Ho Stanford 2019 – New Antibiotics

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