In vitro and in vivo efficacy of catheters impregnated with antiseptics or antibiotics: evaluation of the risk of bacterial resistance to the antimicrobials in the catheters.

OBJECTIVE: To compare the efficacy of a new antiseptic catheter containing silver sulfadiazine and chlorhexidine on the external surface and chlorhexidine in the lumens to an antibiotic catheter impregnated with minocycline and rifampin on its external and luminal surfaces. DESIGN: Experimental trial. METHODS: Antimicrobial spectrum of catheters was determined by zones of inhibition. Resistance to luminal colonization was tested in vitro by locking catheter lumens with Staphylococcus epidermidis or Staphylococcus aureus culture after 7 days of perfusion. In vitro development of resistance to the antiseptic or antibiotic combination used in catheters was investigated. In vivo efficacy was tested (rat subcutaneous model) by challenge with sensitive or antibiotic-resistant bacteria. RESULTS: Antiseptic and antibiotic catheters exhibited broad-spectrum action. However, antibiotic catheters were not effective against Candida species and Pseudomonas aeruginosa. Both catheters prevented luminal colonization. Compared to controls, both test catheters resisted colonization when challenged with S aureus 7 and 14 days' postimplant (P<.05). Repeated in vitro exposure of S epidermidis culture to the antibiotic and antiseptic combinations led to small increases in the minimum inhibitory concentration (15 times and 2 times, respectively). Unlike the antibiotic catheter, the in vitro and in vivo activity of the antiseptic catheter was unaffected by the resistance profile of the test organism. Antiseptic catheters were more effective than antibiotic catheters in preventing colonization by rifampin-resistant S epidermidis in vivo (P<.05). CONCLUSIONS: Antiseptic and antibiotic catheters exhibit similar efficacy; however, when challenged with a rifampin-resistant strain, the antibiotic catheter appeared to be more susceptible to colonization than the antiseptic device.     

In-vitro evaluation of povidone-iodine and chlorhexidine against methicillin-resistant Staphylococcus aureus.

The in-vitro activity of povidone-iodine (PVP-I) and chlorhexidine (CHX) against 33 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) was evaluated by a quantitative suspension test method. Bactericidal potency was measured by the logarithmic reduction factors (LRFs) achieved with each strain, tested at dilutions 25-800 over exposure times 30-300 s using a challenge of approximately 10(7) colony forming units (cfu) ml-1. The mean LRFs achieved over all dilutions, times and strains were significantly higher for PVP-I than CHX. PVP-I exhibited a superior killing effect whether measured by rate of kill or final LRF achieved. This difference was highly significant as judged by analysis of variance (P less than 0.001). Full efficacy of an antiseptic has been defined as a safe LRF greater than five. Over the dilution range 25-200 this was achieved by CHX with only three of 33 strains. In contrast, PVP-I achieved full efficacy with all 33 strains.     

Antiseptic wound ventilation with a gas diffuser: a new intraoperative method to prevent surgical wound infection?

Postoperative wound infections are often a result of peri-operative contamination by Staphylococcus aureus. With a new insufflation device, a gas diffuser, it has become possible to establish a local micro-environment of almost 100% carbon dioxide in an open surgical wound. The device enables ventilation of the wound with an antiseptic agent, which in gaseous form can be delivered as a low uniform dose to all parts of the wound. The use of carbon dioxide (CO2) as a carrier gas eliminates possible inflammability of an antiseptic agent and helps to concentrate it to the site of interest by gravity. Using the above delivery system we have demonstrated the antibacterial effect of gaseous ethanol on S. aureus inoculated on sterile filter disks and blood agar plates, respectively. Ethanol is a very potent antiseptic agent with known properties, which makes it suitable for testing the maximal decontamination level. On filter disks, CO2 carrying vapour from a 95% ethanol solution decreased the number of colony-forming units after 5 min of exposure (P=0.04), and killed all bacteria within 10-15 min (P<0.001). In the presence of organic material, i.e. on exposed blood agar plates, the colony size decreased with exposure time, and no colonies were detected after 60 min of exposure (P<0.001). Antiseptic gas derived from 70% ethanol solution was less effective than that from 95% ethanol (P<0.001). CO2 humidified with water did not have a significant effect on number or size of the colonies. Our findings suggest that intraoperative wound antisepsis with a gas mixture of CO2 and an antiseptic agent delivered with a gas diffuser, may be a simple method to reduce the risk of postoperative wound infection.     

High prevalence of qacA/B carriage among clinical isolates of meticillin-resistant Staphylococcus aureus in Malaysia

The minimum inhibitory concentrations (MICs) of 60 meticillin-resistant Staphylococcus aureus (MRSA) isolates from Malaysia to three antiseptic agents - benzalkonium chloride (BZT), benzethonium chloride (BAC) and chlorhexidine digluconate (CHG) - were determined. All isolates had MICs ranging from 0.5 to 2 mg/L. Antiseptic resistance genes qacA/B and smr were detected in 83.3% and 1.6% of the isolates, respectively. Carriage of qacA/B correlated with reduced susceptibility to CHG and BAC. This is the first report of the prevalence of qacA/B and smr gene carriage in Malaysian MRSA isolates, with a high frequency of qacA/B carriage. The presence of these antiseptic resistance genes and associated reduced susceptibility to antiseptic agents may have clinical implications.     

Measurement of ultrasonic-induced chlorhexidine liberation: correlation of the activity of chlorhexidine-silver-sulfadiazine-impregnated catheters to agar roll technique and broth culture

The diagnosis of intravascular catheter-related infections continues to be a challenge to both the clinician and the microbiologist. To assess the antiseptic effects of silver-sulfadiazine-chlorhexidine-impregnated central venous catheters (SSC) on catheter culture systems, segments of fresh antiseptic- and non antiseptic-impregnated catheters as well as extracted catheters following five days of immersion in PBS were sonicated. The chlorhexidine liberated from the catheter material by ultrasonication was measured by HPLC. Fresh antiseptic-impregnated catheter segments rolled on seeded agar plates produced inhibition zones unlike catheters which had been extracted for >five days in phosphate buffered saline (PBS). Scanning electron microscopy (SEM) revealed that chlorhexidine-silversulfadiazine crystals were located in the superficial catheter matrix. Direct contact of superficially located drug particles with seeded agar plates probably caused the inhibition of bacterial growth. The study suggests that antiseptic compounds readily elute from fresh catheters during solid medium-based culturing processes and ultrasonication. The addition of inhibitors of silversulfadiazine-chlorhexidine to media may be prudent especially when culturing antimicrobial loaded catheters removed after short inwelling times.     

Evaluation of the antimicrobial efficacy of urinary catheters impregnated with antiseptics in an in vitro urinary tract model.

OBJECTIVES: To evaluate the long-term efficacy of urinary Foley catheters (latex and silicone) impregnated with (1) chlorhexidine and silver sulfadiazine (CXS) and (2) chlorhexidine, silver sulfadiazine, and triclosan (CXST) in inhibiting extra-luminal bacterial adherence and to compare their efficacy with that of silver hydrogel latex (SH) and nitrofurazone-treated silicone (NF) catheters. DESIGN: The antimicrobial spectrum of these catheters was evaluated using a zone of inhibition assay. A novel in vitro urinary tract model was developed to study the potential in vivo efficacy of antimicrobial catheters in preventing extraluminal bacterial colonization. The "meatus" was inoculated daily with Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Enterococcus faecalis, Pseudomonas aerginosa, and Candida albicans. The "bladder" portion of the model was cultured daily to determine bacterial growth. RESULTS: Both CXS and CXST catheters had a broader antimicrobial spectrum than SH and NF catheters. In the in vitro model, CXST latex and silicone catheters exhibited significantly better efficacy (3 to 25days) against uropathogens, compared with CXS (1 to 14 days) and control (0 to 5 days) catheters (P = .01). CXST latex catheters exhibited significantly longer protection against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa, compared with SH catheters (P = .01). CXST silicone catheters resisted colonization with Staphylococcus aureus and Staphylococcus epidermidis for a significantly longer period (23 to 24 days) than did NF catheters (9 to 11 days) (P = .01). CONCLUSION: Catheters impregnated with synergistic combinations of chlorhexidine, silver sulfadiazine, and triclosan exhibited broad-spectrum, long-term resistance against microbial colonization on their outer surfaces.     

双歧杆菌预防新生儿呼吸机相关性肺炎的效果

目的探讨阻断新生儿呼吸机相关性肺炎（VAP）胃-肺感染途径的方法,降低VAP发生率。方法将机械通气新生儿随机分为2组,实验组（38例）鼻饲双歧杆菌,对照组（43例）不干预,前瞻性观察2组患儿VAP发生率、胃液pH值、胃细菌定植及其与VAP病原学的同源性等。结果实验组和对照组VAP发生率分别为13.16%（5/38）和46.51%（20/43）,两组比较,差异有统计学意义（χ2=10.52,P＜0.01）。实验组VAP发生时间为机械通气第（5.40±2.07）d,晚于对照组的（4.25±1.00）d（t=3.24,P＜0.01）。第7天,实验组新生儿胃液pH≤3的比率（84.21%）高于对照组（46.51%）（χ2=12.47,P＜0.01）;而胃细菌定植比率（31.58%）低于对照组（74.42%）（χ2=14.92,P＜0.01）。实验组VAP病原菌与胃定植菌同源率（40.00%）低于对照组（75.00%）（χ2=8.00,P＜0.01）。对VAP危险因素进行单因素分析,使用双歧杆菌及胃液pH≤3是保护因素,胃内细菌定植是危险因素,OR值及95%CI均有统计学意义。结论双歧杆菌能降低新生儿胃液pH值,抑制胃内细菌定植,延迟VAP发生时间,有效降低早发性VAP的发生率。     

The in-vitro activity of povidone-iodinecream against Staphylococcus aureus and its bioavailability in nasal secretions

Due to the emergence of mupirocin-resistance in some epidemic strains of methicillin resistant Staphylococcus aureus (EMRSA) and the appearance of EMRSA with intermediate resistance to vancomycin, we evaluated the in-vitro activity of 5% povidone-iodine ('Betadine') cream as a possiblealternative to mupirocin for the elimination of nasal carriage of S. aureus. As judged by enrichment culture, povidone-iodine was bactericidal against three mupirocin-sensitive strains of S. aureus from nasal carriers, and against mupirocin-resistant and -sensitive strains of EMRSA types 3, 15 and 16, after incubation with povidone-iodine for 1.0 min at 32 degrees C. Mupirocin nasal ointment did not prevent growth after 180 min incubation. In a quantitative suspension test, 1:100 dilution of povidone-iodine cream completely eliminated an inoculum of 10(8)cfu/mL of all nine test organisms after incubation at 32 degrees C for 1.0 min, and 1:1000 dilution reduced cfu, by a factor of 10(5). After direct inoculation of the povidone-iodine cream to give 10(5)cfu/g, none of the test strains were recoverable after 30 s, giving a killing rate of approximately 10(4)cfu/s; for mupirocin nasal ointment, the maximum reduction of mupirocin-sensitive strains was ten fold after 3 h. Povidone-iodine activity was not detectable in sensitivity-testing agar, although 0.025% of povidone-iodine was detectable in a 15% nutrient strength tryptone soya agar. Using this minimal medium, the addition of nasal secretions (from any of 11 samples) reduced the activity of povidone-iodine by 80-90%, but mupirocin activity was unaffected. One millilitre of nasal secretions inactivated the equivalent of approximately 22.5 mg of povidone-iodine. These results suggest that povidone-iodine cream may have a role in the prevention of colonization and infection caused by MRSA, including mupirocin-resistant strains.     

Bacterial colonization of enteral feeding tubes

An in-vitro model system was used to determine the number of bacteria infused into a 'patient' when three types of polyurethane enteral feeding-tubes that had been experimentally contaminated with feed containing K . aerogenes on day I, were then perfused with sterile feed for periods of 8 h on three consecutive days (days 2–4). The tubes were syringed with 20 ml sterile water at regular intervals. Viable counts were made on syringe washings, feed collected from the ends of the tubes and feed from the nutrient containers.
On day 1, the total number of K . aerogenes in feed samples collected from the nutrient containers and the ends of the tubes rose from 10² to 103–10⁴ cfu ml^-1 over 8 h. On days 2–4 no organisms were detected in the feed samples from the nutrient containers whereas viable counts on feed samples collected from the tubes and syringe washings rose from 10⁴ to 10⁷ and from 10¹ to 10⁷ cfu ml^-1 respectively.
It can be concluded that a single incidence of feed contamination could lead to a patient receiving contaminated feed from an enteral feeding-tube colonized with bacteria which will not be detected by normal monitoring of the remainder of the system.     

Methicillin-resistant Staphylococcus aureus whole-body decolonization among hospitalized patients with variable site colonization by using mupirocin in combination with octenidine dihydrochloride

The object of this study was to investigate the efficacy of a methicillin-resistant Staphylococcus aureus (MRSA) multisite carriage decolonization in 32 hospitalized carriers--25 from surgical and seven from medical wards. Twenty-four of the patients had wounds (e.g. chronic ulcers, surgical sites) and 17 were spinal cord injury patients. Decolonization was performed by intranasal application of mupirocin, combined with an octenidine dihydrochloride bodywash over a period of five days. Samples from the nose, forehead, neck, axilla and groin were taken 24-48 h before beginning decolonization (sample point I, N=32) and 24-48 h afterwards (sample point II, N=32). Further samples, were taken seven to nine days after the procedure (sample point III, N=25). Contact sheep blood agar plates (24 cm2) were used to quantify MRSA colonies on forehead and neck. MRSA from other sample sites was determined semi-quantitatively. All patients were proven to be MRSA positive at one or more extranasal site(s); 18.8% did not have nasal carriage. The overall decolonization rate for all sites was 53.1% (sample point II) and 64% (sample point III), respectively. The reduction was significant for every site, showing a rate of 88.5% for nose (II, III) and of 56.3% (II) and 68% (III) for all extranasal sites together. Of 32 patients, a median of 6.5 cfu MRSA/24 cm2 was obtained for the forehead before decolonization and 0.5 cfu MRSA/24 cm2 for the neck. A significant reduction (0 cfu MRSA/24 cm2) from both sites was shown after treatment. Before decolonization procedures, median MRSA levels for the nose, groin and axilla were 55, 6 and 0 cfu/swab. After treatment, MRSA from each of these sites was significantly reduced. We conclude that nasal mupirocin combined with octenidine dihydrochloride whole-body wash is effective in eradicating MRSA from patients with variable site colonization.