A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in Non-Hospital Care Settings in 2021.

The scope of antimicrobial stewardship programs has expanded beyond the acute hospital setting. The need to optimize antimicrobial use in emergency departments, urgent, primary, and specialty care clinics, nursing homes, and long-term care facilities prompted the development of core elements of stewardship programs in these settings. Identifying the most innovative and well-designed stewardship literature in these novel stewardship areas can be challenging. The Southeastern Research Group Endeavor (SERGE-45) network evaluated antimicrobial stewardship-related, peer-reviewed literature published in 2021 that detailed actionable interventions specific to the nonhospital setting. The top 13 publications were summarized following identification using a modified Delphi technique. This article highlights the selected interventions and may serve as a key resource for expansion of antimicrobial stewardship programs beyond the acute hospital setting.

Anesthesia awareness and the bispectral index.

BACKGROUND: Awareness during anesthesia is a serious complication with potential long-term psychological consequences. Use of the bispectral index (BIS), developed from a processed electroencephalogram, has been reported to decrease the incidence of anesthesia awareness when the BIS value is maintained below 60. In this trial, we sought to determine whether a BIS-based protocol is better than a protocol based on a measurement of end-tidal anesthetic gas (ETAG) for decreasing anesthesia awareness in patients at high risk for this complication. METHODS: We randomly assigned 2000 patients to BIS-guided anesthesia (target BIS range, 40 to 60) or ETAG-guided anesthesia (target ETAG range, 0.7 to 1.3 minimum alveolar concentration [MAC]). Postoperatively, patients were assessed for anesthesia awareness at three intervals (0 to 24 hours, 24 to 72 hours, and 30 days after extubation). RESULTS: We assessed 967 and 974 patients from the BIS and ETAG groups, respectively. Two cases of definite anesthesia awareness occurred in each group (absolute difference, 0%; 95% confidence interval [CI], -0.56 to 0.57%). The BIS value was greater than 60 in one case of definite anesthesia awareness, and the ETAG concentrations were less than 0.7 MAC in three cases. For all patients, the mean (+/-SD) time-averaged ETAG concentration was 0.81+/-0.25 MAC in the BIS group and 0.82+/-0.23 MAC in the ETAG group (P=0.10; 95% CI for the difference between the BIS and ETAG groups, -0.04 to 0.01 MAC). CONCLUSIONS: We did not reproduce the results of previous studies that reported a lower incidence of anesthesia awareness with BIS monitoring, and the use of the BIS protocol was not associated with reduced administration of volatile anesthetic gases. Anesthesia awareness occurred even when BIS values and ETAG concentrations were within the target ranges. Our findings do not support routine BIS monitoring as part of standard practice. (ClinicalTrials.gov number, NCT00281489 [ClinicalTrials.gov].).

Real-World Experience with Oritavancin Therapy in Invasive Gram-Positive Infections.

INTRODUCTION: Oritavancin is a novel lipoglycopeptide approved for acute bacterial skin and skin structure infections. The pharmacokinetic profile and convenient one-time dosing make oritavancin an enticing option for other serious Gram-positive infections requiring prolonged treatment courses. Unfortunately, data for using oritavancin in these populations are limited. METHODS: We report ten cases of oritavancin use for invasive Gram-positive infections in our health system, and provide a review of the currently available literature regarding oritavancin therapy for invasive infections. RESULTS: Among the ten patients who received oritavancin, the most common infection was methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia (n = 5, 50%). Other indications for oritavancin use included methicillin-resistant S. aureus (MRSA) bursitis (n = 1, 10%), group B streptococcal bacteremia with native tricuspid valve infective endocarditis (n = 1, 10%), coagulase-negative staphylococcal bacteremia (n = 1, 10%), MSSA deep tissue infection (n = 1, 10%), and enterococcal bacteremia (n = 1, 10%). Oritavancin was well tolerated, and 7/10 (70%) patients were successfully treated. CONCLUSION: Oritavancin is a potential option for patients with invasive Gram-positive infections. Further study is warranted.

Emerging echinocandins for treatment of invasive fungal infections.

The echinocandins are a new class of antifungals, developed in response to the need for safe and effective antifungals for the treatment of invasive fungal infections. These agents work by inhibiting 1,3-beta-d-glucan synthase, an enzyme essential for production of cell walls in select fungi. Echinocandins appear to demonstrate favourable activity in vitro against a variety of yeasts (including both Candida albicans and non-albicans Candida) as well as select moulds (including Aspergillus spp.) In general, all echninocandins demonstrate a favourable safety profile and require once-daily parenteral administration. Caspofungin is the first of these agents to be available in the US, and is approved for empirical antifungal therapy in febrile neutropenic patients, candidaemia and select forms of invasive candidiasis, and for management of invasive aspergillosis in patients refractory to or intolerant of other therapies. Micafungin was recently approved by the FDA for treatment of oesophageal candidiasis, and for the prophylaxis of fungal infections in haematopoietic stem cell transplant recipients. Emerging data indicate micafungin may have an important role in the treatment of invasive forms of candidiasis. Anidulafungin is an echinocandin approved in the US for treatment of candidaemia and oesophageal candidiasis. Aminocandin (HMR-3702, IP-960) is an investigational agent, with published experience limited to in vitro studies and animal models of infection.

SYM 2081, an agonist that desensitizes kainate receptors, attenuates capsaicin and inflammatory hyperalgesia.

Excitatory amino acids acting at non-NMDA receptors contribute to transmission of nociceptive information. SYM 2081 ((2S,4R)-4-methyl glutamic acid) desensitizes kainate receptors, one subtype of non-NMDA receptors, to subsequent release of excitatory amino acids and thus may attenuate transmission of nociceptive information. To determine if SYM 2081 can prevent development of hyperalgesia, SYM 2081 (10, 50 or 100 mg/kg, i.p.) was administered prior to injection of capsaicin into the hindpaw of rats, which produces mechanical and heat hyperalgesia. To determine if SYM 2081 can reduce ongoing inflammatory hyperalgesia, SYM 2081 (10 or 100 mg/kg, i.p.) was administered after development of carrageenan-evoked hyperalgesia. Intraplantar injection of capsaicin produced an increase in hindpaw withdrawal frequency to mechanical stimuli (from 4+/-2 to 41+/-7%; mean+/-S.E.M.) and a decrease in withdrawal latency to heat (from 12.3+/-0.3 to 5.9+/-0.4 s) in rats that received vehicle. In contrast, rats that received SYM 2081 (100 mg/kg) prior to injection of capsaicin exhibited a lower hindpaw withdrawal frequency (18+/-4%) and a longer withdrawal latency (7.7+/-0.5 s). Intrathecal (1-100 microg/5 microl), but not intraplantar (10 or 100 microg/50 microl), injection of SYM 2081 attenuated the development of capsaicin-evoked heat hyperalgesia suggesting that SYM 2081's antihyperalgesic effects were due to its central effects. Furthermore, SYM 2081 completely reversed ongoing carrageenan-evoked mechanical hyperalgesia and partially (approximately 50%) reversed ongoing heat hyperalgesia. The present study demonstrates that administration of a high-potency ligand that selectively desensitizes kainate receptors attenuates the development of mechanical and heat hyperalgesia and attenuates ongoing inflammatory hyperalgesia.