Evaluation of a two step testing algorithm to improve diagnostic accuracy and stewardship of Clostridioides difficile infections.

In response to national guidelines, we implemented a two-step testing algorithm for Clostridioides difficile in an effort to improve diagnostic accuracy. Following implementation, we analyzed treatment frequency between discordant and concordant patients. We found that the majority of discordant cases were treated with no significant differences in patient characteristics or outcomes between the concordant and discordant groups. Additionally, there were no differences in outcomes when discordant patients were further stratified by treatment status. Given little added diagnostic accuracy with the addition of EIA toxin testing, our facility resumed diagnosis by PCR testing alone. Further studies are needed to investigate alternative processes for improvement in diagnostic accuracy aside from toxin EIA testing including stool submission criteria and educational programs.

A Multidisciplinary Approach to Improvements in Perioperative Antibiotic Prophylaxis at a Military Treatment Facility.

INTRODUCTION: Surgical site infections complicate 2%-5% of surgeries. According to the Centers for Disease Control and Prevention, half of all surgical site infections are preventable. Adherence to published recommendations regarding perioperative antibiotic administration decreases the incidence of surgical site infections. Members of the Department of Anesthesia noticed casual observations of inaccurate prescribing of antibiotics at our institution, Brooke Army Medical Center, and approached the Antimicrobial Stewardship Program to collaborate on this issue. MATERIALS AND METHODS: A team of anesthesiologists, clinical pharmacists, and infectious disease specialists collaborated with the Department of Surgery to improve this effort as part of a multiyear project from 2018 to 2021. We first assessed adherence to recommended perioperative antibiotic use to establish a baseline and next, noticing gaps, created a project with the goal to improve compliance to >90% across surveyed measures. Our key interventions included educational initiatives, creation of facility-specific guidelines, peer benchmarking, updating order sets, interdisciplinary collaboration, creation of intraoperative reminders and visual aids, and tailored presentations to selected services. RESULTS: Of 292 charts (2.3% of cases from January to October 2018) reviewed pre-intervention, compliance rates were 84% for antibiotic choice, 92% for dose, 65% for redosing, and 71% for postoperative administration. Of doses, 100% were timed correctly, and thus, this variable was not targeted. Post-intervention, our review of 387 charts (10% of cases from May to November 2020) showed no change in correct antibiotic choice (84%) and statistical improvement to 96% for correct dose, 95% for correct redosing, and 85% for correct postoperative administration (P < .05 for all). CONCLUSIONS: Our multidisciplinary approach of collaboration with multiple departments, creating guidelines and providing feedback, improved compliance with perioperative antibiotic administration recommendations.

Comparing outcomes among outpatients treated for pyelonephritis with oral cephalosporins versus first-line agents.

Fluoroquinolones and trimethoprim/sulfamethoxazole (TMP-SMX) are first-line agents for acute pyelonephritis. Oral ß-lactams are second-line agents owing to reported lower efficacy rates, primarily seen with aminopenicillins rather than cephalosporins. The increase in resistance rates and adverse effects associated with first-line agents provides justification to reconsider oral cephalosporins for pyelonephritis. Therefore, the objective of this study was to determine whether there is a difference in urinary tract infection (UTI) recurrence rates between oral cephalosporins and first-line agents in the treatment of acute pyelonephritis. This was a retrospective, single-centre, observational cohort study from 1 December 2018 to 31 May 2020. The study population was adult TRICARE beneficiaries with a diagnosis of acute pyelonephritis who were treated with oral antibiotics. The two cohorts compared were first-line antibiotics (ciprofloxacin, levofloxacin and TMP-SMX) and oral cephalosporins. The primary outcome was UTI recurrence rate at 30 days, which was defined as a repeat clinic visit, emergency department visit or hospital admission for a UTI (cystitis or pyelonephritis). The secondary outcome was to determine independent risk factors for UTI recurrence. A total of 268 cephalosporin and 211 first-line cases were included. The primary composite outcome of UTI recurrence within 30 days occurred in 44 (16%) cephalosporin and 36 (17%) first-line cases (P = 0.851). Independent risk factors for UTI recurrence were chronic kidney disease and Klebsiella spp. isolation. In conclusion, there was no significant difference in UTI recurrence rates between oral cephalosporins and first-line agents in the treatment of acute pyelonephritis in the outpatient setting.

Evaluating outcomes associated with revised fluoroquinolone breakpoints for Enterobacterales urinary tract infections: A retrospective cohort study.

PURPOSE: In 2019, minimum inhibitory concentration (MIC) breakpoints of ciprofloxacin and levofloxacin for Enterobacterales were lowered. This study sought to determine whether there is a correlation between MIC and outcomes in those receiving fluoroquinolones (FQs) for urinary tract infections (UTIs) caused by Enterobacterales pathogens. METHODS: This was a retrospective study of adult patients treated with ciprofloxacin or levofloxacin for a UTI caused by an Enterobacterales pathogen. Patients were placed into low MIC (ciprofloxacin: ≤ 0.25 mcg/mL; levofloxacin ≤ 0.5 mcg/mL), intermediate MIC (ciprofloxacin: 0.5-2 mcg/mL; levofloxacin: 1-4 mcg/mL), or high MIC groups (ciprofloxacin: > 2 mcg/mL; levofloxacin: > 4 mcg/mL). The primary outcome was UTI recurrence, defined as hospital admission, emergency department or clinic visit due to UTI, or antibiotic prescription within 28 days of FQ initiation. RESULTS: A total of 1022 patients were included: 887, 75, and 60 with a low, intermediate, and high MIC, respectively. UTI recurrence within 28 days occurred most frequently in the high MIC group (20.5% vs. 25.3% vs. 60%; P < 0.01). Risk factors for UTI recurrence identified by multivariable analysis were those with a high MIC (high vs. low MIC: OR 5.20, 95% CI 2.99-9.05, P < 0.01; high vs. intermediate MIC: OR 4.72, 95%CI 2.22-10.03, P < 0.01), a complicated UTI (OR 1.85, 95% CI 1.35-2.54; P < 0.01), a history of recurrent UTIs (OR 1.84, 95% CI 1.29-2.62; P < 0.01), or a respiratory disorder (OR 1.58, 95% CI 1.04-2.42; P = 0.03). CONCLUSION: This study supports separate, less stringent FQ MIC breakpoint interpretive criteria for UTIs caused by Enterobacterales pathogens.

Evaluation of the trends and appropriateness of fluoroquinolone use in the outpatient treatment of acute uncomplicated cystitis at five family practice clinics.

WHAT IS KNOWN AND OBJECTIVE: Despite recommendations to avoid fluoroquinolones (FQs) as a first-line treatment for uncomplicated cystitis, recent data suggest that FQs remain widely prescribed. Therefore, the objectives of this study were to evaluate the appropriateness of empiric FQ use compared to nitrofurantoin for uncomplicated cystitis and to determine whether there are any trends or predictors of empiric FQ versus nitrofurantoin use for uncomplicated cystitis. METHODS: This retrospective study included women ages 19-64 years who were seen at five family medicine clinics and were prescribed targeted antibiotics (nitrofurantoin, ciprofloxacin or levofloxacin) for uncomplicated cystitis. Charts were reviewed to collect data, including symptoms, comorbidities, allergies, creatinine clearance, recent antibiotic use and urine culture data. Appropriateness of empiric selection was determined based on national guidelines and local susceptibility data. RESULTS AND DISCUSSION: A total of 677 patient encounters were screened for inclusion. Of those, 567 met the inclusion criteria: 395 nitrofurantoin and 172 FQs. Treatment was considered appropriate in 86.8% and 10.5% of cases that were prescribed nitrofurantoin and FQs, respectively (P < .01). There were four independent predictors of FQ use identified by multivariate logistical regression: clinic at which the patient was treated, age, nitrofurantoin use within 90 days prior to encounter and previous urine culture within one year with an organism non-susceptible to nitrofurantoin. WHAT IS NEW AND CONCLUSION: Despite recommendations against FQs for uncomplicated cystitis, they continue to be widely prescribed, and their use for this indication is often inappropriate. This highlights the need for additional interventions and education to improve use and preserve the utility of FQs.

Improvement in adherence to antibiotic duration of therapy recommendations for uncomplicated cystitis: a quasi-experimental study.

BACKGROUND: Acute uncomplicated cystitis is one of the most common diagnoses for which antibiotic treatment is prescribed in the outpatient setting. Despite the availability of national guidelines, there remains a wide pattern in prescriber choices for therapy. Recent data portray a picture of consistently longer durations than recommended prescribed in outpatient settings. OBJECTIVE: The objective was to evaluate the effect of a system-based intervention on adherence to guideline-recommended durations of therapy for uncomplicated cystitis in the outpatient setting. METHODS: This quasi-experimental study included women aged 18-64 years who were seen at five family medicine clinics at an academic medical centre and were prescribed targeted antibiotics for uncomplicated cystitis (nitrofurantoin monohydrate/macrocrystals 100 mg, trimethoprim-sulfamethoxazole 160/800 mg or ciprofloxacin 250 mg). The intervention involved revising or adding pre-filled, but modifiable, default prescribing instructions in the electronic health record (EHR) for the targeted antibiotics. We evaluated adherence to guideline-recommended duration of therapy as well as days of therapy (DOT) before and after the intervention. RESULTS: A total of 787 pre-intervention and 862 post-intervention cases were included. Adherence to recommended duration of therapy increased from 29.4% to 76.3% (P < 0.01). The average DOT decreased by 23% from 6.6 to 5.1 (P < 0.01). CONCLUSION: A stewardship intervention consisting of revising/adding default prescribing instructions to targeted antimicrobials in an EHR was associated with increased adherence to recommended durations of therapy for uncomplicated cystitis and reduction of unnecessary antibiotic exposure. More studies are needed to confirm effectiveness across multiple medical record platforms.

Evaluation of a pharmacy-driven methicillin-resistant Staphylococcus aureus surveillance protocol in pneumonia.

Background Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of pneumonia and clinicians must determine when empiric antimicrobial therapy directed toward MRSA is needed. Objective To evaluate the effect of a pharmacy-driven protocol utilizing the nasal swab MRSA polymerase chain reaction (PCR) test to discontinue vancomycin on duration of vancomycin therapy and clinical outcomes in patients with suspected community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP). Setting A teaching hospital in Huntington, WV, USA. Methods This retrospective study included adult patients who received at least one dose of vancomycin for suspected CAP or HCAP. The pre-intervention group consisted of patients prior to the addition of the nasal swab MRSA PCR test to the CAP/HCAP order set. The post-intervention group consisted of patients after the addition of the nasal swab MRSA PCR test to the CAP/HCAP order set. Main outcome measure The primary outcome was vancomycin hours of therapy. Results Of the 196 patients included in the study, 121 patients were in the pre-intervention group and 75 patients were in the post-intervention group. The median duration of vancomycin therapy was significantly shorter in the post-intervention group than the pre-intervention group (49 vs. 18 h, p < 0.001). There were no statistically significant differences in the secondary outcomes including hospital length of stay, 30-day readmission rate, and in-hospital all-cause mortality. Conclusion The addition of a pharmacy-driven protocol utilizing the nasal swab MRSA PCR test was associated with shorter duration of empiric vancomycin therapy by approximately 31 h per patient without increasing adverse clinical outcomes.

A Propensity-Matched Analysis Between Standard Versus Tapered Oral Vancomycin Courses for the Management of Recurrent Clostridium difficile Infection.

BACKGROUND: This study was conducted to compare clinical outcomes of oral vancomycin courses without taper versus oral vancomycin courses with taper for treatment of recurrent Clostridium difficile infection (CDI). METHODS: This investigation was a multicenter, retrospective, propensity score-matched analysis study using a Veterans Health Administration national clinical administrative database. Adult patients who were treated for recurrent CDI from any Veterans Affairs Medical Center between June 1, 2011 and October 31, 2016 were included if they were treated with oral vancomycin with or without a tapering regimen. The 2 groups were matched by next-nearest approach from a propensity score formula derived from independent variables associated with the selection of a taper regimen. RESULTS: Propensity score matching resulted in 2 well-matched groups consisting of 226 episodes of patients treated with a vancomycin taper regimen and 678 episodes treated by vancomycin regimen without taper. No difference was found for the primary outcome of 180-day recurrence (59 of 226 [26.1%] for taper regimens versus 161 of 678 [23.8%], P = .48). A secondary outcome of 90-day all-cause mortality met statistical significance, favoring a taper regimen (5.31% vs 9.29%, P = .049); however, secondary outcomes of 90-day recurrence and 180-day all-cause mortality were not different. CONCLUSIONS: Vancomycin taper regimens did not provide benefit over vancomycin regimens without taper in preventing additional CDI recurrence in patients with first or second recurrent episodes in this propensity score-matched analysis.

Assessment of Fosfomycin for Complicated or Multidrug-Resistant Urinary Tract Infections: Patient Characteristics and Outcomes.

BACKGROUND: Bacterial resistance among uropathogens is on the rise and has led to a decreased effectiveness of oral therapies. Fosfomycin tromethamine (fosfomycin) is indicated for uncomplicated urinary tract infections (UTIs) and displays in vitro activity against multidrug-resistant (MDR) isolates; however, clinical data assessing fosfomycin for the treatment of complicated or MDR UTIs are limited. METHODS: We conducted a retrospective evaluation of patients who received ≥1 dose of fosfomycin between January 2009 and September 2015 for treatment of a UTI. Patients were included if they had a positive urine culture and documented signs/symptoms of a UTI. RESULTS: Fifty-seven patients were included; 44 (77.2%) had complicated UTIs, 36 (63.2%) had MDR UTIs, and a total of 23 (40.4%) patients had a UTI that was both complicated and MDR. The majority of patients were female (66.7%) and elderly (median age, 79 years). Overall, the most common pathogens isolated were Escherichia coli (n = 28), Enterococcus spp. (n = 22), and Pseudomonas aeruginosa (n = 8). Twenty-eight patients (49.1%) were clinically evaluable; the preponderance achieved clinical success (96.4%). Fifteen out of 20 (75%) patients with repeat urine cultures had a microbiological cure. CONCLUSIONS: This retrospective study adds to the limited literature exploring alternative therapies for complicated and MDR UTIs with results providing additional evidence that fosfomycin may be an effective oral option.

Clinical utility of a nasal swab methicillin-resistant Staphylococcus aureus polymerase chain reaction test in intensive and intermediate care unit patients with pneumonia.

This retrospective study aimed to validate the concordance between nasal swab methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) test and respiratory culture and to determine the number of potentially preventable days of anti-MRSA therapy in patients with pneumonia. Two hundred adult inpatients in the intensive and intermediate care units were included. The nasal swab MRSA PCR test was positive in 55 (27.5%) patients. MRSA was isolated from respiratory culture in 21 (10.5%) patients. The nasal swab MRSA PCR test demonstrated 90.5% sensitivity, 79.9% specificity, 34.5% positive predictive value, and 98.6% negative predictive value. Anti-MRSA therapy was initiated in 168 (84%) patients. Patients in the study received a combined 782days of anti-MRSA therapy; 300days were considered potentially preventable. This study suggests that the nasal swab MRSA PCR test may be used to guide discontinuation of anti-MRSA antibiotics in patients with clinically confirmed pneumonia in the intensive or intermediate care units.

Critical evaluation of ceftolozane-tazobactam for complicated urinary tract and intra-abdominal infections.

The rise in resistant Gram-negative pathogens continues to challenge clinicians treating infections. These resistant infections have inspired the development of new antimicrobial agents, including ceftolozane-tazobactam, a novel ß-lactam/ß-lactamase inhibitor combination approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) in combination with metronidazole. Ceftolozane exhibits bactericidal activity by inhibiting penicillin-binding proteins (PBPs), with high affinity for PBP1b, PBP1c, and PBP3. The addition of tazobactam protects ceftolozane from hydrolysis by irreversibly binding to some ß-lactamase enzymes. Ceftolozane-tazobactam is active against a wide range of Gram-negative pathogens, including extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa, several streptococcal species, and Bacteroides fragilis. When anaerobic coverage is needed, it should be used in combination with metronidazole. Ceftolozane demonstrates linear pharmacokinetics, low protein binding, and minimal accumulation with repeated dosing. The major pharmacokinetic/pharmacodynamic index for ceftolozane is the percentage of the dosing interval in which the plasma free drug concentration remains higher than the minimum inhibitory concentration (%T.MIC). Phase III clinical trials for the treatment of cUTIs and cIAIs have been completed, showing that it is an effective and safe alternative for the treatment of these infections. The approved dose for cUTIs and cIAIs is 1.5 g (1 g ceftolozane and 500 mg tazobactam) infused over 1 hour every 8 hours. A higher 3 g dose is currently in Phase III trials for the treatment of ventilated nosocomial pneumonia. Dosage adjustments are necessary for patients with moderate-to-severe renal impairment. Current data suggest that ceftolozane-tazobactam is a promising carbapenem-sparing alternative agent for the treatment of cUTIs and cIAIs, including those caused by ESBL-producing Enterobacteriaceae and MDR P. aeruginosa.