Serious Adverse Events and Laboratory Monitoring Regimens for Outpatient Parenteral Antimicrobial Therapy With Cefazolin and Ceftriaxone.

The optimal laboratory monitoring frequency for outpatient parenteral antimicrobial therapy-related adverse events (OPAT-AEs) during cefazolin and ceftriaxone therapy is not well defined. We identified 2.7 OPAT-AEs per 1000 sets of weekly laboratory tests in this population, suggesting that less intensive laboratory monitoring may be safe and reasonable.

Implementation of a Rapid Multiplex Polymerase Chain Reaction Pneumonia Panel and Subsequent Antibiotic De-escalation.

Background: Net effects of implementation of a multiplex polymerase chain reaction (PCR) pneumonia panel (PNP) on antimicrobial stewardship are thus far unknown. This retrospective study evaluated the real-world impact of the PNP on time to antibiotic de-escalation in critically ill patients treated for pneumonia at an academic medical center. Methods: This retrospective, quasi-experimental study included adult intensive care unit (ICU) patients with respiratory culture results from 1 May to 15 August 2019 (pre-PNP group) and adult ICU patients with PNP results from 1 May to 15 August 2020 (PNP group) at Nebraska Medical Center. Patients were excluded for the following reasons: any preceding positive coronavirus disease 2019 PCR test, lack of antibiotic receipt, or non-respiratory tract infection indications for antibiotics. The primary outcome was time to discontinuation of anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy. Secondary outcomes included time to discontinuation of antipseudomonal therapy, frequency of early discontinuation for atypical coverage, and overall duration (in days) of antibiotic therapy for pneumonia. Results: Sixty-six patients in the pre-PNP group and 58 in the PNP group were included. There were significant differences in patient characteristics between groups. The median time to anti-MRSA agent discontinuation was 49.1 hours in the pre-PNP and 41.8 hours in the PNP group (P = .28). The median time to discontinuation of antipseudomonal agents was 134.4 hours in the pre-PNP versus 98.1 hours in the PNP group (P = .47). Other outcomes were numerically but not significantly improved in our sample. Conclusions: This early look at implementation of a multiplex PNP did not demonstrate a statistically significant difference in antibiotic use but lays the groundwork to further evaluate a significant real-world impact on antibiotic de-escalation in ICU patients treated for pneumonia.

Use of a beta-lactam graded challenge process for inpatients with self-reported penicillin allergies at an academic medical center.

Background: The Antimicrobial Stewardship Program (ASP) at Nebraska Medicine collaborated with a board-certified allergist to develop a penicillin allergy guidance document for treating inpatients with self-reported allergy. This guidance contains an algorithm for evaluating and safely challenging penicillin-allergic patients with beta-lactams without inpatient allergy consults being available. Methods: Following multi-disciplinary review, an order set for beta-lactam graded challenges (GC) was implemented in 2018. This contains recommended monitoring and detailed medication orders to challenge patients with various beta-lactam agents. Inpatient orders for GC from 3/2018-6/2022 were retrospectively reviewed to evaluate ordering characteristics, outcomes of the challenge, and whether documentation of the allergy history was updated. All beta-lactam challenges administered to inpatients were included, and descriptive statistics were performed. Results: Overall, 157 GC were administered; 13 with oral amoxicillin and 144 with intravenous (IV) beta-lactams. Ceftriaxone accounted for the most challenges (43%). All oral challenges were recommended by an Infectious Diseases consult service, as were a majority of IV challenges (60%). Less than one in five were administered in an ICU (19%). Almost all (n = 150, 96%) were tolerated without any adverse event. There was one reaction (1%) of hives and six (4%) involving a rash, none of which had persistent effects. Allergy information was updated in the electronic health record after 92% of the challenges. Conclusion: Both intravenous and oral beta-lactam graded challenges were implemented successfully in a hospital without a regular inpatient allergy consult service. They were well-tolerated, administered primarily in non-ICU settings, and were often ordered by non-specialist services. In patients with a self-reported penicillin allergy, these results demonstrate the utility and safety of a broadly adopted beta-lactam GC process.

Impact of specialty on the self-reported practice of using oral antibiotic therapy for definitive treatment of bloodstream infections.

Background: No established guidelines exist regarding the role of oral antibiotic therapy (OAT) to treat bloodstream infections (BSIs), and practices may vary depending on clinician specialty and experience. Objective: To assess practice patterns regarding oral antibiotic use for treatment of bacteremia in infectious diseases clinicians (IDCs, including physicians and pharmacists and trainees in these groups) and non-infectious diseases clinicians (NIDCs). Design: Open-access survey. Participants: Clinicians caring for hospitalized patients receiving antibiotics. Methods: An open-access, web-based survey was distributed to clinicians at a Midwestern academic medical center using e-mail and to clinicians outside the medical center using social media. Respondents answered questions regarding confidence prescribing OAT for BSI in different scenarios. We used χ2 analysis for categorical data evaluated association between responses and demographic groups. Results: Of 282 survey responses, 82.6% of respondents were physicians, 17.4% pharmacists, and IDCs represented 69.2% of all respondents. IDCs were more likely to select routine use of OAT for BSI due to gram-negative anaerobes (84.6% vs 59.8%; P < .0001), Klebsiella spp (84.5% vs 69.0%; P < .009), Proteus spp (83.6% vs 71.3%; P < .027), and other Enterobacterales (79.5% vs 60.9%; P < .004). Our survey results revealed significant differences in selected treatment of Staphylococcus aureus syndromes. Fewer IDCs than NIDCs selected OAT to complete treatment for methicillin-resistant S. aureus (MRSA) BSI due to gluteal abscess (11.9% vs 25.6%; P = .012) and methicillin-susceptible S. aureus (MSSA) BSI due to septic arthritis (13.9% vs 20.9%; P = .219). Conclusions: Practice variation and discordance with evidence for the use of OAT for BSIs exists among IDCs versus NIDCs, highlighting opportunities for education in both clinician groups.

In Outpatients Receiving Parenteral Vancomycin, Dosing Adjustments Produced by Area Under the Curve-Based and Trough-Based Monitoring Differ Only at the Extremes of the Therapeutic Trough Range.

Area under the curve (AUC)-based vancomycin dosing reduces nephrotoxicity but is burdensome. Reviewing 115 adults receiving ≥2 weeks of outpatient vancomycin, we found AUC-based and trough-based dose adjustments discordant only for troughs <12 or >16 mg/L. Selective versus universal outpatient AUC calculation would likely offer similar benefit with reduced workload.

Beta-lactam allergies, surgical site infections, and prophylaxis in solid organ transplant recipients at a single center: A retrospective cohort study.

BACKGROUND: Beta-lactam allergies (BLAs) are common in hospitalized patients, including transplant recipients. BLA is associated with decreased use of preferred surgical site infection (SSI) prophylaxis and increased SSIs, but this has not been studied in the transplant population. METHODS: We reviewed adult heart, kidney, and liver transplant recipients between January 1, 2016 and December 31, 2019 to characterize reported BLA and collect SSI prophylaxis regimens at time of transplant. We compared the use of preferred SSI prophylaxis and SSI incidence based on reported BLA status. Post hoc we collected antibiotic days of therapy (DOT) (excluding pneumocystis prophylaxis) in the 30-day period posttransplant for patients without SSI. We utilized descriptive statistics for comparisons. RESULTS: Of 691 patients included (116 heart, 400 kidney, and 175 liver transplant recipients), 118 (17%) reported BLA. Rash and hives were the two most reported BLA reactions (36% and 24%), categorized as potential T-cell mediated and IgE mediated, respectively. Preferred SSI prophylaxis was prescribed in 13 (11%) patients with BLA and 573 (92%) without BLA (p < .001). No difference could be detected in SSI incidence between BLA and non-BLA patients (4.2 vs. 4.3%, p = 1.0). Of 659 without SSI, 169 (25.6%) received antibiotics within 30 days of transplant; mean antibiotic DOT for BLA and non-BLA patients were 3.5 ± 8.0 versus 2.3 ± 5.8, p = .12. CONCLUSION: BLA transplant recipients received nonpreferred SSI prophylaxis more frequently than non-BLA recipients, but there was no difference in 30-day SSIs between the groups. One-fourth of solid organ transplant recipients received systemic antibiotics within 30 days of transplant.

A Proposal for Addiction and Infectious Diseases Specialist Collaboration to Improve Care for Patients With Opioid Use Disorder and Injection Drug Use-Associated Infective Endocarditis.

ABSTRACT: Patients with injection drug use-associated infective endocarditis and opioid use disorder often receive treatment for the infection that fails to address its underlying cause. People who inject drugs (PWID) and develop serious infections also face disparities in antibiotic management, particularly with regards to use of outpatient parenteral antimicrobial therapy (OPAT). We highlight literature on OPAT in PWID challenging the notion that PWID cannot be managed with OPAT. Given that OPAT use amongst PWID and non-PWID yields similar outcomes, we argue that a bias against OPAT use in PWID is unwarranted and may reflect stigma rather than data. We further note the proven value of comprehensive OUD treatment on endocarditis treatment outcomes, which also addresses the potential safety concerns of OPAT in PWID, and propose a treatment model in which Addiction and Infectious Disease specialists collaborate to integrate opioid use disorder treatment into injection drug use-associated infective endocarditis care.

Clinical and Procedural Evaluation of a Pharmacy Pharmacokinetic Consult Service.

PURPOSE: Though previous studies have shown benefit with pharmacist-managed dosing of antibiotics, many institutions still do not offer such services. Our objective was to determine and report novel outcomes associated with the implementation of a pharmacist-managed pharmacokinetic/pharmacodynamic consult service and to assess the impact of direct pharmacist involvement in therapeutic drug monitoring. METHODS: Retrospective cohort study of patients who received vancomycin or an aminoglycoside in the medical intensive care unit from January 5, 2013, to January 6, 2015, divided into 2 groups: before/after implementation of the consult service on January 6, 2014. RESULTS: Nine-hundred sixty-two patients were included. Groups were similar at baseline. There were fewer critical values after implementation of the consult service (40.8% vs 27.3%, P < .001). The intervention group had significantly more vancomycin troughs within therapeutic range (15.4% vs 32.8%, P = .019). Time from order entry to medication administration was shorter when pharmacists entered the medication order, although this difference was nonsignificant (103 minutes vs 77 minutes, P = .054). CONCLUSION: Implementation of a pharmacist-managed dosing and monitoring program led to significantly decreased rates of critical value drug concentrations and increased rates of therapeutic concentrations, with a 25% (NS) decreased time-to-antibiotic administration, therefore demonstrating the additive value of the pharmacist-managed over pharmacist-monitored approach.

Treatment and clinical outcomes of urinary tract infections caused by KPC-producing Enterobacteriaceae in a retrospective cohort.

BACKGROUND: Optimal treatment regimens for infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are not well-defined. OBJECTIVES: This study describes the treatment and outcomes in patients with urinary tract infection (UTI) caused by KPC-producing Enterobacteriaceae. METHODS: This retrospective cohort study analyzed data from adult inpatients with bacteriuria caused by KPC-positive organisms treated at Barnes-Jewish Hospital from June 1, 2006, to February 1, 2008. KPC-positive isolates were identified utilizing disk-diffusion susceptibility testing and confirmed to contain bla(KPC) via molecular methods. RESULTS: Twenty-one patients met the inclusion criteria and all were classified as having symptomatic UTI. The majority of patients were female (15/21 [71%]), and the mean (SD) age was 62.4 (15.2) years. Successful clinical and microbiologic responses were observed in 16 patients (76%) for both outcomes. Patients with urinary catheters had them removed or replaced in 9 of 15 cases (60%). Antibiotics active against the isolated pathogen were provided in 14 of 21 cases (67%), often after considerable delay (median, 72.5 hours [range, 4-312 hours]). All 7 patients receiving aminoglycoside therapy had successful clinical and microbiologic responses, and in vitro testing of an extended antibiotic panel revealed high susceptibility rates for tigecycline (28/29 [97%]), minocycline (22/29 [76%]), and fosfomycin (25/29 [86%]) against the KPC-positive isolates. CONCLUSIONS: Although receipt of appropriate therapy was delayed in many cases, clinical outcomes investigated revealed [corrected] high rates of successful response in this defined group of patients Aminoglycosides and tetracycline derivatives suggested therapeutic promise in the treatment of KPC-producing Enterobacteriaceae UTI.

Use of cytomegalovirus intravenous immune globulin for the adjunctive treatment of cytomegalovirus in hematopoietic stem cell transplant recipients.

STUDY OBJECTIVE: To describe the characteristics and clinical outcomes of hematopoietic stem cell transplant (HSCT) recipients who received adjunctive cytomegalovirus intravenous immune globulin (CMV-IVIG) for probable or proven CMV disease. DESIGN: Retrospective cohort study. SETTING: Large, university-affiliated, tertiary-care medical center. PATIENTS: Thirty-five adult HSCT recipients who received at least one dose of CMV-IVIG for adjunctive treatment of probable or proven CMV disease between January 1, 1999, and December 31, 2007. MEASUREMENTS AND MAIN RESULTS: All-cause mortality at hospital discharge was the primary outcome. All patients received an allogeneic HSCT. Twenty-six patients (74%) had pneumonitis, nine (26%) had enteritis, and 29 (83%) had CMV viremia. All patients received concomitant antiviral therapy; 31 (89%) received ganciclovir, and 14 (40%) received foscarnet. All-cause mortality at hospital discharge was 49% (17 patients). Patient characteristics associated with mortality included requiring intubation for CMV pneumonia (11 [79%] of 14 nonsurvivors vs 3 (25%) of 12 survivors, p=0.016) and earlier disease onset after HSCT (median 48 days for nonsurvivors vs 106 days for survivors, p<0.001). In the multivariate analysis, only requiring intubation for CMV pneumonia remained a significant risk factor for increased mortality. A low rate of adverse events was attributed to CMV-IVIG, with mild hypertension (two patients [6%]) and erythema and chills (one patient [3%]) being the most common. CONCLUSION: The mortality rate in our study population was similar to previous reports in the literature and may be somewhat lower than rates reported with antiviral monotherapy. Our analysis suggests that factors associated with mortality include the need for intubation and, possibly, earlier onset of CMV disease after HSCT. Treatment with CMV-IVIG appears to be well tolerated in HSCT recipients. These findings support further trials of CMV-IVIG efficacy in this setting.

New antimicrobial agents for use in the intensive care unit.

Timely provision of adequate antimicrobial coverage in an initial anti-infective treatment regimen results in optimal outcomes for bacterial and fungal infections. However, selection of appropriate antimicrobial regimens for treatment of infections in the intensive care unit (ICU) can be challenging due to expansion of resistance, which typically requires use of multidrug anti-infective regimens to provide adequate coverage of important pathogens commonly seen in the ICU setting. Indeed, a recent additional call to action by the Infectious Diseases Society of America (IDSA) has enforced the impact that antimicrobial-resistant pathogens can have on patient care. The term ESKAPE has been coined by this IDSA group to refer to Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species, the etiologic causes of the majority of hospital-acquired infections in the United States that are able to effectively "escape" our antibiotic arsenal and that also mandate discovery of new antimicrobial agents. This article reviews select antibacterial agents and an antifungal agent in late stages of clinical development that appear to have potential for treatment of infections in the ICU.