Introduction

In India, Ceftazidime-Avibactam (CEF-AVI) is approved for use in carbapenem-resistant enterobacteriaceae (CRE) infections while polymyxins are the preferred for empiric therapy in the critically ill. However, polymyxins have limited use in renal impairment whereas CEF-AVI is evolving as an effective alternative to polymyxins in the management of carbapenem-resistant organisms (CRO) infections.

Aim

To retrospectively evaluate the effects of CEF-AVI use on clinical outcomes (14-day all-cause mortality and 7-day clinical cure) in the Indian population with a high risk of CRO infection and limited treatment options (LTOs)

Patient Profile

• 78 in-patients who had received CEF-AVI in a period of one year received CEF-AVI alone or in combination with any other antibiotic including aztreonam for at least one day of therapy (DOT)

  Method

  Study Design

• Retrospective study in a quaternary care center in India

• CEF-AVI was given as a 2.5g intravenous infusion over two hours thrice a day in a patient with normal creatinine clearance, doses were adjusted for renally impaired patients

Endpoints

• Primary endpoint: all-cause mortality at 14 days from the start of CEF-AVI; clinical response at seven days from initiation of CEF-AVI (categorized as improved/not improved in terms of clinical/radiological/laboratory parameters or death)
• Secondary endpoints: time to initiation of CEF-AVI, average DOT on CEF-AVI, and average dose per day of CEF-AVI

Results

Efficacy

• CEF-AVI was empirically initiated in 66.7% patients while 33.3% were on targeted therapy; CEF-AVI was commonly used in occult sepsis (34.6%) followed by primary bacteremia (25.6%) and neutropenic sepsis (14.1%)
• All cause 14-day mortality from the start of CEF-AVI was found to be 23%; the highest proportion of death was observed among patients diagnosed with occult sepsis and secondary bacteremia (33%) then neutropenic sepsis (27.3%)
• CEF-AVI achieved a clinical response at seven days from initiation in 70.5% patients
• CEF-AVI in combination with aztreonam (n=44 patients) showed a 14-day mortality rate of 20.5%
• The median time to initiation of CEF-AVI was one day from sample collection
• The median duration in terms of DOT for CEF-AVI was seven with a median average dose of 7.5 g/day

Figure 1: Effects of CEF-AVI on the primary endpoints

Conclusion

• CEF-AVI demonstrated a good clinical cure rate and survival rate among patients with clinical indications that have limited antimicrobial treatment options
• CEF-AVI can be a promising option in treating various clinical syndromes associated with possible or confirmed multidrug organism infection with LTOs

Cureus 2023; 15(1): e33623