TY - JOUR
T1 - Incidence of infection with multidrug-resistant Gram-negative bacteria and vancomycin-resistant enterococci in carriers
T2 - a systematic review and meta-regression analysis
AU - Willems, Roel P. J.
AU - van Dijk, Karin
AU - Vehreschild, Maria J. G. T.
AU - Biehl, Lena M.
AU - Ket, Johannes C. F.
AU - Remmelzwaal, Sharon
AU - Vandenbroucke-Grauls, Christina M. J. E.
N1 - Funding Information: This study was funded by a grant from the Netherlands Organization for Health Research and Development (grant number 541001010). We thank Wolfgang Viechtbauer for his statistical advice. We thank Rania El Habib for her assistance with acquiring the data. Our acknowledgment does not imply endorsement of our views, and we remain solely responsible for the views expressed herein. Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/6
Y1 - 2023/6
N2 - Background: Carriers of multidrug-resistant bacteria are at risk of infections with these bacteria; the precise size of this risk is unclear. We aimed to quantify the effect of gut colonisation on subsequent risk of infection with multidrug-resistant bacteria. Methods: We performed a systematic review and meta-regression analysis. We searched PubMed, Embase, Web of Science Core Collection, and Google Scholar for follow-up studies published from Jan 1, 1995, to March 17, 2022, that measured the incidence of infections with multidrug-resistant Gram-negative bacteria (MDR-GNB) and from Jan 1, 1995, to March 15, 2022, that measured the incidence of infections with vancomycin-resistant enterococci (VRE). We included original cohort studies and case-control studies that used incidence-density sampling, included 50 or more patients with enteric colonisation or positive urinary samples as a surrogate marker of colonisation, or both, and analysed infections clearly preceded by colonisation. We did not use any language restrictions. We excluded studies not reporting length of follow-up. Summary data were extracted and independently cross-verified by two authors. Carriage was defined as MDR-GNB or VRE, detected in faecal or urinary cultures. Our primary outcomes were cumulative incidence and incidence density of infection in patients colonised by multidrug-resistant bacteria. To estimate pooled incidences, general linearised mixed-effects meta-regressions were used, adjusting for varying follow-up durations. This study is registered with PROSPERO, CRD42020222415. Findings: Of the 301 studies identified, 44 studies (26 on MDR-GNB, 14 on VRE, and four on both MDR-GNB and VRE) from 14 countries were retained for qualitative synthesis, 40 of which were analysed with meta-regression, comprising data for 14 049 patients colonised with multidrug-resistant bacteria. The pooled cumulative incidence of infection was 14% (95% CI 10–18; p<0·0001) at a median follow-up time of 30 days for MDR-GNB (845 cases of infection in 9034 patients colonised) and 8% (5–13; p<0·0001) at 30 days for VRE (229 cases of infection in 4747 patients colonised). Infection incidence density (4·26 infections per 1000 patient-days; 95% CI 1·69–6·82) and cumulative incidence of infection (19%, 95% CI 15–25; p<0·0001; 602 cases of infection in 4547 patients colonised) were highest for carbapenem-resistant Gram-negative bacteria at 30 days. Risk of bias was rated low to moderate. Interpretation: The risk of infection was substantial, with the highest risk for patients colonised with carbapenem-resistant Gram-negative bacteria and the lowest in patients with VRE. These data might help to guide prophylactic and treatment decisions and form a valuable resource for planning clinical trials on targeted prevention.
AB - Background: Carriers of multidrug-resistant bacteria are at risk of infections with these bacteria; the precise size of this risk is unclear. We aimed to quantify the effect of gut colonisation on subsequent risk of infection with multidrug-resistant bacteria. Methods: We performed a systematic review and meta-regression analysis. We searched PubMed, Embase, Web of Science Core Collection, and Google Scholar for follow-up studies published from Jan 1, 1995, to March 17, 2022, that measured the incidence of infections with multidrug-resistant Gram-negative bacteria (MDR-GNB) and from Jan 1, 1995, to March 15, 2022, that measured the incidence of infections with vancomycin-resistant enterococci (VRE). We included original cohort studies and case-control studies that used incidence-density sampling, included 50 or more patients with enteric colonisation or positive urinary samples as a surrogate marker of colonisation, or both, and analysed infections clearly preceded by colonisation. We did not use any language restrictions. We excluded studies not reporting length of follow-up. Summary data were extracted and independently cross-verified by two authors. Carriage was defined as MDR-GNB or VRE, detected in faecal or urinary cultures. Our primary outcomes were cumulative incidence and incidence density of infection in patients colonised by multidrug-resistant bacteria. To estimate pooled incidences, general linearised mixed-effects meta-regressions were used, adjusting for varying follow-up durations. This study is registered with PROSPERO, CRD42020222415. Findings: Of the 301 studies identified, 44 studies (26 on MDR-GNB, 14 on VRE, and four on both MDR-GNB and VRE) from 14 countries were retained for qualitative synthesis, 40 of which were analysed with meta-regression, comprising data for 14 049 patients colonised with multidrug-resistant bacteria. The pooled cumulative incidence of infection was 14% (95% CI 10–18; p<0·0001) at a median follow-up time of 30 days for MDR-GNB (845 cases of infection in 9034 patients colonised) and 8% (5–13; p<0·0001) at 30 days for VRE (229 cases of infection in 4747 patients colonised). Infection incidence density (4·26 infections per 1000 patient-days; 95% CI 1·69–6·82) and cumulative incidence of infection (19%, 95% CI 15–25; p<0·0001; 602 cases of infection in 4547 patients colonised) were highest for carbapenem-resistant Gram-negative bacteria at 30 days. Risk of bias was rated low to moderate. Interpretation: The risk of infection was substantial, with the highest risk for patients colonised with carbapenem-resistant Gram-negative bacteria and the lowest in patients with VRE. These data might help to guide prophylactic and treatment decisions and form a valuable resource for planning clinical trials on targeted prevention.
UR - http://www.scopus.com/inward/record.url?scp=85147263933&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S1473-3099(22)00811-8
DO - https://doi.org/10.1016/S1473-3099(22)00811-8
M3 - Article
C2 - 36731484
SN - 1473-3099
VL - 23
SP - 719
EP - 731
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 6
ER -