Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia.

Enterococcus faecium is a member of the human gastrointestinal (GI) microbiota but can also cause invasive infections, especially in immunocompromised hosts. Enterococci display intrinsic resistance to many antibiotics, and most clinical E. faecium isolates have acquired vancomycin resistance, leaving clinicians with a limited repertoire of effective antibiotics. As such, vancomycin-resistant E. faecium (VREfm) has become an increasingly difficult to treat nosocomial pathogen that is often associated with treatment failure and recurrent infections. We followed a patient with recurrent E. faecium bloodstream infections (BSIs) of increasing severity, which ultimately became unresponsive to antibiotic combination therapy over the course of 7 years. Whole-genome sequencing (WGS) showed that the patient was colonized with closely related E. faecium strains for at least 2 years and that invasive isolates likely emerged from a large E. faecium population in the patient's gastrointestinal (GI) tract. The addition of bacteriophage (phage) therapy to the patient's antimicrobial regimen was associated with several months of clinical improvement and reduced intestinal burden of VRE and E. faecium. In vitro analysis showed that antibiotic and phage combination therapy improved bacterial growth suppression compared to therapy with either alone. Eventual E. faecium BSI recurrence was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage-neutralizing antibody response occurred that coincided with an increased relative abundance of VRE in the GI tract, both of which may have contributed to clinical failure. Taken together, these findings highlight the potential utility and limitations of phage therapy to treat antibiotic-resistant enterococcal infections. IMPORTANCE: Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent E. faecium infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced E. faecium and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.

Plasma and Cerebrospinal Fluid Therapeutic Drug Monitoring of Ceftolozane and Tazobactam During Treatment of Multidrug-Resistant Pseudomonas aeruginosa Meningitis.

We report a case of multidrug-resistant Pseudomonas aeruginosa meningitis treated with ceftolozane-tazobactam with concomitant therapeutic drug monitoring of plasma and cerebral spinal fluid. The data suggest that ceftolozane-tazobactam may be an option for select central nervous system infections; however, treatment decisions should be interpreted on a case-by-case basis.

Rasamsonia sp: An emerging infection amongst chronic granulomatous disease patients. A case of disseminated infection by a putatively novel Rasamsonia argillacea species complex involving the heart.

Chronic granulomatous disease (CGD) is a heterogeneous condition due to defects in NADPH oxidase characterized by granuloma formation and increased susceptibility to invasive infections, in particular moulds. The use of broad-spectrum, mould-active antifungal prophylaxis has improved mortality. However rare resistant moulds have emerged as important pathogens. Diagnosis of these rare fungi requires molecular techniques, and treatment data are limited. Herein, we present a case of with disseminated Rasamsonia infection involving the heart.