Troy Wanandy

Ultrarush versus semirush initiation of insect venom immunotherapy: A randomized controlled trial

BACKGROUND Venom immunotherapy can be initiated by different schedules, but randomized comparisons have not been performed. OBJECTIVE We aimed to compare the safety of 2 initiation schedules. METHODS Patients of any age with prior immediate generalized reactions to jack jumper ant (Myrmecia pilosula) stings were randomized to venom immunotherapy initiation by a semirush schedule over 10 visits (9 weeks) or an ultrarush schedule over 3 visits (2 weeks). In a concurrent treatment efficacy study, the target maintenance dose was randomized to either 50 μg or 100 μg. The primary outcome was the occurrence of 1 or more objective systemic reactions during venom immunotherapy initiation. Analyses were by intention to treat. We also assessed outcomes in patients who declined randomization. RESULTS Of 213 eligible patients, 93 were randomized to semirush (44 patients) or ultrarush (49 patients) initiation. Objective systemic reactions were more likely during ultrarush initiation (65% vs 29%; P < .001), as were severe reactions (12% vs 0%; P= .029). Times to maximal increases in venom-specific IgG(4) were no different between treatments, whereas the maximal increase in venom-specific IgE occurred earlier with ultrarush treatment. Similar differences between methods were observed in patients who declined randomization. One hundred seventy-eight patients were randomized to maintenance doses of either 50 μg (90 patients) or 100 μg (88 patients). The target maintenance dose had no effect on the primary outcome, but multiple-failure-per-subject analysis found that the 50 μg dose reduced the likelihood of reactions. CONCLUSION Ultrarush initiation increases the risk of systemic reactions. A lower maintenance dose reduces the risk of repeated reactions, but the effect on treatment efficacy is unknown.

Filtration of crushed tablet suspensions has potential to reduce infection incidence in people who inject drugs

INTRODUCTION AND AIMS The medical complications of injecting preparations from crushed tablets can be severe, and most can be attributed to the injection of insoluble particles and micro-organisms. Previously we have shown that most of the particles can be removed by filtration, but it was not known whether bacteria could also be filtered in the presence of a high particle load. This study aims to determine the feasibility of filtration to remove bacteria from injections prepared from tablets. DESIGN AND METHODS Injections were prepared from crushed slow-release morphine tablets, in mixed bacterial suspensions of Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa. The injection suspensions were passed through syringe filters of porosity 0.45 or 0.20 μm, or combined 0.8 then 0.2 μm, and the bacterial load was counted. RESULTS Bacterial concentrations in unfiltered injections were 2.5-4.3 × 10(6) colony forming units mL(-1) . Both the 0.20 and 0.45 μm filters blocked unless a prefilter (cigarette filter) was used first. The 0.2 μm filter and the combined 0.8/0.2 μm filter reduced the bacteria to the limit of detection (10 colony forming units mL(-1) ) or below. Filtration through a 0.45 μm filter was slightly less effective. DISCUSSION AND CONCLUSIONS Use of a 0.2 μm filter, together with other injection hygiene measures, offers the prospect of greatly reducing the medical complications of injecting crushed tablets and should be considered as a highly effective harm reduction method. It is very likely that these benefits would also apply to other illicit drug injections, although validation studies are needed.

STABILITY OF THE COMBINATION OF CEFTAZIDIME AND CEPHAZOLIN IN ICODEXTRIN OR PH NEUTRAL PERITONEAL DIALYSIS SOLUTION

♦ Introduction: The objective of this study was to investigate the stability of ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral peritoneal dialysis (PD) solution. ♦ Methods: Ceftazidime and cephazolin were injected into either a 7.5% icodextrin or pH neutral PD bag to obtain the concentration of 125 mg/L of each antibiotic. A total of nine 7.5% icodextrin or pH neutral PD bags containing ceftazidime and cephazolin were prepared and stored at 1 of 3 different temperatures: 4°C in a domestic refrigerator; 25°C at room temperature; or 37°C (body temperature) in an incubator. An aliquot was withdrawn immediately before (0 hour) or after 12, 24, 48, 96, 120, 144, 168 and 336 hours of storage. Each sample was analyzed in duplicate for the concentration of ceftazidime and cephazolin using a stability-indicating high-performance liquid chromatography technique. Ceftazidime and cephazolin were considered stable if they retained more than 90% of their initial concentration. Samples were also assessed for pH, colour changes and evidence of precipitation immediately after preparation and on each day of analysis. ♦ Results: Ceftazidime and cephazolin in both types of PD solution retained more than 90% of their initial concentration for 168 and 336 hours respectively when stored at 4°C. Both of the antibiotics lost more than 10% of the initial concentration after 24 hours of storage at 25 or 37°C. There was no evidence of precipitation at any time under the tested storage conditions. Change in the pH and color was observed at 25 and 37°C, but not at 4°C. ♦ Conclusion: Premixed ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral PD solution is stable for at least 168 hours when refrigerated. This allows the preparation of PD bags in advance, avoiding the necessity for daily preparation. Both the antibiotics are stable for at least 24 hours at 25 and 37°C, permitting storage at room temperature and pre-warming of PD bags to body temperature prior to its administration.

Physical and chemical stability of ceftaroline in an elastomeric infusion device

Background Severe infections such as endocarditis and osteomyelitis require long-term treatment with parenteral antibiotics and hence prolonged hospitalisation. Continuous infusion of ceftaroline through elastomeric devices can facilitate early hospital discharge by managing parenteral antibiotics in patient’s home. Therefore, the purpose of this study was to investigate the stability of ceftaroline in a commonly used elastomeric device. Method A total of 24 elastomeric devices were prepared, and six elastomeric devices containing 6mg/mL of ceftaroline (three in each type of diluents) were stored at one of the following conditions: 4°C for 6 days, 25°C for 24hours, 30°C for 24hours or 35°C for 24hours. An aliquot was withdrawn before storage and at different time points. Chemical stability was measured using a stability indicating high-performance liquid chromatography, and physical stability was assessed as change in pH, colour and particle content. Results Ceftaroline, when admixed with both diluents, was stable for 144, 24 and 12hours at 4°C, 25°C and 30°C, respectively. At 35°C, ceftaroline admixed with normal saline (NS) and glucose 5% was stable for 12hours and for 6hours, respectively. No evidence of particle formation, colour change or pH change was observed throughout the study period. Conclusions Our findings support 12 or 24hours continuous elastomeric infusion of ceftaroline-NS admixture, and bulk preparation of elastomeric pumps containing ceftaroline solution in advance. This would facilitate early hospital discharge of patients eligible for the elastomeric-based home therapy and avoid the need for patient’s caregivers travelling to the hospital on a daily basis.

Physicochemical stability of voriconazole in elastomeric devices

Objectives Voriconazole is the drug of choice for invasive aspergillosis (IA), a leading cause of mortality and morbidity in immunocompromised patients. Prolong intravenous administration of voriconazole is often needed in such patients due to high incidence of oral mucositis and unreliable bioavailability of oral dosage form. Administration of voriconazole through elastomeric pump may facilitate early hospital discharge of clinically stable immunocompromised patients needing prolonged intravenous treatment. Therefore, we investigated the physicochemical stability of voriconazole in one of the commonly used elastomeric pumps at three different temperatures for various time points. Methods A total of 18 elastomeric pumps were prepared and 6 containing 2 mg/mL of voriconazole (3 in 0.9% sodium chloride and 3 in 5% glucose) were stored at either 4°C for 96 hours, 25°C for 4 hours or at 35°C for 4 hours. An aliquot withdrawn immediately before storage (time 0) and at various time points was analysed for chemical stability using high-performance liquid chromatography and for physical stability using visual, pH and microscopic analyses. Results Voriconazole was stable for at least 96 hours, 4 hours and 4 hours at 4°C, 25°C and 35°C, respectively, when admixed with either 0.9% sodium chloride or 5% glucose. No evidence of particle formation, colour change or pH change was observed throughout the study period. Conclusions These findings would allow early hospital discharge using elastomeric intravenous administration of voriconazole in patients in whom oral route of administration is not available.

Investigations into the physical and chemical stability of concentrated co-trimoxazole intravenous infusions

Objectives High dose of intravenous sulfamethoxazole and trimethoprim (co-trimoxazole) is often used in immunocompromised patients for the treatment of Pneumocystis jiroveci pneumonia. Current manufacturer’s dilution recommendation for intravenous co-trimoxazole (1:25 v/v) requires the administration of 2 L of additional fluid per day causing serious complications including pulmonary oedema. Intravenous administration of concentrated solution of co-trimoxazole may minimise the risk of fluid overload associated side effects. Therefore, the objective of the study was to investigate the physicochemical stability of concentrated intravenous co-trimoxazole solutions. Methods Four ampoules of intravenous co-trimoxazole were injected into an infusion bag containing either 480 (1:25 v/v), 380 (1:20 v/v), 280 (1:15 v/v) or 180 (1:10 v/v) mL of glucose 5% solution. Three bags for each dilution (total 12 bags) were prepared and stored at room temperature. An aliquot was withdrawn immediately (at 0 hour) and after 0.5, 1, 2 and 4 hours of storage for high-performance liquid-chromatography (HPLC) analysis, and additional samples were withdrawn every half an hour for microscopic examination. Each sample was analysed for the concentration of trimethoprim and sulfamethoxazole using a stability indicating HPLC method. Samples were assessed for pH, change in colour (visually) and for particle content (microscopically) immediately after preparation and on each time of analysis. Results Intravenous co-trimoxazole at 1:25, 1:20, 1:15 and 1:10 v/v retained more than 98% of the initial concentration of trimethoprim and sulfamethoxazole for 4 hours. There was no major change in pH at time zero and at various time points. Microscopically, no particles were detected for at least 4 hours and 2 hours when intravenous co-trimoxazole was diluted at 1:25 or 1:20 and 1:15 v/v, respectively. More than 1200 particles/mL were detected after 2.5 hours of storage when intravenous co-trimoxazole was diluted at 1:15 v/v. Conclusions Intravenous co-trimoxazole is stable over a period of 4 hours when diluted with 380 mL of glucose 5% solution (1:20 v/v) and for 2 hours when diluted with 280 mL glucose 5% solution (1:15 v/v).

Stability of ampicillin and amoxicillin in peritoneal dialysis solutions

Peritoneal dialysis (PD) is a form of renal replacement therapy frequently used in patients with end-stage renal disease.[1][1] Peritonitis remains one of the major complications of PD, resulting in significant morbidity and occasional mortality.[2][2] Enterococcus and Streptococcus are the most

STABILITY OF MEROPENEM AND PIPERACILLIN/TAZOBACTAM WITH HEPARIN IN VARIOUS PERITONEAL DIALYSIS SOLUTIONS.

Background: Infections caused by ceftazidime-resistant Pseudomonas and extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria are increasing worldwide. Meropenem and piperacillin/tazobactam (PIP/TZB) are recommended for the treatment of peritoneal dialysis-associated peritonitis (PDAP) caused by ceftazidime-resistant Pseudomonas and other resistant gram-negative bacteria. Patients may also receive intraperitoneal heparin to prevent occlusion of their catheters. However, the stability of meropenem or PIP/TZB, in combination with heparin, in different types of peritoneal dialysis (PD) solutions used in clinical practice is currently unknown. Therefore, we investigated the stability of meropenem and PIP/TZB, each in combination with heparin, in different PD solutions. Methods: A total of 15 PD bags (3 bags for each type of PD solution) containing meropenem and heparin and 24 PD bags (3 bags for each type of PD solution) containing PIP/TZB and heparin were prepared and stored at 4°C for 168 hours. The same bags were stored at 25°C for 3 hours followed by 10 hours at 37°C. An aliquot withdrawn before storage and at defined time points was analyzed for the concentration of meropenem, PIP, TZB, and heparin using high-performance liquid chromatography. Samples were also analysed for particle content, pH and color change, and the anticoagulant activity of heparin. Results: Meropenem and heparin retained more than 90% of their initial concentration in 4 out of 5 types of PD solutions when stored at 4°C for 168 hours, followed by storage at 25°C for 3 hours and then at 37°C for 10 hours. Piperacillin/tazobactam and heparin were found to be stable in all 8 types of PD solutions when stored under the same conditions. Heparin retained more than 98% of its initial anticoagulant activity throughout the study period. No evidence of particle formation, color change, or pH change was observed at any time under the storage conditions employed in the study. Conclusions: This study provides clinically important information on the stability of meropenem and PIP/TZB, each in combination with heparin, in different PD solutions. The use of meropenem-heparin admixed in pH-neutral PD solutions for the treatment of PDAP should be avoided, given the observed suboptimal stability of meropenem.

Stability of dobutamine in continuous ambulatory delivery devices

Continuous infusion of dobutamine plays an important role in the management of patients with end‐stage heart failure. Home infusion of dobutamine using a continuous ambulatory delivery device (CADD) facilitates the management of patients in their home, avoiding complications associated with long‐term hospitalization. However, the stability of dobutamine in CADD is currently unknown. Therefore, this study investigated the physicochemical stability of dobutamine in CADDs at three different temperatures over various time points.

Stability of Cefazolin in Polyisoprene Elastomeric Infusion Devices

PURPOSE The aim was to investigate the stability of cefazolin in elastomeric infusion devices. METHODS Elastomeric devices (Infusor LV) that contain cefazolin (3 g/240 mL and 6 g/240 mL) were prepared and stored at 4°C for 72 hours and then at 35°C for 12 hours, followed by 25°C for 12 hours. An aliquot was withdrawn at predefined time points and analyzed for the concentration of cefazolin. Samples were also assessed for changes in pH, solution color, and particle content. FINDINGS Cefazolin retained acceptable chemical and physical stability over the studied storage period and conditions. IMPLICATIONS These findings will allow the administration of cefazolin by the Infusor LV elastomeric device in the outpatient and remote settings.