Journal of Global Antimicrobial Resistance

Background: Antimicrobial resistance (AMR) is a growing global health concern driven largely by inappropriate antimicrobial use. Antimicrobial stewardship programs (ASPs), guided by the Centers for Disease Control and Prevention (CDC) core elements, are essential for optimizing antimicrobial use. However, adherence to these practices and the barriers faced by healthcare workers remain inadequately explored, particularly in resource-limited settings. Objective To assess adherence to the CDC antimicrobial stewardship checklist and identify barriers affecting stewardship practices among healthcare workers at a tertiary care hospital in Uttarakhand, India. Methods A quantitative cross sectional descriptive study was conducted among 355 healthcare workers, including nursing officers and physicians. Data were collected using a sociodemographic questionnaire, the CDC antimicrobial stewardship checklist, and a self-structured barrier assessment tool (test retest reliability r = 0.78). Descriptive and inferential statistics were applied using SPSS version 23.0, with a significance level set at p < 0.05. Results The overall adherence to the CDC antimicrobial stewardship checklist was 52.3%, indicating moderate compliance. Higher adherence was observed in action-oriented interventions, while lower adherence was noted in domains such as accountability, pharmacy expertise, reporting, and education. Major barriers identified included lack of antimicrobial supply (89.0%), shortage of key personnel (88.5%), delays in laboratory reports (85.1%), lack of training (83.9%), and inadequate administrative support (79.2%). Significant associations were found between perceived barriers and factors such as working area, designation, qualification, and work experience (p < 0.05), whereas age and gender showed no significant association. Conclusion Adherence to antimicrobial stewardship practices was moderate, with notable gaps in organizational and educational components. Multiple systemic, resource-related, and behavioral barriers hinder effective implementation. Targeted interventions focusing on strengthening infrastructure, workforce capacity, training, and administrative support are essential to improve stewardship practices in tertiary care settings. Keywords: Antimicrobial resistance, Antimicrobial stewardship program, Barriers, CDC Checklist

Urinary tract infection (UTI) is one of the most common community-acquired bacterial infections mainly caused by extraintestinal pathogenic Escherichia coli (ExPEC) strains. The high-risk Escherichia coli ST131 clone is a major global cause of this disease. The lineage rapid dissemination is associated to multidrug resistance (MDR), production of extended-spectrum beta-lactamase (ESBL), and multiple virulence-associated genes. Although we lack information about ExPEC high-risk clones in Latin America, we recently reported an increase in ST131 dissemination in Rio de Janeiro from 2015 to 2019. The present study aims to characterize virulence and resistance molecular and phenotypic features that may contribute to dissemination of E. coli ST131 in Rio de Janeiro, Brazil. We assessed a 133 E. coli ST131 strains collection obtained from urine of outpatients with suspected UTI, in 2019. We determined antimicrobial susceptibility, fluoroquinolones resistance genes, virulence factors associated genes and biofilm production of all strains and analyzed the frequencies by each clade or subclade. A higher incidence of women (92%) and elderly (65%) subjects was observed. Overall resistance to first- and second-line treatment for UTI antimicrobials ampicillin, ciprofloxacin and sulfamethoxazole-trimethoprim was detected in high rates (40%), with a major impact of subclade C2 strains that were resistant to almost all antimicrobials tested, 52% carry ESBL and 66% of strains harbor the aac(6)-Ib-cr ciprpofloxacin resistance gene. Clade B and subclade C2 showed higher virulence scores among the other clades. They present unique virulence profiles characterized by the presence of papGIII, sfa/focDE, and especially ibeA genes in clade B, and the afa/DrBC, papGII, hlyA, cnf1 genes in subclade C2. Over 50% of our strains are biofilm producers, characterized by weak (24%) and strong producers (32%). ESBL and MDR strains harbor mainly papA, papGII, hlyA, cnf1 and kpsMTII genes that plays a key role in ST131 colonization. Subclade C1 is the major biofilm producer (78%), despite its lower virulence score. We also detected higher incidence of papA (27%), hlyA (19%) genes and the RPAI(malX) marker (84%) in biofilm producer strains with a statistical association of sfa/focDE gene (9%). We can infer that Clade C strains might be responsible for ST131 dissemination and persistence in Rio de Janeiro.

Despite multiple treatment strategies and extensive research on resistance mechanisms, tuberculosis (TB) remains a major global health threat, largely because of the rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. Among various mechanisms complicating the situation, active antibiotic export via efflux pumps is particularly significant, yet largely unexplored. Mycobacterium sp. encodes numerous transporters, many of which are overexpressed in clinical isolates or under drug stress. Here, we examined the possible role of Rv0783c, a putative transporter that is reportedly overexpressed in drug-stressed conditions. Rv0783c conferred resistance to multiple structurally diverse antibiotics, fluoroquinolones and anti-TB drugs in the heterologous hosts, namely, Escherichia coli and Mycobacterium smegmatis. Reduced drug accumulation and active efflux of ethidium bromide (EtBr) confirmed its transport activity, which in turn gets nullified upon using the proton-motive force blocker, CCCP. On the other hand, its expression enhanced biofilm formation, linking antibiotic resistance to persistence-associated phenotype. Furthermore, site-directed mutagenesis confirmed the presence of crucial interacting residues with antibiotics that were identified by in silico analysis. Overall, we demonstrate the role of Rv0783c in the extrusion of first and second-line anti-TB drugs and enhancing biofilm formation.

BackgroundThe never-ending emergence of superbugs casts a shadow over the victorious age of antibiotics. In fact, the triumph of antibiotics was previously viewed in retrospection as our final victory over bacteria. Bacteria like Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli are now raising an alarming number of infections across hospitals and communities around the globe. The objective was to evaluate the implications for antimicrobial stewardship based on identifying the antibiotic resistance profiles, genotype mechanisms, and trends in common pathogenic bacteria found in various hospitals across Iraq. MethodsWe used a two-fold approach that was comprehensive in scope and involved both efficient multicenter surveillance as well as cutting edge genetic analysis to unravel the complex topography of antibiotic resistance. We provided a geographically heterogeneous but diverse set of clinically obtained isolates to participate in hospitals for a period of 24 months and concentrated our efforts on prioritized pathogens K. pneumoniae, A. baumannii, E. coli, P. aeruginosa, and S. aureus that are well known to pose serious threats. Beginning with clinically obtained isolates sourced across the entire globe, we used standardized techniques such as broth microdilution to first undertake phenotyping in a central reference lab to establish microbial identity based on resistance phenotypes to a set of prioritized antibiotics that include carbapenems, third generation cephalosporins, or fluoroquinolones. Finally, we derived data concerning the emergence patterns and geographic distribution of resistant microbes such as MRSA or CRE. We used genome-wide sequencing to unlock information concerning the genetic blueprints for a set of specifically chosen isolates based on their representational diversity across geographic locales, resistance phenotypes, and specific times. ResultsThe sample was made up of Escherichia coli (n = 225), Klebsiella pneumoniae (n = 185), Staphylococcus aureus (n = 135), Pseudomonas aeruginosa (n= 90), and Acinetobacter baumannii (n = 125). Ceftriaxone resistance was found in 80.4% of E. Coli, ciprofloxacin resistance in 45.6%, and meropenem resistance in 15.1%. K. pneumoniae exhibited 38.9% resistance to aminoglycosides and 70.2% resistance to carbapenems. The percentage of MRSA in S. aureus was 55.5%. P. aeruginosa showed 22.2% resistance to colistin, 37.8% resistance to piperacillin tazobactam, and 50.0% resistance to ceftazidime. Imipenem resistance was found in 85.6% of A. baumannii isolates, whereas colistin resistance was found in 28.8% of isolates. In all, 3.4% of isolates are pan-drug-resistant (PDR), 14.6% are extensively drug-resistant (XDR), and 52.1% are multidrug-resistant (MDR). WGS identified common genes such bla_NDM-1, bla_OXA-48, mcr-1, aac (6)-Ib, and plasmid replicons IncF, IncL/M, and IncI2. Carbapenem resistance in Gram-negative bacteria rose by around 18% over the course of five years. ConclusionsThis study shows that the rapid spread of complex genetic information in bacteria causes antibiotic resistance problems. High-level resistance represents an expected consequence of the spread of resistance genes and successful bacteria within healthcare systems. We demonstrate in our results that our expertise in overcoming resistance at a molecular level will play a crucial role in combating infectious diseases in the coming years.

BackgroundVirtual colony count is a kinetic, 96-well turbidimetric assay that has been used since 2003 to determine the antimicrobial activity of antimicrobial peptides including the defensin HNP1. Virtual colony count results differed from traditional colony counting results in studies of the antimicrobial activity of the human cathelicidin LL-37 and related peptides. The difference could possibly have been caused by an inoculum effect. MethodsThe virtual colony count assay was conducted using inocula that varied from 1250 to 1x108 virtual colony forming units (CFUv) per milliliter. ResultsThe virtual colony count assay demonstrated a pronounced inoculum effect of HNP1 against Staphylococcus aureus ATCC 29213, accompanied by biofilm formation observed in the wells of the 96 well plates at all inocula. The S. aureus inoculum effect was not as drastic as previously reported for Escherichia coli. ConclusionsThe inoculum effect is further evidence that biofilm formation is a resistance mechanism used by a variety of bacteria against antimicrobial peptides such as HNP1.

1.1Antimicrobial resistant infections present a concerning and expanding healthcare problem that is compounded by the reduction of antimicrobial research by the pharmaceutical industry. Additionally, the currently used antimicrobials consistently present less than ideal clinical treatment outcomes. This contention is supported by in vitro analysis in appropriate models. Here, in mature methicillin resistant Staphylococcus aureus (MRSA) in vitro cultures, we tested multiple antimicrobials and showed that for a biofilm grown for 72 hours, no antimicrobial tested was able to completely eradicate the biofilm even after 24 hours of exposure. However, the addition of an enzymatic biofilm-dispersal agent (DNase I or Proteinase K), greatly improved the performance of vancomycin and tigecycline in this in vitro model. Despite the improved performance in the presence of the dispersal agent, a high concentration of antimicrobial, 2000 {micro}g/mL, was needed to completely eradicate the infection as demonstrated by analyses using both a traditional XTT assay as well as a subculture assay to account for persister cells. It was shown that the addition of DNase I improved the diffusion of vancomycin through the biofilm. This suggests vancomycin efficacy is limited by the biofilm. The presented work provides a potential avenue for future treatments of MRSA lung infections by utilizing a traditional antibiotic combined with a passive dispersive agent.

Background: Metronidazole (MTZ) is a first-line antibiotic for several enteric infections. Its use is common in low-income countries, where most primary-care consultations are conducted by nurses. However, increasing resistance among some enteric pathogens is a growing concern. Using WHO guidelines, we conducted a register-based cross-sectional study to assess MTZ prescribing practices and their determinants in public and private primary healthcare facilities in South Benin. Methods: We performed a register-based cross-sectional study covering the year 2020 in 11 primary healthcare facilities (5 public and 6 private) in Abomey-Calavi, South Benin, following WHO recommendations. In total, 200 visits per facility were selected using systematic random sampling. The primary outcome was the prevalence of MTZ prescription. Determinants of MTZ prescription were identified using multivariable logistic regression analysis. Results: In total, 2,200 medical visits were analyzed. The median age of patients was 19 years, and 57% were female. Antimalarials were prescribed in 52% of visits. Antibacterial agents were prescribed in the majority of visits, with MTZ being the second most frequently prescribed antibiotic (18%), after aminopenicillins (27%). In multivariable analysis, digestive symptoms (adjusted odds ratio [aOR], 8.65; 95% confidence interval [CI], 6.49-11.6), genitourinary symptoms (aOR, 6.84; 95% CI, 3.18-15.0), and skin lesions (aOR, 2.39; 95% CI, 1.58-3.60) were independently associated with increased odds of MTZ prescription. In contrast, fever (aOR, 0.66; 95% CI, 0.49-0.87), respiratory symptoms (aOR, 0.44; 95% CI, 0.26-0.71), and malaria (aOR, 0.21; 95% CI, 0.15-0.28) were associated with decreased odds. Visits in the private sector were also associated with higher odds of MTZ prescription compared with the public sector (aOR, 2.31; 95% CI, 1.78-3.02). Conclusion: MTZ is the second most commonly prescribed antibiotic in primary care in the study area, with its use largely driven by digestive symptoms. Further studies are needed to assess the appropriateness of this prescription. Additionally, research is warranted to understand better the determinants of higher antimicrobial prescribing in the private healthcare sector.

Antimicrobial resistance (AMR) is classified by the World Health Organization (WHO) as one of humanity's ten global public health threats. This review aimed to estimate the prevalence, temporal trends and regional distribution of AMR in WHO priority bacteria across human, animal and environmental sources in Cameroon. This review was conducted following PRISMA 2020 guidelines, with the protocol registered in PROSPERO. A systematic literature search was conducted in Google Scholar, PubMed, African Journals Online, Hinari, and Africa indexus Medicus. Random effects models were used to estimate pooled prevalence and 95% confidence intervals (CIs), with subgroup analyses by bacterial source, region, and sampling period. Of 1566 articles screened, 115 met the inclusion criteria. The reported data encompassed 16 bacteria-antibiotic combinations in 16,948 isolates. Globally, third-generation cephalosporin (3GC) resistance in E. coli was the most prevalent (49.0%, 95% CI: 39.0-60.0%, I2=97.7%), reaching 77.0% (95% CI: 46.0-98.0%, I2=95.6%) in environmental isolates. The pooled prevalence of ESBL production in all included Enterobacterales was 37.0% (95% CI: 30.0-45.0%). Most of the highest resistance rates were observed in the Littoral region. The resistance rates between 2016 and 2025 were significantly higher than those from 2000 to 2015. These increases were more marked in fluoroquinolone-resistant Salmonella spp (1.0% to 48.0%, I2=97.3%, p<0.001), carbapenem-resistant E. coli (0% to 15%, I2=93.5%, p<0.001), and 3GC-resistant E. coli (34.0% to 64.0%, I2=97.6%, p=0.003). Antimicrobial resistance in WHO priority bacteria in Cameroon is high, unevenly distributed across regions and significantly increasing over time. These results underscore the crucial need for strengthened AMR surveillance to curb the growing threat of AMR in Cameroon.

BackgroundAntibiotic resistance is a global priority in healthcare. Leveraging thousands of whole-genome sequences, here we reveal the core resistance determinants of oral streptococci, focusing on assessing pattern variability and gene exchange across commensals and pathogens. MethodsGenomic information was obtained from the National Center for Biotechnology Information. Determinants of antibiotic resistance were identified using AMRFinderPlus and CARD. ICEscreen was employed for calling of integrative and conjugative elements. Variability and recombination in penicillin-binding protein sequences were assessed with MMseqs2 and fastGEAR. ResultsA total of 2,087 genomes from 15 species were included with members from the mitis, mutans, anginosus, salivarius, and bovis groups. We observed 3,576 hits from 55 unique resistance genes conferring resistance to 11 antibiotic classes. The species with most resistance determinants per genome were identified as Streptococcus mitis (2.7), Streptococcus oralis (2.5), Streptococcus parasanguinis (1.9), Streptococcus gallolyticus (1.3), and Streptococcus anginosus (1.2). The two latter species also presented the most diverse composition of determinants. Over 1,800 integrative and conjugative elements were shown across all genomes, with nearly 18% of them carrying at least one antibiotic resistance gene. Penicillin-binding protein variation analyses showed a high diversity in the mitis group. Even though S. mitis and S. oralis composed less than 4% of the genomes included in the analyses, they were recognized as sources of DNA for over a third of recombination events in pbp1a and nearly half for both pbp2b and pbp2x in resistant isolates of Streptococcus pneumoniae. ConclusionsWe show that tetracycline and macrolide resistance were highly abundant and tightly connected to integrative and conjugative elements. Further, recent recombination data show frequent genetic exchange from oral streptococci to beta-lactam-resistant S. pneumoniae. Finally, assessing the dynamics of genetic exchange across species is central for the development of strategies to mitigate the impact of antibiotic resistance.

Background: With the emergence of drug-resistant strains and an unprecedented threat to control initiatives, tuberculosis remains to be a major public health risk in Ethiopia. Resistance to rifampicin (RR) is an important indicator, since RR is an acceptable surrogate for multidrug-resistant TB (MDR-TB). Over 95% of RR is based on mutations in an 81base pair segment of the rpoB gene, detected using rapid molecular assays. Despite this, detailed molecular epidemiological information is scarce. This study characterized the specific rpoB gene mutation patterns among patients in Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted in 753 Mycobacterium tuberculosis complex (MTBC) clinical samples, corroborated as positive for MTBC from 2020 to 2024; respective probe mutation patterns were generated by the Xpert MTB/RIF platform. Demographic and clinical variables were also assessed for detecting the potential risk factors. Results: The overall RR-TB rate was 2.3% (17/753). Molecular analysis showed a distinct pattern of mutation, with codon 526 mutations being the most frequent, occurring in 54.3% of the resistance mechanisms. This was followed by those at codons 531 (21.7%) and 533 (15.2%). Most significant was the fact that 100% of RR-TB was observed among treatment-naive patients, providing unequivocal evidence that primary transmission is the exclusive cause of resistance in this population. Moreover, there were no statistically significant correlations between RR-TB and demographic factors, including sex, age, or HIV co-infection. Conclusion: The study demonstrates a steady, low-grade epidemic of RR-TB in Addis Ababa, dominated by a virulent bacterial strain with a distinctive mutation at codon 526. These observations highlight the imperative necessity for a strategic shift from a reactive, clinically-oriented model to proactive public health measures. To effectively break the chains of transmission, we recommend the universal application of drug susceptibility testing, enhanced and socially-directed contact tracing, and integrating molecular surveillance into the TB control program.

IntroductionAcinetobacter is a highly diverse genus which includes a range of common pathogenic species such as A. baumannii, A. lwoffii etc. Acinetobacter species causes bacteremia, pneumonia, wound infections, Urinary tract infections in community as well as hospital settings. A. baumannii is one of the ESKAPE pathogen which makes it even more lethal as antibiotics cannot action on this. AimTo isolate Acinetobacter species from various clinical samples and to check their antimicrobial susceptibility pattern by VITEK {square} Compact in SGT Hospital, Gururam, Haryana. ResultsOut of total 6673 samples 595 were the positive isolates from which 35 were Acinetobacter isolates which were received from various wards of the hospital. Occurrence of Acinetobacter was seen more in males(57.14%) as compare to females (46.8%). A total of 31 strains were A. baumannii, 3 were A. lwoffi and 1 strain was of A. haemolyticus. Prominent presence of Acinetobacter was seen in Blood (48.57%) specimen along with pus(22.85%), endotracheal (22.85%), tracheal (2.85%) and eye swabs (2.85%). All the isolates were resistant to piperacillin/tazobactam (100%), ceftriazone (100%), amikacin (100%), gentamicin (100%) ciprofloxacin (91.42%), ceftazidime (91.42%), cefepime (88.57%), levofloxacin (88.57%) and trimethoprim/sulfamethoxazole (80%). Colistin susceptibility was observed in 88.57% of the isolates. ConclusionAcinetobacter is a common pathogen in hospital acquired as well as in community acquired infections as it is a opportunistic pathogen hence to identify the Acinetobacter species and to understand their antimicrobial resistance pattern this study was conducted.

BackgroundBiofilms are central to Salmonella pathogenesis, and targeting their formation is believed to produce less evolutionary pressure of growth inhibition than traditional antibacterials. In this study, we screened the Medicines for Malaria Venture (MMV) Pathogen Box library to identify anti-biofilm agents against S. enterica that possess drug-like properties. Methodology/ Principal FindingsA crystal-violet-based medium-throughput antibiofilm screen of Salmonella enterica serovar Typhimurium ATCC 14028 and a clinical Salmonella enterica serovar Elisabethville isolate was performed on polystyrene surfaces using the 400-compound Pathogen Box library. Compounds that inhibited biofilm formation by >30% and growth by <10% were identified as hits. Salmonella red-dry-rough and motility phenotypes were explored in mechanism of action studies on one hit compound. The Salmonella antibiofilm hit rate was 0.75% for this library. MMV688371 (benzamide) inhibited biofilm formation of S. Typhimurium ATCC 14028 by 33% without inhibiting growth. An ethambutol analogue (MMV687273) and auranofin (MMV688978) met the hit criteria against S. Elisabethville LLD035X. Auranofin showed concentration-dependent, growth-inhibition-independent antibiofilm activity against typhoidal and non-typhoidal Salmonella from Nigeria, and inhibited the motility of S. Elisabethville LLD035X at 5 {micro}M. At 5 {micro}M aurothioglucose, an auranofin gold (I) analogue, and non-gold analogue 1-Thio-beta-D-glucose tetraacetate, inhibited biofilm formation by 61.30% and 11.39%, respectively, pointing to essentiality of the gold (I) moiety for activity. Conclusions/ SignificanceStructurally diverse small molecules can inhibit biofilm formation by Salmonella, and motility inhibition is an important mechanism for this activity. Auranofin inhibits typhoidal and non-typhoidal Salmonella biofilm formation, with its gold content being required for these activities.

1Opportunistic, biofilm-forming pathogens such as Pseudomonas aeruginosa can employ an array of strategies to reduce the impact of antibiotics on their survival. The biofilm matrix can prevent antibiotics from reaching bacteria embedded within it; general changes in metabolic activity alter susceptibility to specific drugs dependent on the target; changes in the membrane and the expression of channel or pump proteins embedded within it affect drug uptake and efflux; and production of antibiotic-degrading enzymes can remove the threat. In this study, we report that biofilm-deficient mutants of two well-studied lab strains of P. aeruginosa (PA14 and PAO1) have wild-type (WT) levels of tolerance to colistin and meropenem when allowed to establish mature populations in an ex vivo pig lung model of cystic fibrosis lung infection. The biofilm defects in the mutants were confirmed using SEM, and cryoSEM was used to visualise the hydrated biofilm matrix in the WT. Using RNA sequencing of the PA14 WT and an isogenic mutant lacking the pel polysaccharide, we were able to identify a small number of differences in the responses of the two genotypes to the lung environment and to exposure to sub-bactericidal colistin in the lung model. Notably, there was differential upregulation of the MexXY-OprM and MexEF-OprN multidrug efflux pumps. However, the relative roles of biofilm matrix versus cellular changes in physiology in conferring antibiotic tolerance in this environment remain to be fully elucidated.

BackgroundAntimicrobial resistance (AMR) surveillance is essential for quantifying and monitoring the burden of AMR among World Health Organization (WHO) priority pathogens. We analysed Tunisian AMR surveillance system (TARSS) data across five sentinel hospitals from 2014 to 2022. MethodsWe conducted a retrospective isolate-level analysis for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. Temporal, ward, and specimen associations were quantified using multivariable logistic regression models. Sex and age categories were explored in secondary models due to missingness. Temporal trends were assessed using Cochran-Armitage test, and co-resistance was summarised for third-generation cephalosporin and carbapenem phenotypes. We also evaluated temporal dynamics of 3GCR and CR profiles. ResultsA total of 35,525 E. coli, 14,325 K. pneumoniae, 9,679 P. aeruginosa, and 5,597 Acinetobacter spp. were reported to TARSS between 2014 and 2022. Mean annual MDR prevalence was high for Acinetobacter spp. (85.1%), moderate for K. pneumoniae (45.5%) and for P. aeruginosa (27.1%), and lower for E. coli (17.5%). Adjusted models indicated increased odds of resistance to several antibiotics, whereas E. coli showed decreased odds. Intensive care unit (ICU) and blood isolates were associated with higher odds of resistance in all pathogens. ConclusionThis nine-year multi-hospital analysis reveals a high prevalence of AMR across the four WHO priority pathogens, settings, and specimen types, with increasing resistance for some pathogen-antibiotic combinations. The higher odds of clinically important resistance amongst ICU and blood isolates support the use of ward-level antibiograms and stratified stewardship and infection prevention measures.

BackgroundAntibiotic pricing is a key determinant of access and stewardship in low- and middle-income countries (LMICs), yet empirical evidence on how prices are formed within pharmaceutical markets remains limited. However, there is little longitudinal evidence on how antibiotic prices behave within national pharmaceutical supply systems. This study evaluated the patterns and determinants of systemic antibiotic pricing in Tanzania using national regulatory import permit data. MethodsWe conducted a retrospective analysis of antibiotic importation records from the Tanzania Medicines and Medical Devices Authority for 2010-2016. Systemic antibiotics for human use imported via oral or parenteral routes were included. Unit prices (USD per smallest unit of measure) were summarized using the median and interquartile range (IQR). Prices were compared by route of administration, supplier country, and product naming practice (INN-named versus brand-named) using Mann-Whitney U and Kruskal-Wallis tests with false discovery rate adjustment. ResultsOf the 14,301 records, 10,894 (76.2%) met the inclusion criteria. Oral antibiotics predominated (89.6%). Although the median oral antibiotic prices declined over time, substantial price dispersion persisted across all study years. Parenteral antibiotics were consistently more expensive (USD 0.755-3.370) and more variable than oral antibiotics. Importation was concentrated in a few medicines, with amoxicillin-clavulanate (16.7%) and amoxicillin (11.4%) accounting for over one-quarter of records, and in a few supplier countries, with India representing 44.9% of the records. Significant price differences between INN-named and branded products were observed for amoxicillin (adjusted p<0.001) and ciprofloxacin (adjusted p=0.018), whereas prices differed significantly by supplier country across major medicines (adjusted p<0.05). Across medicines and years, wide within-product price distributions indicate persistent market segmentation rather than price convergence. ConclusionsAntibiotic import prices in Tanzania exhibit systematic and reproducible variations associated with formulation type, supplier origin, and product naming practices. The findings indicate that procurement structure and supplier participation strongly influence pricing in the import-dependent pharmaceutical market. Monitoring import-level prices can serve as an upstream indicator of market conditions and support evidence-informed procurement, pricing regulations, and antimicrobial stewardship policies in LMIC settings.

Carbapenem-resistant (CR) bacteria have emerged and been spreading beyond healthcare-associated facilities into the environment. It is recognized that toilet bowl water in patient rooms of healthcare-associated facilities can be one of internal reservoirs of CR bacteria. In accordance with this idea, toilet bowl water samples were collected from patient rooms in a tertiary healthcare-associated facility in North Macedonia, and meropenem (MEM)-resistant bacterial isolates were obtained from the toilet bowl water. In this study, because a MEM-resistant C. braakii isolate, that was one of MEM-resistant opportunistic pathogens, was obtained from the toilet water, whole-genome sequencing (WGS) of this isolate was performed to obtain genetic characteristics of the blaNDM-1-positive C. braakii isolate. By the WGS, four contigs were constructed, the longest contig, contig 1 (5,189,681 bp), contained blaCTX-M with some additional antimicrobial-resistance genes (ARGs). Interestingly, blaNDM-1 was detected in contig 2 (177,260 bp) and contig 3 (64,168 bp). Plasmid replicon of contig 2 was IncA/C2 but plasmid replicon of contig 3 was IncN and different from one of contig 2. Genetic structures surrounding blaNDM-1 were different between these two blaNDM-1-positive plasmids implying transfer or insertion of blaNDM-1 had occurred by IS or other mechanism. Further molecular epidemiology will be needed to explain the mechanism that allowed the C. braakii isolate to possess two structurally different blaNDM-1 plasmids.

In this study we explored phenotypic resistance using traditional Kirby-Bauer methods in human and animal derived Campylobacter isolates that were concurrently resistant to both azithromycin and ciprofloxacin to an expanded panel of antimicrobials, including clindamycin, fosfomycin, ampicillin sulbactam and tigecycline. Out of 236 Campylobacter isolates, over 85% of C. jejuni and C. coli were resistant to clindamycin, over 60% were resistant to ampicillin sulbactam and over 30% to fosfomycin. Less than 2% of isolates were resistant to tigecycline and there was no observed resistance to Imipenem.

Klebsiella pneumoniae ST383 has emerged as a high-risk clone, characterized by carbapenem resistance and increasing detection of hypervirulence determinants. We describe a novel ST383 lineage in Lebanon, defined by the acquisition of ICEKp5, which carries the yersiniabactin locus. Three ST383 K. pneumoniae clinical isolates (LBN_CAKp91, LBN_CTKp3, LBN_CTKp11) recovered from a Lebanese medical center were subjected to whole-genome sequencing. Comparative genomic analysis included regional ST383 strains and previously characterized Lebanese isolates. The study isolates formed a tight, monophyletic cluster (3-9 SNPs) that is phylogenetically distinct from the previously reported Lebanese ST383 clone (>164 SNPs) and grouped most closely to an Egyptian ST383 strain (59-65 SNPs). All three isolates carried ICEKp5 with yersiniabactin lineage ybt14, a feature absent in the earlier Lebanese ST383 clone. The isolates were the only ST383 strains to harbor the full spectrum of hypervirulence determinants to date, including capsule regulators (rmpA, rmpA2), aerobactin (iucABCD, iutA), yersiniabactin, and the hypervirulence biomarker peg-344. All isolates carried dual carbapenemases (blaOXA-48 and blaNDM-5) in addition to blaCTX-M-15 and blaCTX-M-14b. The genetic environments of blaOXA-48 and blaNDM-5 were highly conserved across geographically diverse ST383 isolates, indicating common plasmid origins. This study documents the emergence of a novel hypervirulent extensively drug-resistant (XDR) ST383 K. pneumoniae lineage in Lebanon. The acquisition of ICEKp5, combined with plasmid-borne hypervirulence and resistance determinants, reveals the concerning convergence of hypervirulence and XDR. Enhanced surveillance and infection control measures are urgently needed to monitor this emerging high-risk clone.

The spread and rise of antimicrobial resistance poses a risk to public health due to limited effective treatment options. Alternative antimicrobials that are effective against gram-negative multi-drug resistant pathogens. The increasing rate of carbapenem resistance observed in Klebsiella pneumoniae, indicates the need for alternative antimicrobial options. Bacteriophages that target Klebsiella pneumoniae are promising alternative antimicrobial option, with successful treatments being reported. Here we characterized 30 lytic bacteriophages from various environmental sources and tested their effectiveness against nine clinically relevant carbapenem-resistant K. pneumoniae isolates. These phages were characterized through genomic sequencing, bioinformatic analysis, virulence in liquid medium, and host range on different mediums. Bioinformatic analysis revealed a diverse collection of phages that span 9 ICTV recognized families and 13 genera with genome sizes ranging from 39-349 kbp. The phages were able to inhibit bacterial growth, and no virulence or antibiotic resistance genes were detected within the phage genomes. Host range testing demonstrated phages with broad host range have varying infectivity when plated on different common growth mediums. This study includes candidate phages for further potential development as potential antimicrobial agents against CR-KP, and the complexity in understanding phage-host dynamics of non-capsule phages that target against K. pneumoniae.

Background and objectivesCeftazidime-Avibactam (CAZ-AVI) is one of the last options to treat Enterobacteriales and Pseudomonas aeruginosa carbapenem-resistant. We aim to describe the susceptibility profile of bloodstream isolates of Enterobacterales and Pseudomonas aerunosa to ceftazidime-avibactam (CAZ-AVI) among strains resistant to third- and fourth-generation cephalosporins and/or carbapenems. MethodsWe conducted a retrospective descriptive study in two pediatric hospitals of Rio de Janeiro city, Brazil, between January 2023 and February 2025. All blood samples with resistance to third/fourth cephalosporins and/or carbapenem resistance were tested to CAZ-AVI, according to the BRCast methodology. Sensibility of CAZ-AVI and clinical profile of patients and outcomes were described. ResultsWe analyzed 116 blood samples. Of these, 107/116 (92.2%) were resistant to third/fourth-generation cephalosporins with susceptibility to carbapenems, and 9/116 (7.8%) were resistant to both third/fourth-generation cephalosporins and carbapenems. Overall susceptibility to CAZ-AVI was 107/116 (92.2%). The 116 blood samples represented 73 bloodstream infections (BSI) in 66 patients, including 66 single episodes and 7 persistent BSIs. Of the 73 infections, 69(94.5%) were caused by Enterobacterales and 4 (5.5%) by Pseudomonas aeruginosa. Twenty-two (30.1%) infections were detected at hospital admission, and 51 (69.9%) were healthcare-associated infections. Death occurred in 5/73 (6.8%) patients. Length of hospital stay (p=0.01596) were statistically significantly higher in non-survivors compared to survivors. The CAZ-AVI was prescribed for four patients with Enterobacteriales or Pseudomonas aeruginosa infections with clearance from the blood. ConclusionSusceptibility of CAZ-AVI to BSI in children was higher and this antibiotic could be an option to treat carbapenem-resistant infection due to Enterobacteriales and Pseudomonas aeruginosa.