scholarly journals High potency of sequential therapy with only beta-lactam antibiotics

2021 ◽  
Author(s):  
Aditi Batra ◽  
Roderich Roemhild ◽  
Emilie Rousseau ◽  
Sören Franzenburg ◽  
Stefan Niemann ◽  
...  
Keyword(s):  
Genetic Resistance ◽  
Sequential Therapy ◽  
Cross Resistance ◽  
Beta Lactam ◽  
Bacterial Populations ◽  
Beta Lactam Antibiotics ◽  
Trade Offs ◽  
Evolutionary Response ◽  
Sequential Treatments ◽  
Treatment Designs

Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution- informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β- lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs.

scholarly journals High potency of sequential therapy with only beta-lactam antibiotics

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Aditi Batra ◽  
Roderich Roemhild ◽  
Emilie Rousseau ◽  
Sören Franzenburg ◽  
Stefan Niemann ◽  
...  
Keyword(s):  
Genetic Resistance ◽  
Sequential Therapy ◽  
Cross Resistance ◽  
Beta Lactam ◽  
Bacterial Populations ◽  
Beta Lactam Antibiotics ◽  
Trade Offs ◽  
Evolutionary Response ◽  
Sequential Treatments ◽  
Treatment Designs

Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs.

scholarly journals Detection of carbapenemase production in Enterobacteriaceae and Pseudomonas species by carbapenemase Nordmann–Poirel test

2019 ◽  
Vol 11 (02) ◽  
pp. 107-110 ◽  
Author(s):  
Morubagal R. Rao ◽  
Pooja Chandrashaker ◽  
Rashmi P. Mahale ◽  
Sowmya G. Shivappa ◽  
Ranjitha S. Gowda ◽  
...  
Keyword(s):  
Cost Effective ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Gram Negative Bacteria ◽  
Beta Lactam ◽  
Hospital Acquired Infections ◽  
Beta Lactam Antibiotics ◽  
Pseudomonas Species ◽  
Life Threatening ◽  
Hospital Acquired

Abstract PURPOSE: Multidrug-resistant organisms causing community-acquired and hospital-acquired infections are increasing at a dangerous rate. Carbapenemase-producing Enterobacteriaceae and Pseudomonas species are an important source of concern since these organisms are not only resistant to beta-lactam antibiotics but also show cross-resistance to other groups of antibiotics. In the present study, rapid detection of these carbapenemase-producing Enterobacteriaceae and Pseudomonas species by carbapenemase Nordmann–Poirel (Carba NP) test was evaluated by comparing with modified Hodge test (MHT). MATERIALS AND METHODS: Imipenem-resistant Enterobacteriaceae and Pseudomonas species isolated from various samples such as pus, blood, sputum, urine, and endotracheal aspirates were processed for carbapenemase detection by MHT and Carba NP test. Kappa analysis was done to evaluate the percentage agreement between the two tests. RESULTS: Seventy imipenem-resistant Enterobacteriaceae and Pseudomonas isolates were analyzed in the present study for carbapenemase production. 63.41% ofEnterobacteriaceae and 34.48% of Pseudomonas species were carbapenemase producers considering both the methods. By MHT, 36 (51.42%) isolates and, by Carba NP test, 35 (50%) isolates were positive for carbapenemase production out of the 70 isolates. CONCLUSION: Carba NP test when compared to MHT is a simple, rapid, cost-effective biochemical test which can be used in all laboratories in the identification of life-threatening carbapenemase-producing Gram-negative bacteria.

scholarly journals Prevalence of outer membrane porin alteration in beta-lactam-antibiotic-resistant Enterobacter aerogenes.

1996 ◽  
Vol 40 (12) ◽  
pp. 2854-2858 ◽  
Author(s):  
R N Charrel ◽  
J M Pagès ◽  
P De Micco ◽  
M Mallea
Keyword(s):  
Outer Membrane ◽  
Resistance Mechanism ◽  
Enterobacter Aerogenes ◽  
Cross Resistance ◽  
Resistance Pattern ◽  
Beta Lactam ◽  
Antibiotic Resistant ◽  
Beta Lactam Antibiotics ◽  
Lactam Antibiotic ◽  
Additional Resistance

We evaluated the prevalence of impermeability as a mechanism associated with resistance against beta-lactam antibiotics in members of the family Enterobacteriaceae. During a 1-year period, 80 strains were selected from 3,110 routinely isolated strains according to their noticeable cross-resistance pattern to cephalosporins. They were tested for (i) outer membrane nonspecific porins involved in the entry of small hydrophilic molecules; (ii) the MICs of cefepime, cefotaxime, imipenem, and moxalactam; and (iii) beta-lactamase production. Immunological investigations using specific probes showed that 23 of 80 strains presented an alteration of the porin content, most of them expressing an additional resistance mechanism. The prevalence of this porin-deficient phenotype is especially high in Enterobacter aerogenes and concerns 6.4% of the clinical isolates.

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