Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations

Elena Carrara; Alessia Savoldi; Laura J.V. Piddock; Francois Franceschi; Sally Ellis; Mike Sharland; Adrian John Brink; Patrick N.A. Harris; Gabriel Levy-Hara; Anusha Rohit; Constantinos Tsioutis; Hiba Zayyad; Christian Giske; Margherita Chiamenti; Damiano Bragantini; Elda Righi; Anna Gorska; Evelina Tacconelli

doi:10.1016/j.cmi.2021.05.002

Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations

Elena Carrara, Alessia Savoldi, Laura J.V. Piddock, Francois Franceschi, Sally Ellis, Mike Sharland, Adrian John Brink, Patrick N.A. Harris, Gabriel Levy-Hara, Anusha Rohit, Constantinos Tsioutis, Hiba Zayyad, Christian Giske, Margherita Chiamenti, Damiano Bragantini, Elda Righi, Anna Gorska, Evelina Tacconelli

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Objectives: Optimal treatment of carbapenem-resistant Gram-negative bacteria (CR-GNB) infections is uncertain because of the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. Methods: A 36-item questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. Results: A total of 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of the respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in high-income countries versus 59% (194/283) in upper-medium-income countries and 30% (118/196) in lower-middle-income countries/lower-income-countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of ‘combination therapy’ with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) requiring in vitro synergism. Conclusions: Management of CR-GNB infections is far from being standardized. Strategic public health focused randomized controlled trials are urgently required to inform evidence-based treatment guidelines.

Original language	English
Pages (from-to)	66-72
Number of pages	7
Journal	Clinical Microbiology and Infection
Volume	28
Issue number	1
DOIs	https://doi.org/10.1016/j.cmi.2021.05.002
State	Published - Jan 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 The Authors

Funding

AS, EC, AG, GLH, ER, CT, AR, HZ, CG, AJB and ET have no competing interests to be declared. SE, FF and LJVP are employed by GARDP. PNAH declares research grants outside the submitted work from Sandoz , Shionogi and MSD and speakers' fees from Pfizer .

Funders	Funder number
Pfizer
Meso Scale Diagnostics
Sandoz
Shionogi

Keywords

Antibiotic resistance
Bacterial infections
Carbapenem-resistant gram-negative
Combination therapy
Cross-sectional survey

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cmi.2021.05.002

Cite this

Carrara, E., Savoldi, A., Piddock, L. J. V., Franceschi, F., Ellis, S., Sharland, M., Brink, A. J., Harris, P. N. A., Levy-Hara, G., Rohit, A., Tsioutis, C., Zayyad, H., Giske, C., Chiamenti, M., Bragantini, D., Righi, E., Gorska, A., & Tacconelli, E. (2022). Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations. Clinical Microbiology and Infection, 28(1), 66-72. https://doi.org/10.1016/j.cmi.2021.05.002

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title = "Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations",

abstract = "Objectives: Optimal treatment of carbapenem-resistant Gram-negative bacteria (CR-GNB) infections is uncertain because of the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. Methods: A 36-item questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. Results: A total of 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of the respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in high-income countries versus 59% (194/283) in upper-medium-income countries and 30% (118/196) in lower-middle-income countries/lower-income-countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of {\textquoteleft}combination therapy{\textquoteright} with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) requiring in vitro synergism. Conclusions: Management of CR-GNB infections is far from being standardized. Strategic public health focused randomized controlled trials are urgently required to inform evidence-based treatment guidelines.",

keywords = "Antibiotic resistance, Bacterial infections, Carbapenem-resistant gram-negative, Combination therapy, Cross-sectional survey",

author = "Elena Carrara and Alessia Savoldi and Piddock, {Laura J.V.} and Francois Franceschi and Sally Ellis and Mike Sharland and Brink, {Adrian John} and Harris, {Patrick N.A.} and Gabriel Levy-Hara and Anusha Rohit and Constantinos Tsioutis and Hiba Zayyad and Christian Giske and Margherita Chiamenti and Damiano Bragantini and Elda Righi and Anna Gorska and Evelina Tacconelli",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2022",

month = jan,

doi = "10.1016/j.cmi.2021.05.002",

language = "אנגלית",

volume = "28",

pages = "66--72",

journal = "Clinical Microbiology and Infection",

issn = "1198-743X",

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Carrara, E, Savoldi, A, Piddock, LJV, Franceschi, F, Ellis, S, Sharland, M, Brink, AJ, Harris, PNA, Levy-Hara, G, Rohit, A, Tsioutis, C, Zayyad, H, Giske, C, Chiamenti, M, Bragantini, D, Righi, E, Gorska, A & Tacconelli, E 2022, 'Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations', Clinical Microbiology and Infection, vol. 28, no. 1, pp. 66-72. https://doi.org/10.1016/j.cmi.2021.05.002

Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations. / Carrara, Elena; Savoldi, Alessia; Piddock, Laura J.V. et al.
In: Clinical Microbiology and Infection, Vol. 28, No. 1, 01.2022, p. 66-72.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria

T2 - a worldwide cross-sectional survey addressing the use of antibiotic combinations

AU - Carrara, Elena

AU - Savoldi, Alessia

AU - Piddock, Laura J.V.

AU - Franceschi, Francois

AU - Ellis, Sally

AU - Sharland, Mike

AU - Brink, Adrian John

AU - Harris, Patrick N.A.

AU - Levy-Hara, Gabriel

AU - Rohit, Anusha

AU - Tsioutis, Constantinos

AU - Zayyad, Hiba

AU - Giske, Christian

AU - Chiamenti, Margherita

AU - Bragantini, Damiano

AU - Righi, Elda

AU - Gorska, Anna

AU - Tacconelli, Evelina

PY - 2022/1

Y1 - 2022/1

N2 - Objectives: Optimal treatment of carbapenem-resistant Gram-negative bacteria (CR-GNB) infections is uncertain because of the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. Methods: A 36-item questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. Results: A total of 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of the respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in high-income countries versus 59% (194/283) in upper-medium-income countries and 30% (118/196) in lower-middle-income countries/lower-income-countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of ‘combination therapy’ with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) requiring in vitro synergism. Conclusions: Management of CR-GNB infections is far from being standardized. Strategic public health focused randomized controlled trials are urgently required to inform evidence-based treatment guidelines.

AB - Objectives: Optimal treatment of carbapenem-resistant Gram-negative bacteria (CR-GNB) infections is uncertain because of the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. Methods: A 36-item questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. Results: A total of 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of the respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in high-income countries versus 59% (194/283) in upper-medium-income countries and 30% (118/196) in lower-middle-income countries/lower-income-countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of ‘combination therapy’ with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) requiring in vitro synergism. Conclusions: Management of CR-GNB infections is far from being standardized. Strategic public health focused randomized controlled trials are urgently required to inform evidence-based treatment guidelines.

KW - Antibiotic resistance

KW - Bacterial infections

KW - Carbapenem-resistant gram-negative

KW - Combination therapy

KW - Cross-sectional survey

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IS - 1

ER -

Clinical management of severe infections caused by carbapenem-resistant gram-negative bacteria: a worldwide cross-sectional survey addressing the use of antibiotic combinations

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

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Cite this