Administration Of Streptomycin Research Articles

Surveillance of resistance to antituberculosis drugs in developing countries

Resistance to antituberculosis drugs is caused by poor management of tuberculosis control. It gives rise to treatment failure, relapse, further transmission of resistant tuberculosis, and multidrug-resistant tuberculosis. Widespread occurrence of multidrug-resistant tuberculosis would constitute a major threat to tuberculosis control in resource-poor countries. Although the impact of HIV on drug resistance is not yet fully understood, it is likely to exacerbate problems caused by drug resistance. In particular, HIV-related adverse effects of thiacetazone, together with the risks of transmission of HIV by parenteral administration of streptomycin, reduce the armamentarium available to tuberculosis control programmes in high HIV prevalence countries, and could encourage the development of resistance to the remaining drugs. While the prime need is to ensure, by good management and supervision, that resistance does not occur in the first place, surveillance of drug resistance is essential to determine the current scale and nature of the drug resistance problem, as well as to define the correct solutions.

Postnatal changes in rhodamine-123 stained mitochondrial populations are sensitive to protein synthesis inhibitors but mimicked in vitro by atp

The incubation of term fetus mitochondria with ATP mimicked in vitro the increase in the respiratory control index and in the percentage of the rhodamine-123-low fluorescence population that occurred in vivo immediately after birth, suggesting that both phenomena are closely associated. The administration of streptomycin inhibited the increase in the percentage of the low fluorescence population that occurred immediately after birth, while the administration of cycloheximide even reversed these changes. These results suggest that the in vivo interconversion between mitochondrial forms depends on both cytosolic and mitochondrial protein synthesis.

Pharmacology of the antimycobacterial drugs

The management of MDR-TB requires that the clinician become familiar with the "second-line" antimycobacterial agents. These drugs are generally less potent and frequently more toxic than isoniazid and rifampin. Because they are less active, innovative dosing schedules may allow us to take advantage of the few strengths that they possess. This approach will require further research into the dose-response relationships for each agent. Based on our current knowledge of these drugs, practical guidelines for their use have been described. These guidelines include the gradual escalation of the oral doses of PAS, cycloserine, and ethionamide over several days, and the intravenous administration of streptomycin and capreomycin. Both ciprofloxacin and ofloxacin may be used for the treatment of MDR-TB, but data from clinical trials are currently lacking. Finally, because patients with AIDS appear to develop antimycobacterial drug malabsorption over the course of their HIV infection, therapeutic drug monitoring can be used to verify drug absorption in the individual patient. This approach may improve therapy for that patient and prevent the selection of additional drug resistance.

CHEMICAL LABYRINTHECTOMY

The use of aminoglycosides for selective vestibular function ablation without hearing alteration is described in the literature. Parenteral administration of streptomycin for the alleviation of vertigo in cases of bilateral Meniere's disease is well accepted. The instillation of aminoglycosides into the middle ear to produce a similar result, has been successfully used in the treatment of unilateral Meniere's disease. However, the use of chemical vestibulectomy has not gained acceptance as a practical means of treatment when compared to vestibular neurectomy. The reason for this is not clear, but may stem from the lack of definitive protocol for the application and lack of treatment results that have been assessed according to an acknowledged standard (i.e., the American Academy of Otolaryngology Criteria). A prospective study was undertaken to examine the efficacy of chemical vestibulectomy as the treatment for vertigo in unilateral, incapacitating Meniere's disease. A standardized drug administration protocol was utilized, and academy criteria for the assessment of treatment were applied. This report details the first group of patients to complete 2 years of post-treatment follow-up. Based on our experience, we conclude that chemical vestibulectomy is an efficient alternative to surgery. A standardized regimen of drug administration that can be carried out on an outpatient basis is put forward.

Hypothesis: How Streptomycin Treatment Compromises Colonisation Resistance Against Enteric Pathogens in Mice

One week after administration of streptomycin to Swiss white mice, caecal flora composition was altered but total populations of cultivable aerobes and anaerobes were unchanged. However, microscopic estimation of numbers demonstrated a 100-fold decrease in caecal fusiform populations. Streptomycin administration also caused an increase in pH of caecal contents and a decrease in caecal volatile fatty acid (VFA) concentrations. Multiplication rates and populations of Shigella sonnei and enterotoxigenic Escherichia coli were greater after culture in caecal contents obtained from streptomycin-treated mice than in contents obtained from untreated mice. When contents from streptomycintreated mice were adjusted to simulate conditions of VFA concentration and pH of contents of untreated mice, multiplication of the pathogens was retarded and growth curves resembled those obtained with contents from untreated mice. Conversely, when the pH of contents from untreated mice was increased to 7.50 to convert VFA to the dissociated form, growth curves of the pathogens were similar to those obtained with contents from streptomycintreated mice. In vivo, s. sonnei and E. coli associated in significantly greater numbers with the caecal mucosa of streptomycin-treated than untreated mice. This was confirmed in vitro with excised mouse caecal tissue suspended in washed cells of the pathogens. Streptomycin administration enhances susceptibility of mice to colonisation with enteric pathogens apparently by increasing the pH and decreasing VFA concentrations of intestinal contents and by facilitating association of pathogens with intestinal mucosa. This may be a reflection of diminished mucosal fusiform populations resulting from the activity of the antibiotic. Keywords: Streptomycin; Colonisation resistance; Mice.

Inhibition ofShigella sonneiand EnterotoxigenicEscherichia coliby Volatile Fatty Acids in Mice

The role of volatile fatty acids (VFA) in resistance against the colonisation of the intestinal tract ofmice with two enteric pathogens, Shigella sonnei 3SR and enterotoxigenic E. coli 2SR (ETEC 2SR) was determined. The implantation dose 50 (ID50) of S. sonnei 3SR strain for untreated mice was greater than 5.0 x 10 9 viable cells and was 1.8 x 10 6 viable cells for ETEC 2SR. Administration of streptomycin to the mice prior to challenge lowered the ID50 to fewer than one viable cell for both organisms. The antibiotic caused an increase in the pH of caecal contents from 6.66 in untreated animals to 6.94 in treated animals and a decrease in total VFA concentrations from 109.11 microequivalent per ml in untreated animals to 78.31 microequivalent per ml in treated animals. The discontinuation of streptomycin treatment resulted in a gradual restoration of colonisation resistance accompanied by an increase in total VFA concentration and a decrease in pH of caecal contents. These values returned to pre-treatment levels by day 7. VFA were added to nutrient broth in concentrations present in the caeca of either untreated or streptomycin treated mice and the pH levels were adjusted accordingly. S. sonnei 3SR multiplied in broth adjusted to simulate conditions present in the caeca of treated mice but failed to multiply in broth adjusted to simulate conditions present in the caeca of untreated mice. ETEC 2SR, on the other hand, multiplied in both types of broth but its total populations after 24 h incubation were significantly smaller in broth adjusted to simulate conditions present in the caeca of untreated mice. The results demonstrate that the multiplication of both pathogens is inhibited by the presence of VFA. They indicate that VFA operating at the pH level present in the intestinal tract of conventional mice represent important factors responsible for resistance against colonisation with S. sonnei and ETEC. Keywords: Shigella sonnei ; Enterotoxigenic E. coli ; Volatile fatty acids; Mice.

Effect of streptomycin administration on association of enteric pathogens with cecal tissue of mice.

The effect of streptomycin on the ability of Shigella sonnei 3SR and enterotoxigenic Escherichia coli 2SR to associate with cecal tissue of mice in vivo and in vitro was examined. After orogastric challenge, both pathogens associated in significantly greater numbers (P less than or equal to 0.05) with the cecal tissue of streptomycin-treated mice than with the tissue of untreated mice. The population levels of the pathogens were also significantly greater (P less than or equal to 0.05) in the cecal contents of streptomycin-treated mice than in untreated mice. When excised cecal tissues from the two groups of mice were exposed to the pathogens in vitro, the extent of the association of the pathogens was markedly greater with tissues from streptomycin-treated mice than with tissues from untreated mice. There was also a positive correlation between the numbers of the pathogens in the suspending fluid and the extent of the tissue associations. The population size of fusiform organisms, which are the major components of the mucus layer of the ceca of mice, was reduced 100-fold by streptomycin administration. This was determined by microscopic count. Sections of cecal tissue obtained from the mice and stained with hematoxylin and eosin demonstrated that streptomycin administration greatly decreased the number of fusiform bacteria present in the mucosal microbial layer. We speculate that the partial elimination of fusiform organisms from this layer by streptomycin administration provides available association sites for pathogens so that they can successfully colonize the mouse cecum.

Transplacental pharmacokinetics of the antituberculosis drugs.

Information concerning passage of the antituberculosis drugs across the human placenta is sparse and scattered throughout the medical literature. Little mention was made of this subject in recent reviews of the clinical pharmacokinetics of these agents (Holdiness 1984, 1985a). However, a detailed survey indicates 6 of the 12 compounds commonly used have documented transplacental passage in humans (table I). If pregnancy occurs during the treatment of tuberculosis, the risk to the developing fetus must be considered in advising the expectant mother and her obstetrician. The indications for chemotherapy and the basic principles of management of the pregnant women with active tuberculosis are essentially no different from those in the non-pregnant patient (Snider 1984). Therapy with 2 drugs is instituted at standard doses, and the duration of treatment should not be altered by the patient's pregnancy. Retrospective studies by Snider et al. (1980) have revealed a reasonable margin of safety for isoniazid, rifampicin, and ethambutol when utilised during pregnancy; questionable results have precluded the administration of streptomycin. From their research of the literature, these authors showed that 94% of all gestations terminated in delivery of apparently normal term infants. In utero exposure of fetuses to antituberculosis therapy revealed 2.8% with classified birth defects. It was suggested that with the exception of women on streptomycin, the risk of adverse gestational outcomes is no greater among pregnant women on antituberculosis regimens than among healthy pregnant females. Caution must be exercised when considering the teratogenic effects of these drugs as spontaneous abortions, stillbirths, birth defects and prematurity are common even in normal pregnancy. The possible teratogenic effects of this class of antibiotics in animal models and humans have recently been reviewed (Holdiness 1987a) and the reader is referred to this article. Snider (1984) indicated that preventive therapy should be given during the second and third trimesters of pregnancy to selected patients at high risk of development of progressive disease. Treatment should be instituted promptly when a tuberculous infection is detected. Preferred regimens are isoniazid-ethambutol, isoniazid-rifampicin, or isoniazid-ethambutol-rifampicin, although other drugs may be needed if the disease is recurrent or if there is resistance to these primary drugs.

良性発作性頭位げんうん症の臨床的観察 最近１０年間の統計を中心に

Two hundred and eight cases of benign paroxysmal positional vertigo (BPPV) were studied.The number of patients with BPPV has increased recently, especially those over 60 years of age.Head injury, hypertension, prolong bed rest and administration of streptomycin were significant causative factors.A neurotic tendency was more evident in BPPV patients than in normal subjects, but less than in those with Meniere's disease.The change in direction of positioning nystagmus between the sitting and the hanging position, which is supposed to indicate the pathology of the side, coincided with the side of semicircular canal palsy, critical position, hearing disturbance, etc. in 57%-74%.Vertigo disappeared in 40% of the case within the first week and in 40% more within the first month, but BPPV recurred in 30%.Physical exercise was very effective in the treatment of BPPV.

Factors responsible for increased susceptibility of mice to intestinal colonization after treatment with streptomycin.

Streptomycin sulfate (5 mg/ml) was added to the drinking water of Swiss white mice. After treatment for 1 week, the mice were challenged orogastrically with 10(8) Pseudomonas aeruginosa cells. The organism failed to multiply in the intestinal tract of either treated or untreated animals, but could be recovered from contents and tissues after 48 h. In a previous study, Salmonella typhimurium was shown to multiply in the intestines of streptomycin-treated but not untreated mice when 10(3) organisms were used as inoculum. Streptomycin administration had little effect on Eh, protein or carbohydrate concentrations of cecal contents, or intestinal motility. However, it caused a statistically significant increase in water content and pH of contents and a decrease in the concentrations of acetic, propionic, butyric, and valeric acids. S. typhimurium multiplied in pooled cecal contents obtained from both streptomycin-treated and untreated animals, but its multiplication rate and total populations were significantly greater in contents from treated animals. P. aeruginosa did not multiply in contents from either treated or untreated mice. Similar results were obtained when the organisms were inoculated into nutrient broth adjusted to simulate the pH levels and volatile fatty acid (VFA) concentrations in cecal contents of treated and untreated mice. The addition of brain heart infusion broth to cecal contents from untreated animals, in concentrations that support multiplication of S. typhimurium and P. aeruginosa, did not reverse inhibition. The addition of VFA to cecal contents from treated animals to equal the concentration in cecal contents from untreated animals caused inhibition of a magnitude observed in cecal contents from untreated animals. The results indicate that VFA operating at the pH level of cecal contents of conventional mice inhibit the multiplication of both S. typhimurium and P. aeruginosa and restrict colonization of the intestine by these organisms. The decrease in VFA concentrations that occurs as a result of streptomycin administration adequately explains the increased susceptibility of treated mice to colonization with S. typhimurium. It does not explain the increased susceptibility of treated mice to P. aeruginosa colonization, however.

Effect of streptomycin administration on colonization resistance to Salmonella typhimurium in mice.

The addition of 5 mg of streptomycin sulfate per ml to the drinking water of Swiss white mice resulted in a 100,000-fold reduction in the 50% implantation dose of streptomycin-resistant Salmonella typhimurium for the animals. When streptomycin-treated and untreated mice were challenged orogastrically with 10(3) viable S. typhimurium organisms, 100% of the treated and none of the untreated mice excreted the pathogen in their feces. Similarly, translocation of S. typhimurium from the intestinal tract to the liver, spleen, and mesentery occurred in 10 of 10 treated mice but in none of the untreated mice 7 days after challenge with 10(3) CFU. Studies of colonization dynamics showed that S. typhimurium was present at high population levels in the intestines of streptomycin-treated mice and in detectable levels in the liver, spleen, and mesentery within 72 h after challenge with 10(3), 10(5), or 10(8) organisms. In untreated mice challenged with either 10(3) or 10(5) S. typhimurium organisms, the organisms were isolated from ileal and cecal tissues but not from ileal or cecal contents or from extraintestinal tissue 72 h after challenge. When untreated mice were challenged with 10(8) organisms, however, S. typhimurium was present in all organs and in intestinal contents. Streptomycin treatment, therefore, facilitated colonization and development of streptomycin-resistant S. typhimurium populations in intestines of mice and the subsequent translocation of the organisms from the intestinal tract to other tissues.

The Alteration of Vestibular Organ and Endolymphatic Sac after Administration of Streptomycin

The Alteration of Vestibular Organ and Endolymphatic Sac after Administration of Streptomycin

Short-term therapy for streptococcal infective endocarditis. Combined intramuscular administration of penicillin and streptomycin

Short-term therapy for streptococcal infective endocarditis. Combined intramuscular administration of penicillin and streptomycin

III. Comparative Quantitative Analysis

Hypotheses to explain the selective ototoxicity of aminoglycoside antibiotics may be grouped into two categories: 1) a partition effect and 2) innate hair cell selectivity. The results of this study give evidence that, in fact, both mechanisms may interplay. This conclusion is induced from the observations that following the transtympanic administration of streptomycin, dihydrostreptomycin and neomycin: 1) All three drugs elicited nearly the same topographic pattern and degree of damage in the vestibular compartment. 2) All three drugs elicited nearly the same topographic pattern but widely different degrees of damage in the cochlear compartment (neomycin > > streptomycin > dihydrostreptomycin). 3) Neomycin caused the same devastating cochlear hair cell damage as reported for its systemic administration. 4) Dihydrostreptomycin was significantly more vestibulotoxic than cochleotoxic, and streptomycin was both significantly more cochleotoxic than vestibulotoxic and significantly more cochleotoxic than was dihydrostreptomycin. The latter observations are discussed with regard to contrasts with the literature reporting the drug effects following systemic administration.

The early bactericidal activity of drugs in patients with pulmonary tuberculosis.

Counts of colony-forming units of Mycobacterium tuberculosis in sputum were done on selective medium during the first 2 wk of treatment of 124 patients with pulmonary tuberculosis. The 27 chemotherapy regimens studied included daily administration of thiacetazone, p-aminosalicylic acid, pyrazinamide, rifampin, streptomycin, ethambutol, and isoniazid alone and certain 2-drug, 3-drug, and 4-drug combinations. Thiacetazone and p-aminosalicylic acid appeared to be only bacteriostatic. The mean fall in counts and the differences between regimens containing the remaining bactericidal drugs were greater during the first 2 days of treatment than during the remaining 12 days. The early (0-to-2-day) falls were much larger with isoniazid than with other drugs. Rifampin was less bactericidal, and may have reduced the bactericidal activity of the 3-drug and 4-drug combinations, including isoniazid. Although streptomycin and pyrazinamide were only slightly bactericidal alone or in a 2-drug combination, the 3-drug regim...

Propagation of ribonucleic acid coliphages in gnotobiotic mice

To clarify the propagation cycle of bacteriophages in their natural habitats, we tested whether animals could support ribonucleic acid (RNA) phage propagation in their intestines, using germfree mice as the test animal. Propagation of four different antigenic types of RNA phages was tested. No detectable propagation or colonization of RNA phages was observed either in germfree mice or in gnotobiotic mice infected with the F- strain of Escherichia coli. Propagation or colonization was observed when RNA phages were orally introduced into gnotobiotic mice harboring the F+ or F' strain of E. coli. These results were consistent with data for in vitro propagation experiments. Fecal titers of phages were monitored over 24 to 98 days and were found to vary from 10(5) to 10(11) plaque-forming units per g of feces. Streptomycin administration gradually led to the disappearance of bacteria and, concomitantly, the RNA phages. Phages recovered from gnotobiotic mice feces included some of novel antigenic types. The bacterial isolates recovered from gnotobiotic mice harboring F+ bacteria included the original F+ strain, strains which had become F-, and some which had become inefficient hosts for the propagation of RNA phages.

Effects of adenosine triphosphate on the postrotatory nystagmus and disorders of vestibular function (author's transl)

Effects of adenosine triphosphate (ATP) on the postrotatory-induced nystagmus in rabbits and disorders of vestibular function induced by repeated administration of streptomycin in guinea pigs were studied. ATP-2Na exerted little influence on the postrotatory nystagmus in doses of 3 and 10 mg/kg, i.v., while slight suppressive effects were noted with a dose of 30 mg/kg. On the other hand, diphenidol hydrochloride remarkably suppressed the postrotatory nystagmus in a dose of 3 mg/kg i.v.. The disturbance in vestibular function following administration of streptomycin sulfate (400 mg/kg i.m., once daily x 9) was significantly alleviated when concomitant treatment with ATP-2Na (3 mg/kg i.p., 10 mg/kg i.p. and 100 mg/kg p.o., once daily x 14) or diphenidol hydrochloride (50 mg/kg p.o., once daily x 14) was given. ATP as well as diphenidol alleviated disorders in the vestibular function, while ATP had little influence on vestibular function in intact animals.

Bacterial Endocarditis on a Prosthetic Valve: Oral Treatment with Amoxicillin

A patient with endocarditis due to Streptococcus faecalis on an aortic valvular prosthesis was successfully treated using large oral doses of amoxicillin concurrently with intramuscular administration of streptomycin. Oral therapy was employed because of a persistent reaction to intravenously administered antibiotics. Oral therapy for bacterial endocarditis occurring on an artificial valve may be attempted as a last resort when all other accepted therapeutic measures have failed.

Neuromuscular blocking effects of certain antibacterial agents in pigs and lambs

The neuromuscular blocking effects of several antibacterial agents were examined in young pigs and lambs using a sciatic nerve‐gastrocnemius muscle preparation. Intravenous administration of streptomycin, neomycin or tetracycline produced a decrease in indirectly stimulated contractions of the gastrocnemius muscle; whereas, chloramphenicol, sulphadiazine and penicillin‐G had no discernible neuromuscular blocking effects. Present findings confirm the neuromuscular blocking activity of certain antibiotic agents, and indicate the potential for this adverse side effect in food‐producing animal species.

Antibiotic Radioprotection of Mice Exposed to Supralethal Whole-Body Irradiation Independent of Antibacterial Activity

Oral administration of streptomycin, kanamycin, neomycin, or gentamicin to specific pathogen-free C57 x Af mice in their drinking water (4 mg/ml) for 2 weeks before supralethal whole-body irradiation very significantly prolonged their mean survival times (8.2 to 8.9 days vs 6.9 for controls) to values which exceed those reported for germ-free mice (7.3 days). The total fecal concentrations of aerobes and anaerobes were reduced by kanamycin, neomycin, and gentamicin. Streptomycin reduced the anaerobes significantly, but not the aerobes. Unlike germ-free mice, these antibiotic-treated mice did excrete free bile acids, products of bacterial action. Oral antibiotic treatment was ineffective in altering the transit time of the intestinal mucosal cells. Previously reported studies had indicated a correlation between decreased transit time and increased survival after irradiation. No significant correlation between mean survival time after irradiation and mucosal transit time was observed. The data demonstrate that certain antibiotics alter the character of the intestinal bacterial flora and increase protection against supralethal doses of whole-body irradiation. It is concluded that the mechanisms of radioresistance in antibiotic-treated mice and germ-free mice are different and that in both groups radioresistance is the result of more than elimination of postirradiation infection.