title: Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis.
abstract: Carbapenem-resistant Gram-negative bacteria are recognized as a cause of difficult-to-treat infections associated with high mortality.
  
  
  
  To perform a systematic review of currently available data on distribution, characteristics and outcome associated with carbapenem-resistant bloodstream infections in adult neutropenic patients.
  
  
  
  Included studies were identified through Medline, Embase and Cochrane databases between January 1995 and April 2016. Random effect meta-analysis was used to quantify the association between carbapenem resistance and mortality and between carbapenem exposure and resistance.
  
  
  
  A total of 30 studies from 21 countries were included. Overall carbapenem resistance varied from 2% to 53% (median 9%) among studies. Infections due to carbapenem-resistant Pseudomonas spp . were reported in 18 (60%) studies showing high median resistance rates (44% of all carbapenem-resistant Gram-negatives and 19% of Pseudomonas isolates). Resistance of Enterobacteriaceae was less commonly reported and bloodstream infections due to carbapenem-resistant Klebsiella spp. were mainly documented from endemic areas (Greece, Italy, Israel). Carbapenem resistance in Acinetobacter spp. was reported in 9 (30%) studies (median resistance 58% of Acinetobacter isolates). Mortality rates ranged from 33% to 71% (median 50%) in patients with carbapenem-resistant infections. Carbapenem resistance appeared to correlate with mortality (OR 4.89, 95% CI 3.30-7.26) and previous exposure to carbapenems (OR 4.63, 95% CI 3.08-6.96).
  
  
  
  Carbapenem resistance represents a threat to neutropenic patients. In this group, resistance is likely promoted by previous carbapenem use and leads to high mortality rates. The knowledge of resistance patterns is crucial and can direct clinicians in the use of alternatives to carbapenem-based regimens.
authors.affiliation: Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Udine, Italy.|The University of Queensland, UQ Centre for Clinical Research (UQCCR), Brisbane, Australia.
authors.forename: Elda
authors.initials: E
authors.lastname: Righi
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research (UQCCR), Brisbane, Australia.|Department of Clinical and Biomedical Sciences Luigi Sacco, III Division of Infectious Diseases, University of Milan, Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Peri
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research (UQCCR), Brisbane, Australia.
authors.forename: Patrick N A
authors.initials: PN
authors.lastname: Harris
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research (UQCCR), Brisbane, Australia.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Wailan
authors.affiliation: School of Medicine, Universidade de Fortaleza (UNIFOR), Fortaleza, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Liborio
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.|School of Medicine, University of Queensland, Australia.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Lane
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research (UQCCR), Brisbane, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
mesh_terms: D000150:Acinetobacter / Q000187:drug effects; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D015780:Carbapenems / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005260:Female; D014943:Global Health; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality; D006115:Greece; D006801:Humans; D007557:Israel; D007558:Italy; D007709:Klebsiella / Q000187:drug effects; D007710:Klebsiella Infections / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015995:Prevalence; D011549:Pseudomonas / Q000187:drug effects; D018440:beta-Lactam Resistance / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems