INTRODUCTION

An antibiotic, during the 1940s, was defined as a naturally occurring substance produced
by one microorganism which, in low concentrations, inhibited the growth of another
microorganism. The term changed over the years because derivative of antibiotics and several
agents that do not have resemblance to the natural microbial metabolites were developed. They
are known to be powerful medicines that fight certain infections. Antibiotics either stop bacteria
from reproducing or destroy them. A lot of antibiotics are developed but this report will only
include aminoglycosides, glycopeptides and antitubercular antibiotics. Aminoglycosides and
glycopeptides are available as parenteral products which make them less likely to be prescribed
for inpatients because of the administration problem.

Aminoglycosides are used against Gram-negative and some Gram-positive organisms.

They are available as parenteral products and are injected intravenously. The earliest
aminoglycosides include streptomycin and neomycin. Streptomycin limited the use of naturally
occurring aminoglycosides and lead to the development of semisynthetic members. Neomycin,
on the other hand, has high toxicity which is restricted to ophthalmic and topical products. Also,
it can be used in combination for oral preparations. The three most important aminoglycosides
(gentamycin, tobramycin and amikacin) are currently available. They are used against
Pseudomonas aeruginosa.

Glycopeptides target gram-positive bacteria including MRSA (methicillin resistant

Staphylococcus aureus). They contain carbohydrate moieties (glycans) covalently attached to the
side chains of the amino acid residues that constitute the peptide. They prevent peptidoglycan
synthesis by two separate mechanisms. Same with aminoglycosides, they are available as
parenteral products and are injected intravenously. There are two glycopeptide antibiotics
available which are vancomycin and teicoplanin. Vancomycin has a large molecular size which
makes it impenetratable to the outer membrane of Gram-negative bacteria. It is used to treat
infections of aerobic and anaerobic Gram-positive species. While teicoplanin, has a similar
chemical structure but has more fatty side chains which make it more acidic and lipophilic.

Antitubercular antibiotics are used exclusively for the treatment of tuberculosis which is
caused by Mycobacterium species. The treatment consists of two phases, the initial phase and
continuation phase. The course of therapy is normally 4-6 months. Risk is minimized by use of
two or three antibiotics in combination. The first effective treatment for tuberculosis is
streptomycin. It was later on used in combination with isoniazid then later with rifampicin which
is still used in the present day. Rifampicin is used against non-mycobacterial infections which is
active against Gram-positive bacteria and some Gram-negative species except
Enterobacteriaceae or pseudomonads. It also has bactericidal activity at very low concentration
against staphylococci.

This report shall contain the uses and importance of the three antibiotics aforementioned.
DISCUSSION

Aminoglycosides
The aminoglycosides are a large group of broad-spectrum antibiotics processing
significant activity against many Gram-negative bacteria and a more limited range of Gram-
positive organisms. The antibiotics are all bactericidal and administered by injection because
they are poorly absorbed from the GI tract. They are cationic, water-soluble drugs that interfere
with protein synthesis in bacteria by binding to the 30S subunit (which is not possessed by
mammals). Streptomycin was the earliest aminoglycoside discovered in 1944. Streptomycin was
the first effective antibiotic for the treatment of tuberculosis and still used as a second-line drug
although it now has few other applications. Neomycin (1940s) has high toxicity curtailed its use
as a systemic drug and it now largely restricted to ophthalmic and topical products, although in
this limited field its used is widespread. . Oral preparations of neomycin are employed, again
often in combination with other antibiotics, to reduce the bacterial population of the colon prior
to surgery. Three of the most important aminoglycosides currently available are gentamicin,
tobramycin and amikacin. The first two of these are naturally occurring drugs discovered in the
1960s, whilst amikacin is a semisynthetic derivative of kanamycin, which it has superseded.
Gentamycin, is used alone or in combination with - lactam antibiotics (with which it exhibits
synergy) both for blind therapy of infections prior to identification of the infecting organism,
and for the treatment of bacterial endocarditis and serious Gram - negative infections; it has no
activity with anaerobes. Amikacin has similar applications, but is more stable to inactivation by
bacterial enzymes, though rather less potent, than gentamicin. All three antibiotics possess useful
activity against Ps. aeruginosa and are particularly valuable, again with - lactams, for the
eradication or suppression of this organism in the lungs of cystic fibrosis patients; tobramycin is
slightly more active than gentamicin against Ps. aeruginosa and for this reason it is more
frequently used for this purpose than any other. Aminoglycosides have in the past often been
administered twice or three times per day, but the more recent trend has been towards a single,
higher, daily dose. Although not suitable in all situations, once - daily dosing is undoubtedly
more convenient and considered to be at least as safe and efficacious.

Glycopeptides
The only two important glycopeptide antibiotics currently available are vancomycin and
teicoplanin. Like many of the other antibiotics in current use, vancomycin is a relatively old
drug, having been introduced in 1958, but its activity against MRSA resulted in it becoming
progressively more valuable as MRSA became more prevalent. It has a complex tricyclic
glycopeptide structure and its large molecular size means that it cannot penetrate through the
outer membrane of most Gram- negative bacteria, so its use is effectively restricted to the
treatment of infections by aerobic or anaerobic Gram - positive species. In addition to Staph.
aureus, it is active against Staph. epidermidis , streptococci, Cl. difficile and Ent. faecalis,
although resistant enterococci are posing an increasing clinical problem. Vancomycin is
bactericidal to most susceptible bacteria at concentrations near its minimum inhibitory
concentration (MIC) and is an inhibitor of bacterial cell wall peptidoglycan synthesis, although at
a site different from that of - lactam antibiotics. Employed as the hydrochloride and
administered by dilute intravenous injection, vancomycin is indicated in potentially life -
threatening infections that cannot be treated with other, less toxic, antibiotics. Oral vancomycin,
which is not absorbed from the gastrointestinal tract, is the drug of choice in the treatment of
antibiotic - induced pseudomembranous colitis associated with the administration of antibiotics
such as clindamycin and lincomycin. Teicoplanin (1990s) has the same mode of action and
antimicrobial spectrum as vancomycin, as well as a similar chemical structure, but, crucially,
teicoplanin possesses more fatty acid side chains which (1) make the molecule more acidic,
thereby permitting the formulation of a sodium salt that can be given both by intravenous and
intramuscular injection, and (2) make teicoplanin more lipophilic, which affords better tissue
penetration and a longer half - life; as a consequence, teicoplanin is normally administered once
daily rather than twice. Other advantages over vancomycin are a slightly higher potency against
most target organisms and a better toxicity profile, thereby eliminating the need for routine blood
monitoring.

Antitubercular Antibiotics
Tuberculosis maybe cause by any one of three Mycobacterium species, but all three
characteristically grow slowly in the body and may persist for long periods in a near dormant
state. The antibiotics used for the treatment of tuberculosis belong to a variety of chemical
classes that consider them together in the same section for two reasons; first, most of them are
used exclusively, and second, therapy extends over several months, during which time resistance
development is a significant possibility. This risk is minimized by the use of two or three
antibiotics in combination that represents their normal pattern of use such as isoniazid, which
became available about five years later after streptomycin was introduced in the the late 1940s
(first effective treatment for tuberculosis), was used first in combination with streptomycin then
with rifampicin. Multidrug-resistant tuberculosis has become an increasing problem in recent
years which led to simultaneous resistance to isoniazid and rifampicin.
Antibiotics that are orally effective are much preferred since course of therapy is
normally 4-6 months and because unsupervised patients are more likely to take oral medicines,
and in many countries where patients may have difficulty travelling to clinics. The ideal
antitubercular drug should also have the potential to kill rather than nearly inhibit the growth of
the infecting organism.
 The current approach is to treat tuberculosis in two phases: an initial of 2 months using
isoniazid, rifampicin and pyrizinamide, and a 4 month continuation phase with isoniazid and
rifampicin. Second-line drugs maybe used and the duration of treatment possibly extended.
REVIEW OF RELATED LITERATURES

Aminoglycosides
According to Gonzales, Spencer (2002), Aminoglycosides are potent bacterial antibiotics
that act by creating fissures in the other membrane of the bacterial cell. They are particularly
active against aerobic, gram-negative bacteria and act synergistically against certain gram-
positive organisms for the reason that the aminoglycosides cannot penetrate the thick
peptidoglycan layer of a gram-positive bacteria. It is also stated in the given site that Gentamicin
is the most commonly used aminoglycoside followed by Tobramycin, and amikacin. This is
supported by uptodate.com (n.d) that Plazomicin is an aminoglycoside currently under
development in the United States for the treatment of multidrug-resistant organisms. Stated by
the same site, certain aminoglycosides have demonstrated clinically relevant activity against
protozoa (Paromomycin), Neisseria gonorrhoeae (spectinomycin) and mycobacterial infections
(tobramycin, streptomycin and most commonly, amikacin). The source of Aminoglycosides
includes Streptomyces spp. And microsmonospora spp which is stated by antimicrobial
resistance learning site- pharmacology (n.d).

Pharmacology of Aminoglycosides
Aminoglycosides, as stated by Schlecht (n.d) are poorly absorbed orally but are well
absorbed by peritoneum, pleural cavity and the joints and from denuded skin. They are usually
given IV. Aminoglycosides are used in the treatment of severe infections of the abdomen and
urinary tract, as well as bacteremia and endocarditis. They are also used for prophylaxis,
especially against endocarditis. (Gonzales, Spencer; 2002)
Use of Aminoglycosides in Treatment of Infections Due to Intracellular Bacteria.
Soon after antibiotics were introduced into medical practice, authors pointed out the
microorganisms capable of surviving within phagocytic cells may be protected from the killing
actions of antibiotics with a poor ability to cross the eukaryotic cell, leading to therapy failures
and disease relapses. Following the pioneering work of Boventre et al. that showed that mouse
peritoneal macrophages were impermeable to streptomycin in vitro, the aminoglycosudes have
been included in such a category. Failure of streptomycin and other aminoglycosides to treat
infections due to strict or facultative intracellular pathogens (e.g. rickettsial diseases, chlamydial
diseases, and typhoid fever) have reinforced this point of view. However at the same time,
streptomycin was successfully used to treat infections due to facultative intracellular pathogens,
such as tuberculosis (especially tuberculous meningitis) ,plague , brucellosis or tularemia .As for
tuberculosis, clinical data were concordant with the demonstration by Mackaness et al. that
streptomycin could inhibit growth of Mycobacterium tuberculosis within macrophages. Both
these clinical and experimental data have been overlooked for several decades. Later
experiments by Tulkens et al. have confirmed that aminoglycosides are readily incorporated into
phagocytes when these cells are in contact with the antibiotic for prolonged periods (i.e., more
than 24 h).

Glycoproteins
Glycoproteins are proteins found floating in or around the membrane of cells. They move
and can interact with the cell's environment. Glyco is a prefix in science that means 'sugar.'
Glycoproteins are simply proteins with a sugar attached to them (study.com; 2007) The sugars
can be attached to a protein in two locations in the cell, the endoplasmic reticulum, which
produces N-linked sugars, and the Golgi apparatus, which produces O-linked sugars. The N-
linked glycoproteins have a sugar attached to a nitrogen atom, and O-linked glycoproteins have a
sugar attached to an oxygen atom. The different structure of N- and O-linked sugars give them
different functions. Glycoproteins are proteins having covalently bound carbohydrate. They are
found in all living organisms, in both soluble and insoluble forms with diverse functions and
properties. 1-3 Indeed, there are more proteins that contain covalently bound carbohydrate in
their molecule than are devoid of carbohydrate. The carbohydrate content of glycoproteins
ranges from less than 1% to over 80% of the molecule. These carbohydrate units are involved in
various biological activities. (Shylaja, Seshadro; n.d.)
Locations and Functions of glycoproteins:
Glycoproteins are located in cell walls, blood plasma and connective tissues, and they
have fine structural differences depending on their location. They also play key roles in
reproduction and occur on the surface of spermatozoa, increasing the likelihood of a sperm cells
attraction to eggs by altering the permeability of plasma membranes. These proteins may also
adhere to cells and enable development of functional tissues in the body (reference.com; n.d) .
Glycoproteins are involved in nearly every process in cells! They have diverse functions such as
in our immune system, protection of our body, communication between cells, and our
reproductive systems. Let's examine these functions more closely.(study.com; 2007)

Anti-Tuberculosis Antibiotics
Tuberculosis is the main microbial killer of adults in the world, killing over 2 million
people per year (Frieden) and infecting over one-third of the world's population (WHO). The
Philippines has the 9th highest TB incidence worldwide (WHO) despite having free anti-TB
medication (Philippine Department of Health) and a WHO approved TB infrastructure (WHO).
According to one study, TB causes a loss of 500,000 DALYs in the Philippines every year
(Peabody).
Current Tuberculosis Treatment
The National Tuberculosis Programme in the Philippines is an approved DOTS program.
In the Philippines, effective anti-tuberculosis drugs (isoniazid, rifampicin, Pyrazinamide,
Ethambutol, and Streptomycin) are available for free-of-charge through national and local
government health centers (Philippine Department of Health). At the same time, the Philippines
has the 9th highest TB incidence worldwide and is one of three countries that account for 90% of
all new TB cases in the Western Pacific Region (WHO factsheet). Various reasons have been
cited for this discrepancy, including lower than expected use of the health centers (Auer) and
failures to complete treatment. 53% of the population seeks care from private practitioners and
end up paying for medications they could obtain for free (Auer). Further information on
treatment practices may be obtained from the Comprehensive and Unified plan cited at the end
of the paper. Treatment is overall successful.

TB drug treatment for new patients

Patients who have not had any TB treatment before, or they have had less than one month
of anti TB drugs, are considered to be new patients. New patients are presumed to have drug
susceptible TB (i.e. TB which is not resistant to any of the drugs) unless there is a high level of
isoniazid resistance in new patients in the area. The other people who may have drug resistant
TB are people who have developed active TB disease after they have been in contact with a
patient who is known to have drug resistant TB.
For new patients the World Health Organization (WHO) recommends that they should
have six months of TB drug treatment. This should consist of a two month intensive treatment
phase followed by a four month continuation phase.
For the two month intensive TB drug treatment phase they should receive: isoniazid
with rifampicin and pyrazinamide and ethambutol. Followed by isoniazid with rifampicin for the
continuation TB drug treatment phase.
It is essential to take several TB drugs together. If only one TB drug is taken on its own,
then the patient will very quickly become resistant to that drug.
It is recommended that patients take the TB drugs every day for the six months, although
taking them three times a week is possible in some circumstances. It is extremely important that
all the recommended TB drugs are taken for the entire time. The amount of any drug that a
patient needs to take depends on the patients weight.
If only one or two of the TB drugs are taken, or the treatment is interrupted or stopped
early, then the treatment probably wont work. This is because the TB bacteria that a patient has,
develops resistance to the TB drugs. Not only is the patient then still ill, but to be cured they then
have to take drugs for the treatment of drug resistant TB.

Anti-Tuberculosis Antibiotics
Isoniazid is used with other medications to treat active tuberculosis (TB) infections. It is
also used alone to prevent active TB infections in people who may be infected with the bacteria
(people with positive TB skin test). Isoniazid is an antibiotic and works by stopping the growth
of bacteria. This antibiotic treats only bacterial infections. It will not work for viral infections
(such as common cold, flu). Unnecessary use or misuse of any antibiotic can lead to its decreased
effectiveness. Isoniazid may cause severe and sometimes fatal liver problems (eg, hepatitis). The
risk of liver problems is greater in patients older than 35 years old. It may also be increased by
daily use of alcohol, long-term liver problems, or unsanitary injectable drug use. Women,
especially those who are black, are Hispanic, or have just had a baby, may also be at increased
risk. Hepatitis can develop at any time during treatment, but usually occurs during the first 3
months. Your doctor will monitor your liver function and discuss your progress every month.
Contact your doctor right away if you develop unusual fatigue, weakness or fever that lasts
longer than 3 days, general feeling of discomfort, loss of appetite, nausea, vomiting, numbness or
tingling of the hands or feet, dark urine, yellowing of the skin or eyes, or stomach pain or
tenderness. Your doctor may decide to slowly restart isoniazid after these symptoms disappear
and lab tests return to normal. Patients with active liver problems should not use isoniazid. Side
Effects: Nausea/vomiting or stomach upset may occur. If any of these effects persist or worsen,
tell your doctor or pharmacist promptly. Remember that your doctor has prescribed this
medication because he or she has judged that the benefit to you is greater than the risk of side
effects. Many people using this medication do not have serious side effects. Tell your doctor
right away if any of these unlikely but serious side effects occur: numbness/tingling of arms/legs,
painful/swollen joints. Tell your doctor right away if any of these rare but serious side effects
occur: increased thirst/urination, vision changes, easy bruising/bleeding, signs of infection (such
as fever, chills, sore throat that doesn't go away), mental/mood changes (such as confusion,
psychosis), seizures. A very serious allergic reaction to this drug is rare. However, get medical
help right away if you notice any symptoms of a serious allergic reaction, including: rash,
itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
According to Gilman, rifampicin is a semisynthetic antibiotic produced from
Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against
several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA
polymerase activity by forming a stable complex with the enzyme. It thus suppresses the
initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and
extracellular organisms. Rifampicin is an antibiotic which is prescribed to treat a variety of
serious infections. It is frequently prescribed to treat tuberculosis (TB). When prescribed in this
way, it is usually prescribed as just one of a number of medicines to treat the infection.
Alternatively, rifampicin can be prescribed to protect you from getting a serious infection
(including TB, meningitis, or Haemophilus influenzae) because you have been in close contact
with someone who has the infection. Side effects: Fever, Loss of appetite, Malaise, Nausea and
vomiting, Darkened urine, Jaundice (yellowing of the skin and eyes), and Pain or swelling of
your joints.
Pyrazinamide is used for treating active tuberculosis in combination with other
medicines. Pyrazinamide is an antituberculosis agent. It works by killing or preventing the
growth of certain bacteria that cause tuberculosis. This medicine is usually used in combination
with at least one other agent. Side effects: nausea, upset stomach, vomiting, loss of appetite, mild
muscle or joint pain, or fatigue.
Ethambutol is used with other medications to treat tuberculosis (TB). Ethambutol is an
antibiotic and works by stopping the growth of bacteria. This antibiotic treats only bacterial
infections. It will not work for viral infections (such as common cold, flu). Unnecessary use or
misuse of any antibiotic can lead to its decreased effectiveness. This drug may also be used with
other medications to help treat a certain serious infection (Mycobacterium avium complex-
MAC). It may also be used with other medications to prevent the MAC infection from occurring
again in people with advanced HIV disease. Continue to take this medication (and other TB
medications) until the full prescribed amount is finished, even if symptoms disappear. Stopping
the medication too early or skipping doses may allow the bacteria to continue to grow, which
may result in a return of the infection and cause the infection to be more difficult to treat
(resistant). Side effects: Blurred vision, eye pain, red-green color blindness, or any loss of vision
(more common with high doses), joint pain, numbness, tingling, burning pain, or weakness in
hands or feet, and skin rash.

5 Multiple Choice Questions

1. Antitubercular antibiotics are much preferred in which route of administration.

a. O b. IV c. IM d. All the above

2. Drugs used that are available for infections cause by resistant organisms.
a. First-line drugs b. Second-line drugs c. Third-line drugs d. A & B

3. Three most important aminoglycosides currently available.

a. amikacin, capreomycin, cycloserine b. azithromycin, clarithromycin, tobramycin
c. gentamycin, tobramycin, amikacin d. cycloserine, gentamycin, moxifloxacin

4. Is a relatively old drug, having been introduced in 1958 and is currently available as a
glycopeptide antibiotic.
a. Vancomycin b. Streptomycin c. Teicoplanin d. Rifampicin

5. Large group of bactericidal antibiotics used for Gram-positive and Gram-negative species
and preferably administered via IV.
a. Antitubercular antibiotics b. Aminoglycosides c. Glycopeptides
d. Antifungal antibiotics
REFERENCES

Introduction
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http://www.msdmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-
drugs/aminoglycosides

https://www.goldbio.com/category/glycopeptides

Review of Related Literatures

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infect. Immun. @:89-95

Mackaness (G.B. (1952) The action of drugs on intracellular tubercle bacilli. 64: 429-446

Enderlin G., Morales L., Jacobs R.F., Cross J. T. (1994) Streptomycin and alternative agents for
the treatment of tularemia: review of the literature. Clin. Infet. Dis. 19:42-47

Solera J., Martinez-Alfaro., Espinosa A. (1997) Recognition and optimum treatment of

brucellosis. Drugs: 53:245-256

Perry R.D. Fetherston J.d> (1997) Yersinia pestisetiologic agent of plaque. 10:35-66

Meyers B.R (1982) Tuberculosis meningitis. Med.Clin. North Am. 66:755-762

Jenkin C., Benacerraf B. (1960) in vitro studies on the interaction between mouse peritoneal
macrophages and strains of Salmonella and Escherichia coli. J. Exp. Med. 112:403-417

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Gonzalez III, S., (2002). Aminoglycosides: A Practical Review. Retrieved from:

http://www.aafp.org/afp/1998/1115/p1811.html

Schlecht. H.P., (n.d.) Aminoglycosided. Retrieved from:

http://www.msdmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-
drugs/aminoglycosides
Use of Aminoglycosides in treatment of infections Due to Intracellular Bacteria (n.d). Retrieved
from: http://aac.asm.org/content/45/11/2977.full

What are the functions of glycoproteins (n.d). Retrieved from:

https://www.reference.com/science/functions-glycoproteins-9541ff78d0d60647#
What are glycoproteins? (n.d). Retrieved from: http://study.com/academy/lesson/what-are-
glycoproteins-definition-functions-examples.html
Ethambutol. Retrieved from http://www.webmd.com/drugs/2/drug-8082/ethambutol-oral/details
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Auer, Christian, Jesus Sarol Jr, Marcel Tanner and Mitchell Weiss. Health seeking and
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