Naslov
Clinical therapy of gram-positive infections in neutropenic patients: Focus on linezolid

Autori
Jakšić, Branimir

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Seventh International Symposium on Febrile Neutropenia / - , 2005

Skup
Seventh International Symposium on Febrile Neutropenia

Mjesto i datum
Sevilla, Španjolska, 27.01.2005. - 29.01.2005

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Linezolid

Sažetak
Background and introduction. Febrile neutropenia (FN) is an increasingly important clinical problem, due to the fact that new, potent antineoplastic treatment procedures almost invariably cause some degree of neutropenia. Moreover, the immune system (and other body systems) are also damaged or impaired by both disease itself and by therapy. In this setting, the patients are at increased risk of infection which may be life threatening. Gram-positive organisms play an important role and are the most common causative pathogens of bacteremia. The universe of Gram-positive pathogens consists of several subsets with different characteristics of importance for clinical decision processes. Multiple interrelated factors are influencing the therapeutic decision process and are likely to change dramatically over time. Vancomycin is generally used as the standard therapeutic option for important gram positive infections and is therefore useful as a representative to describe essential principles and dilemmas in therapeutic decision making. General consensus has been reached for most indications, but some recent works question empiric addition of vancomycin after failure to respond in 48-60 hours to piperacillin/tazobactam. The role of vancomycin changes due to emergence of new agents developed to increase tolerance and improve efficacy. Focus on linezolid. Linezolid is the first oxazolidinone class anti-infective agent approved by FDA in 2000 for serious infections caused by gram-positive organisms including those organisms with known multidrug resistance: methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium: (VRE infections) ; Nosocomial pneumonia (incl. MRSA and MDRSP) ; Uncomplicated skin and skin structure infections ; Complicated skin and skin structure infections, diabetic foot infections without osteomyelitis ; Community acquired pneumonia (incl. MDRSP). Clinical registration trials supported the above indications, proved the efficacy and demonstrated good tolerance. Subset analyses disclosed potential new indications (neutropenia) in a non-randomized, prospective, open-label compassionate use trial. This warranted a randomized double blind trial comparing linezolid with vancomycin to study the efficacy and tolerance, especially to clarify potentially worrisome myelosupressive effects of linezolid indicated in some reports. Trials in non-neutropenic patients comparing linezolid to vancomycin in MRSA infections demonstrated comparable efficacy and tolerance. The meta-analysis of two registration trials for nosocomial pneumonia identified a subset defined by MRSA infection in which linezolid showed significantly higher cure rates, which also translated into significantly better survival. This finding underlines a general need to define as precisely as possible the subsets of patients who are likely to benefit most from this treatment. A few trials comparing linezolid to quinupristin/dalfopristin did not show an advantage of Q/D. However, in line with a general rule, after increased usage of linezolid, a slight decrease of susceptibility was observed in MDACC. The most recent, prospective, randomized, international, multi-center, double blind trial, in neutropenic cancer patients compared linezolid to vancomycin in over 600 patients. The trial showed that linezolid is a safe and effective therapeutic option for the treatment of febrile neutropenic cancer patients with suspected or proven gram-positive infections. Conclusion. Gram-positive organisms account for 12%-15% infection in patients with neutropenic fever taking into account all sites, but are the most common cause of bacteremia (>70%). There is emerging resistance to vancomycin and other new agents. Potent Gram-positive therapies (vancomycin, linezolid) are generally not initially recomended, but when indicated, it should be instituted promptly. Linezolid plays an important role in the treatment of gram-positive infections. New trials confirm its efficacy and prove that it can be used safely in neutropenic cancer patients, offering new hopes to patients. Treatment of febrile neutropenia remains in evolution. Guidelines should be helpful, not constrictive. Clinical judgment in this multidimensional situation is critical for careful evaluation of all aspects to ensure successful treatment outcome.

Izvorni jezik
Engleski

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