Tetracyclines, Glycylcyclines, and Chloramphenicol

Moffa, Matthew; Brook, Itzhak

doi:10.1016/b978-1-4557-4801-3.00026-6

Cited by 19 publications

(8 citation statements)

References 397 publications

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“…As seen in the previously published transcriptomic data, 22 CHL inhibits peptidyl transferase activity, 32 resulting in increased ribosomal subunit protein gene expression by the bacteria. CHL also reduces guanosine tetraphosphate (ppGpp), a metabolite that controls the stringent response which alters the gene expression for growth and results in alteration/upregulation of genes supporting prolonged survival in the stationary phase.…”

Section: Resultssupporting

confidence: 58%

“…Additionally, its four times daily dosing schedule is inconvenient and the PD activity is largely bacteriostatic. 32 However, our omics-informed MBM helped us understand the underlying mechanisms by which the CHL probe-drug increases PMB efficacy so that we may identify CHL analogs that illicit a similar synergistic effect. Furthermore, this work provides a proof-ofconcept approach to identify novel antibiotic combination treatments that increase PMB efficacy using currently approved compounds or compounds in clinical development.…”

Section: Discussionmentioning

confidence: 99%

“…[27][28][29][30][31] The therapeutic range for CHL is peak serum concentrations between 10 and 20 mg/L with toxicity reported at trough serum concentrations above 25 mg/L for doses ranging from 50 to 100 mg/kg/day. 28,31,32 The average steady-state plasma concentration of PMB is reported as ~2.79 mg/L for doses ranging from 0.45 to 3.38 mg/kg/day. 30 Protein binding for CHL and PMB are ∼60% and ∼58%, respectively.…”

Section: Modeling Time-kill Datamentioning

confidence: 99%

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Proof‐of‐concept for incorporating mechanistic insights from multi‐omics analyses of polymyxin B in combination with chloramphenicol against Klebsiella pneumoniae

Hanafin

Rahim

Sharma

et al. 2023

CPT Pharmacom & Syst Pharma

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Carbapenemase‐resistant Klebsiella pneumoniae (KP) resistant to multiple antibiotic classes necessitates optimized combination therapy. Our objective is to build a workflow leveraging omics and bacterial count data to identify antibiotic mechanisms that can be used to design and optimize combination regimens. For pharmacodynamic (PD) analysis, previously published static time‐kill studies (J Antimicrob Chemother 70, 2015, 2589) were used with polymyxin B (PMB) and chloramphenicol (CHL) mono and combination therapy against three KP clinical isolates over 24 h. A mechanism‐based model (MBM) was developed using time‐kill data in S‐ADAPT describing PMB‐CHL PD activity against each isolate. Previously published results of PMB (1 mg/L continuous infusion) and CHL (Cmax: 8 mg/L; bolus q6h) mono and combination regimens were evaluated using an in vitro one‐compartment dynamic infection model against a KP clinical isolate (108 CFU/ml inoculum) over 24 h to obtain bacterial samples for multi‐omics analyses. The differentially expressed genes and metabolites in these bacterial samples served as input to develop a partial least squares regression (PLSR) in R that links PD responses with the multi‐omics responses via a multi‐omics pathway analysis. PMB efficacy was increased when combined with CHL, and the MBM described the observed PD well for all strains. The PLSR consisted of 29 omics inputs and predicted MBM PD response (R2 = 0.946). Our analysis found that CHL downregulated metabolites and genes pertinent to lipid A, hence limiting the emergence of PMB resistance. Our workflow linked insights from analysis of multi‐omics data with MBM to identify biological mechanisms explaining observed PD activity in combination therapy.

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Section: Resultssupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Modeling Time-kill Datamentioning

confidence: 99%

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Proof‐of‐concept for incorporating mechanistic insights from multi‐omics analyses of polymyxin B in combination with chloramphenicol against Klebsiella pneumoniae

Hanafin

Rahim

Sharma

et al. 2023

CPT Pharmacom & Syst Pharma

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“…and Moraxella catarrhalis . 17 The effectiveness of metronidazole and levofloxacin against these organisms made them the right drug of choice for treating nosocomial infections, as observed in our study. However, levofloxacin has been classified by WHO under the Watch group, which means although it is included in the essential drugs list, it should be reserved for strictly MDR organisms.…”

Section: Discussionsupporting

confidence: 61%

Antibiotic utilization study in a teaching hospital in Nigeria

Sekoni

Oreagba

Oladoja

2022

JAC-Antimicrobial Resistance

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Background Antibiotics have been the bedrock of modern medical care, particularly bacterial infections. However, globally, antimicrobial resistance has become a well-recognized public health threat in recent years, and interventions to reduce its burden have been launched worldwide. Objectives The present study evaluated antibiotic utilization in both hospitalized patients and outpatients in a University Hospital in Nigeria. Methods In a 3 year retrospective study between January 2017 and December 2019, 246 case files of patients were selected for the study based on inclusion and exclusion criteria. In addition, the antibiotic consumption rate for hospitalized and outpatients was determined. Results The total antibiotic consumption for hospitalized patients in this study was 260.9 DDD/100 bed-days, while the outpatient department’s patients were 72.3 DDD/1000 inhabitants per day. Peptic ulcer disease was the most frequent indication for antibiotic use for outpatients, with the fluoroquinolones and macrolides being the most prescribed antibiotic class and antibiotic class with the highest DDD, respectively. The most frequent indication for antibiotic use for hospitalized patients was chronic kidney diseases, with the fluoroquinolones and second-generation cephalosporins being the most prescribed antibiotic class and antibiotic class with the highest DDD, respectively. DDD per 100 bed-days and DDD per 1000 patient-days were highest in 2018. The P values for the years were 0.019, 0.195 and 0.001 for 2017, 2018 and 2019, respectively. Conclusions Our findings revealed irrationality in antibiotic use. Therefore, antimicrobial stewardship programmes should be implemented.

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“…The tetracycline antibiotics (tetracycline, doxycycline, minocycline) are alternative agents for the outpatient management of SSTIs. These agents also interfere with bacterial protein synthesis and are bacteriostatic; they are typically reserved as alternative treatment options for MRSA SSTIs and are not used in invasive infections (Liu et al, 2011;Moffa & Brook, 2015). Important adverse effects include photosensitivity and esophagitis, and these agents should be avoided for treating MRSA infections in patients younger than 8 years because they cause irreversible tooth discoloration when used during tooth development, although this is more common with long-term therapy and does not preclude use for rickettsial infections (Lexi-Comp, 2015;Todd et al, 2015).…”

Section: Adjunctive and Alternative Antibioticsmentioning

confidence: 99%