Bloodstream Infection Due to Piperacillin/Tazobactam Non-Susceptible, Cephalosporin Susceptible Escherichia Coli: A Missed Opportunity for DE-Escalation of Therapy

An increasing number of reports describing Escherichia coli isolates with piperacillin/tazobactam resistance, despite retained cephalosporin susceptibility, suggest further emergence of this phenotypic resistance pattern. In this report, a patient with metastatic breast cancer presented to medical care after two days of chills, nausea, vomiting, reduced oral intake, and generalized weakness. Blood and urine cultures grew E. coli as identified by rapid diagnostics multiplex PCR and MALDI-TOF, respectively. The patient continued to manifest signs of sepsis with hypotension and tachypnea during the first three days of hospitalization despite empirical antimicrobial therapy with intravenous piperacillin/tazobactam. After in vitro antimicrobial susceptibility testing demonstrated a piperacillin/tazobactam minimal inhibitory concentration (MIC) of 64 and a ceftriaxone MIC of ≤1 mcg/mL, antimicrobial therapy was switched from intravenous piperacillin/tazobactam to ceftriaxone. All symptoms and signs of infection resolved within 48 h of starting ceftriaxone therapy. This report describes the clinical failure of piperacillin/tazobactam in the treatment of a bloodstream infection due to E. coli harboring a phenotypic resistance pattern of isolated piperacillin/tazobactam non-susceptibility. The case demonstrates the role of cephalosporins as potential treatment options and highlights the value of early de-escalation of antimicrobial therapy based on rapid diagnostic testing for microbial identification

Direct Measurement of Performance: A New Era in Antimicrobial Stewardship

Penicillin allergies are among of the most commonly reported allergies, yet only 10% of these patients are truly allergic. This leads to potential inadvertent negative consequences for patients and makes treatment decisions challenging for clinicians. Thus, allergy assessment and penicillin skin testing (PST) are important management strategies to reconcile and clarify labeled penicillin allergies. While PST is more common in the inpatient setting where the results will immediately impact antibiotic management, this process is becoming of increasing importance in the outpatient setting. PST in the outpatient setting allows clinicians to proactively de-label and educate patients accordingly so beta-lactam antibiotics may be appropriately prescribed when necessary for future infections. While allergists have primarily been responsible for PST in the outpatient setting, there is an increasing role for pharmacist involvement in the process. This review highlights the importance of penicillin allergy assessments, considerations for PST in the outpatient setting, education and advocacy for patients and clinicians, and the pharmacist’s role in outpatient PST

Stratification of the Impact of Inappropriate Empirical Antimicrobial Therapy for Gram-Negative Bloodstream Infections by Predicted Prognosis

The bloodstream infection mortality risk score (BSIMRS) predicts the outcome of patients with Gram-negative bloodstream infections (BSI) with high discrimination. This retrospective cohort study examined the impact of inappropriate antimicrobial therapy on mortality in adult patients with Gram-negative BSI admitted to Palmetto Health Hospitals in Columbia, SC, USA, from 1 January 2011 to 31 December 2012 after stratification by predicted prognosis at initial presentation using BSIMRS. A multivariate Cox regression model was used to identify independent risk factors for 28-day mortality overall and within each predefined BSIMRS category (\u3c5, 5 to 9, and ≥10). Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) were calculated from a predictive logistic regression model of mortality. Overall, 390 unique patients with first episodes of Gram-negative BSI were identified. The median age was 66 years, and 229 (59%) were women. There was significant association between inappropriate antimicrobial therapy and mortality in patients with BSIMRS of 5 to 9 (adjusted hazard ratio [aHR], 3.55; 95% confidence intervals [CI], 1.22 to 8.31; P = 0.02) and BSIMRS of ≥10 (aHR, 4.99; 95% CI, 1.09 to 22.87; P = 0.04) but not in those with BSIMRS of \u3c5 (aHR, 3.34; 95% CI, 0.17 to 22.77; P = 0.34). RRR, ARR, and NNT were 0.25, 0.02, and 63 for BSIMRS of \u3c5; 0.56, 0.32, and 3 for BSIMRS of 5 to 9; and 0.39, 0.39, and 3 for BSIMRS of ≥10, respectively. There is a significant benefit from appropriate antimicrobial therapy in patients with Gram-negative BSI with guarded (BSIMRS of 5 to 9) and poor (BSIMRS of ≥10) predicted prognosis. Survival difference remains unclear among those with good predicted prognosis (BSIMRS of \u3c5) at initial presentation

Application of Fluoroquinolone Resistance Score in Management of Complicated Urinary Tract Infections

The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived from patients with bloodstream infections caused by Gram-negative bacteria and is based on fluoroquinolone use within the past 6 months, among other clinical and health care exposure criteria. This study aims to examine the utility of the FQRS in patients with complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA, from 1 April 2015 through 31 July 2015 were prospectively identified. Multivariate logistic regression was used to examine the association between prior fluoroquinolone use and resistance. Among 238 patients, 54 (23%) had cUTI due to fluoroquinolone-resistant bacteria. Overall, the median age was 66 years, 162 (68%) patients were women, and 137 (58%) patients had cUTI due to Prior exposure to fluoroquinolones within 3 months (adjusted odds ratio [aOR], 23.4; 95% confidence interval [CI], 8.2 to 76.8; \u3c 0.001) and within 3 to 12 months (aOR, 13.2; 95% CI, 3.1 to 68.4; \u3c 0.001) was independently associated with fluoroquinolone resistance compared to no prior use. The area under the receiver operating characteristic curve for the FQRS increased from 0.73 to 0.80 when prior fluoroquinolone use was extended from 6 to 12 months. FQRSs of ≥2 and ≥3 had negative predictive values of 91% and 90%, respectively. The modified FQRS stratifies patients with cUTI on the basis of the predicted probability of fluoroquinolone resistance with very good discrimination. Application of the modified FQRS may improve antimicrobial utilization in patients with acute pyelonephritis

Asthma and Risk of Non-Respiratory Tract Infection: A Population-Based Case-Control Study

OBJECTIVES: Asthmatics have increased risks of airway-related infections. Little is known about whether this is true for non-airway-related serious infections such as Escherichia coli bloodstream infection (BSI). We assessed whether asthma is associated with a risk of developing community-acquired E coli BSI. DESIGN: The study was designed as a population-based retrospective case-control study. SETTING: This population-based study was conducted in Olmsted County, Minnesota. PARTICIPANTS: The study included 259 all eligible community-acquired E coli BSI cases in Olmsted County, MN between 1998 and 2007 and 259 birthday-matched, gender-matched and residency-matched controls. PRIMARY AND SECONDARY OUTCOME MEASURES: Only community-acquired E coli BSI cases as the primary outcome was included. Asthma status as an exposure was ascertained by predetermined criteria. An adjusted OR and 95% CI for the association between asthma and risk of community-acquired E coli BSI was calculated using conditional logistic regression. RESULTS: Of 259 eligible cases, 179 (69%) were women and mean age was 61±22 years. Of the 259 cases 37 (14%) and 16 (6%) of 259 controls had a prior history of asthma (adjusted OR 2.74; 95% CI 1.11 to 6.76; p=0.029). The population attributable risk of asthma for community-acquired E coli BSI was 9%. Although not statistically significant, there was a borderline association between having a history of food allergy and increased risk of community-acquired E coli BSI (6% vs 2%; adjusted OR 3.51; 95% CI 0.94 to 13.11; p=0.062). CONCLUSIONS: Based on the findings of the current population-based, case-control investigation, a history of asthma may be associated with risk of community-acquired E coli BSI. The impact of asthma on risk of microbial infections may go beyond airways

Evaluating Appropriateness and Diagnostic Stewardship Opportunities of Multiplex Polymerase Chain Reaction Gastrointestinal Testing Within a Hospital System

Objective: This single-center, retrospective, observational cohort study evaluates the appropriateness of the BioFire® FilmArray® Gastrointestinal (GI) multiplex PCR panel testing at a community-teaching hospital. Methods: All adult, hospitalized patients at Prisma Health Richland Hospital with a documented GI multiplex PCR panel from 1 April 2015 through 28 February 2018 were included in the analysis. Inappropriate use of the GI panel was defined as a test obtained without documented diarrhea, greater than 2 days of hospitalization, redundant use with other diagnostic tests (e.g. PCR), or laxative use in the preceding 48 h. Antibiotic use and host variables were compared between groups with positive and negative results. Results: During the study period, 442 GI panels were obtained, among which 268 (61%) were deemed inappropriate. Primary reasons for inappropriate testing were lack of documented diarrhea ( = 92), greater than 2 days of hospitalization ( = 116), having a duplicate PCR test ordered ( = 118), or laxative use in the 48 h before testing ( = 36). A total of 141 (32%) GI panels were positive. The most frequently identified pathogens were (51.1%,  = 72), Enteropathogenic (17.7%,  = 25), and Norovirus GI/GII (12.1%,  = 17). Patients with negative GI panel results were initiated on antibiotics significantly less frequently than those with positive GI panels (62.5% 80.2%,  \u3c 0.00001). Conclusion: Stewardship opportunities exist to optimize the diagnostic application of the GI multiplex PCR panel

Impact of Follow up Blood Cultures on Outcomes of Patients with Community-Onset Gram-Negative Bloodstream Infection

Background: The role of follow up blood cultures (FUBC) in the management of gram-negative bloodstream infection (GN-BSI) remains controversial. This retrospective cohort study examines the association between obtaining FUBC and mortality in GN-BSI. Methods: Hospitalized adults with community-onset GN-BSI at Prisma Health-Midlands hospitals in South Carolina, USA from January 1, 2010 to June 30, 2015 were identified. Patients who died or were discharged from hospital within 72 h were excluded to minimize impact of survival and selection biases on results, respectively. Multivariate Cox proportional hazards regression was used to examine association between obtaining FUBC and 28-day all-cause mortality after adjustment for the propensity to obtain FUBC. Findings: Among 766 patients with GN-BSI, 219 (28.6%) had FUBC obtained and 15 of 219 (6.8%) FUBC were persistently positive. Overall, median age was 67 years, 438 (57%) were women, 457 (60%) had urinary source of infection, and 426 (56%) had BSI due to . Mortality was significantly lower in patients who had FUBC obtained than in those who did not have FUBC (6.3% vs. 11.7%, log-rank = 0.03). Obtaining FUBC was independently associated with reduced mortality (hazards ratio 0.47, 95% confidence intervals: 0.23-0.87; 0.02) after adjustments for age, chronic comorbidities, acute severity of illness, appropriateness of empirical antimicrobial therapy, and propensity to obtain FUBC. Interpretation: Improved survival in hospitalized patients with GN-BSI who had FUBC is consistent with the results of recent publications from Italy and North Carolina supporting utilization of FUBC in management of GN-BSI. Funding: This study had no funding source

Impact of Reappraisal of Fluoroquinolone Minimum Inhibitory Concentration Susceptibility Breakpoints in Gram-Negative Bloodstream Isolates

The Clinical Laboratory Standards Institute lowered the fluoroquinolone minimum inhibitory concentration (MIC) susceptibility breakpoints for and glucose non-fermenting Gram-negative bacilli in January 2019. This retrospective cohort study describes the impact of this reappraisal on ciprofloxacin susceptibility overall and in patients with risk factors for antimicrobial resistance. Gram-negative bloodstream isolates collected from hospitalized adults at Prisma Health-Midlands hospitals in South Carolina, USA, from January 2010 to December 2014 were included. Matched pairs mean difference (MD) with 95% confidence intervals (CI) were calculated to examine the change in ciprofloxacin susceptibility after MIC breakpoint reappraisal. Susceptibility of to ciprofloxacin declined by 5.2% (95% CI: -6.6, -3.8; \u3c 0.001) after reappraisal. The largest impact was demonstrated among bloodstream isolates (MD -7.8, 95% CI: -14.6, -1.1; = 0.02) despite more conservative revision in ciprofloxacin MIC breakpoints. Among antimicrobial resistance risk factors, fluoroquinolone exposure within the previous 90 days was associated with the largest change in ciprofloxacin susceptibility (MD -9.3, 95% CI: -16.1, -2.6; = 0.007). Reappraisal of fluoroquinolone MIC breakpoints has a variable impact on the susceptibility of bloodstream isolates by microbiology and patient population. Healthcare systems should be vigilant to systematically adopt this updated recommendation in order to optimize antimicrobial therapy in patients with bloodstream and other serious infections

Prediction of Fluoroquinolone Resistance in Gram-Negative Bacteria Causing Bloodstream Infections

Increasing rates of fluoroquinolone resistance (FQ-R) have limited empirical treatment options for Gram-negative infections, particularly in patients with severe beta-lactam allergy. This case-control study aims to develop a clinical risk score to predict the probability of FQ-R in Gram-negative bloodstream isolates. Adult patients with Gram-negative bloodstream infections (BSI) hospitalized at Palmetto Health System in Columbia, South Carolina, from 2010 to 2013 were identified. Multivariate logistic regression was used to identify independent risk factors for FQ-R. Point allocation in the fluoroquinolone resistance score (FQRS) was based on regression coefficients. Model discrimination was assessed by the area under receiver operating characteristic curve (AUC). Among 824 patients with Gram-negative BSI, 143 (17%) had BSI due to fluoroquinolone-nonsusceptible Gram-negative bacilli. Independent risk factors for FQ-R and point allocation in FQRS included male sex (adjusted odds ratio [aOR], 1.97; 95% confidence intervals [CI], 1.36 to 2.98; 1 point), diabetes mellitus (aOR, 1.54; 95% CI, 1.03 to 2.28; 1 point), residence at a skilled nursing facility (aOR, 2.28; 95% CI, 1.42 to 3.63; 2 points), outpatient procedure within 30 days (aOR, 3.68; 95% CI, 1.96 to 6.78; 3 points), prior fluoroquinolone use within 90 days (aOR, 7.87; 95% CI, 4.53 to 13.74; 5 points), or prior fluoroquinolone use within 91 to 180 days of BSI (aOR, 2.77; 95% CI, 1.17 to 6.16; 3 points). The AUC for both final logistic regression and FQRS models was 0.73. Patients with an FQRS of 0, 3, 5, or 8 had predicted probabilities of FQ-R of 6%, 22%, 39%, or 69%, respectively. The estimation of patient-specific risk of antimicrobial resistance using FQRS may improve empirical antimicrobial therapy and fluoroquinolone utilization in Gram-negative BSI