Effectiveness of a polyvalent corpuscular Pseudomonas aeruginosa vaccine, antibiotics and their combinations in experimental chronic Pseudomonas aeruginosa infection

The data on the development of the experimental model of P. aeruginosa chronic infection in mice, produced by their intraperitoneal inoculation with the infective agent, and on the study of the properties of this model are presented. The model has been used in the experimental study of the preventive action of P. aeruginosa polyvalent corpuscular vaccine. The comparative study, carried out with the use of the proposed model, has been made with a view to evaluating the effectiveness of different methods for the treatment of P. aeruginosa chronic septic infection by means of antibiotics (polymixin B and tobramycin), P. aeruginosa polyvalent corpuscular vaccine and their combination. The combined use of this vaccine with antibiotics (polymixin B or tobramycin) has proved to give the most pronounced curative effect with respect to P. aeruginosa chronic infection.     

Molecular approach for development of new medicaments for chronic infections treatment

Owing to the progress in cellular microbiology it has been evidently proved that inflammation induced by infectious agents forms the basis of many chronic conditions. Therefore a microbial infection can be considered as a triggering factor of such widespread and significant diseases as infertility, arthritis, atherosclerosis, asthma, gastritis, stomach ulcer and cancer, neurological syndromes and some oncological formations. Practically all pathogenic and conditionally pathogenic bacteria can induce chronic infections of different organs and tissues. It has been revealed that in spite of differences of clinical syndromes and participation of different bacteria in their induction the several general mechanisms of chronic infections are detected. Failure in chronic infections therapy is due to the absence of medicaments to eradicate persistent forms of pathogens. The development of new medicaments for chronic infections treatment should be based on the selection of new specific targets, influence on which would to inhibit the mechanism of chronic infections induction.     

Antibiotic Therapy in Current Surgical Practice

The clinical surgeon is required to assume important responsibilities in the management of microbial infections. To be effective, antibiotics should be used against sensitive organisms, the lesion should be infused adequately, and, ideally, the antibiotic should be bactericidal and compatible with other antibiotic agents in combination. A survey of commonly used antibiotics disclosed that penicillin in its synthetic and natural forms is still the drug of choice in most cases, particularly since, in its different forms, it may be used in combination with other agents to give a wide antibacterial spectrum. As a major surgical problem, Gram-positive septicemia has been superseded by Gram-negative septicemia and attendant endotoxin shock. Most authorities advocate a combination of bactericidal and bacteriostatic antibiotics in the treatment of endotoxin shock. However, while antibiotic therapy is considered crucial in the treatment of this condition, the mortality rate is still high and no uniform regimen of antibiotic therapy has been accepted.     

Therapeutic possibilities in Pseudomonas infections.

Acute pseudomonas infections require treatment with antibiotics producing a bactericidal effect. The most useful are gentamicin, tobramycin, sisomicin and polymyxin B. In resistant strains, amikacin is indicated in addition. Carbenicillin, ticarcillin, carfenicillin or azocillin should never be given alone but in combination with some of the above preparations. Other drugs, such as chloramphenicol, tetracycline or streptomycin, though effective in vitro, should be avoided. Chemotherapy may be complemented by passive immunization either with hyperimmune specific gama globulin or hyperimmune plasma. A programmatic item of combined treatment is active immunization, especially with toxoid vaccine. Chronic processes are not, perhaps with the exception of urinary infections, suitable for antibiotic therapy. For this reason effective polyvalent vaccines should be developed from appropriate strains. It is now certain that in infections caused by mucous strains (most frequently encountered in cystic fibrosis) the vaccine should be prepared from these strains, since they have distinct functional and antigenic characteristics.     

Relation of intrahospital morbidity from staphylococcal infections to some properties of hospital strains]

Analysis of staphylococcus infection morbidity in a large obstetrical hospital for 5 years offered a possibility of establishing an association between the severity of the course of staphylococcus infections in patients, the bacteriophage type of the causative agent and its resistance to antibiotics. The qualitative changes in morbidity in the direction of the prevalence of minor forms and mild course ocurred in parallel with the changes of the leading bacteriophage type from the epidemic 75/77 and 80/81 to the nonepidemic bacteriophage types of the III bacteriophage group and the changes of the antibiograms of the causative agents in the direction of an increase in the number of strains sensitive to antibiotics. Since the severity of the course of staphylococcus infection characterized the pathogenicity of the strain of the causative agent a conclusion could be drawn on the association between the sign of virulence and determinants of the medicinal resistance and definite prophages in the hospital strains of staphylococcus.     

急性血源性骨髓炎全身与局部抗生素治疗体会及重症病例分析

目的:总结急性血源性骨髓炎尤其是重症患者治疗中全身及局部抗生素应用的经验、方法及临床疗效。方法:回顾性分析空军军医大学第二附属医院2016年11月至2019年4月收治的12例急性血源性骨髓炎患者,其中3例为合并肺脓肿的重症败血症患者。对患者首先进行经验性全身抗生素治疗,并进行细菌学分析,然后根据药敏结果进行系统抗生素调整,采用万古霉素负载的硫酸钙/磷酸钙复合物进行局部抗生素缓释治疗,分析治疗前后实验室指标变化、局部影像学变化。结果:细菌学培养显示金黄色葡萄球菌10例,人葡萄球菌1例,阴沟肠杆菌1例;平均随访56.6周;治疗后患者白细胞(WBC)、中性粒细胞百分比(NEUT%)、红细胞沉降率(ESR)、高敏C反应蛋白(hs-CRP)等指标均恢复到正常范围内;影像学显示患者病灶处骨重建及新骨形成良好,无感染复发迹象;12例患者中成功治愈11例,治愈率91.7%;1例转为慢性骨髓炎,二期手术后痊愈;其中3例骨髓炎合并重症败血症、肺脓肿患者经系统抗生素及外科治疗,全部治愈。结论:急性血源性骨髓炎的致病菌主要为甲氧西林敏感金黄色葡萄球菌(MSSA),其治疗要在早诊断的前提下,率先经验性应用抗生素,然后根据药敏结果合理选择足量敏感抗生素。苯唑西林在3例合并败血症、肺脓肿的重症患者治疗中起到了关键作用,同时局部采用硫磷复合物负载万古霉素进行治疗,既可以实现局部抗感染作用,又可以促进新骨形成,有效控制全身感染、消除败血症,临床疗效满意。     

Sensitivity to polyvalent therapeutic staphylococcal bacteriophage as a supplementary criterion of staphylococcal pathogenicity]

It is recommended to use the capacity of pathogenic staphylococci to be lysed by polyvalent therapeutic staphylococcal bacteriophage in the capacity of an additional simple and accessible criterion of staphylococcus pathogenicity. Of 147 strains of the pathogenic plasmacoagulating staphylococci 101 were lysed by the phage and of 166 nonplasmocoagulating nonpathogenic strains--only 6. This test correlated with the other signs of staphylococcus (lecithinase and hemolytic activity). The simplicity and sufficient specificity of this test permits to use it in any practical laboratory. Polyvalent diagnostic phage can be used on the basis of therapeutic bacteriophage by its additional adaptation to the pathogenic strains of staphylococcus.     

Induction of L Forms of Haemophilus influenzae in Culture and Their Demonstration in Human Bronchial Secretions

Transitional forms and round bodies of Haemophilus influenzae were identified in sputa from patients with chronic bronchitis who were receiving penicillin therapy for H. influenzae infections. In vitro growth of L forms of this organism was induced by penicillin and glycine and was studied for comparison with development in vivo. Variant forms demonstrated in sputum were similar to variant forms observed in penicillin-induced L colonies. Recurrence of infection after cessation of therapy was related to reversion of persisting L forms to bacillary forms. That these forms were derived from H. influenzae was established by direct staining with fluoresceinlabeled specific antibody. This demonstration that transitional forms and round bodies of H. influenzae occurred in vivo suggests that L forms of bacteria may be significant in chronic or recurrent infections.     

Etiology of acute suppurative destructive pneumonias in children]

Clinical, immunological and bacteriological studies were carried out in 63 children with the so-called staphylococcus destruction of the lungs. It was shown that in some of the cases destructive process in the lungs, along with the pathogenic staphylococcus, could be caused by the Gram negative bacteria (Proteus, Bac. pyocyaneus, etc.). It was found that in children of different age groups the titre of antistaphylococcus antibodies up to 0.5 AU/ml was normal and pointed to the absence of any inflammatory disease of staphylococcus etiology; a titre of 2 AU/ml - and overcould be considered as diagnostic. In connection with bacterial poly-etiology of acute destruction of the lungs in children it is suggested that it should be designated as "acute purulent destructive pneumonia". The importance of immuno-bacteriological studies in children with diseases with the mentioned pathology is emphasized; these examinations permit to choose proper complex therapy.     

细菌性前列腺炎病原菌及临床耐药情况分析

目的 分析汕头地区慢性前列腺炎（CP）病原菌的分布及耐药情况,为确定病原菌分布情况和临床治疗提供参考依据。方法 细菌鉴定及药敏试验采用VITEK-60全自动细菌鉴定仪。结果 葡萄球菌是汕头地区CP的主要致病菌（67％）,其中表皮葡萄球菌的检出率最高,为21．58％。葡萄球菌引起的CP对苯唑西林、头孢唑林、氨苄西林-舒巴坦、阿莫西林-克拉维酸和红霉素等基本无效;而肠球菌对青霉素耐药率为0。治疗首选万古霉素、呋喃妥因、克林霉素和利福平等抗生素。结论 该地区CP的致病菌以葡萄球菌为主,其中表皮葡萄球菌已成为CP的主要病原菌。为减少浪费、提高疗效,建议根据药敏结果选择抗生素。     

Antibiotic Use in a Small Community Hospital

Audits of medical records were done for similar one-month periods in 1974 and 1977 in a 125-bed community hospital in Hawaii to determine patterns of antibiotic use. One quarter of all hospital patients in both study periods received antibiotics. In 1977 cephalosporins, ampicillin and aminoglycosides were the most commonly used antibiotics. Half of the antibiotics used by surgical specialty departments in both periods were for prophylactic indications. The cost of antimicrobial prophylaxis per patient was reduced by about 57 percent in 1977 compared with 1974. In the 1977 period, 58 percent of patients received proper prophylactic antibiotic regimens; this was statistically higher than the 15 percent of patients given appropriate prophylactic antibiotics in 1974. Fewer than half of the patients in both study periods treated for infections received correct antibiotic therapy. In contrast, 82 percent of infectious disease consultations were considered appropriate by an independent specialist in infectious disease. However, these consultations were obtained in only 15 percent of the patients who received therapeutic antibiotics. It was concluded that audits of patients receiving antibiotics can be effective in the development of appropriate prophylactic surgical regimens. However, during the study period in 1977, we were not able to show large scale improvement in therapeutic antimicrobial use at this community hospital, either by our attempts at physician education or by making infectious disease consultations available.     

Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention

Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy--the use of specific viruses that infect bacteria--is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose) administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose) resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections.     

Epidemiological aspects of antibiotic resistance in hospital microorganisms

A total of 37490 medical histories of patients with "pure" and conditionally "pure" operations were analysed with a purpose of studying the scales of hospital infections in surgical inpatients and the effect of the prophylactic use of antibiotics on the frequency of postoperative complications. It was found that postoperative purulent complications developed in 10-25 per cent of patients. Antibiotics and mainly penicillin and streptomycin were used in the treatment of 75 per cent of patients before, during and after operations. The prophylactic use of the antibiotics in mass operations did not prevent the development of infections. Infiltrates and purulent wounds were more frequent (P less than 0.001) in patients subjected to the antibiotic prophylaxis. This indicates that the use of the antibiotics for preventing possible complications in patients with the "pure" operations and in the majority of patients with the conditionally "pure" operations is not advisable. The strategy of the rational use of antibiotics requires that the staff of the large hospitals should include a chemotherapeutist for defining the tactics of chemotherapy and controlling the use of antibiotics which should promote a decrease in the incidence of hospital infections and in the rate of lethality.     

Target-specific screening of antivirulence preparations for chronic infection therapy

Global spread of clinically significant strains resistant to antibiotics necessitated the development of new approaches to generation of antibacterial preparations. Selection of virulence factors as targets for new preparations is an alternative approach to therapy of infections caused by resistant strains and chronic infectious diseases. Contemporary state of research aimed at target selection among virulence factors of pathogenic for humans bacteria that cause chronic infections, and screening of specific inhibitors of these targets are examined. Analysis of limited data of therapeutic activity of selected preparations, i.e. experimental confirmation of the proposed concept, is provided.     

Immunologic correction with immunoglobulin of toxemia with exicosis in infants with acute intestinal infections]

The clinical course of acute intestinal infections complicated by toxicosis and exicosis was studied in 150 infants undergoing multimodality therapy, including natural human immunoglobulin for intravenous injections. The use of the new complex in the treatment of intestinal toxicoses was accompanied by increasing host immunological reactivity within short periods and decreasing of the treatment duration by 5.0 +/- 1.3 days; there were no persisting and chronic forms of the diseases and fatal outcomes. It was concluded that the use of the immunoglobulin for intravenous injections in the multimodality therapy of intestinal toxicoses in infants made it possible to prevent death in complicated intestinal infections and at the same time to accelerate their recovery.     

Infectious Urethritis in Men and Women: Diagnosis and Treatment

Acute and recurrent infectious urethritis in men and women is commonly seen by physicians. Since specific therapy varies widely with the type of urethritis present, the proper diagnosis must be clearly established if curative drug therapy is to be selected. It is valuable, therefore, to review the diagnosis and therapy of the various forms of infectious urethritis that are recognized today in both men and women.     

Detection of pneumococcal antibodies in children with acute pneumonia and pleurisy by an immunoenzyme method

The samples of sera and pleural fluid from sick children have been analyzed by means of EIA techniques. To detect the time course of antibody production, the antigenic preparations of pneumococci (monovalent capsular polysaccharides, polyvalent polysaccharide vaccine and complex pneumococcal antigen) have been used. Antibody response observed in the forms of pneumococcal infection, studied in this investigation, has proved to be highly variable. It is expedient to determine antibodies to polysaccharide antigens not earlier than on days 10-12 from the beginning of the disease. But, besides the positive dynamics of antibodies, their unchanged level is sometimes observed in the patients at the beginning of the disease. As a rule, there is a coincidence between the dynamics of antibody formation in response to polysaccharide antigens and to complex pneumococcal antigen.     

Multi-drug resistant Bacteroides fragilis recovered from blood and severe leg wounds caused by an improvised explosive device (IED) in Afghanistan

This report summarizes the case of a 23 year-old otherwise healthy male that was injured in an improvised explosive device (IED) blast in support of Operation Enduring Freedom (OEF). He sustained bilateral open tibia and fibula fractures in the setting of being exposed to water contaminated with raw sewage. Despite long-term carbapenem therapy, the patient's wounds were repeatedly noted to have purulent drainage during surgical debridement and cultures from these wounds were persistently positive for Bacteroides fragilis. Apparent clinical failure persisted despite the addition of metronidazole to his regimen and an eventual trial of tigecycline. Susceptibility testing of the B.?fragilis isolate was performed and resistance to penicillin, clindamycin,metronidazole, cefoxitin, meropenem, imipenem, piperacillin/tazobactam, and tigecycline was confirmed. The presence of a nimE gene on a potentially transferrable plasmid was also confirmed by plasmid sequencing. The only antibiotics that displayed in vitro susceptibility were moxifloxacin and linezolid. These antibiotics were initiated in combination with aggressive irrigation and serial surgical debridement. Conversion to left-sided internal fixation became feasible and his left lower extremity was salvaged without residual evidence of infection. The patient completed an eight week course of combination moxifloxacin and linezolid therapy without adverse event. This B.?fragilis isolate displayed simultaneous high-level resistance to multiple antibiotics routinely utilized in anaerobic infections. This was evidenced by clinical failure, in vitro susceptibility testing, and demonstration of genes associated with resistance mechanisms. This case warrants review not only due to the rarity of this event but also the potential implications regarding anaerobic infections in traumatic wounds and the success of a novel treatment regimen utilizing combination therapy with moxifloxacin and linezolid.     

Antibiotic resistance dynamics and isolation rate of staphylococci and enterococci from patients of reconstructive surgery units

The dynamics of isolation of staphylococci and enterococci from clinical material of patients and their antibiotic susceptibility within a 5-year period (2005-2009) was analysed. 5990 isolates were tested: 1250 isolates of Staphylococcus aureus, 3268 isolates of S. epidermidis, 1005 isolates of Enterococcus faecalis and 467 isolates of E. faecium. Grampositive infections were shown to be prevailing within the last 2-3 years, the nosocomial epidermal staphylococci more and more replacing S. aureus (the ratio of S. epidermidis and S. aureus in 2009 was 3.3). The isolation rate of E. faecalis significantly increased (by 3.5 times) and the ratio of E. faecalis and E. faecium in 2009 was 4.3. The microflora composition with respect to the isolation source was analysed and its clinical significance was estimated. The study of the antibiotic susceptibility showed that oxacillin had its own specific niche, while antibiotics active against resistant grampositive cocci, such as rifampicin, fusidic acid, fluoroquinolones (moxifloxacin), cefoxitin, as well as amoxicillin/clavulane in infections due to E. faecalis, might be considered as the drugs of choice. In the treatment of nosocomial infections, when the etiological role of MRSA or VRE is suspected or confirmed, the complex therapy should obligatory include the most active antibiotics (vancomycin or linezolid among them).     

Comparative effectiveness of various antibiotics in the treatment of patients with meningococcal meningitis]

The results of treating 322 patients with various forms of meningococcal infection accepted to a hospital within a year are presented. The patients were divided into 3 groups by the character of etiotropic therapy. The patients of group I were treated with benzylpenicillin and those of group 2 were treated with levomycetin sodium succinate. Group 3 included the patients, the therapy of whom with the above two antibiotics failed and they were subjected to treatment with cefazolin, cefotaxime, amikacin and other broad spectrum antibiotics. Benzylpenicillin generally proved to be the drug of choice in the antibacterial therapy of meningococcal infection. In comparison to levomycetin (chloramphenicol) it provide more rapid clinical recovery of the patients and normalization of the indices of the cerebrospinal fluid. Only failure of benzylpenicillin therapy was considered as an indication to the broad-spectrum antibiotics to be in the complex treatment of the patients. As additional methods for estimating the efficacy of antibacterial therapy it was recommended to employ calculation of the integral indices of hemograms (the leukocyte index of intoxication and the hematologic index of intoxication).