Diseases and pathogenes
Perspectives for the Treatment of Hepatitis B Virus Infections
E. De Clercq
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
Translated and reprinted with permission from "International Journal of Antimicrobial Agents" 1999;12/2:81-97.
There are an estimated 350 million people throughout the world who are chronically infected with hepatitis B virus (HBV). Although HBV infection can be prevented through vaccination, HBV has remained the most significant viral pathogen infecting man. Interferon a is currently the only treatment specifically approved by regulatory authorities throughout the world for chronic hepatitis B. However, interferon therapy is associated with several side effects and variable, and often unsatisfactory, response rates. Recent attempts at developing an effective therapy for HBV infections have capitalized on the HBV-specified DNA polymerase as target enzyme. A variety of nucleosides (and nucleotides) that had proved to be affective against other viral infections are further examined for their anti-HBV potential.
Primarily resulting as a spin-off the search for effective anti-HSV and anti-HBV agents, such compounds as famciclovir (penciclovir), BMS-200475 (entecavir), lamivudine (3าั), (-)FTC, L(-)Fd4C, L-FMAU, DAPD (DXG), bis(POM)-PMEA and bis(POC)-PMPA have been identified as effective and promising candidate anti-HBV drugs. But as it has become obvious, future HBV therapy may reside in combination drug therapy to achieve the highest possible virus reduction and minimize the likelihood of drug resistance development.
Key words: viral hepatitis B, antiviral therapy.
Diagnosis and Treatment of Infective Endocarditis
A.A. Demin, V.P. Drobisheva
Novosibirsk State Medical Academy
Recent approaches to management of infective endocarditis including recognition, empirical treatment, and etiological therapy depending on causative agent (streptococci, staphylococci, gram-negative bacteria, fungi and unknown etiology) are given in the article. Risk factors, diagnostic criteria and options for prophylaxis are described. Possible complications requiring additional therapy are discussed. Clinical and microbiological criteria for evaluation of efficacy of treatment are proposed.
Key words: infectious endocarditis, antimicrobial therapy, antibiotic prophylaxis.
New developments in the treatment of infective endocarditis infective cardiovasculitis
E. Gutschik
Department of Oral Microbiology, Faculty of Health Services, school of Dentistry, University of Copenhagen, Denmark
Translated and reprinted with permission from "International Journal of Antimicrobial Agents" 1999; 13:79-92
The natural history of infective endocarditis has undergone remarkable changes over the past 100 years as regards both the demographic characteristics of the disease and changes in the incidence of the so-called diagnostic signs. Alongside these changes and the development of new and better diagnostic tools and criteria, we are also facing new problems with the precise definition of cardiovascular infections and calculation of the incidence of the disease.
Nosocomial endocarditis presents an emerging problem of diagnosis and treatment after heart valve surgery, with pace-maker catheters, defibrillators and a very large variety of foreign materials used in connection with heart valve surgery. New technological progress including new types of prosthetic valves and use of homografts or the Ross operation will give a greater possibility of choosing the best solution in a particular case. Antimicrobial chemotherapy is mainly based on our understanding of the pathophysiology of the disease and efficacy of the antibiotics achieved in an experimental animal model of endocarditis. Important recommendations of single or combined drug therapy or the dosing regimens of antibiotics are still an expression of expert opinion not always supported by experimental or clinical proof. A typical example is the recommendation of two divided doses of gentamycin for treatment of streptococcal endocarditis. Nevertheless, it is the author's opinion that the development of uncomplicated, easy to handle diagnostic and treatment regimens are justified in order to achieve better compliance with these recommendations.
Key words: Infective endocarditis, treatment, bacterial infection, cardiovasculitis.
Identification and Typing of Cryptosporidium: Molecular Biological Approaches
J. McLauchlin
PHLS Central Public Health Laboratory, London, UK
The coccidian protozoan parasite Cryptosporidium is increasingly recognised as a major cause of diarrhoeal disease worldwide. However, the exact modes of transmission are often unclear. The further understanding of the taxonomy of this group of organisms will be essential to an understanding of both their identification and to ascertain their potential significance to human health when recovered from environmental samples. In human the principal infectious agent is Cryptosporidium parvum. Evidence initially from isoenzyme analysis together with PCR and DNA sequenced-based analyses have all identified at least two "types" of C.parvum, that may represent two different species. Since the host range of these two genotypes differs, the epidemiology of the disease in human may also differ, although this has, to date, been incompletely investigated.
Key words: Criptosporidium, identification, typing.
Clinical and Microbiological Aspects of Cryptosporidiosis
A.V. Dekhnith
Smolensk Stat Medical Academy, Smolensk, Russia
The presented above article by J. McLauchlin is devoted to one of the important problem of modern parasitology identification and typing of protozoa belonging to the genus Cryptosporidium that are one of the most important causes of watery diarrhea worldwide. But in Russia these microorganisms are underestimated that is why editorial board of the journal thinks that it is important to familiarize our readers with epidemiology, clinical aspects, diagnostic, treatment and prophylaxis of cryptosporidiosis.
Key words: Cryptosporidium, cryptosporidiosis, diarrhea
Antimicrobial Resistance
Susceptibility to Antimicrobials of Salmonellae and Shigellae Isolated in Ekaterinburg
L.I. Ahmetova, S.M. Rozanova
Microbiological Laboratory of Center of Laboratory Diagnostics, Ekaterinburg, Russia
The purpose of the study to determine antimicrobial susceptibility of Shigella spp. and Salmonella spp. isolated in Ekaterinburg during JuneSeptember 1999. Susceptibility to ampicillin, ampicillin/sulbactam, ciprofloxacin, norfloxacin, tetracycline, cefotaxime, ceftriaxone and co-trimoxazole was tested by microbiological analisator "Sceptor" (Becton Dickinson, USA).
Among tested microorganisms the most resistant was S. flexneri 98,1% of strains were resistant to ampicillin, 49,1% to ampicillin/sulbactam, 87,8% to tetracycline, 73,6 to co-trimoxazole. Among S. sonnei high rates of resistance to tetracycline (64,1%) and co-trimoxazole (97,6%) were detected. Most of strains of Salmonella spp. were sensitive to tested antimicrobials.
The most active among tested antimicrobials were fluoroquinolones (ciprofloxacin and norfloxacin) to which all tested strains were sensitive, and cephalosporines III (cefotaxime and ceftriaxone) 98,5% of Salmonella spp. strains and 100% Shigella spp. strains were sensitive.
Key words: shigellosis, salmonellosis, antimicrobial resistance.
Antimicrobial Agents
Duration of Antibiotic Use in Surgical Patients
E.P. Dellinger
Department of Surgery, Division of Surgery, University of Washington, USA
While many studies have been completed comparing antibiotics or antibiotic combinations in the treatment of specific infections, few studies have focussed on the necessary duration of treatment. If antibiotics are generally safe, is it necessary to be concerned about the duration of antibiotic therapy as long as the drugs are continued long enough? The remainder of this paper assumes that increased antibiotic use can result in an increase in the number and frequency of resistant bacteria in the hospital environment and an increased risk that the individual patient will acquire new nosocomial "suprainfections" caused by resistant organisms. In addition, the longer that any medication is continued, the greater the risk that a patient will experience an allergic or toxic reaction to the drug. With all drugs less is better if the therapeutic aim has been achieved.
Key words: antimicrobial therapy, antimicrobial prophylatis, intraabdominal infection.
Polymyxins New Approaches to the Old Antimicrobials
S.V. Schetinin
Stavropol State Medical Academy, Stavropol, Russia
Spread of multiresistant bacteria makes us to reconsider our attitude to some well-known old antimicrobials, including polymyxins a class of polypeptide antibiotics that are active against many multiresistant gram-negative nosocomial pathogens Escherichia coli, Klebsiella spp., Enterobacter spp., Salmonella spp., Shigella spp., Haemophilus influenzae, Brucella spp., Pseudomonas aeruginosa, Acinetobacter spp., etc. At the same time Proteus spp., Serratia marcescens, gram-positive bacteria and many anaerobes, in particular Bacteroides fragilis are resistant to polymyxins. Only 2 polymyxins are used in clinical practice polymyxin B and colistin (polymyxin ล) that can be used only as "deep alternative" antibiotics for treatment of multiresistant gram-negative infections, in particular infections caused by Pseudomonas spp. and Acinetobacter spp.
Literature review on clinical experience are also presented in the article.
Key words: polymyxin, antimicrobial therapy, antimicrobial resistance, nosocomial infections.
Pharmacoepidemiology
Antimicrobials Prescription Pattern in Outpatient Adults with Community-Acquired Pneumonia
S.N. Kozlov1, S.A. Ratchina1, N.P. Domnikova2, O.I. Karpov3, V.B. Kuzin4, I.V. Leschenko5, R.J. Likhatchova6, S.V. Nedogoda7, L.S. Stratchounski1
1 Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy, Smolensk, Russia
2 Novosibirsk State Medical Academy, Novosibirsk, Russia
3 Institute of Pharmacology, S.-Petersburg State Medical University named under I.P. Pavlov, S.-Peterburg, Russia
4 Nizjni Novgorod State Medical Academy, Nizjni Novgorod, Russia
5 Ekaterinburg Clinical Hospital N 33, Ekaterinburg, Russia
6 Oupatient department N 7, Moscow, Russia
7 Volgograd State Medical Academy, Volgograd, Russia
Case histories of outpatients with community-acquired pneumonia (CAP) who had not required hospitalization were randomly selected in seven regions of Russia for retrospective analysis. Diagnoses were classified according to the ICD-10; antimicrobials to the ATC classification.
Altogether 778 case histories of patients aged from 16 to 88 (average age 47,1±17,2) were included in the study. The most frequently prescribed group of medications were antimicrobials for systemic use (99,5%), anti-cough and anti-inflammatory preparations (75,5%), vitamins (24,0%) and antihistamines (23,4%). In 71,4% of cases antimicrobials were administered orally, in 28,6% parenterally. The most common antimicrobial prescribed was gentamycin (29,3%), followed by co-trimoxazole (22,7%), ampicillin (20,3%) and ciprofloxacin (17,2%).
For initial antimicrobial treatment monotherapy was used in 83,6% of cases (gentamycin in 18,7%, ampicillin 14,5%, ciprofloxacin 12,5). Combination of 23 antibiotics as initial therapy received 16,4% of patients; the most frequently prescribed combinations were ampicillin + co-trimoxazole (24,4%) and gentamycin + co-trimoxazole (8,7%). Average duration of antimicrobial therapy was 9,9±4,7 days.
Unacceptably large number of various antibiotics was used for treatment of CAP. Most of the "popular" antibiotics are not recommended for empirical therapy by the current guidelines. Further studies are advisable to clarify the reasons for such prescription habits.
Key words: community-acquired pneumonia, antimicrobial therapy, pharmacoepidemiology.
Laboratory Diagnostics
Role and Significance of Molecular Methods in Epidemiological Analysis of Nosocomial Infections
I.A. Shaginyan
Research Institute of Epidemiology and Microbiology Named Under N.F. Gamaleya RAMS, Moscow
The problem of nosocomial infections remains the issue of the day and every year its medical and social significance becomes more and more relevant. Permanently working System for epidemiological monitoring could be one of major elements in the fight against nosocomial infections. Microbiological laboratories that identify and type nosocomial pathogens using molecular methods should be at the basis of the work of the System.
The article characterises molecular methods and their significance surveillance at various stages of nosocomial infections investigations. Molecular markers that lies at the basis of genetic typing are analysed in the paper. The article shows selection criteria for molecular methods used for nosocomial infections epidemiological research, as well as the test results interpretation principles worked out for nosocomial infection pathogens. Optimal methods for typing of pathogens are given in the article, that serve as a proof that molecular methods is a powerful tool of clinical microbiologists, epidemiologists and physicians in their struggle against nosocomial infections. The article underlines the necessity of initiating reference-laboratories for nosocomial pathogens molecular typing that would make the fight against nosocomial infections more effective.
Key words: nosocomial infection, DNA, genetic methods, molecular epidemiology.
Polymerase Chain Reaction in Diagnostic Clinical Microbiology
L.V. Lopukhov1, M.V. Edelstein2
1 Kazan Institute of Biochemistry and Biophysics, RAS, Kazan, Russia
2 Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy, Smolensk, Russia
Today's medicine takes advantage of the latest achievements in natural sciences and successfully employs new techniques to the diagnostics and treatment of diseases. Recently molecular-genetic approaches have been applied in the field of diagnostics of infectious diseases in addition to the conventional culture-based and serological methods. The widespread use of molecular methods not only in the research laboratories but also in clinical practice has been made possible with the introduction in the mid-80s and subsequent progress of the technology of in vitro specific DNA-amplification currently known as Polymerase Chain Reaction (PCR). During the last 15 years PCR has made the analysis of several human and microbial genes a routine practice. The key features of PCR namely the versatility, high specificity and sensitivity and relative ease of use have made it an indispensable tool for many diagnostic applications, including direct detection and identification of microbial pathogens; molecular typing and genetic characterisation of microorganisms; analysis of mutations contributing to the genetic diseases in humans; human DNA fingerprinting. The present paper reviews the very basic principles of PCR and its application in the field of clinical microbiology.
Key words: Polymerase chain Reaction, identification of micoorganisms, antimicrobial resistance.
Guidelines for clinicians
Guidelines for Perioperative Antibacterial Prophylaxis in Urological Surgery
K.G. Naber (Denmark, Chairman), B. Bergman (Sweden), M.C. Bishop (UK), T.E. Bjerklund-Johansen (Norway), H. Botto (France), B. Lobel (France), F. Jimenez Cruz (Spain), F.P. Selvaggi (Italy)
HCO UTI Working Group of the European Association of Urology (EAU)
The present guidelines suggest preferable approaches to the problem of perioperative antibacterial prophylaxis in urological surgery. The following questions are discussed in detail: goals, timing, and duration of perioperative antibacterial prophylaxis, selection and route of administration of antibacterial agents. Recommendations for the different types of urological interventions are given.
These guidelines are designed for urologists and clinical pharmacologists.
Key words: antibacterial prophylaxis, perioperative prophylaxis, urology, surgery.