Using risk factors and markers to predict bacterial respiratory co-/superinfections in COVID-19 patients: is the antibiotic steward’s toolbox full or empty?

Adequate diagnosis of bacterial respiratory tract co-/superinfection (bRTI) in coronavirus disease (COVID-19) patients is challenging, as there is insufficient knowledge about the role of risk factors and (para)clinical parameters in the identification of bacterial co-/superinfection in the COVID-19 setting. Empirical antibiotic therapy is mainly based on COVID-19 severity and expert opinion, rather than on scientific evidence generated since the start of the pandemic. We report the best available evidence regarding the predictive value of risk factors and (para)clinical markers in the diagnosis of bRTI in COVID-19 patients. A multidisciplinary team identified different potential risk factors and (para)clinical predictors of bRTI in COVID-19 and formulated one or two research questions per topic. After a thorough literature search, research gaps were identified, and suggestions concerning further research were formulated. The quality of this narrative review was ensured by following the Scale for the Assessment of Narrative Review Articles. Taking into account the scarcity of scientific evidence for markers and risk factors of bRTI in COVID-19 patients, to date, COVID-19 severity is the only parameter which can be associated with higher risk of developing bRTI. Evidence on the usefulness of risk factors and (para)clinical factors as predictors of bRTI in COVID-19 patients is scarce. Robust studies are needed to optimise antibiotic prescribing and stewardship activities in the context of COVID-19.</p

Levels of antibody IgG sub-classes against hepatitis B in vaccinated infants.

<p>Plasma levels of HbsAg-specific IgG sub-classes in 6 to 7 months old infants born to mothers infected (M+) or not (M−) with <i>T. cruzi</i>, and congenitally infected (B+) or not (B−), and vaccinated at 2, 4 and 6 months against hepatitis B. Results are displayed as box and whiskers (n = 6 M−B−, 13 M+B− and 9 M+B+). * : p<0.05 compared with infants from other groups (Man Withney <i>U</i> test).</p

IFN-γ and IL-13 productions in response to SEB by blood mononuclear cells from newborns and infants.

<p>Newborns and 6 to 7 months-old infants were born either to <i>T. cruzi-</i>infected (M+) or not infected mothers (M−), and either congenitally infected (B+) or not (B−). Cells were cultured during 6 days in the presence of 10 ng/mL SEB (staphylococcal enterotoxin B). Results of cytokines levels measured by ELISA (individual results and geometric means) are shown. * : p<0.05 and ** : p<0.005 (Mann-Withney <i>U</i> test).</p

Production of IFN-γ and IL-13 in response to vaccinal antigens by PBMC from infants from mothers infected (M+) or not (M−),with <i>T. cruzi</i>, and congenitally infected (B+) or not (B−).

a<p>Arithmetic mean±SEM.</p

Cytokine response to PPD in infants vaccinated with BCG.

<p>IFN-γ and IL-13 production in response to tuberculin purified protein derivative of <i>M. tuberculosis</i> (PPD) by PBMC from 6 to 7 months old infants born to mothers infected (M+) or not (M−) with <i>T. cruzi</i>, and congenitally infected (B+) or not (B−), and having received at birth the BCG vaccine. PBMC were cultured during 6 days in the presence of 10 µg/mL PPD. Results of cytokines levels measured by ELISA are shown (individual results and geometric means). The proportions of responders (i.e. showing detectable levels of cytokines) are also shown. * : p<0.05 and ** : p = 0.006 compared with M−B− infants (Mann-Withney <i>U</i> test for means and Fisher test for proportions).</p

Antibody levels against hepatitis B, diphtheria and tetanus vaccines in newborns and infants.

<p>Plasma levels of specific IgG in newborns and 6 to 7 months old infants born to mothers infected (M+) or not (M−) with <i>T. cruzi</i>, and congenitally infected (B+) or not (B−), and vaccinated at 2, 4 and 6 months against hepatitis B, diphtheria and tetanus. Results are shown as geometric means; extreme values are indicated, as well as the proportion of samples showing an antibody level above the indicated threshold of protection. * : p<0.05 (Mann Withney <i>U</i> test).</p