Guy A. Richards

Nosocomial Outbreak of Novel Arenavirus Infection, Southern Africa

This case reinforces the need for strict screening of internationally transferred patients.

Emergence of New Delhi Metallo-Beta-Lactamase (NDM-1) and Klebsiella pneumoniae Carbapenemase (KPC-2) in South Africa

ABSTRACT This report documents emergence of New Delhi metallo-beta-lactamase (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC-2) in K. pneumoniae and Enterobacter cloacae in South Africa. NDM-1 producers have not been described in South Africa, and this is the first instance that KPC producers have been identified in Africa. The two patients infected with these carbapenemase-producing bacteria demised.

Emergence of OXA-48 and OXA-181 Carbapenemases among Enterobacteriaceae in South Africa and Evidence of In Vivo Selection of Colistin Resistance as a Consequence of Selective Decontamination of the Gastrointestinal Tract

ABSTRACT This study reports on the emergence of OXA-48-like carbapenemases among isolates of Enterobacteriaceae in South Africa. In addition, the emergence during therapy of a colistin-resistant OXA-181-producing Klebsiella pneumoniae isolate was documented following selective digestive tract decontamination with oral colistin, which is therefore strongly discouraged.

Recommendations for intensive care unit and hospital preparations for an influenza epidemic or mass disaster: Summary report of the European Society of Intensive Care Medicine's Task Force for intensive care unit triage during an influenza epidemic or mass disaster

PurposeTo provide recommendations and standard operating procedures for intensive care units and hospital preparedness for an influenza pandemic.MethodsBased on a literature review and expert opinion, a Delphi process was used to define the essential topics.ResultsKey recommendations include: Hospitals should increase their ICU beds to the maximal extent by expanding ICU capacity and expanding ICUs into other areas. Hospitals should have appropriate beds and monitors for these expansion areas. Establish a management system with control groups at facility, local, regional and/or national levels to exercise authority over resources. Establish a system of communication, coordination and collaboration between the ICU and key interface departments. A plan to access, coordinate and increase labor resources is required with a central inventory of all clinical and non-clinical staff. Delegate duties not within the usual scope of workers’ practice. Ensure that adequate essential medical equipment, pharmaceuticals and supplies are available. Protect patients and staff with infection control practices and supporting occupational health policies. Maintain staff confidence with reassurance plans for legal protection and assistance. Have objective, ethical, transparent triage criteria that are applied equitably and publically disclosed. ICU triage of patients should be based on the likelihood for patients to benefit most or a ‘first come, first served’ basis. Develop protocols for safe performance of high-risk procedures. Train and educate staff.ConclusionsMortality, although inevitable during a severe influenza outbreak or disaster, can be reduced by adequate preparation.

Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients with severe sepsis.

Adequate data on the pharmacokinetics of once-daily administration of ertapenem in critically ill patients are largely lacking. This single-centre, prospective, open-label study was performed on a cohort of eight critically ill patients with severe sepsis with normal renal function treated with 1g of ertapenem once daily. Samples of venous blood and urine were collected before infusion and at specific time points in the 24-h post-infusion period. Plasma and urine ertapenem levels were determined by reverse-phase high-performance liquid chromatography (HPLC) with ultraviolet detection. The non-protein-bound fraction was determined in the filtrate by HPLC using a Centrifree device. The current study showed a lower maximum plasma concentration (C(max)) (52.3.0mg/L vs. 253 mg/L) and area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) (188 mg h/L vs. 817 mg h/L) but higher volume of distribution at steady state (V(ss)) (26.8L vs. 5.7 L) compared with those observed in young healthy volunteers. For unbound ertapenem, geometric means of C(max) and AUC(0-infinity) were 29.5mg/L and 103.5 mg h/L, respectively, and correlated negatively with hypoalbuminaemia. Unbound levels failed to exceed a minimum inhibitory concentration of 1mg/L for more than 7.1h (30%) of the dosing interval in two patients. The highly variable and unpredictable intersubject pharmacokinetic parameters documented in this study resulted in suboptimal unbound concentrations in some patients. This raises the question as to whether ertapenem is an appropriate agent for initial use in critically ill patients with severe sepsis.

Study of critically ill patients with systemic lupus erythematosus

OBJECTIVES To determine the presenting features, prognostic factors, course, and outcome of critically ill patients with systemic lupus erythematosus admitted to the intensive care unit (ICU). DESIGN Retrospective patient record review. SETTING Two academic teaching hospitals. PATIENTS All patients with systemic lupus erythematosus admitted to the ICUs between January 1982 and July 1993. MEASUREMENTS AND MAIN RESULTS There were 28 female and two male patients. Fifteen patients were white, 11 patients were black, and four patients were Asian. The median age was 29 yrs. The reasons for admission to the ICU were multifactorial. However, most patients were admitted for infective, renal, cardiac, or coagulation complications. Despite aggressive management, 16 (53%) patients died in the ICU or shortly after discharge. The median ICU survival rate (admission to death) was 22 days. The only pretreatment factor that predicted a poor outcome was the presence of renal involvement due to systemic lupus erythematosus. CONCLUSIONS Our study suggests that patients with systemic lupus erythematosus admitted to an ICU often have florid disease manifestations with multifactorial reasons precipitating the admission. The prognosis for such patients is poor, particularly in the presence of renal involvement.

Increased levels of autoantibodies to cardiolipin and oxidised low density lipoprotein are inversely associated with plasma vitamin C status in cigarette smokers

In this study we have measured circulating levels of autoantibodies to cardiolipin and oxidised low-density lipoprotein (ox-LDL) and correlated these with plasma concentrations of the anti-oxidant nutrients vitamin C, vitamin E and beta-carotene, in a group (79) of asymptomatic, male cigarette smokers and in non-smoking control subjects. Cigarette smoking, a well-known risk factor for development of atherosclerosis, was found to be associated with moderately elevated levels of autoantibodies to both cardiolipin and ox-LDL. Increased levels of these autoantibodies were most evident in the older smokers (> 30 years) and were significantly and inversely correlated with plasma vitamin C, but not with vitamin E or beta-carotene. Absorption studies designed to investigate the specificity of these autoantibodies demonstrated a high degree of cross-reactivity of cardiolipin antibodies with ox-LDL, while antibodies to the oxidatively modified lipoprotein tended to be specific for this antigen. These findings suggest that cigarette smoking promotes formation of autoantibodies to both cardiolipin and ox-LDL and that these may be involved in the initiation and/or perpetuation of atherosclerosis. Dietary intake of vitamin C may be a determinant of susceptibility to development of this cardiovascular disorder.

Vitamin E, pulmonary functions, and phagocyte-mediated oxidative stress in smokers and nonsmokers

Relationships among the plasma levels of vitamin E (VE), the numbers and prooxidative activities of circulating phagocytes, serum alpha-1-protease inhibitor (API), and pulmonary functions were investigated in 83 asymptomatic male cigarette smokers and 65 nonsmoking controls. Plasma levels of VE, of cholesterol, and of API were measured using high performance liquid chromatography, spectrophotometry, and nephelometry, respectively, whereas reactive oxidant (ROS) generation by activated blood phagocytes was measured using a whole blood luciginen-enhanced chemiluminescence method. Smoking was associated with significantly increased circulating neutrophil counts (p 0.0001), serum API (p 0.0001) and phagocyte-derived ROS-generation (p 0.0001), and decreased spirometric values (FEV1: p 0.0138 and FEF25-75: p 0.0654). Plasma VE and cholesterol levels were not significantly different between smokers and nonsmokers. However, in smokers both plasma VE and cholesterol correlated significantly and positively with serum API (r 0.24, p 0.03 and r 0.30, p 0.005, respectively), neutrophil counts (r 0.24, p 0.03 and r 0.25, p 0.03, respectively), and phagocyte-derived ROS-generation (r 0.32, p 0.003 and r 0.32, p 0.003, respectively), and significantly and inversely with FEV1 (r -0.23, p 0.03 and r -0.22, p 0.04, respectively) and FEF25-75 (r -0.32, p 0.003 and r -0.26, p 0.02, respectively). In nonsmokers plasma VE, but not cholesterol, was positively correlated with FEV1 (r 0.34, p 0.007) and FEF25-75 (r 0.40, p 0.001). The results suggest that VE protects the lungs of both smokers and nonsmokers and may act as a mobilizable antioxidant in response to smoking-induced oxidative stress.

Respiratory protection for healthcare workers treating Ebola virus disease (EVD): Are facemasks sufficient to meet occupational health and safety obligations?

Title: Respiratory protection for healthcare workers treatingebola virus disease (evd): are facemasks sufficient to meetoccupational health and safety obligations?Author: C. Raina MacIntyre Abrar Ahmad Chughtai HollySeale Guy A Richards Patricia M DavidsonPII: S0020-7489(14)00234-XDOI: http://dx.doi.org/doi:10.1016/j.ijnurstu.2014.09.002Reference: NS 2443To appear in:Please cite this article as: MacIntyre, C.R., Chughtai, A.A., Seale, H.,Richards, G.A., Davidson, P.M.,Respiratory protection for healthcare workerstreating ebola virus disease (evd): are facemasks sufficient to meet occupationalhealth and safety obligations?,

CURB-65, PSI, and APACHE II to assess mortality risk in patients with severe sepsis and community acquired pneumonia in PROWESS.

Background: Patients with community-acquired pneumonia (CAP) comprised 35.6% of the overall phase 3 Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study and 33.1% of the placebo arm. We investigated the use of CURB-65, the Pneumonia Severity Index (PSI), and Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction scores to identify the CAP population from the PROWESS placebo arm at the greatest mortality risk. Methods: Patients were classified as having CAP if the lung was the primary infection site and the patient originated from home. The abilities of CURB-65, PSI, and APACHE II scores to determine the 28-day and in-hospital mortality were compared using receiver operator characteristic (ROC) curves and the associated areas under the curve. Results: PROWESS enrolled 278 patients with CAP in the placebo arm. The areas under the ROC curves for PSI = 5, CURB-65 ≥3, and APACHE II ≥25 for predicting 28-day (c = 0.65, 0.66, and 0.64, respectively) and in-hospital mortality (c = 0.65, 0.65, and 0.64, respectively) were not statistically different from each other. The 28-day mortality of patients with a PSI score of 5, CURB-65 ≥3, and APACHE II ≥25 was 41.6%, 37.9%, and 43.5%, respectively. Conclusions: Despite early diagnosis and appropriate antibiotic therapy, conventionally treated CAP with PSI = 5, CURB-65 ≥3, or APACHE II ≥25 has an unacceptably high mortality. In this study, PSI, CURB-65, and APACHE II scoring systems perform similarly in predicting the 28-day and in-hospital mortality; however, differences in the categorization of severe CAP were observed and there was a significant mortality in patients with a CURB-65 <3 and PSI <5.