Evaluation of Gabapentin and Baclofen Combination for Inpatient Management of Alcohol Withdrawal Syndrome.

Background: Benzodiazepines are considered the gold standard for treatment of alcohol withdrawal syndrome (AWS), a group of symptoms that occur after abrupt cessation of alcohol use, but may be associated with serious adverse effects. Given the safety concerns, alternative treatment options for AWS management have been investigated, including gabapentin and baclofen. Because no available studies have investigated the inpatient use of the gabapentin and baclofen combination for alcohol detoxification, this study aims to evaluate their efficacy and safety in the inpatient hospital setting. Methods: This retrospective cohort study at the Captain James A. Lovell Federal Health Care Center in North Chicago, Illinois, included patients who were aged ≥ 18 years and who were admitted to the general acute medicine floor for the primary indication of AWS from January 1, 2014, to July 31, 2021. The primary outcome was the length of stay, defined as hours from admission to either discharge or 36 hours with a Clinical Institute Withdrawal Assessment of Alcohol (CIWA) score ≤ 8. Electronic health records were reviewed to collect CIWA scores, alcohol withdrawal seizure and delirium tremens incidence, rates of conversions from gabapentin/baclofen to lorazepam, rates of transitions to a higher level of care, and readmission for AWS within 30 days. Results: Mean length of stay in the gabapentin/baclofen group was statistically significantly shorter compared with the benzodiazepine group (42.6 vs 82.5 hours, P < .001). The study found no significant difference between the gabapentin/baclofen and benzodiazepine groups in AWS readmission, adjuvant medications for AWS management, and number of patients who transitioned to a higher level of care. Overall, the safety of gabapentin/baclofen vs benzodiazepine were comparable; however, 1 patient experienced a seizure, and 1 patient experienced delirium tremens during admission in the benzodiazepine group. Conclusions: Gabapentin/baclofen combination seems to be an effective and safe alternative to benzodiazepines and may be considered for managing mild AWS in hospitalized patients, but additional research is needed to examine this regimen.

Steno-sphere: Navigating the enigmatic world of emerging multidrug-resistant Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is an opportunistic pathogen and frequent cause of serious nosocomial infections. Patient populations at greatest risk for these infections include the immunocompromised and those with chronic respiratory illnesses and prior antibiotic exposure, notably to carbapenems. Its complex virulence and resistance profile drastically limit available antibiotics, and incomplete breakpoint and pharmacokinetic/pharmacodynamic (PK/PD) data to inform dose optimization further complicates therapeutic approaches. Clinical comparison data of first-line agents, including trimethoprim-sulfamethoxazole (TMP-SMX), quinolones, and minocycline, are limited to conflicting observational data with no clear benefit of a single agent or combination therapy. Newer antibiotic approaches, including cefiderocol and aztreonam- avibactam, are promising alternatives for extensively drug-resistant isolates; however, clinical outcomes data are needed. The potential clinical utility of bacteriophage for compassionate use in treating S. maltophilia infections remains to be determined since data is limited to in-vitro and sparse in-vivo work. This article provides a review of available literature for S. maltophilia infection management focused on related epidemiology, resistance mechanisms, identification, susceptibility testing, antimicrobial PK/PD, and emerging therapeutic strategies.

Sulbactam-durlobactam: A novel ß-lactam-ß-lactamase inhibitor combination targeting carbapenem-resistant Acinetobacter baumannii infections.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a difficult-to-treat nosocomial pathogen responsible for significant morbidity and mortality. Sulbactam-durlobactam (SUL-DUR), formerly ETX2514SUL, is a novel ß-lactam-ß-lactamase inhibitor designed specifically for the treatment of CRAB infections. The United States Food and Drug Administration (FDA) fast-track approval of SUL-DUR for the treatment of CRAB infections is currently pending after completion of the phase III ATTACK trial, which compared SUL-DUR to colistin, both in combination with imipenem-cilastatin (IMI) for patients with CRAB-associated hospital-acquired bacterial pneumonia, ventilator-associated pneumonia, and bacteremia. The results of this trial demonstrated that SUL-DUR was non-inferior to colistin for CRAB while also possessing a much more favorable safety profile. SUL-DUR was well-tolerated with the most common side effects being headache, nausea, and injection-site phlebitis. With the current landscape of limited effective treatment options for CRAB infections, SUL-DUR represents a promising therapeutic option for the treatment of these severe infections. This review will discuss the pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical studies, safety, dosing, administration, as well as the potential role in therapy for SUL-DUR.

Oral stepdown in Gram-positive bloodstream infections: A step in the right direction.

Bloodstream infections (BSIs) due to Gram-positive organisms have traditionally been treated with prolonged courses of intravenous antimicrobials. However, this dogma is associated with substantial burden to the patient and health care system. Consequently, there is growing interest in the utilization of oral stepdown therapy, defined as the transition of intravenous therapy to an active oral agent, for this indication. This review highlights available literature examining oral stepdown in adult patients with BSI due to commonly encountered Gram-positive pathogens, including Staphylococcus aureus, Streptococcus spp., and Enterococcus spp. Support for oral stepdown in this setting is primarily derived from observational studies subject to selection bias. Nevertheless, this treatment strategy exhibits promising potential in carefully selected patients as it is consistently associated with reductions in hospital length of stay without jeopardizing clinical cure or survivability. Prospective, randomized trials are needed for validation of oral stepdown in Gram-positive BSI and to identify the optimal patient population and regimen.

Risk Factors for Carbapenem-Resistant Enterobacterales Clinical Treatment Failure.

The Centers for Disease Control and Prevention (CDC) categorized carbapenem-resistant Enterobacterales (CRE) infections as an "urgent" health care threat requiring public attention and research. Certain patients with CRE infections may be at higher risk for poor clinical outcomes than others. Evidence on risk or protective factors for CRE infections are warranted in order to determine the most at-risk populations, especially with newer beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotics available to treat CRE. We aimed to identify specific variables involved in CRE treatment that are associated with clinical failure (either 30-day mortality, 30-day microbiologic recurrence, or clinical worsening/failure to improve throughout antibiotic treatment). We conducted a retrospective, observational cohort study of hospitalized patients with CRE infection sampled from 2010 to 2020 at two medical systems in Detroit, Michigan. Patients were included if they were ≥18 years old and culture positive for an organism in the Enterobacterales order causing clinical infection with in vitro resistance by Clinical and Laboratory Standards Institute (CLSI) breakpoints to at least one carbapenem. Overall, there were 140 confirmed CRE infections of which 39% had clinical failure. The most common infection sources were respiratory (38%), urinary (20%), intra-abdominal (16%), and primary bacteremia (14%). A multivariable logistic regression model was developed to identify statistically significant associated predictors with clinical failure, and they included Sequential Organ Failure Assessment (SOFA) score (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.06 to 1.32), chronic dialysis (aOR, 5.86; 95% CI, 1.51-22.7), and Klebsiella pneumoniae in index culture (aOR, 3.09; 95% CI, 1.28 to 7.47). Further research on CRE infections is needed to identify best practices to promote treatment success. IMPORTANCE This work compares carbapenem-resistant Enterobacterales (CRE) infections using patient, clinical, and treatment variables to understand which characteristics are associated with the highest risk of clinical failure. Knowing which risk factors are associated with CRE infection failure can provide clinicians better prognostic and targeted interventions. Research can also further investigate why certain risk factors cause more clinical failure and can help develop treatment strategies to mitigate associated risk factors.

Postextraction infection and antibiotic prescribing among veterans receiving dental extractions.

OBJECTIVE: To characterize postextraction antibiotic prescribing patterns, predictors for antibiotic prescribing and the incidence of and risk factors for postextraction oral infection. DESIGN: Retrospective analysis of a random sample of veterans who received tooth extractions from January 1, 2017 through December 31, 2017. SETTING: VA dental clinics. PATIENTS: Overall, 69,610 patients met inclusion criteria, of whom 404 were randomly selected for inclusion. Adjunctive antibiotics were prescribed to 154 patients (38.1%). INTERVENTION: Patients who received or did not receive an antibiotic were compared for the occurrence of postextraction infection as documented in the electronic health record. Multivariable logistic regression was performed to identify factors associated with antibiotic receipt. RESULTS: There was no difference in the frequency of postextraction oral infection identified among patients who did and did not receive antibiotics (4.5% vs 3.2%; P = .59). Risk factors for postextraction infection could not be identified due to the low frequency of this outcome. Patients who received antibiotics were more likely to have a greater number of teeth extracted (aOR, 1.10; 95% CI, 1.03-1.18), documentation of acute infection at time of extraction (aOR, 3.02; 95% CI, 1.57-5.82), molar extraction (aOR, 1.78; 95% CI, 1.10-2.86) and extraction performed by an oral maxillofacial surgeon (aOR, 2.29; 95% CI, 1.44-3.58) or specialty dentist (aOR, 5.77; 95% CI, 2.05-16.19). CONCLUSION: Infectious complications occurred at a low incidence among veterans undergoing tooth extraction who did and did not receive postextraction antibiotics. These results suggest that antibiotics have a limited role in preventing postprocedural infection; however, future studies are necessary to more clearly define the role of antibiotics for this indication.

Pregabalin as adjunctive therapy in benzodiazepine discontinuation.

PURPOSE: The available evidence for the use of pregabalin as adjunctive therapy in the discontinuation of benzodiazepines is reviewed. SUMMARY: Pregabalin has been studied as an adjunctive pharmacologic treatment for the discontinuation of long-term benzodiazepine use. Unlike carbamazepine, pregabalin has little potential for drug interactions, and its adverse effects are mostly mild and transient. Pregabalin reduces the release of excitatory neurotransmitters by binding to regulatory subunits of voltage-activated calcium channels. The majority of studies evaluated failed to find a significant difference in benzodiazepine discontinuation rates between pregabalin and comparator groups. The long-term efficacy of pregabalin in benzodiazepine discontinuation is also unknown, as patients were only followed for 0-12 weeks after discontinuing the benzodiazepines. Most studies, however, did observe consistent improvement in withdrawal symptoms, anxiety symptoms, and cognitive function with pregabalin use in benzodiazepine discontinuation. Studies varied in design elements, such as whether past benzodiazepine discontinuation attempts occurred, baseline benzodiazepine use characteristics (agent, dose, duration), benzodiazepine discontinuation strategies previously used, and the use of comorbid psychiatric diagnoses and concurrent psychotropics as exclusion criteria. In addition, the literature does not clearly describe whether patients successfully discontinued pregabalin, for which there are reports of substance abuse. CONCLUSION: Based on the current available evidence, pregabalin is not recommended for use in benzodiazepine discontinuation, as the majority of studies did not find a significant difference in benzodiazepine discontinuation rates between pregabalin and comparatory groups despite an improvement in withdrawal and anxiety symptoms.