Objectives: The optimal selection of antibacterials during polymicrobial infections is poorly defined. The objective of the current investigation was to quantify the pharmacodynamics of relevant antimicrobials during co-culture of Pseudomonas aeruginosa with two separate Staphylococcus aureus phenotypes.
Methods: Time-kill experiments were conducted against co-cultures of the P. aeruginosa strain PA01 paired with either the normal phenotype (NP) MRSA isolate COL or the small colony variant phenotype (SCVP) MRSA isolate Ia48. The killing by levofloxacin, gentamicin, clindamycin, vancomycin and polymyxin B was evaluated to investigate drugs with activity against one or both pathogens. A Hill-type function and a mechanism-based model were used to describe bacterial killing.
Results: P. aeruginosa attenuated the activity of clindamycin against NP MRSA, with a reduction in the Emax (maximal killing) from 3.67 (95% CI 2.79-4.56) in monoculture to 1.86 (95% CI 1.35-2.37) during co-culture, whereas a significant protective effect was not observed for other antibacterials. The reduction in NP MRSA killing by clindamycin was described well by a mechanism-based model that generated a maximal killing rate constant of clindamycin against the susceptible NP MRSA subpopulation of 0.267 h-1 in monoculture and 0.0395 h-1 in the presence of P. aeruginosa. During exposure to gentamicin, P. aeruginosa was the dominant organism in co-culture experiments regardless of the drug concentration or S. aureus phenotype; however, the SCVP MRSA was able to dominate the joint population beginning at a levofloxacin concentration of 1.5 mg/L.
Conclusions: The anti-staphylococcal activity of clindamycin was attenuated by the presence of P. aeruginosa.
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