Amoxicillin 

(INN), formerly amoxycillin (BAN), tormoxin (in
India), amoxycillin (cilamox) in Australia,[1] abbreviated amox, is a
moderate-spectrum, bacteriolytic, β-lactam antibioticused to
treat bacterial infections caused by susceptible microorganisms. It is
usually the drug of choice within the class because it is better absorbed,
following oral administration, than other β-lactam antibiotics. It is also a
treatment for cystic acne.[2]
Amoxicillin is susceptible to degradation by β-lactamase-producing
bacteria, which are resistant to a broad spectrum of β-lactam antibiotics,
such as penicillin. For this reason it is often combined with clavulanic acid,
a β-lactamase inhibitor, and marketed under one name. This increases
effectiveness by reducing its susceptibility to β-lactamase resistance.
Mode of action
Main article: Beta-lactam antibiotic

Amoxicillin acts by inhibiting the synthesis of bacterial cell walls. It

inhibits cross-linkagebetween the linear peptidoglycan polymer chains that
make up a major component of the cell walls of both Gram-
positive and Gram-negative bacteria.
[edit]Formulations

Amoxicillin in trihydrate form is available as capsules, chewable and

dispersible tablets plus syrup and pediatric suspension for oral use, and as
the sodium salt for intravenousadministration (although the IV formulation is
not available in the United States[3]). It is one of the most
common antibiotics prescribed for children, and the liquid forms are helpful
where the patient might find it difficult to take tablets or capsules. It has
three ionizable groups. A once daily dosing form (Moxatag) was approved
by the American FDA in January 2008.
[edit]Modes of Delivery
There are several mode to deliver Amoxicillin in body. Recently the
effectiveness of amoxicillin bearing human serum albumin (HSA) and poly-
lactic glycolic acid (PLGA) microparticles in combating Listeria
monocytogenes infection in Swiss albino mice was analyzed. It was found
that that amoxicillin bearing microparticles successfully home the drug to
the infected macrophages and the approach could be well exploited for
elimination of the other important intracellular pathogens as well (ref -2).
Side effects
Side effects are as those for other beta-lactam antibiotics. Side effects
include nausea, vomiting, rashes, and antibiotic-associated colitis. Loose
bowel movements (diarrhea) also may occur. Rarer, but patient-reported
side effects include mental changes, lightheadedness, confusion, anxiety,
sensitivity to lights and sounds and unclear thinking. Immediate medical
care is required upon the first signs of these side effects.
The onset of an allergic reaction to amoxicillin can be very sudden and
intense - emergency medical attention must be sought as quickly as
possible. The initial onset of such a reaction often starts with a change in
mental state, skin rash with intense itching (often beginning in fingertips
and around groin area and rapidly spreading) and sensations of fever,
nausea, and vomiting. Any other symptoms that seem even remotely
suspicious must be taken very seriously.
Use of the amoxicillin/clavulanic acid combination for more than one week
has caused mild hepatitis in some patients. Young children who ingested
acute overdoses of amoxicillin manifested lethargy, vomiting and renal
dysfunction.[4][5]
Nonallergic amoxicillin rash
Somewhere between 3% to 10% of children taking amoxicillin
(or ampicillin) show a late-developing (>72 hours after beginning
medication and having never taken penicillin-like medication previously),
often itchy rash, which is sometimes referred to as the "amoxicillin rash."
The rash can also occur in adults.[6][7]
The rash is described as maculopapular or morbilliform (measles-like;
therefore, in medical literature, it is called "amoxicillin-induced morbilliform
rash"[8]). It starts on the trunk and can spread from there. This rash is
unlikely to be a true allergic reaction, and is not a contraindication for future
amoxicillin usage, nor should the current regimen necessarily be stopped.
However, as mentioned above, this common amoxicillin rash and a
dangerous allergic reaction cannot easily be distinguished by
inexperienced persons, and therefore a health professional should be
consulted if a rash develops. (Pichichero, 2005; Schmitt 2005)
A nonallergic amoxicillin rash may also be an indicator of infectious
mononucleosis: Some studies indicate approximately 80-90% of patients
with acute Epstein Barr virus infection treated with amoxicillin
or ampicillin develop such a rash.[9]
Proprietary preparations

Novamoxin Prescription Drug - 500mg Amoxicillin Trihydrate

Amoxicillin is one of the semisynthetic penicillins discovered
by Beecham scientists. The patent for amoxicillin has expired, thus
amoxicillin is marketed under many trade names, including: Actimoxi,
Alphamox, Amocla, AMK, Amoksibos, Amoxiclav Sandoz, Amoxidal,
Amoxil, Amoxin, Amoksiklav, Amoxibiotic, Amoxicilina, Apo-Amoxi,
Augmentin (with clavulanic acid), Bactox, Betalaktam, Cilamox, Curam,
Dedoxil, Dispermox, Duomox, E-Mox, Enhancin, Gimalxina, Geramox,
Hiconcil, Isimoxin, Klavox, Lamoxy,Largopen, Moxatag, Moxilen, Moxypen,
Moxyvit, Nobactam, Novamoxin, Ospamox, Panklav (with clavulanic acid),
Pamoxicillin, Panamox, Polymox, Samthongcillin, Clamoxyl, Senox,
Sinacilin, Trimox, Tolodina, Tormoxin (India), Wymox, Yucla, Zerrsox and
Zimox.
[edit]Amoxicillin Interaction

Amoxicillin may interact with the following groups of drugs:

 Allopurinol (gout treatment)

 Birth control pills
 Certain antibiotics
 Cancer treatment (methotrexate)
 Uricosuric drugs
 Typhoid vaccine
Beta-lactam antibiotic
From Wikipedia, the free encyclopedia

Core structure of penicillins (top) andcephalosporins (bottom). β-lactam ring in red.

β-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that
contains a β-lactam nucleus in its molecular structure. This includes penicillin derivatives
(penams), cephalosporins (cephems), monobactams, and carbapenems.[1] β-Lactam antibiotics
work by inhibiting cell wall synthesis by the bacterial organism and are the most widely used
group of antibiotics.

Bacteria often develop resistance to β-lactam antibiotics by synthesizing beta-lactamase, an

enzyme that attacks the β-lactam ring. To overcome this resistance, β-lactam antibiotics are
often given with β-lactamase inhibitors such as clavulanic acid.

Clinical use
β-Lactam antibiotics are indicated for the prophylaxis and treatment of bacterial infections
caused by susceptible organisms. At first, β-lactam antibiotics were mainly active only
against Gram-positive bacteria, yet the recent development of broad-spectrum β-lactam
antibiotics active against various Gram-negative organisms has increased their usefulness.
Mode of action
β-Lactam antibiotics are bacteriocidal, and act by inhibiting the synthesis of
the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall
structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the
synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin-binding
proteins (PBPs).

β-Lactam antibiotics block not only the division of bacteria, including cyanobacteria, but also the
division of cyanelles, the photosyntheticorganelles of the glaucophytes, and the division
of chloroplasts of bryophytes. In contrast, they have no effect on the plastids of the highly
developed vascular plants. This is supporting the endosymbiotic theory and indicates
an evolution of plastid division in land plants.[2]

β-Lactam antibiotics are analogues of D-alanyl-D-alanine - the terminal amino acid residues on

the precursor NAM/NAG-peptide subunits of the nascent peptidoglycan layer. The structural
similarity between β-lactam antibiotics and D-alanyl-D-alanine facilitates their binding to the
active site of penicillin-binding proteins (PBPs). The β-lactam nucleus of the molecule
irreversibly binds to (acylates) the Ser403 residue of the PBP active site. This irreversible
inhibition of the PBPs prevents the final crosslinking (transpeptidation) of the nascent
peptidoglycan layer, disrupting cell wall synthesis.

Under normal circumstances, peptidoglycan precursors signal a reorganisation of the bacterial

cell wall and, as a consequence, trigger the activation of autolytic cell wall hydrolases. Inhibition
of cross-linkage by β-lactams causes a build-up of peptidoglycan precursors, which triggers the
digestion of existing peptidoglycan by autolytic hydrolases without the production of new
peptidoglycan. As a result, the bactericidal action of β-lactam antibiotics is further enhanced.

[edit]Modes of resistance
By definition, all β-lactam antibiotics have a β-lactam ring in their structure. The effectiveness of
these antibiotics relies on their ability to reach the PBP intact and their ability to bind to the PBP.
Hence, there are 2 main modes of bacterial resistance to β-lactams:

 Enzymatic hydrolysis of the β-lactam ring: If the bacterium produces the enzyme β-

lactamase or the enzyme penicillinase, the enzyme will break open the β-lactam ring of the
antibiotic, rendering the antibiotic ineffective. The genes encoding these enzymes may be
inherently present on the bacterial chromosome or may be acquired via plasmid transfer
(plasmid mediated resistance), and β-lactamasegene expression may be induced by
 exposure to β-lactams. The production of a β-lactamase by a bacterium does not
necessarily rule out all treatment options with β-lactam antibiotics. In some instances, β-
lactam antibiotics may be co-administered with a β-lactamase inhibitor. However, in all
cases where infection with β-lactamase-producing bacteria is suspected, the choice of a
suitable β-lactam antibiotic should be carefully considered prior to treatment. In particular,
choosing appropriate β-lactam antibiotic therapy is of upmost importance against organisms
with inducible β-lactamase expression. If β-lactamase production is inducible, then failure to
use the most appropriate β-lactam antibiotic therapy at the onset of treatment will result in
induction of β-lactamase production, thereby making further efforts with other β-lactam
antibiotics more difficult.

 Possession of altered penicillin-binding proteins: β-Lactams cannot bind as effectively to

these altered PBPs, and, as a result, the β-lactams are less effective at disrupting cell wall
synthesis. Notable examples of this mode of resistance include methicillin-
resistantStaphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae.
Altered PBPs do not necessarily rule out all treatment options with β-lactam antibiotics.
[edit]Nomenclature

The beta-lactam core structures

β-Lactams are classified according to their core ring structures.

 β-Lactams fused to saturated five-membered rings:

 β-Lactams containing thiazolidine rings are named penams.
  β-Lactams containing pyrrolidine rings are named carbapenams.
 β-Lactams fused to oxazolidine rings are named oxapenams or clavams.
 β-Lactams fused to unsaturated five-membered rings:
 β-Lactams containing 2,3-dihydrothiazole rings are named penems.
 β-Lactams containing 2,3-dihydro-1H-pyrrole rings are named carbapenems.
 β-Lactams fused to unsaturated six-membered rings:
 β-Lactams containing 3,6-dihydro-2H-1,3-thiazine rings are named cephems.
 β-Lactams containing 1,2,3,4-tetrahydropyridine rings are namedcarbacephems.
 β-Lactams containing 3,6-dihydro-2H-1,3-oxazine rings are namedoxacephems.
 β-Lactams not fused to any other ring are named monobactams.
Common β-lactam antibiotics
Penicillins (Penams)
Main article: penicillin

Semisynthetic penicillins are prepared starting from the penicillin nucleus 6-APA.

Narrow-spectrum

 β-lactamase sensitive
 benzathine penicillin
 benzylpenicillin (penicillin G)
 phenoxymethylpenicillin (penicillin V)
 procaine penicillin

 Penicillinase-resistant penicillins
 methicillin
 oxacillin[3]
 nafcillin
 cloxacillin
 dicloxacillin
 flucloxacillin

 β-lactamase-resistant penicillins
 temocillin
Moderate-spectrum

 amoxicillin
 ampicillin
Broad-spectrum

 co-amoxiclav (amoxicillin+clavulanic acid)

Extended-spectrum
Main article: Extended-spectrum_penicillin

 azlocillin
 carbenicillin
 ticarcillin
 mezlocillin
 piperacillin
Cephalosporins (Cephems)
Main article: cephalosporin

First generation

Skeletal formula of cefalexin, a first-generation cephalosporin

Moderate spectrum.

 cephalexin
 cephalothin
 cefazolin
Second generation
Moderate spectrum with anti-Haemophilus activity.

 cefaclor
 cefuroxime
 cefamandole
Second generation cephamycins
Moderate spectrum with anti-anaerobic activity.

 cefotetan
 cefoxitin
Third generation
Broad spectrum.

 ceftriaxone
 cefotaxime
 cefpodoxime
 cefixime

Broad spectrum with anti-Pseudomonas activity.

 ceftazidime
[edit]Fourth generation

Broad spectrum with enhanced activity against Gram positive bacteria and β-lactamase stability.

 cefepime
 cefpirome
[edit]Carbapenems and Penems
Main article: carbapenem

Main article: penem

Skeletal formula of imipenem

Broadest spectrum of β-lactam antibiotics.

 imipenem (with cilastatin)
 meropenem
 ertapenem
 faropenem
 doripenem
Monobactams
Unlike other β-lactams, the monobactam contains a nucleus with no fused ring attached. Thus,
there is less probability of cross-sensitivity reactions.

 aztreonam (Azactam)
 tigemonam
 nocardicin A
 tabtoxinine-β-lactam
β-lactamase inhibitors
Although they exhibit negligible antimicrobial activity, they contain the β-lactam ring. Their sole
purpose is to prevent the inactivation of β-lactam antibiotics by binding the β-lactamases, and,
as such, they are co-administered with β-lactam antibiotics.

 clavulanic acid
 tazobactam
 sulbactam
Adverse effects
Adverse drug reactions
Common adverse drug reactions (ADRs) for the β-lactam antibiotics include diarrhea, nausea,
rash, urticaria, superinfection (includingcandidiasis).[4]

Infrequent ADRs include fever, vomiting, erythema,

dermatitis, angioedema, pseudomembranous colitis.[4]

Pain and inflammation at the injection site is also common for parenterally administered β-

lactam antibiotics.
Allergy/hypersensitivity
Immunologically mediated adverse reactions to any β-lactam antibiotic may occur in up to 10%
of patients receiving that agent (a small fraction of which are truly IgE-
mediated allergic reactions, see amoxicillin rash). Anaphylaxis will occur in approximately 0.01%
of patients.[4][5] There is perhaps a 5%-10% cross-sensitivity between penicillin-derivatives,
cephalosporins, and carbapenems; but this figure has been challenged by various investigators.

Nevertheless, the risk of cross-reactivity is sufficient to warrant the contraindication of all β-

lactam antibiotics in patients with a history of severe allergic reactions (urticaria,
anaphylaxis, interstitial nephritis) to any β-lactam antibiotic.

Jarish Herxheimer reaction: Febrile reaction after first injection of penicillin

in spirochetal infection, e.g., syphilis.

Ciprofloxacin
Ciprofloxacin (INN) is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug
class.[2][3] It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering
with the enzymes that cause DNA to rewind after being copied, which stops DNA and protein
synthesis.

Ciprofloxacin is marketed worldwide with over three hundred different brand names. In the
United States, Canada, and the UK, it is marketed as Baycip, Ciloxan, Ciflox, Cipro, Cipro
XR,Cipro XL, Ciproxin, "Prociflor", and most recently, Proquin. In addition, ciprofloxacin is
available as a generic drug under a variety of different brand names and is also available for
limited use in veterinary medicine.

Ciprofloxacin was first patented in 1983 by Bayer A.G. and subsequently approved by the
United States Food and Drug Administration (FDA) in 1987. Ciprofloxacin has 12 FDA-approved
human uses and other veterinary uses, but it is often used for non-approved uses (off-label).
Ciprofloxacin interacts with other drugs, herbal and natural supplements, and thyroid
medications.[4]

Ofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class

considered to be a second-generation fluoroquinolone.[1][2] Floxin (branded version) had been
discontinued by the manufacturer, in the United States, effective June 18, 2009, though generic
equivalents continue to be available.

The fluoroquinolone (quinolone) class of chemotherapeutic agents are considered by prudent

physicians to be a drug of last resort to treat serious and life threatening bacterial infections.
Ofloxacin (floxin – floxacin) was first patented in 1982 (European Patent Daiichi) and received
approval from the U.S. Food and Drug Administration (FDA) on December 28, 1990. Ofloxacin
is sold under a wide variety of brand names as well as generic drug equivalents, for oral and
intravenous administration. Ofloxacin is also available for topical use, as eye drops and ear
drops (marketed as Ocuflox and Floxin Otic respectively in the United States).

Ofloxacin is a racemic mixture, which consists of 50% levofloxacin (the biologically active

component) and 50% of its “mirror image” or enantiomer dextrofloxacin.[3] When levofloxacin
disks were not available in early clinical trials, a 5-pg Floxin (ofloxacin –floxacin) disk was
substituted. The U.S. Food and Drug Administration (FDA) medical reviewers considered the
two drugs to be one and the same and hence interchangeable.[4][5]

Like other quinolones, ofloxacin has been associated with a significant number of

seriousadverse drug reactions, such as tendon damage (including spontaneous tendon
ruptures) andperipheral neuropathy (which may be irreversible); such reactions may manifest
long after therapy had been completed, and, in severe cases, may result in life-long disabilities.
[6]
Ofloxacin has also been associated with severe psychiatric adverse reactions.

Hepatotoxicity has also been reported with the use of ofloxacin.[7][8] Case reports

of hepatitishave been published for the older fluoroquinolones including ciprofloxacin, ofloxacin,
and norfloxacin.

Dicloxacillin

Dicloxacillin (INN) is a narrow spectrum beta-lactam antibiotic of the penicillin class. It is used

to treat infections caused by susceptible Gram-positive bacteria. It is active against beta-
lactamase-producing organisms such as Staphylococcus aureus,[1] which would otherwise be
resistant to most penicillins. It is very similar to flucloxacillin and these two agents are
considered interchangeable. Dicloxacillin is available under a variety of trade names
includingDiclocil (BMS).

Mode of action
Main article: Beta-lactam antibiotic
Like other β-lactam antibiotics, dicloxacillin acts by inhibiting the synthesis of bacterial cell walls.
It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major
component of the cell wall of Gram-positive bacteria.

]Medicinal chemistry
Dicloxacillin is insensitive to beta-lactamase (also known as penicillinase) enzymes secreted by
many penicillin-resistant bacteria. The presence of the isoxazolyl group on the side-chain of the
penicillin nucleus facilitates the β-lactamase resistance, since they are relatively intolerant of
side-chain steric hindrance. Thus, it is able to bind to penicillin-binding proteins (PBPs) and
inhibit peptidoglycan crosslinking, but is not bound by or inactivated by β-lactamases.

Clinical use
Dicloxacillin is more acid-stable than many other penicillins and can be given orally, in addition
to parenteral routes. However, like methicillin, it is less potent than benzylpenicillin against non-
β-lactamase-producing Gram-positive bacteria.

Dicloxacillin has similar pharmacokinetics, antibacterial activity, and indications to flucloxacillin,

and the two agents are considered interchangeable. It is believed to have lower incidence of
severe hepatic adverse effects than flucloxacillin, but a higher incidence of renal adverse
effects. (Rossi, 2006)

Available forms
Dicloxacillin is commercially available as the sodium salt dicloxacillin sodium in capsules (250
or 500 mg) and injections (powder for reconstitution, 500 and 1000 mg per vial).

Indications
Dicloxacillin is indicated for the treatment of infections caused by susceptible bacteria. Specific
approved indications include: (Rossi, 2006)

 Staphylococcal skin infections and cellulitis – including impetigo, otitis

externa, folliculitis, boils, carbuncles, and mastitis
 Pneumonia (adjunct)
 Osteomyelitis, septic arthritis, throat infections, streptococcus
 Septicaemia
 Empirical treatment for endocarditis
 Surgical prophylaxis
Precautions/contraindications
Dicloxacillin is contraindicated in those with a previous history of allergy
to penicillins, cephalosporins or carbapenems. It should also not be used in the eye, or those
with a history of cholestatic hepatitis associated with the use of dicloxacillin or flucloxacillin.
(Rossi, 2006)

It should be used with caution in the elderly; patients with renal impairment, where a reduced
dose is required; and those with hepatic impairment, due to the risk of cholestatic hepatitis.
(Rossi, 2006)

Flucloxacillin (INN) or floxacillin (USAN) is a narrow-spectrum beta-lactam

antibiotic of thepenicillin class. It is used to treat infections caused by susceptible Gram-
positive bacteria. Unlike other penicillins, flucloxacillin has activity against beta-lactamase-
producing organisms such as Staphylococcus aureus[1] as it is beta-lactamase stable. However,
it is ineffective against MRSA. It is very similar to dicloxacillin and these two agents are
considered interchangeable. Flucloxacillin is also available under a variety of trade names
includingFloxapen (Beecham, now GSK), Flopen (CSL) and Luf (Apex Pharma Limited in
Bangladesh) 

Mode of action
Main article: Beta-lactam antibiotic

Like other β-lactam antibiotics, flucloxacillin acts by inhibiting the synthesis of bacterial cell
walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a
major component of the cell wall of Gram-positive bacteria.

Medicinal chemistry
Flucloxacillin is insensitive to beta-lactamase (also known as penicillinase) enzymes secreted
by many penicillin-resistant bacteria. The presence of the isoxazolyl group on the side-chain of
the penicillin nucleus facilitates the β-lactamase resistance, since they are relatively intolerant of
side-chain steric hindrance. Thus, it is able to bind to penicillin-binding proteins (PBPs) and
inhibit peptidoglycan crosslinking, but is not bound by or inactivated by β-lactamases.

Clinical use
Flucloxacillin is more acid-stable than many other penicillins and can be given orally, in addition
to parenteral routes. However, like methicillin, it is less potent than benzylpenicillin against non-
β-lactamase-producing Gram-positive bacteria.
Flucloxacillin has similar pharmacokinetics, antibacterial activity, and indications to dicloxacillin,
and the two agents are considered interchangeable. It is believed to have higher incidence of
severe hepatic adverse effects than dicloxacillin, but a lower incidence of renal adverse effects.
[2]

Available forms
Flucloxacillin is commercially available as the sodium salt flucloxacillin sodium,
in capsules(250 or 500 mg), oral suspensions (125 mg/5 mL or 250 mg/5 mL), and injections
(powder for reconstitution, 250, 500 and 1000 mg per vial).

Multidrug tolerance or antibiotic tolerance 

is the ability of a disease-causing microorganism to resist killing by antibiotics or
otherantimicrobials. It is mechanistically distinct from multidrug resistance:[1] It is not caused
by mutant microbes, but rather by microbial cells that exist in a transient, dormant, non-dividing
state. Microorganisms that display multidrug tolerance can be bacteria, fungi or parasites.

Relevance to chronic infections

Multidrug tolerance is caused by a small subpopulation of microbial cells termed persisters.
[2]
 Persisters are not mutants, but rather are dormant cells that can survive the antimicrobial
treatments that kill the majority of their genetically identical siblings. Persister cells have entered
a non- or extremely slow-growing physiological state which makes them insensitive (refractory
or tolerant) to the action of antimicrobial drugs. When such persisting microbial cells cannot be
eliminated by the immune system, they become a reservoir from which recurrence
of infection will develop.[3] Indeed, it appears that persister cells are the main cause for relapsing
and chronic infections.[1] Chronic infections can affect people of any age, health, or immune
status.

[edit]Medical importance
Bacterial multidrug or antibiotic tolerance poses medically important challenges.[1] It is largely
responsible for the inability to eradicate bacterial infections with antibiotic treatment. Persister
cells are highly enriched in biofilms, and it has been suggested that this is the reason that
makes biofilm-related diseases so hard to treat.[1] Examples are chronic infections
of implanted medical devices such as catheters and artificial joints, urinary tract
infections, middle ear infections and fatal lung disease (cystic fibrosis).
[edit]Distinction from multidrug resistance
Unlike resistance, multidrug tolerance is a transient, non-heritable phenotype.[1][2][3] Multidrug
tolerant persister cells are not antibiotic resistant mutants. Resistance is caused by newly
acquired genetic traits (by mutation or horizontal gene transfer) that are heritable and confer the
ability to grow at elevated concentrations of antimicrobial drugs. In contrast, multidrug tolerance
is caused by a reversible physiological state in a small subpopulation of genetically identical
cells, [1][2][3] similar to a differentiated cell type.[4] It enables this small subpopulation of microbes
to survive the antibiotic killing of their surrounding siblings. Persisting cells resume growth when
the antimicrobial agent is removed, and their progeny is sensitive to antimicrobial agents. [1][2][3]

[edit]Molecular mechanisms
The molecular mechanisms that underlie persister cell formation and multidrug tolerance are
largely unknown.[1][3] Persister cells are thought to arise spontaneously in a growing microbial
population by a stochastic genetic switch,[3][5] although inducible mechanisms of persister cell
formation have been described.[3][6] Owing to their transient nature and relatively low abundance,
it is hard to isolate persister cells in sufficient numbers for experimental characterization and
only few genes have been identified to date.[1][3] The best understood persistence factor is the
Escherichia coli high persistence gene HipA.[7][8]

Meticillin
Meticillin (INN, BAN) or methicillin (USAN) is a narrow-spectrum beta-lactam antibiotic of
thepenicillin class.

History
It was developed by Beecham in 1959.[1] It was previously used to treat infections caused by
susceptible Gram-positive bacteria, in particular, beta-lactamase-producing organisms such
asStaphylococcus aureus that would otherwise be resistant to most penicillins, but is no longer
clinically used.

Its role in therapy has been largely replaced by flucloxacillin and dicloxacillin, however the
termmethicillin-resistant Staphylococcus aureus (MRSA) continues to be used to
describeStaphylococcus aureus strains resistant to all penicillins.

Methicillin is no longer manufactured because the more stable and similar penicillins such
asoxacillin (used for clinical antimicrobial susceptibility testing), flucloxacillin,
and dicloxacillin are used medically.
[edit]Mode of action
Main article: Beta-lactam antibiotic

Like other beta-lactam antibiotics, methicillin acts by inhibiting the synthesis of bacterial cell
walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a
major component of the cell wall of Gram-positive bacteria. It does this by binding to and
competitively inhibiting the transpeptidase enzyme used by bacteria to cross-link the peptide (D-
alanyl-alanine) used in peptidoglycan synthesis. Methicillin and other beta-lactam antibiotics are
structural analogs of D-alanyl-alanine, and the transpeptidase enzymes that bind to them are
sometimes called penicillin-binding proteins (PBPs). [2]

[edit]Medicinal chemistry
Methicillin is insensitive to beta-lactamase (also known as penicillinase) enzymes secreted by
many penicillin-resistant bacteria. The presence of the ortho-dimethoxyphenyl group directly
attached to the side-chain carbonyl group of the penicillin nucleus facilitates the β-lactamase
resistance, since those enzymes are relatively intolerant of side-chain steric hindrance. Thus, it
is able to bind to penicillin-binding proteins (PBPs) and inhibit peptidoglycan crosslinking, but is
not bound by or inactivated by β-lactamases.

[edit]Clinical use
Methicillin is not used to treat patients because of its unfavorable side-effect profile. But it
serves a purpose in the laboratory to determine the antibiotic sensitivity of Staph aureus to
other beta-lactamase-resistant penicillins