Bruce S. Ribner

Methicillin-resistant Staphylococcus aureus: A consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management

Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen in community hospitals, long-term-care facilities, and tertiary care hospitals. The basic mechanism of resistance is alteration in penicillin-binding proteins of the organism. Methods for isolation by culture and typing of the organism are reviewed. MRSA colonization precedes infection. A major reservoir is the anterior nares. MRSA is usually introduced into an institution by a colonized or infected patient or health care worker. The principal mode of transmission is via the transiently colonized hands of hospital personnel. Indications for antibiotic therapy for eradication of colonization and treatment of infection are reviewed. Infection control guidelines and discharge policy are presented in detail for acute-care hospitals, intensive care and burn units, outpatient settings, and long-term-care facilities. Recommendations for handling an outbreak, surveillance, and culturing of patients are presented based on the known epidemiology.

Persistence of Ebola Virus in Ocular Fluid during Convalescence

Among the survivors of Ebola virus disease (EVD), complications that include uveitis can develop during convalescence, although the incidence and pathogenesis of EVD-associated uveitis are unknown. We describe a patient who recovered from EVD and was subsequently found to have severe unilateral uveitis during convalescence. Viable Zaire ebolavirus (EBOV) was detected in aqueous humor 14 weeks after the onset of EVD and 9 weeks after the clearance of viremia.

Human Ebola virus infection results in substantial immune activation

Significance In 2014, Ebola virus became a household term. The ongoing outbreak in West Africa is the largest Ebola virus outbreak ever recorded, with over 20,000 cases and over 8,000 deaths to date. Very little is known about the human cellular immune response to Ebola virus infection, and this lack of knowledge has hindered development of effective therapies and vaccines. In this study, we characterize the human immune response to Ebola virus infection in four patients. We define the kinetics of T- and B-cell activation, and determine which viral proteins are targets of the Ebola virus-specific T-cell response in humans. Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1–2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients’ discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

Impact of a rigid, puncture resistant container system upon needlestick injuries.

Needlestick injuries in a 720-bed tertiary care hospital were analyzed before and after the introduction of a rigid, puncture resistant, needle disposal system. Following implementation of the system, disposal-related injuries decreased from 0.9 per 100 full-time equivalent employees/year to 0.3 per 100 full-time equivalent employees/year (p less than .005). However, needlesticks associated with procedures (2.2 vs. 4.4 per 100 full-time equivalent employees/year, p less than .0005), and those resulting from loose needles (0.5 vs. 1.9 per 100 full-time equivalent employees/year, p less than .0005), increased. Injuries occurring during needle recapping or the carrying of needles were not significantly altered. Total needlestick injuries increased from 6.0 to 8.7 per 100 full-time equivalent employees/year (p less than .0005). We concluded that a rigid, puncture resistant, needle disposal system can reduce disposal-related needlestick injuries, but must also be perceived as convenient to impact substantially upon needlesticks associated with other activities.

Strict Versus Modified Isolation for Prevention of Nosocomial Transmission of Methicillin-Resistant Staphylococcus aureus

Patients colonized or infected with methicillin-resistant Staphylococcus aureus (MRSA) in a Surgical Intensive Care Unit and Surgical Intermediate Care Unit were placed either in Strict Isolation or cared for with modified isolation precautions. The assignment was determined by the unit in which they were hospitalized. Units were changed from one form of isolation to the other and served as their own controls. Over a 4-month study period, the rate of MRSA transmission did not change when the type of isolation precautions were altered. The ratio of colonized to infected patients also remained constant. Infected patients were usually first detected by clinical specimens, while colonized patients were usually detected by surveillance cultures performed under the study protocol. Following the study, all hospitalized patients with MRSA were placed in modified isolation precautions. Total new acquisitions of MRSA in the hospital have decreased over the subsequent 6-month period.

Successful Delivery of RRT in Ebola Virus Disease

AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease.

Ebola virus disease: preparedness and infection control lessons learned from two biocontainment units.

Purpose of review This review details infection control issues encountered in the management of patients with Ebola virus disease (EVD), with emphasis on how these issues were confronted in two biocontainment patient care units in the United States. Recent findings There is a notable paucity of medical literature to guide infection control policies and procedures when caring for patients with EVD. Thus, the experience of the Serious Communicable Diseases Unit at Emory University Hospital and the Nebraska Biocontainment Unit at the University of Nebraska Medical Center serves as the basis for this review. Facility issues, staffing, transportation logistics, and appropriate use of personal protective equipment are detailed. Other topics addressed include the evaluation of patients under investigation and ethical issues concerning the safe utilization of advanced life support. Summary This review intends to serve as a reference for facilities that are in the process of creating protocols for managing patients with EVD. Given the lack of literature to support many of the recommendations discussed, it is important to utilize the available referenced guidelines, along with the practical experiences of biocontainment units, to optimize the care provided to patients with EVD while strictly adhering to infection control principles.

Comparison of FilmArray and Quantitative Real-Time Reverse Transcriptase PCR for Detection of Zaire Ebolavirus from Contrived and Clinical Specimens

ABSTRACT Rapid, reliable, and easy-to-use diagnostic assays for detection of Zaire ebolavirus (ZEBOV) are urgently needed. The goal of this study was to examine the agreement among emergency use authorization (EUA) tests for the detection of ZEBOV nucleic acids, including the BioFire FilmArray BioThreat (BT) panel, the FilmArray BT-E panel, and the NP2 and VP40 quantitative real-time reverse transcriptase (qRT) PCR assays from the Centers for Disease Control and Prevention (CDC). Specimens used in this study included whole blood spiked with inactivated ZEBOV at known titers and whole-blood, plasma, and urine clinical specimens collected from persons diagnosed with Ebola virus disease (EVD). The agreement for FilmArray and qRT-PCR results using contrived whole-blood specimens was 100% (6/6 specimens) for each ZEBOV dilution from 4 × 107 to 4 × 102 50% tissue culture infective dose (TCID50)/ml, as well as the no-virus negative-control sample. The limit of detection for FilmArray and qRT-PCR assays with inactivated ZEBOV, based on duplicate positive results, was determined to be 4 × 102 TCID50/ml. Rates of agreement between FilmArray and qRT-PCR results for clinical specimens from patients with EVD were 85% (23/27 specimens) for whole-blood specimens, 90% (18/20 specimens) for whole-blood specimens tested by FilmArray testing and matched plasma specimens tested by qRT-PCR testing, and 85% (11/13 specimens) for urine specimens. Among 60 specimens, eight discordant results were noted, with ZEBOV nucleic acids being detected only by FilmArray testing in four specimens and only by qRT-PCR testing in the remaining four specimens. These findings demonstrate that the rapid and easy-to-use FilmArray panels are effective tests for evaluating patients with EVD.

Kinetic analysis of biomarkers in a cohort of US patients with Ebola virus disease

BACKGROUND Ebola virus (EBOV) infection causes a severe and often fatal disease. Despite the fact that more than 30 000 individuals have acquired Ebola virus disease (EVD), the medical and scientific community still does not have a clear understanding of the mechanisms by which EBOV causes such severe disease. METHODS In this study, 54 biomarkers in plasma samples serially collected from 7 patients with EVD were analyzed in an attempt to define the kinetics of inflammatory modulators. Two clinical disease groups were defined (moderate and severe) based on the need for clinical support. Biomarkers were evaluated for correlation with viremia and clinical disease in an effort to identify pathways that could be useful targets of therapeutic intervention. RESULTS Patients with severe disease had higher viremia than those with moderate disease. Several biomarkers of immune activation and control were significantly elevated in patients with moderate disease. A series of pro-inflammatory cytokines and chemokines were significantly elevated in patients with severe disease. CONCLUSIONS Biomarkers that were associated with severe EVD were proinflammatory and indicative of endothelial or coagulation cascade dysfunction, as has been seen historically in patients with fatal outcomes. In contrast, biomarkers that were associated with moderate EVD were suggestive of a strong interferon response and control of both innate and adaptive responses. Therefore, clinical interventions that modulate the phenotype and magnitude of immune activation may be beneficial in treating EVD.

Safe Management of Patients With Serious Communicable Diseases: Recent Experience With Ebola Virus

Health care workers (HCWs) in the emergency medical services (EMS) and hospital settings often encounter patients infected with dangerous communicable diseases. Such patients are usually managed without fanfare, but when it was announced on 1 August 2014 that 2 American HCWs infected with Ebola virus disease would return to the United States for treatment, it drew the worlds attention. The means by which Ebola is spread are well-known. Careful adherence to standard, contact, and droplet precautions, as outlined for HCWs by the Centers for Disease Control and Prevention (CDC) (1), prevents exposure to blood or bodily fluids contaminated with this virus. However, images of infected patients arriving at Emory University Hospital looked much different from what might have been expected. How can the sight of HCWs in space suits be reconciled with published CDC infection control guidelines? In this essay, we offer our rationale for adopting the safeguards that were used. Prevention of disease transmission in health care settings, including EMS transport, involves more than the proper use of personal protective equipment (PPE). It also depends on the development and implementation of appropriate administrative policies, work practices, and environmental controls accompanied by focused education, training, and supervision. Health care workers inconsistently adhere to such basic infection control practices as hand hygiene (2), and EMS provider adherence to infection control precautions and equipment disinfection can be suboptimal (3). Environmental samples from clinical settings inside and outside the hospital have revealed contamination with serious pathogens (46). The Grady EMS Biosafety Transport Program and Emory University Hospital Serious Communicable Disease Unit were established more than a decade ago to support the CDC, which is responsible for conducting research and intervening to control the worlds deadliest pathogens. They also support CDCs quarantine station at Hartsfield-Jackson Atlanta International Airport, the busiest airport in the world and a major portal of immigration to the United States. Our goal in creating a special transport and inpatient care team was to close these and other gaps in practice and to facilitate the best care for patients while ensuring the safety of our HCWs and the general public by meticulous adherence to published CDC guidance. The team is educated about serious communicable pathogens, methods of transmission, available vaccines, preexposure and postexposure prophylaxis and treatment for specific infections, and the importance of strict adherence to standard and transmission-based infection control practices. Understanding the nature of the illnesses they confront helps providers overcome apprehension and fear and enables them to render safe and effective care. Training includes special attention to the proper donning and doffing of various PPE. Emergency medical service medics isolate the driver compartment and envelop the interior of the patient compartment with water-impermeable barriers that prevent contamination of surfaces that are difficult to clean and disinfect, which is especially important for patients with active epistaxis, coughing, or vomiting. Patients may be asked to wear a water-impermeable suit to prevent exposure to sites of cutaneous bleeding or an undergarment capable of collecting large volumes of diarrhea. For management of our patients with Ebola, the team met the PPE standard by wearing a Tyvek suit (DuPont); gloves; and a hooded, powered, air-purifying respirator. Tyvek suits afford a high degree of splash protection, an important consideration in light of the copious bodily fluids involved in Ebola infection, which pose a serious risk for exposure. The hooded, powered, air-purifying respirator provided greater splash protection and was cooler and more comfortable to use. It averted eyewear fogging and prevented HCWs from inadvertently touching their face. Should the patients have suddenly required an aerosol-producing procedure, such as airway suctioning or endotracheal intubation, the team would have been properly protected. Although not strictly required, this approach was practical and allowed our HCWs to confidently focus on safely caring for and transporting these patients without needless anxiety and distraction. Patient delivery directly into the isolation unit limited exposure to other patients or visitors at the hospital. Decontamination and disinfection of the ambulance was facilitated by barrier drapes. All environmental surfaces and waste bags were disinfected with an agent approved by the U.S. Environmental Protection Agency, with appropriate surface contact time. Disinfection of the ambulance, collection of infectious waste, and removal of PPE were directly supervised to ensure no violation of technique or breach of protocol. Even without a recognized exposure, the health care team was monitored for subjective illness and fever to ensure that developing illness was recognized and swiftly evaluated. Although the successful arrival of these patients at the isolation unit was guided by 12 years of planning, practice, and experience, it still yielded new lessons. Seemingly stable patients arriving from Ebola-endemic areas have probably had large volume losses without benefit of laboratory assessment and may have significant electrolyte abnormalities that require continuous cardiac monitoring and intravenous access, an intervention that might otherwise be deferred in austere settings to limit the risk for HCW exposure if vascular access is difficult to obtain. In our case, both patients were transported without incident. We believe that a dedicated team is best suited for transport of patients with confirmed serious communicable illness. Although this is a particularly relevant consideration in communities that are close to CDC quarantine stations or biocontainment laboratories, HCWs in every community may be called on to assist a traveler who has recently returned from an Ebola-stricken region. For the future, because communicable disease threats may emerge inside or outside the United States with little or no notice, EMS agencies and hospitals would be prudent to implement measures to identify patients with communicable illness and ensure that their personnel can confidently and safely provide care anywhere and for all pathogens.