An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial.

BACKGROUND: Bubonic plague is the primary manifestation of infection with Yersinia pestis, accounting for 90% of all plague cases and with 75% of global cases reported in Madagascar. All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The IMASOY trial intends to fill this knowledge gap by comparing two 10-day regimens included in the national guidelines in Madagascar. The primary objective of the trial is to test the hypothesis that ciprofloxacin monotherapy is non-inferior to streptomycin followed by ciprofloxacin for the treatment of bubonic plague, thus avoiding the need for injectable, potentially toxic, aminoglycosides. METHODS: A two-arm parallel-group randomized control trial will be conducted across peripheral health centres in Madagascar in five districts. Males and non-pregnant females of all ages with suspected bubonic or pneumonic plague will be recruited over the course of three plague 'seasons'. The primary endpoint of the trial is to assess the proportion of patients with bubonic plague who have a therapeutic response to treatment (defined as alive, resolution of fever, 25% reduction in the size of measurable buboes, has not received an alternative treatment and no clinical decision to continue antibiotics) as assessed on day 11. DISCUSSION: If successful, the trial has the potential to inform the standard of care guidelines not just in Madagascar but in other countries afflicted by plague. The trial is currently ongoing and expected to complete recruitment in 2022. TRIAL REGISTRATION: ClinicalTrials.gov NCT04110340 . Registered on 1 October 2019.

Adverse drug reactions observed during DOTS.

A total of 8.37% of the 1195 patients treated at NDTB Centre with DOTS under RNTCP between January 2002 to June 2003 presented with adverse drug reactions. Patients showing any sort of adverse reactions were studied in detail by personal interviews and a semi-structured questionnaire. The profile of patients presenting with adverse reactions showed that majority of the patients (53%) had gastrointestinal reactions, the commonest presenting complaint being nausea and vomiting. General aches and pains were complained by about 35% and giddiness was the presenting complaint in 27% irrespective of the use of streptomycin, although giddiness was observed more often in Category II patients (59%). Skin rash and itching was complained by about 17% of patients and 11% complained of arthralgia, while only 1% had hepatotoxicity during treatment. Majority of the adverse reactions (67%) were observed within the first four weeks of treatment and only 0.25% of patients treated with DOTS had interruption of treatment for short periods.

Síndrome antifosfolípido: presentación de un caso con lesiones kaposiformes / Antiphospholipid syndrome: a case report with Kaposi-like lesions

Se comunica una paciente de 44 años de edad que presentaba lesiones kaposiformes profusas, manifestación cutánea infrecuente del síndrome antifosfolípido. Se describen las características clínicas, los hallazgos de laboratorio, así como el tratamiento de esta enfermedad multisistémica (AU)

Quality assurance programme for drug susceptibility testing of Mycobacterium tuberculosis in the WHO/IUATLD Supranational Laboratory Network: first round of proficiency testing.

SETTING: Quality assurance of the WHO/IUATLD global tuberculosis drug resistance surveillance programme. OBJECTIVE: To perform a proficiency test of drug susceptibility procedures within the WHO/IUATLD network of supranational reference laboratories (SRL). DESIGN: Identical culture panels consisting of 20 clinical isolates of Mycobacterium tuberculosis containing both drug susceptible and drug resistant cultures were tested by the 16 laboratories of the network for resistance to streptomycin, isoniazid, rifampicin and ethambutol. The drug susceptibility testing procedures included the proportion, absolute concentration and resistance ratio methods as well as their variants, including the radiometric BACTEC 460 method. RESULTS: The first round of proficiency testing has shown that the specificity of drug susceptibility testing within the SRL network was significantly higher than its sensitivity. The testing of isoniazid and rifampicin shows a high degree of agreement between the labs, but discordant results can be obtained with streptomycin and ethambutol. CONCLUSION: Drug susceptibility procedures for the testing of isoniazid and rifampicin, the two anti tuberculosis drugs which define multidrug-resistant tuberculosis, are highly reliable within the SRL network. Procedures for drug susceptibility testing of streptomycin and ethambutol are still in need of standardization.

[The effect of streptomycin on energy metabolism in inner ear tissues in guinea pigs].

Fifty-four guinea pigs were divided into three groups. Group I was injected with streptomycin sulfate 200 mg/kg body wt.ip. for 8 days; group II was injected with streptomycin sulfate 200 mg/kg body wt. and Chinese angelica 2 ml/kg body wt. ip. for 8 days; group III, serving as control, was injected with corresponding volume of water for injection. Glucose and pyruvate levels were determined chemically, ATP, ADP and AMP were determined by HPLC. The hearing reflex thresholds were measured before injection of drug and sacrifice. The glucose content in inner ear tissues of group I and II was found to be lower than that of the control. The pyruvate content in group I and II was higher than that of the control. The ratio of pyruvate to glucose in the group I and II was significantly higher than that of the control, P < 0.05. ATP level in inner ear tissues in group I (50.3 +/- 39.0 micrograms/mg protein) decreased significantly as compared with the control (167.7 +/- 115.4 micrograms/mg protein), P < 0.05, but not in group II (151.6 +/- 124.3 micrograms/mg protein). The energy change in each group was in the range of 0.80-0.84. The hearing reflex threshold attenuation in group I 8 days after injection of drug was slightly lower than that prior to the injection of the drug. The results suggest that streptomycin might inhibit the uptake and metabolism of glucose and decrease the ATP level in the inner ear tissues, and that the inner ear tissues accelerate the metabolism of amino-acids for compensation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Experimental study of Rhizoma drynariae (Gusuibu) in the treatment of streptomycin ototoxicity].

According to Chinese traditional medical theory, kidney governs ear. Gusuibu is a kind of traditional Chinese drug which has nutritive effect to the kidney. The present study was intended to show whether Gusuibu could reduce streptomycin ototoxicity. Changes in cochlear hair cells, the Preyer's reflexes and auditory brain stem responses in guinea pigs were examined. Statistical analysis showed that hair cell loss in Gusuibu group was significantly milder then that in the control group; hearing threshold was also significantly different between these two groups. It was suggested that Gusuibu may have protective effect against streptomycin ototoxicity.

Treatment of streptococcal infective endocarditis.

Patients with infective endocarditis caused by penicillin-sensitive streptococci (minimal inhibitory concentration for penicillin of 0.1 microgram/ml or less) may be treated successfully with one of the following regimens: aqueous penicillin G administered intravenously for four weeks, intravenous aqueous penicillin G for four weeks combined with streptomycin for the first two weeks of therapy, or parenterally administered penicillin plus streptomycin for two weeks. A cure rate of at least 98 percent may be anticipated with each of these regimens. During a 12-year period among 142 patients treated for two weeks with penicillin and streptomycin, one (0.7 percent) had relapse and four (3 percent) had vestibular toxicity. The major advantage of the two-week regimen is that it is more cost-effective than the four-week regimens. The major disadvantage of the use of streptomycin is the relatively low risk of vestibular toxicity. Patients with enterococcal endocarditis were treated initially for four weeks with aqueous penicillin G together with either streptomycin (streptomycin-susceptible enterococci, 36 patients) or gentamicin (streptomycin-resistant enterococci, 20 patients). Compared with patients who had symptoms for less than three months, patients with symptoms for longer than three months had a higher relapse rate (0 percent versus 44 percent; p less than 0.001) and mortality (2.5 percent versus 25 percent; p less than 0.001). Patients with mitral valve endocarditis had a significantly higher relapse rate (25 percent) than patients with aortic valve infection (0 percent; p less than 0.01]. Gentamicin-associated nephrotoxicity was more frequent (p less than 0.001) among patients treated with more than 3 mg/kg per day of gentamicin than among those treated with 3 mg/kg per day or less (100 percent versus 20 percent). Relapse and mortality rates did not differ significantly between patients treated with low-dose or high-dose gentamicin regimens. Patients who have had symptoms of enterococcal endocarditis for longer than three months or perhaps patients with mitral valve infection should receive at least six weeks of penicillin therapy together with an aminoglycoside; patients without either high-risk factor may be treated successfully for four weeks.

Treatment of streptomycin-susceptible and streptomycin-resistant enterococcal endocarditis.

Fifty-six patients with enterococcal endocarditis received 4 weeks of antimicrobial therapy with penicillin G and streptomycin (36 patients) or, if infections were streptomycin resistant, penicillin and gentamicin (20 patients). Compared with patients who had symptoms for less than 3 months, patients with symptoms for more than 3 months had a higher relapse rate (0% versus 44%; p less than 0.001) and mortality (2.5% versus 25%; p less than 0.001). Patients with mitral valve endocarditis had a significantly higher relapse rate (25%) than patients with aortic valve infections (0%) (p less than 0.01). Gentamicin-associated nephrotoxicity was more frequent (p less than 0.001) among patients treated with greater than 3 mg/kg d of gentamicin than among those treated with 3 mg or less (100% versus 20%). Relapse and mortality rates did not differ significantly between patients treated with low-dose or high-dose gentamicin regimens. Patients who have had symptoms of enterococcal endocarditis for more than 3 months or patients with mitral valve infection should receive at least 6 weeks of antimicrobial therapy, but patients without these high-risk factors can be treated for 4 weeks.

The aminoglycosides. Streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin, sisomicin.

Despite their toxicity, the aminoglycosides remain useful and are often the first choice in the treatment of serious infections due to gram-negative bacilli. Nephrotoxicity has restricted the indications for neomycin to topical and oral use. Emergence of resistant organisms has limited the use of streptomycin to a few specific conditions. Gentamicin, tobramycin, and amikacin are effective against a broad spectrum of gram-negative bacilli including Pseudomonas aeruginosa. Amikacin is the aminoglycoside of choice when gentamicin resistance is prevalent.

Etiological factors in child bronchial asthma.

Available statistics regarding the different activating mechanisms of asthma vary greatly and they are a product of an era wherein only the extrinsic factors were considered to be fundamental in the etiology of bronchospasm. For the present study were selected 700 clinical case histories of children suffering from bronchial asthma. Emphasis was placed on the sex, age of onset, family history, presence of associated allergic disorders, intracutaneous tests and their relation to the anamnesis and evolution of the disease in the treatment period for no less than three years. A purely bacterial cause, without other types of sensitization involved, was present in 54% of the cases, on the contrary, purely extrinsic factors were present in 10% of the cases, summing up to 46%, if their role in the mixed group is taken into consideration. The high percentage of bacterial asthma (94.7%) was found fundamentally in children below one year of age. The results obtained in this demonstrate the great importance of the bacterial factor in child bronchial asthma.

Eosinophilic occlusive pulmonic panarteritis associated with long-term antibiotic therapy.

The administration of antibiotics through central catheters for short periods of time frequently is encountered clinically. This report is an in vivo experimental study of long-term bolus administration of antibiotics through a central catheter inserted in the external jugular vein. Approximately 30 calves, which weighed between 180 and 225 kg, had silicone-rubber catheters inserted for protracted periods of time. Various concentrations of either penicillin, cephalothin, or streptomycin were given intravenously in bolus doses. Minimal doses given for long periods of time or large doses given over short periods of time did not produce any pulmonary vascular lesions. Large doses of antibiotics administered for long experimental periods routinely produced a pulmonary vascular lesion in the medium-size and small-size pulmonary arterioles. The vasculitis consists of a diffuse eosinophilic infiltrate located perivascularly and throughout the intima and media. Associated with the vasculitis was a diffuse hyperplasia of the intima and media which frequently stenosed the vascular lumen. These studies suggest an association between large bolus dosages of antibiotics given over a prlonged period via a central catheter and a constrictive pulmonary arteriolar eosinophilic panvasculitis.

[Diagnostic problems in dizziness or vertigo (author's transl)]. / Differentialdiagnostische Uberlegungen zur Schwindelsymptomatik.

Different causes of dizziness or vertigo can only be recognized by thorough anamnestic explorations. Following a classification in vestibular and nonvestibular causes for vertigo, a further differentiation is possible by defining different characteristic qualities of the symptoms involved. In addition to the classical vestibular forms of vertigo seen, dizziness currently results from drug overdosages, hypertension, polyneuropathy and--less commonly, but equally important--brief epileptic seizures. Psychosomatic and neurotic symptoms may also lead to unsteady gait, dizziness or vertigo, all of which are distinguished only with difficulty by the patient.

Study of adverse reactions to a once-weekly regimen of streptomycin plus a slow-release preparation of isoniazid in high dosage for six months.

A once-weekly regimen of streptomycin (1 g) plus a slow-release preparation of isoniazid (matrix isoniazid) in high dosage, namely 50 mg/kg body-weight for rapid inactivators of isoniazid and 35 mg/kg for slow inactivators, was prescribed for 6 months to 64 tuberculous patients (27 rapid, 37 slow). The regimen was tolerated by most the of the patients. However, 4 rapid and 3 slow inactivators had a modification of the regimen, mainly for giddiness. There were no cases of peripheral neuropathy. No adverse effects on haemopoiesis or hepatic or renal functions were observed in any of the patients. It is concluded that it is feasible to administer matrix isoniazid in dosages considerably higher than ordinary isoniazid, in once-weekly chemotherapy.

[Effect of streptomycin on the hearing function]. / Vliianie streptomitsina na slukhovuiu funktsiiu

One of the main problems of the modern medicines within the last 10-15 years has been so-called drug disease. Toxic effect of the aminoglucoside antibiotics and streptomycin on the vestibular and auditory analysers is one of frequent and severe complications of their use. According to the author's observations treatment of 200 patients with streptomycin resulted in affection of their hearing in 40 to 80 cases. The ototoxicity was confirmed by audiograms, while the level of clinical signs and subjective complains did not always coincided with the audiograms. Audiometry should be performed at the beginning of the treatment and before the repeated courses of streptomycin therapy, and later it should be repeated during the treatment course every 10-15 days. Under the experimental conditions low doses of streptomycin used at early stages induced fine damages in the sensor cells of the cochlea which could be detected only histochemically.

Complete respiratory paralysis caused by a large dose of streptomycin and its treatment with calcium chloride.

Several cases have been reported, in which a rather large dose of streptomycin given intraperitoneally at operation has produced respiratory paralysis. In these cases the treatment has usually consisted of respirator ventilation and administration of atropine and neostigmine. In animal experiments, in which a cessation of breathing has been produced, calcium salts have produced quick recovery. The authors present a case, in which appendicetomy was performed on a 10-year-old girl for a perforated appendix at the end of which, an overdose of intraperitoneal streptomycin was given, followed 10 minutes later by complete cessation of breathing. The patient had to be intubated again and put into a respirator. Neostigmine and atropine were used without noticeable effect. One and a half hours after the breathing had stopped 0.6 g calcium chloride was given intravenously and the girl recovered immediately and completely.