Background
Diagnosis
Antibiotic therapy
Empiric treatment
Advantages | Disadvantages |
---|---|
Broader coverage that includes non-susceptible strains | Possible antagonism |
Anti-bacterial synergy | Possible superinfection |
Prevents emergence of resistance | May increase resistance |
Increased toxicity | |
Increased costs |
De-escalation?
When to stop?
Dosing issues
Pharmacokinetics/pharmacodynamics
Doses of β-lactams
Doses of aminoglycosides
Dosing in obese patients
Dosing during extracorporeal therapies
A special situation: VAP
Diagnosis of VAP
Should we consider preemptive therapy in VAP?
A place for nebulized antibiotics in VAP?
New antibiotics in the pipeline
Drug class | Drug name | Development phase | Potential indications |
---|---|---|---|
Cephalosporin | GSK-2696266 | Phase 1 | Bacterial infections |
Novel cephalosporin + β-lactamase inhibitor | Ceftolozane + tazobactam | Approved March 2015 | Complicated urinary tract infections, complicated intra-abdominal infections, acute pyelonephritis (kidney infection), hospital-acquired bacterial pneumonia/ventilator associated pneumonia |
Ceftaroline + avibactam | Phase 2 | Complicated urinary tract infections | |
Ceftazidime + avibactam (CAZ-AVI) | Approved 2015 | Complicated urinary tract infections, complicated intra-abdominal infections, acute pyelonephritis (kidney infection), hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia | |
Monobactam + novel β-lactamase inhibitor | Aztreonam + avibactam (ATM-AVI) | Phase 1 | Bacterial infections |
Carbapenem + novel β-lactamase inhibitor | Carbavance | Phase 1 | Complicated urinary tract infections, complicated intra-abdominal infections, hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia, febrile neutropenia |
MK-7655 + imipenem/cilastatin | Phase 2 | Complicated urinary tract infections, acute pyelonephritis, complicated intra-abdominal infections | |
Aminoglycoside | Plazomicin | Phase 3 | Bloodstream infections and nosocomial pneumonia caused by carbapenem-resistant Enterobacteriaceae |
Fluoroquinolone | WKC 771 | Phase 1 | Bacterial infections |
WKC 2349 (WCK 771 pro-drug) | Phase 1 | Bacterial infections | |
Avarofloxacin | Phase 2 | Community-acquired bacterial pneumonia, acute bacterial skin and skin structure infections | |
Finafloxacin | Phase 2 | Complicated urinary tract infections, acute pyelonephritis (kidney infection), acute intra-abdominal infections, acute bacterial skin and skin structure infections | |
Nemonoxacin | Phase 2 | Community-acquired bacterial pneumonia, diabetic foot infection, acute bacterial skin and skin structure infections | |
Zabofloxacin | Phase 2 | Community-acquired bacterial pneumonia | |
Delafloxacin | Phase 3 | Acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, uncomplicated gonorrhea | |
Oxazolidinone | Tedizolid | Approved June 2014 | Acute bacterial skin and skin structure infections, hospital-acquired bacterial pneumonia/ventilator acquired bacterial pneumonia |
Cadazolid (quinolonyl-oxalidinone) | Phase 3 |
Clostridium difficile-associated diarrhea | |
Radezolid | Phase 2 | Acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia | |
MRX-I | Phase 1 | Bacterial infections including community-acquired MRSA and vancomycin-resistant enterococci infections | |
LCB01-0371 | Phase 1 | Bacterial infections | |
Lipopeptide and glycopeptide | Oritavancin | Approved August 2014 | Acute bacterial skin and skin structure infections |
Glycopeptide-cephalosporin heterodimer | TD-1607 | Phase 1 | Serious Gram-positive bacterial infections (acute bacterial skin and skin structure infections, hospital-acquired pneumonia/ventilator-associated pneumonia, bacteremia) |
TD-1792 | Phase 2 | Acute bacterial skin and skin structure infections, other serious infections caused by Gram-positive bacteria, including hospital-acquired pneumonia/ventilator-associated pneumonia and bacteremia | |
Lipo-glycopeptide | Dalbavancin | Approved May 2014 | Acute bacterial skin and skin structure infections |
Ramoplanin | Phase 2 |
Clostridium difficile-associated diarrhea | |
Lipopeptide | Surotomycin | Phase 3 |
Clostridium difficile-associated diarrhea |
Macrolide | |||
Ketolide | Solithromycin | Phase 3 | Community-acquired bacterial pneumonia, uncomplicated urogenital gonorrhea |
LptD inhibitor | POL7080 | Phase 2 | Ventilator-associated bacterial pneumonia, low respiratory infections |
Tetracycline | Omadacycline | Phase 2 | Community-acquired bacterial pneumonia, acute bacterial skin and skin structure infections, complicated urinary tract infections |
Eravacycline | Phase 3 | Complicated intra-abdominal infections, complicated urinary tract infections, hospital-acquired bacterial pneumonia | |
Monosulfactam | BAL30072 | Phase 1 | Multidrug-resistant Gram-negative bacterial infections |
Fabl inhibitor | Debio 1452 | Phase 2 | Acute bacterial skin and skin structure infections |
Debio 1450 (Debio 1452 pro-drug) | Phase 1 | Bacterial infections | |
CG-400549 | Phase 2 | Acute bacterial skin and skin structure infections; osteomyelitis | |
LpxC inhibitor | ACHN-975 | Phase 1 | Bacterial infections |
DNA gyrase inhibitor | AZD0914 | Phase 1 | Uncomplicated gonorrhea |
Methionyl-tRNA synthetase (MetRS) inhibitor | CRS-3123 | Phase 1 |
C. difficile infection |
Peptide deformylase inhibitor | GSK-1322322 | Phase 2 | Acute bacterial skin and skin structure infections |
Type 2 topoisomerase inhibitor | GSK-2140944 | Phase 2 | Respiratory tract infections, acute bacterial skin and skin structure infections |
Bicyclolide | EDP-788 | Phase 1 | Bacterial infections |
Pleuromutilin | Lefamulin (BC-3781) | Phase 2 | Acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia |
Elongation factor inhibitor | LFF571 | Phase 2 |
C. difficile-associated diarrhea |
Fusidane | Taksta (fusidic acid) | Phase 2 | Prosthetic joint infections |
Defensin-mimetic | Brilacidin | Phase 2 | Acute bacterial skin and skin structure infections |
SMT19969 | Phase 2 |
C. difficile-associated diarrhea |