Cephalosporins

3.3 Cephalosporins

Brotzu*, in 1948, was pioneer in isolating a novel microorganism from the sea water meticulously sampled very close to a sewage outpours off the coast of Sardinia. Interestingly, he noticed its marked and pronounced antagonism to both Gram-positive and Gram-negative microorganisms.

Almost after seven years, Abraham** at Oxford first and foremost gave the scientific world the report on the isolation of three ‘antibiotic substances’ from the culture of this specific organism, namely: cephalosporin P, penicillin N, and cephalosporin C. Out of these three isolated antibiotics, the first: cephalosporin P has practically accomplished little therapeutic significance; the second: penicillin N (originally termed as cephalosporin N) obtained as the major component and differs significantly from the common penicillin by its antibacterial activity and hydrophilic character; and the third: cephalosporin C showed low toxicity and in vitro activity against the penicillin-resistant Staphylococci.

In view of the above statement of facts, it is quite evident that there exist an apparent contrast with regard to the typical features of cephalosporin C and the penicillins (viz., benzylpenicillin) besides other possible structural modifications as given below:

Points of Contrast Between Cephalosporin C and Penicillins

In the broader perspective the semi-synthetic cephalosporins may be classified into three different manners, namely: (a) chemical structure; (b) β-lactamase resistance; and (c) antibacterial spectrum.

However, in usual widely accepted prevailing practice the cephalosporins are logically and legitimately classified by a more arbitrary system, dividing them into ‘generations, such as: First generation;

Second generation; and Third generation cephalosporins.

It is pertinent to mention two important points with regard to the ‘cephalosporin antibiotics’, namely:

(a) All cephalosporins commence with the prefix ceph- or cef -; however, the latter spelling now being preferred over the former, though both spellings are usually encountered in certain branded drugs; and

(b) The basis for the classification into the said three generations depends primarily and solely upon the antibacterial spectrum shown by the drugs, besides the year they were first introduced.

Note: 1. There are several instances in which the drugs belonging to the ‘second generation’ may have been introduced after the ‘third generation’ of drugs had been accomplished.

2. Categorically, there is no prevalent practice or demarkation to suggest that the drugs belonging to the ‘third generation’ automatically supercede second and first genera tion ones. In fact, cephalosporins from all the three aforesaid categories are still being used across the globe. Prodrugs (e.g., cefuroxime-axetil; cefpodoxime-proxetil) The prodrugs of some cephalosporin antibiotics, for instance: cefuroxime-axetile and cefpodoxime-proxetil have been duly developed having an additional ester moiety attached to the C-4 carboxyl function. However, these tailor-made ‘prodrugs’ get duly hydrolyzed to their respective active agents by the aid of esterases.

Cephamycins These represent another group of cephalosporin antibiotics that are characterized by a 7α-methoxy function, and are usually produced by two cosecutive reactions, namely: hydroxylation and methylation.

Example

Caphamycin C: In this particular instance, the introduction of a carbamate function derived from carbamoyl phosphate on the hydroxymethyl function.

A few important and typical examples of the ‘Cephalosporin Antibiotics’ belonging to the various recognized groups, such as: first generation, second generation, third generation, prodrugs, and cephamycins have been duly summarized below along with their structural variants, names, synonyms and special remarks:

Cephalosporin Antibiotics: Typical Examples

A good number of cephalosporins belonging to the three categorized generations are available in the therapeutic armamentarium, besides the cephamycins, which are given as under:

(i) First generation Cephalosporins: Cefalotin (Cephalothin); D-Cephalexin (D-Cefalexin); Cephapirin; Cefazolin; D-Cephradine (D-Cefradine); D-Cefadroxil;

(ii) Second Generation Cephalosporins: D-Cefactor; D-Cefamandole; Cefuroxime; DCefonicid;

Ceforanide; (iii) Third Generation Cephalosphorins: Cefotaxime; Ceftizoxime; D-Cefoperazone; Ceftazidime; Ceftriaxone; Cefmonoxime, Moxalactam;

(iv) Prodrugs: Cefpodoxime proxetil; Cefuroxime axetil;

(v) Cephamycins: Cephamycin C; Cefoxitin.

A few of these important compounds representing the above said categories shall now be discussed individually in the sections that follows:

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* Brotzu, G., Lav. Ist. Igiene Caligari, (1948)

** Abraham, Newton, Nature, 175, 548, (1955).

3.3.1 First Generation Cephalosporins

The first generation cephalosporin antibiotics are found to be effective against a host of Grampositive microorganisms, including penicillinase-producing Staphylococcus. Besides, being resistant to penicillinase they are found to be inactivated by another cephalosporinase termed as β-lactamase.

The Gram-negative organisms that are observed to be highly sensitive to these compounds are, namely: Escherichia coli; Proteus mirabilis; and Klebsiella pneumoniae. These antibiotics are also found to be less active against Haemophilus influenzae as compared to the extended-spectrum penicillins, such as: ampicillin.

A. Cephalothin

Synonyms Cefalotin; 7-(Thiophene-2-acetamido) cephalosporanic acid).

Biological Source It is a semi-synthetic cephalosporin antibiotic derived from Cephalosporium acremonium.

Chemical Structure

(6R-trans)-3-[(Acetyloxy) methyl]-8-oxo-7-[(2-thienylacetyl) amino]-5-thia-1-azobicyclo [4.2.0] act-2-ene-2-carboxylic acid; (C₁₆H₁₆N₂O₆S₂).

Preparation First of all the 7-aminocephalosporanic acid is N-acetylated with 2-thiopheneacetyl chloride in a dehydro-chlorinating environment. The starting acid may be prepared from the natural antibiotic, cephalosporin C, either by means of enzymatic hydrolysis or by proton-eatalyzed hydrolysis. The cephalothin thus obtained may be purified from acetonitrile.

Characteristic Features

1. It is obtained as a white amorphous powder having mp 160-160.5°C.

2. It has specific optical rotation [α]_D²⁰ + 50° (C = 1.03 in acetonitrile).

Cephalothin Sodium [C₁₆H₁₅N₂NaO₆S₂] [Synonyms Averon-1; Cefalotin; Cemastin; Cephation; Ceporacin; Cepovenin; Coaxin; Keflin; Lospoven; Microtin; Synclotin; Toricelocin].

1. It is obtained as a white to off-white, crystalline powder, almost odourless, moderately hygroscoic and has mp 204-205°C.

2. It has dissociation constant pKa 2.2.

3. It has specific optical rotation [α]_D + 135° (C = 1.0 in water).

4. It has uv_max: 236, 260 nm (ε 12950, 9350).

5. Solubility Profile: It is freely soluble in water, normal saline or dextrose solution; slightly soluble in ethanol; and practically insoluble in most organic solvents.

Uses

1. It is a potent antibacterial agent.

2. It is a first-generation cephalosporin given IM and IV.

3. It is found to be a short-acting antibiotic and exhibits the weakest spectrum of its class.

B. Cephazolin

Synonym CEZ.

Biological Source It is also a semi-synthetic antibiotic derived from 7-aminocephalosporanic acid obtained from Cephalosporium acremonium.

Chemical Structure

7-(1-(1H)-Tetrazolyl acetamido)-3-[2-(5-methyl-1, 3, 4-thiadiazolyl) thiomethyl]-3-cephem-4-carboxylic acid; (C₁₄H₁₄N₈O₄S₃).

Preparation The sodium salt of 7-aminocephalosporanic acid is acylated with 1H-tetrazole-1-acetyl chloride. The acetoxy moiety present in the resulting product is then displaced by reaction with 5-methyl-1, 3- 4-thiadiazole-2-thiol to produce the desired product i.e., cephazolin. It is then further purified from aqueous ethanol.

Characteristic Features

1. Cephazolin is obtained as needles from aqueous acetone having mp 198-200°C (decomposes).

2. It has uv_max (buffer pH 6.4): 272 nm (ε 13150).

3. It is found to be freely soluble in DMF, pyridine; soluble in aqueous acetone, aqueous dioxane, aqueous ethanol, slightly soluble in methanol; and practically insoluble in benzene, chloroform, ether.

Cephazolin Sodium [C₁₄H₁₃N₈NaO₄S₃] Synonyms Acef; Ancef; Atirin; Biazolina; Bor- Cefazol; Cetacidal; Cefamedin; Cefamezin; Cefazil; Cefazina; Elzogram; Firmacef; Gramaxin; Kefzol; Lampocef; Liviclina; Totacef; Zolicef]:

1. It is obtained as white to yellowish white, odourless crystalline powder having a bitter salty taste. It crystallizes out in α-, β-, and g-forms.

2. It is found to be freely soluble in water; slightly soluble in methanol, ethanol; and almost insoluble in benzene, acetone, chloroform.

Uses

1. Totacef may be given IV or IM; however, its Gram-negative activity is essentially limited to E. coli; Klebsiella; and Pr mirabilis.

2. Some Gram-negative organisms and penicillinase-producing staphylococci which are resistant to both Penicillin G and Ampicillin are found to be sensitive to cefazolin.

3. It may be used to treat infections of the respiratory tract skin, soft tissues, tones, joints and urinary tract and endocarditis and septicemia caused by suceptible organisms. However, amongst the UTIs, cystitis* specifically responds much better than pyelonephritis**.

4. It is one of the preferred cophalosporins for most surgical prophylaxis, by virtue of its inherent long half-life (i.e., 1.5 to 2 hours in normal persons but 3 to 42 hours in renal failure).

C. Cefadroxil

Synonyms BL-S578; MJF-11567-3; Baxan; Bidocef; Cefa-drops; Cefamox; Ceforal; Cephos; Duracef; Duricef; Kefroxil; Oracefal; Sedral; Ultracef.

Biological Source It is also an orally active semi-synthetic cephalosporin antibiotic obtained from the species Cephalosporium aeremonium.

Chemical Structure

para-Hydroxycephalexine monohydrate; (C₁₆H₁₇N₃O₅S.H₂O).

Characteristic Features It is obtained as white to yellow white crystals having m_p 197°C (decomposes). It is found to be soluble in water, and fairly stable in acidic medium.

Uses

1. It is intermediate acting and quite effective against Staphylococcus and certain enteric Gramnegative bacilli.

2. Because of its prolonged exeretion criterion, it has an added advantage of catering for more sustained serum and urine concentrations than are usually obtained with other oral cephalosporins.

3. Clinical studies have revealed that cefadroxil administered, 1g twice daily, is as effective as cephalexin given 500 mg four times daily.

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* Cystitis: Inflammation of the bladder usually occurring secondary to ascending urinary tract infections (UTIs).

** Pyelonephritis: Inflammation of kidney and renal pelvis.

3.3.2 Second Generation Cephalosporins

Generally, the ‘second generation cephalosporins’ exhibit the same spectrum of antibacterial activity as that of the first generation cephalosporins. The glaring exceptions being that these are comparatively much more active against certain specific organisms, namely: Haemophilus influenzae, gonococcus, and some enteric Gram-negative bacilli. Interestingly, most of the second generation cephalosporins are adequately absorbed through the oral administration. Some typical examples of second generation cephalosporins shall now be described as under:

A. Cefamandole

Synonyms CMT; Compound 83405.

Biological Sources It is a broad-spectrum semi-synthetic cephalosporin antibiotic obtained from

Cephalosporium acremonium.

Chemical Structure

7-D-Mandelamido-3-[[(1-methyl-1H-tetrazol-5yl) thio]-methyl]-3-cephem-4-carboxylic acid; (C₁₈H₁₈N₆O₅S₂).

Characteristic Features

Cefamandole Nafate [C19H17N6NaO6S2] [Synonyms Bergacef; Cedol, Cefam; Cefiran; Cemado; Cemandil; Fado; Kefadol; Kefandol; Lampomandol; Mandokef; Mandol; Mandolsan; Neocefal; Pavecef]:

1. It is obtained or white odourless needles having mp 190°C (decomposes).

2. It has uvmax (H₂O): 269 nm (ε 10800).

3. Its dissociation constant pKa 2.6-3.0.

4. It is soluble in water, methanol; and almost insoluble in ether, chloroform, benzene, cyclohexane.

It is also found to be soluble in saline TS or dextrose solutions.

Uses

1. It is administered effectively through IM and IV.

2. It is found to be short-acting.

B. Cefuroxime

Several antibiotics belonging to the category of ‘second generation antibiotics’ are absorbed orally.

Interestingly, cefuroxime is available in two different versions; first—as its sodium salt and secondly—as its prodrug cefuroxime axetil that are hydrolyzed once they are absorbed and its absorption rate increased by the intake of food in-take.

Chemical Structure

(6R, 7R)-3-Carbamoyloxymethyl-7-[2-(2-furyl)-2-(methoxy-amino) acetamido] ceph-3-em-4-

carboxylic acid; (C₁₆H₁₆N₄O₈S).

Characteristic Features

1. It is obtained as a white crystalline solid.

2. It has specific optical rotation [α]_D²⁰ + 63.7° (C = 1.0 in 0.2 m pH 7 phosphate buffer).

3. It has uv_max (pH6 phosphate buffer): 274 nm (ε 17600).

Cefuroxime Sodium [C₁₆H₁₅N₄NaO₈S]: [Synonyms Anaptivan; Biociclin; Biofurex; Bioxima; Cefamar; Ceffoprim; Cefumax; Cefurex; Cefurin; Curocef; Curoxim; Duxima; Gibicef; Ipacef; Kefurox; Kesint; Lampsporin; Medoxim; Novocef; Spectrazole; Ultroxim; Zinacef ].

It is a white solid; specific optical rotation [α]_D²⁰ + 60° (C = 0.91 in water); uvmax (water): 274 nm (ε 17400). It is found to be freely soluble in water and buffered solutions; soluble in methanol; very slightly soluble in ether, ethyl acetate, octanol, benzene and chloroform. Its solubility in water in 500 mg/2.5 ml. Its dissociation constant in water pKa 2.5; in DMF 5.1. The stability of cefuroxime sodium salt in water at room temperature stands valid upto 13 hours; and at 25°C for 48 hours nearly 10% decomposition takes place.

Uses

1. Its activity against H. influenzae and ability to penetrate into the CSF makes it specifically useful for the treatment, control and management of meningitis caused by this organism. However, it is also recommended to treat meningitis caused by Strep. pneumoniae, N. meningitidis and Staph. aureus.

2. It exhibits an excellent and super activity against all species of gonococci, hence it is recommended for the treatment of gonorrhea.

3. It may also be employed to treat lower respiratory tract infections normally caused by H. influenzae and parainfluenzae, Klebsiella species, E. coli, Strep pneumoniae and pyrogenes and Staph aureus.

4. It is also approved for use against UTIs caused by E. Coli and Klebsiella; of course, a rather more restricted approval as compared to other second-generation drugs.

5. It is also recommended for use in bone infections, septicemias and surgical prophylaxis.

C. Cefonicid

Biological Source It is essentially an injectable semi-synthetic cephalosporin antibiotic related to cefamandole which is obtained from Cephalosporium acremonium.

Chemical Structure

Characteristic Features

Cefonicid Disodium [C₁₈H₁₆N₆Na₂O₈S₃] [Synonyms SKF-75073; Cefodie; Monocid; Monocidur; Praticef;] The pH of 5% (w/v) solution is between 3.5 to 6.5.

Uses

1. It is administered through IV and IM.

2. It is an intermediate-acting second generation cephalosporin.

3.3.3 Third Generation Cephalosporins

The ‘third generation cephalosporins’ are logically differentiated from the first and second generation cephalosporins by virtue of their extended activity against a wide spectrum of enteric

Gram-negative bacillii, along with the β-lactamase-producing strains.

A few potent and typical examples of drugs belonging to this category shall be discussed in the section that follows:

A. Cefotaxime

Biological Source It is a broad spectrum third generation cephalosporin antibiotic derived from Cephalosporium acremonium. The name cefotaxime applies to the isomer having a synmethoxyamino moiety.

Chemical Structure It is the desacetyl active metabolite of cefotaxime i.e., another third generation cephalosporin.

7-[2-(2-Amino-4-thiazolyl)-2-methoxyimino acetamido] cephalosporanic acid; (C₁₆H₁₇N₅O₇S₂).

Characteristic Features

Cefotaxime Sodium [syn-Isomer]: [C₁₆H₁₆N₅NaO₇S₂] [Synonyms: Cefotax; Chemcef; Claforan; Pretor; Tolycar; HR-756; RU-24756]:

1. It is a white to off-white solid.

2. The pH of a 10% (w/v) solution is approximately 5.5.

3. It has specific optical rotation [α]_D²⁰ + 55° ± 2 (C = 0.8 in water).

4. Its pKa (acid) is 3.75.

5. It is found to be freely soluble in water; and almost insoluble in most organic solvents.

Uses

1. It is found to be active against a good number of Gram-negative bacilli and its action is almost equivalent to the amino glycosides, except against Ps aeruginosa, Acinetobacter and a few Enterobacter.

2. It is highly resistant to the β-lactamases.

3. It is found to be less active than either the first or the second generation cephalosporins.

4. It is a recognized and preferred third generation cephalosporin for Gram-negative meningitis and other serious Gram-negative bacillary infections outside the CNS.

5. It is also recommended widely for surgical prophylaxis.

6. Cefatoxime has a slightly longer half-life which permits 8 to 12 hour dosing in comparison to 6 to 8 hours for cefotaxime.

B. Ceftriaxone

Synonym Cefatriaxone.

Biological Source It is a parenteral third generation cephalosporin antibiotic obtained from

Cephalosporium acremonium.

Chemical Structure [C₁₈H₁₈N₈O₇S₃]

Characteristic Features

Ceftriaxone Disodium Hemiheptahydrate [C₁₈H₁₈N₈Na₂O₇S₃.3½H₂O]: [Synonyms Rocefin; Rocephin(e)]:

1. It is obtained as white crystalline powder having mp > 155°C. (decomposes).

2. It has specific optical rotation [α]_D²⁵-165° (C = 1 in water) (calculated for anhydrous substance).

3. It has uv_max (water): 242, 272 nm (ε 32, 300; 29530).

4. It shows dissociation constant pKa : ~ 3 (COOH); 3.2 (NH³⁺), 4.1 (enolic OH).

5. Its solubility in water at 25°C: ~ 40 g/100 ml.

6. The colour of its solution varies from light yellow to amber depending solely on the concentration (g. L–1) and the duration of storage (hrs.)

7. The pH of a 1% (w/v) solution is nearly 6.7.

8. It is found to be sparingly soluble in methanol; and very slightly soluble in ethanol.

Uses

1. Ceftriaxone sodium is considered as the drug of choice for uncomplicated and disseminated gonococcal infections.

2. It is also an effective alternative for meningitis in infants essentially caused by H. influenzae, N. meningitidis and Streptococcus pneumoniae.

3. It is also recommended for Gram-negative bacillary meningitis and some other serious Gramnegative infections, including complications associated with Lyme disease.*

4. It may also be used for the treatment of bone and joint infections, intra-abdominal infections, lower respiratory tract infections, pelvic infections, skin and urinary tract infections (UTIs).

5. It is also indicated for preoperative prophylaxis, for which its efficiency is almost equivalent to that of cefazolin.

C. Ceftazidime

Synonym GR-20263; Fortaz; Tazicef; Tazidime.

Biological Source It belongs to the class of third generation cephalosporin antibiotic.

Chemical Structure The O-substituted oxime function certainly improves upon the potency of the ‘third generation cephalosporin’, and ultimately exerts resistance to β-lactamases. It is, however, pertinent to mention here that the oximes with syn stereochemistry are appreciably more potent and efficient than the corresponding anti isomers.

1-[[(6R, 7R)-7-[2-(2-(2-amino-4-thiazolyl) glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo-[4.2.0] oct-2-en-3-yl] methyl] pyridinium hydroxide inner salt 72-(Z)-[0-(1-carboxy-1- methylethyl) oxime]; (C₂₂H₂₂N₆O₇S₂).

Characteristic Features

1. It is obtained as an ivory-coloured powder.

2. Its pKa values are : 1.8, 2.7, 4.1.

3. It has uvmax (pH6) : 257 nm (E_1%^1cm 348).

Uses

1. Ceftazidime is a broad-spectrum antibiotic and is administered IV or IM.

2. It is specifically of great interest because of its distinct high activity against Pseudomonas and Enterobacteriaceae, but not enterococci.

3. It is an alternative drug for the treatment of hospital-acquired Gram-negative infections especially in immuno-compromised patients when Ps aeruginosa is a potential causative organism.

4. It is also recommended for use in the treatment, control, and management of bone and joint infections, CNS-infections, gynecological infections, lower respiratory tract infections, septicemia, skin and UTIs.

5. Its activity is fairly comparable to that of cefotaxime and coftizoxime in vitro but is much more active against Pseudomonas aeruginosa and fairly less active against staphylococci and Bacteroides fragilis.

6. It is an agent of choice for the ‘emperical antibiotic therapy’ when pseudomonas happens to be one of the suspected pathogens.

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* Lyme Disease: A multisystem disease caused by the tick-transmitted spirochete Borrelia burgodorferi.

D. Moxalactam

Synonyms Lamoxactam; Latamoxef.

Biological Source It is an oxa-substituted third generation cephalosporin antibiotic (oxacephalosporin).

Chemical Structure [C₂₀H₂₀N₆O₉S]

Characteristic Features

1. Moxalactam is obtained as a colourless powder having mp 117-122°C (decomposes).

2. Its specific optical rotation [α]_D²⁵–15.3 ± 2.6° (C = 0.216 in methanol).

3. It has uv_max (methanol): 276 nm (ε 10200).

Moxalactam Disodium [C₂₀H₁₈N₆Na₂O₉S]  [Synonyms Festamoxin; Moxalactam; Moxam; Shiomarin; LY-12735; S-6059].

1. It has specific optical rotation [α]_D²²-45° (water).

2. It has uv_max (water): 270 nm (ε 12000).

Uses

1. Moxalactam exhibits a spectrum of activity which is almost identical to that of cefotaxime.

However, its usage is very much restricted and limited on account of the occurrence of bleeding disorders of serious nature.

Note: The presence of methyltetrazolethiomethyl moiety may be responsible for causing hypoprothrombinemia; and the a-carboxyl group may attribute to the platelet dysfunction. Perhaps both these vital factors ultimately lead to bleeding disorders.

2. It has an extended Gram-negative spectrum, and are found to be most active against enteric Gram-negative bacilli, but may be less active against certain Gram-positive microorganisms, especially Staphylococcus aureus.

3.3.4 Prodrugs

A major noticeable chief disadvantage of plethora of the current cephalosporins is that they are not rapidly and effectively absorbed through oral route. This specific serious drawback is perhaps due to the nature of the side-chain present at C-3. An attempt has been made to design orally active prodrugs, namely: cefuroxime-axetil and cefpodoxime-proxetil, which have been developed meticulously by providing an additional ester function on the C-4 carboxyl moiety. Nevertheless, these prodrugs are designed in such a manner that they are easily hydrolysed to the active agents i.e., drugs by the esterases.

A. Cefpodoxime Proxetil

Synonyms Banan; Cefodox; Orelox; Otreon; Vantin; CS-807; U-76252;

Biological Source It is a broad spectrum, orally absorbed third generation cephalosporin, tailormade ester prodrug of the active-free-acid metabolite, cefpodoxime.

Chemical Structure The skill and wisdom of a pharmaceutical chemist has made it possible to design an ester of the metabolite, cefpodoxime, in which the free carboxyl function located at C-4 of the thiazine ring i.e., the heterocyclic six-membered ring with one each of S and N atom studded at alternate position in the ring.

1-(Isopropyloxy carbonyloxy) ethyl (6R, 7R)-7 [2-(2-amino-4-thiazolyl)-(Z)-2-(methoxyamino) acetamido]-3-methoxymethyl-3-cephem-4-carboxylate; (C₂₁H₂₇N­O₉S₂).

Uses

1. It is a ‘third generation cephalosporin’-prodrug administered orally.

2. It is found to be an ‘intermediate acting cephalosporin’.

3. Its pharmacologic activity is almost similar to that of cofixime.

3.3.5 Cephamycins

Streptomyces clavuligerus gave rise to the isolation of the natural antibiotic known as Cephamycin C, which essentially has an α-methoxy function at C-7 present in the basic cephalosporin ring system. It has been observed that the steric hinderence caused due to the presence of the additional methoxy moieties, affording thereby a possible resistance to β-lactamase hydrolysis, might be solely responsible for the weak antibacterial activity of both cephamycin C and other natural cephamycins.

Various semi-synthetic structural analogues have been designed either:

(a) By chemical introduction of the α-methyl moiety at C-7 of the basic cephalosporin ring system, or

(b) By modification of the side-chains of the naturally occurring cephamycins.

A. Cefoxitin

Biological Source It is a semi-synthetic derived from the Cephamycin C through the method ‘a’ stated above. The synthesis of Cefoxitin has been successfully carried out by Karady et al.*

Chemical Structure

3-Carbamoyloxymethyl-7α-methoxy-7-[2-(2-thienyl)-acetamido]-3-cephem-4-carboxylic acid; (C₁₆H₁₇ N₃O₇S₂).

Characteristic Features

1. It is obtained as crystals having mp 148-150°C (decomposes).

2. Its dissociation constant pKa is 2.2.

3. Solubility Profile: It is very soluble in acetone; soluble in aqueous NaHCO3; very slightly soluble in water; and almost insoluble in ether and chloroform.

Cefoxitin Sodium [C₁₆H₁₆N₃NaO₇S₂] [Synonyms Betacef; Farmoxin; Mefoxin; Mefoxitin;

Merxin; Cenomycin;]:

1. It is obtained as white crystals with a characteristic odour having mp 150°C.

2. It has specific optical rotation [α]²⁵ 589nm + 210° (C = 1 in methanol).

3. It has dissociation constant pKa 2.2 (acid).

4. Solubility Profile: It is found to be very soluble in water; soluble in methanol; sparingly soluble in ethanol or acetone; and practically insoluble in aromatic and aliphatic hydrocarbons.

Uses

1. It is mostly used as an alternative drug for intra-abdominal infections, colorectal surgery or appendectomy and ruptured viscus by virtue of the fact that it is active against most enteric anaerobes including Bacteroides fragilis.

2. It is also recommended for use in the treatment of bone and joint infections usually caused by S. aureus, gynecological and intra abdominal infections by Bacteriodes species

3. It is also approved for lower respiratory tract infections caused by Bacteroides species; E. coli; H. influenzae; Klebsiella species; S. aureus etc.

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* Karady et al. J. Am. Chem. Soc., 94, 1410, (1972).

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Source:Pharmacognosy And Pharmacobiotechnology By Ashutosh Kar