Imipenem/cilastatin Sodium Research Articles

Intra-Arterial Injection of Temporary Embolic Material Through a Needle Inserted into the Radial or Ulnar Artery for Distal and Proximal Interphalangeal Joint Osteoarthritis: A Retrospective Study of 92 Patients.

To assess the efficacy and safety of intra-arterial injection of imipenem/cilastatin sodium (IPM/CS) via a needle placed into the radial artery or ulnar artery (RA/UA) for distal interphalangeal and proximal interphalangeal joint osteoarthritis (DIP/PIP-OA). This is a retrospective single-arm cohort study. Ninety-two patients [92% women, mean (SD) age 55(8.3) years] with a primary DIP/PIP-OA meet the American College of Rheumatology criteria for hand osteoarthritis with pain ≥ 4 on the 0-10 numeric rating scale (NRS) were enrolled. All procedures were performed by injecting IPM/CS through a 24-gauge needle percutaneously inserted into the RA/UA. Two procedures were planned; the second procedure was scheduled 1-2months after the first. NRS, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, Patient Global Impression of Change (PGIC) scale, and procedure-related adverse events were evaluated. Technical success, defined as injection of IPM/CS into the RA/UA, was achieved in all patients. Clinical success, defined as a reduction of 2 points or more in the NRS at 12months, was 77% (95% confidence interval 68-85%). The NRS improved from the baseline to 3, 6, and 12months (7.8 ± 1.6 vs. 3.8 ± 2.6, 3.9 ± 2.7, and 4.0 ± 2.8, respectively, all p < 0.001). The QuickDASH score improved from the baseline to 12months (27 ± 15 vs. 19 ± 17, p < 0.001) respectively. No major adverse events were observed. Intra-arterial injection of IPM/CS is a feasible treatment option for DIP/PIP-OA.

Association between Baseline Osteoarthritic Features on MR Imaging and Clinical Outcome after Genicular Artery Embolization for Knee Osteoarthritis

PurposeTo explore the association between baseline osteoarthritis (OA)-related magnetic resonance (MR) imaging features and pain reduction after genicular artery embolization (GAE) in patients with mild-to-moderate symptomatic knee OA resistant to conservative therapy. Materials and MethodsThis was a retrospective analysis of patients with mild-to-moderate symptomatic knee OA treated with GAE using imipenem-cilastatin sodium. The clinical outcome was scored at baseline and 6 months after treatment using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). MR images were scored using the MR imaging osteoarthritis knee score. Linear regression was used to evaluate associations of before-treatment MR imaging scores with WOMACpain and WOMACtotal reduction after 6 months. ResultsFifty-four patients (22.2% male; median age, 69.4 years; median WOMACpain at baseline, 12) were evaluated. Of all OA features scored, a higher cartilage full-thickness defect score showed the strongest association with less reduction of both WOMACpain (B,−0.63 [95% confidence interval (CI), −0.91 to −0.34]; P < .001) and WOMACtotal scores (B, −1.77 [95% CI, −2.87 to −0.67]; P < .001) following treatment. The presence of grade 2–3 effusion synovitis (B, −2.99 [95% CI, −5.39 to −0.60]) bone marrow lesions (B, −0.52 [95% CI, −0.86 to −0.19]), osteophytes (B, −0.21 [95% CI, −0.36 to −0.06]), and cartilage defect surface area score (B, −0.25 [95% CI −0.42 to −0.08]) all showed a significant association with less WOMACpain reduction (all P < .05). ConclusionsIn patients with mild-to-moderate symptomatic knee OA treated with GAE, the presence and severity of full-thickness cartilage defects, effusion synovitis, bone marrow lesions, osteophytes, and cartilage surface area scores at baseline are associated with less favorable clinical outcomes at 6 months.

The potential risk factors of nephrotoxicity during vancomycin therapy in Chinese adult patients

ObjectiveTo evaluate potential risk factors that may make patients susceptible to nephrotoxicity in those concomitantly receiving vancomycin in the hospital.MethodsThis was a single-centre retrospective analysis of patients treated with vancomycin...

In vitro interactions of ambroxol hydrochloride or amlodipine in combination with antibacterial agents against carbapenem-resistant Acinetobacter baumannii.

The aim of this study was to investigate the in vitro interactions of ambroxol hydrochloride (ABH) or amlodipine (AML) with commonly used antibacterial agents, including meropenem, imipenem-cilastatin sodium, biapenem, cefoperazone-sulbactam, polymyxin B, and tigecycline, against six carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates. Drug interactions were interpreted using two models, that is, the fractional inhibitory concentration index (FICI) model and the percentage of growth difference (ΔE) model. The results show that a majority of the combination groups exhibited partial synergy and additive interactions, such as the combinations of carbapenems and cefoperazone-sulbactam (SCF) with ABH or AML. While the combination of PB/AML exhibited synergistic interactions against all tested isolates, and PB/ABH exhibited synergistic interactions against two isolates. The FICI and ΔE model correlated very well for the combinations of PBABH and PB/AML against AB2. The combinations of TGC with ABH or AML mainly exhibited additive and indifferent interactions. There were no antagonistic interactions observed in any of the combinations. In conclusion, this study revealed that the non-antibacterial agents ABH or AML can work synergistically or partial synergistically with antibacterial agents against CRAB. This finding is crucial for overcoming the carbapenem resistance of A. baumannii. SIGNIFICANCE AND IMPACT OF THE STUDY: Drug combination is an effective approach for the treatment of resistant bacterial infection. The significance of using drug combination is that it can reduce drug dosage requirements, reduce the toxic effects of agents and prevent or delay the emergence of drug resistance. This study measured the in vitro interactions between non-antimicrobial agents and antibacterial agents against carbapenem-resistant Acinetobacter baumannii and the results of this study provide new insight to find strategies to overcome the carbapenem resistance in A. baumannii.

Efficacy of imipenem and cilastatin sodium in the treatment of severe infection complicated with multiple organ dysfunction and its effect on blood lactate

Objective To investigate the curative effect of imipenem cilastatin sodium in the treatment of patients with severe infection complicated with multiple organ dysfunction, and its effect on blood lactic acid. Methods From January 2012 to January 2017, a total of 124 patients with severe organ failure and multiple organ dysfunction in the Second Hospital of Shanxi Medical University were selected, and they were randomly divided into study group and control group according to the digital meter method, with 62 cases in each group.The study group received a broad-spectrum antibiotic imipenem cilastatin sodium treatment, the control group received levofloxacin treatment.The curative effect, bacterial clearance rate, infection control time and the change of BLA level in the two groups were recorded and compared. Results The total effective rate was 82.26% in the study group and 79.03% in the control group, there was no statistically significant difference between the two groups(χ2=1.187, P>0.05). The bacterial clearance rate in the study group was 80.00%, which was significantly higher than 52.94% in the control group(χ2=5.176, P 0.05). After treatment, the BLA level in the study group was significantly higher than that in the control group(t=12.179, P 0.05). There was no statistically significant difference in BLA level between the two groups after one week of discontinuation(t=1.237, P>0.05). Conclusion Imipenem and cilastatin sodium has good curative effect and bacterial clearance rate in the treatment of patients with severe infection complicated with multiple organ dysfunction.It can control the infection more promptly and has a significant effect on the prognosis of patients.It is worthy of widely clinical promotion and application. Key words: Infection; Multiple organ failure; Anti-bacterial agents; Lactic acid

Imipenem/cilastatin sodium (IPM/CS) as an embolic agent for transcatheter arterial embolisation: a preliminary clinical study of gastrointestinal bleeding from neoplasms

PurposeTo evaluate the feasibility and usefulness of imipenem/cilastatin sodium (IPM/CS) as an embolic agent for intestinal bleeding from neoplasms.Materials and methodsSeven patients who underwent 11 transarterial embolisations (TAEs) using IPM/CS as an embolic material for duodenal or small/large intestinal tumour bleeding from January 2004 to December 2011 were retrospectively evaluated. A mixture of IPM/CS and contrast medium was introduced through the microcatheter positioned at the feeding artery to the tumour until extravasation disappeared or stasis of blood flow to the tumour staining was observed.ResultsHaemostasis was obtained in all patients. Therefore, the technical success rate was 100%. Rebleeding was observed in four patients. All of them underwent repeat TAE using IPM/CS, and haemostasis was obtained successfully. No complication was identified following laboratory and clinical examinations. No haemorrhagic death occurred. Haemorrhagic parameters, including blood haemoglobin and the amount of blood transfusion, improved after TAE.ConclusionThe safety, feasibility, and effectiveness of TAE using IPM/CS as an embolic material for intestinal bleeding from neoplasms were suggested by this study. The mild embolic effect of IPM/CS may be adequate for oozing from tumours. Although rebleeding may occur after embolotherapy using IPM/CS, repeat embolisation is effective as treatment for rebleeding.

新生児, 未熟児におけるImipenem/Cilastatin sodiumの基礎的, 臨床的検討

Pharmacokinetic and clinical studies on imipenem/cilastatin sodium (IPM/CS), a beta-lactam antibiotic of the carbapenem class and its renal dehydropeptidase-I inhibitor in a 1:1 ratio, were performed in neonates, premature infants and an infant. IPM/CS was administered intravenously to 4 neonates and 5 premature infants at a dose level of 10 mg/kg. Plasma levels and urinary excretion of IPM and CS were determined in 2 neonates and 2 premature infants after 30-minute infusion, and in 2 neonates and 3 premature infants after 1-hour infusion. Plasma and cerebrospinal fluid (CSF) concentrations of IPM and CS were determined in 2 cases with purulent meningitis with ages of 2 and 26 days and 1 with purulent meningitis/bacteremia with an age of 4 days. The drug was administered to a total of 31 patients with ages between 0 and 30 days, consisting of neonates, premature infants and an infant (24 suffering with various bacterial infections, 5 treated for prophylaxis of infections and 2 treated for aseptic meningitis diagnosed at the completion of therapy) by intravenous drip infusion in a mean daily dose level of 50.1 mg/kg in 2 to 4 divided doses for 9 days on the average. Clinical efficacy, prophylactic effectiveness and bacteriological response of IPM/CS were evaluated in 29 cases. Adverse effects and abnormal laboratory test results were examined in 31 cases including 2 drop-out cases. The results obtained are summarized as follows. 1. Plasma concentrations of IPM and CS after 30-minute infusion of the drug reached their peaks at the end of administration, and obtained values were 22.4 to 29.0 micrograms/ml for IPM and 26.3 to 34.6 micrograms/ml for CS, thus peak plasma levels of CS were a little higher than IPM. Plasma half-lives of IPM were 1.05 to 2.43 hours, and those of CS were 1.24 to 4.76 hours, and the half-life of CS tended to be longer than that of IPM. Drug concentrations in plasma after 1-hour infusion of IPM/CS reached their peaks at the end of administration and the levels of CS (25.7 to 32.0 micrograms/ml) were a little higher than those of IPM (20.8 to 23.9 micrograms/ml). Plasma half-lives of IPM were 1.40 to 1.63 hours, whereas those of CS were 1.51 to 2.90 hours. The half-life of CS tended to be longer than IPM. 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of imipenem/cilastatin sodium in the treatment of respiratory tract infections

Imipenem/cilastatin sodium (IPM/CS) was administered to 55 patients with respiratory tract infections (RTI). A clinical evaluation of IPM/CS was carried out in 51 patients, 28 with pneumonia, 4 with pulmonary abscess, 1 with pyothorax, 6 with bronchitis, 9 with bronchiectasis, 1 with diffuse panbronchiolitis and 2 with RTI with chronic obstructive pulmonary disease, and the clinical efficacy rate was 78.4%. Causative organisms were isolated in 23 strains out of 20 patients, such as Staphylococcus aureus 4 strains, Staphylococcus epidermidis 1 strain, Streptococcus pneumoniae 1 strain, Branhamella catarrhalis 1 strain, Haemophilus influenzae 2 strains, Klebsiella pneumoniae 4 strains, Pseudomonas aeruginosa 6 strains, Pseudomonas sp. 1 strain, Acinetobacter calcoaceticus 1 strain, Acinetobacter sp. 1 strain and glucose non-fermentative Gram-negative rod 1 strain. An eradication rate of 70.6% was obtained. An overall eradication rate of main causative organisms in RTI including S. aureus, S. pneumoniae, H. influenzae and K. pneumoniae was 75.0%. Clinical adverse effects were observed in 5 patients, and these were eruption in 2, itching in 1, vomiting in 1 and drug fever in 1. Abnormalities in laboratory test results were observed in 8 patients. These disappeared or returned to normal values after completion or discontinuation of IPM/CS administration. IPM/CS appears to be a useful antibiotic for the treatment of RTI, especially severe infections.

Bacteriological and clinical evaluations of imipenem/cilastatin sodium in neonates and premature infants

The antimicrobial activity of imipenem against group B streptococci was investigated. The clinical efficacy of imipenem/cilastatin sodium (IPM/CS) was determined in neonates and premature infants. The results are summarized below. 1. The distribution of MIC values of IPM against 55 clinical isolates of group B streptococci isolated from the vagina of pregnant women peaked at 0.024 micrograms/ml. MIC values of IPM against all clinical isolates tested were 0.05 microgram/ml or less. 2. IPM/CS was used for treatment of bacterial infections in 9 neonates and premature infants. Among these patients, clinical responses were excellent in 5 patients and good in 4 patients. No adverse reaction was observed. Abnormal laboratory test values were observed in 4 patients, eosinophilia in 2 patients and increased platelets in 2. 3. In 7 neonates and premature infants, quantitative cultures for aerobic and anaerobic fecal flora were performed. Fecal flora change was not significantly different than those observed during treatment with latamoxef or cefmenoxime. 4. Ten neonates and premature infants were investigated for effects of IPM/CS on the blood coagulation system. Prolongations of prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed in 1 patient. Abnormal prothrombin (PIVKA II) was detected in the same patient. There was no tendency for inhibition of platelet function.

Evaluation of imipenem/cilastatin sodium in neonatal infections

Ten patients with infections (8 neonates and 2 infants) were treated with 10.2 mg/10.2 mg/kg-37.7 mg/37.7 mg/kg of imipenem/cilastatin sodium (IPM/CS) b.i.d. or t.i.d. by a 1-hour intravenous drip infusion. The plasma concentrations of IPM/CS were determined in 5 of the 10 patients and in the cerebrospinal fluid of 1 patient of the 5. 1. The patients studied included 5 with pneumonia and 1 each with urinary tract infection, omphalitis, suspected meningitis, periproctal abscess and suspected septicemia. Clinical efficacy was evaluated in 9 patients: the patient with suspected meningitis was excluded from the clinical evaluation because the infection was doubtfully due to bacteria. Responses were excellent in 4 and good in 5 patients. No patient with a poor response was observed. All of the 6 etiological isolates obtained from 5 patients (2 strains of Staphylococcus aureus and 1 each of Escherichia coli, Enterococcus faecalis, Streptococcus agalactiae and Bacteroides fragilis) were eradicated. 2. As for side effects, rash was observed in 1 patient and petechiae accompanied by decreases in platelets and reticulocytes and increases in GOT and GPT were observed in another. Other abnormal laboratory test values in addition to the above abnormalities consisted of an increase in GPT in 1 patient and increases in GOT and GPT in another. These side effects and abnormalities in laboratory test values were mild and normalized after discontinuation or completion of IPM/CS administration.(ABSTRACT TRUNCATED AT 250 WORDS)

造血器疾患患者に合併した重症感染症に対するImipenem/Cilastatin sodiumの臨床的検討

1. To evaluate the efficacy and tolerance of imipenem/cilastatin sodium (IPM/CS) in severe infections associated with hematopoietic disorders, IPM/CS was administered to a total of 105 patients. 2. Out of 96 patients evaluable for efficacy, clinical responses were excellent in 23 patients, good in 30, fair in 15, poor in 19 and unknown in 9, and the overall response rate was 60.9%. 3. The most common underlying hematopoietic disease was acute non-lymphocytic leukemia and the most common infections were sepsis and suspected sepsis. 4. Daily dose, severity of infection and neutrophil count had effects on the clinical response. 5. The overall eradication rate of bacteria was 83.7%. 6. Side effects were observed in 10 patients (9.5%) and abnormal laboratory test results in 12 (11.4%). From the above findings, we have concluded that IPM/CS is very useful for the treatment of severe infections in compromised patients with hematopoietic diseases.

Clinical studies on imipenem/cilastatin sodium in the early therapy of preterm premature rupture of the membrane or threatened abortion and premature delivery

The efficacy and safety of early therapy with imipenem/cilastatin sodium (IPM/CS) were studied in patients who had chorioamnionitis with preterm PROM or threatened abortion and premature delivery. The following results were obtained. 1. The clinical efficacy of IPM/CS administered by intravenous drip infusion at daily dosages of 1 to 2 g as concurrent treatment with antiuteronics (ritodrine hydrochloride or terbutaline sulfate) was studied in patients with threatened abortion and premature delivery in the 11th to 34th week of pregnancy (n = 9), or premature PROM in the 23rd to 36th week (n = 9). 2. Response to IPM/CS were good in all of the patients with threatened abortion and premature delivery. Latent periods were prolonged for more than 7 days in 44.4% (4/9) of the patients with preterm PROM. 3. Changes in elastase appeared to be significant as those in CRP for inflammatory markers. 4. These findings combined with our previous results indicate that treatment of preterm PROM before the 32nd of pregnancy prolongs the latent period.

Clinical study of intramuscular imipenem/cilastatin sodium in the field of obstetrics and gynecology

We evaluated the clinical efficacy and safety of intramuscular (as a new route of administration) imipenem/cilastatin sodium (IPM/CS) in patients with intrauterine infections which are typical in the field of obstetrics and gynecology. The obtained results are summarized as follows. 1. Twenty-seven patients were treated with IPM/CS, 250 mg/250 mg b.i.d. (3 patients), 500 mg/500 mg b.i.d. (22) and other dosages (a change in dosing regimen, 2). The duration of treatment ranged from 3 to 11 days and the total dosage during an entire course of treatment varied from 1.5 to 9.0 g. The drug was suspended in a lidocaine solution and administered in the gluteal muscle of the patients. 2. Clinical efficacies were excellent in 7 patients (26%), good in 19 (70%) and poor in 1 (4%) and the overall efficacy rate was 96.3%. All of the 8 patients who had not previously showed improvements with treatment by other antibiotics responded well to this drug. 3. Bacteriologically, the clinical efficacy rate was 95.8% (23/24) and the eradication rate was 76.2% (16/21). 4. No adverse effects due to the drug were observed. As abnormal laboratory test results, transient elevations of GOT and GPT were noted in one patient.

A clinical phase I study on intramuscular imipenem/cilastatin sodium

The safety and pharmacokinetics of imipenem/cilastatin sodium (IPM/CS) were evaluated in comparative studies using single intramuscular injection, intravenous infusion or multiple intramuscular administration. The studies were done employing 30 healthy volunteers. Adverse effects were observed in 5 of 18 volunteers in the single intramuscular dose study. One of them complained of mild itching and mild pain at the injection site, and the other 4 volunteers had mild pain at the injection sites. With the other methods of administration, no adverse effects were observed. No other abnormal physical findings nor abnormal laboratory test values were observed in any of the studies. Imipenem (IPM) was absorbed rather slowly through the muscles, resulting in a low maximum plasma concentration (Cmax) and a prolonged half life (T1/2) upon intramuscular injection compared to the results obtained upon intravenous infusion. The total areas under the curves obtained with these 2 methods were similar, however. Cilastatin (CS) was absorbed rapidly after intramuscular injection, and the Cmax obtained was higher than that obtained for IPM. The T1/2 and the AUC of CS obtained with intramuscular injection were similar to those obtained with intravenous infusion. Cumulative urinary recovery rates obtained with these 2 different routes of administration were not different. Detectable urinary levels of IPM were maintained much longer upon intramuscular injection than upon intravenous infusion. In the multiple dose study, neither IPM nor CS showed tendency to accumulate.

Efficacies of calcium–EDTA in combination with imipenem in a murine model of sepsis caused by Escherichia coli with NDM-1 β-lactamase

We evaluated the efficacy of ethylenediamine-N,N,N',N'-tetraacetic acid, disodium calcium salt (Ca-EDTA), as an inhibitor for New Delhi metallo-β-lactamase-1 (NDM-1) in vitro antibiotic susceptibility and in a mouse model of sepsis caused by Escherichia coli. Ca-EDTA drastically reduced the MICs of carbapenems for all NDM-producing bacteria [imipenem (IPM) ≤1-2μg/ml; meropenem (MEPM) ≤1-4µg/ml]. In the neutropenic murine model of sepsis, the bacterial burden was further reduced by combination therapy using imipenem/cilastatin sodium (IPM/CS) and Ca-EDTA to 2.3×10(3) CFU/liver, compared with 2.9×10(4) CFU/liver for IPM/CS alone. These data demonstrated the possibility of Ca-EDTA for clinical applications. In our understanding, this is the first report examining the effect of Ca-EDTA on a mouse sepsis model caused by NDM-1-producing bacteria.

Domestic imipenem cilastatin sodium for the treatment of severe aspiration pneumonia, a curative effect observation

To evaluate the efficacy and safety of domestic imipenem cilastatin sodium for the treatments of severe aspiration pneumonia. A randomize, open, parallel-controlled trial was conducted. Sixty-eight patients with severe aspiration pneumonia were divided into trial group (n=36) and control group (n=32) by random distribution method. The application of trial group domestic imipenem cilastatin sodium was 1.0 g intravenous drip, every 6-8 hours for 7-14 days. The control group application with imported injection imipenem cilastatin sodium was 1.0 g intravenous drip, every 6-8 hours for 7-14 days. The highest daily temperature (T), heart rate (HR), breathing rate (RR), pulse blood oxygen saturation (SpO(2)), blood oxygen partial pressure (PaO(2)), inhaled oxygen concentration (FiO(2)), oxygenation index (PaO(2)/FiO(2)), airway peak pressure (Paw), minute ventilation (MV) and white blood count (WBC), pro calcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP) index before and 1, 3, 7 days after treatment, and liver and kidney function, chest X-rays, and sputum cultures of drug sensitive test were conducted. And the effectiveness and safety were determined according to the standards. After treatment indexes of the two groups were obviously improved, i. e. T, HR, RR, Paw, MV, the WBC, PCT, CRP were gradually declined, PaO(2)/FiO(2) was gradually raised. There were statistical significance before and 3 days after treatment in the trial and the control group [T: 37.35±0.91 centigrade vs. 38.43±1.06 centigrade, 37.28±0.88 centigrade vs. 38.35±1.11 centigrade; HR: 90.25±10.60 bpm vs. 118.94±15.46 bpm, 89.31±11.17 bpm vs. 124.34±17.87 bpm; RR: 25.14±3.17 bpm vs. 32.28±4.49 bpm, 24.81±2.43 bpm vs. 33.13±4.17 bpm; Paw: 23.03±3.04 cm H(2)O vs. 33.22±4.59 cm H(2)O, 22.75±3.22 cm H(2)O vs. 33.63±4.79 cm H(2)O; MV: 8.67±1.26 L/min vs. 11.80±2.01 L/min, 8.88±1.45 L/min vs. 13.21±2.90 L/min; WBC: 11.26±1.96 ×10(9)/L vs. 14.57±3.10 ×10(9)/L, 12.28±3.38 ×10(9)/L vs. 15.25±4.93 ×10(9)/L; PCT: 6.90±5.46 μg/L vs. 16.97±7.93 μg/L, 6.17±6.13 μg/L vs. 21.26±11.54 μg/L; CRP: 85.50±37.91 mg/L vs. 120.17±45.47 mg/L, 94.31±38.51 mg/L vs. 142.34±53.57 mg/L; PaO(2)/ FiO(2): 182.06±40.88 mm Hg vs. 98.67±20.62 mm Hg, 184.09±43.78 mm Hg vs. 96.22±22.59 mm Hg, all P<0.05]. There was no significant change in SpO(2) before and after treatment in two groups. And the total clinical effective rate in trial and control group were 83.4% and 81.2%, adverse reaction rate were 13.9% and 9.4%, bacterial removal rate were 90.3% and 87.0% respectively, and there was no significant difference between the two groups (all P>0.05). Domestic imipenem cilastatin sodium can effectively control severe aspiration pneumonia, and it is safe and effective antibiotics.

The acute toxicology study of intrathecal injection of Imipenem and Cilastatin Sodium in mice

Objective To study the acute toxicology of intrathecal Imipenem and Cilastatin Sodium injection in mice.Methods Using the ratio method ( n ＝ 24) to determine the minimum toxic and lethal dose,then 2 doses were choosed between them.30 ICR mice were randomly divided into normal control group,low- dose (4 mg/kg) and high dose (6 mg/kg) group (n =10).5 μl drugs were intrathecally injected in the mice of low dose group and high dose group respectively.On the 1st,7th and 14th day,using autonomous activity recorder to measure spontaneous motor activity of mice,pain measurement instrument to measure pain threshold,step -through instruments avoid dark instrument to measure learning and memory,non - invasive tail artery analyzer to measure blood pressure,and eight physiological recorder to trace ECG.On the 15th day,picking the eyeballs of the mice of three groups for blood to measure hematological parameters and BUN,GOP and GOT.Using HE staining to observe the morphological changes of major organs and DSI recorder for conscious EEG.Results ( 1 ) Minimum toxicity amount is 3.87 mg/kg,and the minimum lethal dose is 6.25 mg/kg.( 2 ) After intrathecally injecting of drug,the mice weight,blood pressure,electrocardiogram,and spontaneous activity had no significant differences with the normal control group.Intrathecal administration of high doses in mice increased the plasma GOT,and decreased mouse pain threshold.Meanwhile,its impact on learning and memory are reversible.EEG mainly manifested in that α,β and θ waves reduce and δ increases.(3) The intratheeal mice pathological findings displayed that the hepatic vein dilatation,congestion,renal tubular epithelial cells with mild degeneration,and cerebral cortex with mild edema. Heart,lung did not appear obvious abnormality.Conclusins (1) Safety range of intrathecal Imipenem and cilastatin sodium injection is narrow.(2) Intrathecal injection of imipenem and ciLastatin sodium can lead to liver and kidney of nonspecific injury.(3) High dose of imipenem and cilastatin sodium intrathecal injection can reduce the mouse pain threshold.(4) EEG appears that the α,β and θ decreased,the same time δ increased.It shows that intrathecal injection of imipenem cilastatin sodium has Short -term stimulation toxicity on brain. Key words: Imipenem and Cilastatin Sodium; Intrathecal injections; Acute toxicology; Mice

Physical compatibility of telavancin hydrochloride with select i.v. drugs during simulated Y-site administration

The physical compatibility of telavancin with select i.v. drugs during simulated Y-site administration was evaluated. Telavancin for injection was reconstituted according to manufacturer's recommendations and diluted with 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer's injection to a concentration of 7.5 mg/mL. A Y site was simulated in culture tubes by mixing 5 mL of telavancin solution with 5 mL of a tested drug solution and then switching the order of drug mixing. All mixtures were prepared in duplicate and stored at room temperature. Solutions were inspected for visual, turbidity, and pH changes immediately after preparation and 15, 60, and 120 minutes after preparation. Of the 52 drugs tested, telavancin was physically compatible with 39 drugs in all test solutions. Telavancin was incompatible with amphotericin B deoxycholate, liposomal amphotericin B, digoxin, esomeprazole sodium, furosemide, levofloxacin, and micafungin sodium in all diluents. Colistimethate sodium, cyclosporine, heparin sodium, imipenem-cilastatin sodium, methylprednisolone sodium succinate, and propofol were incompatible with telavancin in specific diluents. Incompatibilities included precipitation, positive Tyndall beam test, and increases in turbidity. There were no substantial changes in pH over the 120-minute study period. Telavancin 7.5 mg/mL in 0.9% sodium chloride injection, 5% dextrose injection, and lactated Ringer's injection was found to be physically compatible for 120 minutes at room temperature with 39 of the 52 drugs tested during simulated Y-site administration. Seven drugs were incompatible in all diluents, and 6 were incompatible in at least one diluent.

53-Year-Old Man With a Swollen Finger

53-Year-Old Man With a Swollen Finger

Clinical study of the effectiveness of imipenem/cilastatin sodium as the antibiotics of first choice in the expectant management of patients with preterm premature rupture of membranes

We carried out a study to evaluate the effectiveness of imipenem/cilastatin sodium (IPM/CS) in the expectant management of patients with preterm premature rupture of membranes (PPROM). The study group (100 women) who presented with PPROM from 24 to 31 weeks of gestation, between 1997 and 1999, were managed expectantly, and received IPM/CS (plus betamethasone) as the antibiotics of first choice. The control group, 40 women, in 1995 and 1996, with PPROM at the same gestational age, were managed expectantly, but received neither these specific antibiotics (IPM/CS) nor betamethasone. The mean time from PPROM to delivery (11 days) in the study group was longer that that (6 days) in the control group. No infant died within 1 year after birth in the study group, and five infants died during this period in the control group. We conclude that IPM/CS, combined with betamethasone, has potential as the antibiotics of first choice when employed for patients with PPROM.