Beta Lactam Antibacterials

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BETA-LACTAM ANTIBACTERIALS

PENICILLINS

Lecturer: D. Bhatia



Mode of Action

The penicillins are bactericidal and act byinhibition of cell wall synthesis insusceptible organisms.

All penicillins cross the blood-brain barrierpoorly



Beta-lactamase sensitive penicillins

Benzylpenicillin (Pen G)

ndications: !treptococcaltonsillitis"pharyngitis# pneumococcalpneumonia and meningitis# syphillis

$harmaco%inetics: widely distributed. T&"' ( ).*-& hour. About ')+ is

metabolised in the liver and about,)+ ecreted unchanged in urine.




Adverse-eects:

/ypersensitivity reactions e.g. rashes

!teven0s 1ohnson !yndrome 1arish-/erheimer reaction maycomplicate penicillin treatment2headache# fever# convulsions #

disturbed convulsions usually within 3hours of administration4.




Phenoxymethylpenicillin (Pen V)

ndications: prophylais of rheumaticfever# treatment of streptoccocal

tonsillitis"pharyngitis

$harmaco%inetics: oral bioavailability iserratic5 about ,)+ is absorbed# reduced

by food. T&"' ( 6) minutes. /alf thedose undergoes hepatic metabolism#and half is ecreted unchanged.




Adverse-eects:

As for ben7ylpenicillin

8astrointestinal reactions include:9ausea

omitting

DiarrhoeaBlac% hairy tongue

;andidiasis and pseudomembranous

colitis




Dose:

Mild to moderate infections: <ral# '*)-*))mg , hourly

Streptococcal pharyngitis: <ral# *))mg&' hourly for &) days

Rheumatic fever prophylaxis: <ral#

'*)mg &' hourly



Beta-lactamase sensitive penicillinswith etended spectrum

Ampicillin

ndications: Broad-spectrum activityagainst several 8ram-positiveorganisms# 8ram negative cocci andsome bacilli. =espiratory tractinfections# gastrointestinal tract

infections. >rinary tract infections 2useis limited due to resistance4.




$harmaco%inetics: <ral absorption ? 3)+#reduced by food. @idely distributed. T&"'

( &-&.* hours. !mall amount

metabolised in liver. '*-,)+ ecretedunchanged by %idneys of oral therapy.

Adverse-eects:

!%in reactions!erious anaphylactic reactions

8astrointestinal intolerance leading todiarrhoea

Dose:




Amoxicillin

ndications: As for ampicillin

$harmaco%inetics: oral absorption?*+# not reduced by food. tpenetrates well into most body uidsbut poorly into the ;!C. T&"' ( &-&.6

hours. ')-6)+ is metabolised in theliver. limination is mainly by renaltubular secretion of unchanged drug.




Adverse-eects: As for ampicillin

!%in rashes and diarrhoea are lesscommon than with ampicillin.

Dose:

<ral# *)) mg hourly



;ombination of penicillins and Beta-lactamase inhibitors

Co-moxicl! 2Amoicillin and ;lavulanic acid4

;lavulanic acid is a beta-lactamase inhibitorand is commercially available in various Eed-dose combinations. ;lavulanic has minimalintrinsic antibacterial action# but thecombination has etended the spectrum ofamoicillin to organisms that have developedresistance due to beta-lactamase production

such as S. aureus, H. inuenza, N.gonorrhoea, E. coli, Salmonella, Shigella,Klebsiella



;ombination of penicillins and Beta-lactamase inhibitors

ndications: As for ampicillin. t also hasgood activity against anaerobicorganisms.

Adverse-eects:

8astrointestinal disturbances includediarrhoea# nausea and vomitting#

abdominal discomfort# anoreia andatulence.

Dose: oral# 6F*mg 6 times daily at the

start of a meal.



Beta-lactamase resistant penicillins

Cloxcillin

ndications: infections due to beta-lactamase producing staphylococci.

$harmaco%inetics: oral absorption?*)+# reduced by food. T&"' ( ).*-&

hour. About ')+ is metabolised in the

liver. 6)-3*+ is ecreted unchangedin the urine and up to &)+ in the bile.





Beta-lactamase resistantpenicillins

"l#cloxcillin

ndications: infections due to beta-lactamase producing staphylococci.

$harmaco%inetics: @ell absorbed orally.$rotein binding G*+. T&"' ( About &

hour. ,)+ of an oral dose is ecreted

unchanged in the urine within , hours.



Beta-lactamase resistantpenicillins

Adverse-eects:

As for cloacillin. ;holestatic hepatitis.

Dose:

<ral# '*)-*)) mg , hourly



mportant points

- Dosage adHustments may need to be made

for age-related decrease in renal function.

- Bacteria have developed resistance

mechanisms to penicillins.- All antibiotics reduce eIcacy of

contraceptives. Additional precautions shouldbe ta%en.

• n7yme induction• Malabsorption of contraceptive hormones due

to antibiotic-induced diarrhoea and vomiting



CEP$AL%SP%RINS



;ephalosporins

The cephalosporins are broad-spectrumsemi-synthetic beta-lactam antibioticswith a mechanism of action similar to

that of the penicillins. nterococci areresistant to all cephalosporins.

There are 3 generations of cephaolsporins:- &st generation - 6rd generation

- 'nd generation - 3th generation



;ephalosporins

Advantages of ;ephalosporins overpenicillin

• They are more resistant to beta-

lactamase attac%.

• They have a 'nd = group 2='4 therefore

there is more room for chemical

modiEcation.• They are broad spectrum drugs and are

widely used.



;ephalosporins

Gene&tion Acti!ity Exmple'

& 8 J ;ephradine;ephadroil

' 8 J"8 - 2some4 ;efaclor;efuroime

6 8 -"8 J 2some4 ;efotaime

;eftriaone3 8 - and 8 J ;efepime

;efpirome



;ephalosporins

Cet&ixone

ndications: bacterial infections# includingmeningitis# caused by susceptible 8ram-

positive and 8ram-negative organisms.H. inuenza

N. meningitiis

N. gonorrhoea9ot eective against !. aeroginosa an

enterococci.



;ephalosporins

$harmaco%inetics: widely distributedafter parenteral administration.$enetrates well into the ;!C#

especially when the meninges areinamed. $rotein binding# *-G*+. T&"'

( 3.6-.F hours. About 3)+ hepatic

elimination. 66-,F+ is ecretedunchanged in the urine.



;ephalosporins

Adverse-eects:

- ;ross-sensivity may occur in patientsallergic to penicillin.

- 9eurotoicity manifested byhallucinations# confusion andconvulsions may occur with high

doses or in renal impairment.- 9ephrotoicity may occur

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Beta Lactam Antibacterials

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