Antimicrobial drugs

quick overview- homework

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School of Life and Health Sciences





Antimicrobial drugs

Current Antibiotics
Drugs



MOHAMMA HUSSAIN ALYAMI
STUDENT ID 109068062

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Introduction

Antibiotic agents have been used for several years since Alexander Fleming
has observed the first antibiotic in 1928, which is called penicillin. Due to the
differences in bacteria structure, they are classified into gram-positive such as
Staphylococcus aureus, and gram-negative such as Klebsiella pneumoniae.

Nowadays, adequate of antibiotics are prescribed with a variety in efficacy,
potency, efficient and specificity. Unfortunately, misuse and inappropriate us
of those agents has driven to increase the bacteria resistance mechanism
(Range & et al, 2012; Katzung, 2009).

In this report, different classes of antibiotics, which are being marketed, will be
presented, according to the pharmacological activity and site of action.


1. Antibiotics that act on the bacteria cell wall synthesis

Beta-lactams and glycopeptides agents are examples of the antibiotics, which
act through inhibition the activity of transpeptidation enzyme. Thus,
peptidoglycan synthesis process will be inhibited which lead to bacteria cell
wall lysis and then bacteria death (Bryskier, 2005).

1.1 Penicillins (Beta-lactam)

They are commonly used and extremely effective either alone or in
combination for many infections. Table 1 shows the most common uses of
penicillin drugs.

Diseases Drugs

Meningitis

I.V Benzylpenecillin (Crystapen®)
(Used widely for many infections)

Bone and joint infections

Flucloxacillin (Floxapen®)

Bronchitis, Pneumonia and Otitis

Amoxicillin (Amoxil®)

Pseudomonas and aeruginosa
infection

Ticracillin and piperacillin

Skin and soft tissue infection

Benzylpenecillin

3. 3
(Table1: Adopted from Range & et al, 2012)


Nevertheless, bacteria produce Beta-lactamase enzyme to resist the activity
of those agents, such as Methicillin-resistant staphylococcus aureus (MRSA).
Accordingly, B-lactamases inhibitors have been used in order to extend
antibiotics agents’ activity (Bryskier, 2005).


 List of Beta-lactamase inhibitors that are conjugated with penicillin
agents:

 Glavulanic acid with penicillin. (Augmentin
®
)
 Sulbactam with Ampicillin. (Unasyn
®
)
 Tazobactam with Pipercillin. (Zosyn
®
)
 Brobactam with Pivampicillin. (Piptazin
®
)
 Ticracillin with Glavulanic acid (Timentin
®
)
(Rotschafer, 1995; Bryskier, 2005; & Netdoctor website, 2011)



1.2 Cephalosporins M5

They are remarkably similar to the penicillin in their basic structures and
considered the second choice for many infections. They have a good stability
to the bacterial Beta lactamase and a broader spectrum. Many generations
have been produced for example1
st
generation, 2
nd
generation, 3
rd
generation,
and 4
th
generation. In comparison, the first and second generations are more
active against gram-positive bacteria, whereas the third is more active against
gram-negative bacteria. However, the fourth generation has a broad spectrum
against both gram negative and positive bacteria. Table 2 shows a list of the
oral and parenteral cephalosporins.






ORAL CEPHALOSPORINS PARENTRAL CEPHALOSPORINS
DRUG TRADE NAME
®
DRUG TRADE NAME
®

Cefaclor

2
ND
generation
(Ceclor)
Cefazolin

Only1
ST
genern
(Ancef)
Cefepime 4
TH
generation

4. 4
Cefadroxil

1
ST
generation
(Duricef)
Cefdinir
(Omnicef)

3
RD
generation
(Omnicef)
Cefditoren

3
RD
generation
(Spectracef)

Cefixime

3
RD
generation
(Suprax)
Cefpodoxime

3
RD
generation
(Vantin)
Cefprozil

2
ND
generation
(Cefzil)
Ceftibuten

1
ST
generation
(Cedax)
Cephalexin

1
ST
generation
(Keflex)
Cefuroxime

2
ND
generation
(Ceftin)
Cephradine

1
ST
generation
(Velosef)
Loracarbef

2
ND
generation
(Lorabid)

(Mxipime)
Cefoperazone

3
RD
generation
(Cefobid)
Cefotaxime

3
RD
generation
(Calforan)
Cefoxitin

2
ND
generation
(Mefoxin)
Ceftazidime

3
RD
generation
(Forta)
Ceftibuten

3
RD
generation
(Cedax)
Ceftizoxime

3
RD
generation
(Cefizox)
Cefuroxime

2
ND
generation
(Zenacef)
Ceftriaxone 3
RD
generation
(Rocephin)




(Table 2: Adopted from National Library of Medicine .2012)


1.3 Carbapenems and Monobactams.

Theses two types of B-lactam ring were developed to resist the Beta-
lactamase enzyme. Imipenem, Meropenem, and Ertapenem are examples
of Carbmpenem, which have a very broad spectrum against a wide range
of bacteria. Aztreonam is the only Monobactam agent used clinically,
which resists to many Beat- lactamase. It is well tolerated by penicillin
allergic patient.


1.4 Glycopeptide M4

Vancomycin (Vancocin
®
) is poorly absorbed from the gut and it thus
given orally for treatment GIT infection. It works mainly against gram-

5. 5
positive bacteria and MRSA. Daptomycin is a lipopeptide antibacterial
and used in combination for MRSA.

2. Antibiotics that act on the bacteria DNA synthesis

Sulfamethoxazole, sulfasalazine, and sufadiazine are the only sulfonamides
drugs used. Sulfonamides drugs act through competing with P-aminobenzoic
acid (PABA), which is a fundamental for folic acid formation for both DNA and
RNA. Co-Trimoxazole is, combination of trimethoprim and sulfamethoxazole,
used for urinary tract, pneumonia, intestines, and ears infections (Range & et
al, 2012; Katzung, 2009).


3. Antibiotics that act on the bacteria protein synthesis

3.1 Tetracyclines

They have a broad-spectrum activity such as tetracycline, oxytetracycline,
demeclocycline, doxycycline, and minocycline. Unfortunately, as the bacteria
resistance increased, the uses of these drugs are declined. However,
Doxycycline is given only once daily which is a choice for patients with renal
impairment.

The main uses are RTI, UTI, stomach ulcer rickettsial and chlamydia
infections (Bryskier, 2005; PubMed health website). Demeclocycline inhibits
secretion of antidiuretic hormone in patients with lung tumor.

3.2 Chloramphenicol

It acts against gram-positive and gram-negative bacteria and rickettsia. It is
used in Haemophilus influenza infections and meningitis in patients whom
cannot use other agents. Nonetheless, it is used rarely due to its serious
toxicities. (See Table 3) M3





3.3 Aminoglycosides

They have dual action, bactericidal and bacteriostatic. Unfortunately, they
have serious side effects such as nephrotoxicity, ototoxicity.M2

6. 6

Gentamycin

Garamycin  Sepsis caused by
aerobic gram-
negative bacteria
Tobramycin

Nebcin

 Mengitis
 Lower RTI
 Septicemia
 Boneand skin
infection.
Amikacin

Amikin



Streptomycin

IM/injection
Streptomycin for
injection USP
 Tuberculosis
 enterococal
endocarditis
Neomycin

Neo-tab  Bowel surgery

Spectinomycin


IM/injection
Trobicin
 Antibiotic
resisitant
gonococcal
infection
 Gonococcal in
penicillin-allergic
patients
(Table 3: Adopted from Bryskier, 2005; Katzung ,2009)



3.4 Macrolides and other

Macrolides drugs work as bactericidal and bacteriostatic; have a lactone ring
with one or more deoxy sugars are attached. They act on the bacteria
ribosome 50S. (See table 4)









DRUG

Trade name ®

Main uses

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(Table 4: Adopted from Range & et al, 2012; Manson, 2007; & www.patient.co.uk)




DRUG

Trade name ®

Main uses


Erythromycin


(Macrolide)


Erythrocin
 Wide variety of
bacteria
Especially gram-
positive bacteria.
Lower RTI, skin, ear
and eye infections
and gonorrhea

Clarithromycin

(Macrolide)

Klaricid

 Bronchitis.
 Pneumonia.
 Peptic ulcer.
 Ear and sinus
infections

Azithromycin

(Macrolide)


Zithromax
 Commonly for:
 Gonorrhea
 Chlamydia
 Ghancroid

Single daily dose
Community-acquired
Pneumonia.


Linezolid
(Oxazolidinones)




Zyvox


 MRSA and
Vancomycin
resistance
enterococci.

Fusidic acid M

Fucidin

 Narrow spectrum
activity.
 Used topically for
staphylococcal
infections.

Clindamycin
(lincosamide)

Cleocin HCl
 Bone and joints
staphylococcal
infections.
 Conjunctivitis (eye
drops).

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4- Antibiotics that disrupt the bacteria cell membrane

Polymixin B and Colistin (polymixinE) disrupt bacteria cell membrane. They
have a rapid bactericidal action on gram-negative bacilli.
They are used topically for treatment eye, ear, and skin infections.

Additionally, Daptomycin disturbs cell membrane through formation
transmembrane channels. It is activity limited to gram-positive organisms
(Katzung, 2009)



5. Drugs that inhibit DNA replication

5.1 Quinolones

They are divided into four generations, which act through inhibition
topoisomerase II. They act against gram-positive and gram-negative
bacteria.

They are used parentally and systemically for several illnesses such as
Pseudomonas aerugiosa respiratory infection, otitis, antrax, cervicitis,
gonorrhea, and prostatitis. (Range, 2012; eMed Expert, 2009).

For example, ciprofloxacin (cipro
®
, cipro I.V.
®
), Gemifloxacin (Factive
®4th
)
Nalidixic acid (NegGam
®1st
), norfloxacin (norxion
®2nd
), Balofloxacin
(Baloxin
3rd
) and ofloxacin (floxin
® 2nd
).



5.2 Rifampicin (Rifadin
®
)

It specifically inhibits RNA polymerase in prokaryotic cells. It is used
against tuberculosis, leprosy, and most bacteria infections (Range, 2012).


5.3 Nitrofurans

Nitrofurantoin, Unknown mechanism of action, is used for urinary tract
infection. It is effective against a variety of gram-positive and gram-
negative bacteria.

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New possible target or drug classes

Recently, new approaches are being conducted to create either new classes
of antibacterial agents or targets, for instance, Inhibition of bacteria virulence
factor have been significantly important due to two reasons; the specify of the
developed antibiotics and the targeted virulence factor is essential for bacteria
lifecycle.
Moreover, inhibition of adhesion and colonization (Virstatin, salicylidene
acylhydrazides), regulatory bacterial function (Antibodies), and inhibition of
the cell surface protein secretion (A salicylsulfamoyl adenosine) and, inhibition
bacteria cell wall resistance (Escaich, 2008). Additionally, new generation of
cephalosporins called Fifth generation as Ceftaroline (was approved oct.2010)
(Beckwith, 2011).


Recommendations






factor have been significantly important due to two reasons; the specify of the
developed antibiotics and the targeted virulence factor is essential for bacteria
lifecycle

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References

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*Beckwith, M.C., 2011. New Drug Bulletin: Ceftaroline Fosamil (TeflaroTM –
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*Bryskier, A. 2005. Antimicrobial Agents: Antibacterials and Antifungals:Beta-
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nd
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