Teicoplanin Minimum Inhibitory Concentration Research Articles

A Comparison of the Minimum Inhibitory Concentration of Antibiotics in Staphylococcus Species Isolated From Orthopedic and Respiratory Medicine Infections.

Antibiotic susceptibility is very important for the successful treatment of orthopedic infections, particularly for implant-related infections. While the minimum inhibitory concentrations (MICs) of Staphylococcus species were well investigated for the isolates from the respiratory tract, investigations for orthopedic pathogens are very limited. We investigated the antibiotic MIC values of Staphylococcus species isolated from orthopedic infections and compared them with those of respiratory medicine isolatesused as a control. The MICs of vancomycin (VCM), arbekacin (ABK), teicoplanin (TEIC), linezolid (LZD), and rifampicin (RFP) of a total of consecutive 259 (89 orthopedic and 170 respiratory) Staphylococcus speciesisolated in our laboratory from January 2013 to July 2016 were retrospectively reviewed. Differences between the MICs of each antibiotic in orthopedic and respiratory samples were determined. The number of methicillin-sensitive Staphylococcus aureus (MSSA) with a VCM MIC of <0.5 μg/mL among respiratory isolates was significantly higher than that among orthopedic isolates, while those with a MIC of 2 μg/mL were significantly lower (P = 0.0078). The proportion of methicillin-resistant coagulase-negative staphylococci (MRCNS) isolates with a VCM MIC of 2 μg/mL was significantly higher in orthopedic samples than that of methicillin-resistant Staphylococcus aureus (MRSA) (P < 0.001) in respiratory isolates. The proportion of MRCNS orthopedic isolates with an RFP MIC of >2 μg/mL was significantly higher (P = 0.0058) than that of other orthopedic staphylococci. The VCM MICs of Staphylococcus species from orthopedic infections were higher than those of respiratory samples, particularly MRCNS from implant-related samples.

Profiling daptomycin resistance among diverse methicillin-resistant Staphylococcus aureus lineages in China.

Daptomycin (DAP) is effective against methicillin-resistant Staphylococcus aureus (MRSA). However, reduced susceptibility to DAP in MRSA may lead to treatment failures. We aim to determine the distribution of DAP minimum inhibitory concentrations (MICs) and DAP heteroresistance (hDAP) among MRSA lineages in China. A total of 472 clinical MRSA isolates collected from 2015 to 2017 in China were examined for DAP susceptibility. All isolates (n = 472) were found to be DAP susceptible, but 35.17% (166/472) of them exhibited a high DAP MIC (MIC >0.5 µg/mL). The high DAP MIC group contained a larger proportion of isolates with a higher vancomycin or teicoplanin MIC (>1.5 µg/mL) than the low DAP MIC group (19.3% vs 7.8%, P < 0.001; 22.3% vs 8.2%, P < 0.001). We compared the clonal complex (CC) distributions and clinical characteristics in MRSA isolates stratified by DAP MIC. CC5 isolates were less susceptible to DAP (MIC50 = 1 µg/mL) than CC59 isolates (MIC50 = 0.5 µg/mL, P < 0.001). Population analysis profiling revealed that 5 of 10 ST5 and ST59 DAP-susceptible MRSA isolates investigated exhibited hDAP. The results also showed that CC5 MRSA with an agrA mutation (I238K) had a higher DAP MIC than those with a wild-type agrA (P < 0.001). The agrA-I238K mutation was found to be associated with agr dysfunction as indicated by the loss of δ-hemolysin production. In addition, agr/psmα defectiveness was associated with hDAP in MRSA. Whole-genome sequencing analysis revealed mutations in mprF and walR/walK in DAP-resistant subpopulations, and most DAP-resistant subpopulations (6/8, 75%) were stable. Our study suggests that the increased DAP resistance and hDAP in MRSA may threaten the effectiveness against MRSA infections.

Dynamic Changes of Staphylococcus aureus Susceptibility to Vancomycin, Teicoplanin, and Linezolid in a Central Teaching Hospital in Shanghai, China, 2008-2018.

Vancomycin, teicoplanin, and linezolid are the major treatment options for methicillin-resistant Staphylococcus aureus (MRSA). The phenomenon of progressive increase in the value of vancomycin minimum inhibitory concentration (MIC) for S. aureus (i.e., vancomycin MIC “creep”), has been reported; however, it is still a controversial concept because the results of research remain inconclusive. In this study, we conducted a retrospective epidemiologic investigation for more than 10 years to elucidate the dynamic changes of the MICs of vancomycin, teicoplanin, and linezolid in S. aureus in a central teaching hospital in Shanghai, China. A total of 2911 S. aureus isolates was recovered from 2008 to 2018, to which the MICs of three antimicrobials were tested by the E-test method and subsequently correlated with the characteristics of oxacillin susceptibility, clonotypes, and antimicrobial consumption during the study period. The proportion of MRSA dramatically decreased from 2008 to 2018 (from 84 to 49%, p < 0.001). Vancomycin MIC decline was identified both in MRSA and methicillin-sensitive S. aureus (MSSA) (both with p < 0.001), and both the dominating MRSA clone ST5 and pre-dominating MRSA clone ST239 displayed vancomycin MIC decline (p < 0.001, p = 0.040), while teicoplanin MIC decline was only identified in MRSA (p = 0.037). Linezolid MIC creep was identified in total S. aureus (p < 0.001), but linezolid in MRSA as well as teicoplanin and linezolid in MSSA displayed no statistically distinct trends of MIC creep or decline. Clinical consumption of linezolid increased significantly from 2012 to 2018 (p = 0.003), which correlated with vancomycin MIC decline in S. aureus (p = 0.005). The results of this study clearly demonstrate the dynamic changes of the MICs of these three primary antimicrobials in S. aureus, and suggest that changes in clinical antibiotic use may affect bacterial resistance.

Prospective Study of Irrational Prescription of Teicoplanin in a Large Academic Hospital: A Dilemma of Antimicrobial Resistance.

Objective:Teicoplanin is an antibiotic used to treat severe Gram-positive infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). In this study, we aimed to evaluate the pattern of teicoplanin rational prescribing to identify the factors which affected rational utilization. In addition, the teicoplanin minimum inhibitory concentration (MIC) was assessed in randomly selected isolates.Methods:In this descriptive-analytical prospective study, a total of 256 patients were randomly selected to evaluate the pattern of teicoplanin use. The required data were gathered to assess the appropriateness of teicoplanin usage. Also, 100 teicoplanin Etests were used for measuring the MIC.Findings:The results showed that the appropriateness rate of teicoplanin usage was 21.9%. The mean MIC was 2.24 ± 5.47 mg/L for the MRSA cultures (33 cultures), including 32 sensitive cultures (97%). In addition, the mean MIC was 28.71 ± 8.29 mg/L for the vancomycin-resistant enterococci (VRE) cultures (67 cultures), including five sensitive cultures (7.5%). Moreover, the analysis revealed that only the hospitalization ward was statistically significantly related to irrational usage (P = 0.014).Conclusion:The high prevalence of the inappropriate use of teicoplanin will lead to the development of antimicrobial resistance. Furthermore, the high rate of VRE cultures resistant to teicoplanin proves that teicoplanin has no advantage over vancomycin for treating VRE infections. Finally, we recommend guidelines' development for the appropriate administration of teicoplanin.

Association between daptomycin susceptibility and teicoplanin resistance in Staphylococcus epidermidis

Staphylococcus epidermidis infections are a common occurrence in hospitals, particularly in catheter-related bloodstream and surgical site infections and infective endocarditis. Higher daptomycin minimum inhibitory concentration (MIC) values may be associated with daptomycin treatment failure among patients with S. epidermidis infections. We therefore conducted a retrospective cohort study to determine the predictive value of daptomycin susceptibility. A retrospective study was undertaken in 1,337 patients with S. epidermidis infections. Data were collected from 1 January 2013 to 31 December 2016 at Ehime University Hospital, and included the following clinicopathological factors for evaluation: age, sex, resistance to vancomycin or teicoplanin, and history of antimicrobial therapy. Multiple analysis was performed using logistic regression to identify factors that independently and significantly affected the daptomycin resistance. Daptomycin-resistant S. epidermidis was identified in 38 (2.8%) patients. According to the multiple analysis, only higher MIC values (≥16 mg/L) for teicoplanin (P < 0.0001) were independently associated with an increased risk of developing daptomycin resistance. In conclusion, higher teicoplanin MIC values may predict resistance to daptomycin treatment in S. epidermidis infections.

Epidemiology of invasive infections caused by vancomycin sensitive and resistant enterococcal strains among oncology patients at the National Cancer Institute of Sri Lanka from 1st of July 2012 to 31st of July 2013

Introduction and Objectives: Enterococci have traditionally been regarded as low grade pathogens but have emerged as an increasingly important cause of nosocomial infections in the last decade. While the Enterococcus faecalis remains the predominate species in clinical infection, Enterococcus faecium isolates are increasing in proportion. This study was carried out to describe the epidemiology of invasive enterococcal infections among oncology patients at the National Cancer Institute of Sri Lanka (NCISL). Methods: 60 patients with invasive enterococcal infections, who were treated as inward patients at the National Cancer Institute of Sri Lanka from 1.7.2012 to 31.7 21013 whose samples were sent for microbiological investigation were included in this study. Speciation of the isolates was done by using a rapid manual analytic system (RapID STR panel-Oxoid). Vancomycin sensitivity was assessed in all enterococcal isolates by disc diffusion method, agar dilution screening method (CLSI guideline 2013)16 and detection of minimum inhibitory concentration (MIC) by using Vancomycin gradient strips. Teicoplanin MIC was assessed only in vancomycin resistant isolates using teicoplanin gradient strips. Associated factors for getting an infection with vancomycin resistant strains were assessed using a data extraction sheet. Results: The incidence of invasive enterococcal infections among oncology patients was 1.1 per 1000 admissions. The incidence of invasive enterococcal infection caused by vancomycin resistant species was 0.16 per 1000 admissions. E. faecium was the dominant species causing invasive enterococcal infections (55%). Using the gradient strip method for determination of vancomycin MIC as the gold standard, the screening agar dilution method had 100% sensitivity and specificity and the disc diffusion test had a low specificity (77.8%). Almost all the participants (96.6%) had acquired the enterococcal infection from the hospital. Vancomycin resistant infections were more common in patients who had haematological malignancies, who were treated with 3rd generation cephalosporins and cytotoxic chemotherapy drugs. Conclusions: E. faecium is the dominant species causing invasive enterococcal infections in oncology patients (55%) and phenotypically compatible with the VanA phenotype of glycopeptide resistant enterococci.

Risk factors associated with MRSA

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infection is associated with increased morbidity and mortality compared with infections caused by methicillin-sensitive Staphylococcus aureus (MSSA). Treatment of MRSA infection is complicated by the fact that these organisms are resistant to multiple antimicrobial agents, so treatment options are limited. The aim of the present study is determine risk factors association with MRSA as compared with MSSA and to compare the minimum inhibitory concentrations (MICs) of vancomycin, teicoplanin, linezolid and erythromycin to MRSA and MSSA.Methods: A nine-month prospective study was carried out. Staphylococcus aureus strains with clinical correlation, isolated from hospitalised patients, were included in the study. MIC of vancomycin, teicoplanin, linezolid and erythromycin was determined by E-test (HIMEDIA). Risk factors such as immunosuppression, previous hospitalisation, surgical procedure done, invasive devices and antibiotic therapy were determined by a pre-set protocol.Results: A total of 62 S. aureus strains were included in the study. Some 40% of S. aureus strains were methicillin resistant. The risk factors, invasive devices, previous hospitalisation and comorbid illness were found to be significantly associated with MRSA. Borderline significant association was observed with immunosuppression and antibiotic therapy. Erythromycin resistance was observed in 56% of MRSA, while no resistance was observed in MSSA. Teicoplanin MIC50 values and mean MIC were found to be lowest in vitro among vancomycin and linezolid against both MRSA and MSSA. The efficacy of teicoplanin, in terms of clinical and microbiological cure, has not been proven to be superior to vancomycin, but it has a better toxicity profile and has demonstrated a reduced risk of adverse events. Conclusions: Minimising risk factors and attention to alternative antibiotics and infection control practices may ease the problem of management of infections with MRSA.

Possibility of Poor Outcomes after Treatment Using Teicoplanin at the Minimum Inhibitory Concentration of &gt;2 μg/mL in Methicillin-resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; Bacteremia

Only minimal information exists regarding the treatment outcomes of patients suffering from methicillin-resistant Staphylococcus aureus (MRSA) bacteremia treated with teicoplanin (TEIC) when the TEIC minimum inhibitory concentration (MIC) is close to the upper limit of the "susceptibility range" according to the Clinical Laboratory Standards Institute (CLSI). We investigated the outcome of TEIC-treated patients in MRSA bacteremia, focusing on TEIC MIC against MRSA. A retrospective cohort study was conducted on patients with MRSA bacteremia. TEIC treatment failure was defined as any of the following: (1) all-cause 60-day mortality, (2) persistent bacteremia until the end of TEIC treatment, or (3) 30-day recurrence of MRSA bacteremia. Nineteen patients were enrolled, of whom 15 exhibited TEIC MICs ≤2 μg/mL and the remaining 4 exhibited >2 μg/mL. The rate of treatment failure and all-cause 60-day mortality in patients with MIC >2 μg/mL were significantly higher than those in patients with MIC ≤2 μg/mL [4 patients (100%) versus 4 patients (26.7%) (p=0.018) and 4 patients (100%) versus 2 patients (13.3%) (p=0.004), respectively]. Three of four patients (75%) with MIC >2 μg/mL had persistent bacteremia, which was quantitatively higher than in patients with MIC ≤2 μg/mL (1 of 7 patients, 14.3%). Our finding suggests that TEIC MIC >2 μg/mL may be related to poor treatment outcome in MRSA bacteremia, and that TEIC should not be used in this case.

Risk factors associated with MRSA

Abstract Background: Methicillin-resistant Staphylococcus aureus (MRSA) infection is associated with increased morbidity and mortality compared with infections caused by methicillin-sensitive Staphylococcus aureus (MSSA). Treatment of MRSA infection is complicated by the fact that these organisms are resistant to multiple antimicrobial agents, so treatment options are limited. The aim of the present study is determine risk factors association with MRSA as compared with MSSA and to compare the minimum inhibitory concentrations (MICs) of vancomycin, teicoplanin, linezolid and erythromycin to MRSA and MSSA. Methods: A nine-month prospective study was carried out. Staphylococcus aureus strains with clinical correlation, isolated from hospitalised patients, were included in the study. MIC of vancomycin, teicoplanin, linezolid and erythromycin was determined by E-test (HIMEDIA). Risk factors such as immunosuppression, previous hospitalisation, surgical procedure done, invasive devices and antibiotic therapy wer...

Population pharmacokinetics of teicoplanin and attainment of pharmacokinetic/pharmacodynamic targets in adult patients with haematological malignancy

ObjectivesTo describe the population pharmacokinetics of teicoplanin in adult patients with haematological malignancies receiving higher than standard doses, and to perform Monte Carlo simulations to determine dosing regimens associated with optimal teicoplanin concentrations. MethodsThis was a hospital-based clinical trial (EudraCT 2013–004535–72). Nine blood samples were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 hours after the last dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were undertaken using Pmetrics. ResultsThirty adult haematological malignancy patients were recruited with a mean (SD) loading dose, age, total body weight, and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) years, 69.1 (15.8) kg, and 72 (41) mL/min, respectively. A three-compartment linear pharmacokinetic model best described the teicoplanin concentration data. Covariates supported for inclusion in the final model were creatinine clearance for clearance and total body weight for volume of the central compartment. The median (IQR) area under the concentration-time curve from 48 to 72 hours (AUC48–72h) was 679 (319) mg.h/L. There was a strong correlation between the AUC48–72h and trough concentration at 72 hours (Pearson correlation coefficient 0.957, p <0.001). Dosing simulations showed that administration of five loading doses at 12-hourly intervals, stratified by total body weight and creatinine clearance, increased the probability of achieving target concentrations within 72 hours. ConclusionsTo increase the number of patients achieving optimal teicoplanin concentrations an individualized dosing approach, based on body weight and creatinine clearance, is recommended.

Vancomycin, teicoplanin, daptomycin, and linezolid MIC creep in methicillin-resistant Staphylococcus aureus is associated with clonality.

The purpose of this study is to evaluate the susceptibility trend of vancomycin, teicoplanin, daptomycin, and linezolid against methicillin-resistant Staphylococcus aureus (MRSA) blood isolates of different clones over an 11-year period.From 2000 to 2010, all bloodstream MRSA isolates from Chang Gung Memorial Hospital in Taiwan were prospectively collected. Three periods, namely 2000 to 2001, 2004 to 2005, and 2010, were included and 124 MRSA isolates were selected from each period. Minimum inhibitory concentrations (MICs) were determined by E-test. All the isolates were molecularly characterized.MRSA molecular epidemiology evolved from 1 predominant pulsotype (type A) to 5 major pulsotypes of 3 clonal complexes (CC). Vancomycin, teicoplanin, and daptomycin MICs creep were observed, particularly for pulsotype A-CC 239-staphylococcal cassette chromosome mec (SCCmec) III though its prevalence dramatically decreased since 2004 to 2005. Throughout the study period, the overall vancomycin modal MIC was stable at 1.5 mg/L, but teicoplanin and linezolid modal MIC increased to 2 and 2 mg/L, respectively. Isolates with teicoplanin and linezolid ≧ 2 ug/mL belonged to multiple clones. Pulsotype F-ST5-SCCmec II with a high rate of teicoplanin MIC ≧ 2 ug/mL continued clonal spread. Teicoplanin MIC had a high correlation with linezolid MIC.Molecular epidemiology MRSA bloodstream isolates in northern Taiwan evolved from 2000 throughout 2010, which was subsequently associated with the changing distribution of antibiotic MICs. While vancomycin MIC level remained unchanged, teicoplanin, daptomycin, and linezolid MIC levels increased. The impact of these changes on clinical treatment response deserves further investigations.

Analysis of the hemolysin and virulence-related genes of incomplete hemolysis Staphylococcus aureus

Objective To analyze hemolysin and virulence-related genes in incomplete hemolytic Staphylococcus aureus. Methods Fifty strains of incomplete hemolytic Staphylococcus aureus were isolated from patients admitted in the Second Affiliated Hospital of Soochow University during 2013 and 2014, and the isolates with complete hemolytic phenotype were also collected at the same period as the control strains. All the strains were inoculated and subcultured on four kinds of sheep blood agar plates supplied by different manufacturers to compare their hemolytic phenotype. The relative mRNA expressions of hemolysin genes (hla, hlb, hlc, hld) in standard strain, complete and incomplete hemolytic phenotype strains were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and valued by 2-△△Ct method. t test was used to compare mRNA expressions of hemolysin genes. Western blot was performed to analyze the expression of α-hemolysin. Antibiotic susceptibility test of incomplete hemolytic strains was performed using broth microdilution method. Resistant gene mecA and virulence genes pvl, tst were detected by PCR. Results The steady and hereditary incomplete hemolysis was observed in 50 strains of incomplete hemolytic Staphylococcus aureus on the sheep blood agar plates from different suppliers. Taking mRNA expression of hla, hlb, hlc, hld in standard strain as 1, the relative mRNA expressions of hemolysin genes in incomplete hemolytic strains were 0.02, 7.51, 0.06 and 0.12 respectively, there were statistical differences between standard strain and incomplete hemolytic strains (t=8.46, -56.40, 8.12 and 7.61, all P<0.05). And the expression of α-hemolysin was decreased in incomplete hemolytic strains. All the strains were identified as methicillin resistant Staphylococcus aureus (MRSA). Three strains exhibited different minimum inhibitory concentrations of teicoplanin and linezolid after subcultured, but the differences had no impact on the final results of antibiotic susceptibility test. mecA, pvl and tst genes were positive in incomplete hemolytic strains. Conclusion Staphylococcus aureus with incomplete hemolytic phenotype is methicillin resistant with higher expression of β-hemolysin and lower expressions of α-hemolysin, γ-hemolysin and δ-hemolysin. It carries plv and tst virulence genes and is of high virulence. Key words: Staphylococcus aureus; Incomplete hemolysis; Hemolysin; Drug resistance; Virulence

More accurate measurement of vancomycin minimum inhibitory concentration indicates poor outcomes in meticillin-resistant Staphylococcus aureus bacteraemia

Meticillin-resistant Staphylococcus aureus (MRSA) is an important pathogen associated with community-acquired and nosocomial infections. The aim of this study was to validate the vancomycin (VAN) minimum inhibitory concentration (MIC) and administration of VAN that may affect the prognosis of patients with MRSA bacteraemia. In total, 140 clinical MRSA strains from blood cultures were collected from January 2009 to December 2013 at a university hospital in Tokyo (Japan). Patient background, their clinical situation and the susceptibility of isolates to anti-MRSA agents in all cases were reviewed, and factors contributing to 30-day mortality were analysed. Susceptibility to anti-MRSA agents was measured by a microdilution susceptibility testing method. The VAN MIC was further evaluated at 0.25μg/mL intervals from 0.5μg/mL to 2.0μg/mL. Multiple logistic regression analysis revealed a 4-fold increase in mortality of patients with a VAN MIC ≥1.5μg/mL [odds ratio (OR)=3.952, 95% confidence interval (CI) 1.471–10.614; P=0.006]. A one-score increase in the Charlson co-morbidity index resulted in a 1.2-fold increase in the risk of death (OR=1.199, 95% CI 1.054–1.364; P=0.006). However, no significant difference was found in the ratio of the VAN 24-h area under the concentration–time curve to MIC between VAN MIC ≥1.5μg/mL and <1.5μg/mL. A significant increase in the MICs of teicoplanin and daptomycin was observed in strains with high VAN MICs. For patients with high VAN MICs, administration of these anti-MRSA antibiotics may have a poor outcome owing to cross-resistance.

Impact of Molecular Epidemiology and Reduced Susceptibility to Glycopeptides and Daptomycin on Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia.

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) bacteremia was associated with high mortality, but the risk factors associated with mortality remain controversial.MethodsA retrospective cohort study was designed. All patients with MRSA bacteremia admitted were screened and collected for their clinical presentations and laboratory characteristics. Minimum inhibitory concentration (MIC) and staphylococcal cassette chromosome mec (SCCmec) type of bacterial isolates were determined. Risk factors for mortality were analyzed.ResultsMost MRSA isolates from the 189 enrolled patients showed reduced susceptibility to antibiotics, including MIC of vancomycin ≥ 1.5 mg/L (79.9%), teicoplanin ≥ 2 mg/L (86.2%), daptomycin ≥ 0.38 mg/L (73.0%) and linezolid ≥ 1.5 mg/L (64.0%). MRSA with vancomycin MIC ≥ 1.5 mg/L and inappropriate initial therapy were the two most important risk factors for mortality (both P < 0.05; odds ratio = 7.88 and 6.78). Hospital-associated MRSA (HA-MRSA), carrying SCCmec type I, II, or III, was associated with reduced susceptibility to vancomycin, teicoplanin or daptomycin and also with higher attributable mortality (all P < 0.05). Creeping vancomycin MIC was linked to higher MIC of teicoplanin and daptomycin (both P < 0.001), but not linezolid (P = 0.759).ConclusionsGiving empirical broad-spectrum antibiotics for at least 5 days to treat catheter-related infections, pneumonia, soft tissue infection and other infections was the most important risk factor for acquiring subsequent HA-MRSA infection. Choice of effective anti-MRSA agents for treating MRSA bacteremia should be based on MIC of vancomycin, teicoplanin and daptomycin. Initiation of an effective anti-MRSA agent without elevated MIC in 2 days is crucial for reducing mortality.

Glycopeptide and daptomycin susceptibility trends among clinical isolates of methicillin-resistant Staphylococcus aureus in a tertiary care center in North India.

Increased vancomycin minimum inhibitory concentration (MIC) levels in Staphylococcus aureus and their association with vancomycin treatment failure are well-known problems. Few studies have recognized progressive increases in glycopeptide MIC levels for S. aureus strains in recent years. This study determined glycopeptide and daptomycin susceptibility among methicillin resistant S. aureus (MRSA) strains. A total of 776 clinical isolates of MRSA recovered from 2009 to 2012 were studied for glycopeptide and daptomycin susceptibility using the E-test method. The vancomycin MIC geometric mean (GM) of the MRSA isolates was 0.923, 0.944, 1.134 and 1.294 mg/L in the years 2009, 2010, 2011 and 2012, respectively, and the trend significantly increased over the years (P < 0.0001). Similarly, the teicoplanin MIC GM was 1.47, 1.49, 1.8 and 2.04 mg/L in the years from 2009 to 2012, respectively (P < 0.0001). MIC shifts were not found for daptomycin (P > 0.232). A significant increase in the MIC for glycopeptides was observed among the clinical MRSA isolates at our center over a 4-year period. However, the daptomycin MIC did not increase in the observed MRSA isolates.

Impact of psm-mec in the mobile genetic element on the clinical characteristics and outcome of SCCmec-II methicillin-resistant Staphylococcus aureus bacteraemia in Japan

Over-expression of alpha-phenol-soluble modulins (PSMs) results in high virulence of community-associated methicillin-resistant Staphylococcus aureus (MRSA). The psm-mec gene, located in the mobile genetic element SCCmec-II, suppresses PSMαs production. Fifty-two patients with MRSA bacteraemia were enrolled. MRSA isolates were evaluated with regard to the psm-mec gene sequence, bacterial virulence, and the minimum inhibitory concentration (MIC) of vancomycin and teicoplanin. Fifty-one MRSA isolates were classified as SCCmec-II, and 10 had one point mutation in the psm-mec promoter. We compared clinical characteristics and outcomes between mutant MRSA and wild-type MRSA. Production of PSMα3 in mutant MRSA was significantly increased, but biofilm formation was suppressed. Wild-type MRSA caused more catheter-related bloodstream infections (30/41 vs. 3/10, p 0.0028), whereas mutant MRSA formed more deep abscesses (4/10 vs. 3/41, p 0.035). Bacteraemia caused by mutant MRSA was associated with reduced 30-day mortality (1/10 vs. 13/41, p 0.25), although this difference was not significant. The MIC90 of teicoplanin was higher for wild-type MRSA (1.5 mg/L vs. 1 mg/L), but the MIC of vancomycin was not different between the two groups. The 30-day mortality of MRSA with a high MIC of teicoplanin (≥1.5 mg/L) was higher than that of strains with a lower MIC (≤0.75 mg/L) (6/10 vs. 6/33, p 0.017). Mutation of the psm-mec promoter contributes to virulence of SCCmec-II MRSA, and the product of psm-mec may determine the clinical characteristics of bacteraemia caused by SCCmec-II MRSA, but it does not affect mortality.

Vancomycin versus teicoplanin in the treatment of serious Gram-positive infections: what do the minimum inhibitory concentration data tell us?

AbstractGlycopeptides are the mainstay of treatment against serious drug-resistant Gram-positive infections. The two principal agents are vancomycin and teicoplanin. Optimal dosing of both these antimicrobial agents, in terms of clinical outcomes and achievement of pharmacodynamic targets, has been shown to be dependent on the minimum inhibitory concentration (MIC). There are no MIC susceptibility data for vancomycin and teicoplanin in South Africa, and susceptibility from a clinical perspective is usually considered to be a class-specifc phenomenon, and thus the two agents are often used interchangeably. The aim of this study was to assess and compare the MIC of teicoplanin with that of vancomycin, using broth microdilution, against a number of clinically signifcant Gram-positive isolates. Staphylococci and enterococci were collected from the Charlotte Maxeke Johannesburg Academic Hospital. Broth microdilution antimicrobial susceptibility testing was performed simultaneously for both vancomycin and teico...

Prognosis of patients with methicillin-resistant Staphylococcus aureusbloodstream infection treated with teicoplanin: a retrospective cohort study investigating effect of teicoplanin minimum inhibitory concentrations

BackgroundThe present study was designed to investigate whether teicoplanin minimum inhibitory concentrations (MICs) of methicillin-resistant Staphylococcus aureus (MRSA) isolates play a role in the prognosis of patient with teicoplanin-treated MRSA bloodstream infection (BSI).MethodsBetween 1 January 2006 and 31 December 2009, adult patients with teicoplanin-treated MRSA BSI in two Taiwan medical centers were retrospectively enrolled. Their blood MRSA isolates were submitted for determination of MICs to various antibiotics and multi-locus sequence types. All-cause mortalities on Days 14 and 30, as well as clinical response at the end of teicoplanin therapy were treated as endpoints.ResultsTwo hundred seventy adult patients were enrolled and 210 blood MRSA isolates were available. Independent risk factors for un-favorable outcome at the end of teicoplanin therapy included septic shock (p < 0.0001) and an elevated C-reactive protein level (p = 0.0064). The independent risk factors for all-cause Day 14 mortality (13.0%) included the presence of auto-immune diseases (p = 0.0235), septic shock (p = 0.0253) and thrombocytopenia (p = 0.0018). The independent risk factors for all-cause Day 30 mortality (26.3%) included age (p = 0.0102), septic shock (p < 0.0001) and thrombocytopenia (p = 0.0059).ConclusionsThe current study didn’t find a significant role for teicoplanin MICs in the prognosis of adult patients with teicoplanin-treated MRSA BSI.

Glycopeptide minimum inhibitory concentration creep among meticillin-resistant Staphylococcus aureus from 2006–2011 in China

Vancomycin minimum inhibitory concentration (MIC) creep has recently been demonstrated by many countries but is rarely reported in China. In this study, a total of 1411 meticillin-resistant Staphylococcus aureus (MRSA) isolates were collected from six hospitals in China during the period 2006–2011 and the MICs of vancomycin, teicoplanin and linezolid were determined by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. MIC50 and MIC90 values (MICs required to inhibit the growth of 50% and 90% of organisms, respectively) as well as geometric mean (GM) MICs were calculated for all isolates in each year, and MIC creep for the drugs was evaluated. All of the MRSA isolates were susceptible to vancomycin and linezolid. Overall, the vancomycin GM MIC of MRSA isolates was 0.906, 0.952, 0.956, 0.947, 1.013 and 1.040mg/L, with a significantly increasing trend over the years (P<0.001). Percentages of MRSA isolates with a vancomycin MIC above 1μg/mL (2μg/mL≥MIC>1μg/mL) were 26.0%, 23.5%, 21.6%, 27.8%, 30.6% and 42.8% from 2006–2011, respectively, and increased over time (P<0.005). The teicoplanin GM MIC increased rapidly from 0.749mg/L in 2008 to 0.973mg/L in 2011, and ca. 5% of isolates were resistant to teicoplanin in the period according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. MIC shifts were not found for linezolid (P>0.05). In conclusion, a tendency towards decreasing susceptibility to glycopeptides in MRSA has emerged in China.

Persistent methicillin-resistantStaphylococcus aureusbacteremia: do we need a new therapeutic strategy?

Persistent methicillin-resistant<i>Staphylococcus aureus</i>bacteremia: do we need a new therapeutic strategy?