Ceftazidime

Assessment report

Assessment report for Zavicefta (ceftazidime, avibactam) 28 April 2016, EMA/CHMP/377887/2016.

Hazard

Persistence OECD308: "Total system half-life (DT50): 2.31 days high organic matter sediment (HOM); 9.99 days low organic matter sediment (LOM). Mineralisation (Day 93): 9.3% HOM, 31.2% LOM. One significant degradation product, M3, >10% of radioactivity in both the HOC and LOC systems. DT50 values = 20.8 and 101 days in the HOC and LOC, respectively. In the LOC a second metabolite M1, had a calculated half-life of 118 days. Mass Balance (day 14) : 88.6% to 112.2% (LOC); 87.2% to 98.4% (HOC). [---] It was noted that the study on ceftazidime transformation in water/sediment systems (OECD 308) showed that both main transformation products M1 and M3 are very persistent as the DT50 values in the low organic content (LOC) system are higher than 60 days. As a result, Zavicefta should be considered as very persistent."

Bioaccumulation OECD107: "LogD_ow< -2.20 (pH5), LogD_ow < -2.21 (pH7), LogD_ow < -2.17 (pH9). The log D values for ceftazidime are < 4.5 at all environmentally relevant pHs, therefore screening for PBT is not required as this does not meet the criteria for classification as a PBT compound."

Chronic toxicity: There are NOEC for 3 trophic levels, lowest NOEC for blue green algae 13 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PECsurfacewater, refined = 0.06 microg/L.

PNEC = Lowest NOEC, 13 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 1.3 microg/L.

PEC/PNECsurfacewater = 0.046. "Unlikely to represent a risk to the aquatic environment."

Fass environmental information

Fass environmental information for Ceftazidim Sandoz och Fortum (ceftazidime) (downloaded 2018-09-17).

Fara

Persistence: "34% primary (parent) degradation in 14 days (OECD 302B). Ceftazidime is not readily biodegradable nor inherently biodegradable. The phrase “Ceftazidime is potentially persistent” is thus chosen."

Bioaccumulation: "Log D_ow = -3.07 at pH 7.4 (TAD 3.02)."

Chronic toxicity: There are NOEC for 3 trophic levels, lowest NOEC for blue green algae 13 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2016. PEC/PNEC = 0.0068 which gives the risk insignificant.

Other information

For antibiotics in general, it is recommended that these drugs are used as restrictively as possible without risking the patient's health.