. 2021 May 1;203(9):1070–1087. doi: 10.1164/rccm.202102-0498ST

Table 2.

GRADE Evidence Table for Studies Assessing Viral + Bacterial Nucleic Acid–based Testing

Certainty Assessment							Impact	Certainty	Importance
No. of Studies	Study Design	Risk of Bias	Inconsistency	Indirectness	Imprecision	Other Considerations	Impact	Certainty	Importance
Duration of antibiotics

3^*	Observational studies	Serious^†	Not serious	Not serious	Serious^‡	None	*Gelfer et al., 2015 (*20): Days of therapy (normalized to 1,000 patient days) were significantly fewer in the virus-only group, compared with groups with virus and bacteria or bacteria only identified as pathogens (1,188 ± 641, compared with 1,661 ± 387 and 1,484 ± 252, respectively; P = 0.003).	Very low	Critical

							*Gilbert et al., 2016 (*19): The length of therapy (normalized to 1,000 patient days) was significantly lower in virus-only patients than in patients with bacterial infection (845 ± 252, compared with 1,380 ± 1,205; P = 0.04).

							*Rezkalla et al., 2019 (*22): Among patients who underwent multiplex PCR testing (n = 70), 22 (31%) had a pathogen identified. The average duration of antibiotics for PCR-negative patients was 8.3 d (range, 0–15 d) compared with 4.9 d (range, 0–12 d) in the PCR-positive group with a viral pathogen (P = 0.0004).

Modification of antimicrobial treatment

4^§	Observational studies	Serious^\|\|	Not serious	Not serious	Serious^¶	None	*Gelfer et al., 2015 (*20): In 18 patients, PCR identified a virus only; in only four of these patients were empiric antibiotics discontinued within 48 h of physician receipt of PCR results.	Very low	Critical

							*Gilbert et al., 2016 (*19): In 25 patients, PCR identified a virus only; discontinuation of empiric antibiotics within 48 h of test results occurred in 8 of the 25 (32%) patients.

							*Guillon et al., 2017 (*21): Pathogen identification using multiplex PCR led to changes in antibiotic treatment in 22% of patients (ICU, n = 63; pulmonary ward, n = 8).

							*Wittermans et al., 2019 (*23): In multivariable analyses, PCR for atypical pathogens was associated with any alteration of antibiotic treatment by Hospital Day 3 (OR, 2.6; 95% CI, 1.4–4.9) and an alteration of atypical coverage (OR, 3.1 95% CI, 1.6–6.0). There was not a significant association between PCR for respiratory viruses and these outcomes.

Definition of abbreviations: CI = confidence interval; ED = emergency department; GRADE = Grading of Recommendations, Assessment, Development, and Evaluation; OR = odds ratio.

Study comparison groups: Studies that compare viral + bacterial testing with no viral + bacterial testing: Wittermans and colleagues (2019) (23). Studies that compare a positive viral + bacterial test result to having a negative viral + bacterial test result: Gelfer and colleagues (2015) (20), Gilbert and colleagues (2016) (19), Guillon and colleagues (2017) (21), and Rezkalla and colleagues (2019) (22).

References 19 and 20 are cluster-randomized trials; however, results presented here are not a comparison of intervention versus control groups. Reference 22 is a cohort study.

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In References 19 and 20, patients were cluster randomized in 1-week blocks to undergo additional diagnostic testing with either a laboratory-generated respiratory pathogen PCR panel or a commercial, faster, and broader multiplex PCR panel. Presented results are a comparison of groups based on pathogen, not based on intervention, and these results are unadjusted. Results from Reference 22 are unadjusted.

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References 19, 20, and 22 included few participants and few events.

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^{^¶}

References 19–21 included few participants and/or few events.