he global pandemic of novel coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019, and has since spread worldwide. 1 As of April 5, 2020, there have been more than 1.2 million reported cases and 69 000 deaths in more than 200 countries. This novel Betacoronavirus is similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV); based on its genetic proximity, it likely originated from bat-derived coronaviruses with spread via an unknown intermediate mammal host to humans. 1 The viral genome of SARS-CoV-2 was rapidly sequenced to enable diagnostic testing, epidemiologic tracking, and development of preventive and therapeutic strategies.Currently, there is no evidence from randomized clinical trials (RCTs) that any potential therapy improves outcomes in patients with either suspected or confirmed COVID-19. There are no clinical trial data supporting any prophylactic therapy. More than 300 active clinical treatment trials are underway. This narrative review summarizes current evidence regarding major proposed treatments, repurposed or experimental, for COVID-19 and provides a summary of current clinical experience and treatment guidance for this novel epidemic coronavirus. MethodsA literature review was performed using PubMed to identify relevant English-language articles published through March 25, 2020. Search terms included coronavirus, severe acute respiratory syndrome coronavirus 2, 2019-nCoV, SARS-CoV-2, SARS-CoV, MERS-CoV, and COVID-19 in combination with treatment and pharmacology. The search resulted in 1315 total articles. Due to the lack of RCTs, the authors also included case reports, case series, and review articles. The authors independently reviewed the titles and abstracts for inclusion. Additional relevant articles were identified from the review of citations referenced. Active clinical trials were identified using the disease search term coronavirus infection on ClinicalTrials.gov and the index of studies of novel coronavirus pneumonia in the Chinese Clinical Trial Registry. 2 SARS-CoV-2: Virology and Drug Targets SARS-CoV-2, a single-stranded RNA-enveloped virus, targets cells through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Following IMPORTANCE The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.OBSERVATIONS No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The mo...

The limited published data suggest that linezolid appears to be an effective alternative to trimethoprim/sulfamethoxazole for the treatment of nocardiosis. Unfortunately, the high cost and potentially serious long-term toxicities of linezolid appear to limit its use and relegate it to salvage therapy alone or in combination with other antimicrobials.

Significant advances in the potency and tolerability of antiretroviral therapy (ART) have led to very high rates of virologic success for most who remain adherent to therapy. As a result, the life expectancy of people living with HIV (PLWH) has increased significantly. PLWH do, however, continue to experience a significantly higher risk of noninfectious comorbidities and chronic age-related complications, including cardiovascular disease and malignancies, which are now the biggest drivers of this excess morbidity and mortality. Therefore, in addition to virologic failure, the management of the treatment-experienced patient increasingly requires optimization of ART to enhance tolerability, avoid drug–drug interactions, and mitigate non-AIDS complications and comorbid conditions. This article will present principles of the management of virologic failure, poor immunologic recovery, and strategies for optimizing ART in the setting of virologic suppression.

CDAD is a debilitating disease with increasing treatment failure rates and recurrences using standard therapies. Clinicians need to look at other options to expand the available treatment arsenal in addition to placing a greater emphasis on prevention.

Purpose: Utilization of rapid diagnostic testing alongside intensive antimicrobial stewardship interventions improves patient outcomes. We sought to determine the clinical impact of a rapid blood culture identification (BCID) panel in an established Antimicrobial Stewardship Program (ASP) with limited personnel resources. Methods: A single center retrospective pre- and post-intervention cohort study was performed following the implementation of a BCID panel on patients admitted with at least 1 positive blood culture during the study period. The primary outcome was time to optimal therapy from blood culture collection. Secondary outcomes included days of therapy (DOT), length of stay, and 30-day mortality and readmission rates. Results: 277 patients were screened with 180 patients included, with 82 patients in the pre-BCID and 98 in the post-BCID arms. Median time to optimal therapy was 73.8 hours (IQR; 1.1-79.6) in the pre-BCID arm and 34.7 hours (IQR; 10.9-71.6) in the post-BCID arm (p ≤ 0.001). Median DOT for vancomycin was 4 and 3 days (p ≤ 0.001), and for piperacillin-tazobactam was 3.5 and 2 days (p ≤ 0.007), for the pre-BCID and post-BCID arms, respectively. Median length of hospitalization was decreased from 11 to 9 days (p = 0.031). No significant change in 30-day readmission rate was noted, with a trend toward lower mortality (12% vs 5%; p = 0.086). Conclusion: Introduction of BCID into the daily workflow resulted in a significant reduction in time to optimal therapy for bloodstream infections and DOT for select broad-spectrum antibiotics, highlighting the potential benefits of rapid diagnostics even in settings with limited personnel resources.

We performed a nested case-control study (ratio of 1:4) on the emergence of tigecycline-resistant multidrug-resistant Klebsiella pneumoniae (TR-MDRKP) isolates among patients who initially presented with a tigecycline-susceptible MDRKP isolate. Out of 260 patients, 24 (9%) had a subsequent clinical culture positive for a TR-MDRKP isolate within the 90-day follow-up period. On logistic regression analyses, receipt of tigecycline (adjusted odds ratio [OR], 5.06; 95% confidence interval [CI], 1.80 to 14.23; P ‫؍‬ 0.002) was the only independent predictor of subsequent isolation of a TR strain.T igecycline, a minocycline derivative, remains one of the few therapeutic options for the treatment of infections caused by multidrug-resistant Klebsiella pneumoniae (MDRKP) isolatesincluding Klebsiella pneumoniae carbapenemase (KPC) producers-and other Gram-negative organisms (1, 2). Of concern, tigecycline nonsusceptibility (i.e., tigecycline resistance [TR]) among Klebsiella pneumoniae isolates has been reported from different continents and ranged between 0% and 11.5% in a recent large study (3-6). Furthermore, several recent case studies identified patients who were treated with tigecycline for an initially tigecycline-susceptible MDRKP (TS-MDRKP) infection but from whom a TR-MDRKP strain was subsequently isolated (7-10). However, the potential of in vivo emergence of TR among MDRKP isolates has so far not been systematically investigated to our knowledge. We intended to study the rates of and risk factors for the in vivo emergence of TR among Klebsiella pneumoniae isolates in a large population of patients who initially presented with a TS-MDRKP.We performed a nested case-control study on the subsequent emergence of TR among all patients from whom a TS-MDRKP strain was previously isolated at a tertiary care center between January 2008 and July 2011. MDRKP was defined as the presence of either an extended-spectrum ␤-lactamase (ESBL)-or KPCproducing Klebsiella pneumoniae isolate, determined as per Clinical and Laboratory Standards Institute (CLSI) guidelines on ESBL testing, carbapenem resistance patterns, and Hodge test results, respectively (11, 12). Food and Drug Administration (FDA) breakpoints were applied to interpret the results of tigecycline susceptibility testing using the disc diffusion method and Etest (susceptible if the zone diameter is Ն19 mm and the isolate MIC is Յ2 g/ml, respectively).A case was defined as a patient from whom a TR-MDRKP was isolated between Ͼ48 h and Ͻ90 days after the day a TS-MDRKP strain was isolated (zero time). A control was defined as a patient from whom a TS-MDRKP strain was isolated during the study period but with no subsequent TR-MDRKP strains. Controls were matched to cases based on the isolate's resistance mechanism (ESBL versus KPC) but otherwise randomly selected in a 1:4 ratio. Cases were compared to controls with regard to a variety of demographic and clinical characteristics. We also recorded (i) all antibiotic exposures within 90 days before zero time and (ii) all antib...

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H. pylori infection remains one of the most significant infections worldwide, and treatment failure rate with the current standard therapy continues to rise. Other treatment options should be explored to meet the emerging challenge.