Effectiveness of hydroxyapatite-vancomycin bone cement in the treatment of Staphylococcus aureus induced chronic osteomyelitis

In the field of local application of antimicrobials, a number of novel drugs and/or new drug delivery systems have been developed in recent years. The present study aimed to investigate hydroxyapatite cement (HAC) as a carrier for vancomycin in the treatment of chronic osteomyelitis due to Staphylococcus aureus strains with various mechanisms of resistance. The release of vancomycin from standard test cylinders was determined in vitro and the efficacy of the delivery system was measured in vivo using a rabbit model of chronic osteomyelitis. First, powdered HAC was mixed with vancomycin at 80, 160 and 240 mg/g. After hardening, formed cylinders were eluted in phosphate buffer and antibiotic release was measured by agar diffusion. High levels of release (1512+/-318 to 1937+/-336 microg/ml) were obtained for 12 to 20 days depending on the dosage of vancomycin. Additionally, bone infection was induced in the tibia of 30 New Zealand white rabbits by injecting either a methicillin-resistant S. aureus strain (MRSA) or a S. aureus strain with a small colony variant (SCV) phenotype. After 3 weeks (chronic infection), all animals were treated by debridement. Moreover, group 1 (challenged with SCVs) and group 2 (challenged with MRSA) were treated by filling the marrow with HAC alone, whereas in groups 3 (SCVs) and 4 (MRSA) the marrow was filled with HAC/vancomycin (160 mg/g). After 6 weeks all animals were sacrificed. At 3 weeks, pathogens were detected in 24 of 30 animals. All swabs of the control groups, positive for S. aureus on day 21, were also positive on day 42 and S. aureus strains recovered were shown to be clonal to the strains used for induction of osteomyelitis. By contrast, no growth was found in the treatment group following 7 days of incubation in BHI bouillon. HAC/vancomycin-treated animals showed no histological evidence of infection on day 42. In the other groups, different stages of chronic osteomyelitis were found histologically. No local or systemic side effects due to HAC or vancomycin were seen. HAC is an effective carrier material for antibiotic compounds even in refractory infections due to MRSA or S. aureus SCVs.     

Vancomycin-loaded nano-hydroxyapatite pellets to treat MRSA-induced chronic osteomyelitis with bone defect in rabbits

Objective  

To investigate nano-hydroxyapatite (nHA) pellets as carriers for vancomycin in the treatment of chronic osteomyelitis and bone defects due to methicillin-resistant Staphylococcus aureus (MRSA) strains.     

Novel borate glass/chitosan composite as a delivery vehicle for teicoplanin in the treatment of chronic osteomyelitis

Composite materials composed of borate bioactive glass and chitosan (designated BGC) were investigated in vitro and in vivo as a new delivery system for teicoplanin in the treatment of chronic osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA). In vitro, the release of teicoplanin from BGC pellets into phosphate-buffered saline (PBS), as well as its antibacterial activity, were determined. The compressive strength of the pellets was measured after specific immersion times, and the structure of the pellets was characterized using scanning electron microscopy and X-ray diffraction. In vivo, the tibial cavity of New Zealand White rabbits was injected with MRSA strain to induce chronic osteomyelitis, treated by debridement after 4 weeks, implanted with teicoplanin-loaded BGC pellets (designated TBGC) or BGC pellets, or injected intravenously with teicoplanin. After 12 weeks’ implantation, the efficacy of the TBGC pellets for treating osteomyelitis was evaluated using hematological, radiological, microbiological and histological techniques. When immersed in PBS, the TBGC pellets provided a sustained release of teicoplanin, while the surface of the pellets was converted to hydroxyapatite (HA). In vivo, the best therapeutic effect was observed in animals implanted with TBGC pellets, resulting in significantly lower radiological and histological scores, a lower positive rate of MRSA culture, and an excellent bone defect repair, without local or systemic side effects. The results indicate that TBGC pellets are effective in treating chronic osteomyelitis by providing a sustained release of teicoplanin, in addition to participating in bone regeneration.     

Prevalence and clinical implications of Staphylococcus aureus with a vancomycin MIC of 4 microg/ml in Korea

In addition to vancomycin-intermediate Staphylococcus aureus (VISA), S. aureus with a vancomycin MIC of 4 microg/ml has been reported to be the cause of therapeutic failure. This study was designed to determine the prevalence of methicillin-resistant S. aureus (MRSA) with a vancomycin MIC of 4 microg/ml and to clarify the clinical characteristics of infections caused by these isolates. During the 8-week period from April to May, 2001, 27 hospitals participated in a nationwide surveillance program for VISA and vancomycin-resistant S. aureus (VRSA) in Korea. After screening on brain-heart infusion agar containing 4 microg/ml of vancomycin as previously described, 100 isolates with confluent growth were tested. The medical records of the patients involved were reviewed. Even though VISA or VRSA was not detected among 3,756 MRSA isolates, 18 (0.5%) had a vancomycin MIC of 4 microg/ml. The infections in 12 of these patients, excluding 5 that were colonized, were 8 chronic osteomyelitis, 1 surgical site infection, 1 pneumonia, 1 intra-abdominal infection, and 1 catheter-related infection. Although 11 cases were exposed to glycopeptides for a long time (median 56 days), the site of infection became culture-negative in only 1 case. Two patients died of their S. aureus infections. MRSA with a vancomycin MIC of 4 microg/ml was rare. Chronic osteomyelitis was the most common type of infection, and prolonged exposure to glycopeptides was associated with reduced susceptibility to vancomycin.     

Daptomycin versus vancomycin for osteoarticular infections due to methicillin-resistant Staphylococcus aureus (MRSA): a nested case–control study

Vancomycin is the standard antibiotic for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. While daptomycin is approved for MRSA bacteremia, its effectiveness in osteoarticular infections (OAIs) has not been established. A 1:2 nested case–control study of adult patients with MRSA OAIs admitted to an academic center from 2005 to 2010 was carried out. Clinical outcomes and drug toxicity in patients treated with daptomycin versus vancomycin were compared. Twenty patients with MRSA OAIs treated with daptomycin were matched to 40 patients treated with vancomycin. The median age of the patients was 52 years (range, 25–90), and 40 (67 %) were male. Most patients had osteomyelitis (82 %), predominantly from a contiguous source (87 %). Forty percent were diabetics. Diabetic patients were more likely to receive vancomycin than daptomycin [20 (50 %) vs. 4 (20 %); p?=?0.03]. Vancomycin was more often combined with antibiotics other than daptomycin [22 (55 %) vs. 5 (25 %); p?=?0.03]. The median total antibiotic treatment duration was 48 (daptomycin) vs. 46 days (vancomycin) (p?=?0.5). Ninety percent of daptomycin-treated patients had previously received vancomycin for a median of 14.5 days (range, 2–36). Clinical success rates were similar between daptomycin and vancomycin at 3 months [15 (75 %) vs. 27 (68 %); p?=?0.8] and 6 months [14 (70 %) vs. 23 (58 %); p?=?0.5], even after propensity score-based adjustment for antibiotic assignment. The frequency of adverse events was similar between treatment groups [1 (5 %) vs. 7 (18 %); p?=?0.2]. Daptomycin and vancomycin achieved similar rates of clinical success and drug tolerability. Daptomycin is a reasonable alternative for treating MRSA OAIs, particularly in patients where therapy with vancomycin has not been well tolerated.     

Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia

We attempted to find a relationship between the microbiological properties of bloodstream isolates of methicillin-resistant Staphylococcus aureus (MRSA) and the efficacy of vancomycin in the treatment of bacteremia. Vancomycin susceptibility testing was performed, and bactericidal activity was determined for 30 isolates from 30 different patients with MRSA bacteremia for whom clinical and microbiological outcome data were available. The majority of these patients had been previously enrolled in multicenter prospective studies of MRSA bacteremia refractory to conventional vancomycin therapy. Logistic regression found a statistically significant relationship between treatment success with vancomycin and decreases in both vancomycin MICs (< or =0.5 microg/ml versus 1.0 to 2.0 microg/ml; P = 0.02) and degree of killing (reduction in log(10) CFU/milliliter) by vancomycin over 72 h of incubation in vitro (P = 0.03). For MRSA isolates with vancomycin MICs < or = 0.5 microg/ml, vancomycin was 55.6% successful in the treatment of bacteremia whereas vancomycin was only 9.5% effective in cases in which vancomycin MICs for MRSA were 1 to 2 microg/ml. Patients with MRSA that was more effectively killed at 72 h by vancomycin in vitro had a higher clinical success rate with vancomycin therapy in the treatment of bacteremia (log(10) < 4.71 [n = 9], 0%; log(10) 4.71 to 6.26 [n = 13], 23.1%; log(10) > 6.27 [n = 8], 50%). We conclude that a significant risk for vancomycin treatment failure in MRSA bacteremia begins to emerge with increasing vancomycin MICs well within the susceptible range. Elucidating the mechanisms involved in intermediate-level glycopeptide resistance in S. aureus should begin by examining bacteria that begin to show changes in vancomycin susceptibility before the development of obvious resistance. Prognostic information for vancomycin treatment outcome in MRSA bacteremia may also be obtained by testing the in vitro bactericidal potency of vancomycin.     

Vancomycin-intermediate Staphylococcus aureus in Korea

Recent reports on some methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin have been a major concern in Korea because of the widespread use of vancomycin due to a high prevalence of MRSA in the country. We describe a 45-year-old man with long-standing pelvic abscess due to MRSA. In spite of vancomycin and teicoplanin treatment for a long period of time, the patient died from MRSA sepsis. The blood culture isolate of MRSA exhibited reduced susceptibility to vancomycin (MIC, 8 microg/ml). This is the first report of a vancomycin-intermediate S. aureus case from Korea.     

Poly (ε-caprolactone) coating delays vancomycin delivery from porous chitosan/β-tricalcium phosphate composites

The orthopedic infection, such as osteomyelitis, especially those caused by Methicillin-resistant Staphylococcus aureus (MRSA), remains a major complication of open fractures. Local vancomycin delivery is considered to provide better methods when avascular zones prevent the delivery of drugs from conventional routes of administration. Chitosan (CS) delivery system has been developed with the disadvantages, such as mechanically weakness, lacking osteoconductivity, and the initial burst of antibiotics into the environment. The aim of this study was to confirm that the prepared CS/β-tricalcium phosphate (β-TCP) composites coated with poly (ε-caprolactone) (PCL), similar to natural bone in components, had a three-dimensional porous structure and could be used as drug carriers to deliver vancomycin in a sustained and controlled manner effectively for 6 weeks at levels to inhibit MRSA proliferation. We prepared porous CS/β-TCP composites by incorporating β-TCP into the system, and coated the composites with PCL of three different concentrations. The morphological structure of composites, including pore size and porosity, was examined. The result showed that CS/β-TCP coated with 2.5w/v% PCL solution had the best coating effect and it retarded the release of vancomycin in a near zero-order mechanism from 0 to 14 days. The drug delivery was significantly delayed after coated with 2.5w/v% PCL. The quantitative release of vancomycin was extended to 42 days. Therefore PCL coating could be used to retard the release of vancomycin from CS/β-TCP composites in a sustained and controlled manner. Porous CS/β-TCP coated with PCL might be one of the candidate vancomycin carriers for treating MRSA-related osteomyelitis. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.     

Daptomycin resistance and treatment failure following vancomycin for methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> (MRSA) mitral valve acute bacterial endocarditis (ABE)

Acute bacterial endocarditis (ABE) is most commonly due to virulent pathogens, i.e., Staphylococcus aureus. S. aureus ABE may be due to methicillin-sensitive (MSSA) or methicillin-resistant (MRSA) strains and, optimally, ABE should be treated with bactericidal antibiotics. Traditionally, vancomycin has long been used to treat MRSA ABE, but it has been shown that vancomycin may increase the staphylococcal the thickness, resulting in permeability-mediated resistance. We present a case of a 72-year-old male with mitral valve MRSA ABE refractory to daptomycin therapy following initial therapy with vancomycin. We were not able to diminish the intensity of the patient’s MRSA bacteremia from his mitral valve ABE, even with high-dose (12 mg/kg day) daptomycin, presumably because of permeability-mediated resistance due to antecedent vancomycin therapy.     

一期带蒂组织瓣联合万古霉素骨水泥及颗粒骨治疗小腿创伤后骨髓炎伴骨及软组织缺损

目的探讨一期带蒂组织瓣联合万古霉素骨水泥及颗粒骨治疗小腿创伤后骨髓炎伴骨及软组织缺损的方法及疗效。方法 2008年6月~2013年3月,收治小腿创伤后骨髓炎伴骨及软组织缺损患者36例。男25例,女11例;年龄22~60岁,平均46.5岁。病程1~5个月,平均2.5个月。软组织缺损面积为4 cm×5 cm~13cm×8 cm,骨缺损长度0.5 cm~2.5 cm,平均1.8 cm。采用带蒂组织瓣移位联合万古霉素骨水泥及颗粒骨植入一期治疗。选择带蒂的腓肠肌肌瓣16例,比目鱼肌肌瓣12例,腓肠神经营养血管肌皮瓣6例,远端蒂股前外侧肌皮瓣2例,同时一期联合万古霉素骨水泥填充及颗粒骨植骨,肌瓣表面游离植皮处理。结果 36例患者均获随访,随访时间24~55个月,平均39.5个月。2例组织瓣远端发生部分坏死,经清创换药及游离植皮后愈合,4例术后创面渗出患者经换药处理后愈合,2例感染未控制,经再次手术病灶清除及灌洗引流后愈合。所有骨折均骨性愈合,愈合时间6~21个月,平均12个月。末次随访时按Johner-Wruhs标准评定疗效,优20例,良12例,可4例,优良率为88.9%。结论一期应用带蒂组织瓣联合万古霉素骨水泥及颗粒骨治疗小腿创伤后骨髓炎伴骨及软组织缺损,有利于创面愈合、感染控制及骨缺损修复,可获得良好的临床疗效。     

游离大网膜移植治疗慢性骨髓炎

目的探讨游离大网膜移植治疗慢性骨髓炎的治疗效果。方法本组8例慢性骨髓炎患者采用吻合血管的游离大网膜移植治疗。结果术后随访1月-22月,所有患者恢复正常.无复发征象。结论游离大网膜移植术既能清除慢性骨髓炎死腔,建立病灶骨及局部组织的血液循环:同时又能刺激骨区成骨细胞活跃,促进病灶的修复。游离大网膜移植术是治疗慢性骨髓炎的有效方法。     

Comparison of Arbekacin and Vancomycin in Treatment of Chronic Suppurative Otitis Media by Methicillin Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of ear infections. We attempted to evaluate the clinical usefulness of arbekacin in treating chronic suppurative otitis media (CSOM) by comparing its clinical efficacy and toxicity with those of vancomycin. Efficacy was classified according to bacterial elimination or bacteriologic failure and improved or failed clinical efficacy response. Ninety-five subjects were diagnosed with CSOM caused by MRSA. Twenty of these subjects were treated with arbekacin, and 36 with vancomycin. The bacteriological efficacy (bacterial elimination, arbekacin vs. vancomycin: 85.0% vs. 97.2%) and improved clinical efficacy (arbekacin vs. vancomycin; 90.0% vs. 97.2%) were not different between the two groups. However, the rate of complications was higher in the vancomycin group (33.3%) than in the arbekacin group (5.0%) (P=0.020). In addition, a total of 12 adverse reactions were observed in the vancomycin group; two for hepatotoxicity, one for nephrotoxicity, eight for leukopenia, two for skin rash, and one for drug fever. It is suggested that arbekacin be a good alternative drug to vancomycin in treatment of CSOM caused by MRSA.     

可塑性纳米-羟基磷灰石/聚β-羟基丁酸与戊酸酯-聚乙二醇-庆大霉素药物释放系统的生物相容性及安全性

BACKGROUND: Gentamicin bead chain is an effective drug delivery system for treatment of osteomyelitis, but it cannot be degraded, need to be removed by second operation, and can breed pathogens. As a result, biodegradable drug delivery systems become a hotspot. Nano- hydroxyapatite/poly(β-hydroxybutyrate-co-β-hydroxyvalerate)-polyethylene glycol-gentamicin (nano-HA/PHBV-PEG-GM-DDS) is considered to be a good choice for the current predicament. OBJECTIVE: To evaluate the acute or chronic toxic reactions of the whole body and local tissues, intracutaneous stimulation, cytotoxicity and hemolytic reactions after bone remodeling and implantation of nano-HA/PHBV-PEG-GM-DDS, thus providing a new kind of material for treating osteomyelitis. METHODS: Plastic nano-HA/PHBV-PEG-GM-DDS was prepared using plastic fibrin glue as microsphere scaffold and nano-HA as the core carrier of GM that was coated with PHBV and PEG. The acute, subacute/chronic toxicity, implantation, hemolysis, cytotoxicity and intracutaneous stimulation tests were performed according to the evaluated criteria of medical implanted materials as well as biological and animal trials recommended in GB/T16886.1-1997. RESULTS AND CONCLUSION: The plastic nano-HA/PHBV-PEG-GM-DDS was nontoxic and caused no apparent changes in liver and kidney function and serum biochemical indexes. Pathological examination showed that the implanted material was covered with tissues, and inflammation changes accorded with the general regularity of inflammatory outcomes. After implantation, the nano-HA/PHBV-PEG-GM-DDS was biodegraded and replaced by osseous tissues. The hemolytic rate of the material extract to the composite diffusion solution was 1.2%, which was below the standard criteria (5%). Human bone marrow cells cultured in vitro with the plastic nano-HA/PHBV-PEG-GM-DDS grew normally with good morphology. There was no stimulation reaction according to the criteria after the diffusion solution was subcutaneously injected into the back of the animal. These findings indicate that the plastic nano-HA/PHBV-PEG-GM-DDS for treating osteomyelitis possesses excellent biocompatibility and security.      

Phenotypic changes of methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> during vancomycin therapy for persistent bacteraemia and related clinical outcome

Persistent bacteraemia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) that fails to respond to glycopeptide therapy is a well-documented clinical problem. There are limited data on changes in agr functionality, vancomycin susceptibility and heteroresistance during MRSA PB. Thus, the frequency of these changes and their clinical significance remain unclear. Only patients with MRSA PB (≥7 days) from a prospective cohort of S. aureus bacteraemia were included. We collected isogenic paired strains and compared vancomycin MIC, vancomycin heteroresistance, and agr functionality between initial and final blood isolates. We also assessed the clinical outcome. A total of 49 patients had MRSA PB over 22 months. Bacteraemia persisted for a median of 13 days and most patients (98%) received glycopeptide as initial therapy. Among 49 isogenic pairs, only one pair showed a vancomycin MIC increase ≥2-fold by broth microdilution method, and only seven (14%) by E-test. Significant portions of initial isolates had vancomycin heteroresistance (49%) and agr dysfunction (76%). Development of vancomycin heteroresistance during PB occurred in four (16%) among 25 initial vancomycin-susceptible isolates, and acquisition of agr dysfunction occurred in two (16%) among 12 initial agr-functional isolates. Changes in the opposite direction occasionally occurred. These phenotypic changes during PB were not associated with mortality, whereas agr dysfunction of the initial isolates was significantly associated with mortality. During MRSA PB, phenotypic changes of MRSA isolates occurred occasionally under prolonged vancomycin exposure but were not significantly associated with clinical outcome. In contrast, initial agr dysfunction could be a predictor for mortality in MRSA PB.     

Risk factors for treatment failure in orthopedic device-related methicillin-resistant Staphylococcus aureus infection

The purpose of this study was to determine the clinical and microbiological risk factors for treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) orthopedic device-related infection (ODRI). A retrospective cohort study of patients with MRSA ODRI who were treated at Geneva University Hospitals between 2000 and 2008 was undertaken. Stored MRSA isolates were retrieved for genetic characterization and determination of the vancomycin minimum inhibitory concentration (MIC). Fifty-two patients were included, of whom 23 (44%) had joint arthroplasty and 29 (56%) had osteosynthesis. All 41 of the retrieved MRSA isolates were susceptible to vancomycin (MIC?≤?2 mg/L) and 35 (85%) shared genetic characteristics of the South German clone (ST228). During a median follow-up of 391 days (range, 4–2,922 days), 18 patients (35%) experienced treatment failure involving MRSA persistence or recurrence. Microbiological factors such as infection with the predominant clone and a vancomycin MIC of 2 mg/L were not associated with treatment failure. Using a Cox proportional hazards model, implant retention (hazard ratio [HR], 4.9; 95% confidence interval [CI], 1.3–18.2; P?=?0.017) and single-agent antimicrobial therapy (HR, 4.4; 95% CI, 1.2–16.3; P?=?0.025) were independent predictors of treatment failure after debridement. Therapy using a combination of antimicrobials should be considered for patients with MRSA ODRI, especially when implant removal is not feasible.     

Use of teicoplanin in community medicine

Administration of parenteral antibiotics to outpatients is increasingly used to reduce hospital costs, to reduce loss of earnings for the patient and to improve the quality of life in patients requiring prolonged antibiotic treatment. The glycopeptides are required for treatment of infections caused by methicillin resistant staphylococci and some enterococci, or for treatment of patients allergic to beta-lactam agents. For home therapy, teicoplanin has some advantages over vancomycin in that it requires only once-daily bolus administration, does not necessitate monitoring of serum concentrations and offers the choice of intravenous or intramuscular administration. Teicoplanin has been used to complete treatment of endocarditis at home in selected patients, streptococcal disease being the most suitable form of endocarditis for this treatment. In open trials, teicoplanin has been found effective in home therapy of osteomyelitis but, as with other agents, prolonged dosage can be associated with adverse effects. It has also been used for home treatment of infections of the respiratory tract, intravascular catheters and soft tissue. Despite its higher acquisition costs, teicoplanin is to be preferred over vancomycin because of the reduced administration and assay costs and fewer adverse effects.     

Vancomycin MIC creep in methicillin-resistant Staphylococcus aureus (MRSA) isolates from 2006 to 2010 in a hospital in China

Purpose: To assess whether vancomycin minimum inhibitory concentration (MIC) creeps among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) in a regional hospital in China. Furthermore, to analyze the causes of vancomycin MIC creeps and the relationship between vancomycin MICs and the outcome among patients with MRSA infection. Materials and Methods: All clinical isolates of MRSA from 2006-2010 were retrieved and tested by the broth microdilution procedure to determine their vancomycin MIC. Meanwhile, related patient records were analyzed. Results: While all isolates were susceptive to vancomycin, the percentage of isolates with a vancomycin MIC = 1 mg/L increased significantly from 2006 (37.0%) to 2010 (75.7%). Meanwhile, vancomycin usage density (DDDs/1000 bed-days) had increased significantly from 2006-2010. Mean linear correlation analysis showed a statistically significant positive correlation (r = 0.905, P < 0.05) between the consumption of vancomycin and the percentage of MRSA isolates with a vancomycin MIC = 1 mg/L. Clinical records revealed high vancomycin MIC was associated with a higher microbiologic failure rate in MRSA bloodstream infections. Conclusions: The data demonstrated vancomycin MIC creep among clinical isolates in our hospital, and the MIC creep may be caused by the increasing usage of vancomycin. Furthermore, the analysis strongly suggested this shift of vancomycin MIC within the susceptible range may be associated with an increasing probability of treatment failure.     

Predictors of clinical and microbiological treatment failure in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia: a retrospective cohort study in a region with low MRSA prevalence

Invasive infections with methicillin-resistant Staphylococcus aureus (MRSA) have been associated with increased morbidity and mortality. The aim of the present study was to identify independent predictors of early mortality and treatment failure in patients with MRSA bacteraemia. A total of 132 adult patients who developed MRSA bacteraemia during hospitalization in the University Hospital of Vienna between 2000 and 2011 were screened and 124 were included in a retrospective cohort study. Patient demographics, source of bacteraemia, antimicrobial treatment and microbiological characteristics were evaluated. The 28-day crude mortality was 30.6%. Predictors of early mortality identified in multivariate Cox regression analysis included higher patientage (adjusted hazard ratio (aHR) 1.03, 95% CI 1.01–1.06, p 0.006), pneumonia (aHR 3.86, 95% CI 1.83–8.12, p <0.001) and failure to use MRSA active treatment (aHR 8.77, 95% CI 3.50–21.93, p <0.001). Ninety-one (73.4%) patients received glycopeptides as specific MRSA treatment. Of 63 patients treated with vancomycin, only 14 (22.6%) patients had aimed trough levels of 15–20 mg/L. Vancomycin MIC ≥ 2 mg/L was detected in 28.2% and was associated with glycopeptide pretreatment (p 0.001). All MRSA isolates were susceptible to linezolid and tigecycline. Persistent bacteraemia ≥ 7 days was documented in 25 (20.2%) patients. Independent determinants for microbiological eradication failure in patients with MRSA bacteraemia included endocarditis (p <0.001) and vancomycin trough levels (p 0.014), but not vancomycin MIC. Failure of clinical and microbiological eradication of MRSA among patients with MRSA bacteraemia was associated with clinical entity rather than with bacterial traits. Pharmacokinetic parameters seem to be decisive on microbiological and clinical success.     

万古霉素骨水泥填塞治疗慢性骨髓炎

目的探讨利用抗生素骨水泥填塞空腔治疗慢性骨髓炎的疗效。方法对慢性骨髓炎患者66例彻底清创后以万古霉素骨水泥填塞骨髓炎病灶空腔,待切口愈合3月后,二次将骨水泥取出,自体骨植骨,骨不连用钢板内固定。结果66例随访6月~3年其中愈合良好64例,复发2例,再次清创后愈合。结论万古霉素骨水泥填塞空腔治疗慢性骨髓炎疗效确定,能有效防止骨髓炎复发,简单易行,治疗费用低廉,具有一定推广意义。     

The VISA/GISA problem: therapeutic implications

The emergence of vancomycin intermediate resistant Staphylococcus aureus (VISA) isolates in Japan, USA, France, Hong Kong and Korea among methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, is of great concern. Vancomycin has been the drug of choice for the treatment of multiresistant MRSA infections in the last three decades, but the management of invasive MRSA infections will become a serious problem if VISA strains become widespread. VISA isolates reported to date have a vancomycin MIC of 8 mg/L, and were isolated from patients with underlying diseases whose long-term vancomycin treatment apparently failed. Since many VISA isolates also have been resistant to teicoplanin, the term glycopeptide-intermediate S. aureus (GISA) is more appropriate. The frequency of GISA isolates appears to be extremely low; to date, only 10 GISA infections have been reported worldwide. However, heterogeneous resistance to glycopeptides (h-GISA) have been reported in Japan, Europe and Thailand. These h-GISA strains showed vancomycin MICs ranging from 1 to 4 mg/L, but had subpopulations that could grow on agar plates containing 4–8 mg/L, which may represent the first step in the development of GISA strains. Although GISA isolates have shown resistance to many antimicrobials, all GISA isolates remain susceptible to co-trimoxazole and some of them to other common antimicrobials. Currently, there are no recommended therapy guidelines for GISA infections, although in recent studies, several new drugs have shown promising activity against GISA strains. In addition, synergy between glycopeptides and β-lactams against GISA strains was observed in some in vivo and in vitro studies. Specific MRSA/GISA control programs, rational antibiotic policies, including the reduction of glycopeptide use, and rapid laboratory detection of GISA and h-GISA strains are the key measures in preventing the spread of these strains.