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

Screen Shot 2019-12-17 at 10.59.34

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

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