Gentamicin

Gentamicin is an aminoglycoside antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. It is often only used for two days until bacterial cultures determine what specific antibiotics the infection is sensitive to. The dose required should be monitored by blood testing. Gentamicin is a type of aminoglycoside The antibiotic is collected from the culture of the Micromonospora by perforating the cell wall of the bacterium. Current research is underway to understand the biosynthesis of this antibiotic in an attempt to increase expression and force secretion of gentamicin for higher titer. Gentamicin is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies gentamicin as critically important for human medicine. It is available as a generic medication.

Medical uses

Gentamicin is active against a wide range of bacterial infections, mostly Gram-negative bacteria including Pseudomonas, Proteus, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Serratia, and the Gram-positive Staphylococcus. Gentamicin is used in the treatment of respiratory tract infections, urinary tract infections, blood, bone and soft tissue infections of these susceptible bacteria.

There is insufficient evidence to support gentamicin as the first line treatment of Neisseria gonorrhoeae infection. Gentamicin is not used for Neisseria meningitidis or Legionella pneumophila bacterial infections (because of the risk of the person going into shock from lipid A endotoxin found in certain Gram-negative organisms). Gentamicin is also useful against Yersinia pestis (responsible for plague), its relatives, and Francisella tularensis (the organism responsible for tularemia often seen in hunters and trappers).

Some Enterobacteriaceae, Pseudomonas spp., Enterococcus spp., Staphylococcus aureus and other Staphylococcus spp. have varying degrees of resistance to gentamicin.

Special populations

Pregnancy and breastfeeding

Gentamicin is not recommended in pregnancy unless the benefits outweigh the risks for the mother. Gentamicin can cross the placenta and several reports of irreversible bilateral congenital deafness in children have been seen. Intramuscular injection of gentamicin in mothers can cause muscle weakness in the newborn. Kidney function should be checked periodically during therapy. Long-term effects of treatment can include hearing loss and balance problems. Hypocalcemia, hypokalemia, and muscle weakness have been reported when used by injection.

Adverse effects

Adverse effects of gentamicin can range from less severe reactions, such as nausea and vomiting, to more severe reactions including:

Inner ear

About 11% of the population who receives aminoglycosides experience damage to their inner ear. The common symptoms of inner ear damage include tinnitus, hearing loss, vertigo, trouble with coordination, and dizziness. To reduce the risk of ototoxicity during treatment, it is recommended to stay hydrated. Typically, if an incorrect tRNA pairs with an mRNA codon at the aminoacyl site of the ribosome, adenosines 1492 and 1493 are excluded from the interaction and retract, signaling the ribosome to reject the aminoacylated tRNA::Elongation Factor Thermo-Unstable complex. However, when gentamicin binds at helix 44 of the 16S rRNA, it forces the adenosines to maintain the position they take when there is a correct, or cognate, match between aa-tRNA and mRNA. This leads to the acceptance of incorrect aa-tRNAs, causing the ribosome to synthesize proteins with wrong amino acids placed throughout (roughly every 1 in 500). The non-functional, mistranslated proteins misfold and aggregate, eventually leading to death of the bacterium. Moreover, it has been observed that gentamicin can cause a substantial slowdown in the overall elongation rate of peptide chains in live bacterial cells, independent of the misincorporation of amino acids. This finding indicates that gentamicin not only induces errors in protein synthesis but also broadly hampers the efficiency of the translation process itself. An additional mechanism has been proposed based on crystal structures of gentamicin in a secondary binding site at helix 69 of the 23S rRNA, which interacts with helix 44 and proteins that recognize stop codons. At this secondary site, gentamicin is believed to preclude interactions of the ribosome with ribosome recycling factors, causing the two subunits of the ribosome to stay complexed even after translation completes, creating a pool of inactive ribosomes that can no longer re-initiate and translate new proteins.

Chemistry

Structure

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Since gentamicin is derived from the species Micromonospora, the backbone for this antibiotic is the aminocyclitol 2-deoxystreptamine. This six carbon ring is substituted at the carbon positions 4 and 6 by the amino sugar molecules cyclic purpurosamine and garosamine, respectively. The R1 and R2 can have the follow substitutions for some of the species in the gentamicin complex.

{| class="wikitable centered"

! colspan="10" class="hintergrundfarbe6" |Gentamicine

!Name

!Structure

!CAS number

!PubChem

!Sum formula

!Molar mass

Gentamicin A