Related Experiment Video

Updated: Aug 18, 2026

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
11:56

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection

Published on: October 25, 2013

Resistance to nalidixic acid. A misconception due to underdosage

T A Stamey, J Bragonje

    JAMA
    |October 18, 1976
    PubMed

    Insights

    Full-dose nalidixic acid (4 gm/day) effectively treats infections, with low resistance development in patients and minimal fecal resistance. Underdosing is the likely cause of observed resistance to this antibiotic.

    Area of Science:

    • Pharmacology
    • Microbiology
    • Infectious Diseases

    Background:

    • Nalidixic acid is an antibiotic used for urinary tract infections.
    • Concerns exist regarding the development of resistance to nalidixic acid.
    • Understanding resistance mechanisms is crucial for effective antibiotic use.

    Purpose of the Study:

    • To evaluate the clinical development of resistance to nalidixic acid.
    • To compare resistance development with nalidixic acid to other antibiotics.
    • To identify factors contributing to nalidixic acid resistance.

    Main Methods:

    • Clinical treatment of 27 patients with 4 gm/day of nalidixic acid.
    • Monitoring resistance in bacteriuric populations.
    • Assessing fecal reservoir resistance.
    • In vitro studies on 100 Enterobacteriaceae strains at varying concentrations and inoculum sizes.

    Main Results:

    • Only 7% of patients developed resistance when treated with 4 gm/day.
    • Fecal resistance was minimal compared to sulfonamides, tetracyclines, and ampicillin.
    • Resistance development in vitro was inversely proportional to nalidixic acid concentration.
    • Extrachromosomal R-factor resistance to nalidixic acid was not observed.

    Conclusions:

    • Full dosage (4 gm/day) of nalidixic acid is effective in preventing resistance.
    • Underdosing is the probable cause of excessive nalidixic acid resistance.
    • Nalidixic acid remains a viable option, especially for multiply-resistant Enterobacteriaceae.

    More Related Videos

    A Reference Broth Microdilution Method for Dalbavancin In Vitro Susceptibility Testing of Bacteria that Grow Aerobically11:28

    A Reference Broth Microdilution Method for Dalbavancin In Vitro Susceptibility Testing of Bacteria that Grow Aerobically

    Published on: September 9, 2015

    Measuring Microbial Mutation Rates with the Fluctuation Assay07:44

    Measuring Microbial Mutation Rates with the Fluctuation Assay

    Published on: November 28, 2019

    Related Concept Videos

    Antibiotic Selection00:57

    Antibiotic Selection

    Overview
    Drug Toxicity: Dose-Dependent Reactions01:24

    Drug Toxicity: Dose-Dependent Reactions

    Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
    Drug toxicity: Idiosyncratic Reactions01:16

    Drug toxicity: Idiosyncratic Reactions

    Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
    Development of Antibiotic Resistance01:30

    Development of Antibiotic Resistance

    Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
    Inhibitors of Bacterial Protein Synthesis01:25

    Inhibitors of Bacterial Protein Synthesis

    Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
    Inhibitors of Bacterial DNA Synthesis01:28

    Inhibitors of Bacterial DNA Synthesis

    Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...