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Biomedical subjects

C H Nightingale

Publications and source records attributed to C H Nightingale.

At least 181 records · Page 10Linked 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↗
PubMed1987

Basic principles of pharmacokinetics.

Pharmacokinetics can be used clinically to empirically describe the serum concentrations of drugs in the body. With a good understanding of the general principles utilized in predicting drug levels, the practitioner can understand the drugs and specific patient populations most likely to benefit from or need careful adjustment in therapeutic drug monitoring.

Humans↗
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

Bacteriologic contamination of intravenous infusion delivery systems in an intensive care unit.

Seventy intensive care unit patients were admitted to a double-blind prospective study to determine the level of contamination associated with the admixture and administration of intravenous solutions and whether intravenous filtersets prevented bacteremia. Patients were randomly assigned a 0.22 micron filterset (real filter) or a filter cartridge without a 0.22 micron membrane (blank filter) on all possible intravenous lines. Forty-six (14.1 percent) real filtersets and 38 (11.3 percent) blank filtersets were found to be contaminated, and overall 30 patients (42.4 percent) were found to have extrinsically contaminated intravenous administration systems at least once during the study. Bacterial adherence to the plastic cartridge was demonstrated to be responsible for culture-positive blank filtersets. Staphylococcus epidermidis was the organism most frequently isolated from real and blank filtersets. Epidemiologic surveillance identified 10 patients with blank filtersets and three patients with real filtersets with clinically significant hospital-acquired bacteremias during the study period. It is concluded that a significant level of extrinsic contamination of intravenous infusion delivery systems occurred on the intensive care unit; documented clinically significant nosocomial bacteremias occurred less often in those patients who had a 0.22 micron bacterial retention filter on all possible intravenous lines.

Bacteriological Techniques↗
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

Penetration and concentration of cefadroxil in sputum, lung and pleural fluid.

The penetrability of cefadroxil in sputum, pleural fluid and lung tissue was examined in patients with acute respiratory infections, or who were undergoing thoracic surgery. The concentration of antibiotic in these tissues after single doses of 500 mg or 1 g was approximately half of that seen in serum, but persisted longer. In all biological matter studied, the concentration of cefadroxil was sufficient to inhibit pathogens such as S. aureus, S. pneumoniae and S. pyogenes, shown to be common causes of respiratory illnesses. Thus, cefadroxil should be a useful agent in the treatment of such infections.

Adolescent↗
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↗
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

Integration of pharmacokinetics and pharmacodynamics of methicillin in curative treatment of experimental endocarditis.

The rabbit model for Staphylococcus aureus endocarditis was used to compare cure rate and pharmacokinetic profile of four dosing regimens of methicillin. Equal daily doses (120 mg/kg) in five day treatment periods were given to 40 rabbits. Doses were given by bolus 20 mg/kg every 4 h (q 4 h), 40 mg/kg every 8 h (q 8 h), 60 mg/kg every 12 h (q 12 h) or by continuous infusion. The methicillin pharmacokinetics resulting from each regimen were monitored along with the course of the infection in each rabbit. For each regimen, time above MBC, peak height, area under the curve (AUC) above MIC and MBC were measured. Post antibiotic effect (PAE) duration and log growth time (LGT) values were obtained from the literature. Significantly more rabbits treated by q 4 h and q 8 h (P less than 0.05) survived 14 days after cessation of methicillin treatment than did rabbits treated q 12 h or continuous infusion. The four regimens differed in peak concentration and time above MBC. Despite producing the highest peak concentrations, the q 12 h regimen was the least effective. The duration above MBC was 2.0, 1.5, and 0.6 hours for q 12 h, q 8 h and q 4 h regimens, respectively. Continuous infusion produced methicillin concentration just above MBC over the entire five day treatment period, but was not as effective as q 4 h or q 8 h regimens. The most successful intermittent bolus regimens were those in which the sum of time above MBC, the duration of PAE, and one LGT were approximately equal to the actual dosage interval.

Animals↗
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↗