Superbugs in the ICU: Jordan Study Reveals Who Is Most at Risk of Untreatable Infections

In the shadow war between modern medicine and bacteria, intensive care units are the front line, and a new study from Jordan suggests the enemy is gaining ground. Researchers analyzing six years of national surveillance data have found that more than one in three Gram-negative bacterial infections in Jordanian ICUs is resistant to carbapenems, the last-line antibiotics that doctors reach for when almost nothing else works. The research, published in BMC Infectious Diseases, draws on 1,180 confirmed Gram-negative isolates collected between September 2018 and September 2024 from 18 intensive care units across 13 public hospitals, making it one of the most comprehensive pictures yet of carbapenem resistance in the country. Its findings are sobering: patients infected with carbapenem-resistant organisms died at a rate of 69.8 percent, compared with 42.0 percent among those whose infections remained treatable, translating into a more than threefold increase in the risk of death.

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