An Open-Labelled PK-PD Study of ELORES in infections caused by ESBL producing gram-negative bacteria

ELORES is a synergistic antimicrobial combination of Ceftriaxone, Sulbactam and EDTA.

Rationale behind combination

It is approved by DCGI 5 years back and it is under old drug category. Ceftriaxone and sulbactam is a synergistic antimicrobial combination with marked in-vitro antibacterial activity against a broad spectrum of organisms. Sulbactam not only potentiates the antibacterial activity of β - lactams but also exhibits a moderate antibacterial activity. By forming a protein complex with β -lactamase, sulbactam irreversibly blocks their destructive hydrolytic activity. Thus, sulbactam addition extends the spectrum of activity of ceftriaxone.

As sulbactam also binds with some penicillin binding proteins, sensitive strains are often rendered more susceptible to the ELORES combination than ceftriaxone alone. Even in bacterial strains that produce either low amounts of *β-*lactamase or none at all, a synergistic effect is observed when sulbactam is associated with β - lactam antibiotic that has a complementary affinity for the target sites.

The presence of the EDTA in the combination provides the following benefits;

1. EDTA makes ceftriaxone effective in Metallo-β - lactamase and other ESBL strains (TEM, SHV, AMP-C, CTX-M).

2. Inhibits Efflux pump by altering genes responsible for OMPs expression

3.  Alters the porosity of bacterial cell membrane and enhances the penetration of ceftriaxone and sulbactum

4.   Prevents transfer of resistance by preventing conjugation

5.   Breaks and prevents biofilm formation

6.   Decrease infection induced hepatotoxicity by its anti oxidant effect.

Thus, ELORES i.e. combination of ceftriaxone, sulbactam and EDTA serves as an effective measure to combat a specific resistance mechanism of β - lactamase producing organisms, in addition to that it also provides synergy against wide range of bacteria. This kind of combination therapy is useful against life threatening infections in hospitalized and out patients.

Standard therapeutic dosage: 1.5 – 3.0 grams once or twice daily.

Severe infections: 3-6g daily, as a single dose or in two divided doses every 24 hours.

The duration of therapy varies according to the course of the disease. As with antibiotic therapy in general, administration of ELORES should be continued for a minimum of 48 to 72 hours after the subject become afebrile or evidence of bacterial eradication has been obtained.

ELORES is the breakthrough in antibiotic therapy with triple mechanism of action. It, along with a chemical vector as third ingredient, is used for a wide range of indications due to its unique capability of fighting against resistance. It is effective against extended spectrum β - lactamases like lower respiratory tract infections, urinary tract infections and pre-and-post operative infections.

This study is planned to understand how the clinical response in patients infected with resistant ESBL pathogen correlate with plasma concentration of the drug vs. in-vitro MIC data in the clinical isolate of that particular patient.