23. Significanceand sources of antimicrobial-resistant

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coc

23. Significance and sources of antimicrobial-resistant
nontyphoidal Salmonella infections in humans
in the United States

Frederick gale
[.Clinical significance of tention wows crated with antimicrobial
‘antimicrobial-resistant agcuts (5,6), Cipndoeacn, 3 Bsorequira

low atinicrabial agen, she mst com
manly prescbod anvinicobil ages fe Sal
‘ponaiainfetions CLIC unpblshe! data.
Selmoneloisceulninconsidesble mar. Gnennecast to uncomslcate gatcentt
Didig im the Unite Sete, Although rouse 3x anthulrobile arena Sothern

nontyphoidal salmonellae

‘Sebmenelsnictions resol fu wil, 4F- meatof patients wid Buccs, mening
Timing guecoinnestinalilvescharaceiasd th, orotherexanoutina Selwmelufec-
byydiartben, fercrandalsderuinlcrmmps.the tons, Approximarely six pescent ofthe ci
infection ean spread 0 the Bloudittem, witcontinned caus eeparsed co CT: ase
bone mastow ox ‘mening licnge oF the invasechola 3,4, Acinic ee
brn leading tu sete and occasionally f+ taut ae vial au lien fering for at
tal nes Fach yeah chere ae mv cainated Let 2400 pera yea wth invasive Se
foeu © four rilion bina Salonga ine mone infections io re US. ‘The selection
Feations inthe US, (1, 2) aug, ay ost of andreas fr che ueatment of nse
mate 80.900 co 160,00 psoas as aeek sve incon Las Becore inenenagly
medical aceon (CLIC wapublihed das). ste, haveves, du co che inucsing
‘Cnc specimens from yerons aha have gintsnce asreng Seimonelle isclates (0
soughe medical atcniua sesut in apprin- —ariwivoiel,parvicully cbloeraph
raatly 40,000 culececoafinnel cist e- cal, ampicillin, ard. cximethuysim:
pve :c the Convers fur Dizze Contes! ssfawelhozazels,
fd Preven (CDC) annuly 3, 5 Ala Sequel se wear such infesone
ferimatal 3000co 1X00 enous arehor (8s Among L272 randomly elec Sa
Diukaed and up v0 500 prtone die of Sal- manele oles ese ac CDC in dhe Nar
Doneicnfosioue cash yea in che US (SI. Con Antimierosal Reistance Monitoring
“Aadmicroblas or: nt indice for Sale Spin 1996.26 were esieane TO Rp
monaco which wafers unoon- cin, 1084 10 ehloraryphenical. and 4%
plata! gaatioemerii, Such infestans re trimeeoprianlfimerhoeazle (7), Kor
felled acl cutnent doesnot rluce te sno all Sebmowelle oles in the

sori ich ave

the duraon or seemty af speiprame, may US Fave heen suscepible ts Muuroquinor
peolongthe exrir sate, and may eral i Loate and thir generation cephaloggnrins
theemeigence of sist infstion, ow Ferthisreason, and terauseu de fvorsble
tribes, seibocies are commntly pre- pharmacodynamia. properties of these
teva fur pottons with Safmonelis foc anmizebiah, ALorequinnlncs and chicd-
Tionewhoccek medical atenion. In wore genceaion cephalnsporins are the drugeot-
condaerall by CIC, 4085 of perona with chee for she reaunent of ina Sina
‘Scinorilenfecionareho sought nediel cee lla inferinns in adults anc children,

din amchl n ch "i
gases

sesputivel. Should Sefmaneladevop a
microbial reficance to dese eo arom
‘ria age, iertve atic
ial ate noe cacent wala

U.Sources of antimicrobial
resiatant nontyphoidal
Salmonelta infections

Ueforé viewing dhe sources of anim
cbinl-risineSttonlainfecion in Bu
tans eis oll i dics he gener cle
oFentinistobial usin theesurgence ofan
‘Umicrobil esianeeandhe somes of Sale
monet nfs humans

‘4. Aatimierblaluse aud antinierblat
resistance

Ancibisier we wsed reat nro
fificcum in hemor, plenty and anioal
they are given pruphylacically rw hecliby
humans; plinns and anima to ptevenc in
fecions te they ae given in Yow dows co
food animals to improve chee gash race
sod Fed conversion. These isa preporler-
nce of evidence the dhe we oF aneero-
bial in hums, pl, animals ese
in antimicrobial resistance, Forshee, she
pssaence of antimicrobial essence io
creases 26 the quantiey oF anvierobial|
gene sed incren

B.Soprees a Soimanela Infections in
amans

Salmonella ive inthe instines fF many
mammals biedsand epee ace shed ico
theensirnmenein che feces ofinferrd ani
mals, Samanela may saevive Ca log per

‘ods in waren soil and 00 o¢ within fds.
[Alihough Semone infections orc rem
‘monly in human, pstton-t0 pero Uans-
ritsion of Sampo is uncommon in che
US. Tn lee developed cavatre, in com
tet, peron rorpeso azsmiasion may be
the sourar fox a greeter proporion of hu
man Seimovelisinketines Hiv prior
tthe development af hospital infeciun
Conta proces in she US, nexseoeal

cosbrenls of salsoualous, parsicuerly in
revvhann ates, were nor infeaguet

Morthurman Seimevede infections inthe
US neta tho the ingeraon of finds con
tantineted with animal fees; many of
these foods ace Gouds of animal origin
Direct feral wansmissne Flowing zone
rast wich animal fecer ix anaes, ‘st com-
tien, source of hunan salmonellevis.
Evidence ppting foods oF anime! iin
ae checuntinane inter af hace salmon
Tons, 974 suggeting dha pern-tarperson
trananiscion isan wneesamon source of ho-
an elmoneltss ip the CS ie provided by
a laut een line af evden fblow.

.caiage ees
Although she prevalence vais, Salmo

esi esc bed from the Feces oF
Fd ania companion asnnalsand wld
animals, In longitudinal suds, wm ani
tral ay estes Semone or long pet
tds of cme Fox exmnpe, many bial in

‘dading paulo ar inkscerd vith Setmonete
tnd shed the cepaiem in thei fore (not
suisingl a bigh proportion of eal pale
‘pet of pouly are comtarinated will $e
rrdnal). Bool ecretion of Salona by
uma conta ieee uncommon,
ang appareney bealh individeals di
fans iad mong pereone wll sae
ellos nee of sera survey of sl
syinans from apparent healthy persue
found » median cage re of Sedmonele
oF 0.15% (6), & review of ove tba
invenigitions determined the malian duct
tion of excretion by persons wih salmon
lors wo be abour four weeks (9

eferiosdse
YVoluneer solic antong heschy adults
suggest Cota large oral infctious done of
‘Semonela 10° 0r mone oegenisns) i ws
ally nocesary r eaune infection in Bigh
proportion of recipients (10). hese ober
asians are supposed by dhe eatin low
Frequency of condaryillnes: vin ruse
hole ia which a pinay ealrureconfitsee
cass Heated and the eaigy af dapeare
tertr outhrenke of salmonllsi, Sach st-

ede mge hind nad ra
ing comment

ole penn antston
tansmiation of ener pacingess wit Low
infecrnus doves eg. Shigellzand Erba
col 159). "las iiequenr eceurrente of
fecunlary inBctons of sslmunelais and
aye cenner aeneical ucicakssugsest
hae periomtorpeion Canemisson of Sa
anela occurs infesuenty

2. Ootvenestigains

Although urbe oly
sion ofthe cass of Shen
coves much insight into the ep
‘oferlinonellove ae been provi theaugl
invatigadons of euthress- Must ouebew
invesigrions are condaceed by rece or
Towa hele departments who separ: food
boune drese outbreaks to CDC as pa of
the Feodboune Diveate Oullncak Sucve
lance Syren. A wal nue of investiga
Gans are eaadueesd cach year by CDC a
cellaboration wich sate sel Joist eal:
dspartoent.

Bereven |08Sand 1992anavergeel 119
ceoreais of fadnonellr were rpc eal
yess @ CLIC. Suey peeent of these our
Teas wert road y Seimancte semen
nveriid, mon of these were tebe
saagunderorskidegge 10) Meny fe
egavited ourbicls wore raced bork 3
‘hee frm of origin and derncnstsaed that
infected heve were the source of the
fourbreak. Auwotig outbreaks eamal by

‘Srouelaserosypes oer us eters
‘are af Soa itm ct ighone! pa
fealaly pouluy and near pends. A null
tnaniber of diicypooelaus and flesh Feuis
snl repeal ete aloo implicae. A Sow
Fee mre ne also etc hack wo
thee fr of origin, Aeboagh susie ute
‘elven nfs fodhondler, eather
than being

probably bscamte infected because they ase
Atecheconseminatal fonds Taken roger.
foothnak invctigtions éerennacate that
foods, pariculscy fod of ancl exgin,

sce am impnnar source of Salone

Spur cosecono' ies

Turher evidence tit foods of ania
urigin ize serocated wich many hewsan
Seinen infct'one is posed fom ine

>esigtionsné persons wh sata S
valinfescone

iether a
ognized ro be seocatal wich an outed
Tow sach neciguin bae been ported,
mnt. pothape becsaeeinvetgeins uf
inevions ae es Hikly to iopl-
-ueacommon ourecbecaussvea soures

tray be wad

‘Casecontrlsnaiee of aporadic ses of
Sdn cnerinlwere conducted ia New
‘Yorkie 1989 113, Celfbra in 1994 12),
sal Un in 1893 G3). The ties each
eronsraed that catiag ta 9F under

cok gees Cae mort impor ikl
For aequinnginfactions. Case-contol
sues of sposadie Sebati casa intel
Ing srecyper other drs Luwciiis include
an investigation: i Soucaedand in 1996 of
indkesinas cansd by a riety of eraypee
onli apicned eggs a the
tan sonnce ain tas

1984 nf infctvns again cated by = aie
rye which ireliatelpoulry (1.
Califia i ONS nF Salmeneliz ain

swbich nlite? raw mil (06) andaerady
of Suman yphinarivn aed mtr
fecnns #1 Minaseoe in 1989 and 1990
which found ge the mame importan:
sour for oth abations {1}

Suton bred event

lbaarny has euniiance of Slow

stl ialess
sation and repoting
sensgiet of Secale ele izes y
ths

sre and aga sregense ever
sl ennrype tae bee len-

0 Sa
‘Bee, Seromping ie iestsanental m deer
ing ourbecs of Solmanaliaafctions. Be

Cause Selnenela ulus within specie
ferueyyes say Haze comman Sources,
ssroq7ing may sh be usefal in dececrin=

ing sources of speci erorypee by ena-
Ling uompazions of Safonetitaunsdlance
xa fiom harap, anial, and oche sources,

wpencoans7

‘tia ad anions
cna

For example begineingin 1969 suse was
marked incense in hon iolaus of Sel
sponala gun deered i the US ers
fal vaher eowntvss. Sahel agons had
pubes: oat inthe US before 1969, bu:
typ 1972 cas rhe iglich mow comin se
rauypetilaed From hmacsia the US (1).
Field investigations ad surveilhnce dana
dexeroiaed Perovias Bskimel co 52 Ge

noes of ee fofecions, Creal to Ge
Fnvestgacinn wir dhe idzacficatior af
‘Semone gona from Poston sesh in
roorine sunvllence sampling uf Bsbeneat
in 1970.

Gmpaisae buen hans ananial

Sulmoralicsureilnec data ns ermsidet
Ihaweet te spidadalogy of sonel-is
Ter pectic sxonype and the cifnencs ia
the specimen eulction practi ioheest

in de sbwiion of speitnens 10 ali
laboretorics within eich aurseilaace et

For hee pean re nenparzons of ie
Sop tx Selimonelis serogpes in humans
snd in animal a often not land may
lead ro dhe enoneone eoalosion chat Sal
‘opel ssonypes which arecomiseu ince
thin animals {for exemple Sabmonelle
‘Cholerasisin vin! and ate in oman
ronpathngeri vo homens. Comparinn of
the most common semeypesncetain aie

ls mul bua has als edn premacure
conclasione tae food animals are aoc che

sos comman source oF certain stn

6 Aisin sotqpng floes

‘Ales idensiction of te parteaar st+
rypes seve poocedies (pe Bhs 97

Tulsed-field gel eleceraphozess,
itoring) maybe ad a forthe diene
tine Svonels(19). Suc supa rer
ics may Be vsy usefili specticnpide-
iological inven, icing the com:
parinon of flats (om paiensand psc

Feed sources io apport eezefue rhe pose
Inve source ofthe eucbresk For example,
inthe 18 oubreas of Simona enertiir
ip 1990 and 1991 im which eggs were imp
cet asthe utc, neebacksand envien
tmental jovestigations os the implicated

{crm fl us dic dezesron fhe bara out
Irae ca of entra, as detmine

by phage type, fiom rhe envieoament
(10096) and fom izes! orgies (28)
Simpler locke soy sagen har be
implicated farms were dhe sources of the
cboea 20),

7. Choate humans

‘Sn 1987 ipseflomacin berene the first
‘Naoto lee ancimieroial yen ened
foe use in the US, Ciptflnacin was soon.
‘one ofthe man comnmonenéiaerobiause
te irstinlecdons anid bya verieryofbac
erat infosiane in butane. Foe exarpte
tiprofloracin wat widely weed 10 eat
Imethicilinersinant Stxplerocens aurent
‘GARSA) infers, an porcine nesoce
Ini infetion inthe US. Ciprofloxacin
France, homens exceged epidly among,
[MRSA ilu in cera baal the ma
jovty af MRSA jolatee were eeitant 10
Cproflorecin within sever masts (2):
Cigronicn sls became widely wed
trex potsone with gstcencec, eluding
‘slices 1990; ciproflnacin wat che

‘aeond ene coummenl-asedaneimieobial
agent ir the persons with Semonellnkec-
tions In £995 was che mosesised ati
sri 1486 of panoas wth Semone in
Teaions who snghe medica cae cecived
ciprafoxacia (CDC unpeblished eats
Considering the mules of prone with
rnuacllec<who sek redial ete each yee,
teas thowtunds of pezuns ih Stole
tnfecsins pela have boen ecard wich
Ciprolonscin in che US. However aoe of
theh272 Selmonalewolaee texted ar COC.
in 956 were reseeaat ro Huorogulnotons
“Why slid fluoroquinolone reseeance
emerge rsily Fallowing Suormsinotone
freausene ming MRSA isolates bot aoe
song Salone oles Sincehwrounssre
fhe mservor for MRSA infections whe
Auorequisslone-reietanc MRSA isolates

evel ip huosan, che cesta ong
ism orm rsquentytraaeaed wo cher
perms Aldhongh fuzoquinolene-sesisant
‘Sens may bave developed in dhe ntrs-

ws

eng fata aon
final trast fpr eth Seen
{anewho ae need wrk “uorequina’one,
it did not apreed a other pexzons becacse

bones re

enon pssaspHs

“Taken ingethe, chute data aaongly in
cae that mast hutnan Slane infcions
in the US esl rom the genio floods
‘oatarninated with Semone and cha an-
sal foes ae wally the source ofthe com

Soueesofantiniaabiabresinant
nontyphcdal Sofmanlia infections

Since most human Sabuanei infor

in ths US are aeqaited Foes ingostion of

Comaminsted fvods, i Flows thar most

snmicrobi-seant Salmanettiaections

Ire nequted fon ingeted aFfondemnen-

‘with sacimizmbial-naleane Seno

edi, Aca, f uni, toe Ean

‘aco bese Saft ioc foal
ral cransmisson flowing coneacr wich
tinal as Peconete-perses tanaetison
of ancimisrobiabsistns Slane ee,
‘Another potent souce of aii
Siaersstant Seinoneteinfetinn iv the
‘meigenceot linicobialressran
‘with previouily-susceptible Sebmomeds io

Licbscemsingresiran lowing aaimie-
Dial trenment. Te tty of ciroflosacn
sexisane SulwouellewFerions in the US
despre ee trequent ox of eproflaracn for
thetceamen of patens with lewd

nugget chia sera nerue afeequents
TE anvils Sabaneta

fectione ate acquied from de ingestion uf

foods conrarvinated with sptincrcbiak-e

sinant Selonels, he exes the ers

ie oFancmiembialresinaut Saloni

Cr mon recy. snceemtstobial eis
ause rele trom she we of ancmtcsbils
‘whasantiniatcial uage rubs in cheese
gence of de autiierbia-éicane Sal
tel. Ags, the ack af poonaci

as Sithmonela in the US dope wideapre
tue oF iproflrarin in hucnana fo he tet
tment of alionellase serangy eggs hat
ansmicrobial ute in urate has a sced

lmpace on the emengers on arcmlcrbiak

saintant Sefmovell, Uae only plausible
source for most of che entergerse and in
creasing prevtnae af aiimieebialaesie-
nt amy Sdmerele alas i the use of
ictal in cnimale, The only exer
Eon maybe sepromycin. esta Salmo
aes which prebabiy real Frente use of
_cepromcn on apple and pees

Evidence nupsting he conclusion that
sicia-reiance amarg Salmons

izolates ia humans reels fot the net of

sito sil in irate clades

{.energen af coca -estaet
Salncne phimorvn defiative ype TO8

{108} nite et tingeee

Giprofloxacn-rsinsant Sifmanele wae
rane inthe United Kingdom Sim prior co
1993, depie e widespread use of
iroiloracn in bmn save 197, Ts te

1995, arco

jrogdnslone ani
novi any lated cprovacn, wat
appeared for

‘plesprend use uf cvedocain i eceinary
sain jualin eine Salrolle

inary nse. Fullaning dhe

rapidly emerged avong husaan foes be
ineingin 194,

2angartionatpattems sressonces

“The specran ef ansileobil scarce
sauong Salon ioaren a hele food
sinus iil wo slaves foe persons
with Soh

nil infec Thisysturof
svoj eit ial sia chr
‘pestrum uf ansible aed ined a=

le bat dismiar 1 Me weteun ofanti-

sicebil aged in unas (9) ‘Ube simile
patorascf sstine remea evden an,
the

lribation (Solmenrlis debbie i

Ԥ fadarin pouty 6 and when one 2
oly ae die redwed

summary

Selnonell infec we cosmos ast
infecons ae itinebur sewce dese

may oa Antimicre>ileare wu indicred

1 Selon gueroeiencs But ate een

weogucronsr

iia apt nib
al forthe tearmencof horsands of paren:
tach yar wich inva infstons. Flas
Ccuinolons and chick yensition eephali-
porns acc dhe dng of choice or ins
indecriona; berate sonimienbia chases
sve limited by inueusing anciedczobial
Fistance Moet ancrmcoial-nsisare Seb
tein nections ate none Kom ingestion
ofconc inated Fide Ansimicrobial sie-
nex antong Safmonelolates resus from
the use of sindbis in fod animal

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‘eta atl ni
w ea npc as
24, Epidemiology of antibiotic resistance:
‘The example af Salmonella

finer atmoth

hs

the aoe

‘There is no dowbs char autnicesbie
agen belong ts wa
dass of deuge in hurnan 3 oererinary

adicin, Their widespreal wcshus gay

Inflaenesd the vexed previence afin
cous dca. Tey ergevarity afer
sent deuge ae avaiable ceeted guint
‘AL nao egg erin misro-rganinn.
Hloweves with incesing sucess and fee
‘quent eof aainitobilchemocheray i
Truman adic and ania husbandry
sixance against antimicrobial agots bas
incensed worldvides well Asc resoe eno
siesta sad ain ceoutce have

siployed ro inverse th prinaigles
of drug siete seid wo develop apcimicto-
bial agentclrctd aps ae carpets,

(On the molar level wo male eyes
of evivance mecheoinme have bess ob

served, Sore ese are ontusallyeasant
ant carts cosspounds, Thief mainly
duct the liso the rage seer hep
sence finns, omeces Lele esi
ance mechanizme. The second ‘cre of
‘oshantem is e-caled aque sevitance

chix ease, specie naitance mechanisms
seeexpresied within shew Saul sssitarse
reckasizes wep be based on sayctiinn
of cae ancbiots, change che erget 5

fr de lace of eng usin flue ef dh
fomngoune Onoe liked seh rerence
fenes can be pred hy conjugate

Foertion or wundccon, This prensa,

ross apes ba

fon DNA hath:
‘Aaioig che mow seriomy,comcemporaey

Tiedheentening batsia wach cass inf

ae is et depend

tions and which became ots and stone 2

fixctvee9 antmierobil

swobasteriatcer, Heemapiiut, Mrvobace:
tia Presi Sep hines, Srptcee al
Prendomonas
Although darn athe veal ace of anei=
ries agenesaceineracandin most cate
nat up-vo.dateecan beetimated thc only
hhdfuf dy sndbiois produced we ust i
human medicine, Since the Swann repoin
1954 shee has ean im epuing dee!
she influencs of stoscrabhl gens i ae
nal husbancry onthe zerance of beceia
Tay the
saimer to this impornt ys esioly
sepesachod by the ure of ma’ seule mackee
viqn, xa maeer ef Fc Pieced the

leolated Fam human yas

csablishmens of she aera uF il
vidual sutnce genes or the epidemi.ogy
oF the eine onanism thereto

‘One of suck gern which is carn
socnotis i ayrilis Sabecnel, Due 03
lengetem wvonioring prgeammes-a ang
courttis he evrapment and open ak

advil vainance snd ie

voll documensed, ese
zolaed inthe meer Mearay elton

isd
Sremmectin Tenzanin cist lowe
sivance, though aleimice oe
these sing ine sais rapaes a se

fe fivavasina’s net :ensing sire

Sat iol urn and solesler tuee

seve the erence 52 R-Sere wich elle

trans ancl moat capellion. owe
sei ac that dine mencreerinee pile
1 thesreenties muienie bube up due
te eramaporiion and ao iacgeteformtcion
wich gue cis onc plasmids solering

chuenernee Ferthemars li ae

evogmeaon«

diated
waco

fer ostnnes¢ 37°C apd 22°C eld be de
recta, efcting condivionein Ga em hab
tac Selene nasancer diving tel Ties
Tigh emperors te hese and lwin the
environment, Acthe begianiagof che cigh:
iessraiesun cuierevaare di shoved
Chroma inegration of resin genes
far the dese ine, Mare ect the eight:
and nines hav been doinaedtyehe ap
pewnce and spread of emaliesisant 8
lpphimerin cone ike DT204 and more
erezraly DTUO4. The Jer oe i Sacre

Snglyisloed in the Foropean and Annet

can epninents ar sow efiiantooneric
[prcd ra hundua ee food chain.
Tenner entenii dse most pa

lminane rors in raany ounces since

‘he end of she sighs ~ is agelyanvii=
vc sitive, sflecsieglover eating pres
snes, Tlomever ination on 65 sei
tne Gerwar fone over the fat ce yes
thaw a wemendnus hecragecity in tele
dhewceyps and genorppie peopeiee, The
‘lta show thst some fats edhbic l=
tives nich ie ofcity cance

ene

Avent censpesneoce ad envi
diggs, Frire ase of anvindctobial
gents in pouliy is going to determine
‘whether sath dangeous anes wil poi
cern and subsite mainly antibodies
Shiv §. ened poplation which can be
trend by antimirobin agen onder i=
‘hratening ciecumranes

eseopantnib et ota