High Vancomycin Minimum Inhibitory Concentration Research Articles

Antibiotic Susceptibility of Staphylococcus Aureus with VanA and MecA Genes.

Staphylococcus aureus (S.aureus) is an emerging antibiotic resistant bacterium responsible for various infections in human. Resistance to methicillin and vancomycin are of prime concern in S. aureus. The study aims to determine the minimum inhibitory concentration (MIC) of Vancomycin and evaluate the existence of mecA and vanA genes, associated with antibiotic resistance. Clinical specimens from three Kathmandu hospitals were processed and S. aureus was identified using conventional microbiological procedures. MRSA was phenotypically identified with cefoxitin (30µg) disc diffusion, while vancomycin susceptibility was assessed using the Ezy MICTM stripes. The mecA and vanA genes were detected by polymerase chain reaction (PCR). Out of 266 S. aureus samples from various clinical specimen subjected for analysis, 77 (28.9%) were found methicillin-resistant (MRSA) and 10 (3.8%) were observed vancomycin-resistant (VRSA). Vancomycin resistant isolates showed a significant correlation between resistance to ampicillin, chloramphenicol, and cefoxitin. The mecA gene was found in 39 of the MRSA isolates, having 50.64% of MRSA cases, while the vanA gene was detected in 4 of the VRSA cases, constituting 40% of VRSA occurrences. The strains with higher vancomycin minimum inhibitory concentration values (≥ 1.5 μg/ml) displayed increased resistance rates to various antibiotics compared to strains with lower minimum inhibitory concentration values (< 1.5 μg/ml). The presence of vanA genes was strongly associated (100%) with vancomycin resistance, while the 10.3% mecA gene was identified from MRSA having resistance towards vancomycin also.

Genetic alterations in methicillin-susceptible Staphylococcus aureus associated with high vancomycin minimum inhibitory concentration

There are many reports on gene mutations observed in methicillin-resistant Staphylococcus aureus (MRSA) showing reduced susceptibility to vancomycin. However, there are limited studies on the genetic alterations that contribute to high vancomycin minimum inhibitory concentrations (MICs) in methicillin-susceptible S. aureus (MSSA). This study aimed to compare MSSA strains with high vancomycin MICs with those with low MICs, and to identify specific genetic alterations associated with increased vancomycin MICs. In total, 124 MSSA strains were analysed, with 62 having vancomycin MICs of 1-2 mg/L (MS-HV) and the remaining 62 having MICs <1 mg/L (MS-LV) as control. Polymerase chain reaction amplification and sequencing were conducted to identify point mutations and amino acid changes in the vraSR, graRS and walRK operons and rpoB gene. The number of single nucleotide polymorphisms (SNPs) and specific mutations in the indicated gene were compared between the two groups. The MS-HV strains had a significantly higher median number of SNPs in studied genes than the MS-LV strains (5 vs 3; P < 0.0001), with higher frequency of SNPs in the graR and walK genes. The MS-HV strains also displayed a significantly higher prevalence of specific mutations in the graR gene (V135I, I136V and V136I) compared with the MS-LV strains. The odds of having a high vancomycin MIC was 5.54 times higher in strains with a mutation in the graR gene, and 5.32 times higher in strains with a mutation in the walK gene, compared with those without these mutations. Mutations in the graR and walK genes may contribute to reduced vancomycin susceptibility in MSSA. This study gives key insights into the mechanisms underlying this phenomenon.

Comparative evaluation of MIC of Vancomycin among methicillin resistant Staphylococcus aureus (MRSA) isolates in tertiary care hospital

Vancomycin, a glycopeptide antibiotic with in-vitro activity against all staphylococci and clinical response to methicillinresistant staphylococcus aureus (MRSA) infection, became the backbone of treatment due to MRSA’s universalresistance to the antimicrobial agents belonging to beta-lactams and There are no other viable options. In patients withstaphylococcal infections, this study demonstrated a significant conflict of minimum inhibitory concentrations (MICs) ofvancomycin for MRSA strains between an automated system, Vitek 2, and the method. test E-strip. In the Microbiologylaboratory of JSS hospital which is a tertiary care center situated in Mysuru, 90 isolates were acquired from variousclinical samples to analyse Vancomycin MIC. Out of 90 isolates, 2.2% MRSA isolates showed highest vancomycin MIC2μg/ml by Vitek-2 method, where no isolates showed MIC up-to 2μg/ml by E-strip method. But the higher vancomycinMIC 1μg/ml was observed in 82.2% by vancomycin E-strip method compared to 37.7% by Vitek-2 method. Lowest MIC0.5μg/ml showed by Vitek-2 method in 58.8% compared to 4.4% by E-strip method. The study concludes that all S. aureusisolates were resistant to methicillin by both Vitek-2 system and cefoxitin disc diffusion method and also identified asVSSA (vancomycin susceptible Staphylococcus aureus) by Vitek-2 and E-test method. Higher vancomycin MIC ≥1μg/mlin 93.3% may be due to using of vancomycin improperly and infrequently in MRSA infection with lowest MIC value.Therefore, this method can also be used as routine laboratory practice or as alternative method where Vitek 2 system orother methods are not available.

Competence Mining of Vancomycin (VAN) in the Management of Infections Due to Bacterial Strains With High VAN Minimum Inhibitory Concentrations (MICs): A Novel Dosing Strategy Based on Pharmacokinetic/Pharmacodynamic Modeling.

The increasing emergence of bacterial strains with high VAN MICs (BSH–VAN–M), such as Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus bovis, results in growing concern that VAN is not effective against these isolates. Due to the limited data on VAN against BSH–VAN–M and the application limits of drugs currently considered to be effective for BSH–VAN–M, exploration of “new usages for old drugs” is reasonable to improve and maximize the efficacy of existing antibiotics. This study aimed to construct a novel dosing strategy to mine the competence of VAN in the management of BSH–VAN–M infections. Herein, we optimized the traditional intermittent i.v. infusion (TIII) method to create an optimal two-step infusion (OTSI). With pharmacokinetic (PK)/pharmacodynamic (PD) modeling at the targeted ratio of the daily area under the concentration-time curve (AUC0–24) to the minimum inhibitory concentration (MIC) (AUC0–24/MIC) of 400, we used Monte Carlo simulations to evaluate the efficacy of 25 VAN regimens (including 15 OTSI regimens and 10 TIII regimens with daily doses of up to 6 g) to treat pneumonia, meningitis, sternal osteomyelitis, mastitis, pleuritis, bacteremia, and bacterial pericarditis resulting from isolates with MICs of ≤64 mg/L and to the current E. faecalis, E. faecium, S. aureus, S. epidermidis, and S. bovis populations with a pooled MIC distribution. Our data indicated that 4 g/day VAN, with an OTSI but not a TIII, for mastitis, pleuritis, bacteremia, and bacterial pericarditis due to isolates with MICs of ≤4 mg/L or to the current E. faecalis, S. aureus, S. epidermidis, and S. bovis populations achieved the desired PK/PD exposure at the AUC0–24/MIC target of 400. This study suggests the superiority and feasibility of OTSI relative to TIII for the competence mining of VAN against BSH–VAN–M from the perspective of PK/PD and provides a new resource for understanding how PK/PD modeling shapes the performance of VAN to meet the growing challenges of BSH–VAN–M infections.

Association between high vancomycin minimum inhibitory concentration and clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia- A retrospective cohort study.

The purpose of this study is to determine the role of high (≥ 1.5 mg/L) vancomycin minimum inhibitory concentration (VMIC) in predicting clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). A retrospective study was conducted at Mayo Clinic, Minnesota. Patients ≥ 18 years with a 3-month follow-up were included. Outcomes were defined as 30-day all-cause in-hospital mortality, median duration of bacteraemia, metastatic infectious complications, and relapse of MRSAB. A total of 475 patients with MRSAB were identified, and 93 (19.6%) of them had high VMIC isolates. Sixty-four percent of patients were male with a mean age of 69.0 years. Active solid organ malignancy and skin and soft tissue infection as source of MRSAB were associated with high VMIC, while septic arthritis as a complication was significantly associated with low VMIC on multivariate analysis. Eighty-one (17.1%) patients died within 30 days of hospitalization, with no significant difference in mortality rates between the two groups. In-hospital mortality, median duration of bacteraemia, and metastatic infectious complications were not significantly associated with high VMIC MRSAB.

Association between high vancomycin minimum inhibitory concentration and clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: a meta-analysis.

To assess the relationship between high vancomycin minimum inhibitory concentrations (MIC), in patients with methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), and both mortality and complicated bacteremia. Embase, Medline, EBM, Scopus and Web of Science were searched for studies published from January 1st 2014 to February 29th 2020. "High" vancomycin MIC cut off was defined as ≥ 1.5mg/L. Three referees independently reviewed studies that compared outcomes in patients with MRSAB stratified by vancomycin MIC. Subgroup analyses were performed for rates of mortality and complicated bacteremia. A total of 13 studies with 2089 patients were included. Overall, mortality was 27.7% and 23.3% in the high and low vancomycin MIC group, respectively. No significant difference was found between vancomycin MIC groups for overall mortality, in-hospital mortality, late mortality, persistent bacteremia, severe sepsis or septic shock, acute renal failure, septic emboli or endocarditis, and osteomyelitis or septic arthritis. Early mortality was significantly associated with low vancomycin MIC. Mortality in studies using broth microdilution method (BMD) and need for mechanical ventilation were significantly associated with high vancomycin MIC. Overall mortality and complicated bacteremia were not significantly associated with high vancomycin MICs in a patient with MRSAB. Randomized controlled trials to assess the utility of vancomycin MIC values in predicting mortality and other adverse clinical outcomes are warranted.

Effect of the vancomycin minimum inhibitory concentration on clinical outcomes in patients with methicillin-susceptible Staphylococcus aureus bacteraemia: a systematic review and meta-analysis

ObjectiveThe use of the vancomycin minimum inhibitory concentration (MIC) as a prognostic predictor in patients with methicillin-susceptible Staphylococcus aureus (MSSA) has been debated in the last decade. We performed a...

Pharmacodynamic comparison of different antimicrobial regimens against Staphylococcus aureus bloodstream infections with elevated vancomycin minimum inhibitory concentration

BackgroundStaphylococcus aureus is one of the major causes of bloodstream infections (BSI) worldwide, representing a major challenge for public health due to its resistance profile. Higher vancomycin minimum inhibitory concentrations (MIC) in S. aureus are associated with treatment failure and defining optimal empiric options for BSIs in settings where these isolates are prevalent is rather challenging. In silico pharmacodynamic models based on stochastic simulations (Monte Carlo) are important tools to estimate best antimicrobial regimens in different scenarios. We aimed to compare the pharmacodynamic profiles of different antimicrobials regimens for the treatment of S. aureus BSI in an environment with high vancomycin MIC.MethodsSteady-state drug area under the curve ratio to MIC (AUC/MIC) or the percent time above MIC (fT > MIC) were modeled using a 5000-patient Monte Carlo simulation to achieve pharmacodynamic exposures against 110 consecutive S. aureus isolates associated with BSI.ResultsCumulative fractions of response (CFRs) against all S. aureus isolates were 98% for ceftaroline; 79% and 92% for daptomycin 6 mg/kg q24h and for the high dose of 10 mg/kg q24h, respectively; 77% for linezolid 600 mg q12h when MIC was read according to CLSI M100-S26 instructions, and 64% when MIC was considered at the total growth inhibition; 65% and 86% for teicoplanin, three loading doses of 400 mg q12 h followed by 400 mg q24 h and for teicoplanin 400 mg q12 h, respectively; 61% and 76% for vancomycin 1000 mg q12 h and q8 h, respectively.ConclusionsBased on this model, ceftaroline and high-dose daptomycin regimens delivered best pharmacodynamic exposures against S. aureus BSIs. Teicoplanin higher dose regimen achieved the best CFR (86%) among glycopeptides, although optimal threshold was not achieved, and vancomycin performance was critically affected by the S. aureus vancomycin MIC ≥2 mg/L. Linezolid effectiveness (CFR of 73%) is also affected by high prevalence of isolates with linezolid MIC ≥2 mg/L. These data show the need to continually evaluate the pharmacodynamic profiles of antimicrobials for empiric treatment of these infections.

Low Serum Trough Concentrations and High Vancomycin Minimum Inhibitory Concentration in Methicillin-Sensitive Staphylococcus aureus From Hemodialysis Patients in Brazil.

The empiric antimicrobial therapy for bacteremia of long-term hemodialysis (HD) outpatients is currently based on the combination of vancomycin and gentamicin because of the high frequency of isolated Staphylococcus species. The vancomycin trough level range from 15 to 20 mcg/mL is expected for therapeutic success against methicillin-resistant Staphylococcus aureus with vancomycin minimum inhibitory concentration (MIC) ≥1.0 mcg/mL. Despite the availability of clinical practice guidelines for vancomycin therapeutic drug monitoring, these target serum concentrations are not reached in many patients. In this study, the authors investigated the vancomycin trough levels in 20 HD patients with S. aureus bacteremia and the antimicrobial susceptibility pattern of 45 S. aureus strains isolated from 45 HD patients. The vancomycin serum concentration was determined by chemiluminescent assay. The MIC was determined by broth microdilution method. None of the HD patients included in this study had vancomycin trough concentrations within the therapeutic range. Also, the vancomycin MIC for most methicillin-sensitive S. aureus isolated from bacteremia was ≥1.0 mcg/mL. The therapeutic range of vancomycin was not achieved, and vancomycin MIC was surprisingly high in methicillin-sensitive S. aureus.

Association between single trough-based area under the curve estimation of vancomycin and treatment outcome among methicillin-resistant Staphylococcus aureus bacteremia patients.

Failure of antibiotic treatment increases mortality of critically ill patients. This study investigated the association between the treatment resolution of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and vancomycin pharmacokinetic variables. A total of 28 critically ill patients were included in this study. All data were collected from medical, microbiology and pharmacokinetic records. The clinical response was evaluated on the basis of clinical and microbiological parameters. The 24-h area under the curve (AUC<SUB>0-24</SUB>) was estimated from a single trough level using established equations. Out of the 28 patients, 46% were classified as responders to vancomycin treatment. The trough vancomycin concentration did not differ between the responders and non-responders (15.02 ± 6.16 and 14.83 ± 4.80 μg mL^-1; P = 0.929). High vancomycin minimum inhibitory concentration (MIC) was observed among the non-responders (P = 0.007). The ratio between vancomycin trough concentration and vancomycin MIC was significantly lower in the non-responder group (8.76 ± 3.43 vs. 12.29 ± 4.85 μg mL^-1; P = 0.034). The mean ratio of estimated AUC<SUB>0-24</SUB> and vancomycin MIC was 313.78 ± 117.17 μg h mL^-1 in the non-responder group and 464.44 ± 139.06 μg h mL^-1 in the responder group (P = 0.004). AUC<SUB>0-24</SUB>/MIC of ≥ 400 μg h mL^-1 was documented for 77% of the responders and 27% of the non-responders (c² = 7.03; P = 0.008). Ratio of trough concentration/MIC and AUC<SUB>0-24</SUB>/MIC of vancomycin are better predictors for MRSA treatment outcomes than trough vancomycin concentration or AUC<SUB>0-24</SUB> alone. The single trough-based estimated AUC may be sufficient for the monitoring of treatment response with vancomycin.

A randomized phase 2B trial of vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations \u2013 results of a prematurely terminated study

BackgroundStudies have suggested the reduced effectiveness of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections with high vancomycin minimum inhibitory concentrations. Alternative agents such as daptomycin may be considered. We conducted a randomized controlled study comparing daptomycin against vancomycin in the treatment of MRSA bloodstream infections with high vancomycin minimum inhibitory concentrations.MethodsPatients were randomized to receive vancomycin or daptomycin for a minimum of 14 days. The primary end point was the rate of all-cause mortality at day 60.ResultsA total of 14 patients were randomized in this study, with 7 patients in each treatment arm. The study was terminated early due to slow patient accrual. At day 60, there was one death in the vancomycin arm and none in the daptomycin arm. The median time to microbiological clearance was 4 days in both arms (IQR 3–5 days in the vancomycin arm and 3–7 days in daptomycin arm). Only one patient in the vancomycin arm had recurrence of bacteremia. Rates of adverse events were similar in both arms. There was one case of musculoskeletal toxicity and one case of drug-related nephrotoxicity - both events occurred in the daptomycin arm. None of the patients in either treatment arm required cessation of study treatment or addition of a second anti-MRSA agent because of worsening infection.ConclusionBased on the limited number of patients evaluated in this study, it remains unclear if alternative, more expensive agents such as daptomycin are superior to vancomycin in the treatment of high vancomycin minimum inhibitory concentration MRSA bloodstream infections. More studies are urgently needed but investigators may wish to consider employing novel, alternative trial methodologies to ensure a greater chance of success.Trial registrationClinicalTrials.gov, NCT01975662. Registered on 5 November 2013.

Vancomycin and daptomycin minimum inhibitory concentrations as a predictor of outcome of methicillin-resistant Staphylococcus aureus bacteraemia.

The aim of this study was to determine the persistence of the adverse prognostic effect of elevated vancomycin minimum inhibitory concentration (MIC) in methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in a setting with low vancomycin use. A retrospective study focusing on episodes of bacteraemia due to MRSA diagnosed from January 2010 through December 2015 was designed. The main outcome measures were 30-day mortality and treatment failure. Multivariate logistic regression analysis was used to identify variables associated with patient mortality and treatment outcome. In total, 79 MRSA bacteraemia episodes were included. The vancomycin MIC was >1.0μg/mL in 53 episodes (67.1%). The presence of high vancomycin MIC was not associated with a higher mortality rate or treatment success. A daptomycin MIC≥0.5μg/mL was present in 16 (26.2%) of 61 episodes for which the daptomycin MIC was obtained and was associated with 30-day mortality in the multivariate analysis (odds ratio=4.72, 95% confidence interval 1.19-18.71). None of the antimicrobials used were associated with a lower risk of treatment failure or mortality. The pernicious effect of high vancomycin MIC disappears in the absence of a predominant use of this antibiotic. However, a high daptomycin MIC in MRSA bacteraemia is associated with higher mortality in patients with bacteraemia, irrespective of antimicrobial treatment choice.

No effect of vancomycin MIC ≥ 1.5 mg/L on treatment outcome in methicillin-susceptible Staphylococcus aureus bacteraemia

The vancomycin minimum inhibitory concentration (MIC) has been shown to affect the outcome of methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. In this study, the outcomes of patients with MSSA bacteraemia with a vancomycin MIC ≥ 1.5 mg/L were assessed. A prospective cohort of patients with MSSA bacteraemia in two tertiary-care hospitals was collected. The vancomycin MIC was determined by Etest. Staphylococcus aureus strains were categorised as low (<1.5 mg/L) or high (≥1.5 mg/L) vancomycin MIC. First- and second-line treatments were recorded and classified as optimal, appropriate and inappropriate. The primary endpoint was 30-day mortality. A total of 250 patients with S. aureus bacteraemia were analysed, of whom 64 (25.6%) had strains with a high vancomycin MIC. History of dialysis (P = 0.001) and ultimately fatal disease (P = 0.005) were associated with strains with a high vancomycin MIC. The 30-day mortality was 24.7% (46/186) in patients with a low vancomycin MIC versus 28.1% (18/64) in patients with a high vancomycin MIC (P = 0.592) and did not differ significantly after adjustment for the appropriateness of the antibiotic treatment. Patients with a high vancomycin MIC were less frequently associated with complicated bacteraemia (15.6% vs. 39.2%; P = 0.001). In conclusion, vancomycin MIC ≥ 1.5 mg/L was not associated with 30-day mortality but was associated with uncomplicated bacteraemia in MSSA bacteraemia, regardless of the first- and second-line treatment.

Predictors of Adverse Outcomes in Children With Staphylococcus aureus Bacteremia.

Staphylococcus aureus bacteremia is a common infection, associated with significant morbidity and mortality in children. Factors associated with adverse treatment outcomes are poorly understood in the pediatric population. Our study compared clinical and microbiologic characteristics of children admitted during a 5-year period (2007-2012) to a large university-based hospital and found to have S aureus bacteremia with outcome measures, in order to identify risk factors associated with treatment failure (defined as 30-day mortality, delayed microbiologic resolution, or recurrence of S aureus bacteremia within 60 days of completing effective antibiotic therapy). In all, 71 patients were found to have S aureus bacteremia, and of these, 17 patients (24%) experienced treatment failure. Based on the logistic regression model, only high vancomycin minimum inhibitory concentration in combination with a high-risk source of infection (i.e., infected graft or device, intra-abdominal infection, or respiratory tract infection) was significantly associated with risk of treatment failure. Infection associated with a high-risk source may increase the chance of treatment failure in pediatric patients with S aureus bacteremia. Vancomycin minimum inhibitory concentration alone was not found to be a predictor of treatment outcomes.

Influence of vancomycin minimum inhibitory concentration on the outcome of methicillin-susceptible Staphylococcus aureus left-sided infective endocarditis treated with antistaphylococcal β-lactam antibiotics: a prospective cohort study by the International Collaboration on Endocarditis

ObjectivesLeft-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ≥1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (≥1.5 mg/L) phenotype. MethodsAll patients with left-sided MSSA infective endocarditis treated with antistaphylococcal β-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (≥1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype. ResultsSixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively). ConclusionsIn this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal β-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire.

Proportion of Staphylococcus aureus with a Vancomycin Minimum Inhibitory Concentration (MIC) of 1 mg/L Increases Between 2012 and 2017 in Singapore

Background Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA). Monte Carlo simulations in the literature suggest that vancomycin may not reach desired pharmacodynamic targets when typical dosing regimens are used to treat S. Aureus (SAU) with an MIC > 1 mg/L. Worse clinical outcomes have also been associated with methicillin-susceptible S. Aureus (MSSA) with higher vancomycin MICs, when treated with β-lactams.Methods Vancomycin MICs (VITEK 2) for SAU isolated from June 2012 to April 2017 were collated from the laboratory records at Tan Tock Seng Hospital, Singapore. Vancomycin MICs for MSSA are underrepresented as susceptibility tests for SAU isolated from blood are initially performed by direct disk diffusion. A reflex Vitek susceptibility is performed on MRSA but not MSSA blood isolates. All nonblood isolates are assessed by Vitek. Duplicates were removed.ResultsAll vancomycin MICs were within the susceptible range of ≤2 mg/L (Table 1). There was an overall temporal increase in proportions of both MRSA and MSSA isolates with an MIC 1 mg/L, from 9 to 30% and 14 to 37%, respectively. There was a reciprocal decrease in the proportion of isolates with MIC ≤ 0.5 mg/L (Figure 1). Proportions with MIC 2 mg/L showed a decreasing trend.Table 12012 (June–December)20132014201520162017 (January–April)MSSA isolates568972101110351152463 ≤0.5 mg/L437869802747833288 1 mg/L8390207282317173 2 mg/L48132622MRSA isolates513763753717633236 ≤0.5 mg/L414705631542544164 1 mg/L40371131698771 2 mg/L59219621These trends remained consistent when all SAU, both MSSA and MRSA together, were split into blood isolates and “other” groups (Figure 2).The data for MRSA bacteremia were analysed separately. The proportion with MIC 1 mg/L increased from 7% in 2012 to 27% in 2017. The proportion with MIC 2 mg/L decreased from 21% in 2012 to zero since 2016.Conclusion The proportion of Staphylococcus aureus isolates with an MIC of 1 mg/L increased more than threefold between 2012 and 2017. This trend is seen in both bloodstream and noninvasive isolates. As the proportion with MIC >1 mg/L has not increased, Monte Carlo simulations would suggest that clinical outcomes may not have been affected despite this upward creep.Disclosures All authors: No reported disclosures.

Determining vancomycin Etest MICs in patients with MRSA bloodstream infection does not support switching antimicrobials

Elevated vancomycin minimum inhibitory concentrations (MIC) have been reported to adversely affect clinical outcome in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). We therefore examined the association between vancomycin MIC and outcome considering various potential confounders. Clinical data and bacterial isolates were prospectively collected from patients with MRSA BSI from 2006 to 2012 as part of the Invasive Staphylococcus aureus Infection Cohort (INSTINCT) study. Antimicrobial susceptibility was assessed by Etest, broth microdilution (BMD) and VITEK 2. Bacterial genotypes were determined by spa typing. Using univariate and Cox regression analyses, we investigated the impact of low (≤1.0mg/L) and high (≥1.5mg/L) vancomycin Etest MIC on clinical outcomes. Ninety-one MRSA BSI episodes were included, of which 79 (86.8%) were caused by spa types t003, t032 and t045. High vancomycin MICs were seen only if using Etest but not confirmed using standard reference BMD. When episodes were stratified into low and high vancomycin Etest MIC groups, 30-day overall mortality was 34.5% and 27.3%, respectively (P=0.64, OR 0.71; 95% confidence interval [CI] 0.27-1.79). Variables significantly associated with all-cause mortality in the Cox model were age (P=0.003), acute physiology score (P=0.0006), and Charlson comorbidity index (P=0.018). Vancomycin MICs may vary dependent on testing methodologies and local MRSA epidemiology. The patients' underlying disease and individual comorbidities rather than elevated vancomycin MICs determine adverse clinical outcomes in MRSA BSI. Routine Etest MIC testing of MRSA isolates is of limited value for treatment decisions.

Methicillin-resistant Staphylococcus aureus infections: A review of the currently available treatment options.

This review is the result of discussions that took place at the 5th MRSA Working Group Consensus Meeting and explores the possible treatment options available for different types of infections due to methicillin-resistant Staphylococcus aureus (MRSA), focusing on those antibiotics that could represent a valid alternative to vancomycin. In fact, whilst vancomycin remains a viable option, its therapy is moving towards individualised dosing. Other drugs, such as the new lipoglycopeptides (oritavancin, dalbavancin and telavancin) and fifth-generation cephalosporins (ceftaroline and ceftobiprole), are showing good in vitro potency and in vivo efficacy, especially for patients infected with micro-organisms with higher vancomycin minimum inhibitory concentrations (MICs). Tedizolid is an attractive agent for use both in hospital and community settings, but the post-marketing data will better clarify its potential. Daptomycin and linezolid have shown non-inferiority to vancomycin in the treatment of MRSA bacteraemia and non-inferiority/superiority to vancomycin in the treatment of hospital-acquired pneumonia. Thus, several options are available, but more data from clinical practice, especially for invasive infections, are needed to assign specific roles to each antibiotic and to definitely include them in the new antibacterial armamentarium.

Epidemiology and microbiology of skin and soft tissue infections.

Skin and soft tissue infections (SSTIs) are a broad spectrum of diseases, including uncomplicated and complicated infections. Herein, we review the current epidemiology and microbiology of SSTIs. In the last decades, a significant growing trend of SSTIs both in the community and healthcare settings with a dramatic increase of the economic burden for these diagnoses was observed. Several observational studies found that SSTIs are a substantial cause of ambulatory and emergency department visits, and of hospitalizations. Although, microbiology of SSTIs changes according to the clinical feature and the severity of illness, Staphylococcus aureus being the leading cause of both uncomplicated infections and complicated infections. Moreover, the increasing prevalence of infections because of multidrug-resistant bacteria, mainly methicillin-resistant S. aureus (both community-acquired and healthcare-associated methicillin-resistant S. aureus), are associated with significantly increased morbidity, mortality, length of hospital stay, and costs, compared with infections because of susceptible strains. Moreover, although it is unclear whether high vancomycin minimum inhibitory concentration is associated with a worse outcome, it poses a further challenge for the clinicians. The understanding of the current epidemiology and microbiology of SSTIs is indicated for an appropriate antimicrobial therapy and an overall optimal management of SSTIs.

High vancomycin MICs within the susceptible range in Staphylococcus aureus bacteraemia isolates are associated with increased cell wall thickness and reduced intracellular killing by human phagocytes

Vancomycin minimum inhibitory concentrations (MICs) at the upper end of the susceptible range for Staphylococcus aureus have been associated with poor clinical outcomes of bloodstream infections. We tested the hypothesis that high vancomycin MICs in S. aureus bacteraemia isolates are associated with increased cell wall thickness and suboptimal bacterial internalisation or lysis by human phagocytes. In total, 95 isolates were evaluated. Original vancomycin MICs were determined by Etest. The susceptibility of S. aureus isolates to killing by phagocytes was assessed in a human whole blood assay. Internalisation of bacterial cells by phagocytes was investigated by flow cytometry. Cell wall thickness was evaluated by transmission electron microscopy. Genotypic analysis of S. aureus isolates was performed using a DNA microarray system. Vancomycin MICs were significantly higher (P=0.006) in isolates that were killed suboptimally (killing index <60%) compared with those killed efficiently (killing index >70%) and tended to correlate inversely (P=0.08) with the killing indices. Isolates in both killing groups were internalised by human neutrophils and monocytes with comparable efficiency. The cell wall was significantly thicker (P=0.03) in isolates in the low killing group. No genotypic differences were found between the isolates in both killing groups. In summary, high vancomycin MICs in S. aureus bacteraemia isolates were associated with increased cell wall thickness and reduced intracellular killing by phagocytes.