Cognitive biases and knowledge deficits leading to delayed recognition of cryptococcal meningitis.

Cryptococcal meningitis is a potentially devastating infectious complication of immunosuppression best characterized in individuals with HIV. Early recognition of and appropriate antifungal therapy for cryptococcal meningitis has a profound effect on outcomes, but with more varied presentations in well-resourced countries recognition may be delayed. We present four cases of cryptococcal meningitis in immunosuppressed patients, each with significant delays in diagnosis. Pulling from recollections of providers and the documented chart assessments, we discuss and tabulate the cognitive biases and diagnostic errors that contributed to delay. We further explore the knowledge deficits regarding cryptococcal meningitis that appeared in these cases. Once meningitis was considered, each of these cases of cryptococcal meningitis was rapidly diagnosed. Diagnostic delay was driven by knowledge deficits, followed by common biases such as availability heuristics and premature closing. These delays could be countered by maintaining broad differential diagnoses, re-evaluating the patient presentation after recognition of immunosuppression, and early consultation of specialists. Delay in diagnosis of cryptococcal meningitis is associated with high morbidity and mortality. By exploring the various case presentations and errors made, we hope to provide a counter to some of the knowledge deficits associated with cryptococcal meningitis, and to provide actionable advice for early consultation to infectious disease specialists in order to improve outcomes.

Validation of an Antimicrobial Stewardship-Driven Verigene Blood-Culture Gram-Negative Treatment Algorithm to Improve Appropriateness of Antibiotics.

Rapid diagnostic testing (RDT) allows for early adjustment of antibiotic therapy. This study examined the potential impact of a stewardship-driven antibiotic treatment algorithm, incorporating RDT into the management of Gram-negative bacteremia. The proposed algorithm would have resulted in 88.4% of cases receiving appropriate antibiotic therapy versus 78.1% by standard of care (P = .014).

A single-center evaluation of the risk for colonization or bacteremia with piperacillin-tazobactam- and cefepime-resistant bacteria in patients with acute leukemia receiving fluoroquinolone prophylaxis.

Fluoroquinolone prophylaxis is indicated to prevent neutropenic fever in patients with acute leukemia. However, fluoroquinolone use has been associated with development of multi-drug-resistant Pseudomonas aeruginosa and extended spectrum ß-lactamase producing gram-negative bacilli. Due to a presumed risk of multi-drug resistance associated with fluoroquinolone prophylaxis, patients admitted to our hospital with neutropenic fever receive empiric carbapenem therapy until cultures are negative for 72 h or identification of an organism. Our study seeks to identify the incidence of multi-drug-resistant organism colonization and bacteremia among patients who receive fluoroquinolone prophylaxis and to evaluate duration of empiric carbapenem therapy. A retrospective review of adult patients with acute leukemia receiving a fluoroquinolone as outpatient infection prophylaxis, admitted to our tertiary cancer center for treatment of neutropenic fever was completed. Surveillance and blood cultures were reviewed for antibiotic resistance. Duration of empiric carbapenem therapy was reviewed. One hundred patients and 177 admissions for neutropenic fever were included. Six patients harbored a piperacillin-tazobactam-resistant organism found during routine surveillance. Among these patients, two bacteremias were identified, one of which was a piperacillin-tazobactam-resistant organism. Five bacteremias were identified among 83 patients with negative surveillance cultures. Among the bloodstream infections, five organisms isolated were fluoroquinolone resistant. No cefepime-resistant organism was isolated on surveillance or bloodstream cultures. Adherence to the institution guideline of narrowing antibiotics after 72 h of negative cultures occurred in only 13% of neutropenic fever cases. The average duration of carbapenem therapy in 177 neutropenic fever episodes was 4.4 days. Our findings show that among our patient population, there is a low risk of bacteremia with a piperacillin-tazobactam-resistant or cefepime-resistant organism. However, prompt de-escalation of carbapenem therapy needs to be reiterated within hospital practice.

Simeprevir: a macrocyclic HCV protease inhibitor.

Simeprevir is a macrocyclic NS3/4A HCV protease inhibitor with potent activity against genotypes 1, 2, 4, 5 and 6 of the hepatitis C virus (HCV). Phase II and III studies of simeprevir combined with pegylated interferon (peg-IFN) and ribavirin (RBV) demonstrated that the combination was safe and effective in HCV genotype 1 patients, with more than 75% of treatment-naive patients attaining a sustained virological response (SVR). Simeprevir is administered once daily as a single 150-mg capsule. It has a moderate drug interaction potential, but less than that of the first-generation HCV protease inhibitors. Based on positive results from the product's phase III clinical program, simeprevir was approved and launched in Japan, the U.S. and Canada in late 2013 for use in combination with peg-IFN/RBV in HCV genotype 1 infections. Phase II interferon-free studies of simeprevir are ongoing.