shows an example of this complexity, in which alterations in membrane
proteins also contribute to the development of ceftazidime resistance.
The patient began with an E coli infection that was
ampicillin resistant, owing to the presence of the TEM-1 gene, but was
ceftazidime sensitive. Within a month, a ceftazidime-resistant strain
had emerged, without the elaboration of an ESBL. Instead, resistance
was effected through acquisition of a heavily expressed SHV-1 and the
concomitant elimination of one of the outer-membrane porins, reducing
access of the antibiotic to the periplasmic space. The combination of
TEM-1 and SHV-1, each relatively inactive against ceftazidime, together
with the diminished uptake of the drug, was sufficient to generate
resistance. Over the next several weeks (by December 23), the SHV-1
gene had mutated to generate SHV-8, by itself sufficient to confer
resistance, so that within a few days (by December 27), the
bacteria had restored production of the missing membrane porin, given
that its elimination was no longer required to resist ceftazidime.
Presumably, its restoration would then benefit the bacteria, since
membrane proteins normally would be expected to serve a variety of
functions unrelated to antimicrobial transit.