Physical Compatibility, Antimicrobial Activity, and Stability of Cefazolin Combined with Gentamicin or Ethanol in Sodium Citrate as a Catheter Lock Solution.

BACKGROUND: Catheters provide vascular access for patients requiring intravenous treatments, but frequently are a source of infection and/or thrombosis. Instilling a solution of an antimicrobial agent with an anticoagulant into the catheter lumen may salvage-infected catheters. OBJECTIVE: The aim is to evaluate the physical compatibility, antibacterial activity, and stability of varying combinations of cefazolin (10 mg/mL), 40% ethanol, 4% sodium citrate with or without gentamicin (1 mg/mL) as a catheter lock solution over 48 h. METHODS: Admixtures were prepared using aseptic technique and stored under four conditions with or without light at 25°C or 37°C. Prepared admixtures were assessed for physical compatibility, antimicrobial susceptibility, and chemical stability in triplicate at 0, 24 and 48 h. Admixture physical compatibility was determined by visual clarity, pH, and ultraviolet (UV) spectroscopy. Antibacterial activity was determined using the Kirby-Bauer disk diffusion method. The chemical stability of cefazolin and gentamicin were assessed using high performance liquid chromatography and UV spectroscopy, respectively. RESULTS: All admixtures maintained clarity for 48 h. All admixtures stored at 25°C and the admixture containing 10 mg/mL cefazolin-4% sodium citrate stored at 37°C sustained antimicrobial activity and were chemically stable. A significant change in pH, antimicrobial activity, cefazolin concentration (<95% of baseline), were observed in admixtures containing ethanol stored at 37°C after 24 h. Gentamicin concentrations remained stable throughout the study. CONCLUSION: The admixture of 10 mg/mL cefazolin-4% sodium citrate sustained antimicrobial activity over 48 h and was chemically stable. However, admixtures containing ethanol stored at 37°C showed incompatibility with decreased antibacterial activity and cefazolin degradation after 24 h.

Use of an On-Site Outpatient Pharmacy for Acquisition of Antiretroviral Medications Compared to Off-Site Pharmacy Options: Impact on Retention in Care and Clinical Outcomes in People Living With HIV.

BACKGROUND: Few published studies have examined the relationship between pharmacy location and retention in care or clinical outcome in people living with HIV (PLWH). OBJECTIVE: The study purpose was to determine whether using an on-site/in-clinic pharmacy to obtain antiretroviral therapy increased retention in care and virologic suppression rates. METHODS: PLWH attending a Ryan White outpatient clinic in an academic center were matched based on age and insurance. Rates of retention in care ( ≥2 medical visits/calendar year) were assessed between patients using a pharmacy on-site in the clinic versus patients use off-site pharmacy options. Virologic suppression [viral load(VL)<200 copies/mL], completing ≥2 VL, and CD4 count were compared between pharmacy types. RESULTS: 137 on-site pharmacy patients and 274 off-site pharmacy patients met inclusion and matching criteria. 91.2% of on-site pharmacy users attended ≥2 clinic visits compared to 83.2% of off-site pharmacy users (P = .0275) and were approximately twice as likely to complete ≥2 clinic visits (odds ratio: 2.032; 1.071-3.857). A similar proportion of the on-site pharmacy group achieved virologic suppression compared to the off-site pharmacy group (92.7% vs 89.1%; P = .239, respectively). CONCLUSIONS: On-site pharmacies may provide an opportunity to positively impact retention in care and clinical outcomes for PLWH.

Development and Evaluation of a Novel Microemulsion of Dexamethasone and Tobramycin for Topical Ocular Administration.

PURPOSE: The purpose of this study was to develop and evaluate a novel dexamethasone- and tobramycin-loaded microemulsion for its potential for treating anterior segment eye infections. METHODS: The microemulsion was evaluated for pH, particle size, zeta potential, light transmittance, morphology, and in vitro drug release. Sterility of the microemulsion was evaluated by direct as well as plate inoculation methods. Anti-inflammatory activity of dexamethasone, bactericidal activity of tobramycin, and cytotoxicity of the microemulsion were assessed and compared to that of the marketed eye drop suspension (Tobradex®). Histological evaluation was performed in bovine corneas to assess the safety of microemulsion in comparison to Tobradex suspension. In addition, the stability of the microemulsion was studied at 4°C, 25°C, and 40°C. RESULTS: The pH of the microemulsion was close to the pH of tear fluid. The microemulsion displayed an average globule size under 20 nm, with light transmittance around 95%-100%. The aseptically prepared microemulsion remained sterile for up to 14 days. The cytotoxicity of the microemulsion in bovine corneal endothelial cells was comparable to that of the Tobradex suspension. The anti-inflammatory activity of dexamethasone and the antibacterial activity of tobramycin from the microemulsion were significantly higher than those of the Tobradex suspension (P < 0.05). Histological evaluation showed an intact corneal epithelium without any signs of toxicity, and the developed microemulsion was found to be stable at 4°C and 25°C for 3 months. CONCLUSION: In conclusion, the developed microemulsion could be explored as a suitable alternative to the marketed suspension for treating anterior segment eye infections.

Compatibility, Stability, and Efficacy of Vancomycin Combined With Gentamicin or Ethanol in Sodium Citrate as a Catheter Lock Solution.

Background: Indwelling catheters deliver lifesaving medical treatments for many chronically ill patients but are frequently a source of infection. Treatment may include an antimicrobial agent(s) and anticoagulant solution dwelling within the catheter. In vitro determinations of solution compatibility and stability are necessary prior to use in patients. Objective: The aim of this study was to determine the physical compatibility, chemical stability, and antimicrobial activity of vancomycin (5 or 10 mg/mL) with gentamicin (1 mg/mL) or 40% ethanol in 4% sodium citrate lock solution over 72 hours. Methods: All solutions were prepared per manufacturer's instructions. Samples were studied under 4 conditions: (1) 25°C with light, (2) 25°C without light, (3) 37°C with light, and (4) 37°C without light. Physical compatibility and chemical stability were assessed at 0, 24, 48, and 72 hours. Antimicrobial susceptibility testing was conducted at 0 and 72 hours. All studies were carried out in triplicate. Results: All solution combinations under each condition remained patent from baseline to 48 hours. One solution combination of vancomycin (5 mg/mL) and ethanol (40% v/v) in 4% sodium citrate revealed a slight turbidity at 72 hours. Clarity and pH remained stable in all other solutions during the entire study period. Chemical compatibility and antibiotic activity ranged from 95% to 105% and 95% to 106% of initial baseline values, respectively, for all solutions under 4 storage conditions. Conclusions: All antibiotic-anticoagulant lock solutions were found to be physically, chemically, and microbiologically stable during the 72-hour study period except vancomycin (5 mg/mL) and ethanol (40% v/v) in 4% sodium citrate solution which showed slight turbidity at 72 hours.

Thermoresponsive fluconazole gels for topical delivery: rheological and mechanical properties, in vitro drug release and anti-fungal efficacy.

The aim of this study was to develop thermosensitive gels using poloxamers for topical delivery of fluconazole (FLZ). Eight different formulations containing 1% FLZ in poloxamer and a particular co-solvent (propylene glycol (PG) or Transcutol-P) of various concentrations were prepared. The gels were characterized for transition temperatures, rheological and mechanical properties. FLZ permeability and antifungal effect of the gels were also evaluated. Except for one formulation, all gels exhibited thermosensitive property, i.e. transformed from Newtonian (liquid-like) behavior at 20 °C to non-Newtonian (gel-like) behavior at 37 °C. Transcutol-P increased the transition temperature of the formulations, while the opposite effect was observed for PG. At 37 °C, formulations with high poloxamer concentrations (17%) resulted in high viscosity, compressibility and hardness. Formulations containing 17% poloxamer and 20% Transcutol-P and 10% PG, respectively, exhibited high adhesiveness. No significant differences in the in vitro antifungal activity of FLZ were observed among the formulations suggesting that the gel vehicles did not influence the biological effect of FLZ. FLZ permeability decreased with increasing poloxamer concentration. Formulations containing 17% poloxamer and 20% Transcutol-P and 10% PG seemed to be promising in situ gelling systems for the topical delivery of FLZ.

Development and characterization of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery.

OBJECTIVE: This study deals with the preparation and evaluation of a pluronic lecithin organogel (PLO gel) containing ricinoleic acid for the transdermal eyelid delivery of dexamethasone and tobramycin. METHODS: Five different PLO gel formulations (F1, F2, F3, F4 and F5) containing tobramycin (0.3%) and dexamethasone (0.1%) were prepared and compared to a conventional PLO gel (light mineral oil PLO gel, F6) with respect to physical appearance and viscosity. The optimized ricinoleic acid PLO gel formulation (F2) was further characterized for pH, gelation temperature, morphology and drug content. Ex vivo permeability of dexamethasone and bactericidal activity of tobramycin from formulation F2 was tested, and values were compared to the marketed Tobradex® eye ointment. RESULTS: No apparent changes in the physical appearance and consistency were observed when ricinoleic acid was used as the oil phase. The pH of the optimized ricinoleic acid PLO gel (formulation F2) was found to be 6.54 with a gelation temperature of 31 °C. The drug content of tobramycin and dexamethasone were found to be 102.8% and 100.14%, respectively. The penetration profile of dexamethasone from formulation F2 was found to be much higher than the marketed Tobradex® eye ointment. F2 showed a better antimicrobial activity and higher zones of inhibition when compared to the marketed Tobradex® eye ointment. CONCLUSION: The findings of this investigation indicate that the ricinoleic acid PLO gel has the potential for use as a transdermal eyelid delivery system.

Risk factors for acute kidney injury in adult patients receiving vancomycin.

BACKGROUND AND OBJECTIVE: Questions have been raised regarding nephrotoxicity from vancomycin. A few small studies have shown that higher trough concentrations of vancomycin result in more nephrotoxicity. The purpose of this study was to evaluate risk factors that may predispose patients to nephrotoxicity in those concomitantly receiving vancomycin. METHODS: This was a single-center retrospective chart review conducted on adult subjects 18 years and older who received at least three doses of vancomycin. Exclusion criteria included sepsis, septic shock, or acute renal failure or stage 5 chronic kidney disease. Subjects were divided into two groups: those who developed nephrotoxicity and those who did not. Data collected included co-morbidities (diabetes mellitus, hypertension, congestive heart failure), creatinine clearance (CLCR), concomitant treatment with potentially nephrotoxic drugs, vancomycin trough concentrations, total daily dose, and duration of therapy. RESULTS: Seventy-seven subjects were included in the nephrotoxic group and 149 were in the control group. The proportion of men in the nephrotoxic group was higher (68 vs. 50 %, p = 0.0135). Hypertension (74 vs. 51 %, p = 0.0009), diabetes (49 vs. 30 %, p = 0.0046), and furosemide use (65 vs. 39 %, p = 0.0009) were more common in the nephrotoxic group. The proportion of subjects with baseline CLCR ≤63.5 mL/min was higher in the nephrotoxic group. Furosemide use (odds ratio [OR] 2.91, 95 % CI 1.64-5.15), hypertension (OR 2.74, 95 % CI 1.5-5.0), and vancomycin trough concentration ≥16.2 µg/mL (OR 2.33, 95 % CI 1.25-4.44) were each associated with nephrotoxicity during vancomycin therapy. CONCLUSIONS: In summary, the patient profile exhibiting the greatest risk (OR 4.99) of developing kidney injury is one who has hypertension, is receiving furosemide therapy, and has vancomycin trough concentrations ≥16.2 µg/mL.

Nebulized oil-in-water nanoemulsion mists for pulmonary delivery: development, physico-chemical characterization and in vitro evaluation.

CONTEXT: This study presents novel nanostructured oil-in-water (o/w) mists based on self-nanoemulsifying (SNE) mixtures capable of delivering poorly water-soluble drugs into the lungs. OBJECTIVE: Formulation development of an o/w nanoemulsion (NE) capable of being nebulized for pulmonary delivery of poorly water-soluble drugs. MATERIALS AND METHODS: SNE mixtures were prepared and evaluated using Tween 80 and Cremophor RH 40 as surfactants; Transcutol P, Capryol 90 and PEG 400 as cosurfactants; and Labrafac Lipophile Wl 1349 (a medium-chain triglyceride) as an oil. Liquid NEs were analyzed by light scattering, zeta potential, transmission electron microscopy (TEM) and in vitro drug release studies. The aqueous NE was nebulized and assessed by light scattering and TEM. The formulation was aseptically filtered and the sterility validated. In vitro cytotoxicity of the formulations was tested in NIH 3T3 cells. The capability of the formulation to deliver a poorly water-soluble drug was determined using ibuprofen. RESULTS: Ibuprofen was found to be stable in the NEs. The formulations were neutrally charged with a droplet size of about 20 nm. TEM images displayed 100 nm oil droplets. The aseptic filtration method produced sterile NE. The nebulized mist revealed properties ideal for pulmonary delivery. The biocompatible aerosol has a nanostructure consisting of several oil nanodroplets enclosed within each water drop. Solubility and in vitro drug release studies showed successful incorporation and release of ibuprofen. CONCLUSION: The developed formulation could be used as an inhalation for delivering material possessing poor water solubility into the lungs.

Educational testing validity and reliability in pharmacy and medical education literature.

OBJECTIVES: To evaluate and compare the reliability and validity of educational testing reported in pharmacy education journals to medical education literature. METHODS: Descriptions of validity evidence sources (content, construct, criterion, and reliability) were extracted from articles that reported educational testing of learners' knowledge, skills, and/or abilities. Using educational testing, the findings of 108 pharmacy education articles were compared to the findings of 198 medical education articles. RESULTS: For pharmacy educational testing, 14 articles (13%) reported more than 1 validity evidence source while 83 articles (77%) reported 1 validity evidence source and 11 articles (10%) did not have evidence. Among validity evidence sources, content validity was reported most frequently. Compared with pharmacy education literature, more medical education articles reported both validity and reliability (59%; p<0.001). CONCLUSION: While there were more scholarship of teaching and learning (SoTL) articles in pharmacy education compared to medical education, validity, and reliability reporting were limited in the pharmacy education literature.

Development and characterization of nanostructured mists with potential for actively targeting poorly water-soluble compounds into the lungs.

PURPOSE: To formulate nanoemulsions (NE) with potential for delivering poorly water-soluble drugs to the lungs. METHOD: A self nanoemulsifying composition consisting of cremophor RH 40, PEG 400 and labrafil M 2125 CS was selected after screening potential excipients. The solubility of carbamazepine, a poorly water-soluble drug, was tested in the formulation components. Oil-in-water (o/w) NEs were characterized using dynamic light scattering, electrophoretic light scattering, transmission electron microscopy (TEM) and differential scanning calorimetry. NEs were nebulized into a mist using a commercial nebulizer and characterized using laser diffraction and TEM. An aseptic method was developed for preparing sterile NEs. Biocompatibility of the formulation was evaluated on NIH3T3 cells using MTT assay. In vitro permeability of the formulation was tested in zebra fish eggs, HeLa cells, and porcine lung tissue. RESULTS: NEs had neutrally charged droplets of less than 20 nm size. Nebulized NEs demonstrated an o/w nanostructure. The mist droplets were of size less than 5 µm. Sterility testing and cytotoxicity results validated that the NE was biocompatible and sterile. In vitro tests indicated oil nanodroplets penetrating intracellularly through biological membranes. CONCLUSION: The nanoemulsion mist has the potential for use as a pulmonary delivery system for poorly water-soluble drugs.

Preparation, characterization, sterility validation, and in vitro cell toxicity studies of microemulsions possessing potential parenteral applications.

CONTEXT: Water-in-oil microemulsions (w/o ME) are ideal for parenteral drug delivery. However, no such formulations have been tested for biocompatibility in in vitro cell cultures. Furthermore, sterilization of w/o MEs is a challenging process that has not been previously developed and validated. PURPOSE: To formulate pharmaceutically relevant water-in-oil (w/o) microemulsion's systems suitable for use as a parenteral formulation. METHODS: w/o MEs were prepared using dioctyl sodium sulfosuccinate (DOSS), ethyl oleate (EO), and water. Formulations were characterized using polarized light microscopy, electrical conductivity, rheology, and dynamic light scattering. An aseptic filtration method for sterilization was developed using membrane filtration. The biocompatibility of selected MEs were evaluated in NIH3T3 cell cultures. Dissolution studies were performed on microemulsions containing methylene blue to evaluate the drug release profile. RESULTS: The maximum amount of water incorporated in the formulations was 14% w/w. DOSS/EO/water microemulsions exhibited Newtonian flow. Particle sizes for these MEs were less than 30 nm in size. Formulations filtered aseptically were free of bacteria when gram-stained and visualized under a microscope. All MEs showed no toxicity to NIH 3T3 cells. DISCUSSION: The absence of birefringence and low conductivity values indicated that the formulations were w/o microemulsions. The filtration method of sterilization was validated by the absence of microbial growth on blood agar plates over a 14-day period. In vitro dye release studies demonstrate sustained release of the model drug over a 72-h time period. CONCLUSION: Characteristics delineated in this study demonstrate the potential for these formulations to be used as parenteral preparations.

Efflux pump contribution to multidrug resistance in clinical isolates of Pseudomonas aeruginosa.

STUDY OBJECTIVE: To determine if increased expression of efflux pumps, mutations in the genes encoding regulatory proteins for efflux pumps, or the combination is associated with multidrug-resistant (MDR) Pseudomonas aeruginosa isolates. DESIGN: Microbiologic evaluation of prospectively collected Pseudomonas aeruginosa isolates. SETTING: University teaching hospital. ISOLATES: One hundred eight unique P. aeruginosa isolates-50 non-MDR and 58 MDR isolates-obtained from pulmonary or blood sources from patients admitted to the intensive care unit between January 1, 1999, and December 31, 2004. MEASUREMENTS AND MAIN RESULTS: Isolates were considered MDR if they were resistant to at least three of the following four drugs: ciprofloxacin, tobramycin, ceftazidime, or imipenem. Possible mutations in efflux regulatory genes mexR, nfxB, and mexZ were analyzed by using polymerase chain reaction amplification and DNA sequencing. Determination of the expression of outer membrane proteins OprM and OprJ was performed by using sodium dodecyl sulfate- polyacrylamide gel electrophoresis immunoblotting. Differences in regulatory gene mutations and outer membrane protein expression were compared between non-MDR and MDR isolates. Among the 108 P. aeruginosa isolates, the MDR isolates were more likely to overexpress OprM compared with non-MDR isolates (64% vs 2%, p<0.001). Mutations in mexR and mexZ were present in 64% and 26% of MDR strains, respectively, but were not associated with OprM overexpression or multidrug resistance. Expression of OprJ was not associated with MDR isolates (odds ratio [OR] 3.7, 95% confidence interval [CI] 0.7-18.5, p=0.11). Mutations in nfxB (12% of MDR strains) were also not associated with multidrug resistance (OR 3.5, 95% CI 0.7-17.8, p=0.13). Eight (100%) of 8 isolates with OprJ expression plus OprM overexpression, 12 (92%) of 13 isolates with combined mexR and mexZ mutations, 5 (100%) of 5 isolates with nfxB plus mexZ mutations, and 16 (100%) of 16 isolates with OprM overexpression plus mexZ mutations were MDR isolates. CONCLUSION: The presence of one regulatory gene mutation or simple expression of a single outer membrane protein was not linked to multidrug resistance. However, OprM overexpression and multiple efflux regulatory gene mutations or efflux protein expression were associated with MDR P. aeruginosa isolates.

Anidulafungin and its role in candida infections.

Candida infections continue to play a significant role not only in critically ill and immunocompromised patients but also in non-compromised patients. The incidence of systemic fungal infections in the United States has been on the rise for the past 30 years. Anidulafungin and all echinocandins inhibit glucan synthase thus inhibiting the formation of 1,3-ß-D-glucan which is an essential component of the fungal cell wall. The decrease in 1,3-ß-D-glucan results in the osmotic lysis of the cell, resulting in fungicidal activity against candida. Anidulafungin is active against most species of candida and resistance to it is very rare. Two potential mechanisms conferring reduced susceptibility to the echinocandins are efflux and target alteration. The efflux pump associated with fluconazole resistance in Candida albicans can confer higher minimum inhibitory concentrations to caspofungin. The second mechanism of resistance is via mutations in the genes which code for 1,3 ß-D-glucan synthase, specifically FKS1. Because of its spectrum of activity, fungicidal nature, and tolerability it is an attractive first-line therapeutic choice for treating candidemia in both non-neutropenic and neutropenic patients. Because it is available only parenterally its role in treating mucocutaneous candidiasis is primarily in patients unable to take oral therapy.

Polymorphism of pertactin gene repeat regions in Bordetella bronchiseptica isolates from pigs.

Bordetella bronchiseptica pertactin (prn) is an outer membrane protein which has been implicated as both an adhesin and a protective antigen that induces immunity against atrophic rhinitis in pigs. Previous studies demonstrated extensive heterogeneity of the prn sequence within two distinct regions of amino acid repeats for B. bronchiseptica isolated from the United States and Europe. By deducing the amino acid sequences of the repeat regions of the prn gene from recent isolates from Korea, two region 1 variants and five region 2 variants were identified. Five pertactin types were distinguished based on combinations of variants of both regions. Interestingly, none of the field isolates have the same pertactin type as the B. bronchiseptica P4 strain widely used to vaccinate pigs.

Enteral glutamine supplementation in critically ill patients with burn injuries: a retrospective case-control evaluation.

STUDY OBJECTIVES: To evaluate the clinical application of enteral glutamine supplementation in critically ill patients and compare the frequency of nosocomial infections in these patients with a historical control group in a burn intensive care unit (BICU), and to assess lengths of stay in the hospital and BICU, mortality rates, and safety profile of glutamine. DESIGN: Retrospective case-control descriptive study. SETTING: A university-affiliated hospital BICU. PATIENTS: Seventeen patients receiving enteral glutamine supplementation and 15 historical control patients who were admitted to the BICU for thermal burn injuries from January 1, 2001-September 30, 2004. MEASUREMENTS AND MAIN RESULTS: Data for patients receiving enteral glutamine supplementation were identified through the pharmacy database, and data for the control patients were identified through the BICU patient registry. No significant differences were noted in baseline characteristics or nutritional parameters and outcomes between the two groups. The mean daily dose and duration of glutamine were 0.52 g/kg and 21.6 days, respectively. The mean number of infections/patient between the glutamine and control groups was similar (2.47 and 2.73, respectively) as was the number of gram-negative infections (1.29 and 1.20, respectively). Bloodstream infections occurred more frequently in the glutamine group (24 vs 8 patients, p=0.0006); however, cellulitis (4 vs 11, p=0.05) and pneumonia (9 vs 15, p=0.15) occurred less often. For the glutamine group versus control group, BICU length of stay (17.9 vs 15.3 days, p=NS), hospital length of stay (32.3 vs 26 days, p=NS), and mortality rates (0% vs 6.7%, p=NS) were similar between groups. No adverse events were attributed to glutamine supplementation. CONCLUSION: Enteral glutamine supplementation was not associated with a change in the cumulative rate of infectious complications compared with the control group, but this was attributed to more cases of bloodstream infections and fewer cases of pneumonia and cellulitis in the glutamine group. Large, prospective, randomized trials designed to detect small but clinically relevant outcomes are needed to definitively determine the effect of enteral glutamine supplementation in the BICU population.

Pulsed-field gel electrophoresis genotyping of Salmonella gallinarum and comparison with random amplified polymorphic DNA.

Salmonella gallinarum is gram-negative bacteria that cause fowl typhoid (FT) in chickens. Since the first outbreak of FT reported in 1992 in Korea, it has widely spread throughout the country. Today, FT is one of the most devastating diseases of poultry. The aim of the present study was to ascertain a genetic relationship among S. gallinarum isolates collected from different regions of Korea over a 10-year period. We examined a total of 38 isolates of S. gallinarum obtained in 29 regions of Korea from 1992 to 2001 including the 9R vaccine strain and the standard strain of S. gallinarum (ATCC 9184). The PFGE profiles produced 12 different patterns with the XbaI-digestion and 11 different patterns with the SpeI-digestion. The RAPD using URP-6 primers showed eight different genotypes with the same Salmonella isolates. The PFGE patterns of the 9R vaccine strain and ATCC 9184 of S. gallinarum were different from the identical type A, the most common genotype among field isolates in our study. In conclusion, a low genetic heterogeneity was observed among Korean S. gallinarum isolates. In addition, PFGE appeared to be a more accurate and reproducible method for genotyping of S. gallinarum isolates than RAPD.

Molecular typing by random amplification of polymorphic DNA (RAPD) and detection of virulence genes of Salmonella enterica subspecies enterica serovar Gallinarum biovar gallinarum.

Salmonella enterica subspecies enterica serovar Gallinarum biovar Gallinarum is the causative agent of fowl typhoid in chickens, outbreaks of which have devastated poultry populations in Korea since 1992. In order to identify genetic differences among S. Gallinarum isolates, bacteria were examined using the random amplified polymorphic DNA (RAPD) method. Of 13 arbitrary primers screened initially, the primer designated as universal rice primer-6 (URP-6) was selected for subsequent typing assays because it produced a distinctive and reproducible DNA fingerprint for a S. Gallinarum reference strain. URP-6-based RAPD analysis assigned 30 S. Gallinarum isolates into 6 types, with 26 isolates (86.6%) belonging to 2 major RAPD types. The distribution of virulence genes in S. Gallinarum isolates was examined by Southern hybridization. All tested isolates had the invasion gene, invA, the virulence plasmid gene, spvB, and the S. Enteritidis fimbrial gene, sefC. The distribution of virulence genes among S. Gallinarum isolates did not correlate with any specific RAPD type.

Formulary Substitution of Proton Pump Inhibitors Based on Acquisition Price: Changes in Usage and Costs of Acid-Suppressant Therapies.

OBJECTIVE: In addition to indications for proton pump inhibitors (PPIs) outside the intensive-care unit (ICU), these medications are frequently used to manage nonvariceal upper gastrointestinal (GI) hemorrhage and to prevent stress-related mucosal bleeding in ICU patients. In September 2004, the P&T committee at the University of Colorado Health Sciences Center substituted three PPIs for one less expensive, preferred PPI product; all dosage forms were included. Our goal was to determine whether switching these PPIs to the least expensive agent would alter their usage and associated costs in the ICU (48 beds) and in non-ICU sites (325 beds). METHODS: We conducted analyses of hospital databases before the formulary switch of January 1, 2004, to June 30, 2004, and after the formulary switch of January 1, 2005, to June 30, 2005, to compare the usage and associated drug costs of PPIs and histamine-2 receptor antagonists (H2RAs) in non-ICU and ICU sites. RESULTS: Case-mix indices and length of stay data were similar before and after the switch. The total number of intravenous (IV) and enteral PPI doses charged before and after the switch increased from 1,544 to 4,143 units and from 11,865 units to 17,201 units, respectively. When we adjusted for patient-days, usage patterns of PPIs in non-ICU sites were similar before and after the switch (0.253 and 0.220 units per patient-day, respectively). In contrast, the use of PPIs in the ICU increased after the formulary switch (from 0.942 to 2.056 units per patient-day) as a result of the increased use of both IV PPIs (0.571 to 1.205 units per patient-day) and enteral PPIs (0.371 to 0.852 units per patient-day). Compared with non-ICU usage, the likelihood of PPI use in the ICU was 2.51 times higher after the switch (95% confidence interval [CI], 2.05-3.07; P < .0001).In the ICU, the concomitant use of IV H2RAs decreased from 2.550 to 1.869 units per patient-day. Compared with non-ICU usage, the likelihood of H2RA use in the ICUs was 0.49 times lower (95% CI, 0.39-0.61; P < .0001).Despite increased PPI usage, the cost of acid-suppressant therapy per patient-day in the hospital was similar before and after the switch ($0.65 and $0.59, respectively).In the ICU, the cost of acid-suppressant therapy per patient-day was reduced from $9.66 to $7.80. Compared with non-ICU sites, the cost of acid-suppressant therapy was reduced by 0.72-fold in the ICU after the switch (95% CI, 0.52-1.00, P = .04). CONCLUSION: Substituting a less expensive PPI did not alter usage outside the ICU, but it was associated with increased usage in the ICU. Conversely, the use of IV H2RAs decreased in the ICU. Despite substantially more PPI use after the formulary switch, the cost of acid-suppressant therapy was unchanged overall; it was lower in the ICU, probably as a result of the acquisition drug cost savings associated with the switch.

Evaluation of diagnostic tests and argatroban or lepirudin therapy in patients with suspected heparin-induced thrombocytopenia.

STUDY OBJECTIVES: To evaluate diagnostic tests for heparin-induced thrombocytopenia (HIT), a serious drug reaction that can occur in patients receiving heparin, and to evaluate treatment with direct thrombin inhibitors-the only initial drug therapy that decreases the risk of thromboembolism associated with immune-mediated HIT. DESIGN: Retrospective cohort study. SETTING: University teaching hospital. SUBJECTS: Patients with HIT treated with argatroban or lepirudin between January 1, 2000, and December 31, 2003. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for dosage and duration of argatroban or lepirudin therapy, HIT diagnostic tests, and clinically significant adverse events. Thirty-four patients received argatroban, 42 received lepirudin. Mean+/-SD doses of argatroban and lepirudin were 1.2+/-0.9 microg/kg/minute and 0.09+/-0.11 mg/kg/hour, respectively; both were 40% lower than the recommended doses. Mean duration of therapy was 10+/-9 days. Supratherapeutic activated partial thromboplastin times were observed in 30 (39%), 10 (13%) , and six (8%) of 76 patients on days 1, 2, and 3, respectively (p<0.0001). Clinically significant bleeding occurred in 6% of patients receiving argatroban and in 5% of those receiving lepirudin (p=0.99); all patients had an activated partial thromboplastin time of longer than 100 seconds. Although platelet-aggregation tests were ordered in 55 (72%) of 76 patients, they were not useful in 16 (29%) because of equivocal or contradictory results. CONCLUSION: Due to supratherapeutic activated partial thromboplastin times, our patients often required doses of argatroban and lepirudin lower than those usually recommended. Thus, direct thrombin inhibitors should be started at low initial doses and titrated to target activated partial thromboplastin times to achieve appropriate efficacy and to avoid increasing the risk of bleeding. Platelet-aggregation tests were least useful for evaluating HIT. Appropriate diagnostic strategies should be used to avoid unnecessary drug use.

Nosocomial infections due to multidrug-resistant Pseudomonas aeruginosa: epidemiology and treatment options.

Pseudomonas aeruginosa is one of the leading gram-negative organisms associated with nosocomial infections. The increasing frequency of multi-drug-resistant Pseudomonas aeruginosa (MDRPA) strains is concerning as efficacious antimicrobial options are severely limited. By searching MEDLINE from January 1966-February 2005 and relevant journals for abstracts, we reviewed the frequency, risk factors, and patient outcomes of MDRPA nosocomial infections in critically ill patients, determined the available antimicrobial therapies, and then provided recommendations for clinicians. The definition of MDRPA was established as isolates intermediate or resistant to at least three drugs in the following classes: beta-lactams, carbapenems, aminoglycosides, and fluoroquinolones. Reported rates of MDRPA varied from 0.6-32% according to geographic location and type of surveillance study. Risk factors for MDRPA infection included prolonged hospitalization, exposure to antimicrobial therapy, and immunocompromised states such as human immunodeficiency virus infection. Emergence of MDRPA isolates during therapy was reported in 27-72% of patients with initially susceptible P. aeruginosa isolates. Patients with severe MDRPA infections should be treated with combination therapy, consisting of an antipseudomonal beta-lactam with an aminoglycoside or fluoroquinolone rather than aminoglycoside and fluoroquinolone combinations, to provide adequate therapy and improve patient outcomes. Synergy has been observed when resistant antipseudomonal drugs were combined in vitro against MDRPA with successful clinical application reported in two centers. Colistin with adjunctive therapy, such as a beta-lactam or rifampin, may be a useful agent in MDRPA when antimicrobial options are limited, but patients should be monitored closely for toxicities associated with this agent. Standardization of terminology for MDRPA isolates is needed for consistency and comparability of surveillance and institutional reports. Clinical studies are needed to identify risk factors for MDRPA development and to determine the economic impact of these infections, as well as to determine the most efficacious antimicrobial regimens and duration of therapy to maximize outcomes in the treatment of MDRPA infections.