Subinhibitory Levels Of Antibiotics Research Articles

Dose-Dependent Effects of Common Antibiotics Used to Treat Staphylococcus aureus on Biofilm Formation

Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), represent serious nosocomial and community infections. Biofilm formation as an important virulence factor may be affected by sub-inhibitory levels of antibiotics. Few studies examined the effects of all therapeutic antimicrobial agents on clinical S.aureus. The current study aimed at observing the inducing and reducing effects of antibiotics, commonly used to treat staphylococcal infections on the production of staphylococcal biofilm. Four MRSA (1ATCC and 3 clinical) and 1 methicillin-susceptible Staphylococcus aureus (MSSA) strains with biofilm forming ability, evaluated by the Congo red agar (CRA) plate test, were employed. Biofilm formation was measured by crystal violet microtiter plate assay. Cefazolin, rifampicin, vancomycin, oxacillin, clindamycin, cotrimoxazole, minocycline, linezolid, azithromycin, and clarithromycin were added to wells ranging from 0.06to 128 µg/mL (1× to 1/1024 MIC dependent on the MIC value of each strain). The current study showed that azithromycin and vancomycin had a significant inducing effect on biofilm formation. In contrast, linezolid, cefazolin, and clarithromycin, and in the second place, clindamycin and minocycline could inhibit the level of biofilm production in the sub-minimal inhibitory concentrations. The findings demonstrated that the biofilm formation as an important virulence factor may be affected by the subinhibitory levels of antibiotics.

A Microbiological Assay for Assessing the Applicability of Advanced Oxidation Processes for Eliminating the Sublethal Effects of Antibiotics on Selection of Resistant Bacteria

Subinhibitory levels of antibiotics in reservoirs highly affected by anthropogenic activity, e.g., wastewater treatment plants, have a profound impact on the development and spread of resistant bacteria in the biosphere. As an aid, advanced oxidation processes (AOPs) have been suggested to eliminate the antibacterial activity of several antibiotics, and this activity has been followed using conventional antibiotic susceptibility tests. While the antibacterial activity can hardly be monitored below the minimum inhibitory concentration (MIC) with these assays, the selective pressure on a bacterial population might remain in this concentration range. To assess the applicability of an AOP for eliminating the subinhibitory effects of antibiotics on selection of resistant bacteria, a microbiological assay is introduced. The test is based on the dynamics of a mixed bacterial population in response to the presence of antibiotics in a concentration range well below the MIC in a synthetic wastewater matrix. Sensiti...

The Dilemma of Antimicrobial Treatment of Shiga Toxin-producing Escherichia coli

The Dilemma of Antimicrobial Treatment of Shiga Toxin-producing Escherichia coli

Different Classes of Antibiotics Differentially Influence Shiga Toxin Production

Shiga toxin (Stx) in Escherichia coli O157:H7 is encoded as a late gene product by temperate bacteriophage integrated into the chromosome. Phage late genes, including stx, are silent in the lysogenic state. However, stress signals, including some induced by antibiotics, trigger the phage to enter the lytic cycle, and phage replication and Stx production occur concurrently. In addition to the Stx produced by O157:H7, phage produced by O157:H7 can infect harmless intestinal E. coli and recruit them to produce Shiga toxin. To understand how antibiotics influence Stx production, Stx lysogens were treated with different classes of antibiotics in the presence or absence of phage-sensitive E. coli, and Stx-mediated inhibition of protein synthesis was monitored using luciferase-expressing Vero cells. Growth-inhibitory levels of antibiotics suppressed Stx production. Subinhibitory levels of antibiotics that target DNA synthesis, including ciprofloxacin (CIP) and trimethoprim-sulfamethoxazole, increased Stx production, while antibiotics that target the cell wall, transcription, or translation did not. More Stx was produced when E. coli O157:H7 was incubated in the presence of phage-sensitive E. coli than when grown as a pure culture. Remarkably, very high levels of Stx were detected even when growth of O157:H7 was completely suppressed by CIP. In contrast, azithromycin significantly reduced Stx levels even when O157:H7 viability remained high.

Indirect Evidence of Transposon-Mediated Selection of Antibiotic Resistance Genes in Aquatic Systems at Low-Level Oxytetracycline Exposures

Subinhibitory levels of antibiotics can promote the development of antibiotic resistance in bacteria. However, it is unclear whether antibiotic concentrations released into aquatic systems exert adequate pressure to select populations with resistance traits. To examine this issue, 15 mesocosms containing pristine surface water were treated with oxytetracycline (OTC) for 56 days at five levels (0, 5, 20, 50, and 250 microg L(-1)), and six tetracycline-resistance genes (tet(B), tet(L), tet(M), ted(O), tet(Q), and tet(W)), the sum of those genes (tet(R)), "total" 16S-rRNA genes, and transposons (Tn916 and Tn 1545) were monitored using real-time PCR. Absolute water-column resistance-gene abundances did not change at any OTC exposure. However, an increase was observed in the ratio of tet(R) to 16S-rRNA genes in the 250 microg L(-1) OTC units, and an increase in the selection rate of Tc(r) genes (relative to 16S-rRNA genes) was seen when OTC levels were at 20 microg L(-1). Furthermore, tet(M) and Tn916/1545 gene abundances correlated among all treatments (r2 = 0.701, p = 0.05), and there were similar selection patterns of tetR and Tn916/1545 genes relative to the OTC level, suggesting a possible mechanism for retention of specific resistance genes within the systems.

Increased phagocytosis and killing of Escherichia coli treated with subinhibitory concentrations of cefamandole and gentamicin in isolated rat livers.

Our purpose was to study whether treatment of Escherichia coli with subinhibitory concentrations of either cefamandole or gentamicin could change bacterial susceptibility to the serum bactericidal effect and to the phagocytic and killing activity of the rat liver reticuloendothelial system. Bacteria were grown overnight with 1/5 or 1/10 of the MIC of each antibiotic. At one-fifth of the MIC, cefamandole induced filamentous elongated bacteria whose viability was decreased by 75%. The susceptibility of control and antibiotic-treated bacteria to serum was tested by measuring the survival of organisms exposed to different concentrations of rat serum in vitro. Susceptibility of bacteria to hepatic macrophage activity was tested by following the hepatic clearance of bacteria after they were added to the perfusate of the isolated rat liver. E. coli treated with subinhibitory concentrations of cefamandole or gentamicin appeared somewhat more resistant to the lytic activity of serum at a concentration of 4%, but not at 20%. Bacteria treated with 1/5 or 1/10 of the MIC of cefamandole or with 1/5 of the MIC of gentamicin were significantly more susceptible to phagocytosis and to the bactericidal activity of liver macrophages. Cefamandole appeared more potent than gentamicin in inducing these effects. The results suggest that subinhibitory levels of antibiotics may alter bacterial cell surface (cefamandole) or may impair the expression of antiphagocytic material (gentamicin), thus favoring phagocytosis and killing by macrophages. Our study provides evidence that antibiotics at subinhibitory concentrations may cooperate with host defence mechanisms against bacterial infections.

Sub-inhibitory levels of antibiotics

Sub-inhibitory levels of antibiotics