To our knowledge, this is the first study to report plasma concentrations over time and urinary recovery of polymyxin B in critically ill patients after intravenous administration. Polymyxin B is eliminated mainly by nonrenal pathways, and the total body clearance appears to be relatively insensitive to renal function. Additional investigations are required to assess the appropriateness of currently recommended doses of this drug for the treatment of severe infections in critically ill persons.

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NDM-1-producing Enterobacteriaceae have emerged rapidly in the hospitals of the Brazilian city where they were first detected. The emergence of NDM-1 in Brazil is of great concern, since it is a severe threat to antimicrobial therapy against Enterobacteriaceae in this country.

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One hundred and twenty-four Pseudomonas aeruginosa isolates were selected for antimicrobial susceptibility testing with anti-pseudomonal agents, MIC determination for polymyxin B and metallobeta-lactamase detection (genes bla SPM , bla VIM-1 , bla NDM-1 and bla IMP ). According to the imipenem and/or meropenem susceptibility profile, a set of randomly selected isolates (12 isolates carbapenem-susceptible and 12 isolates carbapenem-resistant) were evaluated for heteroresistance to polymyxin B. Heteroresistance testing was performed by plating the isolates onto increasing concentrations of polymyxin B (from 0 to 8.0 mg l -1). The population analysis profile (PAP) was defined as the ratio of the number of colony-forming units on the plate with the highest concentration of polymyxin B at which bacterial growth occurred against the number of colonyforming units on the plate without antibiotic. Isolates presenting subpopulations that exhibited growth at polymyxin B concentrations ¢2 mg l -1 were considered heteroresistant. Isolates containing subpopulations that grew at polymyxin B concentrations at least twice as high as the original MIC but ,2 mg l -1 were considered heterogeneous. Antimicrobial susceptibility testing results indicated a variable degree of susceptibility: high levels of resistance to gentamicin (30.6 %) and imipenem (29.0 %); low levels of resistance to aztreonam (1.6 %) and ciprofloxacin (4.8 %). All isolates were susceptible to polymyxin B: MIC 50 and MIC 90 were 1 mg l -1 and 2 mg l -1 , respectively. Thirty-seven isolates (30 %) were carbapenem-resistant. Four isolates resistant to carbapenems were positive for bla IMP . There were no heteroresistant subpopulations in the carbapenem-susceptible group, but three isolates presented heterogeneous subpopulations. The PAP frequency ranged from 2.1¾10 . In the carbapenem-resistant group, one isolate was heteroresistant. Six isolates in this group presented heterogeneous subpopulations. In the resistant population, the PAP frequency ranged from 2.1¾10 "7 to 2.6¾10 . In this study, polymyxin B heteroresistance in P. aeruginosa was uncommon and occurred in only one carbapenem-resistant isolate, despite the fact that several isolates presented heterogeneous subpopulations with increased polymyxin B MICs.