Table 1.

Characteristics of included studies for target trough evaluation

Study	Design of study	Country	Duration of study	Age of patients	Percentage of MRSA and source	Definition of trough levels
Lodise 2009 [9]	Retrospective	America	2005–2006	≥18 Mean ± SD: 55.8 ± 18.1	MRSA infection (30%): Bloodstream, central nervous system, infective endocarditis, intra-abdominal, osteomyelitis, prophylaxis, respiratory tract, skin and soft tissue, urinary tract, unknown.	Highest The highest initial trough levels within 96 h of initiation of therapy
Hermsen 2010 [18]	Retrospective	America	2005–2007	≥19 Median (IQR): Trough < 15 μg/mL 59 (43–75) Trough ≥15 μg/mL 60 (44.5–70)	MRSA infection (100%): Pneumonia, endocarditis, osteomyelitis	Mean Trough levels calculated using the sum of each measured trough level multiplied by the number of days and divided by the total number of treatment days
Clemens 2011 [19]	Retrospective	America	2008–2009	≥18 Mean ± SD: 52.3 ± 16.3	MRSA bacteremia (100%): Skin or soft tissue/bone, intravascular catheter, respiratory, endocarditis, endovascular, abdominal, unknown.	Steady-state The first serum concentration collected ≤30 min before a scheduled dose after completing ≥24 h of vancomycin therapy
Kullar 2011 [20]	Retrospective	America	2005–2010	45–64 Median (IQR): Success 53 (45–64) Failure 54 (46–61)	MRSA bacteremia (100%): Skin/wound, catheter-related, endocarditis, pneumonia, bone and joint, deep abscess, multiple sites, other.	Steady-state Steady-state when available from clinical data. (e.g, immediately before the fourth dose)
Cano 2012 [26]	Retrospective	America	2006–2007	58.5 ± 17.2 Mean ± SD: 58.5 ± 17.2	Percentage of MRSA is not available: Hospital-acquired pneumonia, ventilator-associated pneumonia, health care–associated pneumonia	Highest Highest trough levels collected within 96 h of therapy
Horey 2012 [27]	Retrospective	America	2006–2008	≥18 Mean ± SD: 67.4 ± 12.5	Percentage of MRSA is not available: Empiric, skin and soft tissue, bone and joint, pneumonia, urinary tract infection, bacteremia/endocarditis, miscellaneous	Average The average levels were calculated by first multiplying each trough level by the number of days at that concentration; next, these values, from the total duration of therapy, were added. The sum was then divided by the total number of days of vancomycin exposure to produce a clinical picture of total exposure to vancomycin.
Prabaker 2012 [28]	Retrospective	America	2005–2007	Median 59 or 61 in each group	Percentage of MRSA is not available: Skin/soft tissue/bone infection, pneumonia, bacteremia, other.	Mean Trough levels drawn 30–60 min prior to the fourth dose, and again in 5–7 days or with any large change in renal function
Casapao 2013 [21]	Retrospective	America	2004–2012	≥18 Mean ± SD: 57 ± 15.4	MRSA bacteremia (100%): Infective endocarditis, pneumonia, intravenous catheter-related infection, bone and joint infection, skin and soft tissue infection, unknown.	Initial (No detail information is available.)
Fujii 2013 [29]	Retrospective	Japan	2011	> 18 Median (range), SD: 64 (21–88), 14.2	Percentage of MRSA is not available.	Highest Trough levels determined 3 days after the initiation of vancomycin therapy
Ley 2013 [30]	Retrospective	America	2006–2010	≥18 Mean ± SD: 50 ± 22.6	Percentage of MRSA is not available: Trauma.	Trough levels drawn 1 h prior to the subsequent dose
Barriere 2014 [31]	Retrospective	38 countries	2005–2007	≥18 Mean ± SD: 64.7 ± 16.2	MRSA pneumonia (78%): S. aureus nosocomial pneumonia, multilobar pneumonia, bacteremia.	Median (No detail information is available.)
Ghosh 2014 [22]	Retrospective	Australia	2006–2012	> 18 Median (range): 64.6 (22–95)	MRSA bacteremia (100%): Line-related bacteremia, bone and joint, skin and soft tissue infections, deep abscess, infective endocarditis, pneumonia, abdominal, non-endocarditis vascular, other, no identified focus.	Steady-state Trough levels obtained a minimum of 12 h after the last dose
Song 2015 [23]	Prospective	Korea	2010–2012	≥18 Median (IQR): 67 (53–75)	MRSA bacteremia (100%): Central venous catheter, bone and joint, skin and soft tissue, deep tissue abscess, lower respiratory tract, endovascular infection, urinary tract, intra-abdominal, unknown, high-risk source.	Initial (No detail information is available.)
Hammoud 2016 [33]	Retrospective	America	2011–2012	> 18 Mean: 56	MRSA infection (13%): Skin and soft tissue infection, pneumonia, osteomyelitis, pelvic/abdominal infection	Mean Mean levels calculated based on the theoretical number of days at various troughs for a specific patient
Hirano 2016 [34]	Retrospective	Japan	2007–2014	> 18 Mean ± SD: 68.2 ± 15.8	MRSA infection (100%): Respiratory, skin and soft tissue, bacteremia, Central nervous, Intra-abdominal, urinary tract, mediastinal, bone and joint.	Steady-state Trough levels defined as those determined after the fifth dose or on day 3 after the initiation of therapy
Obara 2016 [32]	Prospective	Brazil	2013–2014	> 18 Median (IQR): Trough 15–20 μg/mL 64.5 (52.3–79.5) Trough ≥20 μg/mL 55.5 (40–70.8)	Percentage of MRSA is not available.	Initial Initial levels obtained immediately before vancomycin fourth dose
Chuma 2018 [35]	Retrospective	Japan	2005–2015	≥18 Median (IQR): 67 (55–75)	MRSA infection (34%): Abdominal, blood stream catheter related, endocarditis, meningitis, soft tissue, pulmonary, urinary.	Initial Initial trough levels measured within 4 days after the beginning of administration
Fu 2018 [24]	Retrospective	Taiwan	2013–2016	≥20 Mean ± SD: 69 ± 14.8	MRSA bacteremia (100%): Bone and joint, catheter-related, endocarditis, pneumonia, surgical wound or skin and soft tissue, unknown.	Mean Pre-dialysis trough levels
Huang 2018 [36]	Retrospective	China	2007–2014	≥80 Mean ± SD: 85 ± 3.9	MRSA infection (24%)	Trough levels obtained within 72 h of commencing therapy, after administering a minimum of three doses
Mogle 2018 [25]	Retrospective	America	2016–2018	≥18 Mean ± SD: 50 ± 17.6	MRSA bacteremia (100%): Skin and soft tissue, catheter related/endovascular, bone and joint, urinary tract, pneumonia, presence of endocarditis, unknown.	Steady-state consecutive steady-state post-distributional serum concentrations obtained within 96 h of therapy
Park 2018 [37]	Retrospective	Korea	2013	≥18 Median (IQR): 58 (45–59)	Percentage of MRSA is not available: Pneumonia, sepsis/Septic shock, skin/skin structure infection, bacteremia, other.	Mean Trough levels measured in blood samples collected just prior to administration of the next dose
Shime 2018 [38]	Prospective	Japan	2014–2015	60–78 Median (IQR): 71 (60–78)	MRSA infection (100%): Bacteremia, lung skin and soft tissue, bone and joint, other.	Highest (No detail information is available.)
de Almeida 2019 [39]	Prospective	Brazil	2017–2018	≥18 Median (IQR): 55.9 (40.6–66.8)	MRSA infection (6.1%): Skin and soft tissue, surgical site, pulmonary, bone, catheter, central nervous system, kidney, others, undetermined.	Steady-state Trough levels measured at the third (after the fourth or fifth dose, corresponding to the steady-state)

N/A not available