Minimum Inhibitory Concentration Creep Research Articles

Minimum inhibitory concentration creep in Enterobacterales – A rising concern

Minimum inhibitory concentration creep in Enterobacterales – A rising concern

Rising Resistance In Uropathogens With An Indication Of Nitrofurantoin Mic Creep.

The irrational use of antibiotics has led to the emergence of multi drug resistant pathogens. The phenomenon of MIC creeps occurs when organisms start showing raised MIC but within susceptible range giving an indication of the prevalence of rise in resistant pathogens in an area. A cross sectional study in a large tertiary care hospital in North India to observe the susceptibility pattern among uropathogens and the possibility of MIC creeps. The Antimicrobial Susceptibility Testing (AST) and Minimum Inhibitory Concentration (MIC) were conducted by Vitek Compact 2. The identification of Extended Spectrum Beta Lactamase (ESBL) producers and Carbapenem Resistant Enterobacteriaceae (CRE) among Escherichia coli were noted. The MIC 50 and MIC 90 for Nitrofurantoin, the most widely used antibiotic for lower UTI, was calculated to investigate the phenomenon of MIC creep. In our study, a total of 2522 urine samples were analyzed: 1538 (61%) were positive with the commonest isolate being E. coli (n=736, 47.8%) followed by Klebsiella spp. (n=178, 11%). Less than 10% of resistance was observed for Fosfomycin, Amikacin, Nitrofurantoin, Imipenem, Meropenem and Colistin. ESBL producers and CRE E. coli were 528 (72% of 736) and 79 (11% of 736) respectively. Overall, 119/736 samples had an MIC ≥128. Amongst the ESBL producers, 96/528 had MIC ≥128 and amongst the CRE, 13/79 had MIC ≥128. E. coli can be used to reflect the trends in development of resistance. In the current study, it was observed that E. coli showed a reduced susceptibility for Nitrofurantoin indicated by a creeping increase in MIC albeit within normal range. Trends in rising MIC should alert prescribers to use drugs such as Nitrofurantoin judiciously. Antimicrobial stewardship practices should be strongly implemented in hospitals to curb rising resistance and obtain better treatment outcomes for patients with infectious diseases.

Staphylococcal Cassette Chromosome mec Typing and Multilocus Variable Number Tandem Repeat Analysis of Methicillin Resistant Staphylococcus aureus Clinical Isolates with Vancomycin Creep Phenomenon.

BackgroundThe association of treatment failure and mortality with vancomycin minimum inhibitory concentration creep (MIC) is a matter of serious concern in patients with severe methicillin resistant Staphylococcus aureus (MRSA) infections. The purpose of the study was to identify and characterize staphylococcal cassette chromosome mec (SCCmec) and clonal types of MRSA strains, exhibiting the vancomycin MIC creep phenomenon.MethodsA total of 3305 S. aureus strains were isolated from various clinical samples of Lahore General Hospital, Lahore, Pakistan. MRSA strains were identified by cefoxitin resistant (≤21mm) followed by mecA and mecC gene genotyping. Vancomycin MIC creep was determined by E-test. Isolates having MIC values >1.5 µg/mL were further subjected for SCCmec typing (I–V and XI) and multiple-locus variable number tandem repeat analysis (MLVA) by amplification of spa, sspA, clfA, clfB, and sdrCDE genes. A dendrogram was created based on the similarity index using bioneumerics software.ResultsAbout 13.3% (440/3305) isolates were MRSA with 99.3% (437/440) and 0.7% (3/440) carried mecA and mecC genes, respectively. In 120 MRSA isolates, the MIC of vancomycin was >1.5µg/mL. In MRSA isolates with high vancomycin MIC (>1.5µg/mL), the most common SCCmec type was SCCmec III (38.3%), followed by SCCmec IVa (15.8%), SCCmec IIIa (13.3%,), SCCmec IVc (7.5%), SCCmec IVe (5.8%), SCCmec IVd (5.8%), SCCmec IVb (4.2%), SCCmec II (2.5%), SCCmec V (1.7%), SCCmec I (1.7%) and SCCmec XI (1.7%). MLVA revealed 60 genotypic groups of MRSA isolates having a 92% similarity index.ConclusionSCCmec III was the most common type in genetically related MRSA isolates showing vancomycin MIC creep. The presence of SCCmec XI may further add burden to infection control measures.

Vancomycin MIC creep progresses in methicillin-resistant Staphylococcus aureus despite the national antimicrobial stewardship campaign: Single facility data in Japan

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial and community infections, and vancomycin (VCM) is widely recommended as a first-line therapeutic drug. Minimum inhibitory concentrations (MICs) of VCM ≤2 μg/mL are defined as susceptible, but increases in these levels, known as “VCM MIC creep” have been reported. The aim of this study was to investigate VCM MIC creep during the promotion of a national antimicrobial stewardship campaign. MethodsWe collected data from 2013 to 2020 on S. aureus isolated at the clinical microbiology laboratory at Okayama University Hospital, Japan. We calculated the annual proportions of MRSA isolation rates by MIC levels for nosocomial and community samples and estimated annual percentage changes in the antimicrobial use density of the VCM. ResultsOf the 1,716 MRSA isolates, no strains showed intermediate or resistant ranges of VCM MIC levels. By 2020, the proportion of MRSA with an MIC of ≤0.5 μg/mL decreased to 35.4%, while that with an MIC of 1 μg/mL increased to 64.1% over time. The annual percentage changes of the VCM antimicrobial use density significantly increased without any trend change point (average 8.1%, p = 0.035). There was no clear correlation between the VCM AUD and annual proportion of nosocomial MRSA with MIC 1 μg/mL (correlation coefficient 0.48; p value = 0.24). ConclusionWe demonstrated a deteriorating situation of VCM MIC creep among MRSA strains isolated at our university hospital during the national antimicrobial stewardship campaign.

In Vitro Activity of Vancomycin, Teicoplanin, Linezolid and Daptomycin Against Methicillin-Resistant Staphylococcus aureus Isolates Collected from Chinese Hospitals in 2018-2020.

IntroductionVancomycin, teicoplanin, linezolid and daptomycin are four major antibacterials used for methicillin-resistant Staphylococcus aureus (MRSA) infection treatment. However, with the increasing failure of clinical MRSA anti-infective treatment, it is urgent to investigate the status of MRSA sensitivity to these four drugs.MethodsIn the present study, 407 non-duplicated MRSA isolates from 6 provinces in China were collected from January 2018 to August 2020. The minimum inhibitory concentrations (MICs) of vancomycin, teicoplanin, linezolid and daptomycin were determined by broth microdilution method, and their MIC50, MIC90, and geometric mean MIC were calculated.ResultsAll 407 MRSA strains were sensitive to these four antibacterials. MIC range of vancomycin, teicoplanin, linezolid and daptomycin was 0.25 to 2 mg/L, 0.125 to 4 mg/L, 0.25 to 4 mg/L and 0.06 to 1 mg/L, respectively. Between 2018 and 2020, there was no “MIC creep” in vancomycin, teicoplanin and daptomycin. The geometric mean MIC of linezolid was not increased, but both MIC50 and MIC90 in 2019 and 2020 MRSA isolates were higher than 2018 isolates.ConclusionAll MRSA isolates remained sensitivity to vancomycin, teicoplanin, linezolid and daptomycin. The linezolid MIC50 and MIC90 increased have been found in this study.

Reduced Daptomycin Susceptibility in Clinical MRSA Isolates Showing Vancomycin MIC Creep Phenomenon

Introduction: Infections caused by Methicillin Resistant Staphylococcus aureus (MRSA) are associated with increased morbidity, longer antimicrobial therapy, etc. First option for treating invasive MRSA infections is glycopeptide vancomycin. Daptomycin, a lipopeptide rapidly bactericidal invitro against MRSA, is an acceptable alternative. Aim: To identify MRSA isolates from clinical specimens and assess their vancomycin and daptomycin susceptibility pattern. Materials and Methods: The cross-sectional study was conducted over a period of six months (January 2019 to June 2019) on 90 clinical samples in a rural teaching hospital in Pune, Maharashtra, India, including all samples except sputum received in the Microbiology laboratory. MRSA isolates were tested for vancomycin and daptomycin susceptibility by Epsilometer (E) test Minimum Inhibitory Concentration (MIC) method. Results: Among 90 MRSA isolates, most were from pus (51) followed by Urine (23), Blood (9), followed by Miscellaneous samples (7). Data analysis was done using Statistical Package for the Social Sciences (SPSS) version 16.0 software. All MRSA isolates in this study were susceptible to daptomycin with MIC in the range of 0.25-1 μg/mL with maximum isolates (39) with MIC of 0.38 μg/mL. Vancomycin MIC creep phenomenon was observed in 68 isolates. All these isolates also showed reduced susceptibility to daptomycin. Conclusion: MRSA in hospital set up mandates strict infection control practices in place. Daptomycin can be a good therapeutic alternative to treat infections caused by MRSA keeping in mind its therapeutic limitations and prior vancomycin usage in the same patient. Empirical therapy should always be based on antibiogram pattern. Adherence to hospital antibiotic policy and constant surveillance of antimicrobial resistance is the need of the hour.

Detection of vancomycin susceptibility among methicillin resistant staphylococcus aureus in a tertiary care hospital

Introduction: Staphylococcus aureus infections in current times have become challenging to treat because of advent of Methicillin Resistant Staphylococcus aureus (MRSA) strains which are concurrently resistant to a wide panel of drugs and posing a threat to clinicians and microbiologists globally. The optimal drug for treatment of such MRSA infections is vancomycin but strains with augmented Minimum Inhibitory concentration (MIC) for this drug also have surfaced. Objectives: To know the frequency of MRSA isolates in various clinical samples with their antimicrobial sensitivity patterns and to equate agar dilution and E-test methods for MIC determination of vancomycin to MRSA strains. Materials and Methods: A total of 50 non repeat clinical isolates of staphylococcus aureus isolates were collected from various clinical specimens and were tested for methicillin resistance using the cefoxitin disc diffusion test (30mg). All MRSA isolates were tested for specific MIC by agar dilution and E-test methods. Results: 29 (58%) isolates were resistant to cefoxitin (MRSA). 13.8% isolates had MIC of 4mg/ml for vancomycin (VISA) by both agar dilution and E-test methods. However by agar dilution method 25 (86.2%) isolates exhibited vancomycin MIC of ? 2 mg/ml and by E-test 68.9% of the isolates showed MIC ? 2 mg/ml. Conclusion: Multidrug resistant MRSA strains are on the rise and alternate drug of choice for these infections; vancomycin also is showing increased MIC so prudent use of this drug is advocated. E-test can detect MRSA strains with intermediate MIC values useful for detection of MIC creep so that vancomycin can be used rationally.

Occurrence of vancomycin MIC creep in methicillin resistant isolates in Saudi Arabia

Background“MIC creep” is a phenomenon that describes an increase of an organism MICs over time and have been reported from different parts of the world. High MIC in MRSA has been theoretically liked to treatment failure and may be a precursor to hVISA and VISA. This study was conducted to assess presence of vancomycin minimum inhibitory concentration (MIC) creeps among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) in Saudi Arabia. MethodsMinimum inhibitory concentration (MIC) of vancomycin by E test of all MRSA isolates of from 2013 to 2018 were reviewed. ResultsOf the 736 isolates evaluated, no isolates with MIC above 2 were found. Majority of MRSA isolates were susceptible to vancomycin with MIC less than 1. There was a significant increase in both Arithmetic and geometric mean MIC for vancomycin during the first three years which progressively declined in the next three years. ConclusionsAlthough most of MRSA isolated remained very susceptible to vancomycin there was evidence of dynamic vancomycin MIC creep over time.

Overview of Quantitative Methodologies to Understand Antimicrobial Resistance via Minimum Inhibitory Concentration.

Simple SummaryAn emerging threat to human and food animal health is the development of antimicrobial resistance in bacteria associated with food animals. One of the primary tools for assessing resistance levels and monitoring for changes in expressed resistance is the use of minimum inhibitory concentration tests, which expose bacterial isolates to a series of dilutions of an antimicrobial agent to identify the lowest concentration of the antimicrobial that effectively prevents bacterial growth. These tests produce a minimum inhibitory value that falls within a range of concentrations instead of an exact value, a process known as censoring. Analysis of censored data is complex and careful consideration of methods of analysis is necessary. The use of regression methods such as logistic regression that divide the data into two or three categories is relatively easy to implement but may not detect important changes in the distributions of data that occur within the categories. Models that do not simplify the data may be more complex but may detect potentially relevant changes missed when the data is categorized. As a result, the analysis of minimum inhibitory concentration data requires careful consideration to identify the appropriate model for the purpose of the study.The development of antimicrobial resistance (AMR) represents a significant threat to humans and food animals. The use of antimicrobials in human and veterinary medicine may select for resistant bacteria, resulting in increased levels of AMR in these populations. As the threat presented by AMR increases, it becomes critically important to find methods for effectively interpreting minimum inhibitory concentration (MIC) tests. Currently, a wide array of techniques for analyzing these data can be found in the literature, but few guidelines for choosing among them exist. Here, we examine several quantitative techniques for analyzing the results of MIC tests and discuss and summarize various ways to model MIC data. The goal of this review is to propose important considerations for appropriate model selection given the purpose and context of the study. Approaches reviewed include mixture models, logistic regression, cumulative logistic regression, and accelerated failure time–frailty models. Important considerations in model selection include the objective of the study (e.g., modeling MIC creep vs. clinical resistance), degree of censoring in the data (e.g., heavily left/right censored vs. primarily interval censored), and consistency of testing parameters (e.g., same range of concentrations tested for a given antibiotic).

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.

Staphylococcus aureus at an Indian tertiary hospital: Antimicrobial susceptibility and minimum inhibitory concentration (MIC) creep of antimicrobial agents.

Staphylococcus aureus causes a variety of symptoms and diseases and has been associated with high morbidity and mortality. A global population drift in clinical S. aureus isolates towards reduced antimicrobial susceptibility is being reported. In this study, the antimicrobial susceptibility profile and minimum inhibitory concentration (MIC) creep of vancomycin, linezolid, teicoplanin and rifampicin against clinical S. aureus isolates at an Indian tertiary centre from January 2012 to December 2016 were investigated. All consecutive, non-duplicate S. aureus isolates (n=1466) recovered from hospitalised patients identified by VITEK®2 were included in the study. Clinical isolates were tested against 20 antibiotics and were evaluated according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Statistical significance of the MIC creeps of four antimicrobials (vancomycin, linezolid, teicoplanin and rifampicin) was ascertained. S. aureus isolates recovered from all clinical samples demonstrated high resistance to ampicillin, ciprofloxacin and penicillin (75-100%) and low resistance to amikacin, linezolid, netilmicin, nitrofurantoin, teicoplanin and vancomycin (0-13%). The MIC90 values (MIC required to inhibit 90% of the isolates) for vancomycin, linezolid and rifampicin decreased, whereas the MIC90 for teicoplanin increased. The change in the geometric mean MIC of rifampicin was found to be statistically significant. A statistically significant and progressive MIC creep was observed for teicoplanin and rifampicin. Despite remaining susceptible, S. aureus is not inert to antibiotic pressure. Implementation of preventive measures in healthcare settings is required worldwide to combat the increasing number of infections by this pathogen.

Escherichia coli encoding blaNDM-5 associated with community-acquired urinary tract infections with unusual MIC creep-like phenomenon against imipenem.

Carbapenemase-producing Escherichia coli are a major clinical concern. The current study aimed to identify NDM-5-producing E. coli associated with community-acquired urinary tract infections (UTIs) co-harbouring extended-spectrum β-lactamases (ESBLs) and showing a phenomenon of imipenem minimum inhibitory concentration (MIC) creep. A total of 973 urine samples were collected from females aged between 18-49 years diagnosed with UTI in Northeast India (June 2014-July 2016). Isolates were identified by standard microbiological methods. The presence of blaNDM and ESBL genes was determined by PCR and sequencing. PCR-based replicon typing was performed. Plasmid stability of all β-lactamase-producers and their transformants was analysed by serial passage, and the MIC creep phenomenon was analysed by studying revertants. Among 34 blaNDM-5-positive E. coli isolates, 21 (61.8%) co harboured blaCTX-M-15, followed by multiple combinations of genes. This study revealed diverse plasmid types (HI1, I1, FIA+FIB, FIA and Y). The strains showed progressive plasmid loss after 31 passages. Most if the isolates had MICs of 0.5μg/mL and 1μg/mL to imipenem, ertapenem and meropenem. However, on studying the MIC creep phenomenon, the MIC was found to be elevated from 0.5μg/mL to 64μg/mL and from 1μg/mL to 128μg/mL. Analysis of revertants shows that the MIC of most NDM-positive isolates was reduced to 16μg/mL after the 30th serial passage. This study observed a unique phenotype of NDM-producers that has not been reported previously. The observed phenomenon poses a global threat as these pathogens may evade phenotypic screening by routine laboratories.

Vancomycin, linezolid and daptomycin susceptibility pattern among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) from Sub- Himalyan Center

INTRODUCTION:The efficacy of vancomycin, drug of choice for methicillin-resistant Staphylococcus aureus (MRSA), has become questionable due to the emergence of MRSA isolates with reduced susceptibility. The present study was conducted to determine the vancomycin, linezolid, and daptomycin susceptibility pattern in clinical isolates of MRSA and to observe minimum inhibitory concentration (MIC) creep over 2 years if any.MATERIALS AND METHODS:MIC of vancomycin, linezolid, and daptomycin were determined by E-test in 198 MRSA isolates and their MIC 50, MIC 90, and geometric mean MIC were calculated.RESULTS:While all isolates were sensitive to vancomycin, linezolid, and daptomycin, MIC 90 of vancomycin increased from 1.5 μg/ml in 2015 to 2 μg/ml in 2016. The percentage of isolates with vancomycin MIC >2 μg/ml doubled in 2016 (12.9%) as compared to 2015 (6.1%). MIC 90 for linezolid remained steady as 3 μg/ml, but geometric mean MIC increased from 2.20 μg/ml in 2015 to 2.29 μg/ml in 2016, and more than 40% isolates showed MIC 3 μg/ml. MIC 90 and geometric mean MIC of daptomycin decreased from 0.75 μg/ml to 0.5 μg/ml and 0.50 μg/ml to 0.36 μg/ml in 2015 and 2016, respectively.CONCLUSION:MIC creep was observed with vancomycin. Although linezolid MIC was within the susceptible zone, more than 40% strains showing MIC 3 μg/ml may herald the future development of either resistant or heteroresistant. Daptomycin showed good sensitivity against MRSA isolates. Therefore, it could be considered as an alternative agent for the treatment of infections caused by MRSA. However, it should be reserved where this class has a clear therapeutic advantage over other anti-MRSA drugs.

Tratamiento de las infecciones por Staphylococcus aureus

Staphylococcus aureus is one of the most frequent causes of infection at both the nosocomial and community levels. Infections caused by this microorganism generate significant morbidity and mortality and are associated with a high medical cost. In fact, staphylococal bacteremia mortality may be as high as 60% depending on the resistance profile and type of patient. The resistance of S. aureus to penicillin is a fact since penicillin began to be used massively in the 1940s. Shortly afterwards, the first methicillin-resistant strains (MRSA) appeared initially in the hospital setting. Today, community-accquired MRSA has become more important than nosocomial in some countries such as the USA. For many years, glycopeptides, and in particular vancomycin, have been the antimicrobial of choice to treat these infections. However, in recent years we have witnessed a progressive increase in minimum inhibitory concentrations (MIC) to vancomycin (MIC creep) which has been a new setback for the treatment of these infections. Linezolid, tigecycline and daptomycin have been alternatives to the glycopeptides that have been used in the last 10 years, however, there have also emerged resistances that have limited its use. After many years without new antimicrobials, new options such as Dalvabancina, Ceftarolina or Tedizolid have recently appeared.

Evaluation of vancomycin MIC creep in Staphylococcus aureus.

Vancomycin is the primary treatment for methicillin-resistant Staphylococcus aureus (MRSA). However, an increasing proportion of MRSA isolates with high minimum inhibitory concentrations (MICs) within the susceptible range (vancomycin 'MIC creep') is being observed. The aim of this study was to assess the vancomycin MIC distribution for S. aureus isolates over a period of 4 years in Centro Hospitalar Baixo Vouga (Aveiro, Portugal) and to identify differences in vancomycin MIC determined by different susceptibility testing methods. For each S. aureus isolate, the vancomycin MIC was assayed by the VITEK®2 automated system and the broth microdilution testing method. The results showed significant differences in vancomycin MIC by different methods (P=0.021, sign test) and did not suggest the presence of vancomycin MIC creep during the study period. Vancomycin MIC creep is a regional problem, therefore it can only be assessed through the evaluation of local susceptibility profiles, and antibiogram based on real MIC assay should be an essential element in local MRSA infection clinical management.

Prevalence and Genetic Mechanisms of Antimicrobial Resistance in Staphylococcus Species: A Multicentre Report of the Indian Council of Medical Research Antimicrobial Resistance Surveillance Network

Purpose: Routine surveillance of antimicrobial resistance (AMR) is an essential component of measures aimed to tackle the growing threat of resistant microbes in public health. This study presents a 1-year multicentre report on AMR in Staphylococcus species as part of Indian Council of Medical Research-AMR surveillance network. MaterialsandMethods:Staphylococcus species was routinely collected in the nodal and regional centres of the network and antimicrobial susceptibility testing was performed against a panel of antimicrobials. Minimum inhibitory concentration (MIC) values of vancomycin (VAN), daptomycin, tigecycline and linezolid (LNZ) against selected methicillin-resistant Staphylococcus aureus (MRSA) isolates were determined by E-test and MIC creep, if any, was determined. Resistant genotypes were determined by polymerase chain reaction for those isolates showing phenotypic resistance. Results: The prevalence of MRSA was found to be range from moderate (21%) to high (45%) among the centres with an overall prevalence of 37.3%. High prevalence of resistance was observed with commonly used antimicrobials such as ciprofloxacin and erythromycin in all the centres. Resistance to LNZ was not encountered except for a single case. Full-blown resistance to VAN in S. aureus was not observed; however, a few VAN-intermediate S. aureus isolates were documented. The most common species of coagulase negative staphylococci (CoNS) identified was Staphylococcus haemolyticus and Staphylococcus epidermidis. Resistance among CoNS was relatively higher than S. aureus. Most phenotypically resistant organisms possessed the corresponding resistance genes. Conclusion: There were localised differences in the prevalence of resistance between the centres. The efficacy of the anti-MRSA antimicrobials was very high; however, almost all these antimicrobials showed evidence of creeping MIC.

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.

The association of molecular typing, vancomycin MIC, and clinical outcome for patients with methicillin-resistant Staphylococcus aureus infections.

There are reports of an increase in vancomycin minimum inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA) over time, a phenomenon referred to as "MIC creep", but some studies have conflicting results. The aim of this study is to evaluate the association of molecular typing, vancomycin MIC, and clinical outcome for patients with MRSA infections. Thirty-two MRSA isolates from Taichung Veterans General Hospital (TCVGH), Taichung, Taiwan during the period of 2003 to 2008 were analyzed for the association of sequence typing, vancomycin MIC, and the correlated clinical outcome for patients with MRSA infections. The vancomycin MICs of 28 additional isolates from 2014 were used for the detection of MIC creep. Among the genotypes of 32 isolates, there were 17 (53.1%) isolates with ST239-SCCmecIII, seven (21.9%) isolates with ST5-SCCmecII, six (18.8%) isolates with ST59-SCCmecIV, and two (6.2%) isolates with ST59-SCCmecVT. Two isolates had an MIC of 2μg/mL and were identified as ST239-SCCmecIII. No statistically significant change in the distribution of MICs of all isolates was observed between 2003 and 2014 (p=0.263). There was no significant difference in the mortality rates between two groups of patients with vancomycin MICs <2μg/mL and ≥ 2μg/mL (p =>0.99). There was no vancomycin MIC creep in the period from 2003 to 2014 in this study. Appropriate prognostic models for assessment of the association among sequence types, vancomycin MICs, and clinical outcome warrant further investigation.

An investigation of vancomycin minimum inhibitory concentration creep among methicillin-resistant Staphylococcus aureus strains isolated from pediatric patients and healthy children in Northern Taiwan.

The phenomenon of vancomycin minimum inhibitory concentration (MIC) creep is an increasingly serious problem in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. In this study, we investigated the vancomycin and daptomycin MIC values of MRSA strains isolated from pediatric patients and MRSA colonized healthy children. Then, we assessed whether there was evidence of clonal dissemination for strains with an MIC to vancomycin of ≥ 1.5μg/mL. We collected clinical MRSA isolates from pediatric patients and from healthy children colonized with MRSA during 2008-2012 at a tertiary medical center in northern Taiwan and obtained vancomycin and daptomycin MIC values using the Etest method. Pulse-field gel electrophoresis (PFGE) and staphylococcal cassette chromosome (SCCmec) typing were used to assess clonal dissemination for strains with an MIC to vancomycin of ≥ 1.5μg/mL. A total 195 MRSA strains were included in this study; 87 were isolated patients with a clinical MRSA infection, and the other 108 strains from nasally colonized healthy children. Vancomycin MIC≥1.5μg/mL was seen in more clinical isolates (60/87, 69%) than colonized isolates (32/108, 29.6%), p<0.001. The PFGE typing of both strains revealed multiple pulsotypes. Vancomycin MIC creeps existed in both clinical MRSA isolates and colonized MRSA strains. Great diversity of PFGE typing was in both strains collected. There was no association between the clinical and colonized MRSA isolates with vancomycin MIC creep.

The Prevalence of Vancomycin-Intermediate Staphylococcus aureus and Heterogeneous VISA Among Methicillin-Resistant Strains Isolated from Pediatric Population in a Turkish University Hospital.

There are limited data regarding the prevalence of vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) among pediatric population. Our objective was to determine the distribution of vancomycin and daptomycin minimum inhibitory concentrations (MICs) and explore the phenomenon of vancomycin MIC creep and the VISA/hVISA prevalence among the methicillin-resistant Staphylococcus aureus (MRSA) strains belonging to pediatric population by population analysis profile-area under the curve (PAP-AUC) and Etest macromethod. Vancomycin and daptomycin susceptibilities of 94 pediatric isolates of MRSA were tested by broth microdilution (BMD) and Etest methods. To determine the prevalence of VISA/hVISA, Etest macromethod and PAP-AUC was performed on all isolates. All isolates were susceptible to vancomycin and daptomycin by both BMD and Etest methods. Twenty-eight (29.8%) isolates had vancomycin MICs of 2 μg/ml by BMD. No increase in vancomycin MICs was observed over time. There were no VISA among 94 MRSA tested but 20 (21.3%) hVISA isolates were identified by PAP-AUC. Results of Etest macromethod were compared to PAP-AUC. Etest macromethod was 60.0% sensitive and 90.5% specific. The hVISA isolates represented 53.6% of isolates with vancomycin MICs of 2 μg/ml. Also, 75% of hVISA isolates had vancomycin MICs of 2 μg/ml. To our knowledge, this is the first study investigating the prevalence of VISA/hVISA among MRSA isolated from pediatric patients by PAP-AUC method. Based on our findings, MRSA isolates, which have vancomycin MIC of 2 μg/ml can be investigated for the presence of hVISA. In this study, daptomycin showed potent activity against all isolates and may represent a therapeutic option for MRSA infections.