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PURPOSE To evaluate the efficacy and safety of intra-arterial infusion of temporary embolic material with/without radiographic monitoring via a needle placed into the radial artery to occlude abnormal neovessels for trapeziometacarpal osteoarthritis. MATERIALS AND METHODS Thirty-one patients having Eaton stage II or III osteoarthritis, with a symptom duration longer than 6 months, resistant to conservative therapy for at least 3 months were prospectively enrolled. All procedures were performed by infusing imipenem/cilastatin sodium through a 24-gauge needle that was percutaneously inserted into the radial artery. Seven patients underwent the procedure with fluoroscopy, and 21 patients underwent the procedure without fluoroscopy. The mean Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, numerical rating scale (NRS), and Patient Global Impression of Change (PGIC) scale were evaluated before and at 2, 6, and 24 months after the first procedure. RESULTS Technical success was 100%. The mean procedure time (from the beginning of local anesthesia to the removal of needle) was 2.9 minutes ± 1.6. The QuickDASH score improved from the baseline to 2, 6, and 24 months (49.2 ± 11.2 vs 22.1 ± 11.2, 20.9 ± 16.6, and 19.5 ± 16.1, respectively, all P

Imipenem/cilastatin sodium/relebactam is a combination of imipenem/cilastatin, a U.S. Food and Drug Administration (FDA)-approved antibiotic, and β-lactamase inhibitor relebactam which has been developed for the treatment of complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) due to drug-resistant bacterial pathogens. The combination (Recarbrio) has been designated as a qualified infectious disease product (QIDP) and obtained FDA approval in 2019 for the treatment of cUTI and cIAI caused by susceptible Gram-negative microorganisms in adult patients with limited or no alternative treatment options. The product was also approved by the European Medicines Agency (EMA) in 2020 for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options.

The objective of this study was to evaluate the physical and chemical stability of imipenem-cilastatin sodium 250 mg/100 mL and 500 mg/100 mL (of each drug component) admixed in 0.9% sodium chloride injection packaged in AutoDose Infusion System bags. Triplicate test samples were prepared by bringing the required amount of imipenem-cilastatin sodium injection to volume with 0.9% sodium chloride injection. A total of 100 mL of each of the test solutions was packaged in each of three ethylene vinyl acetate (EVA) AutoDose bags designed for use in the AutoDose Infusion System for each storage condition. Samples were protected from light and evaluated at appropriate intervals for up to three days at 23°C and 14 days at 4°C. Physical stability was assessed using a multistep evaluation procedure that included turbidimetric and particulate measurement in addition to visual inspection. Chemical stability was assessed with stability-indicating high performance liquid chromatography (HPLC) analytical techniques, based on initial drug concentrations and concentrations at appropriate intervals over the study periods. The admixtures were clear throughout the study when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and exhibited little change throughout the study. HPLC analysis revealed extensive decomposition in the samples, with imipenem being the less stable component. The instability of the imipenem-cilastatin sodium admixtures is consistent with previous studies. Admixtures stored under refrigeration should be used immediately upon warming to room temperature due to the rapid rate of imipenem decomposition. The AutoDose Infusion System bags were not found to affect adversely or improve the physical and chemical stability of this drug.

The plasma sodium valproate (VPA) concentration was significantly lower than the control 0.5, 1, 2 hours after the simultaneous administration of VPA with imipenem/cilastatin (IPM/CS), but the blood cell VPA/plasma VPA concentration was significantly higher at 2 hours after VPA administration. When we injected IPM instead of IPM/CS into rats, the plasma VPA concentration demonstarated similar low levels. The pharmacokinetic parameters of plasma VPA, the volume of distribution (Vd) and clearance (CL) were significantly higher at 1.6 and 1.7 times basal levels white the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve up to 3 hours (AUC0→3) significantly decreased by 0.7 and 0.6 times the basal level after the simultaneous administration of VPA and IPM/CS. The rate of VPA unbound protein was 30.3% before injecting the IPM vein. Although, when IPM was injected inside the vein, it increased by 37.3% at 1 minute and significantly increased by 49.9% at 15 minutes after the administration of IPM. The liver and brain VPA tissue concentration significantly decreased after the simul taneous administration of VPA with IPM/CS.Based on these finding a large amount of unbound type VPA which was produced by competition with a protein binding part of VPA depending on IPM was distributed in the tissue. VPA was especially distributed to blood cells and the kidney. The VPA that had been distributed in the liver later metabolized and was excreted. Therefore, the VPA concentration in plasma, liver and brain was observed to significantly decrease.

Final filters have not been always used for injections in the pediatric ward of our hospital. Since thore has been no report on the particulate matters of five dissolved antibiotics in vial, we measured those amounts using a particle counter. The amounts of particulate matters in the solutions of cefpirome sulfate, flomoxef sodium and panipenem/betamipron were below the limits defined by the Japanese Pharmacopoeial Forum (1996) or United States Pharmacopoeia (USP XXIII). However, particles above 10μm in imipenem/cilastatin sodium and vancomycin hydrochloride immediately after dissolution were about 70% of the limit. Scanning electron micrographs of the filter membrane surface showed the existence of insoluble particulate contaminants in those injections. Final filters are recommended for these antibiotic injections to be used safely in pediatric patients.

Fifty-four very-low birth weight (VLBW) infants with proved or suspected septicemia hospitalized in the neonatal intensive care unit in Asahikawa Kosei Hospital were treated empirically with imipenem/cilastatin sodium (IPM/CS). IPM/CS was infused over a 30-minute period at a mean dose of 20.1±1.1 mg/kg (range, 17.4 to 23.4 mg/kg) and given every 12 hours for a period of 6.1±3.1 days (range, 3 to 16 days). The gestational age of the infants was 26.6±2.1 weeks (range, 24.0 to 31.0 weeks) and their birth weight was 860±234 g (range, 536 to 1478 g). At the time of initial administration of IPM/CS, the age was 30.5±2.9 days (range, 2 to 77 days), and the body weight was 799±289 g (range, 422 to 1748 g). Though 29 patients were administered IPM/CS on suspicion of septicemia, the causative organism could not be isolated. Causative organisms were isolated from the blood in 25 of the 54 patients, and includedAcinetobacter calcoaceticus (n=7),Enterobacter cloacae (n=5), methicillin-resistantStaphylococcus aureus (MRSA; n=5), other gram-negative bacilli (n=5),Staphylococcus epidermidis (n=2), MRSA andKlebsiella pneumoniae (n=1). A clinical cure was achieved in 17 of 25 infants and improvement was noted in an additional 3 infants, while 5 infants were evaluated as treatment failures. The 5 treatment failure patients were all diagnosed with MRSA infections. No adverse effects or abnormal laboratory values due to IPM/CS therapy were observed in these infants.

Antimicrobial susceptibility of the Lyme disease Borrelia, strain HP1 vi, isolated from the tick ixodes persulcatus in Hokkaido, Japan, was determined in vitro and in vivo. A broth dilution technique was used to determine the minimum inhibitory concentrations (MICs) and minimum borreliacidal concentrations (MBCs) of five antimicrobial agents. Strain HP1 vi was most susceptible to minocycline (MBC, 0.2 micrograms/ml). The other antimicrobial agents tested, aspoxicillin, cefmetazole sodium, imipenem cilastatin sodium, and panipenem betamipron, had higher MBCs of 12.5 micrograms/ml, 25 micrograms/ml, > 25 micrograms/ml, and > 25 micrograms/ml, respectively. In vivo antibiotic susceptibility study using a ddY mouse model demonstrated that minocycline and amoxicillin were effective; minocycline had a lower 50% effective dose (ED50) value (6.25 mg/kg) than amoxicillin (30 mg/kg).

Imipenem/cilastatin sodium is a new thienamycin class of antibiotic with a broad spectrum of bactericidal activities. It may be a suitable single first-line therapy for the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. Fifty episodes of CAPD peritonitis were treated with imipenem/cilastatin sodium. On presentation, all patients were given an intravenous loading dose of 1 g of imipenem/cilastatin sodium followed by intraperitoneal imipenem/cilastatin sodium for 10 days. During 1989 (30 episodes), 20 mg imipenem/cilastatin sodium was added to each 2-liter bag of peritoneal dialysis (PD) fluid for 10 days. The primary response rate as defined by polymorphonuclear neutrophils100/ml in PD fluid was 90%. Unfortunately, 17% of the peritonitis relapsed within 14 days of stopping antibiotic. The complete cure rate without relapse was therefore 73%. During 1990 (20 episodes), 100 mg imipenem/cilastatin sodium was added to each 2-liter bag of PD fluid for 10 days. The primary response rate was 95%, the complete cure rate without relapse was 85%. Imipenem/cilastatin sodium is an effective single first-line antibiotic for the treatment of peritonitis in CAPD.

Fifteen children (3-12 years) with peritonitis were given imipenem/cilastatin intravenously (15 or 25 mg/kg) every six hours for 3-14 days. One day during treatment days 2-8, multiple blood and urine samples were collected from each individual over a six hour dosing interval. Twelve children completed the study. The urinary recovery of imipenem and cilastatin averaged 50-70% of the administered dose. The plasma t1/2 for imipenem averaged 55 min. while that for cilastatin was even more rapid (approximately 38 min.). Little or no accumulation of either imipenem or cilastatin was observed for this regimen in this age group of paediatric patients. Steady state conditions prevailed within 2 days of initiation of therapy. The pharmacokinetics of imipenem and cilastatin in paediatric patients 3-12 years of age appear similar to those observed for adults.

A clinical study of impenern/clastatin soditaum (IPM/CS Tienam®, ) was performed in various infections in the field of oral and maxillofacial surgery. Tienam was adminstered by intravenous drip infusion at a daily dose of lg (0.5g×2 times) to 40 patients with various infections.The subjects consisted of 34 maxillary ostitis, 2 phlegmon of the floor of the mouth, 2 parotitis, acute odontogenic maxillary sinusitis and 1 buccal abscess.The following results were obtained. The subjective evaluation was excellent in 23 cases, good in 21 cases and poor in 1 case.The scoring evaluation according to the scale proposed by Japanese Society of Oral Therapeutics and Pharmacology were excellent in 18 cases, good in 21 cases and poor in 1.The effective rate was 97.5% is both subjective and scoring evaluations. We examined bacteriological MIC of IPM/CS, TAPC, CCL, BAPC, AMPC, PIPC and OFLX.As a result, IPM/CS showed most favorable MIC data (90.3%) of all and there were no side effects.The laboratory values shifted favorably with time elapsed.The results indicated the usefulness of IPM/CS in the treatment of various infections in the field of oral surgery.

A seriously ill patient with circulatory collapse, fever, acute renal failure, and progressive respiratory failure had dramatic improvement after treatment with imipenem/cilastatin sodium. During the treatment period, a diagnosis of tularemia was established serologically. This case suggests the efficacy of imipenem/cilastatin in the treatment of tularemia.

The stability of imipenem-cilastatin sodium (Primaxin, Merck Sharp & Dohme) in various intravenous fluids was determined after storage at 4 degrees C or 25 degrees C and after freezing. Samples of imipenem-cilastatin sodium were constituted with 100 mL of each of 17 i.v. fluids to concentrations of 2.5 mg/mL or 5.0 mg/mL of each drug component and stored in glass infusion bottles at constant room temperature (25 degrees C) or constant refrigerated temperature (4 degrees C). The concentration of each solution was determined immediately after constitution by a stability-indicating high-performance liquid chromatographic assay; the concentrations of both drugs were monitored in each i.v. fluid until the time that the concentration of either imipenem or cilastatin decreased to less than 90% of the initial concentration (t90). The exact value of t90 was determined for each solution by linear regression. The solutions were also assessed for changes in pH or color. Cilastatin sodium was more stable in all 17 i.v. fluids than imipenem. The stability of imipenem was dependent on the concentration of that drug in solution; solutions of imipenem 2.5 mg/mL were more stable than solutions of imipenem 5.0 mg/mL. The values of t90 for imipenem in solutions stored at 4 degrees C were greater than the values for solutions stored at 25 degrees C. Imipenem was most stable in 0.9% sodium chloride injection. The pH values of the solutions generally decreased during the study period.(ABSTRACT TRUNCATED AT 250 WORDS)

The chemistry, antimicrobial spectrum, mechanism of action, pharmacology and pharmacokinetics, clinical use, adverse effects, dosage and administration, place in therapy, cost-effectiveness, and formulary considerations of imipenem-cilastatin sodium are reviewed. Imipenem is the first carbapenem antibiotic of the thienamycin class to be used clinically. Imipenem has the widest spectrum of antimicrobial activity of currently available beta-lactam agents and, in contrast to other beta-lactam antibiotics, lacks cross resistance with recently introduced extended-spectrum penicillins and third-generation cephalosporins. Against gram-positive and gram-negative aerobic and anaerobic organisms, imipenem demonstrates excellent activity. Pseudomonas maltophilia, some strains of Pseudomonas cepacia, and Streptococcus faecium are resistant. Strains of methicillin-resistant staphylococci should also be considered resistant to imipenem. For clinical use imipenem is coadministered in equal parts with cilastatin. Cilastatin is a renal dehydropeptidase inhibitor that inhibits the metabolism of imipenem by renal brush-border enzymes, thus increasing imipenem concentrations in urine. Imipenem-cilastatin is administered by the intravenous route only. The adverse reaction profile of imipenem-cilastatin is similar to t that of other beta-lactam antibiotics. Recommended dosage reductions appropriate for renal impairment should be guided by periodic assessments of renal function, with close adherence to recommended dosage schedules, particularly among patients who are predisposed to seizures or receiving anticonvulsant medication. Imipenem-cilastatin performed well in both comparative and noncomparative trials of clinical efficacy and safety. For infections with multiple organisms (e.g., pelvic, intra-abdominal, or soft-tissue infections), imipenem-cilastatin may be a cost-effective and less toxic single-agent alternative to "standard" combination (e.g., aminoglycoside-penicillin plus an antianaerobic agent) therapy. However, in patients with serious pseudomonal infections (e.g., pneumonia), isolates may rapidly acquire resistance to imipenem or be replaced by resistant strains of Ps. aeruginosa when imipenem is used alone. Therefore, when the recovery of Ps. aeruginosa is anticipated or documented, treatment with imipenem-cilastatin should include an aminoglycoside to reduce the likelihood of the emergency of resistant organisms during therapy.

A rapid, quantitative X-ray diffraction method to monitor the relative degree of crystallinity of lyophilized materials is described. The method was applied to determine the degree of crystallinity of imipenem [(5 R, 6 S)-3-[[2(formimidoylamino)ethyl]thio]-6-[(R)-1- hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid] in 60 process related samples of the combination product of imipenem and amorphous cilastatin sodium (sodium (Z)-7-[[(R)-2-amino-2-carboxyethyl]thio]-2-[(S)-2,2- dimethylcyclopropanecarboxamido]-2-heptenoate). This assured optimizing process conditions which affect the improvement of crystallinity.