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M C Arendrup,
E Dzajic,
R H Jensen, H K Johansen,
P Kjaeldgaard,
J D Knudsen,
L Kristensen,
C Leitz,
L E Lemming,
L Nielsen,
B Olesen,
F S Rosenvinge,
B L Røder,
H C Schønheyder
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ABSTRACT: Significant changes in the management of fungaemia have occurred over the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. These changes may impact the epidemiology of fungaemia. We present nationwide data for Denmark from 2010 to 2011. A total of 1081 isolates from 1047 episodes were recorded in 995 patients. The numbers of patients, episodes and recovered isolates increased by 13.1%, 14.5% and 14.1%, respectively, from 2010 to 2011. The incidence rate was significantly higher in 2011 (10.05/100 000) than in 2010 (8.82/100 000), but remained constant in the age groups 0-79 years. The incidence rate was highest at the extremes of age and in males. Candida albicans accounted for 52.1% but declined during 2004-11 (p 0.0155). Candida glabrata accounted for 28% and increased during 2004-2011 (p <0.0001). Candida krusei, Candida tropicalis and Candida parapsilosis remained rare (3.3-4.2%). The species distribution changed with increasing age (fewer C. parapsilosis and more C. glabrata) and by study centre. Overall, the susceptibility rates were: amphotericin B 97.3%, anidulafungin 93.8%, fluconazole 66.7%, itraconazole 69.6%, posaconazole 64.2% and voriconazole 85.0%. Acquired echinocandin resistance was molecularly confirmed in three isolates. The use of systemic antifungals doubled over the last decade (2002-2011) (from 717 000 to 1 450 000 defined daily doses/year) of which the vast majority (96.9%) were azoles. The incidence of fungaemia continues to increase in Denmark and is associated with a decreasing proportion being susceptible to fluconazole. Changes in demography, higher incidence in the elderly and higher antifungal consumption can at least in part explain the changes.
Clinical Microbiology and Infection 04/2013; · 4.54 Impact Factor
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ABSTRACT: Despite intensive eradication therapy, some CF patients with early Pseudomonas aeruginosa infection rapidly develop a chronic infection. To elucidate factors associated with this persistence, bacterial characteristics of early P. aeruginosa isolates were analysed that were either eradicated rapidly or persisted despite multiple antimicrobial treatments. Eighty-six early infection episodes were studied. First P. aeruginosa isolates from patients with eradication (36) or persistent infection (16) were included; isolates from patients with intermittent infection (34) were omitted from the study. Virulence assays, antimicrobial resistance, cytotoxicity and mutation frequencies were analysed in vitro. P. aeruginosa was genotyped by SNP-array. Transcriptomic profiles of two eradicated and two persistent strains were compared. Nineteen per cent of patients developed persistent infection; 42% achieved eradication. Secretion of virulence factors and mutation frequencies were highly variable among both eradicated and persistent isolates and were not different between the groups. Cytotoxicity was present in 57% of eradicated vs. 100% of persistent isolates (p <0.01). None of the isolates were resistant to antibiotics. The isolates were genotypically highly diverse. Multivariate analysis showed that in vitro determined bacterial characteristics could not predict persistence after first P. aeruginosa infection. Preliminary transcriptomic data showed increased expression of some genes related to a metabolic pathway. The early onset of chronic infection was not associated with (in vitro determined) bacterial characteristics only. Although the persistent isolates were more often cytotoxic, for the individual patient it was not possible to predict the risk of persistence based on bacterial characteristics. Unknown factors such as host-pathogen and pathogen-pathogen interactions should be further explored.
Clinical Microbiology and Infection 08/2011; 18(6):567-74. · 4.54 Impact Factor
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ABSTRACT: Different molecular methods for the discrimination of Candida glabrata, C. bracarensis and C. nivariensis were evaluated and the prevalence of these species among Danish blood isolates investigated. Control strains were used to determine fragment length polymorphism in the ITS1, ITS2, ITS1-5.8S-ITS2 regions and in the D1/D2 domain of 26S rDNA using primers designed for this study. A total of 133 blood isolates previously identified as C. glabrata were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the peptide nucleic acid-fluorescent in situ hybridization (PNA-FISH) method. The size of ITS1 allowed differentiation between C. glabrata (483), C. nivariensis (361) and C. bracarensis (385), whereas the ITS2 region was of similar size in C. nivariensis (417) and C. glabrata (418). Sequence analysis of the ITS region suggested that many restriction enzymes were suitable for RFLP differentiation of the species. Enzymatic digestion of the D1/D2 domain with TatI produced unique band sizes for each of the three species. PCR-RFLP and PNA-FISH were in agreement for all of the isolates tested. None of the 133 Danish blood isolates were C. nivariensis or C. bracarensis. Fragment size polymorphism of ITS1 and RFLP of the D1/D2 domain or the ITS region are useful methods for the differentiation of the species within the C. glabrata group. C. bracarensis and C. nivariensis are rare among Danish C. glabrata blood isolates.
European Journal of Clinical Microbiology 05/2011; 30(11):1409-16. · 2.86 Impact Factor
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ABSTRACT: A three-month laboratory-based prospective survey was conducted at four major university hospitals covering one-third of the Danish population in order to determine the prevalence, significance, and susceptibility pattern of aspergilli in airway samples. Samples received in January-March 2007 for routine microbiologic investigation were examined for Aspergillus following routine procedures and with extended incubation (5 days). Identification was done by morphologic criteria and susceptibility testing using EUCAST method for azoles and amphotericin B E-test. Invasive aspergillosis (IA) was evaluated using modified EORTC/MSG criteria. A total of 11,368 airway samples were received. Growth of Aspergillus spp. was found in 129 and 151 patients using routine and extended incubation, respectively. Three patients had proven IA (2%), 11 probable (7%), four had allergic bronchopulmonary aspergillosis (ABPA) (3%), but the majority was colonised (88%). Underlying conditions were cystic fibrosis in 82 patients (55%), chronic obstructive pulmonary disease in 19 (13%) and haematological disorder in 11 (7%). Twenty-six patients (18%) were at intensive care unit and 69 (47%) received steroid treatment. Azole MICs were elevated for five isolates as follows (itraconazole, posaconazole, voriconazole MICs [mg/L]): two A. fumigatus isolates (>4; >4; 2 and >4; 0.125; 1), one A. lentulus isolate (2; 2; 0.5) and two A. terreus isolates (2; 2; 2 and 2; 0.125; 1). For four isolates the amphotericin B MIC was >1 μg/ml (3/112 A. fumigatus, 1/2 A. terreus). In conclusion, Aspergillus appears to be an important pathogen in Denmark. Elevated itraconazole MICs were detected in 4% of the isolates including a multi-azole resistant isolate.
European Journal of Clinical Microbiology 05/2011; 30(11):1355-63. · 2.86 Impact Factor
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ABSTRACT: The clinical consequences of chronic Stenotrophomonas maltophilia infection in cystic fibrosis (CF) patient are still unclear.
All patients treated in the Copenhagen CF centre (N=278) from 1 January 2008 to 31 December 2009 were included. Each patient chronically infected with S. maltophilia for at least 2 years without any other chronic Gram-negative infection were matched to two non-infected CF controls.
Twenty-one patients were chronically infected with S. maltophilia during the 2-year study period. Fifteen were infected for at least 2 years. The patients in the S. maltophilia group had a steeper decline (-3.2%/year vs. -0.3%/year) in FEV(1) compared to the non-infected CF controls (P=0.03). The rate of decline was the same as observed 3 years before the patients became chronically infected.
Chronic infection with S. maltophilia does not lead to a steeper decline in lung function when compared to the period before chronic infection.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 04/2011; 10(5):318-25. · 3.19 Impact Factor
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ABSTRACT: Since 2001, long-term, low-dose azithromycin treatment has been used for CF patients chronically infected with Pseudomonas aeruginosa in the Copenhagen CF centre. Our study investigates changes in incidence of colonization with Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and changes in macrolide sensitivity in these microorganisms during azithromycin treatment.
CF patients treated continuously with azithromycin for at least 3 months were included. Results of microbiological examination, including phage typing results of S. aureus, obtained during treatment were compared to results obtained 2 years before treatment.
70 patients (median age 29.1 years) treated for a median of 4 years (range 0.7-5.1) were included. Before treatment, 44 patients had at least one culture positive for S. aureus compared to 25 patients during treatment (p<0.01). Mean percentage of sputum samples with growth of S. aureus decreased from 12.1% (range 0-82.6%) before treatment to 6.1% (range 0-93.2) during treatment (p<0.0006). Prevalence's of H. influenzae and S. pneumoniae also decreased significantly. Fifteen of 214 isolates (7%) of S. aureus were macrolide resistant before treatment, increasing to 95 of 181 isolates (52.5%) during treatment (p<0.001). Macrolide resistant strains were found in 3 of 44 S. aureus colonized patients before treatment and in 11 of 25 patients at some time during treatment (p<0.03), all belonging to different phage types. First resistant S. aureus isolate was isolated after a median treatment duration of 1.5 years (range 0.3-2.9). No MRSA were isolated. Only 1 macrolide resistant isolate of M. catarrhalis was found during treatment. No macrolide resistance was found in H. influenzae or S. pneumoniae.
Long-term, low-dose treatment with azithromycin in CF patients leads to reduced prevalence of S. aureus, S. pneumoniae, and H. influenzae, but increased macrolide resistance in S. aureus. Reduction in the prevalence of S. aureus will make increasing macrolide resistance clinically insignificant in these patients.
Journal of Cystic Fibrosis 10/2008; 8(1):58-62. · 3.19 Impact Factor
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ABSTRACT: Pseudomonas aeruginosa is a pathogen that often infects patients who are either immunocompromised or have local defects in host defences. It is known that cystic fibrosis (CF) patients are sometimes infected with certain clonal isolates. It is not clear whether these clonal isolates also infect non-CF patients and whether clonality of isolates occurs in other patient groups. The aim of this study was to investigate P. aeruginosa diversity and the occurrence of clones within five distinct paediatric patient groups susceptible to P. aeruginosa infection. P. aeruginosa isolates were cultured from 157 patients (CF first infection (CF-1 group) (29); CF chronic infection (CF-chronic group) (27); urinary tract infection (34); chronic suppurative otitis media (43); and intensive-care hospitalization/immunodeficiency (24)). All 202 phenotypically different isolates were tested for antimicrobial resistance and further typed by pulsed-field gel electrophoresis. Simpson's diversity index was calculated for the five groups. CF-chronic patients carried the highest number of distinct P. aeruginosa phenotypes and genotypes per culture. Isolates from the CF-chronic group were significantly less diverse than those from the other groups. A group of clonal isolates was observed among patients from the CF-chronic and CF-1 groups. These or different clonal isolates were not encountered among the three other patient groups. No characteristic resistance pattern could be identified among isolates from the distinct patient groups and among the clonal isolates. In conclusion, isolates of the CF-chronic group were less diverse than those in the other patient groups with P. aeruginosa infection; clonal isolates were not encountered in non-CF patients. Transmission of clonal CF isolates to other patient groups was not observed.
Clinical Microbiology and Infection 09/2008; 14(10):935-41. · 4.54 Impact Factor
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ABSTRACT: A semi-national laboratory-based surveillance programme for fungaemia was initiated in 2003 that now covers c. 3.5 million inhabitants (64%) of the Danish population. In total, 1089 episodes of fungaemia were recorded during 2004-2006, corresponding to an annual incidence of 10.4/100 000 inhabitants. The annual number of episodes increased by 17% during the study period. Candida spp. accounted for 98% of the fungal pathogens. Although Candida albicans remained predominant, the proportion of C. albicans decreased from 66.1% in 2004 to 53.8% in 2006 (p <0.01), and varied considerably among participating departments, e.g., from 51.1% at a university hospital in Copenhagen to 67.6% in North Jutland County. Candida glabrata ranked second, and increased in proportion from 16.7% to 22.7% (p 0.04). Candida krusei was isolated rarely (4.1%), but the proportion doubled during the study period from 3.2% to 6.4% (p 0.06). MIC distributions of amphotericin B and caspofungin were in close agreement with the patterns predicted by species identification; however, decreased susceptibility to voriconazole, defined as an MIC of >1 mg/L, was detected in one (2.5%) C. glabrata isolate in 2004 and in 12 (14.0%) isolates in 2006 (p 0.03). Overall, the proportion of isolates with decreased susceptibility to fluconazole exceeded 30% in 2006. The incidence of fungaemia in Denmark was three-fold higher than that reported from other Nordic countries and is increasing. Decreased susceptibility to fluconazole is frequent, and a new trend towards C. glabrata isolates with elevated voriconazole MICs was observed.
Clinical Microbiology and Infection 05/2008; 14(5):487-94. · 4.54 Impact Factor
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ABSTRACT: Mannan-binding lectin (MBL) is a collectin plasma protein activating the lectin pathway of the complement system, enhancing opsonophagocytosis and modulating the cytokine response to inflammation. Deficiency of MBL, caused by structural mutations or promoter polymorphisms in the MBL2 gene, has been associated with increased susceptibility to infection and autoimmune disease. Thus, as infective endocarditis remains a severe disease requiring intensive and long-term treatment with antibiotics, we examined whether there was an association between MBL and clinical outcome in 39 well-characterized patients with infective endocarditis. Five patients (13%) had MBL concentrations < 100 microg/l and were considered MBL-deficient. This proportion was similar to that in a healthy control group of blood donors. Mortality 3 months after diagnosis was 20% in patients with MBL-deficiency and 9% in patients with normal MBL. The 5-year mortality was 80% and 25%, respectively. MBL-deficiency was on univariate survival statistics associated with significantly higher mortality on follow-up (P=0 x 03). In conclusion, this is the first report of an association between MBL-deficiency and survival in infective endocarditis. The present observation is important, as replacement therapy in MBL-deficient patients is possible. For certain high-risk subgroups, it opens new perspectives for improvement of treatment and outcome in infective endocarditis.
Clinical & Experimental Immunology 05/2007; 148(1):101-5. · 3.36 Impact Factor
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ABSTRACT: Persons expressing the genetic disease cystic fibrosis (CF) suffer from a high risk of developing impaired glucose tolerance and diabetes. The development of diabetes in CF has been attributed, in the past, to the destruction of pancreatic islets and their resident beta-cells secondary to the destruction of the surrounding tissue by mechanical clogging of the pancreatic exocrine ducts. However, the discovery that autoimmunity to the 60-kDa heat shock protein (hsp60) may cause type I diabetes in NOD mice raises the possibility that hsp60 autoimmunity may be involved in CF diabetes too; could the hyperimmunization to bacterial hsp60 characteristic of CF spread to self-hsp60 and hence to autoimmune diabetes? We now report that rising levels of IgG autoantibodies to hsp60 do indeed precede the appearance of glucose intolerance and diabetes in CF patients. We produced a recombinant human pancreatic hsp60 protein and investigated the IgG antibody response to hsp60 in prediabetic and non-diabetic patients with CF. To detect hsp60 autoantibodies in the presence of high levels of antibodies to bacterial hsp60, we absorbed test sera with the 60-kDa GroEL of Pseudomonas aeruginosa and used an immunostaining technique. Using this technique, 32 prediabetic CF patients were evaluated over a five-year period, three years, on the average, before the onset of glucose intolerance. We found that a significant increase in hsp60 autoantibody preceded impaired glucose tolerance (P=0.042, n=17), diabetes (P=0.011, n=15) and glucose intolerance (P=0.005, n=32). As has been observed in NOD mice and in type I diabetic patients, the hsp60 autoantibodies decline at the outbreak of glucose intolerance in the CF patients. The association of CF diabetes with the rise and fall of hsp60 autoimmunity suggests that the pathogenesis of the diabetes may not be merely mechanical, but arise in the wake of bacterial hyperimmunisation.
Journal of Autoimmunity 10/2001; 17(2):165-72. · 7.37 Impact Factor
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ABSTRACT: In recent years research has focused on a possible connection between bacterial infection and development of diabetes mellitus. In this study, serum antibody responses against bacterial antigens in diabetic and nondiabetic patients with cystic fibrosis (CF) were evaluated. The first part of the study included 252 CF patients of whom 46 (18 %) had diabetes. This study showed that precipitating antibodies (precipitins) against Pseudomonas aeruginosa and other bacteria in crossed immunoelectrophoresis, and IgG antibodies against a 60-kD GroEL of P. aeruginosa, were highly variable and positively correlated with age. Patient material matched for age and sex showed no significant difference between diabetic and nondiabetic CF patients in precipitins or IgG antibodies to P. aeruginosa GroEL. Two longitudinal studies of 9 and 5 y using retrospectively selected sera from 29 prediabetic and 29 cross-matched nondiabetic CF patients were performed. As to precipitins against P. aeruginosa, we found no difference between the prediabetic and the nondiabetic group of patients during the study period. The study revealed, however, a significant increase of 24.6 % (p = 0.008) of IgG antibodies against P. aeruginosa 60-kD GroEL, 3-12 mo before the onset of diabetes in patients with CF, compared with an overall increase of 5 % to 6 % per year in both groups during the observation period. This study shows that diabetes in CF appears after a peak of serum IgG antibodies against GroEL and indicates that development of diabetes in CF patients may not only be caused by a progressive fibrosis of the pancreatic tissue, but may be augmented by a short-term specific immunologic reaction, initially triggered by an ongoing and progressive pulmonary infection.
Pediatric Research 04/2001; 49(3):423-8. · 2.70 Impact Factor
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ABSTRACT: The combination of beta-lactam antibiotics and macrolides is often recommended for the initial empirical treatment of acute pneumonia in order to obtain activity against the most important pathogens. Theoretically, this combination may be inexpedient, as the bacteriostatic agent may antagonize the effect of the bactericidal agent. In this study, the possible interaction between penicillin and erythromycin was investigated in vitro and in vivo against four clinical isolates of Streptococcus pneumoniae with MICs of penicillin ranging from 0.016 to 0.5 mg/L and of erythromycin from 0. 25 to >128 mg/L. In vitro time-kill curves were generated with clinically relevant concentrations of penicillin (10 mg/L) and erythromycin (1 mg/L), either individually or in combination. Antagonism between penicillin and erythromycin was observed for the four isolates. In vivo interaction was investigated in the mouse peritonitis model. After intraperitoneal inoculation, penicillin and erythromycin were given either individually or in combination. For two of the four isolates, mortality was significantly higher in the groups treated with the combination of penicillin and erythromycin than in the groups treated with penicillin alone [32/36 (86%) vs. 3/12 (25%), P<0.05; and 24/36 (67%) vs. 3/12 (25%), P<0.05, respectively]. Using the mouse peritonitis model, in vivo time-kill curves showed that there was antagonism between erythromycin and penicillin for the examined isolate. The antagonism demonstrated in vitro and in vivo between penicillin and erythromycin suggests that ss-lactam antibiotics and macrolides should not be administered together unless pneumococcal infection is ruled out.
Journal of Antimicrobial Chemotherapy 01/2001; 46(6):973-80. · 5.07 Impact Factor
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ABSTRACT: The concentrations of beta-lactam antibiotics after standard doses were measured in blood and apocrine (axilla) and eccrine (forearm) sweat from six adult healthy persons. All persons had ceftazidime (axilla, 28.4 microg/ml; forearm, 11 microg/ml) and ceftriaxone (axilla, 8.9 microg/ml; forearm, 2.5 microg/ml) in sweat, and one person had cefuroxime in sweat (axilla, 7.8 microg/ml) (all data are mean peaks). Three persons had benzylpenicillin (axilla, 2.6 to 0.1 microg/ml) and one had phenoxymethylpenicillin (axilla, 0.4 microg/ml) in sweat. Excretion of beta-lactam antibiotics in the sweat may explain why staphylococci so rapidly become resistant to these drugs.
Antimicrobial Agents and Chemotherapy 11/2000; 44(10):2855-7. · 4.84 Impact Factor
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ABSTRACT: To study the effect of two kinds of Chinese herbal medicine, Radix angelicae sinensis (RAS) ([Chinese characters: see text]) and Shuanghuanglian (SHL) ([Chinese characters: see text]) on chronic Pseudomonas aeruginosa (PA) lung infection in a rat model mimicking cystic fibrosis (CF).
Rats were divided into RAS, SHL and control groups. All rats were challenged intratracheally with alginate embedded PA and the treatments with herbal medicine started on the same day of challenge. The drugs were administered subcutaneously once a day for ten days and the control group was treated with sterile saline. The rats were sacrificed two weeks after challenge.
Significantly improved lung bacterial clearance (P < 0.05, P < 0.01) and milder macroscopic lung pathology (P < 0.005) were found in the two treated groups compared to the control group. In the SH treated group, the neutrophil percent in the peripheral blood leukocytes (P < 0.05), the anti-PA IgG level in serum (P < 0.05), the incidence of lung abcesses (P < 0.005) and the incidence of acute lung inflammation (P < 0.05) were significantly lower than in the control group. The RAS treatment reduced fever (P < 0.05), decreased the incidence of lung abcesses (P < 0.005) and lung mast cell number (P < 0.05), and lowered anti-PA IgG1 level in serum (P < 0.05) when compared to the control group. The anti-PA bacterial activity test in SHL was weakly positive whereas in RAS it was negative.
The treatment with both herbal medicines could increase the resistance of the rats against PA lung infection and they therefore might be potential promising drugs for stimulation of the immnune system in CF patients with chronic PA lung infection.
Chinese Medical Sciences Journal 06/2000; 15(2):83-8.
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ABSTRACT: A prospective, randomised, single-blind comparative trial was carried out to determine whether double beta-lactam treatment with pivampicillin plus pivmecillinam is more effective than pivampicillin alone in the treatment of recurrent and chronic lung infections with Haemophilus influenzae in patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Fifty-six children and young adults with COPD or CF were randomised to the clinical study. The patients were allocated at random to receive perorally either pivmecillinam, 40 mg/kg/day, combined with pivampicillin, 50 mg/kg/day, or pivampicillin 50 mg/kg/day alone for 14 days. A cross-over pharmacokinetic study using the same drugs was carried out in 10 CF patients to determine the antibiotic concentrations in serum and sputum after a single dose of each drug. The clinical study showed no significant differences in clinical scoring, lung function tests or adverse events after treatment with pivampicillin plus pivmecillinam or pivampicillin alone. Follow-up microbiological evaluation 2 and 6 weeks after the end of treatment showed that the offending pathogen was eradicated in 68% of the patients treated with pivampicillin plus pivmecillinam and in 67% of the patients treated with pivampicillin alone. Reinfection with another biotype was more common in the combination group (50% vs. 21%) than in the pivampicillin group. In the pharmacokinetic study the median peak serum concentration occurred two hours after intake of tablets. The efficacy of double beta lactam treatment in lung infections with H. influenzae appears to be equivalent to that of ampicillin on clinical lung symptoms, lung function tests, adverse effects and bacteriology.
Current Medical Research and Opinion 02/1999; 15(4):300-9. · 2.38 Impact Factor
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ABSTRACT: To observe the effect of ginseng extracts on a rat model of chronic Pseudomonas aeruginosa (PA) pneumonia.
Subcutaneous injection with four different doses of ginseng aqueous extracts to the model rats for two weeks.
Milder macroscopic lung pathology and lower incidence of lung abscesses were found in all the four groups received different doses of ginseng treatment compared to the control group (P < 0.05). Histopathology of the lungs was negatively correlated with the ginseng doses (r = -0.95, P < 0.01). The mast cell number in the lung foci in group I, II and IV was significantly lower than that in the control group (P < 0.05). Bacterial clearance in group II and group III was enhanced significantly (P < 0.05) compared with that in the control group. The specific antibody responses were down-regulated in group II, III and IV (P < 0.01), and IgM level in group I was lower compared to the control group (P < 0.01). Serum IgM level was positively correlated with the ginseng doses (r = 0.93, P < 0.05). IgG2a titer in group I was higher than that in the control group (P < 0.05). Serum IgG2a level was positively correlated with the ginseng doses (r = 0.90, P < 0.02). Two weeks after PA lung infection, the serum level of IgG against PA, aeruginosa alginate in group I, II, and III was higher than that in the control and group IV (P < 0.05), and the anti-alginate IgA level in group I, III and IV was lower than that in the control (P < 0.05).
The ginseng dose of 2.5 mg/kg was the best dosage in the present study, and it showed an effect of stimulating T helper type I response.
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 10/1998; 18(9):546-9.
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ABSTRACT: Differences in the course of pulmonary disease in cystic fibrosis (CF) may be altered by different treatment strategies in different CF centers. The Copenhagen clinic uses scheduled, regular and very aggressive treatment of lung infection. The Toronto clinic treats pulmonary infection with oral, inhaled, or intravenous antibiotics, and has emphasized aggressive nutritional therapy. This study compared the clinical status of CF patients treated in the two centers (Toronto, Canada, n=302, and Copenhagen, Denmark, n=214) using a cross-sectional design in terms of Pseudomonas aeruginosa (PA) and Burkholderia cepacia (BC) lung infections, pulmonary function, and levels of PA and BC precipitating antibodies (precipitins). Median ages were similar, but the age distribution was significantly different, with a higher proportion of patients under 10 and > or = 25 years in Toronto, and higher proportion of patients 11-24 years of age in Copenhagen. A higher number of female patients was observed in Copenhagen than in Toronto. Seventy-nine percent of Copenhagen patients, and 52% of Toronto patients were deltaF508 homozygous. Of all the patients, 20.1% of Copenhagen patients and 38% of Toronto patients were deltaF508 heterozygous. Ten percent of Toronto patients had two uncommon mutations. Pulmonary function and nutritional status in both groups were similar despite varying treatment strategies. The prevalence of PA was lower in Danish children and higher in Danish adults than in Canada. These differences are probably due to cohort isolation, which was introduced in Copenhagen in 1981. The prevalence of BC was higher in Toronto than in Copenhagen patients at all ages. In both centers, the number of PA and BC precipitins increased with age in patients chronically infected with PA and BC, respectively, and the number of both PA and BC precipitins rose with declining lung function. This study suggests that the clinic populations had similar pulmonary and nutritional statuses despite differing clinic antibiotic treatment strategies. Microbial colonization seemed to differ, at least in part, because of differences in cohort isolation strategies. Early, aggressive anti-pseudomonal chemotherapy may have reduced pseudomonal colonization among younger patients in Copenhagen. Future studies will be required to assess the impact of this on this cohort's outcome.
Pediatric Pulmonology 08/1998; 26(2):89-96. · 2.53 Impact Factor
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ABSTRACT: The chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) is characterized by a pronounced antibody response and microcolonies surrounded by numerous polymorphonuclear neutrophils (PMN). Poor prognosis is correlated with a high antibody response to P. aeruginosa antigens. An animal model of this infection was established in two strains of mice: C3H/HeN and BALB/c, generally known as Th1 and Th2 responders, respectively, which were challenged with alginate-embedded P. aeruginosa. Mortality was significantly lower in C3H/HeN compared to BALB/c mice (p < 0.025). P. aeruginosa was cleared more efficiently in C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology (p < 0.02), and we found significantly fewer microabscesses in C3H/HeN mice than in BALB/c mice (p < 0.005). In supernatants from P. aeruginosa antigen and concanavalin A-stimulated spleen cells from the two strains of mice, the interferon-(IFN-) gamma levels were higher, whereas IL-4 levels were lower in C3H/HeN mice than in BALB/c mice. The implications of these findings for CF patients with chronic P. aeruginosa lung infection are discussed.
Apmis 12/1997; 105(11):838-42. · 1.99 Impact Factor
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ABSTRACT: In an athymic rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF), we studied the effects of the Chinese herb ginseng. Rats were treated subcutaneously with ginseng extracts (25 mg/kg) once a day for 10 days after challenge with P. aeruginosa embedded in alginate beads. We found that ginseng treatment significantly reduced bacterial load (p < 0.02) and the number of mast cells in the lungs (p < 0.01). Furthermore, it decreased the severity of lung pathology (p < 0.02) and lowered serum anti-P. aeruginosa IgM and IgA antibody levels (p < 0.004, p < 0.04) compared to the control group. The down-regulated specific humoral immunity in the ginseng-treated group and the fact that athymic rats have a severely compromised T-cell-mediated immune reactivity due to the absence of thymus might suggest an activation of innate immunity after ginseng treatment. Our findings indicate that ginseng treatment increases the resistance of the athymic rats to P. aeruginosa lung infection. We therefore think that ginseng has promising potential as a natural medicine for stimulation of the immune system in CF patients with chronic P. aeruginosa lung infections.
Apmis 06/1997; 105(6):438-44. · 1.99 Impact Factor
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ABSTRACT: The predominant pathogen in patients with cystic fibrosis (CF) is Pseudomonas aeruginosa, which results in a chronic lung infection associated with progressive pulmonary insufficiency. In a rat model of chronic P. aeruginosa pneumonia mimicking that in patients with CF, we studied whether the inflammation and antibody responses could be changed by treatment with the Chinese herbal medicine ginseng. An aqueous extract of ginseng was injected subcutaneously, and cortisone and saline were used as controls. Two weeks after challenge with P. aeruginosa, the ginseng-treated group showed a significantly improved bacterial clearance from the lungs (P < 0.04), less severe lung pathology (P = 0.05), lower lung abscess incidence (P < 0.01), and fewer mast cell numbers in the lung foci (P < 0.005). Furthermore, lower total immunoglobulin G (IgG) levels (P < 0.01) and higher IgG2a levels (P < 0.025) in serum against P. aeruginosa sonicate and a shift from an acute type to a chronic type of lung inflammation compared to those in the control and cortisone-treated groups were observed. These findings indicate that ginseng treatment of an experimental P. aeruginosa pneumonia in rats promotes a cellular response resembling a TH1-like response. On the basis of these results it is suggested that ginseng may have the potential to be a promising natural medicine, in conjunction with other forms of treatment, for CF patients with chronic P. aeruginosa lung infection.
Antimicrobial Agents and Chemotherapy 06/1997; 41(5):961-4. · 4.84 Impact Factor
