In Vitro Synergistic Effects of Antimicrobial Combinations on Extensively Drug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Isolates

BACKGROUND: Extensively drug-resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii are a threat to hospitalized patients. We evaluated the effects of antimicrobial combinations on XDR P. aeruginosa and A. baumannii isolates. METHODS: P. aeruginosa and A. baumannii isolates, which were resistant to all antibiotics except colistin (CL), were collected from eight hospitals in Korea. Genes encoding metallo-beta-lactamases (MBLs) and OXA carbapenemases were detected by PCR in eight P. aeruginosa and 30 A. baumannii isolates. In vitro synergy of antimicrobial combinations was tested by using the checkerboard method. RESULTS: Minimum inhibitory concentrations of beta-lactams, aminoglycosides, and fluoroquinolones were very high, while that of CL was low for majority of XDR P. aeruginosa and A. baumannii isolates. Antimicrobial combinations including Imipenem (IPM)-CL, ceftazidime (CAZ)-CL, and rifampin (RIF)-CL exerted only additive/indifferent effects on majority of XDR P. aeruginosa isolates. Proportions of XDR A. baumannii isolates that showed synergistic and additive/indifferent inhibition after treatment with antimicrobial combinations used are as follows: IPM-ampicillin-sulbactam (AMS), 17% and 80% isolates, respectively; IPM-rifampin (RIF), 13% and 81% isolates, respectively; IPM-CL, 13% and 87% isolates, respectively; and RIF-COL, 20% and 73% isolates, respectively. Significant proportion (19%) of XDR P. aeruginosa isolates produced MBLs, and majority (82%) of A. baumannii isolates produced either MBLs or OXA-23. CONCLUSIONS: Our results suggest that combinations of IPM-AMS, IPM-RIF, IPM-CL, and RIF-CL are more useful than individual drugs for treating 13-20% of XDR A. baumannii infections.

Epidemiology and Control of an Outbreak of Vancomycin-Resistant Enterococci in the Intensive Care Units

PURPOSE: This study was aimed to describe a vancomycin-resistant enterococci (VRE) outbreak across three intensive care units (ICUs) of a Korean hospital from September 2006 to January 2007 and the subsequent control strategies. MATERIALS AND METHODS: We simultaneously implemented multifaceted interventions to control the outbreak, including establishing a VRE cohort ward, active rectal surveillance cultures, daily extensive cleaning of environmental surfaces and environmental cultures, antibiotic restriction, and education of hospital staff. We measured weekly VRE prevalence and rectal acquisition rates and characterized the VRE isolates by polymerase chain reaction (PCR) of the vanA gene and Sma1-pulsed-field gel electrophoresis (PFGE). RESULTS: During the outbreak, a total of 50 patients infected with VRE were identified by clinical and surveillance cultures, and 46 had vancomycin-resistant Enterococcus faecium (VREF). PFGE analysis of VREF isolates from initial two months disclosed 6 types and clusters of two major types. The outbreak was terminated 5 months after implementation of the interventions: The weekly prevalence rate decreased from 9.1/100 patients-day in September 2006 to 0.6/100 by the end of January 2007, and the rectal acquisition rates also dropped from 6.9/100 to 0/100 patients-day. CONCLUSION: Our study suggests that an aggressive multifaceted control strategy is a rapid, effective approach for controlling a VRE outbreak.

Effect of Injectable Chitosan Bead Encapsulating Calcium Sulfate on Bony Consolidation in Distraction Osteogenesis

The purpose of this project was to study the effect of injectable chitosan bead encapsulating calcium sulfate, which makes sustained release of chitosan and calcium sulfate after implantation, on early bony consolidation in distraction osteogenesis of a dog model. Forty five dogs were used for this study. An external distraction device was applied to the mandibular body after vertical osteotomy and the mandibular distraction was started five days after the operation at a rate of 1mm per day up to a 10mm distraction. The experimental group was divided into a control group(I), hyaluronic acid group(II), chitosan group(III), calcium sulfate group(IV), and injectable chitosan bead encapsulating calcium sulfate group(V). Normal saline was injected in the group I. In the group II, a 1-ml volume of hyaluronic acid solution was injected into the distracted area. In the group III, a 1-ml of injectable solution of chitosan mixed with hyaluronic acid was implanted. In the group IV, a 1-ml of injectable solution of calcium sulfate mixed with hyaluronic acid was implanted. In the group V, injectable form of powders of chitosan bead encapsulating calcium sulfate mixed with a 1-ml volume of hyaluronic acid was implanted. Bone mineral density was measured in each group at third and sixth week. The mean three point failure load was measured in each group. In histological findings, new bone was generated in all groups. In the group IV and V, the formation of active woven bone was observed throughout the distracted area at sixth week. The amount of new bone formation in the distracted zone was in the order of the group IV and V, group III and group II, and control group. In conclusion, these findings suggest that injectable chitosan bead encapsulating calcium sulfate appears to be effective in early bony consolidation in distraction osteogenesis.

Effect of Calcium Sulfate-Chitosan Composite Pellet on Bone Formation in Bone Defect of Rabbits

This study was carried out on 80 New Zealand white rabbits, each weighing 3-3.5kg. Twenty rabbits were allocated into each of the four groups. After a 1cm sized ostectomy was made on the tibial body with the periosteum preserved, artificial bone substitutes were implanted. Except for control group(I), manufactured chitosan pellets were implanted in group II, Osteoset(R)(calcium sulfate) in group III and manufactured calcium sulfate-chitosan composite pellets in group IV. Results were evaluated using radiographic study, bone mineral density test and histologic examination in 2, 4, 6 weeks and three point bending test in 6 weeks after implantation. In the radiographic study, the formation and corticalization of callus were similar in groups III, IV and this was much earlier than in groups I, II. In the bone mineral density test and three point bending test to contralateral normal tibia in 6 weeks, the values in groups III and IV were statistically significantly higher than in groups I and II(p<0.05). In histologic examination, groups III and IV have more abundant and faster new bone formation than groups I and II. In conclusion, the synergistic effect between calcium sulfate and chitosan in group IV is considered to facilitate new bone formation as effectively as Osteoset(R) does.

Evaluation of Quantitative culture of Clostridium difficile From Fecal Specimens for the Diagnosis of C. difficile-associated Disease / 대한임상미생물학회지

BACKGROUND: C. difficile-associated diarrhea (CDAD), the most frequently identified cause of nosocomial diarrhea, results from the overgrowth of cytotoxin (toxin B)-producing strains. The aim of this study was to evaluate the quantitative culture of Clostridium difficile to improve the laboratory diagnosis of CDAD. METHODS: The quantitative culture and cytotoxin gene results were evaluated based on the findings of colonoscopy and/or histology of the biopsy specimens. RESULTS: Among the 402 specimens with cytotoxin-positive isolates, 301 (74.9%) contained > or =106 CFU/mL of C. difficile. Nine (60%) of the 15 pseudomembranous colitis patients yielded > or =106 CFU/mL of toxigenic isolate. The proportion of cytotoxin gene-positive isolates was higher in the specimens with > or =106 CFU/mL of C. difficile than in those with 102-<103 CFU/mL (86.5% vs. 66.7%). CONCLUSIONS: Quantitative culture may aid in the interpretation of toxigenic C. difficile culture results, and reduce false positivity, thus avoiding unnecessary treatment.