Levofloxacin use at an academic teaching institution.
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Anti-Infective Agents↗
Biomedical subjects
P P Belliveau
Publications and source records attributed to P P Belliveau.
Failure to eradicate vancomycin-resistant enterococci in a university hospital and the cost of barrier precautions.
OBJECTIVE: To describe the effect of infection control interventions on the incidence of vancomycin-resistant enterococci (VRE), the utility of pharyngeal cultures for surveillance for VRE colonization, and the cost of barrier precautions. DESIGN: Evaluation of the occurrence of VRE infection or colonization, rates of vancomycin use, results of surveillance cultures before and after interventions, and the cost of increased barrier precautions. SETTING: University of Massachusetts Medical Center, a 347-bed tertiary-care teaching hospital with eight intensive-care units, one burn unit, and one bone marrow transplant unit. PARTICIPANTS: Patients in the intensive-care units and staff who were involved with patients colonized or infected with VRE. METHODS: Infection control interventions included placement of patients with VRE in private rooms, strict contact isolation, cohorting of patient and nursing staff, prohibiting of equipment sharing, and monitoring of compliance with the vancomycin restriction policy, with hand washing, and of the adequacy of environmental cleaning. Both rectal and pharyngeal cultures were obtained from patients at the beginning of the outbreak, and the utility of pharyngeal cultures was evaluated. The cost of barrier precautions was estimated by comparing the cost of glove and gown use before and after the outbreak began. RESULTS: The interventions decreased the number of new cases of VRE, but total eradication of VRE was not achieved. Compliance with the room-cleaning protocol was 91% (141/155 observations). Hand washing following interaction with patients who were not in isolation was 51%, vs 100% for patients in isolation. Overall, handwashing compliance was 71% (319/449): 56% (130/231) for physicians and 86% (187/218) for nurses (P<.0001). The mean number of doses of vancomycin dispensed per 1,000 patient days decreased from 145 to 114 per 1,000 patient days (P<.001). Compliance with vancomycin-use guidelines was 85%. Forty-six (77%) of 60 surveillance rectal swabs yielded enterococci, as compared to only 4 (11%) of 36 pharyngeal cultures (P<.0001). Expenses on glove and gowns alone increased by over $11,000 per year since the epidemic began. CONCLUSIONS: Implementation of the various infection control measures did not eradicate VRE cases from the hospital. Rectal cultures were more useful than pharyngeal cultures for surveillance of VRE. Controlling VRE epidemics can be costly.
Cross Infection↗
Once-daily dosing of aminoglycosides: review and recommendations for clinical practice.
The use of higher-dose, extended interval (i.e., once-daily) aminoglycoside regimens to optimize bacterial killing is justified by a pharmacodynamic principle of aminoglycosides, namely concentration-dependent killing, and by the partial attribution of the toxicity of aminoglycosides to prolonged serum concentrations. Numerous in-vitro and animal studies have supported using once-daily aminoglycoside dosing. Clinical studies show at least equal effectiveness and no greater toxicity when compared with traditional regimens. A dose of 5-7 mg/kg of gentamicin, tobramycin, or netilmicin, with at least a 24 h dosing interval should be employed and a similar regimen can be applied to amikacin dosing. As yet, there are some patient populations that have not been adequately studied to determine whether or not once-daily aminoglycoside dosing would be a better choice than traditional dosing regimens.
Aminoglycosides↗
Limiting vancomycin use to combat vancomycin-resistant Enterococcus faecium.
The implementation, monitoring, and impact of a program to restrict vancomycin use are described. A vancomycin restriction program was implemented in February 1995 at an acute care teaching hospital after guidelines for vancomycin use were established by a multidisciplinary group. Pharmacists reviewed each vancomycin order, suggested alternative treatments when vancomycin use did not comply with the guidelines, and set duration limits for all orders. Orders requiring greater clinical experience for review were referred to a pharmacist or a physician in the division of infectious diseases. The program was monitored by an infectious diseases pharmacist. Data collected after the program was established showed that the volume of vancomycin use decreased substantially. Problems in enforcing the restriction program included administration of vancomycin for surgical prophylaxis before the order reached the pharmacy, continuing use of vancomycin for initial empirical treatment of febrile neutropenic and immunocompromised patients, inadequate tracking of the evaluations, and deficiencies in the evaluations related to a need for continuing education of the pharmacists about the program. Use of vancomycin decreased after a pharmacy-enforced restriction program was implemented.
Anti-Bacterial Agents↗
Serum bactericidal activity of ceftizoxime and ceftriaxone against pathogens associated with community-acquired and nosocomial pneumonias.
The serum bactericidal activities of ceftizoxime and ceftriaxone against organisms commonly implicated in community-acquired and nosocomial pneumonias were studied. Ceftizoxime 1 g (as the sodium salt) every 12 hours for two doses and ceftriaxone 1 g (as the sodium salt) every 24 hours for two doses were administered to 20 healthy volunteers in a crossover fashion. Blood samples were drawn immediately before and 2,4,6,8,10, and 12 hours after the second ceftizoxime dose and immediately before and 8,12,16,18,20, and 24 hours after the second ceftriaxone dose. Serum drug concentrations were determined by validated high-performance liquid chromatography. Serum bactericidal titers were determined in duplicate for each serum sample against four clinical isolates of each of the following organisms: Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, and Serratia marcescens. The median duration of serum bactericidal activity during the dosage interval was significantly different between antimicrobial regimens only for S. pneumoniae (92% of the dosage interval for ceftizoxime, versus 100% for ceftriaxone). This difference does not appear to be clinically important since ceftizoxime provides adequate serum bactericidal activity for more than 50% of the dosage interval and its effectiveness against pneumococcal pneumonia has been supported in clinical trials. The ceftriaxone and ceftizoxime regimens did not differ significantly in their duration of serum bactericidal activity against six of the seven organisms tested.
Adolescent↗
Stability of cefotaxime sodium and metronidazole in 0.9% sodium chloride injection or in ready-to-use metronidazole bags.
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Anti-Infective Agents↗
Experience with a once-daily aminoglycoside program administered to 2,184 adult patients.
Once-daily aminoglycoside (ODA) regimens have been instituted to maximize bacterial killing by optimizing the peak concentration/MIC ratio and to reduce the potential for toxicity. We initiated an ODA program at our institution that utilizes a fixed 7-mg/kg intravenous dose with a drug administration interval based on estimated creatinine clearance: > or = 60 ml/min every 24 h (q24h), 59 to 40 ml/min q36h, and 39 to 20 ml/min q48h. Subsequent interval adjustments are made by using a single concentration in serum and a nomogram designed for monitoring of ODA therapy. Since initiation of the program, 2,184 patients have received this ODA regimen. The median dose was 450 (range, 200 to 925) mg, while the median length of therapy was 3 (range, 1 to 26) days. The median age of the population was 46 (range, 13 to 97) years. Gentamicin accounted for 94% of the aminoglycoside use, and the majority (77%) of patients received the drug q24h. The 36-, 48-, and > 48-h intervals were used for 15, 6, and 2% of this population, respectively. Three patients exhibited clinically apparent ototoxicity. Twenty-seven patients (1.2%) developed nephrotoxicity (the Hartford Hospital historical rate is approximately 3 to 5%) after a median of 7 (range, 3 to 19) days of therapy. On the basis of a prospective evaluation of 58 patients and follow-up of additional patients via clinician reports, we have noted no apparent alterations in clinical response with our ODA program. This ODA program appears to be clinically effective, reduces the incidence of nephrotoxicity, and provides a cost-effective method for administration of aminoglycosides by reducing ancillary service time and serum aminoglycoside determinations.
Adolescent↗
Implementation of a once-daily aminoglycoside program in a large community-teaching hospital.
Recently, there has been an emergence of interest in the use of once-daily aminoglycoside dosing. In an attempt to take advantage of the pharmacodynamic properties of these agents and to reduce the potential for toxicity, a once-daily aminoglycoside program was developed at this institution. This program uses a fixed intravenous dose of 7 mg/kg with dosing interval adjustments based on estimates of creatinine clearance or a single random serum aminoglycoside concentration. Because this automatic conversion program was initiated hospital-wide, more than 2,400 patients received the regimen with no apparent alteration in clinical success and the incidence of toxicity was lower than that previously observed. The purpose of this report was to describe the implementation process and unique features of this hospital-wide once-daily aminoglycoside program in a 850-bed community-teaching hospital.
Aminoglycosides↗
Serum bactericidal activity of ceftriaxone plus metronidazole against common intra-abdominal pathogens.
The activity of ceftriaxone plus metronidazole against pathogens usually involved in intra-abdominal infections was studied. Metronidazole 1 g and ceftriaxone 1 g (as the sodium salt) were simultaneously administered i.v. over 30 minutes every 24 hours to 12 healthy volunteers for three doses. Serum samples were collected at baseline, just before the last dose, and 12, 16, 20, 22, and 24 hours after the start of infusion of the last dose. Serum bactericidal titers (SBTs) were performed in duplicate for each serum sample from 12 hours on. Serum ceftriaxone and metronidazole concentrations were determined by high-performance liquid chromatography, and the elimination rate and half-life were calculated for each antimicrobial in each volunteer. The minimum inhibitory concentrations (MICs) of each antibiotic for two strains each of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and Bacteroides fragilis were determined by microdilution. Eleven volunteers completed the study. Ceftriaxone and metronidazole maintained SBTs of at least 1:4. Serum ceftriaxone concentrations remained above the MICs for E. coli, P. mirabilis, and K. pneumoniae, and serum metronidazole concentrations remained above the MIC for B. fragilis throughout the study. Ceftriaxone combined with metronidazole resulted in intense and prolonged activity against E. coli, P. mirabilis, K. pneumoniae, and B. fragilis.
Abdomen↗
Stability of aztreonam and ampicillin sodium-sulbactam sodium in 0.9% sodium chloride injection.
The stability of aztreonam, ampicillin sodium, and sulbactam sodium admixed in 0.9% sodium chloride injection and stored at room temperature and under refrigeration was studied. Each of the following admixtures was prepared in 0.9% sodium chloride injection: (1) aztreonam 10 mg/mL; (2) ampicillin 20 mg/mL (as the sodium salt) and sulbactam 10 mg/mL (as the sodium salt); and (3) aztreonam 10 mg/mL, ampicillin 20 mg/mL, and sulbactam 10 mg/mL. Three minibags of each admixture were stored at room temperature and three were refrigerated. Every 12 hours, up to 96 hours, the admixtures were visually inspected and 5-mL samples were withdrawn for high-performance liquid chromatography and pH testing. No color change or precipitation was observed in any sample. In admixtures containing ampicillin, ampicillin was the first or only drug to lose more than 10% of initial concentration. In the ampicillin-sulbactam admixture, ampicillin was stable for 32 hours at room temperature and 68 hours refrigerated. In the aztreonam-ampicillin-sulbactam admixture, ampicillin was stable for 30 hours at room temperature and 94 hours refrigerated. Aztreonam 10 mg/mL, ampicillin 20 mg/mL (as the sodium salt), and sulbactam 10 mg/mL (as the sodium salt) in 0.9% sodium chloride injection were stable in combination for up to 30 hours at room temperature and 94 hours under refrigeration.
Ampicillin↗
Reduction in serum concentrations of ciprofloxacin after administration of ursodiol to a patient with hepatobiliary disease.
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Bacteremia↗
Intracellular and extracellular penetration of azithromycin into inflammatory and noninflammatory blister fluid.
The penetration of azithromycin into the blister fluids of six volunteers was analyzed after a 5-day regimen (total of 1.5 g). Differences in drug concentrations in a paper disk and serum and in the mass of azithromycin from inflammatory blister chamber leukocytes and noninflammatory blister chamber leukocytes were significant (P < 0.05).
Azithromycin↗
Lomefloxacin clinical pharmacokinetics.
Lomefloxacin is a quinolone antibiotic with chemical and microbiological properties similar to most commercially available agents of this class. There are differences, however, between lomefloxacin and other quinolones in activity against specific micro-organisms, a situation that is typical of most antibiotic classes. The pharmacokinetics of lomefloxacin support once- or twice-daily dosage, depending on the pathogen or site of infection. This is a result of its relatively high serum concentrations and long half-life. The outstanding pharmacokinetic features of lomefloxacin are its high degree of tissue distribution, lack of significant metabolism (and, therefore, no competitive drug interactions with other metabolised drugs showing a common metabolic pathway), and good oral absorption. Like most fluoroquinolones, lomefloxacin can chelate with heavy metals. However, this interaction can be eliminated by administering lomefloxacin 2h before the cation-containing products. Dosage adjustments are required in patients with renal dysfunction. However, patients with liver disease do not require alterations in lomefloxacin dosage regimens. The safety profile, lack of significant drug interactions and convenience of administration make lomefloxacin a useful agent in specific clinical settings.
Administration, Oral↗
Stability of metoprolol tartrate in 5% dextrose injection or 0.9% sodium chloride injection.
The stability of metoprolol tartrate 0.40 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags stored at 24.0 +/- 2.4 degrees C was studied. Triplicate admixtures of each solution were prepared. A stability-indicating high-performance liquid chromatographic assay was used to determine metoprolol tartrate concentrations. At 0, 6, 12, 24, and 36 hours, samples were visually assessed then assayed in duplicate. Stability was defined as a < 10% decline in metoprolol tartrate concentration from the time 0 determination. No notable color changes or precipitation was observed in any sample. All samples demonstrated a < 7% reduction in metoprolol tartrate concentration over 36 hours. Metoprolol tartrate 0.40 mg/mL admixed in 5% dextrose injection or 0.9% sodium chloride injection in PVC bags and stored at 24.0 +/- 2.4 degrees C was stable for 36 hours.
Chromatography, High Pressure Liquid↗
Bactericidal activity of low-dose ceftizoxime plus metronidazole compared with cefoxitin and ampicillin-sulbactam.
Eighteen volunteers received ceftizoxime 1 g plus metronidazole 500 mg intravenously every 12 hours, cefoxitin 2 g intravenously every 6 hours, and ampicillin-sulbactam 3 g every 6 hours in a triple-crossover, open-label study to compare serum bactericidal titers (SBTs) against two strains of Escherichia coli and Bacteroides fragilis. Serum was analyzed for drug concentration and bactericidal activity. Ceftizoxime-metronidazole exhibited a significantly greater (p < 0.05) area under the bactericidal curve and percentage of the dosing interval with SBTs of 1:2 or above against E. coli than cefoxitin or ampicillin-sulbactam. The respective values were equal to those of ampicillin-sulbactam for one strain of B. fragilis (both greater than cefoxitin) and greater than cefoxitin and ampicillin-sulbactam for the other strain. A 1-g dose of ceftizoxime given with metronidazole 500 mg every 12 hours should be an effective alternative to standard antibiotic treatment of mixed aerobic-anaerobic bacterial infections.
Adult↗
Oral absorption of trimethoprim-sulfamethoxazole in patients with AIDS.
STUDY OBJECTIVE: To determine the bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) in patients infected with the human immunodeficiency virus (HIV). DESIGN: Open-label, randomized, two-way crossover trial. SETTING: Outpatient clinical research center affiliated with a community-based teaching hospital. PATIENTS: Ten individuals diagnosed with the acquired immunodeficiency syndrome (AIDS) with CD4+ counts less than 200 cells/mm3, receiving TMP-SMX one double-strength tablet 3 times/week as prophylaxis for Pneumocystis carinii pneumonia (PCP), and without documented gastroenteropathy or diarrhea agreed to participate in the trial. One patient withdrew from the study secondary to development of symptomatic PCP. Data were available for analysis from the remaining nine subjects. INTERVENTIONS: Participants received TMP 160 mg and SMX 800 mg orally or intravenously during two study periods. Following dose administration, blood samples were collected at predetermined time points over 36 hours. MEASUREMENTS AND MAIN RESULTS: Analysis of TMP-SMX pharmacokinetic parameters (half-life, total body clearance, area under the serum concentration versus time curve, and peak concentration) failed to reveal any significant differences between intravenous and oral preparations. The calculated bioavailabilities of oral TMP and SMX (mean +/- SD) were 102.7% +/- 19.8% and 109.4% +/- 19.4%, respectively. CONCLUSION: The absorption of TMP-SMX is not adversely affected by HIV infection in the absence of HIV-induced gastroenteropathy or diarrhea.
Acquired Immunodeficiency Syndrome↗