gallium-maltolate and Pneumonia--Bacterial

The practice of prophylactic administration of a macrolide antimicrobial with rifampin (MaR) to apparently healthy foals with pulmonary lesions identified by thoracic ultrasonography (i.e., subclinically pneumonic foals) is common in the United States. The practice has been associated epidemiologically with emergence of R. equi resistant to MaR. Here, we report direct evidence of multi-drug resistance among foals treated with MaR. In silico and in vitro analysis of the fecal microbiome and resistome of 38 subclinically pneumonic foals treated with either MaR (n = 19) or gallium maltolate (GaM; n = 19) and 19 untreated controls was performed. Treatment with MaR, but not GaM, significantly decreased fecal microbiota abundance and diversity, and expanded the abundance and diversity of antimicrobial resistance genes in feces. Soil plots experimentally infected with Rhodococcus equi (R. equi) and treated with MaR selected for MaR-resistant R. equi, whereas MaR-susceptible R. equi out-competed resistant isolates in GaM-treated or untreated plots. Our results indicate that MaR use promotes multi-drug resistance in R. equi and commensals that are shed into their environment where they can persist and potentially infect or colonize horses and other animals.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Drug Resistance, Multiple; Feces; Horse Diseases; Horses; Macrolides; Microbial Sensitivity Tests; Organometallic Compounds; Pneumonia, Bacterial; Pyrones; Rhodococcus equi; Rifampin

To determine the chemoprophylactic effect of gallium maltolate on the cumulative incidence of pneumonia caused by Rhodococcus equi infection in foals.. 483 foals born and raised on 12 equine breeding farms with a history of endemic R equi infections.. Group 1 foals were treated with a placebo and group 2 foals were treated with gallium maltolate (approx 30 mg/kg, PO, q 24 h) during the first 2 weeks after birth. Foals were monitored for development of pneumonia attributable to R equi infection and for adverse effects of gallium maltolate.. There were no significant differences in the cumulative incidence of R equi pneumonia among the 2 groups.. Chemoprophylaxis via gallium maltolate administered orally at approximately 30 mg/kg daily for the first 2 weeks after birth failed to reduce the cumulative incidence of pneumonia attributable to R equi infection among foals on breeding farms with endemic R equi infections. Further investigation is needed to identify strategies for control of R equi infections.

Topics: Actinomycetales Infections; Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Female; Horse Diseases; Horses; Male; Organometallic Compounds; Pneumonia, Bacterial; Pyrones; Rhodococcus equi

Gallium is a trivalent semi-metal with anti-microbial effects because of its incorporation into crucial iron-dependent reproductive enzyme systems. Gallium maltolate (GaM) provides significant gallium bioavailability to people and mice following oral administration and to neonatal foals following intragastric administration. To study the prophylactic and therapeutic effects of GaM against Rhodococcus equi pneumonia in foals, we developed a methylcellulose formulation of GaM (GaM-MCF) for oral administration to neonatal foals. Normal neonatal foals were studied. Six foals received 20 mg/kg and another six foals received 40 mg/kg of GaM-MCF orally. Serial serum samples were collected and serum gallium concentrations were determined using inductively coupled plasma mass spectroscopy. Gallium was rapidly absorbed (T(max) of 4 h), and a mean C(max) of 0.90 or 1.8 microg/mL was achieved in foals receiving 20 or 40 mg/kg respectively. Marked variability existed in C(max) among foals: only half of the foals receiving 20 mg/kg attained serum concentrations of >0.7 microg/mL, a level suggested to be therapeutic against R. equi by previous studies. Mean elimination half-life was 32.8 or 32.4 h for foals receiving 20 or 40 mg/kg respectively. The results of this study suggest that at least 30 mg/kg orally every 24 h should be considered in future pharmacodynamic and efficacy studies.

Topics: Actinomycetales Infections; Administration, Oral; Animals; Animals, Newborn; Anti-Bacterial Agents; Female; Half-Life; Horse Diseases; Horses; Male; Mass Spectrometry; Methylcellulose; Organometallic Compounds; Pneumonia, Bacterial; Pyrones; Rhodococcus equi