Ho Stanford 2019 – New Antibiotics
2017
- delafloxacin (fluoroquin)
- mero-vaborbactam (beta-lactam/beta-lactamase inhib)
- letermovir (for CMV) (PREVYMIS) *available on Stanford formulary
2018
- plazomicin (aminoglycoside) (ZEMDRI) *available on Stanford formulary
- eravacycline (tetracycline)
- omadacycline (tetracycline)
2019
- imipenem/cilastatin/relebactam (beta-lactam/beta-lactamase inhib)
ANTI-MRSA AND +/- VRE
- tedizolid (SIVEXTRO) *available on Stanford formulary
- oritavancan
- dalbavancan (DALVANCE) *available on Stanford formulary
- ceftolazone/tazobactam
- ceftazidime/avibactam
Lefamulin (XENLETA)
- FDA-approved for IV and oral treatment for CAP
- not active against Enterobacteriaceae or Pseudomonas
- in vitro/in vivo against Strep pneumoniae, H flu, mycoplasma pneumoniae, chlamydia pneumoniae, Legionella, and MSSA
Cefiderocol (FETROJA)
- broad in vitro activity against gram negatives -> including CRE
- active against carbapenem-resistant stuff -> CRE, carbapenem-resistant Pseudomonas, carbapenem acinetobacter, and Stenotrophamonas (which is usually sens to levaquin and bactrim)
- interestingly, FDA-approved for UTI but clearly this is a weird population <- this happens b/c they can enroll large numbers of pts (those w/ UTI) for these studies
Plazomicin (ZEMDRI)
- similar bucket of coverage as FETROJA
- a “next-generation” aminoglycoside
- FDA-approved for complicated UTI (again, b/c this population has studies?)
- Enterbacteriaceae who have limited treatment options -> susceptible E coli, Klebsiella, Proteus, Enterobacter cloacae)
- caution with ototoxicity/nephrotoxicity -> if CrCl is low, should do therapeutic drug monitoring
- has good synergism with colistin, mero-, and fosfomycin against gram neg bacteria (particularly those VIM-1 and KPC-producing gram negatives)
*available on Stanford formulary
Cefepime-resistant Enterobacter (DOI: 10.1128/AAC.01477-15 and https://doi.org/10.1093/cid/cit395)
- there is the notion that there are ampC-producing, ESBL-producing Enterbacter cloacae species -> we often treat them with cefepime or a carbapenem
- in vitro data suggests that cefepime retains activity against these ampC producing Enterobacter
TETRACYCLINES
- historically, chlortetracycline was subsequently manufactured to be tetracycline
- then, in the 1970s, the field developed doxycycline and minocycline
- then, in 2005, the production of tigecycline was performed -> broad spectrum of activity with gram positive and gram negative coverage
Eravacycline (XERAVA) (10.1007/s40265-016-0545-8)
- a synthetic tetracycline with widened activity
- more potent than tigecycline
- effective against ESBL-producing Enterbacteriaceae and carbapenem-resistant Acinetobacter baumanii
- not active against Pseudomonas or Burkholderia
- kind of like a better version of tigecycline
- more potent against gram positives and gram negatives than tigecycline -> not great against Pseudomonas
- good for complicated intra-abdominal infections
- don’t need to adjust for renal impairment
Omadacycline (NUZYRA)
- a first-in-class, oral drug -> aminomethylcycline
- available as PO or IV
- activity against the gram positives, gram negatives, and atypical
- of note, good against the tetracycline-resistant bacteria
- FDA-indicated -> community-acquired bacterial PNA and skin/soft-tissue infection
- no adjustment for renal or hepatic impairment
MRSA-ACTIVE ANTIBIOTICS
- vanco
- telavancin
- dalbavancin
- oritavancin^
- daptomycin^ (not great for lung infections nor CNS infections—use linezolid)
- ceftaroline
- linezolid^
- tedizolid^
- quinupristin-dalfopristin^ (but not active against E. faecalis)
- eravacycline^
- omadacycline^
- lefamulin^
^indicates VRE activity as well as MRSA activity
Delafloxacin (BEXDELA)
- new, improved fluoroquinolone which is active in acidic environments (abscess/empyema, vaginal area, urine) -> FDA-indicated for CAP, skin/soft-tissue infection
- watch LFT elevations
- bactericidal like other fluoroquinolones
- more active against MRSA
- gram positive activity -> MRSA, MSSA, Strep pneumoniae, Streptococcus, Enterococcus spp
- gram negative activity -> H flu, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Enterobacteriaceae, Pseudomonas
- anaerobes -> Bacteroides spp, Prevotella spp, C diff, Clostridium perfringens
- intracellular -> Mycoplasma spp, Ureaplasma spp, Chlamydia spp
- mycobacteria -> TB
COMBOS THAT COMBAT THE BETA-LACTAMASE
Ceftolozane/tazobactam (ZERBAXA)
- active against the ampC and ESBL producers -> i.e. ESBL Pseudomonas
- not great against anaerobes and gram positives
- FDA-indicated for
- complicated UTI/pyelo, complicated intra-abd infection (w/ flagyl)
- has been compared with meropenem for intra-abd infection
*available on Stanford formulary
Ceftazidime/avibactam (AVYCAZ)
- similar spectrum of activity as ZERBAXA
- not great against gram positives and anaerobes
- also, FDA-indicated for complicated UTI or complicated intra-abd infection w/ flagyl
*available on Stanford formulary
Meropenem-vaborbactam (VABOMERE)
- the vabo inhibits many of the beta-lactamases -> class A, class C and some class D beta-lactamases
- the class A effect is seen with the restored meropenem activity against Enterobacteriaceae that produce the class A, serine carbapenemase KPC.
- i.e. VABOMERE can now be used for KPC-producing Enterobacteriaceae
- FDA-indicated for complicated UTI, pyelonephritis
