Phage-induced efflux down-regulation boosts antibiotic efficacy.

The interactions between a virus and its host vary in space and time and are affected by the presence of molecules that alter the physiology of either the host or the virus. Determining the molecular mechanisms at the basis of these interactions is paramount for predicting the fate of bacterial and phage populations and for designing rational phage-antibiotic therapies. We study the interactions between stationary phase Burkholderia thailandensis and the phage ΦBp-AMP1. Although heterogeneous genetic resistance to phage rapidly emerges in B. thailandensis, the presence of phage enhances the efficacy of three major antibiotic classes, the quinolones, the beta-lactams and the tetracyclines, but antagonizes tetrahydrofolate synthesis inhibitors. We discovered that enhanced antibiotic efficacy is facilitated by reduced antibiotic efflux in the presence of phage. This new phage-antibiotic therapy allows for eradication of stationary phase bacteria, whilst requiring reduced antibiotic concentrations, which is crucial for treating infections in sites where it is difficult to achieve high antibiotic concentrations.

Staged surgical approach of neonates with esophageal atresia and tracheoesophageal fistula from low- and middle-income countries.

BACKGROUND: Neonates born in low- and middle-income countries (LMICs) with esophageal atresia (EA) and tracheoesophageal fistula (TEF) often do not have access to adequate surgical care. We have partnered with the non-profit organization World Pediatric Project (WPP) to facilitate care for such patients. METHODS: Our protocol included placement of a gastrostomy tube by local surgeons before definitive repair at the Children's Hospital of Richmond at VCU (CHoR). The outcomes of WPP-sponsored patients with EA and TEF in this program (n = 9) were compared to patients born in the U.S. with the same condition at CHoR (n = 9). RESULTS: The baseline characteristics of the groups aside from the age at admission to CHoR and at day of surgery were comparable (0.5 ± 1.3 days vs. 15.3 ± 11.1 days, p < 0.0001; 1.1 ± 3.9 days vs. 37.3 ± 8.3 days, p < 0.0001, respectively). All patients received definitive repair without mortality; the average length of stay after surgery was lower in the WPP group. There were 4 surgical complications in the U.S. group and 1 in WPP group. All patients were weaned off of TPN and all WPP patients are now on a regular PO diet. Every WPP patient has been seen in follow-up in the U.S. and in their home country. CONCLUSION: We provided successful multidisciplinary care for neonates with EA and TEF from LMICs with outcomes similar to the neonates with the same abnormality in the U.S. The partnership with WPP has been invaluable as it has provided essential support to identify and manage these patients. LEVEL OF EVIDENCE: IV.