Risk factors and the impact of bloodstream infections caused by multi-drug resistant bacteria Acinetobacter spp. on public health

Uvod: Infekcija krvi izazvana multirezistentnim bakterijama roda Acinetobacter (MDRA) je praćena značajnim letalitetom i visokim troškovima bolničkog lečenja. Ciljevi istraživanja: Ustanoviti učešće izolata Acinetobacter spp. u strukturi pozitivnih hemokultura i kretanje procenta rezistencije na antibiotike u zdravstvenim ustanovama sekundarnog i tercijarnog nivoa na teritoriji AP Vojvodine u periodu 2013-2015. godina; Utvrditi kod kojih pacijenata se najčešće javljaju infekcije krvi izazvane MDRA; Utvrditi faktore rizika za nastanak bolničke infekcije (BI) krvi izazvane MDRA i uticaj BI krvi izazvane ovim uzročnicima na dužinu trajanja hospitalizacije i na ishod lečenja pacijenata hospitalizovanih u zdravstvenim ustanovama sekundarnog i tercijarnog nivoa u AP Vojvodini. Materijal i metode: Podaci iz protokola mikrobiološke laboratorije Centra za mikrobiologiju Instituta za javno zdravlje Vojvodine su korišteni za retrospektivnu analizu učestalosti izolata Acinetobacter spp. u strukturi hemokultura i za praćenje kretanja procenta rezistentnih izolata Acinetobacter spp. na posmatrane vrste antibiotika u zdravstvenim ustanovama sekundarnog i tercijarnog nivoa u AP Vojvodini u periodu od 01.01.2013. do 31.12.2015. godine. Utvrđivanje faktora rizika za nastanak infekcije krvi izazvane MDRA je sprovedeno kao prospektivna kohortna studija u jedinicama intenzivnih nega (JIN) u zdravstvenim ustanovama u AP Vojvodini u periodu od 01.01.2013. do 31.03.2016. godine. Grupu 1 (n=164), studijsku grupu kohortne studije su činili ispitanici sa BI krvi izazvanom MDRA. Grupu 2 (n=328), kontrolnu grupu kohortne studije, sačinjavali su pacijenti JIN bez izolata Acinetobacter spp. u hemokulturi. Kontrole su bile uključene u istraživanje samo ako je dužina njihovog boravka u JIN (dužina trajanja hospitalizacije do otpusta) bila ista ili duža od dužine boravka para iz studijske grupe do izolacije MDRA iz hemokulture. Kontrole su bile uparene sa slučajem iz studijske grupe u odnosu (1:2) prema: uzrastu (+/-5 godine), vrsti JIN i vremenu (isti kalendarski mesec u kojem je kod para iz studijske grupe izolovana pozitivna hemokultura). U cilju utvrđivanja predisponirajućih faktora za letalni ishod (14-dnevni letalitet) pacijenata u JIN sa infekcijom krvi izazvanom MDRA sprovedena je anamnestička studija. Rezultati: Učešće izolata Acinetobacter spp. u strukturi hemokultura pacijenata uzrasta 18 i više godina hospitalizovanih u zdravstvenim ustanovama u AP Vojvodini u periodu 2013-2015. godina iznosilo je 13,9%. Primoizolati Acinetobacter spp. iz uzoraka hemokultura pacijenata su u 96,1% (198/204) bili multirezistentni. Analizom kretanja rezistencije izolata Acinetobacter spp. na ispitivane antibiotike jedino je na cefepim ustanovljeno statistički značajno smanjenje učešća rezistentnih izolata (od 98,5% u 2014. godini do 83,3% u 2015. godini), (p=0,025). Izolati Acinetobacter spp. su najčešće registrovani kod pacijenata hospitalizovanih u JIN (71,1% (145/204)). Multivarijantnom analizom izdvojili su se nezavisni prediktori za nastanak infekcije krvi izazvane MDRA: prijem iz drugog odeljenja/bolnice, prijemne dijagnoze politrauma i opekotina, prethodna kolonizacija gornjeg respiratornog trakta MDRA, prisustvo dva i više komorbiditeta, prethodna primena mehaničke ventilacije, viši indeks invazivnih procedura, prethodna primena derivata imidazola i prethodna primena četiri i više klasa antibiotika. Pacijenti sa infekcijom krvi izazvanom MDRA su statistički značajno duže boravili u JIN (24.5±17,5) u odnosu na neinficirane kontrole (19,7±12,6), (p=0,001) i statistički značajno češće su imali letalan ishod (51,2% (84/164) u odnosu na pacijente bez infekcije krvi izazvane ovim mikroorganizmom (25,0% (82/328), (p<0,0001). Multivarijantnom analizom, kao nezavisni prediktori letalnog ishoda pacijenata, izdvojili su se: starija životna dob, prijemnom dijagnoza akutne respiratorne insuficijencije i primena neadekvatne antimikrobne terapije nakon izolacije uzročnika iz hemokulture. Zaključak: Učestalost i struktura faktora rizika je ukazala da je snižavanje prevalencije i snižavanje letaliteta moguće ostvariti kombinovanom primenom mera koje obuhvataju racionalnu upotrebu antibiotika širokog spektra u empirijskoj antimikrobnoj terapiji i striktno poštovanje procedura vezanih za primenu invazivnih nastavaka.Aim: Establish the participation of Acinetobacter spp. isolates in the structure of positive hemocultures and the percentage range of resistance to antibiotics in the health institutions of secondary and tertiary level on the territory of AP of Vojvodina in the period from 2013 to 2015; determine which patients most commonly get BSI caused by MDRA; determine risk factors for the occurrence of healthcare-associated infection (HAI) of blood caused by MDRA and the impact of HAI of blood caused by these pathogens to the duration of hospitalization, and the treatment outcome of patients admitted to the health care institutions of secondary and tertiary levels in the AP of Vojvodina. Material and Methods: Data from the protocol of the microbiological laboratory of the Center for Microbiology, Institute of Public Health of Vojvodina were used for retrospective analysis of the frequency of isolates of Acinetobacter spp. in the structure of positive hemocultures and for monitoring the percentage isolates of Acinetobacter spp. resistant to the observed type of antibiotics in health institutions of secondary and tertiary levels in AP of Vojvodina in the period from January 1, 2013 to December 31, 2015. Determining the risk factor for the occurrence of BSI induced by MDRA was conducted as a prospective cohort study in intensive care units (ICU) in the health institutions in AP of Vojvodina in the period from January 1, 2013 to March 31, 2016. Group 1 (n=164), study group of the cohort study included the patients with HAI of blood induced by MDRA. Group 2 (n=328), control group of the cohort study consisted of ICU patients without isolates of Acinetobacter spp. in the hemoculture. Controls were included in the study only if the length of their stay in the ICU (duration of hospitalization until discharge) was the same or longer than the length of the stay of their study group counterparts until the isolation of MDRA from blood culture. Controls were matched with the cases of the study group in the ratio (1: 2) according to: age (+/- 5 years), type of ICU and time (the same calendar month in which positive hemoculture was isolated in the the study group pair). In order to determine the predisposing factors of lethal outcome (14-day lethality) of patients in the ICU with the BSI caused by MDRA, anamnestic study was conducted. Results: Participation of Acinetobacter spp. isolates in the structure of hemocultures of patients, aged 18 and older, hospitalized in medical institutions in AP of Vojvodina in the period from 2013 to 2015 amounted to 13.9%. Acinetobacter spp. primoisolates from the patients' hemoculture samples were in 96.1% (198/204) multi-drug resistant. Analysing the Acinetobacter spp. isolates resistance to the tested antibiotics, Cefepime was the only to prove to cause statistically significant decrease in the share of resistant isolates (from 98.5% in the year 2014 to 83.3% in 2015), (p=0.025). Isolates of Acinetobacter spp. are most frequently registered in patients hospitalized in ICU (71.1% (145/204)). Multivariate analyses separated independent predictors for the occurrence of blood infection caused by the MDRA: patient transfers from another ward/hospital, admission diagnoses of polytrauma and burns, previous colonization of the upper respiratory tract MDRA, the presence of two or more co-morbidity, previous use of mechanical ventilation, higher index of invasive procedures, previous use of Imidazole derivates and the previous use of four or more classes of antibiotics. Patients with BSI caused by MDRA stayed statistically much longer in the ICU (24.5±17.5) as compared to uninfected controls (19.7±12.6), (p=0.001) and significantly more likely to have the lethal outcome (51.2% (84/164)) compared to patients without bloodsteram infections caused by this micro-organism (25.0% (82/328) (p<0.0001). Using multivariate analysis, independent predictors of death of patients, were found to be: advanced age, admission diagnosis of acute respiratory insufficiency and the application of inadequate antibiotic therapy after the isolation of pathogens from the hemoculture. Conclusion: The frequency and the structure of the risk factors suggested that the reduction of the prevalence and lowering of lethality can be achieved by combined administration of measures that include the rational use of broad spectrum antibiotics in the empirical antimicrobial treatment and strict compliance with the procedures related to the use of invasive follow-ups

Risk factors and the impact of bloodstream infections caused by multi-drug resistant bacteria Acinetobacter spp. on public health

Uvod: Infekcija krvi izazvana multirezistentnim bakterijama roda Acinetobacter (MDRA) je praćena značajnim letalitetom i visokim troškovima bolničkog lečenja. Ciljevi istraživanja: Ustanoviti učešće izolata Acinetobacter spp. u strukturi pozitivnih hemokultura i kretanje procenta rezistencije na antibiotike u zdravstvenim ustanovama sekundarnog i tercijarnog nivoa na teritoriji AP Vojvodine u periodu 2013-2015. godina; Utvrditi kod kojih pacijenata se najčešće javljaju infekcije krvi izazvane MDRA; Utvrditi faktore rizika za nastanak bolničke infekcije (BI) krvi izazvane MDRA i uticaj BI krvi izazvane ovim uzročnicima na dužinu trajanja hospitalizacije i na ishod lečenja pacijenata hospitalizovanih u zdravstvenim ustanovama sekundarnog i tercijarnog nivoa u AP Vojvodini. Materijal i metode: Podaci iz protokola mikrobiološke laboratorije Centra za mikrobiologiju Instituta za javno zdravlje Vojvodine su korišteni za retrospektivnu analizu učestalosti izolata Acinetobacter spp. u strukturi hemokultura i za praćenje kretanja procenta rezistentnih izolata Acinetobacter spp. na posmatrane vrste antibiotika u zdravstvenim ustanovama sekundarnog i tercijarnog nivoa u AP Vojvodini u periodu od 01.01.2013. do 31.12.2015. godine. Utvrđivanje faktora rizika za nastanak infekcije krvi izazvane MDRA je sprovedeno kao prospektivna kohortna studija u jedinicama intenzivnih nega (JIN) u zdravstvenim ustanovama u AP Vojvodini u periodu od 01.01.2013. do 31.03.2016. godine. Grupu 1 (n=164), studijsku grupu kohortne studije su činili ispitanici sa BI krvi izazvanom MDRA. Grupu 2 (n=328), kontrolnu grupu kohortne studije, sačinjavali su pacijenti JIN bez izolata Acinetobacter spp. u hemokulturi. Kontrole su bile uključene u istraživanje samo ako je dužina njihovog boravka u JIN (dužina trajanja hospitalizacije do otpusta) bila ista ili duža od dužine boravka para iz studijske grupe do izolacije MDRA iz hemokulture. Kontrole su bile uparene sa slučajem iz studijske grupe u odnosu (1:2) prema: uzrastu (+/-5 godine), vrsti JIN i vremenu (isti kalendarski mesec u kojem je kod para iz studijske grupe izolovana pozitivna hemokultura). U cilju utvrđivanja predisponirajućih faktora za letalni ishod (14-dnevni letalitet) pacijenata u JIN sa infekcijom krvi izazvanom MDRA sprovedena je anamnestička studija. Rezultati: Učešće izolata Acinetobacter spp. u strukturi hemokultura pacijenata uzrasta 18 i više godina hospitalizovanih u zdravstvenim ustanovama u AP Vojvodini u periodu 2013-2015. godina iznosilo je 13,9%. Primoizolati Acinetobacter spp. iz uzoraka hemokultura pacijenata su u 96,1% (198/204) bili multirezistentni. Analizom kretanja rezistencije izolata Acinetobacter spp. na ispitivane antibiotike jedino je na cefepim ustanovljeno statistički značajno smanjenje učešća rezistentnih izolata (od 98,5% u 2014. godini do 83,3% u 2015. godini), (p=0,025). Izolati Acinetobacter spp. su najčešće registrovani kod pacijenata hospitalizovanih u JIN (71,1% (145/204)). Multivarijantnom analizom izdvojili su se nezavisni prediktori za nastanak infekcije krvi izazvane MDRA: prijem iz drugog odeljenja/bolnice, prijemne dijagnoze politrauma i opekotina, prethodna kolonizacija gornjeg respiratornog trakta MDRA, prisustvo dva i više komorbiditeta, prethodna primena mehaničke ventilacije, viši indeks invazivnih procedura, prethodna primena derivata imidazola i prethodna primena četiri i više klasa antibiotika. Pacijenti sa infekcijom krvi izazvanom MDRA su statistički značajno duže boravili u JIN (24.5±17,5) u odnosu na neinficirane kontrole (19,7±12,6), (p=0,001) i statistički značajno češće su imali letalan ishod (51,2% (84/164) u odnosu na pacijente bez infekcije krvi izazvane ovim mikroorganizmom (25,0% (82/328), (p<0,0001). Multivarijantnom analizom, kao nezavisni prediktori letalnog ishoda pacijenata, izdvojili su se: starija životna dob, prijemnom dijagnoza akutne respiratorne insuficijencije i primena neadekvatne antimikrobne terapije nakon izolacije uzročnika iz hemokulture. Zaključak: Učestalost i struktura faktora rizika je ukazala da je snižavanje prevalencije i snižavanje letaliteta moguće ostvariti kombinovanom primenom mera koje obuhvataju racionalnu upotrebu antibiotika širokog spektra u empirijskoj antimikrobnoj terapiji i striktno poštovanje procedura vezanih za primenu invazivnih nastavaka.Aim: Establish the participation of Acinetobacter spp. isolates in the structure of positive hemocultures and the percentage range of resistance to antibiotics in the health institutions of secondary and tertiary level on the territory of AP of Vojvodina in the period from 2013 to 2015; determine which patients most commonly get BSI caused by MDRA; determine risk factors for the occurrence of healthcare-associated infection (HAI) of blood caused by MDRA and the impact of HAI of blood caused by these pathogens to the duration of hospitalization, and the treatment outcome of patients admitted to the health care institutions of secondary and tertiary levels in the AP of Vojvodina. Material and Methods: Data from the protocol of the microbiological laboratory of the Center for Microbiology, Institute of Public Health of Vojvodina were used for retrospective analysis of the frequency of isolates of Acinetobacter spp. in the structure of positive hemocultures and for monitoring the percentage isolates of Acinetobacter spp. resistant to the observed type of antibiotics in health institutions of secondary and tertiary levels in AP of Vojvodina in the period from January 1, 2013 to December 31, 2015. Determining the risk factor for the occurrence of BSI induced by MDRA was conducted as a prospective cohort study in intensive care units (ICU) in the health institutions in AP of Vojvodina in the period from January 1, 2013 to March 31, 2016. Group 1 (n=164), study group of the cohort study included the patients with HAI of blood induced by MDRA. Group 2 (n=328), control group of the cohort study consisted of ICU patients without isolates of Acinetobacter spp. in the hemoculture. Controls were included in the study only if the length of their stay in the ICU (duration of hospitalization until discharge) was the same or longer than the length of the stay of their study group counterparts until the isolation of MDRA from blood culture. Controls were matched with the cases of the study group in the ratio (1: 2) according to: age (+/- 5 years), type of ICU and time (the same calendar month in which positive hemoculture was isolated in the the study group pair). In order to determine the predisposing factors of lethal outcome (14-day lethality) of patients in the ICU with the BSI caused by MDRA, anamnestic study was conducted. Results: Participation of Acinetobacter spp. isolates in the structure of hemocultures of patients, aged 18 and older, hospitalized in medical institutions in AP of Vojvodina in the period from 2013 to 2015 amounted to 13.9%. Acinetobacter spp. primoisolates from the patients' hemoculture samples were in 96.1% (198/204) multi-drug resistant. Analysing the Acinetobacter spp. isolates resistance to the tested antibiotics, Cefepime was the only to prove to cause statistically significant decrease in the share of resistant isolates (from 98.5% in the year 2014 to 83.3% in 2015), (p=0.025). Isolates of Acinetobacter spp. are most frequently registered in patients hospitalized in ICU (71.1% (145/204)). Multivariate analyses separated independent predictors for the occurrence of blood infection caused by the MDRA: patient transfers from another ward/hospital, admission diagnoses of polytrauma and burns, previous colonization of the upper respiratory tract MDRA, the presence of two or more co-morbidity, previous use of mechanical ventilation, higher index of invasive procedures, previous use of Imidazole derivates and the previous use of four or more classes of antibiotics. Patients with BSI caused by MDRA stayed statistically much longer in the ICU (24.5±17.5) as compared to uninfected controls (19.7±12.6), (p=0.001) and significantly more likely to have the lethal outcome (51.2% (84/164)) compared to patients without bloodsteram infections caused by this micro-organism (25.0% (82/328) (p<0.0001). Using multivariate analysis, independent predictors of death of patients, were found to be: advanced age, admission diagnosis of acute respiratory insufficiency and the application of inadequate antibiotic therapy after the isolation of pathogens from the hemoculture. Conclusion: The frequency and the structure of the risk factors suggested that the reduction of the prevalence and lowering of lethality can be achieved by combined administration of measures that include the rational use of broad spectrum antibiotics in the empirical antimicrobial treatment and strict compliance with the procedures related to the use of invasive follow-ups

Streptococcus pneumoniae serotype distribution in Vojvodina before the introduction of pneumococcal conjugate vaccines into the national immunization program

Introduction. Streptococcus pneumoniae is the most common causative agent of bacterial pneumonia and meningitis. Mandatory childhood immunization against pneumococcal diseases is introduced in the new Law on Protection of Population against Communicable Diseases in Serbia. Objective. The objective of this study was to determine the prevalence of pneumococcal serotype distribution in Vojvodina region before routine use of pneumococcal conjugate vaccine in Serbia. Methods. A total of 105 isolates of Streptococcus pneumoniae were collected in the period from January 2009 to April 2016. Based on the results of serotyping in the National Reference Laboratory, we analyzed distribution of circulating serotypes and coverage of conjugate and 23-valent polysaccharide pneumococcal vaccines in different age groups. Results. Among 105 isolates, a total of 21 different serotypes of Streptococcus pneumoniae were determined. The most frequent serotypes were 3 (21.9%), 19F (20.0%), and 14 (10.5%). The serotype coverage of pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13) was 48.6%, 54.3%, and 84.8%, respectively, while pneumococcal polysaccharide vaccine (PPV23) covered 89.5% of the total number of isolates in all age groups. Serotypes included in PCV7, PCV10, and PCV13 represented 72.0%, 76.0%, and 88.0% of the total number of isolates in children ≤5 years, respectively. Vaccine serotype coverage of PCV13 and PPV23 ranged from 87.1% to 90.3% in adults 50-64 years of age, and 77.8% to 85.2% in adults ≥65 years old. Conclusion. Serotype distribution of Streptococcus pneumoniae in the population fairly overlaps with the serotypes contained in pneumococcal vaccines, so that implementation of childhood immunization is justified. The study was done in the Province of Vojvodina but the findings may be applied to Serbia as a whole. [Projekat Ministarstva nauke Republike Srbije, br. ON 175039] <br><br><font color="red"><b> This article has been corrected. Link to the correction <u><a href="http://dx.doi.org/10.2298/SARH1612678E">10.2298/SARH1612678E</a><u></b></font