Cross-reactivity between voriconazole, fluconazole and itraconazole.

WHAT IS KNOWN AND OBJECTIVE: Hypersensitivity to triazoles is a rare occurrence and cross-reactivity between agents is unknown. We present a successful voriconazole challenge in a patient allergic to fluconazole and itraconazole. CASE SUMMARY: A 41-year-old immunocompetent male with coccidioidomycosis developed fever, eosinophilia and maculopapular rash from fluconazole. Switching to itraconazole resulted in worsening of the rash and skin sloughing over 25% of his body. He was given an oral-graded challenge of voriconazole which he tolerated without incident. WHAT IS NEW AND CONCLUSION: This is the first report of a lack of cross-reactivity between itraconazole and voriconazole.

Red tides in the Gulf of Mexico: Where, when, and why?

[1] Independent data from the Gulf of Mexico are used to develop and test the hypothesis that the same sequence of physical and ecological events each year allows the toxic dinoflagellate Karenia brevis to become dominant. A phosphorus-rich nutrient supply initiates phytoplankton succession, once deposition events of Saharan iron-rich dust allow Trichodesmium blooms to utilize ubiquitous dissolved nitrogen gas within otherwise nitrogen-poor sea water. They and the co-occurring K. brevis are positioned within the bottom Ekman layers, as a consequence of their similar diel vertical migration patterns on the middle shelf. Upon onshore upwelling of these near-bottom seed populations to CDOM-rich surface waters of coastal regions, light-inhibition of the small red tide of ~1 ug chl l(-1) of ichthytoxic K. brevis is alleviated. Thence, dead fish serve as a supplementary nutrient source, yielding large, self-shaded red tides of ~10 ug chl l(-1). The source of phosphorus is mainly of fossil origin off west Florida, where past nutrient additions from the eutrophied Lake Okeechobee had minimal impact. In contrast, the P-sources are of mainly anthropogenic origin off Texas, since both the nutrient loadings of Mississippi River and the spatial extent of the downstream red tides have increased over the last 100 years. During the past century and particularly within the last decade, previously cryptic Karenia spp. have caused toxic red tides in similar coastal habitats of other western boundary currents off Japan, China, New Zealand, Australia, and South Africa, downstream of the Gobi, Simpson, Great Western, and Kalahari Deserts, in a global response to both desertification and eutrophication.

Evaluating the influence of National Research Council levels of copper, iron, manganese, and zinc using organic (Bioplex) minerals on resulting tissue mineral concentrations, metallothionein, and liver antioxidant enzymes in grower-finisher swine diets.

Graded levels of a trace mineral premix containing an organic (Bioplex) source of Cu, Fe, Mn, and Zn was evaluated with additional treatments containing organic Zn or Fe. Grower-finisher pigs were fed from 25 to 115 kg BW. The number of pigs in the experiment, the breeding/genetics of the pigs, the management, and the average age of the pigs were previously reported. The experiment was conducted as a randomized complete block design in 7 replicates. Treatments were 1) basal diet without supplemental Cu, Fe, Mn, and Zn; 2) basal diet + 2.5 mg/kg Cu, 50 mg/kg Fe, 1.5 mg/kg Mn, and 40 mg/kg Zn (50% NRC); 3) basal diet + 5 mg/kg Cu, 100 mg/kg Fe, 3 mg/kg Mn, and 80 mg/kg Zn (100% NRC); 4) basal diet + 25 mg Zn/kg; 5) basal diet + 50 mg Zn/kg; and 6) basal diet + 50 mg Fe/kg. Selenium and I were added to all diets at 0.3 and 0.14 mg/kg, respectively. Diets were composed of corn-soybean meal, dicalcium phosphate, and limestone with phytase added to enhance mineral availability. Three pigs per pen were bled at 55, 80, and 115 kg BW and plasma was analyzed for microminerals. When the average replicate BW was 115 kg, 3 pigs per pen of an equal gender ratio were killed. The liver, kidney, and heart were removed and analyzed for microminerals. Liver, duodenum, and jejunal metallothionein and the antioxidant enzymes in the liver containing these microminerals were determined. The results demonstrated that plasma minerals were unaffected at the 3 BW intervals. Liver and duodenum metallothionein protein were greater ( < 0.05) as dietary micromineral levels increased but jejunum metallothionein did not change as microminerals increased. The activity of Cu/Zn superoxide dismutase (SOD) was not affected as the levels of the micromineral increased, whereas the activity of Mn SOD increased slightly ( < 0.05) to the 50% NRC treatment level. Liver Zn (relative and total) increased ( < 0.05) as dietary micromineral levels increased and also when Zn was added singly to the diet. Liver, kidney, and heart Cu and Mn concentrations were similar at the various micromineral levels. The activities of liver enzymes containing graded levels of Zn were not affected by dietary microminerals at 115 kg BW. These results indicate that the supplemental levels of Cu, Fe, and Mn were not necessary for grower-finisher pigs and that these innate microminerals in a corn-soybean meal diet were adequate, whereas a need for supplemental Zn was demonstrated.

Comparison of organic and inorganic zinc sources to maximize growth and meet the zinc needs of the nursery pig.

Zinc is the trace element involved in more biological functions than any other micromineral in the nutrition of the newly weaned pig. Its role in growth via protein synthesis and antioxidant defense makes it a key nutrient in the diet of the newly weaned nursery pig for maximum lean tissue growth and health. In this study, 500 pigs (5 pigs/pen) were weaned at approximately 18 d of age and fed 0, 25, 50, 75, or 100 mg/kg of Zn supplied as organic or inorganic Zn or 50 mg Zn/kg combination with 50% Zn from each source. Pigs were killed at 0, 10, and 35 d of the study to determine mineral tissue concentrations and antioxidant activity in the liver and the amount of metallothionein (MT) protein in the liver, duodenum, and jejunum. Growth performance did not differ for the pigs supplemented with Zn but were greater than those fed the basal diet with no added Zn (P ≤ 0.05). Hepatic Zn concentration was numerically maximized with 75 mg/kg of organic Zn, but 100 mg/kg of Zn of inorganic Zn was necessary to achieve a similar concentration. At d 10, Mn superoxide dismutase in pigs fed no supplemental Zn was lower than when pigs were fed organic Zn (P ≤ 0.05). Hepatic MT responded in a linear manner with organic Zn (P ≤ 0.01) and pigs fed the basal diet had less than those supplemented with Zn (P ≤ 0.01). Duodenal MT was greater at d 10 with organic Zn (P ≤ 0.01) than pigs fed the basal diet, and at d 35, there was a linear response to both organic and inorganic Zn (P ≤ 0.01). As expected, jejunal MT was reduced compared to this protein in the duodenum. The provision of Zn at 50 mg/kg from either source resulted in greater jejunal MT than when Zn was fed as a combination of both sources at the same concentration (P ≤ 0.05). Our data indicate that the needs of the nursery pig, that is, Zn requirements for health and well-being, have changed since the data used to establish the 2012 Nutrient Requirements of Swine (NRC, 2012) was published. Organic minerals are shown in this study to be managed biologically in a different manner than inorganic Zn (sulfate) in the young pig. The newly weaned pig, while changing nutritional sources and physical environments, has extremely high biological demand for antioxidant defense. Our data show that to maximize growth, health, and well-being, 75 mg/kg of organic Zn in a complex nursery diet benefits today's fast growing pigs with a very high lean tissue composition.

Effect of dietary calcium and phosphorus levels on the total tract digestibility of innate and supplemental organic and inorganic microminerals in a corn-soybean meal based diet of grower pigs.

The effects of Ca and P (CaP) levels and micromineral sources on mineral digestibility were evaluated in growing pigs. Treatments consisted of 2 levels of CaP and 3 trace mineral (TM) treatments arranged as a 2 × 3 factorial in a randomized complete block design with 8 replicates. The CaP levels evaluated were: 1) 0.65% Ca and 0.55% P [standard CaP (Std CaP)], and 2) 1.00% Ca and 0.85% P (High CaP). The TM treatments were: 1) Basal, without supplemental TM, 2) Basal supplemented with organic TM, and 3) Basal supplemented with inorganic TM. Both organic and inorganic TM premixes added 15 mg Cu, 150 mg Fe, 10 mg Mn, 0.3 mg Se, and 140 mg Zn/kg diet. Diets were formulated using corn soybean meal with a Ca to P ratio of 1.18 in both CaP treatments. Barrows with an initial BW of 45 kg were acclimated to stainless steel metabolism crates where diets were fed for 14 d before a 10-d collection period. Pigs within replicates were fed equivalent amounts of feed at 0800 and 1600 h each day with water provided free choice. Total feces, urine, and feed orts were collected daily. Essential macro- and microminerals were analyzed by inductively coupled plasma analysis. Increasing dietary CaP decreased the digestibility of Ca and Zn. Phosphorus digestibility did not change when the P inclusion level increased from 0.55 to 0.85% Ptotal. The High CaP level resulted in a lower urinary excretion of most minerals, particularly Cu (P < 0.05) and Mn (P < 0.05), as dietary CaP level increased but the others were not statistically significant. A summary of the ATTD for each of the experimental variables was statistically analyzed and averaged for the experiment. Although there were few statistical differences with individual minerals, they generally demonstrated a decline in digestibility when the High CaP was fed, averaging a 3% lower digestibility consistently than when the Std CaP level was fed. Organic TM averaged an approximately 5% greater digestibility than the average inorganic microminerals with the difference between minerals within each source relatively consistent. These results indicate that CaP level had the greatest effect on mineral digestibility, organic microminerals had a greater digestibility than inorganic minerals, and the innate microminerals had an average apparent digestibility of 45%.

Evaluating the NRC levels of Cu, Fe, Mn, and Zn using organic and inorganic mineral sources for grower-finisher swine.

The dietary effects of Cu, Fe, Mn, and Zn levels, and the addition of Zn and Fe to a nonfortified, micromineral basal diet were evaluated in grower-finisher pigs. Growth, feed efficiency, hematology, carcass characteristics, and loin quality were assessed in growing-finishing pigs (n = 222; initial BW = 24 kg). Corn-soybean meal diets fortified with limestone and dicalcium phosphate with added phytase constituted the basal diets. A study was conducted with 6 dietary treatments and 7 replicates in a randomized complete block design. Treatments consisted of: 1) basal diet without added Cu, Fe, Mn, and Zn microminerals, 2) basal + 50% NRC Cu, Fe, Mn, and Zn requirements, 3) basal + 100% NRC Cu, Fe, Mn, and Zn requirements, 4) basal + 25 mg Zn/kg, 5) basal + 50 mg Zn/kg, and 6) basal + 50 mg Fe/kg. The microminerals were added as an organic mineral proteinate and all diets incorporated organic Se at 0.3 mg/kg. Diets were fed ad libitum over 3 growth phases. At 55, 80, and 115 kg BW, 3 pigs per pen were bled and hemoglobin (Hb) and percent hematocrit (Hct) were determined. At 115 kg BW, 3 pigs per pen were killed and carcass characteristics and loin quality measurements were determined. The ADG, ADFI, and G:F for each of the 3 dietary phases and overall period were not affected by dietary micromineral treatments. The concentration of Hb and percent Hct did not differ because of the treatment at each of the 3 phases. There were no treatment differences in carcass characteristics (HCW, backfat, or LM area). Loin pH, color (L*, a*, and b*), and drip loss did not differ by dietary treatment. Subjective marbling, color, and firmness scores, and intramuscular fat content of loins did not differ as the micromineral level increased above the 1998 and 2012 NRC requirements. The LM from pigs fed supplemental Fe had greater (P < 0.05) firmness and wetness scores than pigs fed the basal diet. These results indicate that there is sufficient amount of innate microminerals (Cu, Fe, Mn, and Zn) in a typical corn-soybean meal based diet to meet the grower-finisher pig's requirement for growth and hematological measurements. Although there was no detrimental effect by eliminating these microminerals from diets, it would seem that a dietary level of 50% of the NRC requirement for Cu, Fe, Mn, and Zn would be warranted.

Effect of dietary inulin and phytase on mineral digestibility and tissue retention in weanling and growing swine.

The effect of dietary phytase and the prebiotic inulin on apparent mineral digestibility, bone mineralization, and tissue mineral contents was evaluated in weanling and growing pigs. In Exp. 1, inulin and phytase were incorporated in a 2 × 3 factorial arrangement of treatments with 8 replicate pens per treatment in a randomized complete block design. There were 2 levels of phytase [0 and 1000 phytase units (FTU)/kg] and 3 levels of chicory inulin (0, 3, and 6%). Weanling pigs (17 d of age; 5 or 4 pigs per pen) with an initial BW of 6.0 ± 0.6 kg were evaluated for 35 d postweaning. Macromineral digestibility was calculated using chromic oxide as an index in fecal samples collected during the final week of the experiment in replicates 1 through 4. On d 36, 1 pig per pen was killed and the heart, liver, kidney, and left tibia were excised and weighed. Inulin did not have any effect on growth performance measurements. Phytase increased (P < 0.05) BW on d 35 and ADG and ADFI during the 21-to-35-d and 0-to-35-d periods. Inulin did not result in increased tissue mineral concentrations on a per unit (mg/kg) or total tissue basis. Phytase increased (P < 0.05) the concentration of Zn in the liver, Mn and Zn in the heart, and Mg and Mn in the kidney. Phytase also increased (P < 0.05) total P, Mg, S, Mn, Se, and Zn in the liver as well as tibia ash. Phytase increased the digestibility of Ca (P < 0.01) and P (P < 0.05). Experiment 2 was conducted with growing pigs (initial BW, 41 ± 5 kg) to evaluate 2 levels of inulin (0 or 6%) and 2 levels of phytase (0 or 1000 FTU/kg) in a 2 × 2 factorial with 6 replicates in a randomized complete block design. Total urine and feces were collected for 10 d from each of 24 barrows after a 21-d acclimation period. Inulin inclusion resulted in reduced Ca digestibility (P < 0.05). Phytase increased (P < 0.05) the digestibility of both Ca and P. These results indicate that dietary inulin does not affect the overall mineral status or growth performance of pigs, whereas phytase increases the utilization of Ca and several microminerals, in addition to P, and also increases growth performance. Inulin and phytase do not appear to interact to affect pig growth or mineral status.

Effect of injected and dietary iron in young pigs on blood hematology and postnatal pig growth performance.

The relationship of injected Fe doses on blood hematology and pig growth performance during both preweaning and postweaning periods was studied. In Exp. 1, the effect of BW of 347 pigs injected with 200 mg of Fe (dextran) intramuscularly (i.m.) at birth on hemoglobin (Hb) and percent hematocrit (Hct) at weaning was assessed. As BW increased there was a decline (P < 0.01) in Hb and Hct. In Exp. 2, Fe injection doses and timing of injected Fe on blood hematology and pig growth were evaluated. Injections were as follows: 1) 200 mg of Fe at birth; 2) 300 mg of Fe at birth; or 3) 200 mg of Fe at birth + 100 mg of Fe at d 10. A total of 269 pigs were allotted within litter to 3 treatments. The 2 greater quantities of injected Fe (i.e., 300 or 200 + 100 mg of Fe) had similar but greater (P < 0.05) Hb and Hct values than pigs receiving 200 mg of Fe, but growth rates were similar at weaning. The effects of injecting 200 mg of Fe at birth and either saline or 100 mg of Fe at 10 d of age were investigated in Exp. 3. Weaned pigs of each group were fed diets with 0, 80, or 160 mg/kg of added Fe for 35 d as a 2 × 3 factorial arrangement with 12 replicates (n = 360 pigs) in a randomized complete block design (RCB). The innate Fe contents of diets averaged 200 mg/kg. The greater Fe injection group (200 + 100 mg) had greater (P < 0.01) Hb and Hct values through 14 d postweaning (P < 0.05) and greater (P < 0.01) Hct values through 21 d postweaning. As dietary Fe increased, Hb was greater only at d 14 (P < 0.05 4), whereas Hct increased linearly to d 35 (P < 0.01) postweaning. Dietary Fe resulted in linear increases (P < 0.01) in ADG from d 21 to 35 and d 0 to 35. In Exp. 4, 3 dietary Fe (80, 160, and 240 mg/kg of diet), 2 injected Fe treatments (200 or 300 mg of Fe) at birth, and birth BW (<1.5 or ≥1.5 kg) were evaluated as a 2 × 2 × 3 factorial arrangement of treatments in a RCB design with 6 replicates (n = 280 pigs). The 300 mg of Fe injection group had lighter BW in both birth BW groups, with a birth BW × injected Fe interaction (P < 0.01). This resulted in the lighter birth BW pigs receiving 200 mg of Fe having greater BW gains to 240 mg/kg of dietary Fe, whereas light birth BW pigs injected with 300 mg of Fe plateaued at 160 mg/kg of Fe. Pigs in the heavy birth BW group injected with 200 or 300 mg of Fe at birth responded similarly to dietary Fe postweaning. These results indicate that blood Hb and Hct were affected by pig BW at weaning, but the additional 100 mg of Fe i.m. at 10 d of age increased blood hematology and that Fe injected preweaning affected initial postweaning performance.

Effect of dietary organic microminerals on starter pig performance, tissue mineral concentrations, and liver and plasma enzyme activities.

Weanling pigs (n = 160) were used to evaluate dietary essential microminerals (Cu, Fe, Mn, Se, and Zn) on performance, tissue minerals, and liver and plasma enzymatic activities during a 35-d postweaning period. A randomized complete block design with 5 treatments and 8 replicates was used in this study. Organic microminerals were added to complex nursery diets at 0 (basal), 50, 100, or 150% of the requirements of microminerals listed by the 1998 NRC. A fifth treatment contained inorganic microminerals at 100% NRC and served as the positive control. Pigs were bled at intervals with hemoglobin (Hb), hematocrit (Hct), glutathione peroxidase, and ceruloplasmin activities determined. Six pigs at weaning and 1 pig per pen at d 35 were killed, and the liver, heart, loin, kidney, pancreas, and the frontal lobe of the brain were collected for micromineral analysis. The liver was frozen in liquid N for determination of enzymatic activities. The analyzed innate microminerals in the basal diet met the NRC requirement for Cu and Mn but not Fe, Se, and Zn. Performance was not affected from 0 to 10 d postweaning, but when microminerals were added to diets, ADG, ADFI, and G:F improved (P < 0.01) from 10 to 35 d and for the overall 35-d period. Pigs fed the basal diet exhibited parakeratosis-like skin lesions, whereas those fed the supplemental microminerals did not. This skin condition was corrected after a diet with the added microminerals was fed. When the basal diet was fed, Hb and Hct declined, but supplemental microminerals increased Hb and Hct values. Liver catalase activity increased (P < 0.01) when microminerals were fed. The Mn superoxide dismutase activity tended to decline quadratically (P = 0.06) when supplemental microminerals were fed above that of the basal diet. Liver plasma glutathione peroxidase activities were greater (P < 0.01) when dietary organic and inorganic micromineral were fed. Liver concentrations of microminerals increased linearly (P < 0.01) as dietary microminerals increased, indicating that the liver was the primary storage organ. Micromineral tissue concentrations were least in pigs fed the basal diet and increased (quadratic, P < 0.01) to the 50% level of organic microminerals in the various tissues collected. The results indicated that innate microminerals, Cu and Mn, from a complex nursery diet may meet the micromineral needs of the weaned pig, but the need for Fe, Se, or Zn was not met by the basal diet.