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 clinical stakes are considerable. The World Health Organization does not publish a global prevalence report for NTM, so estimates come from national cohort studies and systematic reviews, and these consistently show rising incidence and prevalence over recent decades, with a particularly pronounced burden in low-income nations. The M. avium complex remains the predominant species in most countries. These bacteria thrive in humid environments, colonizing showers, hot tubs, thermal springs, and ventilation systems, and people typically acquire infection by inhaling contaminated aerosols. Their capacity to form biofilms allows them to colonize medical devices and water distribution systems, and infections have even followed tattoos, piercings, and cosmetic procedures. While person-to-person transmission is uncommon, evidence suggests potential transmission between cystic fibrosis patients and in specific healthcare settings, adding a troubling dimension to an already difficult problem.

Tigecycline itself is a derivative of minocycline and belongs to the glycylcycline class, engineered to overcome many of the mechanisms that render older tetracyclines ineffective. Its mechanism of action is elegant in its simplicity: the molecule binds to the 30S subunit of the bacterial ribosome, blocking the entry of aminoacyl-tRNA into the A site and thereby halting protein synthesis. Against Gram-positive and Gram-negative bacteria alike, and against certain mycobacteria, this broad-spectrum activity has made tigecycline a valuable last-resort agent. But mycobacteria are formidable adversaries. Their lipid-rich cell walls, packed with mycolic acids and studded with only sparse porin channels, form a permeability barrier that limits antibiotic penetration, and they deploy an arsenal of active resistance mechanisms on top of this passive defense.

The review’s authors searched Scopus, PubMed, the Virtual Health Library, SciELO, Web of Science, and LILACS between September and December 2025, screening 42 potentially relevant articles and ultimately including 28 in their analysis. The evidence they compiled paints a nuanced picture. Early studies reported consistently low minimum inhibitory concentrations, or MIC values, for tigecycline against the M. abscessus complex, with MIC50 values at or below 0.12 micrograms per milliliter and MIC90 values of 0.25 micrograms per milliliter in rapidly growing mycobacteria including M. abscessus, M. chelonae, and M. fortuitum. More recent work, however, has documented heterogeneity, with some clinical isolates showing resistance or reduced susceptibility despite the drug’s initially promising in vitro profile, suggesting that genetic determinants play a substantial role in modulating susceptibility.

One of the most striking findings concerns MabTetX, a flavin-dependent monooxygenase encoded by the gene MAB_1496c that serves as the principal tetracycline resistance determinant in M. abscessus. This enzyme degrades classical tetracyclines, and its expression increases in the presence of tetracycline and doxycycline. Crucially, however, tigecycline does not induce MabTetX expression and is far less affected by the enzyme’s activity, which explains why the drug retains activity against isolates resistant to older tetracyclines. This structural advantage, though, does not prevent resistance from emerging through entirely different adaptive pathways, a theme that runs throughout the review’s molecular analysis.

That adaptive machinery centers on WhiB7, a transcription factor that functions as the master regulator of the intrinsic antibiotic stress response in mycobacteria. When activated, WhiB7 induces a suite of resistance-associated genes including erm(41), eis2, hflX, and members of the ABCF family, promoting adaptive resistance to several antimicrobial classes. Experimental studies showed that deleting whiB7 significantly increases susceptibility to tigecycline, while its expression raises the MIC. The review also highlights the sigH-rshA axis: mutations in rshA, which encodes an anti-sigma factor, disrupt the interaction between RshA and the sigma factor SigH, leading to SigH overexpression and extensive transcriptional reprogramming characterized by reduced ribosomal protein synthesis, enhanced stress adaptation, and increased antibiotic tolerance. A spontaneous M. abscessus mutant carrying an rshA mutation exhibited tigecycline resistance, cross-resistance to imipenem, and a modest growth defect, and subsequent work linked the dysregulated stress response to decreased ribosomal gene expression and transient resistance induced by heat stress.

Efflux pumps add yet another layer of defense. Members of the MmpL family, particularly MmpL5, together with ABCF and Major Facilitator Superfamily transporters, actively export tigecycline from the bacterial cell, driven by ATP hydrolysis. Transcriptomic analyses demonstrated that just 24 hours of exposure to tigecycline significantly induces the expression of these efflux systems, reducing intracellular drug concentrations and limiting binding to the ribosomal target. Notably, many of these transporters appear to be regulated directly or indirectly by WhiB7, underscoring how tightly interconnected the resistance pathways are. Efflux pump inhibitors offer a tantalizing countermeasure: verapamil, the most extensively studied, has been shown to reduce the activity of multiple efflux pumps and potentially lower tigecycline MIC values in some isolates, while CCCP dissipates the proton motive force that powers proton-dependent pumps, and reserpine directly blocks MFS transporters. However, most evidence for these inhibitors comes from combinations with other antimicrobials such as bedaquiline, clofazimine, rifampicin, and macrolides, and their clinical application remains experimental.

In sharp contrast to the rapid growers, slow-growing species present a fundamentally different problem. M. avium, M. intracellulare, and M. kansasii consistently exhibit MIC values exceeding 4 micrograms per milliliter, with reported MIC50 and MIC90 values of at least 8 micrograms per milliliter in some studies. Here, reduced susceptibility appears rooted in intrinsic characteristics, particularly the highly lipid-rich, poorly permeable cell envelope and lower metabolic activity, rather than the adaptive regulatory mechanisms so extensively characterized in M. abscessus. A systematic review of 89 studies confirmed that tigecycline demonstrates greater activity against rapidly growing NTM, while evidence supporting its efficacy in slow-growing species remains limited. The review’s authors conclude that tigecycline is best positioned as a component of combination regimens for rapid-growing NTM, particularly multidrug-resistant isolates, and should rarely, if ever, be used as monotherapy given the growing recognition of adaptive resistance mechanisms.

Significant caveats temper these conclusions. Most available studies rely on in vitro susceptibility testing with relatively small collections of clinical isolates focused mainly on the M. abscessus complex, and substantial methodological variability in broth microdilution protocols, culture media, incubation periods, and isolate selection makes direct comparison across studies difficult. Isolates from different geographic regions may carry regional genetic diversity that further influences susceptibility profiles. Perhaps most critically, standardized clinical breakpoints for tigecycline have not yet been established, which restricts the translation of MIC data into clinical decision-making. Other proposed determinants, such as mutations in the gene MAB_3542c and in rpsA, have not been consistently reproduced, and biofilm formation’s contribution to tigecycline resistance remains poorly quantified.

Looking forward, the review’s authors call for multicenter studies with larger, geographically diverse isolate collections and standardized susceptibility testing protocols. Integrated genomic and transcriptomic approaches will be essential to identify novel resistance determinants and to determine whether the mechanisms described in M. abscessus are conserved across other NTM species. Establishing robust correlations between in vitro susceptibility, molecular mechanisms, and actual clinical outcomes will be critical for defining clinically relevant breakpoints and optimizing tigecycline-based regimens. For now, the message is one of cautious optimism: a drug once considered mainly for other resistant infections may become a cornerstone of therapy against some of the most treatment-refractory mycobacteria, provided clinicians deploy it wisely and researchers close the gaps that still separate laboratory promise from bedside certainty.

Subject of Research: Mechanisms and prevalence of tigecycline resistance in nontuberculous mycobacteria

Article Title: A review of tigecycline resistance in nontuberculous mycobacteria

Article References: Moura, C. D. S., da Silva, W. M. V., & Ramos, J. P. (2026). A review of tigecycline resistance in nontuberculous mycobacteria. Molecular Biology Reports, 53(1), Article 1637. https://doi.org/10.1007/s11033-026-12747-1

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12747-1

Keywords: tigecycline, nontuberculous mycobacteria, Mycobacterium abscessus, antimicrobial resistance, efflux pumps, WhiB7, MabTetX, SigH-RshA, minimum inhibitory concentration, glycylcyclines, combination therapy, drug-resistant bacteria

Fibrinogen sits at the heart of hemostasis. When blood vessels are injured, the enzyme thrombin cleaves fibrinogen into fibrin strands, which weave together into the meshwork of a stable clot. When fibrinogen levels fall below roughly 2.0 grams per liter, the threshold the researchers used to define hypofibrinogenemia in this study, that meshwork becomes fragile or fails to form at all, leaving patients exposed to bleeding risks at a time when many are already fighting severe, multidrug-resistant infections. The problem for clinicians has long been that hypofibrinogenemia in intensive care patients has many potential causes, including sepsis itself, disseminated intravascular coagulation, liver dysfunction, and massive transfusion, making it difficult to know when the antibiotic rather than the underlying illness is to blame.

The research team, led by Xiong Guo, Yao Zhang, Tao Yin, and corresponding author Ping Wang, addressed this ambiguity by focusing on the tigecycline trough concentration, the lowest level of the drug in plasma, measured just before the next dose is administered. Trough concentrations are a cornerstone of therapeutic drug monitoring because they capture the baseline exposure a patient carries between doses. Patients treated between January 2018 and May 2026 were enrolled, and every case of hypofibrinogenemia was adjudicated using WHO-UMC causality criteria, a standardized pharmacovigilance framework that helps separate drug-induced adverse events from those attributable to disease processes. Patients were then divided into a hypofibrinogenemia group and a normal group based on their fibrinogen measurements.

Using multivariable logistic regression, a statistical technique that isolates the independent contribution of each factor while controlling for the others, the team identified three independent risk factors for developing the complication: baseline fibrinogen level, duration of tigecycline treatment, and, critically, the trough concentration of the drug itself. Baseline fibrinogen carried a p-value of 0.022, treatment duration a p-value of 0.007, and trough concentration a p-value of 0.026, all of which reached conventional thresholds of statistical significance. Receiver operating characteristic analysis, which evaluates how well a continuous variable discriminates between patients who do and do not experience an outcome, then translated these risk factors into practical clinical cutoffs. Patients with a trough concentration of 0.27 micrograms per milliliter or higher, a treatment duration of 6.50 days or longer, or a baseline fibrinogen below 4.55 grams per liter faced markedly elevated risk.

Perhaps the most striking finding emerged when the investigators sorted patients into quartiles according to their trough concentrations. The incidence of hypofibrinogenemia rose in a clean, stepwise gradient across the quartiles, climbing from 36.11 percent in the lowest quartile to 82.05 percent in the highest, with a p-value for trend below 0.001. This dose-response relationship is exactly the kind of biological signal that lends credibility to a causal association: as exposure to the drug increases, so does the probability of harm, in a predictable and monotonic fashion. For intensive care physicians, the implication is that a simple blood measurement, available through routine therapeutic drug monitoring, could flag patients heading toward a coagulation crisis before fibrinogen levels collapse.

Beyond establishing who is at risk, the study mapped the natural history of the complication in unusual detail. The median time from the start of therapy to the onset of hypofibrinogenemia was 7 days, meaning clinicians should not assume that early uneventful treatment rules the risk out. Once established, the median duration of hypofibrinogenemia was 6 days. Most reassuring, however, was the recovery phase: after tigecycline was discontinued, fibrinogen levels returned to normal within a median of just 2.5 days. This rapid rebound suggests that the drug’s effect on fibrinogen is, at least in most patients, reversible rather than a sign of lasting injury to the synthetic machinery of the liver, which produces the vast majority of circulating fibrinogen.

The correlation analysis revealed an intriguing internal logic to the recovery process. Fibrinogen recovery time after discontinuation of tigecycline was positively correlated with both the time to hypofibrinogenemia onset and the duration of the hypofibrinogenemia episode, with both correlations reaching a p-value of 0.004. In other words, patients whose fibrinogen fell early, and those whose levels remained suppressed for longer, also took longer to bounce back once the drug was withdrawn. This pattern hints at a cumulative exposure phenomenon: the deeper and more prolonged the disruption, the more time the body’s fibrinogen production requires to restore equilibrium. It also reinforces the practical value of early detection, since patients identified and managed before prolonged suppression sets in may recover faster.

Importantly, the researchers also examined whether hypofibrinogenemia translated into worse short-term survival. Using Cox regression, they assessed 30-day mortality and found no significant association between the complication and death within a month, with a p-value of 0.289. That null finding should not be read as license for complacency, the study’s structure suggests, because the enrolled patients were already among the sickest in the hospital, with severe infections caused by multidrug-resistant pathogens, and competing risks in such a population can obscure the specific contribution of any single complication. Nevertheless, the result provides useful context: tigecycline-induced hypofibrinogenemia appears to be a common and monitorable adverse effect whose clinical management can focus on surveillance and timely drug withdrawal rather than panic.

The mechanistic story behind these observations remains an open question, and the authors are careful not to overclaim. Tigecycline is extensively metabolized and cleared through the liver and biliary system, and previous reports have linked the drug to elevations in liver enzymes, bilirubin, and coagulation parameters including prothrombin time and the international normalized ratio. One plausible explanation is that high cumulative exposure interferes directly or indirectly with hepatic fibrinogen synthesis, or with the clotting cascade more broadly, though the precise molecular pathway has not been pinned down. What the new study adds is a quantitative framework: a specific trough concentration threshold, a specific treatment duration, and a specific baseline fibrinogen level that together allow clinicians to stratify risk before the complication develops.

For the growing field of therapeutic drug monitoring in critical care, the findings carry a broader message. Antibiotics are often dosed by standard weight-based formulas that ignore the enormous pharmacokinetic variability among critically ill patients, whose organ function, fluid status, and protein binding can swing dramatically from day to day. Tigecycline, despite its approval and widespread use against serious Gram-positive and Gram-negative infections, has no well-established therapeutic range for safety, and this study suggests that establishing one could prevent a substantial burden of harm. The work was supported by the Hunan Natural Science Foundation, and the team notes that the risk gradient across concentration quartiles was prominent and progressive. If future prospective studies confirm the cutoffs identified here, routine trough measurement could become as standard a part of tigecycline therapy as the drug’s acclaimed antimicrobial coverage, turning an invisible pharmacokinetic variable into an actionable shield for patients who have little physiological reserve left to spare.

One reason trough monitoring may be especially informative for tigecycline lies in the drug’s unusual pharmacokinetic profile. Unlike most antibiotics, tigecycline distributes extensively into tissues, yielding a large volume of distribution and plasma concentrations that are only a small fraction of total body exposure. Critically ill patients are notoriously variable in this regard: shifts in fluid balance, hypoalbuminemia, hepatic congestion, and evolving organ dysfunction can all reshape how the drug behaves in a given individual, so two patients receiving the same weight-based dose may carry very different internal exposures. A trough measurement offers a practical window into that variability at the bedside.

The choice of a 2.0 grams per liter fibrinogen threshold also deserves comment. Fibrinogen is an acute-phase reactant, meaning it typically rises during inflammation, so many patients with severe infections start therapy with elevated levels. This may explain why a baseline value below 4.55 grams per liter emerged as a risk factor: patients whose fibrinogen reserves are already modest have less buffer before drug-related suppression pushes them into the hypofibrinogenemic range. It also complicates interpretation, since a falling fibrinogen in an inflamed patient may still represent a meaningful decline even if the absolute value remains above conventional cutoffs.

As a retrospective, single-center analysis, the study has inherent limitations that temper broad generalization. Concentration measurements were obtained as part of routine care rather than a standardized sampling protocol, and unmeasured confounders such as concurrent transfusions, blood products, or other fibrinogen-lowering drugs cannot be fully excluded. The authors’ use of WHO-UMC adjudication mitigates but does not eliminate this concern. Nevertheless, the open-access dataset, the dose-response gradient, and the internally consistent timing relationships provide a solid foundation for the prospective validation studies that would be needed before the proposed cutoffs enter routine clinical practice.

Subject of Research: The association between tigecycline trough plasma concentration and tigecycline-induced hypofibrinogenemia in critically ill patients.

Article Title: Tigecycline trough concentration and its relationship with hypofibrinogenemia: from onset and duration to recovery

Article References: Guo, X., Zhang, Y., Yin, T., & Wang, P. (2026). Tigecycline trough concentration and its relationship with hypofibrinogenemia: from onset and duration to recovery. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14419-8

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14419-8

Keywords: tigecycline, hypofibrinogenemia, trough concentration, therapeutic drug monitoring, fibrinogen, intensive care unit, antibiotic adverse effects, coagulation, multidrug-resistant infections, pharmacokinetics, drug safety, BMC Infectious Diseases