Oct 30, 2010

Selection of Antimicrobials...Pharmacology

It depends on the peculiarities of
  • Infecting organism
  • Drug
  • Patient
Objective is to have Selective action on infecting organism;
  • For a desirable period
  • With least effect on the host animal
Organism Related Factors
Target organism (Culture and identification, molecular biological techniques etc)
Sensitivity Pattern (Bacterial Sensitivity Test etc. like disc diffusion test.)
Drug Related Factors
Spectrum of activity: narrow vs. broad spectrum, combination of drugs.
Type of activity:  bacteriostatic vs. bactericidal.
Pharmacokinetic profile: Effective concentration at site of infection for adequate length of time.
Route of administration
Drug interactions (nsaid’s enhances CNS toxicity of fluoroquinolones)
Relative toxicity (penicillins are least toxic, chloramphenicol and clindamycin have serious toxicity)
Antimicrobial policy
Cost of therapy
Host Factors
Host defense mechanisms
Pathological conditions
  • Renal Diseases
  • Hepatic dysfunction
  • Meningitis
Local factors
  • Pus formation
  • Hematomas
  • pH
  • Age
  • Species
  • Pregnancy
  • Genetic Factors 
Bacterial Sensitivity Testing
Disc diffusion method
Tube dilution method
Combination of Antimicrobial Drugs
Objectives of combination
  • To broaden the spectrum of activity
  • To treat mixed infections
  • To achieve synergism
  • To prevent resistance
  • To minimize toxicity
Guidelines for combination of antimicrobial drugs:
  • Bactericidal + bactericidal = synergistic effect
  • Bacteriostatic + bacteriostatic = additive effect
  • Bactericidal + bacteriostatic = antagonistic effect 
Bactericidal: Bacteriostatic 
 Broad spect: Narrow spect
Tissue Distribution Pattern:
Drugs distributed to extracellular fluid
Penicillins, cephalosporins, aminoglycosides
Drugs in total body water
Fluoroquinolones, chloramphenicol, doxycyline, sulphonamides, erythromycin, clindamycin
Drugs to CSF
Sulphonamides, fluoroquinolones, doxycycline, metronidazole, rifampicin
Drugs in Bile
Doxycycline, erythromycin, clindamycin, rifampicin
Drugs in Urine
Fluoroquinolones, sulphonamides, nalidixic acid, nitrofurantoin, cephalosporins, penicillins, vancomycin
Prophylactic Use of Anti-Microbial Agents
  • In dirty contaminated wounds
  • After surgical operations
  • To prevent secondary bacterial infections
  • In disease outbreak
  • In endemic areas with high transmission ratio prevent post-partum infections in dams
Bacterial Resistance to Antimicrobials
Unresponsiveness of micro-organisms to an antimicrobial drug even at the maximum level that is tolerated by the host e.g G – ve to penicillin G and Vancomycin
Natural Resistance
  • Inherently or genetically resistant Due to
  • Lack of penetration of drug into bacterial cell
  • Absence of metabolic pathway or target site affected by drug
  • Rapid inactivation of drug in bact. cell
Acquired Resistance
When an organism becomes resistant to an antimicrobial agent to whom it was previously sensitive Due to Widespread and inappropriate use.
Mechanisms of Acquired Resistance Transmission
Spontaneously occurs in microorganisms
Occurs due to insertion, deletion or substitution of one or more nucleotides in the genome
Single step Mutation
  • Enterococci to streptomycin
  • Staphylococci to Rifampicin
Multi-step Mutation
  • Erythromycin
  • Tetracycline
  • Chloramphenicol
Gene Transfer
Develops by transfer of genetic material coding for resistance from a resistant microorganism to a susceptible organism
Resistant genes can be transferred b/w bacteria through:
Biochemical Mechanisms of Resistance
Alterations in drug penetration:
Decreased penetrability of an antimicrobial agent into the bacterial cell may occur due to either change in permeability of cell wall or alterations in transport systems.
Alterations in binding sites:
Antimicrobials fail to bind to their specific sites and cannot perform their action. e.g.
Alterations in penicillin binding proteins can confer resistance against penicillin
Alterations in metabolic pathways:
Some sulphas resistant bacteria start synthesis of their own PABA.
Drug inactivating enzymes:
These are either inducible or constitutive. e.g
Chloramphenicol is inactivated by acetyltransferases
Aminoglycosides are inactivated by certain transferases
Cross Resistance:
A type of acquired resistance in which bacteria resistant to one antimicrobial agent also become resistant to another antimicrobial without having exposed to the latter
Complete Cross Resistance (two way cross resistance)
Bact. Resistant to one antimicrobial are also resistant to a second drug and vice-versa
i). Neomycin   Kanamycin
ii) Erythromycin Oleandomycin
Partial Cross Resistance (one way cross resistance)
Bact. Resistant to one antimicrobial are also resistant to second drug, but resistance to second antimicrobial does not lead to resistance to first antimicrobial agent.
Gentamycin                 Kanamycin                  Steptomycin 
Adverse Reactions to Antimicrobial Agents
Direct tissue toxicity
  • nephrotoxicity        Aminoglycoside 
  • hepatotoxicity        Tetracyclines,
  • Neurotoxicity         Streptomycin,      
  • Bone marrow depression     Chloramphenicol
Sensitivity reactions (penicillins, cephalosporins, sulphonamides)
Super infection /supra infection
Appearance of a new infection as a result of indiscriminate use of antimicrobial drugs
Common with broad spectrum antimicrobials like tetracycline
Nutritional deficiencies (vitamin K, B)

Failure of Antimicrobial Therapy
  • Improper diagnosis of disease
  • Improper selection
  • Development of resistance
  • Mixed infections
  • Penetration to the site of infection (pus, exudates, tissue debris)
  • Impaired host defense mechanism
  • Improper route of drug administration
  • Inadequate duration
  • Relapse of dormant or refractory organisms
  • Improper management (nursing care)
  • Drug interaction
  • Delayed start of treatment
  • Expired or substandard drugs
  • No compliance with therapeutic regimen
Guidelines for Successful Anti-Microbial Therapy
  • Narrow spectrum (preferred for known organism) VS Broad spectrum (For unknown organism)
  • Bactericidal (Preferred) Vs Bacteriostatic
  • Less toxic (Preferred) Vs Potentially toxic
  • Long interval (Preferred) Vs short interval
  • Oral route (Preferred for less severe infections) Vs parenteral for severe infections)
  • Proper dose and duration of time
  • Proper combination of drugs
  • Avoid misuse (over use)
  • Cheap and easily available
  • Reliable pharmaceutical firm
  • Avoid antimicrobial use for untreatable infections

Chemotherapy & Classification of Antimicrobials

  • It is the branch of Pharmacology which deals with drugs which selectively inhibit or destroy specific pathogenic organisms like bacteria, viruses, fungi and parasites.
  • This term is extended to the use of drugs in the treatment of neoplastic diseases because of similarity between the malignant cells and the pathogenic microbes.
  • The term was first used by Paul Ehrlich in 1913 to describe drugs which attack invading organisms without harming the host.
Terms and Concepts
Chemotherapeutic Agents
The drugs used to interfere with the functioning of foreign cells.
Chemical substances produced by various micro organisms that kill or suppress growth of other micro organisms.
All chemical substances whether natural, synthetic or semi-synthetic that kill or suppress the growth of micro organisms
Selective Toxicity
It is the ability of an antimicrobial agent to kill an invading microorganism without harming the cells of the host.
Antimicrobial Activity
Refers to the ability of a compound to react with the microbial cell molecules in a way that interferes with growth and multiplication of microorganism or causes killing of the microorganism
Bacteriostatic Activity
It is the ability of the antibacterial agent to inhibit the growth and multiplication of bacteria.
Bactericidal activity
It is the ability of an antimicrobial agent to cause the death of the bacteria.
Antimicrobial Spectrum
Refers to the range of pathogenic organisms against which an antimicrobial agent is active.
B.S.A.M. are active against a wide variety of organisms.
N.S.A.M. are active against a few or a class/type of organisms.
Narrow Spectrum
Active against a few or class/type of organisms e.g, G + ve or G-ve.
Broad Spectrum
Active against a wide variety of organisms e.g.  both G + ve & G-ve.
Defined as the antimicrobial activity per miligram (microgram) of a chemotherapeutic agent
Expressed in:
All are determined in vitro.
Minimum Inhibitory Concentration (MIC)
It is the lowest concentration which prevents visible growth of bacteria when grown on serial dilutions in vitro.
Minimum Bactericidal Concentration (MBC)
Lowest concentration which kills the bacteria
Minimum Antibiotic Concentration (MAC)
Concentration which reduces the growth of an organism in vitro by factor of 10 (e.g. one log)
Used to express the activity of some drugs that exert antimicrobial action in vivo at conc. Below the MIC
Post Antibiotic Effect (PAE):
Effect even after antibiotic is out.
Biphasic (EAGLE) Effect
Effect at low doses but not at high doses
Properties of an ideal Antimicrobial Agent (AMA)
  • Powerful action against micro organisms
  • Selective toxicity
  • Slow metabolism
  • Well distributed in the body
  • Good oral bio availability
  • Long elimination half life
  • No bacterial resistance or cross resistance
  • No effect on the host immune system
  • No adverse drug interaction
  • No/Short withdrawal period in food producing animals
  • Economical and easily available
Classification of antimicrobial agents
Based on Mechanism of Action
Inhibit Cell Wall Synthesis: Penicillin, cephalosporin, cycloserine, bacitracin, vancomycin & clotrimazole.
Inhibit Cytoplasmic Membrane Function: polymyxins, amphotericin B & nystatin.
Inhibit protein synthesis: Chloramphanicol, tetracycline, macrolides and aminoglycosides.
Interfere with Intermediary Metabolism: sulphonamides, trimethoprim and sulphons.
Affect nucleic acid metabolism and synthesis: quinolones, rifampicin, and acyclovir
Based on Chemical Structure
sulphadimadine, sulphadiazine, sulphanilamide, sulphaquinoxalone.
Trimethoprim, ormetoprim and baquiloprim
Nalidixic acid, enrofloxacin, difloxacin and ciproflaxocin
Beta-lactam antibiotics:
Penicillin G, ampicillin, cloxacillin, cephazolin, cephalexin
streptomysin, gentamicin, amikacine, tobramycin
Oxytetracycline, tetracycline, doxycyline, minocycline
Macrolide Antibiotics:
Erythromycin and Azithromycin
Nitrofuran – Derivatives:
Nitrofurantoin and furazolidone
Metronidazole and Imidazole
Polypeptide Antibiotics:
Polymyxin B, Colistin and bacitricin
Polyene Antibiotics
Nystatin and amphotericin B
Imidazole derivatives
Ketoconazole, fluconazole and clotrimazole
Based on Therapeutic Uses (Type of Organism)
Penicillin, aminoglycosides, tetracycline, & chloramphenicol,
Amphotericin B, griseofuvin and ketoconazole
Idoxuridine, vidarabine, zidovudine, and ribavirin
Metronidazole, quinapyramine and diminazine
Albendazole, levamisole, niclosamide and praziquntel
Cypermethrin, lindane, amitraz and ethion
Based on Spectrum of Activity
Narrow spectrum antimicrobials:
Penicillin G, streptomycin, erythromycin and vancomycin
Broad Spectrum Antimicrobials:
Tetracycline, chloramphenicol, cephalexin, gentamycin, ampicllin
Based on type of Action
Sulphonamides, chloramphenicol, erythromycin, trimethoprim, clindamycin
Penicillin G, cephalexin, streptomycin, vancomycin, bacitracin and  potentiated  sulphonamides
Based on Source
Natural and Semi-synthetic
Penicillin G, griseofulvin and cephalexin
Streptomycin, tetracycline, erythromycin and    chloramphenicol
Polymyxin B, Colistin and bacitracin
Sulphonamides, trimethoprim, quinolones, nitrofurans and nitro-imidazoles

Oct 29, 2010

Feed Resources for Livestock and Poultry

Increase in demand of animal origin food due to:
  • Population growth
  • Urbanization
  • Changing consumer preferences
  • Export potential
Feed Resources for Livestock


Crop residues
Nutritional quality is very poor because of:
  • Deficient in Protein and energy
  • Low palatability and low intake
  • Low digestibility and feed efficiency
  • Containing higher quantities of indigestible fiber and lignin
  • Stay longer in the rumen, lowering the intake and impair productivity.
Rangelands & Pastures
  • About 60% of the total area of the country is rangelands.
  • Sheep & goats obtain 60% of their feed from rangelands
  • Grasses, shrubs and tree leaves are the potential feed reservoir for livestock in Pakistan and needs improvement.
  • Artificial reseeding, fertilization and other inputs could provide good results.
Agro-Industrial by-products
  • Cotton seed cake & meal
  • Rape seed cake & meal
  • Sunflower cake & meal
  • Linseed cake & meal
  • Soybean meal
  • Sesame seed cake
  • Maize oil cake
  • Maize gluten feed
  • Wheat bran
  • Rice bran
  • Maize bran
  • Rice polishing
  • Cane molasses
  • Palm Kernel Cake
  • Coconut Cake
Live stock sector change
Livestock sector has developed and changed rapidly in response to
  • Shifts in the global economy
  • Rising incomes in many developing countries and
  • Changing societal expectations
The sector is increasingly expected to provide safe and plentiful food for
  • Growing urban populations
  • As well as poverty reduction food security, environmental sustainability and public health
  • These trends and the challenges were identified a decade ago by Delgado et al. (1999), who coined the term “livestock revolution”
Livestock Feed Industry of Pakistan
  • 130 Feed mills in the country
  • Only 10 major feed mills, producing ruminant feed in private sector
  • Generally home mixed concentrate are prepared by livestock farmers.
Raw materials for poultry
Food and Agriculture
  • Contract farming
  • Developments of Hybrid Seed
  • Promotion of mechanization
  • Improve the agronomic practices
  • Facilitation to agriculture farmer
  • Introduction of new varieties
Poultry & livestock sector
  • Studies on Improved Protein and Energy Utilization
  • Search for alternative feed ingredients
  • Low cost unconventional feed resources
  • Use of fiber, as an energy source in poultry diets will be an important means to meet future feed requirements
  • Improved digestibility of unconventional feeds through biotechnological approach
  • Gut environment manipulation for better nutrient utilization 
  • Strict quality control of feed production systems