Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin stops bacterial growth by damaging cell membranes and inhibiting protein synthesis. Specifically, it binds to the 23S rRNA molecule of the bacterial ribosome, which prevents the release of the growing protein (polypeptide chain). Humans have structurally different ribosomes than bacteria, thereby allowing the selectivity of this antibiotic for bacteria. Streptomycin cannot be given orally, but must be administered by regular intramuscular injection. An adverse effect of this medicine is ototoxicity. It can result in permanent hearing loss.
It was first isolated on October 19, 1943 in the laboratory of Selman Abraham Waksman at Rutgers University by Albert Schatz, a graduate student in his laboratory. Waksman and his laboratory discovered several antibiotics, including actinomycin, clavacin, streptothricin, streptomycin, grisein, neomycin, fradicin, candicidin, candidin, and others. Two of these, streptomycin and neomycin, found extensive application in the treatment of numerous infectious diseases. Streptomycin was the first antibiotic that could be used to cure the disease tuberculosis. Waksman is credited with having coined the term antibiotics.
The details and credit for the discovery of streptomycin were strongly contested by Albert Schatz and resulted in litigation. The contention arose because Schatz was the graduate student in charge of performing the lab work on streptomycin; however, it was argued that he was using techniques, equipment and lab space of Waksman's while under Waksman's direction. There is contention as to whether or not Schatz should have been included in the Nobel Prize awarded in 1952. However, the committee stated that the Nobel Prize was awarded not only for the discovery of streptomycin but also for the development of the methods and techniques that led up to its discovery and the discovery of many other antibiotics. The litigation ended with a settlement for Schatz and the official decision that Waksman and Schatz would be considered co-discoverers of streptomycin. Schatz was awarded the Rutgers medal in 1994, at the age of 74. The controversy ultimately had a negative impact on the careers of both Waksman and Schatz and the controversy continues today.Uses : Tuberculosis in combination with other anti-TB drugs
Aminoglycosides are a group of antibiotics that are effective against certain types of bacteria. They include amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, tobramycin and apramycin. Those which are derived from Streptomyces species are named with the suffix -mycin, while those which are derived from micromonospora are named with the suffix -micin.
Aminoglycosides work by binding to the bacterial 30S ribosomal subunit (some work by binding to the 50s subunit), inhibiting the translocation of the peptidyl-tRNA from the A-site to the P-site and also causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth. But their exact mechanism of action is not fully known.Aminoglycosides are potent bactericidal antibiotics that act by creating fissures in the outer membrane of the bacterial cell. They are particularly active against aerobic, gram-negative bacteria and act synergistically against certain gram-positive organisms. Gentamicin is the most commonly used aminoglycoside, but amikacin may be particularly effective against resistant organisms. Aminoglycosides are used in the treatment of severe infections of the abdomen and urinary tract, as well as bacteremia and endocarditis. They are also used for prophylaxis, especially against endocarditis. Resistance is rare but increasing in frequency. Avoiding prolonged use, volume depletion and concomitant administration of other potentially nephrotoxic agents decreases the risk of toxicity. Single daily dosing of aminoglycosides is possible because of their rapid concentration-dependent killing and post-antibiotic effect and has the potential for decreased toxicity. Single daily dosing of aminoglycosides appears to be safe, efficacious and cost effective. In certain clinical situations, such as patients with endocarditis or pediatric patients, traditional multiple dosing is still usually recommended.
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. The most frequent use of aminoglycosides is empiric therapy for serious infections such as septicemia, complicated intraabdominal infections, complicated urinary tract infections, and nosocomial respiratory tract infections. Usually, once cultures of the causal organism are grown and their susceptibilities tested, aminoglycosides are discontinued in favor of less toxic antibiotics.
Streptomycin was the first effective drug in the treatment of tuberculosis, though the role of aminoglycosides such as streptomycin and amikacin has been eclipsed (because of their toxicity and inconvenient route of administration) except for multiple drug resistant strains.
Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with beta-lactam antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. One of the most frequent combinations is Ampicillin (a beta-lactam, or penicillin-related antibiotic) and Gentamicin. Often, hospital staff refer to this combination as "amp and gent" or more recently called "pen and gent" for penicillin and gentamycin.
Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.
Because of their potential for Ototoxicity and Nephrotoxicity (kidney toxicity), aminoglycosides are administered in doses based on body weight. Blood drug levels and Creatinine are monitored during the course of therapy. Serum creatinine measurements are used to estimate how well the kidneys are functioning and as a marker for kidney damage caused by these drugs.
Since they are not absorbed from the gut, they are administered intravenously and intramuscularly. Some are used in topical preparations for wounds. Oral administration can be used for gut decontamination (e.g. in hepatic encephalopathy).
Amikacin (Amikin®), Gentamicin (Garamycin®), Kanamycin (Kantrex®), Neomycin, Netilmicin (Netromycin®), Streptomycin, Tobramycin (Nebcin®)
The first aminoglycoside, streptomycin, was isolated from Streptomyces griseus in 1943. Neomycin, isolated from Streptomyces fradiae, had better activity than streptomycin against aerobic gram-negative bacilli but, because of its formidable toxicity, could not safely be used systemically. Gentamicin, isolated from Micromonospora in 1963, was a breakthrough in the treatment of gram-negative bacillary infections, including those caused by Pseudomonas aeruginosa. Other aminoglycosides were subsequently developed, including amikacin (Amikin), netilmicin (Netromycin) and tobramycin (Nebcin), which are all currently available for systemic use
The use of Netilmicin
Twenty patients with a variety of serious or difficult infections and 5 additional orthopaedic patients with clinical evidence of post-operative wound infection were treated with netilmicin. The results indicate that twice daily dosage with 150 mg intramuscularly, either alone or in combination with other antibiotic therapy, was highly effective. Overall, 25 (96%) infections responded clinically and 19 (73%) were improved bacteriologically. There was no evidence of ototoxicity: a number of patients had impaired renal function which developed during therapy, but all returned to normal or pre-treatment levels by the time that treatment was completed, despite the fact that 15 patients were receiving diuretics. It is suggested in view of its effectiveness, more predictable serum levels after standard dosage and apparent lack of toxicity, that netilmicin should be considered as the first choice aminoglycoside antibiotic instead of gentamicin.