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Article

Rapid Reversal of Carbapenemase-Producing Pseudomonas aeruginosa Epidemiology from blaVIM- to blaNDM-harbouring Isolates in a Greek Tertiary Care Hospital

by
Efthymia Protonotariou
1,*,
Georgios Meletis
1,
Nikoletta Vlachodimou
1,
Andigoni Malousi
2,
Areti Tychala
1,
Charikleia Katsanou
1,
Aikaterini Daviti
1,
Paraskevi Mantzana
1 and
Lemonia Skoura
1
1
Department of Microbiology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, S. Kiriakidi Str. 1, 54636 Thessaloniki, Greece
2
Laboratory of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
*
Author to whom correspondence should be addressed.
Antibiotics 2024, 13(8), 762; https://doi.org/10.3390/antibiotics13080762
Submission received: 30 June 2024 / Revised: 2 August 2024 / Accepted: 10 August 2024 / Published: 12 August 2024
(This article belongs to the Special Issue Microbial Resistance to Carbapenems: Epidemiology, Detection and Treatment Options)
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Abstract

:
Carbapenemase-producing Pseudomonas aeruginosa strains present a specific geographical distribution regarding the type of carbapenemase-encoding genes that they harbor. For more than twenty years, VIM-type enzymes were the only major carbapenemases that were detected among P. aeruginosa isolates in Greece until the emergence of NDM-1-encoding P. aeruginosa in early 2023. In the present study, we present the rapid reversal of the carbapenemase-producing P. aeruginosa epidemiology from blaVIM- to blaNDM-harbouring isolates that occurred in our hospital since then. Between January 2023 and February 2024, 139 isolates tested positive for carbapenemase production with the NG-Test CARBA 5 immunochromatographic assay. Eight isolates were processed with the Hybrispot antimicrobial resistance direct flow chip molecular assay, and the first NDM-producing isolate was further analyzed through whole genome sequencing and bioinformatics analysis. Multiple resistance genes were detected by molecular techniques in accordance with the extensively drug-resistant phenotype. The isolate that was subjected to whole-genome sequencing belonged to the P. aeruginosa high-risk clone ST308, and the blaNDM was located in the chromosome in accordance with previously reported data. During the study period, NDM-producing isolates were increasingly detected, and only five months after their emergence, they overcame VIM producers. Our results indicate the potential of this new clone to spread rapidly and predominate within healthcare institutions, further restricting the already limited treatment options.

1. Introduction

Carbapenem-resistant Pseudomonas aeruginosa (CR-PA), a major pathogen worldwide, is listed as a high-priority pathogen by the World Health Organization (WHO) Bacterial Priority Pathogens List due to its high level of antibiotic resistance and the severe infections it causes, particularly in healthcare settings [1]. In Europe, large difference are observed in the percentages of CR-PA among countries, ranging from 5% to over 50. Regarding Greece, P. aeruginosa’s resistance is quite high for carbapenems, at 48.9% compared to the EU population-weighted mean of 16.5% [2].
Carbapenem resistance in P. aeruginosa is multi-factorial [3]. Different mechanisms may be involved and may even coexist in non-susceptible isolates, like the loss of the OprD porin, the presence of inducible AmpC type β-lactamases, the overexpression of efflux pumps, and the production of carbapenemases. Among them, carbapenemases are by far the most effective because they confer high-level resistance to all or almost all β-lactams, including ceftazidime, cefepime, piperacillin–tazobactam, and carbapenems. Moreover, since carbapenem-resistance genes are often located in mobile genetic elements, they can be easily disseminated between bacterial cells and species [4].
P. aeruginosa presents a remarkable ability to acquire and host carbapenemase-encoding genes and, interestingly, most of the clinically important carbapenemases that can be found in carbapenem-resistant Gram negatives were reported for the first time in P. aeruginosa isolates worldwide. Moreover, P. aeruginosa strains that encode specific carbapenemase genes, like IMP, KPC, VIM, and NDM, present a characteristic geographical distribution and are commonly related with the so-called high-risk clones [5].
NDM is closely related to Enterobacterales and Acinetobacter spp. and has been much less frequently detected in P. aeruginosa [6]. For many years, carbapenemase-producing P. aeruginosa in Greece were almost exclusively harboring genes encoding for VIM-type carbapenemases [7,8,9,10]. Recently, however, there has been a rapid reversal to NDM-encoding P. aeruginosa in our hospital soon after the first isolation in 2023, and such isolates are quickly overcoming the VIM producers.
The present study was designed to monitor the carbapenem-resistant P. aeruginosa epidemiology from February 2023 to February 2024 within our hospital. Additionally, whole genome sequence analysis was conducted on the first NDM-encoding isolate (91845) that was recovered in May 2023 from a blood culture.

2. Results

2.1. Carbapenem Resistant P. aeruginosa Isolates

During the study period, 211 carbapenem-resistant P. aeruginosa isolates were recovered from various hospital wards. Among them, 139 isolates originating from 73 male and 66 female patients were found to be positive for carbapenemase production.

2.2. Detection of Resistance Determinants by the NG-Test CARBA 5 and the Hybrispot Antimicrobial Resistance Direct Flow Chip (AMR)

Overall, the NG-Test CARBA 5 detected 72 VIM producers and 66 NDM producers. One isolate (214929) was found to be positive for both carbapenemases (Table 1).
There was a 100% concordance of the NG-Test CARBA 5 results with those reported by the Hybrispot. Moreover, Hybrispot revealed the presence of additional resistance determinants to other antibiotic classes in the eight isolates tested using this method (Table 2).
Interestingly, after their emergence in P. aeruginosa in our hospital, NDM-encoding genes have been increasingly detected. Moreover, NDM-producing isolates rapidly overcame the VIM producers within this species, as shown in Figure 1.

2.3. Genomic Characterization of NDM-1-Producing Isolate 91845

The NDM-1-producing isolate was genomically characterized for the presence of antimicrobial resistance genes, the presence of virulence genes, and MLST. In addition, the isolate was comparatively analyzed against the most closely related isolates, and the genomic origin of the blaNDM-1 gene, either chromosomal or plasmid, was investigated.
High-depth sequencing of isolate 91845 resulted in 155.95 M reads that were filtered to meet high-quality base calling criteria (Q30 for 96.62% of 150 bp reads). The assembled genome contains 92 contigs with an N50 value of 246.540 bp and a total genome size of 6,919,402 bp. The most closely related isolate, based on the genome-wide nucleotide identity, is a recently isolated clinical strain in Greece (GCA_030504675_1, 99.948% identity), followed by the reference blaNDM-1 human isolate from Singapore (CP020704, 99.93% identity). Two clinical isolates from the neighboring countries Italy (RefSeq assembly: GCF_013276295_1) and Serbia (RefSeq assembly: GCF_022559565.11) were identified as being closely related, with 98.99% and 98.93% identity similarity values, respectively.

2.4. MLST, Antimicrobial Resistance and Virulence Genes

Isolate 91845 belongs to the P. aeruginosa high-risk clone ST308 that has been previously reported to carry carbapenemase genes. The antimicrobial resistance analyses resulted in the following AMR genes: aac(3)-Id, aac(6′)-Ib-cr, aac(6′)-Ib3, aac(6′)-Il, aadA11, aph(3″)-Ib, aph(3′)-IIb, aph(6)-Id, blaNDM-1, blaOXA-10, blaOXA-488, blaPAO, catB7, crpP, dfrB5, floR, fosA, msr(E), qacE, qnrVC1, rmtF, sul1, and sul2. Ten virulence genes were identified: xcpP, exoU, flgC, pchB, mbtH-like, lasI, pilG, pscS, and pscF, hcp1 (Table 3).

2.5. Genomic Origin of the blandm Gene

blaNDM-1 was detected in a 2323 bp contig which also 0included an IS91 family transposase (Figure 2). No plasmid replicons have been detected in the assembled genome by PlasmidFinder, while PlasmidSPAdes did not detect blaNDM-1 in the 27 variable-length plasmid constructs. These results are in line with previous evidence that ST308 P. aeruginosa strains including blaNDM-1 are located in chromosomal regions. However, PLASme and MOB-suite classified the 2323 bp contig as a plasmid sequence originating from Enterobacterales. The prediction is considered as being high confidence, except for a 10 bp ambiguous regions identified by PLASme. In support of this finding, MOB-suite detected an AD312 plasmid (CP034849) originated from Escherichia coli that includes the blaNDM-1-containing contig as well as five other contigs of the same type (contigs 18, 39, 50, 58, and 105).
To further assess whether these AD312-type plasmid contigs resemble known plasmids, blastn searches against complete plasmids were applied, yet with no strong evidence of similar plasmids. To further investigate the potential chromosomal origin of the blaNDM-1 gene, genome-wide pairwise alignment analysis against the reference CP020704 (Singapore) genome was performed. The genomic region neighboring blaNDM-1 in CP020704 has strong homology with the disjoint contigs 50, 79, 80, and 105 of our isolate. Figure 2, showing the 100% blast-based similarity with chromosomal regions, further supports the chromosomal origin of the blaNDM-1 gene. Interestingly, the highly homologous contigs 50 and 105 have been also identified as AD312 plasmids by MOB-suite.

3. Discussion

The New Delhi metallo-β-lactamase was named after its first report back in 2008 from Sweden regarding a patient previously hospitalized in New Delhi, India [11]. Following this initial detection, it soon became obvious that NDM-1 was already widely disseminated in the Indian subcontinent as well as in other countries, although to a lesser extent [12,13,14]. NDMs are categorized as Ambler group B carbapenemases together with other clinically important metallo-enzymes, such as VIM and IMP. Metallo-β-lactamases bear zinc in their active center and commonly hydrolyze all β-lactams except aztreonam and cefiderocol, whereas they are not inhibited by the β-lactamase inhibitors or by boronic acid. NDMs, however, present some additional unique characteristics. They hydrolyze aztreonam and they commonly present negative modified Hodge test results [15]. Resistance to cefiderocol in P. aeruginosa is still rare, but for the time being it is related only to some NDM-1-encoding lineages [16]. In Greece, NDM-1-encoding genes were introduced in late 2011 [17] and, since then, they have been well-established together with KPC, VIM, and OXA-48 carbapenemases among Enterobacterales and especially Klebsiella pneumoniae, as shown also by recent data from our hospital [18,19].
P. aeruginosa is a species that is commonly related to carbapenemases including KPC [20] and most of the clinically important metallo-β-lactamases [21,22,23,24]. Interestingly, there is a clear geographical distribution of isolates harboring different enzymes around the world, with KPCs being mainly located in Latin America, VIM and IMP presenting a global distribution, and NDMs being mostly located in India and Australia [25]. This specific distribution is associated with the spread of specific high-risk clones [5]. In Europe, the first report of NDM-encoding P. aeruginosa was reported from Serbia [26]. In 2010, at the Military Medical Academy, seven carbapenem-resistant P. aeruginosa isolates were recovered. Molecular investigation proved that two of them were the first NDM-producing P. aeruginosa worldwide. The first NDM-positive isolate was recovered from a urine sample of a 61-year-old Serbian woman with an intra-abdominal abscess, while the second one was detected in a wound of a 63-year-old woman who underwent laparotomy for intestinal carcinoma. Both patients had no previous travel history and died shortly after their admission.
The first NDM-1 in Pseudomonas aeruginosa clinical isolates from India were reported between 2011–July 2012. A total of 4 out of 200 P. aeruginosa clinical isolates investigated were NDM producers. The first was isolated from a central venous catheter culture of a 66-year-old man with a necrotizing soft tissue infection of the left lower limb. The second was also isolated from a venous catheter culture and was detected in a male patient with scarring after gallbladder removal surgery. Colistin was used successfully for both patients. The third isolate was found in the urine sample of a 56-year-old man with pyelonephritis. In this case, the treatment included colistin and amikacin. The fourth isolate was detected in a pus sample from a male patient with a compound comminuted fracture of the tibia that developed a surgical site infection [27].
In mid-2012, a case of a patient from Slovakia with NDM-1 P. aeruginosa was reported [28]. The strain was isolated from a 44-year-old patient who was hospitalized in the intensive care unit of the University Hospital in Bratislava, due to acute respiratory failure. The patient’s condition worsened and respiratory support was necessary, as he developed pneumonia. The causative agent of ventilator-associated pneumonia was Acinetobacter baumannii, according to the result of a bronchoalveolar lavage culture. During his hospitalization in the ICU, NDM-producing P. aeruginosa and Enterococcus faecalis were isolated from his blood culture. Ιn 2012, NDM-producing P. aeruginosa was also found in France. This strain was detected in a urine culture of a 63-year-old woman who was admitted to the military hospital in Bégin because of complicated pyelonephritis. It is noteworthy that the patient was hospitalized in Serbia three months before her admission [29]. A few months later, in late May 2013, the first NDM-producing P. aeruginosa was reported from Italy [30]. A 40-year-old man diagnosed with acute lymphoblastic leukemia in first remission was admitted to a hematology unit in Rome in order to undergo stem cell transplantation. Interestingly, the patient had been hospitalized in December 2012 in Belgrad, Serbia. Fifteen days after transplantation, the patient was febrile and neutropenic, and the blood cultures taken on that day were positive for P. aeruginosa. Two days later, the patient rapidly deteriorated and was admitted to the intensive care unit, where he died a few hours later due to septic shock. The isolate was afterwards found to be an NDM producer. The first autochthonous Italian NDM-encoding P. aeruginosa was isolated in August 2019. At that time, a 77-year-old female patient, who lived in a rehabilitation center, was admitted to Bari’s hospital because she suffered from chronic respiratory failure. During her hospitalization, she developed a urinary tract infection, and P. aeruginosa was isolated in the urine culture. The patient did not receive any antibiotics, and three days later she became febrile. At that point, P. aeruginosa was also isolated in her blood cultures. The patient’s condition deteriorated rapidly, and she finally died of sepsis in November 2019 [31].
After their emergence in Greece [32] and for more than 20 years, carbapenemase-producing P. aeruginosa harbored exclusively VIM-type enzymes, most often those of the VIM-2 family [33]. In 2023, NDM-producing P. aeruginosa were reported for the first time from Larisa [34]. The first isolate was recovered on 16 May 2023 from the bronchial secretions of a female patient with previous hospitalizations in various Greek ICUs before her admission at the University Hospital of Thessaly in April 2023. Eight more cases with P. aeruginosa producing NDM carbapenemases were detected in that Hospital during the same time period. There are many important similarities between our characterized isolate 91845 and those reported from Larisa. First, all characterized isolates in Greece belong to the epidemic high-risk international clone ST308. Second, they all present a high identity percentage with the reference blaNDM-1 human isolate from Singapore and, third, the NDM-encoding gene seems to be located in the chromosome.
In the past, another case of rapid reversal in carbapenemase epidemiology for yet another species, namely K. pneumoniae, has also occurred in Greece. More specific, carbapenem-resistant Klebisella pneumoniae KPC changed mostly to the VIM type rapidly after the introduction of ceftazidime/avibactam into clinical practice as a novel agent that effectively inhibited the action of KPC enzymes [35]. In P. aeruginosa, the reason is clearly not the introduction of a new antimicrobial and may rather be attributed to the ST308 potential for rapid spread.
The predominance of NDM-producing versus VIM-producing P. aeruginosa is worsening the already difficult situation regarding the treatment of the respective infections. VIM-type enzymes hydrolyze almost all β-lactams except aztreonam and cefiderocol, whereas NDM-type enzymes hydrolyze β-lactams including aztreonam. Even though cefiderocol is not yet introduced in Greece, the spread of NDM-producing P. aeruginosa could influence its success rates a priori. Indeed, resistance to cefiderocol in P. aeruginosa has been observed up to now only among some NDM-producing isolates. Ceftolozane/tazobactam, ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam are not active against both VIM and NDM carbapenemases because the metallo-β-lactamases are not inactivated by the novel β-lactamase inhibitors. When active, amikacin and fosfomycin could be used to treat effectively urinary tract infections [36,37]. In our hospital epidemiology, however, resistance to these drugs among carbapenemase-producing P. aeruginosa is common. Thus, not surprisingly, genes encoding for aminoglycoside-modifying enzymes and fosfomycin resistance have been detected by the Hybrispot and NGS methods in our study. Polymyxin resistance is rare for carbapenemase-producing P. aeruginosa, and this applies in our case as well. Our isolates are susceptible to colistin by both Vitek2 and the broth microdilution method. Colistin, however, is a formerly abandoned antibiotic that presents nephrotoxicity issues, and its actual clinical usefulness has been widely questioned [38].
Our data suggest that the departments that were first affected by NDM-producing P. aeruginosa were, in chronological order, the internal medicine department A, ophthalmology, neurosurgery, and surgery department B. These departments are located far from one another inside the hospital; nevertheless, connections between them (by moving personnel for, e.g., physiotherapy) can neither be excluded nor verified retrospectively. Additionally, our institution is a tertiary care hospital admitting patients from numerous acute- and long-term care facilities, and as our colleagues from Larisa, Greece, suggested, NDM-producing P. aeruginosa was already circulating in Northern Greece [34]. That being said, we expect to have had multiple index patients; therefore, it would not seem safe to draw conclusions upon intrahospital dissemination.
The present study has some limitations that should be noted. Due to economic restrictions, only one of the study’s isolates was sequenced. The molecular characterization of all isolates would have shed more light on the dynamics of the blaNDM spread among P. aeruginosa in our hospital. More molecular data analysis could evidence a probable clonal expansion and maybe provide more information about the interactions and interplay between VIM-producing and NDM-producing strains, since the first NDM + VIM producer has already been recovered in our hospital (isolate 214929). Depending on how the present situation may develop, this could be an interesting issue for future research.

4. Materials and Methods

4.1. Hospital Setting and Patient Data

The study was conducted in AHEPA University Hospital, which is located in Northern Greece and has a 700-bed capacity. All isolates included in this study were collected as part of the standard of care protocol. Data of the patients were retrieved from the hospital’s electronic database.

4.2. Study Sample

All carbapenem-resistant (resistant to both imipenem and meropenem) P. aeruginosa isolates recovered from all hospital wards between January 2023 and February 2024 were tested for carbapenemase production with the NG-Test CARBA 5 (NG-Biotech Laboratoires, Guipry-Messac, France) immunochromatography assay. In cases of multiple isolations per patient, only one isolate was included in the study. Moreover, the results of the first NDM-1 producer (91845), the first NDM and VIM producer (214929), and of six more isolates presenting weak lines in immunochromatography were confirmed by the HybriSpot antimicrobial resistance direct flow chip (AMR) (Máster Diagnóstica, Granada, Spain) molecular assay. Additionally, the first NDM-1-producing P. aeruginosa (91845) isolated from a blood culture was subjected to whole-genome sequencing (WGS) and bioinformatic analysis.

4.3. Bacterial Identification and Susceptibility Testing

Bacterial identification was carried out by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology (Bruker Daltonics, Bremen, Germany), and antimicrobial susceptibility testing was performed using the Vitek2 system (bioMérieux, Marcy l’Étoile, France). Additionally, confirmatory susceptibility testing was accomplished, where applicable, by using the MICRONAUT-S MDR MRGN-screening system (Bruker Daltonics GmbH & Co. KG, Bremen, Germany). For antimicrobial susceptibility results interpretation purposes, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 clinical breakpoints (v 13.0) were applied.

4.4. NG-Test CARBA 5

The NG-Test CARBA 5 (NG-Biotech Laboratoires, Guipry-Messac, France) is a rapid visual multiplex immunochromatographic assay for the qualitative detection and differentiation of five major carbapenemases from carbapenem-resistant bacterial colonies. The assay consists of one cassette that includes specific areas for the detection of KPC, OXA-48-like, VIM, IMP, and NDM enzymes together with a specific control (C) area. The assay was performed according to the manufacturer’s instructions, and results were interpreted visually at 15 min after incubation in room temperature.

4.5. Hybrispot Antimicrobial Resistance Direct Flow Chip (AMR)

The Hybrispot antimicrobial resistance direct flow chip (AMR) (Máster Diagnóstica, Granada, Spain) is a microarray-based assay for the in vitro detection of multiple antibiotic resistance genes. More specifically, the assay allows the simultaneous detection of 54 antibiotic resistance genetic markers associated with multi-drug-resistant organisms, such as carbapenem-resistant Gram-negative bacteria, extended-spectrum beta-lactamase (ESBL) producers, vancomycin-resistant Enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA). The assay’s markers represent the major gene families including SHV, CTX-M, GES, SME, KPC, NMC/IMI, SIM, GIM, SPM, NDM, VIM, IMP, OXA23-like, OXA24-like, OXA48-like, OXA51-like, OXA58-like, MecA, VanA, and VanB. Additionally, AMR is able to identify P. aeruginosa, Acinetobacter baumannii, E. coli, Klebsiella pneumoniae, and S. aureus.

4.6. Whole-Genome Sequencing and Bioinformatics Analysis

Whole-genome sequencing was performed with theDNBSEQ-G99 high-throughput Sequencing Set based on MGI’s core DNBSEQTM sequencing technology (MGI Tech, Shenzhen, China). Raw sequencing reads were quality-checked and trimmed using fastp [39]. The draft genome was assembled using skesa 2.5.1 [40].
The antimicrobial resistant determinants, the sequence type, and plasmid replicons were detected by Staramr version 0.9.1 [41], which integrates diverse molecular profiling tools including CGE’s multilocus sequence typing [42], Resfinder [43], and PlasmidFinder [44]. To further determine whether a contig originates from a chromosome or a plasmid source of the blaNDM-containing contig, plasmid prediction and construction tools, such as PlasmidSPAdes [45], PLASme [46], and MOB-suite [47], were applied. LASTZ [48] identified highly homologous sequences against reference bla-NDM-1 assembly from the reference Singapore isolate and constructed the pairwise alignment mappings between the two isolates using Proksee [49]. Plasmid sequences were further annotated based on the presence of AMR genes by CARD Resistance Gene Identifier v.5.2.1 [50] and protein families that are linked to the integration/excision, replication/recombination/repair, transfer, and stability/transfer/defense processes of the plasmids bymobileOG-db [51]. FastANI [52] was used to calculate the genome-wide average nucleotide identity against closely related blaNDM-containing P. aeruginosa strains.

5. Conclusions

An ongoing spread of NDM-producing P. aeruginosa is taking place in Greece, where VIM-encoding P. aeruginosa strains are already endemic. The intensification of the existing infection control policies seems to be the only realistic measure to tackle the widespread dissemination of yet another potential threat to public health.

Author Contributions

E.P. contributed to the conception, supervision, drafted the manuscript, and critically revised the manuscript; G.M. contributed to the conception, design, data acquisition and interpretation, drafted the manuscript, and critically revised the manuscript; N.V. contributed to data acquisition and interpretation and drafted the manuscript; A.M. contributed to the laboratory investigation, data acquisition, data interpretation, and drafted the manuscript; A.T. contributed to data acquisition and interpretation; C.K. contributed to data acquisition; A.D. contributed to data acquisition; P.M. contributed to data acquisition and interpretation; L.S. contributed to supervision, interpretation, and critically revised the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The publication of the present data was approved by the AHEPA University Hospital bioethics committee (protocol number: 297/14.6.2024).

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available in the article.

Conflicts of Interest

The authors declare no conflicts of interest.

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Antibiotics 13 00762 g001
Figure 1. Reversal of the carbapenemase-producing P. aeruginosa epidemiology from VIM to NDM in the hospital setting.
Figure 1. Reversal of the carbapenemase-producing P. aeruginosa epidemiology from VIM to NDM in the hospital setting.
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Antibiotics 13 00762 g002
Figure 2. The 2323 bp contig including blaNDM-1 and the neighboring IS91 family transposase.
Figure 2. The 2323 bp contig including blaNDM-1 and the neighboring IS91 family transposase.
Antibiotics 13 00762 g002
Table 1. Carbapenemase-producing P. aeruginosa isolates included in the study. VIM: Verona integron-encoded metallo-β-lactamase; NDM: New Delhi metallo-β-lactamase; BAL: bronchoalveolar lavage; CVC: central venous catheter ICU A: intensive care unit A; INT B: internal medicine department B; NB: neurology department B; INT A: internal medicine department A; BH: hematology department; CARD: cardiology department; SURGC: surgery department C; SURGB: surgery department B; NS: neurosurgery; EMERG: emergency department; OPHT: ophthalmology department; NEPHR: nephrology department; CARDSURG: cardiosurgery.
Table 1. Carbapenemase-producing P. aeruginosa isolates included in the study. VIM: Verona integron-encoded metallo-β-lactamase; NDM: New Delhi metallo-β-lactamase; BAL: bronchoalveolar lavage; CVC: central venous catheter ICU A: intensive care unit A; INT B: internal medicine department B; NB: neurology department B; INT A: internal medicine department A; BH: hematology department; CARD: cardiology department; SURGC: surgery department C; SURGB: surgery department B; NS: neurosurgery; EMERG: emergency department; OPHT: ophthalmology department; NEPHR: nephrology department; CARDSURG: cardiosurgery.
Month/YearIsolate IDDate of IsolationCarbapenemaseSpecimen TypeWardAge (Years)Patient Gender
January 20234012 January 2023VIMRectal surveillance swabICU A99M
3712 January 2023VIMUrineNS68M
4962 January 2023VIMUrineSURGB79M
23424 January 2023VIMUrineNB 61F
1110217 January 2023VIMBloodICU A68F
1295520 January 2023VIMBloodINT A83M
1475323 January 2023VIMRectal surveillance swabICU A77F
1501123 January 2023VIMSputumINT B82M
2035930 January 2023VIMBloodSURGB58M
February 20233494520 February 2023VIMUrineSURGC 45F
3495520 February 2023VIMBALICU A 72F
3898024 February 2023VIMBloodNS81M
4148828 February 2023VIMWoundEMERG70M
4127328 February 2023VIMBloodEMERG87F
March 2023470058 March 2023VIMBALSURGB41M
479308 March 2023VIMUrineEMERG57M
5250814 March 2023VIMUrineNB 74F
April 20238435327 April 2023VIMBloodINT A87M
May 2023863051 May 2023VIMBloodINT A65M
918458 May 2023NDMBloodINT A85M
9624215 May 2023VIMBALICU A64F
9955619 May 2023VIMBloodCARD76M
10083322 May 2023VIMBronchial secretionsICU A70F
10645030 May 2023NDMOcular swabOPHT41F
10656330 May 2023VIMCVCINT A 58M
10690231 May 2023VIMUrineINT B94F
June 20231110316 June 2023VIMBloodINT A85F
1109406 June 2023VIMBloodINT A89F
11390211 June 2023VIMBloodBH66F
11552113 June 2023NDMWoundNS57F
12780830 June 2023VIMSputumINT B57M
July 20231338851 July 2023VIMUrineINT A70M
1297504 July 2023NDMRectal surveillance swabSURGB70M
1299294 July 2023VIMRectal surveillance swabICU A65M
13382010 July 2023VIMBronchial secretionsICU A69M
13631814 July 2023VIMBronchial secretionsICU A61M
13680814 July 2023VIMBloodINT B66M
13864418 July 2023NDMBloodSURGB43M
14212324 July 2023VIMUrineICU A45M
14444727 July 2023VIMSputumINT B83F
August 20231476142 August 2023VIMCVCNS49M
1472882 August 2023VIMBALSURGB50M
1501467 August 2023VIMUrineEMERG78M
1512348 August 2023VIMUrineNB82F
15315311 August 2023ΝDMUrineINT A32F
15380813 August 2023VIMTissue sampleINT A81M
15985824 August 2023VIMUrineINT A76M
16181028 August 2023ΝDMΒALICU A70F
16237729 August 2023ΝDMUrineINT A81F
September 20231644242 September 2023VIMUrineINT B77F
1655414 September 2023ΝDMBloodINT A76F
1657605 September 2023VIMOcular swabOPHT47M
1686038 September 2023ΝDMBloodINT B85M
17017712 September 2023VIMBronchial secretionsINT B61M
17135313 September 2023VIMBronchial secretionsSURGB59M
17262814 September 2023ΝDMUrineINT A84F
17555819 September 2023ΝDMUrineINT A76M
17756921 September 2023VIMUrineINT A61F
17694821 September 2023ΝDMUrineINT A88F
17687621 September 2023ΝDMCVCINT A86F
October 20231845042 October 2023ΝDMBALICU A67F
1844832 October 2023ΝDMUrineICU A71M
1860433 October 2023ΝDMBloodINT B77F
1862744 October 2023VIMBronchial secretionsSURGB71M
1882596 October 2023VIMWoundINT B50F
1884536 October 2023ΝDMUrineINT A69M
1884566 October 2023ΝDMUrineINT B86F
19153011 October 2023ΝDMUrineICU A48M
19655818 October 2023VIMUrineICU A55F
20421930 October 2023ΝDMBronchial secretionsINT B88M
20503231 October 2023ΝDMUrineINT A88F
November 20232063892 November 2023ΝDMWoundBH76M
2076074 November 2023ΝDMUrineINT A70F
2077214 November 2023ΝDMUrineINT B73F
2078835 November 2023ΝDMWoundNS33F
2082766 November 2023VIMRectal surveillance swabICU A46M
2085207 November 2023VIMCVCINT B87F
20829911 November 2023VIMUrineINT A80F
20983212 November 2023ΝDMUrineINT B87M
21271014 November 2023ΝDMRectal surveillance swabSURGB80M
21297121 November 2023ΝDMUrineNS56M
21439722 November 2023VIMBALSURGB78M
21554824 November 2023ΝDMBALICU A61M
21492925 November 2023VIM and NDMWoundCARD70F
21489828 November 2023VIMBloodINT B87F
21977429 November 2023ΝDMUrineINT B81F
December 20232298616 December 2023VIMBALSURGB79M
2310567 December 2023ΝDMUrineCARD92M
2316779 December 2023ΝDMUrineINT A81F
2320439 December 2023ΝDMWoundCARDSURG57F
23247410 December 2023ΝDMBloodICU A43M
23659815 December 2023VIMUrineINT B86M
23883019 December 2023ΝDMUrineNEPHR80F
24050121 December 2023VIMBloodBH13M
24239625 December 2023VIMCVCICU A67F
24260725 December 2023ΝDMUrineINT A73F
24377227 December 2023ΝDMRectal surveillance swabINT A86F
24584731 December 2023ΝDMUrineINT B85F
January 20248302 January 2024VIMUrineEMERG93F
712 January 2024ΝDMUrineINT B62F
5902 January 2024ΝDMRectal surveillance swabINT B98M
9542 January 2024ΝDMUrineNEPHR80F
868315 January 2024ΝDMBloodINT B 82M
865315 January 2024ΝDMSputumINT B67F
1169118 January 2024ΝDMBloodINT A93F
1209319 January 2024ΝDMBloodINT A88M
1370722 January 2024ΝDMGroin surveillance swabICU A52M
1514123 January 2024VIMRectal surveillance swabINT B89F
1519423 January 2024VIMRectal surveillance swabINT B71M
1525323 January 2024ΝDMGroin surveillance swabINT B72F
1518623 January 2024VIMUrineINT A78F
1446323 January 2024VIMUrineINT A87F
1550624 January 2024VIMBALSURGB45M
1601224 January 2024VIMRectal surveillance swabCARD54F
2081131 January 2024ΝDMGroin surveillance swabINT B85M
2081031 January 2024ΝDMGroin surveillance swabINT B80F
February 2024218621 February 2024VIM Cerebrospinal fluid ICU B54M
239474 February 2024NDM Bronchial secretions ICU B87M
242995 February 2024NDM Urine INT A89F
239265 February 2024VIM BAL ICU B60M
262998 February 2024VIM Urine INT B74M
266618 February 2024NDM Groin surveillance swab INT B74M
3060814 February 2024NDM Groin surveillance swab INT A78M
3060614 February 2024NDM Rectal surveillance swab INT A80F
3164715 February 2024NDM Rectal surveillance swab ICU B72M
3263216 February 2024VIM Rectal surveillance swab INT B95F
3263916 February 2024NDM Groin surveillance swab INT B84M
3263616 February 2024NDM Groin surveillance swab INT B87M
3301617 February 2024NDM Blood INT B80F
3501920 February 2024NDM Rectal surveillance swab INT A40M
3801924 February 2024NDM Urine INT B67M
3905026 February 2024VIM Rectal surveillance swab ICU B77M
3890126 February 2024NDM Rectal surveillance swab INT A79M
3918926 February 2024NDM Groin surveillance swab INT B86F
3917726 February 2024NDM Groin surveillance swab INT B78F
4132628 February 2024VIM Rectal surveillance swab INT A76M
4133628 February 2024NDM Groin surveillance swab INT B86M
4125728 February 2024NDM Groin surveillance swab INT A75F
4048628 February 2024VIM Sputum INT B63M
Table 2. Hybrispot results reported for eight P. aeruginosa isolates. VIM: Verona integron-encoded metallo-β-lactamase; NDM: New Delhi metallo-β-lactamase.
Table 2. Hybrispot results reported for eight P. aeruginosa isolates. VIM: Verona integron-encoded metallo-β-lactamase; NDM: New Delhi metallo-β-lactamase.
Isolate IDHybrispot ResultNG-Test CARBA 5 Result
11102blaVIM, sul-1, mut gyrp-T831VIM
91845blaNDM, sul-1, sul-2, aac(6′)-Ib, mut gyrp-T831NDM
127808blaVIM, sul-1, aac(6′)-Ib, mut gyrp-T831VIM
129750blaNDM, sul-1, sul-2, aac(6′)-Ib, mut gyrp-T831NDM
138644blaNDM, sul-1, sul-2, aac(6′)-Ib, mut gyrp-T831NDM
165541blaNDM, sul-1, sul-2, aac(6′)-Ib, mut gyrp-T831NDM
171353blaVIM, sul-1, sul-2, mut gyrp-T831VIM
214929blaNDM, blaVIM, sul-1NDM, VIM
Table 3. Antimicrobial resistance and virulence genes found in P. aeruginosa isolate 91845.
Table 3. Antimicrobial resistance and virulence genes found in P. aeruginosa isolate 91845.
IsolateAntimicrobial Resistance GenesVirulence Genes
91845aac(3)-Id
aac(6′)-Ib-cr
aac(6′)-Ib3
aac(6′)-Il
aadA11
aph(3″)-Ib
aph(3′)-IIb
aph(6)-Id
blaNDM-1
blaOXA-10
blaOXA-488
blaPAO
catB7
crpP
dfrB5
floR
fosA
msr(E)
qacE
qnrVC1
rmtF
sul1
sul2		xcpP
exoU
flgC
pchB
mbtH-like
lasI
pilG
pscS
pscF
hcp1
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Protonotariou, E.; Meletis, G.; Vlachodimou, N.; Malousi, A.; Tychala, A.; Katsanou, C.; Daviti, A.; Mantzana, P.; Skoura, L. Rapid Reversal of Carbapenemase-Producing Pseudomonas aeruginosa Epidemiology from blaVIM- to blaNDM-harbouring Isolates in a Greek Tertiary Care Hospital. Antibiotics 2024, 13, 762. https://doi.org/10.3390/antibiotics13080762

AMA Style

Protonotariou E, Meletis G, Vlachodimou N, Malousi A, Tychala A, Katsanou C, Daviti A, Mantzana P, Skoura L. Rapid Reversal of Carbapenemase-Producing Pseudomonas aeruginosa Epidemiology from blaVIM- to blaNDM-harbouring Isolates in a Greek Tertiary Care Hospital. Antibiotics. 2024; 13(8):762. https://doi.org/10.3390/antibiotics13080762

Chicago/Turabian Style

Protonotariou, Efthymia, Georgios Meletis, Nikoletta Vlachodimou, Andigoni Malousi, Areti Tychala, Charikleia Katsanou, Aikaterini Daviti, Paraskevi Mantzana, and Lemonia Skoura. 2024. "Rapid Reversal of Carbapenemase-Producing Pseudomonas aeruginosa Epidemiology from blaVIM- to blaNDM-harbouring Isolates in a Greek Tertiary Care Hospital" Antibiotics 13, no. 8: 762. https://doi.org/10.3390/antibiotics13080762

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