Publications by authors named "Gunavanthi D Boorgula"

Background: Guideline-based therapy (GBT) for Mycobacterium abscessus (Mab) lung disease achieves sputum culture conversion rates (SCC) of 35%. This poor GBT efficacy is mirrored in the hollow fiber system model of Mab (HFS-Mab). While imipenem is part of GBT, biological effect with or without β-lactamase inhibitors, is unproven.

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Background: Drug susceptibility testing (DST) protocol of omadacycline against non-tuberculous mycobacteria has not yet been established. We developed a method to accurately determine MIC omadacycline MIC against Mycobacterium abscessus (Mab), Mycobacterium avium-complex (MAC), and Mycobacterium kansasii (Mkn).

Methods: First, we identified the oxyrase concentration not affecting Mab, MAC, and Mkn growth followed by omadacycline MIC experiments with and without oxyrase using reference and clinical strains.

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Seventy-five years ago, first-generation tetracyclines demonstrated limited efficacy in the treatment of tuberculosis but were more toxic than efficacious. We performed a series of pharmacokinetic/pharmacodynamic (PK/PD) experiments with a potentially safer third-generation tetracycline, omadacycline, for the treatment of multidrug-resistant tuberculosis (MDR-TB). () H37Rv and an MDR-TB clinical strain (16D) were used in the minimum inhibitory concentration (MIC) and static concentration-response studies in test tubes, followed by a PK/PD study using the hollow fiber system model of TB (HFS-TB) that examined six human-like omadacycline doses.

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Background: Only 35.6%-50.8% of patients with Mycobacterium avium complex (MAC) pulmonary disease achieve sustained sputum culture conversion (SSCC) on treatment with the azithromycin-ethambutol-rifabutin standard of care (SOC).

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Background: Poor sustained sputum culture conversion rates with the standard-of-care therapy highlight the need for better drugs to treat Mycobacterium avium complex pulmonary disease (MAC-PD).

Objective: To determine the pharmacokinetics/pharmacodynamics (PK/PD)-optimized exposure of sarecycline and its potential role in treating MAC-PD.

Methods: We performed MIC studies with MAC ATCC 700898 and 19 clinical isolates and test-tube static concentration-response studies.

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Background: Meropenem in combination with β-lactamase inhibitors (BLIs) and other drugs was tested to identify alternative treatment regimens for multidrug-resistant tuberculosis (MDR-TB).

Methods: The following were performed: (1) MIC experiments; (2) static time-kill studies (STKs) with different BLIs; and (3) a hollow fibre model system of TB (HFS-TB) studies with meropenem-vaborbactam combined with human equivalent daily doses of 20 mg/kg or 35 mg/kg rifampin, or moxifloxacin 400 mg, or linezolid 600 mg vs. bedaquiline-pretonamid-linezolid (BPaL) for MDR-TB.

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Background: Guideline-based therapy (GBT) for pulmonary Mycobacterium abscessus (Mab) disease achieves sustained sputum culture conversion (SSCC) rates of 30%; this is reflected by poor efficacy of GBT in the hollow fiber system model of Mab (HFS-Mab), which killed ∼1.22 log CFU/mL. This study was performed to determine which clinical dose of omadacycline, a tetracycline antibiotic, should be used in combination therapy to treat pulmonary Mab disease for relapse-free cure.

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Background: There is limited high quality evidence to guide the optimal doses of drugs for the treatment of Mycobacterium kansasii pulmonary disease (Mkn-PD).

Methods: We performed (1) minimum inhibitory concentration experiment, (2) isoniazid dose-response study using the hollow fiber system model (HFS-Mkn) to determine PK/PD optimized exposure, and (3) another HFS-Mkn study to determine the efficacy of high dose isoniazid (15 mg/kg/day) with standard dose rifampin (10 mg/kg/day) and ethambutol (15 mg/kg/day). Inhibitory sigmoid maximal effect model and linear regression was used for data analysis.

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Background: Minimum inhibitory concentration (MIC) of slow growing mycobacteria (SGM) often do not correlate with the treatment response. Among the challenges is the identification of MIC of drugs that degrade in solution faster than the doubling time of the SGM.

Methods: First, we identified the rate of omadacycline degradation in solution, and its effect on the rapidly growing methicillin resistant Staphylococcus aureus (MRSA).

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The 12-month therapy duration for the treatment of Mycobacterium kansasii pulmonary disease calls for more efficacious drugs for better treatment outcomes and to shorten the therapy duration. We performed (i) omadacycline MIC with M. kansasii ATCC 12478 strain and 21 clinical isolates, (ii) dose-response study in the hollow fiber system model of M.

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There is limited high-quality evidence to guide the optimal treatment of Mycobacterium kansasii pulmonary disease. We retrospectively collected clinical data from 33 patients with M. kansasii pulmonary disease to determine the time-to-sputum culture conversion (SCC) upon treatment with a standard combination regimen consist of isoniazid-rifampin-ethambutol.

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Recent studies have provided strong evidence indicating that lone star tick bites are a cause of AGS (alpha-gal syndrome, also known as red meat allergy RMA) in humans. AGS is characterized by an increase in IgE antibody production against galactose-alpha-1,3-galactose (aGal), which is a common glycan found in mammalian tissue, except in Old World monkeys and humans. The main causative factor of AGS, the lone star tick (), is broadly distributed throughout the east and midwest of the United States and is a vector of a wide range of human and animal pathogens.

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Objectives: The aim of this study was to determine and compare the efficacy of drugs to treat Mycobacterium kansasii (Mkn) pulmonary disease by performing minimum inhibitory concentration (MIC) determination and time-kill studies.

Methods: We determined the MICs to 13 drugs against the Mkn standard laboratory strain ATCC 12478 and 20 clinical isolates and performed time-kill studies with 18 drugs from different classes using the standard laboratory strain of Mkn. The β-lactam antibiotics were tested with or without the combination of the β-lactamase inhibitor avibactam.

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Rifamycins are integral part of the combination regimen for treatment of pulmonary [MAC] infection, but different practitioners prefer different rifamycins. The objective of the study was to compare microbial kill and resistance emergence of rifamycins using principles of pharmacokinetics/pharmacodynamics. First, we identified rifamycin MICs in 20 MAC isolates from patients followed by concentration-response studies in test-tubes.

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Between March 2014 and February 2017, host-seeking ticks were collected during the late spring and summer months seasonally, and as well as continually through all seasons from several sites in a periurban environment in Pittsburg, Kansas, located in the Central Midwestern United States. All three post-emergent life-stages of Amblyomma americanum, and the adults of three other ticks viz. Dermacentor variabilis, A.

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Ticks are important ectoparasites and vectors of numerous human and animal pathogens. Ticks secrete saliva that contains various bioactive materials to evade the host defense system, and often facilitates the pathogen transmission. In addition, the Lone star tick saliva is thought to be the sensitizer in red meat allergy that is characterized by an allergic reaction to glycan moieties carrying terminal galactose-alpha-1,3-galactose (aGal).

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