helicobacter campylobacter) pylori and acid peptic diseases...

REVIEW

Helicobacter ( Campylobacter) pylori and acid peptic diseases

SIGMUND KRAJDEN, MD, FRCPC, Pl 111 IP SIIERMAN, M D, FRCPC

ABSTRACT: Helicobacter pylori is a spiral-shaped Gram-negative bacteria implicate<l as a cause of histological gastritis, contributing to pept ic ulcer disease and perhaps playing a role in gastric cancer in humans. T he organism is found worldwide; the preva lence of infection increases with age; and colon ization probably persists for !if e. Diagnost ic approaches chat have been used include tissue stains, culture of stomach biopsy spec imens, labelled-urea breath tests and serology. It is too early to advocate treatment for all infected ind ividuals; the benefits and risks have ye t to be carefully stud ied and assessed. Can J Gastroenterol 1990;4(6):237,242

Key Words: Campylobacter pylori, Gastritis, Gastric cancer , Helicobacter, Peptic ulcer

Helicobacter pylori et les affections gastro,duodenales

RESUME: Helicobacter pylori est une bacterie G ram negatif en forme de spirale responsable des gas trites histologiques, contribuant aux ulceres gastro-duodenaux ~t jouant peut-etre un ro le clans le cancer de l'estomac chez l'homme. Cet organisme se trouve partout clans le monde; la prevalence de !' infection augmente avec l'age et la colonisation existe probablement a vie. Les coloran ts histologiques, la culture des pieces de biopsie de l'estomac, les tests respiratoires et la serologie figurent parmi les approches diagnostiques. II serait precoce de recommander le traitement de toutes les personnes infectees, l'etude et ['evaluation attentives des avantages et des risques etant encore a fai re.

St]oseph's Health Centre and Hospital for Sick Children, University ofToromo, Toronto, Ontario

Correspondence and reprints: Dr S Krajden, Director of Microbiology, St Joseph's Health Centre, 30 The Queensway , Toronto, Ontario M6R I 85

Received for publ1carion March 15, 1990. Accepted July 31, 1990

CAN J GASTROENTEROL VOL 4 No 6 SEPTEMBER/OCTOBER 1990

CURVED OR SPIRAL-SHAPED BAC

tena have hcen ohserve<l on the gastric mucosa of animals and man for almost a century. Until recently, they were generally viewed as probable contaminants or commensals. Over the past seven years the conditions for successful cultivation have been defined ( 1,2 ), and report~ of association with active gastritis, duodenal u leers and gastric ulceration have led to a reconsideration of thei r role in human disease (1, 3-5 ).

MICROBIOLOGY Campylobacter pylori, recently t rans

ferred to a separate genus and now known as Helicobacter pylori (6), is a curved S-shaped G ram-negative rod (oxbow shapes are occasionally seen in vitro ), 2.5 µm long and 0.5 µm wide (7). T he organism has a tuft of four to six un ipolar sheathed flagella, making it very moti le; it uses a 'corkscrew' action to propel itself through highly viscous materials. T he cells have smooth surfaces with roun<l ed e nds. Biopsy specimens can be transported in sterile

237

KRA)lll-.N AN() SHIR~l,\N

nonhacterillstalic 1sn10nil s,1linc nr

20% glucose; 111 the laucr solu11on, organism viability ts sustained for 5 h at

4°C (8). Plat mg shnulJ he Jone a:-. snon

as possihle onto nonselect I vc chocolate and 5 ro I 0% sheer or horse blond agar or, 1( contam111at1on ts a problem, nntt1 a selective medium (cg, Sk1rrow\) (2.8,9). After three to five days of tn·

cu hat ion at 37"C in a moi:-.t microacmphil il c1wm1nmcnt (cg, Campypak;

Oxoid, Basingstoke, United Kingdom), smooth, convex, urcular, greyish, translucenl I lo 2 mm colonic, appear (2). Umwth 111 broth is enhanced hy ,1 large surf,Kl' area wilh agitaunn. The llfgan1,m, ,ire pos1t1ve fnr ureasc,

caralasc, ox1dasc, gamma glurnmyl and leucinc aminnpeprid,1ses and hydrogen

sulphide; and ncg;n1ve for indole, hippurate and nllratc (2).

For iden11f1cat 1011 purpnsl's, all

strn ins are rcsisrant tu nal 1d1x ic al 1d and scns1t1vc ro cephalmhm hy J1,k Jlf . fusion. In vitro, H /1\'lnn is suscep11hle 111 cephalnsportm, h1smmh, tclrarydines, ch lorn mp hen 1co I, am tnngl ycosidcs,

erythromyltn, c1pmflnxac 111, nflnxacin, nxol1111c >llld, rifamp111, mctronida:nlc and the pcn1Lill111,. Ir ts resistant w va ncom ye 111, rn mcthnpr1 m -s u [fa. methoxawle, the I Jz hlocker, c1mcrid 111e ,,nd ran1t1d1nc, antacids, ca rhennxa lone and sucrnlfate ( 10). Recently, a new noncult1,·,Hahlc spiral

bacterium has bcl'll found 111 gast rte mucosa. Whtie the numhers arl' small,

they Sl'Cm 10 he nssociatcd wnh u chronic act 1ve type B gastritis. A proposal for their n,11ne 1s Un~rros/itrillim hommis ( l l ).

EPIDEMIOLOGY H pylori has hccn found 111 every

coumry studied ( 12 ). In Cannda and the Unned States lhc prevalence of 111 -

fcction increases with c hrono logical age (2,7,13). H pylori 111fccuon ts rare in asymptomatic c hildren, averages 2Ql)-(,

111 healthy young adults, and is seen 111

50% of SO-year-old subiecrs. There arl' also et hnic differences in thl' prevnll'nce of H pylon colonmnion of lhe amrum. As dctcrmtncJ by a pns1-

t i ve urea breath test, 60% of

asymptomatic middle-aged Chinese arc infected wnh H pylori versus only 24%

ns

of an agl··matched North Amem:an popu l.i t ll ll1 ( I ,) . There is no gender prcdilecuon. If pvlori gastmis has been reported 111 paul'nts wu h acquired im mune Jcficicncy syndrome (,\ll)::,) ( 14 ). Person -Hi-person transm1ssu)n may occur ( 15, 16), hul rhis pussihility requires further study. One recent study documented patient -to-patient trans

mission llf H /iv/on via lhl' fibrcopuc endoscope ( 17). The poss1htl1ry of a natural or experimental model uf H

pylon 111fccnon 111 monkeys and the gnnl nhio11c piglet ex 1sts ( l 8, 19).

PATHOLOGY H />ylon u1loni:c, nat i \'l' ga,t ric

epnhel1um or the mernplasttc gastric epnhclium seen 111 thl' duodenum aJ

jaccnl to ulcers, Barrett's esophagus and ML·ckel's d1verttculum. However, two recent rcpnns found thar thl' organ ism

ab1> mhahih suhgingival plaque and 1kntal pulp (20,21 ). Racterial colon1:atinn of rhc ora l cavity and release of viable organisms 111 saliva may account for some cases of person -to-person

1 ransnw,s1un and for c,1ln111:ali11n of antral mucnsn 111 rhc same patient.

Cener.tll), f I pylori are found withm

rlw muu1us layer or beneath 11 adherent tl 1 rhe apica l plasma membrane of antral cpnhcl1al cells. The organisms appear

to congregate preferentially at nr near the 111tcrcellular JUtKtions and occas1unally penetrate the intcrcellular ,paces (22). H pylon arc rarely seen 111-trncellularly (22), and lhen only cnn

taincJ 111 phagocyt1c \'acuoles. The mucous layer may prolect l ! Jiylori from gaslrlc acid wh I lc the breakdown of urea (via urcase producunn) rn the nmmunium ion may help to pmmnte the

alkaline cond1t1nns which are conducive lO irs survival.

H1stnl11g1c study reveals a loss ti

gast ric mucus, sporadic epi thelial cell necrosis and neurrophd invasion of rhe cp1thcl1al layer associitled with acute ,md chronic 111tlammmory cells 111 the

lamina propna. Wirh electron micrn,copy the surface epithelial cells arc

edematous, degenerated and depleted uf mucus granules; l here b abo a lnss nf

m1crovtll1. In these ,Ire.ts, H Jiylorr attaches t,1 lhc cukaryotic cell surface at a region of pedl'stal formminn (2 3 ). The

relcptur tor 11 />vlon on rl·d hlooJ cells, tissue culture lclb, pig stom.tlh anJ human ant rum 1, ,1 novel gly<.:l'rohpid (24). B,1llcnal ,1Jlws1l,n m,1y h• med1a1ed hy tell surface lihrill:ir protl'm anugcns (,1dhe'1ns) (2'i).

There arc a numher of !actors which could acun1nt fnr 11 />,•Ion 1nJu(t.J dam,,gc l\ 1 gasl n<.: 11ssul' ( 26). Thesl' 111-

cludc: 111tcrfere1Ke wirh g,htm mucu,

produc11on wh 1ch thereby foe ii it .itcs 111

Jury hy g,1strtc ,!lid; amn1<H11a produc lion mediated ,•1;1 the llrl',he rck.1scdhy E--1 />ylon, which m.1y d:1m.1ge lcll, l,y

till reas1ng chc h.td, d1ffu,1un of hydrogen 11ms into muuisal 1.db (26); and t11xins (27). In add1t1<1n, cxtra(t·l

lular pro1c:1scs, phnsphol 1pasl"• anJ lipascs ma) he n .. ·b1sed hy H pvlon and dcgrndc gast ril mucus ( 28,29). Thcn·

fmc, proteolyt 1c and ltpolyt ic au 1, uy oi E--1 /rl'lori could damage hnt h ekmcnt> of mucosa! Jdcncc, 1c, thl' mulu, layer

and the cell memhrnnl's nf the gasmc epithelium I luwcvl'r, add1t1unal studies cnnfirming this pathogenic mech,mism arc required ( 30).

CLINICAL MANIFESTATIONS H />vlori has been lmkcd en ,1 \,Hll't\·

o( disease states in humans. Chronic active (type B) gastritis: lncreasmg evidence sugge,ts t hm H />ylon i~ Lhc et1olog1c agent \1f t ypc B gasmtt,. Chronic aCll\'l' gastrtlls (:,ymptomar1c or asympwmaric) is closdy associateJ with H /rvlon mfect ion (31- 34 ). The

antral mucosa is most nften affecreJ. Clearing of rhc bacteria 1s usu.illy .1,snc1a1cd with a nnrmal1zaunn 111 h1sro,

logic,d findmgs ( "l5 ). Experimental sclf-fccd111g (36, 37) or mndvencnt 111 fccuon wnh the mgan1stm ( 38,39)

results in typical gastric mflammauon. Auwimmune (type A) gastrius anJ

secondary (cg, Crohn'Hltsca~e. Jrug-m

duccd and bile reflux) ga,triw, arc not associated with H pj>lon 1nfcct1nn (3[,32,40,41). Duodenal ul cer disease: The prevalence of H /iylon colon 1wt ion of inflamed ancrum 111 pat 1ents wnh enJn

scop1cally proven duodenal ulcers " fa1rl) high (greatl'r than 70%), hut th1,

may simply reflect I he previously rerngn i :eJ close as-.Pc 1,111on hctween duodenal uker, .md antral 111tlamm,1

CAN J t,ASTROENTIRl)L V\11 4 N\16 SI l'lUHll R/lX'TOlll R 1990

tion (42). lnJecJ, rhcrc arc c1 numhcrof JiscorJant facts io the link hetween duodenal 11lcers ,md infecti<in wit h H pylori: the prevalence of H Jiylori increases with age though duodenal ulcer J1sease is not predom inantly a dise.-1se of the elderly; ulcer crnters heal even though hactena persist; ,lcid h ypersecretion (Zollinger-Ell istm syndrome) leads to duodemd ulcer dbeasc without H pylori present; and there is nn gender predilection lnr H /Jy/ori infcctinn whereas Juodennl ulcer di sea,e predomirnll es in males. Thereforc, other fact0rs must ,tlsn contribute to the pathogcncsis of Jumlenal ulcer discnse.

Compelling evidence that H /iylon tnfection plays a role in duodenal ulcer Jisease comes from the data nf anti microhia I trcatml'nt trials (4 3-45). Antihiotics, hismuth ,mJ Hz anrngonists heal duodenal ulcer di~e.-1se ar the same ratc; however, when Hz blocker therapy is discontinued, ulcer recurrence is frcquent and rnpiJ. When I I pylmi is cleared wi th anrihinrics and bismuth compounds, duodenal ulccr disease recurretKL" is significantly reduced r45). Ulcers that Lio return nftcr amimicrohinl therapy is disc(mtinued are associated with recurrent H /Jylori infection ( 41,4 5).

The gencsb of Ju0Jem1l ulcer~ may require increased exposure to acid in che duodenum leading w format i,m of rnecaplastic gastric cpirhc lium (46) which then becomes colonized by H pylori; this causes fun her inflammation and with funhcr ac,J contact an ulcer results. Alternatively, Levi er ,11 (47) prorosed that H /)ylori col,mi:arion ot the antrum rcsulb in an inappropriate release ,if g;istrin from G cells in the stomach, excess acid production hy parietal cells and duodenal ulcerarron from delivery of excess acrd inl!l the duoden um.

Family memhcrs (symptomatic or a ymptomattc) of dundenal ulcer paricnts have a greater prevc1lence of H pylo1i infection (48). These findings suggest person-to-person spread m a common point sou rce nf infection. However, hacteria I rcMrict ion cndonucleasc dige,t ,malysis of the isnlntcs Jid not revc;il idcntrrnl org;:inisms within fomilies (49).

Benign gastric ulcer: For a number of reasons, H pylori does nnt appe,1r to he the s,)le cause of gastric ulcer. The prevalence of H Jiylori mfect ion in gastm. ulcer is only 60 tn 80%. Nonsteroidal antt-inflamm;icnry drugs account for most gastric ulcers and arc not associated with an increased frequency of H /Jy/on <.Oloni:ation. Barrett's esophagus: When gastric epithelium is found 111 thc esophagus, H pylori can cnloni:e these metaplastic sites (50). H,)we\'L'r, thl· clin1Cal importance is not yet c 1cm ( 51 ) . Nonulcer dyspepsia: Self-feeding expcrimenb with H /J)'lori cause, t ransient dyspeptic symptoms c,m,istcnt with nonulccr dyspepsia (36, 37). The pre,·alence of infect inn with non ulcer dyspcpsia is 40 Ill 60%, which is similar to

that found in an nge-matchcd asymprom,111c control p,ipulatron. Antimicn1hiab provide irregular rclicf llf nnnulcer dyspepsia symptoms, a lrhnugh the inllnmmarnry re:ict ion ts decreased ,f H J1ylori is present ('i2). Currently, therdurc, rherc is no uimpclling <:videncc that H /)vlori is an important rnusativc fact,1r in nonulcl'r dyspcpsm. Gastric cancer: Chrnnic gastritb is

cnnsidcrl·d rhe prccu r:,or lcsllin nf gastric carcinoma ( 5, ). Whether thL·se lcs1nn:, pnigress from superficial actt,'l' gast ritis due to H /iy/on i:, not known. Prcliminary reports suggest, howewr, t h,1t there is an assuciat ion hct ween the presence of these organisms and hmh gast ri c dysplas1a and carcinoma (54,55). In CCl)nnmically advanced countries, tnfcct inn with H {)ylon ,111d the Jcvclopment of gastritis usually occurs in middle age (31 ). l lowcver, in other countries infection with H /Jylon occurs more frequently with n1bet ,if cnlonization at a younger age (56). It 1:, po~sible rhm individ11als in a populnri,m with a high frequency ,l gnst ric carcinnma might hecome infected with H pylori at an early age.

LABORATORY DIAGNOSIS Culture: Culture of hiopsie:, of gast ric mucosa will identify 90% of persons intectcd. Distributi(111 of infccri,1n may he parchy, so culture:, should he ohrained from ar least two ,mtrnl sites to

CAN J GA::-TROENTEROL VnL 4 No 6 SFPTEMBER/OCTOBl:R I 990

H pylori and acid peptic diseases

enhance the rcctivcry of H /Jvlon. The organism h;r, rarcly heen i,ol;ired from the h,Kly of the stomach unless antralt ypc mucllsa is prescnt or thcrc ts mucosa I 1nllamma1 ion ,ind hacterial colontwtton of the anrrnm (57).

Negncive culture, cm result frrnn in;:iJequ;ite sampling ( tc, hiopsy of nonnntral epithelium) , delay in transport n(

specimens, swallowed topical ,mesthetic ( cg, hcnwca i ne) ( 58), prt<H therapy with bismuth compounds or antihiotics, and residual di,infcctant (eg, glucarn ldch ydc) present ,m the biopsy forceps and bi1)psy ot nongastrrc epithelium.

H /Jylori bactercmia has nnt been dcscrihed, perhaps becnuse it docs nnr occur nr currenr commercial hlood culture syqems are in;idequate for its detectilm (59). Histology: H pylori detected hy various tissue stain, cmrclntes well with culrure re,ult, ( n, H ). Gram stain of 'touch ' preparnttllns of hiopsics is a rapid and mexpensivc approach to diagnosis that wrrelates well with results of both cu lture and nthcr sta im (60). The hacteria cnn he detected 111 tissue with hcmatoxylin-l·osin, Giemsa, acrid inc orange, crystal fast violet and silver srnins such as the Warthin-Srnrry, Dieterle and mod1ftL'd Stl'1ncr methods which I ,icili tate the detcctton of hacteria especially when present in small numbers. Mnn,icl,111al antihoJies ,1gain,t H /)ylori havc hecn used to detect the organism 111 c l in,cal ,pec,me ns hy the ,mmunoperoxidase technique (61 ). Biochemical tests: Tests which assay for preformed hacterial un.:ase permits the rapid detcctinn of I I /)ylori in biopsy samples ( 62). In these tests tissue 1s incuhated with urea ;:is a substrate ;:ind phenol red as a colour indicator of changes in pH. I( H /)ylori is present in adequflt e n um her,, hactena I urcase hydrolyzes the urea, which raises the pH and changes the phenol red indicator from yellow to pink. Recently, ,1 Min1-1 ek (BBL Mic.rohiolngy Sy..tems, Maryland) urea disk test has heen evaluated which is hoth sensit ive ;:inJ co:,r effec ti ve (63). S lants nf Christensen's urea agar or broth can also he used for the detection of urease. Rapid urease tests cnrrelme fo1rly well

239

KRAJllEN AND SI 11:RM/\N

wnh othl'r method, of 11 /Jylcm detection (62); howen•r, the prl',ern:e nf Proreus species a~oral cnntammant, Lan result in false positive react1om ( 8). Noninvasive breath test1,: Bacterial urease forms the basis of non11wa.,1ve breath tests ( 1 3 ). A test meal IS given with I le.

or 14C- lahellcd urea l<l delay gast ric emptying. If II tryum I!, present in the stomach, the urea is hydrolyzed and radiolabclled c.irbon dioxide detectl'd in expired breach sample, within l h. Serology: C.rculaung ,md loLal anti bodies ll) H pylon have heen measured by agglutina tion , complement fixat llll1 and en:ymc-l111ked 1mmunnsorhent assny. There 1s a st rong cmrclatinn he tween high serum lg(, and lgA ant ibody levels to H J,ylon, g,Nrit1s and ,1 pos1t1vc culture ( 34,48,64 ). Ant1hod1es can also he detected 111 gastnL 1uice and salivn.

Although t 1tre, of 11 />ylori-speuhl antihody may decrease after 11 /Y'llori mfccuon has been elimmated (65 ), the levels tend to remain elevated for years.

ACKNOWLEDGEMENTS: Philip ~her man ,, chc 1p1cnt 11f ,1 CarL"l'r "c1cn11,1 Award fn,111 thL· M11w,1ry of I k·:1l1h.

REFERENCE I. Wam:n JR, Mar,hall BJ U111dcn11t1cd

c.:ur\"cd haull1 ,iml g,iscrK cp11hcl1um m aLI ive chron1L gasmns. 1 ,imTI 1983;11273

2. Bohnen J, Krajden S, Ander,011 JC, (), ct al. Cam/)vlohadcr [>ylor1J1, ,1wx:1,1tL"d with acid-peptic d1,ca~c m T,,ron111. CmJ Surg 1986;29:442 4

3. M.irshall BJ. Camf>yl1>hc1Cter /nfornfo anJ gastritis. J h1l<.'(l n,, 1986; 15 3:650-9

4. Rlaser MJ. / lel1co/,,ic1er />'!Ion ,md tht· pathogcnc,,, of ga,rmduodcnal mflam· matton. J Infect D,, 1990; 161 :626 3 3.

5. Pcterslln WL. Pcp11c ukl'r An inlcl· ttous JJSca,c 1 Wc,t J t-.kd 1990; 152: 167-71.

6. Goodwm CS, Armstrong JA, ( ' h1hL' f'> T, e1 al. T r,msfer o( Campvlo/l(lcter pylon anJ Camp'!lohacter muswlae fll

I lelicobacter gen. nov. ,1, f lel1coba([er pylon comh. nov. and Hel1cohacter mus telae comb. nov, rcspcc11vely. Int J Sy,t Bacccnol 1989; 39: 397-405.

7. Goodw 111 CS, Arm,mmg JA, Marshall BJ. Campylobacter pylorulis gastru" and peptic ulccrauon. J Clm Pathlll 1986;39:35>65

240

Therefore, ,l'mlngy indicates present or p,lst infcu,on ,ind i, usdul for semprevalcnrc srud1e, (48.56).

TREATMENT In , ll rn su,cepll hd ll y of 11 pylon J oes

not reliably predict effiL acy 111 the eradi c,lt1Lll1 of the orga111sm in humans (66). Many smgle and comh111auon ant 1-nlll:rohml regimens can suppress hac tL'nal growth, but they arc less effective 1n perm,mcntl), clearing the organism. Fifty 10 90% of cu hurl' pos1t 1vc patients will ht·come culwrc-negar,ve 11nmed1-mely after trl'atml'nt wnh colloidal hismuch ,111d amoxycd l 111, smgly or m combmauon. However, only 40% arc

~ult cu lture-negar,vc one month after trl'atment 1sdisLnntinued (67). This 111

d1cates that rclapM: or recurrence of infection h common. Rest riLtion cndonucleasc digest analys is shmvs that these recurrences ,ire usually Jue LL> relapses with the ,ame st rain of organism (68). Th is may m somL' u isl's be related to a re,ervrn r of l he nrgan1sm harboured

8. Kr.11dL"n ~. Roh,wn J, AndL"r,on J, er .ii C1>111pan">n of ,elcct1\·c and non,ckc 11n· mL"d1a for rcu)\'cry of Cwn/)ylohcll ter ,,..,lun fr,1111 anrral hlllpS!l's. J ( ' 1111 M1unb1<,I 1987;2 5: I 117-8.

() G,xxlw1n CS, Blmnm El). W,ml'll JR, W,lll'rs Tl·. S.rndl'rst>n CR, E,Nrnl L. fa,duatllll1 llf i:ultur.,I rci:hmquL"s for 1sol.11111g ( .am/rilohc1ct1?1 [lyfom/1.1 from cndnscopK h11ip,1c, nf gastnL mucosa. J C l m P.u ho! 1985; 38: I 127 11.

10 McNulry C'Al'-1, Dem J, W,,e R "u,ccpuh,li ry of din1Cal i,l1larc, of Cmn/r1loh.:1Crer /riloriJ1\ tll 1 I ,11111 1111uoh1al ,1gcnr,. An11m1unh Agents Chcm<ithcr 1985;28:8 37 8.

II McNulry CAM. Dem JC, Carry A, l.'L al Nl'w spiral h,Ktl'num 111 gastnr mucosa. J Cl111 Parhol I 989;42:585 91

12. Dwyer B, Kaid11r J, Tee W, Mar.11..owsl..1 E, Ra in, K. Ant1l--<xly r<?,ponsl.'s to C11mf>'llohar1cr /l'llrm m J,wr,,L" L"thn1L groups. Scand J Infect Dis 1988,20: 349 50

I 3 Graham DY. Klem PD, Opcl..un AR. B11u1 wn TW. Effrc1 o( agl.' nn 1hc frL" qucn..: y nf ,H.. ll\T Ctm1/>'1lohcicter />'!Ion mfel I inn di;1gnmL"d hy chc { 1

\ ') urL",t hrl'ath lL"st 111 normal ,uhJelt, .md pal 1l.'nrs w1rh pep! iL ulcer d1,l.',hL' J lntect [)" 1988;157·777 80.

14 Mcisclman MS, Milk·r- Lnchpok R, Christ M, Rrnd.111 F C:mnf>,•lohc1Lt1?r /1'1/on 111 thL" ncq,nrL·d 11111nunt· <.kh(1c•11 q "\ ndn,mL" ( ,,,,tn>l'lltl"n ,log\

in dental plaque and dental pulp (20,21,69), or simply Ill mh1 hn1on without l'rad1c.1uo n nf hacter1a from thl' slOm,ll h . I l1ghcr Josl's, rL'peateJ or more prolonged Luu rses nl smglc, double or triple ant1m icroh1als (bismuth and two other ,1gcn1s) ma) d1m1-nate H /1yluri (70,7 l ). I lowever, such regimens arc assOLlilled with 111Lreascd costs m1d adverse effeus 111clud111gJ1arrhea and pse11domembranous colnis. Therefore, the bend1ts VL'r-,us potenual risb musl be carefully comidered. The development llf safe, L01Wen1ent and effl'ctivc therapy will faLiliwte 1hl' mvesuganon of the role uf 11 />ylon m gast rodundenal disease. It is important LO dcfm e wh iLh p.it 1ent pupulauom and disease enllties related ll> H (>'llcm

mfcc lion will henl't"it from therapy Currently, phys1uans must temper 1 reatment wnh common sense and not subjl'ct 111d1v1dual pat 1e1Hs to poss1hly mcffect1ve or 1ox1L rcg11nens nor encourage the spread of resistance 1ocl1111-cally useful ,mumicroh1al agL'nb.

1988;95·209 12. 15 . ShamL's B, KraJdl'l) S, Bah1d,1 ( ',

Uurgis RV, Kurianczyl I , PL"nnl'r JI . lnvc,11g,1t1on of ( -<llll/>ylohc.1crl'T />,Ion , tra111, IM1l;11l·d frnm a hu,hand and 1111 w1fo. ln Ml·gr.,ud i-;, L1111oul1,1t1L" 11 , elk Ga,1rod11<x.knal Parhnlngy and Camp,•lohactcr pvlon NL·\~ York. Else\"1e1 Sul'llCt' l'uhlic.111011, 1989:419 41

16. lkrkmnnJ, Lee A. Pcr,on·to per,011 rr,111,m1sS11>n of C 'mn/rvl11h.:1n<.'T />'ilt>n Lancet I 987;11:680-1.

17. LmgL"nherg W, Rauw, AJ, l1udh1L·r JI 1, Ty1gat (,NJ. P.i11ent-lll·pariL"nt rr,m>1111sS11111 of ( 'w111,yl1>h1c1l>r />vbm 111fl'u1nn hy fihrl'OJ'l ll g,ist rmlu,Kkno· ,i:npy .md h1np,y . I ln(L"Lt [)" 1990;101:507 11 .

18. Rmnsdon MA, Schocnl..yccht FD. C:amf>'1l11hac1er pyl"n 1,ol.11L'd from thl' stom,Kh of monkl'y, MC1rnrn nl!mc,rrma. I ('1111 M1unh1,1I 1988;26: I 72 5 -8.

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