Search

Outpatient parenteral antimicrobial therapy (OPAT) has become more common in clinical settings. Correspondingly, OPAT-related publications have also increased; the objective of this paper was to summarize clinically meaningful OPAT-related publications in 2022. Seventy-five articles were initially identified with 54 being scored. The top 20 OPAT articles published in 2022 were reviewed by a group of multidisciplinary OPAT clinicians. This article provides a summary of the “top 10” OPAT publications of 2022.

Social media platforms have revolutionized how we consume information, along with how to effectively present communication, education, and advocacy efforts. There is profound value in leveraging social media within these aspects for the field of infectious diseases, for divisions and individual clinicians. Herein, we provide the rationale to incorporate social media as a key competency for infectious diseases training and specific guidance on aspects of education and strategic development of new accounts critical for success.

Nontuberculous mycobacteria (NTM) are a group of atypical bacteria that may cause a spectrum of clinical manifestations, including pulmonary, musculoskeletal, skin and soft tissue, and cardiac infections. Antimycobacterial medication regimens for NTM infections require multiple agents with prolonged treatment courses and are often associated with poor tolerance in patients and suboptimal clinical outcomes. This review summarizes NTM pharmacotherapy, including treatment concepts, preferred medication regimens according to NTM species and site of infection, and emerging treatment methods for difficult-to-treat species.

Antimicrobial stewardship and outpatient parenteral antimicrobial therapy (OPAT) collide with the newest Joint Commission requirements for outpatient antimicrobial stewardship. The purpose of this paper was to present key stewardship areas applicable to OPAT and review the data behind them. Data on these topics is emerging. Long treatment durations are being challenged and oral routes are garnering evidence for treatment of traditionally intravenous-only regimens. Stability information and incorporation of pharmacokinetic and pharmacodynamic properties may lead to use of continuous infusions, once daily dosing, or long-acting lipoglycopeptides. Different models for patient follow-up, frequency of monitoring, and adverse effect profiles can be used. As the popularity and necessity of OPAT and stewardship programs increase, there is opportunity for multidisciplinary collaboration. While there are many overlapping stewardship principles in OPAT, there may be appropriately discordant principles in this unique scenario as well.

As outpatient parenteral antimicrobial therapy (OPAT) becomes more common, it may be difficult to stay current with recent related publications. A group of multidisciplinary OPAT clinicians reviewed and ranked all OPAT publications published in 2021. This article provides a high-level summary of the OPAT manuscripts that were voted the “top 10” publications of 2021.

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of eravacycline, a novel fluorocycline antibiotic from the tetracycline family. Data Sources: A PubMed search was conducted for data between 1946 and March 2019 using MeSH terms eravacycline and TP-434. An internet search was conducted for unpublished clinical research. Study Selection and Data Extraction: The literature search was limited to English-language studies that described clinical efficacy, safety, and pharmacokinetics in humans and animals. Abstracts featuring prepublished data were also evaluated for inclusion. Data Synthesis: Eravacycline has in vitro activity against multidrug-resistant organisms, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, extended-spectrum β-lactamase-producing and carbapenem-resistant Enterobacteriaceae, and Acinetobacter. It was approved for the treatment of complicated intra-abdominal infections (cIAIs) in adults following favorable results of 2 phase III trials, IGNITE 1 and IGNITE 4, compared with ertapenem and meropenem, respectively. The most common adverse drug events associated with eravacycline were infusion site reactions (7.7%), nausea (6.5%), vomiting (3.7%), and diarrhea (2.3%). Relevance to Patient Care and Clinical Practice: Eravacycline will likely be most useful for resistant infections when lack of tolerability, resistant phenotypes, or allergies prevent the use of β-lactams. Conclusions: Eravacycline is a new tetracycline antibiotic with a broad spectrum of activity that has demonstrated efficacy in the treatment of cIAIs. Although it has activity against multidrug-resistant organisms, data are limited for other indications.

Objectives: To determine how pharmacists with formal antimicrobial stewardship program (ASP) responsibilities prioritize their time and pharmacists without formal antimicrobial stewardship program responsibilities contribute to ASP activities. Design: A nationwide survey. Respondents: Members of the American College of Clinical Pharmacy who subscribe to the following practice and research network e-mail listservs: infectious diseases, adult medicine, cardiology, critical care, hematology–oncology, immunology and transplantation, and pediatrics. Methods: A survey was distributed via listservs. Respondents were asked about their personal and institutional demographics and ASP activities. Results: In total, 245 pharmacists responded: 135 pharmacists with formal antimicrobial stewardship program responsibilities; 110 pharmacists without formal antimicrobial stewardship program responsibilities. Although most respondents had completed a general pharmacy residency (85%), only 20% had completed an infectious diseases (ID) specialty residency. Among pharmacists with formal antimicrobial stewardship program responsibilities, one-third had no formal training or certification in ID or ASP. Pharmacists without formal antimicrobial stewardship program responsibilities spent ∼12.5% of their time per week on ASP activities, whereas pharmacists with formal antimicrobial stewardship program responsibilities spent 28% of their time performing non-ASP activities. Pharmacists with formal antimicrobial stewardship program responsibilities were more likely than pharmacists without formal antimicrobial stewardship program responsibilities to perform antibiotic guideline development (P < .001), antibiotic-related education (P = .002), and direct notification of rapid diagnostic results (P = .018). Pharmacists with formal antimicrobial stewardship program responsibilities without formal ID training or certification spent less time on ASP activities and were more likely to perform lower-level interventions. Conclusions: Many ASP activities are being performed by pharmacists without formal ID training. To ensure the future success of ASPs, pharmacists with formal antimicrobial stewardship program responsibilities should have adequate training to meet more advanced metrics, and more pharmacists without formal antimicrobial stewardship program responsibilities should be included in basic interventions.

In an effort to “flatten the curve” of SARS-CoV-2, society is urged to practice social distancing. However, the management of other disease states may require some patients to undergo outpatient parenteral antimicrobial therapy (OPAT). Practical considerations for OPAT management during an infectious pandemic are reviewed. These include shortening durations of therapy, utilizing the oral route, avoiding medications requiring therapeutic drug monitoring, selecting antimicrobials with long durations, decreasing frequency of laboratory blood draws, and performing tele-health visits.

Clostridium difficile infection (CDI) is a leading nosocomial disease estimated to cause nearly half a million cases in the United States annually. Recurrent CDI (rCDI) affects ~25% of patients after completion of standard of care therapy and is associated with substantial health care costs and a negative impact on patient's overall markers of quality of life. Bezlotoxumab is the first of its kind monoclonal antibody directed against C. difficile toxin B and indicated for prevention of rCDI in at-risk patients. For the present review, we assessed English-language studies evaluating the clinical efficacy, safety, and pharmacokinetics of bezlotoxumab in humans. Relevant studies were obtained through PubMed, Embase, Cochrane database library, Web of Science, and clinicaltrials.gov. Overall, bezlotoxumab demonstrated a 40% relative reduction rate (absolute rate reduction of ~10%) and a number needed to treat of 10 patients with a favorable safety profile. Special populations, including the elderly, immunocompromised, and patients with end-stage renal disease were evaluated in post hoc analyses with a similarly favorable reduction in rCDI. This review presents and interprets the most recent safety data and the clinical application of bezlotoxumab, highlighting specific high-risk patient populations.

Background: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. Objective: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. Methods: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ≥72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, all-cause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. Results: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-treated patients. Conclusions: Among nafcillin- or cefazolin-treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.

Clostridioides (formerly Clostridium) difficile is responsible for a substantial burden of nosocomial infection. Recurrent C. difficile infection (rCDI) remains a concern due to its high morbidity, mortality, and cost. Despite the updated 2017 IDSA C. difficile treatment guidelines, there remains a lack of well-studied preventive control measures and treatment modalities for rCDI. There are ongoing efforts to develop novel therapies, such as new antibiotics with a lesser impact on gut microbiota and more targeted therapies, such as bacteriotherapy. This mini review highlights key rCDI management updates, preventive measures and ongoing research on novel treatment strategies including bacteriotherapy.

Urinary tract infections (UTIs) are among the most commonly treated bacterial infections. Over the past decade, antimicrobial resistance has become an increasingly common factor in the management of outpatient UTIs. As treatment options for multidrug-resistant (MDR) uropathogens are limited, clinicians need to be aware of specific clinical and epidemiological risk factors for these infections. Based on available literature, the activity of fosfomycin and nitrofurantoin remain high for most cases of MDR Escherichia coli UTIs. Trimethoprim-sulfamethoxazole retains clinical efficacy, but resistance rates are increasing internationally. Beta-lactam agents have the highest rates of resistance and lowest rates of clinical success. Fluoroquinolones have high resistance rates among MDR uropathogens and are being strongly discouraged as first-line agents for UTIs. In addition to accounting for local resistance rates, consideration of patient risk factors for resistance and pharmacological principles will help guide optimal empiric treatment of outpatient UTIs.

Background Infections with adenoviruses (ADVs) can result in considerable mortality and morbidity in solid organ transplant (SOT) recipients. Standard therapy for ADV infections in transplant recipients is not established. At our institution, intravenous cidofovir and immunoglobulin have been used to treat disseminated or invasive ADV in SOT and hematopoietic stem cell transplant recipients. Methods A retrospective case series of SOT recipients treated with cidofovir and intravenous immunoglobulin was performed. Results Five SOT recipients (four renal and one heart transplant) with adenovirus infection were treated successfully with cidofovir and immunoglobulin. Cidofovir was discontinued after the first negative ADV viral load and resolution of clinical symptoms, given the concern for nephrotoxicity in renal transplant recipients. Renal tubular acidosis type 2 and iritis were observed in two patients receiving therapy. Conclusion Symptom resolution and a single negative ADV viral load may be indicators for cidofovir discontinuation.

Palivizumab has been used to treat respiratory syncytial virus (RSV)-infected hematologic malignancy patients at our institution based on limited published data. We conducted this retrospective study to evaluate clinical outcomes and mortality rates of RSV-infected hematologic malignancy patients from 2007 to 2016. A total of 67 patients (19 received palivizumab and 47 received supportive care) were identified. Palivizumab-treated patients had a significantly higher proportion of underlying ischemic heart disease, graft-versus-host-disease, hypogammaglobulinemia, and concomitant pulmonary infections. There were no significant differences in mortality rates or readmission rates between the two groups. The estimated odds ratio for death in patients receiving palivizumab after adjusting for propensity scores and covariates were 0.12 ([0.01, 1.32], p = .08) and 0.09 ([0.01, 1.03], p = .05) respectively. After adjustment for factors associated with severity of illness, there was no difference in mortality among patients treated with palivizumab.

Background Antimicrobial stewardship programs (ASPs) aim to provide optimal antimicrobial therapy to patients quickly to improve the likelihood of overcoming infection while reducing the risk of adverse effects. Rapid diagnostic tests (RDTs) for infectious diseases have become an integral tool for ASPs to achieve these aims. Content This review explored the demonstrated clinical value of longer-standing technologies and implications of newer RDTs from an antimicrobial stewardship perspective. Based on available literature, the focus was on the use of RDTs in bloodstream infections (BSIs), particularly those that perform organism identification and genotypic resistance detection, phenotypic susceptibility testing, and direct specimen testing. Clinical implications of rapid testing among respiratory, central nervous system, and gastrointestinal infections are also reviewed. Summary Coupling RDTs with ASPs facilitates the appropriate and timely use of test results, translating into improved patient outcomes through optimization of antimicrobial use. These benefits are best demonstrated in the use of RDT in BSIs. Rapid phenotypic susceptibility testing offers the potential for early pharmacokinetic/pharmacodynamic optimization, and direct specimen testing on blood may allow ASPs to initiate appropriate therapy and/or tailor empiric therapy even sooner than other RDTs. RDTs for respiratory, central nervous system, and gastrointestinal illnesses have also shown significant promise, although more outcome studies are needed to evaluate their full impact.

Background The potential adverse effects of empiric broad-spectrum antimicrobial use among patients with suspected but subsequently excluded infection have not been fully characterized. We sought novel methods to quantify the risk of adverse effects of broad-spectrum antimicrobial exposure among patients admitted to an intensive care unit (ICU). Methods Among all adult patients admitted to ICUs at a single institution, we selected patients with negative blood cultures who also received ≥1 broad-spectrum antimicrobials. Broad-spectrum antimicrobials were categorized in ≥1 of 5 categories based on their spectrum of activity against potential pathogens. We performed, in serial, 5 cohort studies to measure the effect of each broad-spectrum category on patient outcomes. Exposed patients were defined as those receiving a specific category of broad-spectrum antimicrobial; nonexposed were all other patients in the cohort. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay and nosocomial acquisition of antimicrobial-resistant bacteria (ARB) or Clostridium difficile within 30 days of admission. Results Among the study cohort of 1918 patients, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay >7 days or an ICU length of stay >3 days, and 106 (5.5%) acquired either a nosocomial ARB or C. difficile. The short-term use of broad-spectrum antimicrobials in any of the defined broad-spectrum categories was not significantly associated with either primary or secondary outcomes. Conclusions The prompt and brief empiric use of defined categories of broad-spectrum antimicrobials could not be associated with additional patient harm.

Rapid diagnostic technologies (RDTs) significantly reduce organism identification time and can augment antimicrobial stewardship program (ASP) activities. An electronic survey quantified familiarity with and utilization of RDTs by clinical pharmacists participating in ASPs. Familiarity was highest with polymerase chain reaction (PCR). Formal infectious diseases training was the only significant factor influencing RDT familiarity.Infect Control Hosp Epidemiol 2017;38:863–866

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of bezlotoxumab (BEZ), a novel monoclonal antibody against Clostridium difficile toxin B. Data Sources: A PubMed search was conducted for data between 1946 and April 2017 using MeSH terms bezlotoxumab, MK-6072, or MDX-1388 alone and the terms Clostridium difficile combined with monoclonal antibody or antitoxin. Study Selection and Data Extraction: The literature search was limited to English-language studies that described clinical efficacy, safety, and pharmacokinetics in humans and animals. Abstracts featuring prepublished data were also evaluated for inclusion. Data Synthesis: BEZ is indicated for adult patients receiving standard-of-care (SoC) antibiotics for C difficile infection (CDI) to prevent future recurrence. Two phase III trials—MODIFY I (n = 1452) and MODIFY II (n = 1203)—demonstrated a 40% relative reduction in recurrent CDI (rCDI) with BEZ compared with placebo (16.5% vs 26.6%, P < 0.0001). The most common adverse drug events associated with BEZ were mild to moderate infusion-related reactions (10.3%). Conclusions: In patients treated with SoC antibiotics, BEZ is effective in decreasing rCDI. BEZ has no apparent effect on treatment of an initial CDI episode. In light of increasing rates of CDI, BEZ is a promising option for preventing recurrent episodes. The greatest benefit has been demonstrated in high-risk patients, though the targeted patient population is yet to be defined.

Severe Clostridium difficile infection is associated with a high rate of mortality; however, the optimal treatment for severe- complicated infection remains uncertain for patients who are not candidates for surgical intervention. Thus, we sought to evaluate the benefit of adjunctive tigecycline in this patient population using a retrospective cohort adjusted for propensity to receive tigecycline. We found that patients who received tigecycline had similar outcomes to those who did not, although the small sample size limited power to adjust for comorbidities and severity of illness.

Background Outpatient parenteral antimicrobial therapy (OPAT) allows for long-course intravenous treatment of infections without lengthy hospital stays. Upon discharge, antimicrobial therapy may be broadened to ertapenem or daptomycin for “ease” of once-daily administration. Patients requiring subsequent readmission should be properly tailored to pre-OPAT regimens to minimize collateral damage and reduce cost. This study assessed the continuation of “ease of administration (EOA) regimens” upon hospital readmission during or immediately following OPAT. Methods This was a single-center, retrospective review of adult patients enrolled in OPAT and discharged between January 1, 2014 and September 30, 2017 on ertapenem or daptomycin for “EOA.” This was defined by the presence of the terms “convenience” or “EOA” in OPAT notes or by broadening of coverage to ertapenem or daptomycin upon OPAT enrollment despite adequate therapy with more narrow-spectrum agents. Patients receiving directed carbapenem or daptomycin therapy prior to OPAT enrollment were excluded. The primary outcome was the percentage of patients readmitted during or within 90 days of their OPAT course and maintained on an “EOA regimen” of antibiotics. Secondary outcomes included inpatient therapy cost, rates of Clostridium difficile infection, and adverse drug reactions. Demographics and outcomes were summarized using descriptive statistics. Results Of the 188 patients receiving an OPAT “EOA regimen,” 71 were readmitted, representing 113 unique readmissions. Patients were mostly male (81%) with a median age of 57 years. “EOA regimens” were continued in 27% of hospital readmissions. The Infectious Diseases team was consulted in 48% of cases, and the Antimicrobial Stewardship Team intervened in 26%, prompting de-escalation in a total of 28% of cases. C. difficile infections and adverse events occurred in 7% and 12% of readmissions respectively. The median drug acquisition cost of inpatient “EOA regimens” was $121 per readmission. Conclusion At our institution, OPAT “EOA regimens” were continued in 27% of hospital readmissions indicating a role for improved indication documentation and antimicrobial stewardship involvement. Disclosures C. McCoy, Merck Inc.: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. M. V. Mahoney, Melinta Therapeutics: Consultant, Consulting fee. Cutis Pharma: Consultant, Consulting fee. Tetraphase Pharmaceuticals, Inc.: Consultant, Consulting fee. Roche Diagnostics USA: Consultant, Consulting fee.

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.

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 β-lactam/β-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 β-lactamase enzymes. Ceftolozane–tazobactam is active against a wide range of Gram-negative pathogens, including extended-spectrum β-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.

Urinary tract infections (UTIs) are among the most commonly treated bacterial infections. Over the past decade, antimicrobial resistance has become an increasingly common factor in the management of outpatient UTIs. As treatment options for multidrug-resistant (MDR) uropathogens are limited, clinicians need to be aware of specific clinical and epidemiological risk factors for these infections. Based on available literature, the activity of fosfomycin and nitrofurantoin remain high for most cases of MDR Escherichia coli UTIs. Trimethoprim-sulfamethoxazole retains clinical efficacy, but resistance rates are increasing internationally. Beta-lactam agents have the highest rates of resistance and lowest rates of clinical success. Fluoroquinolones have high resistance rates among MDR uropathogens and are being strongly discouraged as first-line agents for UTIs. In addition to accounting for local resistance rates, consideration of patient risk factors for resistance and pharmacological principles will help guide optimal empiric treatment of outpatient UTIs.

Background Risk stratification of HCAP patients is a possible Antimicrobial Stewardship (AST) intervention for the treatment of multidrug resistant (MDR) Gram-negative (GN) vs. community-acquired pneumonia (CAP) pathogens. This study assessed the impact of a risk stratification guideline for empiric antimicrobial selection relative to acceptance rates and clinical outcomes. Methods In 2017, a guideline for inpatients with HCAP was launched. High risk (HR) of MDR GN was defined as patients admitted to the intensive care unit (ICU), or with >1 risk factor including: receipt of any antimicrobial within 30 days or broad spectrum antimicrobials within 90 days, hemodialysis dependence, or immunocompromised. HR patients were recommended to receive antimicrobials covering MDR GN and low-risk patients to narrower CAP regimens. Patients treated for HCAP post guideline implementation were compared with a historic 2014 cohort for guideline concordance, antimicrobial selection, and clinical outcomes. AST interventions were also assessed. Results Overall, 105 patients in the post-implementation period were compared with 309 historic patients. Guideline-concordant risk-stratified therapy increased 13% [95% CI (3%, 24%)] overall. Clinical failure rates were similar with 11% vs 10% (P = 0.608) in the pre- and post-implementation periods, with an 84% AST acceptance rate (Figure 1). Treatment length decreased [8.1 to 6.6 days (P < 0.001)] and de-escalation increased [31% to 72% (P < 0.001)] as seen in Table 1. Conclusion Introduction of a risk stratified guideline through AST intervention changed practice by matching MDR risk with empiric HCAP therapy. Failure rates were comparable. Secondary benefits included: decreased treatment duration and hospital stay, increased de-escalation rates and decreased MDR GN antimicrobial use in low-risk patients. Disclosures All authors: No reported disclosures.

Background Antimicrobial stewardship programs (ASPs) may improve patient outcomes by reducing antimicrobial adverse effects and resistance. Pneumonia is the most common infectious reason for hospitalization and is a key target for improvement in antimicrobial use. The purpose of this study was to measure the impact of a prospective audit and feedback program for patients with pneumonia in addition to an already robust pre-authorization program at an academic teaching hospital. Methods We analyzed the impact of a prospective audit and feedback initiative among inpatients with pneumonia treated with antimicrobials for at least 72 hours. The primary outcome was the percent of optimal antimicrobial days of therapy received based on hospital-approved pneumonia guidelines, compared pre- and postintervention. This outcome was defined as the number of optimal days of therapy compared with the total days of therapy over the entire study period from the hospital’s perspective. Secondary outcomes included the incidence rate of optimal antimicrobial days of therapy on a patient-specific level, overall antimicrobial days of therapy, length of hospital stay, rates of Clostridium difficile infection (CDI), and in-hospital mortality. Results The study included 248 patients, 125 pre- and 123 postintervention. Forty interventions were made post-implementation, with duration (47.5%) and de-escalation (35%) recommendations most commonly suggested. 50.8% of patients were male, the median [interquartile range (IQR)] age was 71 (60–83) years old, 45.6% of patients had community-acquired pneumonia, and patients had a median (IQR) Elixhauser comorbidity score of 5 (3–6). The overall rate of guideline concordance was 65.8% pre- and 77.5% postintervention (P = 0.041). On an individual level, patients were 17% more likely to have optimal antimicrobials postintervention [Incidence rate ratio 1.17 (95% confidence interval 1.03–1.32, P = 0.013)]. Length of stay, days of therapy, CDI, and in-hospital mortality rates did not differ significantly between groups. Conclusion Initiating a prospective audit and feedback program in addition to pre-authorization led to a significant increase in concordance with hospital pneumonia guidelines, but no difference in secondary outcomes in our patient population. Disclosures M. V. Mahoney, Melinta Therapeutics: Consultant, Consulting fee. Cutis Pharma: Consultant, Consulting fee. Tetraphase Pharmaceuticals, Inc.: Consultant, Consulting fee. Roche Diagnostics USA: Consultant, Consulting fee. C. McCoy, Merck Inc: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee.

The incidence of Neisseria gonorrhoeae infections in the United States has grown over the past decade. The most recent data provided by the Centers for Disease Control and Prevention (CDC) indicate that reported cases have increased by almost 10% over the last 5 years. In conjunction with this rise, the presence of multidrug-resistant strains of N. gonorrhoeae has also emerged. The 2015 CDC guidelines recommend dual therapy with intramuscular ceftriaxone and oral azithromycin as first-line treatment, although components of this regimen are met with a high level of resistance. Although ceftriaxone resistance has not yet been reported in the United States, it is only a matter of time before such isolates are detected, thus ushering in a new era of difficult-to-manage uncomplicated gonococcal infection. The potential public health crisis and patient-associated sequelae (e.g., pelvic inflammatory disease, epididymitis, and human immunodeficiency virus infection) linked with untreatable gonorrhea are cause for great concern. To try to stem this tide, a number of new agents targeted against N. gonorrhoeae are being investigated in clinical trials. In this article, we review the various agents, both currently available and under clinical investigation, and provide recommendations for the management of gonococcal infections.

The rise in resistant Gram-negative bacteria is a major concern and has led to difficulty in treating multidrug-resistant (MDR) infections. Two recently approved combination antibiotics, ceftolozane/tazobactam and ceftazidime/avibactam, may be effective in treating these resistant infections. Ceftolozane is a novel cephalosporin that has been developed in combination with tazobactam, a recognised β-lactamase inhibitor (BLI). Avibactam is a novel BLI combined with ceftazidime, a cephalosporin with an established history. Both of these β-lactam/BLI combination agents have been shown to retain in vitro activity against selected resistant Gram-negative pathogens, including Enterobacteriaceae and Pseudomonas aeruginosa; notably, ceftazidime/avibactam has demonstrated consistent activity against Klebsiella pneumoniae carbapenemase (KPC)-producing organisms. Both agents have been approved for the indications of complicated intra-abdominal infection (with metronidazole) and complicated urinary tract infection, and have ongoing phase 3 trials for the treatment of ventilator-associated and nosocomial pneumonia. This manuscript will review current data available regarding the spectrum of activity and clinical trials that led to the US Food and Drug Administration (FDA) approval of these agents. Both agents appear to be well tolerated and show promise in the treatment of MDR Gram-negative infections.

Background Approximately 30% of patients at our institution have β-lactam (BL) antibiotic allergies documented in their medical record. This translates to high use of non-β-lactams (NBL) or other structurally dissimilar agents. Patients treated with NBL are three times as likely to experience an adverse effect or be readmitted for infection. BL allergy assessment, re-challenge and de-labeling remain an important target for antimicrobial stewardship (AST). Published protocols have been validated at large teaching institutions with improvements in documentation and the care of patients with labeled allergies, including drug challenge protocols and desensitization for true allergies. At BIDMC, a multidisciplinary committee developed a guidance document to include a series of standard questions, medical record review and appropriate clarifications for the medical record. The guideline also includes recommendations an algorithm for the approach to drug challenge or desensitization. Methods The guideline was launched in September 2016 and this study examined the first 4 months of use. The primary endpoint compared the number of full desensitizations requiring ICU admission, and number of graded/full challenges pre- and post-implementation. Aztreonam, which is structurally dissimilar to other BL, was used as a surrogate marker of avoidance of BL. Results Pre-implementation rates of graded challenges and full desensitizations were equivalent. This was bifurcated by 1,000% within 4 months such that the use of graded challenge was 10 times the desensitization rate (Figure 1). Aztreonam use decreased from a 2.33 patient days of therapy (pDOT) per 1,000 days in September to 1.74 in January (Figure 2). The decrease in utilization was most pronounced on the General Medicine units. Utilization was driven most heavily by patients being treated by the Hematology Oncology Service. No adverse reactions were documented during any post guideline β lactam challenges. Conclusion Introduction of a multidisciplinary guideline by AST and Allergy led to preferred utilization of graded challenge over full ICU desensitization and an overall decrease in aztreonam use. Figure 1 Figure 2 Disclosures All authors: No reported disclosures.

Background The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) recommend computerized decision support at the time of prescribing as an antimicrobial stewardship (AST) tool. Providing antimicrobial indications during prescribing can optimize infection-specific therapy through appropriate antimicrobial selection, dosing, and frequency. The Leapfrog group identifies this as a quality measure for their report card system. At Beth Israel Deaconess Medical Center (BIDMC), indication-based dosing has been incorporated in the computerized provider order entry (CPOE) system since 2006. At BIDMC, valacyclovir is only approved for the treatment of varicella zoster (VZV) infection or prophylaxis of solid organ transplant (SOT) patients at low risk for cytomegalovirus. These indications bypass the need for AST approval. Accuracy validation of the selected indications has not been formally performed. Methods A retrospective chart review was performed in patients prescribed valacyclovir during an 8-month period in 2016. Electronic medical records, laboratory reports, and pharmacy records were reviewed to identify the suspected/confirmed infection. The primary outcome was the concordance rate of selected CPOE valacyclovir indication compared with suspected/confirmed infection at the time of ordering. The secondary outcome was the proportion of valacyclovir use per institutional protocol. Results Overall, 117 patients were included, with a median age of 57.9 years, 51 (43.6%) were male, and 4 (3.4%) were located in an intensive care unit. Fifty-nine orders (50.4%) selected VZV as the indication, followed by 21 orders (17.9%) for SOT prophylaxis. Of orders with any CPOE indication, only 59/101 (58.4%) were concordant with suspected/confirmed infection. Of the valacyclovir orders with a VZV indication, 37 (62.7%) were concordant. Of the orders with SOT prophylaxis indications, 5 (23.8%) were concordant. Furthermore, only 46 orders (39.3%) were per BIDMC-protocol. Conclusion Concordance of CPOE indication selection and suspected/confirmed infection for valacyclovir was low. Using CPOE to grant automatic prospective approval must be monitored and audited for accuracy if employed as an AST tool. Disclosures All authors: No reported disclosures.

Background Solid organ transplant (SOT) patients are at high risk for Clostridium difficile infections (CDI) due to chronic immunosuppression and a propensity to receive antimicrobials. Management of CDI in SOT patients poses unique challenges as this population has disease-altered clinical and laboratory parameters. The objective of this study was to assess concordance between various CDI severity scales and the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA) guidelines. Methods This retrospective study included all SOT recipients with a first CDI episode following transplant and time-matched (2:1) to non-SOT patients experiencing first CDI episodes between 2008 and 2016. The primary endpoint was concordance rates of CDI episodes considered mild-moderate or severe/severe-complicated in published CDI scales compared with the SHEA/IDSA guidelines. We also sought to compare the distribution of CDI severity across all scales between SOT and non-SOT patients. Results Overall, 32 SOT patients and 64 non-SOT patients were included. The SOT group had significantly higher leukopenia rates at CDI diagnosis; however, the magnitude of serum creatinine change did not differ between groups. According to the SHEA/IDSA scale, CDI episodes in SOT recipients were categorized as mild-moderate and severe/severe-complicated in 23 (72%) and 9 (28%) patients, respectively. Overall concordance rates among SHEA/IDSA guidelines and other scales ranged from 28% to 72%. Concordance rates were highest for mild-moderate CDI with Belmares and for severe/severe-complicated CDI with ESCMID (Table 1). No scale evenly categorized SOT and non-SOT patients across all severities (Figure 1). Conclusion Severity scales with heavy emphasis on white blood cell counts may not adequately categorize SOT patients. Immunocompromised status may need to be considered on its own when categorizing CDI severity and prescribing therapy. Disclosures C. D. Alonso, Merck: Grant Investigator and Scientific Advisor, Research grant sanofi pasteur: Investigator and Scientific Advisor, Research support GSK: Investigator, Research support; E. B. Hirsch, Merck: Grant Investigator, Grant recipient The Medicines Company: Speaker’s Bureau, Speaker honorarium

Background The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) recommend computerized decision support at the time of prescribing as an antimicrobial stewardship (AST) tool. Providing antimicrobial indications during prescribing can optimize infection-specific therapy through appropriate antimicrobial selection, dosing, and frequency. The Leapfrog group identifies this as a quality measure for their report card system. At Beth Israel Deaconess Medical Center, indication-based dosing has been incorporated in the computerized provider order entry (CPOE) system since 2006. Accuracy validation of the selected indications has not been formally performed. Methods A retrospective chart review was performed of the first 50 patients receiving ≥1 cefepime dose during May 2016. Electronic medical records, laboratory reports, and pharmacy records were reviewed to identify the suspected/confirmed infection. The primary outcome was the concordance rate of selected CPOE cefepime indication compared with suspected/confirmed infection at the time of ordering. The secondary outcome was assessment of dosing agreement between CPOE-selected indication and institutional renal dosing recommendations. With the exception of febrile neutropenia, all other cefepime indications require AST approval for dispensing. Results Patients had a median age of 64 years, 24 (48%) were female, 21 (42%) were located in an intensive care unit (ICU), and 22 (44%) orders were indicated for pneumonia. Concordance of indication selection was 78%. Discordance was largely driven by differing pneumonia severity or ICU status. Combining pneumonia indications increased the concordance rate to 86%. Dosing agreement between CPOE selection and renal dosing recommendations was 72%. Most dosing discrepancies occurred among pneumonia patients, mainly based on defined severity or ICU status and differed by 1 or 2 grams per day. Conclusion The selected CPOE cefepime indication and subsequent dosing recommendations had high concordance rates with suspected/confirmed infections at our institution. This study lends support for the IDSA/SHEA recommendation of incorporating computerized decision support as an AST tool. Disclosures All authors: No reported disclosures.

Background Intraperitoneal (IP) administration of antibiotics is a mainstay of therapy in the treatment of peritoneal dialysis–related peritonitis. The therapeutic options against gram-positive organisms in patients intolerant to vancomycin are limited. Methods This case report and review of the literature used a search of PubMed with the terms “daptomycin,” “intraperitoneal,” and “peritoneal” for 2004 through 7 February 2013 to find relevant publications. Results In addition to our patient, we identified 6 case reports of IP daptomycin for the treatment of peritonitis. Our patient was treated with a 14-day course of IP daptomycin, with resolution of signs and symptoms of peritonitis. She presented again 7 weeks later with signs and symptoms of peritonitis and was treated with a repeat course of IP daptomycin. Among the 6 patients reported in the literature, 4 received loading doses of daptomycin. Daptomycin 20 mg per liter of dialysate was administered in 4 patients, and the other 2 patients received higher doses based on body weight (milligrams per kilogram). Treatment duration averaged 10 or 14 days. In all 6 cases, clinical cure was reported. Conclusions Although limited to case reports, the available literature suggests that IP daptomycin is a viable alternative for peritoneal dialysis–related peritonitis. However, routine use of this agent must be cautioned, because further prospective studies are required.