Infectious Diseases II
Decreased permeability (i.e., porin loss, thickened cell wall)
Target modification (i.e., alteration in penicillin-binding proteins)
Hydrolysis (i.e., Ξ²-lactamases, aminoglycoside-modifying enzymes)
Crowding of patients with high levels of disease acuity and/or antimicrobial use
Colonization pressure: Proportions of people colonized with resistant bacteria. Combated by strict
compliance with infection control procedures to prevent colonization, adequate nurse staffing ratios,
and hand hygiene
Use of invasive devices (endotracheal tubes, intravascular catheters, and urinary catheters)
Previous or prolonged use of antibiotics
please see the IDSA 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections
[Clin Infect Dis. 2024 Aug 7:ciae403. https://doi.org/10.1093/cid/ciae403])
ESBL
Confers resistance to third-generation cephalosporins and aztreonam
Found primarily in E. coli and K. pneumoniae spp. but can also be seen in other Enterobacterales.
Carbapenems should be considered the drug of choice in severe infections.
| d. | NonβΞ²-lactams could be used if they showed sensitivity on AST; however, because ESBLs are |
|---|
usually plasmid mediated, there are often other acquired resistance mechanisms. The rates of
cross-resistance to other classes of antibiotics are 55%β100%.
Ξ²-lactam/Ξ²-lactamase inhibitors and cefepime often have in vitro activity, though clinical failures
have been reported.
A previous post hoc analysis found that use of Ξ²-lactam/Ξ²-lactamase inhibitors was not associated
with worse outcomes for ESBL-producing E. coli bacteremia compared with carbapenems.
ii.
However, a recent prospective randomized controlled noninferiority study evaluating definitive
treatment of ceftriaxone-resistant E. coli or K. pneumoniae found increased mortality with
piperacillin/tazobactam compared with meropenem (12.3% vs. 3.7%). These results do not
support the use of piperacillin/tazobactam in the treatment of ESBL-producing organisms.
iii.
Data are conflicting regarding the use of cefepime for treating ESBL infections. Some studies
show worse outcomes, whereas others show no difference compared with carbapenems. This
may partly be explained by the cefepime MIC distribution. Traditionally (before 2014), the
susceptibility breakpoint for cefepime for Enterobacterales was 8 mcg/mL or less. However,
in 2014, CLSI recommended decreasing the sensitive cefepime MIC breakpoint to 2 mcg/mL.
In addition, a new category for sensitive dose-dependent was created, where maximal doses
of cefepime are recommended for MICs of 4 and 8 mcg/mL. Hence, for many years, cefepime
may have been used in ESBL infections when the MIC was 4β8 mcg/mL, but doses were not
optimized.
iv.
Of interest, a recent investigation correlated cefepime MIC to ESBL Enterobacterales with
mortality, where a cefepime MIC of 1 mcg/mL or less was associated with significantly lower
mortality compared with higher MIC values. Together, given the conflicting clinical results, it
is difficult to endorse the use of cefepime for the treatment of ESBL infections. However, in a
stable patient with an ESBL infection having a cefepime MIC of 1 mcg/mL or less, cefepime
may be considered for consolidative therapy to minimize carbapenem use.