Interactions of Antimicrobial Drugs and Combined Phagocytic/Serum Bactericidal Activity of Defibrinated Human Blood against <i>Serratia marcescens</i>

Abstract

Minimal bactericidal concentrations of the aminoglycoside antibiotics amikacin, gentamicin, and netilmicin killed intraphagolysosomal test bacteria of selected assay strains of Serratia marcescens, though not as efficiently as rifampin. The system employed consisted of 55 vol % of fresh defibrinated human blood treated with 2 mg/ml of phenylbutazone which permitted ingestion of bacteria, but selectively inhibited microbicidal activity of the peripheral blood leukocytes. Extraphagocytic bacteria were killed with the aid of group A (phage tail) bacteriocins of S. marcescens. Inhibitory and subinhibitory concentrations of amikacin, gentamicin, and netilmicin combined with 55 vol % of defibrinated blood, respectively, yielded additive effects against all test strains of S. marcescens utilized and against Escherichia coli control strain ATCC 25922.

<i>Pseudomonas aeruginosa</i>: In vitro Susceptibility to Antimicrobial Drugs, Single and Combined, with and without Defibrinated Human Blood

“…Of par ticular interest was the finding that of the four fluoroquinolones examined, cipro floxacin yielded the most rapid and po tent intraphagocytic bactericidal activity against our control strain of P. aeruginosa. And as noted before in our Serratia marcescens system [36], p-lactam and amino glycoside antibiotics were only feebly or moderately active ingested P. aeruginosa cells; however, polymyxin B occupied an intermediate position.…”

“…4, the least blood-susceptible of all strains, was included in all experiments comprising the first two series of com bined human blood-antimicrobial drug assays. As before [36], we chose to perform time-kill curve experiments [8], inasmuch as these permitted evaluation of the bac tericidal activities of drugs or drug combi nations during various points in time over prolonged incubation periods. In addi tion, Moody et al [25] found conventional inoculum time-kill rates at extravascularly achievable antimicrobial drug concentra tions to be a good predictor for the out come of closed-space P. aeruginosa infec tions at locally neutropenic sites in rab bits.…”

“…The tests (final assay volume = 2 ml) were carried out as described previously [36]. In a first series of 16 experiments, the 2 x MIC, MIC, and 1/2 MIC con centrations of a particular antimicrobial drug were combined with 55% (v/v) of fresh defibrinated hu man blood (donors B., S., and T.) in TSB: controls consisted of the 2 x MIC in TSB, 55% (v/v) of blood alone, and TSB alone, respectively.…”

“…The final series of 5 experiments, which served to assay for the potential intraphagocytic bactericidal activityoftheantimicrobialdrugs [36]against P. aeru ginosa control strain ATCC 27853, were performed using 55% (v/v) of fresh defibrinated human blood, PBZ at a final concentration of 2 mg/ml (added 10 min before onset of the assays), and P. aeruginosa bacteriocin No. b* 2 (final concentration = 32 lethal units/ml: added 30 min after onset of the experi ments), and relevant controls.…”

“…Thus, we decided to examine re cent clinical isolates of P. aeruginosa for their susceptibility to various antimicro bial drugs, single and combined, includ ing triple-drug combinations [39,40,43], in the absence and presence of fresh defibrinated human blood. Furthermore, these antimicrobial drugs were tested for potential intraphagocytic bactericidal ac tivity [36] against a control strain of P. aeruginosa.…”