einstein (São Paulo). 01/Jul/2015;13(3):7-8.

Antibiotics for Gram-negative infections

DOI: 10.1590/S1679-45082015ED3451

We do need them, and we need them now! New antibacterial drugs have been developed on the last 2 years for Gram-positive agents, but not with new targets. There has been real progress in developing antimycobacterial agents, including some new modes of action; however, what we have available today for Gram-negative multiresistant bacteria is the same we had 5 years ago, except for some molecular alterations in antibiotics, but no new bacterial target. Ceftazidime plus avibactam is combination therapy using a new beta-lactamase inhibitor, and similar combinations are also available in developed countries, as ceftozalone plus tazobactam, and meropenem plus RPX7009. The new aminoglycoside being tested is plazomycin, and there is a new quinolone, delafloxacin. Very old agents are being resurrected, such as fosfomycin, and only recently has been discovered what could be called a completely new type of antibacterial agent, teixobactin.

We do know the whole genome of many Gram-negative rods, but knowledge of the genetic make up of those germs did not lead to new imaginative antimicrobial agents. The golden era of antibiotic discovery was between the first discovery, that is, penicillin, in 1940, and the 1980’s; since them there was a dearth of new antibiotic discoveries. There are some reasons for this: first, the low hanging fruits have been collected, the easy discoveries have been made and the easy to find fungii have been studied to verify their capabilities to make antibiotics. Second, the financial incentives to the large pharmaceutical companies regarding antibiotics have never been very favourable. One cannot compare the revenues from antibiotics to gross revenues from chronic use drugs, such as statins or sildenafil and its derivatives. The same rationale applies to antineoplastic agents, which are also used for relatively long time and can be very expensive. Moreover, the new immunobiologics are financially worth the effort of being developed, both to auto-immune and neoplastic diseases. When wisely prescribed, antibiotics will be used for at most 2 to 3 weeks. On the other hand, statins are used for decades; and sildenafil and its derivatives, if they work (and mostly do), will be used by males for as much as they breathe…Third, there are more regulatory restrictions to develop antibiotics. There are relevant reasons for that: after being used in clinical practice, some quinolones proved to be hazardous and had to be recalled, with real damages to financial and to the image of pharmaceutical companies.

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