Multidrug treatment to prevent evolution of resistance

Question

I was just reading an article in PLOS Medicine on the treatment of multidrug resistant TB. They suggest that treatments are more effective if a large number (more than 5) treatments are used simultaneously.

I know also that many infectious diseases are currently treated with combination therapies (eg ACT for malaria, atripla for HIV) to slow the evolution of drug resistance. I was curious if there was a down side to using every (or almost every) available treatment for a given infectious disease, instead of one or a few?

Certainly some treatments come with side effects which are unpleasant enough to avoid them from the start, and there may be instances where different drugs interact to be less effective (or in combination tolerated only in lower, less effective doses). But in general, is there a downside to hitting infectious agents with every potentially effective treatment as a matter of course?

Answer 1

tl;dr - No, not really. HIV is different. No, use what is best (or best assumption based upon symptoms, finding, etc.) for infection.

You are asking several questions.
TB is a very tough bacteria to treat taking many months of therapy for two main reasons:
1. It replicates very slowly. Preventing replication is one major area where antibiotics are effective. Slow replications makes stopping this process take longer as it is difficult to completely break the chain to reproduction.
2. It has the ability to encapsulate itself against the environment making it more difficult to get antimicrobials to penetrate and fight the infection.
This is the simple explanation for why "hitting it" at every angle is the best mode of attack, especially in a situation where you have multi-drug resistance and are forced to use what would normally be "second line" agents.

That being said, Successful eradication should lead to minimal additional drug resistance as all bacterial containing genes that allow for drug resistance to be wiped out and preventing them from being passed along to develop further resistances.
HIV is treated with HAART (highly active antiretroviral therapy) to attack the virus at various modes of replication and entry into the cells. Another example of hitting it at every angle. One strategy utilized in HAART is to use medications specifically for their drug interactions. Retrovir is utilized to increase the drug levels of other agents which allows for utilization of lower dosages. Lower doses = reduced side effects (typically).
Lastly, with a generic infection, overkill is simply overkill. Treatment with appropriate antibiotics is considered better utilization of every possible antibiotic available. More medications means more side effects, increased risk of drug-drug interactions, and cost. Medicine typically follows the path of empiric (best estimation of pathogen and course of treatment for it), followed by a culture to determine exact pathogen, then specific treatment of that pathogen.

Answer 2

Hitting infectious agents with every potentially effective treatment is not recommended as there are best practices and guidelines that are usually available for most clinical situations that you are likely to encounter. However, in the remote event that you've become a pioneer and find yourself treading uncharted seas, you will probably be at liberty like most pioneers to adapt to the situation as a clinician and guided by sound knowledge of microbiology and pharmacology you will be able to eliminate your patient's pathology and restore their physiology.