Hexachlorophene is a soap-compatible bisphenol that has been widely used as an antiseptic, yet its mechanism of action is undefined. The relative threshold concentration for bactericidal effect on a susceptible test organism, Bacillus megaterium, was established to be about 10 μg/mg of cell dry weight. At this or at high (≥100 μg/mg) concentration, adsorptive uptake by cells displayed saturation kinetics. At about 30 μg/mg, the time course of adsorption occurred in three distinct stages. The triphasic pattern was interpreted to represent successive penetration of and adsorption by the cell wall, the protoplast membrane, and the cytoplasm. This interpretation was substantiated by determinations of hexachlorophene adsorption by isolated cell components. Electron microscopy disclosed cytopathology, evidenced as gaps or discontinuities, in the protoplast membrane (but not in the cell wall or cytoplasm) at > 30 μg of hexachlorophene per mg of cell dry weight. Similarly, treatment with > 30 μg/mg allowed a fluorescigenic dye (tolyl-peri acid) to penetrate into the protoplast. However, no detectable cytological manifestations were discerned at the minimum lethal concentration of 10 μg/mg. Apparently, hexachlorophene is physically disruptive at intermediate or high relative concentrations but acts in a more subtle fashion at the minimal lethal concentration.
A comparative study of the different reactions of herpes simplex virus types 1 and 2 to Lysol, Listerine, bleach, rubbing alcohol, Alcide disinfectant (Alcide Corp., Westport, Conn.), and various pHs, temperatures, and UV light exposures was performed. Both types of stock virus (titers of approximately 10(6) and 10(5.5) for types 1 and 2, respectively) were inactivated by 0.5% Lysol in 5 min; by Listerine (1:1 mixtures) in 5 min; by 2,000 ppm (2,000 microliters/liter) of bleach in 10 min; by rubbing alcohol (1:1 mixtures) at zero time; by Alcide disinfectant (0.2 ml of virus plus 2.0 ml of Alcide) at zero time; by pHs 3, 5, and 11 in 10 min; and by a temperature of 56 degrees C in 30 min. A germicidal lamp (model G30TB; General Electric Co., Schenectady, N.Y.) (30 W) at a distance of 48 cm failed to completely inactivate the two types in 15 min. Type 1 showed slightly more resistance to Listerine and bleach and significantly more resistance to heat; moreover, pH 9 did not affect the infectivity of either type after 10 min.
We tested the survival of the Wa strain of human rotavirus on the hands of volunteers and also studied infectious virus transfer between animate and inanimate (stainless steel disks) surfaces. The virus was diluted in a 10% suspension of feces, and 10 microliters (1 X 10(3) to 4 X 10(4) PFU) was placed on each of the four fingerpads of the left hand. One milliliter of 20% tryptose phosphate broth in Earle balanced salt solution was used for virus elution from each fingerpad, and the hands were disinfected with 70% ethanol before they were washed with an antiseptic soap and water. At 20, 60, and 260 min after inoculation, approximately 57, 43, and 7%, respectively, of the input infectious virus could be recovered. For virus transfer, the inoculum (2 X 10(4) to 8 X 10(4) PFU) was allowed to dry, and the donor surface was kept in contact with the recipient surface for 10 s at a pressure of approximately 1 kg/cm2. At 20 and 60 min after virus inoculation, 16.1 and 1.8%, respectively, of the input infectious virus could be transferred from the contaminated hand to a clean disk; when a clean hand was pressed against a contaminated disk, virus transfer was 16.8 and 1.6%, respectively. Contact between a contaminated and a clean hand 20 and 60 min after virus inoculation resulted in the transfer of 6.6 and 2.8%...
To determine the incidence rate of complications associated with vascular catheters in intensive care unit patients and to analyze risk factors for a positive vascular culture, we performed a multicenter study of intensive care unit patients at eight French hospitals. During the study period, 865 intravenous catheters were inserted in 566 patients; 362 (41.8%) were peripheral catheters, and 503 (58.2%) were central catheters. Local complications (i.e., infiltration) occurred significantly more often with peripheral than with central catheters (P less than 0.001); in contrast, fever and bacteremia were significantly more often associated with central than with peripheral catheters (P less than 0.01 and P less than 0.05, respectively). The culture of the vascular-catheter tip was positive for 24% of central catheters (32 of 1,000 catheters days) and for 9% of peripheral catheters (21 of 1,000 catheters days). Staphylococcus epidermidis was the most common microorganism isolated from both peripheral and central catheters, followed by Staphylococcus aureus and Pseudomonas aeruginosa. No significant risk factor associated with positive cultures for peripheral catheters was found by univariate analysis. In contrast, the purpose of the cannula (nutrition and monitoring of central venous pressure)...
During a 6-week period, 10 patients were admitted to a hospital for treatment of knee or shoulder joint infections due to Serratia species. Isolates from eight patients were identified as Serratia marcescens with identical biochemical characteristics and antibiotic susceptibility patterns. Before the onset of infections, all patients had been treated by two orthopedic surgeons who shared an office. Studies revealed that infections were associated with previous joint injections (P = 4.44 X 10(-5] of methylprednisolone and lidocaine. Environmental cultures revealed that a canister of cotton balls soaked in aqueous benzalkonium chloride and two multiple-dose vials of methylprednisolone previously used by office personnel were contaminated with the epidemic strain of S. marcescens. The canister may have served as a potential reservoir for contamination of sterile solutions and equipment used for joint injections, of skin at the injection site, and of hands of personnel. No further cases occurred after the use of aqueous benzalkonium chloride was discontinued.
An outbreak of pseudobacteremia caused by Pseudomonas pickettii biovariant 1 is reported. The common source was the aqueous chlorhexidine solution prepared by the hospital pharmacy. The contamination problem caused by the antiseptic solution was eventually solved by a series of preventive measures.
Pseudomonas putrefaciens has been presented as an opportunistic pathogen in a few isolations from humans. This is the first documented report of a local infection of P. putrefaciens complicated by invasion of the blood stream. The organism was twice isolated from the blood culture and once from the wound exudate of a 73-year-old woman hospitalized for extensive ulcerations on the legs. Parenteral ampicillin and gentamicin together with local antiseptic treatment led to an uneventful recovery.
Nitrofurantoin, a commonly used urinary tract antiseptic, has been associated with idiosyncratic pulmonary and hepatic damage. We have used human lymphocytes in vitro to explore the biochemical basis of susceptibility to nitrofurantoin toxicity. The drug itself did not damage the cells as assessed by trypan blue dye exclusion. In the presence of a mouse hepatic microsomal drug-activating system, however, nitrofurantoin metabolites produced dose dependent toxicity to the lymphocytes. Inhibition of the enzyme epoxide hydrolase did not enhance toxicity; the metabolite thus does not appear to be a furan epoxide. Binding of reactive metabolites to cell macromolecules may lead directly to cell death, or in vivo, by acting as haptens to secondary immunologic responses. The metabolite caused a dose-dependent depletion of lymphocyte glutathione content. Cells from a patient with glutathione synthetase deficiency showed markedly enhanced nitrofurantoin toxicity. The findings suggest that glutathione plays a major role in protecting cells from nitrofurantoin-induced damage, and that studies of lymphocyte toxicity and glutathione metabolism in patients experiencing idiosyncratic reactions to nitrofurantoin may lead to elucidation of the biochemical and genetic basis of drug susceptibility.
A new method of treating pleural empyema or pneumonectomy space infection by irrigation was evaluated in 11 patients. The infected cavities were filled with an antibiotic or antiseptic solution for three hours, and allowed to drain for one hour. This cycle was repeated every four hours for seven to 10 days. When cultures of the infected cavity became sterile the irrigation tube was removed and the wound sealed. Using this method, infection was eradicated after an average of 11 days in five of six patients with pleural empyema and in all five patients treated for an infected pneumonectomy space, including one with a bronchopleural fistula. The results of treating 58 similar cases of intrapleural sepsis over a 10-year period by the standard methods of aspiration, open drainage, decortication, or thoracoplasty were compared with the results of irrigation. In general, cyclical irrigation resulted in a shorter hospital stay and a shorter period of wound drainage than other methods.
Systemic side-effects during irrigation of body cavities with the antiseptic noxythiolin (Noxyflex) have not previously been reported. In two patients undergoing intrapleural lavage with 1% noxythiolin, anorexia and nausea with or without vomiting were observed which suggested systemic absorption. This was confirmed by chemical assays of serum from these patients. The process of absorption was studied in rabbits by injection of noxythiolin into the pleural or peritoneal cavity. Serum levels reached a peak at one to two hours indicating rapid entry into the bloodstream, declined slowly over seven hours, and reached zero before 24 hours. Although side-effects resulted from systemic absorption of noxythiolin during irrigation of the pleural cavity, they were mild and did not contra-indicate the use of noxythiolin as an irrigant. Awareness of the mechanism of side-effects of noxythiolin provides a rational basis for management of symptoms through reduction of the volume or frequency of irrigation.
The results of culture of 668 catheter tips from 422 patients are analysed with relation to the site of the catheter and the age of the patient. Coagulase-negative staphylococci were the most common bacterial isolate, but Gram-negative bacilli were found in the venous lines, femoral artery lines, and peripheral lines. Isolations of Gram-negative bacilli were associated with age, being found mainly in those under 1 year and those over 40 years of age. Typing of coagulase-negative staphylococci revealed that Staphylococcus epidermidis is the only variety found in peripheral lines and in lines inserted after operation for complications (central venous, sub-clavian, and long lines), whereas other types occur (along with Staphylococcus epidermidis) in the other lines (left atrial, arterial, and venous). Use of extra lines for the management of postoperative complications thereby increases the risk of Staphylococcus epidermidis gaining access to the circulation. A subgroup of venous lines used to administer inotropic agents was found to be sterile on culture, and this was the result of the anti-oxidant (sodium metabisulphite) in the inotrope solution acting as an antiseptic.
Povidone iodine is now being increasingly used in hospitals as an antiseptic. The possible habituation of bacteria to iodine was studied by serial passage of two strains of Pseudomonas aeruginosa, two strains of Escherichia coli, two strains of Klebsiella aerogenes, and one strain of Serratia marcescens in subinhibitory concentrations. After 20 passages, no significant change was observed in the minimal inhibitory concentration, minimal bactericidal concentration, and killing times between parent strains and 20th subcultures under standardized conditions.
Glycine is the simplest amino acid and is used as a metabolic product in some bacteria. However, an excess of glycine inhibits the growth of many bacteria, and it is used as a nonspecific antiseptic agent due to its low level of toxicity in animals. The effect of glycine on Helicobacter pylori is not precisely known. The present study was conducted to investigate (i) the effect of glycine on clarithromycin (CLR)-resistant and -susceptible strains of H. pylori, (ii) the effect of glycine in combination with amoxicillin (AMX), and (iii) the postantibiotic effect (PAE). The MIC at which 90% of strains are inhibited for glycine was almost 2.5 mg/ml for 31 strains of H. pylori, including CLR-resistant strains. We constructed isogenic CLR-resistant mutant strains by natural transformation and investigated the difference between clinical wild-type strains and isogenic mutants. There were no differences in the MICs between CLR-resistant and -susceptible strains or between clinical wild-type and mutant strains. The combination of AMX and glycine showed synergistic activity, with the minimum bactericidal concentration of AMX with glycine decreasing to 1/10 that of AMX alone. Glycine showed no PAE against H. pylori. These results suggest that glycine may be a useful antimicrobial agent against H. pylori not only alone but also in combination with antibacterial drugs for the treatment of H. pylori-associated diseases. Glycine may represent a component of a new type of eradication therapy for CLR-resistant H. pylori.
Transferable antibiotic resistance in Haemophilus influenzae was first detected in the early 1970s. After this, resistance spread rapidly worldwide and was shown to be transferred by a large 40- to 60-kb conjugative element. Bioinformatics analysis of the complete sequence of a typical H. influenzae conjugative resistance element, ICEHin1056, revealed the shared evolutionary origin of this element. ICEHin1056 has homology to 20 contiguous sequences in the National Center for Biotechnology Information database. Systematic comparison of these homologous sequences resulted in identification of a conserved syntenic genomic island consisting of up to 33 core genes in 16 β- and γ-Proteobacteria. These diverse genomic islands shared a common evolutionary origin, insert into tRNA genes, and have diverged widely, with G+C contents ranging from 40 to 70% and amino acid homologies as low as 20 to 25% for shared core genes. These core genes are likely to account for the conjugative transfer of the genomic islands and may even encode autonomous replication. Accessory gene clusters were nestled among the core genes and encode the following diverse major attributes: antibiotic, metal, and antiseptic resistance; degradation of chemicals; type IV secretion systems; two-component signaling systems; Vi antigen capsule synthesis; toxin production; and a wide range of metabolic functions. These related genomic islands include the following well-characterized structures: SPI-7...
Mouthwash antiseptic cetylpyridinium chloride (CPC) has potent activity against Candida albicans; however, two of five azole-resistant strains showed reduced CPC susceptibility. To further examine the potential for cross-resistance, CPC-resistant mutants were selected in vitro and their fluconazole susceptibility was tested. MICs were unchanged, and trailing growth generally decreased. With CPC-fluconazole combinations, both antagonism and synergism were observed, which can be explained, in part, by CDR1-CDR2 multidrug transporter upregulation.