the first presentation, Professor Jesús Rodríguez-Baño, Head of the infectious
diseases division at the University Hospital Virgen Macarena (Seville, Spain)
and President-elect of the European Society of Clinical Microbiology and
Infectious Diseases (ESCMID), presented findings from 37 hospitals in 11
-- a group of bacteria that are resistant to
carbapenems. These can kill approximately half of the patients who develop
‘Appropriate and optimal use of antibiotics in patients with bloodstream infections could reduce the emergence of antimicrobial resistance’
starting antibiotic therapy, patients
were assessed for their risk of dying from the infection based on predefined
; low risk
scored between 0-7
and those at high risk scored between 8-15
Fifty-one percent of the patients were
- During the study, 343 patients
received antimicrobial treatment active against the organism responsible
for the infection -- either a single antimicrobial drug or a combination.
- This treatment reduced the mortality
risk of the entire group by more than 50%.
- However, combination therapy showed a reduced risk of death (a decrease of
44%) only in the high-risk patients, and not in the low-risk patients.
Rodríguez-Baño said: "Contrary to present recommendations, combination
therapy can be avoided in a substantial proportion of patients with bloodstream
infections due to CPE. These patients can be identified using the INCREMENT-CPE
score and if they are low risk they can be treated with a single active
helps to avoid the problems due to
combination therapy, such as a higher risk of toxicity, the development of
by the infectious agents to more antimicrobials, and the bigger
The study therefore
suggests that combination therapy is
reserved only for high-risk
patients with CPE bloodstream infections.
Palacios Baena and her colleagues studied 855
patients with bloodstream infections caused by ESBL-E
treated between 2004
and 2012 in the INCREMENT study and who received their first dose within 24
hours before antibiotic sensitivity results became available.
- Patients were again categorized as low risk and high risk categories based
on the probability of their dying within 30 days.
- The patients who started
antimicrobial therapies before the sensitivity of the organism was known
were classified into three groups:
- Patients who were given "choice therapy (CT)" - Carbapenems or another broad spectrum
antimicrobial therapy called beta-lactamase/beta-lactamase inhibitors;
these patients were used as the reference group to compare with the other
- Patients who were given "alternative therapy (AT)"- Other antimicrobial agents, either
alone or in combination, which were known to be effective against ESBL-E
in the laboratory.
- Patients who were given "inactive
therapy (IT)" - Antimicrobial
therapy that proved to be inactive against the infection.
Most of the patients (489, 57%) received choice
therapy, 83 (10%) received alternative therapy, and 283 (33%) received inactive
- A total of 144 patients (17%) died.
- The death rates for CT patients was
17%, for AT patients it was 19%, and for IT patients, 15.5% showing no
statistically significant difference in the death rates of the 3 groups.
- The risk of death in high-risk
patients rose by a third for each point increase on the INCREMENT-ESBL
score. The patients treated with inactive therapy had a nearly three-fold
increased risk of death.
Baena said that the findings of their study showed that early treatment with
antibiotics known to be active against the infection (other than carbapenems)
did as well as those started initially on carbapenems suggesting carbapenem should be reserved for
infections that are ultimately resistant to all other therapy
recent advances in diagnostic techniques, antibiotic sensitivity results are
available within 24 hours and even if
initial treatment was inactive, doctors can switch to the targeted active drug
High-risk patients were the ones most likely to benefit from early
treatment with broad spectrum antibiotics
known to be effective against the infection.
Though further studies
may be needed to validate these findings, carbapenem resistance can be reduced
by avoiding its use in select patients.
To conclude with the
words of Dr Baena, "Many
deaths can be prevented if we use the antimicrobials available to us
appropriately and moderately. It's necessary to strengthen the research into
new molecules and the development of old ones. Patients, politicians and the
general population must be aware that the use of broad-spectrum antimicrobials
needs to be reserved only for when they are really needed, as it is a disaster
for patients who develop an infection due to a microorganism that is resistant
- Belén Gutiérrez-Gutiérrez, Elena Salamanca, Marina
de Cueto, Po-Ren Hsueh, Pierluigi Viale, José Ramón Paño-Pardo, Mario Venditti,
Mario Tumbarello, George Daikos, Rafael Cantón, Yohei Doi, Felipe Francisco
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Azap, Maria Souli, Emmanuel Roilides, Spyros Pournaras, Murat Akova, Federico
Pérez, Joaquín Bermejo, Antonio Oliver, Manel Almela, Warren Lowman, Benito
Almirante, Robert A Bonomo, Yehuda Carmeli, David L Paterson, Alvaro Pascual,
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Calbo, C Badia, M Xercavins, O Gasch, D Fontanals, E Jové. Effect of
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infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a
retrospective cohort study. The Lancet Infectious Diseases, (2017); DOI: 10.1016/S1473-3099(17)30228-1