Vancomycin MICs did not creep in Staphylococcus aureus isolates from 2002 to 2006 in a setting with low vancomycin usage

ABSTRACT A series of 12 Staphylococcus aureus strains of various genetic backgrounds, methicillin resistance levels, and autolytic activities were subjected to selection for the glycopeptide-intermediate S. aureus (GISA) susceptibility phenotype on increasing concentrations of vancomycin. Six strains acquired the phenotype rapidly, two did so slowly, and four failed to do so. The vancomycin MICs for the GISA strains ranged from 4 to 16 μg/ml, were stable to 20 nonselective passages, and expressed resistance homogeneously. Neither ease of acquisition of the GISA phenotype nor the MIC attained correlated with methicillin resistance hetero- versus homogeneity or autolytic deficiency or sufficiency. Oxacillin MICs were generally unchanged between parent and GISA strains, although the mec members of both isogenic methicillin-susceptible and methicillin-resistant pairs acquired the GISA phenotype more rapidly and to higher MICs than did their susceptible counterparts. Transmission electron microscopy revealed that the GISA strains appeared normal in the absence of vancomycin but had thickened and diffuse cell walls when grown with vancomycin at one-half the MIC. Common features among GISAs were reduced doubling times, decreased lysostaphin susceptibilities, and reduced whole-cell and zymographic autolytic activities in the absence of vancomycin. This, with surface hydrophobicity differences, indicated that even in the absence of vancomycin the GISA cell walls differed from those of the parents. Autolytic activities were further reduced by the inclusion of vancomycin in whole-cell and zymographic studies. The six least vancomycin-susceptible GISA strains exhibited an increased capacity to remove vancomycin from the medium versus their parent lines. This study suggests that while some elements of the GISA phenotype are strain specific, many are common to the phenotype although their expression is influenced by genetic background. GISA strains with similar glycopeptide MICs may express individual components of the phenotype to different extents.

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Antibiotic Resistance and Virulence Gene Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolated from Healthy Edible Marine Fish

International Journal of Microbiology ◽

10.1155/2020/9803903 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Justine Fri ◽

Henry A. Njom ◽

Collins N. Ateba ◽

Roland N. Ndip

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Marine Fish ◽

Control Strategies ◽

Virulence Gene ◽

Multidrug Resistant ◽

Methicillin Resistant ◽

Vancomycin Mics ◽

Resistant Strains ◽

Mrsa Strains

Thirty-three (33) isolates of methicillin-resistant Staphylococcus aureus (MRSA) from healthy edible marine fish harvested from two aquaculture settings and the Kariega estuary, South Africa, were characterised in this study. The phenotypic antimicrobial susceptibility profiles to 13 antibiotics were determined, and their antibiotic resistance determinants were assessed. A multiplex PCR was used to determine the epidemiological groups based on the type of SCCmec carriage followed by the detection of staphylococcal enterotoxin-encoding genes sea-sed and the Panton Valentine leucocidin gene (pvl). A high antibiotic resistance percentage (67–81%) was observed for Erythromycin, Ampicillin, Rifampicin, and Clindamycin, while maximum susceptibility to Chloramphenicol (100%), Imipenem (100%), and Ciprofloxacin (94%) was recorded. Nineteen (58%) of the MRSA strains had Vancomycin MICs of ≤2 μg/mL, 4 (12%) with MICs ranging from 4–8 μg/mL, and 10 (30%) with values ≥16 μg/mL. Overall, 27 (82%) isolates were multidrug-resistant (MDR) with Erythromycin-Ampicillin-Rifampicin-Clindamycin (E-AMP-RIP-CD) found to be the dominant antibiotic-resistance phenotype observed in 4 isolates. Resistance genes such as tetM, tetA, ermB, blaZ, and femA were detected in two or more resistant strains. A total of 19 (58%) MRSA strains possessed SCCmec types I, II, or III elements, characteristic of healthcare-associated MRSA (HA-MRSA), while 10 (30%) isolates displayed SCCmec type IVc, characteristic of community-associated MRSA (CA-MRSA). Six (18%) of the multidrug-resistant strains of MRSA were enterotoxigenic, harbouring the see, sea, or sec genes. A prevalence of 18% (6/33) was also recorded for the luk-PVL gene. The findings of this study showed that marine fish contained MDR-MRSA strains that harbour SCCmec types, characteristic of either HA-MRSA or CA-MRSA, but with a low prevalence of enterotoxin and pvl genes. Thus, there is a need for continuous monitoring and implementation of better control strategies within the food chain to minimise contamination of fish with MDR-MRSA and the ultimate spread of the bug.

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Vancomycin In Vitro Bactericidal Activity and Its Relationship to Efficacy in Clearance of Methicillin-Resistant Staphylococcus aureus Bacteremia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00939-06 ◽

2007 ◽

Vol 51 (7) ◽

pp. 2582-2586 ◽

Cited By ~ 173

Author(s):

Pamela A. Moise ◽

George Sakoulas ◽

Alan Forrest ◽

Jerome J. Schentag

Keyword(s):

Staphylococcus Aureus ◽

Median Time ◽

Bactericidal Activity ◽

Peak Plasma ◽

Plasma Concentrations ◽

Accessory Gene ◽

Vancomycin Therapy ◽

Methicillin Resistant ◽

Vancomycin Mics

ABSTRACT We examined the relationship between the time to clearance of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia while patients were receiving vancomycin therapy and the in vitro bactericidal activity of vancomycin. Vancomycin killing assays were performed with 34 MRSA bloodstream isolates (17 accessory gene regulator group II [agr-II] and 17 non-agr-II isolates) from 34 different patients with MRSA bacteremia for whom clinical and microbiological outcomes data were available. Vancomycin doses were prospectively adjusted to achieve peak plasma concentrations of 28 to 32 μg/ml and trough concentrations of 8 to 12 μg/ml. Bactericidal assays were performed over 24 h with ∼107 to 108 CFU/ml in broth containing 16 μg/ml vancomycin. The median time to clearance of bacteremia was 6.5 days for patients with MRSA isolates demonstrating ≥2.5 reductions in log10 CFU/ml at 24 h and >10.5 days for patients with MRSA isolates demonstrating <2.5 log10 CFU/ml by 24 h (P = 0.025). The median time to clearance was significantly longer with MRSA isolates with vancomycin MICs of 2.0 μg/ml compared to that with MRSA isolates with MICs of ≤1.0 μg/ml (P = 0.019). The bacteremia caused by MRSA isolates with absent or severely reduced delta-hemolysin expression was of a longer duration of bacteremia (10 days and 6.5 days, respectively; P = 0.27) and had a decreased probability of eradication (44% and 78%, respectively; P = 0.086). We conclude that strain-specific microbiological features of MRSA, such as increased vancomycin MICs and decreased killing by vancomycin, appear to be predictive of prolonged MRSA bacteremia while patients are receiving vancomycin therapy. Prolonged bacteremia and decreased delta-hemolysin expression may also be related. Evaluation of these properties may be useful in the consideration of antimicrobial therapies that can be used as alternatives to vancomycin for the treatment of MRSA bacteremia.

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Outcomes with daptomycin in the treatment of Staphylococcus aureus infections with a range of vancomycin MICs

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkq200 ◽

2010 ◽

Vol 65 (8) ◽

pp. 1784-1791 ◽

Cited By ~ 22

Author(s):

J. A. Crompton ◽

D. S. North ◽

M. Yoon ◽

J. N. Steenbergen ◽

K. C. Lamp ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Vancomycin Mics

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Comparative Efficacies of Human Simulated Exposures of Telavancin and Vancomycin against Methicillin-Resistant Staphylococcus aureus with a Range of Vancomycin MICs in a Murine Pneumonia Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00062-10 ◽

2010 ◽

Vol 54 (12) ◽

pp. 5115-5119 ◽

Cited By ~ 36

Author(s):

Jared L. Crandon ◽

Joseph L. Kuti ◽

David P. Nicolau

Keyword(s):

Staphylococcus Aureus ◽

Bacterial Load ◽

Infection Model ◽

Time Curve ◽

Unbound Fraction ◽

Methicillin Resistant ◽

Vancomycin Mics ◽

Mrsa Strains

ABSTRACT Telavancin displays potent in vitro and in vivo activity against methicillin-resistant Staphylococcus aureus (MRSA), including strains with reduced susceptibility to vancomycin. We compared the efficacies of telavancin and vancomycin against MRSA strains with vancomycin MICs of ≥1 μg/ml in a neutropenic murine lung infection model. Thirteen clinical MRSA isolates (7 vancomycin-susceptible, 2 vancomycin-heteroresistant [hVISA], and 4 vancomycin-intermediate [VISA] isolates) were tested after 24 h, and 7 isolates (1 hVISA and 4 VISA isolates) were tested after 48 h of exposure. Mice were administered subcutaneous doses of telavancin at 40 mg/kg of body weight every 12 h (q12h) or of vancomycin at 110 mg/kg q12h; doses were designed to simulate the area under the concentration-time curve for the free, unbound fraction of drug (fAUC) observed for humans given telavancin at 10 mg/kg q24h or vancomycin at 1 g q12h. Efficacy was expressed as the 24- or 48-h change in lung bacterial density from pretreatment counts. At dose initiation, the mean bacterial load was 6.16 ± 0.26 log10 CFU/ml, which increased by averages of 1.26 ± 0.55 and 1.74 ± 0.68 log in untreated mice after 24 and 48 h, respectively. At both time points, similar CFU reductions were noted for telavancin and vancomycin against MRSA, with vancomycin MICs of ≤2 μg/ml. Both drugs were similarly efficacious after 24 and 48 h of treatment against the hVISA strains tested. Against VISA isolates, telavancin reduced bacterial burdens significantly more than vancomycin for 1 of 4 isolates after 24 h and for 3 of 4 isolates after 48 h. These data support the potential utility of telavancin for the treatment of MRSA pneumonia caused by pathogens with reduced susceptibility to vancomycin.

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In VitroPharmacodynamics of Vancomycin and Cefazolin Alone and in Combination against Methicillin-Resistant Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05473-11 ◽

2011 ◽

Vol 56 (1) ◽

pp. 202-207 ◽

Cited By ~ 44

Author(s):

Mao Hagihara ◽

Dora E. Wiskirchen ◽

Joseph L. Kuti ◽

David P. Nicolau

Keyword(s):

Staphylococcus Aureus ◽

Combination Therapy ◽

Synergistic Effects ◽

Bacterial Density ◽

Bacterial Killing ◽

Methicillin Resistant ◽

Content Type ◽

Vancomycin Mics ◽

Time Kill

ABSTRACTPrevious studies employing time-kill methods have observed synergistic effects against methicillin-resistantStaphylococcus aureus(MRSA) when a β-lactam is combined with vancomycin. However, these time-kill studies have neglected the importance of human-simulated exposures. We evaluated the effect of human simulated exposures of vancomycin at 1 g every 8 h (q8h) in combination with cefazolin at 1 g q8h against various MRSA isolates. Four clinical isolates (two MRSA isolates [vancomycin MICs, 0.5 and 2.0 μg/ml], a heterogeneous vancomycin-intermediateS. aureus[hVISA] isolate [MIC, 2.0 μg/ml], and a vancomycin-intermediateS. aureus[VISA] isolate [MIC, 8.0 μg/ml]) were evaluated in anin vitropharmacodynamic model with a starting inoculum of 106or 108CFU/ml. Bacterial density was measured over 48 to 72 h. Time-kill curves were constructed, and the area under the bacterial killing and regrowth curve (AUBC) was calculated. During 106CFU/ml studies, combination therapy achieved greater log10CFU/ml changes than vancomycin alone at 12 h (−4.31 ± 0.58 versus −2.80 ± 0.59,P< 0.001), but not at 48 h. Combination therapy significantly reduced the AUBC from 0 to 48 h (122 ± 14) compared with vancomycin alone (148 ± 22,P= 0.017). Similar results were observed during 108CFU/ml studies, where combination therapy achieved greater log10CFU/ml changes at 12 h than vancomycin alone (−4.00 ± 0.20 versus −1.10 ± 0.04,P< 0.001) and significantly reduced the AUBC (275 ± 30 versus 429 ± 37,P< 0.001) after 72 h of incubation. In this study, the combination of vancomycin and cefazolin at human-simulated exposures improved the rate of kill against these MRSA isolates and resulted in greater overall antibacterial effect, but no differences in bacterial density were observed by the end of the experiments.

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Epidemiology of Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections from 2013-2017 at Chiang Mai University: What Changes Occurred from 2007-2011?

10.21203/rs.3.rs-32103/v1 ◽

2020 ◽

Author(s):

Kawisara Krasaewes ◽

Saowaluck Yasri ◽

Phadungkiat Khamnoi ◽

Romanee Chaiwarith

Keyword(s):

Staphylococcus Aureus ◽

Mortality Rate ◽

Methicillin Resistance ◽

Bloodstream Infections ◽

Arterial Graft ◽

Chiang Mai ◽

Methicillin Resistant ◽

Vancomycin Mics ◽

Significant Difference ◽

Tract Infections

Abstract Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an established pathogen that causes hospital- acquired infections worldwide. Bloodstream infection is associated with significant morbidity and mortality. We conducted a study aimed at describing the epidemiology of MRSA bloodstream infections, to determine the minimal inhibitory concentration (MIC) of the antibiotic vancomycin among MRSA isolates, and to determine the rate and risk factors of mortality.Methods: A retrospective study was conducted among patients aged ≥ 18 years whose blood culture grew MRSA at Chiang Mai University from January 2013 to December 2017Results: The annual prevalence of MRSA in S.aureus bloodstream infections from 2013 to 2017 were 32.8, 23.1, 26.8, 19.2 and 15.4%, respectively. This prevalence showed a non-significant decrease (p = 0.086). Eighty-four patients with 84 episodes of MRSA bloodstream infections were enrolled. Fifty-three patients (63.1%) were male, and the median age was 68.5 years (IQR 56, 79). Fifty-eight patients (69%) had bloodstream infections with other sites of infection: pneumonia (28 episodes, 43.1%), skin and soft tissue infections (16 episodes, 24.6%), osteomyelitis (7 episodes, 10.8%), infective endocarditis (4 episodes, 6.2%), septic arthritis (4 episodes, 6.2%), arterial graft infections (4 episodes, 6.2%), and urinary tract infections (2 episodes, 3.1%). Percentage of patients with vancomycin MICs ≥ 1.5 mg/L were 68.2%, 62.5%, 47.4%, 26.7%, and 75% from 2013 to 2017, respectively. (p = 0.325). The mortality rate was 64.3%. There was no significant difference in mortality rate between those infected with MRSA with a MIC of vancomycin < 1.5 and ≥ 1.5 mg/L (p = 0.172). Factors associated with mortality included age ≥ 40 years old (OR 11.35; 95% CI: 1.35–95.78, p = 0.026), presence of alteration of consciousness (OR 11.19; 95% CI: 2.83–44.18, p = 0.001) and concurrent pneumonia (OR 4.44; 95% CI: 1.09–18.14, p = 0.038).Conclusions: Methicillin-resistance among Staphylococcus aureus bloodstream infections showed a non-significant decrease of 50%, from 32.88% and 15.4%, between 2013 and 2017. Concurrent infection with pneumonia increased mortality. Although the vancomycin MIC was unchanged from 2013 to 2017, the mean MICs were > 1.0 mg/L. Careful monitoring of vancomycin MIC creep is crucial for the selection of the appropriate antibiotic dosage to prevent treatment failure.

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Methicillin-Resistant Staphylococcus aureus Endovascular Infection in a Neonate: Prolonged, Safe, and Effective Use of Daptomycin and Enoxaparin

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-25.1.68 ◽

2020 ◽

Vol 25 (1) ◽

pp. 68-74

Author(s):

Joshua I. Chan ◽

Asif Noor ◽

Christie Clauss ◽

Renu Aggarwal ◽

Amrita Nayak

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Vena Cava ◽

Factor V Leiden ◽

Blood Cultures ◽

Factor V ◽

Factor V Leiden Mutation ◽

Unique Challenge ◽

Methicillin Resistant ◽

Vancomycin Mics

We report on a former 28-week gestation neonate with persistent methicillin-resistant Staphylococcus aureus (MRSA) endocarditis, with a heterozygous Factor V Leiden mutation. The neonate became clinically ill after 1 week of life, with positive blood cultures for MRSA. Echocardiography revealed large thrombi in the inferior vena cava and right atrium. Bacteremia persisted despite removal of umbilical arterial and venous catheters and empiric administration of therapeutic doses of vancomycin (minimum inhibitory concentration [MIC] 2 mg/L) and ceftazidime. To narrow therapy, ceftazidime was discontinued, while gentamicin and rifampin were added. Cultures remained positive and, therefore, linezolid was added, and subsequent blood cultures became negative. Since prolonged linezolid use of 2 weeks or longer carries potential adverse effects, antibiotics were changed to daptomycin, which is bactericidal and recommended for treatment of invasive MRSA infections when vancomycin MICs are ≥2 mg/L to minimize vancomycin treatment failure. Enoxaparin was initiated, with anti-Xa assay monitoring. A workup for thrombophilia revealed heterozygous Factor V Leiden mutation. Serial echocardiograms demonstrated decreasing size of the thrombi, which were no longer visualized at 2 months of age. Creatinine kinase remained normal. The infant had no seizures on daptomycin. The management of persistent MRSA bacteremia in neonates associated with a large thrombus poses a unique challenge due to the long duration of treatment. To our knowledge, this is the first case of prolonged and safe daptomycin and enoxaparin use in a preterm neonate. Daptomycin may be considered in cases of clinical failure with vancomycin when a lengthy treatment course is contemplated.

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Assessment of Vancomycin MIC Creep Phenomenon in Methicillin-Resistant Staphylococcus aureus isolates in a Tertiary Care Hospital of Lahore

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.36.7.3273 ◽

2020 ◽

Vol 36 (7) ◽

Author(s):

Faiqa Arshad ◽

Sidrah Saleem ◽

Shah Jahan ◽

Romeeza Tahir

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Tertiary Care Hospital ◽

Geometric Mean ◽

Tertiary Care ◽

Test Method ◽

Care Hospital ◽

Methicillin Resistant ◽

Vancomycin Mics ◽

Mrsa Strains

Objective: To assess vancomycin MIC creep phenomenon in methicillin-resistant Staphylococcus aureus isolated from clinical specimens. Methods: This descriptive study was conducted in Microbiology department of University of Health Sciences, Lahore from January 2016- December 2019. In this study, vancomycin MICs were revealed by E test method for clinical MRSA strains. For the final evaluation, a single isolate from each patient was taken. The reported vancomycin MICs results were used and the values were not rounded up to the next upward value. For every study year, MIC50, MIC90, median and geometrical mean MIC, percentages of susceptible and resistant strains were calculated. Results: A total of 352 MRSA strains were isolated out of 2704 staphylococcal isolates. Our study showed elevated vancomycin MIC among MRSA isolates. The majority of isolates showed MIC values ≥1.5µg/ml. MIC50, MIC 90 was constant throughout four years period. However, geometric mean MIC increased gradually during the study period. The MIC greater than base year median was overall 17.3%. A complete shift can be observed between MIC “1.0” and “2.0” the percent of cases with MIC “1.0” decreased and with MIC “2.0” increased over time crossing each other in 2017. Conclusion: Vancomycin MIC creep was identified in clinical isolates of MRSA, during four years of study period. Even though there is an absence of VISA and VRSA strains; this significant increase in vancomycin MIC trend is indeed worrying for the clinicians about the threat of potential failure of treatment in MRSA infections. doi: https://doi.org/10.12669/pjms.36.7.3273 How to cite this:Arshad F, Saleem S, Jahan S, Tahir R. Assessment of Vancomycin MIC Creep Phenomenon in Methicillin-Resistant Staphylococcus aureus isolates in a Tertiary Care Hospital of Lahore. Pak J Med Sci. 2020;36(7):---------. doi: https://doi.org/10.12669/pjms.36.7.3273 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comparison of Vancomycin Treatment Failures for Methicillin-Resistant Staphylococcus aureus Bacteremia Stratified by Minimum Inhibitory Concentration

Journal of Pharmacy Technology ◽

10.1177/8755122519852679 ◽

2019 ◽

Vol 35 (5) ◽

pp. 203-207 ◽

Cited By ~ 1

Author(s):

Mary Joyce B. Wingler ◽

Darrell T. Childress ◽

Ricardo A. Maldonado

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Retrospective Chart Review ◽

High Rate ◽

Methicillin Resistant ◽

Staphylococcus Aureus Bacteremia ◽

Vancomycin Mics ◽

Significant Difference ◽

Alternative Agent ◽

Vancomycin Treatment

Background: Optimal treatment of methicillin-resistant Staphylococcus aureus bacteremias (MRSABs) with vancomycin minimum inhibitory concentrations (MICs) high within the susceptible range is of concern due to the high rate of mortality and increased prevalence. Objective: The purpose of this study is to evaluate vancomycin treatment failures in patients with MRSAB stratified by vancomycin MIC. Methods: In this retrospective chart review, patients ≥19 years of age with MRSAB between July 2010 and December 2016 were included if they received intravenous vancomycin for ≥72 hours. Vancomycin treatment failures were compared between patients with vancomycin MICs of ≤1 mg/L and 2 mg/L. Vancomycin treatment failure was defined as microbiological failure at 7 days. Inpatient mortality, 30-day readmission, vancomycin-associated nephrotoxicity, and early bacteremia clearance at 48 to 96 hours were assessed as secondary endpoints. Results: Fifty-eight patients were included in the vancomycin MIC ≤1 mg/L group and 22 patients in the vancomycin MIC 2 mg/L group. No significant difference was found in vancomycin treatment failures at 7 days between groups (88% vs 91%, respectively; P = .850). At 96 hours, there was no significant difference in vancomycin treatment failures between groups (72% vs 90%, respectively; P = .127). No significant difference was found in mortality ( P > .99) or 30-day readmission ( P > .99). Conclusions: In this study, vancomycin treatment failures were not more prevalent in patients with vancomycin MIC of 2 mg/L at 7 days. Regardless of MIC, antibiotics should be switched to an alternative agent at 7 days for persistent bacteremia.

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