Treatment Outcomes of Patients with Bloodstream Infections

1
Treatment Outcomes of Patients with Bloodstream
Infections caused by ESBL Producing
Enterobacteriaceae
Contact information Carlos A. DiazGranados, MD,
MS Division of Infectious Diseases Emory
University School of Medicine 46 Armstrong St SE
206 Atlanta, GA 30303 Tel [phone] cdiazgr_at_e
mory.edu
510
Carlos A. DiazGranados 1, Elkin Lemos 2, Carlos
Alvarez 3, Sandra Valderrama 4, Ernesto Martínez
5.
Emory University School of Medicine, Atlanta,
GA1 Fundación Universitaria de Ciencias de la
Salud, Bogotá, Colombia1 Hospital Regional del
Tunal2 Hospital de Occidente de Kennedy2
Clínica de Occidente2 Hospital Simón Bolívar,
Bogotá, Colombia3 Clínica Jorge Piñeros Corpas,
Bogotá, Colombia Hospital Universitario del
Valle, Cali, Colombia5.
This study was funded by the Fundación
Universitaria de Ciencias de las Salud (FUCS),
Bogotá, Colombia.

• Abstract
• Background optimal therapy for bloodstream
  infections (BSI) caused by Extended-Spectrum
  Beta-lactamase (ESBL) producing
  Enterobacteriaceae is unknown.
• Methods we did a retrospective cohort study
  in 8 hospitals in Colombia. Adult patients with
  one positive blood culture for an ESBL producing
  E.Coli or Klebsiella spp. between January 2002
  and December 2005 were eligible. Kaplan-Meier
  curves were used to assess 14-day survival.
• Results 67 cases were ascertained, 54 (81)
  caused by Klebsiella spp. and 13 (19) by E.coli.
  For empiric antimicrobial therapy, survival was
  highest for patients who received carbapenems
  (CA), quinolones (Q) or betalactamase-inhibitors
  (BI) (74, 80 and 74 respectively). Survival of
  patients receiving empiric cefepime (CE) was
  lower than those receiving empiric CA, Q or BI
  and similar to those not receiving empiric
  therapy (62). Patients who received empiric
  aminoglycosides had the lowest survival (30).
  Differences in survival for empiric therapy were
  qualitative since none reached statistical
  significance. For definitive antimicrobial
  therapy, survival was similar for patients who
  received CA, Q, BI, or CE (85, 100, 74 and
  100 respectively). Survival for patients
  receiving definitive CA or BI was significantly
  better than no definitive therapy (p0.001).
  Patients who received Q or CE as definitive
  therapy showed a trend towards higher survival,
  compared to those not receiving definitive
  therapy (p0.054). There were no statistically
  significant differences in survival between
  treatment groups.
• Conclusion Q and BI may be alternatives to CA
  for the treatment of BSI caused by ESBL producing
  Enterobacteriaceae.

Results continuation
Results
67 cases were ascertained, of which 54 (81) were
caused by Klebsiella spp. and 13 (19) by E.coli.
Table 1 shows the cohort characteristics. Table 2
presents the susceptibility patterns of the
isolates to antimicrobials of interest. A
description of antimicrobial regimens used during
the empiric and definitive phases of therapy can
be found in table 3.
Table 1. Clinical features of patients with
ESBL-producing Enterobacteriaceae.
Survival analysis

• Background
• Although carbapenems are regarded as the
  treatment of choice, the optimal therapy for
  bloodstream infections (BSI) caused by
  Extended-Spectrum Beta-lactamase (ESBL)
  producing Enterobacteriaceae is unknown, and the
  role of other classes of antibiotics is
  uncertain.
• Observational studies have reported higher
  rates of clinical failure in patients treated
  with third generation cephalosporins when
  compared to patients treated with carbapenems
  (1).
• Limited or conflicting data is available
  regarding the role of fluoroquinolones,
  betalactam-betalactamase inhibitor combinations,
  cefepime and aminoglycosides (2-8).
• In Latin America, the prevalence of ESBL
  production has been estimated to be 45 for
  Klebsiella spp. and 8.5 for E. coli (9). In
  Colombia prevalence is similar, estimated at 33
  for Klebsiella pneumoniae and 11.8 for E.coli.
  The dominant enzyme class in Colombia is though
  to be CTX-M, although TEM and SHV enzymes are
  also prevalent (10).

Quinolones
Carbapenems
Betalactamase Inhibitors (BI)
Cefepime
Aminoglycosides
No-AB/Ceph/TMP-SMX
Objective To evaluate treatment outcomes of
patients with BSIs caused by ESBL producing
Enterobacteriaceae.
Empiric therapy Survival of patients
receiving empiric Cefepime was lower (p not
significant) than those receiving empiric
Carbapenems, Quinolones or BI and similar to
those not receiving empiric therapy (62).
Patients who received empiric Aminoglycosides had
the lowest survival (30) (p not significant) .
Definitive antimicrobial therapy Survival
was similar for patients who received
Carbapenems, Quinolones, BI, or Cefepime (85,
100, 74 and 100 respectively). Survival for
patients receiving definitive Carbapenems or BI
was significantly better than no definitive
therapy (p0.001). Patients who received
Quinolones or Cefepime as definitive therapy
showed a trend towards higher survival, compared
to those not receiving definitive therapy
(p0.054). No other statistically significant
differences in survival between treatment groups
was found.
Methods

• Study design multicenter (8 hospitals),
  retrospective cohort study.
• Population and sample adult patients with
  one positive blood culture for an ESBL producing
  E.Coli or Klebsiella spp. between January 2002
  and December 2005 were eligible. ESBL
  confirmation was required for inclusion.
• Microbiologic methods participating hospitals
  were required to have had in place one of the
  following methods for ESBL screening and
  confirmation during the study period
• - Screening
• - Disc diffusion according to CLSI
  (former NCCLS) criteria.
• - Automated antimicrobial
  susceptibility testing systems (Vitek -
  bioMerieux or
• Microscan - Dade Behring).
• - Confirmation
• - Disc difussion according to CLSI
  (former NCCLS) criteria.
• - E-test.
• - Automated antimicrobial
  susceptibility testing systems Vitek 2 -
  bioMerieux with
• confirmation capabilities or other
  Vitek or Microscan systems with ESBL confirmation
  
• cards.
• Variables
• - Main exposure variables
• - Empiric antimicrobial therapy
  antimicrobial given within 3 days from the date
  of

• Retrospective design
• Lack of molecular characterization of ESBLs.
• Sample size.

Limitations
Conclusions

• Quinolones and Betalactamase-Inhibitors may be
  alternatives to Carbapenems for the treatment of
  BSI caused by ESBL producing Enterobacteriaceae,
  particularly for the empiric phase of therapy and
  in settings were susceptibility to these agents
  alone or in combination is reasonable.
• Further clinical experience with antibiotics
  other than Carbapenems is warranted to fully
  evaluate the potential usefulness of these
  antibiotics against serious infections due to
  ESBL-producing organisms.
• In this retrospective cohort, we found three
  cases of Klebsiella spp. isolates that produced
  ESBL but that were also resistant to Carbapenems.
  These three isolates were recovered from two
  different hospitals in the capital city of
  Bogotá, raising concerns for possible
  undocumented spread across institutions. Further
  surveillance and molecular testing is warranted
  to confirm and better characterize (KPC,
  Metallo-Betalactamases, or other mechanisms) this
  worrisome resistance pattern.

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