Journal of Antimicrobial Chemotherapy
Advance Access publication 20 October 2006
Comment on: Bactericidal activity of orally
available agents against methicillin-resistant
Houssem Hmouda1*, Chaker Ben Salem2, Kamel Bouraoui2
and Letaief Jemni3
1Medical Intensive Care Unit and Emergency Department,
Sahloul University Hospital, Sousse, Tunisia;2Department of
Clinical Pharmacology, Faculty of Medicine of Sousse,
Tunisia;3Clinique les Oliviers, Sousse, Tunisia
Keywords: microbial infections, trimethoprim/sulfamethoxazole,
451; E-mail: email@example.com
We read with great interest the article written by Kaka et al.1in
the September 2006 issue of JAC. The authors clearly demon-
strated that trimethoprim/sulfamethoxazole is rapidly bactericidal
against methicillin-resistant Staphylococcus aureus (MRSA)
in vitro when compared with most other orally available
antimicrobials. No antibiotic combination exhibited better killing
than trimethoprim/sulfamethoxazole alone. Furthermore, activ-
ities against community-acquired (CA) MRSA and hospital-
acquired (HA) MRSA were similar.
We are reassured with this conclusion, which corroborates our
clinical findings in Tunisia published 13 years ago.2In our
previously published series trimethoprim/sulfamethoxazole was
= 3), arthritis (n = 2), spondylodiscitis with psoas abscess (n = 1),
meningitis (n = 1), prosthetic valve endocarditis (n = 1) and
tered orally at daily doses of trimethoprim 320–480 mg, and
sulfamethoxazole 1600–2400 mg. Trimethoprim/sulfamethoxa-
zole plus rifampicin was used in eight patients. Patients with
polymicrobial soft-tissue infections received penicillin G and/or
metronidazole in addition to trimethoprim/sulfamethoxazole.
Twenty-six patients were cured; one patient with bacteraemia and
osteitis was not cured due to the emergence of resistance.
Trimethoprim/sulfamethoxazole was well tolerated by all patients.
In fact, we were not the only clinicians to remind readers
about the efficacy and safety of trimethoprim/sulfamethoxazole in
the treatment of MRSA infections. 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.3However,
failures during treatment with trimethoprim/sulfamethoxazole
have also been reported.
Based on the findings of Kaka et al., adding rifampicin
to trimethoprim/sulfamethoxazole showed a trend towards
antagonism in vitro. However, in our series all patients (n = 8)
treated with this combination were cured. We were not surprised
by these results since in vitro antagonism does not necessarily
imply failure of treatment. Nevertheless, confirmation of efficacy
further investigation before being recommended for severe
fluoroquinolones-sparing effect are well appreciated. Indeed,
curtailing the use of fluoroquinolones could be beneficial, since
increasing epidemiological, pharmacological and biological
evidence incriminate this antibiotic class as an important risk
factor for the acquisition and dissemination of MRSA.4,5
Therefore, it is urgent for the worldwide medical community
to reexamine the clinical efficacy of older active therapies, such
as trimethoprim/sulfamethoxazole, for treating severe infections
due to MRSA. It is mandatory to conduct trials that compare
agents such as linezolid or vancomycin with trimethoprim/
sulfamethoxazole for the treatment of MRSA. This comparison
is justified by the low cost of trimethoprim/sulfamethoxazole, its
adequate oral bioavailability and its potential vancomycin-sparing
effect. Any new recommendation on the use of trimethoprim/
sulfamethoxazole should be based on strong evidence rather than
sporadic case reports or in vitro studies. The modalities of
treatment (dose, duration), adverse effects, cure rates and failure
should be clarified.
We declare that we have no conflict of interest.
1. Kaka AS, Rueda AM, Shelburne SA III et al. Bactericidal activity of
orally available agents against methicillin-resistant Staphylococcus
aureus. J Antimicrob Chemother 2006; 58: 680–3.
2. Jemni L, Hmouda H, Letaief A. Efficacy of trimethoprim/
sulfamethoxazole against clinical isolates of methicillin-resistant Staphy-
lococcus aureus: a report from Tunisia. Clin Infect Dis 1994; 19: 202–3.
3. Adra M, Lawrence KR. Trimethoprim/sulfamethoxazole for treat-
ment of severe Staphylococcus aureus infections. Ann Pharmacother
2004; 38: 338–41.
4. Weber SG, Gold HS, Hooper DC et al. Fluoroquinolones and the
risk of methicillin-resistant Staphylococcus aureus in hospitalized
patients. Emerg Infect Dis 2003; 9: 1415–22.
5. Bisognano C, Vaudaux P, Rohner P et al. Induction of fibronectin-
binding proteins and increased adhesion of quinolone-resistant Staphy-
lococcus aureus by subinhibitory levels of ciprofloxacin. Antimicrob
Agents Chemother 2000; 44: 1428–37.
Journal of Antimicrobial Chemotherapy
Advance Access publication 24 October 2006
Bactericidal activity of orally available agents
against methicillin-resistant Staphylococcus aureus:
Anjum S. Kaka1,2and Daniel M. Musher1,2*
1Section of Infectious Diseases, Michael E. Debakey Veterans
Affairs Medical Center, 2002 Holcombe Boulevard,
by guest on January 14, 2016