Oligo Name Sequence Target gene/Purpose PCR product sizes Reference
Ct-ERG11-Fexternal TTCTCCCATTGTACACTA
CtERG11/PCR and sequencing 2186bps This study
Ct-ERG11-F1 CATGGTTTGGTTCTGCTG CtERG11/Sequencing --- This study
Ct-ERG11-F2 TCGACAGATCATTTGCTCA CtERG11/Sequencing --- This study
Ct-ERG11-F3 GAGAATGCACATGCCATT CtERG11/Sequencing --- This study
Ct-ERG11-R1 GAATTCGTGACCTTTT CtERG11/Sequencing --- This study
Ct-ERG11-R2 TTTCTTTGAGCAGCGTCA CtERG11/Sequencing --- This study
Ct-ERG11-R3 GAAATGTTCTGGGTGTTCA CtERG11/Sequencing --- This study
Ct-ERG11-Rexternal TACATCCAAATAATGGGC CtERG11/PCR and sequencing 2186bps This study
Ct-UPC2-1-Fexternal ACCATCATCATTATAGCC CtUPC2/PCR and sequencing 2647bps This study
Ct-UPC2-F1 TGTCAAATGTGATGAACA CtUPC2/Sequencing --- This study
Ct-UPC2-F2 ACAATCTTGCTGCAAC CtUPC2/Sequencing --- This study
Ct-UPC2-F3 GATTCTATAAGTTCATTTCAG CtUPC2/Sequencing --- This study
Ct-UPC2-R1 AGATACTGCCAGTGATT CtUPC2/Sequencing --- This study
Ct-UPC2-R2 CAAATCAAGCATATTAAGAC CtUPC2/Sequencing
Ct-UPC2-R3 TAAGAAGCTCCTTCAC CtUPC2/Sequencing
Ct-UPC2-R4 TATCTCCTTGCATGATA CtUPC2/Sequencing
Ct-UPC2-Rexternal. CTAGTATCCACACTTATCTC CtUPC2/PCR and sequencing 2647bps This study
Ct-MRR1-Fexternal ATCAATCATCAAGTACCC CtMRR1/PCR and sequencing 3639bps This study
Ct-MRR1-F1 CATCAGTGAACTATGATAA CtMRR1/ Sequencing --- This study
Ct-MRR1-F2 AATTCTGATCCATATTTCA CtMRR1/ Sequencing --- This study
Ct-MRR1-F3 GGGATTAACTTTATATGAAG CtMRR1/ Sequencing --- This study
Cp-MRR1-F4 AATTATACCATGTGTTTG CtMRR1/ Sequencing --- This study
Ct-MRR1-F5 ATGCTAGAAATATGCCAG CtMRR1/ Sequencing --- This study
Ct-MRR1-F6
TGATAAAGAATCTAAAATGAG CtMRR1/ Sequencing --- This study
Ct-MRR1-R1
AACATATCTAATTCACTCA CtMRR1/ Sequencing --- This study
Ct-MRR1-R2 TGTATTGTTCGTGTCTGT CtMRR1/ Sequencing --- This study
Ct-MRR1-R3 CATCAATAAATGGCATGA CtMRR1/ Sequencing --- This study
Ct-MRR1-R4 TCTGGATCTCTGTTTAAC CtMRR1/ Sequencing --- This study
Ct-MRR1-R5 CAATTTGAATGATTTTCTTC CtMRR1/ Sequencing --- This study
Ct-MRR1-R6 CCATAACTTTAGTTTTACC CtMRR1/ Sequencing --- This study
Ct-MRR1-Rexternal
GATATCCCCAATATTTCCG CtMRR1/PCR and sequencing 3639bps This study
Ct-TAC1-Fexternal TTTCTCTAATCATTTGGGG CtTAC1/PCR and sequencing 3099bps This study
Ct-TAC1-F1 GAAGATGAAGAACCTGAA CtTAC1/ Sequencing --- This study
Ct-TAC1-F2 CTTATAGCATTGACTTGC CtTAC1/ Sequencing --- This study
Ct-TAC1-F3 ATTGACTTCGGTATTTC CtTAC1/ Sequencing --- This study
Table S2. PCR condition and programs used for amplification of target genes.
Loci
PCR Conditions
PCR program
MRR1
Final volume=50µl
10X buffer, 5µl; MgCl2, 2mM, dNTP mix,
0.2mM, Primers Fex and Rex, each 10pm,
Taq polymerase, 2.5 units, MQ water to
adjust in 50 µl
95
ºC, 5min (1 cycle)
35 cycles of; 95
ºC, 30 sec; 52
ºC, 30 sec, and
72
ºC, 4 min
72
ºC, 8 min (1 cycle)
TAC1
Final volume=50µl
10X buffer, 5µl; MgCl2, 2mM, dNTP mix,
0.2mM, Primers Fex and Rex, each 10pm,
Taq polymerase, 2.5 units, MQ water to
adjust in 50 µl
95
ºC, 5min (1 cycle)
35 cycles of; 95
ºC, 30 sec; 52
ºC, 30 sec, and
72
ºC, 3 min
72
ºC, 8 min (1 cycle)
UPC2
Final volume=50µl
10X buffer, 5µl; MgCl2, 2mM, dNTP mix,
0.2mM, Primers Fex and Rex, each 10pm,
Taq polymerase, 2.5 units, MQ water to
adjust in 50 µl
95
ºC, 5min (1 cycle)
35 cycles of; 95
ºC, 30 sec; 52
ºC, 30 sec, and
72
ºC, 2.5 min
72
ºC, 8 min (1 cycle)
ERG11
Final volume=50µl
10X buffer, 5µl; MgCl2, 2mM, dNTP mix,
0.2mM, Primers Fex and Rex, each 10pm,
Taq polymerase, 2.5 units, MQ water to
adjust in 50 µl
95
ºC, 5min (1 cycle)
35 cycles of; 95
ºC, 30 sec; 52
ºC, 30 sec, and
72
ºC, 2 min
72
ºC, 8 min (1 cycle)
HS1 and HS2 of FKS1
Final volume=50µl
10X buffer, 5µl; MgCl2, 2mM, dNTP mix,
0.2mM, Primers Fex and Rex, each 10pm,
Taq polymerase, 1.25 units, MQ water to
adjust in 50 µl
95
ºC, 5min (1 cycle)
35 cycles of; 95
ºC, 30 sec; 52
ºC, 30 sec, and
72
ºC, 30 sec
72
ºC, 8 min (1 cycle)
No. Age/s
ex City/Hospital/Ward hospitalizaDate of tion Date of discharge/d eath Hospitalizati on duration (Days)
Inpatient Catheter Surgery Parenter
al nutrition
SU-221 57/M Shiraz/Namazi/General 23/05/2017 12/06/2017 20 Yes Central venous No No
SU-231 61/F Shiraz/Namazi/General 05/09/2017 25/09/2017 20 Yes Central venous No No
SU-235 50/M Shiraz/Namazi/Infectious 21/08/2017 30/09/2017 39 Yes Central venous Abdominal No
SU-239 52/M Shiraz/Namazi/ICU 10/08/2017 11/10/2017 61 Yes Central venous No No
SU-267 35/F Shiraz/Namazi/General 28/11/2017 06/01/2018 39 Yes Central venous No No
10 BC 65/F Tehran/Imam/ICU 02/12/2017 07/04/2018 130 Yes Central venous Abdominal No
11BC
36/M Tehran/Imam/Infectious 15/01/2018 13/03/2018 62 Yes Central venous abdominalNon- No 24 BC 38/M Tehran/Imam/Neurology 05/01/2018 22/04/2018 109 Yes Central venous,
Urinary No No
75 BC 32/M Tehran/Imam/ICU 17/04/2018 20/06/2018 62 Yes No No No
82 BC
89/M Tehran/Imam/Pulmonary 22/07/2018 28/07/2018 37 No Urinary abdominalNon- No
85(1)
BC 56/F Tehran/Imam/Surgical 25/07/2018 29/07/2018 5 Yes Central venous,Urinary abdominalNon- No
99 BC 60/F Tehran/Imam/Emergency/ICU 26/07/2018 29/07/2018 3 Yes Central venous Abdominal No
107 BC
53/F Tehran/Imam/Surgical 14/07/2018 03/09/2018 51 Yes Central venous abdominalNon- No 113(1)
BC 54/M Tehran/Imam/ICU 21/08/2018 29/08/2018 8 Yes No No No
113(2)
BC 54/M Tehran/Imam/ICU 21/08/2018 29/08/2018 8 Yes No No No
115(1)
BC 37/F Tehran/Imam/General 19/08/2018 05/09/2018 54 Yes Central venous,Urinary No No
115(2)
BC 37/F Tehran/Imam/General 19/08/2018 05/09/2018 54 Yes Central venous,Urinary No No
E-209
3/M Esfahan/Children's MedicalCenter/PICU 14/01/2015 12/02/2015 28 Yes Central venous,Urinary No Yes E-230 3/F Esfahan/Children's Medical
Center/PICU 22/01/2015 06/03/2015 42 Yes Central venous,Urinary Abdominal No E-240
2/F Esfahan/Children's MedicalCenter/PICU 21/02/2015 26/03/2015 35 Yes Central venous Abdominal Yes E-262
2/F Esfahan/Children's MedicalCenter/PICU 21/02/2015 26/03/2015 35 Yes Central venous No No E-368 4/F Esfahan/Children's Medical
Center/CICU 24/06/2015 12/07/2015 18 Yes Central venous Abdominal No
E-369
4/F Tehran/Children's MedicalCenter/PICU 01/04/2015 30/04/2015 30 Yes Central venous Abdominal No E-511
1/M Esfahan/Children's MedicalCenter/PICU 01/01/2016 13/01/2016 13 Yes Central venous No No E-527 10/M Esfahan/Children's Medical
Center/PICU 25/01/2016 19/02/2016 24 Yes Central venous,Urinary No No
Center/NICU E-614 1/M Esfahan/Children's Medical
Center/PICU 22/05/2016 18/06/2016 26 Yes Central venous,Urinary No Yes
E-629
14/M Esfahan/Children's MedicalCenter/PICU 10/05/2016 08/06/2016 20 Yes Central venous,Urinary No No E-699 8m/M Esfahan/Children's Medical
Center/CICU 08/09/2016 05/10/2016 27 Yes Central venous Abdominal Yes
E-703 2m/M Esfahan/Children's Medical
Center/CICU 17/09/2016 17/12/2016 61 Yes Central venous Abdominal Yes
E-787 4/F Esfahan/Children's Medical
Center/PICU 03/06/2017 28/06/2017 25 Yes Central venous,Urinary Abdominal No E-1013 40/F Esfahan/Children's Medical
Center/NICU 01/10/2017 29/10/2017 28 Yes Central venous No Yes
E-1014 11/M Esfahan/Children's Medical
Center/PICU 20/04/2018 11/06/2018 52 Yes Central venous,Urinary No No
4M 70/M Mashhad/22Bahman/General 10/02/2018 30/02/2018 20 Yes Central venous No No
8M
28/F Mashhad/22Bahman/General availableNot Not available Not available availableNot Not available Not available availableNot
N15 90/M Mashhad/22Bahman/General 01/03/2018 26/03/2018 26 Yes Urinary No Yes
N17 70/M Mashhad/Arya/General 25/12/2017 02/02/2018 65 Yes Central venous,
Urinary No No
N18 78/M Mashhad/22Bahman/General 10/02/2018 05/03/2018 25 Yes Central venous No No
N26 78/M Mashhad/Arya/General 24/03/2018 29/04/2018 35 Yes Urinary No Yes
N43 85/M Mashhad/22Bahman/ICU 25/04/2018 15/05/2018 20 Yes Central venous No No
N68 1.5/M Mashhad/Sheykh (21)/General 10/09/2016 25/09/2016 15 Yes Central venous No No
N69 1.5/M Mashhad/Sheykh (21)/General 14/03/2018 26/03/2018 12 Yes Central venous No No
N71 8/M Mashhad/Sheykh (23)/ICU 29/01/2017 15/02/2017 16 Yes Central venous
Non-abdominal No
N72 3/F Mashhad/Sheykh
(25)/Emergency 31/08/2017 23/10/2017 53 Yes Central venous No No
N78 3/F Mashhad/Akbar (31)/Surgery 26/03/2016 20/04/2016 26 Yes Central venous Abdominal No
N98 49/F Mashhad/Imam Reza/Burning Not
available Not available Not available availableNot Not available No data availableNot
N104 58/M Mashhad/Imam Reza/General 02/10/2017 08/11/2017 36 Yes No Abdominal Yes
N107 30/F Mashhad/Imam Reza/Burning 12/11/2016 `10/12/2016 28 Yes Urinary Abdominal No
N111 72/M Mashhad/Imam Reza/General 21/11/2016 30/12/2016 40 Yes Urinary
Non-abdominal No
N140 38/F Mashhad/Imam Reza/General 03/11/2016 12/12/2016 39 Yes No No Yes
N147 42/F Mashhad/Imam Reza/General 09/06/2015 16/07/2015 37 Yes No
Non-abdominal Yes
N163 39/M Mashhad/Imam Reza/General 31/08/2015 10/10/2015 41 Yes Urinary
Non-abdominal Yes
N186 63/M Mashhad/Imam Reza/ICU 25/12/2017 02/02/2018 65 Yes Urinary Abdominal Yes
N195 66/F Mashhad/Imam Reza/Infectious 10/02/2018 05/03/2018 25 Yes Urinary No Yes
N198
58/M Mashhad/Imam Reza/ICU 16/11/2016 17/02/2017 103 Yes No data No availableNot
N210 54/F Mashhad/Imam Reza/ICU 26/10/2015 06/12/2015 40 Yes No Abdominal Yes
N211 56/F Mashhad/Imam Reza/General 25/04/2018 15/05/2018 20 Yes Urinary No Yes
N218 34/F Mashhad/Imam Reza/Burning 26/02/2016 07/03/2016 12 Yes No No Yes
7ALZ 30/M Mashhad/Ghaem/General 20/02/2018 05/04/2018 46 Yes Central venous Abdominal No
8ALZ 29/M Mashhad/Ghaem/Hematology 24/04/2018 11/05/2018 17 Yes Central venous No No
10ALZ 29/M Mashhad/Ghaem/ICU 29/01/2018 05/03/2018 35 Yes Central venous,
Urinary No No
11ALZ 29/M Mashhad/Ghaem/Hematology 20/02/2018 30/03/2018 40 Yes Central venous No No
62ALZ 39/M Mashhad/Ghaem/ Maternity 24/05/2018 01/07/2018 37 Yes Central venous Abdominal No
ICU: Intensive Care Unit, PICU: Pediatric Intensive Care Unit, CICU: Cardiac Intensive Care Unit, NICU: Neonatal Intensive Care Unit, CAS: Caspofungin, FLZ: Fluconazole, NYS: Nystatin, AMB: Amphotericin B, M: Male, F: Female, m: Month.
Supplementary Table S3a. Continue. No. Mechanic
al ventilati
on
Immunosuppres
sant used Neutropenia Underlying conditions exposure with14 days prior antibiotics
Specim en type
Antifungal treatment
(Drug/Dosages/Duration) Outcome Prophilaxy
SU-221 Yes No No Brain tumor, Diabetes Vancomycin,
Ciprofloxacin Blood None Died
SU-231 No Yes No Pneumonia Vancomycin,
Ciprofloxacin, Blood NYS/100,000U/ml/drop/1 day Survived
SU-235 No Yes No GI bleeding, Colon cancer Ceftriaxone,
Clindamycin Blood CAS/50mg/14 days Died
SU-239 Yes Yes No Vascular and heart events Ceftriaxone,
Vancomycin, Cefazolin Blood NYS/100,000U/ml/drop/1 day Died
SU-267 No No No GI bleeding, Addict Vancomycin, Cefazolin Blood None Survive
d FLZ/100mg/10days 10 BC
Yes No No tumors, Abdominal surgeryDialysis, Sepsis, Solid Meropenem,Vancomycin,
Ciprofloxacin Blood
CAS/70mg/stat/50mg/daily/3 days -
L-AMB/3mg/kg/7 days Died 11BC
Yes No No Chronic lung diseases Meropenem,Vancomycin,
Ciprofloxacin Blood FLZ/400mg/daily/14 days
Survive d 24 BC
No No No Cerebral events, Chroniclung diseases, Paraplegia/Auto immune Meropenem, Vancomycin Blood FLZ/400mg/daily/2 days + CAS/70mg/stat/50 mg/daily/2days- L-AMB/3mg/kg/10 days Survive d FLZ/200mg/11days
75 BC Yes No Yes Solid tumors, Abdominal
events Not available Blood FLZ/400mg/daily/14 days Survived
82 BC No No No Cerebral events, Chronic
lung diseases Ciprofloxacin,Clindamycin Blood None Survived
85(1)
BC No No No Dialysis, Solid tumors, Renaldisease Imipenem Blood CAS/70mg/stat/50 mg/daily/5 daysFLZ/400mg/daily/10 days, Died FLZ/400mg/23days 99 BC
Surgical location infection 107 BC
Yes No No heart events, Hepatitis CDiabetes, Vascular and infection Meropenem, Vancomycin, Cefepime, Metronidazole, Linezolid, Rifampin
Blood CAS/70 mg/7 days Survived
113(1) BC
Yes No No
Diabetes, Dialysis, Vascular and heart events, Chronic lung diseases, Solid tumors,
Renal disease Vancomycin, Meropenem, Piperacillin-Tazobactam, Metronidazole, Cefepime
Blood CAS/50 mg/30 days Died
113(2) BC
Yes No No
Diabetes, Dialysis, Vascular and heart events, Chronic lung diseases, Solid tumors,
Renal disease Vancomycin, Meropenem, Piperacillin-Tazobactam, Metronidazole, Cefepime
Blood CAS/50 mg/30 days Died
115(1) BC
Yes No No Sepsis, Leukemia
Vancomycin, Meropenem, Piperacillin-Tazobactam, Metronidazole, Clindamycin
Blood CAS/70mg/stat/50 mg/daily/3 daysFLZ/400mg/daily/2 days, Died FLZ/400mg/43days
115(2) BC
yes No No Sepsis, Leukemia
Vancomycin, Meropenem, Piperacillin-Tazobactam, Metronidazole, Clindamycin
Blood CAS/70mg/stat/50 mg/daily/3 daysFLZ/400mg/daily/2 days, Died FLZ/400mg/28days
E-209
Yes No No Sepsis Clindamycin,Ceftazidime,
Meropenem Blood AMB/15mg/kg/IV/7 days
Survive d E-230
Yes Yes Yes Sepsis, Leukemia
Ceftazidime, Clindamycin, Amikacin, Piperacillin-Tazobactam, Vancomycin, Ampicillin Sulbactam
Blood FLZ/150mg/daily/2 days-AMB/18mg/kg/7 days Died
E-240
Yes No No Solid tumor
Ceftizoxime, Vancomycin, Amikacin, Linezolid,
Metronidazole, Cephalexin
Blood AMB/12mg/kg/5 days Died
E-262 No No No Not available Ceftizoxime,
Vancomycin, Amikacin, Linezolid,
Metronidazole,
Blood CAS/35mg/stat/25mg/daily/7 days Survive d
Cephalexin E-368
Yes No No Sepsis, Vascular and heartevents
Cephalexin, Imipenem, Vancomycin, Ceftriaxone, Piperacillin-Tazobactam
Blood FLZ/150mg/daily/2 days +AMB/18mg/daily /10 days Died E-369
Yes No No Sepsis, Vascular and heartevents
Cephalexin, Imipenem, Vancomycin, Ceftriaxone,
Piperacillin-Tazobactam Blood
CAS/56mg/stat/40mg/daily/3 days Survived E-511
No Yes Yes Leukemia, Sepsis
Ceftazidime, Meropenem, Vancomycin,
Piperacillin-Tazobactam Blood
L-AMB/20mg/3 days Died E-527 No No No Sepsis Ceftazidime, Meropenem, Vancomycin, Piperacillin-Tazobactam
Blood AMB/100mg/kg/7 days Died
E-528 Yes No No Sepsis Meropenem, Vancomycin, Colistin, Ampicillin, Cefotaxime,
Blood AMB/2.5mg/kg/10 days Survived E-614
Yes No No Sepsis, Dialysis
Amikacin, Gentamycin, Linezolid,
Metronidazole, Vancomycin
Blood AMB/12mg/kg/7 days Died
E-629
Yes Yes yes Leukemia, Dialysis, Sepsis
Cefixime, Meropenem, Vancomycin, Trimethoprim-Sulfamethoxazole, Amikacin, Ampicillin Sulbactam Blood
AMB/50mg/kg/10 days Died
E-699
Yes Yes No Sepsis, Vascular and heartevents Ceftazidime,Vancomycin,
Amikacin, Gentamycin Blood AMB/10mg/kg/10 days
Survive d E-703
Yes No No Vascular and heart events
Vancomycin, Trimethoprim-Sulfamethoxazole, Ceftazidime, Piperacillin-Tazobactam, Cefepime.
Blood FLZ/25mg/daily/2 days survived
E-787 No No Yes Solid tumors Ceftriaxone,
Ceftizoxime, Vancomycin,
Blood FLZ/150mg/daily/14
Imipenem E-1013 No No No Sepsis Ceftazidime, Vancomycin, Piperacillin-Tazobactam, Clindamycin, Amikacin
Blood AMB/3mg/kg/10 days Survived E-1014
Yes Yes Yes Sepsis
Amikacin, Gentamycin, Linezolid,
Metronidazole, Vancomycin
Blood CAS/60mg/stat/45mg/daily/3 days-AMB/30mg/kg/10 days Died
4M Yes No No Diabetes, Chronic lung
diseases Meropenem,Ceftriaxone Tracheal FLZ/400mg/daily/10 days -AMB/3mg/kg/7 days Survived
8M Not
available Not available availableNot Not available Amikacin, Ceftazidime,Clindamycin Blood None Died
N15 Yes No No Diabetes, Chronic lung
diseases Vancomycin,Meropenem Blood FLZ/200mg/kg/daily/2 days Survived
N17 No No No Diabetes, Chronic lung
diseases Vancomycin,Meropenem Tracheal FLZ/400mg/daily/7 days +AMB/3mg/kg/7 days Died
N18 Yes No No Chronic lung diseases Vancomycin,
Meropenem Tracheal FLZ/150mg/daily/10 days,AMB/3mg/kg/10 days Died N26
Yes No No Sepsis, Chronic lungdiseases Ciprofloxacin,Vancomycin,
Ampicillin Blood AMB/50mg/kg/7 days
Survive d N43
Yes No No heart events, Chronic lungDiabetes, Vascular and diseases
Ciprofloxacin,
Meropenem Tracheal AMB/3mg/kg/2 days Died
N68 No Yes Yes Leukemia, Sepsis Amikacin, Ceftazidime,
Clindamycin Blood AMB/50mg/kg/19 days Died
N69
No Yes Yes Leukemia, Sepsis Amikacin, Ceftazidime,Clindamycin Blood AMB/50mg/kg/10 days Survived N71 Yes Yes No Leukemia, Sepsis, Bone pain Amikacin, Ceftazidime,
Vancomycin Blood AMB/50mg/kg/2 days Survived
N72 No No No Disease syndrome, Fever,
Respiratory distress Amikacin, Ampicillin,Vancomycin Blood None Died
N78 No No No Sepsis, Biliary obstruction,
Heart failure (Heart arrest) Metronidazole Blood None Died
N98 Not
available Not available availableNot Not available Not available Blood Not available Survived
N104 Yes No No Stomach bleeding Azithromycin,
Ceftriaxone Blood AMB/50mg/kg/10 days Died
N107 Yes No No Diabetes, Sepsis, Abdominal
events Colistin, Ciprofloxacin Blood FLZ/200mg/daily/2 days Survived
N111 Yes No No Sepsis Ciprofloxacin Blood AMB/50mg/kg/12 days Died
N140
Yes No No Sepsis Vancomycin,Ceftazidime,
Ciprofloxacin Blood None Died
Imipenem, Colistin
N163 Yes No No Sepsis, Burning Vancomycin,
Ceftriaxone Blood AMB/50mg/kg/10 days Died
N186
Yes No No Diabetes, Dialysis, Sepsis Vancomycin,Meropenem,
Methicillin Blood None
Survive d N195
Yes No No Sepsis Vancomycin,Meropenem,
Ciprofloxacin Blood FLZ/200mg/daily/4 days
Survive d
N198 Not
available Not available availableNot Not available Vancomycin, ColistinMeropenem, Blood FLZ, CAS, AMB Died N208
Yes No No Sepsis Ciprofloxacin,Meropenem,
Vancomycin. Blood NYS/100,000U/ml/drop/1 day Died N210
Yes No No Sepsis, Burning
Ceftazidime, Imipenem, Gentamycin, Vancomycin, Ciprofloxacin, Amikacin
Blood None Died
N211 Yes No No Sepsis Vancomycin,
Ceftazidime Blood None Died
N218
Yes No No Sepsis Metronidazole,Penicillin,
Cefalotin, Cephalexin Blood None Died
7ALZ No No No Sepsis, Bedridden Ceftriaxone, Ciprofloxacin, Clindamycin, Vancomycin
Blood AMB/50mg/kg/6 days Died
8ALZ
No Yes Yes Leukemia, Sepsis, Mentallyretarded, Emboli Ciprofloxacin,Vancomycin,
Clindamycin Blood None Died
10ALZ
No No No (CABG), Rinse and aspirateDialysis, Heart disease the stomach
Vancomycin, Ciprofloxacin,
Clindamycin, Gentamicin
Blood NYS/100,000U/ml/drop/1 day Died 11ALZ No No No Leukemia, Sepsis Ciprofloxacin, Vancomycin, Meropenem, Gentamicin, Ceftriaxone, Clindamycin
Blood None Died
62ALZ
No No No Cesare, Emboli Cefixime, Meropenem,Vancomycin,
Ceftazidime Blood None
Survive d
ICU: Intensive Care Unit, PICU: Pediatric Intensive Care Unit, CICU: Cardiac Intensive Care Unit, NICU: Neonatal Intensive Care Unit, CAS: Caspofungin, FLZ: Fluconazole, NYS: Nystatin, AMB: Amphotericin B, M: Male, F: Female, m: Month
Table S3b. Summary of clinical profile of patients suffering from candidemia due to Candida tropicalis.
Variable
N
%
Total number of:
*All calculations are based on
episodes
(isolates with ≥30 days
considered as a new case)
isolates
64
patients
62
episodes (after deletion of
repetitive isolates)
62
Sex
Female
26
41.93
Male
36
58.07
Age
Median
37.1yr
City
Tehran
26
41.93
Shiraz
5
8.06
Mashhad
31
50
Hospital ward
ICU
27
43.54
General
16
25.8
Surgery
3
4.83
Other
16
25.8
In/out patient
Inpatient
61
98.3
Outpatient
1
1.61
Risk factors
Catheter
Yes
53
85.48
No
9
14.51
Surgery
Abdominal surgery
17
27.41
Non-abdominal surgery
8
12.9
Without surgery
37
59.67
No
42
67.74
Mechanical ventilation
Yes
37
59.67
No
25
40.32
Immunosuppressive drugs
Yes
14
22.58
No
48
77.41
Neutropenia
Yes
12
19.35
No
50
80.64
Underlying conditions
Leukemia
Yes
9
14.51
No
53
85.48
Hematological malignancies
other than leukemia
Yes
0
0
No
62
100
Diabetes
Yes
10
16.12
No
52
83.87
Dialysis
Yes
7
11.29
No
55
88.7
Sepsis
Yes
31
50
No
31
50
Cerebral events
Yes
4
6.45
No
58
93.54
Burning
Yes
3
4.83
No
59
95.16
Vascular and heart events
Yes
8
12.9
No
54
87.09
Chronic lung diseases
Yes
12
19.35
No
50
80.64
Solid tumor
Yes
7
11.29
No
55
88.7
Trauma and fracture
Yes
0
0
No
64
100
Abdominal events
Yes
10
16.12
No
52
83.87
No
61
98.38
Other
Yes
12
19.35
No
50
80.64
Hospitalization duration
Median
≤30
30
48.38
30-90
29
46.77
>90
3
4.83
Crud mortality rate for C.
tropicalis
Died
Survived
37
25
59.67
40.32
Mortality rate for C. tropicalis per
city
Tehran
Shiraz
13
3
60
50
Mashhad
21
67.74
Mortality per treatment
No treatment
12
30.77
Monotherapy
15
43.59
Combination therapy
10
25.64
Treatment
FLZ (11 in combination)
16
25.8
AMB (10 in combination)
28
45.16
CAS (5 in combination)
11
17.74
VOR
0
0
NYS
4
6.45
Mortality per treatment
FLZ
8
50
AMB
18
64.28
CAS
9
81.81
VOR
0
0
Table S4. Antifungal susceptibility testing data and sequencing of genes conferring resistance to fluconazole.
Patient # Genotype FLZ VRZ MIC values (µg/ml)ITZ MFG AFG AMB ERG11 MRR1 TAC1 UPC2
N4 G4 1 0.5 0.25 1 0.5 1 WT ND ND ND
N8
G5 0.5 0.125 0.5 0.062 0.062 0.5
WT G259R (A87T), T398C (V133A), G3066A (M1022I), C3125A (T1042N), C3131A (T1044N),
A3390G (I1130M) WT G751R (A251T), A866W (Q289L), G1175R (G392E) N15 G2 0.5 0.125 0.125 0.016 0.016 0.25 WT WT T833C (L278S) A293R (N98S), T472K (L158V) N17 G4 4 0.5 1 0.125 0.062 1
WT C1568Y (S523F), A2269R (K757E), A3390R (I1130M) T833C (L278S), T1019W (L340*), G1049R (D350N), T1410G (F470C), G2369A (D790N) NA N18 G4 2 0.62 0.5 0.125 0.031 0.5 WT ND ND ND N26 G6 2 0.5 0.125 0.125 0.062 1 WT C1568T (S523F), A2269R (K757E) T833C (L278S), G1048R (D350N),
T1409G (F470C), G2367A (D790N) G889K (A297S), G1175R(G392E)
N43 G1 2 0.125 0.5 0.031 0.031 0.5 WT ND ND ND N68 G6 0.5 0.5 0.25 0.5 0.5 0.5 WT ND ND ND N69 G6 2 1 0.25 0.031 0.016 1 WT ND ND ND N71 G9 0.125 0.016 0.125 0.008 0.008 1 WT C1568T (S523F), A2269R (K757E) T833C (L278S), G1048R (D350N), T1409G (F470C), G2367A (D790N) G1175R (G392E) N72 G3 0.5 0.25 0.125 0.16 0.008 0.25 WT ND ND ND N78 G4 1 0.031 0.5 0.031 0.008 0.5 WT ND ND ND N98 G4 1 0.5 0.25 0.008 0.008 0.5 WT ND ND ND N104 G4 1 0.25 0.25 0.062 0.031 1 WT G3066R (M1022I), C3125M (T1042N), C3131M (T1044N), T3286W (D1092E), A3390R (I1130M)
T833C (L278S) WT N107 G4 1 0.062 0.25 0.062 0.062 1 WT ND ND ND N111 G4 0.25 0.016 0.25 0.062 0.031 0.5 WT ND ND ND N140 G4 1 0.5 0.25 0.008 0.008 0.5 WT ND ND ND N147 G4 0.5 0.031 0.125 0.062 0.062 0.5 WT G3066R (M1022I), C3125M (T1042N), T833C (L278S), C3131M (T1044N), T3286W (D1092E), T833C (L267S) WT
A3390R (I1130M) N163 G3 1 0.062 0.125 0.016 0.016 0.5 A269W (K90I) ND ND ND N186 G4 2 1 0.25 0.008 0.008 1 WT ND ND ND N195 G4 0.25 0.031 0.125 0.008 0.008 0.5 WT C1568T (S523F), A2269R (K757E) T833C (L278S), G1048R (D350N), T1409G (F470C), G2367A (D790N) G889K (A297S), G1175R (G392E) N198 G1 0.25 0.031 0.5 0.125 0.125 1 WT ND ND ND N208 G4 0.5 0.25 0.25 0.062 0.008 0.5 WT ND ND ND N210 G2 0.125 0.062 0.125 0.125 0.125 0.25 WT WT T833C (L278S) A293R (N98S), T472K (L158V), G751R (A251T) N211 G4 1 0.062 0.25 0.062 0.008 0.5 WT ND ND ND N218 G4 0.25 0.016 0.5 0.5 0.25 1 WT ND ND ND SU-221 G5 0.03 0.015 0.06 0.25 0.125 1
WT G259R (A87T), T398Y (V133A), G3066A (M1022I), C3125A (T1042N), C3131A (T1044N),
T3286W (D1092E), A3390G (I1130M)
T833C (L278S), T1409G (F470C) WT SU-231 G4 0.125 0.06 0.125 0.25 0.125 1 WT ND ND ND SU-235 G2 0.125 0.125 0.125 0.062 0.031 1 WT WT T833C (L278S) A293R (N98S), T472K (L158V), G751R (A251T) SU-239 G2 4 0.06 0.125 0.25 0.25 1 WT WT T833C (L278S) T472Y (L158V), A293R (N98S), T472K (L158V), T1712W (F571Y) SU-267
G1 0.125 0.125 0.125 0.062 0.062 1 A73G (I25A)and T74C (I25A)
WT T833C (L278S), T1409G (F470C),
A2650G (S884G) A293R (N98S), C355M (L119F),G439R (A147T), T472K (L158V) 7ALZ G5 0.25 0.031 0.5 0.125 0.125 1 WT ND ND ND 8ALZ G5 0.5 0.062 0.5 0.062 0.062 0.5 WT ND ND ND 10ALZ G4 0.25 0.25 0.125 0.016 0.016 1 WT ND ND ND 11ALZ G4 1 0.125 0.125 0.125 0.062 0.5 WT ND ND ND 62ALZ G4 0.25 0.016 0.5 0.5 0.25 1 WT ND ND ND
10BC G6 1 0.5 0.5 0.007 0.062 0.5 WT T1223Y (I408T), G3066R (M1022I), C3125M(T1042N), C3131M (T1044N), T3286W (D1092E), A3390R (I1130M)
T833Y (L278S), T1409G (F470C),
G2367R (D790N), G2368R (D790N) (Q289L), G889K (A297S)G751R (A251T), A866W
11BC G2 1 0.5 0.5 0.062 0.062 0.5 WT ND ND ND
75BC G4 4 0.125 0.25 0.031 0.012 1 WT C1568Y (S523F), A2269R (K757E), A3390R(I1130M) T833Y (L278S) WT
82BC G4 4 1 0.25 0.062 0.062 0.5 WT A3390G (I1130M) WT G877A (A263T)
85BC G2 2 0.25 0.125 0.031 0.125 1 WT WT T833C (L278S) A293R (N98S), T472K (L158V)
99BC G5 8 1 0.5 0.031 0.125 2
WT T398Y (V133A), G1939K (A647S), G3066R (M1022I), C3131M (T1044N), T3286W (D1092E),
A3390G (I1130M)
T833C (L278S), T1409G (F470C)
WT 107BC G3 4 0.062 0.125 0.062 0.062 0.5 WT C1568T (S523F), A2269G (K757E) T833C (L278S), T1409G (F470C),G2367A (D790N) WT
113-1BC G4 4 1 0.125 0.007 0.06 1 WT A3390G (I1130M) T833C (L278S), T1409G (F470C) G751R (A251T), A866W(Q289L)
113-2BC G2 8 0.062 0.25 0.125 0.062 0.125
WT WT T833C (L278S) A293R (N98S), T472K (L158V),
A689R (N230S), A721R (T241A)
115-2BC G5 4 0.5 0.06 0.015 0.015 1
WT G259A (A87T), T398C (V133A), G3066A (M1022I), C3125A (T1042N), C3131A (T1044N),
A3390G (I1130M)
WT G751R (A251T), A866W
(Q289L), G1175R (G392E) 115-1BC G5 0.5 0.125 0.125 0.016 0.031 0.5 WT (M1022I), C3125A (T1042N), C3131A (T1044N),G259A (A87T), T398C (V133A), G3066A
A3390G (I1130M) WT G751R (A251T), A866W (Q289L), 209E G6 1 0.5 0.125 0.016 0.016 0.5 WT ND ND ND 230E G6 1 0.062 0.25 0.062 0.062 0.25 WT ND ND ND 240E G4 0.25 0.031 0.125 0.016 0.016 0.5 WT ND ND ND
262E G4 64 4 16 0.008 0.008 1 WT (T1044N), T3276W (D1092E), A3390R (I1130M)G3066R (M1022I), C3125M (T1042N), C3133M G140A (R47Q), A491T (N164I), T833C(L278S) T1020A (Q340H), T1141A(T381S)
368E G6 0.5 0.25 0.25 0.031 0.008 0.5 WT ND ND ND
369E G10 0.25 0.062 0.25 1 0.5 0.5 WT ND ND ND
511E G6 0.25 0.062 0.25 0.062 0.062 1 WT ND ND ND
527E G8 8 1 0.5 0.031 0.016 1
WT A763M (T255P) G140A (R47Q), A491W (N164I),
T833C (L278S), T1409G (F470C), G2367R and G2368R (D790N) G439R (A147T), G751W(A251T), A866W (Q289L) 528E G6 0.5 0.062 0.25 0.125 0.008 0.5 WT ND ND ND 614E G2 0.5 0.25 0.125 0.016 0.031 0.5 WT ND ND ND 629E G5 0.5 0.125 0.25 0.125 0.016 1 WT ND ND ND 699E G2 0.5 0.25 0.25 0.031 0.031 0.5 WT ND ND ND
703E G6 0.5 0.062 0.25 0.008 0.062 1 WT ND ND ND
787E G7 0.5 0.031 0.25 0.031 0.125 1 WT ND ND ND
1013E G5 0.5 0.062 0.125 0.031 0.031 0.25 WT ND ND ND
1014E G4 1 0.25 0.5 0.062 0.008 0.5 WT ND ND ND
*; Stop codon,
ND; Not determined, NA; Not amplified WT; Wild-type, G; Genotype, FLZ; Fluconazole, VRZ; Voriconazole, ITZ; Itraconazole, MFG; Micafungin, AFG; Anidulafungin,
and AMB; Amphotericin B. Regardless of MIC values, all the sequences of HS1 and HS2 of FKS1were wildtype. HS1 and HS2 of FKS1 amino acid sequences are
Statistical analysis section
Genotype and hospitalization duration association
G2
G3
G4
G5
G6
27
53
20
20
61
26
51
65
46
18
5
41
25
17
130
40
26
3
109
39
15
54
28
62
36
54
42
61
28
20
13
8
40
28
30
26
39
20
35
37
15
25
12
20
12
20
35
40
37
62
37
8
35
35
52
65
As the hospitalization duration data were not normally distributed, first they were normalized using Kolmogorov Smirnov.
Tests of Normality
Kolmogorov-Smirnova Shapiro-Wilk
Statistic df Sig. Statistic df Sig.
HosDuration .145 56 .005 .864 56 .000
a. Lilliefors Significance Correction
In order to assess the association between genotypes and hospitalization duration we used the non-parametric Kruskal Wallis Test and the association was not
significant.
Test Statistics
a,bHosDuration
Chi-Square 2.754
df 4
Asymp. Sig. .600
a. Kruskal Wallis Test b. Grouping Variable: Genotype
Association between genotype and fluconazole susceptibility profile using Chi-Square and lack of significant association between these two variables.
Genotype
G2
G3
G4
G5
G6
FLZ-R
1
0
1
1
0
FLZ-S
7
1
19
7
11
Genotype * FLZ Crosstabulation
Count FLZ Total R S SDD Genotype G2 1 7 1 9 G3 0 1 2 3 G4 1 19 4 24 G5 1 7 1 9 G6 0 11 0 11 Total 3 45 8 56Chi-Square Tests
Value df Asymptotic Significance (2-sided) Pearson Chi-Square 10.854a 8 .210 Likelihood Ratio 10.376 8 .240 Linear-by-Linear Association .483 1 .487 N of Valid Cases 56a. 11 cells (73.3%) have expected count less than 5. The minimum expected count is .16.
Association between genotype and voriconazole susceptibility profile using Chi-Square and lack of significant association between these two variables.
Genotyp
e
G2
G3
G4
G5
G6
VRZ-R
0
0
4
1
1
VRZ-S
5
2
12
7
4
VRZ-I
4
1
8
1
6
Genotype * VRZ Crosstabulation
Count VRZ Total R S SDD Genotype G2 0 5 4 9 G3 0 2 1 3 G4 4 12 8 24 G5 1 7 1 9 G6 1 4 6 11 Total 6 30 20 56Chi-Square Tests
Value df Asymptotic Significance (2-sided) Pearson Chi-Square 6.712a 8 .568 Likelihood Ratio 8.236 8 .411 Linear-by-Linear Association .061 1 .805 N of Valid Cases 56
a. 12 cells (80.0%) have expected count less than 5. The minimum expected count is .32.
Association between genotypes and mortality through multivariate logistic variation and path analysis revealed lack of association between these
variables.
G2
G3
G4
G5
G6
Alive
3
1
10
1
6
Dead
5
2
15
7
5
Genotype * outcome Crosstabulation
Count outcome Total Alive Dead Genotype G2 3 5 8 G3 1 2 3 G4 10 15 25
G5 1 7 8 G6 6 5 11 Total 21 34 55
Chi-Square Tests
Value df Asymptotic Significance (2-sided) Pearson Chi-Square 3.550a 4 .470 Likelihood Ratio 3.903 4 .419 Linear-by-Linear Association .159 1 .690 N of Valid Cases 55a. 7 cells (70.0%) have expected count less than 5. The minimum expected count is 1.15.
Variables Alive
B S.E. Wald df Sig. Exp(B)
Step 1a G2 -.693 .949 .534 1 .465 .500
G3 -.875 1.366 .411 1 .522 .417
G4 -.588 .730 .648 1 .421 .556
Constant .182 .606 .091 1 .763 1.200 a. Variable(s) entered on step 1: G2, G3, G4, G5.
Variables Dead
Score df Sig. Step 0 Variables G2 .002 1 .966 G3 .032 1 .859 G4 .064 1 .800 G5 2.616 1 .106 G6 1.560 1 .212a. Residual Chi-Squares are not computed because of redundancies.