Cefquinome
Encyclopedia
Cefquinome is a fourth generation cephalosporin
with pharmacological and antibacterial properties valuable in the treatment of coliform mastitis and other infections. It is only used in veterinary applications.
. 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. The reactive site is a beta-lactam
nucleus, while the main peripheral functional groups are a quaternary quinolinium, an aminothiazolyl moiety and an unusual O-alkylated oxime
.
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.
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 Blood samples were withdrawn from the contralateral jugular vein.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.
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.
. Against gram-negative species, cefquinome has very limited in vitro activity. The in vitro activity of cefquinome does not depend on the composition or pH of the test medium. The broad 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.
. 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 Syndrome (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 spp. and E. coli.
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.
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 feed or water.
Since 1994, in Europe, it was allowed to treat cattle by prescription only. In 1999, swine were included. By 2005, horses were allowed as well.
In the United States, approval 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 cattle.
. Humans can be exposed to bacteria through food-borne transmission, raising chances of becoming exposed to resistant bacterial species, such as Salmonella
or E. coli. The potential for the development of antibiotic resistance increases as usage increases, by selecting bacteria which have acquired beta-lactamase
s.
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 use. Data indicate that there are no changes in resistance patterns of relevant food-borne pathogens.
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...
with pharmacological and antibacterial properties valuable in the treatment of coliform mastitis and other infections. It is only used in veterinary applications.
Properties
Cefquinome is resistant to beta-lactamaseBeta-lactamase
Beta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
. 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. The reactive site is a beta-lactam
Beta-lactam
A β-lactam ring, is a four-membered lactam. It is named as such, because the nitrogen atom is attached to the β-carbon relative to the carbonyl...
nucleus, while the main peripheral functional groups are a quaternary quinolinium, an aminothiazolyl moiety and an unusual O-alkylated oxime
Oxime
An oxime is a chemical compound belonging to the imines, with the general formula R1R2C=NOH, where R1 is an organic side chain and R2 may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substituted oximes form a closely related family of compounds...
.
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.
Studies
Many studies have been conducted, mostly for animal use. One such study was conducted by the Pharma Research in Germany.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
Cephalic vein
In human anatomy, the cephalic vein is a superficial vein of the upper limb.It communicates with the basilic vein via the median cubital vein at the elbow and is located in the superficial fascia along the anterolateral surface of the biceps brachii muscle.Superiorly the cephalic vein passes...
. 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.
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 fittingCurve fitting
Curve fitting is the process of constructing a curve, or mathematical function, that has the best fit to a series of data points, possibly subject to constraints. Curve fitting can involve either interpolation, where an exact fit to the data is required, or smoothing, in which a "smooth" function...
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.
Conclusion
Data indicate that cefquinome has high antibacterial activity in vitro against nearly all strains tested. In general, cefquinome is within the same range as cefpirome and cefotaximeCefotaxime
Cefotaxime is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram positive and Gram negative bacteria...
. Against gram-negative species, cefquinome has very limited in vitro activity. The in vitro activity of cefquinome does not depend on the composition or pH of the test medium. The broad 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.
Intervet
Intervet developed cefquinome (Cobactan) to treat bovine respiratory disease, the most common disease in cattle. An injection, containing 25 mg cefquinome per ml, is given to cattle and pigs.Treatment
In cattle, the injection should help against respiratory disease caused by Mannheimia haemolytica and Pasteurella multocidaPasteurella multocida
Pasteurella multocida is a Gram-negative, non-motile coccobacillus that is penicillin-sensitive and belongs to the Pasteurellaceae family . It can cause avian cholera in birds and a zoonotic infection in humans, which typically is a result of bites or scratches from domestic pets...
. It also helps with acute E. coli mastitis, dermatitis
Dermatitis
-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...
, 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
Pasteurella multocida
Pasteurella multocida is a Gram-negative, non-motile coccobacillus that is penicillin-sensitive and belongs to the Pasteurellaceae family . It can cause avian cholera in birds and a zoonotic infection in humans, which typically is a result of bites or scratches from domestic pets...
, Haemophilus parasuis, Actinobacillus pleuropneumoniae, and Streptococcus suis. Mastitis-Metritis-Agalactia Syndrome (MMA) involved with E. coli, Staphylococcus
Staphylococcus
Staphylococcus is a genus of Gram-positive bacteria. Under the microscope they appear round , and form in grape-like clusters....
, Streptococcus
Streptococcus
Streptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...
, 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 spp. and E. coli.
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.
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 administered to animals with a body weight less than 1.25 kg.
- 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.
Veterinary medicine
Conditions of use are limited to therapeutic, parenteral, and individual animal use. Individual parenteral 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 gastrointestinal 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 feed or water.
Since 1994, in Europe, it was allowed to treat cattle by prescription only. In 1999, swine were included. By 2005, horses were allowed as well.
In the United States, approval 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
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
-like illness commonly found in cattle.
Resistance and food-borne transmission
There are concerns that the use of the drug in animals will lead to increases in antibiotic resistanceAntibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
. Humans can be exposed to bacteria through food-borne transmission, raising chances of becoming exposed to resistant bacterial species, such as Salmonella
Salmonella
Salmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...
or E. coli. The potential for the development of antibiotic resistance increases as usage increases, by selecting bacteria which have acquired beta-lactamase
Beta-lactamase
Beta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
s.
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 use. Data indicate that there are no changes in resistance patterns of relevant food-borne pathogens.
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.
See also
- Beta-lactamaseBeta-lactamaseBeta-lactamases are enzymes produced by some bacteria and are responsible for their resistance to beta-lactam antibiotics like penicillins, cephamycins, and carbapenems . These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam...
- CampylobacterCampylobacterCampylobacter is a genus of bacteria that are Gram-negative, spiral, and microaerophilic. Motile, with either unipolar or bipolar flagella, the organisms have a characteristic spiral/corkscrew appearance and are oxidase-positive. Campylobacter jejuni is now recognized as one of the main causes...
- CefepimeCefepimeCefepime is a fourth-generation cephalosporin antibiotic developed in 1994. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both Gram-negative and Gram-positive organisms than third-generation agents...
- CephalosporinCephalosporinThe cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...
- EnterococcusEnterococcusEnterococcus is a genus of lactic acid bacteria of the phylum Firmicutes. Enterococci are Gram-positive cocci that often occur in pairs or short chains, and are difficult to distinguish from streptococci on physical characteristics alone. Two species are common commensal organisms in the...
- SalmonellaSalmonellaSalmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...
- ZwitterionZwitterionIn chemistry, a zwitterion is a neutral molecule with a positive and a negative electrical charge at different locations within that molecule. Zwitterions are sometimes also called inner salts.-Examples:...