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Biomedical subjects

R Quintiliani

Publications and source records attributed to R Quintiliani.

At least 163 records · Page 9Linked to original sources
PubMed1987

Pseudomonas peritonitis in neutropenic rats treated with amikacin, ceftazidime and ticarcillin, alone and in combination.

Peritonitis in neutropenic rats, caused by a strain of Pseudomonas aeruginosa resistant to amikacin and ticarcillin alone but susceptible to ceftazidime and combinations of amikacin with ticarcillin, amikacin with ceftazidime and ticarcillin with ceftazidime, was investigated. Four hours after a bacterial challenge with a LD70 intraperitoneal dose of P. aeruginosa (1.5 X 10(8) cfu/ml), either amikacin, ticarcillin, ceftazidime, amikacin-ticarcillin, amikacin-ceftazidime, or ticarcillin-ceftazidime was administered at dosing intervals that mimicked the serum concentrations of the drugs found in humans after therapeutic doses. When the serum concentrations did not exceed the MIC, as occurred with amikacin, no difference in survival was observed compared with controls. All other regimens resulted in animal survival during the treatment. When therapy was stopped only those regimens resulting in serum concentrations above the MBC were effective (amikacin-ticarcillin, amikacin-ceftazidime, ticarcillin-ceftazidime). The recovery of viable bacteria from the peritoneum agreed well with mortality.

Agranulocytosis↗
PubMed1987

Effect of mucin on the pharmacokinetics of antibiotics in the rat.

The intramuscular pharmacokinetics of ticarcillin and amikacin in rats receiving 1 ml of 5% mucin suspension (equivalent to 250 mg/kg) administered intraperitoneally were not altered compared with the control animals. However, it is important to investigate the effect of mucin on the pharmacokinetics of antimicrobial agents in animals which are used to evaluate the efficacy of the agents.

Amikacin↗
PubMed1986

A pharmacodynamic model for the activity of antibiotics against microorganisms under nonsaturable conditions.

An exact mathematical solution was derived to a pharmacodynamic model which illustrates bacterial survival in the presence of antibiotics. In this report the survival of Pseudomonas aeruginosa in the medium of an initial concentration of 0.64 mM (320 mg/L) of piperacillin [(2S,5R,6R)-6-[(R)-2-(4-ethyl-2,3-dioxo-1- piperazinecarboxyamido)-2-phenylacetamido]-3,3-dimethyl-7- oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate] was well described by the derived model for up to 24 h. The bacterial killing by the antibiotic and apparent natural growth rate constants were 2955.3 h-1 X mol-1 and 0.5698 h-1, respectively. The functional equation was also fit to the data of ampicillin against Escherichia coli under simulated in vivo conditions. The optimal multiple dosing time and the minimum critical concentration to achieve antimicrobial action can be readily calculated from the developed model. Computer simulations were made to examine the effect on microbial survival of such factors as initial antibiotic concentration (Co), elimination half-life (t1/2), kill rate constant (K) of the antibiotic, and apparent growth rate constant (Kapp) of the test organism.

Ampicillin↗
PubMed1986

Effect of saturable serum protein binding on the pharmacokinetics of unbound cefonicid in humans.

Previous studies have demonstrated high, concentration-dependent serum protein binding of cefonicid. To determine the in vivo pharmacokinetic significance of these observations, the pharmacokinetics of both total and unbound (non-protein-bound) cefonicid was studied in six volunteers after a single intravenous dose of 30 mg/kg. Saturable serum protein binding was observed in vivo; the mean +/- standard deviation free fraction of cefonicid was 17.6 +/- 6.1% immediately after administration and declined to a constant value of approximately 2% as total serum concentrations fell below 100 micrograms/ml. This nonlinear binding was associated with a pronounced decline in unbound serum cefonicid concentrations during the first 3 h after administration, with low or undetectable unbound drug concentrations by 12 h. Renal clearance of total cefonicid averaged 21.1 ml/min per kg and did not vary with time; in contrast, the mean +/- standard deviation unbound cefonicid renal clearance increased from 5.7 +/- 2.1 to 10.8 +/- 1.6 ml/min per kg with time (P less than 0.02). This study may partially explain the poor results obtained with single daily dosing of cefonicid in endocarditis. Dosage regimens of certain antimicrobial agents with high, saturable serum protein binding and extensive renal tubular secretion may be most appropriately designed based on unbound drug pharmacokinetics.

Adult↗
PubMed1986

Efficacy of a twice-daily regimen of cefadroxil in the treatment of respiratory tract infections.

This multicentre open study evaluated the responses of 474 adult and paediatric patients with upper or lower respiratory tract infections to treatment with cefadroxil (25 to 50 mg/kg in children and 500 mg to 1 g in adults) twice daily for 10 to 30 days. Complete or partial cures seen in 81% to 100% of all patients correlated with the eradication of 87% to 100% of the causative pathogens, most commonly beta-haemolytic streptococci, S. aureus or S. pneumoniae. Mild, transient side effects, usually gastrointestinal disturbances or hypersensitivity reactions, were reported in 4.8% of patients. Thus, the safety and efficacy of this oral cephalosporin recommends its use in the treatment of infections of the respiratory tract.

Cefadroxil↗
PubMed1986

Oral bacitracin vs vancomycin therapy for Clostridium difficile-induced diarrhea. A randomized double-blind trial.

The effectiveness of a ten-day course of either oral bacitracin or oral vancomycin hydrochloride for treatment of Clostridium difficile-induced antibiotic-associated diarrhea was compared in a randomized double-blind study. Bacitracin was as effective as vancomycin in resolving diarrhea; most patients responded within five days of therapy with either drug. Three patients receiving bacitracin worsened during therapy; two of these were considered treatment failures. Neither C difficile nor its toxin was detected in stool samples collected on the final day of therapy in 71% of patients (10/14) receiving vancomycin and in 30% (3/10) receiving bacitracin. Five patients receiving bacitracin and three receiving vancomycin had at least one recurrence. Low but nontoxic concentrations of bacitracin were detected in serum samples collected from 11 patients. Oral bacitracin at this dosage level was as effective as vancomycin in resolving the symptoms of C difficile-induced antibiotic-associated diarrhea in most patients but was less effective in eradicating C difficile and its toxin from patients' stools.

Aged↗
PubMed1986

Therapy of Mycobacterium marinum infections. Use of tetracyclines vs rifampin.

We describe four patients with Mycobacterium marinum infections who did not respond to two- to six-week courses of therapy with tetracycline, minocycline, and doxycycline. All four patients had prompt responses to therapy with either rifampin alone (two patients) or rifampin in combination with ethambutol. Results of antimicrobial sensitivity tests may be helpful in guiding therapy. Rifampin may be the drug of choice for treatment of these infections.

Adult↗
PubMed1985

Combination antibiotic therapy: comparison of constant infusion and intermittent bolus dosing in an experimental animal model.

To determine the effect of the mode of administration on antibiotic efficacy, 300 neutropenic rats were infected intraperitoneally with an LD-70 inoculum of Pseudomonas aeruginosa and treated with synergistic combinations of amikacin and ticarcillin by intermittent or constant infusion technique. The treatment regimens were designed to provide the same peak serum concentrations that would be observed in humans receiving these drugs. Drug administration over the 24-h period was controlled to ensure that intermittent and constant infusion techniques achieved the same area under the serum concentration/time curves. Based on cumulative mortality at 96 h and viable bacterial cell counts at the site of inoculation constant infusion of both antibiotics produced the best therapeutic results.

Amikacin↗
PubMed1984

Treatment and prevention of oropharyngeal candidiasis.

As more potent antibacterial drugs are used to combat infections and as more patients with impaired defenses against infection are treated, other organisms, like fungi, have become important pathogens. Fungi of all types may appear in this setting, but Candida species are the most common, usually beginning as an infection in the oropharynx. Although oropharyngeal candidiasis usually remains localized, it may spread elsewhere, leading to a fatal outcome. Controversy still exists regarding the best drug to prevent or treat oropharyngeal candidiasis, but clotrimazole given as a troche may be the best choice at the moment owing to its high clinical success rate, safety, cost effectiveness, and high patient acceptability. There remains a need for more randomized and controlled studies comparing the efficacy of nystatin, ketoconazole, and clotrimazole in high-risk patients in whom invasive candidiasis remains a frequent problem.

Adolescent↗
PubMed1984

Comparative penetration of cefonicid and cefazolin into the atrial appendage and pericardial fluid of patients undergoing open-heart surgery.

The penetration of cefonicid and cefazolin into cardiac tissue was compared after a single 30-mg/kg dose in 30 patients undergoing aortocoronary artery bypass graft surgery. Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various times and assayed for drug content. The concentrations of cefonicid in serum and the atrial appendage were at least twice those observed for cefazolin at a given time after a dose. The mean (+/- standard deviation) atrial appendage-serum ratio was 0.47 +/- 0.14 for cefonicid and 0.34 +/- 0.06 for cefazolin (P less than 0.005). Pericardial fluid concentrations of cefonicid were slightly lower than those observed in patients receiving cefazolin (P greater than 0.05). A single intravenous dose of cefonicid provides high and sustained concentrations in serum and cardiac tissue and thus may be useful in antibiotic prophylaxis of certain surgical procedures; however, further study of the efficacy of this agent in the prevention and treatment of infections associated with Staphylococcus spp. is needed.

Aged↗
PubMed1984

Pharmacokinetics of trimethoprim and sulfamethoxazole in serum and cerebrospinal fluid of adult patients with normal meninges.

The pharmacokinetics of trimethoprim (TMP) and sulfamethoxazole (SMX) in cerebrospinal fluid (CSF) and serum after a single intravenous infusion of 5 mg of TMP and 25 mg of SMX per kg of body weight over approximately 120 min were studied i nine patients who had uninflamed meninges and were undergoing elective myelography. Peak concentrations of TMP and SMX in CSF were 1 microgram/ml and 13.8 micrograms/ml, respectively. The peak TMP concentration in CSF occurred significantly earlier than the peak SMX concentration (60 versus 480 min postinfusion). At 15 h, there was no detectable TMP in the CSF, and there was 4.7 micrograms of SMX per ml of CSF. In the postdistribution phase (in CSF), simultaneous CSF-to-serum concentration ratios ranged from 0.23 to 0.53 for TMP and from 0.20 to 0.36 for SMX. CSF penetration (measured by comparison of the area under the curve of the composite CSF and serum concentration-time curves) was 18% for TMP and 12% for SMX. A loading dose of TMP-SMX (bases on TMP) of 10 to 12 mg/kg and a maintenance dose of 6 mg/kg every 8 h or 8 mg/kg every 12 h (with a 2-h infusion) should yield steady-state peak concentrations of at least 5 micrograms of TMP per ml of serum and 160 micrograms of SMX per ml of serum. Further studies of TMP-SMX administered in these doses in the treatment of serious bacterial infection, including meningitis, are warranted.

Adult↗
PubMed1984

Trimethoprim-sulfamethoxazole for bacterial meningitis.

Trimethoprim-sulfamethoxazole has excellent microbiologic activity against most pathogens that produce meningitis; both components of this drug have high penetration into tissues, including the cerebrospinal fluid. Clinical experience shows that trimethoprim-sulfamethoxazole may be beneficial in the treatment of gram-negative bacillary meningitis caused by organisms only moderately susceptible to third-generation cephalosporins (Enterobacter cloacae, Serratia marcescens) or resistant to these antibiotic agents (Pseudomonas cepacia, Acinetobacter). The success of trimethoprim-sulfamethoxazole in the treatment of four patients with Staphylococcus aureus and two patients with Listeria monocytogenes meningitis shows that this drug may also be useful in treating infrequent types of gram-positive meningitis.

Adolescent↗