Microbial shifts in the swine nasal microbiota in response to parenteral antimicrobial administration.

The continuous administration of antimicrobials in swine production has been widely criticized with the increase of antimicrobial-resistant bacteria and dysbiosis of the beneficial microbial communities. While an increasing number of studies investigate the effects of antimicrobial administration on swine gastrointestinal microbiota biodiversity, the impact of their use on the composition and diversity of nasal microbial communities has not been widely explored. The objective of this study was to characterize the short-term impact of different parenteral antibiotics administration on the composition and diversity of nasal microbial communities in growing pigs. Five antimicrobial treatment groups, each consisting of four, eight-week old piglets, were administered one of the antimicrobials; Ceftiofur Crystalline free acid (CCFA), Ceftiofur hydrochloride (CHC), Tulathromycin (TUL), Oxytetracycline (OTC), and Procaine Penicillin G (PPG) at label dose and route. Individual deep nasal swabs were collected immediately before antimicrobial administration (control = day 0), and again on days 1, 3, 7, and 14 after dosing. The nasal microbiota across all the samples were dominated by Firmicutes, proteobacteria and Bacteroidetes. While, the predominant bacterial genera were Moraxella, Clostridium and Streptococcus. Linear discriminant analysis, showed a pronounced, antimicrobial-dependent microbial shift in the composition of nasal microbiota and over time from day 0. By day 14, the nasal microbial compositions of the groups receiving CCFA and OTC had returned to a distribution that closely resembled that observed on day 0. In contrast, pigs that received CHC, TUL and PPG appeared to deviate away from the day 0 composition by day 14. Based on our results, it appears that the impact of parenteral antibiotics on the swine nasal microbiota is variable and has a considerable impact in modulating the nasal microbiota structure. Our results will aid in developing alternative strategies for antibiotics to improve swine health and consequently production.

Impact of parenteral antimicrobial administration on the structure and diversity of the fecal microbiota of growing pigs.

While antimicrobials are cost-effective tools for prevention and treatment of infectious disease, the impact of their use on potentially beneficent mucosal microbial communities of growing pigs has not been widely explored. The objective of this study was to characterize the impact of parenteral antibiotics administration on the composition and diversity of the resident fecal microbiota in growing pigs. Five antimicrobial treatment groups, each consisting of four, eight-week old piglets, were administered one of the antimicrobials; Ceftiofur Crystalline free acid (CCFA), Ceftiofur hydrochloride (CHC), Oxytetracycline (OTC), Procaine Penicillin G (PPG) and Tulathromycin (TUL) at label dose and route. Individual fecal swabs were collected immediately before antimicrobial administration (control = day 0), and again on days 1, 3, 7, and 14 after dosing. Genomic DNA was extracted, and the V1-V3 hypervariable region of 16S rRNA gene was amplified and sequenced using Illumina Miseq-based sequencing. Across all groups, the most abundant phyla were Firmicutes, Bacteroidetes, and Proteobacteria. Linear discriminant analysis and stacked area graphs, showed a pronounced, antimicrobial-dependent shift in the composition of fecal microbiota over time from day 0. By day 14, the fecal microbial compositions of the groups receiving CHC and TUL had returned to a distribution that closely resembled that observed on day 0, but differences were still evident. In contrast, animals that received PPG, OTC and CCFA, showed a tendency towards a balanced homeostatic microbiota structure on day 7, but appeared to deviate away from the day 0 composition by day 14. Based on our results, the observed changes in fecal microbiota showed antimicrobial-specific variation in both duration and extent. Understanding the impact of these important antimicrobial-induced changes will be a critical step in optimizing the use of antimicrobials in health management programs in the swine industry.

Changes in the equine fecal microbiota associated with the use of systemic antimicrobial drugs.

BACKGROUND: The intestinal tract is a rich and complex environment and its microbiota has been shown to have an important role in health and disease in the host. Several factors can cause disruption of the normal intestinal microbiota, including antimicrobial therapy, which is an important cause of diarrhea in horses. This study aimed to characterize changes in the fecal bacterial populations of healthy horses associated with the administration of frequently used antimicrobial drugs. RESULTS: Twenty-four adult mares were assigned to receive procaine penicillin intramuscularly (IM), ceftiofur sodium IM, trimethoprim sulfadiazine (TMS) orally or to a control group. Treatment was given for 5 consecutive days and fecal samples were collected before drug administration (Day 1), at the end of treatment (Days 5), and on Days 14 and 30 of the trial. High throughput sequencing of the V4 region of the 16S rRNA gene was performed using an Illumina MiSeq sequencer. Significant changes of population structure and community membership were observed after the use of all drugs. TMS caused the most marked changes on fecal microbiota even at higher taxonomic levels including a significant decrease of richness and diversity. Those changes were mainly due to a drastic decrease of Verrucomicrobia, specifically the "5 genus incertae sedis". Changes in structure and membership caused by antimicrobial administration were specific for each drug and may be predictable. Twenty-five days after the end of treatment, bacterial profiles were more similar to pre-treatment patterns indicating a recovery from changes caused by antimicrobial administration, but differences were still evident, especially regarding community membership. CONCLUSIONS: The use of systemic antimicrobials leads to changes in the intestinal microbiota, with different and specific responses to different antimicrobials. All antimicrobials tested here had some impact on the microbiota, but TMS significantly reduced bacterial species richness and diversity and had the greatest apparent impact on population structure, specifically targeting members of the Verrucomicrobia phylum.

A review of cutaneous anthrax and its outcome.

Anthrax is still an endemic disease in some countries in the world and has become a re-emerging disease in western countries with recent intentional outbreak. The aim of this study was to review our clinical experience with cutaneous anthrax cases. From the patient's files, transmission of the diseases, clinical findings and severity of infection, treatment and outcome of patients were recorded. Twenty-two cases were diagnosed as cutaneous anthrax in the last 7 years. Of these cases, 10 cases were severe form of cutaneous anthrax, 10 cases were mild form and 2 cases were toxemic shock due to cutaneous anthrax. The incubation period was between 1 and 17 days. The main clinical characteristics of the cases with severe cutaneous anthrax were fever, hemorrhagic bullous lesions surrounded by an extensive erythema and edema, and leukocytosis. Two cases with toxemic shock had low systolic blood pressure, apathy and toxemic appearance, leukocytosis, hypoalbuminemia & hyponatremia. Penicillin G was given in 15 cases, amoxicillin in 4 and other antibiotics in 3 cases for 3-10 days. Skin lesion left deep tissue scar in 4 cases and were grafted. Physicians working in endemic areas and also in western countries should be aware of all clinical forms of anthrax.

Effects of dry cow treatment of beef cows on pathogenic organisms, milk somatic cell counts, and calf growth during the subsequent lactation.

Spring calving Angus and Angus x Hereford multiparous cows were utilized to determine the effects of intramammary treatment with penicillin G procaine (200,000 IU) and novobiocin (400 mg) at the time of weaning on udder health and calf growth after the subsequent calving. Cows were stratified by age and breed and assigned randomly to receive intramammary treatment (n = 99) at weaning or as untreated controls (n = 97). Quarter milk samples were collected at weaning and at 8 to 14 d after calving. Milk samples were analyzed for somatic cell counts (SCC) and mastitis-causing bacteria. Dry cow treatment decreased (P = 0.005) the number of cows infected after calving. Treatment decreased (P = 0.04) the number of cows that developed new infections and reduced (P = 0.03) the number of quarters with mastitis-causing bacteria after calving that were infected at weaning. Somatic cell counts after calving were greatest (P = 0.008) for cows infected with Staphylococcus aureus. Treatment did not alter (P = 0.19) SCC of quarters after calving that were infected with S. aureus at weaning but reduced (P = 0.002) SCC after calving of quarters that were infected with coagulase-negative staphylococci at weaning. Body weight of calves during early lactation was increased (P = 0.006) if cows with intramammary infection were treated at weaning. Treatment of noninfected cows at weaning increased (P = 0.008) adjusted 205-d weaning weights of calves after the subsequent lactation when compared with untreated noninfected cows. We conclude that treatment of beef cows at weaning with intramammary antibiotics decreased intramammary infections after calving, improved udder health during the subsequent lactation, and increased BW gain of the calves.

Meta-analysis of pharmacokinetic data of veterinary drugs using the Food Animal Residue Avoidance Databank: oxytetracycline and procaine penicillin G.

Investigators frequently face the quandary of how to interpret the often times disparate pharmacokinetic parameter values reported in the literature. Combining of data from multiple studies (meta-analysis) is a useful tool in pharmacokinetics. Few studies have explored the use of meta-analysis for veterinary species. Even fewer studies have explored the potential strengths and weaknesses of the various methods of performing a meta-analysis. Therefore, in this study we performed a meta-analysis for oxytetracycline (OTC) and procaine penicillin G (PPG) given intramuscularly to cattle. The analysis included 28 individual data sets from 18 published papers for PPG (288 data points), and 41 individual data sets from 25 published papers for OTC (489 data points). Three methods were used to calculate the parameters. The first was a simple statistical analysis of the parameter values reported in each paper. The second method was a standard Two-Stage Method (TSM) using the mean concentration vs. time data extracted from each paper. The third method was the use of nonlinear mixed effect modeling (NMEM) of the concentration vs. time data reported in the various papers, treating the mean data as if each set came from an individual animal. The results of this evaluation indicate that all three methods generate comparable mean parameter estimates for OTC and PPG. The only significant difference noted was for OTC absorption half-lives taken from the published literature, a difference attributable to the use of an alternative method of parameter calculation. The NMEM procedure offers the possibility of including covariates such as dose, age, and weight. In this study the covariates did not influence the derived parameters. A combination approach to meta-analysis of published mean data is recommended, where the TSM is the first step, followed by the NMEM approach.

[Comparison of checkerboard and time-kill methods for the analysis of two antibiotics combined]. / Porównanie metod szachownicy i "time-kill" stosowanych do badania zestawienia dwóch antybiotyków.

Activity interaction analysis of two antibiotics by two methods: checkerboard and "time-kill" was compared during this study. Combinations of procaine penicillin, polymyxin B and bacitracin with neomycin and procaine penicillin with dihydrostreptomycin were examined. Checkerboard method is the most widely used technique for antimicrobials interactions analyses. The "time-kill" method, performed by the broth macrodilution technique, provides a dynamic picture of antimicrobial action and interaction over time (based on serial colony counts). Differences of "time-kill" method and the checkerboard technique, allow single visual examination (after 16 to 24 hours of incubation). Additive and inhibition effects were observed in combinations of neomycin with beta-lactam antibiotic (procaine penicillin) and peptide antibiotics (bacitracin and polymyxin B) on clinical strain S. Enteritidis IL 35 "Time-kill" method also confirmed observations mentioned above. In combinations of procaine penicillin with dihydrostreptomycin on strains E. coli IL 531 and E. coli IL 256 synergy effects on checkerboard technique were noticed. Such observation was not confirmed by the "time-kill" method. The methodologies and definitions of synergism are variable and not standardized. This situation should be improved, because comparison of the results obtained by different methods becomes a very difficult task.

Efficacy of intramammary treatment with procaine penicillin G vs. procaine penicillin G plus neomycin in bovine clinical mastitis caused by penicillin-susceptible, gram-positive bacteria--a double blind field study.

The efficacy of intramammary treatments containing procaine penicillin G alone (treatment A) or a combination of procaine penicillin G and neomycin (treatment B) was compared in treating clinical bovine mastitis caused by gram-positive bacteria susceptible in vitro to penicillin G. Both treatments were supplemented with a single intramuscular injection of procaine penicillin G on the first day of treatment. The study was carried out using a double blind design on commercial dairy farms in Southern Finland. A total of 56 quarters were treated with treatment A and 61 with treatment B. The cure rates for both treatments were equal, which suggests that the use of the penicillin G-aminoglycoside combination does not increase the efficacy of the treatment over that achieved by using penicillin G alone in bovine clinical mastitis caused by penicillin-susceptible, gram-positive bacteria.

Penicillin resistance in Streptococcus pneumoniae in Isparta.

OBJECTIVE: The first case reports of infection with penicillin-resistant pneumococci were made in Australia in 1967 and South Africa in 1977. Since this time the increasing emergence of penicillin- resistant strains of Streptococcus pneumoniae have been a serious therapeutic problem. Therefore, the aim of the present study was to determine the penicillin resistance of S. pneumoniae strains isolated in the laboratory. The effect of procaine penicillin treatment against these strains was also investigated. METHODS: Sensitivity testing was done by disc diffusion method using oxacillin discs. Minimal inhibitory concentration (MIC) values were determined in tests with penicillin by the use of E-test (AB Biodisc, Solna, Sweden). Patients were treated with 2 x 800,000 U of i.m. procaine penicillin every 12 h for 10 days. RESULTS: Thirty-seven strains of S. pneumoniae were isolated from the sputa of adult patients who had pneumonia. Moderately resistant (0.12-1.00 microg/mL) and penicillin-sensitive (< or = 0.06 microg/mL) strains were identified in nine (24.3%) and 28 (75.7%) isolates, respectively. There were no high-level penicillin-resistant strains in the study. There was no therapeutic failure. CONCLUSION: These results suggest that procaine penicillin may still be useful in the empirical therapy of pneumococcal pneumonia.

Effect of penicillin or penicillin and dexamethasone in cattle with infectious bovine keratoconjunctivitis.

To evaluate the efficacy of penicillin or penicillin and dexamethasone for treatment of infectious bovine keratoconjunctivitis, 6- to 8-month-old beef heifers with clinical signs of infectious bovine keratoconjunctivitis were randomly assigned to 1 of 3 treatment groups: penicillin only, penicillin and dexamethasone, or control. Cattle assigned to the penicillin group (n = 18) were treated with 3 daily subconjunctival injections of procaine penicillin G. Cattle assigned to the penicillin/dexamethasone group (n = 13) were treated with 3 daily subconjunctival injections of procaine penicillin G and dexamethasone sodium phosphate. Control cattle (n = 14) were not treated. Healing times and frequency of recurrence for corneal ulcers; severity, diameter, and surface area measurements of corneal ulcers; and clinical scores did not differ among the 3 groups. Frequency of Moraxella bovis isolation from specimens of ocular secretions from ulcerated and non-ulcerated eyes was similar in all groups. Minimum inhibitory concentration of penicillin G for 95 of the 102 tested M bovis isolates was 0.3 U/ml, and for 7 others was 0.03 U/ml. When first and last specimens from 42 of 45 calves with isolation of M bovis on serial microbial cultures were compared, the susceptibility of each last isolate was similar to that of the corresponding first isolate.

[Procaine kindling in acute non-allergic reaction to procaine penicillin G]. / Kindling prokainowy w ostrej niealergicznej reakcji na penicyline prokainowa.

On the basis of the analysis of acute nonallergic reaction to a course of procaine penicillin G, the authors have stated that symptoms of this reaction result from the irritation of temporal limbic structures. The authors think that it is connected with procaine kindling mechanism, the procaine component of the drug.

Bovine platelets retain functional activity in the presence of penicillin G.

It has been reported that antibiotics of the penicillin family impair the functional response of human, canine and lapine platelets to a broad range of agonists. In contrast, we have shown that the bovine platelet retained full functional responses to stimulation by adenosine diphosphate (ADP) or platelet activating factor (PAF) following administration of penicillin G to clinically normal cattle at 20,000 IU/kg for three days. The aggregation response to collagen was transiently reduced to approximately 50% of pretreatment values, but only while the drug was detectable in the circulation. When penicillin was added to platelet rich plasma suspensions, ADP-induced aggregation was similar to that of the control untreated platelets, while the PAF-induced aggregation response was reduced by not more than 25%. Only collagen-induced aggregation exhibited a modest dose-dependent inhibitory response in the presence of penicillin. It is postulated that the relative insensitivity of the bovine platelet to penicillin may be related to differences in postreceptor biochemical events compared to the human platelet.

Urogenital infection due to meningococcus in men and women.

The authors report six cases of acute urethritis and three cases of acute cervicitis caused in all instances by Neisseria meningitidis group B. The patients, five heterosexual men, one homosexual man, and three female prostitutes were seen at a venereal clinic in Mexico City. All of them were initially diagnosed as having gonorrhea. Treatment with procaine-penicillin G cured all cases, both clinically and bacteriologically. These experiences reinforce the need to distinguish N. meningitidis from N. gonorrhoeae in the setting of sexually transmitted diseases.

[The ultrastructural organization of Brucella L forms and revertant cultures]. / Ul'trastrukturnaia organizatsiia L-form brutsell i kul'tur-revertantov.

The submicroscopic organization of Brucella cells in the process of L-transformation and reversion has been studied. As revealed in this study, at its initial stages L-transformation is accompanied by the loss of cell-wall peptidoglycan and by considerable polymorphism of Brucella cells. Further stages are characterized by the presence of a great number of closed annular membrane structures both in the cytoplasm and outside the cells. At late stages of L-transformation the destruction of the cytoplasm and the cells has been found to occur. In revertant cultures the restoration of the cell wall has been noted.

Comparative study of cefuroxime axetil and procaine penicillin in the treatment of uncomplicated gonorrhoea.

A total of 311 patients presenting with uncomplicated gonorrhoea were entered into a comparative randomized open-label study and given single-dose treatment with either oral cefuroxime axetil (CAE) or intramuscular procaine penicillin (PP). Neisseria gonorrhoeae was eliminated from 129 (98%) of 131 evaluable patients treated with CAE and 127 (98%) of 129 evaluable patients treated with PP. None of the 4 treatment failures (3 male and 1 female) were caused by beta-lactamase-producing isolates. Both treatments were well tolerated with minor adverse events reported in 3 (2%) of CAE treated patients. We conclude that CAE is an effective, well tolerated treatment for uncomplicated gonorrhoea which has the convenience and acceptability of single-dose oral therapy.

Effects of bovine mammary secretion during the early nonlactating period and antibiotics on polymorphonuclear neutrophil function and morphology.

The effect of bovine mammary secretion during the early nonlactating period and of antibiotic preparations on bovine polymorphonuclear neutrophil (PMN) phagocytic function and morphology were evaluated in a series of in vitro multifactorial experiments. Benzathine cloxacillin (CL), benzathine cephapirin (CE), sodium novobiocin (NO), and a combination of dihydrostreptomycin with procaine penicillin G (DP) were prepared in the presence and absence of a peanut oil aluminum monostearate vehicle. The PMN were isolated from bovine blood, and the effect of each antibiotic preparation on PMN function and morphology was evaluated in a buffer, fat, skin, and a combination of fat with skim from bovine mammary secretion during the nonlactating period. The fat and skim were diluted with buffer to approximate their concentration in mammary secretion. Phagocytic functions of PMN were monitored by fluorescent microscopy, which made it possible to estimate both ingestion and intracellular killing of bacteria by PMN. Changes in PMN morphology were monitored by transmission electron microscopy. The ability of PMN to ingest and kill Staphylococcus aureus ATCC 25923 was significantly decreased by fat, skim, CL, CE, NO, and DP. Effects of some antibiotics on ingestion and killing of bacteria by PMN were influenced by the addition of vehicle and by interactions with mammary secretion. Neutrophil morphology was altered by fat, skim, CL, CE, NO, and DP. The detrimental effects of CL, CE, NO, and DP on PMN morphology were influenced (some significantly) by the presence of vehicle and interactions with mammary secretion. There were significant correlations among secretion- and antibiotic-induced changes in PMN ingestion of bacteria, PMN killing of bacteria, and PMN morphology.