Trospectomycin - An aminocylitol antibiotic- Investigational drugs
Drug Name:Trospectomycin - An aminocylitol antibiotic- Investigational drugs
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Pharmacology/ Pharmacokinetics
Indication:
Upper respiratory tract infections
Summary-
Trospecttomycin is an injectable aminocyclicatol aminoglycoside that is structurally
related to spectonomycin. It has good gram-positive and gram-negative aerobic and
anaerobic activity and may prove to be useful in the treatment of upper respiratory
tract infections, bacterial viginitis, pelvic inflammatory disease and gonorrhoea .
Overall, it appears be well tolerated and the major side effects are pain at the injetion
site and perioral paresthesias.
Trospectomycin is currently in phase III clinical trials
Adverse Reaction:
Side effects-
In one study, mild, transcient and local reactions were seen in 20% of the subjects receiving
trospectomycin vs 22% with placebo, none of the reactions were thought to be drug-related.
Overall, mild and transcient side reactions were seen in 32 of 74 subjects receiving
trospectomycin, 12 had dizziness, or lightheadedness and 17 who received .600mg had
perioral/facial numbness. Results from a silimiar trial using IM injection were comparable
In a multidose trial invoving 10 healthy males, trospectomycin caused significantly more
pain at the injection site. There was no significant increase in peroral parathesias with
increasing doses (especially at the 500 and 750mg doses) .
Perioral parathesias were mild and transcient were seen shortly after dosing and lasted
about 1 to 2 hours. Tolerance did not develop over the 7 days of the study. Clinically
significant orthostatic hypotension occurred after the first dose in patients receiving
500 or 750mg but was not seen with subsequent dosing.
Pharmacology/ Pharmacokinetics:
Pharmacology-
Trospectromycin is a water soluble analog of spectinomycin (Trobicin) that is 8 to 10 times
more potent and has broader spectrum of activity. It has good activity gram positive and
gram- negative aerobic and anaerobic activity, including invitro activity against
Staphylococci, Streptococci, Peptostreptococci, Peptococci, Haemophillus, Gardenerella,
Neisseria, Bacteroides, Chalmydia, Mycoplasma, and Ureaplasma. It has moderate activity
against Enterobacteriaceae and no activity against Pseudomonas.
Trospectomycin acts by binding to the 30S component of ribosome unit thereby inhibiting
protein synthesis. It has greater affinity for the 30S ribosome unit than streptomycin and
therefore higher activity. Cross resistence to spectinomycin has been observed in vitro.
Pharmacokinetics-
Patients (n= 128) were randomized to receive trospectomycin 975 to 1000mg ) by IM injection or by 20 minutes infusion.The IM product was 100% bioavailable. The mean peak plasma concentration and AUC were linear relative to dose, and half-life was 2.1 hrs. serum concentration were < 2mcg/ml 12 hours post dose. suggesting 2 to 3 times daily dosing as the MIC for most organisms is between 2 to 4mcg/ml. In another trial,
trospepetromycin was administered by IV infusion.
While almost no drug was found in the fecaes, 48% to 62% was recovered in the urine during the first 48 hours, suggesting that the drug was slowly released from the tissues. The half life of 2.18 hours did not change with increasing dose.
Clinical Trials
The invitro activity of trespectomycin was compared to that of amykacin (eg Amikin),
cephalothin (eg Keflin) and Vancomycin (Vancocin) against 342 gram-positive organisms
Vancomycin was the most active agent overall and trospectomycin was better than
amikacin, especially for Staphylococci, and Streptococci.
The activity of trospectomycin , clindamycin, (eg Cleocin) metronidazole (eg Flagyl )
imipenem (Primaxin) cefoxitin (Mefoxin) and pipercillin (Pipracil) was evaluated
against 72 strains of Bacterocides . Trospectomycin had very good acivity and was
comparable to imipenem and metronidazole. Its activity was greater than the pipercillin
and cefoxitin.
In another trial trospecomycin was comparable to clindamycin and cefoxitin against
Bacteriodes fragalis and there was no cross resistence between the three drugs.
Of the organisms tested 90% to 100% were resistent to ampicillin(Polycilin) and
Cefaclor (Ceclor) and > 50% were resistent to doxycycline (Vibramycin) .
None of the organisms tested were resistent to trospectomycin
The effect of trospectomycin and several other antibiotics was evaluated against
Mycoplasma pneumoniae, M hominis, and Ureaplasma urealyticum. Trospectromycin
and septinomycin were equivalent to tetracycline (Achromycin) against Mycoplasma
-induced respiratory or genital infections.
To date published in vitro trials with trospectromycin are limited. The efficacy of a single
1g IM dose was evaluated in 10 men with uncomplicated C trachomatis ureathritis
All were culture positive at follow-up on days 4 to 8 . On a follow-up on days 21 to 28
six of the eight men were still culture positive.
It was concluded that a single IM dose for the treatment of uncomplicated C trachomatis
ureathritis is not efective.
