CN102225062A - Pharmaceutical composition for treating infectious diseases caused by Acinetobacter baumannii - Google Patents
Pharmaceutical composition for treating infectious diseases caused by Acinetobacter baumannii Download PDFInfo
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Abstract
The invention relates to a pharmaceutical composition for treating infectious diseases caused by Acinetobacter baumannii, particularly relates to a combined administration medicine of faropenem or pharmaceutical salts thereof and tazobactam or pharmaceutical salts thereof, as well as relates to a medicinal application of the pharmaceutical composition in treating infectious diseases caused by Acinetobacter baumannii. The invention surprisingly finds that faropenem and tazobactam have synergic and accumulative antibacterial actions, and the combination administration of faropenem and tazobactam in a weight ratio of (1:1) to (1-12) has a distinct bactericidal action and is significantly better than single administration of faropenem sodium.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that Acinetobacter bauamnnii causes infectious disease for the treatment of, particularly, relate to faropenem or its pharmaceutical salts and Tazobactam Sodium or its pharmaceutical salts combination medicine, also relate to the medical usage that Acinetobacter bauamnnii causes infectious disease that is used for the treatment of of described pharmaceutical composition.Belong to medical technical field.
Background technology
Acinetobacter bauamnnii (Acinetobacter baumanii) is non-fermentation gram-negative bacteria, is distributed widely in nature and the hospital environment, and be conditioned pathogen.Acinetobacter bauamnnii, Acinetobacter calcoaceticus, unnamed gene kind 3,13TU phenotype are very approaching, so they are referred to as the compound Acinetobacter calcoaceticus of Bao Man.The acinetobacter calcoaceticus that is separated in clinical samples number extremely greatly is Acinetobacter bauamnnii, and the infection that other strain causes is more rare.Identify Acinetobacter bauamnnii: 16sRNA, 23sRNA, 51-like-OXA.
In recent years, the increasing sharply of the multiple antibiotic resistant strain of Acinetobacter bauamnnii, the nosocomial infection of initiation increases year by year, and particularly a plurality of countries have reported a lot of hospital infection outbreak of epidemic by its initiation in succession, cause global extensive concern.Acinetobacter bauamnnii can cause serious even infection lethal such as breathing dependency pneumonia, septicemia, urinary system infection, meningitis, ratio in the nosocomial infection pathogenic bacterium increases very fast, clinically drug-fast Acinetobacter bauamnnii is not had the specific treatment medicine.Once caused infectious disease with cefoperazone/Tazobactam Sodium treatment by Acinetobacter bauamnnii clinically.But, discovered in recent years that cefoperazone/Tazobactam Sodium was more and more to the drug resistance of Acinetobacter bauamnnii, produce cefoperazone/Tazobactam Sodium drug resistance, multidrug resistant mechanism is complicated, has caused multiple antibacterials drug resistance.
In to the monitoring of the bacterial resistance in 3 years of the whole America 2005-2007, find, gram-negative bacteria sensitivity to each antibacterials in these 3 years is comparatively stable, the sensitivity that has only Acinetobacter bauamnnii has downward trend year by year, and drug resistance, general resistant rate be constantly to rise, and it accounts for all that clinical isolating Acinetobacter bauamnnii ratios rise to 30.8% by 6.3%.The carbapenems medicine is the choice drug of treatment Acinetobacter bauamnnii severe infection, but the general Resistant strain of carbapenem is occurring all over the world successively in recent years, from Spain to Norway, alarming multidrug resistant Acinetobacter bauamnnii " invasion " phenomenon has appearred, popular in the wound soldier who stays Afghanistan and the Iraq U.S. army and the British army, cause serious public health problem, the Acinetobacter bauamnnii that Iraq U.S. army takes back is popular in the U.S..
Faropenem sodium, English name: Faropenem sodium, chemical name: (5R, 6S)-6-[(1R)-the 1-ethoxy]-the 7-oxidation-3-[(2R)-the 2-tetrahydrofuran base]-4-thia-1-azabicyclo [3.2.0] hept-2-ene"-2-carboxylic acid list sodium salt.Faropenem is clinical carbapenem antibiotic medicine commonly used.
Sodium-tazobactam, English name Tazobactam Sodium, chemical name: (2S, 3S, 5R)-and 3-methyl-7-oxo-3-(1H-1,2,3-triazole-1-ylmethyl)-4-sulfo--1-azabicyclo [3.2.0] heptane-2-carboxylic acid 4, the 4-dioxide.Sodium-tazobactam is a kind of beta-lactamase inhibitor, and it is low to have toxicity, and good stability presses down advantages such as enzymatic activity is strong.Various types of beta-lactamases (particularly ultraphotic spectrum beta-lactamase) all there is irreversible inhibitory action.
Summary of the invention
Be the infectious disease for the treatment of Acinetobacter bauamnnii effectively, particularly causing, the invention provides a kind of combination medicine of faropenem/Tazobactam Sodium at general drug resistance or multidrug resistant Acinetobacter bauamnnii.For achieving the above object, technical solution of the present invention is as follows:
The invention provides a kind of faropenem or its pharmaceutical salts and Tazobactam Sodium or its pharmaceutical salts and be used for the treatment of application in the medicine that Acinetobacter bauamnnii causes infectious disease in preparation.
Preferably, above-mentioned described application is characterized in that Faropenem sodium and sodium-tazobactam are used for the treatment of application in the medicine that Acinetobacter bauamnnii causes infectious disease in preparation.
Above-mentioned described application, wherein said Acinetobacter bauamnnii comprise carbapenem antibiotic and/or the drug-fast Acinetobacter bauamnnii of beta-lactam antibiotic.For example, Faropenem sodium, piperacillin, piperacillin/Tazobactam Sodium (1: 1), cefoperazone, cefoperazone/Tazobactam Sodium (1: 1) had drug resistance or multidrug resistant Acinetobacter bauamnnii strain.
The above-mentioned described application of the present invention, wherein said infectious disease for example can be selected from and breathe dependency pneumonia, septicemia, urinary system infection, meningitis etc., or even infection serious, lethal.
Preferably, the above-mentioned described application of the present invention, wherein the weight ratio of faropenem and Tazobactam Sodium is 1: 1～1: 12, and the weight ratio of optimal seeking method faropenem and sodium-tazobactam is 1: 1～1: 12, more preferably 1: 1,1: 3,1: 5,1: 8 or 1: 12.
The present invention also provides a kind of medicine that Acinetobacter bauamnnii causes infectious disease that is used for the treatment of, and it comprises faropenem or its officinal salt and Tazobactam Sodium or its officinal salt and optional one or more pharmaceutically acceptable carriers that exist.
As the preferred described medicine that Acinetobacter bauamnnii causes infectious disease that is used for the treatment of, it is characterized in that it comprises Faropenem sodium and sodium-tazobactam and optional one or more pharmaceutically acceptable carriers that exist.
Wherein, described pharmaceutically acceptable carrier is not particularly limited, and can be usual pharmaceutical adjuvant or adjuvant in the pharmaceuticals industry, with the preparation proper drug.
The above-mentioned described medicine of the present invention is not particularly limited, and can be the preparation of suitable various route of administration, and for example oral Preparation such as capsule, tablet, granule etc. also can be injecting and administering preparations, as aqueous injection, lyophilized injectable powder, infusion solution etc.
Preferably, the above-mentioned described medicine that Acinetobacter bauamnnii causes infectious disease that is used for the treatment of, wherein the weight ratio of faropenem and Tazobactam Sodium is 1: 1～1: 12, the weight ratio of optimal seeking method faropenem and sodium-tazobactam is 1: 1～1: 12, more preferably 1: 1,1: 3,1: 5,1: 8 or 1: 12.
The present invention also provides Faropenem sodium to be used for causing with the treatment Acinetobacter bauamnnii with the sodium-tazobactam administration purposes of the medicament of infectious disease in preparation.
The present invention also provides sodium-tazobactam to be used for causing with the treatment Acinetobacter bauamnnii with the Faropenem sodium administration purposes of the medicament of infectious disease in preparation.
The present invention is surprisingly found out that Faropenem sodium and sodium-tazobactam drug combination compositions have collaborative and the antibacterial action that adds up to general drug resistance Bao Man bacterial strain, can cure clinically because the clinical infection that general drug resistance Acinetobacter bauamnnii causes.The present invention tests and has used the imipenem-resistant bacterial strain all to carry the natural inherent blaOXA-51 gene of Acinetobacter bauamnnii chromosome, and the imipenem-resistant bacterial strain Acinetobacter bauamnnii that all carries blaOXA-51 shows as the sensitivity to the faropenem sodium/tazobactam sodium as a result.
The Acinetobacter bauamnnii of this experiment is not only to the imipenum drug resistance, also selected simultaneously simultaneously Faropenem sodium, piperacillin, piperacillin/Tazobactam Sodium (1: 1), cefoperazone, cefoperazone/Tazobactam Sodium (1: 1) drug resistance are used faropenem sodium/tazobactam sodium compositions on these Resistant strains.By to 5 kinds of variable concentrations mass ratioes (1: 1,1: 3,1: 5,1: 8,1: 12) vitro antibacterial activity studies show that, faropenem sodium/tazobactam sodium associating can significantly improve the sensitivity of the imipenem-resistant bacterial strain all being carried the Acinetobacter bauamnnii of blaOXA-51 gene, has clear and definite and strong antibacterial activity.
The present invention tests and has used from 74 strain imipenem-resistant bacterial strains of outpatient service isolation identification 53 strains to carry the blaOXA-51 gene, the 23sRNA gene is carried in 21 strains, blaOXA-51,23sRNA group gene is the natural inherent gene of Acinetobacter bauamnnii chromosome, and antibacterial shows as the sensitivity to beta-lactam antibiotic.
Faropenem sodium all has stronger bactericidal action with the different proportionings of sodium-tazobactam, and 1: 1 to 1: 12 proportioning all is better than the independent medication of Faropenem sodium to the bactericidal action of Bao Man bacterium.
The specific embodiment
Further set forth the present invention below by embodiment, but purport of the present invention and protection domain are not construed as limiting.
Embodiment 1: the research of faropenem sodium/tazobactam sodium vitro antibacterial activity
One, materials and methods
1. test drug:
(1) Faropenem sodium (Faropenem): the new Pharmaceutical production in capital, Zhejiang, lot number DK67-1012281, content 91.6%.
(2) sodium-tazobactam (Tazobactam Sodium): lot number 0481-9801, tire: 93.7%., available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute.
Following ratio proportioning is calculated by weight, and wherein Faropenem sodium weight is with the Faropenem sodium pure calculating of giving money as a gift, and Tazobactam Sodium weight is given money as a gift with sodium-tazobactam and purely calculated by Tazobactam Sodium.
2. test proportioning:
(1) Faropenem sodium
(2) sodium-tazobactam
(3) faropenem sodium-tazobactam sodium (1: 1);
(4) Faropenem sodium+sodium-tazobactam (1: 3);
(5) Faropenem sodium+sodium-tazobactam (1: 5);
(6) Faropenem sodium+sodium-tazobactam (1: 8);
(7) Faropenem sodium+sodium-tazobactam (1: 12).
3. test strain:
This experiment has used from 74 strain imipenem-resistant bacterial strains of outpatient service isolation identification 53 strains to carry bla
OXA-51Gene, the 23sRNA gene is carried in 21 strains, and blaOXA-51,23sRNA group gene is the natural inherent gene of Acinetobacter bauamnnii chromosome, and antibacterial shows as the sensitivity to beta-lactam antibiotic.The Bao Man bacillus of this 74 strain is simultaneously to Faropenem sodium, piperacillin, piperacillin/Tazobactam Sodium (1: 1), cefoperazone, cefoperazone/Tazobactam Sodium (1: 1) also drug resistance, belong to the multidrug resistant Acinetobacter bauamnnii, the Quality Control bacterium is escherichia coli ATCC25922 and Pseudomonas aeruginosa ATCC27853.Bacterial strain is available from attached Shengjing city hospital of Chinese Medical Sciences University.
4. reagent and instrument
M-H meat soup and M-H agar (French Biomerieux SA); Taq archaeal dna polymerase, dNTPs, DNA Maker DL2000, ApaI enzyme (TaKaRa company); Calorstat (Chongqing four reaches company), pulsed field gel electrophoresis instrument (Biorad company); Gel imaging system (genome company), than turbid instrument (French Biomerieux SA), PCR instrument (U.S. Eppendorf company).
5. method
The plate doubling dilution 5.1 in-vitro antibacterial medicine drug sensitive detection is adopted international standards.Measure the minimum inhibitory concentration (M IC) of each antibacterials to various pathogenic bacterium.Critical concentration by U.S.'s laboratory and clinical criteria institute (CILS) regulation in 2009, judge the sensitivity of every strain bacterium, obtain antibacterial responsive rate (S%), the intermediary of the various antibacterials measured led (I%) and resistant rate (R%) antibacterials.Wherein antibacterial is judged to be drug resistance to imipenum MIC 〉=16.
5.2 (pulsed-field gel electrophoresis, PFGE) boiling method extracts bacteria total DNA to pulsed field gel electrophoresis.Genomic DNA is inserted in 1% agarose gel in 0.5mol/L tromethane-ethylenediaminetetraacetic acid (Tris-EDTA) after using the ApaI enzyme action, uses 6V/cm pulsed field gel electrophoresis instrument to detect.The burst length scope continues 24h at 5.0-8.0s.The gel ethidium bromide staining is observed under uviol lamp and the film making retention then.
5.3OXA enzyme gene test: detect 4 groups of OXA enzyme genes with the PCR method.PCR reaction system volume 20 μ L, the PCR condition: 94 ℃ of pre-degeneration 5min, 94 ℃ of degeneration 25s, 56 ℃ of annealing 40s, 72 ℃ are extended 50s, and after 30 circulations, 72 ℃ are extended 6min again.The PCR product is made Preliminary Identification with 1.5% agarose gel electrophoresis and bromination second pyridine dyeing.The PCR primer is given birth to worker engineering company by Shanghai and is synthesized.PCR product electrophoresis is cut glue and is carried out checking order behind the purification.Sequence among sequencing result and the GenBank is compared, determine the product type.
6. to the influence factor of vitro antibacterial activity
(1) bacterial load influence
Measure the different bacterium amounts (10 of 5 kinds of matching method faropenem/sodium-tazobactams with the plate doubling dilution to the test bacterium
4, 10
5, 10
6, 10
7CFU/ml) to the influence of MIC value.
(2) influence of culture medium pH value
Measure 5 kinds of matching method faropenem/sodium-tazobactams to the influence to the MIC value under different pH condition of test bacterium with the plate doubling dilution.
(3) influence of serum albumin content
Measure 5 kinds of matching method faropenem/sodium-tazobactams with the plate doubling dilution test bacterium is observed the influence of serum albumin content to the MIC value in different serum-concentration (25%, 50%, 75%) and the culture medium that does not contain serum.
Two, result
1. the faropenem sodium/tazobactam sodium is to the antibacterial activity in vitro of 53 strain Acinetobacter bauamnniis (blaOXA-51)
The results are shown in Table 1.
Table 1. medicine is to Acinetobacter bauamnnii (blaOXA-51) antibacterial activity in vitro
*More than the Acinetobacter bauamnnii of 53 strains simultaneously to Faropenem sodium, piperacillin, piperacillin/Tazobactam Sodium (1: 1), cefoperazone, cefoperazone/Tazobactam Sodium (1: 1) also drug resistance, belong to the multidrug resistant Acinetobacter bauamnnii.
2. the faropenem sodium/tazobactam sodium is to the antibacterial activity in vitro of Acinetobacter bauamnnii (23sRNA)
The results are shown in Table 2.
Table 2. medicine is to 21 strain Acinetobacter bauamnnii (23sRNA) antibacterial activity in vitro
*More than the Acinetobacter bauamnnii of 21 strains simultaneously to Faropenem sodium, piperacillin, piperacillin/Tazobactam Sodium (1: 1), cefoperazone, cefoperazone/Tazobactam Sodium (1: 1) drug resistance, belong to the multidrug resistant Acinetobacter bauamnnii.
3. to the influence factor of vitro antibacterial activity:
(1) as shown in table 3, the faropenem sodium/tazobactam sodium of different proportionings is respectively 10 at bacterial load
4, 10
5, 10
6With 10
7During CFU/ml, to Acinetobacter bauamnnii MIC value.Illustrate that bacterial load is 10
4-10
7CFU/ml does not have obviously influence to the MIC value of the anti-Acinetobacter bauamnnii of faropenem sodium/tazobactam sodium of different proportionings.
Table 3. Faropenem sodium+sodium-tazobactam is to the influence of Acinetobacter bauamnnii (blaOXA-51) inoculum concentration
(2) as seen from Table 4, the MIC value to Acinetobacter bauamnnii of 5 kinds of matching method faropenem+Tazobactam Sodiums does not have obviously influence in pH 5.0～pH 8.0 scopes.
Table 4 Faropenem sodium+sodium-tazobactam under different pH MIC to the influence of Acinetobacter bauamnnii (blaOXA-51)
(3) as seen from Table 5, human albumin's content in the culture medium, anti-Acinetobacter bauamnnii effect has no significant effect to the Faropenem sodium+sodium-tazobactam of 5 kinds of proportionings.
Table 5. Faropenem sodium+sodium-tazobactam human albumin content is to the influence of Acinetobacter bauamnnii (blaOXA-51) MIC
Embodiment 2: the vivo bacteria corrosion action of injection faropenem sodium/tazobactam sodium
Faropenem sodium and sodium-tazobactam be (1: 1) by weight, and (1: 2), (1: 4), (1: 8), the compositions of (1: 12) has significant antibiotic pool treatment effect to mice infected.
1. be subjected to the reagent thing
Faropenem sodium content 90.6%, lot number: 081212; Xintai City, Shenzhen medicine company limited provides the new Pharmaceutical production in capital, Zhejiang, lot number DK67-1012281, content 91.6%.
Sodium-tazobactam: lot number 0481-9801, tire: 93.7%.Available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute.
The preparation of 2 medicines
Be mixed with desired concn with 0.9% sodium chloride fluid injection.
(1), Faropenem sodium (single dose)
(2), sodium-tazobactam (single dose)
(3), Faropenem sodium+sodium-tazobactam (1: 1)
(4), Faropenem sodium+sodium-tazobactam (1: 3)
(5), Faropenem sodium+sodium-tazobactam (1: 5)
(6), Faropenem sodium+sodium-tazobactam (1: 8)
(7), Faropenem sodium+sodium-tazobactam (1: 12)
3 infectious bacterias and bacterium amount
Be Acinetobacter bauamnnii: establish 7 dosage groups, the equal abdominal cavity of each Mus injects 1 * 10
-5MLD bacterium liquid 0.5ml.Calculate ED with bacteriumization probit
50(each medicine) in M-H meat soup, cultivates 18h with incubated overnight bacterium liquid transferred species for 35 ℃, is experiment bacterium stock solution.Bacterium stock solution is suitably diluted, be diluted to the required final concentration of infection animal with 5% high activity dried yeast liquid.This concentration is different according to different strains, but is the minimum lethal dose (MLD) that causes mice 100% death.
System MLD bacterium liquid: total amount=0.5ml * test Mus number; 10 Mus of each dosage group awarded medicinal liquid (0.5ml/ only irritates stomach) in 1 hour behind every mouse infection 0.5ml MLD bacterium liquid.
4. experimental technique
White mice, Kunming kind, body weight 18～22g, male and female half and half.Chinese Medical Sciences University belongs to second laboratory animal room of hospital to be provided.The quality certification number, the Liao Dynasty is real moving for word 031.Random packet, 10 every group, male and female half and half.
Observe dead mouse number after 7 days, draw the upper limit and the lower limit of trial drug dosage, different with bacterial strain, but be the minimum lethal dose (MLD) that causes mice 100% death.Adopt the low ratio serial dilution, two are faced dosage group dose-difference i value mutually and are 0.1-0.15.Claim the maximum dose level * mice average weight ÷ administration volume * volumetric flask volume ÷ of the dose=medicinal liquid of giving to tire. observe dead mouse number after 7 days, draw the upper limit and the lower limit of trial drug dosage.
5. experimental result
The results are shown in Table 6.
The different matching method faropenem/sodium-tazobactams of table 6. are to the protective effect of Acinetobacter bauamnnii infecting mouse
Compare with the agent of Faropenem sodium list ※ ※ P＜0.001
As shown in table 6, faropenem sodium/tazobactam sodium (1: 2,1: 3,1: 5,1: 8 and 1: 12) obviously is better than the Faropenem sodium single dose to the protective effect of klebsiella pneumoniae abdominal cavity infection mice.
Embodiment 3: the comparative study to the Acinetobacter bauamnnii antibacterial action of faropenem/Tazobactam Sodium and cefoperazone/Tazobactam Sodium
Faropenem sodium and sodium-tazobactam be (1: 1) by weight, and (1: 2), (1: 4), the combination medicine of (1: 8) or (1: 12) has significant antibacterial therapy effect to mice infected.
1. be subjected to the reagent thing
Faropenem sodium (Faropenem): the new Pharmaceutical production in capital, Zhejiang, lot number DK67-1012281, content 91.6%.Cefoperazone+sulbactam sodium (1: 1), Xintai City, Shenzhen medicine company limited provides.
Sodium-tazobactam: lot number 0481-9801, tire: 93.7%.Available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute.
White mice, Kunming kind, body weight 18～22g, male and female half and half.Chinese Medical Sciences University belongs to second laboratory animal room of hospital to be provided.The quality certification number, the Liao Dynasty is real moving for word 031.Random packet, 10 every group, male and female half and half.If 2 dosage groups, the equal abdominal cavity of each Mus injects 1 * 10
-5MLD bacterium liquid 0.5ml.Calculate ED with bacteriumization probit
50(each medicine)
2. medicine preparation
Faropenem sodium+sodium-tazobactam (1: 1); Cefoperazone+sulbactam sodium (1: 1) is mixed with desired concn with 0.9% sodium chloride fluid injection.
Observe dead mouse number after 7 days, draw the upper limit and the lower limit of trial drug dosage, different with bacterial strain, but be the minimum lethal dose (MLD) that causes mice 100% death.Adopt the low ratio serial dilution, two are faced dosage group dose-difference i value mutually and are 0.1-0.15.Claim the maximum dose level * mice average weight ÷ administration volume * volumetric flask volume ÷ of the dose=medicinal liquid of giving to tire. observe dead mouse number after 7 days, draw the upper limit and the lower limit of trial drug dosage.
3. infectious bacteria and bacterium are measured
Incubated overnight bacterium liquid transferred species in M-H meat soup, is cultivated 18h for 35 ℃, be experiment bacterium stock solution.Bacterium stock solution is suitably diluted, be diluted to the required final concentration of infection animal with 5% high activity dried yeast liquid.This concentration is different according to different strains, but is the minimum lethal dose (MLD) that causes mice 100% death.
System MLD bacterium liquid: total amount=0.5ml * test Mus number; 10 Mus of each dosage group awarded medicinal liquid (0.5ml/ only irritates stomach) in 1 hour behind every mouse infection 0.5ml MLD bacterium liquid.
4 experimental results
See Table 7.
The different matching method faropenem/sodium-tazobactams of table 7. are to the protective effect of Bao acinetobacter calcoaceticus infecting mouse
※P＜0.001
As shown in table 7, faropenem sodium/tazobactam sodium (1: 1) obviously is better than cefoperazone/sulbactam sodium (1: 1) dosage to the protective effect of Acinetobacter bauamnnii abdominal cavity infection mice.
Claims (10)
1. faropenem or its pharmaceutical salts and Tazobactam Sodium or its pharmaceutical salts are used for the treatment of application in the medicine that Acinetobacter bauamnnii causes infectious disease in preparation.
2. application according to claim 1 is characterized in that Faropenem sodium and sodium-tazobactam are used for the treatment of application in the medicine that Acinetobacter bauamnnii causes infectious disease in preparation.
3. according to the described application of claim 1-2, wherein said Acinetobacter bauamnnii comprises carbapenem antibiotic and/or the drug-fast Acinetobacter bauamnnii of beta-lactam antibiotic.
4. according to the described application of claim 1-3, wherein said infectious disease can be selected from breathes dependency pneumonia, septicemia, urinary system infection, meningitis etc.
5. according to the described application of claim 1-4, wherein the weight ratio of Faropenem sodium and sodium-tazobactam is 1: 1～1: 12, is preferably 1: 1,1: 3,1: 5,1: 8 or 1: 12.
6. one kind is used for the treatment of the medicine that Acinetobacter bauamnnii causes infectious disease, and it comprises faropenem or its officinal salt and Tazobactam Sodium or its officinal salt and optional one or more pharmaceutically acceptable carriers that exist.
7. according to claim 6ly be used for the treatment of the medicine that Acinetobacter bauamnnii causes infectious disease, it is characterized in that it comprises Faropenem sodium and sodium-tazobactam and optional one or more pharmaceutically acceptable carriers that exist.
8. be used for the treatment of the medicine that Acinetobacter bauamnnii causes infectious disease according to claim 6-7 is described, wherein the weight ratio of Faropenem sodium and sodium-tazobactam is 1: 1～1: 12, is preferably 1: 1,1: 3,1: 5,1: 8 or 1: 12.
9. Faropenem sodium is used for causing with the treatment Acinetobacter bauamnnii with the sodium-tazobactam administration purposes of the medicament of infectious disease in preparation.
10. sodium-tazobactam is used for causing with the treatment Acinetobacter bauamnnii with the Faropenem sodium administration purposes of the medicament of infectious disease in preparation.
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| CN116478966B (en) * | 2022-08-01 | 2023-11-21 | 中南大学湘雅三医院 | Novel acinetobacter baumannii phage endolysin protein, preparation and application thereof |
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| CN101612155A (en) * | 2009-07-23 | 2009-12-30 | 蔡挺 | Remove the method for gram negative bacilli with the piperacillin tazobactam compound preparation |
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| Title |
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| 《中华医院感染学杂志》 20101231 果茵茵等 鲍氏不动杆菌的药物治疗进展 p.2717左栏第4段 1-8 第20 卷, 第17期 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN116478966B (en) * | 2022-08-01 | 2023-11-21 | 中南大学湘雅三医院 | Novel acinetobacter baumannii phage endolysin protein, preparation and application thereof |
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