Evaluation of plasma concentration after intravenous and intramuscular penicillin administration over 24 hr in healthy adult horses.

Penicillin is administered intravenously (IV) or intramuscularly (IM) to horses for the prevention and treatment of infections, and both routes have disadvantages. To minimize these shortcomings, a 24-hr hybrid administration protocol (HPP) was developed. Our objective was to determine penicillin plasma concentrations in horses administered via HPP. Venous blood was collected from seven healthy horses administered IV potassium penicillin G at 0 and 6 hr and IM procaine penicillin G at 12 hr. Blood was collected at 2-hr intervals from 0 to 20 hr and at 24 hr. Plasma penicillin concentrations were measured using liquid chromatography and mass spectrometry. Penicillin susceptibility from equine isolates was examined to determine pharmacodynamic targets. The MIC90 of penicillin for 264 isolates of Streptococcus sp. was ≤0.06 µg/ml. For the 24-hr dosing interval, the mean plasma penicillin concentration was >0.07 µg/ml. Five horses (72%) exceeded 0.06 µg/ml for 98% of the dosing interval, and two horses exceeded this value for 52%-65% of the dosing interval. The HPP achieved mean plasma penicillin concentrations in healthy adult horses above 0.07 µg/ml for a 24-hr dosing interval. However, individual variations in plasma concentrations were apparent and deserve future clinical study.

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.

Oral amoxicillin compared with injectable procaine benzylpenicillin plus gentamicin for treatment of neonates and young infants with fast breathing when referral is not possible: a randomised, open-label, equivalence trial.

BACKGROUND: WHO recommends referral to hospital for possible serious bacterial infection in young infants aged 0-59 days. We aimed to assess whether oral amoxicillin treatment for fast breathing, in the absence of other signs, is as efficacious as the combination of injectable procaine benzylpenicillin-gentamicin. METHODS: In a randomised, open-label, equivalence trial at five sites in DR Congo, Kenya, and Nigeria, community health workers followed up all births in the community, identified unwell young infants, and referred them to study nurses. We randomly assigned infants with fast breathing as a single sign of illness or possible serious bacterial infection, whose parents did not accept referral to hospital, to receive either injectable procaine benzylpenicillin-gentamicin once per day or oral amoxicillin treatment twice per day for 7 days. A person who was off-site generated randomisation lists using computer software. Trained health professionals gave injections, but outcome assessors were masked to group allocations. The primary outcome was treatment failure by day 8 after enrolment, defined as clinical deterioration, development of a serious adverse event including death, persistence of fast breathing on day 4, or recurrence up to day 8. The primary analysis was per protocol and we used a prespecified similarity margin of 5% to assess equivalence between regimens. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000286044. FINDINGS: From April 4, 2011, to March 29, 2013, we enrolled 2333 infants aged 0-59 days with fast breathing as the only sign of possible serious bacterial infection at the five study sites. We assigned 1170 infants to receive injectable procaine benzylpenicillin-gentamicin and 1163 infants to receive oral amoxicillin. In the per-protocol analysis, from which 137 infants were excluded, we included 1061 (91%) infants who fulfilled predefined criteria of adherence to treatment and adequate follow-up in the injectable procaine benzylpenicillin-gentamicin group and 1145 (98%) infants in the oral amoxicillin group. In the procaine benzylpenicillin-gentamicin group, 234 infants (22%) failed treatment, compared with 221 (19%) infants in the oral amoxicillin group (risk difference -2·6%, 95% CI -6·0 to 0·8). Four infants died within 15 days of follow-up in each group. We detected no drug-related serious adverse events. INTERPRETATION: Young infants with fast breathing alone can be effectively treated with oral amoxicillin on an outpatient basis when referral to a hospital is not possible. FUNDING: Bill & Melinda Gates Foundation grant to WHO.

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.

Comminuted fracture of the accessory carpal bone removed via an arthroscopic-assisted arthrotomy.

A 16-year-old American paint horse gelding was presented for evaluation of a left forelimb lameness grade III/V. Radiographs and computed tomography revealed a comminuted fracture of the accessory carpal bone involving the entire articulation with the distal radius and the proximal aspect of the articulation with the ulnar carpal bone. Multiple fragments were present in the palmar pouch of the antebrachiocarpal joint. An arthroscopic-assisted open approach was necessary to remove all fractured fragments. Subsequently the horse was re-admitted for lameness and was treated successfully with antibiotics and long-term supportive bandaging.

Fracture comminutive de l'os du carpe accessoire enlevé à l'aide d'une arthrotomie assistée par arthroscopie. Un cheval American Paint Horse âgé de 16 ans a été présenté pour l'évaluation d'une boiterie de la jambe avant gauche de grade III/V. Les radiographies et la tomodensitométrie ont révélé une fracture comminutive de l'os du carpe accessoire touchant toute l'articulation avec le radius distal et l'aspect proximal de l'articulation avec l'os du carpe cubital. Des fragments multiples étaient présents dans la poche palmaire de l'articulation antébrachio-carpienne. Une approche ouverte assistée par arthroscopie a été nécessaire pour retirer tous les fragments fracturés. Le cheval a ensuite été réadmis pour boiterie et a été traité avec succès à l'aide d'antibiotiques et de pansements de soutien à long terme.(Traduit par Isabelle Vallières).

Successful medical management of intra-abdominal abscesses in 4 adult horses.

Four adult horses with large intra-abdominal abscesses, suspected to be complications of strangles, were treated with systemic antibiotics alone and made a full recovery. The 100% survival rate is significantly better than other reported survival rates. The median duration of treatment (35 days) was shorter than in most previous reports. This study suggests that penicillin G can be used for successful treatment of strangles associated intra-abdominal abscesses in horses.

Gestion médicale réussie d'abcès intra-abdominaux chez 4 chevaux adultes. Quatre chevaux adultes avec des abcès intra-abdominaux de grande taille, suspectés d'être des complications de la gourme, ont été traités seulement à l'aide d'antibiotiques systémiques et se sont rétablis complètement. Le taux de survie de 100 % est significativement meilleur que les autres taux de survie signalés. La durée médiane du traitement (35 jours) a été plus courte que celle indiquée dans la plupart des rapports antérieurs. Cette étude suggère que la pénicilline G peut être utilisée avec succès pour le traitement des abcès intra-abdominaux associés à la gourme chez les chevaux.(Traduit par Isabelle Vallières).

Antimicrobial susceptibility of fecal Escherichia coli isolates in dairy cows following systemic treatment with ceftiofur or penicillin.

The objective of this longitudinal controlled trial was to determine the effect of systemic treatment with ceftiofur on antimicrobial susceptibility of fecal Escherichia coli isolates in dairy cows. Cows with metritis or interdigital necrobacillosis requiring systemic antimicrobial treatment were sequentially assigned to two treatment groups. The first group was treated with ceftiofur hydrochloride and the second with penicillin G procaine. Untreated healthy control cows were selected for sampling on the same schedule as treated cows. Fecal samples were collected on days 0, 2, 7, 14, 21, and 28. In total, 21983 E. coli isolates from 42 cows were analyzed for susceptibility to ampicillin, tetracycline, and ceftiofur using a hydrophobic grid membrane filter system to assess growth on agar containing selected antimicrobial drugs. Temporal changes in both the concentration of E. coli in feces and the susceptibility of E. coli to each drug were analyzed. A significant decrease in the concentration of fecal E. coli on days 2 and 7 post-treatment (but not thereafter) was detected in animals treated with ceftiofur. The proportion of all isolates (95% confidence interval in parentheses) showing reduced susceptibility at day 0 was 3.0% (2.5, 3.6) for ampicillin, 10.6% (9.7, 11.6) for tetracycline, and 4.8% (4.2, 5.6) for ceftiofur; 1.7% (1.3, 2.1) of isolates were resistant to ceftiofur based on growth at 8 µg/mL. Treatment did not have any significant effect on the proportion of isolates expressing reduced susceptibility to antibiotics with the exception of decreased tetracycline susceptibility in the ceftiofur-treated group on day 2. Although we found the potential for selection pressure by documenting the change in E. coli concentration after ceftiofur treatment, an increase in ceftiofur resistance was not found.

Adverse effects associated with inadvertent intravenous penicillin G procaine-penicillin G benzathine administration in two dogs and a cat.

CASE DESCRIPTION: 2 dogs and a cat were inadvertently given penicillin G procaine-penicillin G benzathine IV instead of propofol during induction of anesthesia for routine dental prophylaxis. One dog and the cat required hospitalization because of severe neurologic impairment and cardiopulmonary arrest (cat); the remaining dog did not develop any clinical signs. CLINICAL FINDINGS: In the 2 animals that developed signs consistent with an immediate adverse reaction, clinical signs included muscle tremors, seizures, blindness, vocalization, agitation, and transient loss of vision. Hypothermia, pruritus, hypotension, and cardiac arrest were also documented. TREATMENT AND OUTCOME: The 2 affected patients responded to treatment with anticonvulsant medications, centrally acting muscle relaxants, sedation, and intensive supportive care including IV fluid administration and oxygen supplementation as needed. Cardiopulmonary cerebral resuscitation was performed successfully in the cat. The dog that did not develop any clinical signs was not treated. The 2 affected patients recovered fully and were discharged from the hospital after 3 to 4 days with no apparent sequelae. CLINICAL RELEVANCE: Penicillin G procaine-penicillin G benzathine and propofol are common drugs in veterinary practice and may both be administered to patients undergoing elective procedures. Because of their similar milky white appearance, veterinarians should label syringes and take care to avoid this medication error. There is no specific antidote for penicillin orprocaine toxicosis. Aggressive and immediate treatment is required in patients that develop an adverse reaction to ensure a successful outcome.

Periparturient use of parenteral micronised procaine penicillin to reduce the risk of clinical mastitis in heifers after calving.

Mastitis in primiparous heifers immediately postpartum can be both a significant welfare concern and a heavy economic loss. Interventions successfully researched include intramammary therapies. This study considered the clinical and practical effects of a parenteral approach to controlling clinical mastitis in heifers immediately postpartum. The objective of this field trial was to determine whether preventative treatment of heifers with a single parenteral treatment of 15 million iu micronised procaine penicillin within 12h after calving would reduce the incidence of clinical mastitis in early lactation as detected by farmers. All heifers (n=609) calving on three commercial dairy farms in New Zealand during the spring of 2006 were randomly allocated to either treatment or no treatment. Treatment (15 million iu micronised procaine penicillin) was given at the first milking following calving. All clinical mastitis was recorded. Treatment reduced the odds of having clinical mastitis within the first 7 days in milk by over half (Mantel-Haenszel adjusted OR=0.456; p=0.044); and reduced the odds of having mastitis within the first 100 days in milk by just under half (Mantel-Haenszel adjusted OR=0.518; p=0.027). Treatment had a significant effect on increasing the median days to clinical mastitis (p=0.019; beta=1.961, LCI 1.117, UCI 3.445). Preventative treatment of heifers immediately following calving with 15 million iu micronised procaine penicillin parenterally could be of benefit as part of a control programme aimed at reducing the incidence of clinical mastitis in heifers in their first lactation.

Comparison of three treatment regimens for sheep and goats with caseous lymphadenitis.

OBJECTIVE: To compare the effectiveness of 3 treatment regimens for small ruminants with caseous lymphadenitis. DESIGN: Randomized clinical trial. ANIMALS: 44 client-owned sheep and goats. PROCEDURES: Aspirates were obtained from 48 lesions of 44 enrolled animals and submitted for bacterial culture. Animals were randomly assigned to 1 of 3 treatment groups. Treatment for group A (n = 15 lesions) consisted of opening, draining, and flushing the lesions and SC administration of procaine penicillin G. Treatment for group B (n = 15 lesions) consisted of closed-system lavage and intralesional administration of tulathromycin. Treatment for group C (n = 18 lesions) consisted of closed-system lavage and SC administration of tulathromycin. All animals were reexamined approximately 1 month after treatment, unless treatment failure was detected prior to that time. RESULTS: 43 animals with lesions had positive results (Corynebacterium pseudotuberculosis) for bacterial culture. Proportions of lesions that had resolution of infection by 1 month after treatment did not differ significantly among the treatment groups (group A, 13/14 [92.9%]; 95% confidence interval [CI], 69.5% to 99.6%; group B, 10/12 [83.3%]; 95% CI, 54.9% to 97.1%; and group C, 14/17 [82.4%]; 95% CI, 59.1% to 95.3%). CONCLUSIONS AND CLINICAL RELEVANCE: Acceptable alternatives to opening, draining, and flushing of lesions may exist for treatment of sheep and goats with caseous lymphadenitis. Use of tulathromycin and penicillin in this study constituted extralabel drug use, which would require extended withholding times before milk or meat of treated sheep and goats can be sold for human consumption.

[New drugs for small animals in 2018]. / Neue Arzneimittel für Kleintiere 2018.

In 2018, two active pharmaceutical ingredients were released on the German market for small animals: the ectoparasiticide of the isoxazoline group Lotilaner (Credelio®) and the opioid analgesic Tramadol (Tralieve®). Two established veterinary active pharmaceutical ingredients became available for additional species: the nonsteroidal anti-inflammatory drug Meloxicam (Metacam®) from the oxicam group for guinea pigs and the inhalant anesthetic Sevoflurane (Sevoflo®) from the group of halogenated hydrocarbon compounds, which has additionally been authorized for cats. With the combination of Benzylpenicillin-Benzathine and Benzylpenicillin-Procaine, one temporarily non-available combination of active ingredients was reapproved in new drugs. Additionally, one drug with a new pharmaceutical form and one drug with a higher content of the active ingredient have been launched on the market for small animals.

Cutaneous anthrax in Eastern Turkey: a review of 85 cases.

BACKGROUND: Anthrax is a zoonotic disease diminishing worldwide. Although a very rare disease in developed countries, anthrax is still endemic in developing countries. AIM: To evaluate the clinical history and features, treatment and outcome of our patients with anthrax and emphasize the importance of the disease in our region. METHOD: In this study, the records of all patients diagnosed with cutaneous anthrax admitted to Yüzüncü Yil University Medical Faculty between March 2002 and March 2007, were reviewed, and data on age, gender, occupation, clinical symptoms and findings, location and type of lesions, clinical history, laboratory findings, treatment and outcome were recorded. RESULTS: There were 85 patients [46 (54.1%) male, 39 (45.9%) female; mean age 30.6 years, range 6-72]. All the patients had a history of contact with infected animals or animal products. The infectious agent was found using direct examination of Gram-stained smears from 17 patients (20%), and Bacillus anthracis was isolated from vesicle fluid cultures from 11 patients (12.9%). Diagnosis was based on clinical findings in the remaining 57 patients (67.1%). All patients, except for two with respiratory tract obstruction, made a full recovery. CONCLUSION: Anthrax continues to be an endemic disease in Turkey, and should be considered in patients with a relevant contact history having a painless ulcer and vesicular skin lesions surrounded by a zone of oedema. Gram staining and simple culture methods are useful aids to diagnosis, but diagnosis may have to be based on clinical grounds in the majority of patients.

[Study on interventional methods and the pattern of maternal-fetal transmission of syphilis during pregnancy].

OBJECTIVE: To explore the maternal-fetal transmission patterns and interventional methods of syphilis during pregnancy. METHODS: A total of 847 cases of syphilis in pregnancy confirmed by rapid plasma reagin test (RPR) and treponema pallidum hemoagglutination test (TPHA) were treated with procaine benzylpenicillin intramuscular injection, and with erythrocin oral medication if hypersensitive to benzylpenicillin. Eight hundred forty seven cases of syphilis during pregnancy were followed up for pregnancy outcomes. And their newborn babies were tested using the RPR. The newborns with positive results were given intervention and followed up until 24 months after birth. RESULTS: (1) A total of 733 cases among the total 847 have given birth to living-babies, in which 626 cases were tested using RPR, and the positive rate was 55.1% (345/626). (2) The RPR positive rate, neonatal mortality, preterm birth rate and low birth rate in the newborn of mothers with an RPR titer higher than or at 1:8 were higher than those of mothers with an RPR titer lower than 1:8 (P < 0.01). (3) The neonatal RPR positive rate was related to the timing of the treatment of the women. (1) The neonatal RPR positive rate was 22.4% (15/67) for treatment compared with 49.6% (330/666) for non-treatment before pregnancy (P < 0.01). (2) The positive RPR rate of neonates between treatment before pregnancy and treatment during pregnancy was different, being 22.4% (15/67) and 40.3% (240/595) respectively (P < 0.05) (3) In comparison between treatment both in the early pregnancy and in late pregnancy with only treatment in the late pregnancy, the positive RPR rate of neonates was 28.5% (45/158) and 56.9% (95/167) respectively (P < 0.01). In comparison between treatment both in the mid-term pregnancy and in late pregnancy and treatment in only one period in the terminal, the positive RPR rate of neonates was 37.0% (100/270) and 56.9% (95/167) respectively (P < 0.01). CONCLUSIONS: The maternal-fetal transmission rate and perinatal prognosis are related to maternal RPR titer and the timing of maternal treatment. Inborn syphilis can be prevented and cured in fetal time. For neonates with anti-syphilis treatment in protestation, RPR positive rate is significantly lower than that without treatment in protestation. Treatment prior to pregnancy is a powerful measure to prevent the maternal-fetal transmission of syphilis.

Acute myocardial infarction in a patient suffering from penicillin-induced laryngeal edema : Kounis syndrome aggravated by adrenaline.

Kounis syndrome or allergic angina is defined as the coincidental occurrence of chest pain and allergic reactions accompanied by clinical and laboratory findings of classical angina pectoris. It is triggered by the action of potent vasoactive and inflammatory mediators, which are released from the mast cells during the allergic reaction. Epinephrine is a life-saving medication in anaphylaxis; however, it can aggravate ischemia and induce coronary vasospasm and arrhythmias. Here, we present a patient with Kounis syndrome that was caused by intramuscular injection of procaine penicillin G, and in whom epinephrine administration for treatment of laryngeal edema had provoked severe myocardial ischemia.