Interaction of Purulent Material with Antibiotics Used to Treat Pseudomonas Infections

Abstract

To define factors contributing to the adverse prognosis of patients with gram-negative bacillemia and abscess formation, we studied the interaction between polymyxin B, colistin sulfate, gentamicin, or carbenicillin with purulent material. Carbenicillin activity was not significantly altered by incubation with pus. Equal volumes of antibiotic and purulent sediment decreased the effective concentration of polymyxin B, colistin sulfate, or gentamicin from 100 yg/ml to 3 to 6 ug/ml. One milliliter of purulent sediment bound more than 700 ,ug of gentamicin and 1,500 ,ug of polymyxin B or colistin sulfate. This effect occurred rapidly, proceeded at 4 and 37 C, was stable for 24 to 48 h, and was altered, but not abolished, by varying the pH of the solution. Antibiotic activity could be removed from pus by high concentrations of protamine sulfate, heparin, sodium chloride, or potassium chloride, suggesting binding rather than inactivation.

Peripheral inactivation of gentamicin

“…It is therefore possible that gentamicin and neomycin binding data were artificially enhanced in some previous studies, which used either purulent material lyophilized and suspended in distilled water (Potter et al, 1965), purulent sputum sonicated and autoclaved (Davis & Brans, 1978), or purulent exudates homogenized, frozen and diluted in water (Bryant & Hammond, 1974).…”

“…An intermediate approach was to study the binding of gentamicin to subcellular fractions of noninfected organs or tissues (Kunin, 1970;Komguth, Bayer & Kunin, 1980). The clinical relevance of these studies is as yet uncertain, because most of the results on gentamicin binding have been obtained under somewhat unphysiological conditions: either the gentamicin binding assays were performed in salt buffers of too low an ionic strength (Bryant & Hammond, 1974;Kornguth et ai, 1980), or the binding was assessed after the purulent samples had been strongly homogenized (Bryant & Hammond, 1974;Davis & Bruns, 1978). As will be seen later, both conditions may have considerably enhanced the gentamicin binding properties of the materials tested.…”

“…After having considered the possible physiological effects of pH or pO 2 on the gentamicin antibacterial activity, we have to discuss a complex category of inhibitory substances, namely factors that bind gentamicin molecules, the presence of which reduces the concentration of the free, biologically active drug. This problem has been approached in vitro either by incubating purulent material with gentamicin (Bryant & Hammond, 1974;Davis & Bruns, 1978) or, by testing different groups of purified macromolecules for gentamicin (Deguchi, Ishii & Tanaka, 1978) or neomycin (Potter, Matthews el ai, 1965) binding activity. An intermediate approach was to study the binding of gentamicin to subcellular fractions of noninfected organs or tissues (Kunin, 1970;Komguth, Bayer & Kunin, 1980).…”

Antibiotic tissue penetration and its relevance: impact of tissue penetration on infection response

“…Although not as important for the ,-lactams, the effect of antibiotic binding to cellular components cannot be neglected because the serum antibiotic concentration is the net result of binding in both serum and tissues. In addition to extravascular albumin, antibiotics may bind to such tissue components as cell membranes, intracellular organelles, macromolecules, and products of inflammation (11,27). ,B-Lactams are primarily bound to extracellular serum proteins, and quinolones are primarily bound inside cells (24,27,38,40).…”

Renal pharmacokinetic changes of gentamicin during enterococcal pyelonephritis

“…1164, 1986) and complement activation (13), may lead to hemodynamic and vascular permeability changes which could lead to disturbed distribution of aminoglycoside within the renal parenchyma. Pus, which is also known to bind aminoglycosides (8), could also partially contribute to the persistence of drug within the renal tissue. This factor surely did not play a determinant role for more than a few weeks after therapy, when the acute inflammatory process is slowly replaced by more chronic inflammatory cells and limited amounts of pus.…”