Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species: A systematic review with meta-analysis

Patrick N.A. Harris, Jane Y. Wei, Andrew W. Shen, Ahmed A. Abdile, Stuart Paynter, Rachel R. Huxley, Nirmala Pandeya, Yohei Doi, Kyungmin Huh, Catherine S. O'Neal, Thomas R. Talbot, David L. Paterson

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objectives: This systematic review and meta-analysis compared effects of different antibiotics on mortality in patients with bloodstream infections caused by Enterobacteriaceae with chromosomal AmpC β-lactamase. Methods: Databases were systematically searched for studies reporting mortality in patients with bloodstream infections caused by AmpC producers treated with carbapenems, broad-spectrum β-lactam/β-lactamase inhibitors (BLBLIs), quinolones or cefepime. Pooled ORs for mortality were calculated for cases that received monotherapy with these agents versus carbapenems. Registration: PROSPERO international prospective register of systematic reviews (CRD42014014992; 18 November 2014). Results: Eleven observational studies were included. Random-effects meta-analysis was performed on studies reporting empirical and definitive monotherapy. In unadjusted analyses, no significant difference in mortality was found between BLBLIs versus carbapenems used for definitive therapy (OR 0.87, 95% CI 0.32-2.36) or empirical therapy (OR 0.48; 95% CI 0.14-1.60) or cefepime versus carbapenems as definitive therapy (OR 0.61; 95% CI 0.27-1.38) or empirical therapy (0.60; 95% CI 0.17-2.20). Use of a fluoroquinolone as definitive therapy was associated with a lower risk of mortality compared with carbapenems (OR 0.39; 95% CI 0.19-0.78). Three studies with patient-level data were used to adjust for potential confounders. The non-significant trends favouring non-carbapenem options in these studies were diminished after adjustment for age, sex and illness severity scores, suggestive of residual confounding. Conclusions: Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems.

Original languageEnglish
Pages (from-to)296-306
Number of pages11
JournalJournal of Antimicrobial Chemotherapy
Volume71
Issue number2
DOIs
Publication statusPublished - 01-02-2016
Externally publishedYes

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Citrobacter
Serratia
Enterobacter
Carbapenems
Meta-Analysis
Anti-Bacterial Agents
Infection
Mortality
Quinolones
Therapeutics
Enterobacteriaceae Infections
Lactams
Fluoroquinolones
Observational Studies
Databases

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Harris, Patrick N.A. ; Wei, Jane Y. ; Shen, Andrew W. ; Abdile, Ahmed A. ; Paynter, Stuart ; Huxley, Rachel R. ; Pandeya, Nirmala ; Doi, Yohei ; Huh, Kyungmin ; O'Neal, Catherine S. ; Talbot, Thomas R. ; Paterson, David L. / Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species : A systematic review with meta-analysis. In: Journal of Antimicrobial Chemotherapy. 2016 ; Vol. 71, No. 2. pp. 296-306.
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abstract = "Objectives: This systematic review and meta-analysis compared effects of different antibiotics on mortality in patients with bloodstream infections caused by Enterobacteriaceae with chromosomal AmpC β-lactamase. Methods: Databases were systematically searched for studies reporting mortality in patients with bloodstream infections caused by AmpC producers treated with carbapenems, broad-spectrum β-lactam/β-lactamase inhibitors (BLBLIs), quinolones or cefepime. Pooled ORs for mortality were calculated for cases that received monotherapy with these agents versus carbapenems. Registration: PROSPERO international prospective register of systematic reviews (CRD42014014992; 18 November 2014). Results: Eleven observational studies were included. Random-effects meta-analysis was performed on studies reporting empirical and definitive monotherapy. In unadjusted analyses, no significant difference in mortality was found between BLBLIs versus carbapenems used for definitive therapy (OR 0.87, 95{\%} CI 0.32-2.36) or empirical therapy (OR 0.48; 95{\%} CI 0.14-1.60) or cefepime versus carbapenems as definitive therapy (OR 0.61; 95{\%} CI 0.27-1.38) or empirical therapy (0.60; 95{\%} CI 0.17-2.20). Use of a fluoroquinolone as definitive therapy was associated with a lower risk of mortality compared with carbapenems (OR 0.39; 95{\%} CI 0.19-0.78). Three studies with patient-level data were used to adjust for potential confounders. The non-significant trends favouring non-carbapenem options in these studies were diminished after adjustment for age, sex and illness severity scores, suggestive of residual confounding. Conclusions: Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems.",
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Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species : A systematic review with meta-analysis. / Harris, Patrick N.A.; Wei, Jane Y.; Shen, Andrew W.; Abdile, Ahmed A.; Paynter, Stuart; Huxley, Rachel R.; Pandeya, Nirmala; Doi, Yohei; Huh, Kyungmin; O'Neal, Catherine S.; Talbot, Thomas R.; Paterson, David L.

In: Journal of Antimicrobial Chemotherapy, Vol. 71, No. 2, 01.02.2016, p. 296-306.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species

T2 - A systematic review with meta-analysis

AU - Harris, Patrick N.A.

AU - Wei, Jane Y.

AU - Shen, Andrew W.

AU - Abdile, Ahmed A.

AU - Paynter, Stuart

AU - Huxley, Rachel R.

AU - Pandeya, Nirmala

AU - Doi, Yohei

AU - Huh, Kyungmin

AU - O'Neal, Catherine S.

AU - Talbot, Thomas R.

AU - Paterson, David L.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Objectives: This systematic review and meta-analysis compared effects of different antibiotics on mortality in patients with bloodstream infections caused by Enterobacteriaceae with chromosomal AmpC β-lactamase. Methods: Databases were systematically searched for studies reporting mortality in patients with bloodstream infections caused by AmpC producers treated with carbapenems, broad-spectrum β-lactam/β-lactamase inhibitors (BLBLIs), quinolones or cefepime. Pooled ORs for mortality were calculated for cases that received monotherapy with these agents versus carbapenems. Registration: PROSPERO international prospective register of systematic reviews (CRD42014014992; 18 November 2014). Results: Eleven observational studies were included. Random-effects meta-analysis was performed on studies reporting empirical and definitive monotherapy. In unadjusted analyses, no significant difference in mortality was found between BLBLIs versus carbapenems used for definitive therapy (OR 0.87, 95% CI 0.32-2.36) or empirical therapy (OR 0.48; 95% CI 0.14-1.60) or cefepime versus carbapenems as definitive therapy (OR 0.61; 95% CI 0.27-1.38) or empirical therapy (0.60; 95% CI 0.17-2.20). Use of a fluoroquinolone as definitive therapy was associated with a lower risk of mortality compared with carbapenems (OR 0.39; 95% CI 0.19-0.78). Three studies with patient-level data were used to adjust for potential confounders. The non-significant trends favouring non-carbapenem options in these studies were diminished after adjustment for age, sex and illness severity scores, suggestive of residual confounding. Conclusions: Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems.

AB - Objectives: This systematic review and meta-analysis compared effects of different antibiotics on mortality in patients with bloodstream infections caused by Enterobacteriaceae with chromosomal AmpC β-lactamase. Methods: Databases were systematically searched for studies reporting mortality in patients with bloodstream infections caused by AmpC producers treated with carbapenems, broad-spectrum β-lactam/β-lactamase inhibitors (BLBLIs), quinolones or cefepime. Pooled ORs for mortality were calculated for cases that received monotherapy with these agents versus carbapenems. Registration: PROSPERO international prospective register of systematic reviews (CRD42014014992; 18 November 2014). Results: Eleven observational studies were included. Random-effects meta-analysis was performed on studies reporting empirical and definitive monotherapy. In unadjusted analyses, no significant difference in mortality was found between BLBLIs versus carbapenems used for definitive therapy (OR 0.87, 95% CI 0.32-2.36) or empirical therapy (OR 0.48; 95% CI 0.14-1.60) or cefepime versus carbapenems as definitive therapy (OR 0.61; 95% CI 0.27-1.38) or empirical therapy (0.60; 95% CI 0.17-2.20). Use of a fluoroquinolone as definitive therapy was associated with a lower risk of mortality compared with carbapenems (OR 0.39; 95% CI 0.19-0.78). Three studies with patient-level data were used to adjust for potential confounders. The non-significant trends favouring non-carbapenem options in these studies were diminished after adjustment for age, sex and illness severity scores, suggestive of residual confounding. Conclusions: Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems.

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