Sodium glucose cotransporter 2 (SGLT2) inhibitors provide cardiovascular and renal benefits in type 2 diabetes mellitus, chronic kidney disease, and heart failure, but their use is associated with genitourinary (GU) infections and medication-safety concerns during antimicrobial treatment. This narrative review integrate evidence regarding SGLT2 inhibitor-associated GU infections, antimicrobial-antidiabetic drug interactions, pharmacovigilance, clinical management, and antimicrobial stewardship. Evidence from randomized controlled trials, meta-analysis, observational studies, pharmacokinetic studies and pharmacovigilance databases were used to synthesise on infection risk, drug interactions, management and safety issues in vulnerable populations. To identify relevant evidence narrative review was completed with evidence found in Pubmed, Google scholar, Clinical trial gov between 2020 and 2026. A purposive selection of literature was conducted to identify studies relevant to the article with a methodological strength, and not a systematic search was used.SGLT2 inhibitors demonstrate a more consistent association with genital mycotic infections than urinary tract infections (UTIs). Most GU infections are mild to moderate and can be treated with standard antimicrobial or antifungal therapy without routine discontinuation of SGLT2 inhibitors. SGLT2 inhibitors have low potential for drug-drug interactions, however, exposure to other agents can altered by strong enzyme inducers like rifampin, and this effect varies by SGLT2 inhibitor. Pharmacovigilance complements trial evidence by identifying safety signals, although disproportionality signals require clinical validation. Antimicrobial stewardship also enables treatment, avoidance of unnecessary prophylaxis, evaluation of risk factors, and assessment of concomitant medications and interactions.

<sec><title>BACKGROUND</title>Scaling up TB preventive treatment (TPT) is essential but hindered by operational and financial challenges, including limited cost evidence. This study estimated TPT delivery costs across five sub-Saharan African high-TB-burden countries.</sec><sec><title>METHODS</title>Micro-costing study was conducted from health system perspective across five clinics in Eswatini, Lesotho, Malawi, Uganda, and Tanzania. Data were collected using standardised templates covering overhead, human resources, equipment, consumables, and drugs, using bottom-up and top-down approaches. Human resource time was measured via 648 observations using time-and-motion studies, questionnaires, and timesheets. Costs are reported per patient in 2024 USD.</sec><sec><title>RESULTS</title>Among adults, total cost per individual ranged from US$27 to US$59 for 3 months of isoniazid plus rifapentine (3HP) and from US$22 to US$67 for 6 months of isoniazid (6H). Among children, the cost of 6H ranged from US$32 to US$80, while 3 months of daily rifampicin plus isoniazid (3RH) ranged from US$27 to US$46. Human resources and drugs were the principal cost drivers, accounting for the majority of total costs across all countries. Consultation for TPT initiation and adherence monitoring was the most time-consuming and costly activity.</sec><sec><title>CONCLUSION</title>TPT implementation costs extend significantly beyond drug prices. National programmes must adopt full-cost accounting that prioritises workforce efficiency and service integration to ensure sustainable scale-up.</sec>.

ObjectiveDrug-resistant tuberculosis (TB), particularly multidrug-resistant TB (MDR-TB),tuberculosis, remains a significant public health problem in Western China. This study aimed to evaluate the prevalence of rifampicin and isoniazid resistance, including multidrug-resistant tuberculosis, and to assess the proportion of multidrug-resistant tuberculosis cases among those with rifampicin resistance as detected using GeneXpert MTB/RIF assay, with multidrug-resistant tuberculosis defined based on the MeltPro TB assay.MethodsThis retrospective observational study employed a cross-sectional diagnostic concordance design. In total, 345 patients were enrolled between December 2022 and September 2023; among these, 280 (81.16%) were newly diagnosed. Drug susceptibility profiles were determined using the MeltPro TB and GeneXpert MTB/RIF assays. Multidrug-resistant tuberculosis was defined based on the MeltPro TB assay, which served as the molecular reference rather than a definitive gold standard. Sensitivity and positive predictive value were calculated with 95% confidence intervals against MeltPro-defined multidrug-resistant tuberculosis.ResultsAmong the 345 patients, 22 (6.38%) were isoniazid-monoresistant, 12 (3.48%) were rifampicin-monoresistant, and 33 (9.57%) had multidrug-resistant tuberculosis. Among the 209 samples positive on both MeltPro and GeneXpert MTB/RIF, 30 (14.35%) were rifampicin-resistant according to the GeneXpert MTB/RIF; 25 (83.33%) of these had MeltPro-defined multidrug-resistant tuberculosis. This proportion differed according to treatment history, with 11/16 (68.75%) among newly diagnosed patients versus 14/14 (100.00%) among previously treated patients. The sensitivity of GeneXpert MTB/RIF detected rifampicin resistance against MeltPro-defined multidrug-resistant tuberculosis among newly diagnosed patients was 100.00% (95% confidence interval, 71.51-100.00), and the positive predictive value was 68.75% (95% confidence interval, 44.03-87.07).ConclusionsOnly 68.75% of newly diagnosed patients with GeneXpert MTB/RIF detected rifampicin resistance had multidrug-resistant tuberculosis, indicating that rifampicin resistance is a suboptimal surrogate for multidrug-resistant tuberculosis in this population. These estimates are concordance-based rather than accuracy against a definitive reference standard, and comprehensive testing for both isoniazid and rifampicin susceptibility should be performed in clinical practice to guide treatment and mitigate transmission.

Tuberculosis (TB) remains a major global public health concern, further complicated by the emergence and transmission of drug-resistant strains. Diversity within the Mycobacterium tuberculosis complex (MTBC) may also influence disease progression and treatment response. We conducted a longitudinal study among 126 Xpert MTB/RIF Ultra-confirmed TB patients enrolled and followed at the Antituberculosis Center of Brazzaville between July 2023 and November 2024. MTBC species were identified using the Genotype MTBC assay, and resistance-associated mutations in rpoB, katG, and embB were characterized by targeted Oxford Nanopore sequencing and interpreted using the WHO mutation catalogue and TB-Profiler. The overall treatment success rate was 81.7% (103/126). Among 109/126 samples successfully typed, M. tuberculosis accounted for 92.7% (101/109), Mycobacterium africanum for 3.7% (4/109), while mixed infection accounted for 0.9% (1/109) and inconclusive profiles for 2.8% (3/109). Resistance-associated mutations were assessed in 65 of the 126 enrolled patients with high-quality sequencing data. Among these 65 isolates, 32.3% (21/65) harbored resistance to at least one of the targeted first-line drugs, including isoniazid (23.1%; 15/65), rifampicin (15.4%; 10/65), and ethambutol (9.2%; 6/65). Multidrug-resistant TB was identified in 12.3% (8/65). The predominant mutations occurred at rpoB codon 435, katG codon 315, and embB codon 306. Treatment success was lower among patients infected with strains carrying a resistance-associated mutation (71.4%). Isoniazid resistance was associated with reduced odds of treatment success in unadjusted analysis (OR = 0.22, 95% CI: 0.05-0.93; p = 0.04). These findings suggest a considerable burden of genotypically predicted first-line drug resistance and support expanding molecular drug-susceptibility testing beyond rifampicin in TB surveillance and patient management in the Republic of Congo.

A 57-year-old man with a history significant for Mycobacterium tuberculosis infection presented to the emergency department for a 5-month history of low-volume hemoptysis, fatigue, and unintentional weight loss of 12 lb. He was treated twice in the past for pan-sensitive TB with a standard regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for 12 months. Over the past 5 months, his hemoptysis had progressively worsened, reaching approximately one-quarter of a cup per day. However, on the day before presentation, he experienced an episode of massive hemoptysis amounting to one-half of a cup of bright red blood, prompting him to present to the emergency department. His history included post-TB bronchiectasis diagnosed after the completion of his most recent TB treatment. He had worked as a seasonal landscaper for nearly 30 years with frequent soil exposure and reported daily marijuana smoking for approximately 20 years. He denied prior incarceration or travel to TB-endemic regions and had lived in a metropolitan area throughout his life.

Shugan Formula (SGF) shows clinical hepatoprotective effects, but its mechanism against anti-tuberculosis drug-induced liver injury (ATB-DILI) remains unclear. This study employed LC-MS/MS-based metabolomics to investigate SGF's protective effects in rats. ATB-DILI was induced by oral isoniazid and rifampicin (100 mg·kg[-1] each) for 14 days. During modeling, the rats in the treated groups received low, medium, or high doses of SGF via oral gavage, whereas the PC group was administered obeticholic acid. Serum biomarkers (ALT, AST, IL-6, IL-10, and TNF-α), hepatic oxidative stress markers (MDA, SOD, GST, and GSH-Px), liver histopathology, and serum metabolomics were assessed. SGF treatment significantly reduced serum ALT, AST, TNF-α, and IL-6 levels, decreased hepatic MDA and GST levels, and increased SOD and GSH-Px activities. Metabolomics revealed that SGF attenuated metabolic perturbations induced by liver injury, with the high-dose group being most effective. Key pathways involved amino acid metabolism, bile acid metabolism, and glycerophospholipid metabolism. This study provides scientific evidence for SGF in preventing and treating ATB-DILI.

Staphylococcus epidermidis biofilms are inherently tolerant to antimicrobial treatment, contributing to the persistence and recurrence of biofilm-associated infections. In this study, we examined the phenotypic and proteomic responses of S. epidermidis ATCC 35984 biofilms following exposure to subinhibitory concentrations (1/8× MIC) of levofloxacin, rifampicin, and their combination. Phenotypic analyses revealed clear differences among the treatments. Rifampicin significantly reduced the number of viable biofilm-associated cells, whereas levofloxacin alone had little effect. The combination of rifampicin and levofloxacin produced the most pronounced antibiofilm activity, significantly reducing both biofilm biomass and viability. These findings were supported by confocal laser scanning microscopy, which showed the greatest loss of viable cells and biofilm integrity in the combination-treated biofilms. Label-free quantitative proteomic analysis demonstrated distinct treatment-specific adaptive responses. Rifampicin, either alone or in combination with levofloxacin, triggered broadly increased abundance of proteins involved in translation, energy production, amino acid and nucleotide metabolism, ATP-binding cassette transport, and quorum sensing. In contrast, levofloxacin predominantly suppressed proteins associated with central metabolism, transcription, translation, and biosynthetic pathways. Hierarchical clustering further showed that the proteomic profile of the combination treatment closely resembled that of rifampicin alone, suggesting that rifampicin was the dominant driver of proteomic remodeling. Expression pattern network analysis identified a conserved stress-response signature comprising Fhs, YdaG, PerR, and YcsE across all treatment conditions. Notably, the multidrug efflux pumps NorA and NorC showed decreased protein abundance across all treatment conditions, indicating a potential reduction in efflux-mediated resistance under sub-MIC antibiotic exposure. Taken together, these findings demonstrate that rifampicin retains substantial antibiofilm activity at subinhibitory concentrations and elicits extensive metabolic adaptation, whereas levofloxacin primarily induces a metabolically repressed state. The enhanced activity of the rifampicin-levofloxacin combination appears to arise from complementary effects on biofilm viability and cellular physiology. This study provides new insights into the adaptive responses of S. epidermidis biofilms to sublethal antibiotic stress and highlights the potential of rifampicin-based combination therapies for the management of biofilm-associated infections.

An acute exacerbation in some tuberculosis (TB) cases can lead to widespread infection; this disseminated disease may progress when the body's immune response becomes dysregulated. Although rare, certain patients without obvious immune compromise can develop severe organ dysfunction if inflammation escalates uncontrollably. Respiratory failure can develop rapidly once lung tissue becomes overwhelmed by excessive inflammatory signaling. This presentation is uncommon but severe and is frequently unrecognized in its early stages because symptoms mimic other critical conditions. Mortality increases substantially once acute respiratory distress syndrome (ARDS) develops in the setting of disseminated infection. A 40-year-old man, previously in good health, presented with severe respiratory distress. Oxygen saturation declined rapidly, requiring urgent endotracheal intubation. He subsequently required vasopressor support and prone positioning due to advanced respiratory failure. Laboratory evaluation revealed thrombocytopenia and elevated liver enzymes. Comprehensive microbiological testing did not identify common viral, bacterial, or fungal pathogens. A positive Mycobacterium tuberculosis (MTB) PCR result from bronchial fluid confirmed disseminated TB. His clinical course was complicated by moderate ARDS and a hyperinflammatory state, consistent with an exaggerated immune response to TB. Treatment was initiated with rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy along with systemic corticosteroids (methylprednisolone 40 mg every eight hours). Clinical improvement was observed, and ventilatory support was discontinued following targeted treatment. The patient was discharged with a plan for prolonged anti-tubercular therapy. This case illustrates how disseminated TB can trigger a severe inflammatory response leading to moderate ARDS, even in the absence of underlying immunosuppression. Early recognition of this presentation is critical, and combined treatment with antimicrobial therapy and immunomodulation may improve outcomes.