[go: up one dir, main page]

CA1126138A - Microporous pellets for microorganism testing - Google Patents

Microporous pellets for microorganism testing

Info

Publication number
CA1126138A
CA1126138A CA298,936A CA298936A CA1126138A CA 1126138 A CA1126138 A CA 1126138A CA 298936 A CA298936 A CA 298936A CA 1126138 A CA1126138 A CA 1126138A
Authority
CA
Canada
Prior art keywords
pellet
pellet according
reagent
test reagent
carrier
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA298,936A
Other languages
French (fr)
Inventor
Michael J. Greenway
Charles B. Taskis
Pamela A. Hunter
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beecham Group PLC
Original Assignee
Beecham Group PLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Beecham Group PLC filed Critical Beecham Group PLC
Application granted granted Critical
Publication of CA1126138A publication Critical patent/CA1126138A/en
Expired legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/18—Testing for antimicrobial activity of a material

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Toxicology (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

ABSTRACT OF THE DISCLOSURE

Pellets comprising a non-friable microporous solid solution of a test reagent and an organic carrier provide accurate, easily handled, micro-dosage quantities of the test reagent, which may be used for example in the testing of microorganisms.

Description

~LZ6~3~

This invention relates to test materials. More specifically this invention relates to pellets containing test reagents.
It is well known that the sensitivity of micro-organisms such as bacteria to antibiotics can be determined conveniently on a micro-scale. In one conventional method, a serial dilution of the antibiotic -ls prepared and incorp~rated into suitable media, such as broth clr agar, and each diluti~n strength inoculated in the usual manner with the bacteria. By observing the minimum antibiotic concentration at which bacterial growth is absent, the M.I.C. of the antibiotic can be obtained.
In a secorid conventional method, paper discs impregnated with the antibiotic are placed on agar plates inoculated with the bacteria, and growth observed. A zone around each disc is obtained(provided the antibiotic concentration in the disc is sufficient)in which the difused antibiotic concentration has been high enough to prevent growth.
From the dimensions of the zones and the antibiotic concen-tration in the discs, the M.I.C. of the antibiotic against that bacteria can be calculated.
Also, it is known to test an unknown microorganism Eor its ldentity using materials giving a positive reaction in the presellce o a yiven mLcrooryclnism.
Wehave now discovered that pellets may he prepared containing test reayents. These pellets are convenient easily handled sources o accurate micro-dosage quantities o the test reagents, and may be used, for example, as such L3~

in conventional microorganism testing of the kind hereinbefore de6cribed .
Accordingly, the present invention provides A pellet suitable for use in the testing of microorganism6,which pellek comprises a non-friable microporous so:Lid solution of a test reagent and an organic carrier.
Now thak the pellets of the invention and their desirable properties have been discovered, it is a routine matter for a skilled man to determine suitable organic carriers for use therein. For example, the freeze drying process hereinafter described may simply be repeated with a chosen reagent and carrier and the resultant pellet examined for non-friability and microporosity.
More specifically we have found that any organic carrier is suitable that can be freeze dried to give a non-friable microporous matrix. This matrix is preferably hydrophilic ~nd non-hygroscopic, and is of course bacteriologically inert and compatible with the reagent.
The pellet formed therefrom will suitably be sufficlently rigid to prevent ready deformation thereof by handling.
Conveniently the carrier will be water solublel thereby enabling ready release of reagent from the pellet on contact with aqueous media.
Examples oE suitable organic carriers lnclude certain organic s~nthetic polymers such as polyvinyl pyrrolidorle and polyvinyl pyrrolidone/polyvi.nyl acetate .

L3~3 copolymers; certain organic semi-synthetic polymers such as methyl and hydroxypropylmethylcellulose, and sodium carboxymethylcellulose, and other cellulose polymers; certain saccharides such as sucrose and lactose; and mannitol.
Particularly suitable organic polymers include polyvinyl pyrrolidone (such as the material available from BASF under the trade mark Kollidon (25~ ), and polyvinyl pyrrolidone/polyvinyl acetate copolymers (such as the material available from BASF under the trade mark Kollidon VA64).
The test reagent may be a material capable of giving a positive identification of a particular microorganism, or class of microorganism, such as the cytochrome oxidase reagent.
; The test reagent may also be an anti-bacterial agent.
Examples of suitable anti~bacterial agents include ~-lactam antibiotics such as benzylpenicillin, phenoxy-methylpenicillin, carbenicillin, methicillin, propicillin, ampicillin, amoxycillin, epicillin, ticarcillin, cyclacillin, cephatriazine, ~0 cephaloridine, cephalothin, cefazolin, cephalexin, cefoxitin, cephacetrile, cephamandole, cephapirin, cephradine, cephalo glycine, and other well known penicillins and cephalosporins or pro-drugs therefor such as hetacill.in, me~ampi.cillin, the aaetoxymethyl, pivaloyloxymethyl or phthali.dyl esters o~
ben~ylpenicillin, ampicillin, amoxycillin or cephaloglycine, or the phenyl, tolyl or indanyl ~~esters o carbeniaillin ~? ~

:
" . : . : :

3~

or ticarcillin or the like; and salts thereof when appropriate; aminoglycoside antibiotics such as gentamycih~
macrolide antibiotics such as erthromycin; pseudomonic acid and its salts and esters; the antibiotic known as MM4550 and salts thereof; the antibiotic known as MM13902 and salts thereof; the antibiotic known as MM17880 and salts thereof, thienomycin; and clavulanic acid, its salts, :;~
esters and ethers.
~seudomonic acid has the structure ~I) OH

CHI ~ CZ~CH2~8 COZH ~I) : OH
It is fully described in UK Patent No. 1395907, MM4550 has the structure (II):

¦ O H
H03S~ C ~C (II) O ~ -NH-CO-CH3 MM13~02 has the structure (III):

ll03S-O ~ ~ S -C ~ (III) N ~ C-NH-CO-CH3 ~ ~ , .
: _ 5 _ - : , . :, , ~ .
: .

~, L3~

MM17880 has the structure (IV):

H03S-O ~ S-CH CH -NH-CO-CH (IV) N ~ .

The preparation and properties of MM4550, MM13902 and MM17880 and their salts are fully described in ~K Patent Nos. 1467413, 1489235 and 1483142.

Clavulanic acid has the structure (V):

H~
rr~ CH2H (V~
~ ~ N
~ ~ O ~ C02H
~ The preparation and properties of clavulanic acid, its salts and esters are fully described in Belgian Patent No.
827926 and Offenlegungsschrift No. 2517316. The preparation and properties of the ethers (for exarnple the methyl and ethyl ethers) of clavulanic acid are fully described in 10Offenlegung~schrif~ No. 2646004.

MM4550, MM13902, MM17880 and their salts, and clavu:Lanic acid, its salts, esters and ethers are synergists 15for ~-lactam antibiotics. Thus the test reagen~ in -the pellet will often be a ~-lactam antibiotic and one of the .
- 6 - :

' 6~

aforesaid synergists. Conveniently the weight ratio range of ~-lactam antibiotic to synergist will be about 10:1 to 1:10.
Particularly use~ul synergists for this use are salts of clavulanic acid, such as the lithium, sodium~
potassium and calcium and like salts conventionally ~ormed with penicillins and cephalosporins, particularly the sodium and potassium salts; and ethers of clavulanic acid such as the methyl and ethyl ethers.
Particularly suitable ~-lactam antibiotics for use with clavulanic acid derivatives includ~ a penicillin or a céphalosporin having a side chain (~oined at the 6- or 7-position respectively) o~ formula (VI):

R - CH - C0 - (VI) wherein R is phenyl, p-hydroxyphenyl or cyclohexadienyl or a salt thereof. Suitable penicillins of this type include ampicillin and amoxycillin, and salts thereof such as the sodium and potassium salts. Suitable clavulanic acid derivatives inclùde those clavulanic acid salts listed hereinbefore.
In these formulations the ratio of antibiotic to clavulanlc acid derivative will normally be in the range 10:1 to 1:10 (w/w), for example 5:1 to 1:1.
q'he proportions of the reagent to the carrier in the pellet may be varied a,s desired, provided of course :

- - . , - ~ . . . . .
- , . ~ .

, - ~ .
:
~ : . : . .

31~

there remains sufficient carrier to form the matrix. For example suitable pellets may contain 0.1 -to 25% reagent, more suitably 0.1 to 10~ reagent.
The shape of the pellet is unimportant provided it is destined to be dissolved in a solvent (for example in aqueows media to provide a solution of standard reagent concentration, as in M.I.C. testing by serial dilution).
In such cases the pellets can be spheroid, hemi-spheroid, frustro-conical, discoid, or any other convenient shape.
However when the pellets are to be used in place of paper sensitivity discs in agar plate sensitivity testing, then it is essential that they have at least one flat circular surface for contacting the agar to allow controlled diffusion of reagent therefrom. With this in mind, pellets for this use are suitably of the same general size and shape as the known paper sensitivity discs.
By way of illustration, the pellets will suitably have a largest diameter of about 2 to 10 mm, for example, about 6 mm. Again by way of illustration only, the pellets may suitably weigh 0.001 to 0.1 g, more suitably 0.005 to 0.05 g.
The invention also provides a process Eor the preparation of the pellets as hereinbefore defined, which process comprises freeze drying a solution of the reagent and the carrier.

.. ,. . . -- , ~ ... . : .: -3~

Suitably portions of the solution are filled .into moulds or dropped onto a suitable flat surface, or the like, and the freeze drying step then carried out.
Depending on the solubilities of the reagent and carrier, the necessary solution may be prepared in aqueous, organic or mixed solvents. The reagent and the carrier will be dissolved in the solvent in the relative proportions desired in the pellets to be prepared from that solution.
Examples of suitable solvents include inert volatile solvents such as those solvents suitable for use in freeze drying, for example water, t-butanol, acetonitrile, dimethyl carbonate, :~
dimethyl sulphoxide and the like. Where possible water will be used as the solvent.
Suitably the solution to be f~ee~e dried will contain about 3 to 25% carrier.
It has been found that applying the freeze drying ~.
technique to conventional paper discs wetted with reagent solution has a number of disadvantages, for example poor or incomplete contact with the heat transfer medium and formidable handling problems both beEore and after the drying stage.
These disadvantages are.overcome when the freeze drying -tecllnique is used in the process of this invention.
The pellets o:E this invention should be stored in the presence o.E a desiccant.
The pellets of the invention may be used to provide a known micro-dosage quantity of a rea~ent :Eor use in -the 3~3 testing of micro-organisms. For example (i) When the reagent is an indicator for a particular micro-organism, then the pellets can be used to establish the identity of an unkno~n microorganism~ thereby enabling an effective drug therapy to be designed there against.

(ii) When the reagent is an anti-bacterial agent, the sensitivity of a particular micro~organism to that anti-bacterial agent can be establishèd by conventional M.I.C. or agar plate zone inhibition methods.
The pellets may also be used to provide accurate micro-dosage quantities of the test reagent for purposes other than micro-organism sensitivity testing, for example ~or chemical tests on the reagent itself.
rrhe pellets have the additional advantages that:
(i) They improve the solubility of sparing soluble or insoluble reagents.
(ii) When prepared by freeze drying, they have good stability with reagents unstable in solution or during drying procedures at normal temperatures.
~iii) The use of water soluble carriers therein re~ults in the reagent being completely available to aqueous media.

- - , : . , . .. .. ., . . :~

" , .. .
.
- - .

6~3~3 (iv) They have good reproducibility.
(v) They can be made sterile if so desired.
(vi) They are easily handled, for example with tweezers.
The following Examples illustrate the invention.

~: .

G~38 Example 1 Pellets consisting of sodium amoxycillin and lithium clavulanate in solid solution with Kollidon (25) 110 mg of sodium amoxycillin was dissolved in 25 ml water, 64 mg of lithium clavulanate was dissolved in a separate 20 ml of water. 3 ml of the amoxycillin solution and 2 ml of the clavulanlc acid solution were added to a solution of 2 g of Kollidon (25) in 10 ml water. The solution was then brought to 20 ml with water. 50 mg drops of the solution were placed on a stainless steel tray at room temperature and then frozen at -40C for one hour. A vacuum was then applied and the samples freeze-dried over 24 hours, with a final drying temperature of 40C, to give pellets.
These pellets are hard, non-friable microporous discs.
.

, , ,~. , :, :. . , ~ , ~6~

Example 2 Pellets consisting of disodium ticarcilli_ and lithium clavulanate lO0 mg of disodium ticarcillin was dissolved in 50 ml water. 33 mg of lithium clavulanate was dissolved in a separate lO0 ml of water. 5 ml of the ticarcillin solution and 5 ml of the clavulanic acid solution were added to a solution of 3 g Kollidon VA64 in lO ml o~ water.
75 mg drops of the combined solution were placed on a stainless steel tray at room temperature and then frozen at -40C for 1 hour. A vacuum was then applied and the samples freeze dried over 24 hours, with a final drying temperature of 40C, to give pellets.
~ These pellets were hard, non-friable microporous discs.
The pellets shown in the Table were prepared in similar manner as indicated. They were of a generally discoidal shape, and were all non-friable and microporous.

,. , ,~ , , .. .. . ~
:.- - ~: :

3~3 o _ _ __ _ rd ~ o~ o\ dP
h ~ u~ _ _ _ _ o~ Ln o\: u~
~ UO~
.__ ... __ _ D~ _~ :' = _ = = O = = _ _ :
~.3 ~_ ~1 . _ _ _ ~-~ __~ ___ _ _ .
~ . ~ m ~ ~
o ~ __ __ a) ~ : ~ = = = -~os~ ~ ~
~: ~+ n +
. _ ~ ~_ ~O
~o~ ~
h ~ h ~ O = = _ = \ 0 3 C~ 3 _ 0 3 o ~ ~ ~ o\o :~ o o\ :~: U o~O
n~ U t) O ~ O~)o`~ ~0 C~ o~ ~0 __ ~ Uh 'H0 ~- ~0 I ~0 ~ O
r ~ 1~, h ¦ ~: O O O , t~l , rd ,~
h rv ~ ~ r~ I ~ ~ ~,~ ~,~ O : ~P O O =
rn O ~ oO ~ O o~ O r.~) o Ln O ~D O
r,~l ~rl ~ Ln Ln ~ r,~ n ~ ~ c~ ,~ ~
tDO -- __, . _ , _ -~ rn 3 3 u rv 1 rd U ~ ~ ~ C
r~ rv ~ h ~ O ~S r)~ ~ tn ~ ~ ~ U ,~ ,~
t)7 tJ~ r~ ;~1 S _L ~ . U rd rv ~L ,~ ,~ ~ tn ~ rrJ t:r U ~ r) t:n rd rd ~ O ~ O rV ~1 O .~ .,1 rd O S _L S _l .~) ~r ~ ;~L a ~,, -,.
~; ~ 1 tV ~r~ )-I Ir~ rn U ~n ~ X ~ O ~,l o ~rl O ~rl O O ~~1 0 r~ O ~ O
~ r,~ ~ ¦ ~ P~ r~ ) O p:~ r I I--1 r~l ~1 r,~ ~1 ~I rJ~ r~) Lr~ ~ I ~ I
_ __ I _ ____ _ ____ _ _ _ . _ r,l) r r~ z ~ ~ In u~ r oo a~ o .-1 r~
.~ _ ___ ~ .__.___ ._______ ~, __ , ,, ~ 14 -- :

, 3~3 Notes S.C.M.C. is sodium carboxymethylcellulose.
Kollidon VA64 is a water soluble copolymer of 60%
vinyl pyrrolidone, 40% vinyl acetate.
The pellets of Examples 3 to 12 were a].so made in blister pack tops and in a metal former, yielding pellets of a generally frustro-conical and discoidal shape respecively.
The S.C.PI.C. discs were deformable but not Eriable.

;:

.

Claims (19)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A pellet suitable for use in the testing of micro-organisms, which pellet comprises a non-friable microporous solid solution of a test reagent and an organic bacterio-logically inert carrier which is compatible with the reagent.
2. A pellet according to claim 1, wherein the carrier is a material that can he freeze dried to give a non-friable microporous matrix.
3. A pellet according to claim 1, wherein the carrier is water soluble.
4. A pellet according to claim 3, wherein the carrier is polyvinyl pyrrolidone or a polyvinyl pyrrolidone/polyvinyl acetate copolymer.
5. A pellet according to claim 1, wherein the test reagent is an anti-bacterial agent.
6. A pellet according to claim 5, wherein the test reagent is a .beta.-lactam antibiotic.
7. A pellet according to claim 5, wherein the test reagent is a .beta.-lactam antibiotic and a synergist therefor.
8. A pellet according to claim 7, wherein the test reagent is a penicillin or a cephalosporin having a side chain (join-ed at the 6- or 7- position respectively) of formula (VI):

(VI) wherein R is phenyl, p-hydroxyphenyl or cyclohexadienyl, or a salt thereof; and clavulanic acid, a salt, ester or ether thereof.
9. A pellet according to claim 8, wherein the weight ratio of penicillin or cephalosporin to clavulanic acid derivative is 5:1 to 1:1.
10. A pellet according to claim 1, wherein the reagent re-presents 0.1 to 25% of the pellet.
11. A pellet according to claim 1, wherein the pellet weighs 0.001 to 0.1 g.
12. A pellet according to claim 1, which has a largest diameter of about 2 to 10 mm.
13. A pellet according to claim 1, having a discoidal shape.
14. A pellet according to claim 1, containing a specific micro-dosage of the test reagent.
15. A process for the preparation of the pellet according to claim 1, which process comprises freeze drying a solution of the reagent and the carrier.
16. A process according to claim 15, wherein the solution is filled into moulds, or dropped onto a flat surface, and then freeze dried.
17. A process according to claim 15 or 16, wherein the solvent used to form the solution is water.
18. A process according to claim 15 or 16 wherein the solution freeze dried has a carrier concentration of 3 to 25% (w/v).
19. A method of testing the sensitivity of a microorganism to a test reagent, which method comprises contacting the microorganism with the test reagent when derived from a pel-let according to claim 1.
CA298,936A 1977-03-16 1978-03-15 Microporous pellets for microorganism testing Expired CA1126138A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB11060/77A GB1594001A (en) 1977-03-16 1977-03-16 Pellets suitable for use in the testing of microorganisms
GB11060/77 1977-03-16

Publications (1)

Publication Number Publication Date
CA1126138A true CA1126138A (en) 1982-06-22

Family

ID=9979270

Family Applications (1)

Application Number Title Priority Date Filing Date
CA298,936A Expired CA1126138A (en) 1977-03-16 1978-03-15 Microporous pellets for microorganism testing

Country Status (14)

Country Link
JP (1) JPS5435279A (en)
AU (1) AU523959B2 (en)
BE (1) BE864841A (en)
CA (1) CA1126138A (en)
CH (1) CH636643A5 (en)
DE (1) DE2810056A1 (en)
DK (1) DK152296C (en)
FR (1) FR2384022A1 (en)
GB (1) GB1594001A (en)
IE (1) IE46580B1 (en)
NL (1) NL7802799A (en)
NZ (1) NZ186646A (en)
SE (1) SE7802928L (en)
ZA (1) ZA781368B (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2964817D1 (en) * 1978-09-06 1983-03-24 Beecham Group Plc Pharmaceutical compositions containing two beta-lactam derivatives
EP0012495B1 (en) * 1978-12-08 1983-06-22 Beecham Group Plc Pharmaceutical composition comprising a water soluble salt of amoxycillin and polyvinylpyrrolidone, and a vial containing a unit dose of said composition
AU9098091A (en) * 1990-12-21 1992-07-22 Showa Yakuhin Kako Co., Ltd. Cephalosporinase testing agent
WO1992019763A1 (en) * 1991-05-06 1992-11-12 Baxter Diagnostics Inc. Rapid inducible beta-lactamase screen test
US5350679A (en) * 1993-06-14 1994-09-27 Dow Corning Corporation Repeat insult microbial test method

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3138544A (en) * 1961-05-03 1964-06-23 British Drug Houses Canada Ltd Microbial sensitivity testing device
GB1057000A (en) * 1964-12-10 1967-02-01 Deputy Minister Of The Ministe Method of making tablets for testing the sensitivity of bacteria to an antibiotic
GB1275706A (en) * 1970-07-07 1972-05-24 Inst Pentru Controlul De Stat Microtablets for determining the sensitivity of microorganisms to antibiotics and chemotherapeutics
US3928566A (en) * 1970-08-14 1975-12-23 Du Pont Lyophilized biological products
US3932943A (en) * 1970-08-14 1976-01-20 E. I. Du Pont De Nemours And Company Method of preparation of lyophilized biological products
NZ177159A (en) * 1974-04-20 1978-03-06 Beecham Group Ltd Clavulanic acid, salts, esters and preparation thereof from streptomyces clavuligerus: pharmaceutical compositions
AU1087176A (en) * 1975-03-03 1977-08-11 Miles Lab Water soluble microbial composition
US4153512A (en) * 1976-04-07 1979-05-08 Fisher Scientific Company Storage stable antibiotic susceptibility test kit and method of testing

Also Published As

Publication number Publication date
NL7802799A (en) 1978-09-19
FR2384022A1 (en) 1978-10-13
ZA781368B (en) 1979-02-28
DK152296B (en) 1988-02-15
CH636643A5 (en) 1983-06-15
DE2810056A1 (en) 1978-09-28
GB1594001A (en) 1981-07-30
BE864841A (en) 1978-09-13
FR2384022B1 (en) 1980-08-29
DE2810056C2 (en) 1987-09-03
JPS5435279A (en) 1979-03-15
IE46580B1 (en) 1983-07-27
NZ186646A (en) 1981-03-16
DK152296C (en) 1988-07-11
SE7802928L (en) 1978-09-17
AU3421578A (en) 1979-09-20
DK117678A (en) 1978-09-17
IE780529L (en) 1978-09-16
AU523959B2 (en) 1982-08-26

Similar Documents

Publication Publication Date Title
Greenwood et al. Comparison of the responses of Escherichia coli and Proteus mirabilis to seven β-lactam antibiotics
Kahan et al. Thienamycin, a new β-lactam antibiotic I. Discovery, taxonomy, isolation and physical properties
SE453600B (en) PROCEDURE FOR PREPARING A SALT OF CLAVULANIC ACID
EP0755456B1 (en) A rapid microbiological test for the detection of antibacterial compounds
EP0611001B1 (en) Unit for the detection of residues of antibacterial compounds in liquids
Eliasson et al. Characterization of the plasmid-mediated β-lactamase in Branhamella catarrhalis, with special reference to substrate affinity
CA1126138A (en) Microporous pellets for microorganism testing
US3919415A (en) Substance MM 4550 and process for producing same
Basker et al. Comparative antibacterial activity of azlocillin, mezlocillin, carbenicillin and ticarcillin and relative stability to beta-lactamases of Pseudomonas aeruginosa and Klebsiella aerogenes
GB2128737A (en) Antiobiotic susceptibility test material
Takahashi et al. Cefoxitin resistance by a chromosomal cephalosporinase in Escherichia coli
JPH0813266B2 (en) Selection and differential isolation medium for methicillin-resistant Staphylococcus aureus
Yamaguchi et al. PHOSPHOLIPID BILAYER PERMEABILITY OF beta;-LACTAM ANTIBIOTICS
Greenwood Response profiles: A method of evaluating the activity of β-lactam antibiotics against enterobacteria
US4714675A (en) Stabilized sensitivity test disk
Cornaglia et al. Activities of oral antibiotics on Providencia strains isolated from institutionalized elderly patients with urinary tract infections
JP4438182B2 (en) Drug sensitivity test plate
US5350680A (en) Cephalosporinase testing agent
CA1210308A (en) Test materials
Medeiros et al. Mechanisms of resistance to cephalosporins in ampicillin-resistant Escherichia coli
Noguchi et al. Isolation of two types of Pseudomonas aeruginosa mutants highly sensitive to a specific group of beta-lactam antibiotics and with defect in penicillin-binding proteins
JP2966523B2 (en) Cephalosporinase test agent
Liljequist et al. In vitro activity of amoxicillin plus clavulanic acid against Haemophilus influenzae and Branhamella catarrhalis
GB2026689A (en) Sensitivity discs
SU1400075A1 (en) Strain of vibrio cholerae cholerae ogava bacteria used for producing cheloric toxin

Legal Events

Date Code Title Description
MKEX Expiry