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Table 2 Basic characteristics of case series/case reports included

From: Double-carbapenem therapy in the treatment of multidrug resistant Gram-negative bacterial infections: a systematic review and meta-analysis

Author/
Year
RegionDesignSample sizeSexAgea
(years)
InfectionOrganismDCTCombined antibioticsAntimicrobial susceptibility test (μg/ml)Treatment durationa
(days)
Follow-up timea
(days)
Outcomes
Ceccarelli, 2013 [51]Italycase report1male65SBSI, VAP
combined
MDR, KPC-III-producing KPETP 0.5/1 g q24h
DOR 0.25/0.5/1 g q8h
(4 h infusions)
ETP ≥8 R
DOR R
2830clinical response
microbiological response
Giamarellou, 2013 [26]Greececase report3male (1)
female (2)
54
42
44
SBSI (2), UTI (3)PDR, KPC-II-producing KPETP 1 g q24h
MEM 1/2 g q8h (2)
DOR 2 g q8h (1)
ETP > 8 R
MEM > 16 R
DOR > 8 R
20
14
10
300
21
180
clinical response 3/3
microbiological response 3/3
Oliva, 2014 [38]Italycase report3male (3)API (1), BSI (2)PDR, CPKPETP 0.5/1 g q24h
MEM 1 g q12h/2 g q8h
ETP 128 R (1), 256 R (2)
MEM 128 R (1), 256 R (2)
21
2
24
clinical response 3/3
microbiological response 3/3
demised 1/3
Camargo, 2015 [52]USAcase report1female64IAI, VAP, BSI
combined
XDR, KPC-producing KPETP 1 g q24h
MEM 1 g q12h
CSTETP -
MEM -
CST 12 R
12microbiological failure
emergence of colistin resistance
switched to AVC + ETP
Chua, 2015 [41]Singaporecase report2male (2)62
77
SSI (1), HAP (1)KPC-producing KPETP 0.5/1 g q24h
DOR 0.5/1 g q8h
(4 h infusions)
PMB + CST
PMB
ETP 4 (1), > 32 (1)
DOR 8 (1), − (1)
PMB 1 (1), − (1)
CST -
12
10 + 7
30
13
clinical response 2/2
microbiological response 2/2
demised 2/2
Oliva, 2015 [37]Italycase report1female75CVCIPDR, KPC-producing KPETP 1 g q24h
MEM 2 g q8h
CSTETP 128 R
MEM 256 R
CST 32 R
21clinical response
microbiological response
Tumbarello, 2015 [50]Italycase report8≥18BSIKPC-producing KPETP
MEM
ETP -
MEM -
≥214demised 3/8
Alessandra, 2016 [46]Italycase series15male (10)
female (5)
60.9 ± 10.9UTI (8), SSTI (2), EPI (2), PNA (1), MSI (2)KPC-producing KPETP 1 g (1 h infusions)
MEM 2 g q8h (3 h infusions)
ETP > 8 R (14)
MEM > 16 R (14)
ETP, MEM > 32 R (1)
15 (7–150)60clinical response 12/15
microbiological response 12/15
adverse events 3/15
(nausea, hypernatremia and seizures)
demised 1/15
Cprek, 2016 [47]USAcase series18male (10)
female (8)
62.5(51–67)BSI (7), PNA (5), IAI(2), UTI (3), SSSI (1)CRKPETP 1 g q24h
MEM 2 g q8h (17)
DOR 0.5 g q8h (1)
DOX, GEN
AMK, CIP
TGC + PMB
CIP + TGC
GEN + DOX
CAB > 1 R
DOX, GEN, AMK, CIP, TGC, PMB -
17 (2–72)30clinical response 7/18
microbiological response 11/14
adverse events 2/18
(2 seizures)
demised 5/18
Montelione, 2016 [40]Italycase report1male62APIXDR, CPKPETP 1 g q24h
MEM 2 g q8h
ETP 128 R
MEM 256 R
281095clinical response
microbiological response
Oliva, 2016 [39]Italycase report1female61SSI, HAP, SBSI
combined
KPC-producing ECETP 0.5 g q24h (1 h infusions)
MEM 2 g q12h (3 h infusions)
ETP 16 R
MEM 32 R
10clinical response
microbiological responsedemised
Basaranoglu,2017 [44]Turkeycase report3male (2)
female (1)
3 months
8 months
3
SBSI (1), CRBSI (2)MDR KPETP 0.015 g/kg q12h
MEM 0.02–0.04 g/kg q8h
CIP + TGC
AMK + TGC + CIP
CIP + AMK + CST
ETP > 8 R (1), > 32 R (2)
MEM > 6 R (1), > 32 R (2)
CIP > 2 R (1), > 4 R (2)
TGC 1 S (1), 2 S (1), > 2 R (1)
AMK 16 IR (1), > 64 R (2)
CST -
14
15
26
clinical response 2/3
microbiological response 3/3
Nekidy, 2017 [36]United Arab Emiratescase report1female62SSI, UTI, PNA, BSI combinedMDR KPETP 1 g q24h
MEM 1 g q8h
ETP ≥8 R
MEM -
28 + 7, 10, 14, 28, 14clinical response
microbiological response
Souli, 2017 [45]Greececase series27male (15)
female (12)
59(15–83)BSI (13), UTI (12), VAP (1), EVDI (1)PDR/XDR, KPC-II-producing KPETP 1 g q24h (1 h infusions)
MEM 2 g q8h (3 h infusions)
ETP > 8 IR
MEM ≥2 IR
10 (5–28)28 (9–200)clinical response 21/27
microbiological response 20/27
adverse events 4/27
(generalized rash, eosinophilia and 2 aseptic meningitis)
demised 8/27
Carrasco,2018 [42]Spaincase report1female36BSIXDR, KPC-producing KPETP 1 g q24h
MEM 2 g q8h (3 h infusions)
ETP ≥32 R
MEM ≥32 R
1490clinical response
microbiological response
Galvão, 2018 [43]Brazilcase report1male59SSI, SBSI
combined
XDR, KPC-producing KPETP 1 g q24h
MEM 2 g q8h (4 h infusions)
AMK + LZD
+FCA
ETP ≥8 R
MEM ≥16 R
AMK 4 S
LZD -
FCA -
45multiple organ failure and demised
Liang, 2018 [48]Chinacase report1male50SBSIXDR KPETP 1 g q24h (1 h infusions)
MEM 1 g q8h (3 h infusions)
ETP R
MEM R
9clinical response
microbiological response
Rosa, 2018 [49]USAcase report2male (1)
female (1)
57
35
UTINDM-harboring KP/ECETP 1 g q24h
MEM 1 g q12h (4 h infusions)
FOFETP -
MEM ≥16 R
FOF 12 S (1), 256 R (1)
14clinical response 2/2
microbiological response 2/2
  1. Abbreviations: DCT double-carbapenem therapy, PNA pneumonia, HAP hospital-acquired pneumonia, VAP ventilator-associated pneumonia, BSI bloodstream infection, SBSI secondary bloodstream infection, EPI endovascular prosthesis infection, API Aortic periprosthetic infection, CVCI central venous catheter infection, CRBSI catheter-related bloodstream infection, UTI urinary tract infection, IAI intra-abdominal infection, SSTI skin and soft tissue infection, SSSI skin and skin structure infection, SSI surgical site infection, EVDI external ventricular drainage infection, MSI multiple site infection, KP Klebsiella pneumoniae, EC Escherichia coli, CRKP carbapenem-resistant K. pneumoniae, CPKP carbapenemase-producing K. pneumoniae, KPC K. pneumoniae carbapenemase, KPC-II a type II carbapenem against KPC-producers, KPC-III a type III carbapenem against KPC-producers, NDM New Delhi Metallo-beta-lactamase, MDR multidrug resistant, XDR extensively drug resistant, PDR pandrug resistant, MEM meropenem, ETP ertapenem, DOR doripenem, CAB carbapenem antibiotics, CST colistin, GEN gentamicin, TGC tigecycline, CIP ciprofloxacin, AMK amikacin, FOF fosfomycin, LZD linezolid, PMB polymyxin B, DOX doxycycline, FCA fluconazole, AVC ceftazidime/avibactam, S sensitive, I intermediate, R resistant
  2. -: not reported
  3. a. Data are expressed as mean ± standard deviation (SD), or median (range or interquartile range)