ANTIBIOTICS

BY: SAI MANOGNA (MSIWM013)

Introduction :

Antibiotics are used in the treatment of preventing bacterial infection. They work by destroying or stopping bacteria from reproducing and spreading. Antibiotics do not work against respiratory infections like the common cold, flu, most coughs, and sore throats. The immune system can also cleanse several mild bacterial infections without using antibiotics, but they are not regularly prescribed. Antibiotics must be administered and appropriately taken to help prevent the development of antibiotic resistance.

Antibiotics, also known as antibacterials, are medicines that destroy or slow bacterial growth. In 1929, Alexander Fleming identified penicillin, the first antibiotic compound. Penicillins, Aminoglycosides, Quinolones,  Macrolides, Sulfonamides, Cephalosporins, Carbapenems, and Tetracyclines are common antibiotics. General antibiotic prescription principles are used: first-line antibiotics, reserve wide-spectrum antibiotics only for indicated conditions, prescribe antibiotics for bacterial infections if symptoms are severe or extreme.

Antibiotics can be given in several ways:

Oral antibiotics: pills, capsules, or a liquid drink to treat most cases of mild to severe body infections

Topical antibiotics: creams, lotions, sprays, or drops sometimes used to treat skin infections

Antibiotic injections: these may be administered or infused directly into the blood or muscle and are typically reserved for more extreme infections

Types Of Antibiotics :

There are hundreds of different forms of antibiotics: but most can be grouped into six classes. They are listed below.

Penicillins (such as penicillin and amoxicillin)

Cephalosporins (such as cephalexin)

Aminoglycosides (such as gentamicin and tobramycin)

Tetracyclines (such as tetracycline and doxycycline)

Macrolides (such as erythromycin and clarithromycin)

Fluoroquinolones (such as ciprofloxacin and levofloxacin)

1. Penicillins :

a. Penicillins are an antibiotic of penicillium fungi. An antibiotic is a drug that prevents bacteria ‘s growth or destroys.

b. The 1928 accident discovered penicillin G (also called benzylpenicillin). Alexander Fleming, a Scottish physicist, developed a form of bacteria called Staphylococcus Aureus on an uncovered petri dish when infected with mold spores. He noticed the bacteria near the mold dying. He isolated the mold material that destroyed the bacteria and named it penicillin.

c. Natural penicillins (penicillin G, penicillin V) are active only against gram-positive bacteria. Penicillin V is acid-resistant than penicillin G

d. Penicillin V was isolated from the same mold. All other penicillins are semi-synthetic, made by changing the structure of the original naturally occurring penicillins.

e. Classic semi-synthetic penicillins include ampicillin and oxacillin. These have some degree of beta-lactamase resistance and are effective against some gram-negative bacteria.

f. Most bacteria can be categorized as gram-positive or gram-negative based on variations in their cell wall structure, which can be microscopically differentiated using the dye form.

g. One of the main distinctions is that gram-positive bacteria are more susceptible to antibiotics, whereas gram-negative bacteria are more antibiotic-resistant.

Penicillins such as piperacillin and ticarcillin are penicillins with additional activity against some hard-to-kill types of gram-negative bacteria (Pseudomonas, Klebsiella, and Enterococcus).

A beta-lactamase inhibitor incorporates certain penicillins. A beta-lactamase inhibitor blocks beta-lactamase enzyme activity but tends to have little antibiotic activity. Some penicillins (like oxacillin, dicloxacillin, and nafcillin) are naturally resistant to certain beta-lactamases and are called penicillin-resistant. Others, such as amoxicillin, ampicillin, and piperacillin, may be extended by combining them with a beta-lactamase inhibitor. Clavulanate, sulbactam, and tazobactam all inhibit beta-lactamase.

Penicillins function by preventing bacterial cell wall cross-linking of amino acid chains. This does not affect pre-existing bacteria, but new bacterial cells have fragile cell walls that rupture easily.

Uses: Penicillins are used to treat

 i. Dental abscess

ii. Ear infections

iii. Gonorrhea

iv. Pneumonia

v. Rheumatic fever

vi. Skin infections

vii. Urinary tract infections

2. Tetracyclines:

a. The first tetracyclines were derived from Streptomyces bacteria in the 1940s.

b. These can be used to treat infections caused by susceptible microorganisms such as gram-positive and gram-negative bacteria, chlamydiae, mycoplasma, protozoans and rickettsiae.

c. Tetracyclines inhibit protein synthesis in microbial RNA (an essential molecule for DNA messenger). They are mainly bacteriostatic, thereby stopping bacteria from spreading but not necessarily killing them.

d. Although tetracyclines all function the same way, there are variations between the four tetracyclines (demeclocycline, doxycycline, minocycline, and tetracycline).

Doxycycline is the most commonly used tetracycline. It causes photosensitivity or binds to calcium, causing dental discoloration or bone growth retardation.

Uses: Tetracyclines are used to treat

i. Malaria

ii. Treatment of moderate to severe acne

iii. Anthrax

iv. Infections of an eye, gastrointestinal tract, respiratory tract, and skin

v. infections caused by Campylobacter, Yersinia pestis, Vibrio cholerae, Chlamydiae, and other atypical organisms

3. Cephalosporins :

a. Cephalosporins are a broad group of Acremonium-derived antibiotics (formerly Cephalosporium).

b. Cephalosporins are bactericidal (kill bacteria), similar to penicillins. They bind and block enzyme activity responsible for producing peptidoglycan, an essential bacterial cell wall component. They are called broad-spectrum antibiotics because they affect a wide range of bacteria.

c. Since the first cephalosporin was discovered in 1945; scientists have refined cephalosporin structure to make it more effective against broader bacteria.

d. Whenever structure changes, a new “generation” of cephalosporins is made. There are five generations of cephalosporins.

e. Both cephalosporins begin with cef, ceph, or kef. Notice that this classification scheme is not used consistently across countries.

Currently, there are five “generations” of cephalosporins, each generation varying slightly in their antibacterial range ( i.e., how successful they are in destroying certain types of bacteria). There are variations in administration (such as oral or intravenous administration), absorption, excretion, and how long the body’s cephalosporin activity lasts.

First-generation :

First-generation cephalosporins are the first group of cephalosporins found. Their optimal activity against gram-positive bacteria like staphylococci and streptococci. They have little anti-gram-negative activity.

Second-generation :

Second-generation cephalosporins are more active against gram-negative bacteria, with less gram-positive bacteria.

Third-generation :

The second-generation cephalosporins preceded third-generation cephalosporins. No third-generation cephalosporin treats all scenarios of infectious disease.

Cefotaxime and ceftizoxime provide the best gram-positive coverage of all third-generation agents; ceftazidime and cefoperazone are unique in providing antipseudomonal coverage.

Fourth generation :

Fourth-generation cephalosporins are structurally similar to third-generation cephalosporins. However, they have a different ammonium group that enables them to penetrate the outer membrane of gram-negative bacteria, enhancing their activity. They are also active against β-lactamase generating Enterobacteriaceae that may inactivate cephalosporins of third-generation.

Some fourth-generation cephalosporins have excellent activity against gram-positive bacteria such as staphylococci, penicillin-resistant pneumococci, and streptococci group viridans.

Fifth-generation :

Ceftaroline is currently the only cephalosporin of next-generation available in the U.S. It acts against methicillin-resistant Staphylococcus aureus ( MRSA) and gram-positive bacteria. It also retains later-generation cephalosporin activity and works against susceptible gram-negative bacteria.

Uses: Cephalosporins are used to treat

i. Bone, skin, and ear infections

ii. Urinary tract infections

4. Quinolines:

a. Quinolones are antibiotics that kill or inhibit bacteria.

b. Five separate quinolone groups exist. Another antibiotic class, called fluoroquinolones, was derived from quinolones by modifying their fluorine structure.

c. Quinolones and fluoroquinolones have some common and some differences, such as against which organisms they work.

d. Quinolones and fluoroquinolones affect the role of topoisomerase IV and DNA gyrase so that they can no longer fix DNA or assist in its development.

e. Quinolones and fluoroquinolones vary in their action against the two enzymes produced by bacteria, topoisomerase IV and DNA gyrase.

f. Those more active against topoisomerase IV have more effect on gram-positive bacteria; those active against DNA gyrase are more active against gram-negative bacteria.

g. Quinolones and fluoroquinolones also vary in body absorption, metabolization, and excretion.

Uses: Quinolines are used to treat

i. Unusual infections such as plague and anthrax

5. Macrolides :

a. Macrolide derivatives are either a macrolide or macrolide-related antibiotics.

b. Macrolides are antibiotics found in streptomycetes.

c. They are natural lactones with a complete ring of 14-20 atoms.

d. Macrolides bind to the bacterial ribosome 50S subunit and inhibit ribosomal translocation, leading to bacterial protein synthesis inhibition.

e. Their action is primarily bacteriostatic, but at high concentrations, depending on the type of microorganism.

Uses: Macrolides are used to treat uncomplicated skin infections, pneumonia, pertussis, and other susceptible infections.

6. Aminoglycosides :

a. Aminoglycosides are a class of antibiotics used primarily to treat aerobic gram-negative bacilli infections

b. These are effective against other bacteria such as Mycobacterium tuberculosis Staphylococci. They are often used with other antibiotics.

c. Aminoglycosides can function by inhibiting protein synthesis within bacteria.

d. Bacteria kill rates are increased when higher aminoglycoside concentrations are present.

e. Kidney impairment and hearing loss are the most common side effects of aminoglycosides.

f. Aminoglycosides are usually used when other antibiotics are contraindicated or ineffective.

g. Aminoglycosides are not well absorbed by mouth, so healthcare workers need to be injected.

Others :

a. Carbapenems

These injectable beta-lactam antibiotics have a wide range of bacteria-killing ability. They can be used for mild to life-threatening bacterial infections such as stomach infections, pneumonia, kidney infections, hospital-acquired multidrug-resistant infections, and many other severe bacterial diseases. They are often saved or used as “last-line” agents to help prevent resistance.

b. Antibiotic – Glycopeptide

Members can be used to treat methicillin-resistant staphylococcus aureus (MRSA) infections, complicated skin infections, C. Difficult-associated diarrhea, enterococcal infections such as beta-lactam-resistant endocarditis, and other antibiotics.

c. Sulphonamides

Sulfonamides function against some gram-positive and many gram-negative bacteria, but resistance is widespread. Sulfonamide uses include urinary tract infections ( UTIs), pneumonia treatment or prevention, or ear infections (otitis media).

d. Lincomycins :

Lincomycins have activity against gram-positive aerobes and anaerobes, as well as some gram-negative anaerobes. Lincomycin derivatives may be used to treat severe infections such as pelvic inflammatory disease, lower respiratory tract infections, intra-abdominal infections, and bone and joint infections. Some forms are also used topically to treat acne.

Antimicrobial resistance:

Overuse of antibiotics in recent years means they become less successful, and “superbugs” have arisen. There are bacterial strains that withstand several different forms of antibiotics, including:

Methicillin Staphylococcus aureus (MRSA)

Clostridium difficile (CD)

Multidrug – resistant tuberculosis (MDR-TB) bacteria

Carbapenemase Enterobacteriaceae (CPE)

These infections can be extreme and challenging to manage and are rapidly causing disability and death worldwide.

Antibiotic side-effects

Like any drug, antibiotics can cause side-effects. Most antibiotics do not cause problems if adequately used, and severe side effects are rare.

The most popular side-effects are:

Bloating, indigestion, diarrhea

Some people may be allergic to antibiotics, particularly penicillin, and a form called cephalosporins. This may lead to an extreme allergic reaction (anaphylaxis), a medical emergency in scarce circumstances.

MEDICAL MICROBIOLOGY

BY: RAHUL ANDHARIA (MSIWM001)

Medical Microbiology

Deals with prevention, diagnosis and treatment of infectious diseases caused by infectious agents like bacteria, fungi, parasites and viruses. This field is also known as Clinical microbiology. Understanding of various infectious agents and how this agents causes the disease, development and pathogenesis of the disease are being studied under medical microbiology.

History of medical microbiology:

  • Infectious diseases caused by transfer of seed like entities was first given in the year, 1546 by Girolamo  Fracastoro. He said that the disease can be caused by direct contact or by indirect contact with the infectious agent.
  • Advancements in the field of medical microbiology actually started in the year 1888, when Pasteur institute was established in Paris. Louis Pasteur and Robert Koch are considered as father of medical microbiology due to their contributions in the field.
  • Disapproval of the spontaneous generation theory(theory which claimed that non living matter is involved in giving life to living things), Pasteurization(heating at lower temperatures- less than 100 degree Celsius)methods, vaccines for Tabbies, cholera and anthrax(caused by- Bacillus anthraces) were proposed by Louis Pasteur.
  • Specific microbes are responsible to cause a particular disease. The concept of Germ theory of Disease, was given by Robert Koch. Koch cultured various Micro-organisms in the lab that caused the disease, including bacteria, mycobacterium tuberculosis, which is known to cause Tuberculosis. He used to grow Micro-organisms on solid medium like agar.
  • Koch’s postulates:
    • Organisms suffering from the disease should have the microbes that are responsible for the diseases. Microbes should not be found in healthy organisms.
    • Pure culture must be used to isolate the Micro-organisms from the diseased organism.
    • When the Micro-organism is Administered into a healthy organism, it should confer the disease.

From the same inoculated diseased experimental host, the same Micro-organism must be isolated and it has to be identical to the original agent that was responsible for the disease.

  • Concept of anti-sepsis was given by Joseph Lister. He showed that carbolic compounds, now it’s known as phenol, can be used for wound sepsis and cleaning.
  • Extensive work on TMV(Tobacco mosaic virus) was carried by Dmitri Ivanovsky. He studied TMV and differentiated it with bacteria by preforming a simple experiment in the year 1892, where he showed that when passed through filters, larger bacteria will be retained .
  • Propagation of  polio virus in monkey kidney cell cultures was given by John Enders, Thomas Weller and Frederick Robbins.

Fields in Medical microbiology:

  1. Microbial Physiology: It deals with the studies of growth of Micro-organisms, metabolism of micro-organisms and microbial cell culture. It also deals with pathophysiology of micro-organisms and role of Micro-organisms in diseases.
  2. Microbial Genetics: It involves studying how microbial genes function. Organisation of microbial genome, it’s genomic characteristics are being studied in this field.
  3. Parasitology: involves in depth studies of parasites. Sample studies can be done using feces, blood, urine and sputum samples.
  4. Virology: It deals with detail studies of various types of viruses. Host-viral mechanisms, viruses mode of action in host, diseases caused by viruses are some aspects involved with virology.
  5. Immunology: Immune system studies, which involves studying hosts immune system and it’s role in combating pathogens and foreign substances. Antigen-antibody interactions are primarily used as diagnostic tools in diseases.

Role of Medical microbiology:

  • When a Patient experiences any signs of infections, physicians recommends medical and diagnostic laboratory procedures.
  • Antibiotic sensitivity test, direct stain or culture are the type of tests performed.
  • Different types of testing’s are performed like collection of appropriate specimen and than plating the specimen on appropriate culture medium, inoculating and sub culturing it and than performing different tests to confirm the type of disease. For example- Mantoux test is used for tuberculosis.
  • Serological, biochemical, molecular tests are performed and the types of micro-organisms associated with the disease are identified.
  • Basically it involves testing samples for the presence of infectious agents, and than performing diagnostic procedures.
  • Various subfields have different procedures, like for example- immunology procedures involves performing ELISA to detect antibodies in blood.

Types of Infectious agents:

Bacteria:

There are certain bacteria which are essential for the human body and it’s functions. These are termed as normal flora. For example- gut microbes are involved in synthesis of vitamin k and vitamin B12. During immunocompromised conditions, this microflora can lead to infections.

Invasiveness: can spread within the host body. Structures like capsules helps them to skip phagocytosis. Toxins also help them to defend host machineries.

Immunopathology: host immune response is responsible for pathogenesis in most of the Infections.

Viruses:

They are obligate parasites( they require host system to grow and develop as they cannot synthesise proteins and utilize it’s own energy). Viral diseases are more common in humans, particularly in children.

Invasiveness: They require host machineries to multiply and divide. They make the host system to synthesise viral components and as a result, host machineries are destroyed by viral components leading to viral diseases.

Immunopathology: host immune response is responsible for pathogenesis in most of the Infections.

Fungi:

Invasiveness: mucosal tissues or keratin are the places commonly where fungi can multiply and cause the Infection.

Toxin Production: food contaminated with fungi can cause serious food poisoning.

Immunopathology: When fungal spore or hyphae are inhaled, can cause hypersensitivity.(allergy).

Parasites:

Much more complex than viruses and bacteria. They can cause disease via multiple routes. Example- Giardiasis- Intestinal infection- by giardia, mainly through contaminated food and water.

Applications of Medical microbiology:

  • Vaccine development: understanding pathophysiology of the disease and than preparing a vaccine against it. Basically vaccine generates a immune response which will be lacking when the body is compromised during a disease. Rubella and measles are the two common examples of diseases which have been eradicated by vaccination.
  • Diagnostic tests: cultural tests, serological tests, microscopy, PCR all this diagnosis testing helps to identify infectious agents.

SCOPE

Scope and appliance of microbiology

About

  • Microbiology is a discipline of biology which deals with the study of microscopic organism, their interaction with other organisms and with environment.
  • It includes microscopic level organisms like bacteria, algae, fungi, protozoa and the infectious agent viruses too.
  • Microorganisms present all over the globe form high altitude to the deep seas include hot springs, extremely cold climates, and high pressure even in the salty lakes.
  • Microorganisms are both beneficial and harmful to human. I.e. required in the industrial production of food stuff (bread, yogurt, beer, wine, etc), antibiotics(penicillin, chloromycetin, streptomycin) vaccine, enzymes, vitamins and many more products along with it is harmful in the way by causing fatal disease like small pox, plague, malaria, cholera, HIV, influenza and more.
  • They plays important role in maintaining the stability of ecosystem by recycling the organic and inorganic substance in carbon, nitrogen, sulphur and phosphorus cycle.
  • There were many events in history that tells us how infectious microbes put the human population in danger. Like black death(1346),  yellow fever(1793), Spanish flu(1918), SARS(2002), H1N1 flu(2009), MERS(2014), ebola(2014), etc.
  • In addition to the disease outbreaks microorganism plays major role in food spoilage, detoriation on materials like paper, wood, metal and plastics.
  • In agriculture nowadays genetically improved crops are used to get more yields and disease resistant crop which can be obtained by the involvement of microorganism.
  • As microbes are present everywhere it enhances the scope and contribute in many fields like pharma, agriculture, dairy, food industries, research, nanotechnology, water industry, chemical industry.
  • Microbiologists are the person who studies these microorganisms and their morphology, behaviour, metabolic activity, habitat, reproduction, nutritional requirement, their application and pathogenicity, improvemnet and modifications which leads to the high demand of microbiologist globally.

Fields:

Dairy and food industry:

  • Deals with the microbial production for the food stuff, prevention of spoilage of food and transmission of food borne disease.  

Agricultural microbiology:

  • It include the study of microbial strains which are used to obtain genetically modified crops which are resistant to many diseases and higher yields. Production of bio-fertilizers and maintenance of the rhizo-flora.

Medical microbiology:

  • Study of disease their causative agents, prevention, diagnosis and treatment. In addition in includes various clinical appliance of microbes oh human health.  

Environmental microbiology:

  • The study of microbes and their interaction with environment, role in geochemical cycles, microbial diversity, bio-remediation

Genetic engineering:

  • It deals with the study of modifying microorganism at gene level and engineered microbes are used to produce hormones, enzymes, vaccines, vitamins, antibiotic and other products.

Microbial physiology:

  • Includes the study of microbial morphological structure, metabolism and growth.

Industrial microbiology:

  • Deals with the production of antibiotic, fermented food, aminoacids, vitamins, steroids, enzymes, alcohol. In addition with the strain improvement and process of enhancing product quantity.

Soil microbiology:

  • The study of soil flora and role of microorganism in soil fertility

Water microbiology:

  • Major part of this field is the waste water management as is it a challenging condition for the world with industrial waste discharged in the water bodies and leading to the pollution causing threat for aquatic life.

Applications:

The diversity of microbes on the globe makes microbiology the most complex and largest discipline.

Food:

  • There are a majority of microbes used in the food and dairy industries for the production of food from wine, beer through the cheese, yogurt to manufacturing of bread.
  • Include Process of fermentation, pasteurization, industrial production, processing of food its packaging, food preservation and storage.
  • Microbial spoilage of food production and their prevention.

Environmental microbiology:

  • working of biogeocycle(carbon, nitrogen, sulphur and phosphorus) done by microorganism
  • microorganism are present in free living state and in association with plants in symbiotic relationship.
  • Maintaining the soil fertility without exhausting soil nutrients.
  • Responsible for cleaning toxic substance from the environment. 
  • Some are pathogenic to the plant but there are few strain which act as biological control agents and protect plant against this diseases.

Medical microbiology:

  • Disease causing microbes i.e. bacteria, algae, fungi, protozoa and virus responsible for causing numerous types of diseases ranging from  acute to severe life threatening.
  • Examples are cholera, influenza, malaria, HIV, tuberculosis, plague, etc
  • Their diagnosis, transmission, prevention and cure are the major part of the medical microbiology
  • In contrast to the pathogenicity there are some strains inhibit the growth of other diseases causing microbes by producing antibiotic, hence, used for the production of antibiotics.

Biotechnology:

  • Genetically engineered strain used for the production of therapeutic substance like human growth hormone, insulin, etc
  • Also contribute in the commercial production of  acetone, alcohol, drugs etc

Research:

  • Diversity and unicellular structure of microbes make them easy to study and research over multicellular structure.
  • In addition they can produce millions of copies from a single cell rapidly with very low cost which is good for experiments performed.
  • Short generation time leads to quick result analysis.

Future aspects of microbiology:

  • Due to population explosion in the world there could be scarcity of food in near future in that condition single cell protein can be an alternative.
  • Newly and highly resistant species of diseases causing microbes is a challenge for the present and in the future so r DNA technology is useful to overcome this problem.
  • Treatment of cancer and HIV like diseases
  • Food preservation methods for highly perishable food items