A new qualitative study published in BMC Infectious Diseases by researchers at Manipal Academy of Higher Education and affiliated hospitals in Karnataka, India, offers one of the most detailed portraits to date of that hidden decision-making process. Led by Asha K. Rajan of the Department of Pharmacy Practice and Vishal Shanbhag of the Department of Critical Care Medicine, the team interviewed fifteen physicians drawn from multiple specialities, including critical care, microbiology, infectious diseases and general medicine, all of whom were directly involved in managing critically ill patients with carbapenem-resistant K. pneumoniae bacteraemia. The study was funded by the Indian Council of Medical Research and conducted across institutions including Kasturba Medical College and Dr TMA Pai Hospital in Udupi.

The methodological approach is what sets the work apart from typical antibiotic studies. Rather than testing drugs, the researchers used semi-structured interviews and analysed the transcripts through a constructivist grounded theory framework, a qualitative technique that builds explanatory themes from the ground up through iterative coding, constant comparison and triangulation among investigators, supported by ATLAS.ti software. Participants were purposively sampled to capture a range of perspectives, and reporting followed the COREQ checklist, the recognized standard for transparency in qualitative research. The inductive analysis yielded seven themes and fifteen subthemes, and from these a central insight crystallized: antimicrobial decision-making is not a single choice but an iterative balancing act, one that pits the urgency of early effective treatment against evolving microbiological evidence, patient-specific toxicity, pharmacokinetic uncertainty, stewardship expectations and resource constraints.

The first and perhaps most consequential finding concerns time. Clinicians consistently reported prioritizing clinical risk and urgency before microbiological confirmation was available. In practical terms, this means that when a septic patient deteriorates, physicians often begin empiric therapy against suspected carbapenem-resistant organisms before blood cultures, susceptibility testing or molecular diagnostics can return an answer. The decision at this stage is driven by clinical judgment, local resistance patterns and the fear that delay allows the infection to gain ground. Only later, as culture results, minimum inhibitory concentration values and the patient’s response emerge, do clinicians modify the regimen, narrowing, broadening or switching agents in a continuous cycle of reassessment.

This iterative loop exposes a fundamental tension in modern infectious disease medicine: the diagnostics that should guide therapy are often too slow to shape the earliest and most critical decisions. The study found that although microbiological and molecular diagnostics, including polymerase chain reaction-based assays, were highly valued by physicians, their influence was constrained by turnaround times and interpretative challenges. A culture and susceptibility report that arrives forty-eight to seventy-two hours after admission arrives after the decisive therapeutic window has already begun to close. Physicians described having to act on probability rather than certainty, then retrofitting their choices to the laboratory evidence as it trickled in.

Toxicity and pharmacokinetics added a second layer of complexity. The antibiotics active against carbapenem-resistant K. pneumoniae, such as polymyxins, aminoglycosides and newer beta-lactamase inhibitor combinations, carry well-known risks of nephrotoxicity and other adverse effects, particularly in patients whose kidneys and livers are already compromised by critical illness. The interviewed physicians described continuously weighing efficacy against toxicity, adjusting doses according to patient-specific factors such as renal function and body weight, and relying on therapeutic drug monitoring where available to keep drug concentrations within a safe and effective range. The concept of the minimum inhibitory concentration, the lowest drug concentration that prevents visible bacterial growth, featured in their reasoning as a technical anchor, but its interpretation required expertise that not every setting could supply.

Antimicrobial stewardship, the institutional programs designed to preserve antibiotic effectiveness and curb resistance, emerged as a double-edged force in the interviews. On one hand, stewardship expectations pushed clinicians toward restraint, encouraging them to justify broad-spectrum or last-line agents and to de-escalate when possible. On the other hand, physicians described situations where stewardship dynamics created friction with clinical urgency, forcing them to negotiate between what they believed the patient needed and what the system’s guidelines, formularies and review committees permitted. The study suggests that stewardship is most effective when it functions as a collaborative dialogue rather than a bureaucratic gate, and that strengthening multidisciplinary stewardship is essential for optimizing care in these infections.

Structural constraints formed the third pillar of the findings, and they hit hardest in low- and middle-income settings like the one where the study was conducted. Cost, drug availability and communication gaps between departments, laboratories and prescribing teams all limited the delivery of optimal therapy. A physician might identify the ideal agent only to discover it was out of stock, unaffordable for the patient or unavailable in the required formulation. Communication breakdowns between microbiology and the bedside delayed the integration of laboratory findings into treatment plans. These system-level barriers, the authors argue, mean that improving outcomes requires more than education; it demands context-appropriate decision-support tools, timely diagnostics and interventions that address the supply chain and institutional infrastructure itself.

Perhaps the most forward-looking theme concerned learning. The study found that outcomes evaluation and experiential learning subsequently informed future treatment decisions, meaning that each patient’s trajectory became data for the next. Physicians who watched a regimen fail or succeed carried that experience forward, building an internal decision framework that no guideline could fully replicate. This finding underscores why understanding clinician decision-making processes is essential for designing effective strategies: guidelines that ignore the lived, iterative reality of intensive care prescribing risk being bypassed in the moments that matter most.

The authors conclude that the management of carbapenem-resistant K. pneumoniae bacteraemia extends far beyond drug choice, encompassing clinical urgency, diagnostic integration, pharmacokinetic uncertainty, stewardship dynamics and structural constraints. Their prescription for the future is concrete: decision-support tools calibrated to local contexts, faster diagnostics that can inform the first hours of therapy, strengthened multidisciplinary stewardship and system-level interventions that remove the barriers of cost and availability. As antimicrobial resistance continues to climb the World Health Organization’s priority lists, this study offers a rare and valuable window into the human judgment at the center of the antibiotic crisis, reminding the field that the fight against resistant superbugs is fought not only in laboratories but in the split-second, evidence-hungry decisions of physicians at the bedside.

Subject of Research: Clinician decision-making in antimicrobial treatment of carbapenem-resistant Klebsiella pneumoniae bacteraemia in critically ill patients

Article Title: Antimicrobial treatment decision-making for carbapenem-resistant Klebsiella pneumoniae bacteraemia in critically ill patients: a qualitative study

Article References: Rajan, A. K., Bhat, D., Eshwara, V. K., Varma, M., Umakanth, S., Thunga, G., & Shanbhag, V. (2026). Antimicrobial treatment decision-making for carbapenem-resistant Klebsiella pneumoniae bacteraemia in critically ill patients: a qualitative study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14436-7

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14436-7

Keywords: Klebsiella pneumoniae, antimicrobial resistance, bacteraemia, antimicrobial stewardship, critical care, qualitative research, Antimicrobial, treatment, decision-making, carbapenem-resistant, Klebsiella, pneumoniae

The research team, led by Ji-hwan Yim, Maryum Tanveer, and Gayeon Won at Jeonbuk National University in the Republic of Korea, followed the PRISMA reporting framework to sift through 6,988 records published between January 2000 and July 2025, drawn from PubMed, Scopus, and Web of Science. After removing duplicates and screening titles, abstracts, and full texts, only 19 studies made the cut. That small yield is itself telling. While CRE have been exhaustively documented in clinical settings and livestock, the ecological distribution of these bacteria outside managed systems has remained largely unmapped, leaving scientists with fragmented clues about how far the resistance problem has penetrated the natural world.

The pooled estimate that emerged from the random-effects meta-analysis was 74.49 percent, with a 95 percent confidence interval stretching from 49.75 to 94.04 percent, and a staggering I-squared statistic of 96 percent. But the authors are careful, and rightly so, about what this number actually means. The figure represents the proportion of recovered Enterobacteriaceae isolates that tested positive for carbapenem resistance under the laboratory procedures of the included studies. It is not the prevalence of CRE carriage among wild animals. Because many studies used selective or enrichment culture methods designed to favor the recovery of resistant organisms, susceptible bacteria may have been suppressed in the lab, inflating the apparent proportion. The estimate reflects what happens to isolates once they reach the petri dish, not what is happening inside every fox or gull in the wild.

Stratifying the data by bacterial species revealed CRE-positive proportions of 76.51 percent for Escherichia coli, 72.41 percent for Klebsiella species, and 86.46 percent for other Enterobacteriaceae genera, including Citrobacter and Enterobacter. These subgroup estimates, however, come with wide confidence intervals and substantial heterogeneity, so they should be read with caution. The prominence of carbapenem-resistant E. coli is epidemiologically significant for a different reason: E. coli is both a common intestinal commensal and a notorious reservoir of resistance genes, capable of picking up new genetic material through horizontal gene transfer. Its repeated recovery from wildlife suggests that these animals are being exposed to bacteria that have already learned to survive in human-altered environments.

When the researchers examined sampling environments, the highest descriptive estimate appeared in water-associated sites, at 84.49 percent, followed by captive settings at 79.65 percent, natural habitats at 77.06 percent, and human-associated environments at 72.36 percent. Yet none of these differences reached statistical significance. The only moderator that did was sample type. Fecal samples showed a pooled CRE-positive proportion of 89.29 percent, dramatically higher than the 23.04 percent seen in rectal, cloacal, or wound swabs, a difference that was statistically significant at p less than 0.01. In univariate meta-regression, sample type explained 33.1 percent of the between-study heterogeneity, making it the clearest signal in an otherwise noisy dataset. The authors note that fecal sampling may simply capture more of the gut-associated Enterobacteriaceae where resistance determinants accumulate, or that swab-based methods recover fewer organisms overall, complicating direct comparison.

The molecular findings are where the story turns genuinely alarming. Across the included studies, researchers identified clinically important carbapenemase-encoding genes from all five major families: blaNDM, blaKPC, blaOXA-48-like, blaVIM, and blaIMP. These genes encode enzymes that hydrolyze carbapenem antibiotics before they can kill the bacterial cell, and many of them ride on plasmids, the mobile genetic elements that shuttle resistance between bacterial lineages with alarming efficiency. The geographic patterns broadly mirror those seen in human medicine. NDM variants, particularly NDM-5, dominated in Asia, appearing in studies from Pakistan, India, and China. KPC-lineage enzymes, especially KPC-2, were the most common finding in North and South America, detected in isolates from the United States, Brazil, and Chile. OXA-48 was prominent in Algeria, while Tunisia reported both VIM and IMP genes. Europe showed the broadest diversity, with Spain alone yielding KPC-2, KPC-3, VIM-1, OXA-48, OXA-245, NDM-1, and NDM-5 in E. coli and Klebsiella pneumoniae. Australia contributed a single study identifying IMP-4-producing E. coli.

Sequence type analysis added another layer of concern. Multilocus sequence typing revealed that while most lineages were country-specific, a handful of internationally recognized clones appeared repeatedly across distant regions. E. coli ST38, one of the most recurrent sequence types, was identified in Spain, Algeria, Turkey, and Alaska. ST410, a lineage previously associated with high-risk international dissemination, was detected in Spain and Alaska. ST744 appeared in both Spain and Chile. Among Klebsiella pneumoniae, Spain reported ST11 and ST307, both globally significant hospital-associated lineages, alongside a diverse array of other sequence types. China contributed an unusually rich catalogue of K. pneumoniae and K. quasipneumoniae lineages. The repeated identification of these lineages in wildlife suggests that the same resistant clones circulating in human and environmental settings are also present in wild animals, although the direction of transmission remains unresolved.

That caveat is central to how the authors want their findings interpreted. Carbapenems are almost never used in veterinary medicine; their use is tightly restricted to preserve their effectiveness for the most severe human infections. So how do wild animals, which have never received these drugs, end up carrying bacteria that resist them? The most plausible explanation, the researchers argue, is exposure to resistant bacteria or resistance determinants originating from anthropogenically influenced environments. Wastewater treatment plants do not completely eliminate resistant bacteria or resistance genes, allowing them to persist and spread into surrounding ecosystems. Wildlife species that inhabit or frequent aquatic environments, particularly migratory birds like gulls and storks that move between wetlands, coastal zones, and wastewater-associated habitats, may experience repeated exposure to these contamination sources. The descriptively elevated CRE-positive proportion among Charadriiformes, the taxonomic order that includes many water-associated and migratory species, fits this pattern, even though the difference was not statistically significant.

The methodological scrutiny applied to the evidence base reveals both strengths and weaknesses. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal checklist for prevalence studies, with three reviewers independently evaluating each study. Only three of the 19 studies were classified as low risk across all evaluated domains. Nine studies met or exceeded the recommended minimum sample size of 140, while ten fell short. Statistical analysis methods were adequately described in only seven studies. Publication bias assessment added further nuance: the funnel plot showed asymmetry, and the trim-and-fill method estimated four potentially missing studies, which would lower the pooled estimate from 74.49 percent to 59.64 percent if those studies were included. However, Egger’s regression test did not reach statistical significance, and heterogeneity remained stubbornly high even after adjustment, suggesting that the asymmetry may reflect genuine methodological and ecological diversity rather than selective publication alone.

What emerges from this synthesis is not a declaration that wildlife are driving the CRE crisis, but a sober recognition that they are embedded in the same contaminated landscapes that humans have created. The authors are explicit that transmission direction cannot be established from the available evidence and that wildlife should not be interpreted as confirmed primary reservoirs or active drivers of dissemination. Instead, they propose that wild animals may serve as useful sentinels, biological barometers that reflect the extent of environmental CRE contamination in aquatic, wastewater-associated, and anthropogenically influenced ecosystems. Future surveillance studies, the researchers argue, should report detailed culture and enrichment procedures, distinguish between selective and non-selective isolation approaches, and clearly document the number of individual animals screened alongside the number of isolates recovered. Longitudinal monitoring and genomic transmission studies will be needed to determine whether wildlife play an active role in the persistence and spread of these bacteria, or whether they are simply reflecting, with uncomfortable fidelity, the resistance problem that human activity has seeded into the environment. Either way, the message from the wild is unambiguous: the genes that defeat our last-line antibiotics are already out there, circulating in animals that have never seen a hospital.

Subject of Research: Occurrence and molecular characteristics of carbapenem-resistant Enterobacteriaceae recovered from wildlife: a systematic review and meta-analysis

Article Title: Occurrence and molecular characteristics of carbapenem-resistant Enterobacteriaceae recovered from wildlife: a systematic review and meta-analysis

Article References: Yim, J.-H., Tanveer, M., Ntakiyisumba, E., Hur, J., & Won, G. (2026). Occurrence and molecular characteristics of carbapenem-resistant Enterobacteriaceae recovered from wildlife: a systematic review and meta-analysis. Frontiers in Microbiology, 17, Article 1897815. https://doi.org/10.3389/fmicb.2026.1897815

Image Credits: AI Generated

DOI: 10.3389/fmicb.2026.1897815

Keywords: Occurrence, molecular, characteristics, carbapenem-resistant, Enterobacteriaceae, recovered, wildlife, systematic, review, meta-analysis, scientific research

Klebsiella pneumoniae is a common inhabitant of the human gut and an opportunistic pathogen that can cause pneumonia, bloodstream infections, urinary tract infections, and wound infections, particularly in hospitalized and immunocompromised patients. When the bacterium acquires carbapenemases, enzymes that hydrolyze carbapenems, a class of last-resort beta-lactam antibiotics, treatment options collapse to a handful of toxic or expensive drugs. The World Health Organization classifies carbapenem-resistant K. pneumoniae as a critical priority pathogen, and the burden falls disproportionately on South Asia, where resistance genes circulate widely in hospitals and communities alike.

The enzymes involved are mechanistically distinct. The bla_NDM gene encodes New Delhi metallo-beta-lactamase, a metallo-enzyme that destroys nearly all beta-lactam antibiotics including carbapenems. The bla_OXA-48-like family encodes oxacillinases that are less potent against broad-spectrum cephalosporins but are highly efficient carbapenem hydrolyzers and are notoriously difficult to detect in routine phenotypic testing. When a single isolate carries both genes, the bacterium effectively deploys two independent biochemical strategies against the same class of drugs, and laboratory susceptibility testing can understate the true resistance arsenal. The new study set out to determine whether this molecular redundancy translates into worse outcomes at the bedside.

Researchers led by Pravalika Sathyanarayana, Sharadadevi Y Mannur, and Mahadevamma Lingaiah conducted a prospective observational study at a tertiary care hospital in South India between January 2024 and January 2025. They enrolled ICU patients with culture-confirmed carbapenem-resistant K. pneumoniae infections and used real-time polymerase chain reaction to detect five carbapenemase genes: bla_NDM, bla_OXA-48-like, bla_IMP, bla_VIM, and bla_KPC. Patients were stratified into four genotypic groups, those carrying bla_NDM alone, those carrying bla_OXA-48-like alone, co-producers carrying both, and non-producers, and the primary outcome was 28-day all-cause in-hospital mortality. Written informed consent was obtained from patients or their legally authorized representatives, and the study was approved by the institutional ethics committee and conducted under the Declaration of Helsinki.

The molecular findings were striking. Of the 106 patients, 30, or 28.3 percent, harbored isolates that co-produced both carbapenemases, while 16 patients, or 15.1 percent, died within 28 days of infection. Mortality varied significantly across genotypes, and the highest proportion of deaths occurred among patients infected with co-producing isolates, with 9 of 30 such patients, or 30 percent, dying within the follow-up window. That is roughly double the overall cohort mortality rate and suggests that the dual-enzyme phenotype marks a subset of infections that behave differently in critically ill hosts.

To quantify these associations, the team used Firth penalized logistic regression, a statistical approach designed for situations where outcome events are sparse and conventional maximum-likelihood models can fail or produce unstable estimates. In univariable analysis, mechanical ventilation was associated with a 12.47-fold increase in the odds of 28-day mortality, septic shock with a 25.11-fold increase, and each point increase on the APACHE II illness-severity score with a 29 percent increase in odds. Co-producer status itself carried an unadjusted odds ratio of 4.09, meaning patients with dual-carbapenemase isolates had roughly four times the odds of death compared with the rest of the cohort, a statistically significant association.

The exploratory multivariable model, which adjusted for these competing risk factors, retained three independent predictors: higher APACHE II score with an adjusted odds ratio of 1.24, septic shock with an adjusted odds ratio of 12.23, and carbapenemase co-production with an adjusted odds ratio of 7.50. In other words, even after accounting for how sick patients were on admission and whether they had progressed to septic shock, carrying a dual-carbapenemase strain was associated with more than a sevenfold increase in the odds of dying within 28 days. Model diagnostics showed no problematic multicollinearity, with variance inflation factors ranging from 1.12 to 1.28, and the apparent area under the receiver operating characteristic curve reached 0.975, indicating strong discrimination within this dataset.

The authors are careful to frame these numbers with appropriate scientific caution. The adjusted odds ratio for co-production of 7.50 came with a 95 percent confidence interval stretching from 1.50 to 51.67, an extraordinarily wide range that reflects the limited number of mortality events in the cohort. With only 16 deaths distributed across four genotypic groups, the point estimate is statistically significant but the true magnitude of the effect could plausibly be anywhere from a modest doubling of risk to a fifty-fold increase. The adjusted analysis was therefore explicitly labeled exploratory, and the apparent AUC of 0.975 was not internally validated, meaning its impressive value may partly reflect overfitting to this particular sample.

Residual confounding also looms over the findings. The study did not capture detailed data on antimicrobial management or source control, the surgical or procedural measures used to eliminate the focus of infection, and both are powerful determinants of survival in severe bacterial sepsis. It is conceivable that patients with co-producing strains received less effective empiric therapy, or that their infections were harder to eradicate for reasons unrelated to the resistance genes themselves. The single-center design further limits generalizability, since gene prevalence, prescribing patterns, and ICU case mix vary widely across institutions and regions. The authors call for larger multicenter studies incorporating detailed treatment and source-control data to determine whether the association is reproducible.

Even with those caveats, the study carries a pointed message for clinicians and laboratories. Rapid molecular detection of carbapenemase genes, rather than reliance on phenotypic susceptibility panels alone, can identify high-risk co-producing strains early enough to inform therapy, infection control measures, and conversations with families about prognosis. It also reinforces the urgency of stewardship programs designed to slow the horizontal spread of these plasmid-borne genes, because every co-producing isolate that circulates in an ICU represents a patient population at elevated risk. As antimicrobial resistance continues to outpace the development of new antibiotics, studies like this one demonstrate that the genetic composition of a pathogen is not just an epidemiological detail but a clinical variable that can mean the difference between recovery and death.

Subject of Research: Clinical impact of dual carbapenemase co-production on 28-day mortality in ICU patients with carbapenem-resistant Klebsiella pneumoniae: a prospective study from South India

Article Title: Clinical impact of dual carbapenemase co-production on 28-day mortality in ICU patients with carbapenem-resistant Klebsiella pneumoniae: a prospective study from South India

Article References: Sathyanarayana, P., Mannur, S. Y., & Lingaiah, M. (2026). Clinical impact of dual carbapenemase co-production on 28-day mortality in ICU patients with carbapenem-resistant Klebsiella pneumoniae: a prospective study from South India. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14539-1

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14539-1

Keywords: Clinical, impact, dual, carbapenemase, co-production, mortality, patients, carbapenem-resistant, Klebsiella, pneumoniae, prospective, South