Interpretation of middle ear fluid concentrations of antibiotics: comparison between ceftibuten, cefixime and azithromycin.
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AIMS: The aim of this study was to determine the potential influence of variables such as the cell content in the fluid, and serum levels, on the concentrations of ceftibuten, cefixime and azithromycin in the middle ear fluid of patients suffering from acute otitis media. METHODS: This randomized, open study compared the penetration of ceftibuten (9 mg kg(-1) 18 patients), cefixime (8 mg kg(-1), 16 patients) and azithromycin (10 mg kg(-1) 16 patients) into the intracellular and extracellular compartments of middle ear fluid of 50 paediatric patients (aged 8-14 years) with acute otitis media. Middle ear fluid was extracted by tympanocentesis 4, 12 and 24 h after dosing and divided into two fractions: with cells (as collected) (C+) and cell-free (C-). Antibiotics were assayed in C+ and C- samples by h.p.l.c. RESULTS: Ceftibuten achieved greater penetration into middle ear fluid than cefixime and azithromycin. Higher concentrations of ceftibuten (CTB) and cefixime (CFX) were found in the C- fraction (CTB: 4h 13.3+/-1.86; 12h 4.7+/-1.18; 24h 0.5+/-0.2. CFX: 4h 3.2+/-1.4; 12h 1.5+/-0.5; 24h>(0.1 mgl(-1)) than in the C+ fraction (CTB:4 h 8.4+/-4.3; 12 h 2.88+/-1.19; 24 h 0.3+/-0.27. CFX: 4 h 1.2+/-0.6; 12 h 0.8+/-0.2; 24 h>0.1 mg l(-1)) at the each time point, while the opposite was true for azithromycin (C-: 4 h 0.11+/-0.04; 12 h 0.12+/-0.08; 24 h 0.23+/-0.12. C+: 4 h 0.38+/-0.24; 12 h 0.9+/-0.03; 24 h 1.05+/-0.3 mg l(-1)). CONCLUSIONS: This study demonstrates that the penetration of antibiotics into the middle ear fluid is influenced by its serum concentrations as well as by the cell content in the fluid. Ceftibuten achieved higher middle ear fluid concentrations than cefixime in C+ and C- fractions at all time points. Both ceftibuten and cefixime concentrations are negatively influenced by the cell content in the fluid. In contrast the concentration of azithromycin to the middle ear fluid is positively influenced by the cell content in the fluid. (+info)
Glycosyltransferase domain of penicillin-binding protein 2a from Streptococcus pneumoniae is membrane associated.
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Penicillin-binding proteins (PBPs) are bacterial cytoplasmic membrane proteins that catalyze the final steps of the peptidoglycan synthesis. Resistance to beta-lactams in Streptococcus pneumoniae is caused by low-affinity PBPs. S. pneumoniae PBP 2a belongs to the class A high-molecular-mass PBPs having both glycosyltransferase (GT) and transpeptide (TP) activities. Structural and functional studies of both domains are required to unravel the mechanisms of resistance, a prerequisite for the development of novel antibiotics. The extracellular region of S. pneumoniae PBP 2a has been expressed (PBP 2a*) in Escherichia coli as a glutathione S-transferase fusion protein. The acylation kinetic parameters of PBP 2a* for beta-lactams were determined by stopped-flow fluorometry. The acylation efficiency toward benzylpenicillin was much lower than that toward cefotaxime, a result suggesting that PBP 2a participates in resistance to cefotaxime and other beta-lactams, but not in resistance to benzylpenicillin. The TP domain was purified following limited proteolysis. PBP 2a* required detergents for solubility and interacted with lipid vesicles, while the TP domain was water soluble. We propose that PBP 2a* interacts with the cytoplasmic membrane in a region distinct from its transmembrane anchor region, which is located between Lys 78 and Ser 156 of the GT domain. (+info)
Single-dose oral ciprofloxacin compared with cefotaxime and placebo for prophylaxis during transurethral surgery.
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To determine the efficacy and safety of single-dose oral ciprofloxacin prophylaxis for the prevention of post-operative bacteriuria following transurethral resection of the prostate or bladder tumour, a prospective, randomized, double-blind, placebo-controlled trial was conducted. Five hundred and eighteen patients were randomized in a 2:2:1 ratio to receive ciprofloxacin 500 mg, cefotaxime 1 g or placebo 30-90 min before surgery. Of the 368 efficacy-evaluable patients, five (3.3%) ciprofloxacin, seven (4.8%) cefotaxime and five (7.0%) placebo recipients had post-operative bacteriuria (> or = 10(4) cfu/mL) during post-operative days 2-15. Five (3.4%) ciprofloxacin, five (3.4%) cefotaxime and one (2.4%) placebo recipients were considered clinical failures, of whom one, two and one patients, respectively, had concomitant bacteriuria. Drug-related adverse events were reported in six of 204 (3%) ciprofloxacin, 12 of 197 (6%) cefotaxime and one of 101 (1%) placebo patients. The observed rates of post-operative bacteriuria suggest that a single 500 mg dose of ciprofloxacin is suitable prophylaxis for transurethral surgery. (+info)
Dissemination of a chloramphenicol- and tetracycline-resistant but penicillin-susceptible invasive clone of serotype 5 Streptococcus pneumoniae in Colombia.
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A national surveillance conducted in Colombia between 1994 and 1996 identified serotype 5 Streptococcus pneumoniae as the second most frequent cause of invasive disease in children younger than 5 years of age. All 43 serotype 5 isolates collected during this period were shown to be susceptible to penicillin, erythromycin, cefotaxime, and vancomycin, but most (38 of 43, or 88%) were highly resistant to chloramphenicol. In order to clarify a possible genetic relatedness among these isolates, additional microbiological and molecular characterizations were performed. Most (40 of 43, or 93%) of the isolates were found to be resistant to tetracycline. Pulsed-field gel electrophoresis (PFGE) patterns of chromosomal DNAs revealed that all the 43 isolates were closely related and that 38 of the 43 isolates were representatives of a "Colombian clone" of S. pneumoniae isolates which were recovered throughout the 3-year surveillance period from patients in 13 hospitals located in five Colombian cities. Isolates belonging to this Colombian clone were resistant to chloramphenicol and tetracycline, hybridized with the cat and tetM DNA probes in the same 340-kb SmaI fragment, and had identical PFGE patterns after both SmaI and ApaI digestions. (+info)
In-vitro activity of 29 antimicrobial agents against penicillin-resistant and -intermediate isolates of Streptococcus pneumoniae.
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Antibiotic resistance among isolates of Streptococcus pneumoniae is increasing worldwide. Optimal therapy, though unknown, should be guided by in-vitro susceptibility testing. Currently, vancomycin is the only approved antibiotic that is universally active against multiresistant S. pneumoniae. In-vitro activities were determined for 29 antimicrobial agents against 22 penicillin-intermediate S. pneumoniae (PISP) and 16 penicillin-resistant S. pneumoniae (PRSP) isolates. MICs were determined in cation-adjusted Mueller-Hinton broth with 3% lysed horse blood in microtitre trays. Antimicrobial classes tested included cephalosporins, penicillin, aminopenicillins, macrolides, quinolones, carbapenems and other antimicrobial agents. Among the classes of antimicrobial agents tested, wide differences in susceptibility were demonstrated for both PISP and PRSP. Of the cephalosporins, ceftriaxone and cefotaxime demonstrated the best in-vitro activity for both PISP and PRSP. Of the quinolones, clinafloxacin and trovafloxacin showed the greatest in-vitro activity. Rifampicin and teicoplanin demonstrated excellent in-vitro activity. Promising in-vitro results of newer agents, such as quinupristin/dalfopristin, ramoplanin, teicoplanin and linezolid may justify further evaluation of these agents in clinical trials. (+info)
Serum bactericidal activity of levofloxacin against Streptococcus pneumoniae.
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The objective of this study was to determine the serum bactericidal activity (SBA) of levofloxacin against Streptococcus pneumoniae strains with various degrees of susceptibility to penicillin and cefotaxime. Serum samples of volunteers (n = 12) who had received levofloxacin 500 mg as a single po dose were provided in blinded fashion. SBA was determined, using the microdilution method, in Todd-Hewitt broth supplemented with lysed horse blood inoculated with an overnight culture diluted to yield a final concentration of approximately 10(5) cfu/mL. The serum bactericidal titre was defined as the highest dilution of serum showing no growth (> 99.9% reduction of inoculum). The duration of SBA ranged from 0.75 to 6.3 h (mean 3.85 h), and was independent of the susceptibility of the strains to penicillin and cefotaxime. In conclusion, a single po dose of 500 mg levofloxacin achieved serum concentrations which were bactericidal against penicillin-resistant S. pneumoniae for a mean period of 3.85 h. (+info)
Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis.
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BACKGROUND: In patients with cirrhosis and spontaneous bacterial peritonitis, renal function frequently becomes impaired. This impairment is probably related to a reduction in effective arterial blood volume and is associated with a high mortality rate. We conducted a study to determine whether plasma volume expansion with intravenous albumin prevents renal impairment and reduces mortality in these patients. METHODS: We randomly assigned 126 patients with cirrhosis and spontaneous bacterial peritonitis to treatment with intravenous cefotaxime (63 patients) or cefotaxime and intravenous albumin (63 patients). Cefotaxime was given daily in dosages that varied according to the serum creatinine level, and albumin was given at a dose of 1.5 g per kilogram of body weight at the time of diagnosis, followed by 1 g per kilogram on day 3. Renal impairment was defined as nonreversible deterioration of renal function during hospitalization. RESULTS: The infection resolved in 59 patients in the cefotaxime group (94 percent) and 62 in the cefotaxime-plus-albumin group (98 percent) (P=0.36). Renal impairment developed in 21 patients in the cefotaxime group (33 percent) and 6 in the cefotaxime-plus-albumin group (10 percent) (P=0.002). Eighteen patients (29 percent) in the cefotaxime group died in the hospital, as compared with 6 (10 percent) in the cefotaxime-plus-albumin group (P=0.01); at three months, the mortality rates were 41 percent (a total of 26 deaths) and 22 percent (a total of 14 deaths), respectively (P=0.03). Patients treated with cefotaxime had higher levels of plasma renin activity than those treated with cefotaxime and albumin; patients with renal impairment had the highest values. CONCLUSIONS: In patients with cirrhosis and spontaneous bacterial peritonitis, treatment with intravenous albumin in addition to an antibiotic reduces the incidence of renal impairment and death in comparison with treatment with an antibiotic alone. (+info)
Reduction in the incidence of methicillin-resistant Staphylococcus aureus and ceftazidime-resistant Klebsiella pneumoniae following changes in a hospital antibiotic formulary.
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In 1995, changes in our hospital formulary were made to limit an outbreak of vancomycin-resistant enterococci and resulted in decreased usage of cephalosporins, imipenem, clindamycin, and vancomycin and increased usage of beta-lactam/beta-lactamase-inhibitor antibiotics. In this report, the effect of this formulary change on other resistant pathogens is described. Following the formulary change, there was a reduction in the monthly number (mean +/- SD) of patients with methicillin-resistant Staphylococcus aureus (from 21.9 +/- 8.1 to 17.2 +/- 7.2 patients/1,000 discharges; P = .03) and ceftazidime-resistant Klebsiella pneumoniae (from 8.6 +/- 4.3 to 5.7 +/- 4.0 patients/1,000 discharges; P = .02). However, there was an increase in the number of patients with cultures positive for cefotaxime-resistant Acinetobacter species (from 2.4 +/- 2.2 to 5.4 +/- 4.0 patients/1,000 discharges; P = .02). Altering an antibiotic formulary may be a possible mechanism to contain the spread of selected resistant pathogens. However, close surveillance is needed to detect the emergence of other resistant pathogens. (+info)