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Query: UMLS:C0021311 (Infection)
 38,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A literature review on the pharmacokinetic characteristics of fluoroquinolones in the treatment of patients with various diseases such as diseases accompanied by hepatic insufficiency, mucoviscidosis, diseases in elderly patients, lower respiratory tract infection, septicemia, skin infection and others was analyzed. Infections requiring correction of the routine treatment regiments are indicated.
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PMID:[The pharmacokinetics of fluoroquinolones in different diseases]. 922 1

Infections in cystic fibrosis (CF) due to Burkholderia cepacia are challenging due to their resistance to antibiotics. We explored a new strategy for increasing the permeability of B. cepacia using cationic agents, including amino compounds, to reduce the MICs of standard antibiotics. Twenty-eight B. cepacia isolates from four CF centres in North America and four non-CF B. cepacia were examined by standard microtitre broth dilution methods for susceptibility to a variety of antibiotics in the presence of non-inhibitory concentrations of diaminoacetone (DAA), methylglyoxal bis-guanylhydrazone (MGBH), chlorpromazine (CPZ) and prochlorperazine (PCPZ). The proportion of isolates with greater than four-fold reductions in MIC in the presence of 0.3 mM CPZ or 0.4 mM PCPZ were 90% and 94% for gentamicin, 80% and 83% for tobramycin, 45% and 17% for ceftazidime, and 35% and 17% for amifloxacin. CPZ showed the same degree of reduction in the MIC of azithromycin in 79% strains (MIC50 reduced to 16 from > or = 256 mg/L). Non-CF B. cepacia showed a greater than four-fold reduction in MIC with CPZ for gentamicin, tobramycin and azithromycin and two-fold reduction for ceftazidime. Little or no reduction in MIC was seen with DAA or MGBH for any antibiotic. Addition of magnesium ions to the medium competitively inhibited any MIC reduction effect seen with the cationic agents. CPZ and PCPZ appeared to enhance the permeability of B. cepacia to antibiotics based upon ionic charge characteristics of the antibiotic. No significant differences were seen in outer membrane protein and lipopolysaccharide profiles between the culture treated with CPZ and the respective control culture of strain B. cepacia ATCC 13945. The fluorescent probe 1N-phenylnaphthylamine had no increased access across the outer membrane in the presence of CPZ for B. cepacia ATCC 13945. However, thin-section electron microscopy revealed separation between the outer membrane and the rest of the cytoplasm accompanied by a widening of the periplasmic space. These data provide a rationale for investigating amino compounds as potential permeability-increasing agents against B. cepacia.
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PMID:Enhancement of Burkholderia cepacia antimicrobial susceptibility by cationic compounds. 933 85

Healthy, non-colonized cystic fibrosis (CF) patients (N = 26) were immunized with an octavalent Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine. Vaccination was well tolerated and induced anti-lipopolysaccharide (LPS) antibodies of a high affinity capable of promoting the opsonophagocytic killing of P. aeruginosa by human peripheral lymphocytes. In contrast, anti-LPS antibodies acquired after natural infection possessed a very low affinity and were non-opsonic. To determine if immunization could prevent or delay infections due to P. aeruginosa, the infection rate among immunized patients was compared retrospectively to age and gender-matched controls. After 6 years of clinical follow-up, 15/20 (75%) of control and 8/23 (35%) of immunized subjects were classified as infected (p = 0.022). The persistence of high-affinity antibodies among immunized patients correlated with a significantly lower rate of infection after 4-6 years of observation. Infection of immunized patients was correlated with a dramatic decline in total antibody titer between year 2 and 3 of follow-up. Smooth, typeable strains of P. aeruginosa predominated among immunized patients. In contrast, rough, nontypeable strains were most frequently isolated from nonimmunized patients. Mucoid P. aeruginosa strains were isolated from 6 nonimmunized patients versus only I immunized subject.
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PMID:Immunization of cystic fibrosis patients with a Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine. 938 59

Infection with Burkholderia cepacia due to social contact is well described in patients with cystic fibrosis. However, social transmission to non-cystic fibrosis individuals or chronic colonisation in non-cystic fibrosis individuals has not been described. A report of B cepacia bronchiectasis is presented where a previously healthy mother of two cystic fibrosis children colonised with B cepacia became infected by the same epidemic strain. The implications of this for parents, siblings, and partners of individuals with cystic fibrosis are discussed.
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PMID:Chronic Burkholderia cepacia bronchiectasis in a non-cystic fibrosis individual. 1068 Dec 63

Recombinant human deoxyribonuclease I (DNase I) is an important clinical agent that is inhaled into the airways where it degrades DNA to lower molecular weight fragments, thus reducing the viscoelasticity of sputum and improving the lung function of cystic fibrosis patients. To investigate DNases with potentially improved properties, we constructed a molecular fusion of human DNase I with the hinge and Fc region of human IgG1 heavy chain, creating a DNase I-Fc fusion protein. Infection of Sf9 insect cells with recombinant baculovirus resulted in the expression and secretion of the DNase I-Fc fusion protein. The fusion protein was purified from the culture medium using protein A affinity chromatography followed by desalting by gel filtration and was characterized by amino-terminal sequence, amino acid composition, and a variety of enzyme-linked immunosorbent assays (ELISA) and activity assays. The purified fusion contains DNase I, as determined by a DNase I ELISA and an actin-binding ELISA, and an intact antibody Fc region, which was quantified by an Fc ELISA, in a 2:1 stoichiometric ratio, respectively. The dimeric DNase I-Fc fusion was functionally active in enzymatic DNA digestion assays, albeit about 10-fold less than monomeric DNase I. Cleavage of the DNase I-Fc fusion by papain resulted in a specific activity comparable to the monomeric enzyme. Salt was inhibitory for wild type monomeric DNase I but actually enhanced the activity of the dimeric DNase I-Fc fusion. The DNase I-Fc fusion protein was also less Ca2+-dependent than DNase I itself. These results are consistent with a higher affinity of the dimeric fusion protein to DNA than monomeric DNase I. The engineered DNase I-Fc fusion protein described herein has properties that may have clinical benefits.
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PMID:Expression and characterization of a DNase I-Fc fusion enzyme. 1009 62

Burkholderia cepacia is an important pathogen in cystic fibrosis (CF) and an infrequent cause of nosocomial infection in non-CF patients. This report describes a large hospital outbreak that appeared to involve both patient groups, a previously unrecognized phenomenon. Ribotype restriction fragment length polymorphism (RFLP) profiles and pulsed-field gel electrophoresis-resolved macrochromosomal RFLPs were analyzed, a ribotype-based phylogenic tree was constructed, and case-control and cohort studies were performed. A single dominant clone was found in both CF and non-CF groups. Phylogenic analysis suggests that it has evolved independently and that such highly transmissible strains can emerge rapidly and randomly. Acquisition risk in the CF patients was linked to hospitalization (odds ratio=5.47, P=.0158, confidence interval=1. 28-26.86) and was associated with significantly increased mortality rates. Infection control policies must now consider this threat of transmission between non-CF and CF patients.
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PMID:An epidemic of burkholderia cepacia transmitted between patients with and without cystic fibrosis. 1019 Dec 23

Whether allelic variants of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) independently contribute to pulmonary outcome in CF patients has not been resolved. We used both cross-sectional and mixed-model longitudinal analyses of data from CF patients that were at least 12 years old to determine the influence on pulmonary function (percent predicted forced expiratory volume [FEV(1)]) of the CFTR gene genotype, gender, mucoid Pseudomonas aeruginosa (MPA) infection status, presence of total opsonic antibody to MPA, and, separately, the opsonic antibody activity specific to the mucoid exopolysaccharide (MEP) surface antigen. Two different factors were independently associated with the lack of MPA infection: a high level of MEP-specific opsonic activity (MSOA), implicating an immunologically based mechanism of resistance to infection, and a lack of any type of opsonic antibody to MPA, indicative of no significant exposure or infection. This latter phenotype was found in a subset of CF patients who carried at least one uncommon CFTR gene allele suggestive of a genetic basis for resistance to infection in this group of older CF patients. For CF patients in whom both CFTR gene alleles were identified by screening for the 12 most common variants (75% of alleles), cross-sectional analysis showed that MPA infection was best correlated with lower percent predicted FEV(1), while genotype (two versus one DeltaF508 CFTR gene allele) and a low level of MSOA were associated with increased risk of infection. A mixed-model analysis of longitudinal spirometric measurements that considered multiple risk factors to derive regression equations was used to determine which clinical parameters had the greatest effect on the annual rate of decline in percent predicted FEV(1). This analysis showed that the CFTR gene genotype only modestly modified the constant (y intercept) of the derived equations, while gender and MPA infection status had the largest effects on annual rates of decline in percent predicted FEV(1). These results indicate that the CFTR genotype is usually not a primary determinant of pulmonary function in most CF patients, but gender and MPA infection status are. Infection status is potentially influenced by both immunologic (a high level of MSOA) and genetic factors, such as carriage of a CFTR gene allele that leads to a diagnosis of CF but still confers resistance to infection that is comparable to that of the wild-type CFTR gene.
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PMID:Pulmonary outcome in cystic fibrosis is influenced primarily by mucoid Pseudomonas aeruginosa infection and immune status and only modestly by genotype. 1045 26

Bone marrow suppression is an important adverse reaction to most betalactam antibiotics. Recently it was suggested that piperacillin/tazobactam (PT) also may cause bone marrow toxicity. We retrospectively analyzed 100 i.v. antibiotic treatment courses (mean duration 12.5 days) in 38 patients (median age 14 years) with cystic fibrosis (CF) who were treated in our hospital. Of the patients receiving PT (84%), 6 patients (18.75% of PT-treated patients, 10.3% of PT treatment courses) developed fever, malaise and headache during treatment without signs of acute infection. In one patient definite thrombocytopenia and neutropenia, in two others a milder decrease in leukocyte and thrombocyte counts was observed after the onset of fever. The events were time- and dose-dependent occurring between day 11 and 15 of treatment. Treatment courses lasted longer (14.2 vs 11.3 days; p < 0.05) and patients had received a higher cumulative dose of PT (4919 +/- 1975 mg/kg b.w. vs 3161 +/- 1635 mg/kg; p < 0.02, Student's t-test) in the affected group than in the unaffected group. After discontinuation of PT, fever subsided within 24 h and blood cell counts normalized. We hypothesize that these fever episodes and changes of blood parameters are related to PT therapy.
Infection
PMID:Leukocytopenia, thrombocytopenia and fever related to piperacillin/tazobactam treatment--a retrospective analysis in 38 children with cystic fibrosis. 1062 96

A retrospective analysis of files of patients with cystic fibrosis and pulmonary exacerbations was performed to investigate whether an individual dosage of tobramycin once established by serum level determination allows a reliable prediction of the adequate dosage in a consecutive exacerbation. All patients hospitalized > or = 2 times between May 1997 and September 1998 with pulmonary exacerbation due to Pseudomonas aeruginosa infection susceptible to tobramycin were included. The initial dosage to tobramycin was 5 mg/kg body weight every 12 h followed by drug level determinations to establish the optimal dose. In a consecutive exacerbation the same dosage per kg body weight was used again and drug level determinations were repeated. Sixteen patients (six female = 38%) with a mean age of 24 years (median: 26 years, range: 9-33) were hospitalized for 49 pulmonary exacerbations (2-6 per patient, mean: 3, median: 2.5). During the first episode of tobramycin treatment in the study period all trough levels were < 2 microg/ml (median: 0.6) and the peak levels were 7.1-16.9 microg/ml (median: 11.9). In four patients the peak level was > 12 microg/ml. In 28 consecutive episodes the dosage of tobra myci n was chosen based on optimal results of previous drug level monitoring and in 27 instances (96%) the previously established optimal dose was confirmed. In five consecutive episodes the tobramycin dosage had been increased erroneously and this resulted in abnormally high peak levels in three cases. These findings suggest that a safe and therapeutic tobramycin dosage in an individual patient with cystic fibrosis is predictable based on a previously established optimal dosage.
Infection 1999
PMID:Optimal tobramycin dosage in patients with cystic fibrosis--evidence for predictability based on previous drug monitoring. 1088 41

Pulmonary infections in the immunocompromised adolescent are important causes of significant morbidity and mortality. Advances in the fields of chemotherapy, organ transplantation, and use of corticosteroid and immunosuppressive therapies have led to significant improvement in the outcome of patients with malignancy and a variety of other disorders. HIV infection has become a major additional cause of immune suppression. In turn, physicians are encountering growing numbers of patients with an impaired immune system presenting with respiratory and other infections. This article presents a brief review of defense mechanisms in the respiratory tract, selected conditions leading to impaired immune responses in the adolescent, specific pulmonary pathogens and their evaluation in the immunocompromised adolescent, and general considerations of the management of pulmonary infections in the immunocompromised adolescent. Infections of the upper respiratory tract and pulmonary infections seen in adolescents with cystic fibrosis are not discussed.
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PMID:Pulmonary infections in the adolescent with immunodeficiency. 1106 May 61


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