Administration of a β-lactam Prior to Vancomycin as the First Dose of Antibiotic Therapy Improves Survival in Patients with Bloodstream Infections.

2021

2021 Oct 04

1537-6591

OBJECTIVE: Prompt initiation of antibiotic therapy improves the survival of patients with bloodstream infections (BSI). We sought to determine if the sequence of administration of the first dose of antibiotic therapy (i.e., β-lactam or vancomycin, if both cannot be administered simultaneously) impacts early mortality for patients with BSI.

METHODS: We conducted a multicenter, observational study of patients ≥13 years with BSIs to evaluate the association of the sequence of antibiotic administration with 7-day mortality using inverse probability of treatment weighting (IPTW) incorporating propensity scores. Propensity scores were generated based on: demographics, Pitt bacteremia score, ICU status, highest lactate, highest WBC count, Charlson Comorbidity index, severe immunocompromise, administration of active empiric therapy, combination therapy, and time from emergency department arrival to first antibiotic dose.

RESULTS: Of 3,376 eligible patients, 2,685 (79.5%) received a β-lactam and 691 (20.5%) received vancomycin as their initial antibiotic. In the IPTW cohort, exposed and unexposed patients were similar on all baseline variables. Administration of a β-lactam agent prior to vancomycin protected against 7-day mortality (aOR 0.48 (95% CI: 0.33-0.69)]. Similar results were observed when evaluating 48-hour mortality (aOR 0.45 [95% CI: 0.24-0.83]). Administration of vancomycin prior to a β-lactam was not associated with improved survival in the subgroup of 524 patients with methicillin-resistant Staphylococcus aureus BSI (aOR 0.93 [95% CI: 0.33-2.63]).

CONCLUSIONS: For ill-appearing patients likely to be experiencing a BSI, prioritizing administration of a β-lactam over vancomycin may reduce early mortality, underscoring the significant impact of a relatively simple practice change on improving patient survival.

10.1093/cid/ciab865

Clin Infect Dis

34606585

Improving Outpatient Antibiotic Prescribing for Respiratory Tract Infections in Primary Care; a Stepped-Wedge Cluster Randomized Trial.

2021

2021 Jul 02

1537-6591

<p><strong>BACKGROUND: </strong>Inappropriate antibiotic prescribing is common in primary care (PC), particularly for respiratory tract diagnoses (RTDs). However, the optimal approach for improving prescribing remains unknown.</p>

<p><strong>METHODS: </strong>We conducted a stepped-wedge study in PC practices within a health system to assess the impact of a provider-targeted intervention on antibiotic prescribing for RTDs. RTDs were grouped into tiers based on appropriateness of antibiotic prescribing: tier 1 (almost always indicated), tier 2 (may be indicated), and tier 3 (rarely indicated). Providers received education on appropriate RTD prescribing followed by monthly peer comparison feedback on antibiotic prescribing for (1) all tiers and (2) tier 3 RTDs. Chi-squared testing was used to compare the proportion of visits with antibiotic prescriptions before and during the intervention. Mixed-effects multivariable logistic regression analysis was performed to assess the association between the intervention and antibiotic prescribing.</p>

<p><strong>RESULTS: </strong>Across 30 PC practices and 185,755 total visits, overall antibiotic prescribing was reduced with the intervention, from 35.2% to 23.0% of visits (p&lt;0.001). In multivariable analysis, the intervention was associated with a reduced odds of antibiotic prescription for tiers 2 (OR 0.57; 95% CI 0.52 - 0.62) and 3 (OR 0.57; 95% CI 0.53 - 0.61), but not for tier 1 (OR 0.98; 95% CI 0.83 - 1.16).</p>

<p><strong>CONCLUSION: </strong>A provider-focused intervention reduced overall antibiotic prescribing for RTDs without affecting prescribing for infections that likely require antibiotics. Future research should examine the sustainability of such interventions, potential unintended adverse effects on patient health or satisfaction, and provider perceptions and acceptability.</p>

10.1093/cid/ciab602

Clin Infect Dis

34212177

Pediatric research priorities in healthcare-associated infections and antimicrobial stewardship.

2020

1-4

2020 Nov 26

1559-6834

<p><strong>OBJECTIVE: </strong>To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.</p>

<p><strong>PARTICIPANTS: </strong>The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).</p>

<p><strong>METHODS: </strong>Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.</p>

<p><strong>RESULTS: </strong>A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level "harm index" for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.</p>

<p><strong>CONCLUSIONS: </strong>We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.</p>

10.1017/ice.2020.1267

Infect Control Hosp Epidemiol

33239122

Prescriber perceptions of fluoroquinolones, extended-spectrum cephalosporins, and infection.

2020

1-7

2020 May 29

1559-6834

<p><strong>BACKGROUND: </strong>Fluoroquinolones (FQs) and extended-spectrum cephalosporins (ESCs) are associated with higher risk of Clostridioides difficile infection (CDI). Decreasing the unnecessary use of FQs and ESCs is a goal of antimicrobial stewardship. Understanding how prescribers perceive the risks and benefits of FQs and ESCs is needed.</p>

<p><strong>METHODS: </strong>We conducted interviews with clinicians from 4 hospitals. Interviews elicited respondent perceptions about the risk of ESCs, FQs, and CDI. Interviews were audio recorded, transcribed, and analyzed using a flexible coding approach.</p>

<p><strong>RESULTS: </strong>Interviews were conducted with 64 respondents (38 physicians, 7 nurses, 6 advance practice providers, and 13 pharmacists). ESCs and FQs were perceived to have many benefits, including infrequent dosing, breadth of coverage, and greater patient adherence after hospital discharge. Prescribers stated that it was easy to make decisions about these drugs, so they were especially appealing to use in the context of time pressures. They described having difficulty discontinuing these drugs when prescribed by others due to inertia and fear. Prescribers were skeptical about targeting specific drugs as a stewardship approach and felt that the risk of a negative outcome from under treatment of a suspected bacterial infection was a higher priority than the prevention of CDI.</p>

<p><strong>CONCLUSIONS: </strong>Prescribers in this study perceived many advantages to using ESCs and FQs, especially under conditions of time pressure and uncertainty. In making decisions about these drugs, prescribers balance risk and benefit, and they believed that the risk of CDI was acceptable in compared with the risk of undertreatment.</p>

10.1017/ice.2020.183

Infect Control Hosp Epidemiol

32468967

Implementation of a Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: the Optimizing Antibiotic Strategies in Sepsis (OASIS) II Study.

2018

2018 Nov 22

2048-7207

<p><strong>Background: </strong>Biomarkers can facilitate safe antibiotic discontinuation in critically ill patients without bacterial infection.</p>

<p><strong>Methods: </strong>We tested the ability of a biomarker-based algorithm to reduce excess antibiotic administration in patients with systemic inflammatory response syndrome (SIRS) without bacterial infections (uninfected) in our pediatric intensive care unit (PICU). The algorithm suggested that PICU clinicians stop antibiotics if (1) C-reactive protein &lt;4 mg/dL and procalcitonin &lt;1 ng/mL at SIRS onset and (2) no evidence of bacterial infection by exam/testing by 48 hours. We evaluated excess broad-spectrum antibiotic use, defined as administration on days 3-9 after SIRS onset in uninfected children. Incidence rate ratios (IRRs) compared unadjusted excess length of therapy (LOT) in the 34 months before (Period 1) and 12 months after (Period 2) implementation of this algorithm, stratified by biomarker values. Segmented linear regression evaluated excess LOT among all uninfected episodes over time and between the periods.</p>

<p><strong>Results: </strong>We identified 457 eligible SIRS episodes without bacterial infection, 333 in Period 1 and 124 in Period 2. When both biomarkers were below the algorithm's cut-points (n = 48 Period 1, n = 31 Period 2), unadjusted excess LOT was lower in Period 2 (IRR, 0.53; 95% confidence interval, 0.30-0.93). Among all 457 uninfected episodes, there were no significant differences in LOT (coefficient 0.9, P = .99) between the periods on segmented regression.</p>

<p><strong>Conclusions: </strong>Implementation of a biomarker-based algorithm did not decrease overall antibiotic exposure among all uninfected patients in our PICU, although exposures were reduced in the subset of SIRS episodes where biomarkers were low.</p>

10.1093/jpids/piy113

J Pediatric Infect Dis Soc

30476186

High fluoroquinolone MIC is associated with fluoroquinolone treatment failure in urinary tract infections caused by fluoroquinolone susceptible Escherichia coli.

2017

25

2017 Apr 08

1476-0711

<p><strong>BACKGROUND: </strong>Suboptimal clinical response to fluoroquinolone (FQ) therapy has been clearly documented in patients with Salmonella typhi infection with reduced FQ susceptibility. However, the clinical impact of reduced FQ susceptibility on other infections including E. coli urinary tract infections (UTIs) has never been evaluated.</p>

<p><strong>METHODS: </strong>We conducted a retrospective cohort study of female patients with fluoroquinolone susceptible E. coli (FQSEC) UTIs who received FQ therapy at outpatient services within University of Pennsylvania Health System, Philadelphia. Exposed patients were those with high MIC-FQSEC UTIs (the levofloxacin MIC&nbsp;&gt;&nbsp;0.12 but&nbsp;≤&nbsp;2&nbsp;mg/L) while unexposed patients were those with low MIC-FQSEC UTIs (the levofloxacin MIC&nbsp;≤&nbsp;0.12&nbsp;mg/L). The primary treatment outcome was treatment failure within 10&nbsp;weeks after initiation of FQ therapy.</p>

<p><strong>RESULTS: </strong>From May 2008 to April 2011, we enrolled 29 exposed patients and 246 unexposed patients. Two patients in each group experienced treatment failure; exposed vs. unexposed (6.9 vs. 0.8%; p&nbsp;=&nbsp;0.06). Risk difference and risk ratio (RR) for treatment failure were 0.06 [95% CI -0.03-0.15; exact-p&nbsp;=&nbsp;0.06] and 8.48 [95% CI 1.24-57.97; exact-p&nbsp;=&nbsp;0.06], respectively. After adjusting for underlying cerebrovascular disease, the RR was 7.12 (95% CI 1.20-42.10; MH-p&nbsp;=&nbsp;0.04).</p>

<p><strong>CONCLUSION: </strong>Our study demonstrated the negative impact of reduced FQ susceptibility on the treatment response to FQ therapy in FQSEC UTIs. This negative impact may be more intensified in other serious infections. Future studies in other clinical situations should be conducted to fill the gap of knowledge.</p>

10.1186/s12941-017-0202-4

Ann. Clin. Microbiol. Antimicrob.

28390438

Factors associated with persistent colonisation with methicillin-resistant Staphylococcus aureus.

2017

1-9

2017 Feb 21

1469-4409

<p>We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.</p>

10.1017/S0950268817000012

Epidemiol. Infect.

28219463

The Effect of Total Household Decolonization on Clearance of Colonization With Methicillin-Resistant Staphylococcus aureus.

2016

1-8

2016 Jul 28

1559-6834

<p>OBJECTIVE To determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection. DESIGN Three-arm nonmasked randomized controlled trial. SETTING Five academic medical centers in Southeastern Pennsylvania. PARTICIPANTS Adults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members. INTERVENTION Enrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders. MAIN OUTCOME MEASURES Owing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case. RESULTS Of 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018). CONCLUSIONS Total household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearance Trial registration. ClinicalTrials.gov identifier: NCT00966446 Infect Control Hosp Epidemiol 2016;1-8.</p>

10.1017/ice.2016.138

Infect Control Hosp Epidemiol

27465112

Risk factors for ambulatory urinary tract infections caused by high-MIC fluoroquinolone-susceptible Escherichia coli in women: results from a large case-control study.

2015

1547-51

2015 May

1460-2091

<p><strong>OBJECTIVES: </strong>The prevalence of high-MIC fluoroquinolone-susceptible Escherichia coli (FQSEC) has been increasing. These isolates are one step closer to full fluoroquinolone (FQ) resistance and may lead to delayed response to FQ therapy. Our study aimed to investigate the epidemiology of high-MIC FQSEC in ambulatory urinary tract infections (UTIs).</p>

<p><strong>PATIENTS AND METHODS: </strong>A case-control study was conducted at outpatient services within the University of Pennsylvania Health System, Philadelphia. All female subjects with non-recurrent UTI caused by FQSEC (levofloxacin MIC &lt; 4 mg/L) were enrolled. Cases were subjects with high-MIC FQSEC UTI (levofloxacin MIC &gt;0.12 but &lt; 4 mg/L) and controls were subjects with low-MIC FQSEC UTI (levofloxacin MIC ≤0.12 mg/L). Data on microbiology results and baseline characteristics were extracted from electronic medical records.</p>

<p><strong>RESULTS: </strong>During the 3 year study period (May 2008-April 2011), 11 287 episodes of E. coli bacteriuria were identified. The prevalence of FQSEC, FQ-intermediate susceptible E. coli and FQ-resistant E. coli was 75.0%, 0.4% and 24.6%, respectively. A total of 2001 female subjects with FQSEC UTI were enrolled into our study (165 cases and 1836 controls). Independent risk factors for high-MIC FQ susceptibility included Asian race (OR = 2.92; 95% CI = 1.29-6.58; P = 0.02), underlying renal disease (OR = 2.18; 95% CI = 1.15-4.14; P = 0.02) and previous nitrofurantoin exposure (OR = 8.86; 95% CI = 1.95-40.29; P = 0.005).</p>

<p><strong>CONCLUSIONS: </strong>Asian race, underlying renal disease and previous exposure to nitrofurantoin were identified as independent risk factors for high-MIC FQSEC. There may be some factors that are more common in Asians, which may result in the selection of high-MIC FQSEC. Further studies are necessary to explore these findings.</p>

10.1093/jac/dku548

J. Antimicrob. Chemother.

25630645