[INTRODUCTION - The clinical significance of Gram-negative infections has not diminished in recent years. The number of resistant and multiresistant isolates has increased among Gramnegatives similarly to Gram-positive bacteria. Moreover, panresistant strains (i.e. resistant to all available agents active against Gram-negatives) have emerged. A prospective, multicenter study carried out in 2000 was repeated in 2004 in order to have up to date knowledge of resistance situation of Gram-negative aerobic bacteria and Bacteroides fragilis. In addition, the local data of 2004 were compared to MYSTIC (Meropenem Yearly Susceptibility Test Information) database of year 2004. MATERIALS AND METHODS - The in vitro study protocol-guided was carried out in 20 microbiology laboratories from April 1 to November 15, 2004. Study strains were isolated from relevant samples taken in medical, surgical, haematology, infectious disease wards and intensive care units. The sensitivity of 2099 aerobic Gram-negative and 97 B. fragilis isolates to meropenem and its comparator agents with excellent Gram-negative and/or antianaerob activity was tested according to NCCLS (National Committee for Clinical Laboratory Standards). RESULTS - Meropenem and imipenem have almost retained their 100% activity against Enterobacteriaceae, Acinetobacter and B. fragilis. A very small number of carbapenem nonsusceptible isolates emerged among Enterobacter, Proteus and Acinetobacter strains. Meropenem and especially imipenem sensitivity of Pseudomonas aeruginosa decreased significantly over the 4-year interval (76% vs 67%). The difference between the meropenem and imipenem sensitivity of P. aeruginosa proved significant (<0.001) and a similar difference was found in MYSTIC Programme. The isolation frequency of extended spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella strains was relatively low (4.1% and 8.5%, respectively) in Hungary comparing to that in other European countries. Only the carbapenems inhibited consistently the ESBLproducing strains whereas ceftazidime, cefepime and piperacillin/tazobactam were ineffective versus these strains. The rate of cefepime sensitive strains declined significantly in case of Enterobacter (82%), Citrobacter (90%), Acinetobacter (31%) and P. aeruginosa (69%), whereas it did not change among Serratia and Proteus strains. The activity of ceftazidim has decreased, as well: 61% of Enterobacter, 74% of Citrobacter, 15% of Acinetobacter and 78% of P. aeuginosa isolates were sensitive to it. A trend over time toward greater resistance was noted for piperacillin/tazobactam, however, it remained the most active in vitro agent against P. aeruginosa (83%). This rate is better than that was found in MYSTIC. There was not a clear trend in changes of sensitivity to aminoglycosides in Gram-negatives. A significant decrease in gentamicin and tobramycin sensitivity of E. coli and Klebsiella was noted (<90%), and in gentamicin, tobramycin and amikacin sensitivity of P. aeruginosa (57%, 65%, and 79%, respectively). Ciprofloxacin sensitivity also declined over the years: E. coli 85%, Proteus 83%, Acinetobacter 16%, P. aeruginosa 68%. Aztreonam and polymyxin sensitivity were examined only in case of P. aeruginosa because these two agents may be the drugs of choice in infections caused by multior panresistant strains: all isolates were susceptible to polymyxin, and 84% of them to aztreonam. However, panresistant isolates were not sensitive to aztreonam. Ampicillin/sulbactam may be a possible alternative drug in serious infections caused by multiresistant Acinetobacter: 83% of isolates showed sensitivity to it. Carbapenems, piperacillin/tazobactam and metronidazole were active against B. fragilis in 100%, amoxicillin/clavulanic acid resistance occurred scarcely, whereas clindamycin sensitivity was only 79%. CONCLUSIONS - There is no single antibacterial agent which would be effective against >90% of most frequently occurring Gram-negative aerobic bacteria in Hungary. The high increase in resistance rates over a relatively short 4-year period will result in serious challenges in the therapy. At the same time the Hungarian sensitivity rates are better than those reported by MYSTIC Programme.]