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Efficacy of an oximate-based skin decontaminant against organophosphate nerve agents determined in vivo and in vitro.

Recent Canadian research efforts have been directed towards the development of a reactive skin decontaminant (RSD) lotion active against classical nerve agents and mustard. The formulation presently under study consists of a 1.25 molal solution of potassium 2,3-butanedione monoximate (KBDO) in polyethylene glycol methylether 550. Although this formulation has shown good efficacy, concern has been expressed as to the potential toxicity of the reaction products of KBDO and organophosphate (OP) nerve agents. This report details the high efficacy of this lotion in inactivating OPs as measured by the systemic toxicity of the OP/RSD mixtures in rats. In addition, primary cultures of chick embryo neurons were also used to test the efficacy of the RSD. By relating the anticholinesterase activity in these cultures of the OP/RSD mixture to that of pure OP standards, a sensitive measure of the value of the RSD in inactivating tabun, sarin, soman and VX was obtained. Experiments with all four nerve agents in this in vitro system provided a good correlation with the in vivo data, and also indicated that the inactivation process was time- and agent-dependent and also related to the ratio of OP to RSD.

Acetylcholinesterase↗

Radioimmunoassay of drugs of abuse in hair. Part 1: Methadone in human hair, method adaptation and the evaluation of decontamination procedures.

A method suitable for the determination of methadone in human hair is presented. Adaptation and evaluation of a solid-phase I125 radioimmunoassay, designed for the quantitative measurement of methadone in urine, and development of a pre-analytical wash procedure has enabled a specific, sensitive and accurate analytical procedure to be developed. The specificity of the antiserum towards other drugs or biologically active compounds is evaluated up to a concentration of 100,000 ng ml-1 and accuracy covering a range of 0-450 ng ml-1 is found to be within 6% of expected methadone concentrations prepared in both drug free hair extract and urine. Inter-assay relative standard deviation (RSD) at concentrations of 5.1, 76.0 and 247 ng ml-1 methadone are 5.5, 2.5 and 3.6% respectively (n = 10) and intra-assay RSD at concentrations 2.3, 25.2 and 217 ng ml-1 are 5.3, 3.6 and 6.8% (n = 5). The limit of detection is 0.5 ng ml-1. Extraction of control drug free hair samples spiked with methadone at concentrations of 100, 250 and 400 ng ml-1 achieved recoveries of 86, 80 and 89%, respectively. Control hair samples contaminated with methadone are examined under differing wash procedures to assess their effectiveness in the removal of methadone contaminant. A suitable pre-analytical wash regime is proposed for removal of contaminant derived from external or environmental sources. The mechanics of the wash action and contaminant application to the hair is discussed. It is concluded that the adapted radioimmunoassay and developed pre-analytical decontamination procedure is a suitable technique to employ for the measurement of methadone in human hair, be it prescribed or abused, with concentrations expressed as ng methadone per mg hair.

Decontamination↗

[Does selective digestive decontamination prevent nosocomial infections?].

Paediatric intensive care and haematological units are ideal sites for the development of nosocomial infections. These infections remain a significant source of mortality and morbidity and increase length of stay and costs. Selective digestive decontamination (SDD) includes topical antibiotics during the entire intensive care unit (ICU) stay, parenteral antibiotic administered for three to five days, hand hygiene and surveillance cultures of throat and rectum. Its use is based on the observation that resistant bacteria are often imported by the patients themselves, and the fact that transmission via the hands of carers could be responsible only for infections occurring after one week. In adult patients, seven meta-analyses have demonstrated that SDD reduces the odds ratio for lower airway infections, and sometimes mortality (particularly in surgical and trauma patients). The main criticism against SDD is the possible emergence of antibiotic resistant bacteria, which is a growing problem in Europe and United States of America. Only four studies on SDD in children have been reported in the literature: due to methodological weaknesses and small size of samples, definitive conclusion cannot be drawn. However, one study in a 20 bed paediatric intensive care unit has demonstrated that SDD prevent both infections and the emergence of resistant bacteria. Furthermore, it has been demonstrated that more than 50% of children carrying resistant bacteria are detected within 24 hours of admission, suggesting that they import the resistant strains onto the intensive care unit. Factors that predict facility, administration of i.v. antibiotics within the past 12 months, previous intensive care unit admission and hospitalization of a household contact within the past 12 months. As suggested by several authors, the term selective should mean selection of appropriate patient groups (those at high risk of nosocomial infection, e.g. patients mechanically ventilated for at least 48 hours) and units (excluding those where multiresistance is endemic). Obviously, surveillance of patient and unit bacterial ecology and improvement of antibiotic policy must be reinforced.

Anti-Bacterial Agents↗

Screening and genetic manipulation of plants for decontamination of pollutants from the environments.

In this review, we will describe our study on "nitrogen-philic plants", which can grow with nitrogen dioxide (NO2) as the sole nitrogen source, by screening of naturally occurring plants for the assimilation of nitrogen dioxide and genetic manipulation of plants for those genes involved in the primary nitrate metabolism. Finally, we will briefly describe "Green walls with nitrogen-dioxide-philic plants" for decontamination of pollution in urban areas.

Air Pollutants↗

Transportable frontal chromatographic unit for decontamination purposes based on the twin column concept.

The design and operation of a separation unit based on frontal chromatography is described. The important feature of the design is the array column --> detector --> column which allows process monitoring below the detection limits of the monitor. By using "fraternal twin columns" an in-process calibration of the detector is achieved reducing the waste production. The design contains provisions for on-line destructive and non-destructive monitoring. Tests of the unit prove its versatility with respect to decontamination processes. Due to its compactness, the unit is transportable, if not portable, and the module construction allows easy posting and set-up in areas with restricted access. The unit is capable of processing up to 5 m3 solution per year depending on the chemical system used.

Chromatography, Liquid↗

Antibiotic resistance may affect alkali decontamination of specimens containing mycobacteria.

The influence of genetic modification on the decontamination process of mycobacteria was investigated using a wild type Mycobacterium bovis BCG Pasteur and its isogenic mutant strain. The result showed that the killing effect of sodium hydroxide (NaOH) progressively increased with prolonged incubation (up to 20 minutes), and the deteriorating effect of NaOH was more severe on the genetically modified strain.

Animals↗

Selective intestinal decontamination in advanced chronic heart failure: a pilot trial.

BACKGROUND AND AIMS: Endotoxin, derived from intestinal aerobic Gram-negative bacilli (AGNB), could be an important monocyte activator in chronic heart failure (CHF). The effect of selective decontamination of the digestive tract (SDD) on intracellular monocyte cytokine production, monocyte CD14 expression, circulating endotoxin and cytokines, and flow-mediated dilation (FMD) was studied in patients with severe CHF. METHODS AND RESULTS: Ten patients with CHF (NYHA class III-IV) were enrolled in a non-placebo controlled pilot trial involving the administration of SDD (polymyxin B, tobramycin) for 8 weeks. One patient was later excluded due to cardiac transplantation. Before treatment, after 4 and 8 weeks therapy, and 6 weeks post-treatment, monocyte CD14 expression, intracellular monocyte production of interleukin-1beta [IL-1beta], interleukin-6 [IL-6], tumour necrosis factor (TNF)-alpha with and without lipopolysaccharide (LPS) stimulation were measured. Concentrations of endotoxin and cytokines (IL-1beta, IL-6, TNF-alpha) were also determined. AGNB in faeces, intestinal endotoxin and FMD were assessed at baseline, after 4 weeks of treatment and 6 weeks post-treatment. SDD eradicated intestinal AGNB (P<0.00001) and decreased faecal endotoxin concentrations (P<0.00001). There was a significant decline in monocyte CD14 expression (P=0.03) and in IL-1beta (P=0.0001), IL-6 (P=0.02) and TNF-alpha (P=0.0002) production after 4 and 8 weeks of treatment in the basal state and for IL-1beta (P=0.008) and IL-6 (P=0.005) after LPS stimulation. FMD significantly improved at 4 weeks and returned to baseline after treatment discontinuation (P=0.002). Circulating concentrations of endotoxin and cytokines remained unchanged. CONCLUSION: Reduction of the intestinal endotoxin pool led to a decrease in monocyte CD14 expression and intracellular cytokine production in patients with severe CHF. The improvement of peripheral endothelial function could be a marker of the anti-inflammatory effect of SDD.

Adult↗

The effectiveness of standard povidone iodine surgical preparation in decontaminating external fixator components.

The purpose of this study was to evaluate the effectiveness of standard iodine surgical scrubs to remove bacteria from external fixator components. Sterile adjustable external fixation clamps, Schanz pins, and carbon fibre rods were coated with a sterile protein solution and immersed in solution of coagulase negative Staphylococcus (10(3)organisms/ml). They were then decontaminated in standard fashion using a povidone iodine scrub and paint solution. After neutralisation the components were sonicated, serially diluted, plated on blood agar, and incubated for 24h. Unassembled external fixation components were examined individually, and as assembled pin-rod-clamp constructs with and without manipulation of the clamp. Of the three external fixation components (pins, rods, clamps) the highest number of bacterial colony forming units was seen on the external fixation clamps. Manipulation of the assembled construct significantly increased the mean bacterial colony counts compared to the assembled non-manipulated construct (p=0.0007). Standard surgical preparation does not remove all bacteria from external fixators during subsequent operative procedures.

Anti-Infective Agents, Local↗

Rapid decontamination of gutta-percha cones with sodium hypochlorite.

Gutta-percha cones are now widely used to fill root canals. Because they cannot be sterilized by conventional autoclaving or in a hot-air oven, gutta-percha cones require rapid chairside decontamination before use to maintain the aseptic chain, an essential factor in successful endodontic therapy. The purpose of this study was to compare the effectiveness of different concentrations of sodium hypochlorite (0.25% to 4%) in sterilizing gutta-percha cones artificially contaminated with Staphylococcus aureus and Escherichia coli strains, and Bacillus subtilis spores. After 1 min of treatment, the solutions tested showed bactericidal and sporicidal effects at concentrations of 0.25% and 1%, respectively. At a concentration of 0.25%, the solutions tested were effective in destroying spores after 5 min of exposure. Based on this study, treatment of the cones for 1 min with 1% sodium hypochlorite (Milton's solution) or for 5 min with Dakin's liquid (0.5% sodium hypochlorite) is recommended.

Bacillus subtilis↗

Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial.

BACKGROUND: Selective decontamination of the digestive tract (SDD) is an infection-prevention regimen used in critically ill patients. We assessed the effects of SDD on intensive-care-unit (ICU) and hospital mortality, and on the acquisition of resistant bacteria in adult patients admitted to intensive care. METHODS: We did a prospective, controlled, randomised, unblinded clinical trial. 934 patients admitted to a surgical and medical ICU were randomly assigned oral and enteral polymyxin E, tobramycin, and amphotericin B combined with an initial 4-day course of intravenous cefotaxime (SDD group n=466), or standard treatment (controls n=468). Primary endpoints were ICU and hospital mortality and the acquisition of resistant bacteria. FINDINGS: In the SDD group 69 (15%) patients died in the ICU compared with 107 (23%) in the control group (p=0.002). Hospital mortality was lower in the SDD groups than in the control group (113 [24%] vs 146 [31%], p=0.02). During their stay in intensive care, colonisation with gram-negative bacteria resistant to ceftazidime, ciprofloxacin, imipenem, polymyxin E, or tobramycin occurred in 61 (16%) of 378 SDD patients and in 104 (26%) of 395 patients in the control group (p=0.001). Colonisation with vancomycin-resistant enterococcus occurred in five (1%) SDD patients and in four (1%) controls (p=1.0). No patient in either group was colonised with meticillin-resistant Staphylococcus aureus. INTERPRETATION: In a setting with low prevalence of vancomycin-resistant enterococcus and meticillin-resistant S aureus, SDD can decrease ICU and hospital mortality and colonisation with resistant gram-negative aerobic bacteria.

Adolescent↗

Changing bacterial ecology during a five-year period of selective intestinal decontamination.

The development of bacterial resistance during selective decontamination of the digestive tract (SDD) is controversial. We studied effects on bacterial resistance one year before and during a randomized, placebo-controlled trial of SDD in a surgical intensive care unit. We randomized patients within two different topical regimens (PTA, PCA) or placebo, administered four-times daily to both the oropharynx and gastrointestinal tract. All patients received intravenous ciprofloxacin (200 mg b.d.) for four days. Both SDD regimens successfully reduced aerobic Gram-negative intestinal colonization. There was no increase in resistance of Enterobacteriaceae or Pseudomonas aeruginosa. Acinetobacter calcoaceticus developed multi-resistance over one year, but differences between groups were not significant. We detected a shift towards Gram-positive organisms. Oxacillin-resistant Staphylococcus aureus increased in concert with ciprofloxacin resistance, from 17 to 80.7%, and frequencies of resistance were significantly higher in SDD patients (P < 0.001). Resistance of coagulase-negative staphylococci (CNS) to oxacillin increased initially (25 to 66.9%), but values returned to baseline in controls. Ciprofloxacin resistance in CNS remained higher (P < 0.001) in SDD-treated patients (52.5 vs. 23.3%). The incidence of late respiratory tract infections was unaltered by the prophylactic regimen (SDD 35.2%; Placebo 41.2%; n.s.). We cannot recommend SDD as a prophylactic tool in critically ill patients.

Adult↗

LC determination of a sulphur mustard decontaminant CC-2 in rat serum.

A high-performance liquid chromatographic (HPLC) method was developed for the analysis of N,N'-Dichlorobis (2,4,6-trichlorophenyl) urea (CC-2), a potent sulphur mustard decontaminant, in rat serum. The HPLC analysis, applicable to 0.5 ml volumes of serum, involved double extraction of serum samples with diethyl ether at alkaline pH followed by separation on a RP-18 column and the use of UV detector at 230 nm. The method was sensitive with a limit of quantitation of 10 ng ml(-1) in rat serum and the recovery was always >90%. Excellent linear relationships (r>0.99) were obtained between the measured and added concentration ratios of the serum concentrations over a range of 10-200 ng ml(-1). The precision and accuracy were acceptable as indicated by relative standard deviation ranging from 2.47 to 17.49%, bias values ranging from -4.35 to 13.21%. Moreover, CC-2 was found stable in rat serum even after 3 months of storage at -60 degrees C and being subjected to three freeze-thaw cycles. The assay was found to be sensitive, specific, accurate, precise, and reliable for use in pharmacokinetic studies.

Animals↗

Temperature increases during surface decontamination of titanium implants using CO2 laser.

The purpose of the present in vitro investigation was to measure temperature changes at the implant surface when using pulsed CO2 laser in a simulated implant surface decontamination protocol. Six threaded titanium implants were placed in a fresh resected pig mandible. A 4 x 4 mm defect was created buccally to each implant in order to expose the implant head and approximately 5 threads. Temperature changes were monitored by two thermocouples placed near the dehiscence and at the apical part of the implant. Several setting combinations of the CO2 laser with regard to output power, pulse width, pulse repetition rate and irradiation time were tested on dry and wet (distilled water) surfaces. Only minor temperature increases were measured when lasing wet titanium surfaces, while the temperature at dry surfaces exceeded the proposed thresholds for bone damage at clinically relevant settings. It is concluded that the CO2 laser when used on a wet implant surface in a pulsed mode at 8 W/10 ms/20 hz during 5 s induces a temperature increase of less than 3 degrees C. This would minimize the risk of temperature induced tissue damage as a result of lasing implant surfaces.

Animals↗

Evaluation of the effectiveness of decontamination of dental syringes.

AIM: Steam autoclaving is the gold standard for decontaminating dental instruments, but worldwide disinfection is still widely employed. We have evaluated a range of procedures for their ability to inactivate duck hepatitis B virus contaminating dental syringes. METHODS: Residual infectivity of virus suspensions following 2% glutaraldehyde treatment, ultrasonication or steam sterilisation at 121 degrees or 134 degrees was assayed by injecting day-old ducklings and examining their livers for viral DNA 2.5 weeks later. Dental syringes were contaminated with DHBV positive blood, then treated by the same methods. An anaesthetic cartridge containing water was loaded into the syringe and 400microl aliquots used to inject day-old ducklings. Used dental syringes were examined by Scanning Electron Microscopy. RESULTS: Suspension test:- ultrasonic treatment failed to inactivate DHBV in suspension, but complete inactivation was achieved by 2% glutaraldehyde and autoclaving. Syringe test:- neither ultrasonic treatment nor glutaraldehyde inactivated DHBV. Autoclaving at 134 degrees (3 minutes) permitted transmission to 1/16 ducklings but steam sterilisation at 121 degrees (15 minutes) was effective. Electronmicroscopy demonstrated organic debris (biofilm) in the lumen of used syringes. CONCLUSION: Short autoclaving cycles, albeit at raised temperatures, may fail to inactivate the virus because of poor steam penetration, inadequate heat transfer and the accumulation of protective biofilm.

Animals↗

Gastric decontamination performed 5 min after the ingestion of temazepam, verapamil and moclobemide: charcoal is superior to lavage.

AIMS: The aim was to study the efficacy of gastric lavage and activated charcoal in preventing the absorption of temazepam, verapamil and moclobemide when gastric decontamination was performed immediately after ingestion of the drugs. METHODS: Nine healthy volunteers took part in a randomized cross-over study with three phases. The subjects were administered single oral doses of 10 mg temazepam, 80 mg verapamil and 150 mg moclobemide. Five minutes later, they were assigned to one of the following treatments: 200 ml water (control), 25 g activated charcoal as a suspension in 200 ml water or gastric lavage. Plasma concentrations and the cumulative excretion into urine of the three drugs were determined up to 24 h. RESULTS: The mean AUC(0,24 h) of temazepam, verapamil and moclobemide was reduced by 95.2% (P < 0.01), 92.8% (P < 0.01) and 99. 7% (P < 0.01), respectively, by activated charcoal compared with control. Gastric lavage did not reduce significantly the AUC(0,24 h) of these drugs. The 24 h cumulative excretion of temazepam, verapamil and moclobemide into urine was reduced significantly (P < 0.05) by charcoal but not by gastric lavage. Charcoal reduced the AUC(0,24 h), Cmax and urinary excretion of all three drugs significantly more than lavage. CONCLUSIONS: Activated charcoal is very effective and gastric lavage can be rather ineffective in preventing the absorption of temazepam, verapamil and moclobemide when the treatment is given very rapidly after ingestion of the drugs, before tablet disintegration has occurred.

Absorption↗

Decontamination of drinking water by direct heating in solar panels.

A device was developed for direct heating of water by solar radiation in a flow-through system of copper pipes. An adjustable thermostat valve prevents water below the chosen temperature from being withdrawn. The results show that it is possible to eliminate coliform and thermotolerant coliform bacteria from naturally contaminated river water by heating to temperatures of 65 degrees C or above. Artificial additions of Salmonella typhimurium, Streptococcus faecalis and Escherichia coli to contaminated river water were also inactivated after heating to 65 degrees C and above. The total viable count could be reduced by a factor of 1000. The heat-resistant bacteria isolated from the Mlalakuva River (Tanzania) were spore-forming bacteria which exhibited greater heat resistance than commonly used test bacteria originating from countries with colder climates. To provide a good safety margin it is recommended that an outlet water temperature of 75 degrees C be used. At that temperature the daily production was about 501 of decontaminated water per m2 of solar panel, an amount that could be doubled by using a heat exchanger to recycle the heat.

Decontamination↗

Mechanisms of killing of Bacillus subtilis spores by Decon and Oxone, two general decontaminants for biological agents.

AIMS: To determine the mechanisms of Bacillus subtilis spore killing by and resistance to the general biological decontamination agents, Decon and Oxone. METHODS AND RESULTS: Spores of B. subtilis treated with Decon or Oxone did not accumulate DNA damage and were not mutagenized. Spore killing by these agents was increased if spores were decoated. Spores prepared at higher temperatures were more resistant to these agents, consistent with a major role for spore coats in this resistance. Neither Decon nor Oxone released the spore core's depot of dipicolinic acid (DPA), but Decon- and Oxone-treated spores more readily released DPA upon a subsequent normally sublethal heat treatment. Decon- and Oxone-killed spores initiated germination with dodecylamine more rapidly than untreated spores, but could not complete germination triggered by nutrients or Ca(2+)-DPA and did not degrade their peptidoglycan cortex. However, lysozyme treatment did not recover these spores. CONCLUSIONS: Decon and Oxone do not kill B. subtilis spores by DNA damage, and a major factor in spore resistance to these agents is the spore coat. Spore killing by both agents renders spores defective in germination, possibly because of damage to the inner membrane of spore. SIGNIFICANCE AND IMPACT OF STUDY: These results provide information on the mechanisms of the killing of bacterial spores by Decon and Oxone.

Amines↗