Effects of aztreonam on fecal flora and on vitamin K metabolism

Abstract

The effects of aztreonam on fecal flora and on descarboxy prothrombin (PIVKA-H) in plasma and -y-carboxyglutamic acid (Gla) in urine as an index of vitamin K metabolism were studied in seven children (age range, 2 months to 2 years) with urinary tract infections. Daily doses of aztreonam were 60 to 80 mg/kg. Stool specimens were obtained before the treatment, on days 3 to 5 of aztreonam use, and from 3 to 5 days after the cessation of treatment. The counts of enterobacteria decreased (P < 0.01) and those of streptococci increased (P < 0.05) during aztreonam treatment. The anaerobic organisms, especially bifidobacteria and bacteroides, showed no marked change. PIVKA-IH and Gla were investigated before and during the treatment with aztreonam. PIVKA-II was not detected in seven patients before or during aztreonam use. There were no significant differences in the levels of Gla in urine before or during the treatment.Aztreonam is a monobactam antibiotic which has high activity against many aerobic gram-negative bacilli, but it has low activity against gram-positive cocci and anaerobic bacteria (4, 9). The clinical efficacy of aztreonam in aerobic gram-negative infections has been shown by many investigators (7,24). The impact of antibiotics on fecal flora is well-known, and the effects of some antibiotics on fecal flora have been reported (5,22,25). Although aztreonam might be expected to have little influence on fecal flora because of the features of activity of this agent against bacteria, there are few reports about the effect of aztreonam on fecal flora (6).The hypoprothrombinemia caused by vitamin K deficiency is also one of the important adverse effects induced by antibiotics, especially the broad-spectrum cephalosporins which have the N-methylthiotetrazole side chain, such as moxalactam, cefoperazone, and cefmetazole (12,18,20,21). In this study, we set out to evaluate the effects of aztreonam on fecal flora. We also measured descarboxy prothrombin (PIVKA-II) in plasma and y-carboxyglutamic acid (Gla) in urine in order to discover the effect of this antibiotic on vitamin K metabolism. MATERIALS AND METHODSSeven children (age range, 2 months to 2 years) hospitalized in the Asahikawa Medical College Hospital for the treatment of urinary tract infections were used as subjects for this study. No antibiotics were administered before the study. They received aztreonam intravenously in a 20-mg/kg dose every 6 or 8 h during 3 to 14 days.Stool specimens were obtained before treatment, from days 3 to 5 of antibiotic use, and from 3 to 5 days after the cessation of drug administration. Plasma and urine were taken from patients before treatment and from days 3 to 5 of antibiotic use. Quantitative aerobic and anaerobic cultures were undertaken by a method described previously (22). Stool specimens were immediately put into a sterile transport medium filled with CO2 gas and stored at 4°C until they were cultured. The specimens were homogenized and serially diluted 10-fold in a buffer solution which was prereduced under an...

Modulation of the intestinal flora of mice by treatment with aztreonam and tigemonam

“…Several studies have shown that oral or parenteral treatment with aztreonam in humans causes a pronounced decrease in the number of aerobic gram-negative rods without altering the composition of the anaerobic fecal flora (1,4,5,7,9,11,13). These results are explained by the intrinsic resistance of anaerobic bacteria to aztreonam.…”

Antimicrobial Drug-Induced Thrombocytopenia: A Review of the Literature

“…Certain cephalosporins, such as ceftazidime and ceftriaxone, have also been proposed to increase risk for bleeding in malnourished or debilitated patients, by decreasing intestinal vitamin K-producing flora, particularly Enterobacteriaceae. 28 Furthermore, the older cephalosporins with an N-methylthiotetrazole side chain, including cefotetan, or a free sulfhydryl group, such as ceftriaxone, have been shown to directly cause prolonged prothrombin time, likely by blocking vitamin K epoxide reductase and subsequently decreasing production of vitamin K-dependent clotting factors. 29 Clinically, these effects may not be relevant unless a patient is at a high risk of bleed, has impaired vitamin K production, or has high exposure to β-lactams, either by receiving high doses of the drug or impaired excretion of the drug.…”

Interaction between Warfarin and Linezolid in Patients with Left Ventricular Assist System in Japan

“…Warfarin is a racemic mixture of the R and S stereoisomers of the drug. S-warfarin is primarily metabolized by cytochrome P-450 (CYP) 2C9 isoenzyme, whereas R-warfarin is metabolized by CYP1A2 and 3A4 (20,21). However, several animal and human studies revealed that linezolid is not detectably metabolized by CYP (22), and it did not induce or inhibit the activities of clinically significant human CYP isoforms, including CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 (20,23).…”

“…Hypoprothrombinemia has been reported to occur as a result of antibiotic administration. It has been reported that several antibiotics cause vitamin K deficiency by reducing the number of enteric bacteria which synthesize vitamin K in the intestines (21,22). The suppression of bacterial flora by antibiotics may be a possible mechanism for the interaction of warfarin and antibiotics (21,22).…”

“…It has been reported that several antibiotics cause vitamin K deficiency by reducing the number of enteric bacteria which synthesize vitamin K in the intestines (21,22). The suppression of bacterial flora by antibiotics may be a possible mechanism for the interaction of warfarin and antibiotics (21,22). Recently, Sakai et al reported that the PT-INR increased following concomitant linezolid treatment in five of six patients who were recovering from heart-related surgery (24).…”