Trimethoprim/Sulfamethoxazole for Treatment of Severe <i>Staphylococcus aureus</i> Infections

Adra, May; Lawrence, Kenneth

doi:10.1345/aph.1d156

Cited by 69 publications

(32 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This statement has a remarkable, although often ignored, precedent. TMP-SMX is advocated as a substitute therapy against TMP-SMX-susceptible MRSA in circumstances (1,32) where it is not overtly known to fail. However, TMP-SMX did poorly against experimental endocarditis due to MRSA in rabbits (8), which would have predicted treatment failures.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of Iclaprim against Wild-Type and Thymidine Kinase-Deficient Methicillin-Resistant Staphylococcus aureus Isolates in an In Vitro Fibrin Clot Model

Entenza

Haldimann²,

Giddey

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Iclaprim is a novel diaminopyrimidine antibiotic that is active against methicillin-resistant Staphylococcus aureus (MRSA). However, it is known that the activity of diaminopyrimidines against S. aureus is antagonized by thymidine through uptake and conversion to thymidylate by thymidine kinase. Unlike with humans, for whom thymidine levels are low, thymidine levels in rodents are high, thus precluding the accurate evaluation of iclaprim efficacy in animal models. We have studied the bactericidal activity of iclaprim against an isogenic pair of MRSA isolates, the wild-type parent AW6 and its thymidine kinase-deficient mutant AH1252, in an in vitro fibrin clot model. Clots, which were aimed at mimicking vegetation structure, were made from human or rat plasma containing either the parent AW6 or the mutant AH1252, and they were exposed to homologous serum supplemented with iclaprim (3.5 g/ml), trimethoprim-sulfamethoxazole (TMP-SMX; 8/40 g/ml), vancomycin (40 g/ml), or saline, each of which was added one time for 48 h. In rat clots, iclaprim and TMP-SMX were bacteriostatic against the parent, AW6. In contrast, they were bactericidal (>3 log 10 CFU/clot killing of the original inoculum) against the mutant AH1252. Vancomycin was the most active drug against AW6 (P < 0.05), but it showed an activity similar those of iclaprim and TMP-SMX against AH1252. In human clots, iclaprim was bactericidal against both AW6 and AH1252 strains and was as effective as TMP-SMX and vancomycin (P > 0.05). Future studies of animals using simulated human kinetics of iclaprim and thymidine kinase-deficient MRSA, which eliminate the thymidine-induced confounding effect, are warranted to support the use of iclaprim in the treatment of severe MRSA infections in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The TMP-sulfamethoxazole (TMP-SMX) combination has been used clinically against severe MRSA infections in humans, including endocarditis (1,24,32). Paradoxically, TMP-SMX tended to fail against MRSA experimental endocarditis in rabbits (8) and against experimental enterococcal endocarditis in rats (12).…”

mentioning

confidence: 99%

Efficacy of Iclaprim against Wild-Type and Thymidine Kinase-Deficient Methicillin-Resistant Staphylococcus aureus Isolates in an In Vitro Fibrin Clot Model

Entenza

Haldimann²,

Giddey

et al. 2009

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…vancomycin). Hence, it is a useful supportive therapy in treating deep-seated staphylococcal infections such as endocarditis, osteomyelitis and empyema (19). Linezolid was equal to vancomycin for the treatment of infections caused by resistant gram-positive bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, the majority of the CA-MRSA pediatric infections in the United States and Colombia are caused by the USA300 and USA400 strains (previously MW2) (19,20 …”

Section: Discussionmentioning

confidence: 99%

Empiema necessitans y osteomielitis aguda secundaria a una infección por Staphylo-coccus aureus resistente a meticilina asociado a la comunidad

Contreras¹,

Pérez

Murphy³

et al. 2009

biomedica

View full text Add to dashboard Cite

Staphylococcus aureus is a well recognized pathogen with global distribution. In recent years community-associated, methicillin-resistant S. aureus has emerged as an increasing cause of severe infections among adults and children. Herein, a case is reported of a previously healthy, 19-month-old male, who presented with empyema necessitans and acute osteomyelitis due to a community-associated, methicillin-resistant, S. aureus strain. This report highlights the evolving epidemiology of S. aureus, as important pathogen in the community as well as the hospital setting, and the importance of establishing appropriate guidelines for diagnosis, management and surveillance of this public health problem.Key words: empyema, osteomyelitis, Staphylococcus aureus, pneumonia, vancomycin. Empiema necessitans y osteomielitis aguda secundaria a una infección por Staphylococcus aureus resistente a meticilina asociado a la comunidadStaphylococcus aureus es uno de los principales patógenos a nivel mundial. Durante los últimos años se ha reportado un incremento en el número de casos de S. aureus resistente a la meticilina adquiridos en la comunidad, tanto en niños como en adultos de los Estados Unidos y de otras partes del mundo. En el presente trabajo reportamos un caso de empiema necessitans y osteomielitis aguda en un niño de 19 meses de edad previamente sano. El presente reporte resalta la cambiante epidemiología de S. aureus tanto en la comunidad como en el medio hospitalario y la importancia de establecer guías apropiadas para el diagnóstico, el tratamiento y la vigilancia de este relevante problema de salud pública.

show abstract

“…Since the early 1970s, the efficacy of trimethoprim/sulfamethoxazole in severe S. aureus infections has been reported, particularly for endocarditis, bacteraemia, meningitis, and bone and joint infections. 3 However, failures during treatment with trimethoprim/sulfamethoxazole have also been reported.…”

mentioning

confidence: 99%

Comment on: Bactericidal activity of orally available agents against methicillin-resistant Staphylococcus aureus

Hmouda

Salem

Bouraoui

et al. 2006

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

Trimethoprim/Sulfamethoxazole for Treatment of Severe Staphylococcus aureus Infections

Abstract: In select infections, TMP/SMX may be a useful alternative to vancomycin for treatment of severe S. aureus infections. Additional randomized studies should be conducted comparing this agent with vancomycin and linezolid.

Cited by 69 publications

References 19 publications

Efficacy of Iclaprim against Wild-Type and Thymidine Kinase-Deficient Methicillin-Resistant Staphylococcus aureus Isolates in an In Vitro Fibrin Clot Model

Efficacy of Iclaprim against Wild-Type and Thymidine Kinase-Deficient Methicillin-Resistant Staphylococcus aureus Isolates in an In Vitro Fibrin Clot Model

Empiema necessitans y osteomielitis aguda secundaria a una infección por Staphylo-coccus aureus resistente a meticilina asociado a la comunidad

Comment on: Bactericidal activity of orally available agents against methicillin-resistant Staphylococcus aureus

Contact Info

Product

Resources

About