Comparison of phenoxymethylpenicillin, amoxicillin, and doxycycline for erythema migrans in general practice. A randomized controlled trial with a 1-year follow-up.

OBJECTIVES: To compare the three most commonly used antibiotics for erythema migrans (EM) in Norwegian primary care. METHODS: A randomized, parallel, controlled trial was carried out. Treatments were open to the patients, but blinded for the GPs and investigators. Patients eligible for inclusion were aged ≥18 years and clinically diagnosed with EM. Block randomization was processed in blocks of six. Patients were assigned to receive one of three antibiotic treatments for 14 days: phenoxymethylpenicillin (PCV), amoxicillin, or doxycycline. The primary outcome was the duration of EM in days in the three treatment groups. Patients kept a diary for the 14 days of treatment, in which they registered concomitant symptoms and side effects. The patients consulted their GP after 14 days of treatment and had a 1-year follow-up to monitor any development of disseminated Lyme borreliosis (LB). EMs with a duration of more than 14 days were followed until resolution. ClinicalTrials.govNCT01368341 and EU Clinical Trials Register 2010-023747-15. RESULTS: One hundred and eighty eight patients (PCV: n = 56, amoxicillin: n = 64, doxycycline: n = 68) were included by 44 Norwegian general practitioners (GPs) from June 2011 to November 2013. Follow-up was completed by December 2014. The median duration of EM was altogether 14 days (range 3-293). For the PCV group median duration was 14 days (range 5-91), for amoxicillin 13 days (range 4-179) and for doxycycline 14 days (range 3-293). The duration of EM did not differ significantly between the three antibiotic groups (p 0.277). None of the patients developed disseminated LB within the 1-year follow-up. CONCLUSIONS: We did not find 14 days of PCV, doxycycline, and amoxicillin treatments to differ in effectiveness or safety in the treatment of clinically diagnosed EM in primary care.

Clostridium difficile infections related to antibiotic use and infection control facilities in two university hospitals.

We investigated whether a reduction in antibiotic use at the Aker University Hospital (Aker) led to a reduction in Clostridium difficile-associated diarrhoea (CDAD). We compared the incidence of CDAD in Aker and Tromsoe University Hospitals (Tromsoe) and related it to antibiotic use and facilities for infection control between 1993-2001. For this purpose we also performed point prevalence studies. Total antibiotic use was the same in the two hospitals. In spite of a reduction in the use of broad-spectrum antibiotics in Aker the incidence of CDAD increased during 1993-1999. In Tromsoe the use of broad-spectrum antibiotics and clindamycin was two to three times higher than in Aker, but until 1999 the incidence of CDAD remained constant and only half that of Aker. After 1999 the incidence of CDAD was halved in Aker, and increased three-fold in Tromsoe. Point prevalence studies in 2001 revealed an equal prevalence of antibiotic-associated diarrhoea. The facilities for infection control were better in Tromsoe. The percentage of single rooms were 8% in Aker and 14% in Tromsoe, and the percentage of single rooms with a WC was 6% in Aker and 12% in Tromsoe. The bed occupancy was much higher in Aker than in Tromsoe. Lack of facilities for infection control and higher bed occupancy could have contributed to the higher incidence of CDAD in Aker in spite of decreased use of broad-spectrum antibiotics and clindamycin. To limit CDAD in hospitals the focus must be on both rational antibiotic use and infection control.

Leukotriene B4 receptor levels and intracellular calcium signalling in polymorphonuclear leukocytes from patients with Crohn's disease.

OBJECTIVE: To investigate the leukotriene B4 (LTB4) signal transducing mechanism in polymorphonuclear neutrophils (PMNs) from patients with Crohn's disease. METHODS: Cytosolic free calcium ([Ca2+]i), inositol (1,4,5)-trisphosphate [(1,4,5)-IP3] chemotaxis, LTB4 receptor number and affinity were investigated in peripheral PMNs from 11 patients with Crohn's disease and 11 healthy controls. RESULTS: There was a slight reduction (P = 0.31) in the number of LTB4 receptor sites per cell expressed on PMNs (mean Bmax 931) from nine of the 11 patients studied compared with the healthy controls (mean Bmax 1095). LTB4-mediated (1,4,5)-IP3 formation and the increase in [Ca2+]i were markedly decreased in PMNs from the 11 patients with Crohn's disease [(1,4,5)-IP3, mean +/- SEM 12 +/- 0.84 and 27.4 +/- 1.4 pmol/l/tube for patients and controls, respectively; [Ca2+]i, mean +/- SEM 295 +/- 2.75 and 598 +/- 4.7 nmol/l for patients and controls, respectively]. The decrease in calcium might be related to the decrease in Bmax (P < 0.05). Ionomycin, a calcium ionophore which bypasses the initial steps of LTB4 receptor activation, showed only a minor difference in peak [Ca2+]i between PMNs from patients and controls. LTB4-directed chemotaxis showed that the sensitivity to suboptimal concentrations of LTB4 (1.0 nmol/l) was significantly depressed in PMNs from patients (P < 0.05). CONCLUSION: Peripheral PMNs from patients with Crohn's disease had a small deficit in the expression of LTB4 receptors. This deficiency was paralleled by marked alterations in cellular signalling. Whether these results are specific to Crohn's disease or simply result from the exposure of circulating PMNs to elevated levels of LTB4 remains to be established.

Influence of prescription patterns in general practice on anti-microbial resistance in Norway.

BACKGROUND: The global pandemic of antibiotic resistance is causing considerable concern, and a major reason for the growing world-wide resistance problem is the overuse of anti-infective drugs, especially the use of broad spectrum antibiotics. This is still a relatively minor problem in most of the Nordic countries where the consumption of antibiotics is less than half of that reported from southern Europe and the United States of America (USA). AIM: To describe the resistance pattern among common respiratory tract pathogens in Norwegian general practice, the national consumption of antibiotics, and GPs' prescription patterns for respiratory tract infections. To offer some suggestions as to why Norway has maintained a favourable situation regarding resistant microbes during the past 10 years. METHODS: An analysis of the prescription patterns in Norwegian general practice. RESULTS: There is a low total prescription volume of antibiotics compared with other countries. Penicillin V is the most commonly used antibiotic for the most common airway diseases in general practice in Norway. CONCLUSION: Although there is a low prevalence of antibiotic resistance in Norway, there is still a great potential for reducing the unnecessary antibiotic prescribing for the most common respiratory illnesses.

Possible existence of leukotriene D4 receptors and mechanism of their signal transduction in human polymorphonuclear leukocytes.

Previous work from this laboratory has demonstrated that stimulation of human polymorphonuclear leukocytes (PMN) with the peptidyl leukotriene D4 (LTD4) results in the formation of second messenger signals, i.e. mobilization of intracellular free Ca2+ ([Ca2+]i) and hydrolysis of phosphoinositides (PIP2). Based on these earlier results we have employed radioligand binding techniques to study the presence of LTD4 receptors in intact human PMN leukocytes. The binding of [3H]-LTD4 to LTD4 receptors is rapid, reversible, specific and saturable. Scatchard analysis of the binding data indicates the presence of 116-275 identical receptors per neutrophil with an apparent dissociation constant (KD) of 1,1-2,3 nM. Only one class of binding sites was identified. The LTD4 receptors are located in the plasma membrane and are specific for LTD4 since binding is unaffected by other leukotrienes. Furthermore, LTD4 induces a rapid and persistent translocation of Protein Kinase C (PKC) from the cytosol to the membrane. The LTD4 binding and PKC translocation could be blocked in a concentration dependent manner by the new and specific LTD4 receptor antagonist ICI 198,615. These observations strongly suggest that human PMN might possess specific LTD4 receptors which are coupled to the inositol trisphosphate pathway resulting in a rise in the cytoplasmic free Ca2+ and redistribution of protein kinase C. A mechanism of signal transduction for leukotriene D4 is proposed.

[Tuberculosis among AIDS patients in Ullev]l hospital]. / Tuberkulose hos pasienter med AIDS ved Ullevål sykehus.

Records of patients with concomitant HIV infection and human tuberculosis were analysed. Nine out of 232 AIDS patients (4%) developed human tuberculosis with a preponderance (6/9) of immigrants from sub-Saharan Africa. In three patients the diagnosis was delayed because of atypical manifestations of the disease and lack of typical chest X-ray findings. Tuberculin skin tests were positive in only three patients, and became negative in one patient who developed two episodes of tuberculosis. All the patients who complied with the conventional triple anti-tuberculosis regimen responded well, and no multidrug-resistant tuberculosis was observed.

[Is it possible to influence the utilization of antibiotics?]. / Er det mulig å påvirke bruken av antibiotika?

Excessive and inappropriate use of antibiotics in hospitals contributes to the development of antibiotic resistance and higher costs. At Aker University Hospital the use of antibiotics and the associated costs have increased over the last years. In an attempt to reverse this trend we introduced guidelines for prescribing antibiotics, based on knowledge of the local pattern of resistance. The programme resulted in a reduction of 9% in the use of antimicrobial drugs and of 24% in the associated costs, i.e. a saving of NOK 2.2 million in one year. From 1995 to 1996 there was a further reduction in antibiotic consumption by 7%. We conclude that guidelines for use of antibiotics, and relevant information, can be useful tools in influencing the prescription of such drugs.

Transition of myelofibrosis to polycythaemia vera.

A case of typical myelofibrosis with a huge spleen is described in a 62-year old man. During the subsequent 2-year follow-up, a clinical picture of polycythaemia vera with pancytosis and disappearance of the marrow fibrosis was observed. The pancytosis necessitated treatment with busulphan and frequent phlebotomies. The transformation was associated with prednisone treatment for a suspected haemolytic state. During this treatment, the spleen no longer became enlarged on clinical palpation, although it was still enlarged at post mortem examination, but much less than 2 years earlier.

[Pneumococcal endocarditis of the tricuspid valve. A case report with review of the literature]. / Pneumokokkendokarditt i trikuspidalklaffene. En sykehistorie med en gjennomgang av litteraturen.

The incidence of invasive infections caused by Streptococcus pneumoniae has increased dramatically in Norway the last 5-10 years. We describe a patient with a pneumococcal endocarditis of the tricuspic valve who illustrates some of the diagnostic and therapeutic problems often connected with right-sided endocarditis. We also review literature on pneumococcal endocarditis. Since the introduction of antibiotics, the incidence of pneumococcal endocarditis has decreased significantly. The most important predisposition still seems to be alcoholism. Cases of pneumococcal endocarditis require prolonged and consistent antibiotic treatment. Rapid destruction of the valves is typical, and often demands surgical intervention at an early stage. So far no multiresistant pneumococci have been observed in Norway. The increased incidence of serious pneumococcal infections has recently made it necessary to recommend that pneumococcal vaccine be given on wider indications.

Diagnosis of Hodgkin's disease hampered by an Epstein-Barr virus infection treated with acyclovir.

We report a case of Hodgkin's disease associated with Epstein-Barr virus (EBV) infection in a 75-year-old male. The patient was given a 5-day course of acyclovir to which he responded well, with partial resolution of the lymphoma and return to well-being. A biopsy from the lymphoma after acyclovir treatment showed a change in the histological picture with a reduction in the number of giant cells. Relationships between EBV infection and Hodgkin's lymphoma are discussed.

[Once-daily dosage of aminoglycosides--a therapeutic simplification and an economical benefit]. / Dosering av aminoglykosider en gang i døgnet--en terapeutisk forenkling og et økonomisk fremskritt.

Conventionally, aminoglycosides have been administered in two or three daily doses. Numerous in-vitro and animal experiments and several clinical trials favour a once-daily dosage regimen of aminoglycosides, which provides a more rapid concentration-dependent bacterial killing and is probably less toxic than two or three dosage regimens. In this article the pharmacological and microbiological background for once-daily aminoglycoside administration is reviewed, and some controlled trials are discussed. Recommendations for clinical practice are given.

Platelet survival, platelet factor-4 and bleeding time in myeloproliferative disorders.

In 27 patients with myeloproliferative disorders observations on thrombohaemorrhagic complications, platelet function tests and spleen size were made. Sixteen patients had thrombotic or haemorrhagic episodes. All 27 patients had elevated platelet factor-4 and 25 patients had a shortened platelet survival. Patients with myelofibrosis had a significantly shorter platelet survival than patients with polycythaemia vera (p less than 0.05). Seven out of 23 patients investigated had prolonged bleeding time. The observed abnormalities of platelet function tests were not related to thrombohaemorrhagic complications or spleen size.

Spongy lymphoid myelofibrosis as a predictor of hairy cell leukaemia or a variant of hairy cell leukaemia without hairy cells?

8 patients with clinical and haematological features suggestive of hairy cell leukaemia are described. During their initial illness morphologic and cytochemical evidence of hairy cell leukaemia were lacking in all but 2 patients. A common highly characteristic histopathologic finding was reticulin fibrosis in the bone marrow, present in all patients at first presentation. The term spongy lymphoid myelofibrosis is proposed for such cases, which may represent a variant type of hairy cell leukaemia or an early stage of the disease.