Antibiotic pharmacokinetics in infected pleural effusions

Abstract

Pleural infection is usually treated with empirical broad-spectrum antibiotics, but limited data exist on their penetrance into the infected pleural space. We performed a pharmacokinetic study analysing the concentration of five intravenous antibiotics across 146 separate time points in 35 patients (amoxicillin, metronidazole, piperacillin-tazobactam, clindamycin and cotrimoxazole). All antibiotics tested, apart from co-trimoxazole, reach pleural fluid levels equivalent to levels within the blood and well above the relevant minimum inhibitory concentrations. The results demonstrate that concerns about the penetration of commonly used antibiotics, apart from co-trimoxazole, into the infected pleural space are unfounded.

Keywords: Bacterial Infection; Pleural Disease; Pneumonia; Respiratory Infection.

Figure 1

Mean (±SD) intravenous antibiotic concentration-time curves in the blood (dotted line) and pleural fluid (solid line): (A) amoxicillin, (B) metronidazole, (C) piperacillin (piperacillin-tazobactam), (D) tazobactam (piperacillin-tazobactam), (E) trimethoprim (co-trimoxazole), (F) sulphamethoxazole (co-trimoxazole) and (G) clindamycin. Minimum inhibitory concentrations (MICs) (EUCAST) of amoxicillin: Staphylococcus aureus 1 mg/L, Haemophilus influenza 2 mg/L, Streptococcus Milleri group 0.125 mg/L and Streptococcus pneumoniae 0.06 mg/L. MICs (EUCAST) of metronidazole: prevotella 1 mg/L, Gram-positive anaerobes (class) 0.25 mg/L and fusobacterium 0.125 mg/L. MICs (EUCAST) of piperacillin-tazobactam: S. aureus 2 mg/L, H. influenza 0.5 mg/L, Streptococcus Milleri group 1 mg/L, Escherichia coli 8 mg/L and S. pneumoniae 0.064 mg/L. MICs (EUCAST) of trimethoprim-sulfamethoxazole: S. aureus 0.25 mg/L, H. influenza 0.5 mg/L, S. pneumoniae 1 mg/L, E. coli 0.5 mg/L. MICs (EUCAST) of clindamycin: S. aureus 0.25 mg/L, Streptococcus Milleri group 0.25 mg/L and S. pneumoniae 0.25 mg/L. The MICs listed for common causative organisms are derived from the EUCAST website (https://www.eucast.org/mic_distributions_and_ecoffs/), which describes the MIC of ‘wild-type’ and, therefore, fully sensitive bacteria.