Lack of Bactericidal Antagonism or Synergism<i>In Vitro</i>between Oxacillin and Vancomycin against Methicillin-Susceptible Strains of<i>Staphylococcus aureus</i>

Joukhadar, Christian; Pillai, Satish K.; Wennersten, Christine; Moellering, Robert C.; Eliopoulos, George M.

doi:10.1128/aac.00348-09

Cited by 18 publications

(10 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At least 16 in vitro studies have explored synergy between vancomycin and β-lactams against MRSA isolates, [54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69] all but one of which found evidence of synergy in some or all of the tested strains (►Table 1). These studies varied in their methodology (checkerboard synergy testing or time-kill curves), types of strains tested (MRSA vs. hVISA vs. VISA) and the β-lactams used, but a consistent finding across nearly all the studies was synergistic bacterial killing in most but not all strains tested.…”

Section: In Vitro Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Combination Antibiotic Treatment of Serious Methicillin-Resistant Staphylococcus aureus Infections

Davis

Hal

Tong

2015

Semin Respir Crit Care Med

View full text Add to dashboard Cite

Outcomes from methicillin-resistant Staphylococcus aureus (MRSA) infections are relatively poor, at least in part due to the limitations of vancomycin (the current standard treatment for MRSA). Combination antibiotic treatment for MRSA infections is an attractive alternative as it could address most of vancomycin's shortcomings, including poor tissue penetration, slow bacterial killing, and emerging resistance in some strains of MRSA. However, the theoretical promise of combination therapy for MRSA infections has not been borne out in most in vitro and animal studies. Multiple combinations have been tested and have been either antagonistic, indifferent, or have had conflicting findings in various studies. This includes combinations of two primarily active agents (such as vancomycin plus daptomycin or linezolid), or the addition of gentamicin or rifampin to either vancomycin or daptomycin. However, hope on this front has come from an unexpected quarter. Although MRSA is by definition inherently resistant to nearly all ?-lactam antibiotics, this class of drugs has consistently shown evidence of synergy with either daptomycin or vancomycin in over 25 separate in vitro studies, and a limited number of animal and human observational studies. However, there are currently insufficient data to recommend ?-lactam combination therapy in routine clinical use. Results of current and planned randomized controlled trials of this strategy are awaited.

show abstract

Section: In Vitro Studiesmentioning

confidence: 99%

“…In this study, Joukhadar et al tested 10 clinical isolates of methicillin sensitive S. aureus and found evidence of neither synergy nor antagonism in any strain, both using fixed drug concentrations, and in a dynamic model simulating clinical dosing. 62…”

Section: In Vitro Studiesmentioning

confidence: 99%

Combination Antibiotic Treatment of Serious Methicillin-Resistant Staphylococcus aureus Infections

Davis

Hal

Tong

2015

Semin Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…Empirical addition of nafcillin or cefazolin to vancomycin monotherapy for Staphylococcus aureus is a novel regimen, albeit with well-characterized agents; therefore, the risks should be carefully considered. Bactericidal activity has been evaluated in vitro for the combination of oxacillin and vancomycin for 10 clinical MSSA isolates, and antagonism was not observed [31]. Addition of a β-lactam to vancomycin monotherapy carries a risk of allergic reaction, but serious reactions including anaphylaxis are relatively uncommon with penicillin (0.04%) and cephalosporins (0.02%) and can be screened for with a careful history [32,33].…”

Section: Risks Associated With Combination Therapymentioning

confidence: 99%

The Empirical Combination of Vancomycin and a -Lactam for Staphylococcal Bacteremia

McConeghy¹,

Bleasdale

Rodvold

2013

Clinical Infectious Diseases

View full text Add to dashboard Cite

The high prevalence of methicillin resistance among Staphylococcus aureus bacteremias leads to common use of vancomycin as empirical therapy. However, investigators have reported poor outcomes with vancomycin treatment for methicillin-susceptible Staphylococcus aureus bacteremia. We review the evidence supporting empirical combination of both vancomycin and a β-lactam agent for Staphylococcus aureus bacteremia. Vancomycin therapy for methicillin-susceptible Staphylococcus aureus bacteremia is associated with 2-3 times the risk of morbidity and mortality compared to an antistaphylococcal penicillin (oxacillin and nafcillin) or first-generation cephalosporin (cefazolin). De-escalation of empirical vancomycin to definitive β-lactam therapy still appears inferior to initial β-lactam therapy. Although there is no clinical trial supporting combination therapy, a scientific rationale for benefit exists and should be weighed against the risks (adverse events, antibiotic resistance, and cost) of additional pharmacotherapy. The empirical combination of vancomycin and a β-lactam (either nafcillin, oxacillin, or cefazolin) for staphylococcal bacteremia may improve infection-related clinical outcomes.

show abstract

“…This low in vitro bactericidal activity of vancomycin probably caused the suboptimal results observed in the treatment of serious S. aureus infections (13,20). It has also been reported that the bactericidal activity of ␤-lactams against MSSA may be superior to that of vancomycin (11). In that respect, it is not surprising that our mecA-carrying isolates, which are functionally oxacillin susceptible, responded sufficiently to oxacillin treatment.…”

mentioning

confidence: 78%

Activity of Oxacillin versus That of Vancomycin against Oxacillin-Susceptible mecA -Positive Staphylococcus aureus Clinical Isolates Evaluated by Population Analyses, Time-Kill Assays, and a Murine Thigh Infection Model

Labrou

Michail

Ntokou

et al. 2012

Antimicrob Agents Chemother

View full text Add to dashboard Cite

We compared the activity of dicloxacillin with that of vancomycin against 15 oxacillin-susceptible, methicillin-resistant Staphylococcus aureus (OS-MRSA) clinical isolates. By population analyses, we found that 6 OS-MRSA isolates were able to grow in the presence of up to 8 g/ml dicloxacillin and 9 isolates were able to grow in 12 to >32 g/ml dicloxacillin; all isolates grew in up to 2 g/ml vancomycin. Both drugs exhibited similar bactericidal activities. In experimental infections, the therapeutic efficacy of dicloxacillin was significant (P < 0.05 versus untreated controls) in 10 OS-MRSA isolates and vancomycin was effective (P < 0.05) against 12 isolates; dicloxacillin had an efficacy that was comparable to that of vancomycin (P > 0.05) in 8 isolates. The favorable response to dicloxacillin treatment might suggest that antistaphylococcal penicillins could be used against OS-MRSA infections. Staphylococcus aureus isolates that carry and express the mecA gene are considered methicillin resistant (MRSA) but may exhibit oxacillin MICs ranging from the susceptible range (Յ2 g/ ml) to Ͼ1,000 g/ml (8,16,20). It was generally believed that most mecA-positive S. aureus strains, including those appearing oxacillin susceptible (OS-MRSA), exhibit a degree of oxacillin heteroresistance and the use of ␤-lactams might lead to treatment failure. However, OS-MRSA isolates with no oxacillin heteroresistance (truly oxacillin susceptible) also appeared (9).In a previous study, we reported that the activity of oxacillin against four OS-MRSA isolates was intermediate between that against mecA-negative S. aureus and highly resistant MRSA isolates (9). It was subsequently found that the OS-MRSA isolates of that study harbored specific mutations in their Fem proteins that probably conferred atypical oxacillin responsiveness (6). To further investigate these preliminary observations, we tested and report herein the in vitro and in vivo activities of oxacillin compared with those of vancomycin (treatment of choice for most MRSA infections) against a larger collection of OS-MRSA. The aim of this study was to investigate whether antistaphylococcal ␤-lactams, which were previously shown to exhibit superior activity than vancomycin against methicillin-susceptible S. aureus (MSSA) (11), retain activity against MRSA isolates that appear phenotypically susceptible to oxacillin. To the best of our knowledge, the activity of ␤-lactams has not been tested against OS-MRSA isolates.Bacterial strains and susceptibility testing. Fifteen vancomycin-susceptible OS-MRSA clinical isolates, collected during 2006 and 2007, were studied. A high-level MRSA isolate (isolate 7263; oxacillin MIC, 256 g/ml) and the mecA-negative strain S. aureus ATCC 29213 were included as controls. Isolates were stored at Ϫ80°C in brain heart infusion broth with 15% glycerol before testing. MIC testing of oxacillin and vancomycin was performed by agar dilution according to CLSI guidelines (4).Detection of PBP2a and the mecA gene and MLST. The study isolates were tested for the...

show abstract

Lack of Bactericidal Antagonism or SynergismIn Vitrobetween Oxacillin and Vancomycin against Methicillin-Susceptible Strains ofStaphylococcus aureus

Cited by 18 publications

References 18 publications

Combination Antibiotic Treatment of Serious Methicillin-Resistant Staphylococcus aureus Infections

Combination Antibiotic Treatment of Serious Methicillin-Resistant Staphylococcus aureus Infections

The Empirical Combination of Vancomycin and a -Lactam for Staphylococcal Bacteremia

Activity of Oxacillin versus That of Vancomycin against Oxacillin-Susceptible mecA -Positive Staphylococcus aureus Clinical Isolates Evaluated by Population Analyses, Time-Kill Assays, and a Murine Thigh Infection Model

Contact Info

Product

Resources

About