Comparison of functional-oil blend and anticoccidial antibiotics effects on performance and microbiota of broiler chickens challenged by coccidiosis.

This study aimed to compare the effects of different levels of cashew nutshell liquid (CNSL) and castor oil (CNSL-castor oil) with growth-promoting antibiotics associated with anticoccidials in broiler chickens challenged with coccidiosis. In this work, 2520 one-day-old male broiler chicks (Cobb) were randomly assigned to 84 pens, containing 30 birds each. The experimental design was completely randomized, with seven treatments: enramycin (8 ppm), virginiamycin (16.5 ppm), and tylosin (55 ppm); different doses of CNSL-castor oil (0.5, 0.75, and 1.00 kg/t); and a control diet (without additives). All treatments received semduramicin + nicarbazin (500 g/t; Aviax® Plus) from 0 to 28 d and monensin sodium (100 ppm; Elanco) from 29 to 35 days of age, when the feed was without antibiotics. The challenge was introduced at 14 days of age by inoculating broiler chickens with sporulated Eimeria tenella, Eimeria acervulina, and Eimeria maxima oocysts via oral gavage. In addition to performance parameters, intestinal contents were collected at 28 and 42 days of age for microbiota analysis by sequencing the 16s rRNA in V3 and V4 regions using the Illumina MiSeq platform. Taxonomy was assigned using the SILVA database (v. 138) with QIIME2 software (v. 2020.11). After one week of challenge, the broilers that received tylosin had a higher body weight gain (BWG) than those in the control group (p < 0.05), while the other treatments presented intermediate values. At 28 d, the BWG was lower for the control, CNSL-Castor oil 0.5 kg/t, enramycin, and virginiamycin treatments than that in the tylosin treatment. The inclusion of CNSL-Castor oil at concentrations of 0.75 and 1 kg/t acted as an intermediate treatment (p < 0.05). For alpha diversity, using the Shannon index, it was possible to observe the effect of age, with substantial diversity at 42 d. The Firmicutes phylum had the highest abundance, with values between 84.33% and 95.16% at 42 d. Tylosin showed better performance indices than other treatments. CNSL-castor oil treatments with concentrations of 0.75 and 1 kg/t showed similar results to those of enramycin and virginiamycin. Furthermore, CNSL-castor oil acted as a modulator of intestinal microbiota, reducing the abundance of pathogenic bacteria.

Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2.

Introduction. The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak of SARS-CoV in 2002, and MERS-CoV about 10 years later, SARS-CoV-2 is the third coronavirus in less than 20 years to cross the species barrier and start spreading by human-to-human transmission. It is the most infectious of the three, currently causing the COVID-19 pandemic. No treatment has been approved for COVID-19. We previously proposed targets that can serve as binding sites for antiviral drugs for multiple coronaviruses, and here we set out to find current drugs that can be repurposed as COVID-19 therapeutics.Aim. To identify drugs against COVID-19, we performed an in silico virtual screen with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme for coronavirus replication.Methodology. Initially, no RdRP structure of SARS-CoV-2 was available. We performed basic sequence and structural analysis to determine if RdRP from SARS-CoV was a suitable replacement. We performed molecular dynamics simulations to generate multiple starting conformations that were used for the in silico virtual screen. During this work, a structure of RdRP from SARS-CoV-2 became available and was also included in the in silico virtual screen.Results. The virtual screen identified several drugs predicted to bind in the conserved RNA tunnel of RdRP, where many of the proposed targets were located. Among these candidates, quinupristin is particularly interesting because it is expected to bind across the RNA tunnel, blocking access from both sides and suggesting that it has the potential to arrest viral replication by preventing viral RNA synthesis. Quinupristin is an antibiotic that has been in clinical use for two decades and is known to cause relatively minor side effects.Conclusion. Quinupristin represents a potential anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS-CoV-2 but expect that the biomedical community will expeditiously follow up on our in silico findings.

Microbiota and metabolome responses in the cecum and serum of broiler chickens fed with plant essential oils or virginiamycin.

This study investigated the cecal microbiota and serum metabolite profile of chickens fed with plant essential oils (PEO) or virginiamycin (VIRG) using high-throughput 16S rRNA gene sequencing and untargeted metabolomics approach. The main aim of this work was to explore the biochemical mechanisms involved in the improved growth performance of antibiotics and their alternatives in animal production. The results showed that both PEO and VIRG treatment significantly increased the relative abundance of phyla Bacteroidetes and decreased the abundance of phyla Firmicutes and genus of Lactobacillus in cecal microbiota of chickens. Compared to the control group (CT group), the relative abundance of genus of Alistipes, unclassified Rikenellaceae, Roseburia, and Anaeroplasma was enriched in the PEO group; that of genus Bacteroides, Lachnospiraceae, and unclassified Enterobacteriaceae was enriched in the cecal microbiota of the VIRG group. Untargeted metabolomics analyses revealed that the PEO treatment modified 102 metabolites and 3 KEGG pathways (primary bile acid biosynthesis and phenylalanine metabolism) in the cecal microbiota, and 81 metabolites and relevant KEGG pathways (fructose and mannose metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid.) in the serum of the chicken. Compared to the CT group, VIRG treatment group differed 217 metabolites and 10 KEGG pathways in cecal contents and 142 metabolites and 7 KEGG pathways in serum of chickens. Pearson's correlation analysis showed that phyla Bacteroidetes and genus of Bacteroides, Alistipes, and unclassified Rikenellaceae (in the VIRG and PE group) were positively correlated with many lipid metabolites. However, phyla Firmicutes and genera Lactobacillus (higher in the CT group) were negatively correlated with the lipid and thymine metabolism, and positively correlated with hydroxyisocaproic acid, cytosine, and taurine. This study shows that dietary supplementation with PEO and VIRG altered the composition and metabolism profile of the cecal microbiota, modified the serum metabolism profile.

Does virginiamycin supplementation affect the metabolism and performance of Nellore bulls grazing under low and high gain rates?

This study aimed to evaluate the effect of virginiamycin on the metabolism and performance of growing Nellore bulls under low and high gain rates on pasture. In experiment 1, 80 Nellore bulls (age = 12 ± 2 months, body weight = 258 ± 15 kg) were assigned to 16 paddocks in a 2 × 2 randomized block factorial arrangement. In experiment 2, 12 cannulated Nellore bulls were assigned to three 4 × 4 balanced Latin squares. The factors were: (1) mineral salt without or with virginiamycin, and (2) low or high gain rate. No interaction was noted between factors (p > .10). Animals fed virginiamycin had greater average daily gain (14%, p < .01), body weight (11 kg, p = .05), plasma nonesterified fatty acid (20%, p < .01), serum calcium concentration (2.62%, p = .04), and total protozoa (p = .03) and had the same bacterial proportion (p > .27). Animals with a low gain rate had greater serum urea concentration (19.6%, p < .01) and ruminal ammonia nitrogen (62%, p < .01). Thus, virginiamycin increases the performance and changes the metabolism of growing Nellore bulls under low and high gain rates on pasture.

Antibiotic growth promoters virginiamycin and bacitracin methylene disalicylate alter the chicken intestinal metabolome.

Although dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated with these effects remain poorly defined. A metabolomics approach was used to characterize and identify the biochemical compounds present in the intestine of broiler chickens fed a standard, unsupplemented diet or a diet supplemented with the antibiotic growth promoters, virginiamycin or bacitracin methylene disalicylate. Compared with unsupplemented controls, the levels of 218 biochemicals were altered (156 increased, 62 decreased) in chickens given the virginiamycin-supplemented diet, while 119 were altered (96 increased, 23 decreased) with the bacitracin-supplemented diet. When compared between antibiotic-supplemented groups, 79 chemicals were altered (43 increased, 36 decreased) in virginiamycin- vs. bacitracin-supplemented chickens. The changes in the levels of intestinal biochemicals provided a distinctive biochemical signature unique to each antibiotic-supplemented group. These biochemical signatures were characterized by increases in the levels of metabolites of amino acids (e.g. 5-hydroxylysine, 2-aminoadipate, 5-hydroxyindoleaceate, 7-hydroxyindole sulfate), fatty acids (e.g. oleate/vaccenate, eicosapentaenoate, 16-hydroxypalmitate, stearate), nucleosides (e.g. inosine, N6-methyladenosine), and vitamins (e.g. nicotinamide). These results provide the framework for future studies to identify natural chemical compounds to improve poultry growth performance without the use of in-feed antibiotics.

Influence of protein nutrition and virginiamycin supplementation on feedlot growth performance and digestive function of calf-fed Holstein steers.

Two experiments were conducted to examine the influence of protein and virginiamycin (VM) supplementation on feedlot growth performance, digestion, and metabolizable AA (MAA) supply of calf-fed Holstein steers. Growth performance and dietary energetics were evaluated in 120 Holstein steers (127 ± 9 kg). During the initial 112-d feeding period, a steam-flaked corn-based diet was balanced to meet either 100% (MAB) or 87% (UREA) of MAA requirements. Diets were supplemented with or without 22.5 mg/kg VM in a 2 × 2 factorial arrangement. Subsequently (d 112 to 308), all steers received the UREA diet with or without VM. During the initial 112-d, MAB increased ADG, G:F, and dietary NE ( < 0.01). Thereafter, when all steers received the UREA diet, ADG, G:F, and dietary NE were not different ( > 0.10) across initial supplementation treatments. Overall (d 1 to 308), MAB did not affect ADG ( > 0.10) but enhanced G:F efficiency ( = 0.03) and dietary NE ( = 0.05). During the initial 112-d period and through the remainder of the experiment, VM increased G:F ( < 0.01) and dietary NE ( < 0.01). Four Holstein steers (146 ± 4 kg) with cannulas in the rumen and proximal duodenum were used in a 4 × 4 Latin square design to evaluate initial 112-d treatment effects on digestive function. There were no treatment effects ( > 0.10) on ruminal digestion of OM, NDF, starch, microbial efficiency, or total tract digestion of OM and NDF. The MAB increased indispensable AA flow to the small intestine ( < 0.01) and total tract digestion of N ( < 0.01) and starch ( = 0.04). Observed AA supply to small intestine was in agreement with expected supply ( = 0.96). Virginiamycin decreased ( = 0.04) nonammonia N flow to the small intestine and did not affect ( > 0.10) total tract N digestion. Extrapolating from AA supplies in the metabolism study, MAB satisfied indispensable AA requirements during the initial 112-d period, whereas the UREA diet met 73.5% and 79.2% of methionine and lysine requirements, respectively. During the subsequent periods (d 112 to 308) indispensable AA supplies exceeded theoretical requirements. We conclude that enhancements in energy utilization when diets are balanced to meet MAA requirements of calf-fed Holstein steers during the initial 112-d feedlot period remain appreciable throughout time on feed. Virginiamycin enhanced efficiency of energy utilization throughout the feedlot growing-finishing period.

Effect of Scrophularia striata and Ferulago angulata, as alternatives to virginiamycin, on growth performance, intestinal microbial population, immune response, and blood constituents of broiler chickens.

An experiment was conducted to investigate the comparative effect of Scrophularia striata, Ferulago angulata, and virginiamycin (VM) on performance, intestinal microbial population, immune response, and blood constituents of broilers. A total of 300 Ross 308 male broiler chickens were randomly assigned to 5 treatments, with 5 replicates/treatment (10 chickens/pen). Birds were fed either a corn-soybean meal basal diet (control) or the basal diet supplemented with 200 mg/kg VM; 4 g/kg S. striata (SS1); 8 g/kg S. striata (SS2); 4 g/kg F. angulata (FA1); or 8 g/kg F. angulata (FA2). After 6 wk, the BW, ADG, and feed-to-gain ratio (F:G) of the VM, SS1, and FA1 groups were better (P<0.01) compared with the control group. At 42 d, cecal lactobacillus counts were higher (P=0.032) in SS2 and FA2 groups compared with the control and VM groups. In addition, broilers fed any of the diets exhibited lower coliform counts (P<0.05) in the ileum and ceca than those fed the control diet. Total and IgG antibody titers against SRBC for secondary responses, relative spleen weight, and lymphocyte counts were higher (P<0.05) in birds fed the SS2 or FA2 diet compared with the control group. Moreover, feeding the SS2 or FA2 diet decreased (P<0.05) the blood heterophil/lymphocyte ratio and plasma triglyceride level, whereas only the SS2 diet increased (P=0.037) the white blood cell counts compared with the control diet. All diets, except for the VM diet, decreased (P=0.009) the plasma cholesterol level compared to the control treatment. The plasma high-density lipoprotein cholesterol level was also increased (P=0.042) in the SS2 and FA2 groups. In conclusion, dietary S. striata or F. angulata at a level of 4 g/kg diet enhanced growth performance, which was comparable to that of VM used as an antibiotic growth promoter. Furthermore, a high dose of both herbs (8 g/kg diet) could beneficially affect the intestinal health and immune status of broilers.

Effects of dietary pyrroloquinoline quinone disodium on growth performance, carcass yield and antioxidant status of broiler chicks.

Pyrroloquinoline quinone (PQQ), a putative essential nutrient and redox modulator in microorganisms, cell and animal models, has been recognized as a growth promoter in rodents. Growth performance, carcass yield and antioxidant status were evaluated on broiler chickens fed different levels of PQQ disodium (PQQ.Na2). A total of 784 day-old male Arbor Acres (AA) broilers were randomly allotted into seven dietary groups: negative control group (NC) fed a basal diet without virginiamycin (VIR) or PQQ.Na2; a positive control group (PC) fed a diet with 15 mg of VIR/kg diet; and PQQ.Na2 groups fed with 0.05, 0.10, 0.20, 0.40 or 0.80 mg PQQ.Na2/kg diet. Each treatment contained eight replicates with 14 birds each. The feeding trial lasted for 6 weeks. The results showed that chicks fed 0.2 mg PQQ.Na2/kg diet significantly improved growth performance comparable to those in PC group, and the feed efficiency enhancement effects of dietary PQQ.Na2 was more apparent in grower phase. Dietary addition of PQQ.Na2 had the potential to stimulate immune organs development, and low level dietary addition (<0.1 mg/kg) increased plasma lysozyme level. Broilers fed 0.2 mg PQQ.Na2/kg diet gained more carcasses at day 42, and had lower lipid peroxide malondialdehyde content and higher total antioxidant power in plasma. The results indicated that dietary PQQ.Na2 (0.2 mg/kg diet) had the potential to act as a growth promoter comparable to antibiotic in broiler chicks.

Comparison of direct and indirect estimates of apparent total tract digestibility in swine with effort to reduce variation by pooling of multiple day fecal samples.

The intent of this study was to establish a fecal sampling procedure for the indicator method (IM) to provide digestibility values similar to those obtained by the total collection (TC) method. A total of 24 pigs (52.6 ± 1.5 kg) were fed 1 of 4 diets with a 2 × 2 factorial arrangement of virginiamycin and phytase (PHY) added to a corn-soybean meal diet with no inorganic P supplement. Pigs were housed in metabolism crates for a 5-d TC period after 7 d of adaptation. Immediately after the TC, a fecal collection period followed, using the IM by including 0.25% of Cr2O3 in the feed for 10 d. Fecal collection for the IM started the day after diets containing Cr2O3 were first fed, and continued for 9 consecutive days with a single grab sample per day. Similar portions of feces from d 5 to 9 were also composited into 4 samples to evaluate multi-day pooling combinations. Highly variable means and CV among samples for apparent total tract digestibility (ATTD) were observed at d 1 and 2 using the IM. The mean ATTD for DM, GE, and nutrients appeared to be stabilized by d 5 or 6 in all dietary treatments. The TC data seemed to have lower CV than the IM data for many components. Based on the linear broken-line analysis, fecal Cr concentration plateaued at d 3.75 (P < 0.001) after the first feeding of Cr. Mean ATTD values by the IM were lower than those by the TC method for DM (P < 0.05), GE (P < 0.01), P (P < 0.01), and Ca (P < 0.001). The PHY supplementation improved ATTD of P (P < 0.001) and Ca (P < 0.001) in both collection methods, whereas the PHY effect on ATTD of DM was observed only for the IM (P < 0.05). Differences related to PHY effect on ATTD were detected from d 4 to 9 in a single grab sample for P and DM but the ATTD of DM had inconsistent P-values by day. Fecal sampling after 4 d of initial feeding of marker always allowed detection of treatment effects on ATTD of P but not on ATTD of DM. Results indicated that the IM results in lower digestibility values than the TC method and does not provide the same treatment difference as the TC digestibility for energy and nutrients that are not highly impacted by the dietary treatment. For the IM, ATTD values and fecal Cr concentration stabilize at least on d 5 after initial feeding of diets containing Cr2O3. At least 2-d pooling of feces for the IM appears to be needed to provide greater accuracy and lower variations than a single grab sample.

Effects of feeding plant-derived agents on the colonization of Campylobacter jejuni in broiler chickens.

The aim of this work was to test the potential use of plant-derived extracts and compounds to control Campylobacter jejuni in broiler chickens. Over a 7-wk feeding period, birds were fed a commercial diet with or without plant extracts (Acacia decurrens, Eremophila glabra), essential oil [lemon myrtle oil (LMO)], plant secondary compounds [terpinene-4-ol and α-tops (including α-terpineol, cineole, and terpinene-4-ol)], and the antibiotic virginiamycin. Traditional culture and real-time quantitative PCR techniques were used to enumerate the numbers of C. jejuni in chicken fecal and cecal samples. In addition, BW and feed intake were recorded weekly for the calculation of BW gain and feed conversion ratio. The mean log10 counts of C. jejuni were similar (P > 0.05) across treatments. However, significantly lower levels of fecal Campylobacter counts (P < 0.05) were recorded at d 41 for the α-tops treatment by culture methods. No differences (P > 0.05) in BW gain were obtained for dietary supplementation, except for the E. glabra extract, which had a negative impact (P < 0.001) on BW, resulting in sporadic death. Results from this study suggest that supplemental natural compounds used in the current study did not reduce the shedding of C. jejuni to desired levels.

Synergy of streptogramin antibiotics occurs independently of their effects on translation.

Streptogramin antibiotics are divided into types A and B, which in combination can act synergistically. We compared the molecular interactions of the streptogramin combinations Synercid (type A, dalfopristin; type B, quinupristin) and NXL 103 (type A, flopristin; type B, linopristin) with the Escherichia coli 70S ribosome by X-ray crystallography. We further analyzed the activity of the streptogramin components individually and in combination. The streptogramin A and B components in Synercid and NXL 103 exhibit synergistic antimicrobial activity against certain pathogenic bacteria. However, in transcription-coupled translation assays, only combinations that include dalfopristin, the streptogramin A component of Synercid, show synergy. Notably, the diethylaminoethylsulfonyl group in dalfopristin reduces its activity but is the basis for synergy in transcription-coupled translation assays before its rapid hydrolysis from the depsipeptide core. Replacement of the diethylaminoethylsulfonyl group in dalfopristin by a nonhydrolyzable group may therefore be beneficial for synergy. The absence of general streptogramin synergy in transcription-coupled translation assays suggests that the synergistic antimicrobial activity of streptogramins can occur independently of the effects of streptogramin on translation.

Supplementation of direct-fed microbials as an alternative to antibiotic on growth performance, immune response, cecal microbial population, and ileal morphology of broiler chickens.

An experiment was conducted to investigate the supplementation of direct-fed microbials (DFM) as an alternative to antibiotics on growth performance, immune response, cecal microbial population, and ileal morphology of broiler chickens. A total of 800 one-day-old male broiler chicks (Ross × Ross) were randomly allotted to 4 dietary treatments with 4 replicate pens per treatment (50 birds/replicate pen). The 4 dietary treatments fed for 35 d were a corn-soybean meal basal diet (control); control plus 0.1% virginiamycin, as an antibiotic growth promoter (AGP); control plus 0.1% direct-fed microbials that contained Lactobacillus reuteri (DFM 1); and control plus 0.1% direct-fed microbials that contained a mixture of L. reuteri, Bacillus subtilis, and Saccharomyces cerevisiae (DFM 2). Results showed that dietary AGP and DFM supplementation significantly increased (P < 0.05) the BW gain of broilers during 0 to 21 d. The feed intake was reduced, whereas the feed conversion was improved significantly when birds were fed DFM 2 at 0 to 7 d of age. The white blood cell and monocyte levels were significantly higher in the DFM 2 group compared with the control. In addition, feeding DFM significantly (P < 0.05) increased the plasma immunoglobulin levels where a higher level was observed in DFM 2 compared with those of the other treatments. Neither DFM nor AGP treatments affected the cecal Lactobacillus and Salmonella content; however, cecal Escherichia coli content significantly decreased in broiler chickens fed DFM and AGP. The ileal villus height, and width and total thickness of muscularis externa were significantly increased when birds were fed DFM compared with AGP and control. These results indicate that the dietary supplementation of DFM increases the growth performance of birds at an early age, stimulates the immune response, decreases the number of E. coli, and improves the ileal morphology of broiler chickens. Thus, DFM that contained a mixture of several beneficial microorganisms could be a viable alternative to antibiotics in the broiler diets.

Modulations of the chicken cecal microbiome and metagenome in response to anticoccidial and growth promoter treatment.

With increasing pressures to reduce or eliminate the use of antimicrobials for growth promotion purposes in production animals, there is a growing need to better understand the effects elicited by these agents in order to identify alternative approaches that might be used to maintain animal health. Antibiotic usage at subtherapeutic levels is postulated to confer a number of modulations in the microbes within the gut that ultimately result in growth promotion and reduced occurrence of disease. This study examined the effects of the coccidiostat monensin and the growth promoters virginiamycin and tylosin on the broiler chicken cecal microbiome and metagenome. Using a longitudinal design, cecal contents of commercial chickens were extracted and examined using 16S rRNA and total DNA shotgun metagenomic pyrosequencing. A number of genus-level enrichments and depletions were observed in response to monensin alone, or monensin in combination with virginiamycin or tylosin. Of note, monensin effects included depletions of Roseburia, Lactobacillus and Enterococcus, and enrichments in Coprococcus and Anaerofilum. The most notable effect observed in the monensin/virginiamycin and monensin/tylosin treatments, but not in the monensin-alone treatments, was enrichments in Escherichia coli. Analysis of the metagenomic dataset identified enrichments in transport system genes, type I fimbrial genes, and type IV conjugative secretion system genes. No significant differences were observed with regard to antimicrobial resistance gene counts. Overall, this study provides a more comprehensive glimpse of the chicken cecum microbial community, the modulations of this community in response to growth promoters, and targets for future efforts to mimic these effects using alternative approaches.

Effect of virginiamycin on the apparent ileal digestibility of amino acids by growing pigs.

The objective of this experiment was to measure the influence of virginiamycin on the apparent ileal digestibility (AID) of AA by growing pigs. Fifteen barrows were surgically equipped with a T-cannula in the distal ileum and used in the experiment (initial BW = 35.0 +/- 2.7 kg). Animals were randomly allotted to 3 dietary treatments with 5 pigs per treatment during a 6-wk experiment. Dietary treatments included 1) a basal corn-soybean meal diet, 2) the basal diet supplemented with 11 mg/kg of virginiamycin, and 3) the basal diet supplemented with 22 mg/kg of virginiamycin. Pigs were fed their respective treatment diets during wk 2, 3, and 4, but during wk 1, 5, and 6, all pigs were fed the basal diet. Ileal samples were collected on d 6 and 7 of each week. Results showed that the AID of all indispensable AA, except Arg, His, and Ile, increased (P < 0.05) during wk 2, 3, and 4 compared with wk 1 in pigs fed the diet containing 11 mg/kg of virginiamycin. Pigs fed 22 mg/kg of virginiamycin during wk 2, 3, and 4 had increased (P < 0.05) AID of Trp and Val during these weeks compared with the AID in wk 1. However, the increased AID of AA did not carry over to wk 5 and 6, when virginiamycin was withdrawn from the diet, regardless of the inclusion rate. In pooled data from wk 2, 3, and 4, the AID of CP, the mean of all indispensable AA, and Ile, Leu, Met, Phe, Trp, and Val increased (linear, P < 0.05) as virginiamycin was added to the diets, whereas a tendency (P < 0.10) for a linear or quadratic increase was observed for His, Lys, and Thr. These results indicate that addition of virginiamycin to corn-soybean meal diets fed to growing pigs increases the AID of AA, but this effect is not maintained after the removal of virginiamycin from the diet.

[Pharmacological rationale for choice of antibiotics for intraabdominal infections]. / Infezioni intraddominali: aspetti farmacologici degli antibiotici.

The pharmacodynamic and pharmacokinetic characteristics of antimicrobial agents are the two fundamental pharmacological components which provide a rationale for the choice of therapy for intraabdominal infections, and especially serious infections. The most important PK-PD parameters are well known which can potentiate therapeutic efficacy. Antimicrobial agents can be subdivided into categories based on whether their activity is dependent on concentration or exposure time. Therefore, a correct dosing regimen for the time-dependent molecules (i.e. beta-lactams, linezolid, tigecycline) should prolong the maximum exposure time to maintain serum levels over the minimum inhibitory concentration (MIC). The concentration-dependent molecules, on the other hand, which include aminoglycosides and fluoroquinolones, should be given in order to reach maximum concentrations, since they are bactericidal in direct proportion to their concentrations and possess a prolonged post-antibiotic effect.

Cecal populations of lactobacilli and bifidobacteria and Escherichia coli populations after in vivo Escherichia coli challenge in birds fed diets with purified lignin or mannanoligosaccharides.

Two experiments were conducted to evaluate lignin and mannanoligosaccharides as alternatives to antibiotic growth promoters in broilers. Dietary treatments for the 2 studies were 1) negative control (CTL-, antibiotic free); 2) positive control (CTL+, diet 1 + 11 mg of virginiamycin/kg); 3) mannanoligosaccharide (MOS; diet 1 + BioMos: 0.2% to 21 d and 0.1% thereafter); 4) LL (diet 1 + 1.25% Alcell lignin); and 5) HL (diet 1 + 2.5% Alcell lignin). In experiment 1, each treatment was assigned to 4 pen replicates (52 birds each). Body weight and feed intake were recorded weekly for 38 d. At 28 and 38 d, cecal contents were assayed for lactobacilli and bifidobacteria. Body weight and feed intake did not differ among dietary treatments. At d 38, the lactobacilli population was greatest (P < 0.05) in birds fed MOS, whereas LL-fed birds had greater (P < 0.05) lactobacilli load than those fed CTL+. Bifidobacteria load was greater (P < 0.05) in birds fed MOS or LL compared with those fed CTL+ at both d 28 and 38. However, at d 28 and 38, lactobacilli and bifidobacteria loads were lowest (P < 0.05) in CTL+ or HL-fed birds. In experiment 2, 21-d-old birds from the initial flock were transferred to cages for oral Escherichia coli (O2 and O88 serotypes) challenge (12 birds/treatment). After 3, 6, and 9 d, cecal loads of E. coli were determined. Birds fed HL had a lower E. coli load (P < 0.05) than birds fed CTL- or CTL+ at d 3, and lower than birds fed CTL- at d 6. At d 9, the E. coli load was lower (P < 0.05) in birds fed MOS or HL than in those fed the CTL- or CTL+ diets; LL-fed birds had lower E. coli load than those fed CTL-. Birds fed MOS or LL had a comparative advantage over CTL+ birds in increasing populations of lactobacilli and bifidobacteria and lowering E. coli loads after challenge.

Virginiamycin improves phosphorus digestibility and utilization by growing-finishing pigs fed a phosphorus-deficient, corn-soybean meal diet.

Evaluations of the nutritional effect of antibiotics have largely centered on effects related to the digestibility and utilization of protein and energy. The current study evaluated the potential effect of virginiamycin (VIR) on P digestibility in swine. A total of 70 barrows (mean initial BW = 51 to 64 kg) were used in 4 nutrient-balance experiments. A basal, corn-soybean meal diet that was not supplemented with any inorganic source of P was used in each experiment. In Exp. 1, two diets were tested: basal vs. basal plus 11 mg/kg of VIR. In Exp. 2, four diets were used with a 2 x 2 factorial arrangement of 0 and 11 mg/kg of VIR and 0 and 750 phytase (PHY) units/kg of diet (PU/kg). Experiments 3 and 4 were the same as Exp. 2, except PHY was reduced to 300 PU/kg. For all experiments, VIR improved P digestibility (32.71 to 37.72%, P < 0.001) and Ca digestibility (54.99 to 58.30%, P = 0.002). The addition of PHY improved both P and Ca digestibility (P < 0.001); 750 PU/kg increased P digestibility 27.3% (from 34.6 to 61.9%, P < 0.001), whereas 300 PU increased it 13.8% (from 33.4 to 47.2%, P < 0.001). In an experiment conducted to evaluate the long-term effects of VIR on gut microbial profile, pigs (24 gilts and 8 barrows; mean BW = 29.1 +/- 0.50 kg) were fed a simple corn-soybean meal diet for 16 wk with a 2 x 2 factorial arrangement of VIR (0 and 11 mg/kg) addition and 0.15% dicalcium phosphate deletion. The long-term feeding of VIR in both the control diet and the diet with a marginally reduced P level resulted in a change in ileal microbial profile. A positive numerical increment in the number of phytate-utilizing bacteria was observed in both the normal and P-deleted diets (log unit increments of 12.4 and 17.2% over the respective controls, P = 0.13) when VIR was added. The addition of VIR also tended to affect lactobacilli populations (main effect, P = 0.11; interaction, P = 0.02); VIR decreased lactobacilli in the normal-P diet but did not affect this bacterial population in the P-deleted diet. In conclusion, the antibiotic VIR improves both Ca and P digestibility in pigs. The increase in digestibility is not as great as that provided by PHY, but because the potential mechanism of action (altered microbial populations) differs from that of PHY (direct addition of an enzyme), there can be a degree of additivity in P digestibility improvement when both products are used.

Effects of griseoviridin and viridogrisein against swine dysentery in experimental infection by using mice and pigs.

Griseoviridin, a known antibiotic produced by Streptomyces cacaoi subsp. cacaoi, was found to be active against Brachyspira hyodysenteriae--the bacterium causing swine dysentery. An in vitro synergism is observed when it is used in combination with viridogrisein--a simultaneously produced antibiotic. In mouse experiments, the effect of griseoviridin alone was less than that of lincomycin--a commercially available swine dysentery medication. However, a 1:1 mixture of griseoviridin and viridogrisein revealed a noticeable synergistic effect. In an evaluation using pigs artificially infected with B. hyodysenteriae, a large difference was not observed between the effect of griseoviridin alone and that in combination with viridogrisein. Nevertheless, griseoviridin alone exhibited a therapeutic effect superior to that of lincomycin.

Effect of antibiotic growth promoters on broiler performance, intestinal growth parameters, and quantitative morphology.

The effects of addition of bacitracin methylene disalicylate (BMD) or virginiamycin (VM) to a corn-soybean meal diet on broiler performance and gastrointestinal tract (GIT) growth parameters and morphology were studied at various ages during growth and finishing. Male and female birds were killed at 1, 3, 5, or 7 wk of age for gross and histologic examination of the duodenum and ileum. Feeding either antibiotic increased BW and decreased intestinal length and weight at all times compared with control birds. However, intestinal length and weight decreases were greater in birds fed VM than BMD at 1 and 3 wk of age. The only change found in the duodenum resulting from dietary treatment was an increase in the number of villi per unit length in birds given VM but not BMD or control. In the ileum, the muscularis mucosa was thinner in birds given VM than in those fed the control diet. Chicks supplemented with VM had a smaller total villus area and shorter villus height and crypt depth in the ileum than birds fed the control diet or BMD. Physical changes in the intestine of birds given either antibiotic growth promoter, although not the same, resulted in improved performance.

Comparative efficacies of quinupristin-dalfopristin, linezolid, vancomycin, and ciprofloxacin in treatment, using the antibiotic-lock technique, of experimental catheter-related infection due to Staphylococcus aureus.

We performed in vitro studies to elucidate the bactericidal activity of the antibiotics in an adherent-cell biofilm model. Efficacy studies were performed in a staphylococcal central venous catheter (CVC) infection rat model. Silastic catheters were implanted into the superior cava. Via the CVC the rats were challenged with 1.0 x 10(6) CFU of a live Staphylococcus aureus strain. Twenty-four hours later, the antibiotic-lock technique was started. All animals were randomized to receive daily isotonic sodium chloride solution, quinupristin-dalfopristin (Q/D), linezolid, vancomycin, or ciprofloxacin at the minimal bactericidal concentration (MBC) and at 1,024 microg/ml in a volume of 0.1 ml that filled the CVC. The main outcome measures were MICs and MBCs for both planktonic and adherent cells, quantitative culture of the catheters and surrounding venous tissues, and quantitative peripheral blood cultures. The killing activities of all antibiotics against the adherent bacteria were at least fourfold lower than those against freely growing cells, with the exception of Q/D, which showed comparable activities against both adherent and planktonic organisms. Overall, Q/D at 1,024 microg/ml produced the greatest reduction in the number of cells recovered from the catheters, while at the same concentration, Q/D and vancomycin demonstrated higher activities than ciprofloxacin or linezolid in reducing the number of organisms recovered from the blood cultures. This study points out that treatment outcome of device-related infections cannot be predicted by the results of a standard susceptibility test such as the MIC. Our findings suggest that the clinically used antibiotics cannot eradicate the CVC infection through the antibiotic-lock technique, even at a concentration of 1,024 microg/ml.