Antibiotics

AntibioticsNarrow Spectrum Penicillins
and
Penicillinase Stable Penicillins
Extended Spectrum Penicillins
+
β-Lactamase Inhibitors
1st Generation Cephalosporins
and
2nd Generation Cephalosporins
3rd Generation Cephalosporins
and
4th Generation Cephalosporins
AminoglycosidesTetracyclinesAmphenicolsMacrolidesLincosamidesPleuromutilinsFluoroquinolonesNitroimidazolesNitrofuransPotentiated Sulfonamides (PSA)
AMEGDCCB
Forbidden for Chicken
C

Spectinomycin: D
DCCCCBD
Forbidden for FPS
D
Forbidden for FPS
D
Drugs:Benzylpenicillin-Na/K, Procaine, Benzathine
Phenoxymethyl-Penicillin
Penethamat

Methicillin
Oxacillin
Cloxacillin
Dicloxacillin
Flucloxacillin
Nafcillin
Amoxicillin-Clavulanic Acid

Ampicillin-Sulbactam
Cefalexin
Cefadroxil

Cefapirin
Cefalonium
Cefazoline
Cefalotin

Cefaclor
Cefuroxime Axetil

Cefoxitin
Cefotetan
Cefuroxime
Cefixime
Cefpodoxime
Proxetil

Cefovecin
Ceftiofur
Cefotaxime
Ceftazidime
Ceftriaxone
Cefoperazone

Cefquinome
Spectinomycin

Streptomycin
Dihydrostreptomycin
Neomycin Tobramycin
Kanamycin
Amikacin
Paromomycin
Framycetin
Apramycin

Gentamicin
Tetracycline
Oxytetracycline
Chlortetracycline

Doxycycline
Minocycline
Chloramphenicol
Tiamphenicol
Florfenicol
Tylosin
Erythromycin
Spiramycin
Tilmicosin

Tylvalosin
Tildipirosin
Tulathromycin
Gamithromycin

Azithromycin
Clarithromycin
Roxithromycin
Lincomycin
Clindamycin
Pirlimycin
Tiamulin
Valnemulin
Enrofloxacin
Marbofloxacin
Ciprofloxacin
Difloxacin
Orbifloxacin
Ofloxacin

Pradofloxacin

Metronidazole
Ronidazole
Secnidazole
NitrofurantoineSulfacetamide
Sulfadimidine
Sulfamethoxazole
Sulfachloropyridazine
Sulfadiazine
Sulfaquinoxaline
Sulfachloropyrazine
Sulfasalazine
Sulfadimethoxine

Trimethoprim
Trimethoprim
Baquiloprim
Pyrimethamine
Diaveridine
Structure:Hydrophilic

β-Lactams ring with Thiazolidine ring
Hydrophilic

β-Lactams ring with Thiazolidine ring
+
Suicide inhibitor
Hydrophilic

β-Lactams ring with Dihydrothiazine ring
Lipophilic

β-Lactams ring with Dihydrothiazine ring
Hydrophilic and weak base

Glycoside with Amines
Lipophilic

4 Cycles

Bind Ca2+ and Mg2+
Lipophilic

Small molecule

Phenylpropanoid structure
Lipophilic and weak base

Macrocyclic lactone ring with sugar moieties and Tertiary Amine
Lipophilic and weak base

Similar properties to Macrolides
Lipophilic and weak base

Similar properties to Macrolides
Lipophilic

Quinolone ring with Fluor atom
Lipophilic

Nitro group on heterocycle

Sulfonamides:
PABA Analogue
Precipitates at low pH

Diaminopyrimidines:
Lipophilic
Mechanism of action:PBP Inhibitor
No wall synthesis
PBP and β-Lactamase inhibition
No wall synthesis
PBP Inhibitor
No wall synthesis
PBP Inhibitor
No wall synthesis
30S Inhibitor: Nonsense Protein synthesis30S Inhibitor50S Inhibitor50S Inhibitor50S Inhibitor50S InhibitorDNA Topoisomerase II and IV InhibitorProdrug IC activation
DNA damages
Prodrug IC activation
Macromolecular damages
Folic Acid Synthesis Pathway Inhibitor
Mode of action:Time Dependent Bactericidal Agents

PAE > BID Administration
Time Dependent Bactericidal Agents



PAE > BID Administration
Time Dependent Bactericidal AgentsTime Dependent Bactericidal AgentsConcentration Dependent Bactericidal Agents


PAE > SID Administration
Bacteriostatic AgentsBacteriostatic Agents

Bactericidal Agents at high concentration
Bacteriostatic Agents

Bactericidal Agents at high concentration
Bacteriostatic AgentsBacteriostatic AgentsConcentration Dependent Bactericidal Agents


PAE
Concentration Dependent Bactericidal AgentsTime Dependent Bactericidal AgentsBacteriostatic Agents alone

Time Dependent Bactericidal Agents together
Resistance:Ab ovo:
Mycobacterium
Mycoplasma
Chlamydia
Enterococcus


Acquired:
PBP mutation for MRSA/MRSP

β-Lactamase:
Staphylococcus
Ab ovo:
Mycobacterium
Mycoplasma
Chlamydia



Acquired:
PBP mutation for MRSA/MRSP

Overuse:
Enterobacteriacea
Ab ovo:
Mycobacterium
Mycoplasma
Chlamydia
Enterococcus
Bordetella

Acquired:
PBP mutation for MRSA/MRSP


β-Lactamase:
E. coli
ESBL
Ab ovo:
Mycobacterium
Mycoplasma
Chlamydia
Enterococcus
Bordetella

Acquired:
PBP mutation for MRSA/MRSP


β-Lactamase:
E. coli
ESBL
Rare

Ab ovo:
Anaerobes (Gr+ and Gr-)
Streptococcus

Acquired:
One way Cross resistance


Resistance is common for Spectinomycin
Ab ovo:
Mycobacterium
Pseudomonas

Acquired:
E. coli, Salmonella
Pasteurella
Streptococcus
Staphylococcus
Less resistance problems

Ab ovo:
Mycobacterium
Pseudomonas
Not frequent

Cross resistance with Lincosamides and Amphenicols
Bad situation

Most Gr-
Including Fastidious and E. coli

Cross resistance with Macrolides and Amphenicols




Enterobacteriaceae

Unidirectional Cross resistance with Macrolides
Very frequent

One step mutation

Single shot injection

High in Chicken
Lower in Swine

Frequent cross resistance in MRSA/MRSP
Low resistance

Ab ovo:
Proteus
Pseudomonas
Ab ovo:
Pseudomonas
Campylobacter
Brachyspira
Mycoplasma
Borrelia
Leptospira
Mycobacterium
Enterococcus
Spirochaetes
Many Staphylococcus

Acquired:
Enterobacteriaceae
Proteus
Chlamydia
Anaerobes
Antibacterial spectrum:Almost all Gr+:
Clostridium
Streptococcus

Penicillinase Stable Penicillins only:
Staphylococcus


Narrow Spectrum Penicillins only:
Some Gr-:
Anaerobes
Fastidious
Tick borne:
Leptospira
Borrelia






Almost all Gr+:
Clostridium
Streptococcus




Staphylococcus
Enterococcus




Several Gr-:
Anaerobes
Fastidious
Tick borne:
Leptospira
Borrelia

Prevotella

Enterobacteriaceae: UTI only
1st Generation Cephalosporins:
Gr+: ++++
Streptococcus
Staphylococcus

Gr-: +
Not most β-Lactamase producers







2nd Generation Cephalosporins:
Gr+: +++

Gr-:++
Enterobacteriaceae
3rd Generation Cephalosporins:
Gr+: +++

Gr-: +++
Most β-Lactamase producers

Anaerobes
Fastidious
E. coli
Borrelia

Pseudomonas: Ceftazidime and Cefoperazone

4th Generation Cephalosporins:
Gr+: ++++
Gr-: ++++
Almost everything
Mostly Gr- aerobes:
Fastidious
Enterobacteriaceae Bordetella
Leptospira
Proteus

Mycoplasma: Spectinomycin


Few Gr+ aerobes:
Staphylococcus
(Mycobacterium)


MRSA/MRSP: Amikacin


Pseudomonas: GTA

Protozoa:
Leishmania
Cryptosporidium
All Gr+:
Except (Mycobacterium)

Most Gr-:
Anaerobes
Fastidious
Bordetella
Lawsonia
Rickettsiae
Moraxella
(Enterobacteriaceae)

Wolbachia: Doxycycline
Borrelia and Anaplasma: Doxycycline 1st choice

Chlamydophilae: Tetracycline 1st choice

Protozoa:
Plasmodium
Entamoeba
Babesia
Theileria
Gr+ and Gr-

Aerobes and Anaerobes
Fastidious

Mycoplasma
Chlamydophilae

Rickettsiae
Moraxella

Aeromonas
Vibrio


MRSA / MRSP:
Florfenicol
Good for Gr+

Few Gr-:
Anaerobes
Fastidious
Bordetella
Mycoplasma
Chlamydophilae
Borrelia


Campylobacter: ACE
Rhodococcus: ACE
Brachyspira: Tylvalosin
Lawsonia: Tylosin, Tylvalosin
Good for Gr+

Few Gr-:
Anaerobes


Mycoplasma




Campylobacter



Brachyspira: Lincomycin
Lawsonia

Toxoplasma: Lincomycin
Fine for Gr+:

Some Gr-:
Anaerobes
Fastidious

Mycoplasma








Brachyspira

Lawsonia

Many Gr-:
Anaerobes: Pradofloxacin
Fastidious
Bordetella
Mycoplasma
Chlamydophilae


Enterobacteriaceae

Proteus
Aeromonas

Pseudomonas: CME


Staphylococcus

Streptococcus: Pradofloxacin
Clostridium

Few Gr-:
Anaerobes
Helicobacter and HLO
















Protozoa:
Giardia
Trichomonas
Tritrichomonas
Limited importance:

Staphylococcus
Enterococcus

E. coli















Protozoa
Most Gr+:
Streptococcus
Clostridium
Erysipelothrix
Nocardia
S. hyicus

Many Gr-:
Fastidious
Bordetella




Protozoa:
Coccidia
Toxoplasma
Pharmacokinetics: AbsorptionPoor

Except Phenoxymethyl-Penicillin (PO)
Amoxicillin: Excellent

Ampicillin: Moderate and reduced by feed
GoodMostly Parenteral


Very poor

PO for GI infection only
Short Acting Tetracyclines:
Moderate (binds Ca2+ / Mg2+)

Long Acting Tetracyclines:
Excellent
ExcellentVariableGood

Decreased with food
Good

Decreased with food

Unchanged with water
Excellent

But bad taste

PO F decreased with ions
ExcellentGoodGood

Decreased with Puss
Pharmacokinetics: DistributionPoor


Except Penethamat: Crosses BBB and BMB
GoodVery Good

Crossing the BBB: Ceftazidime, Ceftriaxone, Cefoperazone


High protein binding:
Cefovecin, Ceftiofur
Poor





Doesn’t cross special barriers
Very good

Reaches bones



Crosses the BBB
Excellent

Reaches bones, placenta, prostate, brain

Crosses special barriers
Cross the BBB


Penetrate IC

Concentrate in the lungs
Good

Reaches the bones, placenta, prostate

Crosses the BMB
Doesn’t cross the BBB

Penetrate IC

Concentrate in the lung
Excellent

Reaches the bones, liver, kidneys, skin, eyes, prostate

Doesn’t cross the BBB
Excellent





Crosses the BBB



Penetrates IC
Excellent





Crosses special barriers: BBB, BMB, Prostate

Penetrates IC

Not influenced by Organic materials
Excellent





Crosses special barriers: BBB, Prostate, Abcesses walls
Doesn’t reach therapeutic concentration in tissuesExcellent





Cross special barriers: BBB, BMB, Prostate
Pharmacokinetics: MetabolismNo
No
No
Extensive liver metabolismNo
Low degree
Hepatotoxic on long term
Extensive liver metabolismExtensive liver metabolism

Erythromycin:
CYP450 inhibition
Extensive liver metabolismLiver metabolism



CYP450 inhibition
Partial metabolism
Metabolites are active

CYP450 inhibition
Acetylation in Cats > Crystalluria
Pharmacokinetics: EliminationUrine mainlyUrine (Active)
Concentrated
Urine (Active)

Except Cefaclor in Bile
Urine (Active)

Except: Ceftriaxone and Cefoperazone in Bile
Gamma phase: Kidney accumulationShort Acting Tetracyclines:
Urine Concentrated

Long Acting Tetracyclines:
Large intestine: 75%
Bile: 15%
Urine: 10%
Urine (Mainly inactive)

Bile
Bile (active): 90%

Feces

Long milk WP
Active

Bile: 80-85%
Urine: 15-20%


Bile
Urine
Active

Urine: Mainly
Bile: Partially
Rapid excretion in Urine and Bile

Persisting protein-bound metabolites
Active excretion in Urine
Side effects:Almost non-toxic

Allergy
Dysbacteriosis

Procaine:
Arrythmia and excitement in Foals and Piglets
Almost non-toxic


Allergy
Dysbacteriosis
Mild toxicity


Allergy
Dysbacteriosis

Mild nephrotoxicity
Tissue irritation
Mild toxicity


Allergy
Dysbacteriosis

Mild nephrotoxicity
Tissue irritation
Ototoxic
Nephrotoxic (especially Cats)

Muscle relaxation
Hepatotoxic
Nephrotoxic
Photosensitivity

Arrythmia
Tissue necrosis
Dysbacteriosis
Teeth discoloration
Aplastic Anemia
Pancytopenia

Dysbacteriosis

Accumulates in egg and milk

Bad taste
Painful injection
Cardiotoxicity


Dysbacteriosis

Fatal hyperthermia

Tissue irritation
GI irritation


Fatal Dysbacteriosis

Oesophageal necrosis

Tissue irritation
Low toxicity


Dysbacteriosis

CNS signs

Erythema

Vulvar edema
Tissue irritation
Safe

Cartilage damage
Retinopathy

CNS signs
Forbidden for FPS

Carcinogenic for rodents
CNS signs
Forbidden for FPS

Carcinogenic for rodents
Residue toxicity
Safe

Crystalluria for Cats
KCS for Dogs
Sulfmethemoglobinemia
Vitamin K deficiency
Hemorrhagic syndrome
Immunocomplexes
Pancytopenia
Indication:Narrow Spectrum Penicillins:
Respiratory infections (Fastidious)

GI infections (Clostridium)

Streptococcosis

Anthrax
Tetanus
Swine erysipelas


Extended Spectrum Penicillins:
Mastitis



Respiratory infections (Fastidious)

GI infections (Clostridium)

Streptococcosis

Anthrax
Tetanus
Swine erysipelas





Mastitis
Dermatitis
Soft tissue infections
Osteomyelitis
Septicaemia

UTI

Oral infections

Lyme disease
1st Generation Cephalosporins:
Dermatitis, Soft tissue infections, Mastitis

Preoperative prophylaxis


2nd Generation Cephalosporins:
Similar to Extended Spectrum Penicillins


Cephamycins:
Oral infection
Bite wounds
Respiratory infections (Fastidious)

Dermatitis, Soft tissue infections, Mastitis
Metritis
Septicaemia

Foot rot

BBB Crossing:
Meningitis, Lyme disease
Respiratory infections (Fastidious, Mycoplasma: Spectinomycin)

GI infections (Aerobic): 1st choice


UTI
Mastitis
Osteomyelitis
Topical
Septicaemia


Protozoa infections: Paromomycin
Leishmania
Cryptosporidium
Respiratory infections (Fastidious, Mycoplasma, Bordetella)

Swine pathogens (S. suis, G. parasuis, B. bronchiseptica)

Feline Mycoplasmosis

Mastitis
Metritis
Foot rot
Infectious Keratoconjunctivitis
Ileitis

Nocardiosis
Heartworm
Heartwater

1st choice:
Lyme disease (D)
Anaplasmosis (D)
Chlamydophilosis (T)

Angular limb deformities
Autoimmune diseases
Respiratory infections (Fastidious, Mycoplasma)


Swine pathogens (S. suis, G. parasuis, E. coli)

Fish pathogens (A. salmonicida, V. anguillarum)


(Foot rot)
Infectious Keratoconjunctivitis

MRSA/MRSP
Otitis
Dermatitis
Prostatitis
Meningitis
Respiratory infections (Fastidious, Mycoplasma, Bordetella, Chlamydophilae, Rhodococcus: ACE G)

GI infections (Clostridium, Campylobacter: ACE, Swine dysentery: Tylvalosin
Ileitis: Tylosin, Tylvalosin)

Oral infections, Bite wounds, Anal sacculitis

Lyme disease
Respiratory infections (Mycoplasma, Fastidious: combined with Spectinomycin)

GI infections (Brachyspira, Lawsonia, Clostridium)

Mastitis, Dermatitis

Foot rot, Wound, Abscesses


Toxoplasmosis


Bone, Placenta, Prostate infections
Respiratory infections (Fastidious, Mycoplasma)




GI infections (Brachyspira, Lawsonia, ERE: Valnemulin)


Leptospirosis

Swine erysipelas
Respiratory infections (Fastidious, Mycoplasma, Bordetella)



GI infections
UTI
Osteomyelitis

Acute Mastitis and Prostatitis (E. coli): 1st choice

Oral infections: Pradofloxacin


Soft tissue infections, Pyoderma
Otitis externa
Cat biliary disease
Meningitis


Peritonitis: with Amoxicillin-Clavulanic Acid or Metronidazole









Severe GI infections (Clostridium, Helicobacter)




Oral infections, Anal sacculitis, Abscess


Protozoa infections
Multidrug resistant UTIRespiratory infections (Fastidious, Bordetella, Nocardia)

UTI
Prostatitis
Acute Mastitis
Colitis












Protozoa infections:
Coccidia
Toxoplasma