Pediatrics in Review

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DOI: 10.1542/pir.15-11-4401994;15;440Pediatrics in Review

Kathleen A. Woodin and Susan H. MorrisonBACK TO BASICS: Antibiotics: Mechanisms of Action

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Print ISSN: 0191-9601.Village, Illinois, 60007. Copyright 1994 by the American Academy of Pediatrics. All rights reserved.

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44 0

P ed iatrics in Rev iew V oL 15 No. 11 Novem ber 1994

Ant ib iot ics : M echan ism s o f A ction

K ath leen A . W ood in M D and S usan H . M o rrison M D t

M edica l prac tice rests on the founda tion o f science . C lin icia ns are constan tly m ak ing p rac tica l dec isions and d ea ling

w ith imm ed ia te situa tio ns tha t dem and so lu tion s. T im e should b e taken to fo cu s on th ose sc ien tific prin cip les tha t

u nderlie o ur d iagnostic and therapeu tic m aneuvers. Th is sec tion o f

Ped ia tric s in R ev iew

presen ts se lected top ics tha t

a re re levan t to pra ctice from the area s o f physio lo gy , p harm aco logy , b iochem is try, and o ther d isc ip lin es; c lar ifica tion

o f these w ill a ugm ent the ped ia tric ia n s understand ing o f c lin ica l p rocedures.

In t roduct ion

U n like p hys icians p rac tic ing in the

19 40s, w ho had on ly su lfonam id es

an d p en ic illin to trea t in fectio ns,

p rac tition ers now choose from a

broad and som e tim es o ve rw he lm in g)

n um ber o f an tib io tics . H ow eve r ,

trend s in em erg in g an tim icrob ial re -

sis tance m ay fo rce us to take a g ian t

step b ackw ard to tha t frig h ten ing sit-

ua tion of the past o f h av ing b ac te ria

th at a re e ssen tia lly u n trea tab le by

any of o ur av ailab le an tib io tics .

T h is a r ticle is an o ve rv iew o f som e

of the m ic rob io logy , ph arm aco log y ,

and physio logy c ritica l to the ratio na l

u se o f an tib io tics in tod ay s p rac tice .

I t summ arize s the basic m ech an ism s

of ac tion of som e comm only u sed

an tib io tic s an d b rie f ly d iscu sse s th e

em ergence o f re sis tance to seve ra l

com mon pa tho gens.

S truc tu res o f B ac te r ia

Im po rtan t to A n tib io tic

Act ion

T he ou term os t com pon en t o f m o st

bac ter ia is the cell w a ll, a m ultilay -

e red s truc tu re lo ca ted ex terna l to the

cy to p la sm ic m em bran e. Th e ce ll w a ll

is com po sed of an inn e r laye r o f pep -

tido g lycan , a com plex in te rw oven lat-

tic e o f linear sug ars g lycan ) tha t a re

c ros s-lin ked b y pep tide cha ins. P ep -

tidog lycan prov id es th e r ig id su ppo rt

by w hich the ce ll m a in ta ins its cha r-

acte r is tic sh ap e.

G ram -po sitive an d G ram -n eg a tive

bac ter ia d iffe r in the ir cell w all s truc -

tu res F ig u re) . In G ram -pos itiv e

o rgan ism s, the pep tid og ly can laye r is

a th ick

15

to 80 nm ) m ultilaye r an d

m ay hav e a th in laye r o f te icho ic

acid ou tside the pep tid og ly can . In

con tra st, G ram -neg ativ e o rg an ism s

have a th in 2 nm ) sing le lay e r o f

p ep tidog lycan cove red by a com plex

ou te r m em bran e lay er com po sed o f

lip opo lysacch arides, lipop ro te in s, and

pho sph o lip ids . T he ou te r m em brane

of G ram -nega tive bac ter ia con ta ins

porn pro te ins tha t ac t a s ch an ne ls to

transp ort sm a ll m o lecu le s su ch as

suga rs , m e tals , v itam in s, and an tib io t-

ics in to th e b ac te ria l ce ll.

T he cy top lasm o f bac ter ia con tain s

an inn er nu c leo id reg ion com po sed of

sing le -strand ed c ircu la r D NA and

m atrix th a t con ta ins r ibo som es, nu tr i-

en t g ranu le s , m e tab o lite s , and p la s-

m ids . P la sm ids are doub le -stranded

c ircu lar D NA m olecu les th at can rep -

lica te indep en den tly o f th e bac ter ia l

ch rom o som es . M o st p la sm id s are ex -

trach rom osom a l, b u t som e a re in te -

g ra ted in to th e b acte r ial ch rom osom e .

P la sm ids o ccur in bo th G ram -n ega -

tiv e an d G ram -po sitive o rgan ism s

and a re an im portan t sou rce o f

gene tic in fo rm a tion th a t can convey

re sis tance to v ariou s an tib io tics .

Se lec tive Tox ic ity

A n id ea l an tim ic ro b ia l agen t w ou ld

exh ib it s elec tive tox ic ity ; tha t is , the

d rug w ou ld b e ha rm fu l to th e in fect-

ing m ic roo rgan ism w ithou t h arm ing

the h ost. B ecause pep tido g lycan is

p re sen t in b ac te ria bu t no t in h um an

ce lls , it is an exce llen t ta rg et fo r an ti-

b io tic s . S im ila rly , an tib io tic s th at a f-

fec t p ro tein syn thesis take advan tag e

o f the d iffe rences in size and ch em i-

ca l com position of r ibo som es from

bac te ria an d euk aryo tic o rg an ism s ie ,

th ose hav ing a true nu c leu s su r-

roun ded by a nuc lear m em b rane and

m u ltip le ch rom o som es , as in hum an

ce lls). O th er m e tabo lic s tep s tha t oc -

cu r in bac ter ia b u t n o t hum an s eg ,

syn th esis o f fo lic ac id fo r n uc leo -

tid es ) a lso can b e inh ib ited se lec -

tiv ely b y an tib io tic s .

B ac te ric Id a l V ersus

B ac te rlo s ta t lc P rope rt ies o f

Ant ib iot ics

A favo rab le th erapeu tic ou tcom e fo l-

low ing the adm in istra tion of a spe -

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W E K E N C E L L W L L B Y

IN H IB IT IN G C R O S S L IN K IN G O F

P E P T I DO G L Y C N

Pediatr i cs in Review VoL 15 No. I i November 1994 441

cif ic antibiotic depends on multiple

factors, including those related to the

bacteria eg, resistance mechanisms ,

the antibiotic eg, mechanism of ac-

tion, ability to penetrate to the in-

fected site, and spectrum of activity ,

and the host defenses eg, phagocyto-

sis, opsonization, complement pro-

duction . W hen host defenses are

maximally effective, the contribution

of the antibiotic may be less impor-

tant. For example, a bacteriostatic

agent eg, chloramphenicol, erythro-

mycin, clindamycin, tetracycline that

slows or inhibits protein synthesis

may be adequate when combined

with the host s ability to opsonize

and phagocytize bacteria. In contrast,

a patient whose host defenses are im-

paired may require a bactericidal

agent eg, penicillin, cephalosporin,

am inoglycoside that actually w ill kill

or lyse the bacteria. Bactericidal

agents T able 1 g enerally are used to

treat bacterial endocarditis, meningi-

tis, and osteomyelitis as well as any

bacterial infections in neutropenic

patients.

n t ib io t ic S u s c e p tib ilit y

I f the concentration of an antibiotic

required to inhibit or kill the organ-

ism can be achieved safely in the af-

fected tissue or fluid, a micro-

organism is considered sensitive to a

particular antibiotic. H owever, if the

concentration required is greater than

what can be achieved safely, the mi-

croorganism is considered to be resis-

tant to that antibiotic. M ost in vitro

sensitivity tests are standardized on

the basis of drug concentrations that

can be achieved safely in plasma and

may not take into account increased

drug concentrations that may occur at

specif ic sites eg, bladder or any lo-

cal conditions that may affect the ac-

tivity of the antimicrobial agent.

Me c h a n is m s o f c t io n o f

n t ib i o t i c s

For many antibiotics, the mechanism

of action is not understood fully.

H owever, it is known that antibiotics

can act in the follow ing ways: 1 in-

hibit cell wall synthesis, 2 alter the

permeability of the cell membrane,

3 inhibit protein synthesis, and

4 inhibit nucleic acid synthesis

T able 1 .

Pe nicil lins a n d

Cephalosporins

Penicillins and cephalosporins beta-

lactam antibiotics are among the

most widely prescribed antibiotics be-

cause of their safety profiles. The ba-

sic structure of penicillin consists of

a five-member thiazolidine ring con-

nected to a beta-lactam ring to which

a side chain is attached. In contrast,

the cephalosporins have a six-mem-

bered hydrothiazine ring connected to

the beta-lactam ring. A n intact beta-

lactam ring structure is an essential

requirement for the biologic and anti-

bacterial activity of both penicillins

and cephalosporins. N ew derivatives

of the basic penicillin nuclei continue

to be produced; each has unique ad-

vantages. M odification of the various

side chains on these structures affects

the specif ic antibacterial spectrum as

well as the pharmacokinetic profile of

these drugs.

Beta-lactam antibiotics kill suscep-

tible bacteria by interfering with cell

wall synthesis. T hey are bactericidal,

but only kill organisms undergoing

active cell wall synthesis. T he bio-

synthesis of peptidoglycan in the cell

wall occurs in three stages and in-

volves about 30 different enzymes.

Beta-lactam antibiotics inhibit trans-

peptidases, the enzymes that catalyze

the final cross-linking step of pepti-

dogl ycan sy nthesi s.

There also are receptors called

penicillin binding proteins PBPs in

the bacterial cell membrane and cell

wall for the beta-lactam antibiotics.

Each bacterium has several types of

PBPs that vary in their affinity for

different penicillins and cephalospo-

rins. Some PBPs are transpeptidases

responsible for peptidoglycan cross-

linking and necessary for bacterial

shape; the function of others is

unknown. I nhibition of PBPs causes

abnormal cell shape, division, and

eventual lysis. A ltering the PBPs is

one mechanism by which bacteria

can develop resistance to penicillin.

This resistance may be intrinsic be-

cause of structural differences in

PBPs or a previously sensitive strain

may acquire resistance follow ing a

mutation of PBPs. Resistance of

Str eptococcus pneumoni ae t o peni ci l-

lin and cephalosporins, which has

been reported around the world as

well as in the U nited States, is due to

alterations in PBPs Table 2 .

A ctivation of cell wall autolytic

enzymes ie, autolysins is another

factor that is important in the degra-

dation of the cell wall. The relation-

ship between the inhibition of PBP

activity and the activation of autoly-

sis is unclear and very complex. Tol-

erance to penicillin occurs when the

organism is inhibited but not killed

by an antibiotic that usually is bacte-

ricidal. For example, the growth of

certain tolerant strains of Staphylo-

coccus aur eus can be arrested by

beta-lactam antibiotics, but autolytic

enzymes are not activated.

Production of beta-lactamases, en-

zymes that can cleave the beta-lactam

ring, is an important mechanism for

the inactivation of beta-lactam antibi-

otics and development of resistance

by many bacteria eg, S a ur eu s N ei s-

se r ia gono r rhoeae Pseudomonas sp,

Bacter oides fr agi l i s and some enteric



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442 Ped ia tric s in R eview VoL 15 No . 11 N ovember 1994

IT . I

ME C H A N IS M D R U G S A C T O N

W eaken bacter ial cell wall and cause cell death

. In h ib it c ro ss- link in g of p ep tido g lycan P en ic illin s , ceph alo sporins B ac ter ic ida l

. A ctiv ate au to ly tic enzym es ie , au to ly sins)

. In h ib it o the r step s in pep tid og ly can syn th esis V ancom yc in B ac te ric ida l

In c rea se ce ll m em bran e pe rm eab ility

. C ause leakage of cell con ten ts P o lym yx in NA

I nhibit protein synthesis

. B ind to 5 05 ribosom e subun it C h lo ram ph en ico l B acte r io sta tic

E ry th rom yc in B acte r io sta tic

C la rith rom yc in B acte r io sta tic

C lin dam yc in B acte r io sta tic

. B ind to 3 05 ribosom e subun it Am in og ly co sides B acte r icid a l

T e tracyc line s B acte r io sta tic

I nhibit nucleic acid synthesis

. Inh ib it nuc leo tide syn th esis S u lfon am ides, tr im e thop rim B ac te rio sta tic

. Inh ib it DNA -d ep en den t RNA polym erase R ifam pin B ac te ric ida l

. Inh ib it D NA sup erco iling and DNA syn thesis Q u in o lon es B ac te ric ida l

Note Bacteriosta t ic

gents m ay e c ter ic id l g ins t som e o rganism s a t high concentration s.

D R U G S F O R W H IC H R E S IS TA N C E

O R G A N IS M H A S B E E N R E P O R TE D R E C O MM E N D A TiO N S

Strep to co ccu s pneum on iae {149 }

en icillin {149}ondu ct o xac illin d isk su scep tib ility on

In te rm ed iate - lev el re sis tance is a ll iso la tes

in c rea sing {149}f re sis tan t, check M IC s to p en ic illin ,

H igh -leve l res is tan ce h as b een ce fo tax im e , ce f triaxo ne , vancom yin ,

repo rted in va rious a rea s o r o the rs

w orldw ide an d is inc rea sing {149}f sensitive , suscep tib le to a ll b eta -

in the U nited S ta tes lac tam s

C luste rs o f ca se s m ay o ccu r eg , {1 49}f m en in g itis , trea t w ith v an com yc in

ch ildca re co n tac ts) PLU S th ird -gene ratio n ceph alo spo rin

{149}ep ha lospo rin s O R ch lo ram phen ico l O R im ipen em

T reatm en t failu re s h av e prom pted pend ing suscep tib ility te stin g

su scep tib ility te sting

Enterococcus feca lis {149 }

m p icillin {1 49}f invasiv e d isea se , ch eck M IC s an d treat

Enterococcus faec ium {149}

ancom y in w ith am pic illin PLU S vancom yc in

R es is tan t s tra in s have been PLUS am inog lycoside gen tam ic in )

id en tified p en d ing suscep tib ility tes ting

Neisseria gonorrhoeae {149 }en ic illina se -p ro duc ing s tra in s {149 }en icillin o r d oxy cyc line a re n o t

comm on recom m ended em pir ic the rap ies

{149}e tracyc line {149}on ito r f luo roq u ino lone suscep tib ility

H ig h-lev el p la sm id -m ed ia ted pa tte rn and c lin ica l re sp onse

resis tan ce reported {149}h ird -g en era tion cep ha losp orin s eg ,

{ 1 4 9 }lu o roqu ino lo nes ce ftr iax one ) still seem effectiv e

D ec reased su scep tib ility repo rted



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Ped iatrics in Rev iew V oL iS No . ii No vem ber 1994

44 3

Gram-negati ve baci l l i ). T he inf orma-

ti on f or producing beta- lactamases

can be coded in chromosomes or on

a plasm id. T he beta-lactamases can

be consti tuti ve produced al l the

time) or inducible only produced at

certai n ti mes).

In the case of inducible resi stance,

the organism ini ti al l y w i l l be suscep-

ti ble to a certain antibioti c, but af ter

a short per iod of therapy , the organ-

i sm w i l l become resistant because of

the beta- lactamases that have been

induced. Frequentl y , thi s i s signaled

by only l im i ted improvement or cl i ni -

cal deter iorati on of the patient af ter

an ini ti al improvement. Inducible

beta-lactamase production i s a partic-

ular problem w i th some Gram-

negati v e bacter ia eg, Pseudomonas ,

Enterobac ter, C itro bac ter, A c ine to -

b ac ter , S erra tia

sp) treated w i th

broad-spectr um cephal ospor ins.

B eta- lactamase production by bac-

ter ia can be inhibi ted by the addi ti on

of certain chem ical structures that are

sim i lar i n structure to penici l l i n eg,

clavulanic acid, sulbactam). The in-

hibi tors bind strongly to the beta-lac-

tamases and prevent the subsequent

inacti vati on of the penici l l i n nucleus.

Penici l l i ns have good acti v i ty

against G ram-posi ti ve bacter ia and

oral anaerobes and variable acti v i ty

against G ram -negati v e baci l l i . T hey

are the treatment of choice for syphi -

l is, l eptospi rosi s, or

Listeria

infec-

tions. Penici l l i ns general ly are

classi f i ed according to thei r spectrum

of acti v i ty as determ ined by changes

in thei r side chains relati ve to peni -

ci l l i n: penici l l inase-resi stant penici l l i n

g, methi ci l l i n, nafci l l i n, oxaci l l i n,

cloxaci l l i n, and dicloxaci l l i n) ; am ino-

penici l l i ns ampici l l i n, amox ici l l i n) ;

antipseudomonal penici l l i ns eg, car-

benici l l i n, ti carci l l i n, and azloci l l i n);

and ex tended-spectrum penici l l i ns

eg, mezloci l l i n, piperaci l l i n) .

The cephalosporins are div ided

into generations based on thei r an-

ti mi crobi al acti vi ty . Fi rst-generati on

cephalosporins eg, cephalex in, cef a-

drox i l , and cef azol i n) have good ac-

ti v i ty against Gram-posi ti v e bacteria,

i nc lu di ng p en ic il l in ase- pr od uc in g

S

aureus ,

group A beta-hem ol yti c

streptococci , group B streptococci ,

and

S p ne um o ni ae ,

and modest acti v -

i ty against some Gram -negati v e or-

gani sm s. T he second- generati on

cephalosporins eg, cefaclor, cef urox-

ime, cef urox ime axeti l , cefprozi l , cef -

amandole, cefox i ti n, and cef otetan)

retain acti v i ty against Gram-posi ti v e

organisms but have more acti v i ty

against Gram-negati ve organisms, in-

cluding most strains of

Haemoph i lu s

in f luenzae

and some strains of enteri c

bacter ia. The thi rd-generation cepha-

lospor ins eg, cef i x ime, cefoperazone,

cefotax ime, cefpodox ime proxeti l ,

cef tazidime, cef ti zox ime, and cef tr i ax -

one) are more acti v e against G ram-

negati ve organisms including

Enterobac ter iaceae

and beta- lac tamase -

producing strains of

H in fiu en za e,

M oraxe lla ca ta rrha lL i,

and

N gonor -

rhoeae),

but they are less acti ve than

f i rst-generation cephalosporins against

G ram-posi ti v e organism s. Cef tazidim e

i s acti ve agai nst

Ps eudomona s

sp and

has superior central nervous system

penetrati on compared w ith am inogly co-

sides. Cef tri axone has a prolonged

hal f - l i f e that al l ow s f or once-a-day

dosing. N one of the cephalosporins i s

ef f ecti v e against anaerobes, entero-

cocci , or

L m o no c yt og en es .

B ecause of the structural sim i lar i ty

betw een penici l l i n and f i rst- and sec-

ond-generation cephalosporins, pa-

ti ents may m ani fest cross-reacti v i ty

w hen a member of the other class i s

adm inistered. Immunologic studies

dem onstrate a 20 cross-r eacti vi ty ;

more recent cl i ni cal studies indicate a

f requency as low as 1 . Cross-reac-

ti v i ty betw een penici l l i ns and cepha-

losporins general l y occurs in about

8 of patients w ho have a history of

an al l ergi c reaction to penici l l i n. A l -

though side chains do not seem to be

a f actor in al l ergi c reactions to peni -

ci l l i ns, they may be important in

cephalosporin al l ergy . The patient

w ho is al l ergi c to cephalosporins may

have an al lergy to the beta- lactam

ring, the bulk y side chain, or both.

T he ri sk of al l ergi c reaction w i th the

new er thi rd-generation cephalosporins

i s not known.

WEAKEN CELL WA L L BY

IN HIB IT IN G P EPF ID OG LY CA N

SYNTHESIS

Vancomyc in

V ancomycin i s a complex and unu-

sual tri cycl i c gl ycopeptide that inhib-

i ts cel l synthesis in sensi ti ve bacter ia

by binding tightl y to precursor sub-

uni ts of the cel l w al l and preventing

thei r i ncorporati on into the grow ing

peptidoglycan. The drug is rapidl y

bacter i cidal f or di v iding m icroor-

ganisms. B ecause vancomycin may

be only bacter iostati c f or some en-

terococci , an am inoglycoside is

added to vancomycin therapy in se-

ri ous inf ecti ons known to be caused

by thi s organism eg, infecti ve en-

docarditis).

Earl y preparations of vancomycin

contained impuri ties that probably

contri buted signi f i cantl y to the tox i c-

i ty associated w i th i ts earl y use; thi s

no longer i s a problem. I n recent

years, there has been renew ed interest

i n the use of vancomycin for several

reasons. Fi rst, i t i s structural l y unre-

lated to other antibioti cs, so i t i s use-

f ul i n the patient w ho is al l ergi c to

penici l l i n and cephalosporins. Sec-

ond, i t i s acti ve primari l y against

G ram -posi ti ve bacteria and f orms the

mainstay of therapy for the treatment

of i nf ecti ons caused by methici l l i n-

resistant

S aureu s M RSA , coagu -

l ase-negati ve staphy lococci that are

resi stant to other penici l l i ns, and

S

pneumoniae

strains that are resi stant

to penici l l i n and cephalosporins Ta-

ble 2). V ancomycin i s an important

antibioti c for use in immunocom -

prom ised patients who have ev i -

dence of catheter-related inf ecti ons.

B ecause oral vancomycin i s ab-

sorbed poorl y , high concentrati ons

occur in the stool . T hus, i t can be

used as a more expensive al ternati ve

to metronidazole f or the treatment of

C lo strid ium diffic ile i nfecti ons; me-

tronidazole i s not approved by the

Food and D rug A dm inistrati on f or

use in chi l dren.

R ep or ts o f v ancom yci n- resi st ant

strains of enterococci and

S aureus

have caused ex treme concern in the

medical communi ty . Prudent use of

thi s drug is essential to m inim ize the

development of further resi stance.

M easurement of serum levels of van-

comycin i s recommended to avoid

potential ototox i ci ty and nephrotox i c-

i ty . The incidence of both tox i ci ti es

i s increased w hen vancomycin i s ad-

m ini stered simul taneously w i th an

aminoglycoside.

IN CR EA SE C ELL

PERMEAB IL I TY

Polymyx in B

Polymyx in B is a basic peptide elab-

orated by various strains of

Bac il lus



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G ram -positiv e an d G ram -negativ e b ac teria d if f e r in th e ir ce ll

w all s truc tu res; th e pep tid og ly can lay er is th ick in G ram -positiv e

o rgan ism s and th in in G ram -negativ e o rgan ism s.

444 Pediatr i cs in Review Vol . 15 No. 11 November 1994

sp . I t is a surf ace -ac tiv e ag en t con-

tam ing both lipophilic and lipophob ic

groups w ith in the m o lecu le that in ter-

ac t strong ly w ith phospholip id s and

d isrup t the in teg rity o f cell m em -

branes. T h e perm eability o f the bac-

terial m em brane changes im mediate ly

af ter contact w ith th e d rug . Poly -

m y x in B is p rescrib ed p rim arily f or

ophthalm ic, o tic , or to p ical use in

com binatio n w ith a v arie ty o f o ther

com pound s eg , bac itrac in , neom yc in ,

hydrocor t isone).

IN H IB IT PR O TE IN SY NT H ESIS

R ibosom es are the site o f p ro tein

sy n thesis in bo th bacterial and euk ar-

y o tic ce lls , b u t bac terial and eu k ar-

y o tic ribo som es d if f e r in bo th siz e

and ch em ical com pos ition . B ac terial

rib osom es are 70S in siz e w ith 50S

and 30S subunits) com pared w ith

80S w ith 60S and 40S subunits) in

euk ary o tic ce lls . T hus, an tib io tic s that

ph en ico l usually is caused by a

p lasm id acqu ired b y conjugatio n .

O ther p lasm id s m ay tran sf er resis-

tance to m u ltip le an tib io tics eg,

ch lo ram phenico l, te tracy c lin e, and

beta-lac tam s). O nce acety lated , chor-

am phenico l cannot attach to the

bacterial riboso me .

U se of ch loram phenico l m u st be

lim ited to in f ec tions fo r w hich th e

bene f its o f th e d rug outw eigh the risk

o f th e poten tial tox ic itie s eg, rev ersi-

b le , dose -re lated bone m arrow sup-

press ion , po ten tially f atal id iosy n-

cratic ap las tic anem ia, and g ray

baby sy ndrom e). W hen antim icro-

b ials that hav e equiv alen t ac tiv ity bu t

are poten tially les s to x ic are av aila-

b le, they should b e used . In additio n ,

it is necessary to m on itor serum lev -

e ls w hen treatin g a patien t w ith ch lo-

ramphenico l .

C hloram phen ico l is a broad-spec-

trum antib io tic that is ac tiv e against

R esistance to ery throm y cin can oc-

cur by at least three p lasm id -m ed i-

ated m echan ism s: f ailure o f the drug

to p en etrate the cell, m odif icatio n o f

the targe t site s on the 505 ribo som e

so that the drug fails to b ind , and

produc tion o f an esterase by the bac-

teria to h y dro ly z e the d rug .

G ram -positiv e bac teria accum ulate

about 100 tim es m ore ery throm y cin

th an do G ram -negativ e organism s.

A lth ough ery throm y cin generally is

classif ied as a bac teriostatic ag ent, it

can hav e bacteric id al ac tiv ity again st

a sm all num ber o f rap id ly d iv id ing

bac teria, especially in an alk aline

env ironment.

In patien ts w ho hav e p en ic illin al-

lergy , ery th rom y c in is an ef f ec tiv e al-

te rnativ e agent agains t G ram -positiv e

bac teria such as group A s trep to-

cocc i ,

S pneumon iae

an d

S a ur eu s.

H ow ev er, the em ergence o f res istan t

strains m u st b e m on itored . E ry thro-

m yc in also has good an tim icrob ial

ac tiv ity agains t

Bor detel la per tussi s

Borre l ia

sp ,

Campylobacter

sp ,

Chla-

mydi a t rachom at is C p neum on iae

W A R strain),

M ycoplasma pneu-

moniae

an d

L egi onel la pneumophi la.

Clanthromyc in

af f ec t pro te in sy n th es is can hav e a

se lec tiv e e f f ec t o n sen sitiv e bac teria

w ithou t af f ec ting hum an ce lls .

Ch lo r amphen ic o l

Ch loram phenico l, a n itro benz ene

m o iety , pene trates bac terial cells by

f ac ilitated d if f u sion and bind s rev ersi-

b ly to th e bac terial

505

ribosom al sub-

un it. T his drug lik e te tracy clin es

e f f ec t o n th e 305 ribosom e subunit)

b lock s th e b ind ing of the am inoacy l

transf er R N A tR N A ) to th e accep tor

site on the ribosom e. C hlo ram pheni-

co l h as less o f an e f f ect o n p ro te in

sy n th es is in eu k ary o tic cells than in

bacterial cells . C hloram phen ico l is

prim arily a bac terio static agent, bu t it

m ay be bac teric idal to certain spec ies

eg ,

H i n fl u en za e S p neu mo ni a e N

meningiditis .

M echanism s of res istan ce to ch lor-

am phen ico l inc lud e productio n of an

ace ty ltransf erase by th e bac teria that

inac tiv ates ch lo ram phenico l and in-

ab ility o f ch loram phen ico l to en ter

se lected bac teria. R esistance o f

G ram -negativ e bacteria to ch lo ram -

m any G ram -po sitiv e and -negativ e

bac teria as w ell as against rick e ttsiae .

In particu lar, it is e f f ectiv e again st

m ost anaerobic bac teria, inc lud ing

B

frag i l is

and the m ajo rity o f

Salmo-

nella

sp and

H i nf luenza e

strains. I t

is a recom m ended alternativ e therapy

f or in f ec tion s cau sed by

Brucella

an d

Pasteurella

sp as w e ll as fo r R ock y

M ountain spo tted f ev er. C hloram -

phenico l has b een e f f ec tiv e in som e

S

pneumoniae

in f ec tions resistan t to

pen ic illins and cephalo spo rins .

Ery thromyc in

Ery throm y c in has a m acro lid e struc -

ture com po sed o f a large 13 -carbon

ring to w hich tw o sugars are attached

by gly co sid ic link ag es. E ry throm ycin

and o ther m acro lides inh ib it pro te in

sy n thesis by rev ers ib ly b ind ing to the

50S ribo som e subunit o f sensitiv e

m icroorganism s. I t b lock s the tran slo-

cation s tep in pro te in sy n thesis by

prev en ting the re lease o f the tR N A

from the accep to r to the donor site

on the rib osom e af ter the p ep tide

bond is fo rm ed .

C larith rom y c in , recen tly appro v ed f or

ped iatric use , d if f e rs chem ically f rom

ery throm y cin by hav ing a m ethy l

sub stitu tion on the m acro lide ring . Its

sp ec trum of ac tiv ity is sim ilar to that

o f ery th rom y c in ex cep t f or enhanced

H i nf luenzae

ac tiv ity in c lud ing be ta-

lactam ase-produc ing strains) , and its

longer half -lif e allow s fo r tw ice -a-day

dosin g . C larithrom y c in and its ac tiv e

m etabo lite pene trate w e ll in to body

f lu id s and tissues eg, lung tissue ,

to nsils) , resu lting in in trace llu lar and

tissue concen tration s th at are h igher

than serum concentrations. G astro in-

tes tinal s ide e f f ects o ccur less f re-

quen tly in patien ts rece iv ing

clarithrom y cin 8 to 16 ) than in

those treated w ith ery th rom y c in 20

to 40 ). B ecause it reaches ex ce llen t

lev els in serum , alv eo li, m acrophages ,

and lung tissue , o ther im portan t u ses

o f c larith rom y c in w ill b e in the ther-

ap y o f

M ycobacter ium avium

an d

C

pnewnoniae

TW A R ) in f ec tion s.

Cl indamyc in

C lindam y c in , a deriv ativ e o f an

am ino ac id attached to a su lfu r-con-



7/10

In patien ts w ho hav e pen ic illin alle rgy , e ry th rom y c in is an

e f f e c tiv e alte rnativ e agen t.

Pediatr i cs in Review VoL 15 No. i i November 1994 445

tam ing sugar, has rep laced its paren t

d rug lin com y c in in c lin ical use . C lin -

dam y c in inh ib its pro te in sy n thesis by

rev ersib ly b ind ing to th e 505 rib o-

som e subunit o f sensitiv e m icrorgan-

ism s . A lthough bactericid al fo r som e

o rgan ism s, c lindam y c in generally is

b ac terio static . M echan ism s o f resis-

tance are sim ilar to th ose outlin ed f or

ery thromyc in .

C lindam y c in is ac tiv e against

p neum ococci and group A strep to-

cocc i. I t h as ex ce llen t ac tiv ity against

S aur eus

and m any anaerob ic bacte -

ri a, p ar ti cu l ar ly

B f rag il is.

Clinda-

m y c in is an im portan t an tib io tic f or

th e treatm ent o f in tra-abdom inal or

p elv ic in f ec tion s and as an alterna-

tiv e th erapy in patien ts w ho are al-

le rg ic to p en icillin . B ac terial s trains

th at are resistan t to c lindam y c in gen-

erally are resistan t to ery th rom yc in .

C lindam y c in p en etrates w e ll in to

m ost bod y f lu id s, inc lud ing sputum ,

p leural f lu id , and bone . H ow ev er, it

should not be used f or cen tral nerv -

ous sy s tem in f ec tio ns becau se o f its

p oo r p ene tration in to cereb ro sp inal

f lu id .

the inner cy to p lasm ic m em brane can

be reduced by acid ic or anaerobic

cond itions , su ch as tho se presen t in

an ab scess. Inac tiv ation b y m icrob ial

enz ym es is an im portan t cau se o f the

acquired resistan ce to am inogly co-

sides that occurs f requently . T h e ge-

ne tic in f orm ation f or th ese enz ym es

is acqu ired p rim arily by conjugatio n

and the tran sf er o f D N A as plasm id s

o r resistance f ac tors. S uch plasm id s

are w idespread and m ay dissem inate

resistance to o ther antib io tic s sim ulta-

n eously . A m ik ac in m ay be less v u l-

n erab le to these inactiv atin g en z y m es

than k anam y c in , gen tim ic in , and to-

bram y c in becau se o f pro tec tiv e m o-

lecu lar side chain s.

T h e an tibac terial activ ity o f am i-

nogly co sides is d irec ted prim arily

again st aerob ic G ram -negativ e bac illi;

there is little ac tiv ity again st anaer-

obes or G ram -positiv e bac teria.

S trep tom y c in has b een used in th e

outer m em brane of bac teria. T hen it

is transported in to the inner cy top las-

m ic m em branes w here it is bound

m ain ly to the 30S subunits o f th e

bac terial ribosom es. T he tetracy c lines

inh ib it pro te in sy n thesis b y b lo ck ing

am inoacy l tR N A f rom enterin g the

accep tor site on the m R N A ribosom e

com p lex . T etracy clin es selec tiv e ac-

tion on bac terial cells is b ased on its

greatly in creased uptak e in su scep ti-

b le bacterial ce lls com pared w ith

hum an ce lls; the host cells lack the

ac tiv e transport sy stem presen t in

bacteria.

R esistance to the te tracy c lines f re -

qu en tly is m ediated by p lasm ids and

is an indu cib le trait; that is , the bac-

teria becom e res istan t fo llow ing ex -

po sure to the drug . A num ber o f

tran sf erab le resistance d eterm inants

f or te tracy clin e hav e been id en tif ied .

M icrorganism s that dev e lop resis -

tance to one te tracy c line u sually are

A minog ly c o s id e s

T he am inog ly cosides eg, am ik ac in ,

gen tam icin , tobram y c in , and strep to -

m y c in) contain am ino sugars link ed

to an am ino cy clito l ring b y gly co-

sid ic bonds. A minogly cos ides d if f use

through channels f orm ed by porin

p ro tein s in the outer m em brane of

G ram -n egativ e bac teria and in to the

p erip lasm ic space Figure). T here the

am inogly co sides b ind irrev ersib ly to

poly som es, especially th e 305 rib oso -

m al subunits , and prev en t pro te in

sy n thesis by inh ib iting th e initiation

com plex . In add ition , am inogly co -

sid es cau se m isreading of th e m es-

senger R N A m R N A ) tem p late,

w h ich resu lts in the incorporation o f

in co rrect am ino ac ids in to the grow -

in g pro te in chain . A s a resu lt, the

m em brane is dam aged and the bac te -

ria d ie. U n lik e the o ther in h ib ito rs o f

m icrob ial pro te in sy n th esis, the am i-

nog ly cosides are bactericid al rather

t ha n b ac te ri os ta ti c.

B ac teria m ay be res is tan t to th e

antim icrob ial ac tiv ity o f am inog ly co-

sides if th e d rug fails to pene trate the

ce ll, h as a low af f in ity f or the bac te -

rial ribosom e , or is inactiv ated by

m icrobial enz ym es . T ran sport acro ss

m ultip le drug therapy of resistan t

pu lm onary tu bercu lo sis or d is sem i-

nated m y cobacterial d isease. G enta-

m ic in has been u sed in com b ination

w ith o ther antib io tics fo r its sy n erg is-

tic e f f ects again st certain bac teria eg,

w ith pen ic illin agains t en tero cocci,

w ith nafc illin against

S a ur eu s

wi th

p en ic illin against group B strep to-

co cc i, w ith am pic illin against

L mono-

cytogenes

and w ith o ther drugs

ef f ec tiv e again st

Pseudomonas

sp).

T he c lin ical use f u lness o f am inogly -

co sides is lim ited by the po ten tial f or

o to to x ic ity and nephro to x ic ity , poor

cen tral n erv ous sy stem pene tration ,

and the n eed f or m on itorin g serum

leve ls .

Tetracycline

T he stru ctu re o f te tracy c lin e consists

o f f o ur cy clic rin gs w ith d if f eren t

sub stituen ts in three reg ions ; the lat-

te r subs titu tions resu lt in d if f e ren t

pharm acolog ic properties bu t s im ilar

an tibac terial ac tiv ity . In itially , the te t-

racy c line m oie ty passiv ely d if f uses

th rough the po rn p ro te in s in th e

resistan t to th e congeners as w e ll.

H igh-lev el p lasm id res istan ce to te tra-

cy c line has in creased nationally

am ong strain s o f

N g on or r ho ea e;

consequently , m ono therapy w ith te t-

racy c line o r dox y cy c line no longer is

recom m ended to treat a patien t w ho

has both gono rrhea and ch iam y dial

in f ec tio ns T ab le 2).

T he te tracy c lines hav e bac terio -

static ac tiv ity agains t a v ariety o f

G ram -po sitiv e and G ram -negativ e

bac teria. T etracy clin es are a recom -

m ended treatm en t for early L ym e

d isease , R o ck y M oun tain spo tted

f ev er, and in f ec tio ns caused b y

M

pneumoniae C t rachoma ti s

inc lud-

ing p e lv ic in f lam m ato ry d isease ), and

C p neu mo ni a e

T W A R strain ).

B ecause o f its in creased lipophilic

p ropertie s, d ox y cy clin e attains h igher

cen tral nerv ou s sy s tem concentrations

than o ther te tracy c lines, w hich m ay

be im portan t in th e treatm ent o f early

L ym e disease . T e tracy c lines are no t

g iv en routine ly to ch ild ren y ounger

than 9 y ears o f ag e becau se o f tox ic -

ity to tee th and bones. H ow ev er, cx -



8/10

T he c lin ical u se f u lness o f am inog ly co sides is lim ited by the

p o ten tial f o r o to tox ic ity and neph ro to x ic ity , poor c en tral ne rv ous

sy s tem pene tration , and the need fo r m on ito ring serum lev e ls .

446 Pediatr i cs i n Review VoL 15 No. 11 November 1994

cep tion s hav e been m ade to treat

y ounger ch ild ren w ho hav e R ock y

M ountain spo tted f ev er.

I N H I I T NUCL E I C C I D

S Y N THE S I S

Sulfonamides

S u lfo nam ide is a generic nam e fo r

the deriv ativ es o f p ara-am inobenz ene-

su lf onam id e . S u lf onam id es are struc -

tural analogs and com petitiv e inh ib i-

tors o f th e bac terial en z y m e d ih y d rop -

teroate sy n thase, w hich is responsib le

f or in co rp orating para-am in oben zo ic

acid PA BA ) in to d ihy d roptero ic

acid , th e p recursor o f fo lic acid . T h is

resu lts in a decreased pool o f b ac te -

rial nu cleo tides, w hich are th e build -

ing b lock s f or DN A sy n th esis.

M am m alian ce lls are not af f ec ted by

th is m echanism because they require

p re fo rm ed f o lic ac id f rom th eir d ie t.

S ulf onam id es are bac terio static

ag ents; thus, the f inal erad ication o f

the in f ec tion depend s on the ce llu lar

and hum oral de f ense m echanism s of

the ho st.

S u lfo nam ides hav e a w id e range of

an tim icrob ial ac tiv ity agains t G ram -

positiv e and G ram -n egativ e bac teria.

T hey w ere th e f irst e f f ectiv e chem o-

th erapeutic ag en ts used to cure bac te-

rial d iseases eg , pu erperal sep sis and

m en ingo co ccal in f ectio ns) . S u lf ona-

m ides f requently are used as chem o-

p rophy lax is and also are recom -

m ended f or the treatm ent o f

Toxo-

plasma

in fec t ions .

Tnmethopr im

T rim e thoprim , an antim e tabolite that

af f ec ts fo lic ac id sy n thesis, is a

h igh ly se lectiv e in h ib ito r o f d ih y dro-

fo late redu ctase in low er organism s.

It prev en ts the reduc tion o f d ihy d ro -

fo late to te trah y dro f o late , ano ther

critical p recursor in purine sy n th esis .

B y com bin ing trim e thoprim w ith su l-

f am ethox az o le T M P-SM Z ), tw o se-

qu ential steps o f purine sy n thesis are

d isrup ted sy nerg istically and less re -

s istan ce dev elo ps. T M P-SM Z is used

w ide ly f or th e treatm ent o f urinary

tract in f ec tio ns, resp iratory in f ec tions,

s inusitu s, o titis m ed ia, and gastro in-

testin al in f ec tio ns eg , salm one llosis,

sh ige llo sis, trav e lers d iarrhea). TM P-

SM Z also is the dr ug of choice for

the treatm ent and prophy lax is o f

Pneumocysti s car ini i

in fec t ions .

R i famp in

R if am pin inh ib its DN A -d ep endent

R N A poly m erase at the B subunit o f

th is enz ym e , w hich p rev en ts chain in-

itiation bu t no t e longatio n in R N A

sy nthesis. R ifam p in is bactericid al fo r

bo th in trace llu lar and ex tracellu lar

m icroorgan ism s. R esistan t strain s o f

bac teria hav e altered R N A po lym er-

ase that is no t in h ib ited by rif am p in .

M icroo rgan ism s m ay dev e lop res is -

tan ce to rif am p in rapid ly in v itro as a

one-s tep m utation ; th is also occurs in

v iv o . Fo r th is reason , rif am p in should

not be adm in istered alone , ex cep t f or

short-te rm chem oprophy lax is eg, in -

f ectio ns cau sed by

N m en in gi di ti s

or

H i nf lu en zae

ty p e b ). R if am pin is

used in com b ination w ith o ther

ag en ts to treat tub ercu losis and per-

sisten t group A strep tococcal or

staphy lococcal in f ec tions .

Quino lones

N alid ix ic ac id has been av ailab le for

the treatm ent o f u rinary tract in f ec -

tions f or decades, b u t it h as lim ited

use f u lness becau se bacterial resis-

tance d ev e lo ps rap id ly . N ew er sy n-

the tic f luo roquino lon es eg, norf iox -

acm , cip ro f lox ac in , eno x acin , f lerox a-

cm , lom ef lo x acin , and of lox ac in)

hav e broad-spec trum antim icrob ial

ac tiv ity and are a therapeutic ad -

v an ce . T he ir u se in p ed iatric s has

b een lim ited by the poten tial risk o f

arth ropathy that has b een docum ented

in sev eral sp ec ies o f im m ature ani-

mals .

T h e quino lon es b ind to the A sub-

un its o f D N A gy rase , w h ich are re -

spon sib le fo r cu ttin g DN A strand s,

th us prev en ting sup erco iling , unrav e l-

in g the DN A , and halting DN A rep li-

cation . M ost qu ino lones are no t as

ac tiv e agains t G ram -pos itiv e bac teria

as they are agains t G ram -negativ e

bac teria; th ey are only e f f ec tiv e

against strep tococc i and enteroco cc i

at lev e ls that can be reached in th e

urine.

T he em ergence o f resistance to

f lu oroqu ino lones has been p rob lem -

atic fo r M R SA , m eth icillin -sens itiv e

S a ur eu s P a er u gi no sa

and som e

Serratia

in f ec tions. D ecreased suscep-

tib ility o f

N g on or r ho ea e

to f lu oro -

qu ino lones recen tly has been reported

T ab le 2 ). I t is be liev ed that w ide-

spread and o f ten ind iscrim inate use

o f f luo roquino lones has con tribu ted

to th is resistance prob lem . H ow ev er,

w hen u sed in se lec ted patien ts, th e

qu ino lones can be lif e -sav ing , m ay

allow the patien t to av o id o r sho rten

ho sp italiz atio n , and can be v ery cos t-

e f fec t ive .

Fluo roquino lon es hav e been used

to treat patien ts w ho hav e py e lon e-

ph ritis o r recurren t urinary trac t in -

f ec tion s, prostatitis , gonorrh ea sing le

dose ) and chlam y dia 7-day course)

in f ectio ns, m alignant ex ternal o titis ,

o steom y elitis cau sed by G ram -n ega-

tiv e bacteria, resp iratory in f ec tion s

inc lud ing ex acerbations o f cy stic f i-

brosis, and gas tro in testinal in f ec tion s

eg ,

Shigella Salmonella Campylo-

bacter

in f ec tions and trav e lers d iar-

rhea).

Q uino lones are not approv ed by

the Food and D rug A dm in istration

fo r use in patien ts y ounger than 18

y ears o f age o r in p regnant o r nu rs-

ing w om en . C h ildren w ho hav e cy s-

tic f ib ro sis and are y ounger than 18

y ears o ld hav e b een treated w ith

qu ino lones w ith out ad v erse e f f ec ts

becau se th e b en ef its w ere b eliev ed to

outw eigh the risk s.

m p l ic a t i o n s

U nderstanding th e m any dif f e ren t

m echanism s of ac tion f or av ailab le

an tib io tic s m ay he lp practitio ners

m ak e be tte r clin ical decis ions regard -

ing th e u se o f an tib io tics . A lth ough

the increasing em ergence o f an tib i-

o tic -res istan t p athogen s is alarm ing ,

there are steps th at each phy sic ian

can tak e to s low th is trend T able 3).



9/10

P ed iatr ics in Review VoL 15 N o. ii N ovem ber 1994 447

I

A dmittedly s ome of these recom-

mendatio ns are not easy o r popular.

How ever the alternative may be the

emerg ence o f resistant bac teria that

cannot be treated w ith

an y

o f our

m any antibio tic s.

SUGG ESTED READ ING

General

Br ook s O F Bu te l JS O rns ton LN C t a l.

M e dic al M ic ro bio lo gy

N o rw a lk , C on n :

A pp le ton a nd L an ge ; 1 991

C ra ft J C , S iep m a n N . O v erv iew o f the sa fe ty

p ro file o f c la rith ro m y c in s usp en s io n in

p ed ia tric p atie nts .

P ed ia tr I n fec t

Di s

J

1993;12 :S142 - .S147

O ilm an A G , R a il 1 W , N ie s A S , e t a l. Th e

Pharm acolo gical B asis o f The rap eu tics .

N ew Y ork , N Y : P erg am on P ress ; 1 99 0

K u ce rs A , B e nn e tt N . Th e U se o f A nti bio tic s

4 th e d . P h ila de lph ia , P en n : JB L ipp inco tt

C o m p an y; 19 87

M u ll iga n M i, C ob bs C O . B a cte rio s ta tic ve rsus

b ac te ric id al a ctiv ity . In fe ct D is

Clin

Nor th

Am .

1989 ;3 :389 - 397

Pe tz LD . Im muno lo g ic a l re ac tion s betw een

pe n ic illin s and ce ph a lo sp o rin s : a re v ie w .

J

In fec t D is. 1978 ;137 s upp l ) :S74 - S79

R ee se R E , B e tts R F . H andbook of An tib io tics,

2 nd e d . B oston , M a ss : L ittle B ro w n a nd

C om pa ny; 19 93

R o driequ ez W i, W ie de rm an n V L . R o le o f

n ew er o ra l cep ha los po rin s, flu oroqu in olo nes

a nd m a cro lid es in the tre a tm e n t o f p ed ia tric

in fec tio ns . In : A ro no ff S C , e d .

A d v a n c e s

in

Ped iatric In fe ctious D isea ses , vo l 9 . S t.

L ou is , M o : C V M o sby ; 1 99 4 :1 25 -15 1

AntIbiot ic - res is tant

Pathogens

B re im an R F , B u t le r JC , T eno ve r F C , E llio tt

JA F ac k lam RR . Em ergence o f d rug -

res is ta n t p ne um oc oc ca l in fec t ion s in th e U S .

J AMA . 1994 ;271 :1831- 1835

C e n te rs fo r D is ea se C o n tro l. D ec re ase d

su sce p t ib il ity o f N eisse ria g on orrh oe ae to

flu o ro qu ino lon es : O h io a nd H a w a ii, 1 99 2 -

1 9 9 4 .

MMWR .

1994 ;43 :325 - 327

L eg g ia d ro R J. P e n ic illin a nd c ep ha los po rin -

res is tant

Str ep toco ccu s p n eu mon ia e: an

e m e rg ing m ic rob ia l th rea t.

Pediatr ics .

1 9 9 4 ;

93 :500 - 503

Sloas M M B arre tt FF C h es ney P J, e t a t.

C ep ha losp o r in trea tm en t fa ilu re in pen ic i llin -

a n d c e p h a lo s p o ri n -r e s is t a n t

t re p t o o u s

pneumoniae men ing i t i s . Pedia tr In fect D is J

1992 ; 1 :662 - 666

S m ith A L . A n tib io tic re s is tan ce in pe d ia tric

pa thogens .

I n f e c t

D is C lin N orth Am . 1 9 9 2 ;

6 :177 - 195

Tab le 3 . W ha t P ra c tftlo n e rs C a n D o To U m ft th e

E m e r g e n c e

o f A n tib io tlc res ls tan t P a thogens

{ 49}ash hands thor oughly to avoid spreading r esistant or ganisms to other

patients.

{ 1 4 9 }top and think. Is this a bac terial disease and is an antibio tic needed?

{ 1 4 9 }ducate your patients that v iral illnesse s do no t respond to antibio tics .

{ 1 4 9 }lw ays use the narrow es t-spec trum antibio tic possible.

{ 1 4 9 }ry to lim it the empiric use o f broad-spec trum ag ents.

{ 1 4 9 }tay informed about your hospitals antibio tic resis tance patterns.

{ 1 4 9 }ecognize that ho spitaiw ide antibio tic contro l prog rams may be

implemented in some cases to lim it access to certain antibio tic s .

A S S i S O J U Professor of P edia trics, D ivision s

of Pedia tric In fe ctious D isease s and General

Pedia tr ics ,

U n ive rs ity o f R oc he ste r R oc he st er

NY

P rivate P ra ctic e, P edia tr ic In fec tiou s

Diseases an d Al le rg y Be l lev i l e NJ

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10/10

DOI: 10.1542/pir.15-11-4401994;15;440Pediatrics in Review

Kathleen A. Woodin and Susan H. MorrisonBACK TO BASICS: Antibiotics: Mechanisms of Action

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