Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA)

a multinational prospective cohort study

Andrew J. Stewardson, Kalisvar Marimuthu, Sharmila Sengupta, Arthur Allignol, Maisra El-Bouseary, Maria J. Carvalho, Brekhna Hassan, Monica A. Delgado-Ramirez, Anita Arora, Ruchika Bagga, Alex K. Owusu-Ofori, Joseph O. Ovosi, Shamsudin Aliyu, Hala Saad, Souha S. Kanj, Basudha Khanal, Balkrishna Bhattarai, Samir K. Saha, Jamal Uddin, Purabi Barman & 19 others Latika Sharma, Tarek El-Banna, Rabaab Zahra, Mansab Ali Saleemi, Amarjeet Kaur, Kenneth Iregbu, Nkolika SC Uwaezuoke, Pierre Abi Hanna, Rita Feghali, Ana L. Correa, Maria I. Munera, Thi Anh Thu Le, Thi Thanh Nga Tran, Chimanjita Phukan, Chiranjita Phukan, Sandra L. Valderrama-Beltrán, Carlos Alvarez-Moreno, Timothy R. Walsh, Stephan Harbarth

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

Background: Low-income and middle-income countries (LMICs)are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. Methods: The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE)and carbapenem-resistant Entero-bacteriaceae (CRE)bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. Findings: Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15–61). Crude mortality was 20% (35 of 174 patients)for patients with CSE bloodstream infection and 35% (43 of 123 patients)for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3–6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04–2·94), and decreased probability of discharge alive (0·61, 0·45–0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. Interpretation: Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs. Funding: bioMérieux.

Original languageEnglish
Pages (from-to)601-610
Number of pages10
JournalThe Lancet Infectious Diseases
Volume19
Issue number6
DOIs
Publication statusPublished - 1 Jun 2019

Cite this

Stewardson, Andrew J. ; Marimuthu, Kalisvar ; Sengupta, Sharmila ; Allignol, Arthur ; El-Bouseary, Maisra ; Carvalho, Maria J. ; Hassan, Brekhna ; Delgado-Ramirez, Monica A. ; Arora, Anita ; Bagga, Ruchika ; Owusu-Ofori, Alex K. ; Ovosi, Joseph O. ; Aliyu, Shamsudin ; Saad, Hala ; Kanj, Souha S. ; Khanal, Basudha ; Bhattarai, Balkrishna ; Saha, Samir K. ; Uddin, Jamal ; Barman, Purabi ; Sharma, Latika ; El-Banna, Tarek ; Zahra, Rabaab ; Saleemi, Mansab Ali ; Kaur, Amarjeet ; Iregbu, Kenneth ; Uwaezuoke, Nkolika SC ; Abi Hanna, Pierre ; Feghali, Rita ; Correa, Ana L. ; Munera, Maria I. ; Le, Thi Anh Thu ; Tran, Thi Thanh Nga ; Phukan, Chimanjita ; Phukan, Chiranjita ; Valderrama-Beltrán, Sandra L. ; Alvarez-Moreno, Carlos ; Walsh, Timothy R. ; Harbarth, Stephan. / Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA) : a multinational prospective cohort study. In: The Lancet Infectious Diseases. 2019 ; Vol. 19, No. 6. pp. 601-610.
@article{14d832a2d3814962907fb76dc9a09013,
title = "Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study",
abstract = "Background: Low-income and middle-income countries (LMICs)are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. Methods: The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE)and carbapenem-resistant Entero-bacteriaceae (CRE)bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. Findings: Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15–61). Crude mortality was 20{\%} (35 of 174 patients)for patients with CSE bloodstream infection and 35{\%} (43 of 123 patients)for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95{\%} CI 0·3–6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95{\%} CI 1·04–2·94), and decreased probability of discharge alive (0·61, 0·45–0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. Interpretation: Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs. Funding: bioM{\'e}rieux.",
author = "Stewardson, {Andrew J.} and Kalisvar Marimuthu and Sharmila Sengupta and Arthur Allignol and Maisra El-Bouseary and Carvalho, {Maria J.} and Brekhna Hassan and Delgado-Ramirez, {Monica A.} and Anita Arora and Ruchika Bagga and Owusu-Ofori, {Alex K.} and Ovosi, {Joseph O.} and Shamsudin Aliyu and Hala Saad and Kanj, {Souha S.} and Basudha Khanal and Balkrishna Bhattarai and Saha, {Samir K.} and Jamal Uddin and Purabi Barman and Latika Sharma and Tarek El-Banna and Rabaab Zahra and Saleemi, {Mansab Ali} and Amarjeet Kaur and Kenneth Iregbu and Uwaezuoke, {Nkolika SC} and {Abi Hanna}, Pierre and Rita Feghali and Correa, {Ana L.} and Munera, {Maria I.} and Le, {Thi Anh Thu} and Tran, {Thi Thanh Nga} and Chimanjita Phukan and Chiranjita Phukan and Valderrama-Beltr{\'a}n, {Sandra L.} and Carlos Alvarez-Moreno and Walsh, {Timothy R.} and Stephan Harbarth",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/S1473-3099(18)30792-8",
language = "English",
volume = "19",
pages = "601--610",
journal = "Lancet Infectious Diseases",
issn = "1473-3099",
publisher = "Elsevier",
number = "6",

}

Stewardson, AJ, Marimuthu, K, Sengupta, S, Allignol, A, El-Bouseary, M, Carvalho, MJ, Hassan, B, Delgado-Ramirez, MA, Arora, A, Bagga, R, Owusu-Ofori, AK, Ovosi, JO, Aliyu, S, Saad, H, Kanj, SS, Khanal, B, Bhattarai, B, Saha, SK, Uddin, J, Barman, P, Sharma, L, El-Banna, T, Zahra, R, Saleemi, MA, Kaur, A, Iregbu, K, Uwaezuoke, NSC, Abi Hanna, P, Feghali, R, Correa, AL, Munera, MI, Le, TAT, Tran, TTN, Phukan, C, Phukan, C, Valderrama-Beltrán, SL, Alvarez-Moreno, C, Walsh, TR & Harbarth, S 2019, 'Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study', The Lancet Infectious Diseases, vol. 19, no. 6, pp. 601-610. https://doi.org/10.1016/S1473-3099(18)30792-8

Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA) : a multinational prospective cohort study. / Stewardson, Andrew J.; Marimuthu, Kalisvar; Sengupta, Sharmila; Allignol, Arthur; El-Bouseary, Maisra; Carvalho, Maria J.; Hassan, Brekhna; Delgado-Ramirez, Monica A.; Arora, Anita; Bagga, Ruchika; Owusu-Ofori, Alex K.; Ovosi, Joseph O.; Aliyu, Shamsudin; Saad, Hala; Kanj, Souha S.; Khanal, Basudha; Bhattarai, Balkrishna; Saha, Samir K.; Uddin, Jamal; Barman, Purabi; Sharma, Latika; El-Banna, Tarek; Zahra, Rabaab; Saleemi, Mansab Ali; Kaur, Amarjeet; Iregbu, Kenneth; Uwaezuoke, Nkolika SC; Abi Hanna, Pierre; Feghali, Rita; Correa, Ana L.; Munera, Maria I.; Le, Thi Anh Thu; Tran, Thi Thanh Nga; Phukan, Chimanjita; Phukan, Chiranjita; Valderrama-Beltrán, Sandra L.; Alvarez-Moreno, Carlos; Walsh, Timothy R.; Harbarth, Stephan.

In: The Lancet Infectious Diseases, Vol. 19, No. 6, 01.06.2019, p. 601-610.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA)

T2 - a multinational prospective cohort study

AU - Stewardson, Andrew J.

AU - Marimuthu, Kalisvar

AU - Sengupta, Sharmila

AU - Allignol, Arthur

AU - El-Bouseary, Maisra

AU - Carvalho, Maria J.

AU - Hassan, Brekhna

AU - Delgado-Ramirez, Monica A.

AU - Arora, Anita

AU - Bagga, Ruchika

AU - Owusu-Ofori, Alex K.

AU - Ovosi, Joseph O.

AU - Aliyu, Shamsudin

AU - Saad, Hala

AU - Kanj, Souha S.

AU - Khanal, Basudha

AU - Bhattarai, Balkrishna

AU - Saha, Samir K.

AU - Uddin, Jamal

AU - Barman, Purabi

AU - Sharma, Latika

AU - El-Banna, Tarek

AU - Zahra, Rabaab

AU - Saleemi, Mansab Ali

AU - Kaur, Amarjeet

AU - Iregbu, Kenneth

AU - Uwaezuoke, Nkolika SC

AU - Abi Hanna, Pierre

AU - Feghali, Rita

AU - Correa, Ana L.

AU - Munera, Maria I.

AU - Le, Thi Anh Thu

AU - Tran, Thi Thanh Nga

AU - Phukan, Chimanjita

AU - Phukan, Chiranjita

AU - Valderrama-Beltrán, Sandra L.

AU - Alvarez-Moreno, Carlos

AU - Walsh, Timothy R.

AU - Harbarth, Stephan

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Background: Low-income and middle-income countries (LMICs)are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. Methods: The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE)and carbapenem-resistant Entero-bacteriaceae (CRE)bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. Findings: Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15–61). Crude mortality was 20% (35 of 174 patients)for patients with CSE bloodstream infection and 35% (43 of 123 patients)for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3–6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04–2·94), and decreased probability of discharge alive (0·61, 0·45–0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. Interpretation: Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs. Funding: bioMérieux.

AB - Background: Low-income and middle-income countries (LMICs)are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. Methods: The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE)and carbapenem-resistant Entero-bacteriaceae (CRE)bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. Findings: Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15–61). Crude mortality was 20% (35 of 174 patients)for patients with CSE bloodstream infection and 35% (43 of 123 patients)for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3–6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04–2·94), and decreased probability of discharge alive (0·61, 0·45–0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. Interpretation: Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs. Funding: bioMérieux.

UR - http://www.scopus.com/inward/record.url?scp=85065887931&partnerID=8YFLogxK

U2 - 10.1016/S1473-3099(18)30792-8

DO - 10.1016/S1473-3099(18)30792-8

M3 - Article

VL - 19

SP - 601

EP - 610

JO - Lancet Infectious Diseases

JF - Lancet Infectious Diseases

SN - 1473-3099

IS - 6

ER -