Aminoglycosides and Amikacin

Overview 

  • Powerful and dominating  bactericidal antibiotics that act by creating fissures in the outer membrane of the bacterial cell. 
  • They are very active against aerobic, gram-negative bacteria and act synergistically against certain gram-positive organisms. 
  • Gentamicin is the most generally used aminoglycoside, but amikacin may be incredibly effective against resistant organisms. 
  • Used in the treatment of serious infections of the abdomen and urinary tract, as well as bacteremia and endocarditis.

Limitations 

  • Poorly absorbed from the gastrointestinal tract(GIT). 
  • When used parenterally, adequate drug concentrations are commonly found in bone, synovial fluid and peritoneal fluid. 
  •  Directly excreted by glomerular filtration, resulting in a plasma half-life differing from two hours in a patient with “normal” renal  function to 30 to 60 hours in patients who are functionally a nephric. 

Uses of Aminoglycosides 

  •  Exhibit bactericidal, concentration-dependent killing action and are effective against a wide range of aerobic gram-negative bacilli.
  • Active even when the bacterial inoculum is large, and resistance hardly develops during the course of treatment.

These strong antimicrobials are used as prophylaxis and medication in a variety of clinical situations. 

Generally used in combination with other antibiotics for broad-spectrum coverage. Not certain first-line choices for all of these indications. 

Dosage 

  • Single daily dosing of aminoglycosides is possible because of their immediate  concentration-dependent killing and post-antibiotic effect and has the potential for decreased toxicity.

 

Gentamicin 

Adult Dose for Bacterial Infection

  •    1 mg/kg IM or IV infusion (over 30 to 120 minutes) 

In Urinary Tract Infection.

  • 1 mg/kg IM or IV infusion.

Renal Dose Adjustments

Parenteral Administration:

       -Prolonged intervals (serum creatinine known): single dose (e.g., 1 mg/kg IM or IV) at the dosage interval determined by multiplying the serum creatinine by 8

-Reduced dose (serious systemic infections):

—Administer loading dose (e.g., 1 mg/kg IM or IV).

Tobramycin injection 

 6-7.5 mg/kg/day, regulated in 3 or 4 equally divided doses.

Amikacin injection 

  • 50mg/mL
  • 250mg/mL

General Dosing

15 mg/kg/day divided IV/IM q8-12hr.

Side effects 

  • The toxicities of aminoglycosides comprise nephrotoxicity, ototoxicity (vestibular and auditory) and, hardly, neuromuscular blockade and hypersensitivity reactions. 
  • Nephrotoxicity receives the maximum attention, perhaps because of simpler documentation of reduced renal function, but it is usually reversible.
  • Nephrotoxicity results from renal cortical accumulation. 
  • Examination of urine sediment may disclose dark-brown, fine or granulated casts consistent with acute tubular necrosis but not certain for aminoglycoside renal toxicity. 
  • Although serum creatinine levels are often monitored during aminoglycoside use, an elevation of serum creatinine is more inclined to reflect glomerular damage rather than tubular damage .  
  • Systematic  monitoring of serum creatinine concentrations may alert the clinician to renal toxicity.

In order to decrease the  toxicity, family physicians should know a few key considerations. 

(1) Aminoglycosides should be used just when their unique antibiotic potency is required, such as treatment of infection in critically ill patients, and in nosocomial infections or infections with organisms resistant to less toxic therapies.

(2) Potential risk factors that predispose to nephrotoxicity should be recognized and, when possible, corrected.

Drug Interaction 

Severe Interactions

  • These medications are not generally taken together. 

SELECTED NEPHROTOXIC AGENTS/CIDOFOVIR

AMINOGLYCOSIDES/ATALUREN

ANTIMICROBIAL/LIVE TYPHOID VACCINE 

SELECTED NEPHROTOXIC AGENTS/BACITRACIN.

  • These medications may interact and result in very harmful effects.  

MISC ANTIBIOTICS/NEUROMUSCULAR BLOCKING AGENTS

SELECTED NEPHROTOXIC AGENTS/FOSCARNET.

AMINOGLYCOSIDES/ANESTHETICS

SELECTED NEPHROTOXIC AGENTS/INOTERSEN

SELECTED ANTIMYCOBACTERIALS/LIVE BCG.

Administration

  • Depending on the aminoglycoside selected , the administration can be oral, parenteral, inhalation, intraperitoneal, or intraventricular.
  • Generally parenteral; gentamicin, amikacin, and tobramycin are the most often used aminoglycosides administered via the parenteral route. 
  • Tobramycin may be inhaled utilizing a nebulizer for cystic fibrosis patients undergoing pulmonary exacerbation from infection. 
  •   In addition, gentamicin is an aminoglycoside that can be administered either  intraperitoneally or  intraventricularly. 

Intraperitoneal administration of gentamicin is beneficial in peritoneal dialysis patients who develop peritonitis. Gentamicin administration intraventricularly has proved effective in central nervous system infections.

Contraindications

Should not be given  in patients with myasthenia gravis or multiple sclerosis.

Monitoring

  • Therapeutic drug monitoring is crucial with aminoglycosides to optimize patient outcomes and restrict toxicity. 
  •  Therapeutic drug monitoring has been shown to decrease hospital stay duration and toxicities. 
  •   It is vital to note that monitoring clearance should be analyzed in critically ill, burn, and obese patients due to their abnormal distribution volume.

For toxicity purposes, renal function and cochlear function need monitoring. 

New Aminoglycoside antibiotics classes .

The aminoglycoside class of antibiotics comprises various different agents. 

Indian Brand name.           Generic Name Humatin, Paromomycin         Paromomycin    

Amitax, Cinamica,   Amikacin 

Zemdri (Pro).            Plazomicin       

Tobracin.                 Tobramycin           

Neocin, Nepozin       Neomycin   

Frequently Asked Questions(FAQs)

  1. Why is penicillin contraindicated to patients under aminoglycoside therapy?
  • Aminoglycosides should not be mixed with penicillins or cephalosporins in the exact bottle.
  •  In vitro, penicillins interact chemically with the aminoglycoside antibacterials to construct biologically inactive amides by a reaction between the amino groups on the aminoglycosides and the beta-lactam ring on the penicillins.
  1. Why aminoglycosides are contraindicated in renal failure patients?
  • Basic courses of aminoglycoside antibiotics may result in subclinical kidney damage leading to chronic kidney disease (CKD). 
  • This can manifest at the level of the glomerulus (effecting reduced glomerular filtration rate, GFR) and the tubules (inducing altered excretion of electrolytes).
  1. How do you give gentamicin on dialysis?
  • Extensively  used antibiotics  in the intensive care unit (ICU). 
  • Its dosage is difficult to modify for hemodialyzed ICU patients.
  •  The FDA-approved regimen consists  of the administration of 1 to 1.7 mg/kg of gentamicin at the end of each and every  dialysis session.
  1. Why are aminoglycosides not used as monotherapy?
  • The only indication for systemic aminoglycoside monotherapy is treatment of urinary tract infections(UTI) reluctant to use other antibiotics.
  •  This has become a relatively common indication for these drugs, in specific amikacin, due to increasing rates of quinolone resistance in GNR.
  1. Why amikacin is risky for use in renal disease?
  • The risk of aminoglycoside-induced ototoxicity is higher in patients with renal damage. 
  • High-frequency deafness often occurs first and can be detected just by audiometric testing. 
  • Vertigo may arise and may be evidence of vestibular injury.
  1. Which antibiotics are contraindicated in renal failure? 

Contraindicated or to be avoided if feasible when:- 

  • Antibiotics    Cefepime    GFR <30
  • Phase-prophylactic psychotropic drugs    Lithium    GFR <60
  • Antidiabetic drugs    Glibenclamide, glimepiride    GFR <60
  • Metformin    GFR <60
  1. Does amikacin require renal adjustment?
  • Amikacin is excreted by the renal route, renal function should be examined whenever possible and dosage modified as described under impaired renal function.
  •  The adult dose may be increased to 500 mg every eight hours but should never surpass 1.5 g/day nor be administered for a period extended than 10 days.
  1. Why amikacin is given once daily?
  • For elderly patients a smaller dose of amikacin than the regular day-to-day dose of 15 mg/kg bw, i.e. about 11 mg/kg bw, seems recommendable, when it is provided once daily. 
  • From the data obtained it is also apparent that once-daily dosing of amikacin does not eradicate the necessity for checking serum concentrations of the drug.
  1. Is amikacin used for UTI?
  • Amikacin is a highly effective and beneficial  aminoglycoside against extended spectrum beta lactamase (ESBL) bacteria.
  • Older patients suffer from urinary tract infection (UTIs), and have a greater frequency of infection with resistant bacteria, primarily among frail nursing home residents. 

 

  1. Is amikacin safe in renal failure? 

Amikacin usage in described, decreased doses with prolonged interval between them is helpful  in terms of ototoxicity and nephrotoxicity in patients with chronic kidney disease (CKD). 

  • Every two days’ dosage is slightly more effective than every day dosage in patients with stage 4 CKD.
  1. Can amikacin be given intramuscularly? 
  • Amikacin injection is used as a liquid to be injected intravenously (into a vein) or intramuscularly (into a muscle) every 8 or 12 hours (two or three times a day). 
  • When amikacin is injected intravenously, it is often  infused (injected gradually) over a period of 30 to 60 minutes. 
  1. Can amikacin be given in normal saline? 
  • The solution for intravenous use is formulated by adding the desired dose to 100mL or 200mL of sterile diluent such as normal saline or 5% dextrose in water or any other similar solution. 
  • The solution is administered to adults over a period of 30 to 60-minute. 
  1. When is amikacin given?
  • This medication is given by injection into a vein or muscle as instructed by your doctor. 
  • It is generally given every 8 hours or as advised by your doctor. 
  • The dosage relies on your medical condition, weight, and response to treatment. 
  1. Is amikacin used for Urinary tract infection( UTI)  ?
  • Amikacin is a very  effective aminoglycoside, highly powerful against extended spectrum beta lactamase (ESBL) bacteria. 
  • Older patients suffer  from more urinary tract infection (UTIs), and have an elevated frequency of infection with resistant bacteria, mainly among frail nursing home residents.
  1. Which antibiotic gets rid of a UTI fastest?

Sulfamethoxazole/trimethoprim (Bactrim) is a first choice because it functions very well and can deal with UTI in as little as 3 days when taken twice a day. … 

Nitrofurantoin (Macrobid) is another first choice for UTIs, but it has to be taken for a slightly longer duration  than Bactrim.

  1. What is the normal level for amikacin? 
  • Amikacin trough levels of more than 10 mcg/mL have been related with significant ototoxicity and nephrotoxicity.
  •  Required  trough levels for traditional dosing are less than 8 mcg/mL.