Potentiation of antibiotic activity by EDTA-tromethamine against three clinically isolated Gram-positive resistant bacteria. Anin vitro investigation

Thein vitro synergistic effects of combinations of EDTA-tromethamine and five antimicrobial agents (ampicillin, cephalexin, oxytetracycline, streptomycin and sulphadimethoxine) on three clinically isolated Gram-positive bacteria (Staphylococcus aureus, Staphylococcus hominis andStreptococcus faecium) were investigated. The bacteria had been isolated from three cases of canine otitis resistant to -lactam antibiotic therapy. The antimicrobial activity was evaluated by measuring the minimal inhibitory concentration for the antibiotics alone or in combination with EDTA-tromethamine. EDTA-tromethamine potentiated the activity of cefalexin againstS. aureus andS. hominis, of oxytetracycline againstS. aureus andS. faecium and of streptomycin againstS. faecium. No significant effects were noted on the activity of oxytetracycline againstS. hominis. The remaining combinations gave a slight synergistic effect. As previously shown for Gram-negative resistant bacteria, these data suggest that the association of EDTA-tromethamine and appropriate antibiotic therapy may be useful to overcome persistent infections of soft tissues in domestic animals.Abbreviations cfu colony forming units - EDTA ethylenediaminetetraacetic acid - MIC minimal inhibitory concentration - tromethamine tris(hydroxymethyl)- aminomethane Part of this paper was communicated at the XLVI Congress of the Italian Society of Veterinary Sciences, Venice, 30 September – 3 October 1992     

Inhibitory effects of combinations of oxytetracycline, dimethyl sulfoxide, and EDTA-tromethamine on Escherichia coli

Antibacterial activity against Escherichia coli was obtained with subminimal inhibitory concentrations of oxytetracycline (OTC) and EDTA-tromethamine. Inhibitory effects were not observed using combinations of dimethyl sulfoxide and OTC or dimethyl sulfoxide and EDTA-tromethamine. Neither EDTA-tromethamine nor OTC used alone was capable of the same degree of inhibition. Using a 2-dimensional Microtiter checkerboard technique, the inhibitory activity of these combinations was studied and isobolograms were plotted. A synergistic effect was seen with combinations of OTC and EDTA-tromethamine. Kinetic studies of microbial death, using subminimal inhibitory concentrations of these agents, confirmed these findings.     

Potentiation of thein vitro activity of some antimicrobial agents against selected Gram-negative bacteria by EDTA-tromethamine

Thein vitro synergistic effects of combinations of EDTA-tromethamine and six antimicrobial agents (ampicillin, chloramphenicol, oxytetracycline, streptomycin, nalidixic acid and sulphadimethoxine) on clinically isolated strains ofPseudomonas aeruginosa, Proteus mirabilis andEscherichia coli were investigated. The antibacterial activity was assessed from the minimal inhibitory concentration for the antibiotics alone or in combination with EDTA-tromethamine. EDTA-tromethamine potentiated the antibacterial activity of ampicillin, chloramphenicol, oxytetracycline and streptomycin up to four-fold. There were no significant or consistent synergistic effects with nalidixic acid or sulphadimethoxine.Abbreviations cfu colony-forming units - EDTA ethylenediaminetetraacetic acid - MIC minimal inhibitory concentration - tromethamine tris(hydroxymethyl)aminomethane Part of this paper was communicated at the XLV Congress of the Italian Society of Veterinary Sciences, Palermo, 25–28 September 1991     

Antibacterial action of combinations of oxytetracycline, dimethyl sulfoxide, and EDTA-tromethamine on Proteus, Salmonella, and Aeromonas

Antibacterial effects against Proteus mirabilis, Salmonella typhimurium, and Aeromonas hydrophila were obtained with subminimal inhibitory concentrations of oxytetracycline and EDTA-tromethamine. Antibacterial effects were not observed with subminimal inhibitory concentrations of dimethyl sulfoxide plus oxytetracycline or with dimethyl sulfoxide plus EDTA-tromethamine. Using a 2-dimensional Microtiter checkerboard technique, inhibitory activities of the various combinations of solutions were studied, and isobolograms were plotted. A synergistic effect was seen with combinations of oxytetracycline and EDTA-tromethamine. The greatest synergistic effect was observed when the mixture was caused to react with P mirabilis. These findings were confirmed by kinetic studies of microbial death, using one-fourth minimal inhibitory concentrations of these preparations.     

In vitro action of combinations of antimicrobial agents and EDTA-tromethamine on Pseudomonas aeruginosa

Combinations of EDTA-tromethamine and 7 antimicrobial agents (chloramphenicol, nalidixic acid, oxytetracycline, penicillin, polymyxin-B, streptomycin, and triple sulfa) were tested for synergistic activities against Pseudomonas aeruginosa. Three in vitro tests were used, including minimal inhibitory concentrations of the drugs, a 2-dimensional Microtiter checkerboard technique, and bacterial inhibition studies. A synergistic inhibitory action was observed with combinations of EDTA-tromethamine plus penicillin and EDTA-tromethamine plus oxytetracycline. When chloramphenicol, streptomycin, nalidixic acid, polymyxin-B, or triple sulfa was mixed with EDTA-tromethamine, synergistic action did not occur.     

Treatment of 10 dogs with discospondylitis by fluoroscopy-guided percutaneous discectomy

Ten dogs suffering from discospondylitis were treated by percutaneous discectomy and local and systemic antibiotic therapy. With fluoroscopic guidance, a cylinder 5 mm in diameter was removed from the centre of the intervertebral space, yielding a fenestration and decompressing the disc without producing any spinal instability. The causative bacteria were identified in nine of the 10 biopsy specimens, but in only three urine cultures and four blood cultures. In two cases, the antibiotics used initially had to be changed owing to the organisms' antibiotic resistance. The clinical signs of the dogs improved markedly after two to nine days (mean 4.2 days) and had resolved completely after five to 14 days (mean 9.1 days). In all the cases the disease could be classified histologically as either acute or chronic, and the disease was classified as chronic in one dog. No side effects were observed.     

In vitro effect of combinations of antimicrobial agents and EDTA-tromethamine on certain gram-positive bacteria

Combinations of EDTA-tromethamine and 7 antimicrobial agents (chloramphenicol, nalidixic acid, oxytetracycline, penicillin, polymyxin-B, streptomycin, and a triple sulfonamide preparation) were tested for synergistic activities against Staphylococcus aureus, Corynebacterium renal, Listeria monocytogenes, Erysipelothrix rhusiopathiae, and a beta-hemolytic streptococci. Two in vitro tests were used--minimal inhibitory concentrations of the drugs and a 2-dimensional Microtiter checkerboard technique. A slight synergistic action was seen when L monocytogenes was exposed to combinations of penicillin-EDTA or streptomycin-EDTA.     

Comparison of vedaprofen and meloxicam in dogs with musculoskeletal pain and inflammation

In this randomised, multicentre clinical study, dogs with musculoskeletal pain and inflammation were treated with either vedaprofen or meloxicam administered orally at the recommended dose rates. Clinical examinations were carried out regularly and clinical severity scores assigned. In total, 214 cases (73 acute, 141 chronic) were evaluated. Treatment with vedaprofen and meloxicam was continued for 14 and 17 days, respectively, in the acute cases, and 38 and 39 days in the chronic cases. NSAID treatment resulted in a significant improvement in clinical scores. The overall response to treatment ('responders') at the final clinical examination was 89 per cent and 87 per cent in the acute cases and 72 per cent and 65 per cent in the chronic cases in the vedaprofen and meloxicam groups, respectively. Mild transient gastrointestinal signs were observed in both groups (11 per cent vedaprofen, 12 per cent meloxicam). Adverse effects related to NSAIDs resulted in treatment cessation in 5 per cent of the dogs in each group. Vedaprofen and meloxicam were efficacious in, and well tolerated by, most of the dogs in the study.     

Results of extra-articular stabilisation following open reduction of coxofemoral luxation in dogs and cats

This report describes 14 dogs (mean age six years, mean bodyweight 25 kg) and three cats (mean age 9-3 years, mean bodyweight 6–7 kg) with coxofemoral luxations of one to 91 days duration (median four days). In 47 per cent of the cases concomitant fractures or luxations (including three bilateral luxations) were present. Closed reduction was immediately unsuccessful in five cases and eventually unsuccessful in seven cases, whereas in five cases the nature of the additional trauma required surgical intervention. Via a craniolateral approach to the hip joint, combined with trochanter osteotomy in 24 per cent of the cases, the luxation was reduced and remnants of the capsule were sutured in 82 per cent of the cases. In all cases an extra-articular iliofemoral suture band was applied to limit the range of motion of the femoral head. The technique is described and illustrated in detail. The success rate proved to be strongly related to the suture material and varied from excellent to poor. This extra-articular stabilisation technique had excellent results in acute and chronic coxofemoral luxations in dogs when multifilamentous non-absorbable material was used, even when no additional non-weightbearing sling was used.     

Postoperative radiotherapy and mitoxantrone for anal sac adenocarcinoma in the dog: 15 cases (1991–2001)

The medical records of 15 dogs with anal sac adenocarcinoma (ASAC) treated with concurrent curative‐intent radiotherapy and mitoxantrone (MX) after surgical removal of the primary tumour were reviewed retrospectively. Radiation was prescribed at 15 daily fractions of 3.2 Gy for a total dose of 48 Gy. MX was given intravenously at a dosage of 5 mg m^?2 every 3 weeks for five treatment sessions. Twelve dogs received pelvic irradiation to include the regional lymph nodes (LNs) and three received radiation only to the perineum. At the time of diagnosis, four dogs were hypercalcaemic and seven dogs presented with regional LN metastasis. All the dogs with regional LN metastasis received pelvic irradiation, and in three cases, metastatic LNs were treated in the macroscopic disease setting. The median event‐free survival was 287 days, and the median overall survival was 956 days. Acute and chronic radiation complications were common and non‐life threatening, although chronic complications contributed to the decision to euthanize two dogs. The results observed in this retrospective analysis compare favourably with cases of ASAC in the literature related to treatment with surgery and/or chemotherapy.     

Studies of infectivity and pathogenicity of an isolate of Trypanosoma evansi in Yankasa sheep.

The course of experimental infection and pathogenicity of an isolate of Trypanosoma evansi were investigated using eight infected and six uninfected control Yankasa sheep. The sheep were each infected intravenously via the jugular vein with approximately 2.0 x 10(6) T. evansi parasites. The effects of the parasite on body temperature, packed cell volume (PCV), haemoglobin, erythrocytes, total protein, were monitored three times a week for approximately 9 weeks. Body weights were determined once every week for the duration of the experiment. The results showed that all the infected sheep were positive for the parasite. The prepatent period varied between 3 and 6 days. T. evansi produced parasitaemic waves at an average of 8.3 days interval. Two distinct forms of the disease were produced namely, acute (4-14 days postinfection), and chronic (43-59 days postinfection). Anaemia was a distinct feature of the disease. While the mean rectal temperatures were significantly elevated (P < 0.05), the mean values of the haematological parameters of the infected sheep dropped significantly (P < 0.05) compared to the preinfection levels. Observed clinical signs included pale mucous membrane, epiphora, loss of appetite, emaciation, dullness and rough hair coat together with fluctuating pyrexia which in most cases coincided with rise in parasitaemia. It is suggested that the isolate of T. evansi is pathogenic for Yankasa sheep.     

Feline hypertension: clinical findings and response to antihypertensive treatment in 30 cases

Systolic hypertension was diagnosed in 30 cats. At diagnosis, 16 of those were found to be in chronic renal failure only, while five were azotaemic and either receiving treatment for hyperthyroidism (four cases) or were untreated hyperthyroid cases (one case). Two cases were untreated hyperthyroid cases with no evidence of azotaemia and the remaining seven cases had no definitive diagnosis of the underlying cause of their hypertension. The successful treatment used for the majority of cases was amlodipine, which lowered systolic blood pressure from 202.5+/-16.8 to 153.2+/-21.6 mmHg (mean+/-SD; n=29) within the first 50 days. Each case was followed for at least three months, or to the end of its natural life, and each cat was re-examined every six to eight weeks. Systolic blood pressure was kept below a target value of 165 mmHg in 58 per cent of cases treated for three months or longer. At the time of writing, 19 of the cases had died or been euthanased with a median treatment time of 203 days, one case was lost to follow-up and 10 cases were still alive, nine of which had been treated for six months or more. Amlodipine can be used for long-term control of feline systemic hypertension.     

A possible role of coarse fractionated radiotherapy in the management of gingival squamous cell carcinoma in dogs: A retrospective study of 21 cases from two referral centers in the UK

Surgery with or without the addition of radiotherapy is the treatment of choice for canine oral squamous cell carcinoma (SCC). Fractionated radiotherapy alone is also effective in the long-term control of the disease, however coarse fractionated radiotherapy (CF-RT) for gingival SCC has not been extensively reported. The aim of this study was to describe side effects, clinical response, and median survival time (MST) of dogs with gingival SCC treated with CF-RT in the palliative and adjuvant setting. Twenty-one cases from two referral centres in the UK treated with CF-RT for gingival SCC between July 2013 and June 2019 were retrospectively evaluated. Of the 21 dogs, 11 developed mild acute adverse effects. Oral mucositis was the most common radiation induced toxicity. Three dogs developed chronic severe adverse effects (oro-nasal fistula, bone necrosis and gum recession). Overall clinical response rate was 77% in dogs receiving palliative treatment with MST of 365 days (60–1,095 days). MST was not reached for dogs treated in the adjuvant setting with a mean of 466 days (121–730 days). In cases of advanced gross disease CF-RT might have a role in short term palliation of clinical signs. However, it carries a significant risk of late toxicity for cases with unexpectedly long survival times and further investigations are required to identify an optimal CF-RT protocol. Randomized controlled trials are needed to confirm the role of CF-RT as adjuvant treatment of incompletely resected gingival SCC.     

Treatment of chronic lymphocytic leukaemia in three dogs with melphalan and prednisolone

Three adult dogs with chronic lymphocytic leukaemia (CLL) were successfully treated with melphalan and prednisolone. Based on the immunophenotypic analysis of leukaemic cells, two dogs were diagnosed with B cell CLL and one dog was tentatively diagnosed as having T cell CLL. One dog with B cell CLL had IgM monoclonal gammopathy. The clinical signs and haematological abnormalities associated with CLL in the three dogs improved with the administration of cytoreductive melphalan (3 to 5 mg/m2/day) and prednisolone (4.3 to 30 mg/m2/day) for eight to 210 days. There were no severe adverse effects except a mild increase in plasma alkaline phosphatase activity. Melphalan and prednisolone therapy may achieve remission with few side effects in dogs with CLL.     

Computed tomography as an aid to management of chronic oropharyngeal stick injury in the dog

Objective : To describe the use of computed tomography scanning in the management of dogs with chronic signs after oropharyngeal stick injury. Methods : Dogs with a final diagnosis of chronic oropharyngeal stick injury that underwent a computed tomography scan during their investigation were selected retrospectively from case files at the Royal Veterinary College, London. Results : The six dogs were young (median age 3·1 years) and medium to large breed (19·0 to 42·0 kg). By the time of referral the most common clinical sign was cervical swelling (five dogs). Stick foreign bodies were apparent on the plain computed tomography images in all cases and appeared as well‐demarcated, linear abnormalities. A ventral mid‐line approach was used for foreign body retrieval, and the computed tomography findings corresponded well with the surgical findings, with stick foreign body length ranging from 1 to 7 cm. Closed suction drainage was used in five dogs, for two to four days. Clinical signs fully resolved postoperatively in all cases, although cervical swelling recurred three weeks after surgery in one case. This dog had the smallest foreign body, the greatest number of surgical interventions before referral (three) and the longest disease course before referral (eight months). Clinical Significance : Computed tomography scanning is accurate in identifying the presence and location of chronic stick foreign bodies. Recurrence of disease is possible despite successful retrieval of the wood fragments found by computed tomography scan.     

Impact of milking characteristics and morphology of udder and teats on clinical mastitis in first- and second-lactation Norwegian cattle

Data from the Norwegian progeny testing program were used to examine the impact of milking characteristics and morphology of udder and teats on clinical mastitis in first- and second-lactation Norwegian cattle. The study was designed as a 1-1 matched case-control study with herd, parity, days in lactation and calving season as matching variables. Conditional maximum likelihood logistic regression was used to evaluate the effects of three primary (2 min milk, milk leakage and teat-end-to-floor distance) and six other study variables. Treatment records from the Norwegian health card system on acute and chronic clinical mastitis were used to define cases. The chosen model included 565 matched pairs. Significant risk factors of clinical mastitis were decreasing teat-end-to-floor distance (P = 0.02) and periparturient udder edema (P < 0.01).

Borderline effects were demonstrated by larger than herd-average teat diameter (P = 0.04), udder asymmetry (P = 0.05) and increasing 2 min milk (P = 0.08). Results were compared to a previous study on the same data with log_e somatic cell count as the dependent variable. Inclusion of teat-end-to-floor distance in the genetic improvement scheme may increase the efficiency of genetic selection for mastitis resistance.     

Canine lymphoid leukaemia and lymphoma with bone marrow involvement: A review of 24 cases

Eleven cases of canine lymphoid leukaemia (10 acute and one chronic) were compared with 13 cases of canine lymphoma with bone marrow abnormalities, with regard to presentation, treatment and survival. Breed, age, and sex were similar for the two groups of dogs, but there was a marked difference in presenting signs, haematological parameters and bone marrow analysis, with the leukaemic dogs showing more severe changes. The clinicopathological features of these cases are reported in this paper and discussed with regard to prognosis. The mean survival time was significantly lower (43 days) in dogs treated for acute lymphoblastic leukaemia than for dogs treated for lymphoma with bone marrow abnormalities (351 days).     

Evaluation of the clinical efficacy of meloxicam in cats with painful locomotor disorders.

The ability of two non-steroidal anti-inflammatory drugs to modify the clinical manifestations of pain associated with locomotor disease was assessed. Sixty-nine cats with acute or chronic locomotor disorders were recruited from 14 first opinion UK veterinary practices and randomly allocated to one of two treatment groups. Group A received meloxicam drops (0.3 mg/kg orally on day 1 followed by 0.1 mg/kg daily for four more consecutive days) and group B received ketoprofen tablets (1.0 mg/kg orally once daily for five days). Each cat underwent a full clinical examination before treatment, 24 hours after initiation of treatment and 24 hours after completion of treatment. General clinical parameters (demeanour and feed intake) and specific locomotor parameters (weightbearing, lameness, local inflammation and pain on palpation) were scored using a discontinuous scale scoring system. The two groups did not differ in terms of age, weight, gender distribution or duration of clinical signs; nor did they differ in terms of general clinical or specific locomotor scores pretreatment. Both treatment regimens resulted in a significant improvement in demeanour, feed intake and weightbearing, and a significant reduction in lameness, pain on palpation and inflammation. No significant difference was observed between the two treatment groups with respect to any of the parameters measured and both treatments were associated with minimal observed side effects. Meloxicam and ketoprofen were found to be effective analgesics and well tolerated in cats with acute or chronic locomotor disorders when administered for short-term treatment (five days) in such cases. However, meloxicam was assessed to be significantly more palatable than ketoprofen.     

Orthopaedics

Practice records from November 1994 to April 2000 were searched for cats with a diagnosis of osteoarthritis (OA). Signalment, historical features and findings, treatment and response to treatment were recorded with the aim of planning prospective studies. Thirty-one cases were found. The average age at presentation was 13·8 years (range, nine to 17 years); 67 per cent were female and 33 per cent male. Clinical signs noted included chronic changes of stiff/abnormal gait (12), difficulty/reluctance in jumping (20) and reluctance to move (five). Eleven cases had acute or chronic lameness. Seven of the records indicated that the cat had been overweight. Physical findings included thickened joints (23), pain on joint manipulation (seven) and crepitus (four).Twenty cases had been radiographed. Findings included osteophytes (14), sclerosis (10), periosteal new bone (four) and remodelling (three). Routine blood tests were performed in 15 cats and showed single abnormalities in five cases. Concurrent diseases diagnosed included hyperthyroidism, dental diseases and chronic renal failure. The final diagnosis had been based on the history, examination, diagnostic tests and response to treatment. The joints thought to have been affected by OA were as follows: bilateral elbows (12), bilateral stifles (four), bilateral elbows and stifles (four), unilateral elbow (three), bilateral hips (two), other combinations of joints (six). Seventeen cats had both meloxicam treatment and a follow-up examination (they may have had concurrent treatments). The clinical notes recorded whether the owners considered there to have been an improvement: three showed marked improvement, 11 showed moderate improvement, one showed no improvement, one had an inconclusive response, and side effects stopped treatment in one. One cat showed a marked improvement after treatment with courses of pentosan polysulphate.     

Results of grid keratotomy, superficial keratectomy and debridement for the management of persistent corneal erosions in 92 dogs

Ninety-two cases of persistent corneal erosions in dogs were analyzed for breed, gender, age and which eye was affected. The results of the treatment of 92 persistent corneal erosions in dogs by superficial keratectomy (SK), grid keratotomy (GK), or debridement with a sterile dry cotton swab are presented. These techniques gave better rates of healing than have been previously reported. All cases of persistent corneal erosions healed in this study. However, it must be noted that three cases treated with debridement only failed to heal after several treatments and were eventually treated with SK. After one procedure 80 out of 92 (87%) had healed. After one procedure, 63% of cases treated with debridement healed, 100% of cases treated with SK healed, and 85% of cases treated with GK healed. At the first postoperative visit, 88% (21/24 cases) of ulcers treated by SK had healed, and 75% (39/52 cases) of ulcers treated by GK had healed. Only 25% of the persistent corneal erosions had healed at the first visit after debridement. All 24 cases of persistent corneal erosions treated with SK healed after one treatment in a mean +/- SD of 9.3 +/- 3.9 days (median of 7 days). Fifty-two cases were managed with GK; 44 (83%) of these healed with one procedure and eight cases required a second GK procedure to resolve. A mean +/- SD of 13.4 +/- 5.1 days (median of 11.5 days) following GK was required for the persistent corneal erosions to heal. Nineteen cases were initially managed by debridement with a dry cotton swab under local anesthesia. Sixteen out of these 19 debridement cases healed (giving an overall healing rate of 84%) in a mean +/- SD time of 23.4 +/- 11.1 days (median 21.5). There were three cases that did not heal with debridement. These cases were debrided at 10-20 day intervals for 30-60 days, and were then treated with SK. Two of these cases healed within 7 days, the other case required 18 days to heal. Sixty-three per cent of persistent corneal erosions treated with debridement healed after one procedure; however, only four out of 19 cases (21%) were healed at the first revisit. Complications were rare: corneal edema occurred in two cases following multiple GK, and excessive granulation tissue in one case was managed with a SK. There was the occurrence of an ulcer adjacent to the surgery site in four cases, two cases following GK and two cases following SK.