Cefquinome

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Cefquinome
Systematic (IUPAC) name
1-[[(6R,7R)-7-[[(2Z)-(2-Amino-4-thiazolyl)-
(methoxyimino)acetyl]amino]-2-carboxy-8-oxo-
5-thia-1-azabicyclo[4.2.0-oct-2-en-3-yl]methyl]-
5,6,7,8-tetrahydroquinolinium inner salt
Identifiers
CAS number 84957-30-2
ATC code  ?
PubChem  ?
Chemical data
Formula C23H24N6O5S2 
Mol. mass 528.60 g/mol
Pharmacokinetic data
Bioavailability 87%
Protein binding <5%
Metabolism  ?
Half life 2½ hours
Excretion Renal, unchanged
Therapeutic considerations
Pregnancy cat.

?
Legal status

?(US)
Routes  ?

Cefquinome (4GC) is a fourth generation cephalosporin with pharmacological and antibacterial properties valuable in the treatment of coliform mastitis and other infections. It is used in the treatment of both humans and animals. According to the Washington Post, it is used as a last line of defence to keep humans alive.[1]

Contents

[edit] Properties

Cefquinome is resistant to beta-lactamase. Chemically, its zwitterionic structure can facilitate rapid penetration across biological membranes, including porins of bacterial cell wall. Plus, it has a higher affinity to target penicillin binding proteins. Besides zwitterionic, it is also made of beta-lactam nucleus, quaternary ammonium, and aminothiazolyl moiety.

Cefquinome acts by inhibition of the cell wall synthesis, but it has a relatively short half-life of about two and half hours. It is less than 5% protein bound and is excreted unchanged in the urine.[2]

[edit] Studies

Many studies have been conducted, mostly for animal use. One such study was conducted by the Pharma Research in Germany.

[edit] Test Groups

Groups of albino mice, weighing 191 g, were dosed with 10 and 40 mg of cefquinome per kg. Blood samples were obtained from a cut at the tip of the tail and kept at 4 degrees Celsius. Urine was collected in metabolism cages.

Three male beagle dogs, weighing about 22 kg each, were dosed with 5, 10, and 20 mg/kg at the cephalic vein. Blood samples were drawn from the same vein in the opposite leg. Meanwhile, urine was collected by catheterization.

Pigs, five or six male and female in each group weighing approximately 18 kg each, were injected with 10 mg of cefquinome at the venajuglaris in the base of the left ear. Blood samples were withdrawn from the contralateral jugular vein.

Male and female calves were weighing between 110 and 140 kg were dosed with 10 mg of cefquinome per kg through the vera jucular.

Standard solutions were prepared from pooled murine blood and urine taken from untreated dogs, pigs, and calves.

[edit] Calculations

Cefquinome concentrations were calculated by regression analysis, using the standard curves in which logarithms of the concentration were proportional to the areas of the inhibition zones. Curve fitting was carried out by nonlinear regression with the computer program PHAKOK. Pharmokinetic analysis of the concentration-time data after administration indicated that the best curve fits were usually achieved by using an open two-compartment model.

[edit] Conclusion

Data indicates that cefquinome has high antibacterial activity in vitro against nearly all strains tested. In general, cefquinome is within the same range as cefpirome and cefotaxime. Against gram-negative species, cefquinome has very limited vitro activity. The vitro activity of cefquinome does not depend on the composition or pH of the test medium. The road antibacterial spectrum and the high in vitro activity are reflected by high in vivo efficacy in experimental infections. In mouse models of septicemia, cefquinome possessed high therapetic efficacy. All infections were cured.

[edit] Intervet

Intervet developed cefquinome (Cobactan)) to treat bovine respiratory disease, the most common disease in cattle.[1] An injection, containing 25mg cefquinome per ml, is given to cattle and pigs.

[edit] Treatment

In cattle, the injection should help against respiratory disease caused by Mannheimia haemolytica and Pasteurella multocida. It also helps with acute E. coli mastitis, dermatitis, infectious ulbar necrosis, and interdigital necrobacillosis (which is foul in the foot). In calves, it is E. coli septicaemia.

For pigs, it would treat the bacterial infections of the lungs and respiratory tract caused by P. multocida, Haemophilus parasuis, Actinobacillus pleuropneumoniae, and Streptococcus suis. Mastitis-Metritis-Agalactia Syndrom (MMA) involved with E. coli, Staphylococcus, Streptococcus, and other cefquinome-sensitive organisms will also be treated. In piglets, the mortality rate in cases of meningitis caused by Streptococcus suis is reduced. It is used in the treatment of mild or moderate lesions caused by Staphylococcus hyicus and arthritis caused by Streptococcus and E. coli.

[edit] Usage

Shake the vial well before using.

Swab the septum before removing each dose. Use a dry sterile needle and syringe. An appropriately graduated syringe must be used to allow accurate administration of the required dose volume. This is particularly important when injecting small volumes, for example when treating piglets. The cap may be safely punctured up to 25 times. The 50 ml vial should be used for treating small piglets. When treating groups of animals, use a draw-off needle.

[edit] Caution/Warnings

These are some factors to be aware of before treating.

  • This product should not be used in animals known to be hypersensitive to β-lactam antibiotics.
  • Should not be administer to animals with a bodyweight less than 1.25kg.
  • Use of the product may result in localised tissue reaction. Tissue lesions are repaired by 15 days after the last administration of the product.
  • Hypersensitivity reactions to cephalosporins occur rarely.
  • The product does not contain an antimicrobial preservative.
  • To prevent the claimed infections in piglets, attention should be paid to hygiene and ventilation, and overcrowding should be avoided. When the first piglets are affected, careful examination of all animals in the same pen is recommended to enable an early treatment of any other infected piglets.

[edit] Clinical Usage

[edit] Human Use

The only 4GC approved in US for human use is Maxipime (cefepime HCI). There are two main reasons for cefepime’s primary use in human medicine. For one, cefepime is the only agent approved for empiric monotherapy for neutropenic fever. The other reason is that cefepime is used to treat enteric pathogens of non-food-borne-disease.

[edit] Veterinary Medicine

Conditions of use are limited to therapeutic, parenteral, and individual animal use. Individual parental therapy of bovine respiratory disease data on cefquinome-related residues demonstrate that only very small amounts are present in the intestinal tract of treated cattle with gastro-intestinal activation.

However, treatment should be short, meaning a single injection daily for about a week. Treatment should only be given by prescription. Cefquinome should not be used in feeding and water.

Since 1994, in Europe, it was allowed to treat cattle by prescription only. In 1999, swines were included. By 2005, horses were allowed as well.

In the United States, the situation is pending for treatment of bovine respiratory disease. Even so, this is only available by prescription.

Cefquinome are also used for other illnesses, such as “shipping fever,” a pneumonia-like illness commonly found in cows.[3]

[edit] Concerns

[edit] Resistance and Food-borne Transmission

There are concerns that the use of the drug in animals will lead to increases in antibiotic resistance. Humans can be exposed to bacteria through food-borne transmission, raising chances of becoming exposed to resistant salmonella (E. coli). Resistance can grow if usage widespread, increasing chances for mutation.

E. coli is usually not associated with food-borne infections, except E. coli 0157:H7, for which there is zero tolerance in food.[4] Other food-borne pathogens like Campylobacter and Enterococcus are not considered. This is because cefquinome is not active against these pathogens.

[edit] Salmonella

The use of CEQ may cause resistance in Salmonella present in the intestinal tract of the target animal. Resistant Salmonella may also contaminate the carcass at slaughter and transfer to humans when used as food. When humans are infected and treated with a 4GC, effectiveness may be compromised.

Although 4GC resistance is very rare, they are active against bacteria carrying the AmpC-type β-lactamase resistance mechanism. Since the late 1990s, the US and EU have surveyed and gathered data for 4GCs for both human and veterinary. Data indicates that there are no change in resistance patterns of relevant food-borne pathogens.

[edit] FDA Guidelines

  • Administered products will be used in individual animals for short duration and by prescription only.
  • The extent of use is ranked low.
  • Avoid human drug resistance to fourth-generation cephalosporins by authorizing extra-label prohibition.

[edit] Footnotes

  1. ^ a b Rick Weiss, "FDA Rules Override Warnings About Drug", The Washington Post, March 4, 2007, sec. A01
  2. ^ Intervet, "Cephaguard Injection Data Sheet," http://www.intervet.co.uk/Products_Public/Cephaguard_Injection/090_Product_Datasheet.asp
  3. ^ Associated Press, "Farmers, doctors battle over new drug for dairy cows," April 5, 2007, State and Regional
  4. ^ Carl K. Johnson, "Introduction to Cefquinome (CEQ) and Overview of Microbial Safety Assessment," http://www.fda.gov/cvm/VMAC/VMAV0906Johnson.htm

[edit] References

[edit] See also

[edit] External links