Clinical Research
BibTex RIS Cite

Aminoglycoside Resistance in Common Pathogens

Year 2025, Volume: 7 Issue: 2, 31 - 38, 01.09.2025
https://doi.org/10.55994/ejcc.1729315

Abstract

This study investigated the resistance patterns to aminoglycosides among 137 bacterial isolates derived from various clinical specimens submitted to the Microbiology Laboratory at XXX Training and Research Hospital in the year 2005. The bacterial isolates were Escherichia coli (n=34), Klebsiella pneumoniae (n=30), Pseudomonas aeruginosa (n=30), Acinetobacter baumannii (n=23), and Staphylococcus aureus (n=20). Staphylococcus aureus was further classified into methicillin-susceptible strains (MSSA, n=13) and methicillin-resistant strains (MRSA, n=7). We examined the susceptibility against eight distinct aminoglycosides.
Isepamicin exhibited the lowest overall resistance rates within Gram-negative bacilli, particularly among isolates of P. aeruginosa and A. baumannii derived from intensive care units (ICUs). Streptomycin presented the highest levels of resistance. Statistically significant differences in resistance rates were observed between ICU and non-ICU isolates for gentamicin (χ² = 11.19, p = 0.0037), amikacin (χ² = 8.82, p = 0.0121), and isepamicin (χ² = 9.67, p = 0.0079). This suggests an increased resistance rate in intensive care units.
MRSA strains were more resistant to various aminoglycosides, including gentamicin, tobramycin, and isepamicin, in comparison to MSSA strains. These observed differences were not statistically significant. These resistance patterns highlight the limitations of older drugs like streptomycin and kanamycin.
The sustained efficacy of isepamicin and netilmicin positions them as viable treatment alternatives, particularly for infections caused by multidrug-resistant organisms. The results point to the necessity for routine susceptibility testing, careful antimicrobial stewardship, and judicious antibiotic selection to enhance patient outcomes and address resistance in high-risk environments such as the ICU.

References

  • Hermann T. Aminoglycoside antibiotics: old drugs and new therapeutic approaches. Cell Mol Life Sci. 2007;64(14):1841-1852. doi:10.1007/s00018-007-7034-x
  • Atassi G, Medernach R, Scheetz M, Nozick S, Rodes NJ, Murphy-Belcaster M. et al. Genomics of aminoglycoside resistance in Pseudomonas aeruginosa bloodstream infections at a United States academic hospital. Microbiol Spectr. 2023;11(3):e0508722. doi:10.1128/spectrum.05087-22
  • Shaul P, Green K, Rutenberg R, Kramer M, Berkov-Zrihen Y, Breiner-Goldstein E. et al. Assessment of 6′- and 6′′′-N-acylation of aminoglycosides as a strategy to overcome bacterial resistance. Org Biomol Chem. 2011;9(11):4057-4065. doi:10.1039/c0ob01133a
  • Mueller E, Boucher B. The use of extended-interval aminoglycoside dosing strategies for the treatment of moderate-to-severe infections encountered in critically ill surgical patients. Surg Infect (Larchmt). 2009;10(6):563-570. doi:10.1089/sur.2007.080
  • Kudo F, Eguchi T. Aminoglycoside antibiotics: new insights into the biosynthetic machinery of old drugs. Chem Rec. 2015;16(1):4-18. doi:10.1002/tcr.201500210
  • Juhas, M., Widlake, E., Teo, J., Huseby, D., Tyrrell, J., Polikanov, Y. et al. In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii. J Antimicrob Chemother. 2019;74(4):944-952. doi:10.1093/jac/dky546
  • Niu J, Yan M, Xu J, Xu Y, Chang Z, Suolang S. The resistance mechanism of Mycoplasma bovis from yaks in Tibet to fluoroquinolones and aminoglycosides. Front Vet Sci. 2022;9:840981. doi:10.3389/fvets.2022.840981
  • Xue, X., Mutyam, V., Tang, L., Biswas, S., Du, M., Jackson, L. A. et al. (2014). Synthetic aminoglycosides efficiently suppress cystic fibrosis transmembrane conductance regulator nonsense mutations and are enhanced by ivacaftor. American Journal of Respiratory Cell and Molecular Biology, 50(4), 805-816. https://doi.org/10.1165/rcmb.2013-0282oc
  • Poirel L, Lambert T, Türkoğlu S, Ronco E, Gaillard J, Nordmann P. Characterization of class 1 integrons from Pseudomonas aeruginosa that contain the blaVIM-2 carbapenem-hydrolyzing β-lactamase gene and of two novel aminoglycoside resistance gene cassettes. Antimicrob Agents Chemother. 2001;45(2):546-552. doi:10.1128/aac.45.2.546-552.2001
  • Seupt A, Schniederjans M, Tomasch J, Häußler S. Expression of the MexXY aminoglycoside efflux pump and presence of an aminoglycoside-modifying enzyme in clinical Pseudomonas aeruginosa isolates are highly correlated. Antimicrob Agents Chemother. 2020;65(1):e01166-20. doi:10.1128/aac.01166-20
  • Sou T, Hansen J, Liepinsh E, Backlund M, Ercan O, Grī̄nberga S. et al. Model‐informed drug development for antimicrobials: translational PK and PK/PD modeling to predict an efficacious human dose for apramycin. Clin Pharmacol Ther. 2021;109(4):1063-1073. doi:10.1002/cpt.2104
  • Maraki S, Samonis G, Karageorgopoulos DE, Mavros MN, Kofteridis DP, Falagas ME. In vitro antimicrobial susceptibility to isepamicin of 6,296 Enterobacteriaceae clinical isolates collected at a tertiary care university hospital in Greece. Antimicrob Agents Chemother. 2012;56(6):3067-3073. doi:10.1128/aac.06358-11
  • Duscha S, Boukari H, Shcherbakov D, Salian S, Silva S, Kendall A, et al. Identification and evaluation of improved 4′-O-(alkyl) 4,5-disubstituted 2-deoxystreptamines as next-generation aminoglycoside antibiotics. mBio. 2014;5(5):e01827-14. doi:10.1128/mbio.01827-14
  • Lo J, Kulp SK, Chen C, Chiu H. Sensitization of intracellular Salmonella enterica serovar Typhimurium to aminoglycosides in vitro and in vivo by a host-targeted antimicrobial agent. Antimicrob Agents Chemother. 2014;58(12):7375-7382. doi:10.1128/aac.03778-14
  • Strateva T, Ouzounova-Raykova V, Markova B, Todorova A, Marteva-Proevska Y, Mitov I. Problematic clinical isolates of Pseudomonas aeruginosa from the university hospitals in Sofia, Bulgaria: current status of antimicrobial resistance and prevailing resistance mechanisms. J Med Microbiol. 2007;56(7):956-963. doi:10.1099/jmm.0.46986-0
  • Kandasamy J, Atia-Glikin D, Shulman E, Shapira K, Shavit M, Belakhov V, et al. Increased selectivity toward cytoplasmic versus mitochondrial ribosome confers improved efficiency of synthetic aminoglycosides in fixing damaged genes: a strategy for treatment of genetic diseases caused by nonsense mutations. J Med Chem. 2012;55(23):10630-10643. doi:10.1021/jm3012992
  • Pal V, Khan MH. In vitro evaluation of antimicrobial activity of Psidium guajava leaf extract against selected pathogenic bacteria. J Pharm Negat Results. 2022;13(Suppl 6):1840-1844. doi:10.47750/pnr.2022.13.s06.242
  • Giske CG, Monnet DL, Cars O, Carmeli Y. Clinical and economic impact of common multidrug-resistant Gram-negative bacilli. Antimicrob Agents Chemother. 2008;52(3):813-821. doi:10.1128/AAC.01169-07
  • Lindemann PC, Risberg K, Wiker HG, Mylvaganam H. Aminoglycoside resistance in clinical Escherichia coli and Klebsiella pneumoniae isolates from Western Norway. APMIS. 2012;120(6):495-502. doi:10.1111/j.1600-0463.2011.02856.x
  • Fong D, Berghuis AM. Structural basis of Aph(3′)-IIIa-mediated resistance to N1-substituted aminoglycoside antibiotics. Antimicrob Agents Chemother. 2009;53(7):3049-3055. doi:10.1128/aac.00062-09
  • Ndip RN, Meriki HD, Ndip L, Akoachere JFK, Akenji TN. Pseudomonas aeruginosa isolates recovered from clinical and environmental samples in Buea, Cameroon: current status on biotyping and antibiogram. Trop Med Int Health. 2005;10(1):74-81. doi:10.1111/j.1365-3156.2004.01353.x

Sık Rastlanan Patojenlerdeki Aminoglikozit Direnci

Year 2025, Volume: 7 Issue: 2, 31 - 38, 01.09.2025
https://doi.org/10.55994/ejcc.1729315

Abstract

Bu çalışmada, 2005 yılında XXX Eğitim ve Araştırma Hastanesi Mikrobiyoloji Laboratuvarı’na gönderilen çeşitli klinik örneklerden izole edilen 137 bakteriyel izolatın aminoglikozid direnç paternleri incelenmiştir. İzolatlar arasında Escherichia coli (n=34), Klebsiella pneumoniae (n=30), Pseudomonas aeruginosa (n=30), Acinetobacter baumannii (n=23) ve Staphylococcus aureus (n=20) yer almakta olup, S. aureus izolatları metisiline duyarlı (MSSA, n=13) ve metisiline dirençli (MRSA, n=7) olarak sınıflandırılmıştır. Sekiz farklı aminoglikozide karşı duyarlılık test edilmiştir.
Gram-negatif izolatlar arasında isepamisin için, özellikle yoğun bakım ünitesinden (YBÜ) elde edilen P. aeruginosa ve A. baumannii suşlarında en düşük direnç oranları gözlenmiştir. Streptomisin ise en yüksek direnç oranlarına sahiptir. YBÜ izolatları ile genel izolatlar arasında gentamisin (χ² = 11.19, p = 0.0037), amikasin (χ² = 8.82, p = 0.0121) ve isepamisin (χ² = 9.67, p = 0.0079) için istatistiksel olarak anlamlı direnç farkları saptanmıştır.
S. aureus izolatları arasında MRSA suşları, gentamisin, tobramisin ve isepamisine karşı daha yüksek direnç göstermiştir ancak bu farklar istatistiksel olarak anlamlı bulunmamıştır. Elde edilen bulgular eski jenerasyon antibiyotiklerin (streptomisin, kanamisin) sınırlı etkinliğini yansıtmaktadır.
İsepamisin ve netilmisin gibi ajanlar, çok ilaca dirençli enfeksiyonların tedavisinde değerli seçenekler olarak öne çıkmakta olup, bu çalışma antibiyotik direnciyle mücadelede düzenli duyarlılık testlerinin ve antimikrobiyal yönetimin önemini vurgulamaktadır.

References

  • Hermann T. Aminoglycoside antibiotics: old drugs and new therapeutic approaches. Cell Mol Life Sci. 2007;64(14):1841-1852. doi:10.1007/s00018-007-7034-x
  • Atassi G, Medernach R, Scheetz M, Nozick S, Rodes NJ, Murphy-Belcaster M. et al. Genomics of aminoglycoside resistance in Pseudomonas aeruginosa bloodstream infections at a United States academic hospital. Microbiol Spectr. 2023;11(3):e0508722. doi:10.1128/spectrum.05087-22
  • Shaul P, Green K, Rutenberg R, Kramer M, Berkov-Zrihen Y, Breiner-Goldstein E. et al. Assessment of 6′- and 6′′′-N-acylation of aminoglycosides as a strategy to overcome bacterial resistance. Org Biomol Chem. 2011;9(11):4057-4065. doi:10.1039/c0ob01133a
  • Mueller E, Boucher B. The use of extended-interval aminoglycoside dosing strategies for the treatment of moderate-to-severe infections encountered in critically ill surgical patients. Surg Infect (Larchmt). 2009;10(6):563-570. doi:10.1089/sur.2007.080
  • Kudo F, Eguchi T. Aminoglycoside antibiotics: new insights into the biosynthetic machinery of old drugs. Chem Rec. 2015;16(1):4-18. doi:10.1002/tcr.201500210
  • Juhas, M., Widlake, E., Teo, J., Huseby, D., Tyrrell, J., Polikanov, Y. et al. In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii. J Antimicrob Chemother. 2019;74(4):944-952. doi:10.1093/jac/dky546
  • Niu J, Yan M, Xu J, Xu Y, Chang Z, Suolang S. The resistance mechanism of Mycoplasma bovis from yaks in Tibet to fluoroquinolones and aminoglycosides. Front Vet Sci. 2022;9:840981. doi:10.3389/fvets.2022.840981
  • Xue, X., Mutyam, V., Tang, L., Biswas, S., Du, M., Jackson, L. A. et al. (2014). Synthetic aminoglycosides efficiently suppress cystic fibrosis transmembrane conductance regulator nonsense mutations and are enhanced by ivacaftor. American Journal of Respiratory Cell and Molecular Biology, 50(4), 805-816. https://doi.org/10.1165/rcmb.2013-0282oc
  • Poirel L, Lambert T, Türkoğlu S, Ronco E, Gaillard J, Nordmann P. Characterization of class 1 integrons from Pseudomonas aeruginosa that contain the blaVIM-2 carbapenem-hydrolyzing β-lactamase gene and of two novel aminoglycoside resistance gene cassettes. Antimicrob Agents Chemother. 2001;45(2):546-552. doi:10.1128/aac.45.2.546-552.2001
  • Seupt A, Schniederjans M, Tomasch J, Häußler S. Expression of the MexXY aminoglycoside efflux pump and presence of an aminoglycoside-modifying enzyme in clinical Pseudomonas aeruginosa isolates are highly correlated. Antimicrob Agents Chemother. 2020;65(1):e01166-20. doi:10.1128/aac.01166-20
  • Sou T, Hansen J, Liepinsh E, Backlund M, Ercan O, Grī̄nberga S. et al. Model‐informed drug development for antimicrobials: translational PK and PK/PD modeling to predict an efficacious human dose for apramycin. Clin Pharmacol Ther. 2021;109(4):1063-1073. doi:10.1002/cpt.2104
  • Maraki S, Samonis G, Karageorgopoulos DE, Mavros MN, Kofteridis DP, Falagas ME. In vitro antimicrobial susceptibility to isepamicin of 6,296 Enterobacteriaceae clinical isolates collected at a tertiary care university hospital in Greece. Antimicrob Agents Chemother. 2012;56(6):3067-3073. doi:10.1128/aac.06358-11
  • Duscha S, Boukari H, Shcherbakov D, Salian S, Silva S, Kendall A, et al. Identification and evaluation of improved 4′-O-(alkyl) 4,5-disubstituted 2-deoxystreptamines as next-generation aminoglycoside antibiotics. mBio. 2014;5(5):e01827-14. doi:10.1128/mbio.01827-14
  • Lo J, Kulp SK, Chen C, Chiu H. Sensitization of intracellular Salmonella enterica serovar Typhimurium to aminoglycosides in vitro and in vivo by a host-targeted antimicrobial agent. Antimicrob Agents Chemother. 2014;58(12):7375-7382. doi:10.1128/aac.03778-14
  • Strateva T, Ouzounova-Raykova V, Markova B, Todorova A, Marteva-Proevska Y, Mitov I. Problematic clinical isolates of Pseudomonas aeruginosa from the university hospitals in Sofia, Bulgaria: current status of antimicrobial resistance and prevailing resistance mechanisms. J Med Microbiol. 2007;56(7):956-963. doi:10.1099/jmm.0.46986-0
  • Kandasamy J, Atia-Glikin D, Shulman E, Shapira K, Shavit M, Belakhov V, et al. Increased selectivity toward cytoplasmic versus mitochondrial ribosome confers improved efficiency of synthetic aminoglycosides in fixing damaged genes: a strategy for treatment of genetic diseases caused by nonsense mutations. J Med Chem. 2012;55(23):10630-10643. doi:10.1021/jm3012992
  • Pal V, Khan MH. In vitro evaluation of antimicrobial activity of Psidium guajava leaf extract against selected pathogenic bacteria. J Pharm Negat Results. 2022;13(Suppl 6):1840-1844. doi:10.47750/pnr.2022.13.s06.242
  • Giske CG, Monnet DL, Cars O, Carmeli Y. Clinical and economic impact of common multidrug-resistant Gram-negative bacilli. Antimicrob Agents Chemother. 2008;52(3):813-821. doi:10.1128/AAC.01169-07
  • Lindemann PC, Risberg K, Wiker HG, Mylvaganam H. Aminoglycoside resistance in clinical Escherichia coli and Klebsiella pneumoniae isolates from Western Norway. APMIS. 2012;120(6):495-502. doi:10.1111/j.1600-0463.2011.02856.x
  • Fong D, Berghuis AM. Structural basis of Aph(3′)-IIIa-mediated resistance to N1-substituted aminoglycoside antibiotics. Antimicrob Agents Chemother. 2009;53(7):3049-3055. doi:10.1128/aac.00062-09
  • Ndip RN, Meriki HD, Ndip L, Akoachere JFK, Akenji TN. Pseudomonas aeruginosa isolates recovered from clinical and environmental samples in Buea, Cameroon: current status on biotyping and antibiogram. Trop Med Int Health. 2005;10(1):74-81. doi:10.1111/j.1365-3156.2004.01353.x
There are 21 citations in total.

Details

Primary Language English
Subjects Intensive Care, Clinical Sciences (Other)
Journal Section Original Articles
Authors

Yasemin Durdu 0000-0003-3765-8108

Kadriye Kart Yaşar 0000-0003-2963-4894

Publication Date September 1, 2025
Submission Date July 1, 2025
Acceptance Date August 5, 2025
Published in Issue Year 2025 Volume: 7 Issue: 2

Cite

AMA Durdu Y, Kart Yaşar K. Aminoglycoside Resistance in Common Pathogens. Eurasian j Crit Care. September 2025;7(2):31-38. doi:10.55994/ejcc.1729315