New Delhi Metallo-β-Lactamase (NDM-1)-Producing Klebsiella pneumoniae: Case Report and Laboratory Detection Strategies

Abstract

The spread of antimicrobial resistance among Enterobacteriaceae is a significant clinical threat. We report the first case of an Enterobacteriaceae strain harboring the NDM-1 metallo-␤-lactamase in a pediatric patient in the United States. We describe strategies for the detection of this novel resistance mechanism encountered in an isolate of Klebsiella pneumoniae. CASE REPORTA 13-month-old boy in severe respiratory distress was brought to the emergency department (ED) by his parents following a 3-day history of worsening cough and audible wheezing. At presentation, the patient was tachycardic and lethargic and had a low-grade fever of 38.1°C. The patient's past medical history was notable for episodes of reactive airway disease, managed with nebulized albuterol and short courses of corticosteroids, congenital skeletal abnormalities, multiple upper respiratory tract infections, hydrocele, hypotonia, and developmental delay. Also of note, the patient had returned from a 3-month visit to Pakistan with his family 4 months prior to presentation in the ED. While in Pakistan, the patient was hospitalized following an exacerbation of his lung disease and was intubated and mechanically ventilated for several days.The patient was intubated in the ED, started on empirical ceftriaxone (550 mg intravenously [i.v.] daily) for pneumonia, and admitted to the pediatric intensive care unit. On admission, a chest X-ray revealed right upper and lower lobe opacities, and azithromycin treatment (60 mg i.v. daily) was started. A urine specimen was sent to the microbiology laboratory for culture, and a Foley catheter was placed. Urinalysis revealed no pyuria, but nitrites were detected and less than 10,000 CFU of Klebsiella pneumoniae (strain KP1) and Proteus species grew in routine culture; these organisms were also isolated in similar quantities from a subsequent urine specimen obtained later that day. A nasal wash specimen was obtained for bacterial culture and respiratory virus detection by the Resplex II respiratory virus panel, version 2.0 (Qiagen, Valencia, CA). The respiratory virus panel detected the presence of an enterovirus. Following overnight incubation at 37°C in air supplemented with 5% CO 2 , bacterial culture grew normal oral flora and many K. pneumoniae organisms (strain KP2). Following identification of KP2, empirical antimicrobial coverage was switched from ceftriaxone to meropenem (MEM; 440 mg i.v. every 8 hours [q8h]) on hospital day 4. Also on hospital day 4, the patient's tracheal secretions increased in amount, requiring more-frequent suctioning to maintain a patent airway. A small right pleural effusion was detected by a computed tomography scan on hospital day 4, which subsequently resolved without drainage. On hospital day 5, respiratory secretions obtained by tracheal suction were submitted for bacterial culture, which also grew a K. pneumoniae isolate (KP3). No additional specimens were sent to the laboratory for culture.Antimicrobial susceptibility testing was performed on all three K. pneumoniae isolat...

Phenotypic and Molecular Characteristics of Carbapenem-Resistant Enterobacteriaceae in a Health Care System in Los Angeles, California, from 2011 to 2013

“…bla NDM-1 isolates typically coexpress resistance to aminoglycosides (unlike the isolate seen here), quinolones, and trimethoprim-sulfamethoxazole (47), and resistance to last-line agents such as colistin is well described (49). bla NDM-1 still remains rare in this region, with only 5 cases reported previously in California (13,50,51) and just over 40 isolates in total reported within the whole of the United States (13,52,53). Given the rapid spread of the bla NDM-1 carbapenemase since its discovery in Europe only 5 years ago (5,54,55), timely detection and aggressive infection control approaches to both colonized or infected cases in this region are crucial to prevent its establishment as an endemic carbapenemase in California hospitals or long-term-care facilities.…”

The Problem of Carbapenemase-Producing-Carbapenem-Resistant-Enterobacteriaceae Detection

“…Given the rapid international spread of NDM-producing bacteria, this is an important limitation. In addition, the MHT also suffers from poor specificity because bacteria producing AmpC enzymes combined with porin mutations can give a false-positive result (20,21,22). These limitations have resulted in a decrease in the use of MHT outside the United States where KPC is less common than other carbapenemases, but MHT remains an important part of many testing algorithms because it is simple to perform and uses reagents readily available in most microbiology laboratories.…”

Rapid Detection of New Delhi Metallo-β-Lactamase Gene and Variants Coding for Carbapenemases with Different Activities by Use of a PCR-Based In Vitro Protein Expression Method

“…Therefore, an ideal monitoring assay should not only identify the presence of bla NDM-1 but also reveal functional bla NDM-1 variants. In view of these requirements, the current widely used PCR sequencing method is not sufficient, because phenotypic testing (expression of recombinant protein) is needed to confirm whether a new variant identified by sequencing has an alteration in the function of its coded protein (14,31).…”

“…Phenotypic techniques for detecting carbapenemase activity, such as the modified Hodge Test (MHT) recommended by the Clinical and Laboratory Standards Institute (CLSI) (14,15) and the newly developed Carba NP (16), can be used to detect carbapenemase producers, including those producing NDM-1. However, because all of the phenotypic assays detect NDM-1 together with other carbapenemases, specific molecular methods to detect the bla NDM-1 gene have been widely used to indicate the presence of NDM-1-producing bacteria (17)(18)(19)(20)(21).…”