The study examined patients hospitalized with multidrug-resistant organism bloodstream infections from 1 January 2021 through 30 January 2026. Investigators compared demographic, clinical, microbiological, molecular, treatment-exposure and outcome data between oncologic and non-oncologic groups. ICU admission at the onset of infection was more frequent among oncologic patients, occurring in 25.4% compared with 4.8% of non-oncologic patients (p < 0.001). The primary outcome was 30-day all-cause mortality, assessed using survival analysis and logistic regression.

Among the 204 infections, KPC-producing Enterobacterales were the leading resistance determinant, identified in 147 cases (72.1%). Multidrug-resistant or carbapenem-resistant Acinetobacter species accounted for 35 cases (17.2%), NDM-producing Enterobacterales for 14 (6.9%) and VIM-producing Enterobacterales for six (2.9%). Multidrug-resistant or carbapenem-resistant Acinetobacter species bloodstream infection was more frequent in oncologic patients than in non-oncologic patients, but the difference was not statistically significant: 25.4% versus 13.8% (p = 0.07).

Multivariable analysis found that oncologic status was associated with a 3.19-fold higher odds of death within 30 days (adjusted odds ratio, 95% CI 1.92–5.21; p = 0.010). Infection with multidrug-resistant or carbapenem-resistant Acinetobacter species was also associated with mortality, with an adjusted odds ratio of 2.41 (95% CI 1.12–5.18; p = 0.020). Kaplan–Meier analysis showed lower 30-day survival among oncologic patients (log-rank p = 0.020), while seven-day mortality did not differ significantly between the groups: 13.6% versus 8.3% (p = 0.30). These observations do not establish that cancer or the Acinetobacter phenotype caused the deaths. As a single-center retrospective study based on hospitalized patients, its findings are limited in generalizability and cannot fully account for differences in underlying illness, comorbidity burden or other clinical factors between groups.

Subject of Research: Associations between oncologic status, resistance determinants and 30-day mortality in multidrug-resistant bloodstream infections

Article Title: Bloodstream infections caused by multidrug-resistant organisms in patients with and without cancer: clinical outcomes and resistance determinants in a southern Italian cohort

Article References: Di Gennaro, F., Ritacco, I. A., Giliberti, V., Frallonardo, L., Cibelli, M., De Gennaro, N., Fiordelisi, D., Signorile, F., Brindicci, G., Valenzano, A., Giacchetta, I., Lizzi, L., De Iaco, G., Milano, E., Sibilio, M., Colaizzi, C., Vigna, A., De Santis, L., Santoro, C. R., … Saracino, A. (2026). Bloodstream infections caused by multidrug-resistant organisms in patients with and without cancer: clinical outcomes and resistance determinants in a southern Italian cohort. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14475-0

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14475-0

Keywords: multidrug-resistant organisms, bloodstream infections, cancer patients, 30-day mortality, KPC-producing Enterobacterales, carbapenem-resistant Acinetobacter, retrospective cohort, oncologic status, Bloodstream, infections, caused, multidrug-resistant

The story begins with a clinical isolate recovered on January 20, 2022, from bronchoalveolar lavage fluid collected from a 58-year-old male patient admitted to the intensive care unit. The isolate, designated KP22-83, belonged to the ST11-KL64 lineage of K. pneumoniae, a sequence type that has become notorious worldwide for its capacity to acquire and disseminate carbapenem resistance. Antimicrobial susceptibility testing revealed a deeply troubling multidrug-resistant phenotype: the isolate showed high minimum inhibitory concentrations (MICs) to meropenem, ceftazidime, aztreonam, doxycycline, tobramycin, amikacin, and ciprofloxacin, while remaining susceptible only to polymyxin B, one of the last-resort antibiotics in clinical use. Most alarmingly, the isolate’s MIC to ceftazidime-avibactam reached 640/4 mg/L, an extraordinarily high value that signaled the presence of an unusual resistance mechanism.

Whole-genome sequencing, performed on the Illumina HiSeq 2,500 platform and assembled with SPAdes, identified the culprit: the blaKPC-287 gene, together with 11 additional antimicrobial resistance-associated genes and 34 virulence-associated genes. The resistance genes included aadA2, blaLAP-2, blaSHV-12, blaTEM-1, catA2, dfrA14, fosA6, qnrS1, rmtB1, sul2, and tet(A), a constellation of determinants spanning aminoglycosides, cephalosporins, phenicols, folate pathway inhibitors, fosfomycin, fluoroquinolones, and tetracyclines. The virulence genes were predominantly involved in siderophore-mediated iron acquisition and bacterial adherence, including the enterobactin biosynthesis and transport genes entA, entB, entE, entS, fepA, fepB, fepC, fepD, and fepG; the yersiniabactin-associated genes fyuA, irp1, irp2, ybtA, ybtE, ybtP, ybtQ, ybtS, ybtT, ybtU, and ybtX; the aerobactin-associated genes iucA, iucB, iucC, iucD, and iutA; and the adherence-associated genes fimA, fimE, ompA, ecpA, ecpB, ecpC, ecpD, ecpE, and ecpR. Collectively, these findings characterized KP22-83 as a clinically important multidrug-resistant ST11-KL64 isolate and warranted deeper investigation into the contribution of KPC-287 to its resistance phenotype.

To place KPC-287 in evolutionary context, the team retrieved all KPC protein sequences available in the NCBI database as of May 8, 2026, and aligned them using Clustal Omega. The KPC family now comprises more than 270 assigned variants, and resistance-associated changes are concentrated primarily within three structural regions: the 164–179 omega loop, the 237–243 loop, and the 267–275 loop. Phylogenetic analysis showed that KPC-287 clustered close to KPC-155, indicating a close sequence relationship between the two variants. Nucleotide and amino-acid sequence alignment revealed that KPC-287 differed from KPC-155 by two major changes: a proline-to-glutamine substitution at residue 168 (P168Q) and deletion of alanine at residue 242 (A242del), corresponding to one single-nucleotide substitution and one three-nucleotide deletion, respectively. Both changes fall squarely within the two regions most frequently implicated in the evolution of ceftazidime-avibactam resistance.

Structural analysis using AlphaFold-predicted models added a crucial layer of molecular detail. When the predicted structures of KPC-155 and KPC-287 were superimposed using PyMOL, both variants retained the typical KPC β-lactamase architecture and showed a highly similar global fold, with a root-mean-square deviation (RMSD) of only 0.093. The main structural differences were localized near residue 168 and the Ala242 deletion site. The P168Q substitution may alter local side-chain properties and conformational flexibility, whereas the A242 deletion may affect the arrangement of the adjacent β-strand and loop region. Previous structural studies have established that changes within the omega loop can weaken stabilizing interactions and increase conformational flexibility, potentially improving accommodation of the bulky ceftazidime side chain while altering susceptibility to avibactam, the diazabicyclooctane inhibitor designed to neutralize exactly this class of enzymes. The authors caution, however, that these predicted structural differences do not by themselves establish the individual contribution of each alteration to the resistance phenotype.

That contribution was established through cloning experiments. The DNA fragment containing the native upstream promoter and open reading frame of blaKPC-287 was amplified from KP22-83 genomic DNA and ligated into the pUC19 vector to generate pUC19-KPC-287. This construct was then introduced into two recipient backgrounds: Escherichia coli DH5α and K. pneumoniae ATCC 13883. The results were unambiguous. Introduction of pUC19-KPC-287 increased the ceftazidime-avibactam MIC from less than 0.25/4 mg/L to 64/4 mg/L in both E. coli DH5α and K. pneumoniae ATCC 13883, converting both recipient strains from fully susceptible to highly resistant. In contrast, meropenem MICs remained unchanged after acquisition of pUC19-KPC-287 in both backgrounds. The empty vector had no detectable effect on the susceptibility of either strain. Together, these results establish KPC-287 as a sufficient determinant of high-level ceftazidime-avibactam resistance in both E. coli and K. pneumoniae, while its expression had no measurable effect on meropenem susceptibility, a phenotype that echoes the pattern first described for KPC-31, a D179Y derivative of KPC-3 that was the first clinically described KPC variant associated with ceftazidime-avibactam resistance together with restoration of meropenem susceptibility.

The fitness consequences of KPC-287 carriage were then evaluated through a battery of phenotypic assays. Growth curves were broadly similar among the tested strains, but the pUC19-KPC-287 transformant exhibited slightly lower OD600 values in both DH5α and ATCC 13883 backgrounds, indicating that KPC-287 expression imposed a measurable but limited impairment of bacterial growth. Motility assays on semisolid plates containing 0.3% agar showed that pUC19-KPC-287 carriage significantly reduced migration in both bacterial backgrounds, as indicated by smaller migration diameters after 36 hours of incubation. In vitro competition assays, in which KPC-287-carrying and empty-vector strains were mixed at a 1:1 ratio and serially passaged for 72 hours, showed that relative fitness values remained below 1 and decreased over time in both backgrounds, confirming a competitive disadvantage for the KPC-287-carrying strains. Conversely, the pUC19-KPC-287 transformants produced significantly greater crystal violet-stained attached biomass than the corresponding empty-vector controls in both bacterial backgrounds. The authors note that because no construct carrying an ancestral or alternative KPC allele was included in the same vector and host, the biofilm-associated difference should not be interpreted as a KPC-287 variant-specific effect; it could reflect recombinant expression level, cloning context, host background, or indirect physiological effects.

Perhaps the most clinically consequential finding concerns the mobility of the blaKPC-287 gene itself. Sequence analysis showed that blaKPC-287 was located on a hybrid IncFIIpHN7A8:IncR plasmid, embedded within an insertion sequence-rich region adjacent to ISKpn27, ISSwi1, and IS26. The presence of multiple IS26 copies throughout the plasmid indicated a mosaic multidrug-resistance plasmid architecture with potential for horizontal dissemination and structural rearrangement. Conjugation assays, in which KP22-83 served as the donor and a laboratory-preserved hygromycin-resistant strain YZ6 as the recipient, identified transconjugants carrying blaKPC-287 together with the IncFII and IncR replicon markers, supporting the transferability of the gene in an IncFII/IncR plasmid background under the tested mating conditions. Stability testing added another layer of concern: after 30 consecutive passages, blaKPC-287 remained detectable under both antibiotic-free conditions and subinhibitory ceftazidime-avibactam exposure, with 96 randomly selected colonies per condition analyzed by colony PCR. The gene, in other words, is not only transferable but also stubbornly retained, whether or not the antibiotic combination is present to select for it.

Virulence was evaluated using a Galleria mellonella infection model, in which larvae were infected with K. pneumoniae ATCC 13883, ATCC 13883-pUC19, ATCC 13883-pUC19-KPC-287, KP22-83, or the hypervirulent control strain KP19-2065. KP19-2065 caused the greatest larval mortality, with 40% survival at 72 hours post-infection. Although KP22-83 was less virulent than KP19-2065, it also caused substantial larval mortality, with 50% survival at 72 hours. In contrast, survival was comparable among larvae infected with ATCC 13883, ATCC 13883-pUC19, and ATCC 13883-pUC19-KPC-287, indicating that expression of KPC-287 alone did not measurably enhance larval killing in the ATCC 13883 background. The pronounced virulence observed in KP22-83 is more likely related to its additional virulence-associated determinants, including aerobactin, yersiniabactin, enterobactin, fimbrial, and adherence-associated genes, rather than to KPC-287 itself. The authors acknowledge that the G. mellonella model is useful for preliminary virulence assessment but cannot substitute for mammalian infection models.

Several limitations frame the interpretation of these findings. Cloning in the high-copy-number pUC19 vector may not reflect the native blaKPC-287 expression level, and the observed resistance phenotype may be influenced by gene dosage rather than completely mirroring its effect in the native IncFII/IncR plasmid context. Functional validation was limited to two laboratory hosts, and only one clinical isolate was examined, leaving the prevalence, evolutionary origin, and geographic distribution of KPC-287 unknown. Biofilm was evaluated only by crystal violet staining, and no ancestral or alternative KPC allele was tested in the same vector-host background, so a KPC-287-specific effect on biofilm formation cannot be inferred. Isogenic allele comparisons and mechanistic validation are required to determine whether KPC-287 specifically contributes to biofilm development. Nevertheless, the study identifies KPC-287 as a potentially clinically relevant ceftazidime-avibactam resistance determinant and highlights the urgent need for continuous genomic surveillance and functional characterization of emerging KPC variants. The 2024 World Health Organization Bacterial Priority Pathogens List ranked carbapenem-resistant K. pneumoniae as the highest-priority bacterial threat, and the emergence of variants like KPC-287 that can defeat the therapeutic options designed to counter it only sharpens that concern. As the KPC family continues to expand under therapeutic pressure, the message from this study is clear: the evolution of resistance is not slowing down, and the surveillance of emerging variants must keep pace.

Subject of Research: Characterization of KPC-287 conferring high-level ceftazidime–avibactam resistance in an ST11-KL64 Klebsiella pneumoniae isolate

Article Title: Characterization of KPC-287 conferring high-level ceftazidime–avibactam resistance in an ST11-KL64 Klebsiella pneumoniae isolate

Article References: Gong, Y., Shen, Y., Lu, J., Li, Y., Qin, S., Shi, X., & Tian, X. (2026). Characterization of KPC-287 conferring high-level ceftazidime–avibactam resistance in an ST11-KL64 Klebsiella pneumoniae isolate. Frontiers in Microbiology, 17, Article 1938185. https://doi.org/10.3389/fmicb.2026.1938185

Image Credits: AI Generated

DOI: 10.3389/fmicb.2026.1938185

Keywords: Characterization, KPC-287, conferring, high-level, ceftazidime, avibactam, resistance, ST11-KL64, Klebsiella, pneumoniae, isolate, scientific research

The research team, led by clinical laboratory scientists at the Ministry of Defense hospital alongside collaborators from Umm Al Qura University and Taif University, compiled antibiogram data from 5,626 specimens that yielded significant bacterial growth. These included 3,022 urine samples, 1,438 blood cultures, 875 lower respiratory tract samples such as sputum and tracheal aspirates, and 291 wound swabs. All organisms were identified using standard microbiological techniques, and antibiotic susceptibility testing followed the guidelines of the Clinical and Laboratory Standards Institute. The team tested dozens of antibiotics, spanning old workhorses like ampicillin and gentamicin to modern combinations like ceftazidime-avibactam, designed specifically to defeat bacteria armed with destructive beta-lactamase enzymes.

To move beyond simple snapshots of resistance, the researchers applied binary logistic regression models to each antibiotic individually, treating resistance as a binary outcome and year as a continuous predictor. This approach yielded an odds ratio for each drug, quantifying how the odds of resistance changed with each passing year, along with confidence intervals that indicate whether a trend is statistically reliable. The team also used multinomial logistic regression to track shifts in the composition of bacterial species and the distribution of infection sites over time. The result is one of the more granular pictures of resistance dynamics available for the region, capturing not just which drugs are failing but how quickly, and against which pathogens.

The statistical analysis identified a cluster of antibiotics with statistically significant and rising resistance. Tigecycline, a glycylcycline often deployed against carbapenem-resistant bacteria, showed an odds ratio of 1.442 per year, meaning the odds of resistance climbed roughly 44 percent annually. Ceftazidime-avibactam, a flagship cephalosporin-betalactamase inhibitor combination reserved for multidrug-resistant Gram-negative infections, showed an odds ratio of 1.395. Fosfomycin, aztreonam, cefoxitin, and piperacillin-tazobactam all showed significant year-on-year increases as well. What makes these numbers especially troubling is the identity of the drugs involved: ceftazidime-avibactam and tigecycline are frequently counted among the final therapeutic options against carbapenem-resistant Enterobacterales, a group of bacteria that the World Health Organization regards as one of the gravest threats in modern medicine.

Paradoxically, the news was not uniformly bleak. The carbapenems imipenem and meropenem, long considered benchmark drugs for serious Gram-negative infections, showed stable resistance patterns throughout the study, with odds ratios hovering near one. Resistance to amikacin actually declined significantly, with an odds ratio of 0.798, and trimethoprim-sulfamethoxazole also registered a modest but statistically significant decrease. The authors interpret this split pattern as evidence that the problem is not a uniform drift toward resistance across the entire antibiotic arsenal, but rather a targeted erosion of the newer, broader agents that are pressed into service against the hardest infections, often under intense selective pressure.

Perhaps the most striking finding concerned extended-spectrum beta-lactamase, or ESBL, production among Escherichia coli. Of 2,033 isolates examined for this phenotype, 29 percent, or 607 isolates, were ESBL producers, enzymes that hydrolyze penicillins and most cephalosporins and render first-line treatments ineffective. E. coli dominated the pathogen landscape throughout the study, accounting for 1,540 of the non-duplicate isolates, and its share of infections actually grew over time, rising from 58.5 percent of isolates in 2020 to 66.9 percent in 2024. Meanwhile, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus all declined in relative frequency. The dataset included 614 K. pneumoniae isolates, 172 Acinetobacter isolates, 151 P. aeruginosa isolates, and 105 S. aureus isolates.

The geography of infection also shifted in ways that carry clinical consequences. Urinary tract infections expanded steadily, from 66 percent of specimen sources in 2020 to 79.1 percent in 2024, while lower respiratory tract infections collapsed from 18.3 percent to just 8.9 percent over the same period. Bloodstream and wound infections declined slightly. Combined with the rising dominance of E. coli, these numbers sketch a scenario in which resistant urinary pathogens are becoming the region’s central clinical challenge, a pattern consistent with global surveillance showing ESBL prevalence in some regions climbing from 44 percent to 59 percent over the past decade. For clinicians, this means empirical treatment of urinary infections, one of the most common reasons for antibiotic prescriptions, is increasingly likely to fail without susceptibility confirmation.

The study’s timeframe points to an uncomfortable suspect: the COVID-19 pandemic. During the early waves, large proportions of patients received broad-spectrum antibiotics empirically, despite the disease being viral and bacterial co-infection being uncommon. This practice, combined with the reallocation of healthcare resources and the suspension or weakening of antimicrobial stewardship programs, imposed intense selective pressure on hospital and community bacterial populations. The authors note that recent research has established resistance to tigecycline and ceftazidime-avibactam can emerge in some settings within a single month under such pressure, with non-susceptibility to tigecycline rising from virtually zero percent in 2019 to 71 percent in 2022 in certain clinical contexts, and ceftazidime-avibactam resistance climbing from 27 percent to 70 percent.

The concept of therapeutic exhaustion captures what happens when each successive line of defense erodes faster than new agents can be developed. When carbapenems remain stable but the drugs reserved for carbapenem-resistant infections begin to fail, the effective treatment window narrows from both sides. Previous studies in Saudi Arabia had already documented concerning resistance levels, including reports of 30 percent ESBL positivity and 74 percent multidrug resistance among isolates in some settings. The new data extend that picture longitudinally, showing that the problem is not static but accelerating for precisely the drugs where acceleration matters most.

The authors argue that their findings make a strong case for revitalizing antimicrobial stewardship programs and reassessing empirical treatment guidelines in the region, particularly for urinary tract infections, where presumptive therapy without susceptibility testing may soon become untenable for some patients. They emphasize that resistance patterns differed across bacterial species and infection sites, underscoring the need for site-specific, pathogen-targeted treatment strategies rather than one-size-fits-all protocols. Without strict intervention and careful antibiotic use, they warn, the medical community may soon face infections for which no viable therapeutic options remain. For a region where many tertiary care hospitals historically lacked systematic resistance data, this five-year antibiogram represents both a warning and a template: continuous, statistically rigorous local surveillance is not an academic luxury, but the foundation on which every rational prescribing decision now depends.

Subject of Research: Antimicrobial resistance trends in pathogenic bacteria isolated from clinical specimens at a Saudi hospital from 2020 to 2024

Article Title: Antibiogram of pathogenic bacterial isolates from various samples in Prince Sultan Hospital, Western Region, Saudi Arabia. Retrospective study from 2020 to 2024

Article References: Alqurashi, E. H., Obaid, N. A., Alzahrani, A., Alshareef, F. S., Mohandes, N. M., Althyabi, A. M., Albugami, S., & Almammari, S. (2026). Antibiogram of pathogenic bacterial isolates from various samples in Prince Sultan Hospital, Western Region, Saudi Arabia. Retrospective study from 2020 to 2024. Frontiers in Antibiotics, 5, Article 1872911. https://doi.org/10.3389/frabi.2026.1872911

Image Credits: AI Generated

DOI: 10.3389/frabi.2026.1872911

Keywords: antimicrobial resistance, antibiogram, ESBL, Escherichia coli, tigecycline, ceftazidime-avibactam, carbapenem-resistant Enterobacterales, COVID-19, antimicrobial stewardship, urinary tract infections, Saudi Arabia, clinical microbiology

The study team, led by Jianhong Yu and colleagues in the hospital’s Department of Clinical Laboratory, began with 18,581 laboratory records drawn from twelve quarterly microbiology datasets. Applying the Clinical and Laboratory Standards Institute’s recommended rule of retaining only the first isolate of each bacterial species per patient per calendar year, they removed 1,615 repeat records, leaving 16,966 isolate-level observations from 15,095 unique patients. Yearly volumes rose steadily, from 5,081 isolates in 2023 to 5,536 in 2024 and 6,349 in 2025. Gram-negative organisms dominated the cohort at 75.9 percent, with Gram-positive bacteria accounting for the remaining 24.1 percent. Respiratory specimens were the leading source at 43.5 percent of isolates, followed by urine at 21.3 percent, abdominal fluid at 13.1 percent, pus and secretions at 12.4 percent, and blood at 7.8 percent.

The demographic and care-setting structure of the cohort shaped everything that followed. General wards contributed 91.2 percent of isolates, intensive care units 7.8 percent, and outpatient departments a mere 0.9 percent. By age, 24.2 percent of isolates came from patients under 18 years, 31.3 percent from adults aged 18 to 64, and 44.5 percent from patients 65 and older. Escherichia coli was the most frequently recovered organism at 28.6 percent of the total, followed by Klebsiella pneumoniae at 10.4 percent, Pseudomonas aeruginosa at 9.8 percent, Haemophilus influenzae at 9.2 percent, and Staphylococcus aureus at 8.5 percent. Pediatric isolates were markedly enriched for H. influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, whereas P. aeruginosa, K. pneumoniae, Acinetobacter baumannii, and enterococci were more prominent among older-adult and intensive-care isolates, a distribution that reflects both the sampling frame and the underlying ecology of infection across age groups.

Methodologically, the study took deliberate steps to avoid artifacts that plague many local surveillance reports. All available minimum inhibitory concentrations and inhibition-zone diameters were reinterpreted against a single breakpoint framework, the CLSI M100 35th edition from 2025, eliminating bias from changing interpretive criteria across study years. Bacterial identification relied on the VITEK 2 Compact automated system and VITEK MS MALDI-TOF mass spectrometry, with susceptibility testing performed by VITEK 2 cards, Kirby-Bauer disk diffusion, gradient diffusion, and the ATB system for fastidious organisms. Resistance proportions used antimicrobial-specific tested denominators, so isolates lacking an interpretable result for a given drug were excluded from that drug’s denominator rather than silently counted as susceptible. Temporal associations were estimated with binomial logistic regression, modeling calendar year ordinally and using patient-clustered robust standard errors to account for the fact that the same patient could contribute multiple species or observations across years. Adjusted models included calendar year, age, sex, and care setting, and exploratory organism-drug comparisons were controlled with the Benjamini-Hochberg false discovery rate.

The headline resistance findings split cleanly along two axes. Carbapenem resistance in E. coli remained uncommon throughout, affecting 70 of 4,848 isolates, or 1.4 percent, and showed no significant temporal trend, moving only from 1.3 percent in 2023 to 1.7 percent in 2025. K. pneumoniae carbapenem resistance was similarly low at 63 of 1,769 isolates, or 3.6 percent, fluctuating between 4.4, 2.7, and 3.7 percent across the three years without a monotonic direction. These figures sit well below the CHINET 2025 national surveillance report, which recorded imipenem and meropenem resistance of 2.4 and 2.6 percent for E. coli but a striking 21.9 and 21.0 percent for K. pneumoniae, underscoring how sharply local epidemiology can diverge from national aggregates.

Among the non-fermenting Gram-negative bacteria, the picture was far grimmer and tightly linked to care intensity. Carbapenem-resistant P. aeruginosa accounted for 190 of 1,659 isolates, or 11.5 percent overall, but reached 27.7 percent among ICU isolates compared with 9.9 percent in general wards. Carbapenem-resistant A. baumannii was even more concentrated, at 128 of 380 isolates, or 33.7 percent overall, rising to 68.8 percent in intensive care versus 21.8 percent on general wards. In multivariable models adjusted for age, sex, and calendar year, ICU or critical-care status remained independently associated with both phenotypes, with adjusted odds ratios of 2.80 for CRPA and 4.29 for CRAB, both highly statistically significant. Notably, the unadjusted upward trend in CRPA, which rose from 8.7 percent in 2023 to 13.5 percent in 2025, was attenuated and no longer significant after case-mix adjustment, suggesting that shifting patient composition rather than a pure secular drift may have driven much of the apparent increase. CRAB, by contrast, declined numerically from 38.6 to 29.4 percent without reaching statistical significance.

Two Gram-positive findings deserve particular attention. Methicillin-resistant S. aureus accounted for roughly a quarter of S. aureus isolates, at 24.1 percent in general wards and 24.4 percent in intensive care, slightly below the 28.4 percent reported nationally by CHINET in 2025, and no S. aureus isolate showed resistance to vancomycin or linezolid. More unexpected was the phenotypic linezolid non-susceptibility in Enterococcus faecalis, observed in 60 of 325 isolates, or 18.5 percent, with annual rates holding steady between 17.3 and 19.0 percent and no temporal trend. That figure is substantially higher than the 5.9 percent linezolid resistance rate CHINET reported for E. faecalis in 2025. The authors are careful with the terminology: all enterococcal isolates initially flagged as non-susceptible to vancomycin or linezolid underwent gradient-diffusion retesting, but reference broth microdilution and molecular confirmation were not performed, so the finding is reported as phenotypic non-susceptibility rather than confirmed resistance. Genome-level research has shown that enterococcal linezolid resistance typically arises through 23S ribosomal RNA mutations or transferable genes such as optrA, poxtA, and cfr, with optrA being the most common element in E. faecalis strains of Chinese origin that have spread globally, but confirming any such mechanism here would require the molecular work the study did not perform.

The clearest adjusted temporal signal in the entire dataset came from adult H. influenzae. Ampicillin resistance among isolates from patients aged 18 and older climbed from 35 of 50 isolates, or 70.0 percent, in 2023 to 214 of 243 isolates, or 88.1 percent, in 2025, an absolute increase of 18.1 percentage points with an adjusted odds ratio per year of 1.73 that persisted after case-mix adjustment. Amoxicillin-clavulanate resistance rose even more dramatically, from 8 of 50 isolates, or 16.0 percent, to 145 of 243 isolates, or 59.7 percent, a 43.7 percentage-point jump with an adjusted odds ratio per year of 3.06. Beta-lactamase positivity increased in parallel, from 70.0 to 84.8 percent, and the descriptive MIC distributions shifted accordingly: the ampicillin MIC50 for adult isolates rose from 16 mg/L in 2023 to 64 mg/L in 2024 and 2025, while the amoxicillin-clavulanate MIC50 moved from 4 to 8 mg/L by 2025 with observed values reaching 64 mg/L. The authors note that the concurrent rise in beta-lactamase production, MICs, and amoxicillin-clavulanate resistance is compatible with additional non-beta-lactamase mechanisms such as altered penicillin-binding protein 3, the target of ftsI mutations that drive beta-lactamase-negative ampicillin-resistant and beta-lactamase-positive amoxicillin-clavulanate-resistant phenotypes, but without molecular testing this mechanistic explanation remains hypothetical. They also caution that the adult H. influenzae denominator grew substantially across the study years, so changes in culture ordering, testing utilization, or case mix could have contributed to the observed pattern.

For clinical practice, the authors frame their results as local susceptibility evidence rather than direct evidence of treatment effect. The low carbapenem resistance rates in E. coli and K. pneumoniae point to strong in vitro carbapenem activity against most isolates in this dataset but do not justify indiscriminate empirical carbapenem use. The concentration of CRAB and CRPA in intensive care argues for setting-specific cumulative antibiograms, review of prior cultures and antimicrobial exposure when available, prompt organism identification and susceptibility testing, and susceptibility-guided de-escalation rather than broad anti-CRAB or anti-CRPA coverage for all patients. When linezolid is being considered for enterococcal infection, unexpected non-susceptibility should trigger laboratory verification. The study’s limitations are candidly acknowledged: it was a single-center, retrospective analysis capturing 99.1 percent inpatient data, it lacked linked clinical details such as comorbidities, prior antibiotic exposure, and outcomes, it could not reliably distinguish true infection from colonization, particularly for ICU non-fermenters, and phenotypic results were not confirmed by reference methods. Because patient-level therapy and outcomes were not linked, the data cannot be used to judge stewardship effectiveness or treatment success. What the study does deliver is a template for how institutions outside major metropolitan centers can generate actionable, age- and setting-stratified resistance intelligence, and a reminder that in the fight against antimicrobial resistance, the most useful map is often the one drawn at the level of a single hospital’s own walls.

Subject of Research: Antimicrobial resistance epidemiology and surveillance of clinical bacterial isolates at a tertiary hospital in southwestern China

Article Title: Epidemiological characteristics and antimicrobial resistance profiles of clinical bacterial isolates in a tertiary hospital in Zigong, southwestern China, 2023–2025

Article References: Yu, J., Chen, Y., You, X., & Zhang, S. (2026). Epidemiological characteristics and antimicrobial resistance profiles of clinical bacterial isolates in a tertiary hospital in Zigong, southwestern China, 2023–2025. Frontiers in Cellular and Infection Microbiology, 16, Article 1947772. https://doi.org/10.3389/fcimb.2026.1947772

Image Credits: AI Generated

DOI: 10.3389/fcimb.2026.1947772

Keywords: antimicrobial resistance, carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, Haemophilus influenzae, linezolid non-susceptibility, Enterococcus faecalis, antimicrobial surveillance, intensive care units, CLSI breakpoints, tertiary hospital, China

The research team, led by Shahida Kashif of Liaquat College of Medicine and Dentistry together with Muhammad Sohail of the University of Karachi and collaborators at several Karachi institutions and Taif University in Saudi Arabia, analyzed 308 Gram-negative bacterial isolates recovered from urine samples of patients with catheter-associated urinary tract infections. The samples were collected between June and December 2024, and the work received ethical approval from the Institutional Review Board of Darul Sehat Hospital in Karachi, with written informed consent obtained from all participants or their legal representatives. The study was designed to answer three linked questions: how common carbapenem resistance is in this setting, which carbapenemase-encoding genes are responsible, and what patient characteristics are associated with carrying those genes.

Species identification revealed a familiar hierarchy of uropathogens. Escherichia coli was the dominant organism, accounting for 134 of the 308 isolates, or 43.5 percent, followed by Klebsiella pneumoniae with 96 isolates, or 31.2 percent. The remaining isolates included other Gram-negative species, among them Pseudomonas aeruginosa. This distribution mirrors global patterns of catheter-associated infection, in which Enterobacterales, the family of gut-dwelling bacteria that includes both E. coli and K. pneumoniae, colonize the urinary tract and catheter surfaces with ease. The ubiquity of these organisms in hospital plumbing, on catheter biofilms, and in patients’ own gut flora makes them persistent adversaries in intensive care units and general wards alike.

Antimicrobial susceptibility testing exposed a stark pattern of resistance to the older, cheaper, and more widely used drugs. Resistance to ceftriaxone, a third-generation cephalosporin, was found in 244 of 308 isolates, a rate of 79.2 percent, while resistance to ciprofloxacin, a fluoroquinolone, appeared in 238 isolates, or 77.3 percent. By contrast, resistance to the carbapenems remained lower but far from negligible: 104 isolates, or 33.8 percent, were resistant to meropenem, and 96 isolates, or 31.2 percent, were resistant to imipenem. That roughly one in three Gram-negative uropathogens from catheter-associated infections could shrug off carbapenems underscores how far these last-line drugs have been eroded in this clinical setting, leaving clinicians with progressively fewer options for seriously ill patients.

The molecular core of the study focused on five carbapenemase-encoding genes detected by polymerase chain reaction: bla_NDM, bla_OXA-48, bla_KPC, bla_IMP, and bla_VIM. These genes encode enzymes that hydrolyze carbapenems and most other beta-lactam antibiotics, rendering them ineffective. Among the 104 carbapenem-resistant isolates, bla_NDM, which encodes the New Delhi metallo-beta-lactamase, was by far the most prevalent, detected in 66 isolates, or 63.5 percent. bla_OXA-48, encoding the oxacillinase-48 beta-lactamase, came second at 40 isolates, or 38.5 percent. Notably, bla_KPC, bla_IMP, and bla_VIM were not reported as significant contributors in this collection, marking NDM and OXA-48 as the dominant resistance determinants in these Karachi hospitals.

The distribution of genes across species was not uniform, and this species-specific pattern carries practical implications for diagnostics and treatment. bla_NDM was particularly concentrated in K. pneumoniae, appearing in 31 of 48 carbapenem-resistant K. pneumoniae isolates, or 64.6 percent. bla_OXA-48, by contrast, was more predominant in carbapenem-resistant P. aeruginosa, detected in 4 of 10 such isolates, or 40 percent. The study also documented co-carriage of both bla_NDM and bla_OXA-48 in 12 of the 104 carbapenem-resistant isolates, or 11.5 percent. Dual carriage is especially concerning because enzymes from these two classes, a metallo-beta-lactamase and a class D carbapenemase, together dismantle a broader spectrum of beta-lactam drugs and can complicate the interpretation of phenotypic susceptibility tests, which may fail to flag resistance when multiple mechanisms interact.

Beyond cataloguing genes, the investigators used chi-square tests and binary logistic regression to identify independent predictors of carbapenemase gene carriage, with a p-value of 0.05 or less considered statistically significant. Three clinical factors emerged as independent predictors of gene positivity: admission to the intensive care unit, previous exposure to antibiotics, and catheterization lasting longer than seven days. Each of these factors fits a coherent biological and epidemiological narrative. ICU patients are exposed to the highest densities of resistant organisms and the most intensive antimicrobial use. Prior antibiotic exposure selectively eliminates susceptible strains, clearing the way for resistant ones to colonize. And prolonged catheterization gives bacteria time to form biofilms on the device surface, where they are shielded from both immune defenses and antibiotics and can freely exchange resistance genes on plasmids and other mobile elements.

The public health significance of these findings extends well beyond a single city. Carbapenemase genes, particularly bla_NDM, are notorious for their mobility, hitchhiking on plasmids that move readily between bacterial species and genera. A patient colonized with an NDM-producing E. coli strain can serve as a silent reservoir, disseminating the gene into hospital environments, water systems, and community settings. Because catheter-associated infections are so common, the urinary tract represents one of the largest and most underappreciated reservoirs for these genes in healthcare facilities. The identification of modifiable risk factors, especially catheter duration, provides concrete targets for intervention: strict catheter stewardship, daily assessment of the ongoing need for a catheter, and early removal are inexpensive measures that directly shorten the window in which resistance can emerge and spread.

The study also highlights the importance of molecular surveillance in an era where phenotypic testing alone may not capture the full resistance picture. Rapid PCR-based detection of bla_NDM and bla_OXA-48 in carbapenem-resistant isolates allows infection control teams to isolate carriers promptly, adjust antibiotic therapy, and interrupt transmission chains before outbreaks take hold. The authors note that the co-existence of multiple carbapenemase genes in a meaningful fraction of isolates further argues for comprehensive molecular panels rather than single-gene assays, since treatment decisions and infection control responses may differ depending on which enzymes are present. For laboratories in resource-limited settings, the study’s straightforward PCR approach offers a practical template for building such surveillance capacity.

Published open access in BMC Infectious Diseases with a permanent DOI, the study arrives as the global health community intensifies efforts against antimicrobial resistance, a threat the WHO has identified as one of the top challenges facing public health. The Karachi data, showing E. coli as the predominant uropathogen, bla_NDM as the leading carbapenemase in resistant Enterobacterales, and bla_OXA-48 as the more prevalent mechanism in resistant P. aeruginosa, add a valuable regional data point to the global map of resistance. More importantly, the clear linkage of gene carriage to ICU admission, prior antibiotic exposure, and extended catheterization converts an abstract molecular threat into a set of actionable clinical priorities. If hospitals act on these predictors, limiting unnecessary catheter days and curbing indiscriminate antibiotic use, the study suggests that the spread of carbapenemase genes in catheter-associated infections can be slowed, preserving the effectiveness of last-line antibiotics for the patients who need them most.

Subject of Research: Carbapenemase gene prevalence and risk factors in Gram-negative uropathogens causing catheter-associated urinary tract infections

Article Title: Molecular detection and risk factors of carbapenemase -encoding gene among the Gram-negative uropathogens associated with catheter-associated urinary tract infection

Article References: Kashif, S., Sohail, M., Uddin, F., Ansari, A., Alorabi, M., Khan, R. N., & Husain, S. (2026). Molecular detection and risk factors of carbapenemase -encoding gene among the Gram-negative uropathogens associated with catheter-associated urinary tract infection. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14568-w

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14568-w

Keywords: carbapenemase, bla_NDM, bla_OXA-48, catheter-associated urinary tract infection, antimicrobial resistance, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, risk factors, PCR detection, hospital infection control

Difficult-to-treat resistance is a recently formalized category, and its technical definition matters for understanding why these infections are so alarming. According to the criteria widely adopted from United States Centers for Disease Control and Prevention guidance and reflected in the Clinical and Laboratory Standards Institute’s M100 performance standards, a Gram-negative pathogen is labeled DTR when it is nonsusceptible to all agents in the standard first-line categories: all penicillins and beta-lactam and beta-lactamase inhibitor combinations, all cephalosporins, all carbapenems, the fluoroquinolones, and at least one of the aminoglycosides. In practical terms, a DTR Klebsiella isolate leaves clinicians with almost nothing from the traditional antibiotic armamentarium, forcing reliance on newer beta-lactam and beta-lactamase inhibitor combinations, tetracycline derivatives such as eravacycline, or the last-resort polymyxin colistin, each of which carries its own limitations in efficacy, toxicity, and availability.

The biology of Klebsiella pneumoniae makes it a particularly formidable opponent in cancer care. The organism is a Gram-negative bacillus equipped with an outer membrane rich in porins and a polysaccharide capsule that shields it from complement-mediated killing and phagocytosis. Resistance in DTR strains typically arises through the acquisition of beta-lactamase genes, including extended-spectrum beta-lactamases and carbapenemases such as those of the KPC, NDM, OXA-48-like, and VIM families, which hydrolyze the drugs that would otherwise destroy the cell wall. These genes frequently sit on plasmids that can transfer horizontally between bacterial species, meaning that resistance can spread within a hospital’s microbial ecosystem even when individual bacterial cells do not. For patients whose immune defenses are dismantled by chemotherapy, neutropenia, invasive devices, and repeated hospitalizations, such an organism finds an environment with few natural barriers.

Cancer patients represent a uniquely vulnerable population for these infections, a point the Varanasi team emphasizes by situating their investigation squarely in supportive care rather than pure microbiology. Intensive chemotherapy regimens produce prolonged periods of severe neutropenia, during which the body’s primary cellular defense against bacteria is largely absent. Mucosal barriers lining the gastrointestinal tract are damaged by cytotoxic drugs, allowing intestinal colonizing bacteria to translocate into the bloodstream. Central venous catheters, urinary catheters, and ventilatory support provide direct conduits for microorganisms to bypass skin defenses. Prolonged and repeated hospital admissions increase exposure to the hospital flora, and broad-spectrum prophylactic or empiric antibiotics, often necessary in this population, apply the selective pressure that favors resistant strains over susceptible competitors. The result is a patient population in which multidrug-resistant Gram-negative infections are both more common and more lethal than in the general hospitalized population.

Recent evidence underscores how grim the prognosis has become even in high-resource settings. A retrospective cohort study published in The Lancet Infectious Diseases in 2026 by Walker and colleagues examined survival trends among patients with difficult-to-treat, antibiotic-resistant Gram-negative infections in the United States during the era of next-generation antibiotics, and its inclusion in the Varanasi paper’s reference list signals the authors’ awareness that mortality in this syndrome remains substantial despite the arrival of new drugs. Severe infections caused by difficult-to-treat Gram-negative bacteria, as reviewed by Dettori, Bassetti, and colleagues in Current Opinion in Critical Care, frequently present as bloodstream infections, ventilator-associated pneumonia, or complicated intra-abdominal infections, and delays in appropriate empiric therapy are consistently associated with worse outcomes. In oncology patients, the combination of host immunosuppression and near-total antibiotic resistance creates a clinical scenario in which every hour of ineffective therapy matters.

Accurate susceptibility testing is therefore not a laboratory formality but a life-or-death variable, and this technical dimension occupies a significant place in the Varanasi group’s broader research program. Colistin, the polymyxin antibiotic often reserved for DTR organisms, is notoriously difficult to test reliably. Its large, amphipathic molecule aggregates in aqueous solution and does not diffuse well in agar, which is why traditional disk diffusion performs poorly. The reference standard, broth microdilution, is technically demanding and impractical for many laboratories in resource-limited settings. In response, the Clinical and Laboratory Standards Institute has endorsed broth disk elution as an alternative, a method in which colistin is eluted from a disk into broth before inoculation. A 2025 study by Chandankhede, Karyakarte, and colleagues compared broth disk elution with broth microdilution for carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa, and a prospective study by CV, Priya, Chauhan, and Dhingra specifically evaluated the diagnostic performance of the two methods for carbapenem-resistant Gram-negative bacilli from cancer patients in India. These methodological comparisons matter because an erroneous report of susceptibility, or of resistance, directly changes whether a critically ill cancer patient receives an effective regimen.

The Varanasi investigation itself was structured as a formal healthcare-associated outbreak investigation, a discipline with well-established epidemiological methods. Outbreak investigation in a hospital setting begins with case ascertainment and the construction of a case definition, followed by descriptive epidemiology that maps cases by person, place, and time to identify patterns of transmission. When multiple patients harbor isolates with identical or closely related resistance profiles, the possibility of a common source or of clonal spread via healthcare workers’ hands, contaminated equipment, or the shared hospital environment must be systematically evaluated. The authors acknowledge support for the infection prevention and control assessment component of their investigation from Professor Purva Mathur of the Jai Prakash Narayan Apex Trauma Centre at AIIMS New Delhi and from Dr. A. S. Valan, a public health specialist at the Centers for Disease Control and Prevention India Country Office in New Delhi, indicating that the assessment was aligned with international standards, including the World Health Organization’s 2023 assessment tool on infection prevention and control minimum requirements for tertiary health care facilities.

That WHO tool provides a structured framework for evaluating whether a tertiary facility meets minimum IPC standards across core components such as governance and dedicated IPC staffing, guidelines and protocols, surveillance of healthcare-associated infections, microbiology laboratory capacity, environmental cleaning and sterilization, and the built environment and equipment. In cancer hospitals, the stakes of each component are amplified. High-touch surfaces around immunosuppressed patients, shared bathroom facilities, water systems, and medical devices all represent potential reservoirs for Klebsiella, which can survive on inanimate surfaces for extended periods. Hand hygiene compliance, cohorting of colonized or infected patients, rigorous terminal cleaning of rooms, and antimicrobial stewardship programs that limit unnecessary broad-spectrum exposure form the interlocking defenses that keep resistant organisms contained. An outbreak of DTR Klebsiella in such a setting is therefore as much a systems failure as a microbiological event, and the investigation’s value lies in identifying which links in the chain of transmission broke down.

The broader significance of the study extends well beyond a single institution in northern India. Carbapenem-resistant Klebsiella pneumoniae has been designated a critical-priority pathogen on the World Health Organization’s bacterial priority pathogens list, and the global spread of carbapenemase genes, particularly those encoding NDM-type enzymes that are endemic across the Indian subcontinent, means that cancer centers everywhere face converging threats. The Varanasi paper’s title phrase, beyond the tumor, captures a conceptual shift that supportive oncology has been undergoing: survival in cancer medicine increasingly depends not only on the effectiveness of antineoplastic therapy but on the invisible war being waged against resistant bacteria in the wards, laboratories, and plumbing of the hospitals where treatment occurs. As next-generation antibiotics arrive, their durability will depend on how well healthcare systems prevent the transmission events that this outbreak investigation documents, because every new drug deployed against a resistant cluster applies the selective pressure that can eventually render it ineffective too.

For clinicians and hospital administrators, the message of the study is operational as much as scientific. Rapid detection of DTR phenotypes through reliable susceptibility methods, prompt notification of infection control teams when clusters emerge, disciplined application of contact precautions, and sustained investment in laboratory capacity and IPC infrastructure are the concrete measures that determine whether a cluster remains a cluster or becomes a sustained institutional epidemic. For patients and families, the study is a reminder that modern cancer care is a team effort in which microbiologists, infection preventionists, and oncologists share responsibility for outcomes, and that the fight against antimicrobial resistance is inseparable from the fight against cancer itself.

Subject of Research: Healthcare-associated outbreak of difficult-to-treat Klebsiella pneumoniae infection among cancer patients

Article Title: Beyond the tumor: cluster of difficult-to-treat (DTR) Klebsiella pneumoniae infection in cancer patients—healthcare-associated outbreak investigations

Article References: Bajpai, V., Mishra, A., John, N., Sarode, R., Chaurasia, A., Bharti, S., Kapoor, A., & Mishra, B. K. (2026). Beyond the tumor: cluster of difficult-to-treat (DTR) Klebsiella pneumoniae infection in cancer patients—healthcare-associated outbreak investigations. Supportive Care in Cancer, 34(10), Article 1055. https://doi.org/10.1007/s00520-026-11277-7

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11277-7

Keywords: Klebsiella pneumoniae, difficult-to-treat resistance, antimicrobial resistance, cancer patients, healthcare-associated infection, outbreak investigation, infection prevention and control, carbapenem-resistant Enterobacterales, colistin susceptibility testing, supportive oncology, immunocompromised hosts, hospital epidemiology

The research team, led by Abdi Hayato and Tesfa Gebremeskel of the Department of Pediatrics and Child Health at Arsi University College of Health Sciences, together with Solomon Tejineh of the Department of Public Health, reviewed the records of 217 pediatric patients aged 29 days to 14 years who had culture results available during the study window. Because the study was retrospective, the investigators worked entirely from existing hospital documentation rather than prospectively collecting samples, an approach that trades some methodological control for access to five full years of real-world clinical practice. Ethical clearance came from the Arsi University College of Health Sciences Ethical Review Committee, and individual informed consent was waived because the analysis used anonymized retrospective data, in line with the Declaration of Helsinki.

The raw numbers tell a story of both diagnostic challenge and microbial burden. Of the 217 patient records reviewed, just over half, 52.5 percent, produced any positive culture at all, a figure the researchers describe as the crude culture yield. But positive cultures are not always meaningful: some organisms, particularly coagulase-negative staphylococci, are common skin dwellers that frequently contaminate samples without causing disease. When the team excluded these likely contaminants, the proportion of patients with bacteriologically significant cultures fell to 31.3 percent, or 68 of the 217 children. That distinction matters enormously for clinical interpretation, because treating a contaminant as an infection drives unnecessary antibiotic use, which in turn fuels the very resistance problem the study documents.

From those significant cultures, the researchers identified 112 bacterial isolates across all specimen types. Gram-negative organisms, bacteria whose cell walls are structured in a way that makes them inherently harder to treat and more prone to acquiring resistance genes, accounted for 54.5 percent of the total. Among the Gram-negatives, Klebsiella species emerged as the most frequent pathogen, a genus that has become notorious worldwide for its capacity to harbor powerful resistance enzymes on plasmids, the mobile genetic elements that bacteria swap like trading cards. The predominance of Klebsiella in a pediatric intensive care setting is particularly concerning because the organism thrives in hospital environments, colonizes ventilated patients, and readily spreads through contaminated hands and equipment.

To quantify the severity of resistance, the team applied the World Health Organization’s classification scheme for high-risk phenotypes. These categories include multidrug-resistant organisms, which shrug off multiple antibiotic classes; extensively drug-resistant organisms, which remain susceptible to only a handful of last-line drugs; pan-drug-resistant organisms, against which no available agent works; bacteria producing extended-spectrum beta-lactamases, enzymes that dismantle many penicillins and cephalosporins; and carbapenem-resistant Enterobacterales, which defeat even the carbapenems, the antibiotics typically reserved as a final line of defense. Importantly, these categories are not mutually exclusive, so a single isolate can satisfy several definitions at once. Antimicrobial susceptibility testing was performed on 66 clinically significant isolates, one per patient, providing the analytical backbone of the study.

The susceptibility results were alarming. Among the 66 tested isolates, 45, or 68.2 percent, carried at least one high-risk resistance phenotype. Extended-spectrum beta-lactamase production was the single most common phenotype at 19.7 percent, followed by extensive drug resistance at 15.2 percent, multidrug resistance and pan-drug resistance at 13.6 percent each, and carbapenem resistance at 6.1 percent. Resistance to older beta-lactam antibiotics was close to total: 91.3 percent of isolates resisted ampicillin and 92.3 percent resisted ceftazidime, a third-generation cephalosporin that many treatment guidelines still position as a workhorse drug. In practical terms, for a clinician at this hospital, empiric therapy with those agents would fail roughly nine times out of ten.

Yet the antibiogram was not uniformly bleak. Two drugs retained meaningful activity: amikacin, an aminoglycoside, remained effective against 83.3 percent of tested isolates, and meropenem, a carbapenem, against 85.7 percent. These susceptibility profiles are the study’s most actionable contribution, because an antibiogram, the aggregated map of which drugs still work against which local organisms, is the foundation on which hospital antibiotic stewardship programs are built. The authors suggest that these data can inform the development of such a program at Asella Teaching and Referral Hospital, guiding which agents should be used for empiric therapy and which should be conserved. In settings where diagnostic microbiology is limited, a reliable local antibiogram is often the only rational basis for treatment decisions.

The study also included an exploratory statistical analysis of factors associated with high-risk resistance, using binary logistic regression with a significance threshold of 0.05. One association stood out: each additional day of PICU stay was linked to a dramatically increased odds of high-risk antimicrobial resistance, with an adjusted odds ratio of 7.59 and a 95 percent confidence interval stretching from 1.10 to 52.60. The authors are careful, and rightly so, to flag that this estimate is statistically unstable. The enormous width of the confidence interval reflects the small sample size and the retrospective design, and they explicitly caution that the figure should not be interpreted as a valid per-day effect. Still, the direction of the association is biologically plausible: longer intensive care stays mean more invasive procedures, more ventilator time, more central lines, and more cumulative antibiotic exposure, all of which select for resistant organisms.

The broader context makes these local findings globally significant. Antimicrobial resistance is recognized by the World Health Organization as one of the top public health threats facing humanity, and low- and middle-income countries bear a disproportionate share of the burden, partly because of limited diagnostic capacity, constrained access to newer antibiotics, weaker infection prevention and control infrastructure, and over-the-counter antibiotic availability that encourages misuse. Pediatric intensive care units concentrate all of these risk factors in the most vulnerable patients: children whose immune systems are immature, whose bodies are small, and whose infections can progress from fever to septic shock within hours. Data from such settings are chronically scarce, which is why the authors emphasize that prospective, multicenter surveillance with standardized microbiological protocols is urgently needed across Ethiopia and comparable settings.

What happens next will determine whether this study becomes a turning point or another warning that goes unheeded. The authors call for institutional stewardship development anchored in the antibiogram they have generated, alongside strengthened infection prevention and control measures to interrupt transmission of resistant organisms within the unit. The study’s limitations, its single-center design, retrospective data collection, modest isolate numbers, and the instability of the regression estimate, are real, but they do not diminish the central signal: in this Ethiopian PICU, the era in which standard beta-lactam antibiotics could be relied upon to save critically ill children is effectively over, and the remaining effective drugs, amikacin and meropenem, must be protected before they too are lost. As resistant bacteria continue their quiet global expansion, studies like this one serve as both a measurement and a warning, documenting precisely how much ground has already been surrendered in the fight against one of medicine’s most implacable adversaries.

Subject of Research: Antimicrobial resistance patterns among bacterial infections in a pediatric intensive care unit in Ethiopia

Article Title: Bacterial profile and antimicrobial resistance patterns among pediatric intensive care unit patients in Ethiopia: a retrospective cohort study, 2020–2025

Article References: Hayato, A., Gebremeskel, T., & Tejineh, S. (2026). Bacterial profile and antimicrobial resistance patterns among pediatric intensive care unit patients in Ethiopia: a retrospective cohort study, 2020–2025. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07748-9

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07748-9

Keywords: antimicrobial resistance, pediatric intensive care, Klebsiella, ESBL, carbapenem-resistant Enterobacterales, Ethiopia, antibiogram, Gram-negative bacteria, antibiotic stewardship, retrospective cohort, hospital-acquired infection, BMC Pediatrics

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