Seven-Year Study Tracks Shifting Wave of Drug Resistance in Pseudomonas aeruginosa

One of medicine’s most feared hospital pathogens has just been tracked in unusual detail. A seven-year surveillance study from a secondary care hospital in Saudi Arabia has charted the rise, peak, and partial retreat of drug-resistant forms of Pseudomonas aeruginosa, the Gram-negative bacterium that the World Health Organization ranks among the critical priority pathogens for new antibiotic development. The research, published in Frontiers in Antibiotics, analyzed 368 non-duplicate clinical isolates collected between January 2018 and December 2024 and offers one of the longest longitudinal pictures of resistance in this organism from a single Saudi secondary healthcare setting.

Pseudomonas aeruginosa is a formidable adversary in hospitals. It thrives in moist environments, infects ventilated patients, and causes ventilator-associated pneumonia, bloodstream infections, catheter-associated urinary tract infections, and surgical site infections, particularly in critically ill or immunocompromised people. Its defenses are layered: the bacterium’s outer membrane is intrinsically impermeable to many drugs, it deploys multidrug efflux pumps that expel antibiotics before they reach their targets, it alters the molecular targets those antibiotics are designed to hit, and it produces β-lactamases, enzymes that chemically dismantle penicillin-class drugs. Together these mechanisms allow the emergence of isolates classified as multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat resistant (DTR) — categories that translate directly into prolonged hospitalization, higher costs, and increased mortality.

The study team, led by Wael A. Alghamdi of King Khalid University together with colleagues at Khamis Mushait General Hospital in the Aseer region, took a deliberately rigorous approach to the data. To avoid inflating resistance rates through repeated sampling of the same patients, the researchers deduplicated isolates at the patient level: for each calendar year, only the first P. aeruginosa isolate per patient was counted, with priority given to the most clinically significant source when several specimens were taken on the same day. Because a single patient could still contribute one isolate in different years, the team ran a sensitivity analysis restricted to 352 patients with no repeated observations, ensuring that temporal trends were not an artifact of non-independent data.

Resistance phenotypes were classified according to established international definitions. MDR isolates were non-susceptible to at least one agent in three or more antimicrobial categories; XDR isolates were non-susceptible to all but one or two categories; and DTR isolates, a clinically grounded classification proposed by Kadri and colleagues, were non-susceptible to all the principal first-line antipseudomonal β-lactams and fluoroquinolones. Bacterial identification and susceptibility testing were performed with the MicroScan automated broth microdilution system throughout the study, with results interpreted against the Clinical and Laboratory Standards Institute breakpoints in force at the time. Overall, 92.5 percent of potential susceptibility results were available, and missing results were left unimputed rather than guessed.

The headline finding is a dramatic arc in resistance prevalence. MDR rose from 51.0 percent of isolates in 2018 to a striking peak of 87.3 percent in 2022, before falling back to 69.6 percent in 2024. XDR climbed from 33.3 percent in 2018 to its highest level of 68.3 percent in 2023, then dropped sharply to 39.1 percent in 2024. DTR, the most clinically restrictive category, stayed lower throughout, ranging from 11.8 percent in 2018 to a peak of 31.7 percent in 2023 before declining to 15.2 percent in 2024. When calendar year was analyzed as a categorical variable, the differences across years were statistically significant for MDR (likelihood-ratio χ² = 33.25, P < 0.001) and XDR (χ² = 20.16, P = 0.003), but not for DTR (χ² = 9.57, P = 0.144).

Crucially, the temporal signal survived statistical scrutiny. In multivariable logistic regression models adjusted for age group, sex, nationality, and specimen source — built on the restricted dataset of 352 unique patients — collection year remained significantly associated with MDR (P < 0.001) and XDR (P = 0.013), but not DTR (P = 0.398). Compared with 2018, the adjusted odds of MDR were roughly six-fold higher in 2022 (adjusted odds ratio 6.12, 95 percent confidence interval 2.25–16.63) and nearly three-fold higher in 2023 (aOR 2.98, 95 percent CI 1.13–7.84), while the adjusted odds of XDR were significantly elevated in 2023 (aOR 3.59, 95 percent CI 1.41–9.11). This means the temporal pattern was not explained simply by shifts in the kinds of patients or specimen types being sampled.

The drug-specific data reveal a subtler story beneath the phenotype curves. Ciprofloxacin non-susceptibility surged from 44.0 percent in 2018 to 97.8 percent in 2024 — a near-total collapse of fluoroquinolone utility against these isolates. In contrast, non-susceptibility to the carbapenems imipenem and meropenem actually declined over the same period, falling from 45.7 percent and 41.2 percent to 30.4 percent and 27.3 percent respectively. This divergence suggests that resistance in P. aeruginosa does not move in one direction uniformly: some drug classes erode steadily while others can recover, presumably reflecting changing prescribing pressures, infection control dynamics, and shifts in circulating strains, though the study’s phenotypic design could not disentangle the mechanisms.

The patient and specimen profile of the cohort adds clinical context. Isolates came more often from male patients (68.5 percent), and nearly half came from people over 60 years of age (49.7 percent), a population with greater healthcare exposure and comorbidity burden. Respiratory tract specimens were the most common source, accounting for 35.1 percent of isolates, followed by urine and genital tract samples (28.3 percent) and wound, pus, and tissue specimens (24.7 percent), with blood and sterile body fluids at 12.0 percent. Interestingly, male sex was associated with higher adjusted odds of all three resistance phenotypes, and specimen source was significantly associated with DTR: isolates from urine and from wounds had markedly lower odds of DTR than bloodstream isolates, a pattern consistent with the severity of infections that reach the bloodstream.

What drove the rise and fall? The authors are appropriately cautious. An antimicrobial stewardship program was introduced at the study institution during the surveillance period, and the decline in MDR and XDR prevalence after 2022 and 2023 may be consistent with such interventions taking hold — but the retrospective, observational design makes it impossible to attribute the downturn to any specific measure. The fluctuations may equally reflect changes in antimicrobial prescribing practices, infection prevention measures, and evolving healthcare utilization, including the massive disruption that the COVID-19 pandemic years imposed on hospitals worldwide. Continuous longitudinal surveillance, the authors argue, is precisely what allows institutions to detect these swings and evaluate stewardship efforts over time.

The study also carries important limitations. It was retrospective and laboratory-based, so detailed clinical information — antimicrobial exposure, comorbidities, treatments, and outcomes — was unavailable, and infection could not be reliably distinguished from colonization for every isolate. No molecular characterization was performed, so the phenotypic trends cannot be pinned on clonal expansion or the spread of specific resistance genes. Annual isolate numbers varied considerably, from as few as 41 in 2023 to 75 in 2021, which makes year-to-year percentages sensitive to small changes. Susceptibility was interpreted using CLSI breakpoints in effect at the time of testing, so revisions during the seven-year window may have introduced some variability in longitudinal classification. Residual confounding by unmeasured clinical factors also remains possible.

Even with those caveats, the numbers land with force. A national multicenter surveillance study from Saudi Arabia recently reported that 25.8 percent of clinical P. aeruginosa isolates in the country’s southern region were DTR and 4.5 percent were pandrug-resistant, while regional analyses across the Arabian Gulf have documented rising resistance to carbapenems, fluoroquinolones, and aztreonam. The new single-center data, drawn from a secondary care setting that is often underrepresented in national surveillance reports, reinforce the message that resistance epidemiology is highly heterogeneous across institutions and regions — and that local data are essential for choosing empirical therapy wisely.

Saudi Arabia has responded at the policy level with its National Action Plan for Antimicrobial Resistance (2022–2025), which aims to strengthen surveillance systems, stewardship, and infection prevention nationwide. Studies like this one are the ground truth against which such plans will be judged. The study’s inclusion of the DTR classification alongside MDR and XDR is particularly valuable, because DTR captures the loss of susceptibility to the principal first-line antipseudomonal agents — the drugs clinicians actually reach for first — and has been linked to worse outcomes in Gram-negative infections.

The overall picture is neither pure doom nor easy reassurance. More than two-thirds of isolates in 2024 were still multidrug-resistant, nearly double the 2018 level, and fluoroquinolone resistance has become almost universal. Yet the significant declines in XDR prevalence in 2024, and the recovery in carbapenem susceptibility, show that resistance is not a one-way ratchet: it responds, sometimes relatively quickly, to the ecological pressures a hospital applies. For a pathogen that the global burden studies place among the deadliest sources of antimicrobial-resistance-associated deaths, that dynamism is the most actionable finding of all — a reminder that surveillance is not a bureaucratic exercise but a live instrument for steering therapy, and that stewardship decisions made today will be visible in the resistance curves of tomorrow.

Subject of Research: Longitudinal trends in antimicrobial resistance phenotypes of Pseudomonas aeruginosa in a Saudi hospital, 2018–2024

Article Title: Longitudinal trends in antimicrobial resistance phenotypes in Pseudomonas aeruginosa: a seven-year study

Article References: Longitudinal trends in antimicrobial resistance phenotypes in Pseudomonas aeruginosa: a seven-year study. (n.d.). https://doi.org/10.3389/frabi.2026.1912287

Image Credits: AI Generated

DOI: 10.3389/frabi.2026.1912287

Keywords: antimicrobial resistance, Pseudomonas aeruginosa, multidrug-resistant, extensively drug-resistant, difficult-to-treat resistance, surveillance, antimicrobial stewardship, Saudi Arabia, healthcare-associated infections, carbapenems, fluoroquinolones, hospital epidemiology