Two articles published in the January issue of Antimicrobial Agents and Chemotherapy show that combinations of beta-lactams with the new beta-lactamase inhibitor NXL104 may be effective against bacteria resistant to carbapenems.

Carbapenemic antibiotics are considered one of the most effective classes of antibacterial drugs used in serious infections caused by resistant gram-negative bacteria or mixed flora. Consequently, the emergence and spread in various countries of the world of bacterial strains carrying genes for resistance to carbapenems pose a serious threat to patients. Resistance to carbapenems in many cases is due to the presence of genes coding for different types of enzymes that destroy carbapenem antibiotics - carbapenemases. The most important of these are KPC- (common in the United States) and NDM carbapenemases, which are currently spreading rapidly from India and Pakistan to other countries around the world.

A study led by Professor DM Livermore (Great Britain) has shown that the combination of ceftazidime with NXL104 in vitro remains active against strains of Klebsiella pneumoniae having various carbapenem resistance genes, except for the NDM gene; while the combination of aztreonam with NXL10 is also effective against bacteria that carry the NDM gene.

A second study was carried out by A. Endiamiani et al. in vivo in two models of infection in mice (septicemia and femoral infection) caused by K. pneumoniae, producing beta-lactamases KPC and therefore have a high level of resistance to imipenem and ceftazidime. The authors demonstrated that administering a 4: 1 combination of ceftazidime and NXL104 to animals significantly reduces bacterial wound contamination and increases the survival rates of infected mice.

Determination of the activity and efficacy of various beta-lactams in combination with NXL104 against bacteria resistant to carbapenems requires further detailed studies, both in vitro and in vivo, because these strains are rapidly distributed around the world. NDM-producing strains are thought to have first appeared in India, but are currently found in the United States, many European countries, Israel, Hong Kong, Japan and Kenya. The main carriers of the NDM-1 gene are K. pneumoniae and E. coli, however, resistant strains of Acinetobacter spp. have also been identified, which is a clear demonstration of the ease of propagation of the resistance gene located on the plasmid among different types of bacteria. This fact allows us to consider NDM-carrying bacteria as one of the most serious epidemic threats today.