 3*) reflecting a possible transmission event • Other infecting species identified by nrdA sequencing were A. insuavis (28%), A. dolens (11%), A. spanius (6%), and A. ruhlandii (6%) • The rate of lung function decline was not different amongst species University of Calgary 3330 Hospital Drive NW Calgary, AB CANADA, T2N 4N1 [email protected] # 1226 • Achromobacter species had a prevalence and species distribution similar to other CF based studies in our center • Achromobacter infection was associated with PEx at initial acquisition but did not have a significant impact on PEx risk or rate of FEV 1 % decline following infection • Larger studies are required to elucidate the transmission potential of this organism Conclusions Department of Medicine 1 , Department of Microbiology, Immunology, and Infectious Diseases 2 , Department of Biological Sciences 3 : University of Calgary; Department of Medicine 4 and Biochemistry 5 , The Farncombe Family Digestive Health Research Institute, McMaster University 100 80 60 40 A329-Ax12-20/11/2013 A329-Ax7-28/06/2011 A274-Ax3-19/02/2005 A312-Ax8-20/06/2012 A312-Ax9-23/07/2012 A128-Ax18-21/08/1996 A128-Ax20-09/04/1997 A061-Ax19-08/01/1997 A061-Ax22-08/04/1999 A061-Ax24-15/07/2000 A085-Ax25-21/03/2001 A085-Ax27-17/04/2002 A349-AxN4-14/04/1997 A358-Ax23-16/02/2000 A022-Ax21-22/04/1998 A077-Ax4-15/01/2009 A077-Ax5-11/06/2009 A182-Ax14-19/01/1994 A182-Ax17-06/12/1994 A184-Ax16-05/10/1994 A182-Ax34-13/04/1993 A217-Ax29-18/05/1988 A217-Ax30-18/10/1989 A061-Ax13-05/12/2013 A253-AxN9-15/04/1993 A335-Ax6-01/04/2010 A222-AxN5-18/03/1998 A222-AxN8-18/02/1992 A222-AxN6-03/03/1999 A222-AxN7-20/02/2002 A222-AxN1-19/01/2005 A222-AxN2-09/05/2007 A222-AxN3-28/03/1994 A207-Ax33-13/11/1991 A207-Ax36-24/06/1991 A207-Ax37-27/06/1991 A003-Ax2-16/02/2005 A090-Ax11-26/09/2012 A039-Ax10-13/08/2013 A152-Ax15-16/09/1994 } * Aim • To determine the epidemiology, transmissibility, and clinical outcomes of Achromobacter species in a North American CF cohort Table 1: Baseline data of transient, persistent and control cohorts Baseline data: 2 years prior to incident Achromobacter culture *Azithromycin or tobramycin at time of AX culture or Control study entry; ✝ Chronic co-infection; CFRD – CF related diabetes; CFLD - CF liver disease; DIOS – Distal Intestinal Obstruction Syndrome Figure 1. Patient recruitment Figure 3. Dendogram of Achromobacter PFGE Results Figure 2. Evolution of chronic infection Total (n=34) Transient (n=24) Persistent (n=10) Controls (n=18) P-value (Transient vs. Persistent) P-value (Persistent vs. Control) Age, mean (SD) 26 (9.3) 26 (6.6) 27 (14.3) 23 (6.8) 0.8 0.45 Male, no. (%) 15 (44.1) 9 (37.5) 6 (60.0) 11 (61.1) 0.23 0.95 BMI (SD) 20 (3.0) 20 (2.8) 20 (3.6) 21 (2.7) 0.76 0.5 Pancreatic Insufficiency, no. (%) 29 (85.3) 20 (83.3) 9 (90.0) 13 (72.2) 0.62 0.27 FVC%, mean (SD) 77 (26.8) 81 (28.5) 70 (21.6) 86 (26.2) 0.25 0.11 FEV 1 %, mean (SD) 58 (27.1) 60 (29.1) 55 (22.6) 67 (26.6) 0.63 0.22 * Inhaled tobramycin, no. (%) 7 (20.6) 5 (20.8) 2 (20.0) 4 (22.2) 0.96 0.89 * Azithromycin, no. (%) 4 (11.8) 3 (12.5) 1 (10.0) 4 (22.2) 0.84 0.42 Inhaled Corticosteroid, no. (%) 8 (23.5) 3 (12.5) 5 (50.0) 3 (16.7) 0.02 0.06 P. aeruginosa, no. (%) 28 (82.4) 20 (83.3) 8 (80.0) 12 (66.6) 0.82 0.45 S. aureus, no. (%) 25 (73.5) 17 (70.8) 8 (80.0) 7 (38.8) 0.58 0.04 Home O 2 , no. (%) 4 (11.8) 3 (12.5) 1 (10.0) 0 (0.0) 0.84 0.17 Co-Morbidities: - - - - - - CFRD, no. (%) 5 (14.7) 3 (12.5) 2 (20.0) 3 (16.7) 0.57 0.83 Sinus Disease, no. (%) 10 (29.4) 6 (25.0) 4 (40.0) 10 (55.6) 0.38 0.43 Bone Disease, no. (%) 9 (26.5) 7 (29.2) 2 (20.0) 4 (22.2) 0.58 0.89 CFLD, no. (%) 8 (23.5) 6 (25.0) 2 (20.0) 2 (11.1) 0.75 0.52 DIOS, no. (%) 3 (8.8) 3 (12.5) 0 (0.0) 2 (11.1) 0.24 0.27 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 /// 2007 2008 2009 2010 2011 2012 2013 Patient 6 Patient 9 Patient 12 Patient 18 Patient 21 Patient 23 Patient 24 Patient 25 Patient 26 Patient 33 A. xylosoxidans A. xylosoxidans A. xylosoxidans = Death = Lung Transplant A. insuavis* Unidentified species A. xylosoxidans A. insuavis A. spanius Unidentified species * = Patient lost to follow-up (no sputum collected during this interim period) = Incidence of isolation of Achromobacter; Unless otherwise indicated, end of boxes indicates spontaneous clearance. A. xylosoxidans = Period of clinic follow-up, including ongoing sputum culture = Moved to another center Age: 25 Age: 16 Age: 63 Age: 20 Age: 28 Age: 15 Age: 24 Age: 23 Age: 39 Age: 19 Legend: Patient – Strain – Date (DD/MM/YYYY)

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Page 1: # 1226 Clinical outcomes of Achromobacter species in adult ... · (1984 – 2013) 306 CF Patients 34 (11%) Patients ≥ 1 sputum (+) with Achromobacter 24 Transient Colonizers 10

(1984– 2013)306CFPatients

34(11%)Patients≥1sputum(+)withAchromobacter

24TransientColonizers 10(3.3%)Persistentcolonizers≥50%ofallculturesina1-yearperiod

(minimumof3cultures)≥1positivecultureandnotmeeting

criteriafor“persistent”

ClinicaloutcomesofAchromobacterspeciesinadultcysticfibrosispatients:Acohortstudy

Edwards BD,1 Somayaji R,1, Greysson-Wong J,2 Storey DG,3 Rabin HR,1,2 Surette MG,2,4.5 Parkins MD1,2

Background

• Achromobacter speciesareemergingpathogensincysticfibrosis(CF)withreportedprevalencerangingfrom5-29%

• Thereisapaucityofknowledgeregardingthepathogenicity,transmissioncharacteristics,andclinicalimpact ofthisorganism

Methods

• PatientsattendingtheSouthernAlbertaAdultCFclinicbetween1984– 2013with≥1sputumculturepositiveforAchromobacterspecieswereincluded

• Patientswerecategorizedintotransientandpersistentforanalysis(Figure1);thosewithpersistentinfectionwerealsomatched1:2withasexandage-matchedcontrolCFcohortforanalysis

• Datawascollectedthroughchartreviewtwoyearspre- andpost-initialAchromobacterinfection

• Achromobacterisolateswerecharacterizedwith16srRNA,PFGE,andnrdA genesequencing forspeciationanddetectionofclonality

• Outcomesofpulmonaryexacerbation(PEx)riskatinitialacquisitioncomparedwithpre- andpost-infection,lungfunctiondecline(FEV1%/year)andPExriskpre- andpost-infectionwereassessedwithregressionmodelsusingSTATA14.1(CollegeStn,TX)

• Atotalof34/306patients(11%)withamedianageof24.8yearswereidentifiedwithAchromobacterinfectioninthestudyperiod(Figure1)

• OfthosewithAchromobacterinfection,10/306(3.3%)developedpersistentinfectionandA.xylosoxidanswasthemostcommonspecies(50.0%)(Figure2)

• PatientsweremorelikelytoexperiencePExatinitialisolation(OR2.7;[95%CI1.2– 6.7];p=0.03)comparedwiththepriororsubsequentvisit

• BaselinecharacteristicsofpatientswithAchromobacterinfectionsandcontrolsweresimilar(Table1)

• Therewasnodifferenceinannuallungfunctiondecline(-1.08%[95%CI-2.73-0.57]vs.-2.74%[95%CI-4.02- -1.46];p=0.12)oroddsofPEx(OR1.21[95%CI0.45-3.28];p=0.70)followingpersistentAchromobacterinfection

• Twopatients(A182– apersistent colonizerandA184– atransientcolonizer)culturedAchromobacterxylosoxidans withmatchingPFGEandnrdA profiles(Figure3*)reflectingapossibletransmissionevent

• OtherinfectingspeciesidentifiedbynrdA sequencingwere A.insuavis(28%),A.dolens(11%),A.spanius(6%),andA.ruhlandii(6%)

• Therateoflungfunctiondeclinewasnotdifferentamongstspecies

UniversityofCalgary3330HospitalDriveNWCalgary,ABCANADA,[email protected]

#1226

• AchromobacterspecieshadaprevalenceandspeciesdistributionsimilartootherCFbasedstudiesinourcenter

• Achromobacter infectionwasassociatedwithPExatinitialacquisitionbutdidnothaveasignificantimpactonPExriskorrateofFEV1%declinefollowinginfection

• Largerstudiesarerequiredtoelucidatethetransmissionpotentialofthisorganism

Conclusions

DepartmentofMedicine1,DepartmentofMicrobiology,Immunology,andInfectiousDiseases2,DepartmentofBiologicalSciences3:UniversityofCalgary;DepartmentofMedicine4 andBiochemistry5,TheFarncombeFamily

DigestiveHealthResearchInstitute,McMasterUniversity

100806040

A329-Ax12-20/11/2013A329-Ax7-28/06/2011A274-Ax3-19/02/2005A312-Ax8-20/06/2012A312-Ax9-23/07/2012A128-Ax18-21/08/1996A128-Ax20-09/04/1997A061-Ax19-08/01/1997A061-Ax22-08/04/1999A061-Ax24-15/07/2000A085-Ax25-21/03/2001A085-Ax27-17/04/2002A349-AxN4-14/04/1997A358-Ax23-16/02/2000A022-Ax21-22/04/1998A077-Ax4-15/01/2009A077-Ax5-11/06/2009A182-Ax14-19/01/1994A182-Ax17-06/12/1994A184-Ax16-05/10/1994A182-Ax34-13/04/1993A217-Ax29-18/05/1988A217-Ax30-18/10/1989A061-Ax13-05/12/2013A253-AxN9-15/04/1993A335-Ax6-01/04/2010A222-AxN5-18/03/1998A222-AxN8-18/02/1992A222-AxN6-03/03/1999A222-AxN7-20/02/2002A222-AxN1-19/01/2005A222-AxN2-09/05/2007A222-AxN3-28/03/1994A207-Ax33-13/11/1991A207-Ax36-24/06/1991A207-Ax37-27/06/1991A003-Ax2-16/02/2005A090-Ax11-26/09/2012A039-Ax10-13/08/2013A152-Ax15-16/09/1994

}*

Aim

• Todeterminetheepidemiology,transmissibility,andclinicaloutcomesofAchromobacterspeciesinaNorthAmericanCFcohort

Table1:Baselinedataoftransient,persistentandcontrolcohorts

Baselinedata:2yearspriortoincidentAchromobacter culture*AzithromycinortobramycinattimeofAXcultureorControlstudyentry;✝Chronicco-infection;CFRD– CFrelateddiabetes;CFLD- CFliverdisease;DIOS– DistalIntestinalObstructionSyndrome

Figure1.Patientrecruitment

Figure3.DendogramofAchromobacterPFGE

Results

Figure2.Evolutionofchronicinfection

Total(n=34)

Transient(n=24)

Persistent(n=10)

Controls(n=18)

P-value(Transientvs.Persistent)

P-value(Persistentvs.

Control)Age,mean(SD) 26(9.3) 26(6.6) 27(14.3) 23(6.8) 0.8 0.45Male,no.(%) 15(44.1) 9(37.5) 6(60.0) 11(61.1) 0.23 0.95BMI(SD) 20(3.0) 20(2.8) 20(3.6) 21(2.7) 0.76 0.5

PancreaticInsufficiency,no.(%) 29(85.3) 20(83.3) 9(90.0) 13(72.2) 0.62 0.27FVC%,mean(SD) 77(26.8) 81(28.5) 70(21.6) 86(26.2) 0.25 0.11FEV1%, mean(SD) 58(27.1) 60(29.1) 55(22.6) 67(26.6) 0.63 0.22

*Inhaledtobramycin,no.(%) 7(20.6) 5(20.8) 2(20.0) 4(22.2) 0.96 0.89* Azithromycin,no.(%) 4(11.8) 3(12.5) 1(10.0) 4(22.2) 0.84 0.42InhaledCorticosteroid,no.(%) 8(23.5) 3(12.5) 5(50.0) 3(16.7) 0.02 0.06�P. aeruginosa,no.(%) 28(82.4) 20(83.3) 8(80.0) 12(66.6) 0.82 0.45�S. aureus,no.(%) 25(73.5) 17(70.8) 8(80.0) 7(38.8) 0.58 0.04HomeO2,no. (%) 4(11.8) 3(12.5) 1(10.0) 0(0.0) 0.84 0.17Co-Morbidities: - - - - - -CFRD,no.(%) 5(14.7) 3(12.5) 2(20.0) 3(16.7) 0.57 0.83SinusDisease,no.(%) 10(29.4) 6(25.0) 4(40.0) 10(55.6) 0.38 0.43BoneDisease,no.(%) 9(26.5) 7(29.2) 2(20.0) 4(22.2) 0.58 0.89CFLD,no.(%) 8(23.5) 6(25.0) 2(20.0) 2(11.1) 0.75 0.52DIOS,no.(%) 3(8.8) 3(12.5) 0(0.0) 2(11.1) 0.24 0.27

1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 /// 2007 2008 2009 2010 2011 2012 2013

Patient 6

Patient 9

Patient 12

Patient 18

Patient 21

Patient 23

Patient 24

Patient 25

Patient 26

Patient 33

A. xylosoxidans

A. xylosoxidans

A. xylosoxidans

= Death

= Lung Transplant

A. insuavis*

Unidentified species

A. xylosoxidans

A. insuavis

A. spanius

Unidentified species

* = Patient lost to follow-up (no sputum collected during this interim period)= Incidence of isolation of Achromobacter; Unless otherwise indicated, end of

boxes indicates spontaneous clearance.

A. xylosoxidans

= Period of clinic follow-up, including ongoing sputum culture = Moved to another center

Age: 25

Age: 16

Age: 63

Age: 20

Age: 28

Age: 15

Age: 24

Age: 23

Age: 39

Age: 19

Legend:Patient– Strain– Date(DD/MM/YYYY)

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