Unusual Neisseria species as a cause of infection in patients taking eculizumab.

BACKGROUND: Non-meningococcal, non-gonococcal Neisseria spp. are typically commensal and rarely cause invasive disease. Eculizumab is a terminal complement inhibitor that increases susceptibility to meningococcal disease, but data on disease caused by typically-commensal Neisseria spp. are lacking. This series describes postmarketing reports of typically-commensal Neisseria spp. disease in patients receiving eculizumab. METHODS: We searched the FDA Adverse Event Reporting System (FAERS) and medical literature for reports of commensal Neisseria spp. disease in patients receiving eculizumab, from eculizumab U.S. approval (2007) through January 31, 2018. RESULTS: We identified seven FAERS reports (including one case also reported in the literature) of non-meningococcal, non-gonococcal Neisseria disease, including N. sicca (mucosa)/subflava (n = 2), N. cinerea (n = 2), N. sicca (mucosa) (n = 1), N. mucosa (n = 1, with concurrent alpha-hemolytic Streptococcus bacteremia), and N. flavescens (subflava) (n = 1). Four cases had sources of patient immunosuppression in addition to eculizumab. Three patients had sepsis (n = 2) or septic shock (n = 1). Five patients were bacteremic. All patients were hospitalized; the infections resolved with antibiotics. CONCLUSIONS: Our search identified seven cases of disease from typically commensal Neisseria spp. in eculizumab recipients. These findings suggest that any Neisseria spp. identified from a normally sterile site in an eculizumab recipient could represent true infection warranting prompt treatment.

Disseminated Gonococcal Infections in Patients Receiving Eculizumab: A Case Series.

BACKGROUND: Gonorrhea is the second most commonly reported notifiable condition in the United States. Infrequently, Neisseria gonorrhoeae can cause disseminated gonococcal infection (DGI). Eculizumab, a monoclonal antibody, inhibits terminal complement activation, which impairs the ability of the immune system to respond effectively to Neisseria infections. This series describes cases of N. gonorrhoeae infection among patients receiving eculizumab. METHODS: Pre- and postmarketing safety reports of N. gonorrhoeae infection in patients receiving eculizumab worldwide were obtained from US Food and Drug Administration safety databases and the medical literature, including reports from the start of pivotal clinical trials in 2004 through 31 December 2017. Included patients had at least 1 eculizumab dose within the 3 months prior to N. gonorrhoeae infection. RESULTS: Nine cases of N. gonorrhoeae infection were identified; 8 were classified as disseminated (89%). Of the disseminated cases, 8 patients required hospitalization, 7 had positive blood cultures, and 2 required vasopressor support. One patient required mechanical ventilation. Neisseria gonorrhoeae may have contributed to complications prior to death in 1 patient; however, the fatality was attributed to underlying disease per the reporter. CONCLUSIONS: Patients receiving eculizumab may be at higher risk for DGI than the general population. Prescribers are encouraged to educate patients receiving eculizumab on their risk for serious gonococcal infections and perform screening for sexually transmitted diseases (STDs) per the Centers for Disease Control and Prevention STD treatment guidelines or in suspected cases. If antimicrobial prophylaxis is used during eculizumab therapy, prescribers should consider trends in gonococcal antimicrobial susceptibility due to emerging resistance concerns.

Correlation between hospital-level antibiotic consumption and incident health care facility-onset Clostridium difficile infection.

BACKGROUND: The purpose of this single-center, ecologic study is to characterize the relationship between facility-wide (FacWide) antibiotic consumption and incident health care facility-onset Clostridium difficile infection (HO-CDI). METHODS: FacWide antibiotic consumption and incident HO-CDI were tallied on a monthly basis and standardized, from January 2013 through April 2015. Spearman rank-order correlation coefficients were calculated using matched-months analysis and a 1-month delay. Regression analyses were performed, with P < .05 considered statistically significant. RESULTS: FacWide analysis identified a matched-months correlation between ceftriaxone and HO-CDI (ρ = 0.44, P = .018). A unit of stem cell transplant recipients did not have significant correlation between carbapenems and HO-CDI in matched months (ρ = 0.37, P = .098), but a significant correlation was observed when a 1-month lag was applied (ρ = 0.54, P = .014). DISCUSSION: Three statistically significant lag associations were observed between FacWide/unit-level antibiotic consumption and HO-CDI, and 1 statistically significant nonlagged association was observed FacWide. Antibiotic consumption may convey extended ward-level risk for incident CDI. CONCLUSIONS: Consumption of antibiotic agents may have immediate and prolonged influence on incident CDI. Additional studies are needed to investigate the immediate and delayed associations between antibiotic consumption and C difficile colonization, infection, and transmission at the hospital level.

Days of Therapy and Antimicrobial Days: Similarities and Differences Between Consumption Metrics.

Benchmarks for antimicrobial consumption measured in antimicrobial days are beginning to emerge. The relationship between the traditional measure of days of therapy and antimicrobial days is unclear. We observed a high intermethod correlation (R2=0.99): antimicrobial days were 1.9-fold lower than days of therapy across agents. Individual institutions should correlate these measures. Infect Control Hosp Epidemiol 2016;37:971-973.

Investigating the Extremes of Antibiotic Use with an Epidemiologic Framework.

Benchmarks for judicious use of antimicrobials are needed. Metrics such as defined daily doses (DDDs) and days of therapy (DOTs) quantify antimicrobial consumption. However, benchmarking with these metrics is complicated by interhospital variability. Thus, it is important for each hospital to monitor its own temporal consumption trends. Time series analyses allow trends to be detected; however, many of these methods are complex. We present simple regressive methods and caveats in using them to define potential antibiotic over- and underutilizations.

Vancomycin dosing and monitoring for patients with end-stage renal disease receiving intermittent hemodialysis.

PURPOSE: Vancomycin dosing and monitoring algorithms for patients with end-stage renal disease (ESRD) receiving intermittent hemodialysis are reviewed. SUMMARY: Vancomycin is one of the most commonly administered antimicrobial agents in adult patients with ESRD receiving intermittent hemodialysis. However, despite the availability of many published studies, the single best method of vancomycin administration in this population remains unclear. Many studies evaluating vancomycin dosing in adult patients with ESRD receiving intermittent hemodialysis were limited by a small sample size, inappropriate therapeutic targets, older hemodialysis modalities (e.g., low-flux intermittent hemodialysis), and inconsistencies in the timing of dosing or therapeutic drug monitoring. Pharmacokinetic variables that must be accounted for include a prolonged distribution phase, a redistribution phase and rebound effect after completion of hemodialysis, patient weight, residual renal function, and nonrenal clearance. Optimal vancomycin dosing recommendations are needed, but clinicians should always consider patient-specific variables, the timing of vancomycin administration, the timing of serum vancomycin concentrations, and technical aspects of the dialysis procedure when creating a dosing regimen. CONCLUSION: Individualized vancomycin dosing regimens and therapeutic drug monitoring are necessary for patients with ESRD receiving intermittent hemodialysis to ensure that goal serum vancomycin levels are reached to adequately treat an infection.