History Of Recent Antibiotic Use Research Articles

Evidence for extensive resistance gene transfer among Bacteroides spp. and among Bacteroides and other genera in the human colon.

Transfer of antibiotic resistance genes by conjugation is thought to play an important role in the spread of resistance. Yet virtually no information is available about the extent to which such horizontal transfers occur in natural settings. In this paper, we show that conjugal gene transfer has made a major contribution to increased antibiotic resistance in Bacteroides species, a numerically predominant group of human colonic bacteria. Over the past 3 decades, carriage of the tetracycline resistance gene, tetQ, has increased from about 30% to more than 80% of strains. Alleles of tetQ in different Bacteroides species, with one exception, were 96 to 100% identical at the DNA sequence level, as expected if horizontal gene transfer was responsible for their spread. Southern blot analyses showed further that transfer of tetQ was mediated by a conjugative transposon (CTn) of the CTnDOT type. Carriage of two erythromycin resistance genes, ermF and ermG, rose from <2 to 23% and accounted for about 70% of the total erythromycin resistances observed. Carriage of tetQ and the erm genes was the same in isolates taken from healthy people with no recent history of antibiotic use as in isolates obtained from patients with Bacteroides infections. This finding indicates that resistance transfer is occurring in the community and not just in clinical environments. The high percentage of strains that are carrying these resistance genes in people who are not taking antibiotics is consistent with the hypothesis that once acquired, these resistance genes are stably maintained in the absence of antibiotic selection. Six recently isolated strains carried ermB genes. Two were identical to erm(B)-P from Clostridium perfringens, and the other four had only one to three mismatches. The nine strains with ermG genes had DNA sequences that were more than 99% identical to the ermG of Bacillus sphaericus. Evidently, there is a genetic conduit open between gram-positive bacteria, including bacteria that only pass through the human colon, and the gram-negative Bacteroides species. Our results support the hypothesis that extensive gene transfer occurs among bacteria in the human colon, both within the genus Bacteroides and among Bacteroides species and gram-positive bacteria.

The Effect of Antibiotic Therapy on Recovery of Intracellular Bacteria From Bronchoalveolar Lavage in Suspected Ventilator-Associated Nosocomial Pneumonia

Intracellular bacteria (ICB) within recovered cells (> 7 percent) obtained via bronchoalveolar lavage (BAL) have been described as predictive of subsequent positive quantitative protected specimen brush (PSB) cultures in patients not receiving antibiotics. To determine the effect of prior or current antibiotic therapy on ICB relative to subsequent PSB culture, we prospectively evaluated 49 consecutive episodes of clinically suspected ventilator-associated pneumonia in 36 patients. Three patient groups were defined based on antibiotic administration: group 1 (current antibiotics), n = 31, samples obtained from patients currently receiving antibiotics; group 2 (recent antibiotics), n = 5, samples obtained from patients who received antibiotics > 48 h but < 72 h prior to sampling; and group 3 (no antibiotics), n = 13, samples from patients receiving no previous antibiotics within 7 days prior to sampling. Overall, PSB cultures (> or = 10(3) cfu/ml) were positive in 14 of 49 (29 percent) samples. In group 1, 2 of 31 (6 percent) samples were positive while 5 of 5 (100 percent) samples in group 2, and 7 of 13 (54 percent) in group 3 were positive. The presence or absence of ICB accurately predicted both positive and negative PSB cultures in 43 of 49 episodes. Of 43 correct predictions, 34 were negative predictions (negative ICB, negative PSB culture). The vast majority of these (29) were obtained from group 1, patients currently receiving antibiotics. In contrast, of nine positive predictions (+ICB, +PSB) virtually all (seven) occurred in group 3, patients receiving no antibiotics. In group 3, 13 of 13 PSB cultures were accurately predicted, either positive or negative, by the presence or absence of ICB. Of seven positive PSB cultures in groups 1 and 2, only 2 (28 percent) were accurately predicted by ICB. From both samples, the cultured organism was resistant to all administered antibiotics. These data suggest both prior and current antibiotic therapy reduces recovery of ICB from BAL and reduces predictive accuracy of ICB for subsequent positive PSB cultures. However, negative prediction by ICB for subsequent negative PSB cultures was good. In contrast, ICB obtained from patients not receiving antibiotics are highly predictive of subsequent PSB culture results, both positive and negative. We do not recommend BAL for evaluation of ICB in patients currently receiving antibiotics or with a recent history of antibiotic use.

Human colonic aspirates containing immunoglobulin A antibody to Clostridium difficile toxin A inhibit toxin A-receptor binding

Clostridium difficile toxin A, a 308-kilodalton protein exotoxin, is the principal causative agent of antibiotic-associated, C. difficile-induced colitis. In the current study, the prevalence of specific human serum and secretory antibody to toxin A and the possible protective effect of secretory, intestinal anti-toxin A antibody are examined. Serum (n = 35), colonic aspirates (n = 35), and duodenal aspirates (n = 20) were collected from adults at diagnostic endoscopy. Patients with evidence of colitis or a history of recent antibiotic use were excluded from the study. Specific serum immunoglobulin (Ig) A and IgG antitoxin A antibodies were detected in 60% and 57% of subjects, respectively, by enzyme-linked immunosorbent assay. Fifty-seven percent of colonic aspirates contained IgA antitoxin, whereas only 10% of duodenal aspirates were positive (P = 0.002). Binding of toxin A to its intestinal receptor was studied using [3H]toxin A and purified rabbit ileal brush border membranes. Toxin A binding was significantly inhibited by colonic aspirates with high IgA anti-toxin A antibody levels (0.503 ± 0.055 pmol toxin A bound per milligram of brush border membrane protein, mean ± SE) in comparison with antitoxin A-negative aspirates (0.778 ± 0.089 pmol; P = 0.02) and control (0.766 ± 0.004 pmol; P = 0.03). In the current study, a specific intestinal secretory IgA antibody response to C. difficile toxin A in humans is reported. This antibody response is more evident in the colon, the site of C. difficile infection, than in the upper intestinal tract. Our data suggest that human colonic IgA antitoxin may protect against C. difficile colitis by inhibiting the binding of toxin A to its intestinal epithelial cell receptor.