Carbapenem-resistant Enterobacterales, commonly abbreviated CRE, represent one of the most urgent threats in modern medicine. These Gram-negative bacteria, which include Escherichia coli and Klebsiella pneumoniae among others, have acquired the ability to withstand carbapenems, a class of antibiotics often reserved as a last line of defense against serious infections. The consequences are stark: mortality rates from CRE infections can climb as high as fifty percent, leaving clinicians with vanishingly few therapeutic options. The problem is also accelerating globally, with resistance prevalence rising from just one percent in 2013 to forty-three percent in 2020 in parts of North America, a trajectory that underscores how quickly these organisms can adapt and spread.

The engine driving this resistance is the production of carbapenemase enzymes, a diverse family of beta-lactamases grouped into distinct classes by the Ambler classification system. Class A enzymes such as KPC, Class B metallo-beta-lactamases including NDM, IMP and VIM, and Class D oxacillinases such as OXA-48 each hydrolyze carbapenems through different chemical mechanisms. Because phenotypic tests alone cannot reliably distinguish between these classes, molecular techniques such as multiplex polymerase chain reaction are essential for pinpointing which resistance genes are actually present. In the Indian context, where blaNDM-1 has become widespread, identifying these determinants is critical for predicting transmissibility, constructing empirical antibiograms and strengthening hospital infection control.

Recognizing that systematic molecular data from eastern India were virtually absent, the AIIMS Patna team designed a cross-sectional study conducted between July 2021 and July 2023 in the hospital’s Microbiology laboratory. The research, approved by the Institutional Ethics Committee under approval number AIIMS/Pat/IEC/2021/578 and performed in accordance with the Declaration of Helsinki, analyzed residual clinical isolates collected during routine diagnostic work, with a formal waiver of individual patient consent and no patient-identifiable data collected. To avoid duplication bias, the investigators included only the first isolate per patient per episode of infection, ensuring that repeated cultures from the same admission did not inflate the results.

The scope of the underlying resistance problem was formidable. During the study period, a total of 3,421 Enterobacterales were isolated, drawn overwhelmingly from urine specimens, followed by pus, blood and respiratory samples. Of these, 1,128 isolates, or 32.97 percent, were phenotypically confirmed as carbapenem resistant, a figure drawn from the team’s previously published phenotypic work at the same center. Resistance was markedly higher among inpatients, at 47.74 percent, compared with only 14.48 percent among outpatients. All 213 CRE isolates characterized in detail showed complete resistance to third-generation cephalosporins, near-universal resistance of 99.4 percent to beta-lactam and beta-lactamase inhibitor combinations such as piperacillin-tazobactam, and one hundred percent resistance to aztreonam, a sobering profile that leaves almost no conventional beta-lactam therapy intact.

To confirm which isolates were producing carbapenemase enzymes, the researchers deployed a battery of phenotypic assays, including the Modified Carbapenem Inactivation Method, or mCIM, its EDTA-supplemented variant eCIM designed to identify Class B metallo-beta-lactamases, and combination inhibition tests using phenylboronic acid, cloxacillin and EDTA. Of the 213 CRE isolates, 203 were confirmed carbapenemase producers by mCIM. From this positive pool, a consecutive subset of 98 isolates with viable stored stock and sufficient DNA yield was selected for multiplex PCR-based gene profiling using validated primers originally described by Poirel and colleagues, with amplification performed on a ProFlex thermocycler and amplicons resolved on agarose gels. The authors caution that all gene-detection rates apply to this genotyped subset, which represents 48.3 percent of the mCIM-positive isolates, and should not be extrapolated as prevalence estimates for the entire CRE cohort.

The molecular results were striking. Among the 98 profiled isolates, 60 were Escherichia coli, 33 were Klebsiella pneumoniae, and the remainder comprised Citrobacter freundii and Enterobacter species. blaNDM emerged as the most prevalent gene, detected in 63.27 percent of isolates, with E. coli and K. pneumoniae as the predominant carriers. blaOXA-48 followed closely at 61.22 percent, while blaIMP appeared in 10.20 percent, blaKPC in 5.10 percent and blaVIM in 3.06 percent. Perhaps most concerning was the degree of co-carriage: half of the genotyped K. pneumoniae isolates carried both NDM and OXA-48 simultaneously, and 27.27 percent of E. coli harbored the same dual combination. Individual isolates carrying three resistance genes, such as NDM, OXA-48 and KPC together, were also documented, illustrating how bacterial genomes can accumulate layered defensive armories.

The comparison between phenotypic and genotypic results revealed both reassuring agreement and instructive discrepancies. All isolates carrying blaKPC were mCIM positive and displayed Class A carbapenemase phenotypes, and every isolate harboring a metallo-beta-lactamase gene, whether blaNDM, blaIMP or blaVIM, was positive on both mCIM and eCIM, confirming Class B enzyme production. However, among the 60 isolates carrying blaOXA-48, only two exhibited the phenotypic signature of Class D carbapenemase, a gap the authors attribute partly to limitations in the EUCAST-recommended temocillin zone-diameter threshold used as an indirect confirmatory test. Unexpressed genes, undetected beta-lactamase families such as blaSPM or blaGIM, and PCR inhibitors may all contribute to such mismatches, and the researchers note that amplicons were not confirmed by sequencing, meaning allelic variants cannot be entirely excluded.

These findings carry direct implications for therapy. Given the overwhelming predominance of Class B metallo-beta-lactamases, particularly NDM, the authors argue that empirical treatment of suspected CRE infections in this region should prioritize agents with proven activity against Class B enzymes, such as cefiderocol or the combination of ceftazidime-avibactam with aztreonam. They also emphasize that neither phenotypic nor genotypic testing alone is sufficient, and that balancing both approaches offers the most complete picture of resistance. International comparisons in the study highlight how sharply gene distributions vary by geography, with Thailand reporting NDM rates of ninety percent, China dominated by KPC at 53.4 percent, and Saudi Arabia led by OXA-48 at 76.11 percent, reinforcing that local surveillance data are indispensable for guiding rational antibiotic use.

Beyond its immediate clinical relevance, the study fills a critical gap in India’s national antimicrobial resistance surveillance architecture. Bihar and neighboring eastern states carry enormous infectious disease burdens yet have historically lacked the molecular diagnostic capacity to characterize circulating resistance mechanisms, undermining targeted infection control interventions. By documenting the genotypic landscape of CRE in an underrepresented setting, the AIIMS Patna team supports the objectives of India’s National Action Plan on Antimicrobial Resistance, particularly those concerning laboratory strengthening and evidence-based surveillance. The researchers acknowledge limitations, including the subset-based genotyping design and the absence of sequencing-based strain typing, and they plan future work involving blaNDM allele subtyping and whole-genome sequencing to trace clonal spread. For now, their findings stand as a clear warning and a practical guide: the superbugs of eastern India are armed with a dangerous genetic repertoire, but knowing exactly which weapons they carry is the first step toward disarming them.

Subject of Research: Genotypic profiling of carbapenemase genes in carbapenem-resistant Enterobacterales at a tertiary care hospital in Bihar, India

Article Title: Deciphering the genotypic profiles of Carbapenem-resistant Enterobacterales: A study from a tertiary care hospital in Bihar, India

Article References: Pramurtajyoti, D., Prathyusha, K., Zeeshan, F. M., Asim, S., Pati Binod, K., & Bhaskar, T. (2026). Deciphering the genotypic profiles of Carbapenem-resistant Enterobacterales: A study from a tertiary care hospital in Bihar, India. New Microbes and New Infections, 73, Article 101850. https://doi.org/10.1016/j.nmni.2026.101850

Image Credits: AI Generated

DOI: 10.1016/j.nmni.2026.101850

Keywords: carbapenem-resistant Enterobacterales, antimicrobial resistance, blaNDM, blaOXA-48, carbapenemase genes, multiplex PCR, Klebsiella pneumoniae, Escherichia coli, metallobeta-lactamases, India, hospital surveillance, infection control

Cancer in children is a global health concern, with low- and middle-income countries (LMICs) disproportionately affected by delays in diagnosis and treatment. These delays often stem from multifaceted obstacles including socioeconomic, cultural, and infrastructural factors. The recent initiative in Bungoma County sought to mitigate these impediments by educating communities, healthcare workers, and policymakers on the urgency of early cancer detection. However, the study revealed that, despite these efforts, the campaign did not significantly alter the annual rate of childhood cancer diagnoses.

From January 2023 to December 2024, researchers conducted structured interviews with parents of all children newly diagnosed with cancer at Moi Teaching and Referral Hospital. This qualitative approach was paired with a rigorous quantitative analysis of hospital registry data spanning a decade, from 2014 through 2024. The dual methods allowed for a robust comparison of referral patterns before and after the awareness campaign, illuminating the real-world impact of such public health interventions.

Among the 30 children diagnosed post-campaign, a substantial proportion were afflicted by solid tumors, constituting 60 percent of cases, with hematological cancers comprising 23 percent, brain tumors 10 percent, and rare solid tumors 7 percent. Notably, over half of the solid tumors were detected at advanced stages, a critical factor profoundly influencing treatment options and survival outcomes. The median age of diagnosis was 5.5 years, emphasizing the vulnerability of very young patients in this rural Kenyan context.

The study meticulously measured various forms of delay, which collectively underscored systemic and personal challenges hindering prompt cancer care. Patient delay — the interval from symptom onset to first healthcare visit — averaged 30 days. Physician delay, the duration from first visit to referral for diagnostics, extended dramatically to 104 days, while diagnosis delay itself reached 114 days on median. Health system delays matched diagnosis delays at 114 days, with treatment delays comparatively shorter at 6 days, cumulating in a staggering median total delay of 146 days. These figures highlight critical intervals during which disease progression can advance unchecked.

Crucially, these delays were not merely administrative but deeply entrenched in socioeconomic and cultural realities. Parents reported reliance on traditional medicine and cultural beliefs as initial steps in care-seeking, which often postponed engagement with formal medical services. Further, financial strain emerged as a significant barrier, with travel costs to healthcare facilities, lack of health insurance, and income loss heavily impacting families’ ability to pursue timely diagnosis and treatment. Fear and stigma surrounding cancer also contributed to delayed presentation, illustrating the complex psychosocial terrain navigated by affected families.

The researchers applied statistical tests to examine changes in referral rates before and after the campaign. Though there was a borderline indication of increased referrals post-campaign (Chi-square test p=0.071 and Fisher’s exact test p=0.063), these did not reach conventional significance thresholds. This suggests that, while awareness efforts may have had some influence, they were insufficient alone to overcome the numerous structural and social hurdles impinging on access to pediatric oncology care in this setting.

Several external factors may have confounded the impact of the awareness campaign. Healthcare worker strikes and interruptions in medical supply chains likely exacerbated service delivery delays. Additionally, treatment being sought at alternate facilities not captured in this study may have contributed to underreporting in Moi Teaching and Referral Hospital’s registry. These findings highlight the necessity of strengthening health systems infrastructure alongside community engagement to facilitate meaningful improvements in childhood cancer care.

This study unearths the stark reality that boosting awareness does not directly translate into expedited diagnosis or treatment without parallel enhancements in healthcare delivery capacity and socioeconomic support. Therefore, a multifaceted approach—addressing cultural perceptions, financial empowerment, infrastructural adequacy, and healthcare worker availability—is paramount to dismantling the barriers that chain these vulnerable patients behind in their fight against cancer.

On a scientific level, the persistent high proportion of advanced-stage solid tumors warrants further investigation into early symptom recognition and referral systems. It also raises questions about potential delays at the primary care level, where initial suspicion and timely referral are crucial but often lacking. Enhancing training for healthcare providers in recognizing pediatric oncology signs could be critical in shifting the diagnostic timeline towards earlier intervention.

Moreover, the study’s methodology, blending qualitative interviews with long-range registry data, offers a powerful template for examining health interventions in similar low-resource settings. Such mixed-methods research can unravel the complex interplays between knowledge, behavior, health infrastructure, and clinical outcomes, providing a nuanced blueprint for policy formulation.

However, to turn such research into actionable change, stakeholders must move beyond advocacy and into targeted, resource-backed strategies that tackle the identified barriers. This means channeling investments into community health worker programs, expanding insurance coverage, subsidizing transportation costs, and actively combating misconceptions about cancer through culturally sensitive education campaigns embedded within local traditions.

In sum, this comprehensive assessment from Bungoma County underscores the critical gaps that persist in childhood cancer care, despite well-intentioned awareness efforts. It paints a poignant picture of children with cancer caught in a web of delayed access, entrenched socioeconomic disadvantage, and health system fragility. Addressing these challenges requires a concerted, interdisciplinary, and sustained commitment from governments, non-governmental organizations, and communities alike to ensure that no child is left behind in the journey from diagnosis to cure.

The urgent need for innovation in childhood cancer care delivery in LMICs is clear. Future campaigns must integrate pathways to reduce financial toxicity and leverage local cultural frameworks to foster acceptance and proactive health-seeking. Only through such holistic strategies can the devastating impact of delayed cancer diagnosis and treatment on children in regions like Bungoma be mitigated, offering hope for improved survival and quality of life.

This study serves as a vital wakeup call to the global health community: awareness alone is insufficient. Without dismantling systemic barriers and reshaping socio-cultural narratives, pediatric oncology outcomes will continue to lag, condemning many young lives to preventable suffering and loss. The findings demand urgent translation into policy and action to rewrite the story of childhood cancer care in Bungoma County and beyond.

Subject of Research: Barriers to timely access and care for children newly diagnosed with cancer in Bungoma County, Kenya, post-awareness campaign, examined through parental interviews and long-term hospital registry data.

Article Title: Barriers to care for newly diagnosed children with cancer from Bungoma County after an awareness campaign: insights from parental interviews and registry data

Article References:
Klootwijk, L., Osamong, L.A., Kimaiyo, S. et al. Barriers to care for newly diagnosed children with cancer from Bungoma County after an awareness campaign: insights from parental interviews and registry data. BMC Cancer 25, 1790 (2025). https://doi.org/10.1186/s12885-025-15098-5

Image Credits: Scienmag.com

DOI: 10.1186/s12885-025-15098-5

Keywords: childhood cancer, cancer care barriers, timely diagnosis, pediatric oncology, low- and middle-income countries, healthcare access, traditional medicine, cultural beliefs, health system delays, cancer awareness campaigns