scholarly journals Prospective Comparison of the Clinical Impacts of Heterogeneous Vancomycin-Intermediate Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Susceptible MRSA

2009 ◽  
Vol 53 (8) ◽  
pp. 3447-3452 ◽  
Author(s):  
K. C. Horne ◽  
B. P. Howden ◽  
E. A. Grabsch ◽  
M. Graham ◽  
P. B. Ward ◽  
...  

ABSTRACT Although methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin (RVS-MRSA; including vancomycin-intermediate S. aureus [VISA] and heterogeneous VISA [hVISA]) have been linked with vancomycin treatment failure, it is unclear whether they are more pathogenic than vancomycin-susceptible MRSA (VS-MRSA). We prospectively assessed patients with clinical MRSA isolates during a 10-month period to determine clinical status (infection versus colonization) and therapeutic outcome before correlating these findings with the results of detailed in vitro assessment of vancomycin susceptibility, including population analysis profile (PAP) testing. hVISA and VISA were defined by standard PAP criteria (area-under-the-curve ratio compared to that of the reference hVISA strain Mu3 [≥0.9]) and routine CLSI criteria (vancomycin MIC, 4 to 8 μg/ml), respectively. Among the 117 patients assessed, 58 had RVS-MRSA isolates (56 hVISA and 2 VISA) and 59 had VS-MRSA isolates; the patient demographics and comorbidities were similar. RVS-MRSA was associated with a lower rate of infection than VS-MRSA (29/58 versus 46/59; P = 0.003), including a lower rate of bacteremia (3/58 versus 20/59, respectively; P < 0.001). The cure rates in RVS-MRSA and VS-MRSA groups were not statistically different (16/26 versus 31/42; P = 0.43), but the post hoc assessment of treatment regimes and study size made detailed conclusions difficult. The results of the macro method Etest correlated well with the PAP results (sensitivity, 98.3%, and specificity, 91.5%), but broth microdilution and our preliminary RVS-MRSA detection method correlated poorly. All isolates were susceptible to linezolid and daptomycin. These data suggest that detailed prospective laboratory identification of RVS-MRSA isolates may be of limited value and that, instead, such in vitro investigation should be reserved for isolates from patients who are failing appropriate anti-MRSA therapy.

2015 ◽  
Vol 59 (8) ◽  
pp. 4497-4503 ◽  
Author(s):  
Katie E. Barber ◽  
Jordan R. Smith ◽  
Cortney E. Ireland ◽  
Blaise R. Boles ◽  
Warren E. Rose ◽  
...  

ABSTRACTAnnually, medical device infections are associated with >250,000 catheter-associated bloodstream infections (CLABSI), with up to 25% mortality.Staphylococcus aureus, a primary pathogen in these infections, is capable of biofilm production, allowing organism persistence in harsh environments, offering antimicrobial protection. With increases inS. aureusisolates with reduced susceptibility to current agents, ceftaroline (CPT) offers a therapeutic alternative. Therefore, we evaluated whether CPT would have a role against biofilm-producing methicillin-resistantS. aureus(MRSA), including those with decreased susceptibilities to alternative agents. In this study, we investigated CPT activity alone or combined with daptomycin (DAP) or rifampin (RIF) against 3 clinical biofilm-producing MRSA strains in anin vitrobiofilm pharmacokinetic/pharmacodynamic (PK/PD) model. Simulated antimicrobial regimens were as follows: 600 mg of CPT every 8 h (q8h) (free maximum concentration of drug [fCmax], 17.04 mg/liter; elimination half-life [t1/2], 2.66 h), 12 mg/kg of body weight/day of DAP (fCmax, 14.7 mg/liter;t1/2, 8 h), and 450 mg of RIF q12h (fCmax, 3.5 mg/liter;t1/2, 3.4 h), CPT plus DAP, and CPT plus RIF. Samples were obtained and plated to determine colony counts. Differences in log10CFU/cm2were evaluated by analysis of variance with Tukey'spost hoctest. The strains were CPT and vancomycin susceptible and DAP nonsusceptible (DNS). CPT displayed activity throughout the experiment. DAP demonstrated initial activity with regrowth at 24 h in all strains. RIF was comparable to the drug-free control, and little benefit was observed when combined with CPT. CPT plus DAP displayed potent activity, with an average log10CFU/cm2reduction of 3.33 ± 1.01 from baseline. CPT demonstrated activity against biofilm-producing DNS MRSA. CPT plus DAP displayed therapeutic enhancement over monotherapy, providing a potential option for difficult-to-treat medical device infections.


2013 ◽  
Vol 57 (6) ◽  
pp. 2451-2456 ◽  
Author(s):  
Alasdair P. MacGowan ◽  
Alan R. Noel ◽  
Sharon Tomaselli ◽  
Karen E. Bowker

ABSTRACTAnin vitrosingle-compartment dilutional pharmacokinetic model was used to study the pharmacodynamics of ceftaroline againstStaphylococcus aureus(both methicillin-susceptibleS. aureus[MSSA] and methicillin-resistantS. aureus[MRSA]). Mean serum free concentrations of ceftaroline (the active metabolite of the prodrug ceftaroline fosamil) dosed in humans at 600 mg every 12 h (q12h) were simulated, and activities against 12S. aureusstrains (3 MSSA strains and 9 MRSA strains, 3 of which had a vancomycin-intermediate phenotype) were determined. Ceftaroline produced 2.5- to 4.0-log10-unit reductions in viable counts by 24 h with all strains and a 0.5- to 4.0-log-unit drop in counts at 96 h. The antibacterial effect could not be related to the strain MIC across the ceftaroline MIC range from 0.12 to 2.0 μg/ml. In dose-ranging studies, the cumulative percentage of a 24-h period that the free drug concentration exceeded the MIC under steady-state pharmacokinetic conditions (fTMIC) of 24.5% ± 8.9% was associated with a 24-h bacteriostatic effect, one of 27.8% ± 9.5% was associated with a −1-log-unit drop, and one of 32.1% ± 8.1% was associated with a −2-log-unit drop. The MSSA and MRSA strains had similarfTMICvalues.fTMICvalues increased with increasing duration of exposure up to 96 h. Changes in ceftaroline population analysis profiles were related tofTMIC.fTMICs of <50% were associated with growth on 4× MIC recovery plates at 96 h of drug exposure. These data support the use of ceftaroline fosamil at doses of 600 mg q12h to treatS. aureusstrains with MICs of ≤2 μg/ml. AnfTMICof 25 to 30% would make a suitable pharmacodynamic index target, butfTMICvalues of ≥50% are needed to suppress the emergence of resistance and require clinical evaluation.


2015 ◽  
Vol 9 (02) ◽  
pp. 157-164 ◽  
Author(s):  
Sujintana Wongthong ◽  
Karnjana Dutchanutouch ◽  
Viladda Namsaengkang ◽  
Aroonwadee Chanawong ◽  
Chotechana Wilailuckana ◽  
...  

Introduction: Detection of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is currently problematic. Although the population analysis profile with area under the curve (PAP-AUC) is the gold standard for detecting hVISA strains, this method is time consuming. This study aimed to induce vancomycin non-susceptible Staphylococcus aureus isolates in methicillin-resistant S. aureus (MRSA) and to determine the performance of the vancomycin and teicoplanin disk diffusion test for screening of induced and natural vancomycin non-susceptible isolates. Methodology: Vancomycin resistance was induced in vitro in methicillin-resistant S. aureus by serial passage in media with increasing vancomycin concentrations. All test isolates were confirmed for their susceptibility to vancomycin by using a PAP-AUC method. The performance of the vancomycin and teicoplanin disk diffusion test for detecting both induced and natural hVISA/VISA isolates was analyzed using the MedCal program version 10.2.0. Results: The induction test revealed that 42 of 78 MRSA isolates (53.8%) became hVISA and/or VISA. Using 10, 15, 20, 30 µg vancomycin disks and a 30 µg teicoplanin disk, the highest performance (88.9%) for hVISA/VISA detection (71.1%, sensitivity, 100% specificity, 100% positive predictive value, and 75% negative predictive value) was obtained when a 20 µg vancomycin disk was used at 1.0 McFarland inoculum for a 24-hour incubation. Conclusions: The results indicated that using a 20 µg vancomycin disk and bacterial inoculum of 1.0 McFarland is simple to perform and provides a primary result for hVISA/VISA screening within 24 hours.


Open Medicine ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 475-486 ◽  
Author(s):  
Jia Xu ◽  
Long Pang ◽  
Xiao Xue Ma ◽  
Jian Hu ◽  
Yuan Tian ◽  
...  

AbstractVancomycin has been the primary agent used to treat serious Methicillin-resistantStaphylococcus aureus(MRSA) infection for many years. However, the rise of MRSA infection rates and the extensive use of vancomycin have led to the emergence of reduced vancomycin susceptibility. Therefore, four typicalStaphylococcus aureus(S. aureus)strains from different clinical specimens were derivated by vancomycin in vitro to better clarify their phenotypic and molecular characteristics. Some experiments, such as stepwise selection of vancomycin-resistant strains, pulsed-field gel electrophoresis (PFGE), antimicrobial susceptibility test, population analysis profile-area under the curve (PAP-AUC), molecular typing, transmission electron microscopy, δ-hemolysin expression, autolysis assay, biofilm assay and quantitative real-time polymerase chain reaction (qPCR) for gene expression were carried out to compare the derivated bacteria with their parental strains. Results showed that the observed phenotypes of vancomycin-resistant strains such as hemolysin, autolysis and biofilm significantly reduced, which were associated with vancomycin resistance capability of the selected strain. The changes of phenotype and regulatory genes expression were inversely proportional to the vancomycin minimum inhibitory concentration (MICvan). Most heterogeneous vancomycin intermediateStaphylococcus aureus(hVISA) or VISA strains belonged tospatype t570 andagrgroup II. In summary, the clinical isolated vancomycin susceptibleStaphylococcus aureus(VSSA), hVISA and VISA could be derivated into high vancomycin-resistant VISA in vitro, but it was difficult for them to develop into vancomycin resistantStaphylococcus aureus(VRSA). VISA and hVISA could gradually adapt to the environment with the vancomycin concentration that continuously elevates.


2011 ◽  
Vol 55 (7) ◽  
pp. 3522-3526 ◽  
Author(s):  
Molly Steed ◽  
Celine Vidaillac ◽  
Michael J. Rybak

ABSTRACTThe objective of this study was to investigate the potential role of ceftaroline, a new broad-spectrum cephalosporin, as a therapeutic option for the treatment of daptomycin-nonsusceptible (DNS) methicillin-resistantStaphylococcus aureus(MRSA) infections. Four clinical DNS MRSA strains, R5717, R5563, R5996 (heteroresistant vancomycin-intermediateS. aureus) and R5995 (vancomycin-intermediateS. aureus) were evaluated in a two-compartment hollow-fiberin vitropharmacokinetic/pharmacodynamic model at a starting inoculum of 107CFU/ml for 96 h. Simulated regimens were ceftaroline at 600 mg every 12 h (q12h) (maximum free-drug concentration [fCmax], 15.2 μg/ml; serum half-life [t1/2], 2.3 h), daptomycin at 6 mg/kg q24h (fCmax, 7.9 μg/ml;t1/2, 8 h), and daptomycin at 10 mg/kg q24h (fCmax, 15.2 μg/ml;t1/2, 8 h). Differences in CFU/ml between 24 and 96 h were evaluated by analysis of variance with Tukey's post-hoc test. Bactericidal activity was defined as a ≥3-log10CFU/ml decrease in the colony count from the initial inoculum. The ceftaroline MIC values were 0.25, 0.5, 0.5, and 0.5 μg/ml, and the daptomycin MIC values were 2, 2, 4, and 4 μg/ml for R5717, R5563, R5996, and R5995, respectively. Ceftaroline displayed sustained bactericidal activity against 3 of the 4 strains at 96 h (R5717, −3.1 log10CFU/ml; R5563, −2.5 log10CFU/ml; R5996, −5.77 log10CFU/ml; R5995, −6.38 log10CFU/ml). Regrowth occurred during the daptomycin at 6-mg/kg q24h regimen (4 strains) and the daptomycin at 10-mg/kg q24h regimen (3 strains). At 96 h, ceftaroline was significantly more active, resulting in CFU/ml counts lower than those obtained with daptomycin at 6 mg/kg q24h (4 strains,P≤ 0.008) and daptomycin at 10 mg/kg q24 h (3 strains,P≤ 0.001). Isolates with increased MIC values for daptomycin (all 4 strains) but not for ceftaroline were recovered. Ceftaroline was effective against the 4 isolates tested and may provide a clinical option for the treatment of DNS MRSA infections.


Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 869
Author(s):  
Beatriz Müller Nunes Souza ◽  
Juliana Guerra Pinto ◽  
André Henrique Correia Pereira ◽  
Alejandro Guillermo Miñán ◽  
Juliana Ferreira-Strixino

Staphylococccus aureus is a ubiquitous and opportunistic bacteria associated with high mortality rates. Antimicrobial photodynamic therapy (aPDT) is based on the application of a light source and a photosensitizer that can interact with molecular oxygen, forming Reactive Oxygen Species (ROS) that result in bacterial inactivation. This study aimed to analyze, in vitro, the action of aPDT with Photodithazine® (PDZ) in methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains. The strains were incubated with PDZ at 25, 50, 75, and 100 mg/L for 15 min and irradiated with fluences of 25, 50, and 100 J/cm2. The internalization of PDZ was evaluated by confocal microscopy, the bacterial growth by counting the number of colony-forming units, as well as the bacterial metabolic activity post-aPDT and the production of ROS. In both strains, the photosensitizer was internalized; the production of ROS increased when the aPDT was applied; there was a bacterial reduction compared to the control at all the evaluated fluences and concentrations; and, in most parameters, it was obtained complete inactivation with significant difference (p < 0.05). The implementation of aPDT with PDZ in clinical strains of S. aureus has resulted in its complete inactivation, including the MRSA strains.


2015 ◽  
Vol 53 (11) ◽  
pp. 3543-3546 ◽  
Author(s):  
Riad Khatib ◽  
Kathleen Riederer ◽  
Mamta Sharma ◽  
Stephen Shemes ◽  
Sugantha P. Iyer ◽  
...  

BHI agars supplemented with vancomycin 4 (BHI-V4) and 3 (BHI-V3) mg/liter have been proposed for screening vancomycin intermediately susceptibleStaphylococcus aureus(VISA) and heteroresistant (hVISA) phenotypes, respectively, but growth interpretation criteria have not been established. We reviewed the growth results (CFU) during population analysis profile-area under the curve (PAP-AUC) of consecutive methicillin-resistantStaphylococcus aureus(MRSA) blood isolates, which were saved intermittently between 1996 and 2012. CFU counts on BHI-V4 and BHI-V3 plates were stratified according to PAP-AUC interpretive criteria: <0.90 (susceptible [S-MRSA]), 0.90 to 1.3 (hVISA), and >1.3 (VISA). CFU cutoffs that best predict VISA and hVISA were determined with the use of receiver operating characteristic (ROC) curves. Mu3, Mu50, and methicillin-susceptibleS. aureus(MSSA) controls were included. We also prospectively evaluated manufacturer-made BHI-V3/BHI-V4 biplates for screening of 2010-2012 isolates. The PAP-AUC of 616 clinical samples was consistent with S-MRSA, hVISA, and VISA in 550 (89.3%), 48 (7.8%), and 18 (2.9%) instances, respectively. For VISA screening on BHI-V4, a cutoff of 2 CFU/droplet provided 100% sensitivity and 97.7% specificity. To distinguish VISA from hVISA, a cutoff of 16 CFU provided 83.3% sensitivity and 94.7% specificity; the specificity was lowered to 89.5% with a 12-CFU cutoff. For detecting hVISA/VISA on BHI-V3, a 2-CFU/droplet cutoff provided 98.5% sensitivity and 93.8% specificity. These results suggest that 2-CFU/droplet cutoffs on BHI-V4 and BHI-V3 best approximate VISA and hVISA gold standard confirmation, respectively, with minimal overlap in samples with borderline PAP-AUC. Simultaneous screening for VISA/hVISA on manufacturer-made BHI-V4/BHI-V3 biplates is easy to standardize and may reduce the requirement for PAP-AUC confirmation.


2003 ◽  
Vol 47 (3) ◽  
pp. 923-931 ◽  
Author(s):  
Takaji Fujimura ◽  
Yoshinori Yamano ◽  
Isamu Yoshida ◽  
Jingoro Shimada ◽  
Shogo Kuwahara

ABSTRACT The in vitro antibacterial activity of S-3578, a new parenteral cephalosporin, against clinical isolates was evaluated. The MICs of the drug at which 90% of the isolates were inhibited were 4 μg/ml for methicillin-resistant Staphylococcus aureus (MRSA) and 2 μg/ml for methicillin-resistant Staphylococcus epidermidis, which were fourfold higher than and equal to those of vancomycin, respectively. The anti-MRSA activity of S-3578 was considered to be due to its high affinity for penicillin-binding protein 2a (50% inhibitory concentration, 4.5 μg/ml). In time-kill studies with 10 strains each of MRSA and methicillin-susceptible S. aureus, S-3578 caused more than a 4-log10 decrease of viable cells on the average at twice the MIC after 24 h of exposure, indicating that it had potent bactericidal activity. Furthermore, in population analysis of MRSA strains with heterogeneous or homogeneous resistance to imipenem, no colonies emerged from about 109 cells on agar plates containing twice the MIC of S-3578, suggesting the low frequency of emergence of S-3578-resistant strains from MRSA. S-3578 was also highly active against penicillin-resistant Streptococcus pneumoniae (PRSP), with a MIC90 of 1 μg/ml, which was comparable to that of ceftriaxone. S-3578 also had antibacterial activity against a variety of gram-negative bacteria including Pseudomonas aeruginosa, though its activity was not superior to that of cefepime. In conclusion, S-3578 exhibited a broad antibacterial spectrum and, particularly, had excellent activity against gram-positive bacteria including methicillin-resistant staphylococci and PRSP. Thus, S-3578 was considered to be worthy of further evaluation.


2009 ◽  
Vol 53 (9) ◽  
pp. 3642-3649 ◽  
Author(s):  
Wenjia Sun ◽  
Hongbin Chen ◽  
Yudong Liu ◽  
Chunjiang Zhao ◽  
Wright W. Nichols ◽  
...  

ABSTRACT The prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) among 1,012 vancomycin-susceptible methicillin (meticillin)-resistant S. aureus isolates collected from 14 cities in China from 2005 to 2007 was 13 to 16%, as determined by a combination of (i) measurement by the modified population analysis profile-area under the curve method (PAP-AUC) and (ii) estimation from the measured sensitivity and specificity of a screening method. Two hundred isolates from blood were chosen as a subset for measurement of the sensitivities and the specificities of several previously described screening methods by using the results of PAP-AUC as the reference. During this testing, one isolate was found to be a vancomycin-intermediate S. aureus (VISA) strain so was not used in the evaluation of the screening tests. Of the other 199 isolates, 26 (13.1%) were hVISA, as assessed by PAP-AUC. A screening cascade of culturing the isolates on brain heart infusion agar containing teicoplanin (5 mg/liter) and then subjecting the positive isolates to a macro-Etest method was applied to the 812 non-blood isolates, yielding 149 positive results. From these results and by adjusting for sensitivity (0.423) and specificity (0.861), the prevalence was estimated to be 15.7%. The precision of that estimate was assessed by reapplying the screening cascade to 120 randomly selected isolates from the 812 non-blood isolates and simultaneously determining their heterogeneous vancomycin-intermediate susceptibility status by PAP-AUC. Because PAP-AUC is impractical for use with large numbers of isolates, the screening-based estimation method is useful as a first approximation of the prevalence of hVISA. Of the 27 VISA or hVISA isolates from blood, 22.2% and 74.1% were staphylococcal chromosome cassette mec types II and III, respectively, while 77.8% and 22.2% were agr type 1 and agr type 2, respectively; the MIC ranges were 0.5 to 4 mg/liter for vancomycin and 0.25 to 1 mg/liter for daptomycin.


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