Clinical Study

Trick or Treat-ment? Unmasking the Nightmare Bacteria This Halloween

Unmasking the Nightmare Bacteria This Halloween

Dr. Pallavi Upadhyay • Oct 31, 2025

As we celebrate Halloween this month — horror movies, folklores and stories of scary ghosts, ghouls and monsters fill the air. In reality, some of the most terrifying creatures are not mythical. They are minute and microscopic, capable of causing deadly infections. These are “nightmare bacteria” lurk in healthcare settings and within human microbiota, quietly transmitting infections that resist even the most potent antibiotics.

Antimicrobial resistance (AMR) has emerged as one of the most critical global health concerns of our time. Central to this AMR crisis is the New Delhi metallo-β-lactamase (NDM) enzyme, a potent carbapenemase driving widespread AMR in Enterobacterales.1

This Halloween, we reviewed the current status NDM-associated AMR, clinical impact of these deadly bacteria, and role of molecular diagnostics in timely detection and infection control.

Understanding Nightmare Bacteria

The term “nightmare bacteria”  is an umbrella term coined by the US Centers for Disease Control and Prevention (CDC), to describe pathogens that are resistant to most available antibiotics (including carbapenems – last line of defense against gram negative AMR bacterial strains)2, thus making the treatment interventions more of a “nightmare”.

Noteworthy, most of the nightmare bacteria belong to the carbapenem-resistant Enterobacterales (CRE), such as Klebsiella pneumoniae and Escherichia coli. AMR in these pathogens occur mainly from carbapenemase enzymes that hydrolyze carbapenems and other β-lactam antibiotics.

Main carbapenems include3:

  • KPC (Klebsiella pneumoniae carbapenemase)
  • OXA ((Oxacillinase-48)
  • VIM (Verona integron-encoded metallo-β-lactamase)
  • NDM (New Delhi metallo-β-lactamase)

NDM-CRE has garnered particular attention due to its dramatic global surge, thus posing urgent risk to public health.

NDM-CRE Crisis

NDM was first reported in 2008 in a Klebsiella pneumoniae isolate from a Swedish traveler who was hospitalized in New Delhi, India, for urinary tract infection. Since its discovery, it has spread rapidly worldwide across continents and bacterial species, aided by its plasmid-mediated mobility, driving the rapid emergence of NDM-associated drug resistance at a global scale.4 Thus far, it has been reported in around 70 countries. In the United States, 460% spike in NDM-positive CRE cases were noted from 2019 to 2023, with more than 1800 cases noted in the year 2023 alone.5 These surges, especially in post-pandemic years, have been attributed to notable lapses in infection control practices during the pandemic, increased international travel, empiric therapies, misuse and overuse of antibiotics.

NDM-CRE infections are associated with high mortality rates as they are extremely difficult to treat and include bloodstream infections, pneumonia, urinary tract infections, intra-abdominal infections, and wound infections. Infections are more prevalent in healthcare settings, especially those in intensive care units, emergency rooms, patients with catheters, or patients with a history of extensive antibiotic therapy in the past.5

Current Testing and Treatment Landscape

The ability of NDM to spread through horizontal gene transfer exacerbates the transmission, thus timely and accurate detection of these nightmare bacteria is critical to effective patient outcomes and infection control.6 While traditional culture and susceptibility testing typically takes 24-48 hours, delaying appropriate therapy and containment, biochemical assays and serology-based tests may suffer from limited sensitivity for the detection of several NDM strains.7

Molecular diagnostic approaches such as next generation sequencing (NGS) and multiplex PCRs have become the new gold standard due to their high specificity, sensitivity,  and the capability to detect the exact causal organism and the specific biomarker(s).7,8,9

NGS provides comprehensive genomic information, with the detection of NDM strains and associated resistance genes; however, it is not a common tool for routine diagnostics due to time, cost and infrastructure constraints. Multiplex PCR has become the preferred method for detecting NDM-producing bacteria because it can simultaneously identify multiple carbapenemase genes in a single reaction, in a simpler workflow, in a cost-effective and rapid manner.7-11

Treatment options for NDM-producing organisms are extremely limited. Traditionally, treatment reliance was on colistin, tigecycline, and fosfomycin, although each of these antibiotics have shown to depict limited efficacy as well as adverse effects.11,12

The emergence of newer antibiotics such as cefiderocol, a siderophore cephalosporin. aztreonam + ceftazidime-avibactam, a combination therapy, represents a significant step forward in supporting the clinicians toward effective patient management and antimicrobial stewardship efforts.11-14

Will the Nightmare End? Conclusion and Future Directions

Controlling the spread of nightmare bacteria will require a holistic, multifaceted approach, highlighting the coordinated and collaborative efforts from the healthcare sectors and communities (laboratories, clinicians, and public health systems). While accurate testing that helps guides targeted treatment are essential strategies in curbing and managing NDM infections; prevention via stringent infection control measures, including hand hygiene, contact precautions, and environmental decontamination remains the key strategy to prevent the spread of multi-drug-resistant pathogens. Moreover, as the AMR continues to evolve, the above-mentioned strategies coupled with robust surveillance program are among the most practical strategies to prevent these pathogens from becoming an untenable global threat. Antimicrobial stewardship programs supporting appropriate antibiotic use are crucial components of this comprehensive approach. In the end, advancements and innovations in diagnostics, therapeutics, and data-driven surveillance provide actionable strategies and keep us optimistic towards our fight against nightmare bacteria.

References

  1. Findlay J, Poirel L, Kessler J, et al. New Delhi Metallo-β-Lactamase–Producing Enterobacterales Bacteria, Switzerland, 2019–2020. Emerging Infectious Diseases. 2021;27(10):2628-2637.
  2. CDC. AMD: Eliminating Healthcare-associated Infections and Antimicrobial Resistant Pathogens.
    https://www.cdc.gov/advanced-molecular-detection/php/what-we-do/hai-amr.html    . Accessed 10-27-25.
  3. Papp-Wallace KM, Endimiani A, et al. Carbapenems: past, present, and future. Antimicrob Agents Chemother. 2011;55(11):4943-60.
  4. Halaby T, Reuland AE, Al Naiemi N, et al. A case of New Delhi metallo-β-lactamase 1 (NDM-1)-producing Klebsiella pneumoniae with putative secondary transmission from the Balkan region in the Netherlands. Antimicrob Agents Chemother. 2012;56(5):2790-1.
  5. CDC. CDC report finds sharp rise in dangerous drug-resistant bacteria.
    https://www.cdc.gov/media/releases/2025/2025-cdc-report-finds-sharp-rise-in-dangerous-drug-resistant-bacteria.html    . Accessed 10-27-25.
  6. Belay WY, Getachew M, Tegegne BA, et al. Mechanism of antibacterial resistance, strategies and next-generation antimicrobials to contain antimicrobial resistance: a review. Front Pharmacol. 2024;15:1444781.
  7. Caliskan-Aydogan O, Alocilja EC. A review of carbapenem resistance in Enterobacterales and its detection techniques. Microorganisms. 2023;11(6):1491.
  1. Kumar S, Anwer R, Azzi A. Molecular typing methods & resistance mechanisms of MDR Klebsiella pneumoniae. AIMS Microbiology. 2023 Feb 27;9(1):112.
  2. Noster J, Thelen P, Hamprecht A. Detection of multidrug-resistant Enterobacterales—from ESBLs to carbapenemases. Antibiotics. 2021 Sep 21;10(9):1140.
  3. Hatrongjit R, Chopjitt P, Boueroy P, Kerdsin A. Multiplex PCR detection of common carbapenemase genes and identification of clinically relevant Escherichia coli and Klebsiella pneumoniae complex. Antibiotics (Basel). 2022;12(1):76.
  4. Walker MM, Roberts JA, Rogers BA, et al. Current and emerging treatment options for multidrug resistant Escherichia coli urosepsis: A review. Antibiotics. 2022;11(12):1821.
  5. Tompkins K, van Duin D. Treatment for carbapenem-resistant Enterobacterales infections: recent advances and future directions. Eur J Clin Microbiol Infect Dis. 2021;40(10):2053-2068.
  6. Almangour TA, Aldajani GA, Alhijji A, et al. Treatment of a challenging NDM and OXA-48-producing Klebsiella pneumoniae causing skin and soft tissue infection and exhibiting resistance to the combination of Ceftazidime-Avibactam and Aztreonam: A case report. IDCases. 2024;37:e02020.
  7. Mackow NA, van Duin D. Reviewing novel treatment options for carbapenem-resistant Enterobacterales. Expert Rev Anti Infect Ther. 2024;22(1-3):71-85.

References

  1. Findlay J, Poirel L, Kessler J, et al. New Delhi Metallo-β-Lactamase–Producing Enterobacterales Bacteria, Switzerland, 2019–2020. Emerging Infectious Diseases. 2021;27(10):2628-2637.
  2. CDC. AMD: Eliminating Healthcare-associated Infections and Antimicrobial Resistant Pathogens.
    https://www.cdc.gov/advanced-molecular-detection/php/what-we-do/hai-amr.html    . Accessed 10-27-25.
  3. Papp-Wallace KM, Endimiani A, et al. Carbapenems: past, present, and future. Antimicrob Agents Chemother. 2011;55(11):4943-60.
  4. Halaby T, Reuland AE, Al Naiemi N, et al. A case of New Delhi metallo-β-lactamase 1 (NDM-1)-producing Klebsiella pneumoniae with putative secondary transmission from the Balkan region in the Netherlands. Antimicrob Agents Chemother. 2012;56(5):2790-1.
  5. CDC. CDC report finds sharp rise in dangerous drug-resistant bacteria.
    https://www.cdc.gov/media/releases/2025/2025-cdc-report-finds-sharp-rise-in-dangerous-drug-resistant-bacteria.html    . Accessed 10-27-25.
  6. Belay WY, Getachew M, Tegegne BA, et al. Mechanism of antibacterial resistance, strategies and next-generation antimicrobials to contain antimicrobial resistance: a review. Front Pharmacol. 2024;15:1444781.
  7. Caliskan-Aydogan O, Alocilja EC. A review of carbapenem resistance in Enterobacterales and its detection techniques. Microorganisms. 2023;11(6):1491.
  8. Kumar S, Anwer R, Azzi A. Molecular typing methods & resistance mechanisms of MDR Klebsiella pneumoniae. AIMS Microbiology. 2023 Feb 27;9(1):112.
  9. Noster J, Thelen P, Hamprecht A. Detection of multidrug-resistant Enterobacterales—from ESBLs to carbapenemases. Antibiotics. 2021 Sep 21;10(9):1140.
  10. Hatrongjit R, Chopjitt P, Boueroy P, Kerdsin A. Multiplex PCR detection of common carbapenemase genes and identification of clinically relevant Escherichia coli and Klebsiella pneumoniae complex. Antibiotics (Basel). 2022;12(1):76.
  11. Walker MM, Roberts JA, Rogers BA, et al. Current and emerging treatment options for multidrug resistant Escherichia coli urosepsis: A review. Antibiotics. 2022;11(12):1821.
  12. Tompkins K, van Duin D. Treatment for carbapenem-resistant Enterobacterales infections: recent advances and future directions. Eur J Clin Microbiol Infect Dis. 2021;40(10):2053-2068.
  13. Almangour TA, Aldajani GA, Alhijji A, et al. Treatment of a challenging NDM and OXA-48-producing Klebsiella pneumoniae causing skin and soft tissue infection and exhibiting resistance to the combination of Ceftazidime-Avibactam and Aztreonam: A case report. IDCases. 2024;37:e02020.
  14. Mackow NA, van Duin D. Reviewing novel treatment options for carbapenem-resistant Enterobacterales. Expert Rev Anti Infect Ther. 2024;22(1-3):71-85.

Dr. Pallavi Upadhyay

Director of Scientific and Clinical Affairs

Dr. Pallavi Upadhyay

Director of Scientific and Clinical Affairs

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Unmasking the Nightmare Bacteria This Halloween

Dr. Pallavi Upadhyay • Oct 31, 2025

As we celebrate Halloween this month — horror movies, folklores and stories of scary ghosts, ghouls and monsters fill the air. In reality, some of the most terrifying creatures are not mythical. They are minute and microscopic, capable of causing deadly infections. These are “nightmare bacteria” lurk in healthcare settings and within human microbiota, quietly transmitting infections that resist even the most potent antibiotics.

Antimicrobial resistance (AMR) has emerged as one of the most critical global health concerns of our time. Central to this AMR crisis is the New Delhi metallo-β-lactamase (NDM) enzyme, a potent carbapenemase driving widespread AMR in Enterobacterales.1

This Halloween, we reviewed the current status NDM-associated AMR, clinical impact of these deadly bacteria, and role of molecular diagnostics in timely detection and infection control.

Understanding Nightmare Bacteria

The term “nightmare bacteria”  is an umbrella term coined by the US Centers for Disease Control and Prevention (CDC), to describe pathogens that are resistant to most available antibiotics (including carbapenems – last line of defense against gram negative AMR bacterial strains)2, thus making the treatment interventions more of a “nightmare”.

Noteworthy, most of the nightmare bacteria belong to the carbapenem-resistant Enterobacterales (CRE), such as Klebsiella pneumoniae and Escherichia coli. AMR in these pathogens occur mainly from carbapenemase enzymes that hydrolyze carbapenems and other β-lactam antibiotics.

Main carbapenems include3:

  • KPC (Klebsiella pneumoniae carbapenemase)
  • OXA ((Oxacillinase-48)
  • VIM (Verona integron-encoded metallo-β-lactamase)
  • NDM (New Delhi metallo-β-lactamase)

NDM-CRE has garnered particular attention due to its dramatic global surge, thus posing urgent risk to public health.

NDM-CRE Crisis

NDM was first reported in 2008 in a Klebsiella pneumoniae isolate from a Swedish traveler who was hospitalized in New Delhi, India, for urinary tract infection. Since its discovery, it has spread rapidly worldwide across continents and bacterial species, aided by its plasmid-mediated mobility, driving the rapid emergence of NDM-associated drug resistance at a global scale.4 Thus far, it has been reported in around 70 countries. In the United States, 460% spike in NDM-positive CRE cases were noted from 2019 to 2023, with more than 1800 cases noted in the year 2023 alone.5 These surges, especially in post-pandemic years, have been attributed to notable lapses in infection control practices during the pandemic, increased international travel, empiric therapies, misuse and overuse of antibiotics.

NDM-CRE infections are associated with high mortality rates as they are extremely difficult to treat and include bloodstream infections, pneumonia, urinary tract infections, intra-abdominal infections, and wound infections. Infections are more prevalent in healthcare settings, especially those in intensive care units, emergency rooms, patients with catheters, or patients with a history of extensive antibiotic therapy in the past.5

Current Testing and Treatment Landscape

The ability of NDM to spread through horizontal gene transfer exacerbates the transmission, thus timely and accurate detection of these nightmare bacteria is critical to effective patient outcomes and infection control.6 While traditional culture and susceptibility testing typically takes 24-48 hours, delaying appropriate therapy and containment, biochemical assays and serology-based tests may suffer from limited sensitivity for the detection of several NDM strains.7

Molecular diagnostic approaches such as next generation sequencing (NGS) and multiplex PCRs have become the new gold standard due to their high specificity, sensitivity,  and the capability to detect the exact causal organism and the specific biomarker(s).7,8,9

NGS provides comprehensive genomic information, with the detection of NDM strains and associated resistance genes; however, it is not a common tool for routine diagnostics due to time, cost and infrastructure constraints. Multiplex PCR has become the preferred method for detecting NDM-producing bacteria because it can simultaneously identify multiple carbapenemase genes in a single reaction, in a simpler workflow, in a cost-effective and rapid manner.7-11

Treatment options for NDM-producing organisms are extremely limited. Traditionally, treatment reliance was on colistin, tigecycline, and fosfomycin, although each of these antibiotics have shown to depict limited efficacy as well as adverse effects.11,12

The emergence of newer antibiotics such as cefiderocol, a siderophore cephalosporin. aztreonam + ceftazidime-avibactam, a combination therapy, represents a significant step forward in supporting the clinicians toward effective patient management and antimicrobial stewardship efforts.11-14

Will the Nightmare End? Conclusion and Future Directions

Controlling the spread of nightmare bacteria will require a holistic, multifaceted approach, highlighting the coordinated and collaborative efforts from the healthcare sectors and communities (laboratories, clinicians, and public health systems). While accurate testing that helps guides targeted treatment are essential strategies in curbing and managing NDM infections; prevention via stringent infection control measures, including hand hygiene, contact precautions, and environmental decontamination remains the key strategy to prevent the spread of multi-drug-resistant pathogens. Moreover, as the AMR continues to evolve, the above-mentioned strategies coupled with robust surveillance program are among the most practical strategies to prevent these pathogens from becoming an untenable global threat. Antimicrobial stewardship programs supporting appropriate antibiotic use are crucial components of this comprehensive approach. In the end, advancements and innovations in diagnostics, therapeutics, and data-driven surveillance provide actionable strategies and keep us optimistic towards our fight against nightmare bacteria.

References

  1. Findlay J, Poirel L, Kessler J, et al. New Delhi Metallo-β-Lactamase–Producing Enterobacterales Bacteria, Switzerland, 2019–2020. Emerging Infectious Diseases. 2021;27(10):2628-2637.
  2. CDC. AMD: Eliminating Healthcare-associated Infections and Antimicrobial Resistant Pathogens.
    https://www.cdc.gov/advanced-molecular-detection/php/what-we-do/hai-amr.html    . Accessed 10-27-25.
  3. Papp-Wallace KM, Endimiani A, et al. Carbapenems: past, present, and future. Antimicrob Agents Chemother. 2011;55(11):4943-60.
  4. Halaby T, Reuland AE, Al Naiemi N, et al. A case of New Delhi metallo-β-lactamase 1 (NDM-1)-producing Klebsiella pneumoniae with putative secondary transmission from the Balkan region in the Netherlands. Antimicrob Agents Chemother. 2012;56(5):2790-1.
  5. CDC. CDC report finds sharp rise in dangerous drug-resistant bacteria.
    https://www.cdc.gov/media/releases/2025/2025-cdc-report-finds-sharp-rise-in-dangerous-drug-resistant-bacteria.html    . Accessed 10-27-25.
  6. Belay WY, Getachew M, Tegegne BA, et al. Mechanism of antibacterial resistance, strategies and next-generation antimicrobials to contain antimicrobial resistance: a review. Front Pharmacol. 2024;15:1444781.
  7. Caliskan-Aydogan O, Alocilja EC. A review of carbapenem resistance in Enterobacterales and its detection techniques. Microorganisms. 2023;11(6):1491.
  1. Kumar S, Anwer R, Azzi A. Molecular typing methods & resistance mechanisms of MDR Klebsiella pneumoniae. AIMS Microbiology. 2023 Feb 27;9(1):112.
  2. Noster J, Thelen P, Hamprecht A. Detection of multidrug-resistant Enterobacterales—from ESBLs to carbapenemases. Antibiotics. 2021 Sep 21;10(9):1140.
  3. Hatrongjit R, Chopjitt P, Boueroy P, Kerdsin A. Multiplex PCR detection of common carbapenemase genes and identification of clinically relevant Escherichia coli and Klebsiella pneumoniae complex. Antibiotics (Basel). 2022;12(1):76.
  4. Walker MM, Roberts JA, Rogers BA, et al. Current and emerging treatment options for multidrug resistant Escherichia coli urosepsis: A review. Antibiotics. 2022;11(12):1821.
  5. Tompkins K, van Duin D. Treatment for carbapenem-resistant Enterobacterales infections: recent advances and future directions. Eur J Clin Microbiol Infect Dis. 2021;40(10):2053-2068.
  6. Almangour TA, Aldajani GA, Alhijji A, et al. Treatment of a challenging NDM and OXA-48-producing Klebsiella pneumoniae causing skin and soft tissue infection and exhibiting resistance to the combination of Ceftazidime-Avibactam and Aztreonam: A case report. IDCases. 2024;37:e02020.
  7. Mackow NA, van Duin D. Reviewing novel treatment options for carbapenem-resistant Enterobacterales. Expert Rev Anti Infect Ther. 2024;22(1-3):71-85.

References

  1. Findlay J, Poirel L, Kessler J, et al. New Delhi Metallo-β-Lactamase–Producing Enterobacterales Bacteria, Switzerland, 2019–2020. Emerging Infectious Diseases. 2021;27(10):2628-2637.
  2. CDC. AMD: Eliminating Healthcare-associated Infections and Antimicrobial Resistant Pathogens.
    https://www.cdc.gov/advanced-molecular-detection/php/what-we-do/hai-amr.html    . Accessed 10-27-25.
  3. Papp-Wallace KM, Endimiani A, et al. Carbapenems: past, present, and future. Antimicrob Agents Chemother. 2011;55(11):4943-60.
  4. Halaby T, Reuland AE, Al Naiemi N, et al. A case of New Delhi metallo-β-lactamase 1 (NDM-1)-producing Klebsiella pneumoniae with putative secondary transmission from the Balkan region in the Netherlands. Antimicrob Agents Chemother. 2012;56(5):2790-1.
  5. CDC. CDC report finds sharp rise in dangerous drug-resistant bacteria.
    https://www.cdc.gov/media/releases/2025/2025-cdc-report-finds-sharp-rise-in-dangerous-drug-resistant-bacteria.html    . Accessed 10-27-25.
  6. Belay WY, Getachew M, Tegegne BA, et al. Mechanism of antibacterial resistance, strategies and next-generation antimicrobials to contain antimicrobial resistance: a review. Front Pharmacol. 2024;15:1444781.
  7. Caliskan-Aydogan O, Alocilja EC. A review of carbapenem resistance in Enterobacterales and its detection techniques. Microorganisms. 2023;11(6):1491.
  8. Kumar S, Anwer R, Azzi A. Molecular typing methods & resistance mechanisms of MDR Klebsiella pneumoniae. AIMS Microbiology. 2023 Feb 27;9(1):112.
  9. Noster J, Thelen P, Hamprecht A. Detection of multidrug-resistant Enterobacterales—from ESBLs to carbapenemases. Antibiotics. 2021 Sep 21;10(9):1140.
  10. Hatrongjit R, Chopjitt P, Boueroy P, Kerdsin A. Multiplex PCR detection of common carbapenemase genes and identification of clinically relevant Escherichia coli and Klebsiella pneumoniae complex. Antibiotics (Basel). 2022;12(1):76.
  11. Walker MM, Roberts JA, Rogers BA, et al. Current and emerging treatment options for multidrug resistant Escherichia coli urosepsis: A review. Antibiotics. 2022;11(12):1821.
  12. Tompkins K, van Duin D. Treatment for carbapenem-resistant Enterobacterales infections: recent advances and future directions. Eur J Clin Microbiol Infect Dis. 2021;40(10):2053-2068.
  13. Almangour TA, Aldajani GA, Alhijji A, et al. Treatment of a challenging NDM and OXA-48-producing Klebsiella pneumoniae causing skin and soft tissue infection and exhibiting resistance to the combination of Ceftazidime-Avibactam and Aztreonam: A case report. IDCases. 2024;37:e02020.
  14. Mackow NA, van Duin D. Reviewing novel treatment options for carbapenem-resistant Enterobacterales. Expert Rev Anti Infect Ther. 2024;22(1-3):71-85.

Dr. Pallavi Upadhyay

Director of Scientific and Clinical Affairs

Dr. Pallavi Upadhyay

Director of Scientific and Clinical Affairs

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