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Biomedical subjects

R Quintiliani

Publications and source records attributed to R Quintiliani.

At least 145 records · Page 8Linked to original sources
PubMed1988

Comparative pharmacokinetics of cefotetan and cefoxitin in patients undergoing hysterectomies and colorectal operations.

Forty patients undergoing hysterectomy and 16 patients undergoing colorectal surgery were given intravenous 2 g doses of cefotetan (20 in the hysterectomy group and 8 in the colorectal group) or cefoxitin (20 in the hysterectomy and 8 in the colorectal group) before surgery. Serum samples were obtained simultaneously with tissue samples. Concentrations of each drug in serum and tissue were measured by high-pressure liquid chromatography. In both experiments, the composite drug concentration profile as a function of time in serum was consistent with that observed in nonsurgical patients; that is, a half-life of approximately 3.5 hours and 0.8 hours for cefotetan and cefoxitin, respectively. This also was true of tissue kinetics, in that tissue profiles appeared parallel to, but somewhat lower than, serum. At 20 minutes after administration, the peak myometrium concentration was 158 micrograms/g for cefotetan, and the corresponding serum concentration was 298 micrograms/ml. For cefoxitin, the corresponding values were 66 micrograms/g and 101 micrograms/ml. At 47 minutes, the cefotetan tissue and serum concentrations were 29 micrograms/g and 235 micrograms/ml respectively, and the corresponding values for cefoxitin were 15 micrograms/g and 43 micrograms/ml. Similar relationships were observed with these drugs in colorectal tissue. Although both antibiotics provide good concentrations during the early phase of surgery, cefotetan's concentrations persisted longer, which may be relevant in the prevention of infection in prolonged surgical procedures.

Cefotetan↗
PubMed1988

Microbial pharmacodynamics of piperacillin in neutropenic mice of systematic infection due to Pseudomonas aeruginosa.

Mathematical solutions for two possible pharmacodynamic interactions (linear nonsaturable and nonlinear saturable) between antibiotics and microorganisms derived from the incorporation of clinically relevant antibiotic dosage regimens such as single bolus dosing, multiple doses, and constant infusion at steady state have been obtained. It is concluded that the saturable nonlinear interaction model between the tested antibiotic and microorganism appears appropriate. The model and its derived equations are capable of describing in vivo bacterial growth of P. aeruginosa after single bolus dosing and multiple doses of piperacillin as described by a linear one-compartment pharmacokinetic model. The activity of piperacillin against P. aeruginosa in the neutropenic mouse systemic infection model can be described by an equation with three dynamic parameters: the bacterial growth rate constant kapp, 0.02345 min-1, the bacterial killing rate constant k'kill, 0.02623 min-1, and the Michaelis-Menten type saturation constant Km, 0.05467 microgram/ml. The concept and derived equations for the optimal dosing interval and minimum critical concentration are of clinical importance for the proper selection of antibiotic dosage regimens.

Agranulocytosis↗
PubMed1988

The pharmacokinetics of metronidazole and its metabolites in critically ill patients.

We evaluated the disposition of metronidazole and its two major metabolites in 14 critically ill patients with liver and renal dysfunction. Patients received 500 mg of metronidazole iv for periods of 2-13 days and were studied either during therapy or after their final dose. The metronidazole half-life ranged between 4.95 and 42.4 h. Patients with obstructive liver disease exhibited the longest half-lives (9.15-42.4 h) and lowest clearances (0.281-1.17 ml/min/kg). The presence of obstructive liver disease or renal impairment appeared to prolong the elimination of the hydroxymetabolite. We conclude that the pharmacokinetics of metronidazole and its metabolites are significantly affected in critically ill patients with liver and renal dysfunction.

Adult↗
PubMed1988

Current concepts in the treatment of staphylococcal meningitis.

As natural host defences are suboptimal in cerebrospinal fluid (CSF), and since antibiotics often penetrate poorly into this body site, meningitis remains one of the most difficult infections to cure. When the responsible pathogen is killed only by a relatively high concentration of an antibiotic, or is susceptible only to drugs with moderate penetration into the CSF, then treatment becomes even more complicated. Therapy of staphylococcal meningitis poses all these problems, and is even further complicated by its frequent development in the presence of a foreign body, such as a ventriculoperitoneal or ventriculoatrial shunt. In this review, we discuss the various options open to the clinician in the treatment of meningitis caused by methicillin-susceptible and methicillin-resistant staphylococci, both in the presence and in the absence of a foreign device.

Glycopeptides↗
PubMed1988

Effect of protein binding on drug penetration into blister fluid.

The effect of protein binding on drug penetration into blister fluid was evaluated by using cefonicid, ceftizoxime, and cefotaxime. Drug concentrations in a chamber with a high surface area/volume ratio (i.e., paper disk) follow changes in serum more closely than do those in a chamber with a low surface area/volume ratio. Both the area under the concentration-time curve ratio and the concentration ratio (by the disk method) for cefonicid were statistically lower than the ratios for ceftizoxime and cefotaxime. The high degree of protein binding of cefonicid results in the availability of less drug for diffusion to blister fluid than with the low-protein-binding ceftizoxime and cefotaxime.

Adult↗
PubMed1988

Inadequate mixing in microdilution wells during preparation of antimicrobial dilutions for susceptibility testing.

An equation representing a twofold series of antibiotic dilutions was derived. The theoretical results were then validated with experimental observations of piperacillin against Pseudomonas aeruginosa. Insufficient mixing leads to an erroneously low MIC. It is concluded that maintaining antibiotic concentration equilibrium during microdilution is required for accurate microdilution susceptibility tests.

Microbial Sensitivity Tests↗
PubMed1988

High teicoplanin uptake by human neutrophils.

The cellular/extracellular (C/E) concentration ratio of teicoplanin in polymorphonuclear leukocytes (PMNs) increased rapidly with time (C/E 60 +/- 13 at 20 min). The C/E ratio was time- and concentration-dependent. At 20 min and an initial concentration of 75 +/- 16 micrograms/ml the cellular drug concentration was 4,700 +/- 1,300 micrograms/ml. The mechanism of drug uptake was by an active process and transported (cellular) drug retained its antimicrobial activity. Washing removed 42% of cellular drug. Teicoplanin inhibited PMN chemotaxis at very high concentrations and PMN microbicidal activity at lower concentrations.

Biological Transport, Active↗
PubMed1988

Serum and tissue concentrations of cefoxitin and cefotaxime in women undergoing hysterectomy.

In a comparative study of serum and uterine tissue concentrations of cefoxitin and cefotaxime in patients undergoing hysterectomy, 40 patients were randomised to receive either cefoxitin 2g or cefotaxime 2g by intravenous administration. Serum samples were obtained before drug administration, at the ligation of the uterine arteries and at the end of surgery. Cefoxitin, cefotaxime and desacetylcefotaxime concentrations were determined by high performance liquid chromatography. The composite serum half-lives (determined by linear regression) for cefoxitin, cefotaxime and desacetylcefotaxime were 0.8, 0.7 and 2.1 hours, respectively. Although serum concentrations were higher for cefotaxime than for cefoxitin after a 2g dose, the uterine concentrations (at 40 mins) of cefoxitin were higher (51 micrograms/g vs 16 micrograms/g) than those of cefotaxime. After a 2g dose of cefotaxime the desacetylcefotaxime peak uterine concentration was 8 micrograms/g. Both drugs achieved adequate concentrations in serum and uterine tissue to prevent and treat infections caused by common Enterobacteriaceae such as Escherichia coli, with cefotaxime having a longer apparent duration of activity. However, cefoxitin provided serum and uterine concentrations above the minimum inhibitory concentration of Bacteroides fragilis for a longer period than did cefotaxime.

Adult↗
PubMed1988

Multidisciplinary cost-containment program promoting oral metronidazole for treatment of antibiotic-associated colitis.

A multidisciplinary cost-containment program for promoting oral metronidazole in place of oral vancomycin as initial therapy of antibiotic-associated colitis (AAC) is described. The pharmacy department and the division of infectious diseases implemented the program in two phases. In the first phase, a one-year retrospective drug-use review in patients with AAC treated with oral vancomycin was conducted to determine the average cost of therapy per treatment course. In the second phase, the use of oral metronidazole instead of oral vancomycin for initial treatment of AAC was promoted using inservice-education programs and distribution of pocket-size brochures containing AAC treatment guidelines to medical staff. The pharmacy and therapeutics committee supported the program by endorsing metronidazole as the drug of choice for AAC and by distributing follow-up progress reports of the program to medical staff. Pharmacists on the nursing units were responsible for enforcing the program stipulations regarding vancomycin and metronidazole use and for collecting data on patient-specific drug use. Six months after implementation of the program, the average cost of drug therapy for AAC had decreased by 89%, from $343.24 per patient to $37.50 per patient. The projected annual savings resulting from the program was $38,829.02. All prescribing physicians and dispensing pharmacists complied 100% with the program stipulations regarding drug use. The multidisciplinary program described here was successful in promoting the use of oral metronidazole for initial therapy of AAC.

Administration, Oral↗
PubMed1988

Multidisciplinary cost-containment program promoting less frequent administration of injectable mezlocillin.

A multidisciplinary cost-containment program for promoting less frequent administration of mezlocillin injection is described. The pharmacy department and the division of infectious diseases at Hartford Hospital implemented a program through which regimens of mezlocillin 5 g every eight hours would automatically be substituted for the frequently prescribed regimen of mezlocillin 3 g every four hours. Patients with urinary-tract infections or renal insufficiency and febrile neutropenic cancer patients also received various modified regimens. Use of the modified regimens was promoted through inservice education programs and distribution of newsletters and pocket-size brochures describing the dose-dependent pharmacokinetics of mezlocillin to medical staff. The pharmacy and therapeutics committee supported the program by endorsing the use of the modified regimens and distributing periodic progress reports. Pharmacists on the nursing units were responsible for enforcing the program stipulations regarding modified dosage regimens and for reporting adverse reactions and unexpected therapeutic failures. Ten months after implementation of the program, there was better than 99% compliance with the appropriately modified mezlocillin dosage regimens. Theoretical annual cost savings based on less frequent administration of mezlocillin injection amount to more than $33,000. The multidisciplinary program described here was successful in promoting the use of modified mezlocillin dosage regimens.

Connecticut↗
PubMed1988

Multidisciplinary program for promoting single prophylactic doses of cefazolin in obstetrical and gynecological surgical procedures.

A multidisciplinary cost-containment program for promoting the use of single prophylactic doses of cefazolin for obstetrical and gynecological surgical procedures is described. Following a one-month review of patient charts to identify the antimicrobial regimens used most frequently for prophylaxis in obstetrical and gynecological surgical procedures, the department of pharmacy services, with the cooperation of the pharmacy and therapeutics (P&T) committee and the departments of obstetrics and gynecology and infectious diseases, implemented an educational program to promote the use of single doses of cefazolin for surgical prophylaxis. The program included inservice education and distribution of letters of support and a therapeutics newsletter. Drug stocking patterns in the operating and delivery rooms were changed to make cefazolin more accessible, and the P&T committee formally restricted the use of prophylactic antimicrobial agents in obstetrical and gynecological surgical procedures to single doses of cefazolin unless a consulting infectious-disease physician recommended otherwise. Compliance with the program increased as each step was implemented; data collected 16 months after the program was initiated demonstrated a compliance rate of 78.8%. Based on comparison of data collected before initiation and six months after initiation of the program, an actual cost savings of +7,125 was realized, which extrapolates to +14,250 annually. No apparent adverse effects on patient care were noted. The multidisciplinary approach to promoting the use of single doses of cefazolin was effective.

Cefazolin↗
PubMed1988

Antibiotic streamlining from combination therapy to monotherapy utilizing an interdisciplinary approach.

Streamlining of antibiotic therapy from a more complex to a less complex regimen should reduce hospital costs. Utilizing the expertise of an infectious disease physician and clinical pharmacists, an antibiotic-streamlining program was implemented by (1) daily collection of data on patients receiving two or more parenteral antibiotics, (2) formulation of recommendations of cost-effective alternative therapy when clinically appropriate, (3) oral and/or written communication of the reasons for the recommendation to the patient's physician, (4) follow-up monitoring, and (5) determination of the cost savings by subtracting the actual cost of antibiotic therapy (including labor and supplies) from the cost of the initial regimen if it had been continued without alteration. Streamlining recommendations were made in 340 of 625 patients who were reviewed during the initial seven months. Cases that necessitated streamlining recommendations decreased from 98.6% during the first month to 54.4% during the seventh month, reflecting the educational impact of the program on prescribing habits. Recommendations were followed in 82.6% of the cases, of which 97.2% completed therapy with the streamlined regimen. The projected annual savings of the program was +107,637.

Anti-Bacterial Agents↗
PubMed1987

Economic impact of streamlining antibiotic administration.

Decisions concerning antibiotic administration in the treatment of serious hospital-associated infections present important cost considerations and opportunities for the prescribing physician. There tend to be three distinct stages of therapy for such infections and, especially in the latter two stages, cost containment is enabled by close monitoring of mode, level, and frequency of antibiotic dosing. The first stage of therapy typically lasts about three days, during which time uncertainty exists about what is the cause of the infection. Therapy is given empirically, often with the combination of an aminoglycoside and a beta-lactam antibiotic. The second stage begins about the fourth day, at which time definitive microbiologic and clinical data are available that should allow for streamlining of antibiotic therapy, usually from combination therapy to more cost-effective monotherapy. Unfortunately, even when new data indicate that single, inexpensive therapy is possible, physicians often continue with the initial, expensive empiric drugs. It is at this stage in the patient's hospital stay that routine assessment of antibiotic management would offer the first chance to reduce hospital antibiotic costs without compromising clinical outcome. The third stage of therapy typically begins around the seventh day, when the patient is usually clinically stable and afebrile. At this point, often the only reason for continued hospitalization is so that treatment with parenteral antibiotics may continue. In many of these patients, however, therapy can be switched from the parenteral to the oral drug mode, and thus they can be treated on an outpatient basis. Streamlining antibiotic therapy by changing modes and frequency of administration represents a major step toward effective, responsible cost containment.

Administration, Oral↗