Haemophilus Pleuropneumoniae Research Articles

Optimal regimens based on PK/PD cutoff evaluation of ceftiofur against Actinobacillus pleuropneumoniae in swine

BackgroundActinobacillus pleuropneumoniae formerly known as Haemophilus pleuropneumoniae, can cause pleuropneumoniae in pigs, which lead to significant mortality. Ceftiofur was the first cephalosporin antibiotic used in animals, which was effective against gram-negative and gram-positive bacterium. This study aimed to formulate a rational dosage strategy and review the preceding recommended dosage based on PK/PD modeling and Establish Clinical breakpoint of ceftiofur against Actinobacillus pleuropneumoniae based on the pharmacodynamic-pharmacokinetic cutoff.ResultsThe epidemiologic cutoff value was 0.125 μg/mL. The results of the pharmacodynamic study showed that the MICs of BW39 were 0.5 μg/mL and 1 μg/mL in vitro and ex-vivo, respectively. The minimal bactericidal concentrations (MBCs) under in vitro and ex vivo conditions were both 1 μg/mL. The time-killing profiles of ceftiofur against BW39 were time-dependent with a partly concentration-dependent pattern. Based on the inhibitory sigmoid Emax model, the AUC24 h/MIC values for the bacteriostatic, bactericidal, and elimination effects in serum were 45.73, 63.83, and 69.04 h for healthy pigs separately. According to the Monte Carlo simulation, the COPD was calculated as 2 μg/mL, and the optimized dosage regimen of ceftiofur against Actinobacillus pleuropneumoniae to achieve bacteriostatic, bactericidal, and elimination effects over 24 h was 2.13, 2.97, and 3.42 mg/kg for the 50% target attainment rate (TAR) and 2.47, 3.21, and 3.70 mg/kg for the 90% TAR respectively.ConclusionsIn conclusion, we reveal the EOFF and PK/PD cutoff values of ceftiofur against A. pleuropneumoniae in piglets. However, with the paucity of clinical data for ceftiofur to establish a clinical cutoff against A. pleuropneumoniae, the PK/PD cutoff value of 2 μg/mL will be recommended as surrogate. According to the PK/PD data and the MIC distribution in China, the single bactericidal dose was 3.21 mg/kg for the 90% target, which would be more able to cure Actinobacillus pleuropneumoniae and avoid the emergence of resistance for clinical ceftiofur use in piglet.

Pleuroneumonía porcina: aislamiento de Haemophilus pleuropneumoniae en Chile.

An infectaous outbreak involving Haemophilus pleuropneumoniae affecting a 2000 pigherd farm in the Metropolitan Region is reported for the first time in Chile. A morbidity of 10% and 15% was observed in post weaning and growing finishing pigs, respectively. The mortality rates for post weaning, growing and finishing pigs were 2.6%, 0.5% and 1.1% respectively. The lesions were restricted to the thoracic cavíty and they consis­ted of delimited pneumonic focuses, fibrinous pleuritis and a great amount of serous bloody liquid. Hemorrhagic infarcts were seen microscopically. Bacteriological isolation from pneumonic lesions and mediastinic lymph nodes demonstrated the presence of a pure culture, which according to its biochemical and growing characteristics it correspon­ded to Haemophilus pleuropneumoniae.

Otitis in a weaned pig: a new pathological role for Actinobacillus (Haemophilus) pleuropneumoniae.

A weaned pig exhibiting clinical signs characteristic of a vestibular syndrome (abnormal head tilt and abnormal gait including a tendency to circle) was examined as a representative example of a condition which, in a 12-month period, affected approximately 400 other pigs on the farm of origin. The condition caused significant morbidity and financial loss but the directly attributable mortality was negligible. Post mortem examination revealed a severe suppurative, left-sided otitis media and interna. Mixed growths of bacteria, including Actinobacillus pleuropneumoniae, were isolated from the pus from the middle ear. Otitis caused by mixed bacterial infections has been described previously in pigs and cattle but infection of the porcine middle ear cavity by A pleuropneumoniae is considered to be a new pathological role for this organism. Other findings in this case indicated that otitis media had followed from bacterial colonisation of the auditory (Eustachian) tube. The condition was effectively controlled by prophylactic antibiotic therapy. The authors consider that vestibular syndrome due to otitis media and interna, whether caused by infection with A pleuropneumoniae or not, is probably a relatively common condition in England but its significance may be underestimated and for this reason it may be underrecorded.

5254340 Vaccine suitable for prophylaxis and control, respectively, of the pig disease caused by haemophilus pleuropneumoniae and a method for obtaining extracellular proteinaceous material of haemophilus pleuropneumoniae for use in such vaccines: Leonardus A M G Van Leengoed, Elbarte M Kamp, Lelystad, Netherlands assigned to Centraal Diergeneeskundig Instituut

5254340 Vaccine suitable for prophylaxis and control, respectively, of the pig disease caused by haemophilus pleuropneumoniae and a method for obtaining extracellular proteinaceous material of haemophilus pleuropneumoniae for use in such vaccines: Leonardus A M G Van Leengoed, Elbarte M Kamp, Lelystad, Netherlands assigned to Centraal Diergeneeskundig Instituut

Adjuvant properties of propionibacterium avidum KP-40 in vaccination against endemic viral and bacterial infections II. Swine immunized with inactivated haemophilus pleuropneumoniae vaccine and experimentally infected with different virulent serotypes of H. pleuropneumoniae

Forty 3-month old swine were treated with immunomodulating Propionibacterium avidum KP-40 (PA) and/or vaccinated with a formalin-inactivated mixture of serotypes 1, 3, 5 and 9 of Haemophilus pleuropneumoniae (Pleurovac). Three weeks after revaccination all animals were inoculated with viable single serotypes of Haemophilus pleuropneumoniae. The IgG antibodies induced by vaccination agglutinated all serotypes of Haemophilus pleuropneumoniae, except for serotype 5. Antibody titers were not influenced by the application of PA together with the vaccine. Infection of vaccinated piglets resulted in the development of pleuropneumonia in 8 out of 10 animals, while vaccination together with application of PA lowered the morbidity rate to 1 out of 10 (p < 0.05). The usefulness of a PA prophylaxis was also demonstrated in non-vaccinated piglets infected with Haemophilus pleuropneumoniae. Because of the considerable variability of strains and serotypes of Haemophilus pleuropneumoniae and the generally low prophylactic potency of pleuropneumonia vaccines it is concluded that long-lasting enhancement of non-specific antiinfective resistance caused by PA may lower the risk of endemic infections in vaccinated piglets.

Freeze-substitution of gram-negative eubacteria: general cell morphology and envelope profiles

Freeze-substitution was performed on strains of Escherichia coli, Pasteurella multocida, Campylobacter fetus, Vibrio cholerae, Pseudomonas aeruginosa, Pseudomonas putida, Aeromonas salmonicida, Proteus mirabilis, Haemophilus pleuropneumoniae, Caulobacter crescentus, and Leptothrix discophora with a substitution medium composed of 2% osmium tetroxide and 2% uranyl acetate in anhydrous acetone. A thick periplasmic gel ranging from 10.6 to 14.3 nm in width was displayed in E. coli K-12, K30, and His 1 (a K-12 derivative containing the K30 capsule genes), P. multocida, C. fetus, P. putida, A. salmonicida, H. pleuropneumoniae, and P. mirabilis. The other bacteria possessed translucent periplasms in which a thinner peptidoglycan layer was seen. Capsular polysaccharide, evident as electron-dense fibers radiating outward perpendicular to the cell surface, was observed on E. coli K30 and His 1 and P. mirabilis cells. A more random arrangement of fibers forming a netlike structure was apparent surrounding cells of H. pleuropneumoniae. For the first time a capsule, distinct from the sheath, was observed on L. discophora. In all instances, capsular polysaccharide was visualized in the absence of stabilizing agents such as homologous antisera or ruthenium red. Other distinct envelope structures were observed external to the outer membrane including the sheath of L. discophora and the S layers of A. salmonicida A450 and C. crescentus CB15A. We believe that the freeze-substitution technique presents a more accurate image of the structural organization of these cells and that it has revealed complex ultrastructural relationships between cell envelope constituents previously difficult to visualize by more conventional means of preparation.

豚肺炎由来&lt;I&gt;Actinobacillus&lt;/I&gt; (&lt;I&gt;Haemophilus&lt;/I&gt;) &lt;I&gt;pleuropneumoniae&lt;/I&gt;の血清型と薬剤感受性

豚肺炎由来&lt;I&gt;Actinobacillus&lt;/I&gt; (&lt;I&gt;Haemophilus&lt;/I&gt;) &lt;I&gt;pleuropneumoniae&lt;/I&gt;の血清型と薬剤感受性

Influences of climatic treatments on systemic immunological parameters in pigs

In six experiments, young pigs were exposed to adverse environmental conditions, namely 15°C, 15°C + draught, 25°C + draught, fluctuating temperatures ( 15 25 ° C ) and 15 25 ° C + draught as compared with 25°C. In one experiment, pigs were challenged with Haemophilus pleuropneumoniae (Hpp). At Day 16, percent gammaglobulin, percent neutrophils and percent lymphocytes were significantly affected by climatic treatments. Percentage neutrophils increased when pigs were exposed to the fluctuating temperatures with draught. In all other treatments, however, percent neutrophils decreased. In most treatments percent gammaglobulin and percent lymphocytes increased with time. Percent gammaglobulin did not increase with fluctuating temperature. Percent lymphocytes did not increasein time during exposure to fluctuating temperature with draught. Percent gammaglobulin and specific antibodies to Hpp increased in Hpp-infected pigs. However, the increase was higher in pigs under adverse conditions. It was concluded that different climatic factors influenced the immune system differently, probably because of differences in acclimation.

Drug-susceptibility and isolation of a plasmid in Haemophilus (Actinobacillus) pleuropneumoniae.

We isolated 56 Haemophilus (Actinobacillus) pleuropneumoniae strains from the pneumonic porcine lung tissues and tested them for antimicrobial susceptibility. Two drug-resistant strains were obtained. One, named KH-265, was resistant to streptomycin (SM) and sulfonamide (SA), and the other, named KH-195, was resistant to tetracycline (TC). The minimum inhibitory concentrations (MICs) of drugs for resistant strains were 100 micrograms/mliters for SM, 3200 micrograms/mliters for SA, and 12.5 micrograms/mliters for TC. KH-265 possessed a 8.3Kb nonconjugative plasmid, pMS260, encoding SM and SA resistance, which was transformable to E. coli strains. pMS260 belonged to none of 14 incompatibility groups including Inc. P and Inc. Q, so far tested. It was mobilizable to various causative strains for respiratory infections, Pseudomonas aeruginosa, Bordetella bronchiseptica, Pasteurella multocida and Haemophilus pleuropneumoniae, by RP4 (Inc. P) plasmid.

Production and characterization of monoclonal antibodies against Actinobacillus (Haemophilus) pleuropneumoniae serotype 2.

Four hybridoma cell lines producing monoclonal antibodies (MAbs) against Actinobacillus (Haemophilus) pleuropneumoniae were established by fusion of mouse myeloma and spleen cells obtained from mice immunized with a serotype 2, strain SH-15. Enzyme-linked immunosorbent assay-inhibition tests with antigens obtained from 12 serotype strains of A. pleuropneumoniae and 9 other gram-negative bacteria showed that all the MAbs bound to only serotype 2 strains of A. pleuropneumoniae. The epitopes recognized by the MAbs were located on a carbohydrate moiety of lipopolysaccharide (LPS) of the organism, which was sensitive to periodate oxidation. In immunoblotting analyses of LPS obtained from A. pleuropneumoniae serotype 2, all the four MAbs reacted specifically with the characteristic ladder bands of LPS detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results suggest that O-antigen side chains of the LPS are one of the antigenic determinants responsible for the serotype-specificity of A. pleuropneumoniae.

Responses of Haemophilus pleuropneumoniae to iron restriction: changes in the outer membrane protein profile and the removal of iron from porcine transferrin

Outer membranes from Haemophilus pleuropneumoniae grown under iron-replete and iron-restricted conditions in vitro were analysed by means of SDS-PAGE and immunoblotting. Iron restriction resulted in the appearance of two or more novel polypeptides in the molecular size range of 96-102 kD and an increased amount of a 79 kD polypeptide. These polypeptides were recognized by porcine immune sera indicating their production by H. pleuropneumoniae during growth in vivo. Although soluble siderophore production could not be detected, growth of the organisms on an iron-restricted medium was enhanced by the presence of porcine transferrin but not by bovine or human transferrin. The results suggest that H. pleuropneumoniae possesses a specific transferrin receptor, perhaps in the form of an iron-regulated outer membrane protein.

In vitro evaluation of various quinolone antibacterial agents against veterinary mycoplasmas and porcine respiratory bacterial pathogens

The in vitro activities of 12 quinolones and four antibiotics were determined against 15 veterinary mycoplasmal species and four species of bacteria commonly involved in respiratory infections in pigs. The newer quinolones were markedly more active in vitro against a wide range of mycoplasmas than nalidixic acid and the earlier quinolones. Against Mycoplasma hyopneumoniae ciprofloxacin was the most active quinolone with a geometric mean minimal inhibitory concentration (MIC) against 16 strains of 0.01 microgram ml-1 compared with 0.04 microgram ml-1 for tiamulin, 0.06 microgram ml-1 for tylosin, 0.17 microgram ml-1 for oxytetracycline and 0.23 microgram ml-1 for gentamicin. M hyosynoviae was less sensitive to the quinolones with mean MICs of 0.6 microgram ml-1 for ofloxacin and 0.7 microgram ml-1 for ciprofloxacin compared with 0.034 microgram ml-1, or less, for tiamulin. Norfloxacin and its 6-chloro analogue were both mycoplasmacidal in vitro at five or 10 times their MICs against M hyopneumoniae UCD4. Tiamulin was mycoplasmastatic. The quinolones were also active against porcine Bordetella bronchiseptica and Pasteurella multocida strains and Haemophilus species. Ciprofloxacin was the most active quinolone with mean MICs of 0.58 microgram ml-1 against B bronchiseptica (nine strains), 0.026 microgram ml-1 against P multocida (five strains) and 0.01 microgram ml-1, or less, against Haemophilus pleuropneumoniae (nine strains) and H parasuis (two strains) compared with mean MICs of from 0.5 microgram ml-1 to 64 micrograms ml-1, or more, for the antibiotics. This combination of excellent mycoplasmacidal activity against M hyopneumoniae and good antibacterial activity, suggests that the quinolones have great potential for treating respiratory infections in pigs, including enzootic pneumonia.

ChemInform Abstract: Synthesis of a Cell Wall Component of Haemophilus (Actinobacillus) pleuropneumoniae Type 2.

ChemInformVolume 20, Issue 7 Natural Products ChemInform Abstract: Synthesis of a Cell Wall Component of Haemophilus (Actinobacillus) pleuropneumoniae Type 2. G. H. VEENEMAN, G. H. VEENEMAN Gorlaeus Lab., 2300 RA Leiden, Neth.Search for more papers by this authorH. F. BRUGGHE, H. F. BRUGGHE Gorlaeus Lab., 2300 RA Leiden, Neth.Search for more papers by this authorP. HOOGERHOUT, P. HOOGERHOUT Gorlaeus Lab., 2300 RA Leiden, Neth.Search for more papers by this authorG. A. VAN DER MAREL, G. A. VAN DER MAREL Gorlaeus Lab., 2300 RA Leiden, Neth.Search for more papers by this authorJ. H. VAN BOOM, J. H. VAN BOOM Gorlaeus Lab., 2300 RA Leiden, Neth.Search for more papers by this author G. H. VEENEMAN, G. H. VEENEMAN Gorlaeus Lab., 2300 RA Leiden, Neth.Search for more papers by this authorH. F. BRUGGHE, H. F. BRUGGHE Gorlaeus Lab., 2300 RA Leiden, Neth.Search for more papers by this authorP. HOOGERHOUT, P. HOOGERHOUT Gorlaeus Lab., 2300 RA Leiden, Neth.Search for more papers by this authorG. A. VAN DER MAREL, G. A. VAN DER MAREL Gorlaeus Lab., 2300 RA Leiden, Neth.Search for more papers by this authorJ. H. VAN BOOM, J. H. VAN BOOM Gorlaeus Lab., 2300 RA Leiden, Neth.Search for more papers by this author First published: February 14, 1989 https://doi.org/10.1002/chin.198907289Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume20, Issue7February 14, 1989 RelatedInformation

Protection of mice against the lethal effect of an intraperitoneal infection with Haemophilus (Actinobacillus) pleuropneumoniae after vaccination with capsular proteins

Haemophilus (Actinobacillus) pleuropneumoniae Serotypes 5 and 7 capsular antigens (CA-1) were precipitated from culture supernatants with N-cetyl-N,N,N,-trimethylammonium bromide (Cetavlon). CA-1 contained a carbohydrate to protein ratio of 2:1 for Serotype 5 and 3:1 for Serotype 7. Glucosamine and uronic acid were detected in CA-1 from both serotypes suggesting that the capsule contained hyaluronic acid. All mice immunized intraperitoneally with CA-1 vaccine were protected from death when challenged with 10 × LD 50 of the homologous but not the heterologous serotype. Oil adjuvants and the use of young (6 h) cultures were necessary for CA-1 vaccines to be protective. Deproteinization of CA-1 with chloroform and butanol followed by pronase treatment resulted in failure to protect mice from death. The protective capsular protein antigen in CA-1 vaccine may not originate from the outer membrane (OM) since repeated washing of the OM to elute the capsular protein antigen rendered the OM vaccine completely nonprotective for mice. Vaccines prepared from cell-wall lipopolysaccharide also were nonprotective for mice. Passive immunization of mice with anti-CA-1 antibody produced in rabbits to Serotype 5 was highly protective ( P < 0.01) for mice when challenged with 10 × the LD 50 of the homologous serotype.

Structure of the O-antigen polysaccharide of Haemophilus pleuropneumoniae serotype 3 (ATCC 27090) lipopolysaccharide

The structure of the O-antigen polysaccharide of Haemophilus pleuropneumoniae serotype 3 (ATCC 27090) S-type lipopolysaccharide was investigated by methylation analysis, partial hydrolysis, periodate oxidation, and 1H- and 13C-n.m.r. spectroscopy, and concluded to be composed of linear pentasaccharide repeating-units having the structure: ▪

Production and Characterization of Monoclonal Antibodies to Serotype Specific Antigens of Haemophilus Pleuropneumoniae Serotype 2

Mouse monoclonal antibodies were produced to Haemophilus pleuropneumoniae bacteria of the most common serotype 2. 11 hybridoma cultures were recovered that produced antibodies with moderate to strong reactivity to the antigen. 10 of these antibodies were specific to isolated capsular antigens from H. pleuropneumoniae of serotype 2, while one antibody reacted with capsular antigens from bacteria of all 8 serotypes. One hybridoma producing antibodies with a titre of 1:1000 was cloned and the antibody specificity studied further. The binding of this antibody (1F3) to whole bacteria, and capsular extracts isolated at different temperatures indicate that the antibody is specific for a thermostable polysaccharide antigen present in the cellular capsule of H. pleuropneumoniae of serotype 2.

Untersuchungen des Aminosäure- und Kohlenhydrat-Stoffwechsels porciner Haemophilus-Stämme mittels Dünnschichtchromatographie

The aim of the present study was to investigate porcine reference and field strains of the species Haemophilus (H.) pleuropneumoniae and H. parasuis, as well as H. Taxon "minor group" and Taxon C on their amino acid and carbohydrate metabolism by thin layer chromatography. The 17 reference strains studied showed almost identical results within the different species and taxa in both, amino acid and carbohydrate metabolism patterns. Based on a few differing enzymatic reactions a reduced species- and taxon-specific reaction pattern could be established, which included L-alanine, L-citrulline and L-threonine of the amino acids as well as D-ribose, alpha-D-xylose, mannitol, trehalose, beta-melibiose and alpha-lactose of the carbohydrates. This differentiation system allowed a reliable identification of 7 field strains whereas 4 additional ones, hitherto pre-classified as H. parasuis, could not be associated with any of the above species and taxa.

Synthesis of a cell wall component of haemophilus (actinobacillus) pleuropneumoniae type 2

AbstractCoupling of properly protected repeating tetrasaccharide units of Haemophilus (Actinobacillus) pleuropneumoniae could be realized by regioselective phosphorylation.

Efficacy of a bivalent vaccine containing serovar 2 and 5 strains of Haemophilus pleuropneumoniae in pigs or in guinea pigs.

Efficacy of a bivalent vaccine containing serovar 2 and 5 strains of Haemophilus pleuropneumoniae in pigs or in guinea pigs.

Preparation and characteristics of envelope proteins from haemophilus pleuropneumoniae

Envelope proteins of Haemophilus pleuropneumoniae were extracted by 3 methods and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Three major envelope proteins (45 000 M r, 41 000 M r, 31 500 M r) were distinguished in sonicated cell envelopes together with minor proteins. Using selective solubilisation with sodium lauryl sarcosinate or Triton X-100, outer membrane proteins were distinguished from those of the cytoplasmic membrane. Extraction into LiCl produced a similar profile, but the 41 000 M r and 31 500 M r bands were present in reduced amounts. Extraction into saline at 60°C produced a grossly different pattern, with a major band at 20 000 M r. All 3 major envelope proteins were shown to be heat-modifiable, and the 31 500 M r band was found to be the non-heat-modified form of a a 43 000 M r protein, which showed similar properties to the Protein d of H. influenzae which is related to the OmpA protein of E. coli K-12. The 45 000 M r major protein was also weakly associated with the peptidoglycan in SDS/Triton at low temperature.