Multidrug‐resistant organisms have caused a marked depletion of effective antimicrobials, and the narrow pipeline of antibiotics has demanded the need to find novel therapeutic alternatives including nonantibiotic agents. Bacteriophages (phages) are viruses that use the bacterial machinery to infect, replicate, and kill bacterial cells. Although a marked decline in their use was driven by the discovery of antibiotics, the era of antibiotic resistance has led to a resurgence of phage therapy into clinical practice. The term phage‐antibiotic synergy (PAS) was coined just over a decade ago and described that sublethal concentrations of antibiotics could stimulate phage production by bacterial cells. Recent literature has described PAS and other encouraging interactions with various phage and antibiotic combinations against a variety of bacterial strains. The primary objective of this review is to discuss the positive interactions between phage and antibiotic combinations, with an emphasis on PAS, reductions in bacterial growth or minimum inhibitory concentrations, enhanced biofilm eradication, and alterations in the emergence of bacterial resistance. A peer‐reviewed literature search was conducted (1890–2019) using the PubMed, Medline, and Google Scholar databases. Although more investigation is certainly needed, the combination of bacteriophages with antibiotics is a promising strategy to target organisms with limited or no therapeutic options. This approach may also foster the ability to lower the antibiotic dose and may reduce the potential for antibiotic resistance emergence during therapy.

Background: Long-acting lipoglycopeptides (laLGPs) are FDA approved only for acute bacterial skin and skin structure infections (ABSSSIs). However, these antibiotics show promise for off-label use, reductions in hospital length of stay (LOS) and healthcare cost savings.Objectives: To assess the effectiveness, safety, impact on LOS and estimated cost savings from laLGP treatment for Gram-positive infections.Methods: Retrospective cohort of adult patients who received at least one dose of laLGPs at the University of Colorado Health system. Descriptive statistics were utilized for analysis.Results: Of 59 patients screened, 56 were included: mean age 47 years, 59% male and 30% injection drug users/polysubstance abusers (dalbavancin, 71%; oritavancin, 25%; both, 4%). Most common indications for laLGP: ABSSSIs (36%), osteomyelitis (27%) and endocarditis (9%). Most common isolated pathogens: MSSA and MRSA (25% and 19%, respectively), Enterococcus faecalis (11%) and CoNS (11%). Previous antibiotics were administered for a median of 13 days (IQR = 7.0–24.5 days) and laLGPs for a median of one dose (IQR = 1–2 doses). Ten (18%) patients were lost to follow-up. Clinical failure was found in 7/47 (15%) cases with adequate follow-up. Mild adverse effects occurred in six (11%) patients. Projected reduction in hospital LOS and health-system costs were 514 days (9.18 days/person average) and $963456.72 ($17204.58/person average), respectively.Conclusions: Prospective trials are needed to validate the use of these antibiotics for Gram-positive infections in practice, with the hope that they will reduce hospital LOS and the need for daily antibiotic infusions to provide alternative options for patients not qualifying for outpatient parenteral antimicrobial therapy.

Injection drug use is associated with serious infections. Due to challenges with medical management of addiction, relapses and additional infections are common. Persons who use drugs (PWUD) are more likely to leave against medical advice before completing treatment, which could result in treatment failure. Prolonged intravenous (IV) antimicrobial therapy in PWUD may be complicated by concern for IV catheter misuse, sometimes requiring prolonged hospitalization. Ideal alternatives would provide the following: (1) high success rate; (2) reduced rate of medical complications; (3) improved safety profiles; and (4) improved cost-effectiveness. Long-acting lipoglycopeptides present such opportunity for treatment of serious Gram-positive infections. We performed a system-wide, retrospective analysis of adults admitted to University of Colorado Health from September 2015 to June 2018 and treated with dalbavancin or oritavancin based on clinical judgment of their treating physicians. Fifty-six patients met inclusion criteria (17 PWUD vs 39 non-PWUD). The PWUD group were younger, healthier by Charlson comorbidity index, more likely insured by Medicaid, and admitted for conditions requiring longer treatment. Ten patients were lost to follow-up. Of the patients with follow-up, clinical failure was met in 1 PWUD patient (6%) and 6 non-PWUD patients (15%) (P = .413). The median hospital length-of-stay reduction was 20 days (interquartile range [IQR], 10–30 days) in PWUD vs 11 days (IQR, 9–14 days) in non-PWUD; P = .133. Estimated median savings were $40 455.08 (IQR, $20 900.00–$62 700.00) in PWUD vs $19 555.08 (IQR, $15 375.08–$23 735.08) in non-PWUD; P = .065. Long-acting lipoglycopeptides may be equally effective as standard-of-care, present a safety advantage, and secure earlier discharge and significant cost-savings.

Biofilm-associated multidrug-resistant infections pose significant challenges for antibiotic therapy. The extracellular polymeric matrix of biofilms presents an impediment for antibiotic diffusion, facilitating the emergence of multidrug-resistant populations.

Clostridioides difficile infection (CDI) is a common complication in the hematopoietic stem cell transplantation (HSCT) and hematologic malignancy (HM) population. CDI is associated with increased hospital length of stay, health care and societal costs, morbidity, and mortality. Identifying strategies for secondary prevention of CDI is of extreme importance in the HSCT/HM population. In this study, our primary objective was to evaluate the effectiveness and safety of an oral vancomycin prophylaxis (OVP) protocol for secondary prevention of CDI in a retrospective cohort of adult autologous/allogeneic HSCT recipients and patients with HM who did not undergo HSCT with a first CDI episode treated with concomitant broad-spectrum antibiotics (BSA). Patients were diagnosed and treated for CDI as inpatients and/or outpatients and were divided into 2 groups based on a preprotocol versus postprotocol analysis: the OVP group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently received OVP posttreatment and a no OVP (NOVP) group, comprising patients who received planned monotherapy with oral vancomycin 125 mg every 6 hours for 14 days for a first episode of CDI and subsequently did not receive OVP posttreatment. OVP was defined as vancomycin 125 mg every 12 hours for up to 7 days after BSA discontinuation. The primary endpoint was recurrent CDI (rCDI), defined as symptoms of loose stools/diarrhea with high clinical suspicion for CDI prompting empiric therapy within 60 days of completion of treatment/prophylaxis for the first CDI episode. The incidence of vancomycin-resistant enterococcal (VRE) infection and 60-day mortality were also compared between the 2 groups. Multivariate logistic regression was created from associated variables to identify independent associations with rCDI. A total of 50 patients were included, 21 in the OVP group (42%) and 29 in the NOVP group (58%). The mean patient age was 58 years, and the cohort was 60% male and 86% Caucasian. HSCT was performed in 60% of the patients, and 76% of CDI cases were diagnosed during hospitalization. The rate of rCDI was significantly lower in the OVP group compared with the NOVP group (5% [1 of 21] versus 35% [10 of 29]; P= .016), with no subsequent increase in VRE infection rate (14% [3 of 21] versus 10% [3 of 29]; P = .686). By multivariable logistic regression, rCDI was inversely associated with OVP (odds ratio [OR], .14; 95% confidence interval [CI], .007 to .994; P = .049) and directly associated with outpatient CDI diagnosis (OR, 8.72; 95% CI, 1.816 to 49.158; P = .007). No between-group differences were found in 60-day mortality (10% [2 of 21] for OVP versus 7% [2 of 29] for NOVP; P > 0.999). OVP appears to be safe and effective for secondary prevention of CDI in the HSCT/HM population. Prospective trials are needed to validate the effectiveness of OVP in this vulnerable population to prevent rCDI.

Concerns regarding increased prevalence of daptomycin (DAP)-resistant strains necessitate novel therapies for Enterococcus faecium infections. Obligately lytic bacteriophages are viruses that target, infect, and kill bacterial cells. Limited studies have evaluated phage-antibiotic combinations against E. faecium. Following an initial screen of eight E. faecium strains, three strains with varying DAP/phage susceptibility were selected for further experiments. Phage-to-strain specificity contributed to synergy with antibiotics by time-kill analyses and was associated with lower development of phage resistance.