In vitro and in vivo efficacy of the combination trimethoprim-sulfamethoxazole against clinical isolates of methicillin-resistant Staphylococcus aureus

Elwell, Lynn P.; Wilson, H. R.; Knick, Victoria B.; Keith, Barry R.

doi:10.1128/aac.29.6.1092

Cited by 42 publications

(23 citation statements)

References 12 publications

(8 reference statements)

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“…These data cor roborated those of numerous previous in vestigators with respect to different strains of methicillin-resistant and GRMR S', aureusll, 12,14,[17][18][19][26][27][28][29]31,39,41,46,55,58,59,66,67], In the case of cefamandole, our results supported those of Moorman et al [42] and Thompson et al [59], rather than those of Frongillo et al [23].…”

Section: Discussionsupporting

confidence: 77%

Gentamicin- and Methicillin-Resistant <i>Staphylococcus aureus: </i>in vitro Susceptibility to Antimicrobial Drugs

Traub

Spohr²,

Bauer³

1987

Chemotherapy

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Thirteen nosocomially significant, gentamicin- and methicillin-resistant (GRMR) Staphylococcus aureus isolates, all of phage group III/M (lysotype 42E/47/53/54/75/77/83A/84/85/94/96), were uniformly resistant against augmentin, erythromycin, fosfomycin, gentamicin, methicillin, oxacillin, penicillin G, tetracycline, and tobramycin, but differed in susceptibility to cefamandole, ciprofloxacin, clindamycin, imipenem, josamycin, the synthetic chinolone Ro 23–6240, and ofloxacin. All isolates were susceptible to chloramphenicol, coumermycin, fusidic acid, novobiocin, rifampin, teicoplanin, trimethoprim-sulfamethoxazole (cotrimoxazole), and vancomycin. One isolate was of intermediate susceptibility to netilmicin. On a weight-for-weight basis, the 7 most active drugs were rifampin, coumermycin, cotrimoxazole, novobiocin, teicoplanin, fusidic acid, and vancomycin (in decreasing order) in terms of minimal inhibitory concentrations. With regard to minimal bactericidal concentrations, coumermycin, rifampin, vancomycin, teicoplanin, cotrimoxazole, ofloxacin, and ciprofloxacin (in decreasing order) were the 7 most potent antimicrobial drugs. Freshly defibrinated human blood [65% (v/v)] combined with chloramphenicol and rifampin, respectively, resulted in a weak additive effect (time kill curves). Indifferent effects were observed following combination of blood with ciprofloxacin, cotrimoxazole, coumermycin, fusidic acid, imipenem, netilmicin, novobiocin, ofloxacin, compound Ro 23–6240, teicoplanin, and vancomycin. Rifampin combined with novobiocin, teicoplanin, and vancomycin, respectively, in the presence of 65% (v/v) human blood, resulted in an additive effect. Combinations of rifampin with 9 other antimicrobial drugs in blood yielded essentially indifferent effects.

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Section: Discussionsupporting

confidence: 77%

Gentamicin- and Methicillin-Resistant <i>Staphylococcus aureus: </i>in vitro Susceptibility to Antimicrobial Drugs

Traub

Spohr²,

Bauer³

1987

Chemotherapy

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“…2,7,8 The importance of TMP-SMX dosing in CA-MRSA skin infections has not yet been validated in the clinical setting, and this study suggests these prescribers might not have been familiar with the pharmacokinetic-pharmacodynamic literature for TMP-SMX. It is possible that TMP-SMX, dosed at 2 double-strength tablets twice daily, might be superior to clindamycin, but that cannot be determined from this study.…”

Section: Discussionmentioning

confidence: 94%

Trimethoprim-Sulfamethoxazole or Clindamycin for Community-Associated MRSA (CA-MRSA) Skin Infections

Frei¹,

Miller²,

Lewis³

et al. 2010

The Journal of the American Board of Family Medicine

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Background: In the United States, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as the predominant cause of skin infections. Trimethoprim-sulfamethoxazole (TMP-SMX) and clindamycin are often used as first-line treatment options, but clinical data are lacking.Methods: We conducted a retrospective cohort study of outpatients with skin and soft tissue infections managed from July 1 to December 31, 2006. Patients younger than 18 years of age were excluded, as were those who had no clinical admission or progress notes; were hospitalized within the 90 days before admission; were hospitalized with polymicrobial, surgical site, catheter-related, or diabetic foot infections; or were discharged to places other than home. Patient demographics, comorbidities, diagnoses, cultures, prescribed antibiotics, susceptibilities, surgical procedures, and health outcomes were extracted from electronic medical records. Patients were divided in 2 cohorts for further analysis: TMP-SMX and clindamycin. The primary study outcome was composite failure defined as an additional positive MRSA culture from any site 5 to 90 days after treatment initiation or an additional intervention during a subsequent outpatient or inpatient visit. Baseline characteristics and failure rates were compared using

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“…In addition, synergistic bactericidal activity has been shown in a model of disseminated infection in mice (9). However, to the best of our knowledge, results of treatment of endocarditis caused by MRSA in an experimental model have not been published.…”

mentioning

confidence: 81%

“…Most clinical isolates of S. aureus, including methicillin-resistant strains, are sensitive to TMP-SMX (15), and supposedly the combination acts synergistically to produce a bactericidal effect on staphylococci both in vitro and in vivo (9,25). For these reasons, TMP-SMX is being considered as an effective alternative to vancomycin in the treatment of infections caused by MRSA, including cases of endocarditis (12,28).…”

Section: Discussionmentioning

confidence: 99%

Treatment of experimental endocarditis due to methicillin-susceptible or methicillin-resistant Staphylococcus aureus with trimethoprim-sulfamethoxazole and antibiotics that inhibit cell wall synthesis

Górgolas

Avilés

Verdejo

et al. 1995

Antimicrob Agents Chemother

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Using two strains of Staphylococcus aureus, one susceptible and one heterogeneously resistant to methicillin, for which MICs and MBCs of trimethoprim-sulfamethoxazole (TMP-SMX) were 0.06 and 0.06 g/ml and 0.06 and 0.25 g/ml, respectively (concentrations are those of TMP), we studied the efficacies of TMP-SMX and cloxacillin, teicoplanin, and vancomycin for treatment of experimental staphylococcal endocarditis. Rabbits were treated with dosages of TMP-SMX selected to achieve concentrations in serum equivalent to that obtained in humans treated for Pneumocystis carinii pneumonia. The overall mortality rate of rabbits treated with TMP-SMX was 84% at day 3, not different from that of the control groups (P > 0.1). No sterile vegetations were observed to be present in control groups or in animals treated with TMP-SMX. However, 26, 60, and 75% of rabbits treated with teicoplanin, cloxacillin, and vancomycin, respectively, showed sterile vegetations. For methicillin-susceptible S. aureus (MSSA), the mean vegetation counts were not significantly different between the control group and the group treated with TMP-SMX (P > 0.1). For methicillin-resistant S. aureus (MRSA), treatment with TMP-SMX was more effective than no therapy, decreasing the number of organisms in vegetations (P < 0.01). For both strains, therapy with cloxacillin and therapy with teicoplanin or vancomycin were significantly more effective than therapy with TMP-SMX. Despite high concentrations of teicoplanin in serum which exceeded MBCs for staphylococci more than 50 times at the peak and 10 times at the trough, therapy with cloxacillin or vancomycin was superior to therapy with teicoplanin against both MSSA and MRSA. These data do not support the use of TMP-SMX in treatment of endocarditis and other severe staphylococcal infections with high bacterial counts.Staphylococcus aureus remains an important cause of both uncomplicated and complicated bacteremic infections and is the leading cause of infectious endocarditis in many medical centers around the world (23, 30). Antimicrobial therapy of staphylococcal infections has become more troublesome because of the recent emergence and spread of methicillin-resistant S. aureus (MRSA) strains. Previous reports have documented an increased prevalence of MRSA in hospitals in the United States and Europe (3, 18), and there is at present a scarcity of effective antimicrobial regimens for these strains (12).Beta-lactam antibiotics alone or in combination with aminoglycosides are regarded as first-choice therapy for treatment of methicillin-susceptible S. aureus (MSSA) endocarditis, and vancomycin therapy is recommended for patients with penicillin allergies and for those with serious infections caused by MRSA, including endocarditis (19). However, several recent reports have shown suboptimal clinical outcome in patients with staphylococcal endocarditis treated with vancomycin (13, 16). For these reasons, a continuous search for alternative antimicrobial drugs is of paramount importance.In vitro, most strains of MRSA ...

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In vitro and in vivo efficacy of the combination trimethoprim-sulfamethoxazole against clinical isolates of methicillin-resistant Staphylococcus aureus

Cited by 42 publications

References 12 publications

Gentamicin- and Methicillin-Resistant <i>Staphylococcus aureus: </i>in vitro Susceptibility to Antimicrobial Drugs

Gentamicin- and Methicillin-Resistant <i>Staphylococcus aureus: </i>in vitro Susceptibility to Antimicrobial Drugs

Trimethoprim-Sulfamethoxazole or Clindamycin for Community-Associated MRSA (CA-MRSA) Skin Infections

Treatment of experimental endocarditis due to methicillin-susceptible or methicillin-resistant Staphylococcus aureus with trimethoprim-sulfamethoxazole and antibiotics that inhibit cell wall synthesis

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