Which disease is best treated with an aminoglycoside antibiotic?
Aminoglycoside antibiotics may be used to treat the following infections and infectious diseases:Hepatic encephalopathy (confusion related to liver failure)Tuberculosis.Otitis externa.Conjunctivitis.Parasitic amebic infections of the intestinal tract.Plague.Tularemia.More items...•
What bacteria do aminoglycosides cover?
Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some Mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides.
What are some examples of aminoglycosides?
The aminoglycosides include gentamicin, amikacin, tobramycin, neomycin, and streptomycin. Gentamicin is the most commonly used antibiotic in UK neonatal units. Aminoglycosides are polar drugs, with poor gastrointestinal absorption, so intravenous or intramuscular administration is needed. They are excreted renally.
What are the main indications of aminoglycosides?
Since this drug class has demonstrated effectiveness in multi-drug resistant Gram-negative pathogens, aminoglycosides are indicated for empiric therapy in patients with severe illness; this includes empiric treatment for patients with infective endocarditis, sepsis, complicated intraabdominal infections, and ...
What are the two major side effects of aminoglycosides?
The major side effects of aminoglycosides are kidney injury, hearing impairment and vestibular toxicity.
What are the main side effects of aminoglycosides?
What Are Side Effects of Aminoglycosides?Nephrotoxicity (deterioration of kidney function due to poisonous effect of the drug)Ototoxicity: may cause hearing loss.Neurotoxicity: may cause paralysis.Allergic reactions.Anemia (low hemoglobin in blood)Thrombocytopenia (low platelet count)
Why are aminoglycosides toxic?
GENERAL FEATURES OF AMINOGLYCOSIDE NEPHROTOXICITY Aminoglycosides are nephrotoxic because a small but sizable proportion of the administered dose (≈5%) is retained in the epithelial cells lining the S1 and S2 segments of the proximal tubules (135) after glomerular filtration (30).
What is a contraindication for an aminoglycoside?
As far as contraindications go, aminoglycosides shouldn't be used in clients with renal or hepatic disease, pre-existing hearing loss, and active infections that could be worsened by the effect of these antibiotics on normal defense mechanisms.
How long is the post antibiotic effect of aminoglycosides?
This phenomenon is termed the postantibiotic effect (PAE). The exact duration of the PAE is species and drug dependent. Aminoglycosides and fluoroquinolones produce in vitro PAEs against gram-negative bacilli of 2 to 6 hours.
How do you take aminoglycosides?
Aminoglycoside antibiotics may be given once a day (every 24 hours) or several times a day (for example, every 8 or 12 hours). Sometimes they are given only every day and a half (every 36 hours) or even less often (once every 2 or more days).
What patient population would be administered aminoglycosides with extreme caution?
Aminoglycosides should be used with caution in patients with pre-existing auditory, vestibular or renal impairment, patients that have a family history of aminoglycoside induced auditory toxicity or a maternal relative with deafness due to mitochondrial mutation A1555G or, in patients of advanced age (80 years or over) ...
Which condition would the nurse monitor for in a patient who is taking an aminoglycoside antibiotic?
Nurses should monitor the patient receiving aminoglycosides for signs of decreased renal function such as declining urine output and increasing blood urea nitrogen (BUN), creatinine, and declining glomerular filtration rate (GFR).
Do aminoglycosides cover Gram-positive?
Aminoglycosides are active against various Gram-positive and Gram-negative organisms. Aminoglycosides are particularly potent against members of the Enterobacteriaceae family, including Escherichia coli, Klebsiella pneumoniae and K.
Do aminoglycosides cover MRSA?
Recent studies demonstrated that aminoglycosides also possessed potential activity against MRSA, so aminoglycosides may be useful weapons to fight against MRSA. The present work aims to summarize the current scenario of aminoglycosides with anti- MRSA potential, covering articles published between 2010 and 2020.
Why are aminoglycosides ineffective against anaerobes?
Aminoglycosides are not active against anaerobes because their uptake across bacterial cell membranes depends on energy derived from aerobic metabolism. Consequently, they have markedly reduced activity in areas of low pH and oxygen tension (e.g., abscesses).
Which aminoglycoside is best for Pseudomonas?
The aminoglycosides tobramycin, gentamicin, and amikacin are commonly used to treat hospital-acquired infections caused by Pseudomonas aeruginosa. These infections generally require treatment with a combination of antimicrobials in order to achieve a greater bactericidal effect and reduce the levels of resistance1.
Why are aminoglycosides used in antibiotics?
Aminoglycosides are a class of antibiotics used to treat serious infections caused by bacteria that either multiply very quickly or are difficult to treat. Aminoglycosides are called bactericidal antibiotics because they kill bacteria directly. They accomplish this by stopping bacteria from producing proteins needed for their survival.
Where are aminoglycosides administered?
Because aminoglycosides are normally used to treat serious infections, they are typically administered into the veins of the body (intravenously, or IV). However, some aminoglycosides can be taken orally, or as ear or eye drops. Examples of aminoglycosides include:
What is the drug that prevents patients from moving during surgery called?
Certain drugs called neuromuscular blocking agents, often used to prevent patients from moving during surgery, enhance some of the side effects of aminoglycosides.
Can aminoglycoside cause paralysis?
Although side effects and their severity may vary from person to person, the higher the dose of an aminoglycoside you receive, or the longer the duration of use, the greater your risk of side effects.
Can aminoglycosides be taken by mouth?
Aminoglycosides are very powerful antibiotics, and their side effects can be severe — especially when taken by mouth or IV.
What are the aminoglycosides used for?
Aminoglycosides are also an important component of combination therapy for multidrug-resistant tuberculosis (MDR-TB) and certain non-tuberculous mycobacterial (NTM) infections. Current MDR-TB treatment guidelines recommend inclusion of one of the following agents during the intensive phase of therapy: amikacin, kanamycin, streptomycin, or capreomycin, a cyclic peptide antibiotic that is often considered as an aminoglycoside because of its mechanism of action. Each of these agents possesses potent bactericidal activity against M. tuberculosis(Ho et al. 1997) and the choice of agent depends on previous injectable use (if any) and the likelihood of resistance. A meta-analysis including 32 studies with >9000 treatment episodes did not reveal any clear differences in efficacy among the available agents (World Health Organization 2011). Similar to treatment of MDR-TB, combination therapy for patients with fibrocavitary, severe nodular/bronchiectatic or macrolide-resistant lung disease because of the M. aviumcomplex generally includes amikacin or streptomycin (Griffith et al. 2007). Among the rapidly growing mycobacteria, amikacin is the preferred agent for infections because of M. fortuitumor M. abscessus, whereas tobramycin is the most active agent against M. chelonae(Griffith et al. 2007).
Why are aminoglycosides used in decontamination?
The purpose of these decontamination regimens is to eradicate potential pathogens from the oropharynx and digestive tract of patients at risk for nosocomial or postoperative infections. Selective digestive decontamination (SDD) consists of the oropharyngeal and gastric administration of non-absorbable antibiotics lacking anaerobic activity (often a polymyxin, an aminoglycoside, and amphotericin) along with a short course of systemic antibiotic therapy, whereas selective oropharyngeal decontamination (SOD) consists of application of non-absorbable antibiotics to the oropharynx alone. More than 50 randomized studies and 10 meta-analyses of SDD/SOD have been published. Overall, these data suggest that SDD/SOD are associated with improved survival in ICU patients (Price et al. 2014) and SDD is associated with a reduction in the rate of postoperative infection, including anastomotic leakage, in patients undergoing elective GI surgery (Abis et al. 2013; Roos et al. 2013). Despite these successes in the use of SOD and SDD to improve patient outcomes in the setting of low levels of antibiotic resistance, controversy remains regarding their effectiveness in the setting of high levels of antibiotic resistance as well as their impact on antibiotic resistance. No relationship between the use of SDD or SOD and the development of antimicrobial resistance has been shown in individual studies or meta-analyses in the setting of low antibiotic resistance (Daneman et al. 2013; Plantinga and Bonten 2015) and an international multicenter study of the effects of SDD and SOD on ICU-level antibiotic resistance in countries with higher levels of resistance is currently ongoing (clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02208154","term_id":"NCT02208154"}}NCT02208154).
What is the relationship between aminoglycosides and pharmacodynamics?
The relationship between aminoglycoside pharmacokinetics (PKs) and pharmacodynamics (PDs) has been studied extensively in mice. The PK/PD variable that is most often correlated with efficacy of aminoglycosides is the ratio of area under the concentration–time curve (AUC) to MIC, although peak concentration also appears to play a role. The magnitude of the PK/PD target for aminoglycosides is not as well defined as it is for other antibiotic classes because of, until recently, the lack of development of new aminoglycosides. Available data suggests that significant variations in the PK/PD target exist between species and body site of infection. For example, an AUC/MIC target of 100 was reportedly associated with a 1- to 2-log10kill in the mouse neutropenic thigh infection model with amikacin and K. pneumoniae(Craig 2011), whereas this same group reported better efficacy at the same dose level and with the same strain in the mouse lung infection model (Craig et al. 1991). These results were potentially a result of a longer measured PAE in the lung compared with the thigh (Craig et al. 1991).
What is a plazomicin?
Plazomicin is a new aminoglycoside that was specifically engineered to be resistant to the action of the AMEs that are prevalent in key Gram-negative pathogens (Armstrong and Miller 2010). It is synthesized from a sisomicin scaffold that is intrinsically refractory to modification by APH(3′)-III, -VI, and -VII and ANT(4′), which confer amikacin resistance because of an absence of the 3′- and 4′-OH groups. Modification at the N-1 position via addition of a hydroxylaminobutyric acid substituent sterically hinders the action of the AAC(3), ANT(2″), and APH(2″) enzymes, which confer resistance to gentamicin and tobramycin. Finally, addition of a hydroxyethyl substituent at the 6′ position inhibits the action of the AAC(6′) enzymes, which confer resistance to a broad range of agents, including amikacin, tobramycin, and gentamicin (Fig. 4). Importantly, these modifications to sisomicin do not reduce intrinsic potency as has been associated with previous efforts to protect the 6′ position and, as predicted, lead to improved activity against Enterobacteriaceae (MIC90≤2 mg/L) that are resistant to currently available aminoglycosides (Nagabhushan et al. 1982; Aggen et al. 2010). Plazomicin retains vulnerability to modification by AAC(2′)-I, a chromosomal AME found in P. stuartiiand some mycobacterial species. However, this enzyme is rare, has not been found on a mobile element and has not been shown to have clinical relevance in Mycobacteriumspp. In addition, plazomicin, like all 4,6-linked aminoglycosides, is inactive against isolates that produce RMTs. As described above, this mechanism of resistance frequently travels on mobile genetic elements with NDM-positive Enterobacteriaceae, and, thus, plazomicin is not active against many isolates harboring this enzyme (Berçot et al. 2011; Livermore et al. 2011; Mushtaq et al. 2011; Poirel et al. 2014).
How does rRNA methyltransferase modify aminoglycosides?
Target site modification leading to aminoglycoside resistance occurs via the action of 16S rRNA methyltransferases (RMTs). These enzymes modify specific rRNA nucleotide residues in a manner that blocks aminoglycosides from effectively binding to their target (Beauclerk and Cundliffe 1987; Cundliffe 1989; Wachino and Arakawa 2012). There are two general classes of RMTs that are characterized by the specific nucleotide residues that they modify. These include enzymes that render bacteria resistant to 4,6-di-substituted aminoglycosides via methylation of the N7 position of nucleotide G1405(Thompson et al. 1985; Beauclerk and Cundliffe 1987) and those that affect both 4,6- and 4,5-di-substituted aminoglycosides through methylation of the N1 position of nucleotide A1408(Skeggs et al. 1985; Beauclerk and Cundliffe 1987; Mingeot-Leclercq et al. 1999).
How does resistance to aminoglycosides work?
Aminoglycoside resistance takes many different forms including enzymatic modification, target site modification via an enzyme or chromosomal mutation, and efflux. Each of these mechanisms has varying effects on different members of the class and often multiple mechanisms are involved in any given resistant isolate. Resistance to aminoglycosides via target site mutations has not been observed because nearly all prokaryotes, with the exception of Mycobacteriumspp. (Bercovier et al. 1986) and Borreliaspp. (Schwartz et al. 1992), encode multiple copies of rRNA. Although contemporary large-scale surveillance programs provide an understanding of phenotypic aminoglycoside resistance among important pathogens, these studies have generally not focused on the epidemiology of specific resistance mechanisms (Jones et al. 2014; Sader et al. 2015).
How do aminoglycosides inhibit protein synthesis?
Aminoglycosides inhibit protein synthesis by binding, with high affinity, to the A-site on the 16S ribosomal RNA of the 30S ribosome (Kotra et al. 2000). Although aminoglycoside class members have a different specificity for different regions on the A-site, all alter its conformation. As a result of this interaction, the antibiotic promotes mistranslation by inducing codon misreading on delivery of the aminoacyl transfer RNA. This results in error prone protein synthesis, allowing for incorrect amino acids to assemble into a polypeptide that is subsequently released to cause damage to the cell membrane and elsewhere (Davis et al. 1986; Mingeot-Leclercq et al. 1999; Ramirez and Tolmasky 2010; Wilson 2014). Some aminoglycosides can also impact protein synthesis by blocking elongation or by directly inhibiting initiation (Davis 1987; Kotra et al. 2000; Wilson 2014). The exact mechanism of binding and the subsequent downstream effects varies by chemical structure, but all aminoglycosides are rapidly bactericidal (Davis 1987; Mingeot-Leclercq et al. 1999) and typically produce a prolonged postantibiotic effect (PAE) (Zhanel et al. 1991) The PAE has been shown to be directly related to the length of time that the bacteria take to recover from the inhibition of protein synthesis (Stubbings et al. 2006). It is hypothesized that this is dependent on the eventual disassociation of the antibiotic from its target and exit from the cell.
Sar of Aminoglycosides
Streptomycin, neomycin, gentamicin, paromomycin, sisomicin, ribostamycin, tobramycin, nebramycin, dibekacin, amikacin, and kanamycin are all aminocyclitol-containing antibiotics. Streptomyces and Micromonospora species produce them.
Mechanism of Action
They only need a brief contact period and are most successful against rapidly multiplying susceptible bacterial populations.
Types of Aminoglycosides
There are several different antibiotics in the aminoglycoside class. The US Food and Drug Administration (FDA) has approved gentamicin, tobramycin, amikacin, plazomicin, streptomycin, neomycin, and paromomycin for clinical use in the United States.
Clinical Use
The recent appearance of infections caused by Gram-negative bacterial strains with advanced antimicrobial resistance trends has led doctors to reconsider their use of these antibiotics.
Common Side Effects
Aminoglycosides are extremely powerful antibiotics with serious side effects, particularly when taken orally or intravenously.
Warnings and Precautions
If you're allergic to aminoglycosides or any of the inactive ingredients in these products, stay away from them.
Why is it important to monitor aminoglycosides?
Therapeutic drug monitoring is necessary with aminoglycosides to optimize patient outcomes and limit toxicity. However, there is no universal agreement on the method of monitoring. Therapeutic drug monitoring has been shown to reduce hospital stay duration and toxicities. Studies also suggest that therapeutic drug monitoring reduces mortality. It is important to note that monitoring clearance should be considered in critically ill, burn, and obese patients due to their abnormal distribution volume. [15]
How long can you use aminoglycosides?
For directed treatment, aminoglycoside use for longer than 48 hours is acceptable. They are part of directed combination treatment for brucellosis, listeriosis, CNS nocardiosis, and Pseudomonas aeruginosainfection. Aminoglycosides monotherapy is for tularemia, resistant mycobacteria, bacteremia caused by Campylobacterspp.and Yersinia spp., and drug-resistant gram-negative pathogens. The Infectious Diseases Society of America Guidelines should be referenced to see if an aminoglycoside is the correct agent to use for a particular patient. [1][2]
What are the adverse effects of aminoglycosides?
The main noted adverse effects of aminoglycosides are ototoxicity, nephrotoxicity, and neuromuscular blockade. Therefore, patients should be educated to look out for warning signs of these adverse effects before the initiation of aminoglycoside therapy. [1]
What subunit does aminoglycoside bind to?
Aminoglycosides have bactericidal activity in which they bind to the bacteria ribosomal 30S subunit. Specifically, they are believed to bind to the A-site (aminoacyl) on the 16S rRNA, a component of the ribosomal 30S subunit. Through this binding, the genetic code gets misread, and the translation is disrupted, leading to the bacteria being unable to carry out protein synthesis. [3][4]
Is amikacin an aminoglycoside?
Aminoglycosides have a broad spectrum of activity covering aerobic organisms, including gram-negative bacteria and mycobacteria. There are several drugs within the aminoglycoside class, including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin, and FDA-approved indications vary between the for these individual aminoglycosides. This activity reviews the indications, contraindications, mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent to members of the interprofessional team who wish to prescribe aminoglycosides.
Can aminoglycosides be used for genitourinary infections?
Typically, in these settings, aminoglycosides should not be used for more than two days, due to toxic ity to the patient .
Is aminoglycoside a new class of antimicrobials?
Although not a new class of antimicrobials, aminoglycosides have continued to prove their clinical value in fighting infections. Aminoglycosides have a broad spectrum of activity covering aerobic organisms, including gram-negative bacteria and mycobacteria. Because there are several drugs within the aminoglycoside class, including gentamicin, tobramycin, amikacin, neomycin, plazomicin, paromomycin, and streptomycin, FDA approved indications vary between the different individual aminoglycosides.
How do aminoglycosides work?
Aminoglycosides work by preventing bacteria from producing proteins they need to grow and multiply. These antibiotics are poorly absorbed into the bloodstream when taken by mouth (orally), so they are usually injected into a vein or sometimes a muscle.
What are the different types of antibiotics?
Plazomicin. Streptomycin. Tobramycin. Infections caused by gram-negative bacteria, such as Pseudomonas aeruginosa, Escherichia coli, and Klebsiella species. Hearing loss. Dizziness. Kidney damage. These antibiotics are poorly absorbed into the bloodstream when taken by mouth (orally), so they are usually injected into a vein or sometimes a muscle. ...
Can you take aminoglycosides while pregnant?
Use of Aminoglycosides During Pregnancy and Breastfeeding. If aminoglycosides are taken during pregnancy harmful effects on the fetus (such as hearing loss) are possible, but sometimes the benefits of treatment may outweigh the risks. (See also Drug Use During Pregnancy .)
What is aminoglycoside used for?
Aminoglycosides are mainly used in the treatment of aerobic gram-negative bacilli infections. They are also effective in treating other bacterial infections, including: Complicated urinary tract infections. Pneumonia and upper respiratory tract infections. Endocarditis ( inflammation of the heart valves)
How do aminoglycosides affect the cell membrane?
Aminoglycosides act through inhibition of protein synthesis. Once inside the bacterial cell, they bind to the A- site in ribosomal RNA of the 30S subunit and cause a misreading of transfer RNA codons. This subsequently leads to the interruption of normal bacterial protein synthesis and results in the formation of an incorrect protein, which may damage the cell membrane. The damaged cell membrane allows an increased amount of drug to enter the bacteria, eventually leading to its death.
What are aminoglycosides?
What do I need to know about aminoglycoside antibiotics? The aminoglycosides are broad-spectrum, bactericidal antibiotics that are commonly prescribed for children, primarily for infections caused by Gram-negative pathogens . The aminoglycosides include gentamicin, amikacin, tobramycin, neomycin, and streptomycin.
What are the most common antibiotics used for children?
The aminoglycosides are broad-spectrum, bactericidal antibiotics that are commonly prescribed for children, primarily for infections caused by Gram-negative pathogens. The aminoglycosides include gentamicin, amikacin, tobramycin, neomycin, and streptomycin. Gentamicin is the most commonly used antib …. What do I need to know about aminoglycoside ...