Title: Optimal timing of prophylactic antibiotics in surgery corresponds with a peak in penicillin-binding protein expression in infecting bacteria
Authors: Vandecasteele, S
Van Eldere, Johan
Merckx, R
Peetermans, Willy #
Issue Date: 2003
Host Document: Clinical microbiology and infection vol:9 issue:S1 pages:46
Conference: European Congress of Clinical Microbiology an Infectious diseases edition:13th location:Glasgow date:10-13 May 2003
Article number: O251
Abstract: Objectives: The probability of surgical-wound infections in clean-contaminated surgery is the lowest when prophylactic antibiotics are given between 2 h before incision and the time of incision. Administration between incision and 3 h after incision and between 3 and 24 h after incision increases the risk for infection 2.4 and 5.8 times, respectively (NEJM, 1992, 326, 281–6).
Surgical wound infections are often related to foreign bodies such as sutures, drains and prosthesis. This study aims to evaluate penicillin-binding protein expression (the target of beta-lactam antibiotics) during the first 24 h of in vivo foreign body related infection.
Methods: One hundred and sixty polyurethane fragmentswere contaminated with a homogenously methicillin-resistant Staphylococcus epidermidis and implanted subcutaneously in a rat model for foreign body infections. The samples were explanted at 8 time points (0, 15, 120, 240, 360, 720 and
1440 min) during the first day of infection and the expression of pbp2a gene was quantified with RT quantitative PCR as the cDNA/gDNA quotient as previously described (BBRC, 2002).
Results: After implantation, pbp2a expression increased and peaked between 15 and 60 min, whereafter a progressive decrease was observed (P<0.001 for evolution, 1-way ANOVA; with expression at t¼15, 60 and 120 min being significantly higher than expression at t¼1 day, Bonferroni test). The mean peak expression after 60 min of in vivo infection was 11.1 times higher than the mean through expression after 24 h of in vivo infection (P<0.0001, t-test).
Discussion: pbp2a has a higher expression during early but not during late in vivo foreign-body associated growth. Thus, the prophylactic administration of antibiotics in the hours before incision results in peak tissue-concentrations
when the molecular target have their highest expression level. When the prophylactic antibiotics are given too early, tissue concentrations will already be below the MIC at the time of infection. When the prophylactic antibiotics
are given too late, the molecular targets of these antibiotics will already have a lower expression level.
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory for Clinical Infectious and Inflammatory Disorders
Laboratory for Experimental and Clinical Microbiology (-)
Laboratory of Clinical Bacteriology and Mycology
# (joint) last author

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