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Final upgrading: Extreme-drug-resistant (XDR) Acinetobacter baumannii carrying blaOXA-23 in a patient with acute necrohaemorrhagic pancreatitis Luísa Vieira.

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Presentation on theme: "Final upgrading: Extreme-drug-resistant (XDR) Acinetobacter baumannii carrying blaOXA-23 in a patient with acute necrohaemorrhagic pancreatitis Luísa Vieira."— Presentation transcript:

1 Final upgrading: Extreme-drug-resistant (XDR) Acinetobacter baumannii carrying blaOXA-23 in a patient with acute necrohaemorrhagic pancreatitis Luísa Vieira Peixe REQUIMTE. Laboratório de Microbiologia, Faculdade de Farmácia, Universidade do Porto, Portugal

2 Hospitals Food and animal production environment Humans community Environment VRE, Enterobacteriaceae- PL/TEM- 52; PL/CTX-M-15, Pseudomonas- VIM Enterococcus gentaR, Tn1546 PL/CTX-M-14; PL/CTX-M-15 (Enterobacteriaceae) VRE-CC17 Acinetobacter OXA-23 Salmonella-intI1 OXA-30, sul3 Enterobacteriaceae- PL/TEM-52 Salmonella-intI1MDR, Enterobacteriaceae- PL/TEM-52 Goals Strategies Characterization of bacteria, genes and mobile genetic elements from different ecological niches (1) Emergence and International dissemination of MDR strains: VRE, ESBL-producing Enterobacteriaceae, Carbapenemase-producing Pseudomonas and Acinetobacter, Salmonella MDR (2) New genetic structures carrying antibiotic resistance genes driving co-selection and maintenance of resistant bacteria, e.g., In100 (3) Interchange of genetic elements/bacteria between different ecological niches Food producing animals and food of animal origin are a reservoir of clinically relevant clones/resistance genes Worrisome contribution of hospital sewage for aquatic environmental contamination by resistant bacteria We Evidenced: Epidemiology study of antibiotic resistant bacteria in order to implement containment measures, methodologies for their detection, and design of new compounds REQUIMTE- Microbiology Research Group Goals AAC :1001 JAC (In press) AAC :1545 CMI :1131 JAC :297 CMI :1047 JAC :1139 EID :1985 AAC :836 AAC :3465 AAC :451 JAC :1370 AAC :3613 AEM :3743 AAC :2140 AEM :3364 CMI :755 AAC :3220 Main Achievements

3 Acinetobacter baumannii - Emergent Pathogen Acinetobacter on the news!

4 Significant nosocomial pathogen Especially in immunocompromised patients or with underlying diseases Mainly Pneumonia (also bacteremia, meningitis, skin and wound infections) Mainly ICU 64% of mortality rates associated to severe nosocomial infections Recent reports of community acquired infections Pneumonia (rarely meningitis, cellulitis) Alcohol abuse, diabetis, cancer, or bronchopulmonary diseases Possible Vector role Lowman W et al.,J. Med Microbiol Garcia-Garmendia JL et al. Clin. Infect. Dis Acinetobacter baumannii - Emergent Pathogen

5 Genus Acinetobacter 32 described Acinetobacter groups or named species Bouvet and Grimont, 1986: Acinetobacter baumannii A. calcoaceticus- A. baumanii complex (Gerner- Smidt, J. Clin. Microb., 1991) Acinetobacter baumannii Acinetobacter calcoaceticus Genomic species 3TU Genomic species 13TU Phenotypically difficult to distinguish 65-75% relatedness in DNA-DNA hybridization Gram-negative coccobacillus Non-fermenters Oxidase – Strict aerobes Identification: rDNA16S sequence, rpoB sequence, DNA restriction analysis 16S rDNA (ARDRA) Nosocomial infections: A. baumannii, groups 13TU & 3 Ecological distribution of A. baumannii: undefined reservoir

6 WHY? Important factor for their pathogenic potential: efficient means of horizontal gene transfer(?) Survival capabilities Acquisition of virulence genes Ability to acquire resistance to antibiotics Acinetobacter baumannii - Emergent Pathogen A. baylyi ADP1, A. baumannii AYE and A. baumannii SDF chromosomes. (PLOS One, 2008) ?

7 Acinetobacter baumannii - Emergent Pathogen Ability to acquire resistance to antibiotics An 86-kb Resistance Island in epidemic A. baumannii Strain AYE 45 resistance genes

8 Acinetobacter baumanii infections- major epidemiological features Propensity for clonal spread Involvement in hospital outbreaks Endemicity in certain hospitals Resistance to multiple antimicrobial agents Many recent outbreaks have been caused by multidrug-resistant (MDR) strains of A. baumannii Stoeva et al., CMI Quinteira et al. AAC Manikal et al., CID 2000

9 Perez et al., AAC Meropenem Yearly Susceptibility Test Information Collection [MYSTIC], Asensio et al., Enferm. Infecc. Microb. Clin Lolans et al., AAC Acinetobacter isolates resistant to carbapenems 37%

10 Carbapenem resistance in Acinetobacter baumannii Impaired permeability related to porin changes Penicillin binding protein modifications Metallo-β-lactamases (Ambler class B β-lactamases) IMP, VIM, SIM [IMP-5 (one isolate Portugal)] Carbapenem-hydrolyzing oxacillinases (Ambler class D β- lactamases)

11 OXA-23 (23,27,49) OXA-58 OXA-40/24 (25,26,40) Acquired Carbapenem-Hydrolyzing Oxacillinases Three diferent groups Plasmidic /Chromosomal location 99% 60% <48%

12 Distribution of OXA-23,-25,-26,-27,-40/24,-58 Acquired Carbapenem-Hydrolyzing Oxacillinases OXA-23 (23,27,49) OXA-58 OXA-40/24 (25,26,40) Chromosomal or, mostly, plasmid location Quinteira et al, AAC 2007 Poirel & Nordman, CMI 2006 Lolans et al, AAC 2006 OXA-40 plasmid located in A. baumannii and A. haemolyticus Qi et al, AAC 2008

13 OXA-40 distribution in Portugal 1- HPA, Penafiel Index Case – 1995 OXA-33 (accession no. AY082394) => OXA-40 Da Silva et al., 1999 JCM 2- HGSA, Porto 3- HUC, Coimbra 4- HSM, Lisboa 5- CHCB, Covilhã 6- CHCR, Caldas da Rainha Da Silva et al., 2004 JAC OXA-40 A. baumannii Iberian clone

14 OXA-23 -A. baumannii producers in Portugal isolates; one patient - Hosp. S.Teotónio 37 years old woman with a history of alcohol abuse. Diagnostic: necrohaemorrhagic pancreatitis Therapy: meropenem+ fluconazol Day 9: Imipenem-resistant Ac. baumannii blood and intraperitoneal liquid Ampicillin and amikacin, given for nineteen days Isolation of XDR A. baumannii from intraperitoneal liquid Pancreatic abcess resected The patient was discharged after 18 weeks of hospitalization. PCR and sequencing revealed bla OXA23 Chromosomal location of bla OXA23 (I-Ceu-I analysis)

15 : Outbreak Hosp. Pedro Hispano (n=8) Outbreak Hosp., Amarante (n=7) Hosp. Sto António (n=1) (bronchial secretions; urine; blood) patient (Community) 2007: 1 patient (Community) OXA-23 -A. baumannii producers in Portugal (pus) PFGE and MLST: OXA-23 producing clone

16 Conclusions Emergence of OXA-23 producing A. baumannii in portuguese hospitalised patients Spread of an OXA-23 producing clone Associated to outbreaks and sporadic cases In an ambulatory patient which can further promote community dissemination With an enlarged resistance profile An alarming XDR (Extreme Drug Resistant) isolate, that evolved during therapy with ampiciliin and amikacin. Less resistant strains were already able to disseminate throughout Iberia, causing mortality events.

17 Acknowledgments Filipa Grosso Sandra Quinteira Carla Novais Elisabete Machado Patrícia Antunes Ana Raquel Freitas Raquel Branquinho Francisco Freitas (Hosp. S. Teotónio, Viseu) Helena Ramos (Centro Hospitalar do Porto, Porto) Luis Grañeda (Centro Hospitalar Cova da Beira, Covilhã) Mariana Viana (Hospital de Amarante) Luísa Cavaleiro e Valquíria Alves (Hospital Pedro Hispano, Matosinhos) Miguel Monteiro

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