Antibiotics

Amoxicillin-clavulanic acid is a combination of a beta-lactamase antibiotic (amoxicillin) and a beta-lactamase inhibitor (clavulanic acid). Clavulanic acid irreversibly binds to the beta-lactamase enzyme, which would otherwise degrade the amoxicillin, allowing the amoxicillin to act against the susceptible organism.

It is commonly used for treatment of UTI’s; skin, bone, and soft tissue infections; infections involving anaerobes; and respiratory tract infections. Recent guidance from the Working Group of the International Society for Companion Animal Infectious Diseases states that amoxicillin-clavulanic acid is an acceptable option for treatment of uncomplicated UTI but “is not recommended initially because of the lack of evidence regarding the need for clavulanic acid and the desire to use the narrowest spectrum that is possible while maintaining optimal efficacy”. The drug should not be administered to horses, rabbits, guinea pigs, hamsters, or gerbils.

Commonly isolated organisms that are naturally resistant to amoxicillin-clavulanic acid include Pseudomonas aeruginosa and Enterobacter spp. Resistance among staphylococci is increasing due to the increased prevalence of methicillin-resistant staphylococci (MRS).

Ampicillin and amoxicillin have similar antimicrobial activity, and amoxicillin has the advantage of achieving higher tissue concentrations because of better absorption from the intestine, and has more rapid and longer action compared with ampicillin.

The result for ampicillin susceptibility testing may be used to predict the susceptibility of the isolate to amoxicillin i.e. if the isolate is sensitive to ampicillin then it will also be sensitive to amoxicillin. Ampicillin or amoxicillin are drugs of choice for mixed aerobic-anaerobic infections such as cat-bite infections, and can be used in the treatment of canine urinary tract infections, as well as treatment of streptococcal infections.

Commonly isolated organisms that are naturally resistant to ampicillin include Acinetobacter, Pseudomonas aeruginosa, Klebsiella, Yersinia and Enterobacter. Resistance among staphylococci is widespread and is increasing due to the increased prevalence of methicillin-resistant staphylococci (MRS).

Cephalosporins are an important class of antibiotics with numerous different drugs in use. They are members of the beta-lactam group and differ from antibiotics such as ampicillin in their increased resistance to beta-lactamases and increased ability to penetrate the cell wall.

Cephalexin has the advantage of oral administration and is widely used in small animal medicine for the treatment of canine skin infections and canine and feline urinary tract infections. Although the risk is cross-reaction is rare, cephalexin should not be administered to animals with hypersensitivity to penicillin, and care should be taken when handled by veterinary staff or owners with known allergy to penicillin. It should not be used in herbivores.

Commonly isolated organisms that are naturally resistant to cephalexin include Pseudomonas aeruginosa, Acinetobacter, Yersinia and Enterococcus. Resistance among staphylococci is increasing due to the increased prevalence of methicillin-resistant staphylococci (MRS). Cephalexin displays good activity against streptococci and Actinomyces.

Clindamycin is a member of the lincosamide group, and although different structurally to the macrolide group (e.g. erythromycin) they share many pharmacological features. Lincomycin is the original antibacterial compound of the class, with only clindamycin showing increased activity.

Clindamycin may be administered orally, intravenously, parenterally, or subcutaneously. It has the advantage of accumulating in neutrophils, macrophages, and abscesses. This makes it particularly effective against anaerobic organisms, either in monotherapy or in combination with fluoroquinolones or aminoglycosides. Clindamycin should not be administered to horses, rabbits, guinea pigs, hamsters, or chinchillas.

Commonly isolated organisms that are naturally resistant to clindamycin include aerobic Gram-negative organisms (e.g. E. coli, Proteus mirabilis, Pseudomonas aeruginosa). It has good activity against streptococci and staphylococci. It is important that the laboratory tests for inducible resistance to clindamycin.

Enrofloxacin and marbofloxacin are members of the fluoroquinolone group that also includes ibafloxacin, ofloxacin, and pradofloxacin. They are typically well absorbed orally, exhibit low toxicity, penetrate nearly every tissue and cell in the body, and have extended elimination half-lives, allowing for every 24- or 48-hour dosing. At appropriate drug concentration:MIC ratios, the fluoroquinolones are rapidly bactericidal, and may exhibit a prolonged in vivo post-antibiotic effect (PAE) on certain bacteria.

Both are usually active against both Gram-negative and Gram-positive organisms, with slightly higher MIC’s required for Gram-positive bacteria due to a different target within the organism. Fluoroquinolones are not recommended in younger dogs (< 18 months depending on breed) or cats younger than 16 weeks.

However, the potential for fairly rapid selection of resistance in some pathogens is a disadvantage of this class of drugs. This can be minimised by appropriate dose selection, based on the MIC. The total amount of drug given daily, rather than the dosing regimen, primarily determines the in vivo potency of these drugs. Resistance is low among Enterobacteriaceae but is widespread in isolates of Pseudomonas aeruginosa and is relatively high in strains of Staphylococcus schleiferi. Because of the mechanism of resistance, cross-resistance to other fluoroquinolones is common as well as to other classes of antibiotics.

ESBL’s are a broad group of enzymes ( >400) that act against beta-lactam antibiotics. They are of particular importance in human medicine as they transfer resistance to a large group of antibiotics. They are most commonly associated with certain members of the Enterobacteriaceae – particularly Klebsiella, E. coli, Enterobacter, Proteus and Serratia; and to a lesser extent in Pseudomonas aeruginosa.

ESBL’s are not widespread among small animal bacterial isolates, however their incidence is increasing, and all relevant strains are tested for this as a matter of course at IDEXX Laboratories. Any beta-lactam antibiotics that affected by an ESBL will have their sensitivity results automatically amended so that no false-sensitive results are reported.

This is most commonly associated with staphylococci although it may be present among corynebacteria and streptococci.

Unless specifically looked for, organisms show apparent in vitro susceptibility to clindamycin, but resistance will quickly develop if the infection is treated with clindamycin leading to treatment failure.

Testing for ICR is always performed and reported on staphylococcal isolates and the incidence has remained relatively low, although there has been a significant increase in prevalence among methicillin-resistant Staphylococcus pseudintermedius in 2014.

Following the discovery and use of penicillin, resistance was quickly discovered, and synthetic penicillins such as methicillin (now referred to as meticillin) were created. Once resistance to methicillin was discovered in Staphylococcus aureus, the strains were referred to as methicillin-resistant S. aureus (MRSA).

Methicillin is no longer manufactured and it has been superseded by oxacillin, however the nomenclature has remained. Oxacillin is not used in a therapeutic role; instead it is used in reference laboratories for sensitivity testing to determine whether or not the strain is resistant to all beta-lactams.

Oxacillin resistance gained headlines through the spread of MRSA in hospitals and other healthcare facilities. In the veterinary arena, there has been a marked increase in recent years in the prevalence of methicillin-resistant staphylococci, particularly S. pseudintermedius (MRSP) and to a lesser extent S. schleiferi (MRSS). Of particular concern is the resistance to other classes of antibiotics exhibited by MRSP, often leaving very few antibiotic treatment options open to the veterinarian.

These compounds consist of a combination of two antibacterials – a sulphonamide and trimethoprim – that are antibiotics in their own right and together exhibit synergistic activity, usually at least 10 times higher than if the individual components were administered separately. The most common combination in small animal use is sulfadiazine-trimethoprim, in the ratio of 5:1.

Potentiated sulphonamides are bacteriocidal, broad-spectrum antibiotics, and are recommended as a first-line treatment for uncomplicated UTI’s and are useful in treating prostatic infections due to good tissue penetration. They are also used for respiratory and enteric infections, and are widely used for equine patients due to their oral formulation.

Commonly isolated organisms that are naturally resistant to potentiated sulphonamides include Pseudomonas aeruginosa and Mycoplasma spp. Resistance has progressed steadily since its introduction but is not considered widespread.