Antibiotic resistance in porcine pathogenic bacteria and relation to antibiotic usage.

BACKGROUND: Optimal treatment and prudent use of antimicrobials for pigs is imperative to secure animal health and prevent development of critical resistance. An important step in this one-health context is to monitor resistance patterns of important animal pathogens. The aim of this study was to investigate the antimicrobial resistance patterns of five major pathogens in Danish pigs during a period from 2004 to 2017 and elucidate any developments or associations between resistance and usage of antibiotics. RESULTS: The minimum inhibitory concentration (MIC) for Escherichia coli, Actinobacillus pleuropneumoniae, Streptococcus suis, Bordetella bronchiseptica, and Staphylococcus hyicus was determined to representatives of antibiotic classes relevant for treatment or surveillance. Escherichia coli isolates were mostly sensitive to fluoroquinolones and colistin, whereas high levels of resistance were observed to ampicillin, spectinomycin, streptomycin, sulfonamides and tetracycline. While resistance levels to most compounds remained relatively stable during the period, resistance to florfenicol increased from 2.1% in 2004 to 18.1% in 2017, likely in response to a concurrent increase in usage. A temporal association between resistance and usage was also observed for neomycin. E. coli serovars O138 and O149 were generally more resistant than O139. For A. pleuropneumoniae, the resistance pattern was homogenous and predictable throughout the study period, displaying high MIC values only to erythromycin whereas almost all isolates were susceptible to all other compounds. Most S. suis isolates were sensitive to penicillin whereas high resistance levels to erythromycin and tetracycline were recorded, and resistance to erythromycin and trimethoprim increasing over time. For S. hyicus, sensitivity to the majority of the antimicrobials tested was observed. However, penicillin resistance was recorded in 69.4-88.9% of the isolates. All B. bronchiseptica isolates were resistant to ampicillin, whereas all but two isolates were sensitive to florfenicol. The data obtained have served as background for a recent formulation of evidence-based treatment guidelines for pigs. CONCLUSIONS: Antibiotic resistance varied for some pathogens over time and in response to usage. Resistance to critically important compounds was low. The results emphasize the need for continuous surveillance of resistance patterns also in pig pathogenic bacteria.

Budd-Chiari and inferior caval vein syndromes due to membranous obstruction of the liver veins: successful treatment with angioplasty and transcaval transjugular intrahepatic porto-systemic shunt.

The case is presented of a 25-year-old Caucasian patient with Budd-Chiari syndrome due to membranous obstruction of the liver veins and inferior caval vein syndrome as a result of secondary hyperplasia of the caudate lobe of the liver, obstructing the caval vein. Diagnosis was established by intravascular pressure measurements, ultrasound examinations and caval and liver vein angiograms. Treatment consisting of stent placement in the outlet of a hepatic vein and subsequent transjugular intrahepatic porto-systemic shunt (TIPS) insertion via the caval vein was successful. After 34 months of follow-up the stents remain open and the patient is symptom free. This successful combination of stent placement and TIPS has not been described before. The case report is followed by a review of the literature on the use of angioplasty in short hepatic vein stenosis and TIPS in Budd-Chiari syndrome. It is concluded that angioplasty and TIPS are safe and efficient procedures to reduce liver engorgement and complications of portal hypertension in selected patients with Budd-Chiari syndrome.

A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumour, which has a poor prognosis. Surgical resection can be curative but most patients are inoperable and most chemotherapy agents have minimal activity in this disease. Seocalcitol, a vitamin D analogue, induces differentiation and inhibits growth in cancer cell lines and in vivo. The vitamin D receptor is expressed in hepatocytes and more abundantly in HCC cells. In total, 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year (with possible extension for responders). The dose was titrated according to serum calcium levels. The treatment effect was evaluated by regular CT scans. Out of 33 patients evaluable for tumour response, two had complete response (CR), 12 stable disease and 19 progressive disease. The CRs appeared after 6 and 24 months of treatment, and lasted for 29 and at least 36 months (patient still in remission when data censored). Seocalcitol was well tolerated; the most frequent toxicity was hypercalcaemia and related symptoms. Most patients tolerated a daily dose of 10 micro g of Seocalcitol. This is the first study showing activity, by reduction in tumour dimensions, of a differentiating agent in patients with an advanced bulky, solid tumour. Seocalcitol may have an effect in the treatment of HCC, especially in early disease when a prolonged treatment can be instituted. The survival benefit with or without tumour response should be determined in controlled studies.

[Transjugular intrahepatic portosystemic shunt in the treatment of portal hypertension]. / Transjugulaer intrahepatisk portosystemisk shunt-behandling af portal hypertension.

The transjugular intrahepatic portosystemic shunt (TIPS) represents an important advance in the treatment of complications of portal hypertension. The results from the first 10 TIPS procedures in Arhus are reported. We found, as also documented in other clinical series, that TIPS is more effective in controlling acute haemorrhage than treatment with sclerotherapy and specific medical treatment. Seven out of 10 were treated for acute haemorrhage, and two patients were treated for recurrent variceal bleeding in spite of at least 20 procedures of sclerotherapy and pharmaceutical therapy. One patient was treated with TIPS due to refractory ascites. All 10 TIPS procedures were satisfactory, in four patients it was necessary to embolize collaterals. There were no acute complications associated to the TIPS procedures, but one patient developed stenosis of the shunt within one year, and another chronic encephalopathy. Two patients died, one because of sepsis with Candida albicans, and the other of intracerebral bleeding 16 months after the TIPS procedure.

[Should recurrent Cytomegalovirus infections in patients with liver transplantation be treated?]. / Skal recidiverende cytomegalovirus-infektioner hos levertransplanterede patienter behandles?

Cytomegalovirus (CMV) is the single most important viral pathogen in organ transplantation. Treatment strategy for CMV infection and disease is not well established in transplantation. We report a case of primary CMV infection and two relapses in a woman with a liver transplant in whom spontaneous clearing of the second CMV relapse was seen. A 23 year-old CMV-seronegative woman received a liver transplant with a CMV-negative organ. Six weeks after transplantation she had her primary CMV infection proved by seroconversion and virus isolation. She had no clinical symptoms. Treatment with ganciclovir for five weeks resulted in declining CMV-antigen positive cells from 300/200.000 PMNs to CMV-antigen negativity. Only a slight antibody response was seen. At week 13 the first relapse occurred evidenced by antigenaemia. Ganciclovir was reinstituted for six weeks resulting in reduced antigenaemia. At week 22 liver biopsy was performed due to slightly elevated ALAT. The biopsy showed evidence of focal CMV hepatitis and blood analysis showed 120 CMV-antigen positive cells/200.000 PMNs. In spite of this, ganciclovir was not reinstituted, but the immunosuppressive treatment was reduced to a minimum to stimulate the patient's immune response to CMV. During the following months the patient gradually developed IgG antibody, cleared the antigen and levels of liver enzymes returned to normal. We suggest that ganciclovir treatment, may be omitted in cases of relapse with minimal clinical symptoms, slight antigenaemia and a beginning antibody response and that, the immunosuppressive treatment should be reduced instead. Such an approach requires careful clinical monitoring of the patient.

[Recommendations for treatment of paracetamol poisoning. Danish Medical Society, Study of the Liver]. / Rekommandation for behandling af paracetamolforgiftning.

Based on recent reports concerning the efficacy of N-acetylcysteine (NAC) in paracetamol (acetaminophen) poisoning, guidelines for treatment and control of these patients are reviewed by a study group under the Danish Association for the Study of the Liver. It is recommended that NAC-treatment is initiated immediately after referral and continued for 36 hours in all cases. Further NAC-treatment should not be discontinued before a decrease in INR has been observed.

Effect of omeprazole and cimetidine on prepyloric gastric ulcer: double blind comparative trial.

We conducted a six week double blind randomised study of 176 patients with prepyloric gastric ulcer to determine whether the proton pump inhibitor, omeprazole 30 mg daily would accelerate healing and pain relief, as compared with cimetidine 1 g daily. At two, four, and six weeks after entry ulcers healed in a larger percentage of patients treated with omeprazole (54, 81, and 86%) than of those treated with cimetidine (39, 73, and 78%) ('intention to treat' cohort; p less than 0.05 at two weeks). A higher proportion of patients on omeprazole became free of pain during the first week of treatment (p less than 0.05). No major clinical or biochemical side effects were noted. Omeprazole is an efficient treatment for patients with prepyloric gastric ulcers.

Assessment of D-dimer in plasma: diagnostic value in suspected deep venous thrombosis of the leg.

D-dimer, a fibrin degradation product containing the gamma-gamma crosslink of fibrin, can now be assayed by the use of highly specific monoclonal antibodies. Such assays are not influenced by fibrinogenolysis and measurements can be performed on citrated plasma. The diagnostic values of four such assays--two based on ELISA technique and two on latex agglutination--were evaluated in 108 out of 118 consecutive patients admitted with suspected deep venous thrombosis of the leg. With cut-off limits defined by a pilot study and with venography as reference, a negative D-dimer test was confirmed in 45 of 46 patients (98%; 95% confidence limits: 88-99.9%) after ELISA-M, in 43 of 44 (98%; 88-99.9%) after ELISA-S, in 54 of 67 (81%; 69-89%) after Latex-M and in 40 of 44 (91%; 78-97%) after Latex-S. A positive D-dimer test was confirmed in 61% (48-73%), 59% (46-71%), 63% (47-78%), and 55% (42-67%) respectively. These data suggest the use of one of the ELISA assays for screening. A negative D-dimer test excludes deep venous thrombosis, whereas a positive D-dimer should be followed by venography. By this procedure a 40% reduction of venographic examinations can be expected.

Hypogammaglobulinaemia in systemic lupus erythematosus: report of a case with evidence for spontaneously activated T suppressor cells.

A patient with hypogammaglobulinaemia associated with systemic lupus erythematosus (SLE), a healthy HLA-A, B, C, D-identical and mixed lymphocyte culture (MLC)-negative sibling, and two mutually HLA-A, B, C, D-identical siblings were investigated. Blood mononuclear cells from the patient contained a high proportion of T lymphocytes with the suppressor/cytotoxic phenotype, and in vitro no development of Ig-secreting cells was observed in response to pokeweed mitogen (PWM) or to Epstein-Barr virus (EBV), as opposed to cell cultures from the siblings. In cell cultures from the two healthy HLA-identical siblings, T-lymphocytes as well as monocytes/macrophages (M phi's) could be replaced with corresponding cells from the sibling without major alterations of the pokeweed mitogen (PWM)-induced B cell response. In PWM-stimulated co-cultures of B cells from the patient with healthy HLA-identical T cells, moderate numbers of IgM-secreting cells developed, but not IgG- or IgA-secreting cells. T cells from the patient co-cultured with healthy HLA-identical B cells suppressed their Ig-secretion; this effect was abolished by irradiation of the T cells. The in vitro generation of T suppressor cells by concanavalin A (ConA) was normal. No evidence for abnormal suppressor function of monocytes/macrophages was obtained. Thus in this patient, spontaneously activated T suppressor cells as well as defective B cells were associated with hypogammaglobulinaemia.

Chronic lymphocytic leukaemia of T cell origin. Clinical variation possibly due to involvement of different T lymphocyte subpopulations.

Based on the literature and 2 patients studied, we suggest that at least 2 different clinical entities are included in the concept of T CLL: (i) a clinical variant characterized by a relatively benign course, splenomegaly without lymphadenopathy, low lymphocyte count and granulocytopenia; the proliferating lymphocyte is morphologically mature, of medium size and a cytoplasm with azurophilic granules staining positively for acid phosphatase and corresponding to parallel tubular arrays as demonstrated by electron microscopy. The cells form E-rosettes, have no surface-membrane-bound Ig, but Fc-receptors for IgG. With monoclonal antibodies, the phenotype is OKT3+, OKT4- and OKT8+, theoretically corresponding to the suppressor/cytotoxic T lymphocyte subset, but functionally the cells demonstrate killer cell (responsible for ADCC), but not natural or suppressor cell activity. (ii) another clinical variant with an aggressive course, massive hepato-splenomegaly, lymph node enlargement and very high lymphocyte counts; the lymphocytes are small without cytoplasmic granules; their immunological and functional characteristics have not been determined, but morphologically the cells correspond to the T helper/inducer lymphocyte subset. Thus, involvement of different T lymphocyte subsets may be the reason for the clinical variation in T CLL.

Concanavalin-A-activated suppressor cells in patients with juvenile rheumatoid arthritis.

Concanavalin-A-induced suppressor cell activity was investigated in 63 patients with a definite diagnosis of juvenile rheumatoid arthritis. Peripheral blood lymphoid cells from these patients did not have the same ability as cells from normal individuals to suppress the proliferative response of autologous cells, responding to phytohaemaglutinin, Candida albicans antigen, or allogeneic cells. No correlation was found between suppressor activity, disease activity, or number of joints involved. Nor was there any significant association between decreased suppressor cell activity and HLA-A, -B, -C, -D antigens, although there was a tendency towards association between decreased suppressor cell activity and HLA-B27.

Evans' syndrome in IgA deficiency. Episodic autoimmune haemolytic anaemia and thrombocytopenia during a 10 years observation period.

A 26-year-old male with a 10-year history of complete selective IgA deficiency and recurrent autoimmune anaemia and thrombocytopenia (Evans syndrome) is presented. Both serum IgA and saliva secretory IgA were below the detection limit (less than 0.05 mg/l). No other features of autoimmunity were seen. The patient had a normal % of peripheral blood lymphocytes with surface IgM and IgG cells and normal in vitro lymphocyte transformation after stimulation with mitogens and antigens. The pleomorphic and randomly appearing immunologic features of selective IgA deficiency are emphasized by the present case.

HLA-DR typing in cadaver kidney donors and recipients in Copenhagen.

Among 224 cadaver kidney transplantations performed since Spring 1977, successful DR typing of both donor and recipient could be done in 149 cases. Assessment of DR match grade and clinical data was done independently. The minimum observation time was 3 months and the time of follow up was 1 December, 1980. There was an effect of DR matching which became significant when only 1. transplants were considered and high risk recipients (i.e. diabetics) excluded. Transfusions were of minor importance on graft survival and the difference was only obvious in the first year after transplantation. Matching for HLA-A, B antigen had no obvious effect on graft survival in this material.

Leucocyte migration test with autologous colonic mucosa as antigen in patients with ulcerative colitis.

The leucocyte migration agarose technique (LMAT) was applied in a study of the migration of peripheral leucocytes in 16 patients with ulcerative colitis using three different autologous types of tissue as antigen: rectal mucosa, skin and buccal mucosa. In all cases the migration indices were within normal limits, and they did not differ from a group of control patients suffering from peptic ulcer, irritable colon, or haemorrhoidal tumours. The present study does not support the theory of cellular hypersensitivity against colonic mucosa in patients with ulcerative colitis.

Leucocyte migration test with autologous colonic mucosa as antigen in patients with ulcerative colitis.

The leucocyte migration agarose technique (LMAT) was applied in a study of the migration of peripheral leucocytes in 16 patients with ulcerative colitis using three different autologous types of tissue as antigen: rectal mucosa, skin and buccal mucosa. In all cases the migration indices were within normal limits, and they did not differ from a group of control patients suffering from peptic ulcer, irritable colon or haemorrhoidal tumours. The present study does not support the theory of cellular hypersensitivity against colonic mucosa in patients with ulcerative colitis.