Resistance

Blood, CSF
Don't test other types, still may have a positive growth despite patient recovery which can lead to excessive antibiotic treatment

2-3 days of treatment at a minimum, unless a specific test comes back which definitavely says treatment is ineffective

Resistance genes are in the bacteria, and are upregulated in response to antibiotic, or downregulated without antibiotic present

In inducible resistance, initial testing may show the bacteria is susceptible, but when dosed in the body, certain antibiotics may induce resistance and cause resistance not seen in laboratory testing

Resistance where the downregulation of the bacterial resistance genes have been mutated, which makes the bacteria constantly produce it's resistance mechanism at high levels

Found in gram negative resistance, the bacteria downregulates expression of porin channels found on its outer cell membrane. This makes it harder for drugs to access the cell wall. Not found in gram positive bacteria, as the cell wall is already exposed.

Chromosomal and constitutive, resulting in high level resistance

Carbapenem resistance by Pseudomonas aeruginosa (OprdD porin loss)
Cephalosporin/carbapenem resistance in klebsiella and enterobacter species

Occurs in both gram positive and negative bacteria, although more clinically relevent in gram negative as the double membrane allows more opportunity to pump out drugs. Pumps antibiotics out of the bacteria so it cannot work against it.

chromosomal and either inducible or constitutive, with or low or high level resistance

Resistance nodulation division (RND) family

Flouroquinolones, they are suceptible to many types of efflux pumps, and will likely cause selection of antibiotic resistant pseudomonas if used as monotherapy

A low level resistance expressed across many classes of antibiotics (eg, resistance to both flouroquinolones and beta lactams)

E. Coli*
Enterobacter
Klebsiella

Flouroquinolones and trimethoprim sulfamethoxazole

It is an efflux pump which is encoded by a Plasmid in E. Coli, meaning it can be easily transfered between different gram-negative bacteria

macrolide efflux, found in streptococcus pneumoniae (gram postive), which produces low level resistance

Can still be treated with macrolides at higher doses unless it is in the CNS

Provides low level resistance to early fluoroquinolones (Norfloxacin, ciprofloxacin) in staph aureus. Present in all staph aureus, and treatment with fluoroquinolones will select for high resistance. Makes treatment of MRSA with fluoroquinolones impossible.

Chromosomal constitutive resistance that results in low level resistance, ocurring in both positive and negative bacteria, by making the cell wall or membrane harder for drugs to penetrate.

Thickening of cell walls which prevents penetration into areas of cell-wall synthesis

Change cell membrane consistency to limit interaction

Target site in bacteria is altered so antibiotic can't bind. Chromosomal resistance that is typically consitutive but may be inducible, found in both gram positive and negative bacteria. High level resistance.

LOW LEVEL resistance through slight alteration of penicillin binding proteins

High level resistance to all beta lactams except ceftaroline via production of mutant PBP (PBP 2a)

Mutations of either DNA gyrase or topoisomerase IV (or both for high level resistance)

Change in the end terminus of the peptidoglycan amino acids from D-alanine D-alanine to D-alanine D-lactate

macrolide, lincosamide, and group B streptogramin resistance, found in staphylococci and streptococci

erm gene causes methylation of ribosomal binding site

susceptible to both erythromycin and clindamycin

Resistant to both erythromycin and clindamycin

Resistant to erythromycin
falsely susceptible to clindamycin
Must then run a D-test to identify if it is actually MLSb

DNA gyrase mutation so it cannot bind

Never, mutations to RNA polymerase causes high level resistance in both gram negative and positive bacteria

Mutated dihydrofolate reductase or dihydropteroate synthase enzymes

Occurs in gram positive and negative, but more clinically significant in gram negative. Chromosomal or plasmid/transposon, and either inducible or constitutive. Results in high level resistance.

plasmid mediated

chromosomal beta lactamase that Breaks down ampicillin and all other beta lactams. Inducible or constitutive, Found in gram-negative SPACE pathogens

Serratia
Pseudomonas
Acinetobacter and Aeromonas
Citrobacter
Enterobacter (and Klebsiella)* ~10% risk of resistance with these

Cefepime
Ceftolozane/Tazobactam
Carbapenems

Avibactam, Relebactam, and Vaborbactam all work

Clavulanic acid, sulbactam, and tazobactam do not

Plasmid borne beta lactamase, which can confer high or low level resistance. Break down all beta lactams except carbapenems

Klebsiella and E.coli

The most common type of ESBL found on E.Coli.

All of them in vitro, but limited clinical data

Again, avi, rele, and vaborbactam are the most effeciacious

Carbapenems
Ceftolozine/tazobactam
ceftazidime/avibactam

Ampicillin/sulbactam and piperacillin/tazobactam may be ok for UTIs

Must confirm susceptibility and site of infection
for systemic infections: fluoroquinolones and TMP/SMX
For UTIs: Fluoroquinolones, TMP/SMX, aminoglycosides, fosfomycin, nitrofurantoin

If it is resistant to ertapenem (MICs >2mg/L) and susceptible to meropenem (MICs <1mg/L), then it is likely not carbapenemase producing

Extended infusion of meropenem

If it is resistant to both ertapenem and meropenem, then it is likely carbapenemase producing

Ceftazidime-avibactam
then, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol
if not a bloodstream or UTI infection, can consider tigecycline or eravacycline

Meropenem-vaborbactam
Ceftazidime-avibactam (can cause selection of resistance)

Ceftazidime-avibactam
Cefiderocol

Ceftazidime/avibactam and aztreonam