Phenotypic tolerance: the search for beta-lactam antibiotics that kill nongrowing bacteria

PMID: 3529321Jul 1, 1986Paper

Phenotypic tolerance: the search for beta-lactam antibiotics that kill nongrowing bacteria

Reviews of Infectious Diseases

E Tuomanen

Abstract

beta-Lactam antibiotics rapidly kill bacteria during logarithmic growth but fail to kill nongrowing cells. This trait is the most universal example of phenotypic tolerance (the ability of bacteria to evade the bactericidal activity of antibiotics). Both nongrowing and slowly growing bacteria are found very frequently during infection in vivo, and phenotypic tolerance to the bactericidal activity of antibiotics as a consequence of reduced growth rate can be detected in vivo. With the use of an in vitro model system of nongrowing bacteria, a select group of beta-lactam antibiotics has been found that demonstrates a striking and unusual ability to kill nongrowing bacteria despite phenotypic tolerance to conventional beta-lactam antibiotics. These same compounds also effectively kill phenotypically tolerant cells in cerebrospinal fluid and serum. The extension of bactericidal activity to nongrowing and slowly growing bacteria may be a major advance in efforts to improve the chemotherapy for infectious diseases.

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Phenotypic tolerance: the search for beta-lactam antibiotics that kill nongrowing bacteria

Abstract

Citations

Effect of clavulanic acid and/or polymorphonuclear neutrophils on amoxicillin bactericidal activity against Streptococcus pneumoniae

Postantibiotic and bactericidal effect of imipenem against Pseudomonas aeruginosa

Remarks on the screening of antibiotics for antibacterial activity

Degree and stability of tolerance to penicillin in Streptococcus pyogenes

Instrumentation for antimicrobic susceptibility testing: yesterday, today, and tomorrow

M. tuberculosis persistence, latency, and drug tolerance

Biofilms in infectious disease and on medical devices

Biofilms and their role in infections in urology

A novel mechanism of growth phase-dependent tolerance to isoniazid in mycobacteria.

The evolution of contact-dependent inhibition in non-growing populations of Escherichia coli.

Sensitivity of biofilms to antimicrobial agents

Development and qualification of a pharmacodynamic model for the pronounced inoculum effect of ceftazidime against Pseudomonas aeruginosa

Testing of experimental compounds in a relapse model of tuberculosis using granulocyte-macrophage colony-stimulating factor gene-disrupted mice

Pharmacodynamic effects of telavancin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains in the presence of human albumin or serum and in an in vitro kinetic model

Oxacillin, cephalothin, and vancomycin tube macrodilution MBC result reproducibility and equivalence to MIC results for methicillin-susceptible and reputedly tolerant Staphylococcus aureus isolates.

Role of autolysins in the activities of imipenem and CGP 31608, a novel penem, against slowly growing bacteria.

Two bactericidal targets for penicillin in pneumococci: autolysis-dependent and autolysis-independent killing mechanisms.

Influence of growth rate on susceptibility to antimicrobial agents: biofilms, cell cycle, dormancy, and stringent response.

Influence of growth rate on susceptibility to antimicrobial agents: modification of the cell envelope and batch and continuous culture studies.

Influence of growth media on Escherichia coli cell composition and ceftazidime susceptibility.

Increase in susceptibility of Pseudomonas aeruginosa to carbapenem antibiotics in low-amino-acid media.

Bactericidal effects of antibiotics on slowly growing and nongrowing bacteria.

Effect of beta-lactams on peptidoglycan metabolism of Haemophilus influenzae grown in animals.

Comparison of the antibacterial efficacies of ampicillin and ciprofloxacin against experimental infections with Listeria monocytogenes in hydrocortisone-treated mice.

Antimycoplasmal activities of new quinolones, tetracyclines, and macrolides against Mycoplasma pneumoniae.

Establishment of aging biofilms: possible mechanism of bacterial resistance to antimicrobial therapy.

Deregulation of the arginine deiminase (arc) operon in penicillin-tolerant mutants of Streptococcus gordonii.

Efficacies of moxifloxacin, ciprofloxacin, and vancomycin against experimental endocarditis due to methicillin-resistant Staphylococcus aureus expressing various degrees of ciprofloxacin resistance

In vitro activities of moxifloxacin and other fluoroquinolones against Mycoplasma pneumoniae

Persistent bacteremia in rabbit fetuses despite maternal antibiotic therapy in a novel intrauterine-infection model.

Phenotypic tolerance: antibiotic enrichment of noninherited resistance in bacterial populations

Age of inoculum strongly influences persister frequency and can mask effects of mutations implicated in altered persistence.

Protective action of ppGpp in microcin J25-sensitive strains.

The Escherichia coli mqsR and ygiT genes encode a new toxin-antitoxin pair

Contributions of PBP 5 and DD-carboxypeptidase penicillin binding proteins to maintenance of cell shape in Escherichia coli

Peptidoglycan hydrolases of Escherichia coli.

A novel mechanism of programmed cell death in bacteria by toxin-antitoxin systems corrupts peptidoglycan synthesis

A new approach for the discovery of antibiotics by targeting non-multiplying bacteria: a novel topical antibiotic for staphylococcal infections.

Rapid evaluation in whole blood culture of regimens for XDR-TB containing PNU-100480 (sutezolid), TMC207, PA-824, SQ109, and pyrazinamide.

The ToxAvapA toxin-antitoxin locus contributes to the survival of nontypeable Haemophilus influenzae during infection

Antibacterial compounds of Canadian honeys target bacterial cell wall inducing phenotype changes, growth inhibition and cell lysis that resemble action of β-lactam antibiotics

A model of optimal dosing of antibiotic treatment in biofilm

Construction of a penicillin-tolerant laboratory mutant of Staphylococcus aureus

ppGpp accumulation in Pseudomonas aeruginosa and Pseudomonas fluorescens subjected to nutrient limitation and biocide exposure

The intrinsic resistance of Escherichia coli to various antimicrobial agents requires ppGpp and sigma s

Thioridazine in PLGA nanoparticles reduces toxicity and improves rifampicin therapy against mycobacterial infection in zebrafish

Solution structure and biophysical properties of MqsA, a Zn-containing antitoxin from Escherichia coli

Targeting non-multiplying organisms as a way to develop novel antimicrobials

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