Browsing by Subject "Metronidazole"

Now showing 1 - 4 of 4
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    Association of Chlamydia trachomatis burden with the vaginal microbiota, bacterial vaginosis, and metronidazole treatment
    (Frontiers Media, 2023-12-12) Ardizzone, Caleb M.; Taylor, Christopher M.; Toh, Evelyn; Lillis, Rebecca A.; Elnaggar, Jacob H.; Lammons, John W.; Dehon Mott, Patricia; Duffy, Emily L.; Shen, Li; Quayle, Alison J.; Microbiology and Immunology, School of Medicine
    Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming units (IFU) and Ct genome copy number (GCN), and 16S rRNA gene sequencing was used to determine the composition of the vaginal microbiota. We observed a six-log spectrum of IFU and an eight-log spectrum of GCN in our study participants at their enrollment visit, but BV, as indicated by Amsel’s criteria, Nugent scoring, or VALENCIA community state typing, did not predict infectious and total Ct burden, although IFU : GCN increased with Amsel and Nugent scores and in BV-like community state types. Ct burden was, however, associated with the abundance of bacterial species in the vaginal microbiota, negatively with Lactobacillus crispatus and positively with Prevotella bivia. Women diagnosed with BV were treated with metronidazole, and Ct burden was significantly reduced in those who resolved BV with treatment. A subset of women naturally cleared Ct infection in the interim, typified by low Ct burden at enrollment and resolution of BV. Abundance of many BVAB decreased, and Lactobacillus increased, in response to metronidazole treatment, but no changes in abundances of specific vaginal bacteria were unique to women who spontaneously cleared Ct infection.
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    Biodegradable nanofibrous drug delivery systems: effects of metronidazole and ciprofloxacin on periodontopathogens and commensal oral bacteria
    (Springer-Verlag, 2014-12) Bottino, Marco C.; Arthur, Rodrigo A.; Waeiss, R. Aaron; Kamocki, Krzysztof; Gregson, Karen S.; Gregory, Richard L.; Department of Restorative Dentistry, IU School of Dentistry
    OBJECTIVES: The purposes of this study were to fabricate biodegradable polydioxanone (PDS II®) electrospun periodontal drug delivery systems (hereafter referred to as matrices) containing either metronidazole (MET) or ciprofloxacin (CIP) and to investigate the effects of antibiotic incorporation on both periodontopathogens and commensal oral bacteria. MATERIALS AND METHODS: Fibrous matrices were processed from PDS polymer solution by electrospinning. Antibiotic-containing PDS solutions were prepared to obtain four distinct groups: 5 wt.% MET, 25 wt.% MET, 5 wt.% CIP, and 25 wt.% CIP. Pure PDS was used as a control. High-performance liquid chromatography (HPLC) was done to evaluate MET and CIP release. Dual-species biofilms formed by Lactobacillus casei (Lc) and Streptococcus salivarius (Ss) were grown on the surface of all electrospun matrices. After 4 days of biofilm growth, the viability of bacteria on biofilms was assessed. Additionally, antimicrobial properties were evaluated against periodontopathogens Fusobacterium nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa) using agar diffusion assay. RESULTS: A three-dimensional interconnected porous network was observed in the different fabricated matrices. Pure PDS showed the highest fiber diameter mean (1,158 ± 402 nm) followed in a descending order by groups 5 wt.% MET (1,108 ± 383 nm), 25 wt.% MET (944 ± 392 nm), 5 wt.% CIP (871 ± 309 nm), and 25 wt.% CIP (765 ± 288 nm). HPLC demonstrated that groups containing higher amounts (25 wt.%) of incorporated drugs released more over time, while those with lower levels (5 wt.%) the least. No inhibitory effect of the tested antibiotics was detected on biofilm formation by the tested commensal oral bacteria. Meanwhile, CIP-containing matrices inhibited growth of Fn and Aa. CONCLUSION: CIP-containing matrices led to a significant inhibition of periodontopathogens without negatively impairing the growth of periodontal beneficial bacteria. CLINICAL RELEVANCE: Based on the proven in vitro inhibition of periodontitis-related bacteria, future in vivo research using relevant animal models is needed to confirm the effectiveness of these drug delivery systems.
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    Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole
    (American Society for Microbiology, 2024) Randell, Rachel L.; Balevic, Stephen J.; Greenberg, Rachel G.; Cohen-Wolkowiez, Michael; Thompson, Elizabeth J.; Venkatachalam, Saranya; Smith, Michael J.; Bendel, Catherine; Bliss, Joseph M.; Chaaban, Hala; Chhabra, Rakesh; Dammann, Christiane E. L.; Downey, L. Corbin; Hornik, Chi; Hussain, Naveed; Laughon, Matthew M.; Lavery, Adrian; Moya, Fernando; Saxonhouse, Matthew; Sokol, Gregory M.; Trembath, Andrea; Weitkamp, Joern-Hendrik; Hornik, Christoph P.; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee; Pediatrics, School of Medicine
    Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN_METRO, NCT01222585) study. First, we used linear correlation to compare 42 paired DBS and plasma metronidazole concentrations from 21 preterm infants [mean (SD): post natal age 28.0 (21.7) days, GA 26.3 (2.4) weeks]. Using the resulting predictive equation, we estimated plasma metronidazole concentrations (ePlasma) from 399 DBS collected from 122 preterm and term infants [mean (SD): post natal age 16.7 (15.8) days, GA 31.4 (5.1) weeks] from the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP, NCT01994993) trial. When evaluating the PTN_METRO model using ePlasma from the SCAMP trial, we found that the model generally predicted ePlasma well in preterm infants with GA ≤31 weeks. When including ePlasma from term and preterm infants with GA >31 weeks, the model was optimized using a sigmoidal Emax maturation function of postmenstrual age on clearance and estimated the exponent of weight on volume of distribution. The optimized model supports existing dosing guidelines and adds new data to support a 6-hour dosing interval for infants with postmenstrual age >40 weeks. Using an opportunistic DBS to externally validate and optimize a metronidazole population pharmacokinetic model was feasible and useful in this vulnerable population.
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    Risk of antibiotics associated with Clostridioides difficile infection: Antibiotic stewardship in action
    (Cambridge University Press, 2022-08-26) Dysangco, Andrew T.; Pierce, Tamra M.; Bravata, Dawn M.; Medicine, School of Medicine
    We examined risk associated with antibiotics used for Clostridioides difficile infection (CDI) at a single site from 2018 through 2020. Overall, 78 patients had nonrecurrent infections. Among inpatient antibiotics, intravenous meropenem had the highest CDI rate (3.56 per 1,000 days of therapy; n = 2 cases). Among outpatient antibiotics, metronidazole had the highest rate (0.071 per 1,000 pills dispensed; n = 3 cases).