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Biomedical subjects

N Frimodt-Møller

Publications and source records attributed to N Frimodt-Møller.

At least 19 recordsLinked to original sources

[Antibiotic treatment of infections in general practice. Effect of audit assessed by prescriptions data from health insurance registry and physicians' own registration].

The aim was to study whether an audit of treatment of infections in general practice resulted in changed prescribing habits. In 1995-1996 forty-six general practitioners (GP's) from the County of Roskilde participated in an audit regarding infectious diseases (incl. course participation and preparation of treatment guidelines). The effect evaluation was done on the basis of 1) two self-registrations of antibiotic prescriptions carried out with one year's interval, and 2) prescribing data from the National Insurance database collected over two periods, before the first and second self-registration respectively. The number of patients not receiving antibiotics increased significantly from 47.2% to 52.4% after intervention. The self-registration did not show any change in choice of antibiotics, while the registry data showed a shift from broad-spectrum to narrow-spectrum penicillin. This change was, however, also found among the GP's, who did not participate in the audit. The study demonstrated that audit can result in changes in prescribing patterns, but at the same time emphasizes the need for inclusion of external data sources and control groups in the evaluation of intervention effects.

Adult↗

Correlation of MIC methods and tentative interpretive criteria for disk diffusion susceptibility testing using NCCLS methodology for fusidic acid.

Three hundred and eight staphylococci and 43 Streptococcus pyogenes were tested by agar dilution, microbroth dilution, E-test, and disk diffusion using 5, 10 and 50 microg disks, as outlined by the NCCLS, in order to correlate the different MIC methods and to establish tentative species specific interpretive zone diameter breakpoints for fusidic acid. MIC results of the three methods were comparable. For Staphylococcus aureus, using MIC breakpoints of < or = 0.5 mg/L for susceptible and > or = 2 mg/L for resistant tentative interpretive zone diameters of > or = 20 mm and > or = 21 mm for susceptible and < or = 17 mm and < or = 18 mm for resistant are suggested for the 5 microg and the 10 microg disk, respectively. The 50 microg disk did not separate susceptible from resistant isolates. For streptococci a uniform MIC distribution of 2-8 mg/L was found.

Anti-Bacterial Agents↗

Prevalence of and detection of resistance to ampicillin and other beta-lactam antibiotics in Haemophilus influenzae in Denmark.

The susceptibility of Haemophilus influenzae to penicillin V and G, ampicillin and cefuroxime was investigated by MIC, disc and tablet diffusion methods, using chocolate agar as test medium, to determine the prevalence of ampicillin-resistant isolates and the optimal method for their detection. Eighty-six isolates were clinical isolates collected prospectively from July to September 1998 and 22 isolates were clinical isolates with decreased susceptibility to ampicillin previously referred to the reference laboratory. Eighty-seven isolates were ampicillin-susceptible and 16 were ampicillin-resistant. Thirteen produced beta-lactamases. Among the consecutive isolates 12.8% were resistant. With each of the Rosco Neo-sensitabs containing penicillin G, 2.5 microg ampicillin and 33 microg ampicillin, 3 very major errors occurred (resistant isolates misinterpreted as susceptible) and 5-13 major errors (susceptible isolates misinterpreted as resistant). The AB biodisk containing ampicillin (10 microg) was superior to the penicillin V and G discs, i.e. only 1 very major error occurred and major and minor errors were infrequent. The cefuroxime disc identified 4/8 beta-lactamase-negative ampicillin-resistant isolates. Thus, for susceptibility testing with chocolate agar as test medium, the use of an inoculum of 10(5) colony-forming units, 10 microg ampicillin discs and interpretative zone diameters of > or = 28 mm indicating susceptibility and < or = 25 mm indicating resistance was found to produce reliable identification of ampicillin-resistant isolates of H. influenzae.

Ampicillin↗

Comparison of Etest and a tablet diffusion test with the NCCLS broth microdilution method for fluconazole and amphotericin B susceptibility testing of Candida isolates.

Three methods were compared for the susceptibility testing of yeast isolates to fluconazole and amphotericin B: two fagar diffusion methods (Etest and a tablet diffusion test) and the National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution method. Given as MIC(50)s (range), fluconazole endpoints were: for the 24 h broth microdilution test, 0.25 mg/L (0.06-32 mg/L); for the Etest, 0.38 mg/L (0.064-24 mg/L); and for the NCCLS broth microdilution test, 2 mg/L (0.06->or=64 mg/L). With breakpoints of <3 mg/L for susceptible and >16 mg/L for resistant, the Etest and the 24 h microdilution test classified the isolates in agreement with the classification obtained by the NCCLS method. Results obtained by Etest were in closer NCCLS method than those obtained with the tablet test. Amphotericin B endpoints were lower for the 24 h microdilution and Etests than MICs obtained by the NCCLS broth microdilution method. Reproducibility was high for all tests; however, disadvantages of both diffusion tests were microcolonies in the inhibition zone and dependence on stringent standardization of inoculum.

Amphotericin B↗

Penicillin pharmacodynamics in four experimental pneumococcal infection models.

Clinical and animal studies indicate that with optimal dosing, penicillin may still be effective against penicillin-nonsusceptible pneumococci (PNSP). The present study examined whether the same strains of penicillin-susceptible pneumococci (PSP) and PNSP differed in their pharmacodynamic responses to penicillin by using comparable penicillin dosing regimens in four animal models: peritonitis, pneumonia, and thigh infection in mice and tissue cage infection in rabbits. Two multidrug-resistant isolates of Streptococcus pneumoniae type 6B were used, one for which the penicillin MIC was 0.016 microg/ml and the other for which the penicillin MIC was 1.0 microg/ml. Two additional strains of PNSP were studied in the rabbit. The animals were treated with five different penicillin regimens resulting in different maximum concentrations of drugs in serum (C(max)s) and times that the concentrations were greater than the MIC (T(>MIC)s). The endpoints were bacterial viability counts after 6 h of treatment in the mice and 24 h of treatment in the rabbits. Similar pharmacodynamic effects were observed in all models. In the mouse models bactericidal activity depended on the T(>MIC) and to a lesser extent on the Cmax/MIC and the generation time but not on the area under the concentration-time curve (AUC)/MIC. Maximal bactericidal activities were similar for both PSP and PNSP, being the highest in the peritoneum and blood (approximately 6 log10 CFU/ml), followed by the thigh (approximately 3 log10 CFU/thigh), and being the lowest in the lung (approximately 1 log10 CFU/lung). In the rabbit model the maximal effect was approximately 6 log10 CFU/ml after 24 h. In the mouse models bactericidal activity became marked when T(>MIC) was > or =65% of the experimental time and C(max) was > or =15 times the MIC, and in the rabbit model bactericidal activity became marked when T(>MIC) was > or =35%, Cmax was > or =5 times the MIC, and the AUC at 24 h/MIC exceeded 25. By optimization of the Cmax/MIC ratio and T(>MIC), the MIC of penicillin for pneumococci can be used to guide therapy and maximize therapeutic efficacy in nonmeningeal infections caused by PNSP.

Animals↗

[Ciprofloxacin and pivampicillin in acute epididymitis in men above the age of 40 years].

Ciprofloxacin 500 mg orally twice daily was compared to pivampicillin 700 mg orally twice daily for 10 days in 172 men (41-85 years) with acute epididymitis. Failure of treatment occurred in 48 patients, in 15/76 (19.7%) receiving ciprofloxacin versus in 33/82 (40.2%) receiving pivampicillin (p = 0.006). Ciprofloxacin 500 mg orally twice daily is more effective than pivampicillin 700 mg orally twice daily and has fewer adverse events.

Acute Disease↗

[Staphylococcus aureus endocarditis in Denmark 1982-1991. Clinical picture, complications and antibiotic therapy in non-drug addicts].

The central S. aureus surveillance in Denmark made it possible to analyze the clinical features of S. aureus endocarditis in a nation-wide population of non-drug addicts. Almost all cases of bacteraemia with S. aureus are reported to the Staphylococcus laboratory, Copenhagen. The medical records were reviewed in cases from 1982 to 1991 in which the diagnosis of endocarditis was reported or suspected. Two hundred and sixty patients fulfilled the diagnostic criteria. In 83 patients the diagnosis of endocarditis was not suspected clinically. The overall mortality rate among those patients whose disease was diagnosed clinically was 46% and significantly associated with late congestive heart failure, age and involvement of the central nervous system. A more frequent use of echocardiography as a screening method seems essential to improve the prognosis of patients with S. aureus endocarditis. Involvement of the CNS constitutes a relative indication for early valve replacement.

Adolescent↗

Treatment with a monocolonal antibody to IL-8 attenuates the pleocytosis in experimental pneumococcal meningitis in rabbits when given intravenously, but not intracisternally.

The role of interleukin (IL)-8 as mediator in the recruitment of leucocytes into the CSF was investigated during experimental pneumococcal meningitis. Rabbits were inoculated intracisternally with approximately 10(6) CFU Streptococcus pneumoniae, and treated (i) intravenously with 5 mg of a monoclonal antibody to IL-8 (n = 7) or 5 mg of an isotype control antibody (n = 6); (ii) intracisternally with anti-IL-8, 100 microg (n = 5), 10 microg (n = 4), 1 microg (n = 4), 0.1 microg (n = 2). Ten rabbits served as untreated control group. Intravenous treatment with anti-IL-8 attenuated the pleocytosis significantly compared to untreated rabbits (P < 0.04) or rabbits treated with an isotype control antibody (P < 0.02). In contrast, intracisternal treatment with anti-IL-8 failed to attenuate the pleocytosis (P > 0.05). These results show, that IL-8 plays an important role in the recruitment of leucocytes during experimental pneumococcal meningitis, and that the functional activity of IL-8 in this process appears to be on the bloodstream side of the microvascular endothelium of the brain.

Animals↗

Development of a long-term ascending urinary tract infection mouse model for antibiotic treatment studies.

A model of ascending unobstructed urinary tract infection (UTI) in mice was developed to study the significance of the antibiotic concentration in urine, serum, and kidney tissue for efficacy of treatment of UTI in general and pyelonephritis in particular. Outbred Ssc-CF1 female mice were used throughout the study, and Escherichia coli was used as the pathogen. The virulence of 11 uropathogenic E. coli isolates and 1 nonpathogenic laboratory E. coli strain was examined. Strain C175-94 achieved the highest counts in the kidneys, and this strain was subsequently used as the infecting organism. The model gave reproducible bladder infections, i.e., bacteria were recovered from 22 of 23 control mice after 3 days, and histological examination of kidney tissue showed that of 14 infected kidneys, 7 (50%) showed major histological changes, whereas 3 of 36 uninfected kidneys showed major histological changes (P = 0.018). Once the model was established, the efficacies of different doses of cefuroxime and gentamicin, corresponding to active concentrations in urine only or in urine, serum, and kidney tissue simultaneously, were examined. All cefuroxime doses resulted in significantly lower counts in urine than control treatments, but the dose which produced concentrations of cefuroxime only in urine and not in serum or kidney tissue had no effect on kidney infection. Even low doses of gentamicin (0.05 mg/mouse) resulted in concentrations in renal tissue for prolonged times due to accumulation. All gentamicin doses had a significant effect (compared to the effect of the control treatment) on bacterial counts in urine and kidneys. The antibiotic effect on bacterial counts in bladders was negligible for unknown reasons. Use of the mouse UTI model is feasible for study of the effect of an antibiotic in the urinary system, although the missing antibacterial effect in the bladder needs further evaluation.

Animals↗

Inhibition of leukocyte entry into the brain by the selectin blocker fucoidin decreases interleukin-1 (IL-1) levels but increases IL-8 levels in cerebrospinal fluid during experimental pneumococcal meningitis in rabbits.

The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis. In the present study, the effect of fucoidin treatment on the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-8 into the CSF was investigated. Rabbits (n = 7) were treated intravenously with 10 mg of fucoidin/kg of body weight every second hour starting 4 h after intracisternal inoculation of approximately 10(6) CFU of Streptococcus pneumoniae type 3 (untreated control group, n = 7). CSF samples were obtained every second hour during a 16-h study period. Treatment with fucoidin caused a consistent and significant decrease in CSF IL-1 levels (in picograms per milliliter) between 12 and 16 h (0 versus 170, 0 versus 526, and 60 versus 1,467, respectively; P < 0.02). A less consistent decrease in CSF TNF-alpha levels was observed in the fucoidin-treated group, but with no significant difference between the two groups (P > 0.05). In contrast, there was no attenuation in CSF IL-8 levels. Indeed, there was a significant increase in CSF IL-8 levels (in picograms per milliliter) in the fucoidin-treated group at 10 and 12 h (921 versus 574 and 1,397 versus 569, respectively; P < 0.09). In conclusion, our results suggest that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-alpha into the CSF during pneumococcal meningitis, whereas IL-8 may be produced by local cells within the brain.

Animals↗

Risk factors for hospital-acquired Staphylococcus aureus bacteremia.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) acquired in hospitals continues to be a frequent and serious complication to hospitalization, and no previous case-control studies dealing with risk factors of this severe disease are available. METHODS: Based on a 1-year prospective analysis, the data from all patients with hospital-acquired SAB admitted to 4 hospitals in Copenhagen County, Denmark, from May 1, 1994, through April 30, 1995, were evaluated. Eighty-five patients with hospital-acquired SAB were matched to 85 control patients with a similar primary diagnosis at admission (matched controls). Of these, 62 patients with hospital-acquired SAB were compared with 118 other patients with a similar time of admission, who were randomly selected with no clinical evidence of SAB (unmatched controls). RESULTS: The incidence of hospital-acquired SAB was 0.71 per 1000 hospital admissions. The presence of a central venous catheter (odds ratio, 6.9; 95% confidence interval [CI], 2.8-17.0), anemia (odds ratio, 3.3; 95% CI, 1.4-7.6), and hyponatremia (odds ratio, 3.3; 95% CI, 1.5-7.0) was significantly associated with hospital-acquired SAB in a conditional and a usual logistic regression analysis. Nasal carriage was not an independent risk factor, but nasal carriers among patients in surgery (odds ratio, 4.0; 95% CI, 1.3-13.0) had a significantly higher risk for hospital-acquired SAB compared with matched and unmatched controls. The presence of hospital-acquired SAB increased the mortality rate 2.4-fold (95% CI, 1.1-5.2). CONCLUSIONS: The presence of a central venous catheter is an important risk factor, and hyponatremia and anemia are associated with the development of hospital-acquired SAB. Furthermore, hospital-acquired SAB in itself increases mortality.

Adolescent↗

Clinical features of Staphylococcus aureus endocarditis: a 10-year experience in Denmark.

BACKGROUND: Both morbidity and mortality resulting from Staphylococcus aureus endocarditis are known to be high, and the incidence of this disease seems to increase. The Statens Serum Institut, Copenhagen, Denmark, made it possible for us to analyze the clinical features of S aureus endocarditis in a nation-wide population of non-drug addicts. METHODS: Almost all Danish cases of bacteremia due to S aureus are reported to the Staphylococcus laboratory, Statens Serum Institut. The medical records were reviewed in cases reported from 1982 to 1991 in which the diagnosis of endocarditis was reported or suspected. RESULTS: A total of 260 patients, 145 males and 115 females, fulfilled the diagnostic criteria. The median age was 67.5 years. In 83 patients, the diagnosis of endocarditis was not suspected clinically. The overall mortality rate among those patients whose disease was diagnosed clinically was 46%. Among the subset of patients who received medical therapy only and appropriate antistaphylococcal treatment, mortality was significantly associated with late congestive heart failure, age, and involvement of the central nervous system. CONCLUSIONS: A raised awareness of the paucity of clinical findings and a more frequent use of echocardiography as a screening method seem essential to improve the prognosis of patients with S aureus endocarditis. Involvement of the central nervous system constitutes a relative indication of early valve replacement.

Adolescent↗

Presence of erm gene classes in gram-positive bacteria of animal and human origin in Denmark.

A classification of the different erm gene classes based on published sequences was performed, and specific primers to detect some of these classes designed. The presence of ermA (Tn554), ermB (class IV) and ermC (class VI) was determined by PCR in a total of 113 enterococcal, 77 streptococcal and 68 staphylococcal erythromycin resistant isolates of animal and human origin. At least one of these genes was detected in 88% of the isolates. Four isolates contained more than one erm gene. ermB dominated among the enterococci (88%) and streptococci (90%) and ermC among staphylococci (75%) with ermA (Tn554) present in some isolates (16%). Variations in the presence of the different genes when comparing staphylococcal isolates of human and animal origin were observed.

Animals↗

A double-blind, randomized, controlled multicentre study to compare the efficacy of ciprofloxacin with pivampicillin as oral therapy for epididymitis in men over 40 years of age.

OBJECTIVE: To compare the efficacy and safety of ciprofloxacin 500 mg orally twice daily with pivampicillin 700 mg orally twice daily for 10 days in men with acute epididymitis and over 40 years of age. PATIENTS AND METHODS: The study comprised 172 men who entered a prospective, controlled, randomized, double-blind, trial of pivampicillin and ciprofloxacin. The median (range) age of the 158 patients eligible for the efficacy analysis was 58 (41-85) years; 41% had previously had a urinary tract infection and 27% had previously had epididymitis. Only one patient had a urethral catheter and 38% were sexually active. About half of the patients were admitted to hospital. RESULTS: No bacteria could be cultured from samples in 53% of the patients; Escherichia coli could be cultured from 35% and the remaining isolates were the expected urinary pathogens. None of the patients had Gonococci and only one in each group had Chlamydia. Mycoplasma hominis was detected in three patients only and M. genitalium was detected in three, while Ureaplasma was detected in 24 (15%). The treatment failed in 48 patients; in 15 of 76 (20%) receiving ciprofloxacin and in 33 of 82 (40%) receiving pivampicillin. This corresponds to a reduction in the risk of failure of 20.5% (95% confidence limits 6.6-40.2%, P=0. 006). The principal cause of failure was an unsatisfactory clinical response requiring changed antibiotic treatment in 27 patients; adverse events were responsible for failure in 14. The in vitro resistance of cultured bacteria was low in both groups, at approximately 4%. Adverse events, mainly gastro-intestinal, occurred in 17 of 83 (21%) patients starting on ciprofloxacin and in 33 of 89 (37%) receiving pivampicillin (P=0.04). CONCLUSION: For epididymitis in men over the age of 40 years ciprofloxacin 500 mg orally twice daily is more effective than pivampicillin 700 mg orally twice daily. Furthermore, ciprofloxacin has a lower incidence of adverse events.

Administration, Oral↗

Detection of clinical vancomycin-resistant enterococci in Denmark by multiplex PCR and sandwich hybridization.

Since the first cases of human infection with vancomycin-resistant enterococci (VRE) were reported in the late eighties, there has been a dramatic increase in VRE all over the world. So far, there have not been any reports of clinical VRE in Denmark. In this study we have investigated 131 clinically important enterococci sent to Statens Serum Institut from all over Denmark during the period July 1995 to May 1997. The susceptibility to vancomycin, teicoplanin, ampicillin and gentamicin was tested by the agar dilution method. In addition, two methods were developed to detect the different genotypes of glycopeptide resistance described in enterococci: a multiplex PCR assay for detection of vanA, vanB, vanC-1, vanC-2/3 ligase genes including 16S rRNA gene control primers and a sandwich hybridization assay to confirm vanA and vanB PCR-positive strains. The highest frequency of resistance to the tested antibiotics was found in the Enterococcus faecium group. Four strains were found with acquired resistance to glycopeptides: one E. faecium and one E. gallinarum were vanA positive, and two E. faecium isolates were vanB positive. These strains were isolated from different hospitals in different periods of time, and all patients recovered from their infections with VRE. Today, the PCR and sandwich hybridization methods are used for screening of vancomycin-resistant enterococci in humans as part of the Danish surveillance programme.

Ampicillin↗