Dalbavancin Use in Persons Who Use Drugs May Increase Adherence Without Increasing Cost.

Background: Dalbavancin (DAL) may obviate concerns regarding misuse of IV access in persons who use drugs (PWUD) completing treatment for infections in an outpatient setting. However, hesitancy to adopt its use exists due to the cost-prohibitive nature of DAL and perceived issues with insurance reimbursement. Our study looks to determine the financial impact of DAL use in actual, measured cost, and health care utilization, data as well as the effect on treatment completion rates. Methods: This is a retrospective cohort comparing cost information and treatment completion rates of patients who received DAL to a random sample of patients with Staphylococcus aureus bacteremia prior to the institutional availability of DAL. Results: From June 2020 to January 2022, 29 PWUD received DAL. Dalbavancin use resulted in the completion of intended duration in 19 patients (66%) compared with 11 (55%) without DAL. The contribution margin with DAL use was $7180 compared with $6655 without; this was not statistically significant (P = 0.47). Conclusion: Dalbavancin use in PWUD may increase treatment completion, with no statistically significant difference in contribution margins.

Clinical failure of dalbavancin for MRSA bacteremia in patient with severe obesity and history of IVDU.

Dalbavancin is a lipoglycopeptide antibiotic used off-label to treat serious gram-positive infections, including infections secondary to methicillin-resistant Staphylococcus aureus (MRSA). Dalbavancin has unique pharmacokinetic parameters and has a role in therapy for treating vulnerable patients, including intravenous drug users, who have challenges complying with typical care plans for serious infections. While there is data indicating successful clinical use of dalbavancin in patients with history of intravenous drug use as well as pharmacokinetic-pharmacodynamic data assessing dalbavancin in obesity, there is a lack of information regarding clinical effects of dalbavancin in patients with extreme obesity, especially in patients with concomitant drug use. This case report describes a 40-year-old morbidly obese female actively using intravenous drugs who developed prolonged MRSA bacteremia without a recognizable focus. Despite partial treatment with dalbavancin, the patient developed osteomyelitis and discitis of the spine with associated epidural phlegmon, likely complications of the MRSA bacteremia.

Pneumococcal Urinary Antigen Testing in United States Hospitals: A Missed Opportunity for Antimicrobial Stewardship.

BACKGROUND: The Infectious Diseases Society of America recommends pneumococcal urinary antigen testing (UAT) when identifying pneumococcal infection would allow for antibiotic de-escalation. However, the frequencies of UAT and subsequent antibiotic de-escalation are unknown. METHODS: We conducted a retrospective cohort study of adult patients admitted with community-acquired or healthcare-associated pneumonia to 170 US hospitals in the Premier database from 2010 to 2015, to describe variation in UAT use, associations of UAT results with antibiotic de-escalation, and associations of de-escalation with outcomes. RESULTS: Among 159 894 eligible admissions, 24 757 (15.5%) included UAT performed (18.4% of intensive care unit [ICU] and 15.3% of non-ICU patients). Among hospitals with ≥100 eligible patients, UAT proportions ranged from 0% to 69%. Compared to patients with negative UAT, 7.2% with positive UAT more often had a positive Streptococcus pneumoniae culture (25.4% vs 1.9%, P < .001) and less often had resistant bacteria (5.2% vs 6.8%, P < .05). Of patients initially treated with broad-spectrum antibiotics, most were still receiving broad-spectrum therapy 3 days later, but UAT-positive patients more often had coverage narrowed (38.4% vs 17.0% UAT-negative and 14.6% untested patients, P < .001). Hospital rate of UAT was strongly correlated with de-escalation following a positive test. Only 3 patients de-escalated after a positive UAT result were subsequently admitted to ICU. CONCLUSIONS: UAT is not ordered routinely in pneumonia, even in ICU. A positive UAT result was associated with less frequent resistant organisms, but usually did not lead to antibiotic de-escalation. Increasing UAT and narrowing therapy after a positive UAT result are opportunities for improved antimicrobial stewardship.

Improving Management of Hospitalized Adults With Uncomplicated Cellulitis or Cutaneous Abscess.

Implementation of a guideline for the management of hospitalized adults with uncomplicated skin and soft-tissue infections may decrease unnecessary antibiotic use. For cellulitis, treatment with vancomycin and broad-spectrum antibiotics decreased significantly. For cutaneous abscess, treatment with broad-spectrum antibiotics decreased significantly. There were no differences in rates of treatment failure, recurrence, or adverse events.

Activation of the Classical Mitogen-Activated Protein Kinases Is Part of the Shiga Toxin-Induced Ribotoxic Stress Response and May Contribute to Shiga Toxin-Induced Inflammation.

Infection with enterohemorrhagic Escherichia coli (EHEC) can result in severe disease, including hemorrhagic colitis and the hemolytic uremic syndrome. Shiga toxins (Stx) are the key EHEC virulence determinant contributing to severe disease. Despite inhibiting protein synthesis, Shiga toxins paradoxically induce the expression of proinflammatory cytokines from various cell types in vitro, including intestinal epithelial cells (IECs). This effect is mediated in large part by the ribotoxic stress response (RSR). The Shiga toxin-induced RSR is known to involve the activation of the stress-activated protein kinases (SAPKs) p38 and JNK. In some cell types, Stx also can induce the classical mitogen-activated protein kinases (MAPKs) or ERK1/2, but the mechanism(s) by which this activation occurs is unknown. In this study, we investigated the mechanism by which Stx activates ERK1/2s in IECs and the contribution of ERK1/2 activation to interleukin-8 (IL-8) expression. We demonstrate that Stx1 activates ERK1/2 in a biphasic manner: the first phase occurs in response to StxB1 subunit, while the second phase requires StxA1 subunit activity. We show that the A subunit-dependent ERK1/2 activation is mediated through ZAK-dependent signaling, and inhibition of ERK1/2 activation via the MEK1/2 inhibitors U0126 and PD98059 results in decreased Stx1-mediated IL-8 mRNA. Finally, we demonstrate that ERK1/2 are activated in vivo in the colon of Stx2-intoxicated infant rabbits, a model in which Stx2 induces a primarily neutrophilic inflammatory response. Together, our data support a role for ERK1/2 activation in the development of Stx-mediated intestinal inflammation.

Reappearance and treatment of penicillin-susceptible Staphylococcus aureus in a tertiary medical centre.

OBJECTIVES: The purpose of this study was to describe trends in the prevalence and treatment patterns of penicillin-susceptible Staphylococcus aureus (SA) infections. METHODS: This was a cross-sectional study of MSSA isolates from blood cultures at a tertiary-care centre between 1 January 2003 and 31 December 2012. All blood cultures positive for MSSA drawn during the study period were used to calculate the prevalence of penicillin-susceptible SA. Repeat cultures were excluded if they were isolated within 6 weeks of the index culture. The analysis was then restricted to inpatient blood cultures to assess treatment patterns. Antibiotics administered 48-96 h after the culture were analysed. RESULTS: A total of 446 blood cultures positive for MSSA were included in the analysis. There was a distinct trend showing an increase in the percentage of penicillin-susceptible SA over 10 years from 13.2% (95% CI 4.1%-22.3%) in 2003 to 32.4% (95% CI 17.3%-47.5%) in 2012 (P trend <0.001). During the study period, penicillin use for penicillin-susceptible SA bacteraemia increased from 0.0% in 2003-04 to 50.0% in 2011-12 (P trend = 0.007). CONCLUSIONS: Over a decade, there was an ∼3-fold increase in penicillin susceptibility among MSSA blood cultures at a large tertiary-care facility. Although treatment with penicillin increased over the study period, only 50% of penicillin-susceptible SA was treated with penicillin in the final study period. This study suggests that while susceptibility to penicillin appears to be returning in SA, the use of penicillin for penicillin-susceptible SA bacteraemia is low.

Carbapenem-resistant enterobacteriaceae: analyzing knowledge and practice in healthcare providers.

Background. Gram negative antibiotic resistance is increasing worldwide as both carbapenem-resistant enterobacteriaceae (CREs) and Enterobacteriaceae producing extended spectrum ß-lactamases (ESBLs) become more common. Objective. We analyzed clinicians' knowledge regarding resistant gram-negative organisms with respect to infection control practices, prescribing practices and assessment of their patients' risk for resistant infections. Design. Online survey. Participants. Target population included clinicians who prescribe antibiotics i.e., medical doctors and mid-level practitioners, at three Massachusetts hospitals. Methods. Questionnaires were sent to 3 Tufts-affiliated teaching hospitals to assess level of knowledge and elucidate perceptions about gram-negative resistance. Results. We received 434 responses from 3332 non-infectious disease clinicians (13%) surveyed at the three hospitals. 51.1% of clinicians correctly scored 50% or greater on the knowledge questions. Internal medicine clinicians had higher knowledge scores than non-internal medicine clinicians (62% vs 45%; OR = 1.67, p = 0.02). Clinicians within three years of training had higher scores than those with more than 10 years of training (64.3% vs 44%; OR = 2.3, p = 0.002). Clinicians with fewer years since training and those with higher knowledge scores were more likely to appropriately consider certain patients at risk for resistant infections (p < 0.05). 54.4% of clinicians were very concerned about gram-negative antibiotic resistance. 64.6% of clinicians felt comfortable de-escalating antibiotics as cultures are available. Conclusion. We found overall low knowledge scores and much variability in the way clinicians assess whether certain patient populations are at risk for antibiotic resistance. Internal medicine clinicians and those with fewer years since completion of their training scored higher and more appropriately considered patients at risk for resistance. The majority of clinicians are concerned about gram-negative resistance and indicated they would de-escalate antibiotic therapy if they had susceptibility information. These results will help focus and target our teaching and awareness-raising strategies.

Managing community-acquired pneumonia during flu season.

The clinical findings of influenza overlap those of community-acquired bacterial pneumonia (CABP), and influenza infection can be complicated by bacterial infections. Reviewed here are the epidemiology, pathophysiology, diagnosis, and management of community-acquired pneumonia (CAP) with special emphasis on considerations during influenza season.