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The membrane destabilising action of the antibacterial agent chlorhexidine.

The antibacterial agent chlorhexidine has long been used as an agent for medical antisepsis. This compound is a membrane active agent which probably has its major antibacterial action by interference with the function of cellular membranes. The results demonstrated an inhibition of oxygen utilisation by bacteria which was related to falls in cellular ATP levels. There was an effect on the outer membranes of Gram-negative bacteria which allowed the release of periplasmic enzymes. The inner membrane was not ruptured but its functionality was breached and there was an inhibition of active uptake of small molecules which did not appear to be related to cellular ATP levels.

Adenosine Triphosphate↗

Safety of Hibitane. II. Human experience.

Chlorhexidine has been widely used in medical practice since its introduction on to the marked in the early 1950s. Primarily it has been used for topical antisepsis, e.g. pre-surgery skin preparation, burns prophylaxis, and prior to obstetrical/gynaecological procedures. This extensive experience has demonstrated the virtual absence of sensitization and a low irritancy potential for the compound. Only one significant adverse effect has been identified during medical use, namely, the production of sensorineural deafness after direct instillation into the middle ear, a property shared by several commonly used antiseptics. The encouraging reports of the use of chlorhexidine for plaque control prompted further safety investigations. It has been shown that absorption after oral ingestion is very low, and long-term oral use has not produced changes in haematological and biochemical parameters. Occasional oral intolerance of mouthrinse formulations has been reported, although no histological abnormalities were present in gingival biopsies taken after 18 months' daily use. Very occasionally, a reversible swelling of the parotid glands has been reported after use of chlorhexidine in mouthrinse formulations, but not after other methods of administration. Tooth discoloration, which shows wide inter-individual variation is seen after all dental formulations. This undesirable cosmetic effect would appear to represent the only significant argument against everyday prophylactic oral use of chlorhexidine.

Administration, Oral↗

Fowlicidin-3 is an alpha-helical cationic host defense peptide with potent antibacterial and lipopolysaccharide-neutralizing activities.

Cathelicidins are an important family of cationic host defense peptides in vertebrates with both antimicrobial and immunomodulatory activities. Fowlicidin-1 and fowlicidin-2 are two newly identified chicken cathelicidins with potent antibacterial activities. Here we report structural and functional characterization of the putatively mature form of the third chicken cathelicidin, fowlicidin-3, for exploration of its therapeutic potential. NMR spectroscopy revealed that fowlicidin-3 comprises 27 amino-acid residues and adopts a predominantly alpha-helical structure extending from residue 9 to 25 with a slight kink induced by a glycine at position 17. It is highly potent against a broad range of Gram-negative and Gram-positive bacteria in vitro, including antibiotic-resistant strains, with minimum inhibitory concentrations in the range 1-2 microM. It kills bacteria quickly, permeabilizing cytoplasmic membranes immediately on coming into contact with them. Unlike many other host defense peptides with antimicrobial activities that are diminished by serum or salt, fowlicidin-3 retains bacteria-killing activities in the presence of 50% serum or physiological concentrations of salt. Furthermore, it is capable of suppressing lipopolysaccharide-induced expression of proinflammatory genes in mouse macrophage RAW264.7 cells, with nearly complete blockage at 10 microM. Fowlicidin-3 appears to be an excellent candidate for future development as a novel antimicrobial and antisepsis agent, particularly against antibiotic-resistant pathogens.

Amino Acid Sequence↗

Prevalence of udder bacteria in milk samples from four dairy goat herds.

The prevalence of udder bacterial infections in 4 commercial goat herds in New South Wales was examined. Coagulase negative staphylococci were the predominant bacteria isolated being cultured from 13.3% of the 896 halves tested. Other bacteria isolated were Staphylococcus aureus (less than 1% of halves), streptococci (0.6%) and coliforms (2.0%). The low prevalence of udder bacteria contributing to the contamination of the milk was attributed to the milking management practices carried out in these herds, in particular pre-milking and post-milking antisepsis.

Animals↗

Preoperative ocular disinfection by the use of povidone-iodine 5%.

Numerous disinfective methods have been proposed in order to prevent intraocular infections during eye operations. In a clinical-laboratory study we evaluated the effectiveness of povidone-iodine solution 5% as a preventive - preoperative means of conjunctival antisepsis prior to ocular surgery. Conjunctival cultures were performed on 100 patients. Group A (50 patients) had their fornices washed with normal saline immediately before surgery. In Group B (50 patients) one drop of povidone-iodine solution 5% was applied prior to preoperative wash of the fornices with normal saline. Thirty-three out of 50 eyes from Group A had positive cultures (66%). Only 15 out of 50 eyes from Group B had positive cultures (30%). Bacteria flora differed in the two groups, with Group A exhibiting more dangerous strains. Preoperative-preventive disinfection with povidone-iodine 5% may prove to be advantageous to ocular surgery.

Bacteria↗

Survival of Serratia marcescens in benzalkonium chloride and in multiple-dose medication vials: relationship to epidemic septic arthritis.

In an epidemic of septic arthritis due to Serratia marcescens, the intra-articular injection of contaminated methylprednisolone may have played a key role. The epidemic strain was found in used multiple-dose vials of methylprednisolone and in a canister of cotton balls soaked in benzalkonium chloride. The cotton balls had been used for antisepsis and disinfection. Growth characteristics of the epidemic strain of S. marcescens were compared with those of control strains of S. marcescens which had been obtained from unrelated nosocomial outbreaks. The epidemic strain was able to survive in 1:100 dilutions of benzalkonium chloride and was able to grow to greater than 10(5) CFU/ml in multiple-dose vials of methylprednisoline; control strains could not be recovered after 24 h in the same solutions. The preservative in methylprednisolone is gamma-myristyl picolinium chloride, a compound chemically related to benzalkonium chloride. We speculate that the epidemic strain of S. marcescens, which was resistant to benzalkonium chloride, had cross-resistance to gamma-myristyl picolinium chloride. If the cotton balls were used to disinfect the tops of the multiple-dose vials of methylprednisolone, small numbers of organisms subsequently introduced into the solution could have grown to high concentrations.

Arthritis, Infectious↗

Comparison of four antiseptic preparations for skin in the prevention of contamination of percutaneously drawn blood cultures: a randomized trial.

A number of skin antiseptics have been used to prevent the contamination of blood cultures, but the comparative efficacies of these agents have not been extensively evaluated. We therefore sought to compare the efficacy of four skin antiseptics in preventing blood culture contamination in a randomized, crossover, investigator-blinded study conducted in an emergency department and the inpatient wards of a university hospital. The patient group included all patients from whom blood samples were obtained percutaneously for culture. Skin antisepsis was performed with 10% povidone-iodine, 70% isopropyl alcohol, tincture of iodine, or povidone-iodine with 70% ethyl alcohol (i.e., Persist). The blood culture contamination rate associated with each antiseptic was then determined. A total of 333 (2.62%) of 12,692 blood cultures were contaminated during the study period compared to 413 (3.21%) of 12,859 blood cultures obtained during the previous 12-month period (relative risk = 0.82; 95% confidence interval, 0.71 to 0.94; P = 0.006). During the study, the contamination rates were determined to be 2.93% with povidone-iodine, 2.58% with tincture of iodine, 2.50% with isopropyl alcohol, and 2.46% with Persist (P = 0.62). We detected no significant differences in the blood culture contamination rates among these four antiseptics, although there was some evidence suggesting greater efficacy among the alcohol-containing antiseptics. Among the evaluated antiseptics, isopropyl alcohol may be the optimal antiseptic for use prior to obtaining blood for culture, given its convenience, low cost, and tolerability.

2-Propanol↗

The start of life: a history of obstetrics.

Obstetric intervention originally consisted of extraction of the baby, usually by the breech, to save the mother's life in obstructed labour. Forceps, introduced in the 17th century, were later refined by men-midwives like William Smellie. In Victorian times, Simpson championed chloroform anaesthesia, Lister pioneered antisepsis, and caesarean section was introduced. In 1935, however, Britain's maternal mortality rate was still around 400/100,000. It fell dramatically after antibiotics appeared and is now 11.4. In the 1960s ultrasound and electronic fetal monitoring became widely used. In 2000 the British caesarean section rate reached 20%. Worldwide, childbirth still causes 600,000 maternal deaths a year.

Cesarean Section↗

Strategy of control of nosocomial infections: application of disinfectants such as povidone-iodine.

At Morioka Yuai Hospital, the Infection Control Division was set up 5 years ago, and it has made efforts to actively control infections. In particular, the division succeeded in increasing the frequency of general round table discussions for patients with infections. We strongly recommend to frequently gargle with Isodine at operations. Recently, we have followed up patients with infections caused by MRSA, Pseudomonas aeruginosa and Serratia or carriers of these bacteria, and determined the drug sensitivities of clinical isolates. In addition, because of the current highly aged society, a high percentage of inpatients has various underlying diseases. In particular, there are quite a few cases in which pneumonia occurs as an opportunistic infection. From studies in these patients and patients of the dental department, it has been shown that oral microorganisms clearly decrease in count by careful tooth brushing and gargling with Isodine, with prevention of pneumonitis caused by oral microorganisms. As we consider that antisepsis with povidone-iodine is useful for the prevention of nosocomial and opportunistic infections, we would like to report the findings of our study currently under way.

Anti-Infective Agents, Local↗

Antimicrobial effectiveness of povidone-iodine and consequences for new application areas.

The microbicidal action spectrum of povidone-iodine (PVP-I) is broad - even after short onset times. Unlike local antibiotics and other antiseptic substances, no resistance develops. The high degree of bactericidal efficiency in respect of highly resistant gram-positive pathogenic micro-organisms, such as methicillin-resistant Staphylococcus aureus (MRSA) and enterococcus strains, is particularly significant for hospital hygiene. An in vitro study with 10 genotypically different MRSA isolates showed an optimum bactericidal effect (logarithmic reduction factor value >5) without protein load after just 30 s exposure and even in a dilution of Betaisodona solution (Mundipharma GmbH) of 1%. With protein load (0.2% albumin), the optimum in microbicidal effectiveness shifts to concentrations > or = 10% Betaisodona solution referring to an exposure time of 30 s. Since recent results are now also available on the toxicological safety of PVP-I preparations for the ciliated epithelium of the nasal mucosa and the good tolerability on skin and other mucous membranes is a known factor, a controlled clinical study is currently being carried out to eliminate colonizations of MRSA. Evidence has also recently been produced of the antiviral activity of PVP-I against herpes simplex, adeno- and enteroviruses, as well as its high degree of efficiency against Chlamydia. Hence alongside the classical fields of application, such as the disinfection of the skin and hands, mucosa antisepsis and wound treatment, there are also useful indications for the substance, i.e. rinsing of body cavities and joints and application to the eye.

Adenoviridae Infections↗

Comparative testing of liposomal and aqueous formulations of povidone-iodine for their angioirritative potential at the chorioallantoic membrane of ex ovo cultivated chick embryos.

BACKGROUND: Due to its excellent microbicidal activity, povidone-iodine (PVP-I) is used for local anti-infective treatment, especially for wound antisepsis of the skin. Previous studies have shown that liposomal PVP-I formulations are less cytotoxic and that a special liposomal PVP-I hydrogel provides wound healing efficacy. OBJECTIVE: In the present study, the angiotoxic activity of the liposomal and the aqueous PVP-I formulations were comparatively tested at the chorioallantoic membrane (CAM) of chick embryos. METHODS: Test preparations were administered onto the CAM of ex ovo cultivated chick embryos. At different time intervals, the local irritation of the blood vessels was examined microscopically and assigned to a score of vascular injury. RESULTS: Angioirritative reactions of the CAM were manifest as coagulation, vascular congestion and hemorrhages. The liposomal formulations containing 0.1, 0.5 or 1% PVP-I were found to be significantly less angiotoxic than the corresponding aqueous formulations. CONCLUSION: The angioirritative potential of PVP-I is significantly reduced by its liposomal encapsulation.

Animals↗

Povidone-iodine liposomes--an overview.

In recent years, liposomes have been increasingly explored as novel drug delivery systems, and several liposome-based drug products have been approved in Europe, the USA and Japan. Depending on size, composition and surface characteristics, liposomes interact specifically with biological structures. Liposomal drug products provide a topical activity at the desired locus of action and are deemed more effective and less toxic than conventional drug formulations. The combination of povidone-iodine (PVP-I) and liposomes unites the exceptional microbicidal activity of the antiseptic substance with the excellent tolerability and lack of immunogenicity of liposomes; in addition, liposomes provide a moist molecular film for the wound environment. The multilamellar vesicles act as microreservoirs hence prolonging the release of the active ingredient. Although no commercial product for repeated application on the eye is currently available, PVP-I has been used in ophthalmology not only for pre- and postoperative antisepsis, but also for the treatment of bacterial and viral conjunctivitis and for prophylaxis against ophthalmia neonatorum. For these indications, liposomal formulations with 2.5 and 5.0% PVP-I were developed. These eye drops are isotonic with tear fluid at pH 6. First in vitro tests demonstrated an excellent antimicrobial efficacy, and a placebo-controlled clinical study on volunteers showed a very good local tolerability. A study on rabbits demonstrated positive results of the PVP-I liposome eye drops compared to placebo and the broadspectrum antibiotic Polyspectran in a standardized model of Staphylococcus aureus deep eye infection. The other aim is a well-tolerated liposomal PVP-I hydrogel for improved antiseptic wound treatment with moisturizer. It has been reported that liposomes are enriched at the wound bottom for direct action against infection and support of wound healing. An animal study on the efficacy and tolerability of different formulations of a hydrogel with PVP-I liposomes in deep dermal burn wounds has indicated an outstanding quality of wound healing with smooth granulation tissue, less inflammation, less wound contraction and no hyperkeratotic reactivity, especially with the 3% PVP-I liposome formulation.

Administration, Cutaneous↗

The role of Joseph Lister in developing the absorbable ligature.

Joseph Lister is associated with pioneering work on antisepsis. However an important but less well-known contribution to surgical progress was his work on the absorbable suture. This article details the problems Lister faced in operative surgery, his observations and experiments that lead to his development of an absorbable suture.

Absorbable Implants↗

Junctional care: the key to prevention of catheter sepsis in intravenous feeding.

Investigation of an outbreak of infection related to intravenous feeding catheters, predominantly with Staphylococcus epidermidis, suggested that the probable origin was the connections in the delivery system. Equipment and policy changes were then instituted: a catheter with integral hub was used, the connections were reduced from two to one, and improved antisepsis at the connection was devised. These actions resulted in a sustained, significant reduction in the catheter sepsis rate, supporting the hypothesis that junctional care is vital to the avoidance of catheter infection.

Catheters, Indwelling↗

Combined abdominal aortic aneurysmectomy and other abdominal operations.

BACKGROUND AND AIM: Co-existence of intra-abdominal non-vascular disease with an abdominal aortic aneurysm (AAA) poses a difficult surgical challenge. MATERIAL AND METHODS: Review of hospital records of 602 patients undergoing elective surgery for AAA during a 9-year period identified 61 (10.3%) patients with a co-existent intra-abdominal non-vascular disease requiring surgery. RESULTS: The concomitant operations were 26 cholecystectomies, 11 inguinal hernia repairs, 2 small bowel resections, 5 left and 5 right hemicolectomies and 1 low anterior resection for colorectal carcinoma, 1 gastrectomy for gastric carcinoma, 5 nephrectomies, one salvage cystectomy for renal carcinoma and 1 left liver lobectomy for hepatrocellular carcinoma. Additional procedures for benign diseases prolonged the operative time by a mean of 35 (range 20-105) minutes and the major operations for malignancy by 120 (range 60-225) minutes. The overall hospital mortality and morbidity rates in the whole series of AAA (n = 602) remained as low as 0.66% and 13.6% respectively. There was no mortality and only two complications occurred in patients undergoing the combined procedure (n = 61). During a follow up period of 4-70 months, no graft infections were detected. CONCLUSION: In selected patients, the one stage approach is safe and effective. Attention should be given to the technical details and the rules of antisepsis. In elderly patients with AAA, a co-existent malignancy should be actively excluded.

Aortic Aneurysm, Abdominal↗

Selecting antibacterial agents for the control of surgical infection: mini-review.

An analysis of the recent literature on the control of surgical infections confirms the role of antimicrobial agents which guarantee valid perioperative antisepsis in both clean and clean-contaminated surgery. Current chemotherapy is able to check serious postoperative infectious complications by reducing the risk of septic shock with use of a glycopeptide-aminoglycoside-betalactam combination together with anti-inflammatory drugs.

Aminoglycosides↗

The role of lomefloxacin in the treatment of chronic prostatitis.

The choice of antimicrobial agents for treatment of prostatitis should be based on two factors: in vitro sensitivity of isolated pathogens and potential intraprostatic penetration of the molecule. Unfortunately, only a few antibiotic agents penetrate prostatic fluid which is the primary site of infection. Lomefloxacin, a once-daily difluoroquinolone, could play a central role in the therapy of prostatitis because it has sufficient liposolubility, low ionization (pKa), low protein binding, small molecular size, long serum elimination half-life and it can pass from interstital fluid across prostatic cells into the lumen. This study was carried out on 12 patients (mean age 65 years) with normal hepatic and renal function, divided into two groups of 6 subjects each. Lomefloxacin was administered for perioperative antisepsis at the dose of 400 mg orally once a day for 4 days. Serum and tissue were sampled in the two groups of patients 4 h (Group A) and 8 h (Group B) respectively after the last drug administration. Tissue penetration was higher than serum, with a T/S >2 in the prostatic capsule and seminal blister, and a T/S >1.6 in the adenomatous tissue, in both groups of patients. In addition, the prostatic tissue concentrations exceeded the MIC for the main pathogens usually involved in urogenital infections. Therefore, because of its pharmacokineitic and pharmacodynamic characteristics, lomefloxacin is proposed as an efficacious therapeutic option, even for the treatment of chronic prostatitis.

Aged↗

Fires in the operating room and intensive care unit: awareness is the key to prevention.

Recent recommendations from the Centers for Disease Control (CDC) to use alcohol-based substances for hand hygiene and skin antisepsis could introduce new fire hazards in the operating room (OR). This potential for an increase in the number of fires in the hospital setting with wide spread use of alcohol-based agents warrants heightened awareness of the risks and implementation of safety measures when using these agents. Here, we report a patient who, during a tracheostomy, sustained severe burns resulting from a fire in the OR. In this case, the use of an alcohol-based antiseptic was the major contributing factor to the surgical fire.

Aged↗