I'm trying to investigate the history of resistance. Just how good was penicillin when it first emerged? Were there any gram positives it couldn't get?

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    Doesn't look like a stupid question to me! – o0'. Jun 20 '15 at 7:00
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    Oh, that's mainly for the StackOverflow, where my questions are pretty basic. – Carbon Jun 20 '15 at 18:30

No, it would not have been effective against everything.

For instance, bacteria with with sufficient β-lactamase production would have been resistant. This enzyme is very ancient as well, having evolved a billion years ago. Thus, while I don't know of any species that was resistant as a whole, individual resistant bacterium existed before penicillin's clinical adoption. This was proven in the Lederberg Experiment, which showed that resistant bacteria existed in a colony before contact with penicillin, as opposed to appearing as a mutation afterwards.

What is clear, however, is that the efficacy of penicillin has been degrading. When initially made available for general anti-bacterial use, penicillin was incredibly effective against staphylococci and streptococci, two very prolific causes of infections. It didn't last - as early as 1946, reports of penicillin resistant Staphylococcus aureus were appearing around the world, and now most strains of the bacteria have became resistant. By the 1960s it had evolved into the scourge known as MSRA.

When penicillin was introduced in 1944 over 94% of Staphylococcus aureus isolates were susceptible; by 1950 half were resistant. By 1960 many hospitals had outbreaks of virulent multi-resistant S. aureus.

- Livermore, David M. "Antibiotic Resistance in Staphylococci." International Journal of Antimicrobial Agents 16 (2000): 3-10.

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    Cool. Didn't realize how prevalent resistant bacteria already were - resistance is both a selection and evolution process, then. – Carbon Jun 24 '15 at 16:28
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    @ProbablyAStupidQuestion "natural" selection is a key part of the evolutionary process after all ;) – Semaphore Jun 24 '15 at 16:30
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    Bacteria are so small, prolific, and short-lived that any anti-bacterial in the long run is doomed to be evolved around. – T.E.D. Jun 24 '15 at 17:30

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