final program.qxd - Parallels Plesk Panel

PP 6.21
A serious staphylococcal knee and soft tissue infection responsive to linezolid only,
after failure of all other therapeutic attempts. Discrepancy between favorable in
vitro bacteriological testing and a worsening clinical course
Roberto Manfredi, Sergio Sabbatani
Infectious Diseases, University of Bologna, Italy
Introduction
To offer therapeutic alternatives for the emerging, multiresistant, serious gram-positive
infections, novel molecules (quinupristin/dalfopristin, linezolid, daptomycin, tigecyclyne),
have been recently introduced, and are made available when multiresistant gram-positive
cocci are documented, like absence of susceptility to all available drugs, including
glycopeptides. However, linezolid encompasses unique tissue penetration and diffusion
features (regarding soft tissues, lungs, joints, and central nervous system), which make
this last drug extremely promising in all circumstances where the penetration rate into
infectious foci becomes critical.
Clinical experience
A very intriguing case report of a severe, staphylococcal knee arthtiris associated to an
extensive local cellulitis/necrotizing fasciitis and hematogenous dissemination occurring
after a surgical curettage, was characterized by a complete lack of response to a
prolonged vancomycin/teicoplanin plus rifampicin therapy, based on the apparently
favorable in vitro sensitivity assays of methicllin-resistant Staphylococci, but rapidly
responded to i.v. (followed by oral) linezolid administration. The complete lack of clinical
activity of a two-week glycopeptide-rifampicin administration cannot be explained by the
in vitro measured MIC90 values of isolated pathogens,which showed complete sensitivity
of Staphylococcus aureus against vancomycina/teicoplanin and rifampicin, and
susceptibility of a concurrent hematogenous S. epidermidis strain to glycopeptidesrifampicin.
Since an abscess formation and an underlying osteomyelitis were carefully
excluded by adequate instrumental examinations, from a theoretical point of view the
active glycopeptide-rifampicin molecules should have been provided appropriate cure.On
the other hand, from a strictly clinical issue, only a two-week administration of i.v.
linezolid followed by one more week of oral linezolid, allowed to obtain a complete
clinical-bacteriological cure, and a complete function recovery, without any sequelae after
a two-year follow-up.
Conclusions
When the management of severe, multiresistant gram-positive infections is of concern, the
in vitro activity of single drugs and therapeutic classes should be carefully evaluated in
relation with the expected penetration and diffusion rates of these drugs into the relevant
organs and tissues involved by the ongoing infectious localizations. Otherwise,
apparently unexplained failures may occur also when in vitro studies point out a
complete activity of the tested compounds.
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