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Fig 1.

Study flow diagram.

Results of systematic review identification, screening, and inclusion.

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Table 1.

Overview of review characteristics.

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Table 1 Expand

Fig 2.

ROBIS.

Results of the risk of bias evaluation of included systematic reviews using the ROBIS tool (Risk of Bias in Systematic Reviews), categorized per its four domains; D1 -study eligibility criteria, D2 –identification and selection of studies, D3 –data collection and study appraisal, D4 –Synthesis and findings.

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Fig 2 Expand

Fig 3.

Citation matrix for reviews reporting mortality of prolonged infusions versus intermittent infusions of beta-lactams.

Green—primary studies included in systematic review, Red—primary study not included in systematic review, Black—primary studies published after systematic review and therefore ineligible for possible inclusion.

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Fig 3 Expand

Fig 4.

Effect of prolonged versus intermittent infusions of beta-lactam antimicrobials on mortality.

*Lee 2017 –Did not report event rates. RR was therefore not converted to OR. **Roberts 2016 –individual patient data analysis.

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Fig 4 Expand

Fig 5.

Pairwise CCA for reviews reporting mortality of prolonged vs. intermittent infusions of beta-lactams.

Colors indicate degree of overlap, as calculated with CCA, for visual clarity. White = ≤5%, green 5.1–9.9%, yellow 10–14.9%, red ≥15%.

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Fig 5 Expand

Fig 6.

Citation matrix for reviews reporting clinical cure of prolonged infusions versus intermittent infusions of beta-lactams.

Green—primary studies included in systematic review, Red—primary study not included in systematic review, Black—primary studies published after systematic review and therefore ineligible for possible inclusion.

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Fig 6 Expand

Fig 7.

Effect of prolonged versus intermittent infusions of beta-lactam antimicrobials on clinical cure.

*Lee 2017 –Did not report event rates. RR was therefore not converted to OR. **Roberts 2016 –individual patient data meta-analysis. ***Chant 2013 –reported treatment failure. RR = 0.60 [0.40–0.87], I2 = 69%. Results were inverted to represent clinical cure or success.

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Fig 7 Expand

Fig 8.

Pairwise CCA of reviews reporting clinical cure of prolonged versus intermittent infusions of beta-lactams.

Colors indicate degree of overlap, as calculated with CCA, for visual clarity. White = ≤5%, green 5.1–9.9%, yellow 10–14.9%, red ≥15%.

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Fig 8 Expand

Fig 9.

Citation matrix for reviews reporting microbiologic cure of prolonged infusions.

Green—primary studies included in systematic review, Red—primary study not included in systematic review, Black—primary studies published after systematic review and therefore ineligible for possible inclusion.

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Fig 9 Expand

Fig 10.

Effect of prolonged infusions versus intermittent infusions of beta-lactam antimicrobials on microbiologic cure.

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Fig 10 Expand

Fig 11.

Pairwise CCA for reviews reporting microbiologic cure of prolonged versus intermittent beta-lactam infusions.

Colors indicate degree of overlap, as calculated with CCA, for visual clarity. White = ≤5%, green 5.1–9.9%, yellow 10–14.9%, red ≥15%.

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Fig 11 Expand

Fig 12.

Citation matrix for reviews reporting length of stay of prolonged infusions versus intermittent infusions of beta-lactams.

Green—primary studies included in systematic review, Red—primary study not included in systematic review, Black—primary studies published after systematic review and therefore ineligible for possible inclusion.

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Fig 12 Expand

Fig 13.

Pairwise CCA for reviews reporting length of stay of prolonged versus intermittent infusions of beta-lactams.

Colors indicate degree of overlap, as calculated with CCA, for visual clarity. White = ≤5%, green 5.1–9.9%, yellow 10–14.9%, red ≥15%.

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Fig 13 Expand

Fig 14.

Citation matrix for review reporting adverse events of prolonged infusions versus intermittent infusions of beta-lactams.

Green—primary studies included in systematic review, Red—primary study not included in systematic review, Black—primary studies published after systematic review and therefore ineligible for possible inclusion, Grey—included primary studies not reported for the specified outcome.

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Fig 14 Expand

Fig 15.

Pairwise CCA for reviews reporting adverse events or prolonged versus intermittent infusions of beta-lactams.

Colors indicate degree of overlap, as calculated with CCA, for visual clarity. White = ≤5%, green 5.1–9.9%, yellow 10–14.9%, red ≥15%. N/A indicated where primary studies included were not reported by systematic review.

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Fig 15 Expand

Fig 16.

Citation matrix for reviews reporting cost of prolonged versus intermittent infusions of beta-lactams.

Green—primary studies included in systematic review, Red—primary study not included in systematic review, Black—primary studies published after systematic review and therefore ineligible for possible inclusion.

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Fig 16 Expand

Fig 17.

Pairwise CCA for reviews reporting cost of prolonged versus intermittent infusions of beta-lactams.

Colors indicate degree of overlap, as calculated with CCA, for visual clarity. White = ≤5%, green 5.1–9.9%, yellow 10–14.9%, red ≥15%. N/A indicated where primary studies included were not reported by systematic review.

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Fig 17 Expand

Fig 18.

Citation matrix for reviews reporting emergence of resistance of prolonged versus intermittent infusion of beta-lactams.

Green—primary studies included in systematic review, Red—primary study not included in systematic review, Black—primary studies published after systematic review and therefore ineligible for possible inclusion, Grey—included primary studies not reported for the specified outcome.

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Fig 18 Expand

Fig 19.

Pairwise CCA for reviews reporting emergence of resistance of prolonged versus intermittent infusion of beta-lactams.

Colors indicate degree of overlap, as calculated with CCA, for visual clarity. White = ≤5%, green 5.1–9.9%, yellow 10–14.9%, red ≥15%. N/A indicated where primary studies included were not reported by systematic review.

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Fig 19 Expand

Fig 20.

Citation matrix for reviews reporting PK/PD outcomes of prolonged versus intermittent infusions of beta-lactams.

Green—primary studies included in systematic review, Red—primary study not included in systematic review, Black—primary studies published after systematic review and therefore ineligible for possible inclusion.

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Fig 20 Expand

Fig 21.

Pairwise CCA for reviews reporting PK/PD outcomes of prolonged versus intermittent infusion of beta-lactams.

Colors indicate degree of overlap, as calculated with CCA, for visual clarity. White = ≤5%, green 5.1–9.9%, yellow 10–14.9%, red ≥15%. N/A indicated where primary studies included were not reported by systematic review.

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Fig 21 Expand