BackgroundMultidrug-resistant Enterobacteriaceae (MDRE) represent a critical threat in intensive care units, particularly in low- and middle-income countries, where surveillance data remain scarce. This study characterized the epidemiology and predictors of multidrug resistance among Enterobacteriaceae isolates in a Somali tertiary hospital.MethodsThis retrospective descriptive study analyzed 758 unique Enterobacteriaceae isolates from culture-positive specimens between January 2019 and December 2024, using disk diffusion for eight agents; For colistin, broth microdilution (CLSI M07) was applied to isolates screening non-susceptible on disk diffusion, and genera with intrinsic polymyxin resistance (Proteus, Serratia, Morganella) were excluded from the colistin denominator. Multidrug resistance (MDR) was defined as nonsusceptibility to ≥3 antimicrobial classes. Bivariate associations and multivariable logistic regression identified the independent predictors of MDR.ResultsThe overall prevalence of multidrug resistance was 37.9%. Klebsiella spp. demonstrated the highest MDR prevalence (54.9%), while Escherichia coli had lower odds of resistance (aOR, 0.27; 95% CI 0.19–0.38). Sputum specimens harbored the highest proportion of MDR isolates (44.9%), followed by blood (35.8%) and urine (19.0%). The prevalence of MDR remained relatively stable at 24–25% in 2019–2020, subsequently declined to 15% in 2021, and then escalated dramatically. Colistin retained the greatest in vitro activity: acquired resistance was documented in 1.2% (9/735 tested) of isolates from genera without intrinsic polymyxin resistance, all of them multidrug-resistant (9/283, 3.2%, versus 0/452 of non-MDR isolates; p = 0.001). A further 21/758 isolates (2.8%) belonged to genera intrinsically resistant to colistin. Because confirmatory broth microdilution was applied only to isolates screening non-susceptible, the colistin figure is a conservative lower-bound estimate. Tigecycline was tested in only 20.4% of isolates, among which resistance was 17.4%.ConclusionsMultidrug-resistant Enterobacteriaceae are escalating alarmingly in Somali ICUs, with ciprofloxacin resistance of 95.4% among tested MDR isolates, which severely constrains empiric therapeutic options. The urgent implementation of antimicrobial stewardship programs, restricted-use protocols for carbapenems and colistins, and strengthened infection prevention measures are essential. National engagement with the WHO GLASS surveillance is critical.
BackgroundAntibiograms support empirical therapy by providing local antimicrobial susceptibility data, guiding clinical decisions, and stewardship efforts. Rising multidrug-resistant (MDR) bacteria highlight the importance of continuous antimicrobial resistance (AMR) surveillance to inform local treatment guidelines.ObjectivesThe purpose of this study was to assess AMR rates in clinical pathogenic isolates obtained from community-acquired infections at a general hospital in Western Saudi Arabia.MethodsAntibiogram data were analyzed retrospectively from January 2020 to September 2024, focusing on pathogenic bacteria and AMR isolates.Results and conclusionThis study shows high rates of ESBL-producing E. coli and the rapid emergence of resistance to last-resort antibiotics, indicating therapeutic exhaustion despite stable resistance to older drug classes. These trends, likely driven by antibiotic overuse during COVID-19, highlight shrinking treatment options and the urgent need to strengthen antimicrobial stewardship and reassess empirical therapies.
Antimicrobial resistance (AMR) is a leading global health threat. Primary care accounts for approximately 80% of human antibiotic use, making novel non-antibiotic strategies for common self-limiting infections an urgent need. Traditional, Complementary and Integrative Medicine (TCIM), including homeopathy, is widely used worldwide; the existing literature on homeopathy suggests a directional signal of potential reductions in antibiotic use in both human and veterinary settings, though the evidence base remains heterogeneous and methodologically limited. The ENHANCE (rEsearch programme oN Homeopathy and Antimicrobial resistaNCE) international collaborative Programme was established in 2023 to systematically evaluate homeopathy’s role in antimicrobial stewardship (AMS) through five integrated workstreams: 1) population studies, 2) AMR literature monitoring, 3) Condition-specific systematic reviews, 4) Core outcome set development, and 5) Primary evidence generation. Completed outputs include systematic reviews for otitis media (2024) and tonsillitis (2026), the first internationally agreed Core Outcome Set for acute otitis media (COS-AOM, 2025), and a nationally representative UK survey showing that homeopathic product use occurs in about 5% of the population (an estimated 2.7 million people), with 4% (around 2.2 million people) consulting homeopathic practitioners (2026). Ongoing work includes systematic reviews and core outcome sets for tonsillitis and sinusitis, and the design of pragmatic primary care trials and real-world evidence studies aligned with WHO- and One Health AMR and AMS strategies. ENHANCE provides the methodologically rigorous, internationally coordinated infrastructure needed to determine whether homeopathy can meaningfully contribute to antibiotic-sparing stewardship.
BackgroundStrengthening antimicrobial stewardship (AMS) programs is a major public health strategy to reduce inappropriate antibiotic use (AMU) and averting antibiotic resistance (AMR). Evidence on AMU and AMS program implementation is widely documented in Tanzania mainland, consistent with previous studies done and other low-and middle-income countries. However, there is limited information on AMU and AMS programs to guide the implementation of the Zanzibar Action Plan on AMR. The objective of this study was to determine the prevalence of AMU, identify factors associated with AMU, and to assess the performance of AMS programs in pediatric wards across hospitals in Zanzibar.MethodsThis repeated cross-sectional study employed the World Health Organization Point Prevalence Survey (WHO-PPS) tool at two time points (February to April 2024 and December 2024 to May 2025), complemented by a one-time WHO-Health Care Facility Core Element Indicators Tool conducted in April 2024 to assess AMS performance. The WHO-PPS study population was children ≤13 years admitted to pediatric wards in five public hospitals in Zanzibar. Healthcare providers and AMS team members reported on Core Element Indicators. The WHO-PPS data were analyzed using descriptive statistics and multivariate modified Poisson regression, while AMS performance was computed as percentage scores per hospital.ResultsOf 943 paediatric patients, 826 (87.6%) received at least one antibiotic. Gentamicin, ampicillin, and ceftriaxone were the most commonly prescribed antibiotics. Watch-category antibiotics accounted for the majority of prescriptions (53.8%), followed by Access (45.8%) and Reserve (0.4%). Community-acquired infections were the predominant indication for antibiotic use, 60.4%, with pneumonia and sepsis being the most common diagnoses. Bacteriological culture testing was performed in only 10.9% of patients, while adherence to national treatment guidelines was 77.8%. Significant predictors of AMU included hospital tier (regional: aPR 1.39, 95%CI 1.30-1.50; and district level: aPR 1.35, 95%CI 1.26-1.46); and higher disease severity shown by ultimately fatal McCabe score, aPR 1.20, 95%CI: 1.07-1.33). The AMS program performance was below the 50% functionality threshold, with low scores observed in leadership, accountability, monitoring and surveillance, and reporting and feedback, alongside limited progress in the establishment of DTC/IPC/AMC committees and implementation of AMS actions.ConclusionsAntibiotic use among admitted children was markedly prevalent, notably by the Watch category of antibiotics, and limited reliance on bacteriological culture and suboptimal AMS program performance across hospitals in Zanzibar. These findings highlight important opportunities to strengthen AMS programs and diagnostic practices. Future research should evaluate the appropriateness of antibiotic prescribing and explore barriers to effective AMS implementation across hospitals in Zanzibar.
Antimicrobial resistance (AMR) poses a major threat to animal health, food security, and public health globally, with poultry production systems recognized as important contributors to antimicrobial use. Veterinary professionals and veterinary paraprofessionals play a central role in antimicrobial stewardship through prescribing practices, farmer education and disease prevention strategies. This mixed-methods pre–post intervention study assessed changes in knowledge, attitudes and practices related to antimicrobial stewardship among veterinary personnel involved in poultry production in selected districts of Zambia, before and after implementation of antimicrobial stewardship interventions under the Combating antimicrobial resistance and antimicrobial residues in Zambian Poultry (CAZAAP) project. Baseline and endline quantitative KAP surveys were conducted among veterinary professionals and paraprofessionals in Lusaka Province (Chongwe, Chilanga district) and Copperbelt Province (Ndola, Kitwe districts), complemented by qualitative key informant interviews exploring contextual drivers of antimicrobial use and stewardship practices. Knowledge of antibiotics and AMR was generally high across both provinces, with improvements observed in correct definitions of AMR, antibiotic residues, and withdrawal periods between baseline and endline. Positive attitudes toward antimicrobial stewardship were widely reported, including recognition that AMR was an important animal and public health issue and that biosecurity and vaccination can result in reduced antibiotic use. Changes were observed in several stewardship-related practices, including reductions in inappropriate antibiotic use for viral infections, decreased prophylactic antimicrobial use, and improved biosecurity practices. However, important gaps persisted, particularly limited access to treatment guidelines, inconsistent prescription practices, and low utilization of laboratory diagnostics. Qualitative findings revealed widespread farmer self-medication, over-the-counter access to antibiotics through agrovet shops and pharmacies, weak regulatory enforcement, and economic pressures influencing antimicrobial use practices. Overall, the findings suggest that although awareness of AMR among veterinary professionals is generally high, antimicrobial stewardship challenges in Zambia’s poultry sector are driven not only by knowledge limitations but also by broader structural and governance constraints. Strengthening antimicrobial stewardship will therefore require integrated One Health interventions combining professional training, improved diagnostics, regulatory strengthening, and farmer-centered education.
IntroductionAcinetobacter baumannii, a World Health Organization (WHO) critical-priority pathogen, causes difficult-to-treat nosocomial infections. The link between resistance genes, biofilm, and virulence carriage remains poorly understood in clinical isolates of high−burden South Asian settings. This study intended to thoroughly describe and explain linkages among clinical isolates collected in Haryana, India.MethodsA total of 200 non-duplicate A. baumannii isolates underwent antimicrobial susceptibility testing by broth microdilution against 17 antibiotics, interpreted according to CLSI M100 guidelines (32nd edition). Biofilm forming capacity was quantified using the standardized microtiter plate crystal violet assay. Polymerase chain reaction (PCR) was used to detect six carbapenemase genes (blaOXA-23, blaOXA-24, blaOXA-58, blaNDM-1, blaVIM, and blaIMP), beta-lactamase genes (blaPER-1, AmpC, and blaTEM), and virulence genes (bap, ompA, and csuE). Concordance was assessed by Cohen’s κ; gene-resistance and gene-biofilm links were tested using regression and non−parametric analyses. A total of 200 pure, non−duplicate A. baumannii isolates were included and contaminated cultures were excluded. Sample size adequacy was assessed using Buderer’s formula based on expected sensitivity, specificity, carbapenem-resistance prevalence, 95% confidence level, and desired precision.ResultsAmong 200 isolates, 54% were MDR, 34% XDR, and 61% carbapenem-resistant. The blaOXA-23 gene, present in 61%, showed near-perfect concordance with carbapenem resistance (κ = 0.81). Composite carbapenemase carriage improved concordance (κ = 0.88). Biofilm capacity was unrelated to overall resistance, but strong biofilm formers had higher colistin MICs (p = 0.001). Virulence genes (bap, ompA, and csuE) were linked to strong biofilm formation (p < 0.001) without resistance escalation.ConclusionsblaOXA−23 emerged as the dominant genetic driver of carbapenem resistance, underscoring its value in rapid diagnostics. Colistin tolerance was linked to biofilm−associated phenotypes rather than cumulative resistance.
Tuberculosis (TB) is a global health challenge and is curable, but tools for rapid treatment monitoring are limited. Current methods, like smear microscopy, lack sensitivity, while culture-based approaches require weeks for results and specialized biosafety facilities. This paper presents a comprehensive protocol for the PATHFAST TB LAM Ag assay, a rapid chemiluminescent enzyme immunoassay that quantifies lipoarabinomannan (LAM) mainly in sputum and likely other biological samples within one hour. This protocol details sample collection, heat inactivation for biosafety, and the automated measurement process. Heat inactivation at 100 °C for 20 minutes renders samples non-infectious while preserving LAM for detection. The assay demonstrates excellent analytical performance with a detection limit of 6.67 pg/mL and a linear measurement range of 10.0–50,000 pg/mL. Published clinical evaluation demonstrated 88.8% (95% CI: 80.0–94.0%) sensitivity and 100% (95% CI: 83.9–100%) specificity compared to culture, with strong correlation to bacterial load. The PATHFAST TB LAM Ag assay successfully tracks bacterial decline during treatment, with LAM concentration reductions mirroring culture results but available significantly faster. Unlike culture methods that suffer from contamination (4.2-9.6% invalid results), the PATHFAST TB LAM Ag assay consistently provides valid results. This protocol enables implementation of a rapid, quantitative TB treatment monitoring tool that enhances biosafety, reduces turnaround time, and maintains performance comparable to conventional methods, addressing critical needs in both clinical care and drug development settings.
IntroductionFourier transform infrared spectroscopy (FTIR) has been evaluated as a typing method for a number of pathogens; however, very little research has been conducted on the genus Serratia. MethodsWe examined whether FTIR was able to correctly cluster clinical isolates of Serratia to a comparable degree as whole genome sequencing (WGS) coupled with a subsequent bioinformatic comparison, the gold standard for determining phylogenetic relationships in epidemiology. FTIR was performed with the IR Biotyper (Bruker, Bremen, Germany) using the standard settings. Over a period of six weeks, 28 Serratia isolates found in clinical and environmental hygiene samples investigated in our laboratory were collected and preserved. Retrospective strain typing was performed using both methods, and the results were subsequently compared. ResultsOur study showed a PPV of 0.842 for the correct identification of closely related isolates and an NPV of 1.0 for the correct identification of unrelated isolates. Concordance was measured using the Adjusted Rand index (AR) and the Adjusted Wallace coefficient (AW), with WGS and subsequent bioinformatic analysis as the reference method. This resulted in an AR of 0.742. DiscussionOur findings indicate, although with some limitations, the utility of using the IR Biotyper as a rapid and cost-effective first-line screening tool for investigating the epidemiological relatedness of Serratia spp. in a clinical microbiology laboratory when an outbreak is suspected. Consequently, the FTIR method may provide a complementary analytical addition to the arsenals of clinical microbiology laboratories that carry out epidemiological surveillance to aid infection control in clinical settings.
Bacteriocin production by lactic acid bacteria (LAB) is strongly conditioned by growth-medium composition, and adjusting ingredients offers a low-cost route to enhanced yield. Response surface methodology (RSM) based on a three-factor, five-level central composite design (CCD) was used to optimize supplementation of an African oil bean seed (Pentaclethra macrophylla Benth) extract broth with glucose, sodium citrate and potassium chloride for two LAB isolated from the seed and identified by 16S rRNA sequencing, Lactococcus lactis MT186647 and Lactobacillus fermentum MT186598. Twenty runs per organism were performed; bacteriocin activity was determined by the zone of inhibition against Staphylococcus aureus ATCC 19095 by agar well diffusion. For both isolates, glucose exerted a significant negative linear effect and all three supplements significant negative quadratic effects, while no two-factor interaction reached significance, indicating an additive response. The second-order models accounted for 71.85% (L. lactis; p = 0.060) and 73.15% (L. fermentum; p = 0.050) of the variation, with significant lack-of-fit; the regression was therefore only marginally significant, and the predicted R² was 0.00%, indicating no demonstrated ability to predict new runs. The desirability-based optima (6.35/0.55/1.78 g/L glucose/sodium citrate/potassium chloride for L. lactis; 6.44/0.55/1.59 g/L for L. fermentum; predicted zones 13.12 and 12.74 mm) are best interpreted as an estimated optimal region rather than a quantitatively predictive optimum. Validation under these optima combined with the previously established optimal culture conditions (1.9% NaCl, 31 °C, initial pH 6.0) produced zones of 15.22 mm (L. lactis) and 14.96 mm (L. fermentum), exceeding the supplementation-only model estimates by 16.0% and 17.4% and the previously reported culture-condition-only outcomes (13.33 and 11.75 mm) by 14.2% and 27.3%. Because these differences were not tested statistically and partly reflect the fixed 1.9% NaCl (optimized separately and absent from the supplement CCD), the two optimization layers are interpreted as combining additively rather than demonstrating an established synergy. Moderate, balanced supplementation with inexpensive, food-grade additives can substantially enhance bacteriocin yield, supporting further development, subject to confirmatory multi-point validation, of L. lactis MT186647 and L. fermentum MT186598 as starter or protective cultures for the controlled fermentation of P. macrophylla to Ugba.
Introduction:The rising threat of antimicrobial resistance, particularly the phenomenon of MIC creep, poses a significant challenge to the clinical effectiveness of key antibiotics. Linezolid is a crucial last-resort agent for treating severe infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to evaluate the temporal trends of linezolid minimum inhibitory concentrations (MICs) in clinical S. aureus isolates at a tertiary care hospital over an eight-year period. Methods:A retrospective study was conducted on clinical S. aureus isolates over eight years from 2017-2024 in a tertiary care hospital. MICs were determined using the VITEK-2 system and interpreted according to CLSI guidelines. Data were analyzed using IBM SPSS Statistics version 20.0. Results:From 2017 to 2024, A total of 4,325 S. aureus isolates were analyzed, comprising 2,682 (62.01%) MSSA and 1,643 (37.98%) MRSA. The mean linezolid MIC for MSSA increased from 1.41 ± 0.53 µg/mL (2017) to 1.72 ± 0.45 µg/mL (2024), and for MRSA from 1.34 ± 0.47 µg/mL (2017) to 1.78 ± 0.42 µg/mL (2024). A progressive rightward shift in MIC distribution from 1 µg/mL to 2 µg/mL was observed in both groups. Spearman's rank correlation demonstrated a significant positive trend (MSSA: rs = 0.893, p = 0.001; MRSA: rs = 0.857, p = 0.001), consistent with the "MIC creep." All isolates remained within the CLSI susceptibility breakpoint (≤ 4 µg/mL), and no high-level resistance was detected. Conclusion:Linezolid continues to be highly effective; however, the progressive MIC creep from 1 µg/mL to 2 µg/mL indicates emerging reduced susceptibility. These findings stress the need for ongoing MIC surveillance and strict antibiotic stewardship to preserve linezolid efficacy.
Accelerating antibiotic development from natural products. Natural products with antimicrobial activity can act through multiple mechanisms to overcome antibiotic resistance. These include directly inhibiting bacterial growth, reversing resistance by blocking efflux pumps and disrupting biofilms, and strengthening host defenses. Together, these strategies help restore antibiotic effectiveness, overcome resistance, and support more sustainable approaches to treating infections. Image created by Dr Ankita Nag in BioRender. (https://BioRender.com/6c0p6qp), licensed under CC BY 4.0.Infographic illustrating key natural sources of antimicrobial compounds, such as plants, microbes, fungi, endophytes, and marine life, alongside antimicrobial strategies including inhibiting bacterial survival, enhancing host defense, and reversing resistance, with a diagram detailing bacterial drug resistance mechanisms like drug modification, target polymorphism, impermeability, and efflux.
IntroductionIn contemporary clinical practice, novel tetracycline-class antimicrobial agents have been increasingly utilized due to their favorable pharmacological profiles. However, the potential association between novel tetracycline-class drugs and coagulation dysfunction is relatively underreported in the literature. This study utilizes the FDA Adverse Event Reporting System (FAERS) to identify and analyze risk signals for coagulation disorders associated with three commonly used the novel tetracyclines in clinical practice. The findings are expected to provide valuable references for clinicians in the targeted monitoring of adverse drug reactions.MethodsCoagulation dysfunction reports associated with the novel tetracycline-class drugs, submitted to the FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2024, were collected. Data mining was performed using the ROR, PRR, BCPNN, and MGPS. All data extraction was conducted using R software (version 4.4.2).It should be noted that FAERS is a spontaneous reporting system without exposure denominators and is subject to reporting bias and confounding factors.ResultsA total of 346 coagulation dysfunction reports with the novel tetracycline-class drugs as suspected drugs were screened, including 327 for tigecycline, 6 for omadacycline, and 13 for eravacycline. Disproportionate reporting signals of coagulation dysfunction were detected for both tigecycline and eravacycline, with tigecycline showing the strongest signal [ROR = 46.85 (42.29-51.91)]. Subgroup analyses by age, gender, and dosage revealed a higher proportion of male patients receiving tigecycline and eravacycline. while tigecycline and eravacycline exhibited a stronger disproportionate reporting signal in male patients over 65 years old. Omadacycline showed stronger disproportionate reporting signal at a daily dose of 100 mg. The peak onset time for omadacycline was consistently 9 days. However, all subgroup findings for omadacycline and eravacycline should be interpreted with extreme caution due to the limited number of reports. These observations are considered exploratory rather than confirmatory.ConclusionDisproportionality analysis identified prominent signals of coagulation dysfunction signals associated with tigecycline and eravacycline. Distinctive reporting patterns of coagulation abnormalities were observed across the three novel tetracyclines, with visible discrepancies in patient age, gender, therapeutic indications, daily dosage, clinical outcomes, and adverse event onset time. Based on the above findings, clinicians should maintain high vigilance against the potential coagulation abnormalities induced by novel tetracyclines, and implement standardized and rational therapeutic drug monitoring during clinical medication practice.
Background:Interpretation of urine culture results requires key clinical information such as symptom status, catheterization, and multidrug-resistant organism (MDRO) risk. However, this information is frequently absent from routine request forms, contributing to overtreatment of asymptomatic bacteriuria (ASB) and suboptimal antimicrobial prescribing. This study evaluated the impact of implementing a structured urine-culture request form as part of a diagnostic and therapeutic stewardship program. Methods:This prospective, non-randomized interventional study was conducted at an 1800-bed tertiary-care hospital in India (March 2023-March 2024). Patients undergoing urine culture testing in Urology/Nephrology departments used a structured request form capturing symptoms, risk factors, and clinical context (test arm), while General Medicine continued routine forms (control arm). Primary outcomes included ASB treatment, MDRO detection, recurrence, and guideline-concordant prescribing. Patients were followed for one year. Results:A total of 484 patients were included (198 test arm, 286 control arm). Antibiotic treatment for ASB was significantly lower in the test arm compared with the control arm (3.6% vs 67.0%; p < 0.001), without adverse outcomes. Guideline-compliant prescribing was higher in the test arm (73.7% vs 26.2%; p < 0.001). MDRO prevalence was higher in the test arm (32.2% vs 11.3%), reflecting greater clinical complexity rather than the intervention itself. Recurrent urinary tract infection (UTI) within one year was significantly lower in the test arm (14.1% vs 29.0%; p < 0.001). Conclusions:Introducing a structured urine-culture request form improved diagnostic clarity and antibiotic prescribing, particularly by reducing unnecessary treatment of ASB and increasing guideline compliance, without compromising patient outcomes. This low-cost intervention represents a practical and scalable diagnostic stewardship strategy for improving UTI management.
BackgroundEmpirical antibiotic prescribing during the COVID-19 pandemic may have accelerated antimicrobial resistance, particularly in resource-constrained settings with limited diagnostic and stewardship capacity. This study characterized antibiotic prescribing patterns and identified predictors among hospitalized COVID-19 patients in rural Central India.MethodsThis retrospective observational study included 951 laboratory-confirmed COVID-19 patients (aged ≥18 years, hospitalized ≥48 hours) admitted between March 2020 and December 2021. Antibiotic use was assessed using WHO ATC/DDD methodology and Drug Utilization 90% (DU90%) analysis. Predictors of antibiotic prescription were evaluated using multivariable logistic regression. Empirical prescribing was defined as antibiotic initiation without microbiological confirmation.ResultsAmong 951 patients (mean age 53 ± 15.8 years; 64% male), 54% had ≥1 comorbidity and 74% required oxygen; 20% required mechanical ventilation. Antibiotics were prescribed to 90% (858/951); 46% received two agents and 8% ≥3 agents. The DU90% segment consisted of WHO “Watch” antibiotics, mainly amoxicillin-clavulanate (40.87 g/100 patient-days), doxycycline (18.26), and azithromycin (17.12). However, the use of meropenem (4.04 DDD gm/100 patients) a WHO Reserve group carbapenem is particularly alarming. Elevated C-reactive protein (>10 mg/dL) was the strongest predictor of antibiotic use (adjusted OR 29.28, 95% CI 17.53–48.89; p<0.001). Antibiotic recipients had longer median hospital stays (11 vs 8 days). Overall mortality was 26%.ConclusionsEmpirical antibiotic use was extremely high and driven by WHO “Watch” and “reserve” group agents, largely associated with elevated CRP in the absence of culture testing. Strengthening diagnostics and stewardship programs is urgently needed to reduce unnecessary broad-spectrum antibiotic exposure.
The disease tuberculosis, caused by Mycobacterium tuberculosis, is one of the leading causes of global human mortality. The rise of multidrug and extensively drug-resistant strains of the pathogen and the limited efficacy of the BCG vaccine is one of the major concerns worldwide. Conventional chemotherapy for tuberculosis is often very long and has several side effects. These factors lead to an urgent need for alternative, non-toxic therapeutic strategies with minimal side effects. Antimycobacterial peptides (AMPs), are a class of natural compounds that have shown a broad spectrum of anti-mycobacterial activity with a low propensity for the development of anti-mycobacterial resistance. This review summarizes the current antimycobacterial peptides, highlighting their structural features, physicochemical determinants, and their mechanism of action. Some of the key peptides have been critically discussed with respect to their membrane targeting mechanism. The role of structural modifications, such as disulfide bonding, cyclization, hydrophobicity tuning, and post-translational modifications, in enhancing antimycobacterial efficacy and stability is also examined. Consequently, the broad mechanism of action of these peptides and their role in the development of anti-tuberculosis drugs have been emphasized. This article combines mechanistic and structural insights to show how antimycobacterial peptides could become new anti-TB drugs. It also provides a guide for developing and improving peptide therapies for tuberculosis.
Antimicrobial resistance (AMR) poses a rapidly escalating threat to public health, food security, and environmental sustainability across Africa, where limited diagnostic capacity, unregulated antibiotic use, and weak pharmaceutical pipelines exacerbate treatment failures. Bacteriophage-derived endolysins have emerged globally as promising next-generation antimicrobials due to their rapid bacteriolytic activity, low resistance potential, and modular engineering flexibility. Despite significant advances in endolysin discovery, engineering, and clinical translation worldwide, their deployment in Africa remains negligible. This disparity raises a critical question: why have phage endolysins not progressed beyond early-stage research in Africa despite their relevance to the continent’s AMR burden? This review provides a critical analysis of the translational barriers hindering the development, adoption, and commercialization of phage endolysins for AMR control in Africa. Drawing on published African and global literature, we identify interconnected scientific, infrastructural, regulatory, economic, and policy-related constraints that limit progress from laboratory discovery to real-world application. Key barriers include limited genomic and protein engineering capacity, absence of regional phage and endolysin repositories, inadequate biosafety and regulatory frameworks for biologics, dependence on imported reagents and expression systems, and weak integration of lysin technologies into national AMR and One Health action plans. We further highlight a mismatch between globally prioritized lysin targets and Africa’s dominant clinical, agricultural, and environmental pathogens. By reframing the African endolysin landscape through a translational failure lens, this review moves beyond descriptive summaries to propose actionable pathways for overcoming these barriers. We outline strategic priorities for capacity building, regulatory harmonization, funding mechanisms, and regional collaboration necessary to enable Africa’s participation in the global endolysin pipeline. Addressing these translational bottlenecks is essential for ensuring equitable access to lysin-based antimicrobials and for positioning Africa as an active contributor to next-generation AMR solutions rather than a passive end-user.
Background:Culture-based biomarkers of TB treatment response monitoring, e.g., Mycobacterial Growth Indicatory Tube (MGIT), are compromised when bacteria enter a non-replicating persister phase limiting the measurement of antibiotic efficacy and resistance. Understanding how antibiotic exposure to antibiotics alters bacterial physiology could help develop more effective TB therapies. We developed a novel assay with simultaneous measurement of 16S rRNA (bacterial burden) and its precursor, pre-16S rRNA (metabolic activity), and tested it on samples from patients in a trial of optimised-dose rifampicin. Methods:We developed a multiplex reverse transcriptase quantitative PCR assay (RT-qPCR) to measure relative gene expression of pre-16S rRNA and 16S rRNA in pre-treatment (control) and sequential samples from patients in the Phase II HIGHRIF2 (NCT00760149) clinical trial. We constructed a mathematical model to assess changes in pre-16S gene expression relative to 16S rRNA over time, facilitating the comparison of rifampicin doses' efficacy. Findings:In a retrospective study of 19 patients, pre-16S rRNA and 16S rRNA decreased steadily during the initial 36 days of treatment. This was evidenced by the rising cycle threshold (Cq) values slope 0.404 and 0.212, respectively, however, pre-16S rRNA decreased significantly quicker (P<0.0001). The changes in the relative gene expression of pre-16S rRNA during treatment fitted a double exponential decay curve (R2 = 0.996). According to this model, 1200 mg RIF-containing therapy exerted the most potent and rapid impact on pre-16S rRNA expression (Maximum suppression (Rmin)=1.694, T (time) =9.78 days), and also resulted in the swiftest daily reduction in bacterial load (-0.072 log10 CFU ml-1/day). Interpretation:The pre-16S rRNA and 16S rRNA gene expression multiplex PCR reported here provides an easy to use and rapid marker of drug efficacy and has potential to assess the efficacy of existing or novel drug combinations.
Gingivitis is a reversible inflammatory condition of gingival tissues and is majorly driven by the formation and accumulation of microbial biofilm. Untreated gingivitis often leads to periodontitis and ultimate tooth loss. The management of gingivitis through conventional methods relies mainly on the use of chemical antiseptics and antibiotics and the removal of plaque. However, the long-term use of the chemicals and antibiotics may alter the microflora and may also lead to antimicrobial resistance. This has led to increased interest in the usage of natural products-based herbal and traditional medicine as safer alternative medicine. This review provides a comprehensive overview of the pathogenesis of gingivitis with an emphasis on the microbial interaction and conversion of the microflora as the disease progresses. It evaluates the potential of major medicinal plants and their bioactive components used to cure the disease gingivitis. The antimicrobial, anti-inflammatory, antioxidant, and tissue-healing mechanisms of these medicinal plants are discussed alongside evidence from clinical trials. The review further highlights the limitations, such as the lack of standardized formulations and dosage variability differences among the various traditional and herbal medicinal practitioners, which prevents universal adoption of traditional medicine for treating gingivitis. In addition, advanced technologies such as the use of artificial intelligence for developing odontonutraceuticals, and next-generation polyherbal have also been explored. This review established the traditional and herbal medicine as an effective strategy for treating and managing gingivitis.
