Non-fermenting Gram-negative bacilli, abbreviated NFGNB, are a heterogeneous group of bacteria that do not ferment glucose and thrive in moist hospital environments. The two most clinically important members are Pseudomonas aeruginosa and the Acinetobacter calcoaceticus-baumannii complex, both of which have climbed the World Health Organization’s priority lists for antibiotic research because they increasingly shrug off nearly every drug in the formulary. In the Agartala cohort, Pseudomonas aeruginosa dominated, accounting for 88.3 percent of the isolates, while the Acinetobacter calcoaceticus-baumannii complex made up the remaining 11.7 percent. Soft tissue infections, which range from superficial wound infections to deep, life-threatening involvement of fascia and muscle, represent a particularly dangerous niche for these organisms because damaged tissue provides an entry point and local blood supply may be compromised.

The central therapeutic problem examined in the study is the loss of two critical drug classes. Carbapenems, once considered the reliable last line of defense against Gram-negative infections, are rendered ineffective when bacteria produce metallo-beta-lactamases, or MBLs, enzymes that use a zinc ion at their active site to hydrolyze the beta-lactam ring common to penicillins, cephalosporins, and carbapenems alike. When carbapenems fail, clinicians often turn to colistin, a polymyxin antibiotic so toxic to the kidneys that it was largely abandoned in the 1970s and then revived as a drug of last resort. Colistin resistance, in turn, can be mediated by mcr genes, mobile genetic elements that modify the lipopolysaccharide of the bacterial outer membrane so that the drug can no longer bind. The prospect of bacteria carrying both mechanisms simultaneously is what keeps infection control specialists awake at night, because it effectively removes the final pharmacological safety net.

To quantify the scale of the problem, the researchers first used the combined disk test, a phenotypic assay in which carbapenem disks are placed on bacterial lawns with and without a chelating agent such as EDTA that strips zinc from metallo-beta-lactamases. If the inhibition zone around the disk expands in the presence of the chelator, the enzyme is identified as an MBL. This screening identified MBL production in 25 of the Pseudomonas aeruginosa isolates and 13 of the Acinetobacter calcoaceticus-baumannii complex isolates. The team then confirmed and characterized the resistance at the molecular level using PCR to detect three major MBL gene families: blaNDM, blaIMP, and blaVIM. Among the isolates carrying MBL genes, blaNDM, which encodes the New Delhi metallo-beta-lactamase, was clearly predominant, consistent with the gene’s well-documented dominance across the Indian subcontinent and its global dissemination through travel and medical tourism.

On the colistin front, the picture was equally concerning. Resistance to colistin was observed in 19.5 percent of the Acinetobacter calcoaceticus-baumannii complex isolates, a substantial proportion given that colistin is frequently the only remaining option for these infections. The researchers screened for the full panel of known mobile colistin resistance genes, mcr-1 through mcr-9, using PCR. The most alarming finding was the detection of two strains harboring both blaNDM and mcr-3 simultaneously, meaning these bacteria could destroy carbapenems with a metallo-enzyme and block colistin binding with an MCR-3 modified cell surface. The mcr-3 gene is particularly interesting from an evolutionary standpoint because, unlike the more widely studied mcr-1 which originated in Escherichia coli from livestock, mcr-3 has been documented in diverse bacterial species and environments, and recent work has suggested that the MCR-3 enzyme may even help bacteria evade host phagocytosis, adding a virulence dimension to its resistance role.

Detecting resistance genes is only half the story; understanding how resistant strains move through a hospital is equally important for stopping them. For this, the team turned to ERIC-PCR, enterobacterial repetitive intergenic consensus polymerase chain reaction, a genomic fingerprinting technique that amplifies DNA regions between repetitive elements scattered across bacterial chromosomes. Because the spacing and number of these elements vary between strains, the resulting banding patterns serve as a rapid, low-cost proxy for genetic relatedness. The researchers analyzed the banding profiles using GelJ software and constructed phylogenetic trees with MEGA11 to visualize which isolates were likely clonal descendants of a common ancestor.

The fingerprinting results revealed clonal dissemination within the hospital, with genetically related isolates clustering particularly in the surgery and burn wards. This is epidemiologically significant because burn patients and surgical patients share predictable risk factors: breached skin barriers, prolonged hospital stays, indwelling devices, and heavy exposure to broad-spectrum antibiotics that select for resistant organisms. When a single clone establishes itself in such a ward, standard cleaning and hand hygiene failures allow it to colonize successive patients. Notably, the clustered isolates mostly shared cluster-specific resistance patterns, meaning that members of the same genetic lineage carried the same resistance gene profile. This concordance between genotype and resistance phenotype suggests that resistance determinants are being inherited vertically along with the clone itself rather than acquired independently by unrelated strains, which strengthens the case that transmission of whole organisms, not just horizontal gene transfer, is driving the observed pattern.

The co-occurrence of blaNDM and mcr-3 in the same strains deserves particular emphasis because it represents a convergence of two resistance mechanisms that were historically carried by different bacterial populations in different reservoirs. Carbapenem resistance has long been entrenched in hospital settings, while mcr genes were first identified in food animals and agricultural environments, raising fears that the agricultural and clinical reservoirs would eventually merge. The Agartala findings provide direct evidence that this convergence is happening in clinical isolates from soft tissue infections, not merely in surveillance studies of gut carriage. Each additional resistance mechanism stacked onto a circulating clone narrows the therapeutic window further; an infection caused by a strain producing NDM and carrying mcr-3 leaves clinicians with very few options, potentially including older, more toxic agents or combination therapies with limited evidence behind them.

The authors of the study, Ankan Chakrabarti, Tapan Majumdar, and Sibabrata Bhattacharya, frame their findings as a call for continuous molecular surveillance, rigorous hospital infection control, and stringent antibiotic stewardship. The seven-year prospective design strengthens the conclusions because it captures trends across time rather than a single snapshot, and the combination of phenotypic, molecular, and typing methods provides a layered picture of the resistance problem. The study was conducted with ethical approval from the institutional ethics committee and informed consent from participants, and the authors report no competing interests. While the data come from a single tertiary care center in Northeast India, the mechanisms documented there are not geographically confined; blaNDM and mcr genes travel readily through plasmids, transposons, and the international movement of patients.

For the broader scientific and public health community, the study underscores several practical lessons. First, soft tissue infections should not be overlooked as a reservoir of extreme drug resistance, since much surveillance attention focuses on bloodstream and respiratory isolates. Second, genotyping methods such as ERIC-PCR, despite being older and less granular than whole-genome sequencing, remain valuable tools for resource-limited laboratories to detect outbreaks early and trace transmission routes between wards. Third, the detection of mcr genes in Acinetobacter, an organism in which colistin resistance has more often been attributed to chromosomal mutations than to mobile genes, signals that mobile colistin resistance is expanding its host range among non-fermenting bacilli. As hospitals worldwide grapple with the post-antibiotic era, studies like this one from Agartala serve as an early warning: the bacteria that cause the most difficult infections are accumulating resistance determinants faster than new drugs are arriving, and the window for containment through surveillance, hygiene, and disciplined antibiotic use is narrowing with each clonal cluster identified.

Subject of Research: Genomic characterization of metallo-beta-lactamase and mcr-mediated resistance in non-fermenting Gram-negative bacilli from soft tissue infections

Article Title: Genomic characterization of non-fermenting gram-negative bacilli with metallo beta lactamase production and mcr based colistin resistance causing soft tissue infections: a seven-year hospital based prospective cross-sectional study

Article References: Chakrabarti, A., Majumdar, T., & Bhattacharya, S. (2026). Genomic characterization of non-fermenting gram-negative bacilli with metallo beta lactamase production and mcr based colistin resistance causing soft tissue infections: a seven-year hospital based prospective cross-sectional study. Molecular Biology Reports, 53(1), Article 1629. https://doi.org/10.1007/s11033-026-12802-x

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12802-x

Keywords: antimicrobial resistance, metallo-beta-lactamase, NDM, mcr genes, colistin resistance, Pseudomonas aeruginosa, Acinetobacter baumannii, soft tissue infections, ERIC-PCR, nosocomial infection, carbapenem resistance, hospital surveillance

Cellulitis is a bacterial infection of the skin and the soft tissue beneath it, most often caused by streptococci or staphylococci that slip through cracks in the skin’s protective barrier. The result is a red, hot, swollen and painful area of skin, usually on the lower legs, often accompanied by fever and malaise. Although antibiotics can usually clear the infection, cellulitis imposes a substantial burden on health systems, because severe cases require intravenous therapy and hospital admission, and a considerable share of patients return with new episodes months or years later. Despite how frequently clinicians encounter the disease, risk factors reported in the literature have been inconsistent, which is precisely the gap the Vienna team set out to close.

The researchers designed their investigation as a retrospective case-control study, a design that compares people who have a condition with people who do not, and then looks backward to identify exposures or characteristics that differ between the two groups. In this case, the cases were 1,395 patients treated for cellulitis, while the controls numbered 667. Using regression models, the team analyzed which variables were associated with three distinct outcomes: the initial development of cellulitis, the occurrence of recurrent episodes, and prolonged hospitalization. Statistical models of this kind produce odds ratios, figures that express how much more likely an outcome is in the presence of a given factor, together with confidence intervals that indicate the precision of the estimate and p-values that signal statistical significance.

The results paint a remarkably consistent picture. Male sex emerged as a strong risk factor for developing cellulitis in the first place, with an odds ratio of 2.68, meaning men in the dataset had nearly triple the odds of women. Higher baseline age also mattered, with each additional year of age modestly but significantly raising the odds, reflected in an odds ratio of 1.03 per year. These demographic findings align with the clinical intuition that older patients and male patients are overrepresented on wards treating soft tissue infections, but the study places those impressions on firm quantitative footing.

The most striking findings concerned breaches of the skin barrier, which dwarfed every other risk factor in magnitude. Patients with tinea pedis, the fungal infection commonly known as athlete’s foot, had an odds ratio of 72.48 for developing cellulitis, an enormous effect that underscores how the fissures and scaling produced by a seemingly minor fungal problem can open the door to serious bacterial invasion. Ulcers carried an odds ratio of 45.79, traumatic wounds an odds ratio of 229.26, stasis dermatitis an odds ratio of 10.81, and eczema an odds ratio of 13.14. In other words, almost any condition that compromises the integrity of the skin, whether through inflammation, ulceration or injury, dramatically multiplies the risk that bacteria will gain entry and establish an infection in the underlying tissue.

Fluid-related conditions formed a second major cluster of risk. Venous insufficiency, in which faulty valves in the leg veins allow blood to pool and fluid to leak into the tissues, was associated with an odds ratio of 2.36. Lymphoedema, the swelling that results from impaired drainage of lymph fluid, carried an odds ratio of 11.21, and oedema not otherwise specified an odds ratio of 13.12. The biological logic is compelling: fluid-rich, swollen tissue is thought to impair local immune defenses and circulation, creating an environment in which bacteria that have breached the skin can proliferate more easily. Clinicians have long observed that patients with chronically swollen legs are prone to cellulitis, and this study quantifies just how pronounced that vulnerability is.

Metabolic and chronic systemic conditions also left their mark. Diabetes mellitus was associated with an odds ratio of 1.58 for disease onset, chronic kidney disease with an odds ratio of 2.29, and obesity with an odds ratio of 2.74. Each of these conditions is known to affect immunity, tissue perfusion or wound healing in ways that could plausibly facilitate infection. Diabetes impairs both immune cell function and microvascular circulation, chronic kidney disease is linked to immune dysfunction and fluid overload, and obesity is associated with chronic low-grade inflammation, altered lymphatic drainage and skin fold problems that can compromise the barrier function of the skin.

Perhaps the most clinically consequential finding is that obesity did not merely raise the risk of a first episode. It was also a consistent risk factor for multiple disease episodes, with an odds ratio of 1.73, and for prolonged hospitalization, with an odds ratio of 1.72. This means that patients with obesity were not only more likely to develop cellulitis in the first place but also more likely to experience the disease repeatedly and to require longer hospital stays when they did. In an era when obesity rates continue to climb globally, this finding suggests that the burden of cellulitis on health systems may grow in parallel, and it highlights weight management as a potential long-term strategy for reducing both the incidence and the severity of the disease.

The authors conclude that male sex, higher age, breaches of the skin barrier, oedema, diabetes mellitus, chronic kidney disease and obesity may act as strong risk factors for cellulitis, with obesity additionally predisposing patients to recurrent episodes and extended hospitalization. The practical implications are significant. For patients with athlete’s foot, ulcers, eczema or leg swelling, meticulous skin care and prompt treatment of these conditions could represent a highly effective form of prevention, given the enormous odds ratios attached to barrier defects. For patients with lymphoedema or venous insufficiency, compression therapy and careful management of swelling may reduce infection risk. And for the growing population of patients with obesity, the study adds another compelling reason to address weight as a modifiable factor in infectious disease risk.

As with any retrospective case-control study, the findings describe associations rather than proven causal relationships, and the retrospective design means the researchers relied on previously recorded data rather than prospective observation. Nevertheless, the large number of patients analyzed and the breadth of risk factors examined make this one of the most comprehensive assessments of cellulitis epidemiology available. By systematically separating the factors that drive the first infection from those that drive recurrence and prolonged hospital stay, the Vienna team has given clinicians a clearer map of where to focus preventive efforts, from treating fungal foot infections and managing leg swelling to recognizing obesity as a factor that shapes the entire trajectory of this common and costly infection.

Subject of Research: Risk factors for the onset, recurrence and prolonged hospitalization of cellulitis patients

Article Title: Risk factors for onset, recurrence and prolonged hospitalization in patients with cellulitis: a retrospective case-control study

Article References: Borst, C., Steiner, I., Stegmüller, S., Peichl, D., Egger, E., Symmank, D., Chromy, D., & Weninger, W. (2026). Risk factors for onset, recurrence and prolonged hospitalization in patients with cellulitis: a retrospective case-control study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14500-2

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14500-2

Keywords: cellulitis, skin infection, risk factors, obesity, tinea pedis, lymphoedema, diabetes mellitus, chronic kidney disease, case-control study, hospitalization, dermatology, infectious diseases