**Author details**

cystic fibrosis isolates [139]. Colistin is frequently associated with nephro- and neurotoxicity

Another interesting option for the treatment of MDR *P. aeruginosa* is fosfomycin, an old antibacteial that has regained attention because of its *in vitro* activity against such isolates [140]. Fosfomycin inactivates the enzyme pyruvil-transferase, which is required for the synthesis of the cell wall peptidoglycan. In a review of the existing fosfomycin studies, 81.1% of 1529 patients were successfully treated for infections caused by *P. aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Enterobacter* spp. and *Klebsiella* spp. Fosfomycin was administered together with aminoglycosides, cephalosporins and penicillines [141]. More studies are needed however to determine the future role of fosfomycin against MDR *P. aeruginosa* isolates.

The application of combination therapy instead of monotherapy in cases of non-MDR *P. aeruginosa* remains to date a controversial issue [14]. Combination treatment against MDR strains instead seems to be some times necessary (for example in cases of pan-resistance or resistance to all except a single agent). In such cases better results are expected by the additive or subadditive activity of a combination or by the enhancement of a single active agent by an

Several old and newer studies have showed the increased activity *in vitro* of various antibiotic combinations against MDR *P. aeruginosa* (Table 7) even though, the mechanisms of positive

*P. aeruginosa* is a nosocomial pathogen of particular clinical concern not only because of its extraordinary resistance mechanisms armamentarium but also for its formidable ability to

interaction between the various agents are rarely known [142].

**Table 7.** Enhanced activity of antibiotic combinations against MDR *P. aeruginosa*.

**Antibiotic combination References** Ticarcillin, Tobramycin, Rifampin [143] Cephalosporins, Quinolones [144] Ceftazidime, Colistin [145] Macrolides, Tobramycin, Trimethoprim, Rifampin [146] Polymyxin B, Rifampin [147] Polymyxin B, Imipenem [148] Colistin, Meropenem [149]

but both these adverse effects seem to be dose-dependent and reversible [140].

**6. Combination therapy**

44 Infection Control

otherwise inactive drug [142].

**7. Conclusion**

Georgios Meletis1,2 and Maria Bagkeri3

\*Address all correspondence to: meletisg@hotmail.com

1 Aristotle University of Thessaloniki, School of Medicine,Thessaloniki, Greece

2 Department of Clinical Microbiology, Veroia General Hospital,Veroia, Greece

3 Department of Internal Medicine,Agios Dimitrios General Hospital of Thessaloniki, Greece
