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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
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 nichesFood 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.2008.52:1001JAC.2008. (In press)AAC.2007.51:1545CMI. 2006. 12:1131JAC.2006.58:297CMI.2006.12:1047 JAC.2005.56:1139EID.2005.11:1985AAC. 2005. 49:836AAC.2007.51:3465 AAC. 2005. 49:451 JAC. 2007.60:1370AAC.2004.48:3613AEM.2006.72:3743 AAC. 2005. 49:2140AEM.2005.71:3364CMI.2004.10:755AAC.2006.50:3220
Main Achievements
Acinetobacter baumannii - Emergent Pathogen
Acinetobacter on the news!
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. 2008Garcia-Garmendia JL et al. Clin. Infect. Dis. 2001
Acinetobacter baumannii - Emergent Pathogen
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 baumanniiAcinetobacter calcoaceticusGenomic species 3TUGenomic species 13TU
Phenotypically difficult to distinguish65-75% relatedness in DNA-DNA
hybridization
Gram-negative coccobacillus Non-fermentersOxidase –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
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)
?
Acinetobacter baumannii - Emergent Pathogen
Ability to acquire resistance to antibiotics
An 86-kb Resistance Island in epidemic A. baumannii Strain AYE45 resistance genes
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. 2008Quinteira et al. AAC. 2004Manikal et al., CID 2000
Perez et al., AAC. 2007.Meropenem Yearly Susceptibility Test Information Collection [MYSTIC], 2004. Asensio et al., Enferm. Infecc. Microb. Clin. 2008 Lolans et al., AAC. 2006
Acinetobacter isolates resistant to carbapenems
37%
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)
OXA-23 (23,27,49) OXA-23 (23,27,49)
OXA-58OXA-58
OXA-40/24 (25,26,40)OXA-40/24 (25,26,40)
Acquired Carbapenem-Hydrolyzing Oxacillinases
Three diferent groups
Plasmidic /Chromosomal location
99%
99%60%
<48%
Distribution of OXA-23,-25,-26,-27,-40/24,-58
Acquired Carbapenem-Hydrolyzing Oxacillinases
OXA-23 (23,27,49) OXA-23 (23,27,49) OXA-58OXA-58OXA-40/24 (25,26,40)OXA-40/24 (25,26,40)
Chromosomal or, mostly, plasmid location
Quinteira et al, AAC 2007
Poirel & Nordman, CMI 2006Lolans et al, AAC 2006
OXA-40 plasmid located in A. baumannii and A. haemolyticus
Qi et al, AAC 2008
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, Porto3- HUC, Coimbra4- HSM, Lisboa5- CHCB, Covilhã6- CHCR, Caldas da Rainha
Da Silva et al., 2004 JAC
12
3
4
5
6
OXA-40 A. baumannii Iberian clone
OXA-23 -A. baumannii producers in Portugal• 2006
• 2 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.
R S R R R RR R R R R R
β-lactams Amikacin Gentamicin Ciprofloxacin Tigecycline Colistin
PCR and sequencing revealed bla OXA23
Chromosomal location of bla OXA23
(I-Ceu-I analysis)
2006-2007:• Outbreak 2006- Hosp. Pedro Hispano (n=8)• Outbreak 2007- Hosp., Amarante (n=7)• Hosp. Sto António (n=1)
(bronchial secretions; urine; blood) 1
234
5
R S/R S/R R R R
Tigecycline Colistinβ-lactams Amikacin Gentamicin Ciprofloxacin
2007: 1 patient (Community)1 patient (Community)
R R R R R S
β-lactams Amikacin Gentamicin Ciprofloxacin Tigecycline Colistin
OXA-23 -A. baumannii producers in Portugal
(pus)
PFGE and MLST:
OXA-23 producing clone
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.
Acknowledgments
Filipa Grosso Sandra QuinteiraCarla NovaisElisabete MachadoPatrícia AntunesAna Raquel FreitasRaquel 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