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 journalArticlepeer-review

11 Scopus citations


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 languageEnglish
Pages (from-to)66-72
Number of pages7
JournalClinical Microbiology and Infection
Issue number1
StatePublished - Jan 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 The Authors


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 .

FundersFunder number
Meso Scale Diagnostics


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


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