Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).

A Review of ß-Lactam-Associated Neutropenia and Implications for Cross-reactivity.

OBJECTIVE: To review the incidence, management, and current understanding of the pathophysiology of ß-lactam-induced neutropenia and to critically evaluate the practicality and safety of direct substitution to an alternative ß-lactam in the setting of this reaction. DATA SOURCES: A literature analysis using the PubMed and Ovid search engines (July 1968 to October 2020) was performed using the search terms neutropenia, leukopenia, ß-lactam, nonchemotherapy, agranulocytosis, and G-CSF (granulocyte colony-stimulating factor). STUDY SELECTION AND DATA EXTRACTION: The included English-language studies evaluated the incidence, mechanism, and/or management of ß-lactam-induced neutropenia in pediatric or adult patients. DATA SYNTHESIS: Drug-induced neutropenia is a well-documented adverse reaction of ß-lactam antibiotics, with an incidence of approximately 10% following at least 2 weeks of intravenous therapy. However, multiple gaps in knowledge remain in the mechanism of pathophysiology and optimal management of this reaction. Both direct toxic and immune-mediated mechanisms have been implicated. Although the cornerstone of management includes cessation of the offending agent, controversy exists on the appropriateness of direct substitution or future use of an alternative ß-lactam. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Given the frequency of use and superiority of ß-lactams over alternative therapy for several infectious disease states, practical recommendations are needed on the management and safe use of ß-lactams following ß-lactam-induced neutropenia. CONCLUSION: Future use of ß-lactams with differing R1 side chains, particularly those from a separate class, should not be deemed contraindicated following ß-lactam-induced neutropenia and may be considered when indicated, with close laboratory monitoring.

Antiretroviral considerations in HIV-infected patients undergoing bariatric surgery.

WHAT IS KNOWN AND OBJECTIVE: With the advent of antiretroviral therapy and the resultant decrease in mortality among adults living with human immunodeficiency virus (HIV), there is now an increased incidence of obesity and obesity-related comorbidities in these patients. Bariatric surgery is becoming an increasingly common treatment option for patients who are classified as clinically obese. There are limited data regarding the use of antiretroviral therapy in patients who have undergone bariatric surgery. The purpose of this review was to evaluate the available literature regarding antiretroviral therapy and pharmaceutical properties in this special population. METHODS: Literature review was performed through PubMed, utilizing search terms of bariatric surgery, sleeve gastrectomy, Roux-en-Y, HIV infection, obesity and antiretroviral. Direct medical information requests to antiretroviral pharmaceutical manufacturers were also completed. RESULTS: Several case series and case reports have been published which demonstrate minimal risk of complications and maintenance of virologic suppression in the vast majority of patients. Bariatric surgery appears to be an effective mechanism for assistance in controlling obesity in patients infected with HIV; however, numerous factors may impact the safe and effective use of antiretroviral therapy. WHAT IS NEW AND CONCLUSION: Due to the physiologic changes and postoperative management following bariatric surgery, evaluation of the patients' medication regimens must be considered and several factors should be taken into account when choosing the appropriate antiretroviral regimen for these patients. Furthermore, communication between the patients' surgeon, HIV provider and a clinical pharmacist should occur prior to surgery to ensure the patient is optimized to achieve the best outcome including maintaining virologic suppression.

Idiosyncratic Valproic Acid-Induced Hepatotoxicity in a Sickle Cell Patient.

Objective: Suspected idiosyncratic valproic acid-induced hepatotoxicity in a sickle cell patient with chronic migraines is reported. Case Summary: A 32-year-old female with a medical history significant for sickle cell anemia and cerebral palsy was admitted to an inpatient medicine service for moderate to severe right flank pain with worsening transaminitis and hyperbilirubinemia. The patient reported taking valproic acid for approximately 6 years for the prevention of chronic migraines. An extensive workup was inconclusive for an etiology of underlying liver disease for the presenting symptoms. Valproic acid was discontinued on hospitalization day 3, resulting in a rapid improvement of the signs and symptoms of hepatotoxicity. Discussion: Several mechanisms of idiopathic valproic acid-induced hepatotoxicity have been proposed, including the accumulation of hepatotoxic metabolites, induction of oxidative stress, and deficiency of l-carnitine. Drug-induced hepatotoxicity is typically confirmed following improvement on withdrawal of the suspected agent and exclusion of any underlying etiologies. For this particular patient case, the Council for International Organizations of Medical Sciences scale was also used to evaluate the probability of the hepatotoxicity being drug related. Objective causality assessment with this scale revealed a probable adverse drug event. Conclusion: Idiopathic valproic acid-induced hepatotoxicity was suspected in a 32-year-old female with a history of sickle cell anemia and cerebral palsy following improvement of transaminitis and abdominal pain on discontinuation of valproic acid therapy and exclusion of an underlying etiology. This case reveals the clinical significance of prompt pharmacist identification and management of the potential adverse drug event.

Pharmacotherapeutic Considerations in the Treatment of Nontuberculous Mycobacterial Infections: A Primer for Clinicians.

Nontuberculous mycobacteria (NTM) can cause a variety of infections, including serious pulmonary disease. Treatment encompasses polypharmacy, with a targeted regimen of 2-5 active medications, depending on site of infection, species, and clinical characteristics. Medications may include oral, intravenous, and inhalational routes. Medication acquisition can be challenging for numerous reasons, including investigational status, limited distribution models, and insurance prior authorization. Additionally, monitoring and managing adverse reactions and drug interactions is a unique skill set. While NTM is primarily medically managed, clinicians may not be familiar with the intricacies of medication selection, procurement, and monitoring. This review offers insights into the pharmacotherapeutic considerations of this highly complex disease state, including regimen design, medication acquisition, safety monitoring, relevant drug-drug interactions, and adverse drug reactions.

An app a day: Results of pre- and post-surveys of knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship principles among nurses who utilized a novel learning platform.

Background: Nurses perform several functions that are integral for antimicrobial stewardship (AMS). However, nurses are underrepresented in research and underutilized in implementation of AMS interventions. The objective of this pilot study was to assess the effect of asynchronous microlearning on inpatient nursing staff knowledge, attitudes, and practices (KAP) regarding AMS principles. Methods: A team of pharmacists, physicians, and nurses developed 9 case-based, multiple-choice questions with accompanying educational explanations on associated AMS principles. One case was delivered to participants daily via an institutional web-based application (QuizTime). A KAP survey with 20 questions on a 5-point Likert scale was administered before and after the intervention. Survey results were compared using a Wilcoxon signed-rank test. Results: Participants' mean survey score after the intervention demonstrated statistically significant improvement for 18 (90%) of 20 items compared to before the intervention. Participants' confidence improved in key AMS activities: (1) differentiating between colonization and infection (mean difference, 0.63; P < .001), (2) identifying unnecessary urine cultures and inappropriate treatment of urinary tract infections (mean difference, 0.94; P < .001), (3) recognizing opportunities for intravenous to oral therapy conversion (mean difference, 1.07; P < .001), and (4) assessing for antibiotic-associated adverse effects (mean difference, 0.54; P < .001). Conclusions: Nursing education provided through an asynchronous, microlearning format via a mobile platform resulted in statistically significant improvement in most KAP topics. Nurses are integral members of a multidisciplinary AMS team, and novel education methods can help equip them with the necessary AMS tools. This pilot study forms the basis for expanded AMS educational efforts in all healthcare professionals.

Post-Dialysis Parenteral Antimicrobial Therapy in Patients Receiving Intermittent High-Flux Hemodialysis.

Patients with end-stage renal disease (ESRD) requiring intermittent hemodialysis (IHD) are at increased risk of infection, which represents a leading cause of mortality in this population. The use of additional vascular access devices such as peripherally inserted central catheters to treat such infections should be minimized in patients with ESRD requiring IHD in order to mitigate complications such as infection and thrombosis and to maintain venous patency for hemodialysis access. Intravenous antimicrobial dosing following IHD has the advantages of avoiding additional access devices and providing convenience for patients and providers. Vancomycin, cefazolin, and aminoglycosides have historically been regarded as the primary intravenous antimicrobials administered with IHD given their relatively low cost, convenient dosing, and longevity of clinical use. Despite this, a growing body of literature is evaluating the use of an expanded list of antimicrobials that may be employed using post-dialysis dosing for patients requiring IHD; however, the available data are largely limited to pharmacokinetic studies and small cohorts of infected patients or uninfected subjects. Post-dialytic dosing of intravenous antimicrobials may be considered on a patient-by-patient basis after careful consideration of clinical, microbiological, and logistical factors that may influence the probability of treatment success. This document reviews and evaluates currently available information on the post-dialytic administration of an expanded list of intravenous antimicrobials in the setting of thrice-weekly, high-flux IHD.

Assessing an intervention to improve the safety of automatic stop orders for inpatient antimicrobials.

BACKGROUND: Automatic stop orders (ASOs) for antimicrobials have been recommended as a component of antimicrobial stewardship programs, but may result in unintentional treatment interruption due to failure of providers to re-order an antimicrobial medication. We examined the impact of a multifaceted intervention designed to reduce the potential harms of interrupting antimicrobial treatment due to ASOs. METHODS: An intervention was implemented that included pharmacist review of expiring antimicrobials as well as provider education to encourage use of a long-term antimicrobial order set for commonly used prophylactic antimicrobials. Pharmacist interventions and antimicrobial re-ordering was recorded. Percent of missed doses of a commonly used prophylactic antimicrobial, single strength co-trimoxazole, was compared pre- and post-intervention using a chi-squared test. RESULTS: From November 1, 2015 to November 30, 2016, there were 401 individual pharmacist interventions for antimicrobial ASOs, resulting in 295 instances of antimicrobial re-ordering. The total percent of presumed missed single strength co-trimoxazole doses was reduced from 8.4% to 6.2% post-intervention (P<0.001). CONCLUSIONS: This study found that a targeted intervention was associated with a reduction in unintended antimicrobial treatment interruption related to ASOs.