bFosfomycin is a potential option for vancomycin-resistant enterococcus (VRE) infections despite limited in vitro and clinical data. In this study, 32 VRE isolates from renal transplant patients with urinary stent infections were susceptible to fosfomycin, daptomycin, and linezolid and resistant to amoxicillin, minocycline, and nitrofurantoin based on their MIC 50 s and MIC 90 s. Fosfomycin was bacteriostatic at 0.5 to 16؋ the MIC (32 to 2,048 g/ml); synergy occurred when fosfomycin was combined with daptomycin (2.8 to 3.9 log 10 CFU/ml kill; P < 0.001) or amoxicillin (2.6 to 3.4; P < 0.05). These combinations may be potent options to treat VRE urinary infections pending investigation of clinical efficacy. Solid-organ transplant recipients are at increased risk for colonization with vancomycin-resistant enterococcus (VRE) and vulnerable to active infections with this organism (1). At our institution, a 7-French, 16-cm double-J stent is inserted through the ureter into the renal pelvis and then into the bladder at the time of kidney transplantation. Biofilm development often precipitates colonization of the stents and results in sequestered, stationaryphase bacteria that further resist the effects of antibiotics.Fosfomycin, a phosphonic acid derivative initially isolated in 1969 from cultures of Streptomyces species, is an oral therapy for uncomplicated urinary tract infections (UTIs) (2). It is often bactericidal against multidrug-resistant Gram-positive and Gramnegative pathogens, although it has not been well studied against VRE. The antibacterial activity of fosfomycin is achieved by inhibiting the enzyme N-acetylglucosamine (UDP-GlcNAc) enolpyruvyl transferase (MurA), which synthesizes UDP-N-acetylenolpyruvylglucosamine, an essential component in the biosynthesis of peptidoglycan (2). It is highly concentrated in the urine, with peak values of 1,053 to 4,415 g/ml within 4 h after a single oral 3-g dose (2). Fosfomycin has gained recent interest as a potential therapeutic option for treating infections caused by VRE despite limited efficacy data (3).The aim of this study was to investigate fosfomycin activity in vitro alone and in combination with other antibiotic treatment options against VRE urine isolates collected from renal transplant patients with urinary stent infections. We present synergistic combinations with fosfomycin that may be useful treatment options for these situations.(Portions of this work were presented at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2011 [4].) Thirty-two VRE (Enterococcus faecium) isolates were collected from renal transplant patients with urinary stent infections from 2007 to 2010 at a tertiary medical center. Enterococcus faecalis ATCC 29212 was used as a control strain. The antibiotics evaluated were amoxicillin, fosfomycin, nitrofurantoin, and minocycline, purchased from Sigma-Aldrich (St. Louis, MO), as well as linezolid (Pfizer, NY) and daptomycin (Cubist, Lexington, MA), which were commercially purchased.Antibiotic activi...

Ganciclovir-resistant cytomegalovirus (GR-CMV) is emerging as a significant infection in the abdominal transplant population. GR-CMV is difficult to manage, and treatment options are limited. We report a descriptive case series of 15 patients who had documented GR-CMV at our center and review the literature on treatment of GR-CMV. The first case in this series was detected in 2012; the majority of cases occurred after January 1, 2014, with approximately 50% occurring in 2015. UL97 and UL54 viral genome mutations were present in 100% and 40% of CMV-infected patients, respectively. GR-CMV infection occurred ≤ 1 year posttransplantation in 11 patients (73%). All patients experienced dose reduction of valganciclovir (the oral prodrug of ganciclovir) before the development of GR-CMV. Initial treatment for GR-CMV included a variety of regimens, all including reduction in maintenance immunosuppression. Of the 6 patients with detectable GR-CMV by polymerase chain reaction (PCR) who were discharged without GR-CMV treatment and had a length of stay (LOS) less than 14 days, 83% were subsequently readmitted for treatment of GR-CMV within 2 months (60% in < 20 days); none received leflunomide. Of six patients with a LOS ≥ 14 days, 80% had CMV PCR below quantification on hospital discharge, and only one patient was readmitted in less than 20 days; 83% received leflunomide. Following GR-CMV, there was a 50% rejection incidence, 27% graft loss, and 20% mortality. For patients with more than three admissions for GR-CMV treatment, 100% had a major complication: 60% rejection, 20% graft loss, and 40% mortality. Common clinical characteristics of patients with GR-CMV included high-risk serostatus, lymphocyte depletion, and history of valganciclovir dose reduction. Overall, outcomes were poor. It appears that hospital readmission rate was reduced when CMV was treated to negativity with an initial treatment regimen of reduced immunosuppression, foscarnet, intravenous immunoglobulins, and leflunomide.

Classical stewardship efforts have targeted immunocompetent patients; however, appropriate use of antimicrobials in the immunocompromised host has become a target of interest. Cytomegalovirus (CMV) infection is one of the most common and significant complications after solid-organ transplant (SOT). The treatment of CMV requires a dual approach of antiviral drug therapy and reduction of immunosuppression for optimal outcomes. This dual approach to CMV management increases complexity and requires individualization of therapy to balance antiviral efficacy with the risk of allograft rejection. In this review, we focus on the development and implementation of CMV stewardship initiatives, as a component of antimicrobial stewardship in the immunocompromised host, to optimize the management of prevention and treatment of CMV in SOT recipients. These initiatives have the potential not only to improve judicious use of antivirals and prevent resistance but also to improve patient and graft survival given the interconnection between CMV infection and allograft function.

Although sufficient power was not obtained to detect statistically significant differences between the intervention and control groups, a 0% incidence of recurrent CDI while receiving VPPx in this high-risk patient population is compelling because it pertains to the avoidance of CDI-related morbidity and mortality in transplant recipients. Future prospective studies are needed to better evaluate the impact of this preventive strategy.

BackgroundThe goal of this study was to identify predictors for development of Pneumocystis jirovecii pneumonia (PJP) in kidney and simultaneous kidney and pancreas transplant recipients in the present era of universal primary prophylaxis.MethodsWe reviewed adult recipients of kidney transplant or simultaneous pancreas and kidney transplant at the University of Wisconsin between January 1, 1994 and December 31, 2016. Patients diagnosed with PJP during this time frame were included. Controls were randomly selected from among those whose post-transplant course was not complicated by PJP, matched on time since transplant through incidence density sampling with a 3:1 ratio.Results28 (0.45%) of 6270 recipients developed PJP between 1994 and 2016. Median time since transplant was 4.6 years (interquartile range (IQR): 1.4–9.6 years). Affected recipients were older, had more HLA mismatches, and were more likely to have had BK viremia, CMV viremia and invasive fungal infections than matched controls. CMV viremia remained the only significant risk factor in multivariate analysis, and was a strong predictor (OR 6.27; p = 0.002). Ninety percent of the cases with prior CMV viremia had been diagnosed in the year preceding the diagnosis of PJP; among these, median time from diagnosis of CMV to diagnosis of PJP was 3.4 months (IQR: 1.74–11.5 months) and median peak CMV viral load prior to diagnosis of PJP was 3684.5 IU/mL (IQR: 1034–93,300 IU/mL). Additionally, 88.9% of patients with CMV in the preceding year had active infection at time of PJP diagnosis. Patient and graft survival were significantly worse at 2 years in recipients with PJP than our control group (42.4% vs. 88.5, and 37.9% vs. 79.9%; p < 0.001).ConclusionsDespite the low overall incidence of PJP in the era of universal prophylaxis, outcomes are poor. We suggest extending or re-initiating PJP prophylaxis for at least 6 months in the setting of CMV viremia due to the relatively low risk of therapy and potential significant impact on disease prevention.