Comparison of hypersensitivity reactions of intravenous iron: iron isomaltoside-1000 (Monofer® ) versus ferric carboxy-maltose (Ferinject® ). A single center, cohort study.

AIMS: Intravenous iron supplementation is widely used to treat iron deficiency and iron deficiency anemia when oral iron administration is ineffective or poorly tolerated. Hypersensitivity reactions (HSRs) during infusions are rare, but can be life-threatening. This study aimed to compare the risk for HSRs with the intravenous administration of iron isomaltoside-1000 and ferric carboxymaltose for the treatment of iron deficiency and iron deficiency anemia. METHODS: This was a single-centre cohort study. Nurses and physicians were instructed to fill out an HSR registration form with every administration of intravenous iron. HSRs were distinguished into serious and non-serious HSRs using the Ring and Messmer classification. RESULTS: HSRs occurred in 18/836 (2.1%) ferric carboxymaltose and 43/496 (8.7%) iron isomaltoside-1000 administrations. The crude risk for HSRs was 75% lower after ferric carboxymaltose treatment (RR = 0.248, 95% CI: 0.145-0.426, P < 0.0001). The risk for grade II HSRs was 88% lower after ferric carboxymaltoside (RR = 0.123, 95% CI: 0.051-0.294). The likelihood of HSRs was 3.4 times higher after the administration of iron isomaltoside-1000 (95% CI: 1.910-6.093, P < 0.0001). Regardless of the type of intravenous iron, patients with comorbidities have a factor 3.6 higher risk (95% CI: 1.899-6.739, P < 0.0001). CONCLUSIONS: Ferric carboxymaltose is associated with a 75% lower risk for HSRs compared with iron isomaltoside-1000 in our population. The presence of a comorbidity raises the likelihood of an HSR by a factor of three regardless of the type of intravenous iron infusion. Further research is needed to clarify the underlying mechanism in various patient groups.

Evaluation of in vitro synergy between vertilmicin and ceftazidime against Pseudomonas aeruginosa using a semi-mechanistic pharmacokinetic/pharmacodynamic model.

The aim of this study was to develop a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model to evaluate the in vitro synergy between vertilmicin and ceftazidime against Pseudomonas aeruginosa. The in vitro antimicrobial activity of vertilmicin alone was initially assessed by static and dynamic time-kill experiments against three bacterial strains, including MSSA, MRSA and P. aeruginosa. The combined killing effect with ceftazidime was then evaluated in a static time-kill study against P. aeruginosa. Vertilmicin displayed a concentration-dependent killing effect against the three bacterial strains, and its short half-life may possibly have a dramatic impact on antimicrobial activities. A two-compartment pharmacodynamic model consisting of drug-susceptible and -resistant compartments was developed to characterise the relationship between drug exposure and bacterial response for the time-kill curves from both monotherapy and combination therapy. Loewe additivity was incorporated into the pharmacodynamic model to describe the drug-drug interactive effect in the combination therapy. For monotherapy, the estimated EC50 of the dynamic time-kill study against each strain was close to its MIC but was higher than that of the static time-kill study. The EC50 of combination therapy was estimated at 2.67 mg/L compared with 4.54 mg/L in monotherapy, indicating an enhanced bactericidal capacity. The drug-drug interactive effect was not significantly synergistic but highly varied at each specific combination. Potential synergistic combinations could be screened using PK/PD modelling and simulation. These results demonstrated that PK/PD modelling provides an innovative approach to assist dose selection of combination vertilmicin and ceftazidime for future clinical study design.