513. A randomized control trial on the effect of oral calcium carbonate to fecal levofloxacin concentration and microbiota diversity in healthy volunteers taking oral levofloxacin
Authors: Janphet Ophat , Kawang Kornthara , Phaisal Weeraya , Chariyavilaskul Pajaree , Kueakulpattana Naris , Chatsuwan Tanittha , Nilaratanakul Voraphoj 
Published: December 2022

Background

Levofloxacin(LVX) is used in treatment against bacterial infections but also affect the intestinal microbiota. Calcium(Ca) can form complex with LVX and prevent its absorption. Taking them at least 2 hours apart does not affect LVX peak plasma concentration(Cmax). Since, our in vitro study showed that Ca can increase LVX minimal inhibitory concentration (MIC) in some bacteria, we conducted a randomized control trial(RCT) to study whether oral CaCO3 can lower fecal LVX concentration and preserve gut microbiota diversity in healthy volunteers.

Methods

We conducted a RCT involving 20 healthy volunteers. All of them received a 5-day course of once-daily 500 mg LVX oral tablet at 8:00 AM. They were randomly assigned to treatment (taking 1,000 mg CaCO3 oral tablet twice daily at 12:00 PM and 6:00 PM) and control group (no CaCO3). The primary outcome was fecal LVX concentration by MIC and high performance liquid chromatography (HPLC) on day 2 and 5 after taking LVX. The secondary outcomes were fecal microbiota diversity by Shannon index (H) by 16s rDNA analysis, LVX Cmax by HPLC on day 1 and 5, and drug adverse events(AEs) in 4 weeks period. Figure 1.Demonstrates study methods.

Results

Each 10 volunteers were randomly assigned to treatment and control group. Mean fecal LVX concentration was higher in treatment than control group, 100.50 vs 53.21 µg/ml by MIC at day 5 (95% confidence interval [CI] 4.912, 89.73; p = 0.0242). There was no difference in mean fecal LVX concentrations by HPLC between treatment and control at day 2 and day 5. There was no difference in Cmax LVX at day 1 and day5 in treatment and control. No difference of fecal H, but treatment group had significantly declined in H(p = 0.0019). No serious AE, mild AEs were reported (3 in treatment and 5 in control groups), including nausea and diarrhea.

Primary outcome

Secondary outcome

Conclusion

In this study, CaCO3 is significantly related to higher fecal LVX level by MIC but does not significantly affect the LVX Cmax. However, rather than protecting gut microbiota from LVX, CaCO3 may lower gut microbiota diversity in the presence of LVX. Therefore, co-prescription of LVX and CaCO3 should be cautioned even without the concern about the absorption like when LVX is administered intravenously or when both drugs in oral forms are taken at different times.

Shannon index diversity

Figure 1 showed the Shannon diversity index. The mean diversity index of treatment group at day 0 was a bit higher than control group without statistical significance (p = 0.923). On day 2 and 5 of levofloxacin treatment, mean diversity index was higher in control group than in treatment group, also without statistical significance (p = 0.426 on day 2 and 0.237 on day 5). On day 14, mean diversity index was higher in treatment group. On day 28, mean diversity index was returned close to baseline at day 0.

Figure 3. Taxonomic profile

Details of microbiota composition in different taxa were demonstrated in Figure 2, different color represented different taxa compositions at genus level.

Disclosures

All Authors: No reported disclosures.