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Biomedical subjects

R Quintiliani

Publications and source records attributed to R Quintiliani.

At least 109 records · Page 6Linked to original sources
PubMed1993

The vanB gene confers various levels of self-transferable resistance to vancomycin in enterococci.

Thirty-nine strains of Enterococcus faecium and Enterococcus faecalis resistant to vancomycin and susceptible to teicoplanin on disk susceptibility testing (phenotypic class B) were isolated in 15 hospitals in Europe and the United States. The MICs of vancomycin for these strains ranged from 4 to 1024 micrograms/mL. Part of the vancomycin resistance gene vanB from E. faecalis V583 hybridized with a single but variably sized HindIII-KpnI fragment of total DNA from all 39 strains. This indicates that a single class of resistance determinants accounts for the VanB phenotype. No hybridization was detected with DNA from intrinsically resistant Enterococcus gallinarum or Enterococcus casseliflavus. Hybridization with DNA from enterococcal strains susceptible to or with acquired resistance to vancomycin and teicoplanin was not observed. The genes conferring resistance to vancomycin were self-transferable to other Enterococcus strains in 14 of the 39 strains. It thus appears that vanB confers various levels of conjugative vancomycin resistance in enterococci.

Bacterial Proteins↗
PubMed1993

Evaluation of the efficacy of ciprofloxacin against Streptococcus pneumoniae by using a mouse protection model.

A mouse protection model was used to investigate the association of the pharmacokinetics and pharmacodynamics with the in vivo efficacy of ciprofloxacin compared with that of penicillin G in the treatment of mice infected with Streptococcus pneumoniae ATCC 6303. Mice were inoculated intraperitoneally with 10 times the minimum lethal dose of S. pneumoniae. For determination of the 50% protective dose, subcutaneous antibiotics were begun 1 h after infection and were continued for 24 h. The 50% protective doses of ciprofloxacin and penicillin G were 25.52 +/- 1.95 and 0.307 +/- 0.006 mg/kg of body weight, respectively, an 83-fold difference in efficacy. For 100% protection with penicillin G, the time that the drug concentration needed to remain above the MIC was 51 min, a value easily achieved in most clinical situations. For 100% protection with ciprofloxacin, the peak concentration/MIC ratio must reach a value of 10.6. This ratio is rarely achieved with this drug against S. pneumoniae in clinical practice. These pharmacodynamic differences probably contribute to the reported differences in clinical success between these agents.

Animals↗
PubMed1993

Vancomycin therapeutic drug monitoring: is it necessary?

OBJECTIVE: To review the literature and assess the validity of obtaining vancomycin serum drug concentrations in patients. DATA SOURCES: A MEDLINE search of the English literature and a bibliographic review of articles pertaining to vancomycin serum concentrations, their use, and the rationale of cited therapeutic ranges. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of vancomycin concentrations in the clinical setting, methods for predicting these concentrations, and studies that reported efficacy or toxicity associated with vancomycin use and possible correlation of serum concentrations. DATA SYNTHESIS: The usefulness of vancomycin serum concentrations, the determination of a therapeutic range of values, and their correlation to antibacterial efficacy and drug toxicity in the clinical setting are controversial. Old reports of toxicities need to be critically examined due to lack of information and the actual frequency of toxic reactions. The efficacy of vancomycin's antibacterial effect and its correlation with reported therapeutic ranges may advocate obtaining a vancomycin trough concentration in certain groups of patients. CONCLUSIONS: Determination of serum vancomycin concentrations in the clinical setting and their usefulness in patient care is questionable and unnecessary in the majority of patients.

Animals↗
PubMed1993

Oral ciprofloxacin, ofloxacin, and lomefloxacin as alternatives to intravenous antimicrobial therapy.

Ciprofloxacin, ofloxacin, and lomefloxacin are oral fluoroquinolones with ideal characteristics for oral antimicrobial therapy. These agents provide 1) appropriate and reliable serum concentrations, 2) broad antimicrobial activity, 3) proven efficacy in the treatment of serious infections, and 4) good tolerability. Although cations decrease the absorption of these drugs, there are proven means of avoiding these interactions. Therefore, these agents could easily be utilized as alternatives to prolonged intravenous treatment of many infectious diseases in patients who do not have conditions which impair drug absorption.

Administration, Oral↗
PubMed1993

Pharmacokinetics of minocycline and vancomycin in rabbits.

The pharmacokinetic disposition of minocycline and vancomycin was studied in New Zealand White rabbits before initiating an experimental staphylococcal endocarditis protocol. Minocycline was administered in a multiple-dose regimen of 3 mg/kg i.v. every 12 h, 3 mg/kg i.v. every 8 h, and 6 mg/kg i.v. every 8 h. Vancomycin was given in a similar fashion using regimens of 75 mg/kg i.v. every 12 h and 50 mg/kg i.v. every 8 h. Multiple serum samples were obtained after the fifth dose and drug concentrations were analyzed by microbiologic assay. The pharmacokinetic parameters for each of the drug regimens were calculated using a two-compartment model by nonlinear least-squares regression. No statistically significant differences were noted in the volume of distribution or the half-life of the individual dosing regimens for either agent. As a result of this study, it appears that a minocycline regimen of 6 mg/kg i.v. every 8 h and a vancomycin regimen of 50 mg/kg i.v. every 8 h are appropriate dosing schemes for a comparative study of these agents in rabbits.

Animals↗
PubMed1993

Use of pharmacodynamic concepts in developing a cost-effective dosing method for piperacillin.

Because they were almost always used in combination with an aminoglycoside, piperacillin and mezlocillin were considered therapeutic alternatives at Hartford Hospital, a 900-bed teaching facility. To determine an appropriate comparative dose, the bactericidal activities of 5 gm of mezlocillin and 4 gm and 3 gm of piperacillin were compared. The results demonstrated that 4 gm of piperacillin possessed stronger bactericidal activity than either 3 gm of piperacillin or 5 gm of mezlocillin. Hartford Hospital has since approved an antibiotic management program using 4 gm of piperacillin every 8 hours, thereby reducing the daily cost of antibiotic therapy. The modified program offers the hospital measurable cost savings without jeopardizing the quality of care.

Cost-Benefit Analysis↗
PubMed1992

Lomefloxacin concentrations in bone after a single oral dose.

We studied the penetration characteristics of lomefloxacin in bone in 30 patients with osteoarthritis undergoing total hip replacement. Patients were given a single oral 400 mg dose at various times from 1 to 12 hours prior to removal of bone samples. The peak plasma and bone (subchondral bone from femoral head) concentrations reached approximately 4.0 micrograms/mL at 2 hours post-dose and 3.0 micrograms/mL at 3 hours post-dose, respectively. At 12 hours post-dose both plasma and bone concentrations were still greater than 1.0 microgram/mL. Two hours after dosing the average bone-to-plasma ratio was greater than 0.6. These data indicate that a single 400 mg oral dose of lomefloxacin attains bone concentrations that are above its usual minimum inhibitory concentrations for susceptible organisms.

Administration, Oral↗
PubMed1992

Cellulitis due to Streptococcus pneumoniae: case report and review.

Although Streptococcus pneumoniae remains the most common cause of community-acquired bacterial pneumonia, its involvement in skin infection is notably infrequent. A review of the literature uncovered only 13 cases of pneumococcal cellulitis in adults. Distinguishing features of skin infection by S. pneumoniae included the presence of bullae, brawny erythema, and a violaceous hue in the affected skin area. Most patients with pneumococcal cellulitis had chronic illnesses or were immunocompromised because of drug or alcohol abuse. Even with appropriate antimicrobial therapy, many patients required prolonged hospitalizations and surgery for cure. We report a case of primary pneumococcal cellulitis with secondary bacteremia in an alcoholic patient who required extensive surgical therapy and whose course was additionally complicated by acute glomerulonephritis.

Acute Disease↗
PubMed1992

Effect of sucralfate on pharmacokinetics of fleroxacin in healthy volunteers.

The effect of sucralfate on the pharmacokinetics of fleroxacin was assessed in 20 healthy male volunteers. The study was of a two-way crossover design in which subjects were randomized to one of the following two regimens at the time of entry: (i) a single 400-mg dose of fleroxacin alone or (ii) a 400-mg dose of fleroxacin given once and 1 g of sucralfate given every 6 h starting 24 h before fleroxacin treatment and continuing for 48 h after fleroxacin treatment. Blood samples were collected immediately before fleroxacin administration and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 h postdosing. Fleroxacin concentrations in plasma and urine were determined by high-performance liquid chromatography. While concurrent of fleroxacin and sucralfate resulted in a decrease in the area under the plasma concentration-time curve, a decrease in the maximum concentration, and an increase in the time to the maximum concentration (P < 0.05), these changes were modest compared with the interaction of other quinolones with sucralfate. The relative bioavailability of fleroxacin given with sucralfate, calculated from the area under the concentration-time curve, was 76% compared with that of fleroxacin alone. This is significantly better than the bioavailabilities of other quinolones (1.8 to 12.3%) when they are administered with sucralfate.

Adult↗
PubMed1992

Penetration of fleroxacin and ciprofloxacin into skin blister fluid: a comparative study.

The penetration of multiple-dose concentrations of oral fleroxacin (400 mg every 24 h) and ciprofloxacin (500 mg every 12 h) into skin blister fluid in 12 healthy volunteers was determined in a randomized crossover study. Serum, blister fluid, and paper disk samples were analyzed by large-plate microbiologic assay. The mean areas under the concentration-time curve (AUC) for serum were 88.6 and 18.2 micrograms.h/ml/70 kg for fleroxacin and ciprofloxacin, respectively. The mean AUC for blister fluid and paper disks were 71.2 and 15.0 micrograms.h/ml/70 kg and 77.8 and 15.4 micrograms.h/ml/70 kg for fleroxacin and ciprofloxacin, respectively. Calculated penetration into interstitial fluid ranged from 74 to 92% for fleroxacin and 56 to 96% for ciprofloxacin; penetration was calculated by using the ratio of maximum drug concentration or AUC in blister fluid and paper disks to maximum drug concentration or AUC in serum. There was no significant difference between fleroxacin and ciprofloxacin in the percent penetration into skin blister fluid.

Administration, Oral↗
PubMed1992

The relative bioavailability of temafloxacin administered through a nasogastric tube with and without enteral feeding.

The relative bioavailability of a single oral dose of temafloxacin given with and without enteral feeding was determined in 18 healthy male volunteers in a randomised crossover study. Subjects were administered 600mg of temafloxacin orally as an intact tablet, or a crushed tablet suspended in water administered through a nasogastric tube with or without an enteral feeding solution [Osmolite (Ross) 100 ml/h started 2h before administration of temafloxacin and continued for 4h postdose]. Plasma samples were analysed by a high performance liquid chromatographic technique. Mean peak plasma concentrations (Cmax) for the oral tablet, crushed tablet, and crushed tablet with enteral feeding solution were 3.95 +/- 1.02, 4.85 +/- 0.69, and 4.69 +/- 0.61 mg/L/70kg, respectively, and mean calculated area under the concentration-time curve from time 0 to 48h (AUC(0-48h)) values were 48.1 +/- 11.0, 54.5 +/- 6.52, and 49.7 +/- 5.89 mg/L.h/70kg, respectively. In terms of AUC(0-48h) and Cmax, the relative bioavailability of temafloxacin after nasogastric delivery of crushed temafloxacin given with and without an enteral feeding solution was equivalent to the reference oral regimen.

Administration, Oral↗
PubMed1992

Comparison of the efficacy, safety, and therapeutic usage of HA-1A and E5 in the treatment of gram-negative sepsis.

Clinical trials have shown that the murine monoclonal antibody E5 and the human hybrid monoclonal antibody HA-1A increase survival of patients with gram-negative sepsis. However, significant reduction in mortality associated with E5's use was limited to patients who had not progressed to refractory shock. Patients treated with E5 compared to placebo receivers were also significantly more likely to experience resolution of organ failures. Significant reductions in morbidity and mortality associated with HA-1A's use were limited to patients with gram-negative bacteremia, and occurred even in patients with shock. Treatment with HA-1A also had a significant positive effect on resolution of the major complications of sepsis (shock, disseminated intravascular coagulation, acute renal failure, acute hepatic failure, or adult respiratory distress syndrome) in patients with documented gram-negative bacteremia. Both products appear to be safe, with generally mild, transient, and clinically insignificant adverse effects reported.

Antibodies, Monoclonal↗
PubMed1992

Determining the formulary status of quinolone antibiotics: one institution's approach.

Streamlining antibiotic therapy--ie, simplifying regimens, route of administration, or both--is necessary in the modern treatment of hospitalized patients with infectious diseases. Due to their pharmacokinetic profiles and comparative efficacy and safety, the quinolone class of antibiotics is an ideal class for which to direct streamlining efforts. Including only one agent of this class on the formulary, however, is inadequate. Having several quinolones available, and thus expanding the local hospital market for them, enables more physicians to be contacted and educated by manufacturers' sales representatives as part of the hospital's antibiotic management program. By assisting in the education efforts, pharmaceutical representative help to conserve hospital resources, both in terms of cost and personnel. In addition, having more than one supplier of quinolones encourages competition, which favors price reductions.

Anti-Bacterial Agents↗