The research, published in Frontiers in Antibiotics, analyzed 200 non-duplicate clinical and environmental isolates of A. baumannii collected between 2022 and 2024 from a hospital network in the Delhi-NCR region. The team, led by Shyam Tripathi and V. Samuel Raj of SRM University, subjected every isolate to antimicrobial susceptibility testing by broth microdilution against 17 antibiotics, interpreted according to the Clinical and Laboratory Standards Institute M100 guidelines. Biofilm-forming capacity was quantified using the standardized microtiter plate crystal violet assay, while polymerase chain reaction detected six carbapenemase genes, three beta-lactamase genes, and three virulence genes. Sample size adequacy was verified using Buderer’s formula, ensuring the collection was statistically powered for the genotype-phenotype comparisons at the heart of the study.

The resistance landscape the researchers uncovered was stark. Among the 200 isolates, 54 percent were multidrug-resistant, 34 percent were extensively drug-resistant, and 61 percent were carbapenem-resistant. Fluoroquinolone resistance was near-universal, with 84 percent of isolates resistant to both ciprofloxacin and levofloxacin. Cephalosporin resistance ranged from 74.5 to 75.5 percent, and aminoglycoside resistance reached 67.5 percent for amikacin. Colistin, one of the last-resort polymyxin antibiotics, retained activity against 90 percent of isolates according to EUCAST criteria, while tigecycline remained active against 62 percent. These figures align with regional surveillance data from the ATLAS network, which identified nearly 87 percent carbapenem-resistant A. baumannii across South and Southeast Asia, far exceeding the roughly 40 percent rates observed in Europe.

At the genetic level, one carbapenemase gene towered above all others. The blaOXA-23 gene, an Ambler class D oxacillinase frequently mobilized by the insertion sequence ISAba1 and disseminated globally within the international clonal complex 2 lineage, was present in 61 percent of isolates. Other acquired carbapenemase genes, including blaOXA-24, blaOXA-58, blaNDM-1, blaVIM, and blaIMP, were detected only sporadically at frequencies of 3 percent or less. The intrinsic blaOXA-51 gene, used for species confirmation, was carried by all 200 isolates, while AmpC was widespread at 79 percent and blaPER-1 appeared in 60.5 percent of the collection.

The statistical concordance between blaOXA-23 carriage and phenotypic carbapenem resistance was remarkable. Cohen’s kappa reached 0.81, classified as almost-perfect agreement, with 92.6 percent of gene-positive isolates resistant to carbapenems compared with just 11.5 percent of gene-negative isolates. The odds ratio was 96.26 with a 95 percent confidence interval of 36.45 to 254.24. When the researchers considered composite carbapenemase carriage, defined as the presence of at least one carbapenemase gene, concordance improved further to kappa 0.88, with sensitivity of 98.4 percent and specificity of 88.5 percent. Carbapenemase gene burden also correlated strongly with meropenem MIC escalation, with a Spearman rank correlation coefficient of 0.816. From a diagnostic standpoint, these findings powerfully support integrating blaOXA-23 PCR into frontline resistance screening, ideally through rapid molecular platforms that can deliver results within one to two hours of isolate recovery.

Yet the study’s most provocative finding concerns what did not correlate. Biofilm-forming capacity, measured by crystal violet staining of attached biomass in 96-well polystyrene plates, was completely unrelated to cumulative antimicrobial resistance burden. Resistance burden, defined as the number of antibiotic classes showing resistance, did not differ significantly across weak, moderate, and strong biofilm producers, with median values of 12, 12, and 11 respectively. Kruskal-Wallis analysis confirmed no significant group difference, and Spearman correlation showed no monotonic association. XDR and PDR status likewise showed no significant relationship with biofilm phenotype. This null result challenges the widely assumed coupling between multidrug resistance and enhanced biofilm production in A. baumannii, and it converges with independent evidence from Chennai, India, where 247 isolates showed biofilm formation in 99 percent of strains without direct correlation to resistance phenotype.

There was one notable exception to this decoupling. Strong biofilm producers showed significantly higher colistin MIC values compared with weak producers, with a p-value of 0.001. The researchers offer a mechanistically coherent explanation rooted in the chemistry of polymyxin action. Colistin exerts its bactericidal effect by electrostatic exchange of divalent cations such as calcium and magnesium from the lipid A portion of lipopolysaccharide, destabilizing the bacterial outer membrane. The anionic extracellular polymeric substance matrix of A. baumannii biofilms, which contains poly-beta-(1,6)-N-acetylglucosamine, alginate-like polysaccharides, and extracellular DNA, sequesters these cations and physically prevents colistin from reaching its site of action at the bacterial surface. This represents a biofilm-associated phenotypic tolerance mechanism rather than confirmed genetic colistin resistance, as pmrAB mutations and lipid A modifications were not investigated. The practical implication is direct: routine colistin MIC testing performed on planktonic bacteria will systematically underestimate the effective concentration required to eradicate biofilm-associated infections, particularly in device-associated settings or ventilator-associated pneumonia.

The virulence genes told an equally compelling story of functional separation. All three virulence determinants analyzed, the biofilm-associated protein gene bap, the outer membrane protein A gene ompA, and the chaperone-usher pili gene csuE, were strongly and independently associated with strong biofilm formation. Among bap-positive isolates, 78.8 percent were strong biofilm producers compared with just 4.1 percent of bap-negative isolates. Similar patterns held for ompA and csuE, and blaPER-1 carriage was also linked to enhanced biofilm capacity. Critically, however, none of these virulence genes were associated with increased antimicrobial resistance burden. Mann-Whitney U analysis showed no significant difference in resistance burden according to bap, ompA, csuE, or blaPER-1 carriage, all with p-values above 0.05. These findings support the concept that virulence and antimicrobial resistance may evolve independently under different hospital selection pressures, with the biofilm-virulence axis establishing a distinct persistence mechanism that does not expand the spectrum of conventional resistance.

Three clinically actionable recommendations emerge from this work. First, blaOXA-23 PCR may serve as a useful rapid screening tool in high-carbapenem-resistance settings, though it should complement rather than replace phenotypic susceptibility testing because a small subset of blaOXA-23-positive isolates remained carbapenem-susceptible, possibly reflecting absence of upstream ISAba1 promoter activation or low-level gene expression. Second, phenotypic biofilm quantification may be considered as a supplementary risk-stratification tool in device-associated A. baumannii infections, particularly where colistin therapy is contemplated, given the elevated colistin MICs among strong biofilm formers. Third, the high prevalence of virulence-gene-driven biofilm capacity underscores the need for anti-biofilm adjunct strategies, including biofilm-disrupting agents, improved device coatings, and combination regimens pairing newer agents such as cefiderocol or sulbactam-durlobactam with biofilm-disrupting compounds.

The researchers acknowledge important limitations that temper the strength of their conclusions. The retrospective design using archived isolates did not allow longitudinal monitoring of resistance trends or correlation with patient outcomes. Advanced molecular typing approaches such as multilocus sequence typing and whole-genome sequencing were not undertaken, meaning clonal relationships, international lineage assignments, and plasmid-mediated transmission could not be fully delineated. ISAba1 mapping upstream of blaOXA genes and gene-expression analysis were also not performed, leaving the mechanisms underlying blaOXA-23-positive but carbapenem-susceptible discordant isolates unresolved. Growth kinetics were not assessed in parallel with the biofilm assay, so growth-rate effects on optical-density-based biofilm biomass cannot be fully excluded. Despite these constraints, the study demonstrates with statistical precision that biofilm formation and carbapenem resistance diverge as functionally independent adaptive strategies in A. baumannii. Resistance genotyping and biofilm phenotyping provide complementary rather than redundant information, and understanding this decoupling may prove essential for optimizing infection severity stratification and therapeutic decision-making in the ongoing battle against this critical-priority pathogen.

Subject of Research: Microbiology

Article Title: Carbapenem resistance genes and biofilm−virulence uncoupling in Acinetobacter baumannii

Article References: Tripathi, S., Rani, K., Berlia, R., Sharma, A., Hari, A., Gaur, P., Raj, P. S. S., & Raj, V. S. (2026). Carbapenem resistance genes and biofilm−virulence uncoupling in Acinetobacter baumannii. Frontiers in Antibiotics, 5, Article 1888133. https://doi.org/10.3389/frabi.2026.1888133

Image Credits: AI Generated

DOI: 10.3389/frabi.2026.1888133

Keywords: Acinetobacter baumannii, carbapenem resistance, blaOXA-23, biofilm, virulence genes, antimicrobial resistance, colistin, genotype-phenotype concordance, Frontiers in Antibiotics, India, Carbapenem, resistance

The study team, led by researchers from Banadir University, Somali National University, Hormuud University, and the Mogadishu-Somalia-Turkey Recep Tayyip Erdoğan Training and Research Hospital, systematically reviewed 4,464 initial isolates from the laboratory information management system. After removing duplicates (n = 2,118), non-bacterial organisms (n = 54), and non-Enterobacteriaceae Gram-negative isolates (n = 1,534), 758 unique Enterobacteriaceae isolates representing individual patient episodes were retained for analysis. This deduplication strategy, retaining only the first recorded culture episode per patient, avoids over-representation of patients with repeated cultures and ensures each isolate reflects a distinct clinical event. The cohort was drawn from Emergency and General Intensive Care Units admitting approximately 2,000 to 2,500 critically ill patients annually, a population uniquely vulnerable to resistant infections owing to invasive mechanical ventilation, central venous and urinary catheterization, and repeated broad-spectrum antibiotic exposure.

Microbiologically, the cohort was dominated by two genera. Escherichia coli accounted for 48.3% of isolates and Klebsiella spp. for 45.9%, together representing 94.2% of the entire collection. Enterobacter spp. (2.2%), Proteus spp. (2.0%), Serratia spp. (0.7%), Citrobacter spp. (0.5%), Pantoea spp. (0.3%), and Morganella morganii (0.1%) made up the remainder. The demographic profile showed that 63.5% of isolates came from male patients, with the age distribution spanning 5.0% aged 20 years or younger, 37.9% aged 21–40, 24.7% aged 41–60, and 32.5% over 60. Sputum specimens predominated at 62.3% of the collection, followed by urine (21.5%) and blood (16.2%), reflecting the high burden of suspected lower respiratory tract infection among mechanically ventilated patients in this setting.

Antimicrobial susceptibility testing followed Clinical Laboratory Standards Institute (CLSI) M100 performance standards using the Kirby-Bauer disk diffusion method on Mueller-Hinton agar. Eight antimicrobials representing eight distinct classes were tested: colistin, meropenem, piperacillin-tazobactam, cefoperazone-sulbactam, amikacin, tigecycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Because disk diffusion is not recommended for colistin susceptibility testing in Enterobacteriaceae owing to poor agar diffusion, colistin interpretation relied on broth microdilution using CLSI M07 reference methodology. Under CLSI M100 criteria, only intermediate (MIC ≤2 µg/mL) and resistant (MIC ≥4 µg/mL) categories are recognized for colistin against Enterobacterales, with no susceptible category defined. A critical methodological correction was applied during the study: 21 isolates (2.8% of the cohort) belonging to Proteus spp., Serratia spp., and Morganella morganii are intrinsically resistant to polymyxins as a consequence of constitutive lipid A modification encoded by the arnBCADTEF operon, which neutralizes the anionic charge of lipopolysaccharide and prevents polymyxin binding. These isolates were excluded from the denominator used to estimate acquired colistin resistance, yielding a corrected denominator of 737.

The species-level pattern of multidrug resistance emerged as the study’s most consequential microbiological finding. Klebsiella spp. demonstrated the highest MDR prevalence at 54.9%, with over half of all Klebsiella isolates resistant to at least one agent in three or more antimicrobial classes. Enterobacter spp. followed at 52.9%, while Escherichia coli showed a markedly lower MDR rate of 22.1%. In the multivariable logistic regression model, relative to Klebsiella spp., E. coli isolates had significantly reduced odds of multidrug resistance (adjusted odds ratio 0.27; 95% confidence interval 0.19–0.38; p < 0.001), and Proteus isolates similarly showed lower odds (AOR 0.19; 95% CI 0.05–0.70; p = 0.012). Neither patient sex, age group, nor ICU type was significantly associated with MDR status in the adjusted analysis. The model explained approximately 10.5% of the variance in MDR status (pseudo R² = 0.105), indicating that bacterial species identity is the primary driver of resistance in this cohort, while demographic and specimen variables available in the retrospective laboratory database account for only a small fraction of the observed variation.

Specimen source showed a significant bivariate association with multidrug resistance (χ² = 34.81, p < 0.001). Sputum specimens harbored the highest proportion of MDR isolates at 44.9%, followed by blood at 35.8% and urine at 19.0%. In the multivariable model, sputum isolates showed a non-significant trend toward higher odds of MDR relative to blood (AOR 1.40; 95% CI 0.90–2.17; p = 0.136), while urine isolates tended toward lower odds (AOR 0.61; 95% CI 0.34–1.09; p = 0.097). The predominance of respiratory specimens carrying the highest resistance burden is consistent with the epidemiology of ventilator-associated pneumonia, in which mechanically ventilated patients undergo protracted exposure to broad-spectrum beta-lactams administered empirically for suspected lower respiratory tract infection, creating an intensely selective environment within respiratory secretions that preferentially enriches for highly resistant Gram-negative bacilli.

The antimicrobial susceptibility landscape revealed profound therapeutic constraints. Among tested multidrug-resistant isolates, ciprofloxacin resistance reached 95.4%, trimethoprim-sulfamethoxazole resistance 92.9%, and meropenem resistance 77.5%. Piperacillin-tazobactam resistance among MDR isolates was 94.3%, cefoperazone-sulbactam 83.9%, and amikacin 54.8%. These figures leave virtually no oral or first-line therapeutic option for patients infected with MDR strains. By contrast, colistin retained the greatest in vitro activity: among the 737 isolates from genera without intrinsic polymyxin resistance, acquired resistance was documented in only 1.2% (9/735 tested). All nine colistin-resistant isolates were multidrug-resistant, comprising six Klebsiella spp., two E. coli, and one Pantoea sp. The proportion of colistin resistance among MDR isolates was 3.2% (9/283) versus 0/452 among non-MDR isolates (p = 0.001), a pattern more compatible with therapy-selected chromosomal resistance within an already-resistant population than with independent plasmid acquisition, although the authors caution that with only nine isolates this observation is hypothesis-generating rather than conclusive. Because confirmatory broth microdilution was applied only to isolates screening non-susceptible on disk diffusion, the colistin figure represents a conservative lower-bound estimate, and heteroresistant subpopulations below the detection threshold of standard broth microdilution may have been misclassified as non-resistant.

Tigecycline resistance was 17.4% among the 155 isolates in which it was tested, but the agent was tested in only 20.4% of the cohort, and testing was clinically directed rather than systematic, preferentially applied to isolates already known to be extensively resistant. The authors note that resistance proportions for agents with low testing coverage are subject to ascertainment bias in the direction of overestimation and should be regarded as provisional pending systematic panel testing. Testing coverage ranged from 99.7% for colistin and 95.0% for meropenem to 15.0% for trimethoprim-sulfamethoxazole, and all susceptibility proportions reported use the number of isolates actually tested for each agent as the denominator.

The temporal trajectory spanning the pre-pandemic, pandemic, and post-pandemic periods offers unique insights into how extraordinary disruptions in healthcare delivery interact with resistance patterns in low-resource settings. The 2021 decline rests on the smallest annual sample in the series (n = 70; 95% CI 7.9–24.3%) and is temporally compatible with several explanations the dataset cannot distinguish, including transient benefits of intensified infection prevention measures during the acute COVID-19 phase, reduced patient volume, and altered specimen submission practice. Notably, the specimen mix in 2021 differed markedly from surrounding years, with sputum accounting for 20 of 70 isolates compared with 127 of 176 in 2022; since sputum isolates carried the highest MDR prevalence, part of the apparent 2021 decline may reflect this compositional shift rather than a change in underlying resistance. The subsequent resurgence to 54% by 2024 aligns with documented global post-pandemic antimicrobial resistance trends, including disruptions to stewardship programs and increased antimicrobial consumption. A 2024 analysis from the WHO Global Antimicrobial Resistance and Use Surveillance System demonstrated statistically significant positive correlations between beta-lactam and fluoroquinolone consumption and increased recovery of resistant E. coli and Klebsiella spp. from bloodstream infections across participating countries. However, the authors emphasize that antimicrobial consumption data were not available for this institution, and the temporal association documented here should be read as a signal warranting prospective investigation rather than as evidence that post-pandemic health-system disruption caused the resurgence.

Somalia currently lacks a functional national antimicrobial resistance surveillance system, established WHO GLASS participation, or a formally adopted National Action Plan on Antimicrobial Resistance. This institutional absence stands in sharp contrast to regional peers, where two-thirds of WHO African Region countries have developed national action plans and 30 of 47 countries participate in WHO GLASS. The authors call for urgent institutional responses including the establishment of a quarterly institutional antibiogram, creation of a multidisciplinary Antimicrobial Stewardship Committee, and restricted-use protocols for carbapenems and colistin requiring infectious disease consultation and documented clinical justification. At the national level, they advocate formal engagement with the WHO GLASS framework, development of a Somalia-specific National Action Plan incorporating multicenter surveillance and molecular resistance characterization, and establishment of a sentinel hospital surveillance network anchored at three to five geographically representative hospitals. The single-center design means the findings should be interpreted as indicative of high-acuity tertiary ICU settings in urban Somalia rather than nationally representative estimates, and multicenter prospective studies are essential to validate these findings across Somalia’s diverse healthcare landscape. Given that global data report 30-day mortality rates of 50–57% among ICU patients with carbapenem-resistant Enterobacteriaceae bacteremia, the clinical urgency of the resistance escalation documented in this Mogadishu ICU could not be clearer.

Subject of Research: Antimicrobial Resistance

Article Title: Epidemiology and predictors of multidrug-resistant Enterobacteriaceae in intensive care units of a tertiary hospital in Somalia: a five-year retrospective study (2019–2024)

Article References: Zubair, O. S., Abdi, Y. H., Ali, T. A., Issack, Z. I., & Ahmed, A. A. (2026). Epidemiology and predictors of multidrug-resistant Enterobacteriaceae in intensive care units of a tertiary hospital in Somalia: a five-year retrospective study (2019–2024). Frontiers in Antibiotics, 5, Article 1889216. https://doi.org/10.3389/frabi.2026.1889216

Image Credits: AI Generated

DOI: 10.3389/frabi.2026.1889216

Keywords: antimicrobial resistance, Enterobacteriaceae, intensive care units, Somalia, Klebsiella, colistin, antimicrobial stewardship, WHO GLASS, Epidemiology, predictors, multidrug-resistant, intensive

The study, published in BMC Infectious Diseases by Sinan Mermer of the Department of Infectious Diseases and Clinical Microbiology and Ertuğrul Çağlayan of the Department of Microbiology at Medical Point Hospital, İzmir University of Economics, examined bloodstream infections caused by Gram-negative bacilli in ICU patients. The researchers focused on two things: how common carbapenem resistance had become among these isolates, and how susceptible the resistant organisms remained to amikacin, an aminoglycoside, and colistin, a polymyxin that many microbiologists regard as a last-resort antibiotic.

The headline finding is stark. Among Gram-negative bloodstream isolates from the ICU, 85.4 percent were carbapenem-resistant. That figure means that in this setting, the great majority of Gram-negative bacteria recovered from the blood had already lost susceptibility to carbapenems, the beta-lactam antibiotics that are often considered the backbone of empirical therapy for serious infections in critically ill patients. Two species dominated the resistant population: Acinetobacter baumannii, with 94.5 percent of isolates resistant, and Klebsiella pneumoniae, with 92.6 percent resistant. Together these two organisms accounted for more than 80 percent of the carbapenem-resistant isolates in the study.

Both organisms are familiar adversaries. Acinetobacter baumannii is a resilient environmental survivor that thrives on hospital surfaces and medical equipment, and it has an extraordinary capacity to accumulate resistance determinants. Klebsiella pneumoniae, a normal inhabitant of the human gut, has become one of the most successful carriers of carbapenemase enzymes worldwide, spreading through hospitals and long-term care facilities with alarming efficiency. When either organism enters the bloodstream, mortality is high, and the window in which effective therapy changes outcomes is narrow, often measured in hours rather than days.

The technical explanation for carbapenem resistance in these organisms lies largely in enzymes. Carbapenemases come in several molecular classes. The Klebsiella pneumoniae carbapenemase, or KPC, is a class A serine beta-lactamase that hydrolyzes carbapenems and most other beta-lactams. Metallo-beta-lactamases, such as NDM enzymes, belong to class B and use a zinc ion in their active site, which makes them intrinsically resistant to inhibition by conventional beta-lactamase inhibitors. Oxacillinases of the OXA family, particularly OXA-23 and OXA-58, are the dominant carbapenemases in Acinetobacter baumannii. Because these enzymes are often encoded on plasmids or integrated into mobile genetic elements, they can move between strains and species, which is why resistance in one ICU isolate can foreshadow resistance in the next patient’s infection.

Against this backdrop, the study’s second question becomes clinically urgent. Amikacin is an aminoglycoside that binds to the bacterial 30S ribosomal subunit, causing misreading of mRNA and halting protein synthesis. It was introduced in the 1970s and was largely sidelined as safer beta-lactams proliferated, but it has retained activity against many carbapenem-resistant organisms because the resistance mechanisms that defeat beta-lactams do not affect ribosomal binding. Colistin works differently: it is a cationic polypeptide that disrupts the outer membrane of Gram-negative bacteria by binding to lipopolysaccharide, displacing calcium and magnesium ions that stabilize the membrane. Its clinical revival over the past two decades has been driven almost entirely by necessity, since it often remains active against organisms resistant to everything else, despite nephrotoxicity and the awkward pharmacokinetics that stem from its development in an era before modern dosing studies.

In the new study, amikacin showed moderate activity, particularly against Klebsiella pneumoniae, while colistin retained some in vitro activity against the resistant isolates. The authors are careful, however, to attach a significant caveat: methodological limitations in susceptibility testing mean these findings should be interpreted with caution. That caution is well grounded. Colistin susceptibility testing is notoriously difficult. The polymyxin molecules adhere to plastic surfaces and diffuse poorly in agar, which makes disk diffusion unreliable, and broth microdilution, the reference method recommended by both EUCAST and CLSI, is technically demanding and not universally available in routine laboratories. Gradient methods and automated systems can misclassify isolates, and the clinical breakpoints themselves have been revised in recent years as pharmacokinetic and pharmacodynamic data accumulated. A laboratory report of colistin susceptibility can therefore be a less certain guide to treatment than clinicians might assume.

The study’s context matters as much as its numbers. In many regions, novel beta-lactam and beta-lactamase inhibitor combinations, such as ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam, are either unavailable or unaffordable, and agents active against metallo-beta-lactamase producers remain scarce. Where access to these drugs is restricted, clinicians fall back on the older arsenal: colistin-based combination regimens, aminoglycosides, tigecycline, and sometimes high-dose carbapenems in organisms with only moderately elevated minimum inhibitory concentrations. The authors conclude that in settings with a high incidence of carbapenem-resistant Gram-negative bacilli and restricted access to novel agents, amikacin and colistin may be considered in selected cases, guided by local susceptibility data.

That emphasis on local data is the study’s most actionable message. Resistance rates for these organisms vary enormously between hospitals, regions, and even units within the same institution, driven by local clonal spread and differing antibiotic use. A susceptibility rate measured in one ICU cannot be safely extrapolated elsewhere, which is why the authors argue that early appropriate antimicrobial therapy should be guided by local resistance patterns rather than by global guidelines alone. For a clinician facing a septic ICU patient, the difference between an 85 percent resistance rate and a 40 percent one changes the entire calculus of empirical therapy, from the choice of initial regimen to the urgency of escalation once culture results return.

The findings also carry a broader warning for antimicrobial stewardship. Reliance on colistin and aminoglycosides is not a stable solution. Colistin resistance in Klebsiella and other Gram-negatives, typically mediated by modifications to lipopolysaccharide that reduce the drug’s binding target, has been documented worldwide and can emerge during therapy. Aminoglycoside resistance arises through modifying enzymes and ribosomal mutations and can be selected rapidly under drug pressure. Every course of a last-resort antibiotic consumes a finite resource, and the study’s authors implicitly frame their results accordingly: these older drugs retain value, but that value depends on surveillance, susceptibility testing of adequate quality, and stewardship programs that prevent indiscriminate use. As carbapenem resistance in ICU bloodstream infections approaches saturation levels, the margin between effective therapy and therapeutic failure narrows to the precision of the laboratory and the speed of the clinician, and studies like this one document exactly how thin that margin has become.

Subject of Research: Carbapenem resistance and susceptibility to amikacin and colistin among Gram-negative bloodstream isolates in ICU patients

Article Title: Do amikacin and colistin retain activity against carbapenem-resistant gram-negative bloodstream isolates in a single-center ICU?

Article References: Mermer, S., & Çağlayan, E. (2026). Do amikacin and colistin retain activity against carbapenem-resistant gram-negative bloodstream isolates in a single-center ICU?. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-13988-y

Image Credits: AI Generated

DOI: 10.1186/s12879-026-13988-y

Keywords: carbapenem-resistant Gram-negative bacilli, bloodstream infection, intensive care unit, amikacin, colistin, antimicrobial resistance, Acinetobacter baumannii, Klebsiella pneumoniae, antimicrobial stewardship, susceptibility testing, EUCAST, surveillance

The microbes recovered from his hip were among the most feared organisms in modern medicine. Of nine intraoperative tissue samples, eight grew carbapenem-resistant, carbapenemase-producing Acinetobacter baumannii, and two grew OXA-48-producing carbapenem-resistant Klebsiella pneumoniae. Alongside these Gram-negative threats, the cultures also yielded methicillin-resistant Corynebacterium amycolatum, Corynebacterium striatum, Staphylococcus epidermidis, and Enterococcus faecalis. In other words, the infection was polymicrobial and multidrug-resistant, involving bacteria for which carbapenems, usually considered the last-line class for Gram-negative infections, no longer worked. Reports of such organisms causing periprosthetic joint infection are rare, and treatment options are correspondingly scarce, which is precisely why the surgical team chose to document every step of their protocol.

The underlying difficulty in any implant-related bone and joint infection is the biofilm. Bacteria attached to an implant surface or to dead bone encase themselves in a protective matrix that acts as a physical barrier against antibiotics and immune cells. For many species, the concentration of drug needed to eradicate bacteria in a biofilm, the minimal biofilm eradication concentration, can be up to one thousand times higher than the concentration that kills the same bacteria floating freely in a laboratory culture. Systemic antibiotics alone therefore often fail, and the only reliable route to cure is meticulous surgical removal of infected tissue and foreign material, combined with antimicrobial therapy that reaches the joint in sufficient quantities. Periprosthetic joint infection of the hip occurs in roughly 0.5 to 2 percent of primary total hip replacements and up to 15 percent of revision procedures, and the stakes are high: failed treatment can end in amputation, a catastrophic functional outcome that surgeons strive to avoid.

The Slovenian team, led by Urban Vadnjal together with Samo Roškar, René Mihalič, Mitja Rak, and Rihard Trebše, followed a written institutional algorithm for fracture-related and periprosthetic joint infection, and the case report emphasizes that strict adherence to each step was central to the outcome. The first operation involved radical debridement of the infected hip and insertion of a temporary antibiotic-loaded cement spacer. Four 42.9-gram sachets of bone cement preloaded with gentamicin and clindamycin were supplemented with an additional 4 grams of vancomycin and 2 grams of meropenem, so that the spacer itself became a local drug-delivery depot occupying the dead space left after debridement. Nine microbiological and three histological samples were taken before any empirical antibiotics were started, allowing therapy to be tailored to the actual pathogens rather than guessed at.

Empirical treatment began immediately after sampling with intravenous piperacillin-tazobactam and vancomycin, the latter dosed by plasma concentration monitoring. Once the antibiograms of the isolated bacteria returned, therapy was escalated on the third postoperative day to a combination of vancomycin, fosfomycin, and colistin, a polymyxin reserved for the most resistant Gram-negative infections, given as a 9-million-unit loading dose followed by 4.5 million units every twelve hours. Crucially, the team also began intra-articular infusions: 400 milligrams of vancomycin in 5 milliliters every twenty-four hours, and 125,000 international units of colistin in 2 milliliters daily, delivered through a catheter placed in the joint. The pharmacy department designed these preparations based on the physicochemical properties and cytotoxicity profiles of the drugs, and on measured concentrations in drainage fluid, aiming for the smallest possible volume in which each antibiotic remained fully soluble.

The regimen was then refined repeatedly as definitive resistance data arrived. Fosfomycin was stopped one week after surgery when the laboratory confirmed resistance, and intravenous tigecycline was introduced instead. Two weeks postoperatively, vancomycin and tigecycline were withdrawn and replaced with teicoplanin and ceftazidime-avibactam, a beta-lactam and beta-lactamase-inhibitor pair active against some carbapenem-resistant Enterobacterales. At eighteen days, with the full resistance profile in hand, the team settled on a final targeted combination: intravenous ceftazidime-avibactam to cover the Klebsiella pneumoniae, dose-adjusted intravenous vancomycin to cover the Gram-positive organisms, and continued daily intra-articular colistin against the Acinetobacter baumannii. All intravenous and local therapy was stopped at three weeks, by which time the C-reactive protein had fallen below 5 milligrams per liter and the catheter was removed under a watertight seal protocol with regular dressing changes.

What followed was a deliberate antibiotic holiday of two weeks, after which a second revision procedure in January 2022 allowed the team to test whether the infection had truly been suppressed. Debridement and tissue sampling were repeated, and the spacer was exchanged for a new one made from three sachets of gentamicin- and clindamycin-loaded cement supplemented with 3 grams of vancomycin and 3 million units of colistin. A short seven-day course of intravenous vancomycin, ceftazidime-avibactam, and intra-articular colistin accompanied the exchange. This time the cultures came back sterile, and histology showed no evidence of acute inflammation, the biological green light the team needed to proceed to definitive reconstruction.

At the end of February 2022, the hip was rebuilt with trabecular metal augments, a dual-mobility acetabular shell, and a cementless femoral component, supported by a brief five-day course of intravenous vancomycin and ceftazidime-avibactam. Because no susceptible oral antibiotic existed for any of the pathogens involved, the entire treatment course was administered parenterally, a demanding logistical undertaking that required regular monitoring of serum creatinine, urea, and electrolytes to guard against kidney toxicity, particularly from the colistin and the glycopeptides. The patient left hospital walking with crutches, the surgical wound fully healed.

At the most recent follow-up in June 2026, three and a half years after the reconstruction, there were no clinical or laboratory signs of infection. The patient walked without assistive devices over shorter distances, had good hip mobility and strength, and reported no pain at rest with only mild discomfort on exertion. His Harris hip score was 78, with the main functional limitation being a foot drop and Achilles tendon contracture dating back to the original polytrauma rather than the infection. Radiographs showed a stable implant with no osteolysis, loosening, or periprosthetic fracture, and the residual limb length discrepancy was approximately 2 centimeters.

The authors are careful about what the case can and cannot prove. A single patient cannot isolate the contribution of intra-articular antibiotics from the many other moving parts: extensive debridement, multiple revision procedures, spacer exchange, systemic combination therapy, and multidisciplinary management all plausibly contributed. Local drug delivery is attractive in principle because it sidesteps systemic toxicity, poor perfusion of scarred tissue, and a blunted immune response around the infected joint, and the approach was first described in the early 1990s and popularized in 2017 as a way of treating infected hip replacements. But the team frames it as a salvage option to be considered alongside, not instead of, rigorous surgery. Their broader message is procedural rather than pharmacological: hospitals treating fracture-related and periprosthetic infections need well-established algorithms and the discipline to follow them at every step, because in severe multidrug-resistant cases a multiple-stage protocol, with intra-articular infusions added to standard intravenous regimens, may be what stands between a patient and a dead-end outcome.

Subject of Research: Treatment of a polymicrobial, multidrug-resistant chronic hip infection with staged revision surgery and combined systemic and intra-articular antibiotic therapy

Article Title: Clinical case of polymicrobial and multidrug-resistant posttraumatic chronic hip infection treatment

Article References: Vadnjal, U., Roškar, S., Mihalič, R., Rak, M., & Trebše, R. (2026). Clinical case of polymicrobial and multidrug-resistant posttraumatic chronic hip infection treatment. Journal of Bone and Joint Infection, 11(5), 565-568. https://doi.org/10.5194/jbji-11-565-2026

Image Credits: AI Generated

DOI: 10.5194/jbji-11-565-2026

Keywords: periprosthetic joint infection, fracture-related infection, multidrug-resistant bacteria, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, biofilm, intra-articular antibiotics, antibiotic-loaded cement spacer, hip revision surgery, colistin, ceftazidime-avibactam, antimicrobial resistance

The team, led by Farah H. Omer of the University of Mosul and including investigators from the University of Babylon, the University of Anbar, and Ahvaz Jundishapur University of Medical Sciences in Iran, set out to answer a deceptively simple question: what is actually swimming in the water leaving hospitals in a mid-sized Iraqi city? To find out, they passed wastewater samples through cellulose ester membrane filters, a technique that traps bacteria on the filter surface while the liquid passes through. The trapped organisms were then cultured on cetrimide agar, a selective medium that favors Pseudomonas species and produces characteristic green pigmented colonies of P. aeruginosa. Suspected colonies were identified with a VITEK2 automated system, a workhorse of clinical microbiology laboratories, and every isolate was confirmed by polymerase chain reaction targeting the ecfX gene, a species-specific genetic marker that leaves little room for misidentification.

With the isolates confirmed, the researchers turned to antibiotic susceptibility testing using the disc diffusion method, following standards set by the Clinical and Laboratory Standards Institute. The results were sobering. Resistance to aztreonam, a monobactam antibiotic often used against gram-negative infections, reached 65.5 percent of isolates, while 58.8 percent resisted ceftazidime, a third-generation cephalosporin that is a mainstay of treatment for Pseudomonas infections. Ceftazidime resistance in this species is known to be multigenic and complex, involving combinations of reduced permeability, efflux pumps, and hydrolytic enzymes, which makes its high prevalence in wastewater isolates particularly concerning. Against this grim backdrop, one drug stood out: colistin, an older polymyxin antibiotic that has been revived as a last-resort agent, inhibited 89.9 percent of the isolates, making it by far the most effective compound tested.

The most alarming statistic, however, was the burden of multidrug resistance. Using standard definitions, the team classified 82.4 percent of the isolates, 98 of the 119 recovered, as multidrug-resistant, meaning they were nonsusceptible to at least one agent in three or more antimicrobial categories. That proportion rivals or exceeds what is often reported from clinical settings, where selective pressure from therapeutic antibiotic use is intense. Its presence in wastewater implies that the hospital drain is functioning as a selective reactor: bacteria exposed to a cocktail of residual antibiotics, disinfectants, and heavy metals are winnowed down to the hardiest strains, which then multiply and disperse. Environmental microbiologists have documented similar patterns in hospital effluents in the Czech Republic, South Africa, and elsewhere, but the Iraqi data underscore how widespread the phenomenon has become and how little containment typically occurs between the hospital sink and the municipal sewer.

Resistance alone does not make a bacterium dangerous; it must also carry the tools to cause disease. The researchers therefore screened every isolate by PCR for fourteen virulence genes spanning the major weapon systems of P. aeruginosa. The results read like a catalogue of the pathogen’s most feared capabilities. The toxA gene, which encodes exotoxin A, a potent inhibitor of protein synthesis that damages host cells, was present in 100 percent of the isolates. The lasB gene, which encodes elastase B, an enzyme that degrades elastin and other tissue proteins and helps the bacterium invade and spread, was found in 65.5 percent. The exoT gene, part of the type III secretion system that injects toxic effectors directly into host cells, appeared at the same frequency of 65.5 percent. Every one of these genes contributes to the tissue destruction and immune evasion that make P. aeruginosa infections so difficult to treat in burn wounds, lungs, and catheterized patients.

The wider virulence screen painted a picture of genetically well-armed populations. Genes encoding phospholipases C (plcH and plcN), which disrupt host cell membranes; exoenzymes S, T, U, and Y, the type III secreted effectors with distinct cytotoxic and immunomodulatory roles; alkaline protease (apr); the quorum-sensing and phenazine biosynthesis genes phzI and phzII, which govern pigment production and intercellular signaling; and the alginate biosynthesis genes algD and algU, which underpin the mucoid, antibiotic-impermeable biofilm phenotype, were all detected across the collection. The simultaneous presence of exoS and exoU alleles, which are usually considered largely mutually exclusive in clinical strains, has been noted before in environmental isolates and hints that wastewater populations may recombine and shuffle virulence determinants in ways that clinical populations do not.

Perhaps the most intriguing analytical step was the search for statistical relationships between virulence genes and antibiotic susceptibility. The team reported significant positive correlations between several gene pairs and specific drugs: algU with ciprofloxacin; phzII with piperacillin; phzI with imipenem, ceftazidime, and amikacin; plcN with imipenem; plcH with amikacin, piperacillin, and piperacillin-tazobactam; exoY with piperacillin; exoT with ceftazidime; and exoS with colistin. Correlation does not establish causation, and the authors did not claim direct genetic linkage between these loci and resistance mechanisms. But such associations are consistent with a scenario in which virulence and resistance traits are being co-selected in the same bacterial lineages, whether through shared mobile genetic elements, biofilm lifestyles that favor both traits, or the linkage of virulence determinants with efflux systems that pump out antibiotics. If hospital effluent consistently selects for strains that are both drug-tolerant and toxin-armed, the public health stakes rise considerably.

The study was approved by the Ethics Committee of the University of Babylon in November 2025 and involved no human or animal samples, sidestepping many of the logistical hurdles of clinical surveillance while capturing something clinical surveillance often misses: the environmental fate of pathogens after they leave the ward. Previous work in Iraq has documented cephalosporin resistance in clinical P. aeruginosa from Basra and the presence of resistance genes in water samples from Baghdad, and studies from Iran, China, Mexico, and Bangladesh have traced resistant and virulent strains in drinking water, groundwater, soil, and food. The Babylon data fit into this global mosaic and suggest that in regions where wastewater treatment is limited or absent, hospital effluents may serve as a continuous, largely unmonitored source of high-risk bacteria entering rivers, irrigation systems, and communities.

The authors’ conclusion is blunt: hospital effluents are critical sources of multidrug-resistant and virulent P. aeruginosa, and there is an urgent demand to improve wastewater management. That demand carries technical implications. Effective interventions could include on-site pretreatment of hospital effluent before discharge, enhanced monitoring of resistance and virulence markers in sewer networks, and stewardship programs that reduce the quantity of antibiotics entering the drain in the first place. The near-universal presence of toxA and the high frequency of lasB and exoT in these environmental isolates suggest that virulence screening, not just resistance testing, should inform risk assessments of hospital wastewater. As antimicrobial resistance continues to erode the clinical arsenal, with colistin remaining one of the few reliably effective agents, the drains of the world’s hospitals have become more than plumbing. They are, according to this study, active evolutionary arenas where the next generation of dangerous pathogens may be assembling, one selective pressure at a time.

Subject of Research: Virulence genes and antibiotic resistance in Pseudomonas aeruginosa from Iraqi hospital wastewater

Article Title: Virulence arsenal and antibiotic resistance backgrounds in Pseudomonas aeruginosa isolates from hospital wastewater samples from Iraq

Article References: Omer, F. H., Al-Khafaji, N. S. K., Shakir, B., Almjalawi, A., Al-Alaq, F. T., Al-Dahmoshi, H. O. M., Al-Ouqaili, M. T. S., Ahmad, F., & Saki, M. (2026). Virulence arsenal and antibiotic resistance backgrounds in Pseudomonas aeruginosa isolates from hospital wastewater samples from Iraq. Molecular Biology Reports, 53(1), Article 1654. https://doi.org/10.1007/s11033-026-12865-w

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12865-w

Keywords: Pseudomonas aeruginosa, hospital wastewater, antimicrobial resistance, multidrug resistance, virulence genes, toxA, lasB, Iraq, colistin, PCR, public health, wastewater management

Researchers led by Oluwawemimo Adebowale of the Federal University of Agriculture, Abeokuta, surveyed 48 integrated farms in Lagos and Ogun states between May and September 2023, using structured interviews with farmers alongside on-site assessments of biosecurity. The results, published in BMC Agriculture, offer the first baseline data on antimicrobial use in this emerging Nigerian farming system, and they reveal a landscape of heavy antibiotic reliance, patchy disease prevention, and knowledge gaps that could accelerate the global crisis of antimicrobial resistance.

The scale of drug use on these farms is striking. Farmers reported deploying at least ten different classes of antibiotics, including fluoroquinolones, tetracyclines, macrolides, aminoglycosides, penicillins, sulphonamides, lincosamides, cephalosporins, nitrofurans, and polymyxins. In poultry, the most commonly used drugs were enrofloxacin, reported by 89.4 percent of farmers, oxytetracycline at 80.9 percent, doxycycline and tylosin at 78.7 percent, and colistin at 63.8 percent. For fish, oxytetracycline and enrofloxacin dominated. Many of these compounds fall into the World Health Organization’s highest priority critically important antimicrobials for human medicine, meaning they are drugs on which doctors depend when other treatments fail. Colistin, a polymyxin widely used on the surveyed farms, is considered a last-resort antibiotic in human medicine, reserved for infections that no other drug can touch.

The WHO classifies antibiotics into three stewardship tiers known as AWaRE: Access, for first-line drugs with low resistance risk; Watch, for broader-spectrum drugs that require careful monitoring; and Reserve, for last-line treatments. The study found that farmers were using drugs from all three groups, including Watch and Reserve categories, often without veterinary oversight. Nearly 96 percent of farmers purchased antimicrobials from veterinary pharmacies, and 79.2 percent used them to prevent disease rather than to treat diagnosed infections, a practice that blankets healthy animals in drugs and creates intense selection pressure for resistant microbes.

The biology of the integrated system amplifies the risk. When poultry droppings containing antibiotic residues and resistant bacteria wash into fish ponds, the aquatic environment becomes a mixing vessel where resistance genes can move between bacterial species. A previous Nigerian study cited by the researchers confirmed that multidrug-resistant gram-negative bacteria from chicken excreta were disseminating into pond environments and fish. Because bacteria readily exchange resistance genes through horizontal gene transfer, a pond fertilized with medicated poultry waste is essentially an evolutionary accelerator. Fish raised in that water, and inadequately cooked before consumption, can carry resistant pathogens to the dinner table.

Disease pressure on these farms helps explain the drug dependence. Chronic respiratory disease was the most commonly reported chicken ailment, affecting 68.8 percent of farms in the previous year, followed by infectious coryza and bacterial gastroenteritis from salmonellosis and colibacillosis. Among fish, fin rot was the leading complaint. Yet the study found that preventive measures were applied unevenly: nearly all farmers vaccinated and dewormed their chickens, but fewer than one in ten reported routine vaccination of fish, leaving aquaculture largely unprotected and dependent on reactive drug use when outbreaks struck.

Biosecurity, the frontline defense that reduces the need for antibiotics in the first place, was found wanting. Only 54.1 percent of farms had established biosecurity protocols at the time of the visit, and field assessors judged just 37.5 percent of farmers as having good biosecurity measures in practice. The overall biosecurity score averaged 64.7 percent, with more than half of participants rated as poor. Two-thirds of farms reported migratory wild birds on the premises, a known vector for disease introduction, while fewer than a third had designated biosecurity work zones separating clean and dirty operations. In a system where poultry and fish share water, waste, and space, such lapses leave multiple doors open for pathogens.

Perhaps the most encouraging finding is that knowledge and attitude appear to be levers for change. Farmers’ knowledge of antimicrobial use correlated positively with their actual practices, as did their attitudes, and the two were strongly linked to each other. Farmers who understood the risks tended to think differently about drugs, and farmers who thought differently tended to use them more responsibly. More than 94 percent of respondents said they were willing to attend training on appropriate antimicrobial use, with workshops, seminars, and veterinary extension officers identified as the preferred channels. The farmers themselves identified the main drivers of indiscriminate drug use as lack of awareness and training, quackery, inadequate access to veterinary services, weak antibiotic policy enforcement, and poor biosecurity.

The study’s authors are careful to note its limits. The sample of 48 farms is small, reflecting the fact that integrated fish-chicken farming is still an emerging system in Nigeria, and the findings may not generalize to the entire country. The survey also relied on self-reported data and did not directly test for resistant bacteria on the farms, which the researchers flag as a priority for future work using microbiological and genomic methods. Still, the correlations they documented, however modest in magnitude, point to a clear intervention strategy: educate farmers, strengthen biosecurity, and the demand for antibiotics should fall.

The stakes extend well beyond Nigerian farm gates. At the 2024 United Nations General Assembly high-level meeting on antimicrobial resistance, world leaders committed to reducing human deaths from drug-resistant infections by 10 percent by 2030, a goal that depends heavily on curbing antibiotic overuse in animal agriculture. Nigeria’s Federal Ministry of Livestock Development, working with the Food and Agriculture Organization, has already developed national biosecurity guidelines for poultry and aquaculture farmers, and Lagos and Ogun states have been beneficiaries of related training, which may partly explain the relatively positive knowledge scores in this study. But the researchers warn that without policy changes and sustained antimicrobial stewardship programs, meeting the WHO target that Access-group antibiotics account for the majority of national consumption will be difficult, especially in Africa. Integrated farms like those surveyed here represent a genuine opportunity for sustainable food production, the study concludes, but only if the invisible plumbing of resistance that connects chicken waste, pond water, and the human food chain is acknowledged and managed before it becomes a public health emergency.

Subject of Research: Antimicrobial use and biosecurity in integrated commercial fish-chicken farming in Southwest Nigeria

Article Title: Cross-sectional study of antimicrobial use on integrated commercial fish-chicken farming in Southwest Nigeria: the link with on-farm biosecurity, farmers’ knowledge, and attitudes

Article References: Adebowale, O., Oyawole, O., Sanni, I., Odunfa, O., Oladejo, O. O., Folorunsho, E. O., Ajibola, A. B., & Nelson, G. U. (2025). Cross-sectional study of antimicrobial use on integrated commercial fish-chicken farming in Southwest Nigeria: the link with on-farm biosecurity, farmers’ knowledge, and attitudes. BMC Agriculture, 1(1), Article 10. https://doi.org/10.1186/s44399-025-00012-y

Image Credits: AI Generated

DOI: 10.1186/s44399-025-00012-y

Keywords: antimicrobial resistance, antimicrobial use, integrated fish-chicken farming, biosecurity, aquaculture, poultry, Nigeria, WHO AWaRE classification, colistin, antimicrobial stewardship, One Health, food safety

The research, published in New Microbes and New Infections, analyzed the medical records of 218 pediatric patients aged zero to eighteen years who received intravenous colistin for at least 72 hours for confirmed multidrug-resistant Gram-negative bacterial infections between 2010 and 2024. Seventy-four children received colistin as monotherapy, while 144 received colistin-based combination therapy with at least one additional antibiotic active against Gram-negative bacteria. The investigators, led by Ajaree Rayanakorn, Peninnah Oberdorfer, and Wasan Katip, set out to answer a question that has divided infectious disease specialists for years: does adding a second drug to colistin actually save lives in children, or does it merely add cost, complexity, and potential side effects?

The stakes are considerable. Multidrug-resistant Gram-negative bacteria, including Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and carbapenem-resistant Enterobacteriaceae, are among the most feared pathogens in modern hospitals. Reported mortality rates from these infections range from 26 to 80 percent, and a meta-analysis cited by the authors found that patients with these infections face a 1.78-fold higher risk of death compared with those infected by other organisms. The burden falls especially heavily on the World Health Organization’s South-East Asia region. In Thailand alone, approximately 19,000 additional deaths each year are attributed to multidrug-resistant bacteria, and more than 80 percent of those deaths involve Gram-negative organisms. The World Health Organization has designated the development of new treatments for these pathogens as a global research priority, but new drugs remain scarce, leaving older agents like colistin as last-resort options.

Colistin, also known as polymyxin E, works through a mechanism that differs from most modern antibiotics. The molecule carries both hydrophilic and lipophilic properties, allowing it to attack the lipopolysaccharide component of Gram-negative bacterial membranes. By disrupting the membrane structure, colistin exerts a direct bactericidal effect, and pediatric studies have reported clinical cure rates of up to 89 percent in multidrug-resistant Gram-negative infections. However, its clinical efficacy as a single agent remains controversial, and in vitro experiments have repeatedly shown that colistin can act synergistically with carbapenems, cephalosporins, sulbactam-containing regimens, fluoroquinolones, and fosfomycin. Those laboratory findings drove widespread adoption of combination therapy in clinical practice, even though rigorous clinical evidence, particularly in children, has been largely absent.

To untangle the effects of treatment from the effects of illness severity, the Thai team employed a sophisticated statistical technique known as inverse probability of treatment weighting. This is critical because, in everyday practice, sicker children tend to receive combination therapy. In the unadjusted data, the combination group indeed appeared more severely ill: their median Pediatric Index of Mortality 3 score was higher, septic shock was more common, ventilator-associated pneumonia occurred more frequently, and roughly half were receiving vasoactive drugs compared with about a third of the monotherapy group. Propensity scores were estimated through multivariable logistic regression incorporating variables including sex, age, pediatric Glasgow Coma Scale, pediatric Sequential Organ Failure Assessment score, PIM3 score, septic shock, intensive care unit status, vasoactive drug use, baseline serum creatinine, ventilator-associated pneumonia, and bacteremia. After weighting, all standardized mean differences fell below the 0.1 threshold, indicating that the two groups had become statistically comparable across these measured prognostic factors.

The results were striking in what they did and did not show. After the weighting adjustment, colistin-based combination therapy was not associated with any significant difference in the primary outcome of 30-day mortality compared with monotherapy, with an adjusted odds ratio of 2.50 and a wide confidence interval spanning 0.69 to 9.15. Nor did the combination improve mortality at the end of treatment, clinical response, or the rate of nephrotoxicity, the most feared side effect of colistin, which was defined using consensus criteria based on serum creatinine increases or the RIFLE kidney injury classification. Across all of these clinical endpoints, the two strategies performed essentially the same.

There was, however, one clear exception. Children receiving combination therapy were significantly more likely to achieve microbiological response, meaning that follow-up cultures from the originally infected site no longer grew the multidrug-resistant organism. After adjustment, the odds of microbiological clearance were 3.62 times higher in the combination group, a result that reached statistical significance with a p-value of 0.037. The authors suggest this enhanced bacterial eradication may reflect genuine synergistic activity between colistin and carbapenems, particularly against Acinetobacter baumannii, which dominated the cohort, accounting for more than 82 percent of isolates in both treatment groups. The most frequently used combination regimen was colistin with meropenem, given to nearly 63 percent of the combination group.

The disconnect between better bacterial clearance and no survival benefit is a recurring puzzle in antimicrobial research, and the authors offer several plausible explanations. Outcomes in critically ill children are shaped by host immune response, organ dysfunction, baseline disease severity, and comorbidities, any of which may blunt the clinical impact of eradicating bacteria. Colistin also penetrates lung tissue poorly, which matters in a cohort where roughly 70 percent of infections were pulmonary. Microbiological clearance may simply arrive too late in the course of critical illness to alter its trajectory. The findings align with a systematic review and meta-analysis by Wang and colleagues, which likewise found no mortality or clinical response differences between colistin monotherapy and combination therapy but demonstrated improved microbiological eradication with combination regimens. On the safety front, the absence of excess nephrotoxicity in the combination group is reassuring and supports the view that colistin-associated kidney injury is primarily dose-dependent and driven by patient-specific risk factors rather than synergistic toxicity between colistin and its partners.

The study’s limitations deserve careful attention. As a retrospective, single-center analysis at a 1,400-bed tertiary teaching hospital, its findings may not generalize to institutions with different resistance patterns and prescribing habits. The cohort, while among the largest pediatric studies in this field, remained modest in size, and the wide confidence intervals around key estimates, particularly the 30-day mortality odds ratio, reflect that imprecision. The inclusion of all multidrug-resistant Gram-negative infections, rather than only carbapenem-resistant organisms, complicates extrapolation to the subgroup where combination therapy is most often recommended. Residual confounding from unmeasured variables, including the timing of antibiotic initiation and dosing appropriateness, cannot be excluded, and the predominance of Acinetobacter baumannii may limit applicability to other pathogens. The authors themselves characterize the results as hypothesis-generating rather than definitive.

Even with those caveats, the study carries practical weight for clinicians confronting these infections in children. The message is not that combination therapy is useless, but that its benefits may be narrower than assumed: it may help clear bacteria without adding kidney risk, yet it does not appear to reduce mortality. The authors conclude that the decision to use combination therapy should be individualized, potentially reserved for situations where rapid bacterial clearance is most critical, such as bloodstream infections or ventilator-associated pneumonia caused by Acinetobacter baumannii. For many other children with multidrug-resistant Gram-negative infections, colistin alone may deliver comparable clinical outcomes. Confirming that conclusion will require the kind of study that has long been missing in this vulnerable population: large, multicenter, prospective trials, ideally randomized, designed specifically to define optimal treatment strategies for pediatric patients facing some of the most dangerous bacteria in modern medicine.

Subject of Research: Colistin monotherapy versus combination therapy for pediatric multidrug-resistant Gram-negative infections

Article Title: Efficacy and safety of colistin monotherapy versus colistin-based combination therapy in pediatric patients with multidrug-resistant gram-negative infections: A propensity score analysis

Article References: Rayanakorn, A., Oberdorfer, P., & Katip, W. (2026). Efficacy and safety of colistin monotherapy versus colistin-based combination therapy in pediatric patients with multidrug-resistant gram-negative infections: A propensity score analysis. New Microbes and New Infections, 74, Article 101857. https://doi.org/10.1016/j.nmni.2026.101857

Image Credits: AI Generated

DOI: 10.1016/j.nmni.2026.101857

Keywords: colistin, multidrug-resistant Gram-negative bacteria, pediatric infections, combination therapy, Acinetobacter baumannii, meropenem, nephrotoxicity, propensity score analysis, antimicrobial resistance, Thailand, hospital-acquired pneumonia, microbiological response

Colistin, also called polymyxin E, occupies a special and precarious position in modern medicine. It is a cationic polypeptide that attacks the outer membrane of Gram-negative bacteria, and after decades of limited use because of kidney toxicity, it was reintroduced in recent years as a final defense against multidrug-resistant infections. With few new antibiotics in the development pipeline, clinicians increasingly depend on colistin when carbapenem-resistant pathogens strike hospital patients. The emergence of bacteria that resist this drug is therefore not a routine scientific concern but a genuine emergency in global public health, and the new study demonstrates that the ocean may be serving as an unexpected reservoir and highway for the genes responsible.

The mechanics of colistin resistance matter for understanding why the new results are so significant. Resistance can arise in two ways. Intrinsic resistance develops through chromosomal mutations that alter lipid A, the lipopolysaccharide component of the bacterial outer membrane that colistin targets, reducing the drug’s ability to bind. Acquired resistance, by contrast, depends on the horizontal transfer of mcr genes, usually carried on plasmids, which are mobile DNA elements that can shuttle between bacterial cells. Since the discovery of the mcr-1 gene in Escherichia coli plasmids a decade ago, researchers have identified ten mcr variants, from mcr-1 through mcr-10, and watched them disperse across continents, animal populations, and clinical settings. What remained poorly understood was how extensively these genes had colonized marine ecosystems.

To answer that question, the Brazilian team designed a natural experiment spanning roughly 330 kilometers of the Rio de Janeiro coastline plus the Fernando de Noronha Archipelago, a volcanic island group about 360 kilometers offshore in the Western Atlantic. Their sampling sites deliberately covered a gradient of human influence. At one extreme sat Bom Jesus Cove in Guanabara Bay, a tropical urban estuary receiving raw sewage, oils, and industrial contaminants from Rio de Janeiro city. At the other extreme lay the submarine caves of Fernando de Noronha, protected within a national marine park and accessible only by SCUBA diving. Between those poles, the researchers sampled the Cagarras Archipelago, a no-take marine protected area unfortunately positioned near the Ipanema submarine sewage outfall; the biodiverse waters of Arraial do Cabo, including the Gruta Azul submarine cave; and Ilha Grande Bay, one of the world’s largest tropical bays, which faces growing pressure from coastal settlements and maritime traffic.

The laboratory work was methodical and technically demanding. From 1,550 total bacterial isolates, the team focused on 308 Gram-negative bacilli identified as potential hosts of acquired colistin resistance determinants. Bacteria were cultured on Luria Bertani and MacConkey agar from water samples, washed and swabbed from pieces of floating plastic, and extracted from sponge tissue through serial dilution across four growth media. Identification proceeded by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry on a Bruker Microflex LT platform, and DNA was extracted using a thermal lysis protocol with Chelex 100 resin. Polymerase chain reaction screening then probed each strain for eight mcr variants, and any positive strains were tested further for beta-lactamase genes, quinolone resistance genes, aminoglycoside resistance genes, sulfonamide resistance genes, and class 1, 2, and 3 integron-integrase genes.

The results were striking in both breadth and detail. Of the 308 potential host strains, 101 carried at least one mcr variant, generating 128 total gene occurrences. Water samples contributed 59.4 percent of the positive strains, plastic litter 35.6 percent, and marine sponges 5.0 percent. The mcr-9 variant dominated with 33 occurrences, followed by mcr-3 with 23, mcr-2 with 18, and mcr-1 with 17. That mcr-9 topped the list is noteworthy because global metagenomic surveys have often ranked mcr-1 as the most dispersed variant. The mcr-9 gene is known to circulate on IncHI2 plasmids that interconnect human, animal, and environmental isolates, suggesting an efficient dissemination network that the ocean may now be extending.

The bacterial hosts carrying these genes were equally concerning. Among ten identified genera, Enterobacter, Acinetobacter, Vibrio, and Klebsiella predominated. Enterobacter species alone accounted for 31 strains and harbored the greatest mcr diversity, with every variant except mcr-5 and mcr-7 detected in the genus. More alarming still, mcr-positive Enterobacter was not confined to polluted Bom Jesus Cove but turned up in marine sponges and cave waters in Fernando de Noronha, an area with restricted human access. One Enterobacter hormaechei strain, isolated from a sponge in Sapata Cave, simultaneously carried mcr-2, mcr-9, and the sulfonamide resistance gene sul1. Four strains carried three mcr variants at once, including Klebsiella pneumoniae isolates from pristine sponges and from floating plastic, and an Enterobacter cloacae from Noronha water. Both K. pneumoniae and E. cloacae belong to the notorious ESKAPE group of pathogens, and their carriage of multiple resistance genes in aquatic matrices highlights the risk of waterborne transmission to humans.

The co-occurrence of resistance genes painted an even darker picture. Nearly half of the mcr-positive strains, 46.5 percent, also carried other antimicrobial resistance genes or integron-integrases, with sulfonamide resistance genes, particularly sul1, the most frequent companions, followed by the beta-lactamase genes blaTEM and blaSHV. In Bom Jesus Cove, the team detected the carbapenemase gene blaKPC alongside mcr-3 in Enterobacter bugandensis and Raoultella ornithinolytica strains, a combination that effectively eliminates two of the last therapeutic options for infections caused by these organisms. Integron-integrases, genetic platforms that capture and shuffle gene cassettes, co-occurred with mcr exclusively in the polluted cove, suggesting bacterial adaptation to intense anthropogenic selective pressure. Because changes in membrane permeability in mcr-positive bacteria can reduce sensitivity to multiple drugs, these combinations can compound into true multidrug resistance, complicating treatment of hospital-associated infections.

The gradient of pollution left a measurable fingerprint on the data. In Bom Jesus Cove, 27 of 104 water-isolated strains tested positive for mcr, and 36 of 82 strains from floating plastic litter carried the genes, a prevalence of roughly 44 percent that represents the highest in the study. The finding positions plastic debris as both a reservoir and a vector for antimicrobial resistance, offering microbes a stable, drifting substrate on which biofilms can form, exchange genes, and travel with currents. At the Cagarras Archipelago, 40 percent of water-isolated strains were positive despite formal protection, a legacy of the nearby sewage outfall. Arraial do Cabo showed 36.5 percent prevalence among water isolates and Ilha Grande Bay 36.3 percent. In Fernando de Noronha, prevalence dropped to about 5 percent of candidate host strains, with two of 17 water isolates and five of 15 sponge isolates positive, proving that resistance persists even where human pressure is minimal.

What emerges from the study is a warning that antimicrobial surveillance cannot remain confined to clinics and farms. Marine sponges, submarine caves, and drifting plastic are now documented hotspots of colistin resistance, and the genes involved sit on mobile elements capable of jumping into human pathogens. The Brazilian coastline, with its juxtaposition of dense urban pollution and remote protected archipelagos, offered an ideal natural laboratory, but the pattern it revealed is almost certainly global. The researchers argue for integrated monitoring programs that treat the ocean as a critical node in the antimicrobial resistance network, alongside conservation strategies that reduce sewage discharge and plastic pollution. As colistin remains a last resort for patients out of options, every mcr gene circulating in seawater, attached to plastic, or sheltering inside a sponge represents a card stacked against future medicine, and the ocean, it turns out, is dealing them freely.

Subject of Research: Distribution of mobile colistin resistance (mcr) genes in bacteria from Brazilian marine environments

Article Title: Widespread occurrence of mobile colistin resistance genes in Brazilian marine environments

Article References: Brunelli, R. C., de Jesus Carvalho Baptista, T. V., de Oliveira Nithack Marques, M., da Silva Oliveira Alves, G., Abdon, B. B., Mello, M. P., Paranhos, R., Gallo, M. N., Vinzon, S. B., Lage, A., Sandes, J., Muricy, G., Klautau, M., Lopes, M. V., Dias, G. R., Canellas, A. L. B., & Laport, M. S. (2025). Widespread occurrence of mobile colistin resistance genes in Brazilian marine environments. Ocean Microbiology, 1(1), Article 3. https://doi.org/10.1186/s44375-025-00003-z

Image Credits: AI Generated

DOI: 10.1186/s44375-025-00003-z

Keywords: antimicrobial resistance, colistin, mcr genes, marine microbiology, plastic pollution, Guanabara Bay, Fernando de Noronha, Enterobacter, Klebsiella pneumoniae, integrons, marine sponges, One Health