Infection Control & Hospital Epidemiology
493 The first (or index) case occurred in hospital 1 in May 2017 on a
female patient hospitalized at an isolation unit. This patient had many comorbidities (ie, diabetes, hypertension, Alzheimer disease, and previous hemorrhagic stroke) and was admitted to the hospital due to urinary tract infection. On May 21, 2017, she was diagnosed with nonventilation pneumonia and presented both KPN and Enterobacter cloacae from blood cultures. Despite therapy, she died during hospitalization on July 1, 2017. TheKPNisolate belonged to PFGE pattern A and ST340. Various studies have demonstrated that the KPN phylogenetic
Fig. 1. New Delhi metallo-β-lactamase producing Klebsiella pneumoniae (NDM KPN) case distribution along time.
These hospitals belong to a regional medical complex with different locations and professionals. Their microbiology laboratory has applied the same metallo-β-lactamase (MβL) screening procedure with commercial carbapenem disks with and without EDTA (0.1 M) since 2016. Patients admitted are routinely screened for the pres- ence of multidrug-resistant
Enterobacteriaceae.Thelabidentified 50 KPN-MβL–positive carbapenem-resistant single strains using theVitekMSsystem (bioMeriéux, Marcy-I’Étoile, France).One sam- ple per patient was considered, and the blaNDM-1 gene was detected using multiplex real-time polymerase chain reaction (qPCR).6 Overall, 45 isolates were identified from hospital 1, and 5 were
identified from hospital 2. Among them, 41 were from surveillance cultures (rectal swabs) and 9 were from clinical samples (5 urine, 3 blood and 1 tracheobronchial aspirate). At the moment of isola- tion, 14 of these 50 patients had a diagnosis of hospital-acquired infection (HAI) according to established criteria (7 nonventilation pneumonia, 4 bloodstream, 2 catheter, and 1 skin and soft-tissue infections). In 5 of 14 patients, NDM-KPN was potentially associ- ated with the HAI(3 blood and 2 urine cultures). In 5 of the 14 HAI patients, other microorganisms were considered causative agents, and in 4 these patients, no agents were isolated from infections (NDM KPN from surveillance only). At admission, 7 of the 14 HAI patients presented with community infections, 4 with ortho- pedic or trauma, and 2 with neurological conditions. Also, 5 of these 14 HAI patients had multiple comorbidities. Notably, 7 of these 14 patients were later discharged with improved conditions, and 7 of these patients died during their hospital stay. Antimicrobial susceptibility testing was performed by Vitek 2
System (bioMeriéux), and high-level resistance was detected for all β-lactams, ciprofloxacin, and gentamicin (ie, using the guide- lines of the Clinical Laboratory Standards Institute [CLSI]). All strains were susceptible to colistin (minimum inhibitory concen- tration [MIC],≤2 μg/mL), and 40 of 50 were resistant to tigecycline (MIC, >2 μg/mL) (ie, using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria). ESβLs (ie, blaTEM, blaSHV, and blaCTX-M) and quinolone resistance genes (qnrS) were detected in all isolates. A molecular investigation was performed using pulsed field gel-electrophoresis (PFGE), and mul- tilocus sequence typing (MLST). PFGE showed 2 different pat- terns, A and B. Pattern A was found in 44 of 45 strains from hospital 1 and in 5 of 5 strains from hospital 2. Only 1 strain from hospital 1 showed a distinct PFGE pattern (pattern B). MLST was performed in 5KPNstrains, 4 belonging to patternAand 1 belong- ing to pattern B. Also, 4 pattern A strains belonged to the same ST340, clonal complex 258 (CC258). The pattern B strain belonged to ST2570, a different and nonphylogenetically related strain.
lineage belonging to CC258 (including ST258, ST11, ST340, and ST437) is vastly adapted tohuman populations and tohospital infec- tions.7 Previous reports ofKPNST340 and ST11 carryingNDMand other resistance mechanisms (ESβLs and qnr genes) have been doc- umented in Brazil.4,5 The emergence and spread of NDM KPN is worrying and represents a new worldwide challenge because it may carry several high-level antimicrobial resistance mechanisms. The KPN pattern B and ST2570 strain was recovered from a
blood culture of a patient hospitalized on a different unit in hos- pital 1 on October 6, 2017. This patient was initially hospitalized on September 20, 2017, due to a skin and soft-tissue infection and various comorbidities (ie, human immunodeficiency virus [HIV], treated tuberculosis, and chronic obstructive pulmonary disease [COPD]) and with many previous hospital passages. The blood culture was positive for NDM KPN on October 6, 2017, and the HAI was a skin and soft-tissue infection. Unfortunately, this patient was sent to the intensive care unit (ICU) and died 15 days later, despitemedical care and antimicrobial therapy (includingmer- openemand polymixin B).Notably, the detection of theKPNST2570 isolate seems relevant. Eibach et al8 described ESβL-producing KPN ST2570 in samples fromlocal and imported poultry
inGhana.To the best of our knowledge, this is the firsthumancase (bloodstreaminfec- tion and sepsis) caused by anNDM-KPN ST2570. It has been shown that NDM plasmid-bearing microorganisms might have significant environmentalpresence,9,10 which could be gene sources to other spe- cies. We do not know which role the ST2570 isolate played in this outbreak, but it presence raises an interesting discussion, especially in a patient with multiple comorbidities and admittances. Could dis- tinct KPN lineages adapted to poultry be the linkage between CC258 and environmental NDM isolates? We report the first major outbreak of NDM KPN in hospitals
from a single city in Brazil. Most isolates belonged to a well-adapted and documented CC258 (ST340). One case was caused by a distinct and not phylogenetically related ST2570. This outbreak highlights the relevance ofmonoclonal isolate dissemination between environ- ments, despite hospital control policies. Apparently, monoclonal dissemination of well-adapted isolates takes place before plasmid dissemination to other clones or species.
Author ORCIDs. Jussimara Monteiro 0000-0002-1230-4816 Financial support. No financial support was provided relevant to this article.
Conflicts of interest. All authors report no conflicts of interest relevant to this article.
References
1. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, Walsh TR. Characterization of a new metallo-beta-lactamase gene, bla (NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009;53:5046–5054.
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