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Query: UNIPROT:Q29983 (MIC)
 21,138 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of triple therapy with ciprofloxacin, trimethoprim and either sulphadiazine or sulphamethoxazole on the MICs and development of resistance of three strains of Pseudomonas aeruginosa, two strains of Staphylococcus aureus and one of Burkholderia cepacia was compared with that of single or dual therapy with these agents using an agar dilution method. Ciprofloxacin MICs were 0.2-0.8 mg/L for the P. aeruginosa and S. aureus strains. For trimethoprim the MIC ranges were 64-128 and 0.25-1 mg/L for P. aeruginosa and S. aureus, respectively. For the sulphonamides the ranges were 64-2500 and 20-39 mg/L for P. aeruginosa and S. aureus, respectively. All combinations of agents were effective at lower concentrations than the single agents. The combination of ciprofloxacin, sulphonamide and trimethoprim showed enhanced activity against all test organisms. The highest ciprofloxacin concentration was one-tenth of the normally attainable serum concentration of 2.5 mg/L. Thus peak plasma concentrations of > or =8 x MIC for ciprofloxacin against P. aeruginosa and S. aureus are theoretically achievable in the presence of clinically acceptable concentrations of trimethoprim and a sulphonamide, making the development of resistance less likely. The development of resistance, as shown by the proportional increase in MICs, was repressed by the triple regimen as compared with the development of resistance to agents used singly or in pairs. Killing curve determinations also demonstrated the advantage of the triple-agent therapy against all organisms tested: the combination of ciprofloxacin 0.5 mg/L, trimethoprim 1 mg/L and sulphadiazine 20 mg/L had an initial bactericidal effect against log-phase inocula of 10(6) cfu/mL of two clinical strains of P. aeruginosa and one clinical strain of S. aureus. The pseudomonas strains were reduced by 2-4 log cycles. Both recovered over 24 h but did not exceed the initial inoculum. The S. aureus was reduced to 10(2) cfu/mL in 4 h and did not recover over 24 h. A repeat dose of the triple therapy against the more resistant of the P. aeruginosa strains after 12 h also had a bactericidal effect. These data suggest the possibility of an effective exclusively oral therapy for the treatment of lung infections in cystic fibrosis patients.
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PMID:In-vitro investigation of the antibacterial activity of agents which may be used for the oral treatment of lung infections in CF patients. 973 34

The pharmacokinetics of meropenem were studied after single i.v. infusions of 15 mg meropenem/kg body weight in eight subjects with cystic fibrosis (CF) and eight healthy volunteers matched for age, sex, and weight. Significantly shorter terminal half-lives (mean, 0.74 h vs. 0.99 h) and mean residence times (mean, 1.09 h vs. 1.39 h) were noted in CF subjects. Plasma and renal clearances tended to be higher and distribution volumes smaller among the patients, but differences were not statistically significant. The results are consistent with the findings for many other beta-lactam agents used in CF patients. Assuming a MIC90 of 4 mg/l for meropenem against Pseudomonas aeruginosa, the time above the MIC was less than 3.3 h in six of the eight CF patients. This finding should be kept in mind when designing treatment regimens with meropenem in CF subjects.
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PMID:Pharmacokinetics of meropenem in patients with cystic fibrosis. 1005 54

Pseudomonas aeruginosa endobronchial infection causes significant morbidity and mortality among cystic fibrosis patients. Microbiology results from two multicenter, double-blind, placebo-controlled trials of inhaled tobramycin in cystic fibrosis were monitored for longitudinal changes in sputum microbial flora, antibiotic susceptibility, and selection of P. aeruginosa isolates with decreased tobramycin susceptibility. Clinical response was examined to determine whether current susceptibility standards are applicable to aerosolized administration. Treatment with inhaled tobramycin did not increase isolation of Burkholderia cepacia, Stenotrophomonas maltophilia, or Alcaligenes xylosoxidans; however, isolation of Candida albicans and Aspergillus species did increase. Although P. aeruginosa tobramycin susceptibility decreased in the tobramycin group compared with that in the placebo group, there was no evidence of selection for the most resistant isolates to become most prevalent. The definition of resistance for parenteral administration does not apply to inhaled tobramycin: too few patients had P. aeruginosa with a tobramycin MIC >/=16 microgram/mL to define a new break point on the basis of clinical response.
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PMID:Effect of chronic intermittent administration of inhaled tobramycin on respiratory microbial flora in patients with cystic fibrosis. 1019 Dec 22

The purpose of this study was to compare resistance and cross-resistance development in Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients to commonly used antipseudomonal antibiotics. Isolates were repeatedly exposed to subinhibitory concentrations of either azlocillin, tobramycin, ceftazidime or ciprofloxacin. On 10 consecutive occasions, samples were removed from the half-MIC well of a microtitre plate and regrown in drug-free medium to provide the next inoculum for MIC determination. The increase in MIC at the end of the treatment period was significant (p<0.05) for all selecting antibiotics. Cross-resistance to unrelated antibiotics was not observed, but was significant (p<0.05) in all beta-lactams (ticarcillin, piperacillin, ceftazidime and cefsulodin) studied where azlocillin was the selecting antibiotic. The addition of clavulanic acid to ticarcillin and of tazobactam to piperacillin had no effect on cross-resistance. The development of resistance to azlocillin was associated with increased beta-lactamase activity and a change in isoelectric point of the beta-lactamases. The result of this study supports a rotational policy for antipseudomonal antibiotics in CF patients.
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PMID:Development of resistance and cross-resistance in Pseudomonas aeruginosa exposed to subinhibitory antibiotic concentrations. 1037 86

The in vitro activity of tobramycin was compared with those of six other antimicrobial agents against 1,240 Pseudomonas aeruginosa isolates collected from 508 patients with cystic fibrosis during pretreatment visits as part of the phase III clinical trials of tobramycin solution for inhalation. The tobramycin MIC at which 50% of isolates are inhibited (MIC(50)) and MIC(90) were 1 and 8 microg/ml, respectively. Tobramycin was the most active drug tested and also showed good activity against isolates resistant to multiple antibiotics. The isolates were less frequently resistant to tobramycin (5.4%) than to ceftazidime (11.1%), aztreonam (11.9%), amikacin (13.1%), ticarcillin (16.7%), gentamicin (19.3%), or ciprofloxacin (20.7%). For all antibiotics tested, nonmucoid isolates were more resistant than mucoid isolates. Of 56 isolates for which the tobramycin MIC was > or = 16 microg/ml and that were investigated for resistance mechanisms, only 7 (12.5%) were shown to possess known aminoglycoside-modifying enzymes; the remaining were presumably resistant by an incompletely understood mechanism often referred to as "impermeability."
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PMID:Activities of tobramycin and six other antibiotics against Pseudomonas aeruginosa isolates from patients with cystic fibrosis. 1058 75

The aim of this study was to evaluate the effect of antibiotics at subminimal inhibitory concentrations (sub-MIC) on fluorescent pseudomonas adherence to A549 pneumocyte cells. Pseudomonas fluorescens MF0 isolated from contaminated raw milk and Pseudomonas aeruginosa NK125502 isolated from a cystic fibrosis patient's lung adhered to A549 cells. As previously shown for P. aeruginosa, P. fluorescens bound to A549 cells in a dose-dependent manner over a wide range of bacterial concentrations. Bacterial growth in the presence of polymyxin B or gentamicin at MIC/2 had no effect on the adherence of NK125502 and MF0 to A549 cells. Instead, MIC/2 and MIC/8 of cefsulodin or chloramphenicol decreased the adherence of the two strains. A decrease in MF0 adherence was also observed with cefsulodin at MIC/32. We conclude that, in addition to their antibacterial activity, cefsulodin and chloramphenicol could be effective in preventing Pseudomonas adherence to respiratory epithelium.
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PMID:Effects of antibiotics on adherence of Pseudomonas aeruginosa and Pseudomonas fluorescens to A549 pneumocyte cells. 1067 64

Twenty P. aeruginosa isolates were collected from six cystic fibrosis (CF) patients, aged 27 to 33, in 1994 (9 isolates) and 1997 (11 isolates) at the CF Center, Copenhagen, Denmark, and were typed by pulse-field gel electrophoresis (PFGE) or ribotyping. Five of the patients had isolates with the same PFGE or ribotyping patterns in 1997 as in 1994, and ciprofloxacin had a two- to fourfold higher MIC for the isolates collected in 1997 than those from 1994. Genomic DNA was amplified for gyrA, parC, mexR, and nfxB by PCR and sequenced. Eleven isolates had mutations in gyrA, seven isolates had mutations at codon 83 (Thr to Ile), and four isolates had mutations at codon 87 (Asp to Asn or Tyr). Sixteen isolates had mutations in nfxB at codon 82 (Arg to Leu). Increased amounts of OprN were found in six isolates and OprJ in eight isolates as determined by immunoblotting. No isolates had mutations in parC or mexR. Six isolates had mutations in efflux pumps without gyrA mutations. The average number of mutations was higher in isolates from 1997 than in those from 1994. The results also suggested that efflux resistance mechanisms are more common in isolates from CF patients than in strains from urine and wounds from non-CF patients, in which mutations in gyrA and parC dominate (S. Jalal and B. Wretlind, Microb. Drug Resist. 4:257-261, 1998).
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PMID:Molecular mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. 1068 43

Aminoglycoside-resistance mechanisms were characterized in Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients during a recent clinical trial of inhaled tobramycin. Impermeability, in which bacteria have reduced susceptibility to all aminoglycosides, was the predominant mode of resistance in isolates obtained both before and after 6 months of cyclic treatment with tobramycin or placebo administered by aerosol. Enzymatic resistance mechanisms were found in fewer than 10% of resistant isolates. P. aeruginosa from individual patients could be grouped on the basis of genetic relatedness. When enzymatic resistance was involved, all isolates in a group had elevated tobramycin MICs. When impermeability occurred, MICs of a genotypic group varied from susceptible to resistant. These findings suggest that impermeability resistance occurs in only a fraction of the P. aeruginosa population in lungs of persons with CF and that this form of resistance arises by a process involving multiple small changes in MIC.
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PMID:Aminoglycoside-resistance mechanisms for cystic fibrosis Pseudomonas aeruginosa isolates are unchanged by long-term, intermittent, inhaled tobramycin treatment. 1072 May 51

Once-daily administration of aminoglycosides is routinely used in many institutions. However, comparative efficacy data for patients with cystic fibrosis (CF) are lacking. The purpose of the present study was to compare the predicted pharmacodynamic activity of tobramycin at 10 mg/kg of body weight/day administered every 24 h (q24h), q12h, and q8h. Pharmacokinetic (PK) data were derived from analysis of data on the drug concentration in sera from 60 adult CF patients. Individual maximum a posteriori probability Bayesian PK parameter values were used to construct serum concentration-versus-time curves and to determine various indices (peak concentration/MIC ratio [peak/MIC], area under the concentration-time curve/MIC ratio [AUC/MIC], and time that the concentration was less than the MIC [T<MIC]) for the three regimens described above. MICs of 1, 2, and 4 microg/ml for Pseudomonas aeruginosa were assumed in the simulations. Irrespective of the MIC, significantly lower peak/MIC but shorter T<MIC were noted when regimens of q8h versus q12h (P < 0.001), q8h versus q24h (P < 0.001), and q12h versus q24h (P < 0.001) were compared. This analysis suggests that the potential benefit of achieving a greater peak/MIC with once-daily aminoglycoside administration may be offset by the significantly greater T<MIC in CF patients compared with that achieved with multiple-daily-dosing regimens. Clinical trials are necessary to determine if once daily aminoglycoside administration is efficacious in the CF population before its routine use can be recommended.
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PMID:Pharmacokinetics of tobramycin in adults with cystic fibrosis: implications for once-daily administration. 1072 74

Pseudomonas aeruginosa is the most common pathogen infecting the lungs of patients with cystic fibrosis (CF). Improved antimicrobial chemotherapy has significantly increased the life expectancy of these patients. However, accurate susceptibility testing of P. aeruginosa isolates from CF sputum may be difficult because the organisms are often mucoid and slow growing. This study of 597 CF isolates of P. aeruginosa examined the correlation of disk diffusion and Etest (AB BIODISK, Solna, Sweden) results with a reference broth microdilution method. The rates of interpretive errors for 12 commonly used antipseudomonal antimicrobials were determined. The disk diffusion method correlated well (zone diameter versus MIC) for all of the agents tested. However, for mucoid isolates, correlation coefficients (r values) for piperacillin, piperacillin-tazobactam, and meropenem were <0.80. The Etest correlation with reference broth microdilution results (MIC versus MIC) was acceptable for all of the agents tested, for both mucoid and nonmucoid isolates. Category interpretation errors were similar for the disk diffusion and Etest methods with 0.4 and 0.1%, respectively, very major errors (false susceptibility) and 1.1 and 2.2% major errors (false resistance). Overall, both agar diffusion methods appear to be broadly acceptable for routine clinical use in susceptibility testing of CF isolates of P. aeruginosa.
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PMID:Comparison of agar diffusion methodologies for antimicrobial susceptibility testing of Pseudomonas aeruginosa isolates from cystic fibrosis patients. 1079 Jan 6


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