MBL Production Research Articles

Prevalence of Multidrug Resistant Pseudomonas aeruginosa Isolated from Clinical Specimens in Tertiary Care Hospital.

Pseudomonas aeruginosa is an opportunistic pathogen, which causes nosocomial infections in human. The rapid increase in drug resistance of this pathogen is a global concern. The aim of this study was to determine the clinical burden of P.aeruginosa, its antibiotic susceptibility pattern along with metallo-β-lactamase (MBL) detection. The descriptive cross-sectional study was conducted in Upendra Devkota Memorial National Institute of Neurological and Allied Sciences from January to August 2021. Isolation and identification of P. aeruginosa from clinical specimens was performed by using standard laboratory procedure. All bacterial isolates were phenotypically screened for multidrug resistance using Kirby Bauer disc diffusion method. All the multidrug resistant P.aeruginosa were phenotypically screened for MBL producer by Imipenem-EDTA combined disc diffusion test (CDDT). A total of 770 samples were processed of which 36 isolates of P. aeruginosa were obtained. P.aeruginosa was isolated mainly from tracheal aspirates, sputum, blood and urine. Among 36 isolates, 50% were found to be multidrug resistant (MDR). More percentage of P.aeruginosa isolates were found resistant to aztreonam, ofloxacin and levofloxacin (52.8%). Furthermore, this study reveals antibiotics like piperacillin/tazobactam and carbapenem were found to be good choice for the treatment of infection caused by this organism. Among MDR isolates 66.7% were found to be MBL producer. The data in this study highlights the prevalence of multidrug resistant, MBL producer, and colistin resistant P.aeruginosa in clinical specimens. In this study, carbapenems and piperacillin/tazobactam were found to be most effective antimicrobial drugs for empirical therapy in P.aeruginosa infections.

Aztreonam/avibactam activity against a large collection of carbapenem-resistant Enterobacterales (CRE) collected in hospitals from Europe, Asia and Latin America (2019-21).

Aztreonam/avibactam is under development to treat infections caused by Gram-negative bacteria. We evaluated the in vitro activities of aztreonam/avibactam and comparators against a global collection of carbapenem-resistant Enterobacterales (CRE), including ceftazidime/avibactam-resistant isolates. Isolates were consecutively collected (24 924; 1/patient) from 69 medical centres in 36 countries during 2019-21. Isolates were susceptibility tested by CLSI broth microdilution. All CRE isolates (n = 1098; 4.4%) were in silico screened for carbapenemase (CPE) genes after genome sequencing. CRE susceptibility results were stratified by CPE, geography and resistance phenotype. Aztreonam/avibactam inhibited 99.6% of CREs at ≤8 mg/L (MIC50/90, 0.25/0.5 mg/L), including 98.9% (345/349) of ceftazidime/avibactam-resistant isolates. Aztreonam/avibactam activity was consistent across geographical regions (98.9%-100.0% inhibited at ≤8 mg/L), but susceptibility to comparators varied markedly. Susceptibility (CLSI criteria) for ceftazidime/avibactam and meropenem/vaborbactam ranged from 80.2% and 77.5% in Western Europe to 39.5% and 40.3% in the Asia-Pacific region, respectively. Aztreonam/avibactam retained activity against isolates non-susceptible to colistin (99.7% inhibited at ≤8 mg/L) or tigecycline (98.6% inhibited at ≤8 mg/L). A CPE gene was identified in 972 CRE isolates (88.5%). The most common CPEs were KPC (43.1% of CREs), NDM (26.6%) and OXA-48-like (18.7%); 57 isolates (5.2%) had >1 CPE gene. Aztreonam/avibactam inhibited 99.9% of CPE producers at ≤8 mg/L, whereas ceftazidime/avibactam and meropenem/vaborbactam exhibited limited activity against isolates producing MBL and/or OXA-48-like enzymes. Aztreonam/avibactam activity was not adversely affected by clinically relevant CPEs. Our results support aztreonam/avibactam development to treat infections caused by CRE, including MBL producers.

Enterobacteriaceae isolates from clinical and household tap water samples: antibiotic resistance, screening for extended-spectrum, metallo- and ampC-beta-lactamases, and detection of blaTEM,blaSHV and blaCTX-M in Uyo, Nigeria.

Infections caused by multidrug-resistant (MDR) bacteria, extended spectrum β-lactamase (ESBL), metallo-β-lactamase (MBL) and AmpC-β-lactamase (AmpC-βL)-producers are increasing globally. This study identified bacteria in clinical and tap water samples and determined the prevalence of MDR, and β-lactamase enzymes and genes. Isolates were identified by the Vitek 2 (bioMérieux, France) automated system. Antibiotic resistance and screening for β-lactamase enzymes and genes was done using disc diffusion method and Vitek 2 automated system, CHROMagar-ESBL, combined double disc, inhibition-based method and multiplex polymerase chain reaction, respectively. The Enterobacteriaceae isolates obtained were Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Salmonella spp., Proteus mirabilis, Enterobacter aerogenes, Shigella sonnei, Proteus vulgaris, Enterobacter sakazakii, Klebsiella oxytoca, Citrobacter diversus, and Serratia liquefaciens. Of the 674 isolates from clinical samples, 36.5%, 28.5%, and 19.9% were ESBL, MBL, and AmpC-βL producers, respectively. A low prevalence of AmpC-βL and MBL producers were obtained, with no significant difference (p<0.05) between the prevalence of ESBL and non-ESBL producers. Isolates exhibited varied levels of resistance to gentamicin, amoxicillin-clavulanic acid, ciprofloxacin, and tetracycline. The results showed that 54.6% of ESBL producers, 57.9% of MBL producers, and 62.8% of AmpC-βL producers were MDR strains. Of the 141 representative isolates tested, 36.9%, 15.6%, and 20.6% had only blaTEM, blaSHV, and blaCTX-M, respectively; 5.7% possessed both blaTEM and blaSHV; 7.1% possessed both blaTEM and blaCTX-M and 4.3% had both blaSHV and blaCTX-M. This study found a high prevalence of β-lactamase producers, indicating the need for further research on the molecular epidemiology of β-lactamase producers and their impacts in the region.

Multi-drug Resistance, β-Lactamases Production, and Coexistence of bla NDM-1 and mcr-1 in Escherichia coli Clinical Isolates From a Referral Hospital in Kathmandu, Nepal.

The ability of pathogenic Escherichia coli to produce carbapenemase enzymes is a characteristic that allows them to resist various antibiotics, including last-resort antibiotics like colistin and carbapenem. Our objectives were to identify rapidly developing antibiotic resistance (AR), assess β-lactamases production, and detect mcr-1 and bla NDM-1 genes in the isolates. A prospective cross-sectional study was carried out in a referral hospital located in Kathmandu from November 2019 to December 2020 using standard laboratory and molecular protocols. Among 77 total E. coli isolates, 64 (83.1%) of them were categorized as MDR. Phenotypically 13 (20.3%) colistin-resistant, 30 (46.9%) ESBL and 8 (12.5%) AmpC producers, and 5 (7.8%) ESBL/AmpC co-producers were distributed among MDR-E. coli. Minimum inhibitory concentrations (MIC) against the majority of MDR isolates were exhibited at 1 g/L. Of these 77 E. coli isolates, 24 (31.2%) were carbapenem-resistant. Among these carbapenem-resistant bacteria, 11 (45.9%) isolates were reported to be colistin-resistant, while 15 (62.5%) and 2 (8.3%) were MBL and KPC producers, respectively. Out of 15 MBL producers, 6 (40%) harbored bla NDM-1, and 8 (61.5%) out of 13 colistin-resistant pathogens possessed mcr-1. The resistance by colistin- and carbapenem were statistically associated (P < .001). However, only 2 (18.2%) of the co-resistant bacteria were found to have both genes. Our study revealed the highly prevalent MDR and the carbapenem-resistant E. coli and emphasized that the pathogens possess a wide range of capabilities to synthesize β-lactamases. These findings could assist to expand the understanding of AR in terms of enzyme production.

Evaluation of and risk factors for the metallo-beta-lactamase enzyme with respect to production of carbapenem-resistant Pseudomonas and Acinetobacter species

Purpose: To investigate the frequency of MBLs in Pseudomonas and Acinetobacter species with E-test, to determine the risk factors and to evaluate the demographic and clinical features of infected patients. Materials and methods: Imipenem or meropenem resistance of Pseudomonas and Acinetobacter isolated from several clinical samples with conventional methods were evaluated with imipenem EDTA E-test and the presence of Metallo-β-lactameses MBL was examined. Several isolates were screened for VIM-1, VIM-2, IMP-1, and IMP-2 with a PCR test. Results: Of 46 carbapenem resistant Acinetobacter isolates, 41 (89%), as well as of 19 carbapenem resistant Pseudomonas isolates, 5 (26%) had MBL positivity with imipenem-EDTA E-test. A history of Intensive Care Unit stay, mechanical ventilation and cephalosporin use were found to be significant risk factors with respect to MBL production. Conclusion: Detection of MBL production in Acinetobacter and Pseudomonas species especially in ICU patients is of prime importance to control infection rapidly and effectively, which contribute to prevention of outbreaks.

Correlation between Mechanism of Carbapenem Resistance and in vitro Efficacy of Ceftazidime-Avibactam and Meropenem-Vaborbactam on Carbapenem-Resistant Enterobacterales and Pseudomonas Aeruginosa

Objective: To determine the mechanism of Carbapenem resistance, type of Carbapenemase produced and in vitro efficacy of Ceftazidime-Avibactam (CAZ-AVI) and Meropenem-Vaborbactam (MEV) against Carbapenem-resistant Enterobacterales and in vitro efficacy of Ceftazidime-Avibactam against Carbapenem-resistant Pseudomonas aeruginosa. Study Design: Cross-sectional study. Place and Duration of Study: Microbiology Department, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Mar to Aug 2020. Methodology: The mechanism of Carbapenem resistance in Enterobacterales and P.aeruginosa was determined by mCIM and eCIM methods. In vitro, the susceptibility of isolates to Ceftazidime-Avibactam and Meropenem-Vaborbactam was determined by disk diffusion technique according to CLSI 2020 guidelines. Results: Out of 249 Carbapenem -resistant isolates, there were 192(77.1%) Enterobacterales and 57(22.9%) P.aeruginosa. From 192 Enterobacterales, 174(90.6%) were Carbapenemase producers while 18(9.4%) used ‘other mechanisms. From 174 Carbapenemase producers, metallo-β-lactamases were produced by 141(73.4%) while serine Carbapenemases by 33(17.2%). Out of 33 serine Carbapenemase producers,19(57.6%) were sensitive to CAZ-AVI and 6(18.2%) to MEV. Out of 141 MBL producers, 31(22%) were sensitive to CAZ-AVI and 18(12.8%) to MEV. Out of 57 P.aeruginosa, 30(52.6%) were Carbapenemase producers and 1(3.4%) were sensitive to CAZ-AVI while 27(47.4%) were non-Carbapenemase producers and 13(48%) were sensitive to CAZ-AVI. MBL production predominated. Conclusion: The in vitro efficacy of these antibiotics against MBL producers and serine Carbapenemase producers was not satisfactory.

Phenotypic Detection of Carbapenem Resistance in Clinical Isolate of Klebsiella Pneumoniae in Tertiary Care Hospital

The emergence and rapid spread of Multidrug resistant isolates of Klebsiella pneumoniae causing nosocomial infections, which require the great afford for the treating the patients by the clinician. The emergence of Metallo β-lactamase (MBL) producing isolates poses a challenge to routine microbiology laboratories. The purpose of this study was to assess the accuracy of various phenotypic methods for detecting MBL production among K. pneumoniae isolate. The current study may provide the necessary data to formulate a hospital antibiotic policy and to prevent the spread of multidrug resistance in the community. Total 240 K. pneumoniae isolates were included in our study which was isolated from various clinical samples from patients visiting a tertiary care hospital in central India. A total of 148 (61.7%) of K. pneumoniae were isolated from male patients whereas 92 (38.3%) isolates were from female patients. Out of 240 K. pneumoniae, 102 (42.5%) was detected Imipenem resistance by conventional (Kirby-Bauer) disc diffusion method which was confirmed by minimum inhibitory concentration (MIC) test (Epsilometer test). By the MIC Carbapenem resistance K. pneumoniae were confirmed for MBL producer by using phenotypic test. Combined disc synergy test (CDST) (Imipenem 10 mcg and Imipenem 10mcg + 0.5 m EDTA) and Modified Hodge test (MHT).The MHT test found most sensitive approach for detecting MBL in K. pneumoniae. This procedure is simple and clear and it may use in routine clinical labs for detection of MBL because carbapenems are last resort for treating bacterial infections. In recent years, carbapenem resistance has rampantly increased across the globe.

Resistance to Some New Drugs and Prevalence of ESBL- and MBL-Producing Enterobacteriaceae Uropathogens Isolated from Diabetic Patients.

Diabetes is a leading non-communicable disease and a risk factor for relapsing infections. The current study was aimed at investigating the prevalence and antibiotic susceptibility of carbapenem-resistant (CR) uropathogens of the family Enterobacteriaceae in diabetic patients. The data of 910 bacterial isolates was collected from diagnostic laboratories during January 2018 to December 2018. The bacterial isolates were identified using traditional methods including colonial characteristics, biochemical tests, and API (20E). Antimicrobial susceptibility and phenotypic characterization of ESBL, MBLs, and KPC was determined by utilizing CLSI recommended methods. The phenotypically positive isolates were further analyzed for resistance-encoding genes by manual PCR and Check-MDR CT103XL microarray. Susceptibility to colistin and cefiderocol was tested in accordance with CLSI guidelines. The data revealed that most of the patients were suffering from type 2 diabetes for a duration of more than a year and with uncontrolled blood sugar levels. Escherichia coli and Klebsiella pneumoniae were the most frequently encountered pathogens, followed by Enterobacter cloacae and Proteus mirabilis. More than 50% of the isolates showed resistance to 22 antibiotics, with the highest resistance (>80%) against tetracycline, ampicillin, and cefazolin. The uropathogens showed less resistance to non-β-lactam antibiotics, including amikacin, fosfomycin, and nitrofurantoin. In the phenotypic assays, 495 (54.3%) isolates were found to be ESBL producers, while ESBL-TEM and -PER were the most prevalent ESBL types. The resistance to carbapenems was slightly less (250; 27.5%) than ESBL producers, yet more common amongst E. coli isolates. MBL production was a common feature in carbapenem-resistant isolates (71.2%); genotypic characterization also validated this trend. The isolates were found to be sensitive against the new drugs, cefiderocol and eravacycline. with 7−28% resistance, except for P. mirabilis which had 100% resistance against eravacycline. This study concludes that a few types of ESBL and carbapenemases are common in the uropathogens isolated from the diabetic patients, and antibiotic stewardship programs need to be revisited, particularly to cure UTIs in diabetic patients.

590. Activities of Cefepime-Taniborbactam and Ceftazidime-Avibactam against Cefepime-Resistant Respiratory Gram-Negative Pathogens in a Hollow Fiber Infection Model

Abstract Background Cefepime-taniborbactam (FTB) combines cefepime (FEP), a fourth generation cephalosporin with taniborbactam, a novel inhibitor of metallo (MBL)- and serine β-lactamases (SBL). FTB 2.5g IV q8h was safe and effective in adults with complicated urinary tract infection in a Phase 3 trial (NCT03840148). FTB is also under development for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Methods An in vitro hollow fiber infection model (HFM) was used to assess resistance emergence in MBL- and/or SBL-producing Klebsiella pneumoniae (KP, n=5) and Pseudomonas aeruginosa (PA, n=3) treated with humanized exposures of FTB or ceftazidime-avibactam (CZA). Dense (≥ 7 log10 CFU/mL) log phase cultures were inoculated into HFM cartridges and treated with human equivalent doses of FEP (2g q8h), FTB (2.5g q8h), or CZA (2.5g q8h) for 4 days. KP strains collectively harbored NDM (n=2), VIM (n=1), CTX-M (n=4), SHV-ESBL (n=1), CMY (n=1), KPC (n=1), and OXA-48 (n=1). PA strains produced either VIM (n=1), CTX-M (n=1), or KPC (n=1). Pharmacokinetic profiles of FTB and CZA in HFMs, based on free drug exposures in plasma of healthy volunteers, were confirmed by LC-MS/MS. For CZA HFMs with MBL-producing strains, EDTA was added to sequester zinc to restore CZA susceptibility (MIC ≤ 8 mg/L). Viable bacteria were quantitated by serial dilution plating; subpopulations with elevated MICs (≥ 4x) were monitored on FTB- or CZA-supplemented agar. Results FEP, FTB, and CZA MICs ranged 16 to &amp;gt; 128 mg/L, 0.5–8 mg/L, and 2 to &amp;gt; 128 mg/L, respectively. FEP was inactive (n=7) or bacteriostatic (n=1, FEP MIC=16 mg/L). FTB was bactericidal (≥ 3 log kill) against all 8 strains; subpopulations with elevated FTB MICs were not detected. Against MBL producers, CZA was inactive without EDTA and was bacteriostatic (n=2) or bactericidal (n=2) only when EDTA was added to disable MBLs. Against non-MBL producers, all of which were CZA-susceptible, CZA was either bactericidal (n=1) or bacteriostatic (n=2) or allowed growth due to emergence of resistance (n=1). Conclusion Humanized exposures of FTB in a HFM were bactericidal against high inocula of MBL- and/or SBL-producing, multidrug-resistant respiratory pathogens and prevented emergence of resistance for 4 days. The results support development of FTB for HABP/VABP. Disclosures Lindsay M. Avery, PharmD, Venatorx Pharmaceuticals: Employee|Venatorx Pharmaceuticals: Stocks/Bonds Lindsay M. Avery, PharmD, Venatorx Pharmaceuticals: Employee|Venatorx Pharmaceuticals: Stocks/Bonds Mitchell Edwards, n/a, Venatorx Pharmaceuticals: Employee|Venatorx Pharmaceuticals: Stocks/Bonds Fan Yi, PhD, Venatorx Pharmaceuticals: Employee|Venatorx Pharmaceuticals: Stocks/Bonds Philip E. Sabato, PharmD, MS, Venatorx Pharmaceuticals: Employee|Venatorx Pharmaceuticals: Stocks/Bonds Greg Moeck, PhD, Venatorx Pharmaceuticals: Employee|Venatorx Pharmaceuticals: Stocks/Bonds Daniel C. Pevear, PhD, Venatorx Pharmaceuticals: Employee|Venatorx Pharmaceuticals: Stocks/Bonds.

126. Frequency of Carbapenemases in United States Hospitals (2016-2020) and Activity of Meropenem-Vaborbactam and Comparator Agents Tested Against These Isolates

Abstract Background We used SENTRY Antimicrobial Surveillance Program data to evaluate the prevalence of carbapenemase enzymes in US hospitals and the activity of meropenem-vaborbactam (MEV) and comparators against these isolates. Methods A total of 22,725 Enterobacterales isolates were consecutively collected in 34 US hospitals and susceptibility tested by reference broth microdilution methods. CLSI breakpoints were applied. Carbapenem-resistant Enterobacterales (CRE) isolates, classified by resistance to imipenem or meropenem, were submitted to whole genome sequencing and data analysis for the detection of carbapenemases. Results Overall, 1.0% (222) of the isolates were CRE. A decrease in CRE prevalence was noted in 2020 (0.8%) compared to 2016 (1.2%). blaKPC variants were detected among 174 (78.4% of the CRE) isolates including 95 blaKPC-3, 75 blaKPC-2, and 1 each of blaKPC-4, blaKPC-6, blaKPC-58, and the Ω-loop variant blaKPC-59.blaSME was detected among 7 S. marcescens. Metallo-β-lactamases (MBLs; 4.0% of the CRE) and OXA-48-like (1.8%) were detected among 9 and 4 isolates, respectively: 7 harbored blaNDM-1/-5; 2 isolates carried blaVIM-1; and 4 isolates carried blaOXA-48/-232. MEV (MIC50/90, 0.03/2 mg/L) inhibited 93.2% of the CRE isolates and was the most active agent tested against all isolates. Comparator β-lactam agents had limited activity against these isolates (0 to 5%). Amikacin and tigecycline were the most active comparators and inhibited 78.8% and 95.0% of the CREs, respectively. Ceftazidime-avibactam (CAZ-AVI; MIC50/90, 1/4 mg/L) was tested against 169 (2017-2020) of these isolates, inhibiting 93.5%. Against 181 isolates producing class A serine-carbapenemases, MBV (MIC50/90, 0.03/0.5 mg/L) inhibited 98.9% of all isolates and CAZ-AVI inhibited 99.2% of the 129 isolates collected in 2017-2020. The activity of all agents was limited against MBL producers. Conclusion The occurrence of carbapenemases declined in the study period, but KPC-producing isolates are dominant among CRE from US hospitals. Small numbers of isolates carrying MBLs and/or OXA-48-like enzymes (&amp;lt; 0.1% of overall) were noted. MEV and CAZ-AVI are very active against isolates producing class A serine-carbapenemases. Disclosures Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Valerie Kantro, BA, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Cory Hubler, BS, Melinta: Grant/Research Support|Shionogi: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support.

144. Gram Negative Bacteria with Increased Minimal Inhibitory Concentration for Cefiderocol among Pediatric Patients in a Northern Italy Hospital.

Abstract Background Cefiderocol is a siderophore cephalosporin active against Gram negative (GN) carbapenem resistant bacteria, approved in Italy in September 2020 for adult patients. In pediatric population off label use is allowed when severe infections from multidrug resistance (MDR) GN bacteria occur. Recently, some authors reported the emergence, among strains of Enterobacterales resistant to ceftazidime avibactam, of cross-resistance with cefiderocol. The aim of this study is to describe GN strains with increased Minimal Inhibitory Concentration (MIC) for cefiderocol isolated in our hospital. Methods This is a retrospective, single-center study conducted in Istituto Giannina Gaslini Pediatric Hospital (Genoa, Italy) from 1st January 2020 to 31st April 2022. We collected all strains of MDR GN bacteria whit increased MIC for cefiderocol isolated in our hospital. Cefiderocol susceptibility testing was performed by disk diffusion assay with the disk of 30 μg (Kirby-Bauer method, KB) according to EUCAST’s recommendations and KB breakpoints. We collected demographical data, previous colonization (if note), carbapenemases production, clinical outcomes (infections from MDR; death at 7 and 30 days; ICU admission). Results Overall, 10 GN strains with increased MIC for cefiderocol were collected. 9/10 were Enterobacterales (4 Escherichia coli, 2 Enterobacter cloacae complex, 3 Klebsiella pneumoniae), one was Acinetobacter baumannii. 8/10 patients were admitted to other hospital in the six months before admission in our hospital, data about previous colonization were unknown. All MDR isolated produced metallo-β-lactamase [MBL] (5/10 New Delhi metallo-β-lactamase [NDM], 5/10 Verona integron-encoded metallo β-lactamase [VIM]). Four patients developed infection due to MDR (2 urinary tract infections, 1 bloodstream infection, 1 surgical wound), 2/4 patients died during the hospitalization. Conclusion Our study confirms that MDR producing MBL carbapenemases may have reduce susceptibility to cefiderocol, even if never exposed to this siderophore cephalosporin. Due to the possibility of cross resistance with MDR resistant to ceftazidime/avibactam, cefiderocol should be carefully prescribe in empirical treatment of MBL producers strains. Disclosures All Authors: No reported disclosures.

1688. Aztreonam-Avibactam Activity against a Large Collection of Carbapenem-Resistant Enterobacterales (CRE) collected in Hospitals from Europe, Asia, and Latin America (2019-2021)

Abstract Background Aztreonam-avibactam (ATM-AVI) is being developed to treat infections caused by Gram-negative bacteria. We evaluated the in vitro activities of ATM-AVI and comparators against a global (ex-US) collection of carbapenem-resistant Enterobacterales (CRE), including ceftazidime-avibactam (CAZ-AVI) resistant (R) isolates. Methods 24,924 isolates were consecutively collected (1/patient) from 69 medical centers in 36 countries in 2019-2021. Isolates were susceptibility tested by CLSI broth microdilution and CRE isolates (n=1,098; 4.4%) were further evaluated. CRE isolates were from Europe (EU; n=681), Latin America (LATAM; n=240) and Asia-Pacific region (APAC; n=177). An ATM-AVI PK/PD breakpoint of ≤8 mg/L was applied for comparison. CRE isolates from 2019-2020 were screened for carbapenemase (CPE) genes by whole genome sequencing (WGS). Susceptibility results were stratified by geography and CPE gene. Results ATM-AVI inhibited 99.6% of CREs at ≤ 8 mg/L (MIC50/90, 0.25/0.5 mg/L), including 98.9% (345/349) of CAZ-AVI-R isolates (Table). ATM-AVI activity was consistent across geographic regions (98.9-100.0% inhibited at ≤8 mg/L), but susceptibility to comparators varied markedly. Susceptibility rates for CAZ-AVI, meropenem-vaborbactam and imipenem-relebactam were 73.6%, 59.1% and 55.5% in EU, 74.1%, 78.3% and 68.0% in LATAM, and 38.6%, 39.8% and 31.4% in APAC, respectively. The most active comparator was tigecycline (MIC50/90, 0.5/2 mg/L; 93.4% susceptible [S]). ATM-AVI retained activity against isolates non-S to colistin (99.7% inhibited at ≤ 8 mg/L) or tigecycline (98.6% inhibited at ≤8 mg/L). A CPE gene was identified in 608 of 692 isolates (87.9%) submitted to WGS. The most common CPEs were KPC (40.9% of CREs), NDM (26.9%), and OXA-48-like (20.1%); 37 isolates (5.3%) had &amp;gt; 1 CPE gene. ATM-AVI inhibited 100.0% of CPE-producers at ≤ 8 mg/L independent of CPE type or geography, whereas current available β-lactamase inhibitors combinations exhibited limited activity against isolates producing MBL or OXA-48-like. Conclusion ATM-AVI activity was not adversely affected by clinically relevant CPEs. Our results support the development of ATM-AVI to treat infections caused by CRE, including MBL producers. Disclosures Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support.

1684. Antimicrobial Activity of Aztreonam-Avibactam Against a Large Collection of Stenotrophomonas maltophilia and Burkholderia cepacia Species Complex Causing Infections in United States (US) Medical Centers (2016-2021)

Abstract Background S. maltophilia has become a major cause of hospital-associated pneumonia. Aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBLs), including those intrinsically produced by S. maltophilia. Avibactam (AVI) is a non-β-lactam β-lactamase inhibitor that inhibits serine β-lactamases such as ESBLs, KPCs, AmpCs, and some OXAs. ATM-AVI is being developed for treatment of serious infections caused by Gram-negative bacteria, including MBL producers. We evaluated the activity of ATM-AVI against S. maltophilia and B. cepacia from US hospitals. Methods 1,565 S. maltophilia and 219 B. cepacia were consecutively collected (1/patient) in 77 US medical centers in 2016-2021 and susceptibility tested by CLSI broth microdilution method. Only isolates determined to be the probable cause of infection were included. CLSI/US FDA breakpoints were applied when available. Results The isolate collection were recovered mainly from patients with pneumonia (73.3%) and bloodstream infection (BSI; 10.1%). ATM-AVI was very active against S. maltophilia, with MIC50/90s of 2/4 mg/L and 98.3% of isolates inhibited at ≤8 mg/L, including 100.0% of isolates from BSI and 97.9% of isolates from pneumonia. Trimethoprim-sulfamethoxazole (TMP-SMX; MIC50/90, ≤0.5/1 mg/L; 95.7% susceptible [S]) and minocycline (MIC50/90, 0.5/2 mg/L; 99.2%S) also were very active against S. maltophilia, while ceftazidime and levofloxacin were active against 21.3% and 76.2% of isolates per CLSI criteria, respectively (Table). ATM-AVI was also very active against B. cepacia, with MIC50/90s of 4/16 mg/L and 88.1% inhibited at ≤8 mg/L, including 93.3% and 87.3% of isolates from BSI and pneumonia, respectively. The most active comparators tested against B. cepacia were ceftazidime (84.9%S), meropenem (84.5%S), TMP-SMX (83.5%S), and minocycline (80.0%S). Conclusion ATM-AVI demonstrated potent in vitro activity against S. maltophilia and B. cepacia from US hospitals and may represent a valuable option to treat infections caused by these organisms. Clinical studies are urgently warranted to evaluate the efficacy of ATM-AVI as well as reevaluate the susceptibility breakpoints for antibiotics currently used to treat infections caused by these organisms. Disclosures Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support SJ Ryan Arends, PhD, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Shionogi: Grant/Research Support Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

1686. Antimicrobial Activity of Aztreonam-avibactam, Ceftazidime-Avibactam, and Comparator Agents against Pseudomonas aeruginosa from Cystic Fibrosis Patients

Abstract Background Aztreonam-avibactam (ATM-AVI) is under clinical development for the treatment of serious infections caused by Gram-negative bacteria, including MBL producers. Four other β-lactamase inhibitor combinations (BL/BLI) have been recently approved by the US FDA: ceftazidime-avibactam (CAZ-AVI), ceftolozane-tazobactam (C-T), meropenem-vaborbactam (MEM-VAB), and imipenem-relebactam (IMI-REL). We evaluated the in vitro activity of these 5 BL/BLIs and comparators against P. aeruginosa (PSA) causing cystic fibrosis (CF) pulmonary exacerbation. Methods 383 PSA isolates (1/patient) were recovered from 35 medical centers in the US (n=187) and 12 European countries (EU; n=196) in 2018-2021 and susceptibility tested by CLSI broth microdilution method. Results ATM-AVI inhibited 83.4%/85.2% of isolates from US/EU at ≤8 mg/L. CAZ-AVI (MIC50/90, 2/8 mg/L; 96.3%/95.4% susceptible [S] in US/EU) was the most active agent, followed by IMI-REL (94.7%/92.5%S in US/EU) and C-T (89.8%/91.3%S in US/EU). MEM-VAB (not approved for PSA in the US) and MEM showed similar activity. Tobramycin (TOB)-S rates were 73.3%/85.7% in US/EU (Table 1). Among TOB-non-S (NS) isolates, 84.6% were CAZ-AVI-S and 73.1% were inhibited at ATM-AVI MIC of ≤8 mg/L. CAZ-AVI retained good activity against C-T-NS (61.1%S), IMI-REL-NS (62.1%S), piperacillin-tazobactam (PIP-TAZ)-NS (86.7%S), meropenem (MEM)-NS (86.6%S), and ciprofloxacin (CIP)-NS (92.1%S) isolates (Table 2). Multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes were observed among 40.1%/30.1% and 24.6%/16.8% of isolates from US/EU, respectively. Among MDR isolates, 90.7%/84.7% were CAZ-AVI-S, 65.3%/66.1% were inhibited at ≤8 mg/L of ATM-AVI, and 78.7%/76.3% were TOB-S in US/EU. CAZ-AVI and TOB retained activity against 87.0%/75.8% and 39.1%/63.6% of XDR isolates in US/EU, respectively. Conclusion ATM-AVI and CAZ-AVI exhibited potent activity against PSA isolated from CF patients in US and EU and retained good activity against isolates resistant to other antimicrobials, including MDR and XDR organisms; both compounds showed greater activity than TOB. ATM-AVI and CAZ-AVI may represent a valuable option to treat CF patients with pulmonary exacerbations due to PSA infection. Disclosures Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Leonard R. Duncan, PhD, AbbVie: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.

142. Evaluation of Meropenem-Vaborbactam Susceptibility and Underlying Resistance Mechanisms among Clinical KPC-producing Klebsiella pneumoniae

Abstract Background Meropenem-vaborbactam (MV) is the first carbapenem/β-lactamase inhibitor combination developed to restore meropenem susceptibility against KPC-producing carbapenem-resistant Enterobacterales(CRE). Vaborbactam (VAB) potently inhibits Ambler class A and C β-lactamases by reversible covalent binding of boronate to serine side chains of β-lactamases. Resistance to MV in non-metallo-β-lactamase (MBL) producing Klebsiella pneumoniae (KP) isolates has been described but remains rare. We sought to identify the major molecular mechanisms associated with MV resistance in KPC-producing KP (KPC-KP) isolates. Methods Clinical isolates with elevated MV MICs were identified by the consult service. Additional clinical isolates with mutations in ompK35 or ompK36 genes were selected from a historic database. Isolates with MBL or OXA-48-like genes were excluded. Controls were comprised of MV susceptible KPC-KP isolates. MICs determination was done using Sensititre automated broth microdilution (BMD) according to CLSI. VAB and avibactam concentrations were held at 8 µg/ml and 4 µg/ml, respectively. Whole genome sequencing (WGS) was performed on all isolates. Genome libraries were prepared using Illumina Nextera XT and sequencing was performed on MiSeq and MinION. Results A total 119 KPC-KP isolates were included in the study. All isolates were resistant to meropenem. Twenty-one KPC-KP with elevated MV MICs were identified. All MV resistant isolates harbored mutations in ompK36 genes. Glycine/aspartate (GD 134-135) insertion, premature stop codon in ompK36 genes, and concomitantly elevated blaKPC copy number were predominant among MV resistant isolates. No insertion elements in ompK36 gene promoter region were found. Two MV resistant isolates exhibited unique mutations in blaKPC and envZ genes. See table for WGS and MIC results. Table 1.Whole genome sequencing and MICs of MV resistant KPC-KP isolatesα: Truncated at nodes 14 and 76, partial genotype consistent with blaSHV-12WT: Wild type*: Premature stop codonGD: Duplication of Glycine (G134) and Aspartate (D135)FS: Frameshift mutationins: insertionMEM: meropenemMVB: meropenem-vaborbactamCZA: ceftazidime-avibactamCFD: cefiderocolN/A: not availableTable 2.Whole genome sequencing and MICs of MV susceptible KPC-KP isolates Conclusion MV resistant KPC-KP isolates were reliably analyzed using WGS to reveal the contribution of omp gene mutations and blaKPC copy number to this phenotype. Elevated MV MICs were additionally recognized among clinical isolates from a historic database preceding MV availability. In the absence of MBL production, caution remains warranted with the use of MV empirically against KPC-KP due to non-β-lactamase mediated resistance mechanisms. Disclosures Daniel D. Rhoads, M.D. PhD, Luminex: Advisor/Consultant|Talis Biomedical: Advisor/Consultant|Thermo Fisher: Advisor/Consultant Federico Perez, M.D., Accelerate: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support Robert A. Bonomo, MD, NIH VA: Grant/Research Support|VenatoRx Merck Wockhardt Cystic Fibrosis Foundation: Grant/Research Support.

Multidrug-Resistant Acinetobacter: Detection of ESBL, MBL, bla NDM-1 Genotype, and Biofilm Formation at a Tertiary Care Hospital in Eastern Nepal.

The Acinetobacter species is an important hospital-acquired pathogen. The rapid development of resistance to multiple drugs and the ability to form biofilm make these bacteria more adaptable to survive in healthcare facilities, thus posing a challenge to their effective management. This study aimed to characterize clinical isolates of Acinetobacter spp and to study their antimicrobial susceptibility patterns and ability to form biofilm. Resistant Acinetobacter was further analyzed for the detection of extended-spectrum β-lactamases (ESBLs), metallo β-lactamases (MBLs), carbapenemase production, and presence of blaNDM-1 gene. A total of 324 Acinetobacter species were isolated from various clinical specimens which were submitted to the Department of Microbiology, B.P. Koirala Institute of Health Sciences, Dharan, Nepal, and were studied for antibiotic susceptibility testing, detection of ESBL and MBL production, and formerly biofilm formation was performed by standard microbiological methods. PCR was carried out to determine the presence of the blaNDM-1 gene. The predominant Acinetobacter species isolated was A calcoaceticus-baumannii Complex (Acb complex) 167 (51.5%). Among those, all A. species 128 (40%) were multidrug resistant (MDR). In which 13 (4.0%) were ESBL producers, 70 (61.9%) were MBL, and 12 (10.6%) were carbapenemases producers. The blaNDM1 gene was present in 33 isolates. Thirty-seven percent (121/324) of isolates formed biofilm. The majority of A. species were resistant to cefotaxime 73.8% (239) and cefepime 74.4% (241). A significant proportion of biofilm producers were MDR (p < 0.001). Drug-resistant Acinetobacter formed a substantial proportion of this hospital's samples with a large presence of the bla NDM-1 gene. A matter of great concern is the association of multidrug-resistant phenotype with biofilm formation. This situation warranted stringent surveillance and adherence to infection prevention and control practices.

A STUDY OF BACTERIOLOGICAL AETIOLOGICAL AGENTS IN POST OPERATIVE ABDOMINAL WOUND INFECTIONS IN A TERTIARY CARE HOSPITAL

Background and Objectives: Surgical Site Infection (SSI) continues to be a major healthcareassociated infection. Primary objective: To isolate, identify and study the aerobic bacteriological spectrum of Abdominal Surgical Site Infection. Secondary objective: 1) To study the antibiotic sensitivity pattern. 2) To detect multidrug resistant strains in abdominal Surgical Site Infection. Materials and Methods: A total of 139 patients with post operative wound infections were included in this study during the course of one year from 1/10/16 to 30/09/2017. The study group included patients who underwent surgical procedure in a tertiary care hospital and developed Surgical Site Infection while in Hospital or after discharge within 30 days post surgery. These patients were followed up closely from the period of developing SSI to the time of discharge and during follow up in the hospital. Specimens such as double swabs for open surgical wounds and aspirates for localized infections were collected. Double swabs were inoculated into the following media: 5% Sheep Blood agar (SBA), MacConkey agar (MA), Salt agar (SA) and Glucose broth. Needle aspirates were also inoculated into Chocolate Agar (CA) in addition to the above media. The organisms were identied by conventional biochemical reactions and antibiotic sensitivity was done according to the CLSI guidelines 2017. Results: Out of the 139 cases in the study, the incidence of SSI's following abdominal surgeries were 41.7 %. The commonest age group for developing SSI was spread equally in the age groups between 51 – 60 and 61 – 70 years (20.14% each). Of the risk factors, Diabetes mellitus (40.28%) were associated with SSI's in 56 patients. Maximum number of cases were after Staging Laparotomies / Tumor excision for GIT Carcinoma- 48 (35.25%). 13.66 % cases were after Appendicectomy; LSCS - 12.23 %, Laparotomy- Peritonitis 10.79 %, Laparotomy- Intestinal obstruction 3.59 %, Hernioraphy 9.35 %, Tubectomy 3.59 %, TAH 7.19 %, Laparotomy -Abdominal injury 0.71 % and others 4.31 %. There were 58 (41.7%) of cases with microbial isolates and 81 (58.3%) cases were sterile. S.aureus was the predominant organism in Abdominal Surgical Site Infection 20 (34.48%), followed by E.coli and Klebsiella pneumoniae 15 (25.85%) each. Out of 15 Klebsiella pneumoniae 53.33 % were ESBL producers and 33.33 % were MBL producers. Where as in 15 E.coli isolates, 80 % were ESBL producers and 6.67 % MBL producers. Discussion: Surgical Site Infection (SSI) are the most common Health care associated infection in low and middle income countries. Surgical Site Infection was found to be higher in patients above 50 years of age which can be due to multiple factors like a low healing rate, malnutrition, mal-absorption, increased catabolic processes and low immunity. Diabetes mellitus is a major risk factor associated with Surgical Site Infections. Patients requiring prolonged hospitalization were more prone to Surgical Site Infections. Enterococcus which is a member of the normal ora of the Gastrointestinal and Genitourinary tract in humans is an emerging pathogen in abdominal Surgical Site Infections. Interpretation and Conclusion: The prevalence of multidrug resistant organisms is to be considered as a warning sign for the emerging spread of antibiotic resistance and the need for urgent implementation of strict antibiotic policy and infection control measures. Identication of SSI's involves interpretation of clinical and laboratory ndings, and it is crucial that a surveillance programme uses denitions that are consistent and standardized; otherwise inaccurate or uninterpretable SSI rates will be computed and reported.

DETECTION OF METALLO-BETA-LACTAMASE PRODUCING PSEUDOMONAS AND ACINETOBACTER SPECIES FROM DIFFERENT CLINICAL SPECIMENS IN A TERTIARY CARE HOSPITAL AT PUDUCHERRY.

Introduction Pseudomonas and Acinetobacter species are frequently isolated non-fermenting gram negative bacteria in a variety of hospital acquired infections. Metallo-beta-lactamases have become a serious threat in treating infections because of their multiple drug resistance including carbapenems. To determine Objectives the prevalence of MBL production among Pseudomonas and Acinetobacter species and to evaluate the different phenotypic MBL detection methods. A total of 104 isolates of carbapenem resistant Pseudomonas (78) and Materials and methods Acinetobacter (26) from different clinical specimens were tested for MBL production by Modied Hodge Test, Combined Disk Test and Double Disk Synergy Test. Antibiotic susceptibility was performed by Kirby- Bauer Disk Diffusion method. Results Pseudomonas aeruginosa (11.29%) Acinetobacterbaumanii (11.53%) were the predominant MBL producers. MBL production was detected 61.53%, 84.61% and 38.46 % by DDST( Doule disc synergy test), CDT (Combined disc test), and MHT (Modied Hodge test) respectively. Colistin and Polymyxin B are the only option available for treating such infections. MBL Conclusion production among Pseudomonas and Acinetobacter species are increasing due to the continuous use of carbapenems and selective antibiotic pressure. Strict antibiotic policy and infection control practices help prevent the further spread.

Molecular Characterization Of Non-Fermenting Gram-Negative Bacilli And Its Virulence Markers From Various Clinical Samples In A Tertiary Care Center, South India

Introduction: Non-fermentative Gram-negative bacilli (NFGNB) are an important cause of healthcare-associated infections, and theyare primarily opportunistic pathogens.Aim and objectives: To isolate and characterize the non-fermenting Gram-negative bacilli (NFGNB) from various clinical samples ina tertiary care center. To detect the virulence markers and drug resistance using molecular methods.Material and methods: Non-fermentative Gram-negative bacilli (NFGNB) from various clinical samples were identified using standardbacteriological identification methods. Conventional PCR for detection of MBLs genes of P. aeruginosa such as blaIMP, blaVIM, blaNDMand a virulence marker, Exo S gene and also MBL genes of A. baumannii such as blaIMP, blaVIM, blaNDM, blaOXA-23, blaOXA-58, and avirulence marker, OmpA gene.Results: Out of 104 NFGNB isolates Pseudomonas aeruginosa was the most common bacteria comprising 62% (n=65), followed byAcinetobacter baumannii 25% (n=26), Acinetobacter lwoffii 4% (n=4), Pseudomonas flourescens 3% (n=3), Burkholderia cepacia 3%(n=3), Stenotrophomonas maltophilia 1% (n=1), Myroides odoratimimus 1% (n=1), and Rhizobium radiobacter 1% (n=1). The resultof P. aeruginosa showed that the blaVIM gene was expressed in 25 %(n=2), the blaNDM gene was expressed in 50 %(n=4) and blaIMPwas found in 25 %(n=2). For A. baumannii, the blaNDM gene was expressed in 33% (n=6), blaOXA-23 gene was expressed in 78%(n=14), blaOXA-58 gene was expressed in 56% (n=10) with no expression of blaIMP and blaVIM genes.Conclusion: In our study we report the increased prevalence of MBL genes in P. aeruginosa and A. baumannii. This highlights theimportance of accurate identification of MBL producers and judicious use of carbapenems. Early identification and continuedsurveillance of these multidrug resistant organisms will help to prevent their spread in a hospital environment.

Blood Stream Infection Caused by Carbapenem-resistant Chryseobacterium indologenes Harboring blaNDM-1 Gene Isolated from a Tertiary Care Hospital in Tripura: An Emerging Threat.

Chryseobacterium indologenes has recently been identified as an inherently drug-resistant organism, responsible for a wide spectrum of infections, mainly device-associated infections in hospital settings. The presence of carbapenem resistance due to blaNDM-1 metallo-β-lactamase (MBL) gene further complicates the matter, leading to widespread dissemination of carbapenem resistance. This study aims to find out the presence of blaNDM-1 gene among C. indologenes strains causing bloodstream infections in a tertiary care hospital. During 1 year of the study period, blood culture samples were collected from patients with features of bacteremia, and C. indologenes strains were isolated and identified as per protocol. Antibiotic sensitivity test was performed by using VITEK 2 Compact Automated AST machine (Biomerieux, France). Carbapenem-resistant strains were subjected to a combined disk diffusion test for detecting the presence of MBL enzyme. Strains positive for MBL production were subjected to a polymerase chain reaction (PCR) for detection of blaNDM-1 gene. Out of 21 strains isolated during the study period, 12 strains (57.1%) were carbapenem-resistant. Among them, seven strains (58.3%) were MBL producers. After PCR, 3 strains (42.9%) were found to be harboring blaNDM-1 gene Discussion: As per our knowledge, this is the first report of blaNDM-1 gene harboring C. indologenes strain from Northeast India. This shows the emerging therapeutic dilemma due to the narrowing of treatment options against bloodstream infections due to C. indologenes strains. Strict antimicrobial stewardship has to be implemented to prevent the further compounding of the problem.