Real-World Application of Oral Therapy for Infective Endocarditis: A Multicenter, Retrospective, Cohort Study.

BACKGROUND: We sought to compare the outcomes of patients treated with intravenous (IV)-only vs oral transitional antimicrobial therapy for infective endocarditis (IE) after implementing a new expected practice within the Los Angeles County Department of Health Services (LAC DHS). METHODS: We conducted a multicentered, retrospective cohort study of adults with definite or possible IE treated with IV-only vs oral therapy at the 3 acute care public hospitals in the LAC DHS system between December 2018 and June 2022. The primary outcome was clinical success at 90 days, defined as being alive and without recurrence of bacteremia or treatment-emergent infectious complications. RESULTS: We identified 257 patients with IE treated with IV-only (n = 211) or oral transitional (n = 46) therapy who met study inclusion criteria. Study arms were similar for many demographics; however, the IV cohort was older, had more aortic valve involvement, were hemodialysis patients, and had central venous catheters present. In contrast, the oral cohort had a higher percentage of IE caused by methicillin-resistant Staphylococcus aureus. There was no significant difference between the groups in clinical success at 90 days or last follow-up. There was no difference in recurrence of bacteremia or readmission rates. However, patients treated with oral therapy had significantly fewer adverse events. Multivariable regression adjustments did not find significant associations between any selected variables and clinical success across treatment groups. CONCLUSIONS: These results demonstrate similar outcomes of real-world use of oral vs IV-only therapy for IE, in accord with prior randomized, controlled trials and meta-analyses.

Effect of mortality from COVID-19 on inpatient outcomes.

When hospitals first encountered coronavirus disease 2019 (COVID-19), there was a dearth of therapeutic options and nearly 1 in 3 patients died from the disease. By the summer of 2020, as deaths from the disease declined nationally, multiple single-center studies began to report declining mortality of patients with COVID-19. To evaluate the effect of COVID-19 on hospital-based mortality, we searched the Vizient Clinical Data Base for outcomes data from approximately 600 participating hospitals, including 130 academic medical centers, from January 2017 through December 2020. More than 32 million hospital admissions were included in the analysis. After an initial spike, mortality from COVID-19 declined in all regions of the country to under 10% by June 2020 and remained constant for the remainder of the year. Despite this, inpatient, all-cause mortality has increased since the beginning of the pandemic, even those without respiratory failure. Inpatient mortality has particularly increased in elderly patients and in those requiring intubation for respiratory failure. Since June 2020, COVID-19 kills one in every 10 patients admitted to the hospital with this diagnosis. The addition of this new disease has raised overall hospital mortality especially those who require intubation for respiratory failure.

Reducing Catheter-associated Urinary Tract Infections via Cost-saving Diagnostic Stewardship.

We conducted a quality improvement project at our large, public, tertiary-care, academic hospital to reduce the standardized infection ratio (SIR) of hospital-acquired catheter-associated urinary tract infections (CAUTIs). Our diagnostic stewardship program, based on education and audit and feedback, significantly reduced inpatient urine culture orders and CAUTI SIR.

Osteomyelitis Complicating Sacral Pressure Ulcers: Whether or Not to Treat With Antibiotic Therapy.

The treatment of osteomyelitis in patients with stage IV sacral pressure ulcers is controversial. We conducted a systematic literature review and did not find evidence of benefit of antibacterial therapy in this setting without concomitant surgical debridement and wound coverage. Furthermore, many patients with chronically exposed bone do not have evidence of osteomyelitis when biopsied, and magnetic resonance imaging may not accurately distinguish osteomyelitis from bone remodeling. The goal of therapy should be local wound care and assessment for the potential of wound closure. If the wound can be closed and osteomyelitis is present on bone biopsy, appropriate antibiotic therapy is reasonable. We find no data to support antibiotic durations of >6 weeks in this setting, and some authors recommend 2 weeks of therapy if the osteomyelitis is limited to cortical bone. If the wound will not be closed, we find no clear evidence supporting a role for antibiotic therapy.

Busting the Myth of "Static vs Cidal": A Systemic Literature Review.

We sought to determine if clinical data validate the dogma that bactericidal antibiotics are more clinically effective than bacteriostatic agents. We performed a systematic literature review of published, randomized, controlled trials (RCTs) that compared a bacteriostatic agent to a bactericidal agent in the treatment of clinical, bacterial infections. Of 56 identified trials published since 1985, 49 found no significant difference in efficacy between bacteriostatic and bactericidal agents. In 6 trials it was found that the bacteriostatic agent was superior to the bactericidal agent in efficacy. Only 1 trial found that the bactericidal agent was superior; in that case, the inferiority of the static agent was explainable by underdosing of the drug based on pharmacokinetic-pharmacodynamic analysis. Thus, virtually all available data from high-quality, RCTs demonstrate no intrinsic superiority of bactericidal compared to bacteriostatic agents. Other drug characteristics such as optimal dosing, pharmacokinetics, and tissue penetration may be more important efficacy drivers.

2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults.

These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.

Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults.

These guidelines are intended for use by infectious disease specialists, orthopedic surgeons, neurosurgeons, radiologists, and other healthcare professionals who care for patients with native vertebral osteomyelitis (NVO). They include evidence and opinion-based recommendations for the diagnosis and management of patients with NVO treated with antimicrobial therapy, with or without surgical intervention.

Madura foot: two case reports, review of the literature, and new developments with clinical correlation.

"Madura foot" or pedal mycetoma is a rare destructive infection of the skin and subcutaneous tissues of the foot, progressing to involve muscle and bone. The infection can be caused by both bacteria and fungi. Infection typically follows traumatic implantation of bacteria or fungal spores, which are present in soil or on plant material. Clinically, this entity can be difficult to diagnose and can have an indolent and progressive course. Early diagnosis is important to prevent patient morbidity and mortality. We present two cases of pedal mycetoma, review the literature, review new developments in diagnosis, and discuss magnetic resonance imaging (MRI) features of this unusual entity.

Choosing patients over placebos: oral transitional therapy vs. IV-only therapy for bacteraemia and infective endocarditis.

BACKGROUND: The belief that antibiotics must be administered intravenously (IV) to treat bacteraemia and endocarditis has its origins 70 years ago and has engrained itself in the psyche of the medical community and the public at large. This has led to hesitancy in adopting evidence-based strategies utilizing oral transitional therapy for the treatment of these infections. We aim to reframe the narrative around this debate, focusing on patient safety over vestigial psychology. OBJECTIVES: This narrative review summarizes the current state of the literature regarding the use of oral transitional therapy for the treatment of bacteraemia and infective endocarditis, focusing on studies comparing it to the traditional, IV-only approach. SOURCES: Relevant studies and abstracts from PubMed reviewed in April 2023. CONTENT: Treating bacteraemia with oral transitional therapy has been studied in 9 randomized controlled trials (RCTs), totalling 625 patients, as well as numerous large, retrospective cohorts, including 3 published in the last 5 years alone, totalling 4763 patients. We identified 3 large, retrospective cohort studies; one quasi-experimental, pre-post study, and 3 RCTs of patients with endocarditis, totalling 748 patients in the retrospective cohorts and 815 patients in prospective, controlled studies. In all these studies, no worse outcomes were observed in the oral transitional therapy arm as compared with IV-only therapy. The main difference has consistently been longer durations of inpatient hospitalization and increased risk of catheter-related adverse events like venous thrombosis and line-associated blood stream infections in the IV-only groups. IMPLICATIONS: There are ample data showing that choosing oral therapy reduces hospital stay and has fewer adverse events for patients than IV-only therapy, all with similar or better outcomes. In selected patients, choosing IV-only therapy may serve more as an anxiolytic "placebo" for the patient and provider rather than a necessity for treating the actual infection.

SARS-CoV-2 cycle threshold (Ct) values predict future COVID-19 cases.

AIM: Anticipating local surges in COVID-19 cases has predominantly been based on observation of increasing cases. We sought to determine if temporal trends in SARS-CoV-2 Cycle threshold (Ct) values from clinical testing were predictive of future cases. METHODS: Data were collected from a large, safety-net hospital in Los Angeles, California. Ct values for all SARS-CoV-2 detections by the GeneXpert system (Cepheid) between October 2020 to March 2021 were analyzed. RESULTS: A total of 2,114 SARS-CoV-2-positive samples were included. Cases increased dramatically in December 2020, peaking the first week of January, before returning to pre-surge numbers by mid-February. Ct values fell during this same period, with values in December and January (25.6 ± 7.8 and 27±7.9, respectively) significantly lower than those of the other months (30±9.3 to 37.7 ± 6.3). Average weekly Ct values for all patients negatively correlated with the number of tests run two weeks in the future (r= -0.74, p<0.0001), whereas Ct values for asymptomatic patients negatively correlated most strongly with total number of tests performed one month later (r= -0.88, p<0.0001). Predictive modeling using these Ct values correctly predicted whether cases would increase or decrease 65% of the time for a subsequent surge (May-July 2021). CONCLUSIONS: During the largest COVID-19 surge in Los Angeles to date, we observed significantly lower Ct values (representing higher levels of viral RNA) suggesting that increased transmission of COVID-19 was temporarily associated with higher viral loads. Decreasing Ct values appear to be a leading indicator for predicting future COVID-19 cases, which can facilitate improved hospital-level surge planning.

How to change the course: practical aspects of implementing shorter is better.

BACKGROUND: Based on multiple randomized-controlled clinical trials, shorter antibiotic courses are equally effective as traditional longer courses for many types of infections. However, longer courses are still being used widely in the clinical practice. OBJECTIVES: To describe four components involved in the successful implementation of shorter antibiotic courses in our health care institutions, including an academic, public hospital and a community hospital staffed primarily by private practitioners. SOURCES: Clinical trials and peer-reviewed publications. CONTENT: We provide practical advice on how to support the change in clinical practice to shorten antibiotic duration. Specifically, we list the steps that we have successfully used to develop and implement an institutional practice change regarding the duration of antibiotic therapy: (a) establishing consensus documents outlining a data-driven expected practice for using antibiotics, (b) antibiotic stewardship programme support, (c) provider education, and (d) reinforcing behaviour through psychological and other tools. The implementation of these processes has successfully led to shorter antibiotic courses and decreased antibiotic use in our diverse practice settings. IMPLICATIONS: Intentional improvement in decreasing the duration of antibiotic therapy can be achieved by a specific antibiotic stewardship programme strategy and tactics. The implementation of shorter antibiotic courses has effects at individual and societal levels in an era of increasing antibacterial resistance and health care costs.

Oral Is the New IV. Challenging Decades of Blood and Bone Infection Dogma: A Systematic Review.

BACKGROUND: We sought to determine if controlled, prospective clinical data validate the long-standing belief that intravenous (IV) antibiotic therapy is required for the full duration of treatment for 3 invasive bacterial infections: osteomyelitis, bacteremia, and infective endocarditis. METHODS: We performed a systematic review of published, prospective, controlled trials that compared IV-only to oral stepdown regimens in the treatment of these diseases. Using the PubMed database, we identified 7 relevant randomized controlled trials (RCTs) of osteomyelitis, 9 of bacteremia, 1 including both osteomyelitis and bacteremia, and 3 of endocarditis, as well as one quasi-experimental endocarditis study. Study results were synthesized via forest plots and funnel charts (for risk of study bias), using RevMan 5.4.1 and Meta-Essentials freeware, respectively. RESULTS: The 21 studies demonstrated either no difference in clinical efficacy, or superiority of oral versus IV-only antimicrobial therapy, including for mortality; in no study was IV-only treatment superior in efficacy. The frequency of catheter-related adverse events and duration of inpatient hospitalization were both greater in IV-only groups. DISCUSSION: Numerous prospective, controlled investigations demonstrate that oral antibiotics are at least as effective, safer, and lead to shorter hospitalizations than IV-only therapy; no contrary data were identified. Treatment guidelines should be modified to indicate that oral therapy is appropriate for reasonably selected patients with osteomyelitis, bacteremia, and endocarditis.

Fosfomycin vs Ertapenem for Outpatient Treatment of Complicated Urinary Tract Infections: A Multicenter, Retrospective Cohort Study.

BACKGROUND: We sought to determine the comparative efficacy of fosfomycin vs ertapenem for outpatient treatment of complicated urinary tract infections (cUTIs). METHODS: We conducted a multicenter, retrospective cohort study involving patients with cUTI treated with outpatient oral fosfomycin vs intravenous ertapenem at 3 public hospitals in Los Angeles County between January 2018 and September 2020. The primary outcome was resolution of clinical symptoms 30 days after diagnosis. RESULTS: We identified 322 patients with cUTI treated with fosfomycin (n = 110) or ertapenem (n = 212) meeting study criteria. The study arms had similar demographics, although patients treated with ertapenem more frequently had pyelonephritis or bacteremia while fosfomycin-treated patients had more retained catheters, nephrolithiasis, or urinary obstruction. Most infections were due to extended-spectrum ß-lactamase-producing E. coli and Klebsiella pneumoniae, 80%-90% of which were resistant to other oral options. Adjusted odds ratios for clinical success at 30 days, clinical success at last follow-up, and relapse were 1.21 (95% CI, 0.68-2.16), 0.84 (95% CI, 0.46-1.52), and 0.94 (95% CI, 0.52-1.70) for fosfomycin vs ertapenem, respectively. Patients treated with fosfomycin had significant reductions in length of hospital stay and length of antimicrobial therapy and fewer adverse events (1 vs 10). Fosfomycin outcomes were similar irrespective of duration of lead-in intravenous (IV) therapy or fosfomycin dosing interval (daily, every other day, every third day). CONCLUSIONS: These results would support the conduct of a randomized controlled trial to verify efficacy. In the meantime, they suggest that fosfomycin may be a reasonable stepdown from IV antibiotics for cUTI.