International Journal of Antimicrobial Agents

Rationale: Infections due to Extended-spectrum {beta}-lactamases-producing Enterobacterales (ESBL-PE) require empirical treatment with carbapenems. ESBL-PE carriage is considered as a risk factor for ESBL-PE involvement during ICU infection. Our aim was to determine factors that may predict the actual involvement of ESBL-PE. Methods: A two-periods bicentric ambispective study including ICU ESBL-PE carriers patients from April 2011 to January 2019. All ESBL-PE carriers who developed an infection were analyzed. Results: 6112 patients and 4902 patients were screened during the two periods. 384 and 232 ESBL-PE carriers were identified. Total number of infectious episodes were 146 and 114, respectively. A total of 144 pneumonias, 42 urinary tract infection and 45 digestive infections were studied. An ESBL-PE was involved in 35 (24.3%) episodes of pneumonia, and 44 (37.9%) of extra-pulmonary infections. The most frequent ESBL-PE involved were K. pneumoniae, E. cloacae and E. coli. Similar species and phenotypes were present in colonisation and infection in 29 (82.8%) of pneumonia and in 40 (90.9%) of extra-respiratory infection. Multivariate analysis identified Klebsiella pneumonia or Enterobacter cloacae carriage as risk factor for ESBL-PE involvement in pneumonia and E. coli carriage and detection of ESBL-PE carriage before ICU admission as protective factors. Conclusion: In our study an ESBL-PE involvement is infrequent in pneumonia. A known carriage before ICU admission and E. coli carriage are factors associated with the absence of ESBL-PE un the episode of respiratory infection. A confirmation of our findings could lead to a reduction in the empirical use of carbapenems in this population.

Background: Antimicrobial resistance poses a major threat to global public health. Large language models (LLMs) offer new possibilities for optimizing antibiotic prescribing decisions, but the capabilities of general-purpose versus domain-specific medical LLMs under different prompting strategies remain to be clarified. Methods: This double-blind, randomized-sequence evaluation used a 2X2 factorial design comparing four AI conditions-the domain-specific model MedGo and the general-purpose model DeepSeek V3.5, each under standard direct prompting and chain-of-thought (CoT) prompting-alongside real physician prescriptions across 59 complex inpatient infection cases. Five parallel regimens were generated per case and independently evaluated by three senior clinicians (1-5 comprehensive score and five domain sub-scores). ChatGPT 5.2 was additionally assessed as an automated evaluation tool. Results: Score ranking: real physicians > MedGo-CoT > DeepSeek-CoT > MedGo> DeepSeek (Friedman test, p<0.001). In base mode, MedGo significantly outperformed DeepSeek (Holm-adjusted p=0.040). CoT improved both models (Holm-adjusted p<0.001 for DeepSeek; p=0.024 for MedGo) and reduced score dispersion. MedGo-CoT significantly outperformed DeepSeek-CoT in individualized adjustment (adjusted p<0.001) and dosing precision (adjusted p=0.005). ChatGPT-expert correlation was negligible (overall Kendall {tau}=0.153, p=0.003; subgroup {tau}=0.06-0.20, all p>0.05). Conclusions: Domain-specific medical LLMs enhanced by CoT approach the antibiotic decision-making level of real physicians, with advantages in individualization and dosing precision. However, notable deficiencies persist in antimicrobial stewardship ecological awareness and automated evaluation reliability, underscoring the continued indispensability of senior clinical expertise.

ObjectivesFosfomycin (FOS) remains an important therapeutic option for urinary tract infections caused by uropathogenic Escherichia coli (UPEC), but specific virulence traits as biofilm formation, metabolic adaptation, and antimicrobial resistance may limit its efficacy. This study investigated whether the natural compound, trans-cinnamaldehyde (t-CA) potentiates FOS activity against UPEC and explored the underlying mechanisms of its effect MethodsThe interaction between t-CA and FOS was assessed using checkerboard assays, time-kill analysis. We evaluated biofilm viability and structure using confocal and scanning microscopy as well as catheter-associated biofilm models. Next, effects on membrane integrity, cell-surface properties, membrane potential, intracellular pyruvate levels, and resistance evolution during serial passage were evaluated. Molecular docking was used to explore potential interactions of t-CA with enzymes involved in pyruvate metabolism. Galleria mellonella infection model was employed to evaluate in vivo therapeutical efficiency. Resultst-CA potentiated FOS activity against laboratory, reference, and clinical UPEC strains, with synergistic or additive interactions observed across the tested collection. The combination enhanced bacterial killing, reduced biofilm viability and biomass, and disrupted biofilm architecture. In catheter-associated biofilms, combined treatment markedly impaired surface-associated UPEC communities. t-CA reduced extracellular matrix abundance and altered cell-surface hydrophobicity and membrane potential without inducing detectable oxidative stress. Mechanistically, t-CA affected pyruvate homeostasis, reduced intracellular pyruvate levels, and phenotypically intersected with the BtsSR pyruvate-sensing pathway. Serial exposure to FOS alone rapidly increased MIC, whereas t-CA limited this phenomenon and did not itself promote reduced susceptibility. The compounds combination also improved survival of UTI89-infected G. mellonella larvae. Conclusionst-CA enhances FOS activity against UPEC through complementing the antibiofilm and metabolic effects. By weakening biofilm matrix integrity, perturbing pyruvate homeostasis, and limiting FOS-associated MIC elevation, t-CA represents a promising adjuvant candidate for improving FOS efficacy against biofilm-associated UPEC infections.

Septic shock caused by fungal organisms is characterized by high mortality and diagnostic complexity. We used the Premier Healthcare Database to characterize antifungal use and fungal diagnoses among adults with septic shock requiring vasopressors admitted between October 2022 through July 2024. Among 12.8 million admission at 886 hospitals, 554,948 met septic shock criteria and were included for analysis. A fungal diagnosis was established in 11,405 (2.1%) of encounters; of these, 3,565 (31.3%) received intravenous antifungal therapy within one day of vasopressor initiation. In the overall cohort, antifungal therapy was initiated in 29,824 (5.5%) within one day of vasopressor initiation; of these, 3,656 (12.2%) were ultimately diagnosed with a fungal infection. In the 116 hospitals reporting microbiological data, a subgroup of 489 encounters with septic shock and culture-confirmed candidemia was identified. In this subgroup, intravenous antifungal therapy was initiated in 43.8% within one day, 63.8% within three days, and 78.9% within seven days. These findings highlight a profound decoupling between fungal diagnosis and treatment--few patients receiving antifungals were diagnosed with an infection that would be treated by these agents, while less than half of patients with septic shock and candidemia received timely treatment. Strategies for greater precision in empiric antifungal use in septic shock are needed to improve safety, stewardship, and outcomes.

Background and Aims The optimal treatment for first episodes and first recurrences of Clostridioides difficile infections (CDI) is unknown and there is emerging evidence for pulse and taper (P-T) regimens. Therefore, we sought to estimate the relative efficacy of treatment options. Methods MEDLINE and CENTRAL were searched from database inception to May 21, 2025 and unpublished conference abstracts were searched from recent infectious disease conferences. RCTs on the treatment of first episodes or first recurrences of CDI comparing fixed-dose or P-T regimens of fidaxomicin or vancomycin were included. The primary and secondary outcomes were 40- and 56-day CDI recurrence, respectively. A random-effects network meta-analysis on the risk ratio (RR) scale was conducted using a standard regimen (10-14 days) of vancomycin as the comparator. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). Results 8 RCTs were included comprising a total of 2181 patients. For 40-day recurrence, fidaxomicin P-T had the highest probability of ranking best (RR=0.10, 95%Confidence Interval [95%CI]=0.10-0.49, SUCRA=1.00), followed by vancomycin P-T (RR=0.49, 95%CI=0.32-0.76, SUCRA=0.61), fixed-dose fidaxomicin (RR=0.61, 95%CI=0.49-0.76, SUCRA=0.39), and, finally, fixed-dose of vancomycin (SUCRA=0.00). The treatments ranked in the same order for 56-day recurrence, though only 3 RCTs reported on this timepoint. Conclusion Vancomycin P-T, fidaxomicin P-T, and fixed-dose fidaxomicin were all superior to a fixed-dose vancomycin. Head-to-head comparative effectiveness RCTs are needed to quantify their relative effect sizes of and impact on long-term prevention of recurrent CDI.

The minimum inhibitory concentration (MIC) is a standard measure for describing the lowest effective dose concentration of an antimicrobial compound in clinical practice; yet, conventional assays often require a substantial amount of antimicrobial compound, limiting their use with scarce, purified agents. Here, we describe a simple and reproducible technique to evaluate the MIC for purified compounds with a limited sample size. The protocol describes the MIC steps against a bacterial strain while minimizing the use of reagents and materials. It is helpful for screening purified natural products as antimicrobial agents and in early-stage drug discovery. The protocol adapts standard microplate-based assays for two-fold dilution of the compound, ensuring their applicability in microbiological studies. The MIC value of the standard antibiotic kanamycin against Staphylococcus aureus, Vibrio fischeri, Klebsiella pneumoniae, and Escherichia coli was determined using our method, and was found to be consistent with the conventional broth microdilution method, validating its reliability. Therefore, this method offers a practical and viable solution for antimicrobial drug discovery, addressing the disparity between limited compound availability and comprehensive microbiological assessment of MIC.

Background Klebsiella pneumoniae (Kpn) is a major cause of neonatal sepsis in Africa. 3rd generation cephalosporin and gentamicin resistant Kpn is the norm in many sites, rendering WHO recommended first- and second-line antimicrobials ineffective. An understanding of which neonates and infants are most at risk of sepsis caused by Kpn would support the case for improved access to WHO watch and reserve antimicrobials (i.e. carbapenems) for patients most likely to benefit from them. Methods A prospective case-control study was conducted at Queen Elizabeth Central Hospital, Malawi. Cases were infants <3 months of age with blood or CSF culture confirmed Kpn infection. Controls were healthy infants from the same wards and were matched 2:1. Univariate and multivariate logistic regression were performed on mean-centred data to determine risk factors for infection with Kpn. Results We analysed data from 38 cases and 76 controls between August 2021 and April 2023. Mortality at 3 months of age was 21/38 (29%) for cases, with 14/38 (37%) identified postmortem and 6/76 (7.9%) for controls (OR 14.0 (95% CI 4.59, 49.2, p>0.001). Cases were more likely to be born out of QECH than controls (42% vs. 24%, p = 0.043), and cases had lower birthweights (median 2200g vs. 2850g, p = 0.005). Multivariate logistic regression analysis revealed that increasing birthweight was protective against Kpn infection (OR: 0.858 [95% CI: 0.745, 0.987] per 100g increase), while longer hospital stay was associated with increased odds of infection (OR: 1.148 [95% CI: 1.012, 1.1.303] per additional day). Most infecting isolates (34/38 [89%]) were resistant to first- and second-line antimicrobial agents, but all were sensitive to meropenem and 33/36 [92%] to amikacin. Conclusion Low birthweight infants with prolonged hospital stay were at greatest risk of Kpn infections that were typically resistant to WHO first- and second-line antimicrobial therapy. These infants should be prioritised for antibiotics that have the potential to be life-saving. The overlapping and evolving nature of these risk factors makes it difficult to design a simple tool to support empiric initiation of meropenem. Neonates critically ill with Kpn sepsis cannot, however, afford to wait for blood culture confirmation before receiving effective treatment. This highlights the need for empiric decision making frameworks that allow rapid initiation of effective therapy in high-risk neonates.

Objectives To evaluate two-year, side-by-side outcomes of a prospective audit and feedback (PAF)-based antimicrobial stewardship program (ASP) in a quaternary ICU in Ghana, comparing diagnostic stewardship, antimicrobial prescribing patterns, and clinician adherence to stewardship recommendations between 2024 and 2025. Longitudinal PAF data from low- and middle-income countries (LMIC) quaternary ICUs are scarce; this study addresses that evidence gap. Methods A retrospective comparative analysis of routine Antimicrobial Stewardship (AMS) surveillance data was conducted at the University of Ghana Medical Centre ICU: 102 visits in 2024 and 63 in 2025. Proportions were compared by chi-square or Fishers exact test; continuous variables by Mann-Whitney U. Wilson score 95% confidence intervals (CIs) were computed for primary proportions. Results Biomarker-guided prescribing rose from 86.3% to 100% of visits (p=0.005) and culture and sensitivity testing from 74.5% to 90.5% (p=0.02). Targeted (culture-guided) therapy increased significantly from 23.5% to 41.7% of antibiotic recipients (p=0.03), while empiric prescribing declined correspondingly. Overall antibiotic utilization remained high in both years (96.1% vs 95.2%; p=1.00), and meropenem use rose from 42.9% to 56.7% (p=0.13). AMS interventions were recommended in 67.6% and 63.5% of visits, respectively. Clinician acceptance improved markedly from 40.6% (95% CI: 29.8-52.4%) to 67.5% (95% CI: 52.0-79.9%) (p=0.01). Conclusions Two years of PAF in a Ghanaian quaternary ICU demonstrated progressive program maturation: universal biomarker adoption, a significant shift toward targeted prescribing, and markedly enhanced clinician acceptance. Persistently high antibiotic utilization and rising carbapenem dependence underscore the need for sustained surveillance and carbapenem-sparing strategies in LMIC critical care.

Background: Localized skin and soft tissue infections may need systemic antibacterials, but local inflammation can delay symptom recovery. We evaluated whether topical fresh Taraxacum mongolicum wet dressing added to ceftriaxone was associated with short-term benefit in selected clinically stable adults. Methods: In this single-center, assessor-blinded, three-arm randomized trial, 180 adults aged 18-74 years were randomized 1:1:1 to topical T. mongolicum plus intravenous ceftriaxone, topical T. mongolicum alone, or ceftriaxone alone for 7 days. The primary outcome was day-7 clinical response assessed by blinded independent assessors using prespecified global clinical improvement criteria. Analyses followed the intention-to-treat principle; sensitivity analyses assessed robustness. Results: Day-7 clinical response rates were 91.67% (55/60), 76.67% (46/60), and 68.33% (41/60) in the combined, T. mongolicum, and ceftriaxone groups, respectively (overall P = 0.006). Compared with ceftriaxone alone, combined therapy had a higher response rate (risk difference, 23.3 percentage points; 95% CI, 9.6 to 37.0; risk ratio, 1.34; 95% CI, 1.11 to 1.62). Sensitivity analyses were directionally consistent. Secondary outcomes and bacterial clearance favored the combined group. No serious adverse events were reported. Conclusions: In selected clinically stable adults with localized skin and soft tissue infections, adjunctive topical fresh T. mongolicum plus ceftriaxone was associated with improved short-term outcomes compared with ceftriaxone alone. Findings require cautious interpretation because this was a single-center, partially blinded trial without a placebo dressing control. The dressing should not replace antibiotics, drainage, or urgent care when indicated. Trial registration: International Traditional Medicine Clinical Trial Registry, ITMCTR2026000549.

The Project to Accelerate New Treatments for Tuberculosis (PAN-TB) aims to accelerate development of shorter, simpler and safer pan-TB combinations. We previously identified 3 out of 25 first-generation novel PAN-TB 4-drug combinations, that cured 90% of mice in less than 3 months, at clinically relevant doses in the relapsing mouse model of TB. These regimens include BPa830Sut, BPa286Sut and BQSut286 (B: bedaquiline; Pa: pretomanid; 830: GSK3211830; 286: GSK2556286; Sut: sutezolid; Q: quabodepistat). Here, we assess the efficacy of these combinations where the original candidates are substituted next-generation or more advanced compounds (ganfeborole (656) for 830, sorfequiline, S for B, TBD09 for Sut and TBD11 for 286) and the individual contributions of specific agents. Six novel regimens demonstrated bactericidal activity more rapid than comparators PHMZ (Rifapentine P, Isoniazid H, Moxifloxacin M, Pyrazinamide Z) and BPaMZ. Modelled cure/relapse data showed that SPa286Sut, SPaSut and SPa656Sut cured 90% of mice in about 1 month, while SPa286, SPaQTBD11 and SPaTBD09 in less than 2 months, faster than PHMZ. Consistent with our previous findings, the fastest-curing regimens centered on a diarylquinoline (S), a nitroimidazole (Pa) and an oxazolidinone (TBD09 or Sut) together with an Rv1625c agonist (TBD11 or 286), DprE1 inhibitor (Q) or a LeuRS inhibitor (656). Notably, significant contributions to sterilizing efficacy were demonstrated for S in all combinations and for Pa, Sut, TBD09, Q and TBD11 or 286 in specific S-containing combinations. These findings suggest potential for these novel agents and combinations to improve treatment of both DS-and DR-TB.

Background Cervical precancer (CIN2/3) remains undertreated in low- and middle-income countries due to limited access to screening and healthcare providers, contributing towards high cervical cancer mortality rates. Self administered intravaginal therapies, such as artesunate, may help to expand access to cervical precancer treatment. However, data on the systemic absorption and pharmacokinetics of intravaginal artesunate are lacking. Objective This study aimed to characterize the pharmacokinetics and safety parameters of intravaginally administered artesunate. Methods This is a Phase I, single arm, open label pharmacokinetic study of 12 healthy women in Kisumu, Kenya who self-administered 200 mg artesunate vaginal pessaries once daily for 5 consecutive days under direct observation with daily safety assessments. Participants returned each day for supervised dosing and adverse-effect assessments on days 1 to 4 without pharmacokinetic blood sampling. On day 5, participants administered the final dose and underwent serial blood sampling at 0.25, 0.5, 1, 2, 4, 6, and 8 hours. Plasma concentrations of artesunate and dihydroartemisinin (DHA), its active metabolite, were quantified and pharmacokinetic parameters estimated using non-compartmental analysis. Results Artesunate and its active metabolite dihydroartemisinin (DHA) were detectable in all participants, with mean (SD) Cmax values of 83.7 (42.7) ng/mL and 97.0 (53.1) ng/mL, respectively, and a mean DHA AUC(0.T)h of 504.2 (281.1) ng.h/mL. Additionally, the mean Tmax values for Artesunate and DHA are 4.17(1.59) hours and 6.33 (1.67) hours respectively. Due to delayed absorption (Tmax), area under the serum concentration versus time curve (AUC), apparent clearance, and elimination half-life could not be calculated. The treatment was well tolerated with no serious adverse events. Conclusion Peak DHA concentrations (range 19.7 to 180.6 ng/mL) were substantially lower than those reported for intravenous and oral administration with interpatient variability (CV 54.8% for Cmax and 55.8% for AUC0 T) hours) consistent with those reported for other non-intravenous routes of administration. Intravaginally-administered artesunate yielded low, yet measurable, systemic exposure with delayed Tmax. These findings support further investigation of intravaginal artesunate as a safe self-administered treatment for cervical precancer.

Background: Antimicrobial resistance (AMR) disproportionately affects low- and middle-income countries (LMICs) such as Pakistan, where obstetric and gynaecological (OBGYN) patients carry high antibiotic exposure. Specialty-specific drug utilization data with concurrent stewardship audit remain scarce. This study evaluated antibiotic prescribing patterns, consumption metrics, and antimicrobial stewardship program (AMS) compliance in OBGYN inpatients at a public sector tertiary care hospital. Methods: A prospective cross-sectional study was conducted in OBGYN wards of Dow University Hospital, Karachi, from 1 September to 31 October 2025. Women receiving [&ge;]1 systemic antibiotic were included. Daily AMS rounds were conducted by an Infectious Diseases physician and pharmacist. Antibiotic consumption was measured as Defined Daily Doses (DDD) and Days of Therapy (DOT) per 1,000 patient-days (total = 821). Antibiotics were classified by WHO AWaRe (2023) framework. Results: Of 812 total admissions, 278 patients (34.2%) received [&ge;]1 antibiotic and were enrolled (205 obstetric, 73 gynaecological), generating 636 prescriptions (mean 2.29/patient). Surgical prophylaxis was the predominant documented indication (213, 33.5%); 65.1% carried no documented indication. By AWaRe classification, 53.6% were Access-group and 46.1% Watch-group. Ceftriaxone (38.4%) and metronidazole (36.8%) together represented 75.2% of prescriptions. Combined DDD/1,000 patient-days was 1,758.6 and DOT/1,000 patient-days was 1,852.7. AMS compliance was 0%. Conclusions: This study documents high antibiotic prescribing burden, near-universal documentation failure, and zero AMS compliance in OBGYN inpatients at a Pakistani public sector hospital. The predominance of Watch-group antibiotics and undocumented surgical prophylaxis highlights structural stewardship gaps. Findings support urgent need for institutional OBGYN antibiotic guidelines and structured pharmacist-led AMS programs.

Controlled human infection models (CHIMs) are increasingly used in infectious disease research to study pathogen dynamics and evaluate interventions under controlled conditions. However, these studies are resource-intensive and involve ethical and safety constraints, making efficient study design critical. Dose-finding is a key early component in CHIMs, where the aim is to identify a challenge dose that achieves a target infection probability. Traditional rule-based designs are commonly used but can be inefficient, motivating the use of model-based adaptive approaches such as the Bayesian Continual Reassessment Method (CRM). Although CRM has been extensively studied and widely adopted in Phase I oncology trials for identifying the maximum tolerated dose of therapeutics, its application in CHIM settings remains limited, particularly when the endpoint of interest is infection. This tutorial provides step-by-step guidance for implementing a Bayesian CRM in dose-finding CHIMs, using an oropharyngeal Neisseria gonorrhoeae challenge as a motivating case study. The framework outlines key design components, including dose-grid specification, dose-response model, prior elicitation, Bayesian updating, decision rules, and stopping criteria, with particular emphasis on a clinically interpretable parameterisation. Trial operating characteristics are evaluated through simulation studies under multiple dose-response scenarios and prior-predictive analyses, and compared with a commonly used '3+3' type rule-based design. This work highlights the advantages of Bayesian model-based designs for dose-finding in CHIMs over classic rule-based designs and provides a structured, reproducible framework for implementing CRM, supporting their application in future CHIM studies.

Two new antibiotics, zoliflodacin and gepotidacin, were recently approved for the treatment of urogenital gonorrhea. While combination therapy could, in principle, delay the emergence and spread of resistance, doing so depends on the absence of antagonism between the co-administered drugs. Using in vitro checkerboard testing, we observed no evidence of antagonism for all pairwise combinations of zoliflodacin, gepotidacin, and ciprofloxacin, including in strains with elevated ciprofloxacin MICs.

BackgroundNeurulation is a fundamental process in the formation of the central nervous system (CNS). The process begins with the folding and fusion of the neural plate to form the neural tube which subsequently gives rise to the development of the brain and spinal cord. Environmental and genetic factors that disrupt neurulation can induce neural tube defects (NTDs) and consequently cause additional developmental complications, including motor impairments. Purinergic signaling is a conserved form of extracellular communication (i.e. paracrine, synaptic signaling) that plays a role in early development. This signaling is mediated by purine nucleotides and nucleosides, which activate metabotropic P2Y and ionotropic P2X purinoceptors, respectively. Distinct patterns of intracellular calcium dynamics are observed throughout vertebrate development, from fertilization through organogenesis, including neurulation. Among P2X receptors, P2X4 is an ATP-modulated, Ca2+-permeable, ligand-gated ion channel characterized by having the highest Ca2+ permeability and is known to be modulated by ivermectin (IVM). ObjectiveOur investigation focuses on assessing the effects of IVM treatment during neurulation and evaluating the impact of this drug on phenotype, motor behavior and neuromuscular junction (NMJ) structure at tadpole stage. These results were compared with those obtained following separate treatments with compounds that specifically block glycine, GABA(A) and nACh receptors, all which have been described as IVM targets. ResultsIn this study we demonstrate the transcriptional expression for both P2X and P2Y purinergic receptors during neurulation, as well as the expression of P2X4. Following IVM neurula-treatments, we observed neural tube defects (NTDs), pigmentation changes, motor paralysis and alterations in neuromuscular junction (NMJ) structure, particularly affecting axonal branching. In contrast, treatment with the blockers strychnine, bicuculline and -bungarotoxin, used to assess the involvement of GlyR, GABA(A)R and 7nAChR, respectively, failed to show similar outcomes. ConclusionsIn summary, our results highlight the critical role of purinergic signaling during early development, particularly P2X4 receptor mediated signaling during neurulation which may account for the pharmacological effects induced by the positive allosteric modulator ivermectin.

Background: Group A streptococcal (GAS) pharyngitis drives substantial antibiotic prescribing in children. The 10-day standard burdens adherence and prolongs exposure, increasing selective pressure for resistance. Yet, whether shorter courses achieve comparable outcomes remains unresolved. Purpose: To address how the duration of oral antibiotics affects clinical outcomes in children and adolescents with suspected or confirmed GAS pharyngitis. Data Sources: MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to July 2025. Reviewers also searched reference lists of eligible trials and relevant systematic reviews. Study Selection: Randomized trials enrolling children and adolescents [&le;]18 years with suspected or confirmed GAS pharyngitis comparing different durations of oral antibiotics, or oral antibiotics against placebo or no treatment. Data Extraction: Paired reviewers independently screened records, extracted data, and assessed risk of bias. Data Synthesis: We performed random-effects dose-response meta-analyses with restricted cubic splines and rated the certainty of evidence using GRADE. Forty-five trials enrolling 22,636 participants met eligibility criteria. Across outcomes, low to moderate certainty evidence suggests that 3, 5, and 10 days of antibiotic treatment may produce little to no difference. Moderate certainty evidence supports similar effects of 5 and 10 days on clinical cure, relapse, and adverse events. Evidence comparing 3 and 10 days carries lower certainty. Serious adverse events were rare: no deaths, 4 cases of acute rheumatic fever, and 4 cases of post-streptococcal glomerulonephritis among 776, 8,818, and 9,096 participants, respectively, making clinically important differences across treatment durations unlikely. Limitations: Evidence on 3-day courses came almost exclusively from trials of azithromycin, limiting inference about shorter penicillin regimens. Findings apply most directly to high-income settings. Conclusion: These findings challenge the long-standing 10-day standard for pediatric GAS pharyngitis and show that 5 days of oral antibiotics are likely as effective and safe as 10 days.

Background and objectives Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of cirrhosis with ascites, carrying one- and two-year mortality rates exceeding 70% and 80%, respectively. Fluoroquinolone prophylaxis is the cornerstone of SBP prevention. Real-world longitudinal data on prescribing practices and clinical outcomes from Indian tertiary care centers are sparse. We aimed to evaluate fluoroquinolone prescribing patterns, guideline adherence, and six-month clinical outcomes in SBP patients at a tertiary academic center in North India. Methods This was a pre-specified sub-analysis of a 15-month analytical longitudinal study at AIIMS Rishikesh. Adults (age >/=18 years) admitted with SBP and initiated on fluoroquinolone prophylaxis were enrolled consecutively and followed for six months. Prescribing practices were compared against EASL and AASLD recommendations. The primary outcome was the rate of guideline-directed prescribing. Secondary outcomes included clinical cure at discharge, six-month cure, relapse, regimen modification, adverse drug reactions, and treatment compliance. Categorical variables were compared by Fisher's exact test or chi-squared test (SPSS). Results Forty-eight SBP patients were included (mean age 44.75 +/- 11.94 years; 85.4% male). Guideline-directed fluoroquinolone prophylaxis was prescribed to all patients (100%). Norfloxacin 400 mg once daily was predominant (85.4%), followed by levofloxacin (10.4%) and moxifloxacin (4.2%). Cure at discharge was 85.4%. At six months, 64.6% maintained sustained cure and 22.9% relapsed. Regimen modification occurred in 22.9%, most commonly antimicrobial substitution. Nausea was the only adverse drug reaction (4.8%). Treatment compliance was 73.8%. No patient underwent therapeutic drug monitoring. Conclusions Fluoroquinolone prescribing for SBP prophylaxis at AIIMS Rishikesh was fully concordant with standard guidelines. Despite complete adherence, a relapse rate of 22.9% and frequent regimen modification underscore the limitations of long-term fluoroquinolone prophylaxis, likely reflecting emerging quinolone resistance. Strengthening antimicrobial stewardship is essential to sustain prophylaxis effectiveness in Indian tertiary care settings.

Antimicrobial resistance represents a continuing threat to clinical infection management, with methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli identified by the World Health Organization as priority pathogens. This study evaluated the antimicrobial activity, synergistic potential, and chemical composition of six plant-derived preparations (three ethanolic extracts: nettle, thyme, rosemary; and three essential oils: lavender, lemongrass, doTERRA Peace blend) against MRSA, methicillin-sensitive S. aureus (MSSA), and E. coli K-12 by disc diffusion, broth microdilution, post-exposure culturability, antimicrobial interactions assessed by checkerboard assay, and GC-MS profiling. Disc diffusion produced no interpretable zones of inhibition for any plant preparation tested; however, broth microdilution revealed reproducible inhibitory activity within published ranges across the panel. Three essential oils achieved a median Minimum Inhibitory Concentration (MIC) of 0.39 mg/mL against MRSA despite presenting compositionally distinct chemotypes: lavender was linalool-dominated (61% combined), lemongrass was citral-dominated (76%), and the doTERRA blend was sesquiterpene-rich. Rosemary ethanolic extract achieved the same potency (0.39 mg/mL) against MSSA. No preparation produced a bactericidal reduction (>=3 log10 CFU/mL) at any timepoint, with all reductions transient and recovering by 24 hours. Checkerboard combinations of plant preparations with vancomycin and ciprofloxacin were uniformly classified, according to the Fractional Inhibitory Concentration Index (FICI), as indifference/no interaction, attributable in part to inoculum-mediated effects on vancomycin MIC. To analyse the relationship between chemical composition and antimicrobial outcomes, we introduce a Chemotype Similarity Index (CSI), a chemometric framework quantifying pairwise compositional similarity between essential oils by Pearson correlation and relating it to log2-MIC differences across strains. CSI revealed a strain-dependent chemistry-activity relationship, convergent against MRSA, monotonic against MSSA, and absent against E. coli, indicating that compositional similarity predicts antimicrobial outcomes on a strain-specific basis. The convergence of three chemotypically divergent essential oils with the same anti-MRSA potency suggested a shared membrane-disrupting mechanism operating through distinct chemical routes. Although exploratory at this scale, the CSI framework provides a reusable analytical scaffold for linking phytochemical composition to antimicrobial activity, and identifies the MRSA convergence as a specific direction for mechanistic investigation into the development of plant-derived antimicrobial adjuncts.

Background Severe Clostridioides difficile infection (CDI) morbidity and mortality disproportionately affect Black and Hispanic patients in the United States. Antibiotic exposure is the primary modifiable risk factor for CDI, and clindamycin is among the agents most strongly associated with related harm. Characterizing inequities in prescribing is critical. Dentistry is a major source of clindamycin prescriptions. Academic dental clinics serve diverse patient populations and provide an ideal setting to evaluate prescribing across racial and ethnic groups. We therefore examined antibiotic use and cumulative clindamycin exposure as measures of CDI-associated risk. Methods We conducted a retrospective study of electronic health records from 5 US academic dental institutions from 2021 through 2023. We analyzed 552,428 encounters among 132,770 patients with documented race/ethnicity to estimate adjusted odds of receiving any oral antibiotic and clindamycin by race/ethnicity. Secondary outcomes evaluated total antibiotic exposure among dental provider-prescribed antibiotics, focusing on higher-than-standard cumulative dosing of clindamycin (>8400 mg) and amoxicillin (>10,500 mg). Results Oral antibiotic prescribing occurred in 1.9% of encounters. Compared with White patients, Black, Hispanic, and Other race patients had slightly lower adjusted odds of receiving any oral antibiotic, while Black patients had greater odds of receiving a higher-than-standard cumulative clindamycin dose when clindamycin was prescribed (adjusted odds ratio, 2.19; 95% confidence interval, 1.25-3.82). Conclusion Racial and ethnic inequities in dental antibiotic prescribing extended beyond antibiotic receipt to cumulative clindamycin exposure. Although CDI outcomes were not directly measured, these prescribing differences may have implications for disparities in CDI-associated harm and warrant further investigation.

Background: Phenotypic antibiotic susceptibility testing (AST) for Helicobacter pylori (H. pylori) has relied on bacterial culture for three decades, requiring 5-7 days to yield results. Genotypic rapid tests can only detect known resistance mutations and fail to reliably identify amoxicillin resistance. To our knowledge, no culture-free rapid phenotypic AST method for H. pylori has been previously reported. Methods: We developed a phenotypic AST method based on fluorescence rapid on-site evaluation (ROSE) technology that completely bypasses bacterial culture. Gastric mucosal biopsy specimens from 40 H. pylori-positive patients were homogenized and co-incubated with an acridine orange/ethidium bromide (AO/EB)-based viability staining reagent and three first-line antibiotics (amoxicillin, clarithromycin, and levofloxacin) at concentrations corresponding to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for H. pylori, at 37C for 1 hour. Fluorescence intensity was measured using a microplate reader. A reduction in fluorescence relative to an antibiotic-free control indicated susceptibility, whereas no significant reduction indicated resistance. Conventional culture-based AST (E-test) served as the reference method. The overall concordance rate, sensitivity, specificity, and Cohen's kappa coefficient were calculated. Results: Fourteen of the 40 samples had unsuccessful culture and were excluded, leaving 26 samples for statistical analysis of each antibiotic. The overall concordance rates between the ROSE method and culture-based AST were 84.6% (22/26) for amoxicillin, 76.9% (20/26) for levofloxacin, and 69.2% (18/26) for clarithromycin. Cohen's kappa coefficients indicated moderate agreement for all three antibiotics ({kappa} = 0.523, 0.539, and 0.412, respectively). Unlike genotypic methods, the ROSE method successfully assessed amoxicillin susceptibility in all 40 patients, a critical first-line antibiotic for which no reliable genetic resistance marker currently exists. The turnaround time was approximately 1 hour (55-65 minutes), compared with 5-7 days for culture-based methods; preliminary estimates indicated a cost reduction of approximately 3,000-5,000 Chinese yuan (CNY) per patient, mainly attributable to the elimination of culture media, prolonged incubation, and repeat clinic visits. Conclusions: This study reports, for the first time, a culture-free 1-hour phenotypic AST for H. pylori. The method enables same-day, susceptibility-guided treatment decisions, addressing an unmet clinical need spanning three decades. Algorithm optimization and a prospective randomized controlled trial are currently underway to further improve diagnostic accuracy and validate clinical utility.