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Objective: The aim of the study was to assess the pneumococcal antibody response in autoimmune inflammatory rheumatic disease (AIIRD) patients receiving 23-valent pneumococcal polysaccharide vaccine (PPV23) as a prime vaccination or revaccination. Method: Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIIRD patients receiving biological disease-modifying anti-rheumatic drug (bDMARD) treatment for rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis. Patients with a non-protective level of pneumococcal antibodies (geometric mean pneumococcal antibody level

OBJECTIVES: The aims of this cross-sectional study were to assess the pneumococcal antibody coverage in patients with autoimmune inflammatory rheumatic disease (AIRD) and to identify predictors associated with inadequate protective antibody levels.METHOD: Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIRD patients with a diagnosis of rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis attending the Department of Rheumatology at the North Denmark Regional Hospital. Immunization against pneumococcal infection was defined as a geometric mean level ≥ 1 μg antibodies/mL. Clinical information about vaccination status and disease/treatment history was retrieved from the medical file system.RESULTS: Results of antibody measurement and vaccination status were available from 346 AIRD patients, of whom 200 (58%) were registered as receiving pneumococcal vaccination, whereas the remaining 146 patients (42%) were not. Of all 346 patients, only 61 (18%) were measured with an adequate level of protective antibodies (30% vs 1%, respectively). Methotrexate treatment at the time of vaccination and increasing age were identified as predictors of poor vaccination outcome in multiple logistic regression analysis.CONCLUSIONS: This post-vaccination study showed that less than one-fifth of the AIRD patients are adequately protected against pneumococcal infection, although the immunization programme had been implemented in more than half of the study population. Development of improved vaccination strategies is required to achieve a higher immunization coverage rate and more efficient lasting antibody response.

Objectives: In recent years, studies have proved that the stomach is not sterile as previously believed and thereby harbors a unique gastric microbiota. Since most studies have investigated the bacterial composition of the gastric microbiota, the investigation of other microorganisms is still in its infancy. To date, the fungal composition of the stomach (the gastric mycobiota) has gained more attention in microbiota studies. Nevertheless, there is a lack of studies investigating the gastric mycobiota and the association to the pathogenesis of gastric diseases. We aim to investigate the composition of the gastric mycobiota of patients diagnosed with dyspepsia or gastric cancer and define the persistent and transient fungal colonizers of the stomach. Patients and Methods: Gastric biopsies from twenty-two patients diagnosed with dyspepsia and twelve patients diagnosed with gastric cancer were analyzed by 18S rDNA sequencing to compare the gastric mycobiota. The gastric biopsies were either unwashed or washed to distinguish fungal adherence. To compare the mycobiota from cancer tissue and normal tissue, the gastric biopsies from gastric cancer patients were taken from two sites; antrum (AN) and corpus from cancer area (CA). Results: The distribution and composition of the gastric mycobiota in gastric cancer and dyspeptic patients were significantly distinct. The most prominent difference was observed in the relative abundance of the fungal genus Malassezia as it was significantly increased in gastric cancer patients. Malassezia is an opportunistic pathogen, which has been shown to promote the formation of several cancer types. Thereby the results in this study indicate that Malassezia may play a role in the formation of gastric cancer, however, further investigation is needed. Conclusions: The results from this study show that the gastric mycobiota might has an important role for the pathogeneses of human gastric diseases, as significant changes in the gastric mycobiota are observed in gastric cancer patients compared to dyspeptic patients. This advocates more research within the role of gastric mycobiota as more knowledge can lead to new therapeutics.

Background Severe pneumococcal infections contribute to increased mortality in patients with rheumatic diseases, and is preventable by vaccination against Streptococcus pneumoniae. EULAR recommends that pneumococcal vaccination should be strongly considered in patients with rheumatic diseases, however, need and timing of revaccination for this patient group remains unknown1. Since 2009, rheumatological patients from our department have been vaccinated against S. pneumoniae prior to initiation of bDMARD therapy, by use of the 23-valent pneumococcal polysaccharide vaccine (PPV23). To our knowledge, we are the only centre in Denmark to vaccinate these patients routinely. Objectives The aim of the study was to determine the prevalence of rheumatological patients receiving bDMARD therapy with a protective level of antibodies against S. pneumoniae, and to identify possible factors of relevance affecting antibody production. Methods Antibodies against 12 pneumoccocal serotypes were measured in the period of June to December 2017 in patients receiving bDMARD therapy initiated before March 1st 2017. A geometric mean level of all serotypes above 1 µg/ml was considered a protective antibody level. The patients had been diagnosed with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis or juvenile idiopathic arthritis. The study group consisted of both vaccinated and unvaccinated individuals, where unvaccinated individuals initiated bDMARD therapy before vaccination occurred routinely. Differences in protection between vaccinated and unvaccinated patients were evaluated using the χ2 test. We included the following variables in a logistic regression model, to analyse factors of possible significance to the protective level of antibodies: age, sex, diagnosis, methotrexate (MTX) and/or prednisolone treatment at time of vaccination, and years since vaccination. Results A total of 319 patients were included in the study: 186 (58%) vaccinated and 133 (42%) unvaccinated patients. Among the vaccinated patients, 30% had a protective antibody level versus 0% of the unvaccinated patients (p Logistic regression analysis showed that a significantly smaller proportion of patients treated with MTX at time of vaccination had a protective antibody level compared with patients not treated with MTX (p=0.03; odds ratio: 2.3; 95% CI [1.1;4.7]). The same applied for advanced age at time of vaccination (p=0.04), whereas years since vaccination did not decrease antibody protection significantly (p=0.12). Conclusions Only one third of PPV23 vaccinated rheumatological patients treated with bDMARD were observed with a GML of pneumococcal antibodies above 1 µg/ml. This suggests that a majority of these patients are not protected adequately against pneumococcal disease in spite of vaccination. MTX treatment at time of vaccination and advanced age were both independently associated with lack of protective antibody level. Reference [1] van Assen S, Agmon-Levin N, Elkayam O, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis2011;70(3):414–422. Disclosure of Interest None declared

The effect of ciprofloxacin on eight strains of Staphylococcus aureus were examined. A post-antibiotic effect was observed in all strains, varying between 1.65 and 2.75 hours, with concentration of ciprofloxacin at 5 times the Minimum Inhibitory Concentration (MIC) exposed for 1 hours. Killing-kinetic studies at 5 times the MIC showed a decrease in the numbers of organisms by approximately 2.1 log10 after 6 hours, independent of the growth phase. A significantly increased susceptibility of S. aureus to the bactericidal activity of ciprofloxacin during recovery from the PAE-phase was demonstrated.

Population analyses of the susceptibility to ciprofloxacin of eight strains of Pseudomonas aeruginosa, including mucoid strains and strains resistant to aminoglycosides or anti-Pseudomonas beta-lactams, were carried out. All strains were sensitive as judged by the broth-dilution technique, but four strains were found to yield resistant mutants with a frequency of less than 10(-6). Two strains yielded mutants homogeneously sensitive to ciprofloxacin at a level 8-16 times the MIC of the parent strains. Two other strains yielded mutants resistant to different higher concentrations of ciprofloxacin. One of these mutants was examined for production of ciprofloxacin-inactivating enzyme; no enzyme production could be detected. Cross-resistance was found with another quinolone antibiotic, ofloxacin, but not with aminoglycosides or beta-lactam antibiotics.

With the purpose of determining whether the risk of infection with a particular clone of Mycobacterium tuberculosis is influenced by the human immunodeficiency virus (HIV) status of the host, we analyzed and compared 68 mycobacterial isolates obtained from HIV-seropositive patients with tuberculosis (TB) in Dar es Salaam, Tanzania, with 66 mycobacterial isolates obtained from HIV-seronegative patients with TB in the same geographical region by using both DNA fingerprinting and classical phenotyping methods. One hundred one different IS6110 fingerprinting patterns were observed in the 134 isolates. The level of diversity of the DNA fingerprints observed in the HIV-seropositive group was comparable to the level of the diversity observed in the HIV-seronegative group. Resistance to a single anti-TB drug was found in 8.8% of the tested isolates, and 3.2% of the isolates were resistant to more than one anti-TB drug. The drug susceptibility profiles were not significantly difference between the two groups of isolates compared in the present study. Phenotypic characteristics which classify M. tuberculosis strains as belonging to the Asian subgroup correlated with a low IS6110 copy number per isolate. However, the occurrence of Asian subgroup strains was not associated with the HIV status of the patients. The results of the study suggested an equal risk of infection with a defined M. tuberculosis clone for HIV-seropositive and HIV-seronegative individuals.

This study was undertaken to describe the epidemiology, clinical manifestations and prognosis of childhood tuberculosis in Copenhagen, with special attention to differences between Danish children and children of foreign origin. Medical records for all children with tuberculosis cared for in the hospitals of the Copenhagen area 1984-1993 were reviewed. Sixty-six patients were identified. Sixteen of 20 Danish patients (80%) and 67% of foreign children had respiratory tuberculosis. Tuberculosis located in cervical lymph nodes was found only in children of foreign origin. Five patients had meningitis. The high incidence among foreign children reflects the incidence in their home countries, but poorer living conditions among ethnic minorities in Denmark may facilitate transmission of tuberculosis. Severe manifestations of tuberculosis still occur, even in a low incidence country.

We reviewed case records of 22 children who were diagnosed as having nontuberculous mycobacterial infection. All children were previously healthy. In 20 cases the infection presented as cervical lymphadenitis. The patients were between ten months and 14 years old, and two thirds were between 13 and 36 months old. The majority (74%) were girls. Mycobacterium avium/intracellulare was isolated most frequently (55%). The report describes the diagnosis and treatment of childhood mycobacterial cervical adenopathy. All patients except one were treated surgically. We found considerable differences in both preoperative and operative management. When excision of the lymph node (as opposed to needle biopsy) was performed, diagnosis could be made earlier and repeated surgical procedures could be avoided.

A collection of 99 clinical isolates of Streptococcus pneumoniae, chosen due to their different susceptibilities to penicillin, were investigated with respect to their susceptibility to the macrolides azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, spiramycin, and to clindamycin and tetracycline by the agar dilution method. We found complete cross resistance among the macrolides. The pneumococci were either susceptible, MICor = 0.5 micrograms/ml, or resistant, MICor = 16 micrograms/ml, to the tested macrolides, giving a bimodal distribution. In addition, complete cross resistance was observed between clindamycin and macrolides. Pneumococci resistant to macrolides were also resistant to tetracycline, and 26% of the macrolide-susceptible strains were tetracycline resistant.

The extent of synergistic killing and duration of the post-antibiotic effect (PAE) was evaluated in streptomycin-susceptible strains of Streptococcus faecalis and Streptococcus faecium with 20 mcg/ml of ampicillin or 10 mcg/ml of vancomycin in combination with decreasing concentrations of streptomycin (20, 10, 5, 2, 1, 0.5 mcg/ml). The bactericidal activity or duration in recovery period declined progressively in a linear pattern with decreasing concentrations of streptomycin. One log10 or greater reduction in viable counts was seen with streptomycin concentrations of 2 mcg/ml or higher with both ampicillin and vancomycin. A synergistic increase in recovery period (PAE greater than or equal to 0.5 h) of ampicillin or vancomycin was observed with concentrations of streptomycin in excess of 2 mcg/ml and 1 mcg/ml, respectively. These results suggest that lower dosage of streptomycin in the therapy of enterococcal infections will probably result in a higher relapse rate.

Seven strains of Streptococcus faecalis, of which two possessed high-level resistance to streptomycin (MIC greater than or equal to 2000 mcg/ml), and two strains of Streptococcus faecium were evaluated with respect to killing-effect and duration of post-antibiotic effect (PAE) of ampicillin and vancomycin in combination with streptomycin, gentamicin, tobramycin and netilmicin. No synergistic combination effects were seen with the two strains highly-resistant to streptomycin or with the two Streptococcus faecium strains to netilmicin and tobramycin. When these strains were excluded, no significant difference in average killing could be detected between the four aminoglycosides. The mean prolongation in recovery period of susceptible strains was significantly longer with combinations of ampicillin and netilmicin or streptomycin as compared with either gentamicin or tobramycin. A similar relationship was seen for combinations of vancomycin with the four aminoglycosides.

The post-antibiotic effect of ciprofloxacin on five strains of Pseudomonas aeruginosa was examined. Ciprofloxacin demonstrated rapid bactericidal action at concentrations achievable in serum. After removal of the drug persistent suppression of bacterial growth followed by regrowth was observed for all strains after exposure of the organisms to various concentrations of ciprofloxacin for limited periods of time (0.25-3 h). The duration of this post-antibiotic effect increased with the concentration of the drug and duration of exposure up to a point of maximal response. This point was reached after approximately 2.2 h using a ciprofloxacin concentration 5-10 times the MIC and 1-2 h of treatment.

The influence of various incubation conditions on synergism with cell wall-active agents combined with streptomycin was studied in a Streptococcus faecalis strain. It could be shown that both a synergistic increased killing effect and a synergistic prolongation of post-antibiotic effect (PAE) were not dependent on an active process, as they occurred both in an anaerobic atmosphere and when an electron transport inhibitor (sodium azide) was added to the media. Moreover, it was demonstrated that if a drug, alone or in combination with streptomycin, had a PAE, there was an increased susceptibility to a subinhibitory concentration of streptomycin (1/4xMIC) when added to a culture recovering from its PAE. These findings confirm the commonly held belief in a mechanistic mechanism of synergism: That cell wall-active agents modify in some way the cell-envelope, thereby enhancing aminoglycoside uptake and killing in Streptococcus faecalis.

Determination of post-antibiotic effect (PAE) and time-kill studies were made with twelve strains of Streptococcus faecalis and nine strains of Streptococcus faecium, comparing the effect of ampicillin alone with a combination of ampicillin and streptomycin at achievable serum concentrations. Bactericidal synergism (greater than or equal to one log10 decrease in viable counts) and prolongation in PAE (greater than or equal to 0.5 h) were demonstrated in all streptomycin-susceptible strains (Minimum inhibitory Concentration less than 2000 mcg/ml), whereas only one of five highly streptomycin-resistant strains exhibited a synergistic effect. A significant correlation between the magnitude of increased killing and the increase in recovery period by the combinations of ampicillin and streptomycin was demonstrated.

Nine strains of Streptococcus faecalis and Streptococcus faecium were studied with respect to ampicillin, ciprofloxacin, imipenem, piperacillin, vancomycin and streptomycin. Two strains were highly resistant (MIC greater than or equal to 2,000 micrograms/ml) to streptomycin. Evaluation and comparison of the killing activity with killing curves, and duration of the postantibiotic effect (PAE) after exposure for 1 h with regrowth curves was done with combinations of antibiotics or alone. The overall killing effect of ciprofloxacin with streptomycin was antagonistic, whereas synergism (greater than or equal to one log10 decrease in viable counts) was observed in streptomycin-susceptible strains with combinations of streptomycin and ampicillin, imipenem, piperacillin or vancomycin. In addition, prolongation of PAE (greater than or equal to 0.5 h) was seen only in streptomycin-susceptible strains. Thus, seven (100%) strains showed a synergistic increase in PAE to combinations with ampicillin and vancomycin, three (43%) to imipenem, four (57%) to piperacillin, but none to the combination of streptomycin and ciprofloxacin. A significant correlation was observed between the magnitude of increased killing and the extent of increase in recovery period with combinations of streptomycin with either ampicillin or vancomycin.

Time-kill studies were made with thirteen strains of Pseudomonas aeruginosa, comparing the activity of ciprofloxacin plus piperacillin with the combination of tobramycin and piperacillin. Synergism was demonstrated in an equal number of strains with both combinations. No antagonism was demonstrated. The reproducibility of the killing-curve method suggests that at least two different concentrations should be used and that a decrease in viable counts below 2 log10 after 24 hours does not exclude a synergistic action.

The differences in the synergistic potential for either killing effect or increase in duration of post-antibiotic effect (PAE) seen with various beta-lactam-aminoglycoside combinations in two strains of Streptococcus faecalis were further studied to examine this relationship in more detail. It was seen that a strain which produced a synergistic increase in recovery period (PAE greater than or equal to 0.5 h), comparing the beta-lactam antibiotics alone and when combined with streptomycin, showed increased sensitivity (greater than or equal to 1 log10 reduction in viable counts) to a subinhibitory concentration of streptomycin added to a culture recovering from the PAE; this was not demonstrated with a strain showing no increase in PAE when briefly exposed to a combination therapy, although its corresponding killing curve was clearly synergistic. Moreover, it was seen that the differences in the synergistic prolongation of recovery period when combining various aminoglycosides at 1/4 x MIC with ampicillin were consistent with the different duration of PAE with the particular aminoglycoside alone at the MIC.

Sixteen to twenty-two months old untreated CBA and C57/B1 mice judged to die within 24 hours had a higher percentage of dead leukocytes in lymph nodes, spleen and thymus than had like-aged old mice and young (2–8 months) healthy mice. Furthermore, dying CBA and DBA mice showed enhanced in vitro cytotoxicity of spleen lymphocytes towards syngeneic fibroblasts and YAC target cells.