Fitness cost of antibiotic susceptibility during bacterial infection.

Advances in high-throughput DNA sequencing allow for a comprehensive analysis of bacterial genes that contribute to virulence in a specific infectious setting. Such information can yield new insights that affect decisions on how to best manage major public health issues such as the threat posed by increasing antimicrobial drug resistance. Much of the focus has been on the consequences of the selective advantage conferred on drug-resistant strains during antibiotic therapy. It is thought that the genetic and phenotypic changes that confer resistance also result in concomitant reductions in in vivo fitness, virulence, and transmission. However, experimental validation of this accepted paradigm is modest. Using a saturated transposon library of Pseudomonas aeruginosa, we identified genes across many functional categories and operons that contributed to maximal in vivo fitness during lung infections in animal models. Genes that bestowed both intrinsic and acquired antibiotic resistance provided a positive in vivo fitness advantage to P. aeruginosa during infection. We confirmed these findings in the pathogenic bacteria Acinetobacter baumannii and Vibrio cholerae using murine and rabbit infection models, respectively. Our results show that efforts to confront the worldwide increase in antibiotic resistance might be exacerbated by fitness advantages that enhance virulence in drug-resistant microbes.

Rapid adaptation of antibiotic therapy for community-acquired peritonitis using direct cultures on antibiotic agar plates: pilot study.

BACKGROUND: Treatment of peritonitis requires prompt surgery and antibiotic therapy. It usually takes two or three days to obtain definitive results of peritoneal cultures and to adapt empirical antibiotic therapy. We assessed the potential time gain associated with direct culture of peritoneal samples on antibiotic agar (AA). METHODS: Peritoneal samples from 31 consecutive patients undergoing surgery for suspected community-acquired peritonitis were cultured according to the standard method and on AA containing one of the following five regimens: amoxicillin/clavulanic acid + gentamicin, ticarcillin/clavulanic acid + gentamicin, cefotaxime +metronidazole, piperacillin/tazobactam, or ertapenem. We compared the treatment modifications made by physicians aware only of the results of the standard method with the modifications the AA method would have indicated. RESULTS: Fewer isolates were identified by direct culture on AA than by the standard method (17 vs. 45; p = 0.0001), but definitive results were obtained much more rapidly (median 1 [range 1-3] days vs. 3 [range 2-7] days; p < 0.0001). Antibiotic regimens were changed for 14 patients on the basis of the results of the standard method (broader antibiotic spectrum and narrower spectrum in seven patients each). With the AA method, these changes could have been indicated after a median of 1 (range 1-2) days instead of 4 (range 1-11) days (p = 0.0006). The AA method missed only one resistant bacterial strain and isolated nine strains not detected by the standard method, including an extended-spectrum beta-lactamase-producing Escherichia coli. A complicated outcome was more frequent in patients having isolates found with the AA but not the standard method (86% vs. 21%; p = 0.003). CONCLUSION: Use of the AA method for culture of peritoneal samples from patients with community-acquired peritonitis speeds appropriate adaptation of antibiotic therapy and warrants further investigation.