Background
Methods
Search strategies
Search strategy for the evaluation of VCM target trough concentrations
Search strategy for the evaluation of VCM target AUC values
Search strategy for the evaluation of different monitoring strategies
Study selection
Study selection for the evaluation of VCM target trough concentrations
Study selection for the evaluation of the VCM target AUC values
Study selection for the evaluation of different monitoring strategies
Data extraction
Outcomes analysis
Outcome analysis for the evaluation of VCM target trough concentrations
Outcome analysis for the evaluation of the VCM target AUCvalues
Outcome analysis for the evaluation of different monitoring strategies
Assessment of the risk of bias
Analysis of the results and statistical analyses
Results
Search results
Characteristics
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) |
Study | Design of study | Country | Duration of study | Age of patients | Patient’s condition | Definition of AUC values | Target AUC/MIC breakpoint |
---|---|---|---|---|---|---|---|
Zelenitsky 2013 [40] | Retrospective | Canada, America, Saudi Arabia | 1996–2005 | ≥18 Mean ± SD: 55.9 ± 16.7 | MRSA-associated septic shock | Values calculated (i) within the first 72 h of therapy based on the measured and extrapolated serum levels, and (ii) at steady-state using the daily dose divided by the population pharmacokinetic model derived vancomycin clearance | ≥ 451 |
Ghosh 2014 [22] | Retrospective | Australia | 2006–2012 | > 18 Median (range): 64.6 (22–95) | MRSA bacteremia | D/(CLcr × 0.79) + 15.4] × 0.06 | ≥ 398 |
Jung 2014 [41] | Retrospective | Korea | 2009–2012 | ≥18 Median (IQR): 69 (34–93) | MRSA bacteremia | Values estimated fitting vancomycin serum levels to a two-compartment volume clearance model using the maximum a posteriori probability Bayesian approach | ≥ 398.5 |
Song 2015 [23] | Prospective | Korea | 2005–2007 | ≥18 Median (IQR): 67 (53–75) | MRSA bacteremia | The total vancomycin dose in milligrams for 24 h over the vancomycin clearance | ≥ 392.7 |
Makmor-bakry 2019 [42] | Retrospective | Malaysia | N/A | ≥18 Mean ± SD: 59.2 ± 14.5 | MRSA bacteremia | Values estimated from the trough level and published vancomycin population PK values | ≥ 400 |
Study | Design of study | Country | Duration of study | Age of patients | Patient’s condition | Definition of AUC values | Target AUC breakpoint |
---|---|---|---|---|---|---|---|
Chavada 2017 [43] | Retrospective | Australia | 2006–2012 | > 18% of patient age ≥ 70: AKI 50.0% Non-AKI 41.1% | MRSA bacteremia | Values estimated by the maximum a posteriori Bayesian estimation, using a priori pharmacokinetic parameters of a previous population pharmacokinetic model | ≥ 563 |
Zasowski 2018 [44] | Retrospective | America | 2014–2015 | > 18 Mean ± SD: 61.7 ± 16.8 | Confirmed or suspected bacteremiaor pneumonia | Values estimated via the maximum a posteriori probability Bayesian function using a previously published 2-compartment population pharmacokinetic model as the Bayesian prior | ≥ 683 |
Meng 2019 [15] | Prospective | America | 2018 | ≥18 Median ± SD (IQR): AKI 51 ± 19 (37–62) Non-AKI 63 ± 17 (50–69) | Pulmonary, skin and soft tissue infection, osteoarticular, febrile neutropenia, abdominal, pelvic, intrathoracic, bacteremia, central nervous system, endocarditis, cardiovascular implantable, electronic device infections, vascular graft | Values obtained by a Stanford hospital–specific spreadsheet calculator with prebuilt pharmacokinetic equations using Microsoft Excel (http://med.stanford.edu/bugsanddrugs.html) | ≥ 600 |
Brunetti 2020 [45] | Retrospective | America | 2011–2018 | ≥18 Mean ± SD: 57 ± 16.4 | N/A | Values estimated by DoseMe software, which uses a Bayesian approach | > 600 |
Lodise 2020 [46] | Prospective | America | 2014–2015 | ≥18 Mean ± SD: 60.7 ± 17.3 | MRSA bloodstream infection | Values estimated post hoc using the maximal a posteriori probability procedure | ≥ 550 |
Study | Design of study | Country | Duration of study | Age of patients | Number of patients | Target AUC (mg*hr./L) | Target trough (mg/L) | Rate (%) of MRSA | |
---|---|---|---|---|---|---|---|---|---|
AUC-guided | Trough-guided | ||||||||
Finch 2017 [47] | Retrospective, quasi-experimental study | America | 2014–2015 | ≥ 18 Mean ± SD: 59.1 ± 16.9 | 734 | 546 | 400–600 | 15–20 | N/A |
Neely 2018 [48] | 3-year, prospective, serial cohort study | America | 2012–2016 | ≥ 18 Mean (range): 48.7 (18–93) | 177 | 75 | 400–800 | 10–20 | 10 |
Meng 2019 [15] | Prospective observational quality assurance study | America | 2017–2018 | ≥ 18 Median ± SD (IQR): Trough-guided 58 ± 17 (46–67) AUC-guided 62 ± 17 (46–68) | 117 | 179 | 400–800 | 10–20 | 9 |
Oda 2020 [49] | Single-centered retrospective study | Japan | 2016–2020 | ≥ 19 Median (range): Trough-guided 68.5 (19–84) AUC-guided 64.0 (19–87) | 22 | 52 | 400–600 | 15–20 | 36 |