Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q29983 (MIC)
 21,138 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P. aeruginosa and Staphylococcus were isolated respectively from 46.7 and 30.9 per cent of the children with mucoviscidosis. Proteus, Klebsiella and hemophilic bacilli were isolated from 11.2, 2.8 and 2.8 per cent of the patients respectively. All the isolates of Proteus, 95.8 per sent of the staphylococcal strains and 16.7 per cent of the P. aeruginosa strains were highly sensitive to gentamicin. No gentamicin resistant strains were detected. The studies on the gentamicin pharmacokinetics showed that the maximum levels of the drug in the blood and sputum of the children treated with the antibiotic injected intramuscularly in doses of 1.2 and 2-2.5 mg/kg were attained in 1 hour. The concentration of gentamicin in the sputum amounted to 60-80 per cent of its concentration in the blood serum. Within 11 hours the antibiotic sputum levels were higher than the MIC for the organisms sensitive to gentamicin. After a single endobronchial administration of the drug it was detected in the sputum for 6 days in concentrations exceeding the MIC for the moderately sensitive strains.
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PMID:[Microflora study and the pharmacokinetic characteristics of gentamycin in children with mucoviscidosis]. 669 4

Nine patients with cystic fibrosis have been treated with azlocillin alone and later with azlocillin combined with an aminoglycoside (gentamicin or tobramycin) for 50 treatment courses. In the initial series when azlocillin was employed alone, a gradual increase in MIC during successive courses was observed in Pseudomonas aeruginosa. When the beta-lactam antibiotic was combined with an aminoglycoside, the MIC was either maintained or reduced. Objective criteria like peak expiratory flow, erythrocyte sedimentation rate, fever, body weight or bacterial cultures could not clearly identify the combination therapy as better clinically than azlocillin monotherapy. However, the patients subjective and our clinical impression is that the combination therapy was better. The clinical course and the lack of increased resistance on combination therapy make a combination of azlocillin and an aminoglycoside preferable to the beta-lactam alone.
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PMID:Azlocillin with and without an aminoglycoside against respiratory tract infections in children with cystic fibrosis. 694 8

Inadequate therapeutic results in the treatment of bacterial infections in patients with Cystic Fibrosis prompted a reevaluation of pharmacokinetic parameters of orally and parenterally administered drugs in these patients. Gentamicin, Azlocillin and Ticarcillin are eliminated faster in patients with Cystic Fibrosis. Serum concentrations show a rapid decrease over 60 to 90 minutes and surpass MIC values of Pseudomonas isolates for a maximum of only 60 minutes. 70% to 90% of the administered amount of drug is eliminated within two hours in the urine. Concomitantly determined clearance rates for creatinine didn't show abnormalities, however they pointed towards an additional tubular secretion of Gentamicin which is not seen in healthy controls. Cephalexin, Epicillin and both components of Cotrimoxazol show a delay in oral absorption. The renal elimination of Cephalexin and Trimethoprim is unaltered, but the excretion of Epicillin and Sulfametrol is enhanced again. This is seen by a delay and decrease in the maximal serum concentration (Cmax), but increased urine recovery. Doubling of the dose of gentamicin administered as i. v. infusion over 45 to 60 minutes results in smooth serum curve, the MIC values of most encountered organisms are surpassed for 3 hours and more. The clinical applicability of this recommendation however awaits further investigations concerning efficacy and safety.
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PMID:[Pharmacokinetic of antibiotics in patients with mucoviscidosis (author's transl)]. 730 88

Amiloride (A) for aerosolized therapy in cystic fibrosis (CF) is under investigation. Antipseudomonal properties of A and A analogs in vitro have recently been described. This study was performed to determine if there was suppression of P. cepacia growth after a limited 2-hour exposure to (subinhibitory) concentrations of A +/- tobramycin (T) or to the analog 5-(N,N-hexamethylene) amiloride (HMA) in vitro. The MIC of each drug against five different P. cepacia strains was determined. Cells were prepared in Mueller Hinton broth to [10(6)] colony forming units (CFU)/mL and incubated at 35 degrees C for 2 hours in the presence and absence of subinhibitory A, HMA, T, or A+T. The CFU were measured before and at 1-hour intervals after dilutional removal of drug. The post-antibiotic effect (PAE) was defined as the time (in minutes) required for the test culture counts to increase 10-fold minus the time required for control counts to increase 10-fold. At 400 micrograms/mL or 200 micrograms/mL, the PAE for A against five different strains was 139 +/- 23 and 83 +/- 24 (mean +/- SD) minutes, respectively. For 100 micrograms/mL and 50 mu cg/mL HMA, the PAE was 122 +/- 38 and 65 +/- 25 minutes. For T and A+T (200 micrograms/mL + 32 micrograms/mL) the PAE ws 168 +/- 30 and 258 +/- 30 minutes. We conclude that A and the analog HMA in (subinhibitory) concentrations have a suppressive effect on P. cepacia after drug removal and potentiate the effect of T in vitro.
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PMID:In vitro suppression of Pseudomonas cepacia after limited exposure to subinhibitory concentrations of amiloride and 5-(N,N-hexamethylene) amiloride. 752 19

The activities of FK037, cefpirome, ceftazidime and cefepime against 71 aminoglycoside-resistant, 35 aminoglycoside-sensitive, 29 cystic fibrosis Pseudomonas aeruginosa isolates, and 31 Pseudomonas spp. strains were studied using the agar dilution technique (final inoculum 10(4) c.f.u./spot). The MIC90 for aminoglycoside-sensitive P. aeruginosa against FK037, cefpirome, ceftazidime and cefepime was 32, 16, 8 and 16 mg/l, respectively. The MIC90 for P. aeruginosa strains resistant to one or more aminoglycosides was similar for FK037, cefpirome and ceftazidime (128 mg/l) and two dilutions lower for cefepime (32 mg/l). The MIC90 for P. aeruginosa isolates highly resistant to all three aminoglycosides (MIC > or = 128 mg/l) was 64 mg/l for FK037 and cefpirome, and 32 mg/l for ceftazidime and cefepime. The MIC90 for P. aeruginosa from patients with cystic fibrosis was 32 mg/l for all four cephalosporins tested, and 8, 32 and 64 for tobramycin, gentamicin and amikacin, respectively. Xanthomonas maltophilia was resistant to all four cephalosporins and three aminoglycosides. The activity of ceftazidime and cefepime was one to two dilutions greater against P. cepacia and P. picketti than of FK037 and cefpirome. The activity of ceftazidime was two dilutions greater than the other three cephalosporins against P. fluorescens. In kinetic time kill curves against P. aeruginosa, all four cephalosporins demonstrated similar activity at 6 and 24 h when tested at 1 x MIC. At 2 x MIC, regrowth was less at 24 h for cefepime, cefpirome and FK037 than for ceftazidime. In time kill curves for P. aeruginosa, synergy was clearly demonstrated at 1/4 MIC and 1/2 MIC concentrations for FK037 and tobramycin.
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PMID:Comparative antimicrobial activity of FK037, cefpirome, ceftazidime and cefepime against aminoglycoside-sensitive and aminoglycoside-resistant Pseudomonas aeruginosa and Pseudomonas spp. 784 22

Staphylococcus aureus strains resistant to mupirocin (MIC > 4000 mg l-1) were recovered from children and staff at a school for children with eczema and/or asthma or cystic fibrosis after mupirocin had been used to treat eczematous lesions. At least three distinct strains of S. aureus were involved and resistance was shown to be due in most isolates to a transmissible plasmid. The need for monitoring the extended use of this valuable antibiotic is emphasized.
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PMID:Mupirocin-resistant Staphylococcus aureus in a specialist school population. 791 87

Chronic Pseudomonas aeruginosa colonization of the lower respiratory tract of patients with cystic fibrosis frequently results in pulmonary exacerbations requiring treatment with antimicrobial agents. Multiple morphotypes with different antibiotic susceptibilities are often isolated from a single sputum sample. Determination of MICs of antibiotics for each sputum morphotype is used to guide therapy but is time-consuming and expensive. We explored an alternative assay for determining MICs for all P. aeruginosa morphotypes cultured from a homogenized sputum sample. We sought correlations of those MICs with the MIC for the most resistant morphotypes tested separately. The MICs determined for a mixture of morphotypes correctly predicted the highest MICs (+/- one dilution) determined for isolated morphotypes 73.5% of the time. The MIC for the mixed morphotypes correctly predicted susceptibility in 90.4% of samples. In contrast, determination of the MIC for the mixture of morphotypes correctly predicted resistance in only 57.0%. For sputa containing susceptible isolates, testing the mixed culture may provide adequate susceptibility data with significant laboratory time and cost savings. However, for sputa with resistant strains, the traditional method of testing isolated morphotypes should still be used.
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PMID:Accuracy and cost of antibiotic susceptibility testing of mixed morphotypes of Pseudomonas aeruginosa. 802 5

In 31 adult patients with cystic fibrosis (CF) who were chronically infected with Pseudomonas aeruginosa we examined the effect of giving regular three monthly oral ciprofloxacin. Patients received ciprofloxacin or placebo for 10 days every 3 months for 1 yr in a randomized, double-blind, placebo-controlled study. During each course of treatment patients receiving ciprofloxacin reported an improvement in cough, sputum production and peak expiratory flow (PEF) P = < 0.005. During the year of study patients receiving ciprofloxacin showed an improvement in PEF when compared with those receiving placebo (P = < 0.05) but the changes in FEV1 and FVC were not statistically different in either group. Regular oral ciprofloxacin was well tolerated but did not prevent hospital admissions or reduce the number of courses of intravenous antibiotics throughout the year. The median MIC to ciprofloxacin in the active treatment group rose from 0.5 mg l-1 to 0.75 mg l-1 during treatment. We conclude that CF patients are likely to benefit from oral ciprofloxacin for exacerbations of respiratory symptoms. However, regular treatment with ciprofloxacin over 1 yr improves PEF but does not reduce the rate of hospital admissions with acute exacerbations of respiratory symptoms.
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PMID:Regular three monthly oral ciprofloxacin in adult cystic fibrosis patients infected with Pseudomonas aeruginosa. 829 Jul 42

Cefpirome is a new broad-spectrum beta-lactam antibiotic that exhibits minimal concentration dependent killing and produces prolonged postantibiotic effects only with Staphylococcus aureus. These pharmacodynamic characteristics suggest that the goal of optimal dosing regimens for cefpirome is to provide serum levels above the MIC of infecting pathogens for most of the dosing interval. Cefpirome has a half-life of 2.0 hours in normal volunteers that increases to 3.1 to 4.4 hours in elderly patients. Serum concentrations following 0.5, 1.0 and 2.0 grams of cefpirome are above the MIC of common pathogens for more than half of the dosing interval. For many of the Enterobacteriaceae, serum concentrations are above the MIC for over 12 hours. The drug distributes primarily into extracellular fluid and does provide potentially therapeutic concentrations in cerebrospinal fluid (CSF). The drug is eliminated primarily by the kidney and requires dosage modification when the creatinine clearance is below 50 ml/min. The half-life of the drug is not significantly altered in patients with cystic fibrosis and hepatic dysfunction. The integration of the drug's pharmacokinetic and pharmacodynamic characteristics support the use of a 12-hour dosing interval for the treatment of serious infection.
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PMID:The pharmacokinetics of cefpirome--rationale for a twelve-hour dosing regimen. 829 Sep 1

The purposes of this study were to determine and compare the single- and multiple-dose pharmacokinetics of cefepime in patients with and without cystic fibrosis. Twelve patients with cystic fibrosis hospitalized for treatment of acute pulmonary exacerbations were studied. In addition, pharmacokinetic data for seven of the patients with cystic fibrosis were compared with those for seven age-matched control patients. The cefepime dose was 50 mg/kg of body weight (maximum, 2 g) administered as a 30-min intravenous infusion every 8 h for a minimum of 8 days. Serial plasma and urine samples, obtained after the first and last doses, were analyzed for cefepime content by a validated high-pressure liquid chromatographic assay. By standard noncompartmental analysis, the pharmacokinetic parameters ascertained were area under the concentration in plasma-time curve, elimination half-life, total body clearance, renal clearance, and volume of distribution at steady state. In addition, the maximum concentration in plasma was recorded. Mean (+/- standard deviation) results of the first dose analysis in patients with cystic fibrosis were as follows: maximum concentration in plasma, 142.6 (+/- 26.07) micrograms/ml; area under the concentration in plasma-time curve, 265.3 (+/- 114.31) micrograms.h/ml; elimination half-life, 1.8 (+/- 0.53) h; total body clearance, 127.2 (+/- 50.94) ml/min; renal clearance, 91.1 (+/- 38.86) ml/min/kg; volume of distribution at steady state, 14.1 (+/- 4.31) liters. Analysis for the last dose in patients with cystic fibrosis did not vary appreciably from these values, nor did those from the controls. Thus, it appears that the first-dose pharmacokinetics of cefepime are predictive of those at steady state. In order to consistently exceed the MIC for Pseudomonas aeruginosa for the entire dosing interval in patients with cystic fibrosis, a higher dose and/or different dosing interval compared with those used in this study may be necessary.
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PMID:Pharmacokinetics of cefepime in cystic fibrosis patients. 836 68


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