Glutethimide overdose--clinical and kinetic observations of glutethimide and a metabolite.
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Adult↗
Biomedical subjects
J C Rotschafer
Publications and source records attributed to J C Rotschafer.
Pharm.D. for all: who will provide the necessary resources?
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Education, Pharmacy↗
Therapeutic options for cefotaxime in the management of bacterial infections.
Clinical studies of cefotaxime administered every 8 and 12 h have demonstrated comparable clinical and microbiologic success when compared to traditional 6-h regimens. This phenomena may be explained, in part, by the pharmacokinetic and pharmacodynamic properties of cefotaxime and the antimicrobially active metabolite desacetyl-cefotaxime. Although cefotaxime levels cannot be maintained above the bacterial minimum inhibitory concentration (MIC) for all infecting pathogens with extended dosing intervals, concentrations of desacetyl-cefotaxime remain above the effective concentration for a variety of organisms throughout the extended interval. Cefotaxime dosage adjustment may be accomplished in nonimmunocompromised patients with infections outside the central nervous system including uncomplicated urinary tract and lower respiratory infections. Infections caused by bacteria with MIC90 values < or = 1 microgram/ml usually respond to 8- or 12-h dosage intervals. Less susceptible organisms with MIC90 values between 2 and 8 micrograms/ml, such as Serratia marcescens, may initially require cefotaxime administered every 6 or 8 h. Extended intervals should be avoided or used cautiously in patients that are neutropenic, immunocompromised, or hypermetabolic. Upon evidence of clinical and microbiologic response, therapy may be continued with alternative stepdown therapy.
Administration, Oral↗
The influence of serum albumin and alpha 1-acid glycoprotein on vancomycin protein binding in patients with burn injuries.
Ten patients with burn injuries (mean total body surface area burn = 29% +/- 16) were studied at various points in the course of their burn therapy. Alpha 1-Acid glycoprotein, albumin, and vancomycin concentrations were determined with either a trough or peak vancomycin quantitative determination. Alpha 1-Acid glycoprotein concentrations ranged from 125 to 333 mg/dl and albumin concentrations ranged from 1.7 to 4.2 gm/dl. Vancomycin protein binding, as determined by ultrafiltration, averaged 29% +/- 6%. There was a strong (r = 0.92) relationship between percent protein-bound vancomycin and albumin. There was a poor statistical relationship between percent protein-bound vancomycin and alpha 1-acid glycoprotein (r = 0.28). Alpha 1-Acid glycoprotein appeared to have virtually no effect on the protein-binding characteristics of vancomycin over the range of concentrations studied.
Adult↗
Wide variation in single, daily-dose aminoglycoside pharmacokinetics in patients with burn injuries.
Five to seven mg/kg single, daily-dose aminoglycoside regimens have been recently advocated as effective alternatives to traditional aminoglycoside regimens. The rationale for single, daily-dose aminoglycoside therapy is to produce an optimal ratio between aminoglycoside peak concentrations (Cmax) and pathogen minimal inhibitory concentration to maximize bacterial killing and to produce an aminoglycoside-free period during the 24-hour dosing interval. Single, daily-dose aminoglycoside therapy has not been recommended to date for use in the population of patients with burn injuries. The purpose of this study was to determine the magnitude and variability of aminoglycoside Cmax and the duration of the aminoglycoside-free period after simulated single, daily-dose regimens in patients with burn injuries. Fifty-two patients receiving gentamicin or tobramycin in the burn unit were studied retrospectively to determine the individualized pharmacokinetic parameters and the simulated Cmax and 24-hour after the dose trough minimum concentrations for 5 and 7 mg/kg single, daily-dose aminoglycoside regimens. Patients were only included in the final analysis if they had been treated for burn wound infections and exhibited a calculated creatinine clearance exceeding 60 ml/min (N = 40). Mean [percentage coefficient of variation] Cmax/minimum concentrations were 15.4[30.5]/0.03[200.0] and 21.6[30.6]/0.04[200.0] mg/L for 5 and 7 mg/kg daily doses, respectively. The mean coefficient of variation time to reach an extrapolated concentration of 0.1 mg/L was 15.9[30.8] hours and 17.0[30.6] hours for the 5 and 7 mg/kg daily doses, respectively. Substantial variability in aminoglycoside Cmax and duration of the aminoglycoside-free period was observed. These data suggest that many patients with burn injuries are not candidates for single, daily-dose aminoglycoside therapy because of restrictive creatinine clearance criteria and pronounced variability in length of the aminoglycoside-free interval. If single, daily-dose aminoglycoside therapy is to be used in this patient population, therapeutic drug monitoring is recommended to screen for appropriate candidates and to optimize Cmax and minimal inhibitory concentration ratios and duration of the aminoglycoside-free interval.
Adolescent↗
Characterization of synergy between ofloxacin, ceftazidime, and tobramycin against Pseudomonas aeruginosa.
The purposes of this study were to investigate the potential for synergy between ceftazidime, tobramycin, and ofloxacin against two clinical isolates (PSA 9258, and PSA 9263) of Pseudomonas aeruginosa utilizing time-concentration-kill curves. A pharmacodynamic model was used to simulate one-compartment pharmacokinetics for single-, double-, or triple-drug combinations utilizing two different elimination half-lives (T1/2). Each duplicate experiment was conducted for 24 h in cation-supplemented Mueller-Hinton broth. Synergy, indifference, and antagonism were defined as reductions of > or = 2.0, > or = 0 to < or = 2, or < or = 0 in mean log10 CFU/ml (CFU = colony-forming units) in bacterial counts at any time point during the 24-hour experiment, respectively. Time-concentration-kill curve studies simulating a peak concentration (CP) = 6 micrograms/ml and T1/2 = 5.5 h for ofloxacin combined with ceftazidime (CP = 80 micrograms/ml; T1/2 = 2 h) resulted in 2.18 and 1.81 log CFU/ml mean decreases in bacterial counts for PSA 9258 and 9263, respectively. Simulated ofloxacin pharmacokinetic parameters (CP = 6 micrograms/ml); T1/2 = 5.5 h) combined with tobramycin (CP = 8 micrograms/ml; T1/2 = 2 h) produced 2.26 and 0.6 log CFU/ml mean reductions in bacterial counts for PSA 9258 and 9263, respectively. Time-concentration-kill curve results were inconsistent with checkerboard synergy experiments which indicated antagonism for ofloxacin/tobramycin combinations (fractional inhibitory concentrations = 2.0/2.5) and indifference for ofloxacin/ceftazidime combinations (fractional inhibitory concentrations = 1.0/1.0). In secondary experiments, tobramycin (T1/2 = 2 h) and ceftazidime (T1/2 = 2 h) at concentrations of one fourth and equal to the minimum inhibitory concentration were combined with ofloxacin (CP = 6 micrograms/ml; T1/2 = 5.5 h). When ofloxacin was combined with tobramycin equivalent to the minimum inhibitory concentration, mean reductions in bacterial counts were 3.74 and 5.59 CFU/ml. These results suggest that an enhanced antipseudomonal activity may result by the combination of clinically achievable concentrations of ofloxacin with minimum inhibitory concentration equivalent concentrations of tobramycin.
Anti-Bacterial Agents↗
Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation.
BACKGROUND: The purpose of this study was to determine if mixing of fluoroquinolones with a common enteral feeding formulation, Ensure (Ross Products Division, Abbott Laboratories, Columbus, OH), would alter the measured in vitro quinolone concentrations over a 24-hour period. METHODS: Tablets of ciprofloxacin (500 mg), levofloxacin (500 mg), and ofloxacin (300 mg) were crushed and mixed with 240 mL of Ensure, water and calcium chloride (500 mg/L), water and magnesium chloride (200 mg/L), water and calcium chloride and magnesium chloride, and water alone. Fluoroquinolone concentrations of the mixtures were measured, via high-performance liquid chromatography, at baseline and serially over 24 hours. Experiments were performed in duplicate, at three temperatures (5 degrees C, 25 degrees C, and 37 degrees C). RESULTS: Average decreases of 82.5% +/- 1.5% for ciprofloxacin, 61.3% +/- 5.2% for levofloxacin, and 45.7% +/- 10.1% for ofloxacin (mean +/- 95% CI) were observed in vitro for Ensure over the two experimental sets at baseline. Serial analysis revealed no further significant change in any of the quinolone concentrations over the remaining 24-hour period. No significant decrease was noted with the quinolones when mixed in water and calcium, water and magnesium, water and calcium and magnesium, or water alone. This phenomenon appears to be unaffected by time and temperature. CONCLUSIONS: These data suggest there is an immediate and significant loss of fluoroquinolone when mixed with Ensure. An explanation for the loss of fluoroquinolone remains unclear.
Anti-Infective Agents↗
Pseudomonas aeruginosa susceptibility in a university hospital: recognition and treatment.
Pseudomonas aeruginosa continues to be a leading cause of nosocomial bacteremia and other serious, often life-threatening infections. The incidence of P. aeruginosa infection appears to be increasing. The resilience of Pseudomonas in the hospital environment, its endogenous virulence factors, and its current level of resistance to antimicrobials make it a formidable pathogen, particularly in a compromised host. Despite the availability of several effective antipseudomonal antibiotics, infections caused by this pathogen are still associated with significant morbidity and mortality. Early recognition and prompt intervention with appropriate antimicrobial agents are vital to successful management. Combination therapy with an aminoglycoside and an extended-spectrum penicillin or cephalosporin is recommended in the initial management of suspected or documented P. aeruginosa infections.
Aminoglycosides↗
Selective decontamination of the digestive tract in intensive care patients: review and commentary.
OBJECTIVE: To evaluate the benefits, risks, and costs of antimicrobial regimens used for selective decontamination of the digestive tract (SDD) in intensive care unit (ICU) patients. DATA SOURCES: Information was obtained from clinical trials, review articles, abstracts, and textbooks. Key indexing terms included antibiotics, selective decontamination, and infections. STUDY SELECTION: Research articles describing controlled clinical trials of SDD in medical or surgical ICU patients were reviewed. Trials that investigated transplant, cirrhotic, leukemic, or oncology patient populations were excluded. DATA EXTRACTION: The details of studies that evaluated nosocomial infection or nosocomial pneumonia rates were extracted. These included study design, demographics, SDD regimens, severity of illness scores, and colonization, infection, and mortality rates. DATA SYNTHESIS: The use of SDD in mechanically ventilated surgical or trauma ICU patients reduces the incidence of colonization, nosocomial pneumonia, and overall infection rates, but does not change the overall mortality rate. Administration of antibiotic and antifungal agents in a nasogastric suspension is required for SDD. The addition of systemic prophylactic antibiotics or oropharyngeal paste was not required to decrease nosocomial infections. The most frequently studied SDD regimen (colistin/amphotericin B/tobramycin) is not feasible for use in the US because of exorbitant drug costs. Less expensive alternatives include norfloxacin/nystatin, or colistin/nystatin/gentamicin. CONCLUSIONS: Additional research is required before SDD regimens can be routinely recommended in surgical and trauma ICU patients. A multicenter study is warranted to determine the long-range benefits, potential for resistance, and cost-effectiveness of SDD.
4-Quinolones↗
Current management of human bites.
Human bites should be considered dangerous injuries with potentially serious complications. Their characteristics vary from an uninfected abrasion to a serious infection such as cellulitis or osteomyelitis. An estimated 10% of the injuries become infected; suspected pathogens include oral and skin flora. Management consists of history and examination, wound care, surgical intervention if necessary, assessment of risk of disease transmission, and appropriate antibiotic prophylaxis or treatment. The best choice for oral or intravenous antibiotic therapy remains the combination of a beta-lactam antibiotic with a beta-lactamase inhibitor. Among the most serious human bites are clenched fist injuries, which often require surgical intervention and intravenous antibiotic therapy.
Anti-Bacterial Agents↗