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Biapenem is a carbapenem antibiotic， and can be used for the treatment of sepsis， pneumonia， lung abscess， chronic respiratory lesions secondary infection， complex urinary tract infection and pyelonephritis， etc. This article reviewed the studies on the pharmacokinetics， pharmacodynamics and therapeutic drug monitoring （TDM） of biapenem. The pharmacokinetic parameters of biapenem are not significantly different in healthy subjects， and there is no accumulation after multiple doses of biapenem. However， there are large differences in pharmacokinetic parameters in patients with severe disease and patients with abnormal renal function compared with healthy subjects， which leads to conventional treatment regimens not achieving the desired outcome. In terms of pharmacodynamics， biapenem can improve the rate of reaching the target value by increasing the frequency of administration and prolonging the infusion time. For patients with anuria in end-stage renal disease， dosing intervals can be extended to avoid drug accumulation. However, for patients with severe infection, a daily dose of 1.2 g still can not control infections caused by Acinetobacter baumannii or Pseudomonas aeruginosa, which limits its use in patients with severe disease. It is recommended to implement TDM in severe patients and patients with abnormal renal function， and explore the best dosing regimen for biapenem in combination with pharmacokinetic models to ensure that the time that the free blood concentration of biapenem remains above minimum inhibitory concentration as a percentage of the time between doses （%fT＞MIC） is within the effective range，so that biapenem can exert a greater efficacy in severe patients and patients with abnormal renal function. For medical institutions that cannot carry out TDM， the efficacy of biapenem can be maximized by increasing the frequency of administration and prolonging the infusion time. For infections caused by P. aeruginosa， A. baumannii and Serratia marcescens with high drug resistance rates， it is recommended to combine or replace other antibiotics.
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Objective:To investigate the clinical effects of moxifloxacin combined with biapenem on controlling inflammatory responses and improving immune function in older adult patients with severe pneumonia.Methods:120 older adult patients with severe pneumonia, who received treatment in the Second People's Hospital of Lishui from February 2017 to March 2020, were included in this study. They were randomly assigned to receive either biapenem (control group, n = 55) or moxifloxacin combined with biapenem (observation group, n = 65) for 7 days. Inflammatory response control, immune function improvement, and adverse reactions were assessed in each group after treatment. Results:After treatment, levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and procalcitonin (PCT) in the observation group were (24.51 ± 4.24) ng/L, (12.51 ± 3.15) mg/L and (4.62 ± 1.05) μg/L, respectively, which were significantly lower than those in the control group [(48.74 ± 4.67) ng/L, (26.80 ± 4.24) mg/L, (8.92 ± 1.10) μg/L, t = 29.77, 21.14, 21.87, all P < 0.001). The proportion of CD 3+ and CD 4+ cells and CD 4+ / CD 8+ ratio in the observation group were (63.27 ± 3.72)%, (39.97 ± 2.18)%, 1.79 ± 0.16, respectively, which were significantly higher than those in the control group [(55.58 ± 2.28)%, (35.18 ± 2.62)%, 1.41 ± 0.15, t = 17.08, 10.93, 13.34, all P < 0.001). Total effective rate was significantly higher in the observation group than in the control group [96.92% (63/65) vs. 83.64% (46/55), χ2 = 6.32, P < 0.05]. There was no significant difference in the incidence of adverse reactions between observation and control groups [10.77% (7/65) vs. 9.09% (5/55), χ2 = 0.09, P > 0.05]. Conclusion:Moxifloxacin combined with biapenem based on routine treatment for severe pneumonia in older adult patients can greatly strengthen anti-inflammatory effects, improve immune function, and enhance clinical efficacy without increasing adverse drug reactions.
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OBJECTIVE: To establish a method for analysis of related substances in biapenem with micellar electrokinetic capillary chromatography(MEKC). METHODS: In order to improve the separation selectivity, a zwitterionic surfactant, 3-(N, N-dimethylhexadecylammonium)-propanesulfonate(PAPS) was used. The optimal separation conditions were as follows: the total length of the capillary was 48.5 cm (the effective length was 48 cm), the buffer was 90 mmol•L-1 tris(hydroxymethyl)aminomethane (tris)-phosphate buffer containing 17 mmol•L-1 PAPS and 3 mg•mL-1 polyoxyethylene 23 lauryl ether (Brij 35), the applied voltage was 22 kV, and the capillary temperature was controlled at 30℃. Further more, the specificity, linearity, precision, repeatability, stability and durability were studied. The contents of related substances in biapenem commercial samples were analyzed. RESULTS: The MEKC method, which was a comparable analysis method to HPLC, successfully separated the adjacent impurities of biapenem by using the zwitterionic surfactant PAPS. The specific test showed that this method was especially suitable for the detection of biapenem dimers A, B and open-ring compound. CONCLUSION: In this method, MEKC with zwitterionic surfactant is for the first time applied to the analysis of related substances in biapenem (amphoteric drugs). It provides a feasible analysis method with high sensitivity, good specificity and reproducibility for the quality control of biapenem.
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OBJECTIVE@#To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis.@*METHODS@#Biapenem/clavulanate (BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis (Mtb) multidrug-resistant (MDR) isolates, extensively drug-resistant (XDR) isolates, and the H37RV strain. BP/CL activity against the H37Rv strain was assessed in liquid cultures, in macrophages, and in mice..@*RESULTS@#BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units (CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment (isoniazid + rifampin + pyrazinamide) after 2 months of treatment.@*CONCLUSION@#BP/CL may provide a new option to clinically treat MDR tuberculosis.
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Animals , Mice , Anti-Infective Agents , Pharmacology , Therapeutic Uses , Cell Line , Drug Evaluation, Preclinical , Macrophages , Mycobacterium tuberculosis , Thienamycins , Pharmacology , Therapeutic Uses , Tuberculosis, Multidrug-Resistant , Drug TherapyABSTRACT
Objective To observe the clinical efficacy of combination of biapenem and levofloxacin in the treatment of severe pneumonia caused by multi -drug resistant Pseudomonas albuginea .In order to provide effective treatment for the patients with severe pneumonia resulted from resistant Pseudomonas albuginea .Methods Sixty patients with severe pneumonia were enrolled in this study .All patients had multiple drug resistant Pseudomonas aeruginosa infection.They were randomly divided into two groups according to the digital table method ,30cases in each group.All patients were treated with mechanical ventilation ,anti-infection,phlegm,asthma and hemodynamic stability.The control group was treated with cefperazone -sulbactam and levofloxacin .The treatment group was treated with biapenem and levofloxacin.The body temperature,white blood cell count(WBC) and procalcitonin(PCT) level, oxygenation index ( PaO2/FiO2 ) , the total clinical effective rate , pulmonary rales disappeared time and the time of chest radiograph showing the pulmonary exudate absorption significantly were compared before treatment and 7 days after treatment.Results After treatment,the WBC,body temperature,PCT,PaO2/FiO2 of the control group were (13.16 ±2.89)109/L,(37.58 ±0.92)℃,(195.36 ±10.63),(9.36 ±1.56)μg/L,respectively,which of the treatment group were (5.36 ±2.65) ×109/L,(36.41 ±0.52)℃,(235.14 ±8.65),(5.63 ±1.69)μg/L, respectively,and the differences between the two groups were statistically significant (t=2.72,2.93,2.82,3.25,all P<0.05).The total effective rate was 40.0％in the control group and 56.7％in the treatment group.The difference was statistically significant(χ2 =12.64,P<0.01).The time of reduction of lung rales in the lungs and the obvious absorption time of chest radiographs in the control group were (9.35 ±3.25)d,(10.63 ±1.57)d,respectively,which in the treatment group were (5.87 ±1.46)d,(7.65 ±1.87)d,respectively,the differences between the two groups were statistically significant (t=2.31,2.45,all P<0.05).Conclusion The clinical effect of biapenem and levofloxacin is better than cefoperazone sulbactam combined with levofloxacin in the treatment of patients with severe pneumonia result from multidrug-resistant Pseudomonas aeruginosa .
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Objective:To provide ideas for the participation of clinical pharmacists in clinical individualized medication.Methods:Clinical pharmacists participated in the clinical consultation for one senior patient with acute cholangitis treated with biapenem.Results:The consultation comments and suggestions proposed by clinical pharmacists were accepted by clinics,which played an important role in assisting doctors in the rational drug use and significantly improved the medical treatment.Conclusion:Clinical pharmacists should participate in individualized medication and help clinicians optimize drug therapy,which can improve the safety and efficacy of medication.
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OBJECTIVE: To provide the basis for biapenem against Acinetobacter baumannii infection in ICU patients in our hospital. METHODS: One hundred-five strains of ABA were collected. The MICs of biapenem against bacteria were measured by double broth dilution method. Four therapeutics regimens (0.3 g, q12 h; 0.3 g, q8 h; 0.3 g, q6 h; 0.6 g, q12 h) in traditional short-time infusion, extended infusion(3, 4h) and two-step infusion(1.5-5.5 h) were simulated by using the Monte Carlo simulation, then the PTAs and CRFs were calculated. RESULTS: CFRs of all treatments of biapenem against ABA infection in ICU subjects were 90% except biapenem 0.3g, q12 h(0.5 h) and 0.3 g, q12 h (two-step infusion for 1.5h). PTAs of the whole regimens were >90% when MIC≥2 mg·L-1. Extended infusion and two-step infusion got the similar PTAs and CFRs with a similar time when the regimens obtained target, more than short infusion obviously. CONCLUSION: Biapenem alone should avoid for ABA infection as expiry therapy in ICU population in our hospital. Extended infusion and two-step infusion should be priority selection as target therapy according to sensitivity test.
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OBJECTIVE:To investigate the clinical efficacy and bacteriological efficacy of biapenem in the treatment of acute bacterial infection,and its effects on serum IL-6 and hs-CRP levels. METHODS:A total of 241 patients with acute bacterial infec-tion of respiratory system and urinary tract system selected from our hospital during Apr. 2015-Apr. 2016 were divided into control group(119 cases)and observation group(122 cases)according to random number table. Control group was given Meropenem for injection 0.5 g added into 100 mL 0.9% NaCl injection intravenously,tid. Observation group was given Biapenem for injection 0.3 g added into 100 mL 0.9% NaCl injection intravenously,bid. Treatment course of 2 groups lasted for 7-14 d. Clinical effica-cies,bacteriological efficacies,serum interleukin-6(IL-6)and hypersensitive C-reactive protein(hs-CRP)levels,the occurrence of ADR were compared between 2 groups. RESULTS:The total response rate,bacterial culture positive rate,bacterial clearance rate and the incidence of ADR were 88.24%,56.30%,87.14%,13.45% in control group and 93.44%,55.74%,93.06%,10.66% in observation group,without statistical significance(P>0.05). Before treatment,there was no statistical significance in serum IL-6 or hs-CRP levels between 2 groups(P>0.05). Compared with before treatment,serum IL-6 and hs-CRP levels of 2 groups were decreased significantly after treatment,with statistical significance(P<0.05);there was no statistical significance between 2 groups(P>0.05). CONCLUSIONS:Biapenem in the treatment of acute bacterial infection of respiratory system and urinary tract system has excellent efficacy,and can significantly reduce inflammatory factor level with good safety. Response rate and safety of biapenem are similar to those of meropenem,so drugs should be selected according to specific condition of patients.
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OBJECTIVE:To investigate the clinical efficacy and bacteriological efficacy of biapenem in the treatment of acute bacterial infection,and its effects on serum IL-6 and hs-CRP levels. METHODS:A total of 241 patients with acute bacterial infec-tion of respiratory system and urinary tract system selected from our hospital during Apr. 2015-Apr. 2016 were divided into control group(119 cases)and observation group(122 cases)according to random number table. Control group was given Meropenem for injection 0.5 g added into 100 mL 0.9% NaCl injection intravenously,tid. Observation group was given Biapenem for injection 0.3 g added into 100 mL 0.9% NaCl injection intravenously,bid. Treatment course of 2 groups lasted for 7-14 d. Clinical effica-cies,bacteriological efficacies,serum interleukin-6(IL-6)and hypersensitive C-reactive protein(hs-CRP)levels,the occurrence of ADR were compared between 2 groups. RESULTS:The total response rate,bacterial culture positive rate,bacterial clearance rate and the incidence of ADR were 88.24%,56.30%,87.14%,13.45% in control group and 93.44%,55.74%,93.06%,10.66% in observation group,without statistical significance(P>0.05). Before treatment,there was no statistical significance in serum IL-6 or hs-CRP levels between 2 groups(P>0.05). Compared with before treatment,serum IL-6 and hs-CRP levels of 2 groups were decreased significantly after treatment,with statistical significance(P<0.05);there was no statistical significance between 2 groups(P>0.05). CONCLUSIONS:Biapenem in the treatment of acute bacterial infection of respiratory system and urinary tract system has excellent efficacy,and can significantly reduce inflammatory factor level with good safety. Response rate and safety of biapenem are similar to those of meropenem,so drugs should be selected according to specific condition of patients.
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OBJECTIVE: To research population pharmacokinetics of biapenem in critical patients after repeated dosing. METHODS: Blood samples were collected according to the different time points after intravenous administration of 300 mg for many times in the group of critical patients. High-performance liquid chromatography (HPLC) was used to determine the drug concentration in plasma.And pharmacokinetic parameters was caculated. RESULTS: The main pharmacokinetic parameters for critical patients were as follows: ρmax was (6.66±2.93)mg·L-1, Tmax was (0.51±0.04) h, AUC0-∞ was (18.98±16.95) mg·h·L-1, T1/2 was (2.06±1.93) h, Cl was (20.9±17.4) L·h-1, Vd was (46.43±3.5) L. CONCLUSION: The pharmacokinetic parameters of biapenem in critical patients with a significant difference was found in healthy people. So need according to pharmacokinetic characteristics of patients to develop personalized anti-infection plan.
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Objective To investigate the clinical effect of biapenem and levofloxacin in the treatment of pulmonary infection caused by extensive drug resistant bacillus.Methods 182 patients with pulmonary infection caused by extensive drug resistant bacillus from the department of respiratory in our hospital were selected and divided into two groups, 91 cases in the control group were given cefoperazone sodium and sulbactam sodium +levofloxacin treatment, 91 cases in the experiment group received biapenem +levofloxacin treatment, serum levels of white blood cell count(WBC), high sensitivity C-reactive protein(hs-CRP),procalcitonin(PCT),serum amyloid A(SAA), recovery time of clinical symptoms, signs and laboratory examination, the clinical effect, bacteriological effect and incidence of adverse reactions were compared after treatment.Results The effective rate in the control group(74.72%)was lower than the experiment group(86.81%), with significant difference (P<0.05); compared with the control group, the bacterial clearance rate was higher, bacterial unclearance rate, partial clearance rate, replacement rate were higher in the experiment group after treatment, serum levels of WBC,hs-CRP,PCT,SAA were lower after treatment, recovery time of body temperature, pulmonary signs, abnormal shadow of chest X-ray, WBC, hs-CRP were shorter, with significant difference ( P<0.05 ); there was no significant difference in the incidence of adverse reactions between the two groups.Conclusion The clinical effect of biapenem and levofloxacin in the treatment of pulmonary infection caused by extensive drug resistant bacillus was exactly, can effectively remove bacteria, control infection, shorten the treatment time, and the safety was high.
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Objective To establish a new method for the rapid and sensitive determination of biapenem. Methods A simple, rapid and sensitive flow injection chemiluminescence(CL) method for the determination of biapenem was developed based on the fact that biapenem could enhance the CL of the luminol (LMN)-potassium ferricyanide reaction system under an alkaline condition. Results Under the optimal experimental conditions, we obtained a linear relationship between the CL intensity and the concentration of biapenem in the range of 0.02%0.6 mg/L with a detection limit of 7.3 x10-3 mg/L. The relative standard deviation was 1.76% for the eleven-time determination of 0.2 mg/L biapenem. Conclusion The method shows high sensitivity, low detection limit and good repeatability. It has been successfully applied to the determination of biapenem for injection and the results are satisfactory.
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Objective To establish a new method for the rapid and sensitive determination of biapenem. Methods A simple, rapid and sensitive flow injection chemiluminescence(CL) method for the determination of biapenem was developed based on the fact that biapenem could enhance the CL of the luminol (LMN)-potassium ferricyanide reaction system under an alkaline condition. Results Under the optimal experimental conditions, we obtained a linear relationship between the CL intensity and the concentration of biapenem in the range of 0.02~0.6 mg/L with a detection limit of 7.3×10-3 mg/L. The relative standard deviation was 1.76% for the eleven-time determination of 0.2 mg/L biapenem. Conclusion The method shows high sensitivity, low detection limit and good repeatability. It has been successfully applied to the determination of biapenem for injection and the results are satisfactory.
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Objective To evaluate the efficacy and safety of biapenem in treatment of bacterial infections of the respiratory and urinary systems. Methods A total of 288 patients with infections of the respiratory and urinary system were included in this multicenter, blinded, randomized, and parallel controlled trial. The patients were randomly assigned to receive biapenem (experimental group, n = 144) ormeropenem (control group, n = 144). Results The clinical curative rates of the experimental group and control group were 95. 10% (136/143) and 92. 25% (131/142), respectively, with those for respiratory system infection being 93. 06%(67/72) and 94. 29% (66/70) and those for urinary infection being 97. 18% (69/71) and 90. 28% (65/ 72), respectively. The bacterial eradication rates in the experimental group and control group were 88. 00% (66/75) and 92.65%(63/68), respectively, with those for the respiratory infectionbeing 83. 33% (30/36) and 90. 62% (29/32) and those for urinary infection being 92. 31% (36/39) and 94. 44% (34/36), respectively. There were no significant differences between the two groups regarding the clinical curative rates or bacterial eradication rates (P>0. 05). The side-effect rate was 2. 08%(3/ 144) in the experimental group and 8. 33% (12/144) in the control group, with significant differences found between the two groups (P = 0. 030 6). Conclusion Compared to meropenem, biapenem has similar efficacy in treatment of respiratory and urinary system infection, but with study.
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Background & objectives: Biapenem is a newly developed carbapenem to treat moderate and severe bacterial infections. This multicenter, randomized, parallel-controlled clinical trial was conducted to compare the clinical efficacy, bacterial eradication rates and safety of biapenem and meropenem in the treatment of bacterial lower respiratory tract infections and urinary tract infections (UTIs) at nine centres in China. Methods: Patients diagnosed with bacterial lower respiratory tract infections or UTIs were randomly assigned to receive either biapenem (300 mg every 12 h) or meropenem (500 mg every 8 h) by intravenous infusion for 7 to 14 days according to their disease severity. The overall clinical efficacy, bacterial eradication rates and drug-related adverse reactions of biapenem and meropenem were analyzed. Results: A total of 272 enrolled cases were included in the intent-to-treat (ITT) analysis and safety analysis. There were no differences in demographics and baseline medical characteristics between biapenem group and meropenem group. The overall clinical efficacies of biapenem and meropenem were not significantly different, 94.70 per cent (125/132) vs. 93.94 per cent (124/132). The overall bacterial eradication rates of biapenem and meropenem showed no significant difference, 96.39 per cent (80/83) vs. 93.75 per cent (75/80). Drug-related adverse reactions were comparable in biapenem and meropenem groups with the incidence of 11.76 per cent (16/136) and 15.44 per cent (21/136), respectively. The most common symptoms of biapenem-related adverse reactions were rash (2.2%) and gastrointestinal distress (1.5%). Interpretation & conclusions: Biapenem was non-inferior to meropenem and was well-tolerated in the treatment of moderate and severe lower respiratory tract infections and UTIs.
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Objective To study mechanisms of lipopolysaccharide (LPS) release from Acinetobacter baumannii (A. baumannii) induced by biapenem (BIPM), meropenem (MEM) and levofloxacin (LVFX). Methods A. baumannii was ex-posed to different concentrations of BIPM, MEM, LVFX, and ceftazidime (CAZ) at different time points. The LPS release was measured by tachypleus amebocyte lysate (TAL) test. Quantities of bacteria exposing to 0.5 MIC antibiotics were measured. The morphology of bacteria treated with different antibiotics for 7-hour was evaluated by light microscope. Results The LPS releases of A. baumannii treated with four kinds of antibiotics were significantly less than those of control group. In the later period, LPS releases of A. baumannii exposed to the high concentration of antibiotics tended to smooth. The cell quanti-ties of bacteria were significantly lower in treatment group than that of control group. The cells of A. baumannii treated with CAZ and LVFX showed long filamentous shape. The bacteria exposed to MEM and BIPM showed obviously globular. At the same time, some bacterial cells were induced to lysis rapidly by BIPM. Conclusion The level of LPS release is influenced by kinds of antibiotics, concentration and incubation period. All kinds of antibiotics could induce morphological changes of A. baumannii, which may be related to the different mechanisms that bacteria induce the different levels of LPS release.
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Objective To evaluate the effect and safety of thymosin combined with biapenem in the treatment of severe lower respiratory tract infection of gram negative bacilli.Methods 54 patients with severe lower respiratory tract infection of gram negative bacilli were randomly divided into study group (group A) and control group (group B),group A was treated with thymosin and biapenem,group B biapenem.All patients were treated for 7 ～ 14 days in a course.The clinical effect,treatment time of biapenem,the bacterial clearance rate and adverse drug reaction betweeen two groups were compared.Results The clinical effective rate of group A and B were 84.6％ and 82.1％,respectively,there was no statistical difference (P ＞ 0.05).Treatment time of biapenem in group A and B was (8.2 ±3.4) days and (13.2 ± 3.6) days,respectively,there was statistical difference (P ＜ 0.05).The bacterial clearance rate of group A and B were 86.7％ and 80.7％,respectively,there was no statistical difference between two groups (P ＞ 0.05).Conclusion The treatment time of thymosin combined with biapenem treatment of gram-negative bacilli severe respiratory tract infection was shorter than that of biapenem alone treatment,and it was safe,effective,and worthy of ciinical application.
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ObjectiveTo evaluate the efficacy of biapenem in percutaneous nephrolithotripsy for the prevention and control infections.MethodsA retrospective study was accomplished.The clinical data of 68 patients with PCNL which used biapenem for prevention and control infection from Aug 2009 to Feb 2011 in the hospital of Hubei Provincial Corps of CAPF were collected,the treatment effect of biapenem in percutaneous nephrolithotripsy was evaluated.Results57 cases use the injection biapenem each 0.3g,2 times a day intravenously 7 to 14 days could effectively prevent postoperative infections in perioperative period;11 cases of urinary infection and systemic inflammatory response syndrome after pereutaneous nephrolithotripsy use injection biapenem each 0.3g,every 8-hour intravenously 7 to 14 days,were effective treatment of postoperative infections.ConclusionBiapenem was effective in the prevention of infection in percutaneous nephrolithotripsy.
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Objective To explore the clinical efficacy of biapenem treatment of in hepatic failure complicated with bacterial infection.Methods 30 patients with hepatic failure complicated with bacterial infection were randomly divided into two groups.Treatment group were administered biapenem(Zhengda Tianqing Pharmaceuticals)0.6g/d,while the control group were administered cefopergone sodium tazobactam sodium for Injection(Qili Haikou Pharmaceuticals)4.0g/d for one week.Results There were significan differences in the curative rate and effective rate of biapenem and cefopergone sodium tazobactam sodium,which were 86.67％ 73.33％ and 53.33％ 、33.33％respeitively(P＜0.05).Conclusion Biapenem in treatment of hepatic failure complicated with bacterial infections was effective against infection with mild adverse reactions.