Antibiotics have saved countless lives since they were discovered nearly 90 years ago. However, decades of overuse have caused some bacteria to evolve antibiotic resistance, which poses a huge threat to public health. The Centers for Disease Control estimates that at least 2 million Americans are infected with antibiotic-resistant bacteria each year, and at least 23,000 people die as a direct result. 

Solving this problem is going to be a monumental undertaking, but, given the need for treatments that can safely defeat these bacteria, once next-generation antibiotics cross the finish line, they will likely be huge sellers.

Paratek Corp. (PRTK), Nabriva Therapeutics (NBRV), and Cempra (MLNT) are three small-cap biotechs that all have potential new antibiotics in clinical trials. Which is the best bet for investors today? 

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The leader

One of the leaders in this race is Paratek, whose lead compound is called omadacycline -- a once-daily treatment being developed to combat community-acquired bacterial pneumonia (CABP). 

Paratek provided investors great news from a phase 3 study that pitted omadacycline against the current standard-of-care treatment, moxifloxacin, in treating CABP. The study showed that omadacycline successfully demonstrated non-inferiority after initiation of therapy. Specifically, the early clinical response rate for omadacycline was 81.1% while moxifloxacin was 82.7%. What's more, omadacycline was shown to be safe and well tolerated by patients. Management stated that it planned to file for regulatory approval in the U.S. and Europe in 2018. 

The FDA has already granted omadacycline both a Qualified Infectious Disease Product designation and Fast Track status. When combined with the upbeat phase 3 data, investors have plenty of reasons to be optimistic about omadacycline's chances.

The challenger

Nipping on Paratek's heels is Nabriva Therapeutics. This company's lead compound, lefamulin, is another next-generation antibiotic being studied as a hopeful treatment for CABP.

Enthusiasm for lefamulin is running high in the wake of the company's recently completed LEAP 1 trial. In that phase 3 study, lefamulin demonstrated non-inferiority when compared to moxifloxacin with or without adjunctive linezolid. Drilling down to the specifics, lefamulin showed an early clinical response rate of 87.3% whereas moxifloxacin's rate was 90.2%. Lefamulin's safety data was also impressive.

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From here, the company is kicking off its LEAP 2 study, which is a second pivotal phase 3 trial that will compare oral lefamulin to moxifloxacin. Enrollment is expected to be completed soon, and top-line data should be available in early 2018.

While lefamulin is exciting, the need for a second phase 3 trial puts Nabriva one step behind Paratek in the race to bring a drug to market.

The turnaround

Once upon a time, Cempra boasted a commanding lead over both Paratek and Nabriva in this race. Its next-generation antibiotic solithromycin produced encouraging phase 3 data, and was submitted to the FDA for approval last year. Cempra was so confident in solithromycin's odds of success that management had even started to build out its commercial team.

You can guess what happened next. Cempra received the dreaded "complete response letter" -- the FDA's version of a rejection -- a few months after the drug was submitted. The agency raised concerns related to liver toxicity and manufacturing. They also told Cempra that they wanted to see data from a new phase 3 trial that was 10 times larger than the one that was submitted.

Predictably, investors found this news to be unpleasant, and reacted accordingly. The company has been picking up the pieces ever since.

In August, we learned that Cempra is merging with a privately held biotech called Melinta. Melinta is also studying next-generation antibiotics, and has already crossed the finish line with a drug called Baxdela as a treatment for acute bacterial skin and skin structure infections caused by susceptible bacteria. The company believes Baxdela could be a treatment for CABP, too. Once this merger is complete, Cempra will be stronger than ever, and could offer investors multiple shots on goal.

A Foolish investing strategy 

While Paratek's lead makes it appear to be the best bet today, Cempra's history provides an instructive reminder about what can go wrong for clinical stage biotechs. Cempra also looked like a slam dunk for a short period of time, but when it comes dealing with regulators, nothing is ever certain.

Given this reality, a smart investing strategy might be to buy a starter position in all three of these stocks. That would reduce your portfolio risk from any one of them imploding due to a negative regulatory decision, while still exposing you to plenty of upside potential if one or more of them truly hits pay dirt.