Mechanisms of carbapenem resistance in Acinetobacter baumannii

Pripadnici roda Acinetobacter su nefermentativni mikroorganizmi široko rasprostranjeni u vodi i na zemlji. Pojedine vrste unutar roda sastavni su dio fiziološke flore kože i sluznica te su sposobni preživjeti duži vremenski period na suhim i vlažnim površinama. Acinetobacter baumannii je oportunistički uzročnik hospitalnih infekcija, prvenstveno u imunokompromitiranih bolesnika. Sve do 1970-ih godina, većina izolata unutar roda Acinetobacter bila je osjetljiva na široki spektar različitih antibiotika. Razvoj rezistencije na karbapeneme novijeg je datuma i posljedica je stvaranja metalo-β-laktamaza (karbapenemaza), oksacilinaza koje imaju sposobnost hidrolize karbapenema, gubitka proteina u vanjskoj membrani, izbacivanja antibiotika iz stanice ili kombinacije navedenih mehanizama rezistencije. Smatra se da su karbapenemaze i oksacilinaze koje hidroliziraju karbapeneme najznačajni u ekspresiji rezistencije na karbapeneme u kliničkih izolata A. baumannii. Enzimi koji imaju sposobnost hidrolize karbapenema u kliničkim izolatima A. baumannii pripadaju molekularnoj klasi D (OXA enzimi, oksacilinaze) ili molekularnoj klasi B (metaloenzimi iz grupe IMP, VIM i SIM karbapenemaza). Veliko kliničko značenje danas imaju oksacilinaze koje se dijele u četiri filogenetske skupine specifične za izolate A. baumannii: OXA-23 skupina, OXA-40 skupina, OXA-58 skupina i najveća OXA-51 skupina, poznata i kao prirodno kromosomski kodirane oksacilinaze. OXA-51 skupina oksacilinaza uglavnom ima slabu sposobnost hidrolize karbapenema, ali prisustvo insercijske sekvencije ISAba1 smještene neposredno uz blaOXA-51 like gen djeluje kao promotor rezistencije ili smanjene osjetljivosti na karbapeneme. Zabrinjavajući porast rezistencije na karbapeneme zabilježen je posljednjih godina među izolatima A. baumannii u nekoliko bolnica u Hrvatskoj. Molekularna osnova smanjene osjetljivosti na karbapeneme istražena je na velikom broju izolata iz KBC Split, a šesnaest izolata uključeno je i u međunarodni ARPAC (Antibiotic Resistance, Prevention and Control) projekt. Genotipizacija pomoću dvije metode (RAPD i PFGE) potvrdila je pripadnost hrvatskih izolata Europskom klonu I (sekvencijska grupa 2).Organisms of the genus Acinetobacter are ubiquitous and widely distributed in soil and water. They are frequently present on human skin and mucous membranes and are able to survive for long periods on dry and humid surfaces. Acinetobacter baumannii is an opportunistic pathogen that is mostly involved in nosocomial infections in immunocompromised patients. Until the 1970s, most isolates were susceptible to a wide range of antibiotics. Carbapenem resistance results from production of metallo-β-lactamases, carbapenem hydrolyzing oxacillinases, loss of outer membrane proteins, efflux and often combined mechanisms of resistance. These resistance mechanisms pose a serious therapeutic threat, since carbapenems are frequently used to treat otherwise resistant A. baumannii infections. Carbapenemases found in Acinetobacter belong to molecular class D (OXA enzymes) or class B (metalloenzymes of IMP- and VIM-type or SIM-1). The OXA carbapenemases are divided into four phylogenetic subgroups: acquired enzymes OXA-23-like, OXA-40-like and OXA-58-like and OXA-51-like enzymes that are intrinsic to A. baumannii. OXA-51-like enzymes are normally expressed at low levels but can be over expressed as consequence of the insertion of an ISAba1 sequence upstream of their genes. Recently an increase in the prevalence of carbapenem resistant Acinetobacter baumannii isolates was observed in few medical centers in Croatia. The investigation of the background of carbapenem resistance in relevant clinical isolates of A. baumannii from Split University Hospital was performed during last years and sixteen different strains of carbapenem resistant A. baumannii were included in ARPAC project (Antibiotic Resistance, Prevention and Control). The molecular typing by random amplified polymorphic DNAanalysis (RAPD), followed by pulsed-field gel electrophoresis (PFGE) belonged isolates to the same PFGE type as a part of sequence group 2 (European \u27clone I\u27 lineage)

Epidemiology and resistance of clinical isolates of Acinetobacter baumannii in Croatia over a ten-year period – what has changed?

Acinetobacter baumannii zauzima posebno mjesto unutar skupine uzročnika teških infekcija, poznatije kao “ESKAPE” mikroorganizmi. Ovaj mikroorganizam postao je vodeći uzročnik hospitalnih infekcija u 21. stoljeću, te su brojna istraživanja usmjerena na epidemiologiju, rezistenciju i nadzor nad ovim patogenom. Epidemiologija i molekularna osnova rezistencije kliničkih izolata Acinetobacter baumannii u Hrvatskoj tijekom posljednja dva desetljeća bitno se promijenila u većini zdravstvenih ustanova, uz visoki postotak rezistencije na karbapeneme, kinolone i aminoglikozide, te prisutnost multiplo-rezistentnih izolata. U ovom pregledu naglasak je stavljen na rezultate istraživanja epidemiologije i rezistencije kliničkih izolata iz Hrvatske.Among the „ESKAPE“ group of serious pathogens Acinetobacter baumannii is under a great concern worldwide. This microorganism has become a leading nosocomial pathogen of the 21th century, and numerous studies are focused on the epidemiology, resistance and control measures of this pathogen in the hospital setting. The epidemiology and molecular basis of resistance of clinical isolates of Acinetobacter baumannii in Croatia over the last two decades has changed significantly in most health institutions, with a high percentage of resistance to carbapenems, quinolones and aminoglycosides, and the presence of multi-resistant isolates. In this review, emphasis was placed on the results of research on epidemiology and resistance of clinical isolates from Croatia

Multidrug-resistant Acinetobacter baumannii (MRAB) – ten years after the onset of these isolates in Croatia

Tijekom proteklih desetljeća Acinetobacter baumannii je postao jedan od vodećih uzročnika bolni~kih infekcija širom svijeta. Studija koja je istraživala prevalenciju infekcija u jedinicama intenzivnog liječenja među 75 zemalja na pet kontinenata potvrdila je da je A. baumannii na petom mjestu po učestalosti infekcija. Dijelom je to posljedica njegove izuzetne sposobnosti da perzistira u bolničkoj sredini i brojnih mehanizama rezistencije, izazivajući infekcije prvenstveno u jedinicama intenzivnog liječenja kod oboljelih s opekotinama, mehaničkom potpornom ventilacijom, teško bolesnih i oslabljenih bolesnika. Do danas su poznati i opisani brojni mehanizmi rezistencije prisutni kod ovog mikroorganizama, pa ipak njegovo širenje unutar bolničkih sredina vrlo je teško kontrolirati. Ovaj problem izuzetno je naglašen u nekoliko najvećih hrvatskih bolnica gdje su opisane epidemije uzrokovane multiplorezistentnim A. baumannii (MRAB).leading nosocomial pathogens throughout the world. In a prevalence study of infections in intensive care units conducted among 75 countries of the five continents, this microorganism was found to be the fifth most common pathogen. This is partly due to its intrinsic aptitude to persist in the hospital setting and acquire multiple resistance mechanisms, with many infections concentrated in intensive care, burns or high dependency units treating severely ill or debilitated patients receiving mechanical ventilation. While we know a great deal about the mechanisms responsible for antimicrobial resistance in this microorganism we see ourselves unable to stop it. This problem continues to escalate in several largest Croatian hospitals reporting outbreaks caused by multidrug-resistant A. baumannii (MRAB)

Smanjena osjetljivost na dezinficijense bakterije Acinetobacter baumannii u obliku biofilma na staklu i keramici

The aim of this study was to determine the susceptibility of hospital and environmental Acinetobacter baumannii isolate biofilms on ceramics and glass to common disinfectants benzalkonium chloride and chlorhexidine. For this purpose wedeveloped a new method for biofilm cultivation and quantification on ceramics. The biofilm bacteria were more resistant to disinfectants than the planktonic populations, as more than 50 % of the biofilm population and none of the planktonic population survived 5-minute exposure. Furthermore, biofilm populations on ceramic tiles were significantly more resistant than those on glass coverslips, even though the amount of biofilm was practically the same on ceramics and glass. The reason for reduced susceptibility of A. baumannii biofilms on ceramics may be related to surface/disinfection interactions. Our findings suggest that biofilms on ceramic surfaces can be an important source of A. baumannii infection in hospital environmentsVrsta Acinetobacter baumannii prepoznata je kao trenutačno vodeći uzročnik bolničkih infekcija sa smrtnim ishodom. Trajna prisutnost A. baumannii u bolnicama posljedica je ponajviše otpornosti na antibiotike te sposobnosti ove bakterije da stvara biofilm. U radu je testirana osjetljivost biofilma kliničkih i okolišnih izolata vrste A. baumannii na najčešće korištene dezinficijense, benzalkonijev klorid i klorheksidin. Predložena je nova metoda za uzgoj biofilma na keramičkim pločicama te su rezultati uspoređeni s biofilmom koji je nastao na staklu. Bakterije unutar biofilma bile su otporne na dezinficijense; pri koncentraciji dezinficijensa koja je potpuno uništila planktonske bakterije, unutar biofilma preživjelo je više od 50 % populacije, čak i nakon petominutnog izlaganja dezinficijensima. Značajno je opažanje da su bakterije u obliku biofilma na keramici znatno otpornije na dezinficijense od bakterija u obliku biofilma na staklu, iako je brojnost bakterija bila podjednaka. Navedeni rezultati upućuju na zaključak da je međudjelovanje materijala i dezinficijensa važan čimbenik koji određuje učinkovitost dezinfekcije. Sposobnost stvaranja biofilma na keramičkim površinama moguće je ishodište i značajno stanište bakterija A. baumannii u bolničkom okružju

Antibacterial effect of „Sanosil super25“ on multiple resistant bacteria Acinetobacter baumannii and Klebsiella pneumoniae

Višestruko rezistentne bakterije, uzročnici hospitalnih infekcija, kao što su Acinetobacter baumannii i Klebsiella pneumoniae, predstavljaju globalni problem 21. stoljeća. Osobito zabrinjava sve učestalija pojava otpornosti ovih mikroorganizama na komercijalno dostupne dezinficijense. Cilj našeg istraživanja bio je utvrditi učinkovitost dezinfekcije proizvoda „Sanosil super25“, u odnosu na vodikov peroksid i to na višestruko rezistentne izolate A. baumannii i K. pneumoniae. Ispitane su vrijednosti MTC (maksimalno tolerirajuća koncentracija); MIC (minimalna inhibirajuća koncentracija) i MBC (minimalna baktericidna koncentracija). MTC Sanosila (<1.25 ppm) bila je dvostruko manja u odnosu na vodikov peroksid. MIC-e Sanosila (1.25 ili <1.25 ppm) su bile 4 puta manje u odnosu na vodikov peroksid. MBC koja rezultira izostankom vijabilnih bakterija za Sanosil je bila <1.25 ppm već nakon 5 min kontakta, što je barem 8 puta niža koncentracija u odnosu na vodikov peroksid. Rezultati su pokazali da je Sanosil super25 bio učinkovitiji u sve tri kategorije, u odnosu na vodikov peroksid.Multi-resistant bacteria, the causes of nosocomial infections, such as Acinetobacter baumannii and Klebsiella pneumoniae, represent a global problem of the 21st century. The increasing resistance of these microorganisms to commercially available disinfectants is of a particular concern. The aim of our study was to determine disinfection effectiveness of the product "Sanosil super25", in relation to hydrogen peroxide, to multiple resistant isolates of A. baumannii and K. pneumoniae. The tested parameters were: MTC values (maximum tolerated concentration); MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration). The MTC of Sanosil (<1.25 ppm) was twice as low as that of hydrogen peroxide. Sanosil MICs (1.25 or <1.25 ppm) were 4-fold lower than hydrogen peroxide. The MBC resulting in the absence of viable bacteria for Sanosil was <1.25 ppm after only 5 minutes of contact, which is at least 8 times lower concentration than hydrogen peroxide. The results showed that Sanosil super25 was more effective in all three categories, compared to hydrogen peroxide

Influence of Passive Smoking on Basic Anthropometric Characteristics and Respiratory Function in Young Athletes

The primary objective of this study is to investigate the maintenance difference in basic anthropometric characteristics and to outline the dynamics of respiratory function change in youngsters athletes exposed to passive smoking (PS) and athletes not exposed to passive smoking in their families (NPS). High and weight were determined as basis anthropometric characteristics. Measured parameters for respiratory function were vital capacity (VC), forced expiratory volume in the first second (FEV1), maximum expiratory flow (PEF), forced expiratory flow at 50% forced vital capacity (MEF 50) and forced expiratory flow at 25% forced vital capacity (MEF 25). Significant statistical differences in separate spirometric variable were found in three variables (FEV1, MEF50, and MEF25) for group older youngsters. Analysis of variance showed statistical differences between athletes unexposed to passive smoking (NPS) and athletes exposed to passive smoking (PS) in even four spirometric variables (VC, FEV1, MEF50 and MEF25)

Novel material for medical use based on Ag-zeolite/polyvinyl chloride composite

The aim of this work was to study antibacterial activity of silver-exchanged natural clinoptilolite/polyvinil chloride composites (AgZ/PVC) toward clinical isolates of Acinetobacter baumannii, which causes various nosocomial infection. Polyvinil chloride (PVC) mostly used for endotracheal tubes usually acts as a reservoir for bacteria causing infections with a high level of mortality

Antibacterial Activity of Pinus pinaster Bark Extract and its Components Against Multidrug-resistant Clinical Isolates of Acinetobacter baumannii

The aim of this research was to test the antibacterial activity of Pinus pinaster aqueous bark extract (PABE) and its basic components against multidrug-resistant isolates of Acinetobacter baumannii belonging to European clone I and II, isolated previously from the clinical outbreaks. The minimum bactericidal concentration of PABE against both clones of A. baumannii was 200 mg ml–1, while lower concentrations showed high antibacterial activity. After 24 h of treatment with 100, 50 or 10 mg ml–1 of extract, the reduction in the number of A. baumannii isolates belonging to European clone I and II was 85.8 ± 2.5 %, 78.5 ± 1.1 %, 66.3 ± 2.5 % and 90.2 ± 1.7 %, 78.6 ± 1.2 %, 69.8 ± 0.7 %, respectively. Several basic components: caffeic acid, catechin, epicatechin, gallic acid and vanillin, detected in the extract by high performance liquid chromatography, contributed to the antibacterial activity of the extract against both clones of A. baumannii. However, the antibacterial activity of extract was higher than that of each tested basic component suggesting that proanthocyanidins, which were present in quite a large amount in the extract, might have also contributed to the activity of the extract. Antibacterial activity of PABE against A. baumannii reveals that complex and inexpensive natural product might be useful in combat against naturally competent bacteria that easily acquire resistance against antibiotics

Klinički prikaz genitourinarne tuberkuloze sa sumnjom na abdominalnu neoplazmu

Genital tuberculosis is a rare and unexpected disease in European countries including Croatia. Diagnosis of female genital tract tuberculosis is challenging and is rarely pin-pointed by clinical symptoms because of their low specificity. The authors decided to present a case of genitourinary tuberculosis in a young, immunocompetent fertile woman with high clinical suspicion of abdominal tumor mass. Although considered a desease of the past, rare clinical presentation of genital tuberculosis should be expected and taken into account.Genitalna tuberkuloza rijetka je i neočekivana bolest u zemljama Europske unije uključujući i Hrvatsku. Postavljanje dijagnoze tuberkuloze genitalnog sustava otežano je nespecifičnim simptomima. Prikazujemo slučaj genitourinarne tuberkuloze kod mlade imunokompetentne žene generativne dobi gdje je klinička dijagnoza upućivala na abdominalnu neoplazmu. U vremenu velikih društvenih promjena prisutnih posljednjih godina rijetke kliničke prezentacije tuberkuloze i dalje su moguće kao diferencijalna dijagnoza

Prvi hrvatski pedijatrijski bolesnik s Geotrichum capitatum respiratornom infekcijom

Geotrichum capitatum can cause infections in humans and its importance has recently been recognized in patients with immunosuppressive conditions. In this report we present the first Croatian pediatric patient with pneumonia in whom G. capitatum was isolated in three sequential bronchoalveolar lavage and tracheal aspiration specimens.Geotrichum capitatum može uzrokovati infekcije u ljudi i njegov značaj je nedavno prepoznat u imunosuprimiranih bolesnika. U ovom radu prikazujemo prvog hrvatskog pedijatrijskog bolesnika s pneumonijom u kojeg je G. capitatum izoliran u tri uzastopna bronhoalveolarna lavata i aspirata traheje