Carbapenem-resistant Gram-negative bacteria, often abbreviated CR-GNB, represent one of the most feared threats in contemporary medicine. Carbapenems belong to the beta-lactam family of antibiotics, chemically related to penicillin, and they work by blocking the enzymes bacteria use to build their cell walls. Their broad activity and stability against many beta-lactamase enzymes have long made them the drugs of last resort for serious infections caused by organisms such as Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli. When bacteria acquire or evolve mechanisms to defeat these drugs, typically by producing carbapenemases or by remodeling the porous outer membrane and efflux pumps characteristic of Gram-negative cells, clinicians are left with a dwindling arsenal of older, more toxic agents such as colistin, often with limited evidence to guide dosing. The World Health Organization has repeatedly flagged carbapenem-resistant Gram-negatives as a critical priority for new antibiotic development, and the burden falls disproportionately on low- and middle-income countries where surveillance and infection control resources can be stretched thin.

Jordan has been something of a data gap in this global picture. While regional neighbors and high-income countries have produced extensive resistance surveillance, detailed predictors of carbapenem resistance among Jordanian ICU patients have been scarce. The new study, led by Mohammad Gharaibeh of the Jordanian Ministry of Health and Tamer Osman of the US Naval Medical Research Unit EURAFCENT, set out to close that gap by mining the country’s national surveillance system. The team included every patient with a laboratory-confirmed Gram-negative infection across the participating public hospital ICUs over the six-year window. Laboratory identification and antimicrobial susceptibility testing followed the Clinical and Laboratory Standards Institute’s M100 standards, the widely used benchmark for interpreting minimum inhibitory concentrations, and the researchers applied multivariate logistic regression to disentangle which clinical factors independently predicted resistance rather than merely correlating with it.

The headline number is stark: 451 of the 1,180 isolates, or 38 percent, were carbapenem-resistant. The microbiology behind that figure is not uniform, however. Acinetobacter baumannii and Klebsiella species emerged as the predominant resistant pathogens, a pattern consistent with global trends, since both organisms are notorious for acquiring plasmid-borne carbapenemase genes and for surviving on dry hospital surfaces and medical equipment. Escherichia coli, by contrast, remained mainly carbapenem-susceptible in this dataset, offering a small measure of reassurance that resistance in Jordan is concentrated in the organisms most adept at hospital survival rather than uniformly distributed across the Gram-negative spectrum. That distinction matters for clinicians, because it suggests that empiric treatment decisions for suspected ICU infections should weigh the likely organism as much as the local resistance prevalence.

When the researchers adjusted for confounding factors, four independent predictors of carbapenem resistance stood out. Infections acquired inside the ICU, rather than present on admission, carried roughly two and a half times the odds of being carbapenem-resistant, with an odds ratio of 2.44. Pneumonia more than doubled the odds as well, at an odds ratio of 2.77, a finding that aligns with the well-documented role of ventilator-associated pneumonia as a reservoir for resistant organisms in the airways of intubated patients. The use of invasive devices, including central lines, urinary catheters and endotracheal tubes, raised the odds 3.37-fold, reflecting how these devices breach the body’s natural barriers and provide surfaces for biofilm formation, where bacteria embedded in a protective extracellular matrix can exchange resistance genes and evade both antibiotics and immune defenses. Most striking of all, admission to a high-risk ICU unit tripled the odds of resistance, with an odds ratio of 3.33, underscoring that the ecology of individual units, shaped by their case mix, antibiotic pressure and staffing, can be as decisive as any single patient characteristic.

Each of these risk factors tells a mechanistic story. ICU-acquired infection implies prolonged exposure to the hospital environment, where resistant strains circulate on hands, equipment and surfaces, and where selective pressure from broad-spectrum antibiotic use favors organisms that have already learned to resist carbapenems. Pneumonia in ventilated patients combines device exposure with a compromised lower respiratory tract, where secretions colonized by resistant Gram-negatives can seed frank infection. Invasive devices act as literal bridges from the contaminated environment into normally sterile body sites, and their duration of use is one of the most consistently modifiable factors in hospital epidemiology. The high-risk unit finding suggests that resistance is not randomly distributed but clusters where the most vulnerable patients, the heaviest device use and the most intensive antibiotic prescribing converge, creating conditions in which resistant strains can amplify and spread from patient to patient.

The mortality data give these risk factors their weight. Nearly 70 percent of patients with carbapenem-resistant infections died, compared with 42 percent of those with susceptible infections, and after statistical adjustment the resistant group faced a 3.15-fold increased risk of death, with a confidence interval running from 2.392 to 4.145. Part of that excess mortality reflects the biology of resistance itself: when first-line and second-line antibiotics fail, definitive therapy is delayed, allowing infection to progress, and the salvage regimens that remain, such as colistin-based combinations, are less effective and more nephrotoxic than the carbapenems they replace. Part of it also reflects the fact that patients who develop resistant infections tend, by the very risk factors identified here, to be sicker and more device-dependent to begin with. Either way, the numbers reinforce a message that infectious disease specialists have been repeating for years: preventing resistance is inseparable from preventing death in critical care.

The authors argue that their findings point toward concrete, actionable interventions. Strict hand hygiene remains the single most cost-effective barrier against transmission, particularly for organisms like A. baumannii that persist in the environment. Antimicrobial stewardship programs, which audit and constrain the use of broad-spectrum antibiotics, reduce the selective pressure that allows resistant strains to outcompete susceptible ones. And the proper management of invasive devices, including daily review of whether each catheter and line is still needed, prompt removal when it is not, and aseptic insertion and maintenance technique, directly targets the strongest modifiable predictor identified in the study. Because the analysis drew on a national surveillance network spanning 13 public hospitals, the results are less vulnerable to the single-center biases that plague much of the resistance literature, although the retrospective design still means that only associations, not proven causal chains, can be established.

For the region and beyond, the study carries a warning and a template. The warning is that in Jordanian public hospital ICUs, as in many settings across the Middle East and other low- and middle-income regions, carbapenem resistance has reached a prevalence at which empiric therapy decisions, infection control investment and surveillance infrastructure can no longer be treated as optional. The template is the surveillance system itself: a coordinated national network, standardized laboratory methods aligned with CLSI benchmarks, and shared analysis between the Ministry of Health and international research partners, funded in this case through the Armed Forces Health Surveillance Division’s Global Emerging Infections Surveillance program. As resistance genes continue to move across borders with patients, food and the environment, the Jordanian experience suggests that knowing exactly who is at risk, the device-bearing, the ventilated, the long-staying, the patients in the highest-pressure units, is the first step toward keeping the last-line antibiotics working for the patients who need them most.

Subject of Research: Risk factors for carbapenem-resistant Gram-negative bacterial infections in intensive care units in Jordan

Article Title: Risk factors associated with carbapenem-resistant Gram-negative bacterial infections in intensive care units in Jordan

Article References: Gharaibeh, M., Sayyouh, O., El-Shokry, M., Nasrat, S., Ramadan, M., Khraisat, W., Alamer, L., Natour, A., Aljbour, M., Abushawer, Z., Abdallah, N., Migdadi, N., Harb, S., Awad, E., Bataienh, E., Battah, S., Ikermawi, R., Said, M., Alhawarat, M., & Osman, T. (2026). Risk factors associated with carbapenem-resistant Gram-negative bacterial infections in intensive care units in Jordan. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-13526-w

Image Credits: AI Generated

DOI: 10.1186/s12879-026-13526-w

Keywords: carbapenem resistance, Gram-negative bacteria, intensive care units, antimicrobial resistance, hospital-acquired infections, Acinetobacter baumannii, Klebsiella, pneumonia, invasive devices, infection control, Jordan, surveillance

Klebsiella pneumoniae has long been divided into two epidemiological personalities. Classical strains colonize hospitals, infecting newborns, elderly patients and the immunocompromised, and are a leading cause of hospital-acquired infections and neonatal septicemia. Hypervirulent strains, by contrast, strike healthy people in the community, causing devastating syndromes such as pyogenic liver abscess, endophthalmitis and meningitis. For years these two worlds barely overlapped: hospital strains were resistant but relatively tame, while community strains were virulent but broadly susceptible to antibiotics. The US Centers for Disease Control and Prevention and the World Health Organization have both flagged carbapenem-resistant K. pneumoniae, or CRKP, as one of the most urgent threats in medicine, with new antimicrobials desperately needed.

That tidy separation collapsed in 2016, when strains of the ST11 lineage began acquiring pLVPK-like virulence plasmids, the mobile genetic elements that carry the genes behind hypervirulence. The resulting carbapenem-resistant hypervirulent K. pneumoniae, or CR-hvKP, fuses the worst features of both worlds. A fatal hospital outbreak in China described in 2018 first sounded the alarm, and the new study now provides a global, decade-scale accounting of what happened next. Within the ST11 lineage, two capsular subtypes, KL64 and KL47, emerged as the principal vehicles of CRKP, and their fortunes diverged dramatically.

The data show that KL47 was the dominant subtype from 2011 to 2015, after which its numbers plateaued. KL64, by contrast, entered a phase of explosive growth beginning in 2016 and overtook KL47 to become China’s predominant CRKP subtype, accounting for 40.5 percent of ST11-CRKP strains versus 28.9 percent for KL47. Regional patterns were stark: KL64 dominated Zhejiang province with 62.3 percent of strains and Sichuan with 58.7 percent, while KL47 held sway in Beijing, Jiangsu and Anhui. Globally, the picture was equally uneven, with KL24 dominant in Spain, Poland, Russia and Pakistan, KL105 predominant in the United Kingdom, and KL64 leading in Brazil and Uruguay. Of the ST11-CRKP strains examined, 89.7 percent carried carbapenemase genes, most commonly KPC-2 at 77.8 percent, followed by OXA-48 and NDM-1.

The decisive difference between the two subclones lay in how faithfully they maintained the virulence plasmid. Among 2,390 KL64 isolates, 60.5 percent carried the aerobactin gene, a key iron-scavenging virulence factor typically housed on pLVPK-like plasmids, compared with just 27.3 percent of 1,706 KL47 isolates. Detection of the RmpADC genes, which enhance capsular expression, showed an even wider gap: 40.7 percent in KL64 against 2.1 percent in KL47. The trajectory of aerobactin carriage tracked KL64’s rise almost perfectly. From 2015 to 2020, aerobactin-positive KL64 strains climbed from 58.9 percent to 86.6 percent of that subclone, while KL47’s aerobactin rate stayed flat in single digits. Patients infected with aerobactin-carrying strains faced significantly worse outcomes, with an odds ratio of 2.34 for severe disease.

Complete genome sequencing of 125 KL64 and 87 KL47 isolates exposed the molecular mechanism. Among aerobactin-positive strains, 98.7 percent of KL64 carried the gene on a plasmid, and 94.8 percent of those plasmids were intact and highly similar to the canonical pLVPK plasmid. In KL47, by contrast, only 41.2 percent of plasmids were intact; 58.8 percent had fused with IncFIB(pNDM-Mar)-like plasmids, leaving behind truncated remnants retaining little more than aerobactin and tellurium-resistance genes, and 41.4 percent of KL47 strains had lost the plasmid entirely, with virulence genes scattered onto the chromosome. Genome-wide comparison confirmed the disparity in gene retention: 71.2 percent of KL64 plasmids preserved the bulk of pLVPK genes, while most KL47 plasmids showed deletions exceeding 30 percent of the reference genome, with half losing more than 45 percent.

The fusion events themselves revealed a fascinating evolutionary intermediate. Twelve of fourteen truncated plasmids arose when pLVPK recombined with IncFIB(pNDM-Mar), a replicon type so rare it appeared almost exclusively in these hybrids. In thirteen strains, the recombination went further: genes from both parent plasmids, including aerobactin and type IV secretion system components, were transferred into the chromosome at a highly conserved insertion site marked by IS26 sequences. These chromosomal integrations appeared in hospitals across multiple regions, hinting that the instability of pLVPK in the KL47 background pushes the plasmid toward destructive recombination, while the KL64 genomic environment accommodates it intact. The researchers suggest this reflects classic plasmid fitness economics: acquiring a large virulence plasmid imposes metabolic costs that vary with host background, and KL47 appears to resolve those costs by shedding or chopping up the plasmid, whereas KL64 tolerates it stably enough to reap the full virulence benefit.

Geography and ecology help explain why ST11, rather than its American counterpart ST258, became the CR-hvKP powerhouse. Only 15 of 3,726 ST258-CRKP strains, a mere 0.4 percent, had acquired pLVPK-like plasmids, versus 33.9 percent of ST11-CRKP strains. The likely reason is proximity: hypervirulent KL1 and KL2 strains, the natural reservoirs of pLVPK, are concentrated in Asia, where intestinal colonization rates of K. pneumoniae in healthy Chinese adults reach 62.1 percent. In China, 48.4 percent of ST11-CRKP strains carry pLVPK-like plasmids, while in the United States only 0.5 percent of ST258-CRKP strains do. Intensive care units appear to be critical mixing vessels. In Sichuan, only 7.7 percent of human ST11-CRKP strains had acquired pLVPK-like plasmids, but 40 percent of environmental strains from neuro-intensive care and respiratory ICU surfaces had, underscoring the role of hospital environments in catalyzing plasmid transfer.

The evolutionary stakes are high. Strains carrying pLVPK-like plasmids survive environmental stress better, establish intestinal colonization more effectively and are associated with higher mortality than ordinary CRKP infections, and the loss of pLVPK sharply reduces extraintestinal spread. The authors acknowledge limitations, including geographic sampling bias toward well-resourced Chinese provinces and reduced data availability after 2020 due to sequencing submission lag. Even so, the message for surveillance is unambiguous. Monitoring plasmid-mediated virulence, not just resistance genes, may be essential to anticipate which CRKP clones will explode next, particularly in critical care settings where horizontal gene transfer can rewrite a pathogen’s arsenal within a single hospital ward. As the ST11-KL64 story demonstrates, in the arms race between antibiotics and bacteria, the plasmid is the engine of conquest.

Subject of Research: Plasmid-mediated fitness advantages underlying the global spread of carbapenem-resistant hypervirulent Klebsiella pneumoniae ST11-KL64.

Article Title: A fitness advantage from the pLVPK plasmid fuels the global spread of a carbapenem-resistant hypervirulent Klebsiella pneumoniae high-risk clone: ST11-KL64

Article References: Ren, Y., Li, X., Ju, L., Yao, Y., Chen, X., & Wang, X. (2026). A fitness advantage from the pLVPK plasmid fuels the global spread of a carbapenem-resistant hypervirulent Klebsiella pneumoniae high-risk clone: ST11-KL64. International Microbiology. https://doi.org/10.1007/s10123-026-00888-z

Image Credits: AI Generated

DOI: 10.1007/s10123-026-00888-z

Keywords: Klebsiella pneumoniae, pLVPK plasmid, carbapenem resistance, hypervirulence, ST11-KL64, aerobactin, genomic surveillance, horizontal gene transfer, CR-hvKP, plasmid stability, antimicrobial resistance, public health