Dynamic interactions of biofilms of mucoid Pseudomonas aeruginosa with tobramycin and piperacillin

Abstract

The dynamic interaction of planktonic and biofilm cells of mucoid Pseudononas aeruginosa with tobramycin and piperacillin was investigated in a chemostat system. The results indicated that planktonic and young biofilm cells of the 2-day-old chemostat culture of P. aeruginosa were susceptible to killing by chemostatcontrolled doses of either 250 ,ug of piperacillin per ml plus 5 ,ug of tobramycin per ml or 500 ,ug of piperacillin per ml plus 5 jig of tobramycin per ml. Complete eradication of the planktonic and young biofilm cells was observed after exposure of the cells to six chemostat-controlled doses of these antibiotics at 8-h intervals for 7 days. Regrowth of the organism was not observed after the termination of antibiotic therapy on day 7. A different picture was observed when antibiotic treatment was initiated on day 10 after inoculation. Viable old biofilm cells were reduced to approximately 20%o after exposure to the chemostat-controlled doses of500 jLg ofpiperacillin per ml plus 5 jig of tobramycin per ml. Complete eradication of old biofilm cells could not be achieved, and regrowth of the organism occurred after the termination of antibiotic therapy. These data suggest that young biofilm cells of mucoid P. aeruginosa can be effectively eradicated with the combination of piperacillin and tobramycin, while old biofilm cells are very resistant to these antibiotics and eradication of old biofilm cells is not achievable with the chemostat-controlled doses of piperacillin and tobramycin used in this study.

Alginate Overproduction AffectsPseudomonas aeruginosaBiofilm Structure and Function

“…However, the effect of alginate overproduction on P. aeruginosa biofilm formation remains undetermined. Some reports have suggested that mucoid P. aeruginosa biofilms are more resistant to antibiotics than nonmucoid biofilms (2,35). However, these studies were limited in that the strains used for comparison were not isogenic derivatives.…”

Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent

“…Once established, the chronic P. aeruginosa lung infection tolerates the highest deliverable doses of antibiotics (Anwar et al, 1992) and cannot be eradicated (Koch & Hoiby, 1993). The inflammatory response to the chronic infection is mainly characterized by the constant influx of polymorphonuclear leukocytes (PMNs), which surround the bacteria (Baltimore et al, 1989).…”

Antimicrobial Tolerance of Pseudomonas aeruginosa Biofilms Is Activated during an Early Developmental Stage and Requires the Two-Component Hybrid SagS

“…More recent evidence suggests a contribution of the biofilm physiology to tolerance, as biofilm bacteria are physiologically distinct from planktonic bacteria, expressing specific protective factors, such as multidrug (MDR) efflux pumps and stress response regulons (6,7,9,10,13,(22)(23)(24)(25). Moreover, bacteria within microbial communities were found to employ a specific regulatory mechanism to resist the action of antimicrobial agents.…”

“…This enhanced tolerance is thought to be multifactorial, requiring a combination of different mechanisms, and is distinct from mechanisms more commonly associated with planktonic cells, such as acquisition of resistance through random mutation or uptake of plasmid-borne resistance markers (6)(7)(8)(9)(10)(11). Mechanisms contributing to high antimicrobial tolerance in biofilms are thought to include reduced metabolic and growth rates (12)(13)(14), the presence of dormant persister cells that are not killed by exposure to antibiotics (15), restricted diffusion of certain types of antimicrobial agents (11,16,17), starvation-induced growth arrest (18), and the maturity or developmental stage of the biofilm (13,19). The notion of multifactorial mechanisms contributing to biofilm tolerance is supported by several observations.…”