Urinary Concentrations and Bactericidal Activity Against Amoxicillin-Nonsusceptible Strains of Escherichia coli with Single-Dose, Oral, Sustained-Release Amoxicillin/Clavulanic Acid: A PhaseI, Open-Label, Noncomparative Clinical Trial in Healthy Volunteers

ABSTRACT The aim of this study was to explore bactericidal activity of total and free serum simulated concentrations after the oral administration of cefditoren (400 mg, twice daily [bid]) versus the oral administration of amoxicillin-clavulanic acid extended release formulation (2,000/125 mg bid) against Haemophilus influenzae. A computerized pharmacodynamic simulation was performed, and colony counts and β-lactamase activity were determined over 48 h. Three strains were used: ampicillin-susceptible, β-lactamase-negative ampicillin-resistant (BLNAR) (also resistant to amoxicillin-clavulanic acid) and β-lactamase-positive amoxicillin-clavulanic acid-resistant (BLPACR) strains, with cefditoren MICs of ≤0.12 μg/ml and amoxicillin-clavulanic acid MICs of 2, 8, and 8 μg/ml, respectively. Against the ampicillin-susceptible and BLNAR strains, bactericidal activity (≥3 log10 reduction) was obtained from 6 h on with either total and free cefditoren or amoxicillin-clavulanic acid. Against the BLPACR strain, free cefditoren showed bactericidal activity from 8 h on. In amoxicillin-clavulanic acid simulations the increase in colony counts from 4 h on occurred in parallel with the increase in β-lactamase activity for the BLPACR strain. Since both BLNAR and BLPACR strains exhibited the same MIC, this was due to the significantly lower (P ≤ 0.012) amoxicillin concentrations from 4 h on in simulations with β-lactamase positive versus negative strains, thus decreasing the time above MIC (T>MIC). From a pharmacodynamic point of view, the theoretical amoxicillin T>MIC against strains with elevated ampicillin/amoxicillin-clavulanic acid MICs should be considered with caution since the presence of β-lactamase inactivates the antibiotic, thus rendering inaccurate theoretical calculations. The experimental bactericidal activity of cefditoren is maintained over the dosing interval regardless of the presence of a mutation in the ftsI gene or β-lactamase production.

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An open label, adaptive, phase 1 trial of high‐dose oral nitazoxanide in healthy volunteers: an antiviral candidate for SARS‐CoV‐2

Clinical Pharmacology & Therapeutics ◽

10.1002/cpt.2463 ◽

2021 ◽

Author(s):

Lauren E Walker ◽

Richard FitzGerald ◽

Geoffrey Saunders ◽

Rebecca Lyon ◽

Michael Fisher ◽

...

Keyword(s):

Healthy Volunteers ◽

Phase 1 ◽

High Dose ◽

Open Label ◽

Phase 1 Trial ◽

Dose Oral

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Bioavailability of Two Single-Dose Oral Formulations of Omeprazole 20 mg: An Open-Label, Randomized Sequence, Two-Period Crossover Comparison in Healthy Mexican Adult Volunteers

Clinical Therapeutics ◽

10.1016/j.clinthera.2008.04.004 ◽

2008 ◽

Vol 30 (4) ◽

pp. 693-699 ◽

Cited By ~ 4

Author(s):

Jorge Luis Poo ◽

Juan Francisco Galán ◽

Alejandra Rosete ◽

Alberto de Lago ◽

Iván Oliva ◽

...

Keyword(s):

Single Dose ◽

Open Label ◽

Oral Formulations ◽

Dose Oral ◽

Adult Volunteers ◽

Crossover Comparison

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Isolation of Extended-Spectrum β-lactamase- (ESBL-) Producing Escherichia coli and Klebsiella pneumoniae from Patients with Community-Onset Urinary Tract Infections in Jimma University Specialized Hospital, Southwest Ethiopia

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2018/4846159 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Mengistu Abayneh ◽

Getnet Tesfaw ◽

Alemseged Abdissa

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Klebsiella Pneumoniae ◽

Clavulanic Acid ◽

Urinary Tract Infections ◽

Southwest Ethiopia ◽

Extended Spectrum ◽

Specialized Hospital ◽

Amoxicillin Clavulanic Acid ◽

Tract Infections

Background. Klebsiella pneumoniae and Escherichia coli are the major extended-spectrum β-lactamase- (ESBL-) producing organisms increasingly isolated as causes of complicated urinary tract infections and remain an important cause of failure of therapy with cephalosporins and have serious infection control consequence. Objective. To assess the prevalence and antibiotics resistance patterns of ESBL-producing Escherichia coli and Klebsiella pneumoniae from community-onset urinary tract infections in Jimma University Specialized hospital, Southwest Ethiopia, 2016. Methodology. A hospital-based cross-sectional study was conducted, and a total of 342 urine samples were cultured on MacConkey agar for the detection of etiologic agents. Double-disk synergy (DDS) methods were used for detection of ESBL-producing strains. A disc of amoxicillin + clavulanic acid (20/10 µg) was placed in the center of the Mueller–Hinton agar plate, and cefotaxime (30 µg) and ceftazidime (30 µg) were placed at a distance of 20 mm (center to center) from the amoxicillin + clavulanic acid disc. Enhanced inhibition zone of any of the cephalosporin discs on the side facing amoxicillin + clavulanic acid was considered as ESBL producer. Results. In the current study, ESBL-producing phenotypes were detected in 23% (n = 17) of urinary isolates, of which Escherichia coli accounts for 76.5% (n = 13) and K. pneumoniae for 23.5% (n = 4). ESBL-producing phenotypes showed high resistance to cefotaxime (100%), ceftriaxone (100%), and ceftazidime (70.6%), while both ESBL-producing and non-ESBL-producing isolates showed low resistance to amikacin (9.5%), and no resistance was seen with imipenem. In the risk factors analysis, previous antibiotic use more than two cycles in the previous year (odds ratio (OR), 6.238; 95% confidence interval (CI), 1.257–30.957; p = 0.025) and recurrent UTI more than two cycles in the last 6 months or more than three cycles in the last year (OR, 7.356; 95% CI, 1.429–37.867; p = 0.017) were found to be significantly associated with the ESBL-producing groups. Conclusion. Extended-spectrum β-lactamases- (ESBL-)producing strain was detected in urinary tract isolates. The occurrence of multidrug resistance to the third-generation cephalosporins, aminoglycosides, fluoroquinolones, trimethoprim-sulfamethoxazole, and tetracyclines is more common among ESBL producers. Thus, detecting and reporting of ESBL-producing organisms have paramount importance in the clinical decision-making.

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Comparison of Repeated Doses of Ivermectin Versus Ivermectin Plus Albendazole for the Treatment of Onchocerciasis: A Randomized, Open-label, Clinical Trial

Clinical Infectious Diseases ◽

10.1093/cid/ciz889 ◽

2019 ◽

Vol 71 (4) ◽

pp. 933-943 ◽

Cited By ~ 2

Author(s):

Linda Batsa Debrah ◽

Ute Klarmann-Schulz ◽

Jubin Osei-Mensah ◽

Bettina Dubben ◽

Kerstin Fischer ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Single Dose ◽

Combination Treatment ◽

Primary Outcome ◽

Onchocerca Volvulus ◽

Open Label ◽

Annual Treatment ◽

Repeated Doses ◽

Better Than

Abstract Background Improved treatment for onchocerciasis is needed to accelerate onchocerciasis elimination in Africa. Aiming to better exploit registered drugs, this study was undertaken to determine whether annual or semiannual treatment with ivermectin (IVM; 200 µg/kg) plus albendazole (ALB; 800 mg single dose) is superior to IVM alone. Methods This trial was performed in Ghana and included 272 participants with microfilariae (MF), who were randomly assigned to 4 treatment arms: (1) IVM annually at 0, 12, and 24 months; (2) IVM semiannually at 0, 6, 12, 18, and 24 months; (3) IVM+ALB annually; or (4) IVM+ALB semiannually. Microfiladermia was determined pretreatment and at 6, 18, and 36 months. The primary outcome was the proportion of fertile and viable female worms in onchocercomata excised at 36 months. Results Posttreatment nodule histology showed that 15/135 (11.1%), 22/155 (14.2%), 35/154 (22.7%), and 20/125 (16.0%) living female worms had normal embryogenesis in the IVM annual, IVM semiannual, IVM+ALB annual, and IVM+ALB semiannual groups, respectively (P = .1229). Proportions of dead worms also did not differ between the 4 groups (P = .9198). Proportions of patients without MF at 36 months (1 year after the last treatment) were 35/56 (63%) after annual IVM, 42/59 (71%) after semiannual IVM, 39/64 (61%) after annual IVM+ALB, and 43/53 (81%) after semiannual IVM+ALB. Conclusions The combination treatment of IVM plus ALB was no better than IVM alone for sterilizing, killing adult worms, or achieving sustained MF clearance. However, semiannual treatment was superior to annual treatment for achieving sustained clearance of Onchocerca volvulus MF from the skin (P = .024). Clinical Trials Registration ISRCTN50035143

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