Sensitivity of the causative agent of tularemia to antibiotics

Sensitivity of the tularemia causative agent of different geographical races to antibiotics such as streptomycin, tetracycline, gentamicin, rifampicin (20 strains), ampicillin, polymyxin M, erythromycin, oleandomycin (361 strains) and lincomycin (294 strains) was studied. High sensitivity of the tularemi a microbe to streptomycin, tetracycline, rifampicin (MIC of 10 gamma/ml), gentamicin (MIC of 1 gamma/ml) and resistance to 50 gamma of ampicillin and 1000 gamma/ml of polymyxin M were found. Combined use of 50 gamma of ampicillin and 100 gamma/ml of polymyxin M added to the nutrient medium for growth inhibition of the foreign flora on isolation of the tularemia causative agent from the infected material including stable laboratory animal carcases was recommended. Marked differences in sensitivity of the strains of different geographical races to the macrolides and lincomycin were observed. The strains of the non-Arctic and Central Asiatic races were of low resistance to the above drugs (the MIC of erythromycin, oleandomycin and lincomycin were 10--50, 50--400 and 25--100 gamma/ml respectively. Within the holarctic race 40 per cent were low resistant and 60 per cent were highly resistant to these drugs. The above drugs should not be used for treatment of tularemia cases.     

Sensitivity of various races of the tularemia microbe to erythromycin, oleandomycin and polymyxin]

Sensitivity of 66 strains of the tularemia microbe to erythromycin, oleandomycin and polymyxin was studied. It was shown that all the strains were resistant to polymyxin. The strains of the non-artic and Central Asiatic races and 64 per cent of the strains of the holarctic race were resistant to erythromycin and oleandomycin.     

Sensitivity of pathogenic clostridia to antibiotics]

By the sensitivity levels of the gas infection causative agents, i. e. pathogenic Clostridia to antibiotics, the latter were conditionally divided into 4 groups. The 1st group included the most active antibiotics, such as tetracyclines,, penicillins, cephalosporins, rifampicin, 7-chlor-7-desoxylincomycin. Their minimum inhibitory and bactericidal concentrations did not usually exceed 2 gamma/ml. For most of the strains the inhibitory and bactericidal concentrations amounted to the tenth and hundredth fractions of gamma/ml. The antibiotics of the 2nd group, i. e. erythromycin, lincomycin,ristomycin and levomycetin inhibited multiplication and viability of pathogenic Clostridia in concentrations of 20 gamma/ml. Erythromycin was most active among them The 3rd group consisted of oleandomycin, novobiocin, geliomycin and azalomycin, the minimum inhibitory concentrations of them being 20 to 50 gamma/ml. The antibiotics of the 4th group, i. e. neomycin, monomycin, kanamycin, streptomycin, polymyxin and others affected pathogenic Clostridia at very high concentrations, amounting to the hundrenth and thousandth of gamma/ml.     

Recipient capacity of clinical strains of staphylococci belonging to different phage groups]

The recipient capacity of the strains of Staph. epidermidis and Staph. areus belonging to different phage groups, as well as the possibility of epidemic distribution of the erythromycin resistance marker among the clinical staphyloccal strains on using the defective phage obtained from strain 8325 P IIde was studied. The defective phage P IIde may be the source of epidemic distribution of the drug resistance among the competent strains of Staph. aureus. All erythromycin sensitive strains of Staph. aureus lysed by the phages of groups I and III proved to be competent recipients of the erythromycin resistance marker. The strains of Staph. aureus of phage group II and phage type 80/81, as well as the strains of Staph. epidermidis were not competent recipients under our experimental conditions. It was not possible to transfer the high level of erythromycin resistance (1000 gamma/ml) on transduction to the strains of phage group I with a relatively low level of resistance to this antibiotic (20-50 gamma/ml.     

Cytopathic effect of the tularemia microbe on a culture of peritoneal macrophages

Morphological analysis of the process of interaction of tularemia microbe strains differing by virulence with macrophages demonstrated that all these strains produced a lethal effect on macrophages obtained from the animales sensitive to the infection. The macrophages obtained from the animals were but little sensitive to tularemia and were resistant to the action of the causative agent of this infection. The data obtained led to a supposition on the presence in the tularemia causative agent of a factor responsible for its lethal action on the macrophages.     

Biological characteristics of spectinomycin-resistant strains of the tularemia pathogen

Sensitivity of 2 subspecies of the tularemia causative agent to spectinomycin, an aminoglycoside antibiotic, was studied in vitro. The MIC of the antibiotic with respect to strains 503/847 and Schu was 40 micrograms/ml and with respect to strain A-Cole 20 micrograms/ml. The frequency of spontaneous spectinomycin resistant mutants was low. The mutants grown on a medium containing spectinomycin in a concentration of 100 micrograms/ml were highly resistant to the antibiotic (at least 10000 micrograms/ml). By the main biological properties and virulence the spectinomycin resistant mutants did not differ from the initial strains.     

Phosphatase and penicillinase activities as stable traits for the differentiation of the racial classification of Francisella tularensis]

In the causative agent of tularemia new markers correlating with different subspecies of this microbe have been detected. Thus, F. tularensis strains belonging to the American and Central Asian subspecies are characterized by phosphatase activity, which makes it possible to use the phosphatase test for their differentiation from the strains of the holarctic variety. F. tularensis subsp. mediasiatica are incapable of producing beta-lactamase which differentiates them from the representatives of the varieties holarctica and tularensis. These newly discovered signs are stable and do not depend on the virulence of the cultures under study and on the conditions of the cultivation of F. tularensis.     

Erythromycin and oleandomycin concentration in the body of angina patients taking the preparations orally]

The antibiotic levels in patients suffering from angina were studied with the agar-diffusion method. The drugs were used orally in single and multiple doses (every 6 hours): erythromycin in doses of 4000 and 6000 gamma/kg and oleandomycin in doses of 4000 and 8000 gamma/kg. When erythromycin was used in a single dose of 4000 gamma/kg, its levels in the objects tested, i.e. the blood serum, saliva, mucus from the tonsil surface and tissue did not reach the concentrations corresponding to the sensitivity levels of the microbes to the antibiotic (0.75 gamma/ml). When the drug was used every 6 hours, the concentration increased. Still, it reached the above level only in the blood and tonsil surface mucus. Only when the antibiotic was used repeatedly in doses of 6000 gamma/kg, its levels in the examined objects reached 0.75 gamma/ml. When oleandomycin was used in single and repeated doses of 4000 gamma/kg, its levels were always lower than those providing sensitivity of beta-hemolytic streptococci to it (1.0 gamma/ml). The antibiotic use in doses of 8000 gamma/kg provided the required level in all the object examined.     

Culture properties of the causative agent of tularemia isolated in natural foci in Stavropol Territory, the Kalmyk ASSR and the Armenian SSR

The strains isolated in natural foci of the Stavropol Territory and the Armenian SSR have been found to belong to the holarctic race of Francisella tularensis, biovar II. In natural foci of the Kalmyk ASSR the strains belonging to biovars I and II have been isolated. The study of the tularecinogenicity of the cultures has revealed the existence of strains which are not sensitive to their own tularecins. The phenomenon of tularecinogenicity in F. novocida has been established. Avirulent strain 319/38 belonging to the non-arctic race is recommended as an indicator strain for the determination of tularecinogenicity.     

Sensitivity of beta-hemolytic streptococci to antibiotics]

Susceptibility of 64 beta-hemolytic streptococcal strains isolated from the patients with sore throat was studied by the method of serial dilutions in fluid nutrient medium (Konikov broth). Heterogenecity with respect to the sensitivity was investigated in 34 strains among separate populations of the microbes (10 to 15 in every strain). The MIC of benzylpenicillin, oxacillin and erythromycin ranged within 0.007--0.24 U/ml, 0.02--0.36 gamma/ml and 0.005--0.1 gamma/ml respectively. The MIC of benzylpenicillin with respect to separate populations most sensitive to it was 0.007--0.015 U/ml, while that with respect to the lease sensitive populations ranged from 0.015 to 0.24 U/ml. The respective values for oxacillin were 0.02--0.12 and 0.18--0.36 gamma/ml and those for erythromycin were 0.005--0.025 and 0.05--0.1 gamma/ml. Therefore, the beta-hemolytic streptococci isolated from the patients with sore throat were characterized by a rather high sensitivity to the antibiotics which was important precondition for their efficiency in treatment of the patients with the above disease.     

Biological properties of sherry yeasts in the presence of antimicrobial preparations

The wine yeasts Cheres were not sensitive to high concentration (500 gamma/ml) of benzylpenicillin, streptomycin, tetracycline, oxytetracycline, chlortetracycline, morphocycline, erythromycin, oleandomycin, monomycin, neomycin, kanamycin, polymyxin, ampicillin, oxacillin, methicillin, ceporin, ristomycin, levomycetin, furadonin and furazolidone. In concentrations of 50 to 500 gamma-ml oleadomycin, chlortetracycline, oxytetracycline, kanamycin and ristomycin inhibited synthesis of the Cheres yeast biomass. Benzylpenicillin, polymyxin, neomycin and ampicillin in concentrations of 50 to 100 gamma/ml had a stimulating effect on the yeast biomass synthesis.     

Rapid evaluation of the effectiveness of antibacterial drugs in experimental tularemia

Rapid estimation of the protective effect of antibacterial drugs on Fransiella tularensis for not more than 2 days was shown possible in experiments on albino mice infected with tularemia. High efficacy of aminoglycosides (kanamycin, gentamicin, streptomycin, amikacin, netilmicin, tobramycin, sagamycin, ribostamycin and sisomicin), tetracyclines (tetracycline, doxycycline, minocycline and methacycline), rifampicin, phosphomycin and oxolinic acid was determined with the recommended rapid method. Amoxycillin, ampicillin, piperacillin, carbenicillin, erythromycin, levomycetin, cefradine, cefmetazole, cefatrizine, cefoxitin, cefsulodin and bactrim (biseptol) proved to be inefficient against the tularemia causative agent.     

Drug Resistance of Staphylococci

Examination of cross resistance to macrolide antibiotics in erythromycin resistant staphylococcal strains isolated from clinical sources in the United States showed that there were two types of cross resistance, group A (13.4%) and group C (86.6%). Group A possessed multiple resistance to the macrolide antibiotics, erythromycin, oleandomycin, leucomycin and spiramycin, and was also resistant to lincomycin. In group C, resistance to erythromycin alone or to both erythromycin and oleandomycin could be induced by exposure to erythromycin.     

Isolation of the causative agent of tularemia from an inoculum from skin lesions in the ulcerobubonic form of the disease

A case of tularemia in a human patient infected through the sting of a gadfly (Tabanus) is described. The causative agent of the disease was isolated from the patient with the ulcerobubonic form of the disease by the method of the direct inoculation of the contents of the patient's cutaneous effect. The properties of the isolated culture were established; the strain thus obtained was classified as a representative of the geographical race Francisella tularensis holarctica 01s. The causative agent circulating in the human patients was found to be fully virulent.     

Phage-typing of brucella strains collected in Italy during 1982-83

62 strains of Brucella genus, freshly isolated from man and animals in several geographical areas in Italy, were tested for sensitivity to the phages: Tb, Wb, Fi, BK2 and R. The strains from human source, all classified like Br. melitensis biotype II, had three sensitivity patterns to phages. Some of the strains from cattle are Br. abortus biotype I, with the standard sensitivity pattern to the phages, but among cattle strains too, the largest part may be classified as Br. melitensis biotype II, and shows the same phage sensitivity pattern of the human strains. The strains from sheep are Br. melitensis biotype II, with only two phage sensitivity pattern; but it is to emphasize that some strains from goats are Br. abortus for sensitivity to phage Tb. It is also note the strains from buffaloes, which are Br. abortus biotype I with a very high degree of sensitivity to all the testes phages, included the R phage, which is supposed active on rough strains while these are smooth.     

Serotypes and biotypes and antibiotic susceptibility of Haemophilus influenzae encountered in a clinical laboratory in Taiwan.

Forty-four serologically and biochemically typable Haemophilus influenzae isolates from clinical specimens in Taiwan were subjected to analysis in their relationship with source of isolation and age distribution. It was found that all isolates from blood and cerebrospinal fluid were serotype b, biotype I, and all were in children less than 4 years of age. Serotypes b and e, biotypes I and III were encountered to have the highest incidence of infection caused by H. influenzae in this area. All H. influenzae isolates were further tested for susceptibility to several selected antibiotics. All strains of this organism were susceptible to erythromycin and chloramphenicol. All but two strains were susceptible to tetracycline, whereas more strains were resistant to carbenicillin, gentamycin, keflin, and penicillin. Thirty-four percent strains were found to be resistant to ampicillin and all were beta-lactamase producer. No direct correlation between ampicillin resistance and serotypes or biotypes was recognized.     

Isolation of the causative agent of tularemia from Siberian lemmings in Eastern Taymyr]

The authors present the results of bacteriological and serological study for tularemia of 498 lemmings caught in Taimyr. Positive results were revealed in 4 out of 98 sera examined in the indirect hemagglutination test. In carrying out 67 biological tests on albino mice there were isolated for the first time in the Soviet Union 6 cultures of the causative agent of tularemia from the spleen of lemmings. By morphological, cultural and virulent properties the cultures obtained failed to differ from those isolated in other regions of the Soviet Union, and, consequently, we referred to the holoarctic race. Thus, it was established by the authors (both serologically and bacteriologically) that there existed tundra foci of tularemia.     

Change in phagocytic activity toward the agent of tularemia in highly sensitive animals with mixed infections]

An increase of the ingestive and digestive capacity of neutrophils to the homologous causative agent and tularemia microbe was revealed by the opsonophagocytic test in Microtus arvalis, albino mice and guinea pigs infected with sublethal Yersinia pseudotuberculosis and Salmonella typhimurium doses. In subsequent tularemia infection some of the animals displayed a reduction of the septicemia intensity, prolongation of the disease and elevation of the susceptibility threshold. Period of manifestation of the inhibitory action on tularemia coincided with that of the increase in phagocytic activity     

Comparative analysis of antibiotic sensitivity of Streptococcus pneumoniae strains isolated from patients and carriers

The data on antibiotic sensitivity of 38 strains of S. pneumoniae isolated from children and 46 strains isolated from carriers are presented. The isolates from the carriers had significantly higher sensitivity to benzylpenicillin, ampicillin, methicillin, oxacillin, cefazolin, erythromycin, oleandomycin and lincomycin. Resistance to gentamicin was more frequent in the strains isolated from the carriers. Among the strains of S. pneumoniae isolated from the patients and carriers representatives of serovar K19 were more frequent. There were no statistically reliable difference in them by sensitivity to benzylpenicillin, ampicillin, cefazolin, lincomycin and rifampicin. Still, the isolates from the carriers were much more sensitive to methicillin, oxacillin, oleandomycin and erythromycin.     

Persistence of Francisella tularensis McCoy et Chapin tularemia agent in the organism of highly sensitive rodents after oral infection

In the literature there are no data on the possibility of obtaining in experiment non-fatal tularemia infection (persistence) in rodents highly sensitive to it (Group I) when using highly virulent strains circulating in nature for infection by natural routes. Our detailed experiments on 1483 adult voles Microtus rossiaemeridionalis Ogn. (syn. M. subarvalis Meyer et al.) of laboratory origin using virulent strains of Francisella tularensis holarctica Ols. et Meshch. and natural alimentary infection by feeding on bodies of died animals or forced dosed administration of a mixture of dead and living bacteria to the voles through the oesophagus demonstrated the possibility of the animals to survive tularemia with subsequent long-term chronic carrier state of the infectious agent. They also confirmed the ability of voles to eat readily cadavers of their kin (cannibalism, necrophagia). Experiments with the fully virulent strain 503 and feeding on cadavers were carried out on 439 voles. 203 animals died from acute tularemia, 43 from side effects and 193 survived. Two of the latter (0.5%) exhibited chronic bacterial carrier state, and agglutinins to tularemia microbe (1:320) were found in their blood. From 309 voles subjected to dosed feeding, 153 died from acute tularemia, 27 from side effects and 129 survived. Two of them were bacterial carriers and 6 (1.9%) showed agglutinins (1:160-1:1280). In experiments with strain 165, spontaneously less virulent for guinea pigs, 433 voles were fed on cadavers. 170 of them died from acute tularemia, 53 from side effects, and 210 animals survived. Among the latter, 14 animals (3.2%) were found immune to 100 LD50 of the highly virulent strain 1298. In dosed feeding of 302 voles with the strain 165, 90 animals died from acute tularemia, 59 from side effects, and 153 survived, including 63 animals (20.7%) immune to 100 LD50. The surviving immune voles exhibited seroconversion and long-term persistence of the infectious agent in the internal organs (up to day 257-313--period of observation), accompanied bacteriuria in some cases. Histological examination of the kidney revealed, for the first time, important pathological changes of glomerulonephritis type with elements of pyelonephritis. Protracted stay of the agent in the organism of the vole does not affect its virulence. Persistence of tularemia agent in the organism of voles highly sensitive to tularemia in alimentary administration to them of living and dead bacteria is achieved as a result of anticipatory development of immunological reactions in response to a massive dose of killed antigen, against the background of which the accumulation of simultaneously administered