Title Epidemiološke i mikrobiološko-molekularne značajke kampilobakterioza u Splitsko–dalmatinskoj županiji : 2007. – 2012.
Title (english) Epidemiological and microbiological-molecular characteristics of campylobacteriosis in Split-Dalmatia County : 2007-2012
Author Merica Carev
Mentor Marija Tonkić (mentor)
Committee member Ozren Polašek (predsjednik povjerenstva)
Committee member Ivana Goić Barišić (član povjerenstva)
Committee member Alemka Markotić (član povjerenstva)
Granter University of Split School of Medicine Split
Defense date and country 2019, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Medical Microbiology
Universal decimal classification (UDC ) 616 - Pathology. Clinical medicine
Abstract Porast incidencije kampilobakterioze i porast otpornosti izolata kampilobaktera na
antibiotike tijekom posljednjeg desetljeća smatraju se značajnim javnozdravstvenim
problemom u razvijenim zemljama. Međutim, u SDŽ i u RH su postojeći podatci o
kampilobakteriozi nedostatni zbog poteškoća u mikrobiološkoj dijagnostici i
prijavljivanju ove bolesti. Također, istraživanja otpornosti bolesničkih izolata
kampilobaktera na antibiotike i njihova genotipizacija u RH prethodno nisu rađeni.
Cilj ovog istraživanja je bio sustavnim praćenjem podataka o svim laboratorijski
potvrđenim infekcijama kampilobakterima među ambulantnim i hospitaliziranim
bolesnicima u SDŽ od 2007. do 2012. godine (tzv. „aktivnim sustavom nadzora“),
procijeniti incidenciju kampilobakterioze u SDŽ i ispitati povezanost incidencije s
demografskim, prostornim, klimatskim, poljoprivrednim i mikrobiološkim čimbenicima.
Ispitani su i otpornost na antibiotike gradijent strip testom te genetska struktura najčešće
vrste kampilobaktera C. jejuni metodom gel elektroforeze u električnom polju (PFGE).
U SDŽ je zabilježeno ukupno 2 658 laboratorijski potvrđenih infekcija
kampilobakterima u šestogodišnjem razdoblju istraživanja. Ukupna prosječna stopa
incidencije tog razdoblja je bila 96/100 000 stanovnika; najniža je bila u ruralnim
područjima županije (61/100 000), a najviša u urbanim područjima (131/100 000). Stope
incidencije su bile najviše u dobnoj skupini 0-4 godine i među muškarcima. Ukupne
prosječne stope incidencije te stope incidencije prema dobi i spolu su bile značajno veće u
urbanim nego u suburbanim (P < 0,001) i ruralnim (P < 0,001) područjima županije.
Najveći mjesečni broj infekcija kampilobakterima je zabilježen u lipnju. Bio je
umjereno povezan s višim prosječnim mjesečnim temperaturama (r=0,58) i nižom
relativnom vlažnosti zraka (r=-0,27), dok prosječna mjesečna količina oborina nije bila
povezana s mjesečnim brojem izolata kampilobaktera. Poljoprivredne aktivnosti u SDŽ
nisu bile povezane sa stopama incidencije kampilobakterioze.
Ispitivanje osjetljivosti i genotipizacija C. jejuni provedeni su od 1.5.2012. do
31.5.2013. testiranjem 77 uzastopnih izolata C. jejuni hospitaliziranih bolesnika i 77
izolata ambulantnih bolesnika, koji su izolirani istoga datuma kada i izolati
hospitaliziranih bolesnika.
Na ciprofloksacin je bilo otporno (CipR) 60% testiranih izolata C. jejuni. a na
tetraciklin 24%, od kojih je 89% bilo i korezistentno na ciprofloksacin (TcR/CipR).
Otpornost C. jejuni na gentamicin i eritromicin je bila vrlo niska (< 0,7%). Izolati su bili
genetski heterogeni s djelomično organiziranom klonskom strukturom.
Između 2010. i 2012/13. godine zabilježen je značajan porast rezistencije na
ciprofloksacin i TcR/CipR korezistencije. Porast udjela TcR/CipR korezistentnih izolata C.
jejuni je bio povezan s naglim pojavljivanjem klonskih grupa TcR/CipR korezistentnih
izolata u kratkom tromjesečnom razdoblju, na maloj prostornoj udaljenosti i uz
specifičnu, ravnomjernu dobnu raspodjelu među bolesnicima svih dobnih skupina, što
sugerira da je riječ o novonastalim (emergentnim) sojevima na ovom području.
Otpornost izolata nije bila povezana sa spolom niti s hospitalizacijom bolesnika.
Međutim, visoka otpornost izolata na ciprofloksacin i pojava TcR/CipR korezistentnih
izolata može značajno ograničiti terapijski izbor antibiotika. Stoga je potrebno daljnje
praćenje i istraživanje mehanizama nastanka i prijenosa otpornosti. Pri tom je neophodna
suradnja humane i veterinarske medicine.
Iako se incidencija kampilobakterioze u SDŽ može smatrati umjereno visokom,
demografske značajke oboljelih i sezonalnost kampilobakterioze u SDŽ se ne razlikuju od
značajki ove bolesti u drugim razvijenim zemljama. Međutim, osobitost
kampilobakterioze u SDŽ je naglašena razlika ukupnih prosječnih stopa incidencija te
stopa incidencije prema dobi i spolu u između urbanih i ruralnih područja županije
Rezultati istraživanja ukazuju na nove i specifične epidemiološke značajke
kampilobakterioze, obrasce otpornosti i genotipove C. jejuni u SDŽ i RH, što je osnova za
planiranje preventivnih mjera, kontrolu ove bolesti i optimalan izbor empirijske
antimikrobne terapije.
Abstract (english) The incidence of campylobacteriosis and number of antibiotic-resistant
Campylobacter strains has been increasing worldwide in the last decade, contributing to
the increasing public health burden of Campylobacter infections. Campylobacteriosis
incidence and disease pattern(s) in Split-Dalmatia County (SDC), and throughout Croatia,
are largely unknown due to deficiencies in illness reporting and laboratory diagnosis.
Notification of laboratory-confirmed cases, which is commonly used in surveillance
systems in the EU and the US is absent in Croatia. To date, no surveillance data on
antibiotic resistance or molecular characterization of human C. jejuni isolates have been
reported for Croatia.
Data from population-based laboratory surveillance were used to examine the
epidemiological pattern of campylobacteriosis in a sentinel site, SDC, from 2007 to 2012,
and to evaluate the association between disease incidence and demographic, geographical,
climatic, agricultural, and microbiological factors. Antibiotic susceptibility testing and
pulsed-field gel electrophoresis (PFGE) genotyping of isolates were performed.
A total of 2 658 laboratory-confirmed Campylobacter infections were recorded.
Overall mean incidence was 96/100 000, ranging from 61/100 000 in rural to 131/100 000
in urban areas; rates were highest in the age group 0-4 years. Overall mean and age- and
sex-specific incidences were significantly higher in urban versus suburban (P < 0.001)
and rural areas (P < 0.001). The number of infections peaked in early summer and was
correlated with higher average monthly temperature (r = 0.58) and lower humidity (r = -
0.27), but not with precipitation. Incidence was not associated with agricultural activities.
From May 2012 to May 2013, 153 consecutive C. jejuni isolates were collected
from stool samples of all patients hospitalized with gastroenteritis (n = 76) and matched
positive outpatients (by the date of laboratory submission) (n = 77). The gradient strip
method (E-test; bioMerieux) was used to determine the minimum inhibitory concentration
(MIC) for antibiotics. All isolates were analyzed according to the standardized
Campylobacter PFGE protocol of the Centers for Disease Control and Prevention.
Approximately 60% of C. jejuni isolates were resistant to ciprofloxacin, whereas
24% of isolates were resistant to tetracycline; of the latter, 89% were also coresistant to
ciprofloxacin. Resistance to erythromycin and gentamicin was infrequent (< 0.7%).
Antibiotic-resistant strains were generally not associated with the need for hospitalization;
however, effective treatment options for Campylobacter infections may be limited.
C. jejuni isolates were genetically highly diverse and exhibited a weak clonal
structure However, the prevalence of coresistant strains increased sharply after 2010, and
these coresistant strains were more prevalent in infections caused by clonal PFGE types,
with distinct patterns of temporal occurrence and age distribution in infected patients,
suggestive of newly identified strains. Further in-depth studies are essential to evaluate
whether this phenomenon is linked to C. jejuni epidemiology in food animals and
agricultural ecosystems.
Epidemiological features of campylobacteriosis in SDC from 2007 to date parallel
those in developed countries with respect to demography and seasonality. However, a
distinct campylobacteriosis pattern with consistently higher urban versus rural incidence
was observed. An increase and a high prevalence of CipR and TcR/CipR coresistant C.
jejuni were detected. These data signal recent and new campylobacteriosis patterns, which
may help formulate further preventive measures.
Keywords
kampilobakterijske infekcije
Campylobacter jejuni
Keywords (english)
Campylobacter Infections
Campylobacter jejuni
Language croatian
URN:NBN urn:nbn:hr:171:707592
Study programme Title: Basic and clinical medical sciences Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva, polje kliničke medicinske znanosti (doktor/doktorica znanosti, područje biomedicine i zdravstva, polje kliničke medicinske znanosti)
Type of resource Text
File origin Born digital
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Created on 2023-05-10 10:46:16