Aerosolization of tobramycin (TOBI) with the PARI LC PLUS reusable nebulizer: which compressor to use? Comparison of the CR60 to the PortaNeb compressor

Aerosol output, aerosol output rate, and aerosol size distribution are influenced by the compressed air flow rate through the nebulizer cup. Testing a nebulizer-compressor with a drug for inhalation in cystic fibrosis (CF) patients is mandatory prior to starting therapy. Tobramycin solution for inhalation (TSI), TOBI, is licensed in Europe with a recommendation for a "suitable" compressor connected to the PARI LC Plus nebulizer. To select a compressor, five devices were tested in a previous in vitro study and this resulted in a subsequent in vivo study. Two compressors [CR60 and PortaNeb (PN)] were compared in an open, randomized, crossover single dose pilot study in 10 CF patients to assess the most suitable device for inhalation of a tobramycin solution (TSI), TOBI, with the PARI LC Plus nebulizer. Lung function (FEV1 and FVC), pharmacokinetics [PK; safety (Cmax, Ctrough)], lung deposition (indirect method AUC0-6), nebulization time, and patients' experiences (questionnaire) were determined and compared. It was found that values of Cmax and AUC0-6 were higher with the CR60 than with the PortaNeb: 0.70 versus 0.54 mg/L, p = 0.005, and 2.54 versus 2.01 h.mg/L, p = 0.017, respectively. Tmax after use of the CR60 appeared earlier (0.64 vs. 0.85 h, p = 0.005). Transient airway narrowing was measured in three patients (2 x PN;1 x CR60) versus subjective chest tightness in seven patients (CR60 > PN). A shorter nebulization time for CR60 of 13.2 min compared to PN 16.1 min (p = 0.022) was observed, which was the main reason why patients preferred the CR60 (n = 7). No toxic serum levels were reached after inhalation of TSI. The CR60 compressor may seem advantageous based on a higher lung deposition and a shorter nebulization time, but a study in a large CF population to provide information on a possible higher risk of toxicity of TSI is called for.     

Elevated serum tobramycin concentrations after treatment with tobramycin inhalation in a preterm infant

High-dose inhaled tobramycin has been increasingly used for treatment and suppression of Pseudomonas aeruginosa pulmonary infections, especially in patients with cystic fibrosis. The advantage of inhalation over other routes of administration is minimal systemic absorption, which reduces the potential for adverse effects. However, cases of adults who had elevated serum concentrations and experienced systemic adverse effects due to excessive systemic absorption after inhaled tobramycin have been reported. We describe a prematurely born infant with numerous congenital and acquired disorders who required assisted mechanical ventilation and a 60-day stay in the neonatal intensive care unit (NICU). Tracheostomy and mechanical ventilatory support were required throughout the infant's hospital stay. The patient developed several pulmonary infections caused by various bacteria. He was treated with multiple antibiotics, including two different dose preparations of inhaled tobramycin 80 mg and 300 mg, administered through the tracheostomy and the ventilator. The infant was given a total of five preparations of tobramycin 80 mg/dose and three of 300 mg/dose, for a total cumulative dose of 1,300 mg over a 6-day period. His tobramycin concentrations increased, prompting discontinuation of the inhaled tobramycin. The infant died on day 60. To our knowledge, this is the first report of elevated tobramycin concentrations after inhalation in an infant. Although studies have found that tobramycin is safe and effective, certain patient populations are more at risk for toxicity. Tobramycin concentrations should be closely monitored in patients with significant underlying renal disorders, especially those in age-group extremes.     

Inhalation of tobramycin in cystic fibrosis. Part 1: the choice of a nebulizer.

Forteen commercially available jet and ultrasonic nebulizers were investigated with the aim to select the most suitable type of apparatus for the inhalation of a 10% tobramycin solution. Two different techniques for measurement of particle size distribution were evaluated: laser diffraction and cascade impactor analysis. The final selection of the nebulizers is based on particle size distribution, output and stable performance during nebulization. All 14 nebulizers (eight jet and six ultrasonic) were filled with a solution of 10% m/v tobramycin (as sulphate) in water. The volume in the tested devices ranged from 4.5 to 10 ml (=450-1000 mg tobramycin) in accordance with the prescribed usage by the suppliers. The nebulizers were connected with a special designed adapter to a laser diffraction analyser in order to measure particle size distribution of the aerosol. Inhalation was simulated with a static flow of 40 l/min. The particle size distribution (expressed as X(10), X(50), and X(90)) was determined after 10 s, 1.5, 3, 4.5, 6, 9 and 12 min of nebulization. Furthermore, the tobramycin solutions were assayed for tobramycin content before and after nebulization. For all nebulizers, the mean particle size distribution, depicted as X(50), was within the range of 1-5 mm. There were no relevant differences between the nebulizers in concentration or particle size distribution during nebulization. The output of the nebulizers is a result of both nebulization and evaporation. The output, expressed as volume of tobramycin solution, ranged from 0.06 to 0.50 ml/min. The output of tobramycin ranged from 1.2 to 39.5 mg/min. For clinical practice 300-600 mg have to be nebulized within 20-30 min. It was concluded that only three jet nebulizers [Porta-Neb Sidestream (PNS), Porta-Neb Ventstream (PNV) and Pariboy Pari LC+ (PLC)] have a reasonable output and an acceptable particle size distribution for the administration of a 10% tobramycin solution in the therapeutic dosage range.     

Toxic serum trough concentrations after administration of nebulized tobramycin

The goal of administering nebulized antibiotics is to provide patients with a high concentration of drug at the infection site with minimal systemic effects. In two studies in which nebulized tobramycin 300 mg twice/day was administered, systemic peak concentrations were below 0.2 and 3.62 microg/ml, and trough concentrations were undetectable, making toxicity from this route of administration negligible. A 19-year-old woman who received a heart transplant was administered tobramycin inhalation solution for Acinetobacter baumanii pneumonia; her serum trough concentrations were found to be toxic (> 2.0 microg/ml). Her risk factors for experiencing these toxic concentrations were renal failure and administration of the drug by positive pressure ventilation. Although nebulized tobramycin is safe under routine circumstances, clinicians must be aware of its potential for toxicity in patients with renal dysfunction or in those receiving positive pressure ventilation.     

Dry powder inhalation of antibiotics in cystic fibrosis therapy: part 2. Inhalation of a novel colistin dry powder formulation: a feasibility study in healthy volunteers and patients.

The aim of the present study was to perform a proof of principle study with a new colistin dry powder inhalation system in six healthy volunteers and five patients with cystic fibrosis. All subjects were asked to inhale 25 mg colistin sulfate dry powder. The patients were also asked to nebulize 160 mg colistin sulfomethate as a solution. Colistin serum concentrations were determined as an indirect parameter to compare both forms of administration. Pulmonary function tests were performed. Peak serum colistin concentrations ranged from 14 to 59 microg/l in volunteers after inhalation of 25 mg as dry powder. In patients, peak concentrations ranged from 18 to 64 microg/l after nebulization of 160 mg colistin sulfomethate solution and from 77 to 159 microg/l after inhalation of 25 mg colistin sulfate dry powder. Pulmonary function tests were not significantly different after inhalation of the dry powder by the volunteers nor after nebulization of the solution by the patients. In some patients a decrease in pulmonary function and moderate to severe cough was observed after inhalation of the dry powder. The new colistin inhaler provides an attractive alternative for nebulized colistin and was highly appreciated by the patients. The decrease in pulmonary function and cough in patients is a drawback, which may be overcome by dose reduction and a further improvement of the new dosage form.     

Effect of four intravenous infusion methods on tobramycin pharmacokinetics

The influence of four intermittent intravenous infusion methods on the determination of tobramycin pharmacokinetic values and predicted doses was evaluated in 11 healthy adult volunteers. Each subject received tobramycin (as the sulfate salt) 1.5 mg/kg by each of four i.v. infusion methods: (1) minibag via gravity flow (MG), (2) minibag with the secondary infusion tubing inserted below a volumetric pump (MP), (3) metered chamber via volumetric pump (MC), and (4) syringe pump (SP). Infusion rates were initially set to administer each dose over a 30-minute period. Sixteen blood samples were obtained over an eight-hour period before and at various time intervals after each dose and were analyzed for tobramycin content by fluorescence polarization immunoassay. Area under the serum concentration-time curve from time zero to infinity (AUC0-infinity) was calculated by the trapezoidal rule. Serum tobramycin concentration data for each subject were fitted to a biexponential decay model with zero-order input. beta and V beta were calculated from fitted data. One-compartment pharmacokinetic values, elimination rate constant (kappa), apparent volume of distribution (V), and predicted doses to achieve steady-state peak concentrations of 6 micrograms/mL were calculated by the method of Sawchuk and Zaske. There were no significant differences in either beta or kappa among the infusion methods. V beta values (mean +/- S.D.) for the methods were 0.240 +/- 0.025 (MG), 0.257 +/- 0.025 (MP), 0.221 +/- 0.027 (MC), and 0.231 +/- 0.032 (SP) L/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tobramycin as a pharmacologic tracer to compare airway deposition from nebulizers

STUDY OBJECTIVE: To assess the utility of inhaled tobramycin as a pharmacologic tracer for comparing lung deposition from a prototypic breath-actuated jet nebulizer connected to an electronic pressure sensor designed to coordinate nebulization with inspiration with that from a continuously operating standard jet nebulizer. DESIGN: Prospective open-label study. SETTING: University-affiliated research center. SUBJECTS: Six healthy adult volunteers. INTERVENTION: All subjects received inhaled tobramycin 80, 160, and 320 mg from each nebulizer during six visits, as well as oral tobramycin 32 mg at a seventh visit to confirm the absence of significant gastrointestinal absorption. During each visit, urine was collected before drug administration and in 12-hour segments throughout the first 48 hours after administration. MEASUREMENTS AND MAIN RESULTS: Lung deposition of tracer after each of the seven treatments was quantified by measuring urinary tobramycin excretion over 48 hours with use of an enzyme-multiplied immunoassay technique. The ratio of tobramycin excreted after breath-actuated nebulization to that after standard nebulization, normalized for dose, was used to compare lung deposition by the two devices. Urinary excretion of tobramycin was linear and proportional to dose for both nebulizers. For every 1 mg of tobramycin that the standard nebulizer deposited into the lungs, the breath-actuated nebulizer deposited 1.22 mg (95% confidence interval 1.04-1.43). CONCLUSIONS: Tobramycin can be used as a pharmacologic tracer for comparison of relative airway deposition by nebulizers.     

Urinary concentrations and antimicrobial activity of tobramycin in healthy volunteers receiving a single oral dose of a novel formulation for improved absorption

Oral antibiotics for the treatment of urinary tract infections are scarce. In this ex vivo phase 1 annex study, the clinical safety, urinary concentrations and bactericidal activity of a new formulation for improved oral absorption of tobramycin (Tobrate?) were evaluated. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of five test strains, one reference strain and four clinical uropathogenic strains were determined in cation-adjusted Mueller–Hinton broth (CA-MHB) and in pooled antimicrobial agent-free subjects' urine at different pH values (5.5, 6.5, 7.5 and 8.5). Urinary concentrations and urinary bactericidal titres (UBTs) following single oral administration of 600?mg Tobrate? were measured in nine healthy volunteers up to 24?h. The MIC/MBC values in CA-MHB were 2–4/2–4?mg/L for two Escherichia coli strains, 2/2?mg/L for Klebsiella pneumoniae, 0.5/1?mg/L for Pseudomonas aeruginosa and 8/1?mg/L for Proteus mirabilis. MBCs in pooled alkaline urine were significantly lower than those in acidic urine. The mean maximum urinary concentration following 600?mg tobramycin was 83.9?mg/L (2–4?h collection period). The highest reciprocal median UBT values for each test strain were between 2 and 4 during the collection periods 2–4?h and 4–8?h, respectively. The new enteric oral tobramycin formulation significantly improved the very poor oral absorption of standard tobramycin salt. For all pathogens tested, maximum urinary concentrations of tobramycin were at least two times above the urinary MBC. A twice- or three-times daily dosage regimen and alkalising co-medication may further improve urinary bactericidal activity.     

Acute renal failure associated with inhaled tobramycin.

PURPOSE: A case of nephrotoxicity possibly caused by tobramycin inhalation solution is presented. SUMMARY: A 62-year-old Caucasian woman was admitted for treatment of decreased urine output and sepsis secondary to Pseudomonas aeruginosa. Her past medical history was significant for multiple diseases, including chronic renal insufficiency (baseline serum creatinine concentration [SCr] 2 mg/dL). One month postadmission, the patient was diagnosed with health care-associated pneumonia. The patient was initiated on piperacillin-tazobactam and tobramycin 2 mg/kg i.v. She was changed to imipenem-cilastatin with continuation of i.v. tobramycin. A month after discontinuation of her antibiotic regimen, the patient was diagnosed with P. aeruginosa pneumonia. The patient received imipenem-cilastatin, vancomycin, and inhaled tobramycin 300 mg twice daily. At that time, her SCr was 2 mg/dL. Inhaled tobramycin was continued for four weeks, and the patient's SCr steadily rose to a peak of 4.5 mg/dL. During week 1 of treatment, multidrug-resistant P. aeruginosa and methicillin-resistant Staphylococcus aureus were diagnosed. The patient continued to receive i.v. imipenem-cilastatin, vancomycin, and inhaled tobramycin with an SCr of 1.9 mg/dL. However, at the end of week 2, the patient's SCr began to slowly rise (2.3 mg/dL). At week 3, imipenem-cilastatin was discontinued; inhaled tobramycin was continued. The patient's SCr continued to rise (3.2 mg/dL). At week 4, her SCr rose to 4.5 mg/dL, resulting in initiation of hemodialysis and discontinuation of inhaled tobramycin. The patient's SCr never returned to baseline, and renal function was never regained. CONCLUSION: Acute renal failure requiring dialysis occurred in a high-risk patient receiving an extended course of treatment with inhaled tobramycin.     

The choice of compressor effects the aerosol parameters and the delivery of tobramycin from a single model nebulizer.

Recent U.S. Phase III trials of the aerosolized delivery of tobramycin to cystic fibrosis (CF) patients demonstrated a significant improvement in pulmonary function and in sputum bacterial density. These trials used the Pari LC Plus nebulizer and DeVilbiss Pulmo-Aide compressor. This compressor is not generally available in Europe, and its power requirements do not match the European power supply. Thus alternate compressors were evaluated, using the LC Plus nebulizer, in preparation for European clinical trials. Aerosol particle size distribution, nebulization time (min), and the respirable dose of tobramycin (mg within 1-5 mu) were obtained for seven compressor models. The respirable quantity delivered by each of the European compressors (240 Volts, 50 Hz) was compared to the LC Plus and PulmoAide compressor (120 Volts, at 60 Hz). The U.S. system delivered 71.4 mg of the 300 mg instilled dose within the respirable range; using the European compressors, between 63.0 and 74.8 mg was delivered. With a 97% confidence that the delivered tobramycin was within 20% of the standard, we conclude that the SystAm 23ST, MedicAid CR50 and CR60, Pari Master and the Pari Boy compressors are equivalent to the U.S. standard; the Hercules and the SystAm 26ST compressors were not statistically equivalent to the standard. Using the LC Plus nebulizer, five European compressors delivered doses of TOBI that are similar to the doses delivered by the DeVilbiss PulmoAide compressors, and thus may be expected to produce clinical results similar to those of the U.S. trials.     

The effect of tobramycin on the renal handling of vancomycin

Studies in experimental animals and humans have suggested that enhanced renal and auditory toxicity occur with concurrent vancomycin and aminoglycoside treatment. In volunteers, systemic vancomycin clearance at steady-state was measured simultaneously with renal clearances of vancomycin, creatinine, inulin, and para-aminohippurate. Group 1 (n = 9) received vancomycin 5 mg/kg IV for 1 hour, then 1.1 mg/kg/hr for 3 hours. Group II (n = 7) received vancomycin plus tobramycin (2 mg/kg IV over 30 min). Groups did not differ demographically. Audiograms were obtained before and after vancomycin. Plasma samples were collected serially for vancomycin and tobramycin pharmacokinetic studies. Serum concentration versus time data were fit to a two-compartment model for vancomycin and a one-compartment model for tobramycin. For all volunteers, creatinine, inulin and para-aminohippurate clearance, and audiograms were not altered from baseline and were not statistically different between groups. No significant effect of tobramycin on vancomycin pharmacokinetics was observed. conversely, vancomycin had no significant effect on tobramycin pharmacokinetics. The nephrotoxic synergism of vancomycin and tobramycin is not explained by short-term differences in renal handling.     

Can tobramycin inhalation be improved with a jet nebulizer?

Data on the pharmacokinetics of antibiotics after inhalation are limited. The aim of this pilot study was to assess the pharmacokinetics of tobramycin under optimalized and standardized aerosol circumstances and, furthermore, to be able to consider possible treatment of exacerbations with inhalation therapy. Six patients were studied after inhalation of 600 mg tobramycin. A jet nebulizer loaded with a 10% solution of tobramycin in water was used. The percentage of the dose that was systemically absorbed ranged from 1.0% to 16.6%. The maximum serum levels of tobramycin ranged from 0.77 mg/L to 3.63 mg/L (mean 1.70 +/- 1.01). The pharmacokinetic data were best described by a two-compartment model. Compared to intravenous administration, the long terminal half-life (mean 9.47 h +/- 3.28 h) could be explained by the slow absorption of tobramycin from the site of administration (flip-flop model). Despite standardized aerosol conditions, considerable interpatient variability was observed. However, the relatively low serum levels allow a further increase of the dose.     

Use of vancomycin and tobramycin polymethylmethacrylate impregnated beads in the management of chronic osteomyelitis

Over the past several years there has been a growing interest in the use of locally implanted beads containing antibiotics for the treatment of chronic osteomyelitis. This method has been popularized in Europe and, with few exceptions, gentamicin has been the only antibiotic used. There have been only a few reports from the U.S. and there is little information regarding the pharmacokinetics of antibiotics used in this fashion. To our knowledge this is the first report using vancomycin. Three patients with chronic osteomyelitis were treated with vancomycin and/or tobramycin polymethylmethacrylate beads. These beads were extemporaneously compounded and implanted for up to six weeks. From the site of bead implantation local fluid aliquots were collected for the measurement of antibiotic concentrations. In two patients, initial tobramycin concentrations exceeded 400 mg/L. In one patient receiving vancomycin, initial localized concentrations were approximately 100 mg/L. In all three patients therapeutic concentrations of localized antibiotic were maintained with immeasurable systemic concentrations throughout the period of bead placement. Localized antibiotic therapy for the management of chronic osteomyelitis represents a potential therapeutic alternative to long-term parenteral therapy. Data presented here suggest that other antibiotics, such as vancomycin and tobramycin, can be used successfully in polymethylmethacrylate beads and provide preliminary facts for future investigations of such applications.     

Bicompartmental kinetics of tobramycin analysed with a wide range of covariates

The pharmacokinetics of tobramycin was studied in adult patients (N = 151) admitted either for initial suspicion of Gram-negative infection or for prophylaxis. In addition to age, weight, height and creatinine clearance (CrCL), a range of other covariates were also analysed, including type of pathology, co-medication, fever, sex and ethnicity (Basque or not). All patients received 100mg tobramycin every 8 h and samples were collected at three time points after the first dose and at two time points after the fourth dose and assayed with a fluorescence polarisation immunoassay. The population mixed effects bicompartmental parameters were obtained from 725 concentration measurements using NONMEM, FOCE method, and were: systemic clearance, CL = 6.03 L/h (between-subject coefficient of variation (CV) %, 29.4%); volume of distribution, V = 15.04 L (7.3%); and intercompartmental constants, k(12) = 0.192 h(-1) (56%) and k(21) = 0.55 h(-1) (no CV% determined). Covariate modelling was performed within NONMEM. Two alternative significant covariate models (Models 1 and 2) are proposed, with functions of CrCL and/or sex (Model 2). However, for clinical purposes, differentiation by sex is insignificant. Model 1 is for CL = 3.1 + 0.05.CrCLL/h (17.3%); V = 14.6 L (12%); k(12) = 0.224 h(-1) (63%) and k(21) = 0.468 h(-1). Stochastic simulation was used to predict the expected concentration 95th percentiles after the recommended 7 mg/kg dose and for minimum inhibitory concentration (MIC) = 1 mg/L, as well as alternative once-daily dosing regimens for MIC = 2 mg/L. It is seen that once-daily high-dose tobramycin is an appropriate strategy with respect to pharmacodynamic indices, C(peak)/MIC or AUC/MIC (where C(peak) is the peak plasma concentration and AUC is the area under the concentration-time curve).     

Stability of parenteral solutions of tobramycin sulfate.

The stability and physical compatibility of tobramycin sulfate in commonly used intravenous fluids were evaluated; in addition, pH values were obtained on 1 mg/ml tobramycin solutions, and microbiological potencies were obtained on 1 mg/ml and 0.2 mg/ml concentrations for 24- and 48-hour periods at 25 C. Most solutions were stable for 48 hours at room temperature. However, it is recommended that solutions of tobramycin sulfate be discarded after 24 hours to minimize the potential for inadvertent introduction of microorganisms during manipulations in the hospital environment.     

Controlled release infusion kinetics of tobramycin

Ten healthy male volunteers received two doses of tobramycin (2 mg/kg) in a crossover fashion, first by intravenous piggyback (IVPB), then by the CRIS infusion system after a washout period. Serum samples were drawn both during and after the infusions. Twenty-four-hour urine collections were assayed for tobramycin. Residual fluid from the lines of both delivery systems was measured and assayed for tobramycin concentration. All samples were run in duplicate, using an enzyme-multiplied immunoassay technique assay. The results indicate that there was a statistically higher amount of drug delivered via the CRIS system (98.3 +/- 0.3% versus 90.4 +/- 2.3%). No significant difference was found in urinary recovery between the two groups. Peak serum levels were significantly higher with the CRIS system, with 8/10 subjects having at least one serum level greater than 10 micrograms/ml, as compared to 0/10 when given by IVPB. Peak serum levels occurred at 30 min in all subjects given tobramycin through the CRIS system, compared to 50-60 min when delivered by IVPB. This difference in peak serum levels is primarily related to the rate of drug delivery and to the difference in the dose delivered to each subject. The significance of the serum concentration profiles is discussed.     

Serum bactericidal activity against Klebsiella pneumoniae in volunteers receiving increasing doses of tobramycin with or without cefamandole

Ten volunteers received intravenously in a randomly allocated order and on separate days the following regimens: cefamandole (15 mg/kg); tobramycin (1.5 mg/kg); tobramycin (3 mg/kg); cefamandole (15 mg/kg) + tobramycin (1.5 mg/kg); cefamandole (15 mg/kg) + tobramycin (3 mg-kg). Tobramycin serum levels were 3.7 +/- 0.7 micrograms/ml one hour after infusion of the 1.5-mg/kg and 7.8 +/- 1.6 micrograms/ml after the higher dose. Cefamandole serum levels were 26.0 +/- 5.2 micrograms/ml at the same time. Serum bactericidal activity and killing-rate studies were performed on a collection of 18 strains of Klebsiella pneumoniae. Against cefamandole-sensitive strains, all regimens were satisfactory (median serum bactericidal activity 1:16 to 1:64). Tobramycin (3 mg/kg) and both combinations were slightly more active on cefamandole-resistant strains (1:16 to 1:32) than cefamandole (1:2) and tobramycin low dose (1:8). Except for cefamandole alone, all regimens were equivalent in killing studies.     

Comparative toxicity of netilmicin and tobramycin in dogs

Beagle dogs (four/group) were dosed intramuscularly with netilmicin or tobramycin once daily at doses of 20, 40, or 80 mg/kg. The dogs were dosed for 30 days or until death or sacrifice because of poor condition. Weekly otological examinations (response to Galton whistle) were conducted to evaluate effects on hearing. Hematologic, serum chemical and urinalysis data were collected weekly. Kidneys and cochleas were examined histologically. Dogs given 40 and 80 mg/kg of tobramycin became azotemic and died or were sacrificed in a moribund condition 9 to 22 days after dosing was initiated. Serum urea nitrogen and creatinine levels increased in $\text{2}\text{4}$ dogs given tobramycin at 20 mg/kg. No clinical signs of toxicity or unusual serum chemical changes occurred in the dogs dosed with netilmicin. Hearing did not appear to be affected by either compound. Microscopic examination of kidneys revealed tubular epithelial necrosis ranging from mild (netilmicin) to severe (tobramycin). Steady-state serum drug concentrations were established at all dose levels for netilmicin. In contrast, serum concentrations of tobramycin increased at all dose levels apparently as a result of nephropathy. Under the conditions of this study, netilmicin was clearly less toxic than tobramycin.     

Cost savings associated with use of gentamicin versus tobramycin

A hospital's use and costs of tobramycin sulfate versus gentamicin sulfate before and after a tobramycin use review were compared. Retrospective audits of 100 charts of adult patients in a 515-bed hospital were performed for two six-month periods in 1983-84. Tobramycin use was considered appropriate in patients with serum creatinine concentrations greater than 1.5 mg/dL or pre-existing renal disease, in any patient over 70 years of age, and in patients with neutropenia, documented pseudomonas infection, or infection with an organism shown to be resistant to gentamicin but sensitive to tobramycin. Tobramycin use was not justifiable in 37 (18.7%) of 198 patients whose charts were evaluable. Use of gentamicin in these 37 patients would have saved $14,300. The infection control committee was notified of the audit results; the audit results and recommendations for tobramycin use were included in a letter to all physicians; and the infectious disease service held educational conferences on tobramycin use. In the first six months after the corrective measures, mean monthly tobramycin use decreased by 38% and gentamicin use increased by 48.9%. Total aminoglycoside costs decreased 30.2% and total aminoglycoside use decreased 12.5%. In the second six months after intervention, mean monthly tobramycin use was 11% less than before intervention, and mean monthly gentamicin use was 13% greater than before intervention. Total aminoglycoside costs were 3.6% less and total aminoglycoside use was 4% less than before the audit. The tobramycin use audit and subsequent interventions with prescribers were effective in reducing tobramycin use and costs for approximately six months; decreases in tobramycin use and costs were smaller during the second six months after intervention.     

Monitoring clozapine: are fingerprick blood and plasma clozapine levels equivalent to arm venipuncture blood and plasma levels?

The objective of this pilot study was to determine whether fingerprick blood and plasma clozapine levels were equivalent to arm venipuncture blood and plasma levels for the purpose of therapeutic monitoring. A convenient sample of 10 outpatients from the Elgin Program of Assertive Community Treatment Team (PACT) participated in the study. Blood samples were obtained simultaneously from both the arm and finger in patients at steady state to measure clozapine levels. Each site provided a blood and plasma clozapine level, and they were compared. Clozapine levels from arm and finger sites were found to be equivalent in both blood and plasma. Although plasma clozapine levels were consistently greater than those in whole blood by a mean value of 27%, the plasma therapeutic threshold level (350-400 micro g/L) was considered an adequate target for monitoring. A fingerprick blood sample of 50 micro L was sufficient to measure clozapine levels accurately at steady state. We therefore concluded that fingerprick blood testing is as effective as the traditional arm venipuncture method in obtaining accurate clozapine levels. This procedure may provide certain benefits for the seriously mentally ill.