Pseudomonas aeruginosa ventricular assist device infections: findings from ineffective phage therapies in five cases.

Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in P. aeruginosa endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.

Membrane stripping in group B streptococcus carriers does not impede adequate intrapartum antibiotic prophylaxis: a retrospective study.

Objective: Membrane stripping in group B streptococcus (GBS) carriers poses an increased risk of inadequate antibiotic prophylaxis, potentially due to accelerated labor, thereby potentially impacting the management of GBS colonization during delivery. We compared the adequacy of intrapartum antibiotic prophylaxis between pregnant women colonized with GBS, who underwent membrane stripping and those who did not. The study aimed to determine whether the performance of membrane stripping, by potentially shortening labor duration, increases the risk of inadequate antibiotic prophylaxis dispensation. Study design: A retrospective cohort study was conducted on GBS screen-positive women with a full-term singleton pregnancy in cephalic presentation, who were eligible for vaginal delivery. The exposed group consisted of women who underwent membrane stripping, while the unexposed group consisted of women who did not undergo membrane stripping. The primary outcome was defined as inadequate duration of antibiotic prophylaxis during labor, wherein less than 4 h of beta-lactam antibiotics were administered prior to delivery. Neonatal outcome was compared between the groups. Results: This retrospective cohort study comprised 1,609 women, with 129 in the exposed group (stripping group) and 1,480 in the unexposed group (no stripping group). Adequate intrapartum antibiotic prophylaxis was received by 64.3% (83/129) of the exposed group, compared to 46.9% (694/1,480) of the unexposed group (p = 0.003). Membrane stripping was associated with increased odds of receiving adequate prophylaxis (OR 1.897, 95% CI 1.185-3.037, p = 0.008). After excluding women who presented to the labor ward in active labor and delivered in less than 4 h, both the exposed and unexposed groups had similarly high rates of adequate intrapartum antibiotic prophylaxis (87.5% vs. 85.8%, respectively). No significant difference was observed in adverse neonatal outcomes between the groups. Conclusion: The provision of membrane stripping did not impede adequate intrapartum antibiotic prophylaxis and was correlated with a higher rate of sufficient prophylaxis in comparison to non-swept patients. These observations suggest that membrane stripping can be considered a safe option for ensuring adequate antibiotic prophylaxis in women colonized with GBS.

Protocol for phage matching, treatment, and monitoring for compassionate bacteriophage use in non-resolving infections.

Phage therapy has re-emerged as a promising treatment for non-resolving infections. Given the lack of approved phage treatments, there is a need to establish a compassionate use pipeline. Here, we present a protocol for phage matching, treatment, and monitoring for compassionate bacteriophage use in non-resolving infections. We describe steps for consultation and request implementation, evaluating and comparing different aspects of phage activity, and phage production. We then detail procedures for multidisciplinary meetings, ethics approvals, phage therapy, and follow-up. For complete details on the use and execution of this protocol, please refer to Onallah et al.1,2.