Healthcare personnel can be exposed to elevated levels of glutaraldehyde vapor when equipment is processed in poorly ventilated rooms, when spills occur, when glutaraldehyde solutions are activated or changed, , or when open immersion baths are used.
Acute or chronic exposure can result in skin irritation or dermatitis, mucous membrane irritation eye, nose, mouth , or pulmonary symptoms , Epistaxis, allergic contact dermatitis, asthma, and rhinitis also have been reported in healthcare workers exposed to glutaraldehyde , Glutaraldehyde exposure should be monitored to ensure a safe work environment. The silica gel tube and the DNPH-impregnated cassette are suitable for monitoring the 0.
The passive badge, with a 0. ACGIH does not require a specific monitoring schedule for glutaraldehyde; however, a monitoring schedule is needed to ensure the level is less than the ceiling limit. For example, monitoring should be done initially to determine glutaraldehyde levels, after procedural or equipment changes, and in response to worker complaints Engineering and work-practice controls that can be used to resolve these problems include ducted exhaust hoods, air systems that provide 7—15 air exchanges per hour, ductless fume hoods with absorbents for the glutaraldehyde vapor, tight-fitting lids on immersion baths, personal protection e.
If engineering controls fail to maintain levels below the ceiling limit, institutions can consider the use of respirators e. In general, engineering controls are preferred over work-practice and administrative controls because they do not require active participation by the health-care worker.
Court of Appeals , limiting employee exposure to 0. If glutaraldehyde disposal through the sanitary sewer system is restricted, sodium bisulfate can be used to neutralize the glutaraldehyde and make it safe for disposal. The literature contains several accounts of the properties, germicidal effectiveness, and potential uses for stabilized hydrogen peroxide in the health-care setting.
Published reports ascribe good germicidal activity to hydrogen peroxide and attest to its bactericidal, virucidal, sporicidal, and fungicidal properties Tables 4 and 5 The FDA website lists cleared liquid chemical sterilants and high-level disinfectants containing hydrogen peroxide and their cleared contact conditions. Hydrogen peroxide works by producing destructive hydroxyl free radicals that can attack membrane lipids, DNA, and other essential cell components.
Catalase, produced by aerobic organisms and facultative anaerobes that possess cytochrome systems, can protect cells from metabolically produced hydrogen peroxide by degrading hydrogen peroxide to water and oxygen. This defense is overwhelmed by the concentrations used for disinfection , Hydrogen peroxide is active against a wide range of microorganisms, including bacteria, yeasts, fungi, viruses, and spores 78, Bactericidal effectiveness and stability of hydrogen peroxide in urine has been demonstrated against a variety of health-care—associated pathogens; organisms with high cellular catalase activity e.
Synergistic sporicidal effects were observed when spores were exposed to a combination of hydrogen peroxide 5. Other studies demonstrated the antiviral activity of hydrogen peroxide against rhinovirus The product marketed as a sterilant is a premixed, ready-to-use chemical that contains 7. The mycobactericidal activity of 7. When the effectiveness of 7. No complaints were received from the nursing or medical staff regarding odor or toxicity.
A new, rapid-acting Manufacturer data demonstrate that this solution sterilizes in 30 minutes and provides high-level disinfection in 5 minutes This product has not been used long enough to evaluate material compatibility to endoscopes and other semicritical devices, and further assessment by instrument manufacturers is needed. Under normal conditions, hydrogen peroxide is extremely stable when properly stored e.
Corneal damage from a hydrogen peroxide-soaked tonometer tip that was not properly rinsed has been reported Hydrogen peroxide also has been instilled into urinary drainage bags in an attempt to eliminate the bag as a source of bladder bacteriuria and environmental contamination Although the instillation of hydrogen peroxide into the bag reduced microbial contamination of the bag, this procedure did not reduce the incidence of catheter-associated bacteriuria As with other chemical sterilants, dilution of the hydrogen peroxide must be monitored by regularly testing the minimum effective concentration i.
Compatibility testing by Olympus America of the 7. Iodine solutions or tinctures long have been used by health professionals primarily as antiseptics on skin or tissue. Iodophors, on the other hand, have been used both as antiseptics and disinfectants. FDA has not cleared any liquid chemical sterilant or high-level disinfectants with iodophors as the main active ingredient. An iodophor is a combination of iodine and a solubilizing agent or carrier; the resulting complex provides a sustained-release reservoir of iodine and releases small amounts of free iodine in aqueous solution.
The best-known and most widely used iodophor is povidone-iodine, a compound of polyvinylpyrrolidone with iodine. This product and other iodophors retain the germicidal efficacy of iodine but unlike iodine generally are nonstaining and relatively free of toxicity and irritancy , Several reports that documented intrinsic microbial contamination of antiseptic formulations of povidone-iodine and poloxamer-iodine caused a reappraisal of the chemistry and use of iodophors The reason for the observation that dilution increases bactericidal activity is unclear, but dilution of povidone-iodine might weaken the iodine linkage to the carrier polymer with an accompanying increase of free iodine in solution Iodine can penetrate the cell wall of microorganisms quickly, and the lethal effects are believed to result from disruption of protein and nucleic acid structure and synthesis.
Published reports on the in vitro antimicrobial efficacy of iodophors demonstrate that iodophors are bactericidal, mycobactericidal, and virucidal but can require prolonged contact times to kill certain fungi and bacterial spores 14, , , Three brands of povidone-iodine solution have demonstrated more rapid kill seconds to minutes of S.
The virucidal activity of 75— ppm available iodine was demonstrated against seven viruses Other investigators have questioned the efficacy of iodophors against poliovirus in the presence of organic matter and rotavirus SA in distilled or tapwater Besides their use as an antiseptic, iodophors have been used for disinfecting blood culture bottles and medical equipment, such as hydrotherapy tanks, thermometers, and endoscopes. Antiseptic iodophors are not suitable for use as hard-surface disinfectants because of concentration differences.
Iodophors formulated as antiseptics contain less free iodine than do those formulated as disinfectants Iodine or iodine-based antiseptics should not be used on silicone catheters because they can adversely affect the silicone tubing Ortho-phthalaldehyde is a high-level disinfectant that received FDA clearance in October It contains 0. OPA solution is a clear, pale-blue liquid with a pH of 7. Tables 4 and 5. Preliminary studies on the mode of action of OPA suggest that both OPA and glutaraldehyde interact with amino acids, proteins, and microorganisms.
However, OPA is a less potent cross-linking agent. This is compensated for by the lipophilic aromatic nature of OPA that is likely to assist its uptake through the outer layers of mycobacteria and gram-negative bacteria OPA appears to kill spores by blocking the spore germination process Studies have demonstrated excellent microbicidal activity in vitro 69, , , , For example, OPA has superior mycobactericidal activity 5-log 10 reduction in 5 minutes to glutaraldehyde.
The mean times required to produce a 6-log 10 reduction for M. OPA showed good activity against the mycobacteria tested, including the glutaraldehyde-resistant strains, but 0.
Increasing the pH from its unadjusted level about 6. The level of biocidal activity was directly related to the temperature. A greater than 5-log 10 reduction of B. The influence of laboratory adaptation of test strains, such as P. Resistant and multiresistant strains increased substantially in susceptibility to OPA after laboratory adaptation log 10 reduction factors increased by 0. Other studies have found naturally occurring cells of P. OPA has several potential advantages over glutaraldehyde.
It has excellent stability over a wide pH range pH 3—9 , is not a known irritant to the eyes and nasal passages , does not require exposure monitoring, has a barely perceptible odor, and requires no activation. OPA, like glutaraldehyde, has excellent material compatibility.
A potential disadvantage of OPA is that it stains proteins gray including unprotected skin and thus must be handled with caution Meticulous cleaning, using the correct OPA exposure time e. Personal protective equipment should be worn when contaminated instruments, equipment, and chemicals are handled In April , the manufacturer of OPA disseminated information to users about patients who reportedly experienced an anaphylaxis-like reaction after cystoscopy where the scope had been reprocessed using OPA.
Of approximately 1 million urologic procedures performed using instruments reprocessed using OPA, 24 cases 17 cases in the United States, six in Japan, one in the United Kingdom of anaphylaxis-like reactions have been reported after repeated cystoscopy typically after four to nine treatments.
Preventive measures include removal of OPA residues by thorough rinsing and not using OPA for reprocessing urologic instrumentation used to treat patients with a history of bladder cancer Nevine Erian, personal communication, June 4, ; Product Notification, Advanced Sterilization Products, April 23, A few OPA clinical studies are available.
Furthermore, OPA was effective over a day use cycle High-pressure liquid chromatography confirmed that OPA levels are maintained above 0. OPA must be disposed in accordance with local and state regulations. These label claims differ worldwide because of differences in the test methodology and requirements for licensure.
Peracetic, or peroxyacetic, acid is characterized by rapid action against all microorganisms. Special advantages of peracetic acid are that it lacks harmful decomposition products i.
It remains effective in the presence of organic matter and is sporicidal even at low temperatures Tables 4 and 5. Peracetic acid can corrode copper, brass, bronze, plain steel, and galvanized iron but these effects can be reduced by additives and pH modifications. Little is known about the mechanism of action of peracetic acid, but it is believed to function similarly to other oxidizing agents—that is, it denatures proteins, disrupts the cell wall permeability, and oxidizes sulfhydryl and sulfur bonds in proteins, enzymes, and other metabolites In the presence of organic matter, — ppm is required.
For viruses, the dosage range is wide 12— ppm , with poliovirus inactivated in yeast extract in 15 minutes with 1,—2, ppm. In one study, 3. Peracetic acid 0. With bacterial spores, —10, ppm 0. An automated machine using peracetic acid to chemically sterilize medical e. As previously noted, dental handpieces should be steam sterilized. Simulated-use trials have demonstrated excellent microbicidal activity , , and three clinical trials have demonstrated both excellent microbial killing and no clinical failures leading to infection 90, , Currently, ionophore antibiotics are mainly used in livestock and veterinary industry for anti-parasite treatment [ 29 ].
The cytotoxicity of these antibiotics and poor selectivity in turn limits their further development into antibacterial agents. However, with the development of molecular biology, enniatins have been developed into an antibacterial agent for the treatment of upper respiratory tract infections [ 30 ].
Therefore, in any case, the importance of natural products should not be ignored, and many compounds like to enniatin A1 have exhibited have huge prospects. Interestingly, in addition to in vitro bacteriostatic and bactericidal effects, enniatin A1 also showed synergistic effects against M. However, on which way such significant anti-tuberculosis potency improvement was achieved between enniatin A1 and rifamycin is still unknown.
Recent research revealed that rifamycin exhibited three forms in solutions: A-, B-, and C-type [ 17 ]. The specific intermolecular interaction between water and rifamycin antibiotics resulted in the generation of more lipophilic structure C-type or more hydrophilic structure A-type during the transport of the antibiotic to the molecular target-RNA polymerase [ 17 ]. In addition, the equilibrium between A-and C-type conformers in rifamycin improves their adaptation to the changing nature of bacteria cell membranes, especially to efflux pump systems [ 17 ].
An interaction between enniatin A1 and rifampicin can contribute to the formation of a more lipophilic structure of rifampicin in solution, which could allow rifampicin to overcross the natural cell walls of M. The interaction may affect the affinity of rifamycin antibiotics for efflux pump systems. Our further experiments demonstrated that after exposure to enniatin A1, the membrane potential and intracellular ATP levels of M. Maintaining the stability of bacterial cell membrane function is necessary to ensure cell homeostasis, and destroying bacterial cell membrane function and energy metabolism will seriously affect the survival of bacteria [ 32 ].
Our results suggest that enniatin A1 may be good adjuvant for improving efficacy of rifampicin against Mycobacteria strains. Moreover, antibiotics targeting membrane function may be able to reduce the emergence of resistant strains. Bedaquiline was from TargetMol Shanghai, China.
Minimum inhibitory concentrations MICs against M. Briefly, bacteria were grown to log phase optical density nm [OD] of 0. The last row of the plate was used as a drug-free control. RIF was used as antibiotic control. A color change from blue to pink indicates the bacterial growth. The lowest drug concentration to stop this color change was defined as MIC. In brief, the MICs of the tested compound and anti-tuberculosis drugs against M. Diploid serial dilutions of compounds were prepared in 96 well micro-plate.
MIC was defined as described above. The fractional inhibitory concentration FIC of each compound was calculated as the MIC of the compound in combination divided by the sum of MICs of compounds used alone. At day 0, 2, 4, 8 and 12, cultures were ten-fold serially diluted and plated in 7H11 agar plates. THP-1 cells were seeded into well plates and incubated with a final concentration of nM phorbol myristate acetate PMA for 48 h to induce cell differentiation into macrophages.
Cells were infected with M. After 4 h of infection, the extracellular bacteria were removed by washing with phosphate-buffered saline PBS, pH7. Culture was replaced with 1 mL of the compound-containing media.
And then, the infected macrophages were lysed by adding 1 mL 0. Diluting the cell lysate and plating on 7H11 agar plates to calculate CFUs. Triplicate cultures of each strain were analyzed during a single experiment and the experiments were repeated at least three times. Intracellular ion content was measured as described previously [ 37 , 38 ]. Briefly, a volume of 10 mL logarithmic phase of M. The culture was centrifuged at 12, rpm for 5 min. Bacteria were re-suspended in Bugbuster solution and incubation on a shaker at room temperature for 24 h.
After staining, the cells were centrifuged and re-suspended in the same buffer to an OD of 0. When the cytoplasmic membrane integrity is destroyed, the dye can cause a great enhancement in fluorescence intensity by binding to nucleic acids. In this assay, M. Background fluorescence was measured before addition of compound. Bacteria were re-suspended in 2. Samples were washed with 0. Samples were dehydrated with gradient absolute ethanol and isoamyl acetate. Briefly, M. All authors have read and agreed to the published version of the manuscript.
Sample Availability: Samples are notavailable from the authors. National Center for Biotechnology Information , U.
Journal List Molecules v. Published online Dec Find articles by Gaoyan Wang. Find articles by Wenqi Dong. Find articles by Hao Lu. Find articles by Wenjia Lu. Find articles by Jiajia Feng. Find articles by Xiangru Wang. Find articles by Huanchun Chen.
Author information Article notes Copyright and License information Disclaimer. Received Nov 15; Accepted Dec Abstract Background : Tuberculosis remains a global disease that poses a serious threat to human health, but there is lack of new and available anti-tuberculosis agents to prevent the emergence of drug-resistant strains.
Keywords: Mycobacterium tuberculosis , natural compound, enniatin A1, bactericidal, synergy, membrane potential. Introduction Tuberculosis remains a global infectious disease that poses a serious threat to human health, causing about 10 million new cases and more than 1. Open in a separate window. Figure 1.
Results 2. Tuberculosis in vitro and Intracellular As shown in Table 1 , the MICs of the compound against a range of gram-positive and gram-negative strains were determined, and the MIC of the compound against M. Figure 2. Table 1 MICs of enniatin A1 against microorganisms.
Tuberculosis The bactericidal effect of enniatin A1 against M. Figure 3. Antimicrobial Activity of Enniatin A1 in Combination with Classical Anti-Tuberculosis Drugs In order to determine the antibacterial activity of enniatin A1 combined with classical anti-tuberculosis drugs, the chessboard method was used to perform drug interaction experiments.
Table 2 Combination of enniatin A1 and anti-tuberculosis drugs against M. Figure 4. Figure 5. Discussion With the extensive use of anti-tuberculosis drugs, the problem of drug resistance of tuberculosis has become increasingly severe, posing serious challenges to existing methods of tuberculosis control. Materials and Methods 4. Kill Kinetic Assay M. Activity of EnniatinA1 against Intracellular M.
Tuberculosis THP-1 cells were seeded into well plates and incubated with a final concentration of nM phorbol myristate acetate PMA for 48 h to induce cell differentiation into macrophages.
Measurement of Intracellular Ion Content Intracellular ion content was measured as described previously [ 37 , 38 ]. Scanning Electron Microscopy of M.
Bovis BCG 1. Author Contributions C. Conflicts of Interest The authors declare no conflict of interest. Footnotes Sample Availability: Samples are notavailable from the authors. References 1. The cidal mode of action of EA fraction was detected by treating bacterial cultures at mid log phase. Scanning electron microscopic study supported morphological disintegration of bacterial cells.
In addition, reduction of the activity of EMP pathway, TCA cycle and gluconeogenic enzymes in all bacteria suggested the interference of antibacterial principles with central carbohydrate metabolic pathways. In addition, DPPH free radical as well as superoxide radical scavenging assay also suggested strong antioxidant potential of AE1 with an IC50 value of On the basis of above facts it can be concluded that the strain AE1 will be a good source of bioactive compounds having medicinal importance.
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