A multifaceted intervention improves antibiotic stewardship for skin and soft tissues infections.

OBJECTIVE: Assess the effectiveness of a multifaceted stewardship intervention to reduce frequency and duration of inappropriate antibiotic use for emergency department (ED) patients with skin and soft tissue infections (SSTI). We hypothesized the antibiotic stewardship program would reduce antibiotic duration and improve guideline adherence in discharged SSTI patients. DESIGN: Nonrandomized controlled trial. SETTING: Academic EDs (intervention site and control site). PATIENTS OR PARTICIPANTS: Attending physicians and nurse practitioners at participating EDs. INTERVENTION(S): Education regarding guideline-based treatment of SSTI, tests of antimicrobial treatment of SSTI, implementation of a clinical treatment algorithm and order set in the electronic health record, and ED clinicians' audit and feedback. RESULTS: We examined 583 SSTIs. At the intervention site, clinician adherence to guidelines improved from 41% to 51% (aOR = 2.13 [95% CI: 1.20-3.79]). At the control site, there were no changes in adherence during the "intervention" period (aOR = 1.17 [0.65-2.12]). The between-site comparison of these during vs. pre-intervention odds ratios was not different (aOR = 1.82 [0.79-4.21]). Antibiotic duration decreased by 26% at the intervention site during the intervention compared to pre-intervention (Adjusted Geometric Mean Ratio [95% CI] = 0.74 [0.66-0.84]). Adherence was inversely associated with SSTI severity (severe vs mild; adjusted OR 0.42 [0.20-0.89]) and purulence (0.32 [0.21-0.47]). Mean antibiotic prescription duration was 1.95 days shorter (95% CI: 1.54-2.33) in the time period following the intervention than pre-intervention period. CONCLUSIONS: A multifaceted intervention resulted in modest improvement in adherence to guidelines compared to a control site, driven by treatment duration reductions.

Interprofessional/interdisciplinary teamwork during the early COVID-19 pandemic: experience from a children's hospital within an academic health center.

The COVID-19 pandemic has created multiple, complex and intense demands on hospitals, including the need for surge planning in the many locations outside epicenters such as northern Italy or New York City. We here describe such surge planning in an Academic Health Center that encompasses a children's hospital. Interprofessional teams from every aspect of inpatient care and hospital operations worked to prepare for a COVID-19 surge. In so doing, they successfully innovated ways to integrate pediatric and adult care and maximize bed capacity. The success of this intense collaborative effort offers an opportunity for ongoing teamwork to enhance efficient, effective, and high-quality patient care.

Risk Stratification and Personal Protective Equipment Use in Pediatric Endoscopy During the Coronavirus Disease 2019 Outbreak: A Single-center Protocol.

SARS-CoV-2, the novel coronavirus causing coronavirus disease 2019 (COVID-19), is now a global pandemic. Human-to-human transmission has been documented to occur through respiratory secretions, feces, aerosols, and contaminated environmental surfaces. Pediatric patients present a unique challenge as they may have minimal symptoms and yet transmit disease. Endoscopists face risk for infection with viruses like SARS-CoV-2, as the aerosol generating nature of endoscopy diffuses respiratory disease that can be spread via an airborne and droplet route. We describe our center's methodology for pediatric patient risk stratification to facilitate responsible use of endoscopic resources during this crisis. We also describe our recommendations for use of personal protective equipment by endoscopists, with the goal of ensuring the safety of ourselves, our anesthesiology and endoscopy staff, and our patients.

Neonatal Resuscitation and Postresuscitation Care of Infants Born to Mothers with Suspected or Confirmed SARS-CoV-2 Infection.

The first case of novel coronavirus disease of 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was reported in November2019. The rapid progression to a global pandemic of COVID-19 has had profound medical, social, and economic consequences. Pregnant women and newborns represent a vulnerable population. However, the precise impact of this novel virus on the fetus and neonate remains uncertain. Appropriate protection of health care workers and newly born infants during and after delivery by a COVID-19 mother is essential. There is some disagreement among expert organizations on an optimal approach based on resource availability, surge volume, and potential risk of transmission. The manuscript outlines the precautions and steps to be taken before, during, and after resuscitation of a newborn born to a COVID-19 mother, including three optional variations of current standards involving shared-decision making with parents for perinatal management, resuscitation of the newborn, disposition, nutrition, and postdischarge care. The availability of resources may also drive the application of these guidelines. More evidence and research are needed to assess the risk of vertical and horizontal transmission of SARS-CoV-2 and its impact on fetal and neonatal outcomes. KEY POINTS: · The risk of vertical transmission is unclear; transmission from family members/providers to neonates is possible.. · Optimal personal-protective-equipment (airborne vs. droplet/contact precautions) for providers is crucial to prevent transmission.. · Parents should be engaged in shared decision-making with options for rooming in, skin-to-skin contact, and breastfeeding..

Ventriculoperitoneal shunt infection with Mycobacterium fortuitum: a rare offending organism.

Postsurgical infection is one of the greatest potential morbidities of ventriculoperitoneal shunt surgery. The majority of infections can be linked to contamination with skin flora at the time of surgery, a phenomenon that has been well described. However, there is a paucity of literature regarding infection with nontuberculous mycobacteria. The authors report a case of postoperative ventriculoperitoneal shunt infection with Mycobacterium fortuitum and review the available neurosurgical literature and treatment strategies.

Bartonella endocarditis-associated glomerulonephritis: a case report and review of the literature.

Infectious endocarditis is associated with a number of systemic manifestations, including kidney disease. Kidney manifestations, including hematuria, parenchymal infarction, and glomerulonephritis, may affect as many as 40%-50% of patients with infective endocarditis. In a minority of cases of infective endocarditis, routine bacterial cultures do not yield an offending organism. Bartonella species are a known and relatively common cause of culture-negative endocarditis and have been associated with the development of endocarditis-associated glomerulonephritis. We present a case of Bartonella endocarditis-associated glomerulonephritis in which recognition of a characteristic immunofluorescent pattern and thorough investigation of the clinical history led to this uncommon diagnosis.

A combination of secondhand cigarette smoke and Chlamydia pneumoniae accelerates atherosclerosis.

OBJECTIVE: Secondhand smoke (SS) induces chronic infection of endothelial cells by Chlamydia pneumoniae (Cpn) in vitro. We investigated the in vivo effect on atherosclerosis following exposure to SS and infection with Cpn both independently and in combination in ApoE-/- mice. METHODS AND RESULTS: Plaques were largest in the combined SS+Cpn-exposed mice with 12-57% greater cross-sectional area compared with all other groups (P<0.03). Quantitative RT-PCR (qRT-PCR) from aortic roots revealed a synergistic upregulation of both OX40L (CD134L) and MyD88 in SS+Cpn mice (P<0.05). This upregulation occurred despite decreased numbers of macrophage, dendritic cell, CD4 T cell and smooth-muscle-cell infiltrates as determined by quantitative IHC and qRT-PCR. To elucidate whether enhanced apoptosis correlated with reduced plaque cellularity, area of Tdt-mediated dUTP nick labeling positive (TUNEL+) cells and expression of key bridging molecules necessary for efferocytosis (Mertk, Tgm2, FasL and C1qa) were examined. In SS+Cpn mice, there was an increase of the area of TUNEL+ cells in plaque cores (P<0.001) and a downregulation of efferocytosis gene expression (P<0.05). Systemic expression of cytokines in sera (Luminex) showed no differences between groups, suggesting that focal disease mechanisms within the plaque predominated. CONCLUSIONS: The combination of SS exposure and Cpn infection enhanced atherosclerosis more than either variable did independently by activating inflammatory cells and by promoting growth and maturation of lesions via defective phagocytic clearance and accumulation of apoptotic cells.

Effect of flash-heat treatment on antimicrobial activity of breastmilk.

BACKGROUND AND OBJECTIVES: The World Health Organization recommends human immunodeficiency virus (HIV)-positive mothers in resource-poor regions heat-treat expressed breastmilk during periods of increased maternal-to-child transmission risk. Flash-heat, a "low tech" pasteurization method, inactivates HIV, but effects on milk protein bioactivity are unknown. The objectives were to measure flash-heat's effect on antimicrobial properties of lactoferrin, lysozyme, and whole milk and on the digestive resistance of lactoferrin and lysozyme. METHODS: Flash-heated and unheated breastmilk aliquots from HIV-positive mothers in South Africa were "spiked" with Staphylococcus aureus and Escherichia coli and then cultured for 0, 3, and 6 hours. Lysozyme and lactoferrin activities were determined by lysis of Micrococcus luteus cells and inhibition of enteropathogenic E. coli, respectively, measured spectrophotometrically. Percentages of proteins surviving in vitro digestion, lactoferrin and lysozyme activity, and bacteriostatic activity of whole milk in heated versus unheated samples were compared. RESULTS: There was no difference in rate of growth of E. coli or S. aureus in flash-heated versus unheated whole milk (p = 0.61 and p = 0.96, respectively). Mean (95% confidence interval) antibacterial activity of lactoferrin was diminished 11.1% (7.8%, 14.3%) and that of lysozyme by up to 56.6% (47.1%, 64.5%) by flash-heat. Digestion of lysozyme was unaffected (p = 0.12), but 25.4% less lactoferrin survived digestion (p < 0.0001). CONCLUSIONS: In summary, flash-heat resulted in minimally decreased lactoferrin and moderately decreased lysozyme bioactivity, but bacteriostatic activity of whole milk against representative bacteria was unaffected. This suggests flash-heated breastmilk likely has a similar profile of resistance to bacterial contamination as that of unheated milk. Clinical significance of the decreased bioactivity should be tested in clinical trials.

Tobacco smoke induces a persistent, but recoverable state in Chlamydia pneumoniae infection of human endothelial cells.

We investigated the extent to which tobacco smoke could induce persistence of Chlamydia pneumoniae in human endothelial cells. Aortic and coronary artery endothelia were infected in the absence or presence of non-cytotoxic concentrations of tobacco smoke medium. Following exposure to smoke medium, chlamydial inclusions were smaller and demonstrated fewer genome copies as determined by real-time PCR. Enumeration of inclusion-forming units (IFU) established a significant smoke-mediated, dose-dependent inhibition of elementary bodies (EB). Host cell apoptosis did not contribute to the observed restriction of productive infection. Ultrastructure analysis demonstrated an arrest in chlamydial development following smoke-exposure, with a predominance of reticulate bodies (RB) observed inside inclusions. Recovery of viable IFU was achieved with removal of smoke-medium and addition of L-tryptophan. In the presence of smoke, C. pneumoniae infection demonstrated all the characteristics of persistence in human endothelia cells. This is the first time that primary human arterial endothelial cells have been shown to support chlamydial persistence. Tobacco smoke is a well-characterized risk factor for progression of atherosclerosis, but a novel means of inducing chlamydial persistence in vascular cells. Thus, smoking may additionally contribute to atherosclerotic disease by inducing a persistent chlamydial infection in arterial endothelium.

Tobacco smoke induces persistent infection of Chlamydophila pneumoniae in HEp-2 cells.

We examined tobacco smoke exposure and its effect on the life cycle of Chlamydophila pneumoniae (C. pneumoniae) in HEp-2, a human respiratory epithelial cell line. Using noncytotoxic concentrations of smoke medium, chlamydiae were grown in tissue culture and infectious particles were quantitated indirectly by immunocytometry of infected indicator cells. Chlamydial genome copy number was assessed with real-time polymerase chain reaction, and ultrastructure was examined by transmission electron microscopy. There was a significant reduction (56-64%; p<0.05) in the number of infectious elementary bodies following smoke exposure compared to untreated cultures. Under the same conditions, at late time points, smoke-exposed cultures showed significantly fewer chlamydial DNA copies (p<0.04). Moreover, smoke exposure induced large aberrant bodies that predominated within the inclusion. Following in vitro smoke exposure, alterations in the developmental cycle of C. pneumoniae included: inhibition of productive infection, reduced bacterial cell division, and formation of aberrant bodies. Thus, using this novel system, we were able to induce chlamydial persistence. Tobacco smoke exposure may represent a risk for establishment of a chronic reservoir of C. pneumoniae infection within respiratory epithelium.

Mapping the viral genetic determinants of endothelial cell tropism in human cytomegalovirus.

Endothelial cells are natural sites of infection for human cytomegalovirus (HCMV) and are increasingly recognized to play an important role in viral dissemination, as well as provide access to underlying tissues and organs. However, the viral factors required for endothelial cell tropism are poorly defined. The goals of the project were to develop a system to study endothelial cell infectivity factors in HCMV, and map the viral genetic determinants required for these tropism functions. HCMV infection of primary aortic endothelial cells (AEC) was studied as a means to evaluate aspects relevant to both pathogenesis of acute infection and chronic vascular diseases. A series of HCMV virus strains was screened for endothelial tropism by comparing replication efficiencies on AEC. A virus strain that was efficient for replication (AD169varATCC), and a virus strain that was restricted for replication (Toledo), were selected for further analysis and characterization. We present evidence for a novel HCMV endothelial tropism factor that functioned following viral internalization across the endothelial cell plasma membrane and prior to nuclear entry. This factor may be involved in intracellular transport of the virion capsid-tegument structure. Complementation approaches using pseudotype virus infection of AEC demonstrated that the tropism defective strain could be rescued in trans. This supported the existence of a viral encoded tropism determinant. Using a gain of function approach, endothelial cell infectivity of the non-tropic HCMV strain Toledo was rescued with AD169 cosmid sequences. Tropism-specific viral genetic determinant(s) may be mapped to a region of the AD169 viral DNA encompassing UL48-56.