Study on Reduced Antibiotic Treatment vs Broad Spectrum Betalactam in Patients With Bacteremia by Enterobacteriaceae

Conditions

Enterobacteriaceae Infections

Keywords

Enterobacteriaceae, Bacteremia, Escalation, Bacterial resistance, Bloodstream infection, Recurrence

Brief summary

The continuous increase in the bacterial resistance rate and the slow arrival of new therapeutic options have turned into an antibiotic crisis. One of the strategies proposed by stewardship programs to try to change this situation described worldwide is the use of antibiotics with the lowest possible antimicrobial spectrum. Enterobacteriaceae bacteremia is a good example of how this strategy would be applied. The empirical treatment of nosocomial bacteremia by Enterobacteriaceae comprises in several cases one or two antibiotics with antipseudomonal activity, being much less common than desirable a subsequent change to narrower spectrum antibiotics based on susceptibility data (de escalation). This is because the safety of de escalation is based only on expert advice and some observational studies, so their efficacy and safety is questioned by many clinicians and therefore its use is lower than desired. In fact, a recent systematic review of the Cochrane Library concluded that randomized studies to support this practice are needed. Investigators propose a real clinical practice-based randomized trial to compare the efficacy and safety of continuing with an antipseudomonal agents vs. de-escalation according to a pre-specified rule, in patients with bacteraemia due to Enterobacteriaceae.

López-Cortés LE, Delgado-Valverde M, Moreno-Mellado E, Goikoetxea Aguirre J, Guio Carrión L, Blanco Vidal MJ, López Soria LM, Pérez-Rodríguez MT, Martínez Lamas L, Arnaiz de Las Revillas F, Armiñanzas C, Ruiz de Alegría-Puig C, Jiménez Aguilar P, Del Carmen Martínez-Rubio M, Sáez-Bejar C, de Las Cuevas C, Martín-Aspas A, Galán F, Yuste JR, Leiva-León J, Bou G, Capón González P, Boix-Palop L, Xercavins-Valls M, Goenaga-Sánchez MÁ, Anza DV, Castón JJ, Rufián MR, Merino E, Rodríguez JC, Loeches B, Cuervo G, Guerra Laso JM, Plata A, Pérez Cortés S, López Mato P, Sierra Monzón JL, Rosso-Fernández C, Bravo-Ferrer JM, Retamar-Gentil P, Rodríguez-Baño J, SIMPLIFY study group.

2024-01-0921 citations

10.1016/s1473-3099(23)00686-2

Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to <i>Enterobacteriaceae</i> (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial

Luis Eduardo López-Cortés, Clara Rosso-Fernández, María Núñez‐Núñez, Lucía Lavín-Alconero, José María Bravo-Ferrer et al. (10 authors)

BMJ Open2017-06-018 citations

10.1136/bmjopen-2016-015439

Interventions

DRUGAntipseudomonal beta-lactam antibiotic

Pharmaceutical form: solution for infusion

DRUGDe-escalation(short-spectrum antibiotic)

Pharmaceutical form: solution for infusion

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 90 Years

Healthy volunteers

No

Inclusion criteria

1. ≥18 years old hospitalized patients with bacteremia from any source with isolation of an enterobacteria in blood cultures. 2. Active empiric treatment with antipseudomonal betalactamic at 48 hours from the symptoms of sepsis and the blood culture.The patient could have received any other type of antibiotic therapy up to 24 hours after blood extraction. 3. Microorganism susceptible at least one treatment from the experimental arm. 4. Patients with intravenous treatment at least 3 days from the randomization o 5 days from the initial blood culture. 5. Patients to sign the informed consent form.

Exclusion criteria

1. Palliative care or life expectance \< 90 days. 2. Pregnancy or lactation period. 3. To isolate the Extended-spectrum β-lactamases producing Enterobacteriaceae 4. Late randomization \>48 hours after the enterobacteriaceae blood culture´s identification 5. Severe neutropenic (\< 500 céls/mm3) at the randomization. 6. Treatment of infection \> 28 days (endocarditis and osteomyelitis) or meningitis.

Design outcomes

Primary

Measure	Time frame	Description
Clinical cure at day 3-5 after treatment.	Day 3-5 after end of treatment.	Clinical cure: complete resolution of infection symptoms (bacteremia) present at the day on which the assessment is done and patient is alive.

Secondary

Measure	Time frame	Description
Late clinical and microbiological response.	Day 60	The infection was completely resolved at day 60 (patients without infection symptoms)
Mortality	At 7,14 and 30 days	Death for any reason
Length of hospital stay	At 7,14 and 30 days	Defined as the from admission to hospital discharge
Recurrences (relapse or reinfection) rate	Day 60 after treatment	—
Early clinical and microbiological response.	After 5 days of treatment	The infection was completely resolved after 5 days of treatment (patients without infection symptoms and a negative blood culture).
Impact of the study treatment on intestinal microbiota	Screening, Day 7-14, Day 12-21, Day 30	Effect of study treatment on colonization of the intestinal tract with multi drug resistant gram negative bacilli
Treatment duration.	It is not allowed treatment duration more than 28 days	Evaluate the study treatment duration.
Secondary infections.	60 days	Evaluate the development of secondary infections other than the initial bacteremia.
Safety of antibiotic treatment	60 days	Gathering any related adverse event from the informed consent form signature up to 60 days

Countries

Spain

Outcome results

None listed