Emergence of ST63 Pandrug-Resistant Acinetobacter pittii Isolated From an AECOPD Patient in China

Acinetobacter sp. is among the ESKAPE organisms which represent the major nosocomial pathogens that exhibited a high resistance rate. A. pittii, frequently associated with antimicrobial resistance particularly to carbapenems, is one of the most common Acinetobacter species causing invasive infection. Pandrug resistant A. pittii has rarely been reported. Here, we report the case of a patient with acute exacerbations of chronic obstructive pulmonary disease three years after double lung transplantation and developed severe pneumonia associated with pandrug resistant A. pittii infection. Phenotypic and genomic characteristics of this pandrug resistant isolate (17-84) was identified, and the mechanisms underlying its resistance phenotypes were analyzed. Isolate 17-84 belonged to ST63, carried a non-typable and non-transferable plasmid encoding multiple acquired resistance genes including carbapenemase gene bla OXA-58. Point mutations and acquired resistance genes were identified which were associated with different drug resistance phenotypes. To our knowledge, this is the first detailed phenotypic and genomic characterization of PDR A. pittii causing severe infections in clinical settings. Findings from us and others indicate that A. pittii could serve as a reservoir for carbapenem determinants. The emergence of such a superbug could pose a serious threat to public health. Further surveillance of PDR A. pittii strains and implementation of stricter control measures are needed to prevent this emerging pathogen from further disseminating in hospital settings and the community.

[1]  Evangelos I. Kritsotakis,et al.  Systematic review and meta-analysis of the proportion and associated mortality of polymicrobial (vs monomicrobial) pulmonary and bloodstream infections by Acinetobacter baumannii complex , 2021, Infection.

[2]  S. Hamada,et al.  Genomic Characterization of Clinical Extensively Drug-Resistant Acinetobacter pittii Isolates , 2021, Microorganisms.

[3]  R. Saito,et al.  Prevalence and Characterization of Carbapenem-Hydrolyzing Class D β-Lactamase-Producing Acinetobacter Isolates From Ghana , 2020, Frontiers in Microbiology.

[4]  Evangelos I. Kritsotakis,et al.  Excess mortality due to pandrug-resistant Acinetobacter baumannii infections in hospitalized patients. , 2020, The Journal of hospital infection.

[5]  R. Kaas,et al.  ResFinder 4.0 for predictions of phenotypes from genotypes , 2020, The Journal of antimicrobial chemotherapy.

[6]  A. Nguyen,et al.  Overexpression of blaOXA-58 Gene Driven by ISAba3 Is Associated with Imipenem Resistance in a Clinical Acinetobacter baumannii Isolate from Vietnam , 2020, bioRxiv.

[7]  S. Karakonstantis,et al.  A systematic review of implications, mechanisms, and stability of in vivo emergent resistance to colistin and tigecycline in Acinetobacter baumannii , 2020, Journal of chemotherapy.

[8]  Evangelos I. Kritsotakis,et al.  Treatment options for K. pneumoniae, P. aeruginosa and A. baumannii co-resistant to carbapenems, aminoglycosides, polymyxins and tigecycline: an approach based on the mechanisms of resistance to carbapenems , 2020, Infection.

[9]  Rosemary C. She,et al.  A Nutrient-limited Screen Unmasks Rifabutin Hyperactivity for XDR Acinetobacter baumannii , 2020, Nature Microbiology.

[10]  Paige M. K. Larkin,et al.  Discovery of a Novel Hypervirulent Acinetobacter baumannii Strain in a Case of Community-Acquired Pneumonia , 2020, Infection and drug resistance.

[11]  Y. Funayama,et al.  Characteristics of invasive Acinetobacter infection: A multicenter investigation with molecular identification of causative organisms. , 2020, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[12]  M. H. Wong,et al.  Over-Expression of ISAba1-Linked Intrinsic and Exogenously Acquired OXA Type Carbapenem-Hydrolyzing-Class D-ß-Lactamase-Encoding Genes Is Key Mechanism Underlying Carbapenem Resistance in Acinetobacter baumannii , 2019, Front. Microbiol..

[13]  P. Navalesi,et al.  Successful treatment with cefiderocol for compassionate use in a critically ill patient with XDR Acinetobacter baumannii and KPC-producing Klebsiella pneumoniae: a case report. , 2019, The Journal of antimicrobial chemotherapy.

[14]  J. Vila,et al.  In vitro and in vivo Virulence Potential of the Emergent Species of the Acinetobacter baumannii (Ab) Group , 2019, Front. Microbiol..

[15]  Evangelos I. Kritsotakis,et al.  Pandrug-resistant Gram-negative bacteria: a systematic review of current epidemiology, prognosis and treatment options. , 2019, The Journal of antimicrobial chemotherapy.

[16]  I. Biswas,et al.  Accurate identification of clinically important Acinetobacter spp.: an update , 2019, Future science OA.

[17]  Yu-Chieh Liao,et al.  Molecular Epidemiology of Emerging Carbapenem Resistance in Acinetobacter nosocomialis and Acinetobacter pittii in Taiwan, 2010 to 2014 , 2019, Antimicrobial Agents and Chemotherapy.

[18]  Y. Huang,et al.  Detection of co-harboring OXA-58 and NDM-1 carbapenemase producing genes resided on a same plasmid from an Acinetobacter pittii clinical isolate in China , 2019, Iranian journal of basic medical sciences.

[19]  M. Kempf,et al.  Acinetobacter pittii isolated more frequently than Acinetobacter baumannii in blood cultures: the experience of a French hospital. , 2018, The Journal of hospital infection.

[20]  Hong Yang,et al.  Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network , 2017, Antimicrobial Agents and Chemotherapy.

[21]  Ryan R. Wick,et al.  Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads , 2016, bioRxiv.

[22]  C. Tribuddharat,et al.  Distribution and expression of the Ade multidrug efflux systems in Acinetobacter baumannii clinical isolates. , 2016, Canadian journal of microbiology.

[23]  N. Woodford,et al.  In Vitro Activity of Eravacycline against Carbapenem-Resistant Enterobacteriaceae and Acinetobacter baumannii , 2016, Antimicrobial Agents and Chemotherapy.

[24]  M. Kempf,et al.  Reservoirs of Non-baumannii Acinetobacter Species , 2016, Front. Microbiol..

[25]  D. Gu,et al.  Substitutions of Ser83Leu in GyrA and Ser80Leu in ParC Associated with Quinolone Resistance in Acinetobacter pittii. , 2014, Microbial drug resistance.

[26]  V. Chongsuvivatwong,et al.  Clinical Outcomes of Hospital-Acquired Infection with Acinetobacter nosocomialis and Acinetobacter pittii , 2014, Antimicrobial Agents and Chemotherapy.

[27]  Fangfang Xia,et al.  The SEED and the Rapid Annotation of microbial genomes using Subsystems Technology (RAST) , 2013, Nucleic Acids Res..

[28]  J. Boyce,et al.  Biological Cost of Different Mechanisms of Colistin Resistance and Their Impact on Virulence in Acinetobacter baumannii , 2013, Antimicrobial Agents and Chemotherapy.

[29]  Y. Zhou,et al.  Dissemination and characterization of NDM-1-producing Acinetobacter pittii in an intensive care unit in China. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[30]  Donoghue,et al.  Acinetobacter baumannii , 2012, Virulence.

[31]  M. Falagas,et al.  Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[32]  Alessandra Carattoli,et al.  Characterization and PCR-Based Replicon Typing of Resistance Plasmids in Acinetobacter baumannii , 2010, Antimicrobial Agents and Chemotherapy.

[33]  M. Adams,et al.  Rapid Determination of Quinolone Resistance in Acinetobacter spp , 2009, Journal of Clinical Microbiology.

[34]  M. Berriman,et al.  DNAPlotter: circular and linear interactive genome visualization , 2008, Bioinform..

[35]  Patricia Siguier,et al.  ISfinder: the reference centre for bacterial insertion sequences , 2005, Nucleic Acids Res..

[36]  B. Distad,et al.  Treatment options , 2002, Dental Abstracts.

[37]  J. A. McCulloch,et al.  Emergence of carbapenem-resistant Acinetobacter pittii carrying the blaOXA-72 gene in the Amazon region, Brazil. , 2019, Diagnostic microbiology and infectious disease.

[38]  S. Pournaras,et al.  Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages. , 2013, International journal of antimicrobial agents.

[39]  M. Ferraro.  Performance standards for antimicrobial susceptibility testing , 2001 .