An Evaluation of Guideline Concordance in the Management of Intra-Abdominal Infections.

Background: Optimal treatment of intra-abdominal infections (IAIs) is multifaceted, typically requiring surgical intervention and antimicrobial therapy. Treatment of IAIs aligned with the 2017 revised Surgical Infection Society (SIS) guidelines may improve patient outcomes. Here we compare clinical outcomes of patients who received guideline concordant and discordant therapy for treatment of IAIs. Patients and Methods: This was a retrospective observational study of patients admitted from January 2013 to June 2016 with IAIs. Guideline concordant treatment was based on three criteria: source control, antibiotic choice, and antibiotic duration. The primary outcome was a composite of in-hospital mortality and 30-day re-admission. Multivariable logistic regression was used to determine independent factors associated with the composite end point. Results: A total of 221 patients were included, with guideline concordant treatment occurring in 117 (53%) patients. In-hospital mortality or 30-day re-admission occurred in 15 (12.8%) patients in the guideline concordant group compared with 24 (23.1%) in the guideline discordant group (p = 0.046). Empiric antibiotic choice was the most common component of discordance to guidelines (61% of patients). In multivariable analysis, guideline concordant treatment was associated with a decrease in the composite outcome (adjusted odds ratio [aOR] = 0.461, p = 0.045). In contrast, the presence of empiric methicillin-resistant Staphylococcus aureus (MRSA)/vancomycin-resistant Enterococcus (VRE) coverage (aOR: 2.645, p = 0.030), and moderate-to-severe liver disease (aOR: 8.081, p = 0.027) were associated with an increased risk for the composite outcome. Conclusions: Concordance to recommendations from the 2017 revised SIS guidelines is of critical importance in the optimal management of IAIs and further investigation of interventions to improve concordance are warranted.

Risk factors for cytomegalovirus viremia and disease developing after prophylaxis in high-risk solid-organ transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) D+/R- solid-organ transplant (SOT) recipients carry increased risk of developing CMV disease; however, other risk factors in these patients have not been delineated. METHODS: We examined 20 demographic and clinical variables for their association with the development of CMV disease, as defined by an independent endpoint committee (IEC) and also by the investigator (investigator treated [IT]), or CMV viremia within 12 months of transplant in D+/R- transplant recipients who received prophylaxis with valganciclovir or oral ganciclovir for 100 days. RESULTS: Recipients with low creatinine clearance (Ccr,<40 mL/min) at screening had a significantly increased hazard of developing IEC-defined CMV disease (hazards ratio [HR]=4.28, confidence interval [CI] 1.69, 10.83). Females were twice as likely (HR=2.19, CI .21, 3.99) to develop IEC-defined CMV disease than males. These variables were associated with an increased risk of IEC-defined CMV disease in time-dependent models. Recipients with blood group A were also more likely to develop IEC-defined CMV disease than those with group O (HR=2.36 CI 1.24, 4.51) in the logistic regression model only. Prophylactic drug, organ type, recipient age, rejection episodes, and maintenance immunosuppression regimen were not associated with IEC-defined CMV disease. Female sex was the only variable associated with the development of CMV viremia (odds ratio [OR]=1.65; CI 1.03, 2.65) and IT CMV disease (OR=1.78; CI 1.08, 2.93). CONCLUSIONS: Low Ccr at screening and blood type A are risk factors for IEC-defined CMV disease, and female sex was a risk factor for IEC- and IT-defined CMV disease and viremia in high-risk SOT recipients. These variables should perhaps be considered when optimizing treatment.

Absence of cytomegalovirus-resistance mutations after valganciclovir prophylaxis, in a prospective multicenter study of solid-organ transplant recipients.

We investigated the emergence of cytomegalovirus (CMV) ganciclovir-resistance mutations in 301 high-risk solid-organ transplant (SOT) recipients after oral prophylaxis, for 100 days, with either valganciclovir or ganciclovir. For patients treated with ganciclovir, the incidence of CMV UL97 mutations was 1.9% (2/103) at the end of prophylaxis and 6.1% (2/33) for patients with suspected CMV disease up to 1 year after transplantation. No resistance mutations were detected in samples from valganciclovir-treated patients. Dual polymerase (UL54) and UL97 resistance mutations were not seen. Valganciclovir was associated with negligible risk of resistance and thus constitutes a useful alternative to ganciclovir prophylaxis for CMV in high-risk SOT recipients.

Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients.

We compared the efficacy and safety of valganciclovir with those of oral ganciclovir in preventing cytomegalovirus (CMV) disease in high-risk seronegative solid organ transplant (SOT) recipients of organs from seropositive donors (D+/R-). In this randomised, prospective, double-blind, double-dummy study, 364 CMV D+/R- patients received valganciclovir 900 mg once daily or oral ganciclovir 1000 mg three times a day (tid) within 10 days of transplant and continued through 100 days. CMV disease, plasma viremia, acute graft rejection, graft loss and safety were analyzed up to 6 and 12 months post-transplant. Endpoint committee-defined CMV disease developed in 12.1% and 15.2% of valganciclovir and ganciclovir patients, respectively, by 6 months, though with a difference in the relative efficacy of valganciclovir and ganciclovir between organs (i.e. an organ type-treatment interaction). By 12 months, respective incidences were 17.2% and 18.4%, and the incidence of investigator-treated CMV disease events was comparable in the valganciclovir (30.5%) and ganciclovir (28.0%) arms. CMV viremia during prophylaxis was significantly lower with valganciclovir (2.9% vs. 10.4%; p=0.001), but was comparable by 12 months (48.5% valganciclovir vs 48.8% ganciclovir). Time-to-onset of CMV disease and to viremia were delayed with valganciclovir; rates of acute allograft rejection were generally lower with valganciclovir. Except for a higher incidence of neutropenia with valganciclovir (8.2%, vs 3.2% ganciclovir) the safety profile was similar for both drugs. Overall, once-daily oral valganciclovir was as clinically effective and well-tolerated as oral ganciclovir tid for CMV prevention in high-risk SOT recipients.

Clinical utility of cytomegalovirus viral load testing for predicting CMV disease in D+/R- solid organ transplant recipients.

Despite prophylaxis, cytomegalovirus (CMV) disease is common in donor seropositive (D+)/recipient seronegative (R-) transplant patients after cessation of prophylaxis. Early detection of CMV may allow for pre-emptive therapy to prevent active disease. The clinical utility of quantitative plasma viral load measurements for predicting CMV disease was determined in 364 D+/R- organ transplant patients receiving prophylaxis (100 d of valganciclovir or oral ganciclovir). Measurements were performed every 2 weeks until day 100 and at months 4, 4.5, 5, 6, 8 and 12 post-transplant. CMV disease occurred in 64 (17.6%) patients by 12 months. Using a positive cut-off value of >400 copies/mL, sensitivity was 38%, specificity 60%, positive predictive value 17%, and negative predictive value 82% for prediction of CMV disease. Therefore, routine monitoring would have predicted disease in only 24/64 (38%) patients. The test characteristics were not improved by changing the viral load cut-off point for defining a positive result. Similarly, single time point measures at the end of prophylaxis or month 4 had low sensitivity for disease prediction. Overall, regular CMV plasma viral load measurements were only of modest value in predicting CMV disease.