Veterinary · Para-clinical · also MSVE VPT-411
Antibacterial, antifungal, antiprotozoal, anthelmintic, ectoparasiticide and anticancer drugs, and the prudent use that slows antimicrobial resistance.
In the exams: ICAR AIEEA-PG 13 Unit IV (drug resistance); ICAR AICE-JRF core group 07; EAEVE Day One prescribing competences
Veterinary chemotherapy is the use of drugs that kill or inhibit organisms infecting an animal, or tumour cells growing in it, while sparing the animal. This subject covers the antibacterial classes one by one, then the antifungal, antiprotozoal, anthelmintic and ectoparasiticide drugs, and a chapter on anticancer drugs. For each class you should know the mechanism, spectrum, pharmacokinetic and pharmacodynamic (PK/PD) behaviour, the species in which it is dangerous, how resistance arises, and where it sits in regulation.
The second half of the subject is antimicrobial stewardship. Every antimicrobial dose selects for resistance in the target pathogen and in the animal's commensal flora, and resistant bacteria and genes move between animals, people and the environment. Veterinarians therefore carry two duties: to treat the patient in front of them effectively, and to protect the usefulness of these drugs for later patients of every species. Stewardship covers the WHO and WOAH importance rankings, the rules on antimicrobial use in food animals in the European Union, the United States and India, and the programmes that measure and reduce use in practices and farms.
The subject is examined everywhere. Indian postgraduate entrance (ICAR AIEEA-PG, Veterinary Science unit IV) asks about mechanisms of drug resistance and drug classes; the ICAR PhD entrance asks for depth on mechanisms, PK/PD and resistance genes. North American, British, Australasian and South African licensing exams test applied choices: the right drug for the infection and species, species toxicities, and the legal limits on use in food animals. EAEVE and RCVS Day One competences expect a new graduate to prescribe responsibly and explain why. No drug dose in this manual should be used without checking it against the product label and the national formulary of the country where you work, because licensed doses, withdrawal periods and legal status vary between countries and products.
Chemotherapy is the use of chemicals that harm an infecting organism or a tumour cell more than they harm the host. The idea rests on selective toxicity: the drug hits a target the host lacks or has in a different form. Bacteria have a peptidoglycan cell wall, 70S ribosomes made of 30S and 50S subunits, their own DNA gyrase and topoisomerase IV, and they must make folic acid themselves. Mammals have none of these, which is why penicillins, aminoglycosides, fluoroquinolones and sulphonamides can be given at all. Antibacterials are grouped in four ways. By target: cell wall synthesis (beta-lactams, glycopeptides, fosfomycin), cell membrane (polymyxins), protein synthesis at the 30S subunit (aminoglycosides, tetracyclines) or the 50S subunit (macrolides, lincosamides, amphenicols, pleuromutilins), nucleic acid synthesis (fluoroquinolones, rifamycins, nitroimidazoles) and intermediary metabolism (sulphonamides, trimethoprim). By effect: bactericidal drugs kill, bacteriostatic drugs stop growth and leave the kill to host defences; the line depends on drug concentration and organism, so it is a tendency rather than a fixed property. By spectrum: narrow (penicillin G, mostly Gram-positive and some anaerobes) or broad (tetracyclines, potentiated sulphonamides, fluoroquinolones). By PK/PD pattern, which decides how a dose is spaced.
Pharmacokinetics describes what the body does to the drug; pharmacodynamics what the drug does to the organism. For antibacterials the link between the two is the minimum inhibitory concentration (MIC), the lowest concentration that prevents visible growth in a standard test. Three indices predict success. Time-dependent drugs kill best when free concentration stays above the MIC for a large part of the dosing interval, written %fT>MIC; beta-lactams are the classic example, so they are given frequently, by infusion or as long-acting formulations, and raising the peak adds little. Concentration-dependent drugs kill faster the higher the peak; aminoglycosides are judged by Cmax/MIC (a ratio of about 8-10 is the commonly quoted target) and are given once daily, which also lowers kidney toxicity. Fluoroquinolones are judged by AUC24/MIC, the area under the 24-hour free-drug curve divided by the MIC; targets of about 125 for Gram-negative infections and lower values for Gram-positive organisms are widely quoted, though the exact figure depends on species and immune status. Tetracyclines, macrolides such as azithromycin and glycopeptides are described as co-dependent and are also judged by AUC/MIC. The post-antibiotic effect (PAE) is continued suppression of growth after concentration falls below the MIC; it is long for aminoglycosides and fluoroquinolones against Gram-negative bacteria, which supports long dosing intervals. The mutant prevention concentration (MPC) is the concentration that blocks growth of the least susceptible single-step mutant; the range between MIC and MPC is the mutant selection window, where resistant mutants are enriched. Dosing that spends little time inside this window slows resistance.
A culture and susceptibility test tells the clinician whether an isolate is likely to respond. Broth microdilution exposes the isolate to two-fold dilutions of each drug (for example 0.25, 0.5, 1, 2, 4 µg/mL) and reports the MIC. Disk diffusion (the Kirby-Bauer method on Mueller-Hinton agar) measures the zone of inhibition around a drug-impregnated disk; the zone diameter is converted to a category. An MIC means nothing alone; it is interpreted against a breakpoint. A clinical breakpoint divides isolates into susceptible (S), intermediate or, in EUCAST terms, susceptible at increased exposure (I), and resistant (R), and it is set from MIC distributions, PK/PD data and clinical outcome for a stated host species, infection site and dosing regimen. CLSI publishes veterinary-specific breakpoints (its VET01 standard and VET01S tables); EUCAST sets human breakpoints and its veterinary subcommittee VetCAST is developing animal ones. Where no veterinary breakpoint exists, laboratories borrow human values, which may not fit an animal's pharmacokinetics. An epidemiological cut-off value (ECOFF) is different: it separates the wild-type population from isolates with acquired resistance mechanisms and is used for surveillance, not to predict cure. MIC50 and MIC90 are the MICs that inhibit 50% and 90% of isolates in a collection. A susceptible result can still fail if the drug does not reach the site or a biofilm protects the organism, and MICs of different drugs cannot be compared directly.
Combinations are justified to widen cover in a life-threatening infection before culture results arrive, to gain synergy, or to stop resistance emerging during treatment. Synergy means the combined effect exceeds the sum: a beta-lactam damages the cell wall and lets an aminoglycoside enter, and trimethoprim with a sulphonamide blocks two steps of folate synthesis. Antagonism is classically described when a bacteriostatic drug (a tetracycline) is combined with a drug that needs active growth to kill (a penicillin). Macrolides, lincosamides and amphenicols bind close to each other on the 50S subunit and should not be combined. Rifampicin is always combined with another drug because single-step resistance appears quickly. Choosing a drug follows a sequence: is the infection bacterial and does it need an antimicrobial at all; which organisms are likely at this site in this species; will the drug reach the site at an effective concentration; what are the species-specific toxicities; is the drug legal for this species and, in a food animal, what withdrawal period follows; and where does it sit in the national or WHO/WOAH importance ranking. Treatment failure has many causes besides resistance: wrong diagnosis, poor compliance, under-dosing, an undrained focus and immunosuppression.
Sulphonamides are structural analogues of para-aminobenzoic acid (PABA). They compete with PABA for dihydropteroate synthase, so the bacterium cannot make dihydrofolic acid. Mammals take preformed folate from the diet and are unaffected, which is the basis of selective toxicity. Alone, sulphonamides are bacteriostatic. Trimethoprim, a diaminopyrimidine, inhibits bacterial dihydrofolate reductase, the next step, and binds the bacterial enzyme far more strongly than the mammalian one; ormetoprim and baquiloprim are related drugs. The two together produce sequential blockade, which is often bactericidal and slows resistance. Commercial potentiated sulphonamides contain one part trimethoprim to five parts sulphonamide, although the two drugs have different kinetics and the ratio in plasma is not the same as in the bottle. The spectrum is broad: many Gram-positive and Gram-negative aerobes, some protozoa (Toxoplasma, coccidia) and Nocardia, with weak activity against anaerobes and none against Pseudomonas aeruginosa. Sulphonamides are inactive in pus and necrotic tissue, because dead cells release PABA, thymidine and purines that bypass the block; drainage and debridement come first. Sulphonamides are classified by duration and absorption: short-acting systemic (sulfadiazine, sulfamethazine also called sulfadimidine), long-acting (sulfadimethoxine), poorly absorbed gut-active (sulfaguanidine, phthalylsulfathiazole) and topical (silver sulfadiazine for burns, sulfacetamide for the eye). Sulfasalazine is cleaved in the colon into sulfapyridine and 5-aminosalicylic acid and is used for its anti-inflammatory effect in canine colitis.
Sulphonamides are acetylated in the liver in most species and excreted in urine. Dogs acetylate poorly, which is one reason they show idiosyncratic reactions. Older, less soluble sulphonamides and their acetyl metabolites precipitate in acidic, concentrated urine and cause crystalluria and renal tubular damage; water must be freely available. In dogs, sulphonamides can cause keratoconjunctivitis sicca (a direct toxic effect on lacrimal acinar cells, so tear production should be checked during long courses), immune-mediated reactions including polyarthritis, fever, skin eruptions, thrombocytopenia and hepatopathy (Doberman pinschers are over-represented), and reduced thyroid hormone concentrations during prolonged treatment. In horses, intravenous trimethoprim-sulphonamide given with alpha-2 agonist sedatives such as detomidine has been associated with fatal arrhythmias, and any oral antimicrobial can trigger colitis. Sulphonamide residues in pork and milk have historically been among the commonest residue violations, and sulfamethazine is a residue of regulatory concern. In the United States, extra-label use of sulphonamides in lactating dairy cattle is prohibited except for the approved uses of named sulphonamides; other countries regulate through maximum residue limits and withdrawal periods. Sulphonamides and trimethoprim are ranked low on importance lists (EMA category D, 'prudence'), which makes them a reasonable first-line choice where susceptibility allows. Nitrofurans (furazolidone, nitrofurazone, nitrofurantoin) are reduced inside the bacterium to reactive intermediates that damage DNA. Their residues are mutagenic and carcinogenic, and they are prohibited in food-producing animals in the European Union, the United States, India and many other countries; residue monitoring looks for tissue-bound metabolites. Nitrofurantoin is still used for lower urinary tract infection in dogs and cats because it reaches useful concentrations only in urine. Nitroimidazoles (metronidazole, dimetridazole, ronidazole, tinidazole) are activated by reduction under anaerobic conditions, so they act on obligate anaerobes and on protozoa such as Giardia, Trichomonas and Entamoeba. They are likewise prohibited in food animals in the EU and US because of genotoxicity concerns. In dogs high or prolonged doses of metronidazole cause a vestibulo-cerebellar syndrome that usually resolves when the drug is stopped; it is bitter and causes salivation in cats.
Beta-lactams share a four-membered beta-lactam ring. They bind penicillin-binding proteins (PBPs), the transpeptidases that cross-link peptidoglycan in the final step of cell-wall synthesis. The weakened wall fails under osmotic pressure and autolysins complete the kill, so beta-lactams are bactericidal against growing bacteria. They are time-dependent and mostly have short half-lives. Mycoplasma, which lacks a cell wall, is intrinsically resistant. Toxicity to mammals is low; hypersensitivity is the main risk. Natural penicillins (benzylpenicillin, also called penicillin G, and phenoxymethylpenicillin, penicillin V, which is acid-stable for oral use) are narrow-spectrum: streptococci, non-beta-lactamase-producing staphylococci, Clostridium, Erysipelothrix, Actinomyces, Trueperella and many anaerobes. Benzylpenicillin is given as the sodium or potassium salt for rapid high levels, or as procaine and benzathine salts that release slowly from intramuscular depots. Procaine penicillin accidentally given intravenously to horses causes excitement, collapse or death from procaine, and procaine can cause positive tests in competition horses. Penicillinase-resistant penicillins (cloxacillin, oxacillin, methicillin) withstand staphylococcal beta-lactamase; cloxacillin is widely used in intramammary dry-cow products. Aminopenicillins (ampicillin, amoxicillin) extend the spectrum to some Gram-negatives such as E. coli, Proteus and Pasteurella but are destroyed by beta-lactamases. Ureido- and carboxypenicillins (piperacillin, ticarcillin) reach Pseudomonas aeruginosa. Beta-lactamase inhibitors (clavulanic acid, sulbactam, tazobactam) bind beta-lactamases irreversibly and protect the partner drug; amoxicillin-clavulanate is one of the most used drugs in small-animal practice.
Cephalosporins are grouped in generations by spectrum. First generation (cefalexin, cefazolin, cefadroxil, cephapirin, cefalonium) are strong against Gram-positive cocci including beta-lactamase-producing staphylococci and moderate against some Enterobacterales; cefalexin is a standard drug for canine pyoderma and cefazolin for surgical prophylaxis. Second generation (cefuroxime, cefoxitin) gain Gram-negative activity; cefoxitin, a cephamycin, has anaerobic activity. Third generation (ceftiofur, cefovecin, cefpodoxime, ceftriaxone, cefotaxime, ceftazidime) are much more active against Enterobacterales; ceftiofur is widely licensed for cattle and pigs, and cefovecin is a long-acting injection for dogs and cats whose very high plasma protein binding gives a dosing interval of about two weeks. Fourth generation (cefquinome, cefepime) add stability to some beta-lactamases. Third- and fourth-generation cephalosporins are classed as highest priority critically important by WHO and are restricted in many countries (EMA category B), because their use selects for extended-spectrum beta-lactamase (ESBL) and AmpC producers. Carbapenems (imipenem, meropenem) are human last-line drugs; they are not authorised for animals in the EU and their veterinary use elsewhere should be confined to documented, susceptible, life-threatening infections with no alternative, if it is legal at all. Hindgut fermenters (rabbits, guinea pigs, hamsters, chinchillas) given oral penicillins, aminopenicillins or cephalosporins can develop fatal clostridial enterotoxaemia because the Gram-positive flora is destroyed. Resistance is chiefly beta-lactamase production, altered PBPs (the mecA gene in methicillin-resistant Staphylococcus aureus and S. pseudintermedius encodes PBP2a, conferring resistance to almost all beta-lactams) and, in Gram-negatives, porin loss and efflux. Glycopeptides (vancomycin, teicoplanin) bind the D-alanyl-D-alanine terminus of peptidoglycan precursors and act only on Gram-positive bacteria. They are not authorised for animals in the EU and US. The glycopeptide avoparcin was used as a growth promoter in Europe until 1997, when it was banned because its use was linked to vancomycin-resistant enterococci in animals and the food chain; this is the standard example of growth-promoter use selecting for resistance to a human drug. Fosfomycin inhibits MurA, the first committed step of peptidoglycan synthesis; it is used in poultry and pigs in some countries and is regarded as critically important to human medicine.
Aminoglycosides include streptomycin and dihydrostreptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin and apramycin. They are polar, positively charged molecules that cross the outer membrane through porins and the inner membrane by an oxygen-dependent transport process. Inside, they bind the 30S ribosomal subunit and cause misreading of messenger RNA; the faulty proteins damage the membrane and let more drug in. The result is rapid, concentration-dependent killing with a long post-antibiotic effect. Because uptake needs oxygen, aminoglycosides do not act on anaerobes, and activity falls in acidic, hypoxic pus. Their spectrum is aerobic Gram-negative bacilli (Enterobacterales; Pseudomonas for gentamicin, tobramycin and amikacin), staphylococci and some mycobacteria. They are poorly absorbed from the gut, which is why oral neomycin is used for enteric effect and to reduce ammonia-producing flora in hepatic encephalopathy, but systemic use needs injection. They distribute in extracellular fluid, cross membranes poorly, do not reach cerebrospinal fluid well and are excreted unchanged by glomerular filtration. Combined with a beta-lactam they are synergistic. Amikacin resists most of the modifying enzymes that inactivate gentamicin and is often kept for resistant Gram-negative infections.
Three toxicities define the class. Nephrotoxicity follows uptake and accumulation in proximal tubular cells; risk rises with dehydration, prolonged treatment, high trough concentrations, concurrent NSAIDs or loop diuretics, and old age. Once-daily dosing gives a high peak for killing and a long drug-free trough that lets tubular cells clear the drug, so it is both more effective and less toxic than divided dosing; therapeutic drug monitoring of trough concentrations is used in horses, foals and critically ill dogs. Casts in urine sediment and a rise in urine gamma-glutamyl transferase are early signs, appearing before azotaemia. Ototoxicity affects the cochlea (deafness, more with neomycin and amikacin) or vestibular apparatus (ataxia, nystagmus, more with streptomycin and gentamicin); cats are notably sensitive to vestibular damage. Neuromuscular blockade, from reduced acetylcholine release at the motor end-plate, can cause apnoea when aminoglycosides are given with anaesthetics or neuromuscular blockers, or are instilled into body cavities; calcium reverses it. In food animals aminoglycosides persist in the kidney for many months, giving very long withdrawal periods; several regulators discourage systemic use of gentamicin in cattle for this reason. Resistance is mainly by aminoglycoside-modifying enzymes (acetyltransferases, phosphotransferases and nucleotidyltransferases), often plasmid-borne; 16S rRNA methyltransferases give high-level resistance to almost all members; reduced uptake also occurs. Spectinomycin is an aminocyclitol that binds the 30S subunit, is bacteriostatic and lacks the typical aminoglycoside toxicity.
Polymyxin B and colistin (polymyxin E) are cationic polypeptides. They bind the negatively charged lipid A of lipopolysaccharide, displace stabilising calcium and magnesium, and disrupt the outer and inner membranes of Gram-negative bacteria in a detergent-like way. They are bactericidal and have no Gram-positive activity; Proteus and Serratia are intrinsically resistant. Absorption from the gut is negligible, so oral colistin has been used in pigs, calves and poultry for enteric Gram-negative infection. Systemically they are nephrotoxic and neurotoxic. Polymyxin B also binds circulating endotoxin and is used at low doses in horses with endotoxaemia, with attention to kidney function. Colistin became a human last-resort drug for carbapenem-resistant Enterobacterales, and in 2015 the plasmid-mediated mcr-1 gene, which modifies lipid A, was reported from pigs and people in China and then found worldwide. This changed policy: WHO ranks polymyxins as highest priority critically important, the EU places them in category B with sales reduction targets, and India banned colistin for food-producing animals, poultry, aquaculture and animal feed supplements in 2019.
Tetracyclines (chlortetracycline, oxytetracycline, tetracycline, and the more lipophilic doxycycline and minocycline) bind the 30S subunit and block attachment of aminoacyl-tRNA to the acceptor site. They are bacteriostatic and broad-spectrum: Gram-positive and Gram-negative bacteria, Mycoplasma, Chlamydia, Rickettsia, Anaplasma, Ehrlichia, Borrelia, Leptospira and some protozoa. They chelate divalent and trivalent cations, so oral absorption falls when given with milk, calcium, magnesium, aluminium or iron, and they are deposited in growing teeth and bone, which causes yellow discoloration of the teeth. Rapid intravenous injection in cattle and horses can cause collapse, attributed to calcium chelation and to the propylene glycol vehicle of some products, so injections are given slowly. In cats, doxycycline tablets or capsules can lodge in the oesophagus and cause oesophagitis and stricture; a water or food bolus should follow each dose. In horses tetracyclines can disturb the hindgut flora and cause colitis, and intravenous doxycycline has caused fatal cardiovascular reactions. Doxycycline is cleared largely by non-renal routes and is the tetracycline of choice in renal impairment and for canine ehrlichiosis. Long-acting oxytetracycline formulations are used in ruminants, for example against respiratory disease, anaplasmosis and infectious keratoconjunctivitis. Resistance is by efflux pumps (tet(A), tet(B)) and ribosomal protection proteins (tet(M), tet(O)), both common and transferable; tetracyclines are often the most heavily used class by weight in food animals and are EMA category D. Chloramphenicol, thiamphenicol and florfenicol bind the 50S subunit and inhibit peptidyl transferase. They are bacteriostatic, broad-spectrum (including anaerobes, Rickettsia and Chlamydia) and lipid-soluble, so they penetrate the eye, brain and prostate. Chloramphenicol causes a rare, idiosyncratic, often fatal aplastic anaemia in humans that is not dose-related, attributed to its para-nitro group; for that reason it is prohibited in food-producing animals in the EU, US, India and most other countries, and people handling it should avoid skin contact and inhalation. In animals it causes dose-related, reversible bone-marrow suppression, to which cats are more sensitive. It inhibits hepatic cytochrome P450 enzymes and prolongs the action of drugs such as barbiturates. Florfenicol lacks the para-nitro group, does not carry the aplastic anaemia risk and is licensed for bovine respiratory disease, pig respiratory disease and fish.
Macrolides bind the 23S rRNA of the 50S subunit and block the exit tunnel for the growing peptide. They are mainly bacteriostatic, time- or AUC-dependent, and active against Gram-positive bacteria, Mycoplasma, Campylobacter, Pasteurella and Mannheimia (for the newer veterinary drugs), Lawsonia and Rhodococcus equi. They are weak bases that concentrate in acidic compartments and inside phagocytes and lung tissue; in the udder they are ion-trapped in milk. Erythromycin is also a motilin agonist and is used as a gastrointestinal prokinetic. Tylosin is used in pigs and poultry and for chronic diarrhoea in dogs. Tilmicosin is used in cattle and pigs; it is cardiotoxic, accidental self-injection has killed people, and injectable use is limited to the labelled species. Tulathromycin, gamithromycin and tildipirosin are long-acting injectables for respiratory disease in cattle and pigs, giving single-dose treatment and metaphylaxis. Azithromycin and clarithromycin, combined with rifampicin, are standard for R. equi pneumonia in foals; foals on erythromycin can develop hyperthermia with reduced sweating, and adult horses given macrolides risk severe colitis, as can mares exposed through foal faeces. Resistance comes from erm genes that methylate 23S rRNA (giving macrolide-lincosamide-streptogramin B, or MLSB, cross-resistance), from mef efflux pumps and from ribosomal mutations. WHO treats macrolides as critically important because they are key drugs for human Campylobacter infection. Lincosamides (lincomycin, clindamycin, pirlimycin) bind the 50S subunit near the macrolide site. They act on Gram-positive cocci and anaerobes, and clindamycin is also active against Toxoplasma gondii and is used for osteomyelitis, dental and soft-tissue infections in dogs and cats. Pirlimycin is an intramammary drug for cattle. Lincosamides are dangerous to horses, rabbits, guinea pigs and hamsters, in which they cause severe and often fatal colitis or enterotoxaemia; oral lincomycin in ruminants causes ruminal disturbance. Pleuromutilins (tiamulin, valnemulin) bind the peptidyl transferase centre of the 50S subunit and are used in pigs and poultry against Brachyspira (swine dysentery), Mycoplasma and Lawsonia. Tiamulin inhibits the hepatic metabolism of ionophore anticoccidials (monensin, narasin, salinomycin), so feeding the two together causes ionophore toxicity with muscle damage, paralysis and death; the interaction is dose-related and a standard exam point.
Quinolones began with nalidixic acid, a narrow urinary antiseptic; adding a fluorine at position 6 produced the fluoroquinolones. Veterinary members include enrofloxacin, marbofloxacin, danofloxacin, difloxacin, orbifloxacin, ibafloxacin and pradofloxacin; ciprofloxacin and norfloxacin are mainly human drugs, and enrofloxacin is partly de-ethylated to ciprofloxacin in most species. They inhibit DNA gyrase (topoisomerase II), the main target in Gram-negative bacteria, and topoisomerase IV, the main target in many Gram-positive bacteria, trapping the enzyme-DNA complex and breaking chromosomal DNA. They are rapidly bactericidal and concentration-dependent, judged by AUC24/MIC and Cmax/MIC, with a post-antibiotic effect. The spectrum covers Enterobacterales, Pasteurella, Mannheimia, Haemophilus and Histophilus, staphylococci, Mycoplasma and, at higher exposure, Pseudomonas; most older members are weak against streptococci and anaerobes, while pradofloxacin has better anaerobic activity. They are well absorbed orally in monogastrics (absorption falls with cations such as antacids and sucralfate), have large volumes of distribution, penetrate tissues and cells well and are excreted by kidney and liver.
Fluoroquinolones damage articular cartilage in young, rapidly growing animals, especially large-breed puppies and foals, so they are generally avoided in these patients. Enrofloxacin at high doses causes acute retinal degeneration and blindness in cats; the cat's sensitivity is linked to a defect in a retinal drug transporter, and label dose limits for cats must be respected. They can lower the seizure threshold and should be used with care in epileptic patients. Because fluoroquinolones are first-line human drugs for serious Gram-negative and Campylobacter and Salmonella infections, WHO lists them as highest priority critically important, WOAH flags them as veterinary critically important with caveats against first-line and prophylactic use, and the EU places them in category B (restrict). In the United States, extra-label use in food-producing animals is prohibited, and in 2005 the FDA withdrew approval of enrofloxacin for poultry after use in poultry was linked to fluoroquinolone-resistant Campylobacter in people. Resistance arises stepwise from point mutations in the quinolone resistance-determining regions of gyrA and parC, from up-regulated efflux and reduced porins, and from plasmid-mediated genes (qnr proteins that protect gyrase, the aac(6')-Ib-cr acetyltransferase, and qep or oqx efflux pumps); single mutations raise the MIC modestly and successive mutations produce high-level resistance, which is why the mutant selection window matters for this class. Rifampicin (rifampin) binds the beta subunit of bacterial DNA-dependent RNA polymerase, encoded by rpoB. It is lipid-soluble, penetrates cells and abscesses, and is active against staphylococci, Rhodococcus equi and mycobacteria. Single-step rpoB mutations give resistance rapidly, so it is always combined with another drug. It is a potent inducer of hepatic cytochrome P450 enzymes, shortening the action of many co-administered drugs, and colours urine, tears and saliva red-orange. Fusidic acid inhibits elongation factor G and is used topically for staphylococcal skin and eye infections in dogs and cats. Mupirocin, an isoleucyl-tRNA synthetase inhibitor, is a topical human drug used occasionally against MRSP in dogs; human-health bodies discourage its veterinary use. Topical antiseptics such as chlorhexidine and hypochlorous acid are increasingly used instead of systemic antimicrobials for superficial skin infection.
Intrinsic resistance is a property of every member of a species: Mycoplasma lacks a cell wall and ignores beta-lactams, anaerobes lack the oxygen-dependent transport that aminoglycosides need, Pseudomonas aeruginosa has an impermeable outer membrane and efflux pumps, enterococci are inherently resistant to cephalosporins, and Gram-negative bacteria exclude vancomycin. Acquired resistance appears in strains of a normally susceptible species, by mutation or by gaining genes. Whatever the origin, there are four biochemical routes. First, enzymatic inactivation: beta-lactamases hydrolyse the beta-lactam ring; aminoglycoside-modifying enzymes acetylate, phosphorylate or adenylate the drug; chloramphenicol acetyltransferase inactivates chloramphenicol. Second, altered or protected target: PBP2a encoded by mecA in methicillin-resistant staphylococci, erm methylation of 23S rRNA, gyrA and parC mutations, ribosomal protection proteins for tetracyclines, and mcr-encoded modification of lipid A. Third, reduced access: loss of outer-membrane porins and multidrug efflux pumps that export several unrelated classes. Fourth, target bypass or overproduction: resistant dihydropteroate synthase (sul1, sul2, sul3) and dihydrofolate reductase (dfr) genes. Cross-resistance means one mechanism covers several drugs, usually in the same class (all beta-lactams with mecA; macrolides, lincosamides and streptogramin B with erm). Co-resistance means separate genes for different classes travel together on one mobile element, so using any one drug selects for all of them; this is co-selection. Heavy metals and some biocides can co-select in the same way.
Spontaneous mutations arise at low frequency in any large bacterial population; an antimicrobial then selects the mutants. Horizontal gene transfer is the faster route. Conjugation passes plasmids, often carrying several resistance genes, from donor to recipient through direct contact and works between different species and genera, including from commensal E. coli in the gut to pathogens. Transformation is uptake of free DNA from the environment. Transduction is transfer by bacteriophages. Transposons ('jumping genes') move between chromosome and plasmids, and integrons, especially class 1 integrons with their integrase gene and often a sul1 gene, capture and express arrays of resistance gene cassettes. Some clones then spread successfully: livestock-associated MRSA of clonal complex 398 colonises pigs, veal calves and poultry and the people who work with them; ESBL- and AmpC-producing E. coli circulate between poultry, poultry meat and people; methicillin-resistant Staphylococcus pseudintermedius, often resistant to most systemic classes, has become a major problem in canine dermatology. ESBLs (CTX-M types are now the most common worldwide) hydrolyse third-generation cephalosporins and are inhibited by clavulanate; plasmid AmpC enzymes such as CMY-2 also hydrolyse cephamycins (cefoxitin) and are not inhibited by clavulanate; carbapenemases (KPC, NDM, OXA-48 types) are the most feared because few options remain.
Not all survival is resistance. Tolerance and persistence describe bacteria that survive exposure without a rise in MIC, often because they are dormant. Biofilms, structured communities in a self-made matrix on implants, catheters, damaged tissue or inside the udder, can survive concentrations far above the planktonic MIC; removing the implant or debriding is often essential. Resistance has several costs. Clinically, it causes treatment failure, longer illness, more culling and deaths, and pushes clinicians toward broader, more toxic or more important drugs. For public health, resistant bacteria and genes pass from animals to people by direct contact, through food, and through manure, wastewater and the environment, and they pass back; this two-way flow is why antimicrobial resistance is a One Health problem. Because of compensatory mutations and co-selection, resistance often falls only slowly when use is reduced. Surveillance runs nationally (for example the US NARMS and EU harmonised monitoring) and globally through WHO GLASS and WOAH ANIMUSE.
The World Health Organization ranks antimicrobial classes by importance to human medicine. Two criteria decide whether a class is critically important: it is the sole or one of few therapies for serious human infection, and it treats infections caused by bacteria that may come from non-human sources or carry resistance genes from them. Classes meeting both are 'critically important', those meeting one are 'highly important' and the rest 'important'. Within the critically important group, the highest priority critically important antimicrobials (HPCIA) in the 6th revision (2018) were third-, fourth- and fifth-generation cephalosporins, glycopeptides, macrolides and ketolides, polymyxins and quinolones. In 2024 WHO reissued the list as the WHO Medically Important Antimicrobials List, adjusted the categories and added a group of antimicrobials authorised for use in humans only, which it recommends should not be used in animals; check the current edition rather than memorising one version. The World Organisation for Animal Health (WOAH) publishes a complementary List of Antimicrobial Agents of Veterinary Importance, grading classes as veterinary critically important (VCIA), highly important (VHIA) or important (VIA) for animal health. WOAH recommends that fluoroquinolones, third- and fourth-generation cephalosporins and colistin not be used for prevention in feed or water without clinical signs, not be used as first-line treatment unless justified, and not be used at all as growth promoters.
The EU banned all antimicrobial growth promoters from 1 January 2006, after earlier bans on individual drugs such as avoparcin. Regulation (EU) 2019/6 on veterinary medicinal products applies from 28 January 2022. It prohibits routine use and use to compensate for poor hygiene or husbandry, prohibits use to promote growth, restricts prophylaxis to individual animals in exceptional cases and metaphylaxis to situations where the risk of spread is high and no alternative exists, requires a prescription after clinical examination or other proper assessment, and limits an antimicrobial prescription's validity to five days. Implementing Regulation (EU) 2022/1255 designates antimicrobials reserved for human use, which may not be used in animals at all, including under the cascade; it includes carbapenems and glycopeptides among others. The European Medicines Agency's Antimicrobial Advice Ad Hoc Expert Group (AMEG) categorises classes for veterinary prescribers: A 'Avoid' (not authorised in veterinary medicine), B 'Restrict' (third- and fourth-generation cephalosporins, polymyxins and quinolones, to be used only when culture and susceptibility show nothing in C or D will work), C 'Caution' (for example macrolides, lincosamides, pleuromutilins, amphenicols, most aminoglycosides and aminopenicillin-beta-lactamase inhibitor combinations) and D 'Prudence' (for example natural penicillins, aminopenicillins without inhibitors, tetracyclines and sulphonamides with trimethoprim).
In the United States, FDA Guidance for Industry #209 and #213 ended production (growth-promotion and feed-efficiency) uses of medically important antimicrobials in feed and water from January 2017 and put the remaining therapeutic feed uses under veterinary oversight through the Veterinary Feed Directive (21 CFR 558.6), which requires a veterinarian-client-patient relationship (VCPR) and does not allow extra-label use in feed. Guidance #263 moved the remaining over-the-counter medically important antimicrobials, such as some injectable and intramammary products, to prescription status in June 2023. Extra-label drug use under AMDUCA and 21 CFR Part 530 is allowed only within a VCPR, and 21 CFR 530.41 prohibits extra-label use in food animals of chloramphenicol, nitrofurans, nitroimidazoles, fluoroquinolones and glycopeptides, among other substances, and restricts extra-label use of cephalosporins (other than cephapirin) in major food species. India issued a National Action Plan on AMR in 2017, banned colistin for food-producing animals, poultry, aquaculture and feed supplements in 2019, and through FSSAI residue regulations prohibits a list of substances, including chloramphenicol and nitrofurans, in food-animal production with tolerance limits for others; state action plans and regulatory detail are still developing and should be checked against current gazette notifications. Across most countries the direction is the same: no growth promotion with medically important drugs, prescription-only access, recorded use, withdrawal periods and maximum residue limits (MRLs) set under Codex Alimentarius or national law, and special protection for the highest-priority classes.
Prudent or responsible use means using antimicrobials only when they are needed, choosing the right drug, giving it correctly, and recording and reviewing what was done. The WOAH Codes and the Codex Code of Practice on foodborne antimicrobial resistance set out the core rules. Make a diagnosis first and confirm that the problem is bacterial and that it will not resolve without treatment. Take samples for culture and susceptibility testing whenever practical, and always for recurrent, severe or non-responding cases, before treatment begins. Prefer narrow-spectrum drugs from the lowest importance category that will work; reserve critically important classes for cases where testing shows no alternative. Use local treatment (intramammary, topical, otic) in place of systemic treatment where it is effective. Give the labelled dose for the labelled duration, based on an actual weight; under-dosing selects resistance. Use the shortest effective course; for many conditions shorter courses have proved as effective as traditional long ones. Record every treatment and observe withdrawal periods. Prevent the need for antimicrobials: vaccination, colostrum management, biosecurity, ventilation, stocking density, nutrition and breeding for disease resistance are stewardship measures too. Three terms must be distinguished. Treatment is giving an antimicrobial to clinically sick animals. Metaphylaxis (control) is treating a group in which some animals are clinically sick, to treat those and to protect the rest that are likely incubating infection. Prophylaxis (prevention) is giving antimicrobials to animals with no clinical sign of disease.
Antimicrobial stewardship is the organised, continuing effort that turns those principles into habit in a practice, hospital, farm or company. Programmes borrowed from human hospitals share a set of elements: commitment from leadership, a named person accountable, a written policy, practice-level prescribing guidelines, action on prescriptions, tracking of use and resistance, reporting back to prescribers, and education of staff and clients. Common actions are a formulary ranking drugs as first-line, second-line and restricted, approval before a restricted class is dispensed, prescription audit with feedback, and clear client advice. Species guidelines help: the International Society for Companion Animal Infectious Diseases (ISCAID) publishes guidance for urinary tract infection, respiratory disease and superficial bacterial folliculitis in dogs and cats, which advises, for example, against treating subclinical bacteriuria in most patients, favouring topical antiseptic therapy for superficial pyoderma and avoiding antimicrobials in most cases of acute diarrhoea and of uncomplicated infectious respiratory disease. In dairy herds, selective dry-cow therapy treats only quarters or cows with evidence of infection (by somatic cell count, culture or clinical history) and uses an internal teat sealant in the rest.
Use must be measured before it can be reduced. National sales data are expressed in milligrams of active substance per population correction unit (mg/PCU), where the PCU is an estimate of the weight of livestock at risk of treatment; the European Surveillance of Veterinary Antimicrobial Consumption project (ESVAC, now continued under the EU's ESUAvet reporting) used this unit and showed large differences between countries. Farm and practice data are better expressed as defined daily doses or defined course doses for animals (DDDvet, DCDvet) or as treatment incidence, which allow for differences in dose between drugs. Some countries benchmark farms and veterinarians against each other: the Netherlands set national reduction targets and benchmark thresholds for each livestock sector from around 2009, and Denmark's 'yellow card' scheme sets limits on use in pig herds; both achieved large falls in use without loss of productivity. Success is judged by falling use of the most important classes, falling resistance in surveillance, and stable or improving animal health and welfare; a fall in use bought by leaving sick animals untreated is not stewardship.
Fungi are eukaryotes, so selective targets are fewer than in bacteria; most antifungals attack ergosterol, the fungal counterpart of cholesterol, or the fungal cell wall. Polyenes (amphotericin B, nystatin, natamycin) bind ergosterol and form pores in the membrane; they are fungicidal. Amphotericin B is given intravenously for systemic mycoses such as blastomycosis, cryptococcosis and histoplasmosis and is nephrotoxic, so it is given with saline loading, kidney monitoring and, where affordable, in lipid-complex or liposomal forms that reduce toxicity. Nystatin is not absorbed and treats candidiasis of the skin, mouth and gut. Azoles inhibit lanosterol 14-alpha-demethylase, a cytochrome P450 enzyme, blocking ergosterol synthesis; they are mostly fungistatic. Imidazoles include ketoconazole (oral), miconazole, clotrimazole and enilconazole (topical). Ketoconazole also inhibits mammalian steroid synthesis and hepatic drug metabolism, is hepatotoxic and is poorly tolerated by cats. Triazoles are more selective: itraconazole is used for dermatophytosis in cats (often in pulse regimens), Malassezia, aspergillosis and systemic mycoses; fluconazole is water-soluble, excreted in urine and penetrates cerebrospinal fluid, making it a choice for cryptococcal meningitis and urinary candidiasis; voriconazole and posaconazole extend activity against moulds, but voriconazole has caused neurological and visual adverse effects in cats. Allylamines (terbinafine) inhibit squalene epoxidase and accumulate in keratin. Griseofulvin disrupts fungal microtubules and is deposited in new keratin; absorption improves with a fatty meal; it is teratogenic and contraindicated in pregnancy, and it can cause severe bone-marrow suppression, notably in cats infected with feline immunodeficiency virus. Flucytosine is converted inside fungal cells to fluorouracil and is combined with amphotericin B for cryptococcosis; it has caused skin eruptions in dogs. Topical therapy (enilconazole or lime sulphur rinses, miconazole-chlorhexidine shampoo) and environmental decontamination are essential parts of dermatophytosis control, and dermatophytosis is a zoonosis.
Coccidiosis caused by Eimeria in poultry, cattle, sheep, goats and rabbits, and by Cystoisospora in pigs, dogs and cats, is controlled mainly by drugs given in feed or water and, in poultry, increasingly by live vaccines. Ionophores (monensin, lasalocid, salinomycin, narasin, maduramicin, semduramicin) are polyether antibiotics that carry cations across parasite membranes and disrupt ion gradients. They are also used in cattle to improve feed efficiency and reduce bloat and lactic acidosis. Horses are extremely sensitive and develop fatal myocardial and skeletal muscle necrosis after eating feed containing ionophores, dogs are also sensitive, and tiamulin increases ionophore toxicity in pigs and poultry. Synthetic or 'chemical' anticoccidials include amprolium, a thiamine analogue that competes for thiamine uptake (high or prolonged use can cause polioencephalomalacia in ruminants); the triazinones toltrazuril and diclazuril, which act on all intracellular stages and are used as single oral treatments in piglets, calves and lambs; decoquinate and clopidol, which act on parasite mitochondrial respiration; nicarbazin; robenidine; halofuginone; and sulphonamides, which remain useful for treatment of outbreaks. To slow resistance, broiler producers use shuttle programmes (different drugs in starter and grower feeds within one flock) and rotation programmes (changing drug between flocks), and alternate drug use with vaccination. Anticoccidials in layer and dairy rations are tightly regulated because of egg and milk residues; follow the label and national law.
Babesiosis is treated with imidocarb dipropionate or diminazene aceturate. Imidocarb is also active against Anaplasma, gives some weeks of protection and leaves long tissue residues; it has anticholinesterase-like effects (salivation, colic, diarrhoea) that atropine can prevent. Diminazene aceturate treats babesiosis and trypanosomosis; it has a narrow safety margin and camels and dogs are particularly sensitive. For trypanosomosis, isometamidium chloride is used mainly for prophylaxis over several months and diminazene for treatment; the two are used as a 'sanative pair', switching between them to manage resistance, which is widespread in parts of Africa. Theileriosis (Theileria annulata in Asia, North Africa and southern Europe; T. parva, East Coast fever, in eastern and southern Africa) is treated with the hydroxynaphthoquinone buparvaquone. Cryptosporidiosis in neonatal calves has no fully effective drug; halofuginone lactate reduces oocyst shedding and diarrhoea when used to the label and has a narrow margin between effective and toxic doses. Giardia is treated with fenbendazole or metronidazole plus bathing and hygiene. Canine leishmaniosis is managed with meglumine antimoniate or miltefosine combined with long-term allopurinol, which can cause xanthine urolithiasis; treated dogs often remain infected.
Benzimidazoles (thiabendazole, albendazole, fenbendazole, oxfendazole, mebendazole, oxibendazole) and the pro-benzimidazoles (febantel, netobimin, thiophanate, converted to active drug in the body) bind parasite beta-tubulin and stop microtubule formation, starving the worm of glucose uptake and transport. They are broad-spectrum against nematodes, ovicidal, and some (albendazole, at higher label doses) act on adult liver fluke; albendazole is teratogenic in early pregnancy. Triclabendazole is a benzimidazole used almost only against Fasciola and is active against early immature as well as adult flukes. Macrocyclic lactones comprise the avermectins (ivermectin, abamectin, doramectin, eprinomectin, selamectin) and milbemycins (moxidectin, milbemycin oxime). They open glutamate-gated chloride channels in nematode and arthropod nerve and muscle, causing flaccid paralysis, and are active against nematodes and many ectoparasites ('endectocides') but not flukes or tapeworms. Mammals lack these channels, and P-glycoprotein at the blood-brain barrier keeps the drugs out of the brain; dogs homozygous for the MDR1 (ABCB1) deletion, common in Collies and related herding breeds, develop neurotoxicity at doses safe for other dogs. Imidazothiazoles (levamisole) and tetrahydropyrimidines (pyrantel, morantel, oxantel) are nicotinic acetylcholine receptor agonists that cause spastic paralysis; levamisole has a narrow safety margin and also stimulates immunity. Piperazine is a GABA agonist causing flaccid paralysis, mainly against ascarids, and antagonises pyrantel, so the two are not combined. Newer classes are monepantel (a nematode-specific nicotinic receptor subtype), derquantel (a nicotinic antagonist) and emodepside (SLO-1 potassium channel). Against cestodes and trematodes, praziquantel increases calcium permeability of the tegument and is the drug of choice for Echinococcus and Taenia in dogs; salicylanilides (closantel, rafoxanide, oxyclozanide) and the substituted phenol nitroxynil uncouple oxidative phosphorylation, and closantel binds plasma albumin so strongly that it persists for weeks and protects against Haemonchus and Oestrus ovis; clorsulon inhibits fluke glycolytic enzymes.
Anthelmintic resistance is the heritable ability of worms to survive a dose that normally kills them. It is now common in small ruminant nematodes, especially Haemonchus contortus, Teladorsagia and Trichostrongylus, with multiple-drug resistance in many countries; in horse cyathostomins to benzimidazoles and pyrantel, with shortened egg reappearance periods after macrocyclic lactones; in Parascaris to macrocyclic lactones; in cattle Cooperia and Ostertagia to macrocyclic lactones; in Fasciola hepatica to triclabendazole; and in the dog hookworm Ancylostoma caninum, where multiple-drug-resistant strains have been reported in the United States. Benzimidazole resistance is linked to single-nucleotide changes in the isotype-1 beta-tubulin gene (codons 200, 167 and 198), which molecular tests can detect. Resistance is measured mainly by the faecal egg count reduction test (FECRT): eggs per gram are counted before and 10-14 days after treatment (the interval depends on drug), or in treated and untreated groups, and the percentage reduction is calculated as 100 x (1 - post-treatment count / pre-treatment count). The long-used WAAVP criteria classed resistance as a reduction below 95% with the lower 95% confidence limit below 90%; the revised WAAVP guideline of 2023 sets expected efficacy thresholds by host and drug and changes the statistics, so use the current guideline. Management rests on refugia, the part of the worm population not exposed to the drug (on pasture or in untreated animals), which dilutes resistant survivors. Practical measures: treat on faecal egg counts or clinical indicators rather than by calendar; use targeted selective treatment, for example by the FAMACHA anaemia score for Haemonchus or by weight gain; weigh animals and dose to the heaviest in a group, since under-dosing selects resistance; use combinations of unrelated classes where licensed; quarantine-drench and test new stock; and avoid moving all treated animals to clean pasture at once.
Organophosphates (for example diazinon, coumaphos) inhibit acetylcholinesterase irreversibly and carbamates (carbaryl, propoxur) reversibly; poisoning causes muscarinic, nicotinic and central signs and is treated with atropine and, for organophosphates before the enzyme 'ages', an oxime such as pralidoxime. Synthetic pyrethroids (permethrin, cypermethrin, deltamethrin, flumethrin) keep insect sodium channels open; cats metabolise them poorly and dog spot-ons containing concentrated permethrin cause tremors and seizures in cats. Pyrethroids are highly toxic to fish. Amitraz, a formamidine, acts on octopamine receptors in mites and ticks and on alpha-2 adrenoceptors in mammals; poisoning causes sedation, bradycardia and hyperglycaemia, reversed by alpha-2 antagonists such as atipamezole, and it causes colic in horses. Phenylpyrazoles (fipronil) block GABA-gated chloride channels; fipronil is toxic to rabbits. Neonicotinoids (imidacloprid, nitenpyram) and spinosyns (spinosad) act on insect nicotinic receptors. Isoxazolines (afoxolaner, fluralaner, sarolaner, lotilaner) block GABA- and glutamate-gated chloride channels in fleas and ticks and are given orally or topically; regulators have warned of neurological adverse events such as tremor, ataxia and seizures in some dogs and cats. Insect growth regulators break the life cycle: juvenile hormone analogues (methoprene, pyriproxyfen) and chitin synthesis inhibitors (lufenuron; fluazuron for cattle ticks). Resistance is serious in the cattle tick Rhipicephalus microplus, resistant to organophosphates, pyrethroids, amitraz, macrocyclic lactones and fluazuron in different regions. The same prudent-use logic applies: identify the parasite, treat only when needed, dose correctly, rotate unrelated classes and use non-chemical control.
Cytotoxic drugs kill dividing cells, so their main toxicities fall on tissues with fast turnover: bone marrow (neutropenia, usually reaching its lowest point about one week after many drugs), gut epithelium (vomiting, diarrhoea, inappetence) and, in some breeds, hair follicles. Veterinary protocols aim at remission with good quality of life, and most dogs and cats have mild or no side effects. Drugs are cell-cycle phase-specific (antimetabolites act in S phase, vinca alkaloids in M phase) or phase-nonspecific (alkylating agents). Each dose kills a constant fraction, not a constant number, of tumour cells (the log-kill idea), so repeated cycles are needed and treatment works best when tumour burden is small. Combination protocols use drugs with different mechanisms and non-overlapping toxicities to increase kill and delay resistance; CHOP-based protocols (cyclophosphamide, doxorubicin as the 'hydroxydaunorubicin', vincristine as 'Oncovin', and prednisolone) are the standard for canine multicentric lymphoma. Doses for most cytotoxics are calculated per square metre of body surface area (BSA), estimated as BSA (m²) = K x weight(kg)^(2/3) / 100, with K about 10.1 for dogs and 10.0 for cats; because small animals have more surface per kilogram, some drugs are dosed per kilogram in small dogs and cats to avoid toxicity. Drug resistance arises from efflux by P-glycoprotein (the product of ABCB1) and other mechanisms; dogs with the MDR1 deletion suffer severe toxicity from vincristine, vinblastine and doxorubicin, which are P-glycoprotein substrates. Before each dose a neutrophil count is checked and treatment delayed if it is too low; the threshold is set by the protocol. Any dose quoted in a protocol must be checked — confirm against the product label and your national formulary.
Alkylating agents cross-link DNA. Cyclophosphamide is activated in the liver; its metabolite acrolein causes sterile haemorrhagic cystitis, so it is given in the morning with encouragement to urinate, sometimes with furosemide. Chlorambucil is an oral drug for chronic lymphocytic leukaemia, low-grade lymphoma and feline small-cell intestinal lymphoma. Lomustine (CCNU) is lipid-soluble, crosses the blood-brain barrier, is used for mast cell tumours, histiocytic sarcoma and brain tumours, and causes cumulative hepatotoxicity in dogs and delayed thrombocytopenia. Melphalan is used for multiple myeloma. Antimetabolites mimic normal metabolites: methotrexate inhibits dihydrofolate reductase, cytarabine is a pyrimidine analogue used for lymphoma and meningoencephalitis, and 5-fluorouracil is a pyrimidine analogue that causes fatal neurotoxicity in cats and must never be used in them, including topically. Anthracyclines (doxorubicin, epirubicin) intercalate DNA, inhibit topoisomerase II and generate free radicals; doxorubicin causes cumulative, dose-related cardiomyopathy in dogs, nephrotoxicity in cats, severe tissue necrosis if it leaks outside the vein, and acute hypersensitivity reactions during infusion. Vinca alkaloids (vincristine, vinblastine) bind tubulin and arrest mitosis; they are vesicants, and vincristine also causes peripheral neuropathy and constipation. Platinum drugs cross-link DNA: cisplatin causes fatal pulmonary oedema in cats and is never used in them, and in dogs it is nephrotoxic and needs saline diuresis; carboplatin is less nephrotoxic and is myelosuppressive, and is used in both species. L-asparaginase depletes asparagine, which lymphoma cells cannot make, and can cause anaphylaxis. Corticosteroids (prednisolone) are lympholytic, but prednisolone alone before a full protocol can induce multidrug resistance and shorten later remission. Tyrosine kinase inhibitors (toceranib, masitinib) block KIT and other receptors and are licensed for canine mast cell tumours. NSAIDs that inhibit COX-2 (piroxicam, meloxicam) have measurable activity against canine urothelial carcinoma. Cytotoxics are rarely used in food animals, because of residues. Most cytotoxic drugs are carcinogenic, teratogenic or mutagenic to people. Staff should prepare them in a biological safety cabinet or with closed-system transfer devices, wear chemotherapy-tested gloves and impermeable gowns, avoid crushing or splitting tablets, and dispose of sharps and waste as cytotoxic waste. Pregnant staff should not handle them. Drugs and active metabolites are excreted in urine and faeces for days after treatment, so owners need written advice on wearing gloves when cleaning up, keeping children and pregnant people away from excreta, and washing hands. National occupational safety rules and the practice's written protocol take precedence.
Learn each class as a set of answers to the same questions: what is the target, is it cidal or static, time- or concentration-dependent, what does it cover and miss, which species does it harm, how do bacteria resist it, and how important is it to people. Draw the folate pathway and the ribosome once and place the drugs on them. Practise the arithmetic that exams ask: Cmax/MIC, AUC/MIC, time above MIC from a half-life, MIC50 and MIC90 from a list, FECRT percentage and body surface area. Memorise the short list of drugs banned in food animals and the species toxicities, because both are asked every year and both prevent real harm.
A practitioner five years out applies this subject daily: deciding whether a cough, a red skin or a diarrhoeic calf needs an antimicrobial at all, sampling for culture before treating recurrent and severe cases, reading an MIC report against the right breakpoint, choosing a first-line drug from the practice formulary, and explaining the course and withdrawal period to the client. On farms the work is herd-level: selective dry-cow therapy, metaphylaxis decisions for respiratory disease, faecal egg counts and FECRTs before choosing an anthelmintic, coccidiosis programmes, and keeping treatment records that will satisfy an auditor. In companion practice it includes MRSP pyoderma, urinary infections, and safe administration of chemotherapy protocols.
A senior clinician or practice owner sets the stewardship programme: writes the practice formulary and restricted list, audits prescribing against it, benchmarks antimicrobial use per farm or per consultation, and trains younger colleagues and lay staff. On large units they design vaccination, biosecurity and housing changes that remove the need for routine treatment, and negotiate with integrators and retailers whose contracts now set limits on use of critically important classes. They also handle the difficult cases: resistant infections, adverse drug reactions to report to the regulator, residue violations, and clients who demand antibiotics. They brief regulators and industry bodies on what restrictions are workable in the field.
A researcher with long experience works on the evidence that rules and guidelines rest on: PK/PD modelling and population pharmacokinetics to set dosing regimens and clinical breakpoints for veterinary species, surveillance design and the genomics of resistance transfer between animals, people and the environment, field trials of shorter courses and of alternatives such as vaccines, phage and immunomodulators, and the epidemiology of anthelmintic and acaricide resistance with molecular markers. They sit on committees that revise WHO, WOAH, Codex, CLSI and VetCAST documents and national action plans, and they must judge which data are strong enough to change practice.
This manual gives no dose regimens apart from the body-surface-area method: doses, intervals, withdrawal periods and MRLs vary by product and country and must be taken from the label and national formulary. It does not list every licensed product or every national restriction; Indian state-level rules and FSSAI tolerance tables in particular are described only in general terms and should be checked against current gazette notifications. The exact category assignments in the 2024 WHO Medically Important Antimicrobials List are summarised, not reproduced, and the 2023 WAAVP FECRT thresholds are referred to rather than tabulated. Aquaculture and bee medicines, antiviral drugs, therapeutic drug monitoring targets and the detailed molecular biology of each resistance gene are covered only briefly. Alternatives to antimicrobials (vaccines, bacteriophage, probiotics, zinc oxide withdrawal in pigs) are mentioned but not reviewed.
Original practice questions written to the syllabus and pattern of the exams named in each question's examTags. They are not past papers and do not reproduce any board's questions.
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