World Health Organization (WHO) bacterial priority pathogens list
| Bacteria | Priority group | Resistance type |
|---|---|---|
| Enterobacterales | critical | carbapenem-resistant |
| Enterobacterales | third-generation cephalosporin-resistant | |
| Acinetobacter baumanii | carbapenem-resistant | |
| Salmonella Typhi | high | fluoroquinolone-resistant |
| Shigella spp. | fluoroquinolone-resistant | |
| Enterococcus faecium | vancomycin-resistant | |
| Non-typhoidal Salmonella | fluoroquinolone-resistant | |
| Neisseria gonorrhoeae | third-generation cephalosporin and/or fluoroquinolone-resistant | |
| Staphylococcus aureus | methicillin-resistant | |
| Pseudomonas aeruginosa | carbapenem-resistant | |
| Group A Streptococci | medium | macrolide-resistant |
| Streptococcus pneumoniae | macrolide-resistant | |
| Haemophilus influenzae | ampicillin-resistant | |
| Group B Streptococci | penicillin-resistant |
Summary of antibiotics that can be used against carbapenemase-producing strains (Rejestr produktów leczniczych 2012; 2014; 2015a; 2015b; Electronic Medicines Compendium 2024; European Medicines Agency 2018; 2020a; 2020b; 2022; 2024b; 2024c)
| Substance | Spectrum | Indications |
|---|---|---|
| Colistin | P. aeruginosa, K. pneumoniae, E. coli, A. baumanii | Sepsis, lower RTI, UTI, RTI in CF patients |
| Fosfomycin | K. pneumoniae, E. coli, Citrobacter spp., Proteus spp. | Acute, uncomplicated cystitis; profuse, asymptomatic bacteriuria; UTI prevention before surgery and transurethral diagnostic procedures |
| Nitrofurantoin | E. coli, enterococci, staphylococci, Citrobacter spp., Klebsiella spp., Enterobacter spp. | Acute or recurrent lower UTI; inflammation of the renal pelvis (spontaneous or after surgery) |
| Tobramycin | P. aeruginosa, Corynebacterium spp., MSSA, Citrobacter spp., Haemophilus spp., Salmonella spp., Shigella spp, P. vulgaris | HAP (incl. severe pneumonia), exacerbations of lower RTI in CF patients, complicated and recurrent UTI; intra-abdominal infections; skin and soft tissue infections (incl. severe burns) |
| Amikacin | P. aeruginosa, S. aureus, Citrobacter freundii, E. coli, K. pneumoniae, P. mirabilis, P. vulgaris | HAP (incl. severe pneumonia), abdominal infections (incl. peritonitis and post-operative infections), complicated and recurrent UTI, skin and soft tissue infections and burns; bacterial endocarditis |
| Cefiderocol | E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, Enterobacter cloacae complex | Infections caused by aerobic Gram-negative bacteria, complicated UTI, pyelonephritis |
| Eravacycline | E. coli, K. pneumoniae, S. aureus, E. faecalis, E. faecium, Streptococcus spp. | Complicated intra-abdominal infections in adults |
| Lefamulin | S. pneumoniae, S. aureus, L. pneumophila, M. pneumoniae, C. pneumoniae | Community-acquired pneumonia (in case of ineffective treatment with recommended drugs) |
| Imipenem with relebactam | E. coli, H. influenzae, K. pneumoniae, P. aeruginosa, S. mercescens, | HAP, VAP; bacteremia in HAP, infections with aerobic Gram-negative bacteria in case of limited treatment options |
| Meropenem with vaborbactam | E. coli, K. pneumoniae, Enterobacter cloacae complex, Citrobacter spp., P. aeruginosa, S. mercescens, S. aureus, S. epidermidis, S. agalacitiae, B. fragilis, C. perfringens, Prevotella spp. | Complicated abdominal pneumonia, complicated UTI, pyelonephritis, HAP and VAP |
| Ceftazidime with avibactam | C. freundii, E. cloacae, E. coli, K. oxytoca, K. pneumoniae, P. aeruginosa, P. mirabilis, S. mercescens | Complicated intra-abdominal infection, complicated UTI, pyelonephritis, HAP, VAP, infections caused by aerobic Gram-negative microorganisms in adults and children > 3 months of age |
| Plazomycin | E. coli, K. pneumoniae, P. mirabilis, E. cloacae | UTI and pyelonephritis |
Drugs against GES carbapenemases producing strains in development (Soszyńska-Morys 2023; European Medicines Agency 2024a)
| Substance | Class | Spectrum | Research phase | Additional information |
|---|---|---|---|---|
| durlobactam + sulbactam | Inhibitor of β-lactamases of classes A, C and D, according to Ambler | Acinetobacter baumanii | Phase 3 clinical trials, completed | The combination shows greater activity against MDR |
| taniborbactam | Non-β-lactam inhibitor of β-lactamases of classes A, B, C, and D, according to Ambler | P. aeruginosa, Enterobacterales | Phase 3 clinical trials of taniborbactam with cefepime in UTIs, completed | Enables the use of cefepime against carbapenem-resistant strains |
| cefepime + enmetazobactam | β-lactam (cephalosporin) + β-lactamase inhibitor | ESBL-producing bacteria, Enterobacterales resistant to 3rd generation cephalosporins, Carbapenem-resistant K. pneumoniae | CHMP issued a marketing authorization for a medicinal product containing cefepime and enmetazobactam (2024) | Therapeutic area: pyelonephritis, UTI, HAP and VAP |
A comparison of the main features of selected GES-type carbapenemases_ Some of the GES-type antibiotic resistances are ESBL-type enzymes, which do not have carbapenemase properties_ Some of them do have carbapenemase activity_
| Enzyme | Mutation | Gene location | Microrganism | Year and country of identification | Referencesm |
|---|---|---|---|---|---|
| GES-1 | A170G | Plasmid | K. pneumoniae | 1998, France | Poiler et al. 2000 |
| GES-2 | G170N | Plasmid | P. aeruginosa | 2000, South Africa | Poiler et al. 2001 |
| GES-4 | G170S | Plasmid | K. pneumoniae | 2002, Japan | Queenan and Bush 2007 |
| GES-5 | G170S | Chromosomal | P. aeruginosa | 2007, Spain | Viedma et al. 2009 |
| GES-6 | G170S | Plasmid | K. pneumoniae | 2004, Greece | Queenan and Bush 2007 |
| GES-11 | G243A | Plasmid | A. baumannii | 2008, France | Moubareck et al. 2009 |
| GES-14 | G170S, G234A | Plasmid | A. baumannii | 2008, described in Belgium | Mabrouk et al. 2017 |
| GES-16 | Gln38Glu, G170S | Plasmid | S. marcescens | 2011, Brazil | Escandón et al. 2017 |
| GES-18 | G170S, V80I | Plasmid | P. aeruginosa | 2010, Belgium | Bebrone et al. 2013 |
| GES-20 | A165S | Chromosomal | P. aeruginosa | 2011, Mexico | Garza-Ramos et al. 2015 |