Evasion of Antimicrobial Activity in Acinetobacter baumannii by Target Site Modifications: An Effective Resistance Mechanism
Abstract
:1. Introduction
2. Current Status of Antimicrobial Resistance in A. baumannii
Intrinsic Resistance in A. baumannii
3. Mechanisms of Antimicrobial Resistance
3.1. Antimicrobial Modification
3.2. Antimicrobial Efflux and Decreased Permeability
3.3. Antimicrobial Sequestration
3.4. Modification of the Target Site
4. Antimicrobials Whose Effect Is Evaded by Target Site Modification in A. baumannii
4.1. Polymyxin Resistance
Colistin Resistance in A. baumannii
4.2. Resistance to β-Lactams
4.3. Rifampicin Resistance
4.4. Resistance to Fluoroquinolones
4.5. Macrolides Resistance
4.6. Tetracycline Resistance
4.7. Oxazolidinone Resistance
4.8. Aminoglycoside Resistance
5. Treatment Options for A. baumannii Infections
5.1. Current Treatment Options
- Use antimicrobial associations.
- Administer them by optimizing the pharmacokinetic/pharmacodynamic (PK/PD) ratio.
- Give preference to antimicrobials that retain some degree of in vitro activity.
- Optimize other therapeutic measures, e.g., surgical debridement or removal of infected tissues or devices.
- Be sure that it is an infection instead of a colonization before starting the treatment.
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- Bacteremia: In cases associated with catheters or intravascular devices, give priority to their removal. Start the scheme with carbapenems, aminoglycosides, and rifampicin.
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- Pneumonia: Give preference to combined therapy for community-acquired pneumonia; for ventilator-associated pneumonia, when the patient has endotracheal intubation and mechanical ventilatory support, the patient should be placed in a semi-sitting position between 30° and 45°, preferably in a kinetic bed, which provides position changes with head elevation, in order to reduce the production of secretions. There is not enough evidence to support the generalized use of endotracheal cannulas impregnated with antiseptics for the reduction of VAP. (GPC IMSS624-13).
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- Urinary Tract Infection: Give preference in the plan to aminoglycosides and carbapenems. Use the Foley catheters for as long as necessary and remove them as soon as possible.
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- Central Nervous System Infection: Give preference in the plan to carbapenems and rifampicin for systemic use. Evaluate intraventricular or intrathecal use with aminoglycosides; however, their use is controversial since there are not much data in this regard.
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- Abdominal infection. In this site, it is essential to give priority to surgical treatment; start the plan with tigecycline, sulbactam, carbapenems, or aminoglycosides.
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- Skin and soft tissue infection: Prioritize surgical treatment by removing dead and contaminated tissue; initiate scheme with tigecycline, carbapenems, and aminoglycosides.
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- Infection or Osteoarticular: Give priority to surgical treatment by scraping bone and dead tissue; perform surgical lavage. Give preference in the plan to aminoglycosides and carbapenems.
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- Sulbactam, if MIC is less than or equal to 32 mg/L;
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- Meropenem or imipenem, if MIC is less than or equal to 16 mg/L;
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- Colistin: Less than or equal to 1 mg/L;
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- Tigecycline, if MIC is less than or equal to 4 mg/L.
5.2. Alternative Therapies without Antibiotics
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Antimicrobial Family | Antimicrobials | |
---|---|---|
β-lactams | Penicillins | Ampicillin a |
Amoxicillin-clavulanate a | ||
Ticarcillin Mezlocillin Piperacillin | ||
Piperacillin-tazobactam | ||
Cephalosporins | Cefoxitin Cefotetan Cefepime Ceftazidime Cephalothin Ceftriaxone Cefotaxime | |
Monobactams | Aztreonam a | |
Carbapenems | Ertapenem a Imipenem Meropenem | |
Amphenicols | Chloramphenicol a | |
Phosphonates | Fosfomycin a | |
Sulfonamides and diaminopyrimidines | Trimetroprim a Trimethoprim/sulfamethoxasol | |
Aminoglycosides | Amikacin Gentamicin Trobamycin | |
Macrolides | Erythromycin Azithromycin | |
Tetracyclines | Glycylcyclines Tigecycline Doxycycline Minocycline | |
Fluoroquinolones | Ciprofloxacin Norfloxacin Levofloxacin Moxifloxacin Gatifloxacin | |
Nitrofurans | Nitrofurantoin | |
Polymyxins | Polymyxin B Colistin |
Criteria | Condition | Options | |||
---|---|---|---|---|---|
Using Tigecycline (4) as a backbone | If MIC is less than or equal to 2 mg/L (sensitive) | Associated with aminoglycosides (gentamicin or amikacin) | Associated with sulbactam | Associated with rifampicin | Associated with carbapenem |
If MIC is equal to 4 mg/L (intermediate) | Associated with sulbactam + carbapenem | Sulbactam + fosfomycin | Sulbactam + rifampicin | Sulbactam + aminoglycoside (amikacin/gentamicin) | |
If MIC is greater than 8 mg/L (resistant), do not use tigecycline. Substitute MINOCYCLINE | Carbapenem (imipenem or meropenem) + sulbactam + rifampin | Carbapenem + sulbactam + aminoglycosides | Carbapenem + aminoglycoside rifampicin | ||
Using β-lactam-β-lactamase inhibitors | Do not use if the strain is carbapenem-resistant. | Meropenem/vaborbactam | Imipenem/relebactam | Ceftazidime/avibactam | Ceftolozane/tazobactam or aztreonam/avibactam |
For carbapenem-resistant strains | A. baumannii that does not produce MBL | Ampicillin/sulbactam and trimethoprim/sulfamethoxazole | Ampicillin-sulbactam + polymyxins (polymyxin b/colistin) | Sulbactam/avibactam | Ampicillin/sulbactam with ceftazidime/avibactam |
New alternatives | |||||
New antimicrobials | Minocycline alone or in association | Eravacycline | Cefiderocol (resistant strains have been found and availability is limited | ||
Based on phages and probiotics | vB_Ab-M-G7 | Bϕ-C62 | Βϕ-R2096 | Endolysins of phage ØABP-01 | Bifidobacterium brief on digestive tract infections |
Molecule-based | DS-8587 is a new fluoroquinolone that acts by inhibiting DNA topoisomerase | BAL 30072 monosulfactam; active against many Gram-negative bacteria, including those producing metallo-β-lactamases and KPC, and has a synergistic effect with carbapenems | GC-072 in preclinical phase. It is an oxoquinolizine compound | Gallium nitrate or gallium protoporphyrin IX whose activity is to sequester Fe ions | Rose Bengal (SecA inhibitor) in combination with imipenem or meropenem |
Bacteriocins | ST4A produced by E. mundtii | Nisin in clinical trials on pathogens associated with VAP |
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Martínez-Trejo, A.; Ruiz-Ruiz, J.M.; Gonzalez-Avila, L.U.; Saldaña-Padilla, A.; Hernández-Cortez, C.; Loyola-Cruz, M.A.; Bello-López, J.M.; Castro-Escarpulli, G. Evasion of Antimicrobial Activity in Acinetobacter baumannii by Target Site Modifications: An Effective Resistance Mechanism. Int. J. Mol. Sci. 2022, 23, 6582. https://doi.org/10.3390/ijms23126582
Martínez-Trejo A, Ruiz-Ruiz JM, Gonzalez-Avila LU, Saldaña-Padilla A, Hernández-Cortez C, Loyola-Cruz MA, Bello-López JM, Castro-Escarpulli G. Evasion of Antimicrobial Activity in Acinetobacter baumannii by Target Site Modifications: An Effective Resistance Mechanism. International Journal of Molecular Sciences. 2022; 23(12):6582. https://doi.org/10.3390/ijms23126582
Chicago/Turabian StyleMartínez-Trejo, Arturo, Juan Manuel Ruiz-Ruiz, Luis Uriel Gonzalez-Avila, Andrés Saldaña-Padilla, Cecilia Hernández-Cortez, Miguel Angel Loyola-Cruz, Juan Manuel Bello-López, and Graciela Castro-Escarpulli. 2022. "Evasion of Antimicrobial Activity in Acinetobacter baumannii by Target Site Modifications: An Effective Resistance Mechanism" International Journal of Molecular Sciences 23, no. 12: 6582. https://doi.org/10.3390/ijms23126582